Shinya Saito

Chiba-East National Hospital, Tiba, Chiba, Japan

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Publications (11)18.18 Total impact

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    ABSTRACT: Accumulated studies have shown that ω-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have protective roles against inflammatory responses such as hyperlipidemia, diabetes mellitus (DM) and cardiovascular diseases. Here we examined the effects of administering EPA to hyperlipidemic patients and other patients undergoing cardiac surgery to determine whether this treatment would increase plasma EPA levels and to clarify the association between EPA treatment and adiponectin production in hyperlipidemic patients. We also assessed the effect of preoperative EPA administration on postoperative adverse events such as postoperative atrial fibrillation (POAF) and postoperative infection in the cardiac surgery patients. The EPA administration significantly increased the serum EPA concentrations in both patient populations (p<0.001). In the hyperlipidemic patients, the EPA administration significantly increased plasma adiponectin levels (p<0.05), accompanied by a decrease in insulin resistance designated by the HOMA-IR (homeostasis model assessment of insulin resistance) score (p<0.05) and Hs-CRP (high sensitivity C-reactive protein) value (p<0.05). In the cardiac surgery patients, no significant effect of EPA on cardiac adverse events such as POAF was observed. However, our results clearly demonstrated that both the neutrophil-to-lymphocyte ratio and the 2nd-line antibiotic requirement in the EPA group were significantly decreased compared to the untreated control group (p<0.05). We suggest that EPA administration may exert anti-inflammatory effects in patients with hyperlipidemia and in those undergoing cardiac surgery, possibly through an increase in plasma adiponectin levels.
    Acta medica Okayama 12/2014; 68(6):349-61. · 0.65 Impact Factor
  • Hiromi Iwagaki, Shinya Saito
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    ABSTRACT: We studied the effects of preoperative administration of Hochuekkito (TJ-41) on the host response of patients undergoing gastrectomy or colectomy in a prospective, randomized, multicenter clinical trial. Forty-eight patients were randomized into two groups: one received 7.5 g/day of TJ-41 for 7 days before surgery (n = 22); and the other served as the control group (n = 26). The body temperature and pulse rate in patients in the TJ41 group were significantly better controlled during the study compared with those in the control group. The concentration of serum cortisol on the first postoperative day in the TJ-41 group was also significantly lower compared with that in the control group. These results clearly indicate that the preoperative administration of TJ-41 may ameliorate an excessive postoperative inflammatory response and prolonged immunosuppressed state, resulting in fewer postoperative infectious complications.
    Nippon Geka Gakkai zasshi 09/2013; 114(5):241-5.
  • Kampo Medicine 01/2010; 61(1):56-83.
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    ABSTRACT: Lipopolysaccharide (LPS) is one of the major causes of septic shock. The polymyxin B-immobilized filter column (PMX) was developed for the adsorption of endotoxin by direct hemoperfusion and has been used for the treatment of LPS-induced septic shock. In this study, we demonstrated that PMX also specifically bound monocytes from the peripheral blood leukocytes of septic patients by mean of an analysis of bound cells using immunocytochemical and electron microscopic techniques. The specific removal of monocytes from septic patients may produce beneficial effects by reducing the interaction between monocytes and functionally associated cells including vascular endothelial cells.
    Acta medica Okayama 03/2009; 63(1):65-9. · 0.65 Impact Factor
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    ABSTRACT: Activation of inflammatory response during cardiopulmonary bypass (CPB) may lead to considerable post-operative mortality. Recently, pentoxifylline (PTX), a methylxanthine derivative, has been reported to be effective in inhibiting proinflammatory cytokine production. This study aimed to determine whether or not PTX prevented CPB-induced systemic inflammatory response syndrome (SIRS) in patients undergoing cardiovascular surgery. Thirty adult patients were randomly separated into 2 experimental groups and 1 control group of 10 patients each. The experimental group received peroral PTX administration (Group 1: 600 mg/day, Group 2: 900 mg/day), while the control group did not. In Group 1 and Group 2, PTX administration was started on preoperative day 5 and continued for 5 days. Serum levels of PTX and IL-6 were measured just before and at 4 h after CPB using HPLC and ELISA, respectively. Respiratory index (RI) before and at 4 h after CPB was calculated, and serum levels of C-reactive protein (CRP) and fibrinogen on postoperative day 1 were also determined. There were no significant differences in age, body weight, sex, surgical procedures, CPB time, haemodynamics or risk factors among the 3 groups. Serum IL-6 level and RI index after CPB in Group 2 were significantly decreased compared with those in Group 1 and the control group. These results, therefore, suggested that preoperative daily administration of 900 mg/day PTX contributed to the attenuation of CPB-induced SIRS and had a beneficial effect on the postoperative course after cardiovascular surgery.
    Acta medica Okayama 05/2008; 62(2):69-74. · 0.65 Impact Factor
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    ABSTRACT: Liver damage after hepatectomy is still a serious concern. The present study was designed to clarify the relations between liver injury/surgical stress and cytokines after hepatectomy, in patients with viral hepatitis. Ten consecutive patients undergoing hepatectomy were studied, all with hepatocellular carcinoma due to viral hepatitis. Blood samples for interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), hepatocyte growth factor (HGF), soluble Fas (sFas), soluble Fas Ligand and soluble tumor necrosis factor receptor (sTNFR) assays were collected before the operation and at the end of the operation. There was a significant and positive correlation between the change in the serum level of HGF and preoperative liver function (ICG-R15). Notably, there were significant correlations between surgical stress and IL-6, HGF and sFas, but not sIL-6R and sTNFR. Furthermore, there was significant correlation between postoperative liver function (total bilirubin, albumin) and HGF, IL-6. There was a close relationship between surgical stress and HGF, IL-6 and sFas after hepatectomy in patients with viral hepatitis. It was useful for the evaluation of surgical stress of hepatectomy to estimate the serum level of HGF, IL-6 and sFas.
