T Sanaka

Tokyo Women's Medical University, Edo, Tōkyō, Japan

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Publications (98)164.05 Total impact

  • Tsutomu Sanaka, Madoka Ishii, Aiko Miyazaki
    Nippon rinsho. Japanese journal of clinical medicine 11/2010; 68 Suppl 9:426-9.
  • Tsutomu Sanaka
    Nippon rinsho. Japanese journal of clinical medicine 11/2010; 68 Suppl 9:514-8.
  • Nihon Toseki Igakkai Zasshi 01/2010; 43(1):77-85.
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    ABSTRACT: Adiponectin is an adipocyte hormone that ameliorates insulin resistance and prevents diabetes. Patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are at a high risk of developing diabetes and cardiovascular diseases. Since treatment with angiotensin II receptor blockers retards the development of diabetes, the effects of losartan on serum adiponectin levels were examined with regard to insulin sensitivity in pre-diabetic patients. Sixty-five patients with IFG/IGT (42 males, 23 females, 63+/-13 years old) were randomized to receive 25-100 mg of losartan (n=33) or a calcium channel blocker (CCB, n=32) for 3 months. Before and after the treatment, changes in blood pressure, insulin sensitivity (HOMA-R) and serum concentrations of high molecular weight (HMW)-adiponectin and free fatty acid (FFA) were assessed. At baseline, the HMW-adiponectin concentration negatively correlated with the patient's body mass index, HOMA-R and triglyceride levels, and positively correlated with high-density lipoprotein (HDL)-cholesterol levels. However, the HMW-adiponectin concentration showed no correlation with blood pressure. HMW-adiponectin concentrations were similar between the losartan group and the CCB group. Both the losartan and CCB treatments similarly and significantly reduced the mean blood pressure (107+/-7 mmHg to 95+/-7 mmHg, p<0.0001, and 104+/-6 mmHg to 93+/-9 mmHg, p<0.0001, respectively). Losartan treatment resulted in a significant increase in HMW-adiponectin concentrations (45.9%) and a significant decrease in HOMA-R (23.9%) and FFA concentrations (26.5%); the percent changes were greater than those induced by CCB treatment (p<0.001, p<0.05 and p<0.01, respectively). We conclude that losartan increases the serum HMW-adiponectin concentration and concurrently improves insulin sensitivity in subjects with IFG/IGT. These results suggest that losartan may prevent diabetes by increasing serum adiponectin levels.
    Hypertension Research 09/2008; 31(8):1611-8. · 2.79 Impact Factor
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    ABSTRACT: Although pathological changes in the vascular lesions of malignant nephrosclerosis have been quantified, little is understood about interstitial changes. We quantified pathological changes such as glomerular damage (glomerular sclerosis and collapse), vascular patency and interstitial fibrosis to determine statistical correlations with clinical data. We examined 25 patients who were diagnosed with malignant hypertension and investigated correlations among age, urinary protein, SUN, 1/Cre, systolic BP and diastolic BP (from medical charts), interstitial fibrosis, glomerular damage, acute tubular damage (semiquantified by scoring) and arterial and arteriolar patency (from renal biopsies). Interstitial fibrosis inversely correlated with 1/Cre (p=0.0114), interlobular arterial patency (p= 0.0139) and total vascular patency (p = 0.0499). Glomerular damage tended to correlate with urinary protein, but the values did not reach the level of statistical significance (p=0.0666). On the other hand, glomerular damage correlated with neither interstitial fibrosis nor vascular patency. Acute tubular damage closely correlated with both diastolic (p= 0.0086) and systolic (p = 0.0075) BP. Interstitial damage increases with decreasing interlobular arterial patency and renal function decreases with increasing interstitial damage. Since acute tubular damage that can progress to chronic interstitial damage closely correlates with BP, the control of BP might indirectly influence the prognosis of renal function.
    Nippon Jinzo Gakkai shi 02/2008; 50(4):488-98.
  • Nihon Toseki Igakkai Zasshi 01/2008; 41(11):785-792.
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    ABSTRACT: The presence of peripheral arterial disease substantially increases the risk for both morbidity and mortality among end-stage renal disease patients. Low-density lipoprotein (LDL) apheresis has been also applied for the treatment of peripheral arterial disease to reduce LDL levels, resulting in the improvement of the blood flow to the ischemic limbs. In this study, we investigated the continuous changes of the tissue blood flows in the lower limbs and head during LDL-apheresis treatment by a non-invasive method (the non-invasive continuous monitoring method (NICOMM) system). In this study, the tissue blood flow in both the head and lower limbs showed a significantly enhancement from before to after treatment. The tissue blood flow in the lower limbs showed a significantly larger improvement than that in the head. The short-term effects of LDL apheresis were confirmed by using the NICOMM system; thus, this system will be useful for the determination of the appropriate schedule of LDL apheresis for long-term effectiveness.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 11/2007; 11(5):325-30. · 1.53 Impact Factor