    Hepato-gastroenterology 01/2008; 55(85):1400-3. · 0.77 Impact Factor
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    ABSTRACT: Liver regeneration after surgical resection is still a serious concern. The present study is designed to understand the relations between liver injury/regeneration and cytokines after hepatectomy with viral hepatitis. Twenty-one consecutive patients undergoing liver resection were studied, which included two patients with biliary tract cancer, three patients with hepatic metastases from colorectal cancer, and sixteen patients with primary liver tumor. They were also divided into two groups according to the existence of chronic viral hepatitis: 10 patients with viral hepatitis and 11 patients without viral hepatitis. Viral hepatitis reduced pre-operative liver function (ICG-R15 and platelet count) with raised levels of sFas. Interestingly, this also reduced postoperative surge of IL-6, but not HGF, though they were equally at basal levels pre-operatively. Recovery of liver size, calculated with resected liver mass and volumetry with CT scan, was deteriorated in liver with viral hepatitis, but any difference of postoperative liver damage was observed between two groups. Viral infection, somehow, increased sFas level pre-operatively, but does not influence the post-operative liver injury. Deficient response of IL-6, but not HGF, may be a major cause for poor liver regeneration after hepatectomy in patients with viral hepatitis independent from liver injury.
    Hepato-gastroenterology 01/2008; 55(85):1439-44. · 0.77 Impact Factor
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    ABSTRACT: Interleukin (IL)-18, which is elevated in the plasma during acute rejection after organ transplantation, is known to induce the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40 and CD40 ligand (CD40L) on monocytes, the production of interferon (IFN)-gamma and IL-12 and the proliferation of lymphocytes during the human mixed lymphocyte reaction (MLR). Ciprofloxacin (CIP), which is useful for the clinical treatment of infections due to its antibacterial properties after transplantation, was shown to suppress the IFN-gamma and IL-12 production, the lymphocyte proliferation and the ICAM-1, B7.1, B7.2 and CD40 expression on monocytes during MLR in the presence of IL-18. CIP also induced the production of prostaglandin (PG) E2. In order to determine whether the effects of CIP on the expression of the activation markers were due to CIP-dependent production of PGE2, we examined the effect of cyclooxygenase (COX)-2 and protein kinase A (PKA) inhibitors on the actions of CIP. Thereby, the inhibitors were found to abolish the actions of CIP. These results therefore suggest that CIP might exert its immune modulatory effects via the production of PGE2.
    Clinical Immunology 05/2006; 119(1):110-9. · 3.77 Impact Factor
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    ABSTRACT: Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E(2) in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E(2) and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E(2) and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.
    Antimicrobial Agents and Chemotherapy 09/2005; 49(8):3228-33. · 4.57 Impact Factor
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    ABSTRACT: Clinical and experimental studies suggest that impairment of the mucosal barrier system increases gut-derived endotoxin in the portal blood, which causes liver injury. The aim of this study was to elucidate the mechanism of liver injury caused by gut defence failure. Wistar rats were administered either enteral lipopolysaccharide (LPS) or LPS via the portal vein. Blood samples were collected via the inferior vena cava at necropsy. Serum aspartate transaminase (AST) and alanine transaminase (ALT) were analysed by standard enzymatic procedures and cytokines [tumour necrosis factor-alpha, interleukin (IL)-1beta, interferon-gamma, IL-6 and hepatocyte growth factor (HGF)] were measured by enzyme-linked immunosorbent assay. Livers were removed and snap-frozen in liquid nitrogen. CD14, CD68, Toll-like receptor (TLR) 2, TLR4 and Fas ligand (FasL) were analysed immunohistochemically. Expression of TLR2, TLR4 and CD14 mRNA was determined by reverse transcriptase-polymerase chain reaction. In enterally-treated rats, AST and ALT were not increased and cytokine levels were under the limits of detection in the absence of a rise in HGF. Enteral administration of LPS increased HGF dose-dependently. Injection of LPS in the portal vein resulted in significant increases in AST, ALT, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and IL-6 levels, but no change in HGF levels. Immunohistochemical analysis revealed that intraportal LPS administration increased CD14, TLR4, CD68 and FasL. Reverse transcriptase-polymerase chain reaction analysis demonstrated that TLR4 mRNA expression was upregulated 0.5 h after intraportal LPS administration. s Our data suggest that Kupffer cell activation mediated by intraportal LPS via TLR4 is involved in liver injury, possibly through both tumour necrosis factor-alpha/IL-1beta and FasL, and that lack of HGF activity in the impaired gut could not counteract liver injury.
    European Journal of Gastroenterology & Hepatology 11/2004; 16(10):1017-25. · 1.92 Impact Factor
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    ABSTRACT: Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines. such as IL-10, have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic rats (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, vIL-10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high vIL-10 level in the splenic vein in NAR transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent allogeneic response in hepatocyte transplantation.
    Cell Transplantation 02/2003; 12(4):379-87. · 4.42 Impact Factor