  • Nippon Jinzo Gakkai shi 02/2007; 49(8):871-8.
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    ABSTRACT: In clinical practice, the prediction of changes in blood pressure during hemocatharsis therapy depends on invasive monitoring, the physician's experience, or blood pressure measurement when patients ask for it. It is extremely difficult to predict blood pressure variation in patients under general anesthesia or with disturbance of consciousness. Therefore, the prediction of blood pressure variation during hemocatharsis therapy is an important issue. To address this issue, we invented a new noninvasive continuous blood flow monitor using arteriolar blood flow measurement by laser Doppler flowmetry. Then we examined and determined some extremely important phenomena, including the relationship between rapid blood pressure change and arteriolar blood flow, and failures of the cerebral blood flow autoregulatory mechanism, through measurements in clinical practice of hemodialysis, specific hemocatharsis therapy, and drug monitoring. The results suggest that blood pressure variation during hemocatharsis therapy is highly predictable by arteriolar blood flow measurement. Therefore, this new method for arteriolar blood flow measurement might be widely useful for patients under anesthesia, anesthesia monitoring in neonatal infants and animals (no conversation ability), as well as for hemocatharsis therapy.
    Journal of Artificial Organs 02/2007; 10(1):36-41. · 1.41 Impact Factor
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    ABSTRACT: We compared the histological changes before and after treatment in 14 cases of myeloperoxidase antineutrophil cytoplasmic autoantibodies (MPO-ANCA) related nephritis in whom we were able to perform two renal biopsies. The results show that the clinical findings and acute glomerular and tubulointerstitial injuries decreased, while chronic glomerular injuries increased. No changes were seen in minor glomerular abnormalities(MGAs) or chronic tubulointerstitial injuries between the first and second biopsies. In the vascular system, no treatment related aggravation of arteriosclerosis occurred and it was found that fibrinoid necrosis disappeared with treatment. Finally, in MPO-ANCA related nephritis, the care given between the first and second biopsies caused acute glomerular injuries to become chronic glomerular injuries, but no changes were detected in the MGA. We believe that the changes in acute tubulointerstitial injuries reflected an improvement in renal function, since the acute tubulointerstitial injuries obviously improved in response to PSL, contributing to the improved renal function. In other words, MPO ANCA-related nephritis is a condition that involves "acute glomerulonephritis+ acute tubulointerstitial nephritis + angiitis," and it is thought that the characteristics of each are independent. We believe that the renal function improved as the acute tubulointerstitial nephritis improved, while the acute glomerular injuries developed into chronic glomerular injuries.
    Nippon Jinzo Gakkai shi 02/2007; 49(4):438-45.
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    ABSTRACT: Creatol (CTL) is a hydroxyl radical adduct of creatinine (Cr). The serum methylguanidine (MG) level and the MG/Cr molar ratio are reported to be biomarkers for oxidative stress. The aim of this study was to examine whether urinary excretion of CTL, another oxidative stress-related marker, is increased in patients with chronic renal failure (CRF). One hundred twenty-four non-dialyzed patients with chronic renal failure (serum Cr level, 1.3-10.0 mg/dL) were recruited from our hospitals. Urine and serum levels of CTL and MG were determined by high-performance liquid chromatography with the use of 9, 10- phenanthrenequinone as a fluorogenic reagent. The CTL/Cr and (CTL+MG)/Cr molar ratios in spot urine samples were also compared with those in 24-h urine samples. The urinary CTL/Cr and (CTL+MG)/Cr molar ratios increased with decreases in Cr clearance in patients with CRF. Correlations between serum and spot urine (CTL+MG)/Cr and between serum and spot urine CTL/Cr were quite similar to those in 24-h urine samples. CTL/Cr and (CTL+MG)/Cr molar ratios in both 24-h urine and spot urine samples appear to be useful indices of the severity of CRF.
    Renal Failure 02/2007; 29(3):279-83. · 0.94 Impact Factor
  • Tsutomu Sanaka
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 09/2006; 10(4):303-4. · 1.53 Impact Factor
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    ABSTRACT: Advancement in blood purification therapy extends not only to consoles and dialyzers, but also to patient management during blood purification therapy. However, no monitor has been devised for hemodynamics during blood purification therapy that is carried out continuously and non-invasively. By studying the laser Doppler flowmeter (LDF), we have developed a probe that can continuously measure changes in blood flow in tissues of the head and lower extremities during blood purification therapy. By applying the improved LDF, we have developed a non-invasive continuous monitoring method (NICOMM). Hemodynamics in various types of blood purification therapies were also studied by simultaneously measuring with an automatic oscillometric sphygmomanometer.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 09/2006; 10(4):380-6. · 1.53 Impact Factor
  • Chieko Higuchi, Hideki Nishimura, Tsutomu Sanaka
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    ABSTRACT: Conventional peritoneal dialysis fluid (PDF) is a bioincompatible solution because of several components. These unphysiological compositions might contribute to the development of peritoneal fibrosis. In the present overview we summarize the influence of each composition of PDF (acidic pH, high concentration of glucose and glucose degradation products; advanced glycation end-products and lactate) on the peritoneal fibrotic changes in long peritoneal dialysis (PD) patients. We also summarized the report of new approaches to the prevention of peritoneal fibrosis in Japan.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 09/2006; 10(4):372-9. · 1.53 Impact Factor
  • Tsutomu Sanaka
    Nippon rinsho. Japanese journal of clinical medicine 03/2006; 64 Suppl 2:509-12.
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    ABSTRACT: Ets-1 proto-oncogene exhibits multiple activities in the transcriptional regulation of numerous genes including metalloproteinase (MMP)-1, -3 and -9. MMPs play an important role in the remodelling of extracellular matrix in various renal diseases. However, the role of the Ets-1-MMP axis in advanced renal diseases is uncertain. In the present study, we investigated whether Ets-1 is involved in interleukin (IL)-1-mediated expression of MMPs in tubulointerstitial cells. Rat renal fibroblasts (NRK-49F) and tubular epithelial cells (NRK-52E) were cultured and allocated to an IL-1beta-treated group (10 ng/ml), a platelet-derived growth factor (PDGF)-BB-treated group (25 ng/ml) and a control group. Protein and mRNA were extracted after 1, 6, 12 and 24 h of treatment. Parallel flasks were treated with 2 muM ets-1 antisense oligodeoxynucleotides (ODNs) before exposure to IL-1beta. The expression of Ets-1 protein was evaluated by western blotting. The activities of MMPs were evaluated by gelatin zymography. The expression of ets-1 and/or MMP-9 mRNA was evaluated semiquantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR). In NRK-49F cells, Ets-1 protein increased significantly by 6.8-fold at 6 h, and MMP-9 activity increased significantly by 9.9-fold at 12 h in the IL-1beta-treated group compared with controls. MMP-2 and -3 activities also increased significantly in the IL-1beta-treated group. In NRK-52E cells, Ets-1 protein was 3.1 times higher at 1 h, and the latent form of MMP-9 activity increased 3.4-fold at 6 h in the IL-1beta group compared with controls. However, MMP-2 or MMP-3 activities were not markedly altered by IL-1beta treatment compared with controls. When the cells were treated with ets-1 antisense ODNs before IL-1beta treatment, Ets-1 protein expression decreased at least 50%, and MMP-9 activity was clearly inhibited in both cells. We also confirmed that MMP-9 activity was upregulated on days 21 and 28 in renal cortex of rat crescentic glomerulonephritis. The Ets-1 transcriptional factor may participate in IL-1beta-mediated MMP-9 expression in tubulointerstitial cells.
    Nephrology Dialysis Transplantation 12/2005; 20(11):2333-48. · 3.37 Impact Factor
  • Tsutomu Sanaka, Tomoyoshi Hosokawa
    Nippon rinsho. Japanese journal of clinical medicine 07/2005; 63 Suppl 6:373-8.
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    ABSTRACT: Nonphysiological solutions containing high glucose levels have been considered an important factor in the etiology of fibrotic changes in long-term continuous ambulatory peritoneal dialysis (CAPD) patients. At the same time, increased Plasminogen Activator Inhibitor (PAI)-1 secretion has been reported to correlate with fibrotic changes. We suspected that the high glucose content of peritoneal dialysis solution may induce peritoneal sclerosis via up-regulation of PAI-1 gene expression. In this study, we evaluated the effects of glucose on PAI-1 activity in peritoneal fibrosis in a rat model of CAPD. The effects of glucose on the expressions of PAI-1 and several other genes correlated with collagen metabolism were also examined in cultured rat peritoneal mesothelial cells and fibroblasts. Sprague-Dawley rats were intraperitoneally injected twice daily for 28 days with phosphate-buffered saline (PBS) (control group), PBS containing 4% glucose (glucose group), or PBS containing 4% glucose plus a PAI-1 inhibitor (PAI-1 inhibitor group). Thickening of the peritoneum with increase the deposition of collagens type I and III in the submesothelial interstitium were observed in the glucose and the PAI-1 inhibitor group, but these were less severe in the PAI-1 inhibitor group. Glucose stimulated expression of the mRNA of PAI-1, collagen type I and III, and tissue inhibitor of metalloproteinase (TIMP)-1 in fibroblasts but not in mesothelial cells. Glucose stimulated matrix metalloproteinase (MMP)-13 mRNA expression in both cell types. The PAI-1 inhibitor suppressed expression of the mRNAs induced by glucose. In conclusion, glucose induces peritoneal fibrosis, including changes in collagen metabolism, by stimulating PAI-1 expression.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 05/2005; 9(2):173-81. · 1.53 Impact Factor
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    ABSTRACT: In vitro studies have shown that pH and glucose degradation products (GDPs) in the dialysate are determinant factors for the biocompatibility of peritoneal dialysis (PD) treatment. The present study was thus designed to evaluate whether a newly developed PD solution, which features neutral pH levels and a low GDP concentration, influences tissue damage of the peritoneal membrane in an in vivo setting, and which factor is more critical to the histological changes. Rats were injected 3 times per day during 1 or 4 weeks with 10 ml of various PD fluids (group G, acidic pH, high GDPs; group S, neutral pH, low GDPs; or group A, acidic pH, low GDPs). When the experimental period was over, the mesothelial cell monolayers of the animals were taken and studied with population analysis, and peritoneal membranes were obtained from the abdominal wall for immunohistochemical examination with proliferating cell nuclear antigen (PCNA) and for measurement of thickness of the peritoneal specimens. The density of the mesothelial cell monolayer and the number of fibroblast-like cells in group S were significantly less than in group G at 1 and 4 weeks' injection. PCNA-positive nuclei in group S were significantly less than in group G for only the 1-week injection set (group G, 2.03 +/- 0.95; group S, 0.85 +/- 1.18 nuclei/1 x 10(4) microm2). At 4 weeks, the peritoneal thickness of group S (6.32 +/- 0.53 microm) was significantly less than that of group G (7.94 +/- 0.77 microm), There was no significant difference between groups S and A throughout the whole study period except for the result of the number of fibroblast-like cells. These results indicate that a PD solution with a neutral pH and low GDPs proved more biocompatible with the peritoneal membrane than a solution with an acidic pH and high GDPs. Furthermore, the level of the GDPs has more impact on tissue damage of the peritoneal membrane than the pH in the short term.
    Nephron Experimental Nephrology 02/2005; 100(1):e30-9. · 2.01 Impact Factor
  • Jun Niwayama, Tsutomu Sanaka
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    ABSTRACT: The management of blood pressure in hemodialysis patients greatly affects not only their quality of life, but also the duration of dialysis (dialysis life). Approximately 25% of dialysis patients suffer from continuous low blood pressure; however, the relationship between blood pressure and blood flow during dialysis has not been established. We hypothesized that with complete extracorporeal circulation, blood purification methods might affect blood flow, resulting in a change in blood pressure. The purpose of this study was to develop a noninvasive continuous monitoring method (NICOMM) as a microcirculation monitor by devising a laser-Doppler flowmeter (LDF) system with a wavelength of 780 nm. The aim was to use this system to simultaneously measure blood flow rate in both the head and the foot during dialysis and to determine the effectiveness of NICOMM by measuring blood flow and arterial distensibility. When exhibiting a significant decline in blood pressure at 240 min after the initiation of hemodialysis, a drop in blood flow in parallel with the blood pressure fall was recorded by the LDF. However, no changes were observed, in the readings by a continuous hematocrit monitor (Crit-Line monitor, CLM). Furthermore, a significant correlation was registered between mean arterial blood pressure and blood flow rate in the earlobe tissue from 180 min after the initiation of hemodialysis to the completion of hemodialysis (p < 0.001, r = 0.78). Comparisons were made by measuring vascular dehydration using the CLM. NICOMM showed more stable readings than the CLM in monitoring blood flow in response to changes in blood pressure.
    Hemodialysis International 01/2005; 9(1):56-62. · 1.44 Impact Factor

Publication Stats

408 Citations
164.05 Total Impact Points

Institutions

  • 1999–2010
    • Tokyo Women's Medical University
      • • School of Medicine
      • • Department of Medicine IV (Nephrology)
      Edo, Tōkyō, Japan
  • 1996–2007
    • Tokyo Junshin Women's College
      • Kidney Center
      Edo, Tōkyō, Japan
  • 2005
    • Ajinomoto-Genetika Research Institute
      Moskva, Moscow, Russia
  • 2003
    • Showa University
      Shinagawa, Tōkyō, Japan