Biomedical subjects

Ichiro Shimizu

Publications and source records attributed to Ichiro Shimizu.

32 records · Page 2Linked to original sources

PubMed2004

Antioxidant and antiapoptotic activities of idoxifene and estradiol in hepatic fibrosis in rats.

Oxidative stress plays a causative role in the development of hepatic fibrosis and apoptosis. Estradiol (E2) is an antioxidant, and idoxifene is a tissue-specific selective estrogen receptor modulator. We have previously demonstrated that E2 inhibits hepatic fibrosis in a rat model of hepatic fibrosis induced with dimethylnitrosamine (DMN), and suppresses activation of the nuclear factor (NF)-kappaB proinflammatory transcription factor in cultured rat hepatocytes undergoing oxidative stress. This study reports on the antioxidant and antiapoptotic role of idoxifene and E2 in the DMN model of hepatic fibrosis. The DMN model rats were administered with idoxifene or E2, and were examined activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and expression of Bcl-2 family proteins in the liver. During the course of hepatofibrogenesis after DMN treatment, serum levels of lactate dehydrogenase (LDH), a biomarker for necrosis, and hepatic levels of malondialdehyde (MDA), an end product of lipid peroxidation, increased rapidly for 3 days. On day 14, serum LDH levels normalized, and hepatic fibrosis developed with increased levels of MDA and collagen and decreased production of SOD and GPx in the liver. Fibrotic liver also showed downregulation of Bcl-2 and Bcl-X(L) expression and upregulation of Bad expression. Idoxifene and E2 suppressed DMN-mediated necrosis, lipid peroxidation, the loss of antioxidant enzyme activity, and proapoptotic status in Bcl-2 family protein expression as well as hepatic fibrosis. These findings indicate that, in addition to their antiinflammatory and antifibrotic action, idoxifene and E2 could enhance antioxidant and antiapoptotic activity in hepatic fibrosis in rats.

Administration, Oral↗

PubMed2004

Mechanical cardiac support system for patients with postcardiotomy cardiogenic shock: analysis of risk factors for survival.

OBJECTIVE: Mechanical cardiac support system (MCSS) has been used for adult patients in postcardiotomy cardiogenic shock and has been shown to provide excellent oxygenation and hemodynamic support. However, MCSS has a number of disadvantages that include high incidence rate of complications (e.g. stroke, bleeding) and limited duration of sufficient support. The objective of this study is to identify perioperative and postoperative factors for survival in patients having MCSS. METHODS: From January 1991 to April 2001, MCSS has been applied to 22 adult patients in postcardiotomy cardiogenic shock. These patients' charts were retrospectively reviewed. RESULTS: Of 22 patients, 9 patients (41%) were successfully weaned, and 6 (27%) were hospital survivors. The duration of assist ranged from 21 to 211 hours (median 66 hours). In 7 (78%) out of 9 patients who could be weaned from MCSS, MCSS were required for less than 3 days. Major complications were reexploration for bleeding (18%), leg ischemia (45%), renal dysfunction (77%), liver dysfunction (59%), infection (31.8%), hypoxia due to lung dysfunction (36%) and cerebral dysfunction (41%). pH, base excess, HCO3-, urine output, transfused platelets at first 24 hours of MCSS and preoperative body surface area were significant predictors for survival. CONCLUSION: The indices of insufficient hemodynamic support such as progression of acidosis or poor urine output are significant predictors for early death. Early conversion from MCSS to long-term assist device, such as left ventricular assist device, should be considered when these factors are associated with poor cardiac recovery.

Acidosis↗

PubMed2004

Influence of large intrahepatic blood vessels on the gross and histological characteristics of lesions produced by radiofrequency ablation in a pig liver model.

AIMS: To determine whether the presence of large intrahepatic blood vessels (>/=3 mm) affect radiofrequency (RF)-induced coagulation necrosis, the gross and histological characteristics of RF-ablated areas proximal to or around vessels were examined in normal pig livers. METHODS: An RF ablation treatment using a two-stepwise extension technique produced 12 lesions: six contained vessels (Group A), and the other six were localized around vessels (Group B). RESULTS: Gross examination revealed that the longest and shortest diameters of the ablated lesions were significantly larger in Group B than in Group A. In Group A, patent vessels contiguous to the lesion were present in a tongue-shaped area, whereas the lesions in Group B were spherical. Staining with nicotinamide adenine dinucleotide diaphorase was negative within the ablated area; but, if vessels were present in the ablated area, the cells around the vessels in an opposite direction to the ablation were stained blue. CONCLUSIONS: Roll-off can be achieved with 100% cellular destruction within a lesion that does not contain large vessels. The ablated area was decreased in lesions that contained large vessels, suggesting that the presence of large vessels in the ablated area further increases the cooling effect and may require repeated RF ablation treatment to achieve complete coagulation necrosis.

Animals↗

PubMed2004

Rupture of the gallbladder in a patient with acquired factor VIII inhibitors and systemic lupus erythematosus.

A 54-year-old woman with a 21-year history of systemic lupus erythematosus (SLE) was admitted to the Matsuyama Red Cross Hospital due to subcutaneous and gingival hemorrhaging. She was diagnosed with acquired factor VIII inhibitors based on a prolonged activated partial-thromboplastin time (APTT) and factor VIII inhibitors. Steroid pulse and factor VIII plasma concentrate were administered to her, not long after which she was transferred to Ehime University Hospital due to gallbladder hematoma. Although her APTT and factor VIII activity were improved after treatment with human factor VIII, she died of multiple organ failure. The autopsy demonstrated a ruptured gallbladder.

Autoantibodies↗

PubMed2004

[Guanase].

Explore the source record for details and available documents.

Guanine Deaminase↗

PubMed2003

Inhibitory effect of a soluble transforming growth factor beta type II receptor on the activation of rat hepatic stellate cells in primary culture.

BACKGROUND/AIMS: Oxidative stress, including the generation of reactive oxygen species (ROS) that acts as a signaling mediator for transforming growth factor (TGF)-beta, plays a key role in hepatic fibrosis. Hepatic stellate cells (HSCs) produce and respond to TGF-beta in an autocrine manner with increased collagen expression. It has previously been reported that the adenovirus-mediated overexpression of a soluble receptor against the extracellular domain of the TGF-beta type II receptor prevents hepatofibrogenesis in vivo, although its inhibitory role and mechanism in HSC activation remains to be elucidated. METHODS: In this study, we report on an examination of the actual role of TGF-beta inhibition on oxidative stress and the activation of cultured rat HSCs, using the adenovirus-mediated soluble TGF-beta type II receptor. RESULTS: This soluble receptor secreted from the adenovirus-infected cells binds to TGF-beta. Infection of HSCs with this adenovirus attenuated intracellular levels of TGF-beta1 mRNA and protein, NADH oxidative activity, ROS generation and lipid peroxidation, and prevented HSC activation. CONCLUSIONS: These findings suggest that this adenovirus-mediated soluble TGF-beta receptor may lead to an interruption of the TGF-beta autocrine loop in activated HSC, in part, by inhibiting oxidative stress.

Adenoviridae↗

PubMed2003

Idoxifene and estradiol enhance antiapoptotic activity through estrogen receptor-beta in cultured rat hepatocytes.

Oxidative stress plays a causative role in the development of hepatic fibrosis and apoptosis. Estradiol (E2) is an antioxidant, and idoxifene is a tissue-specific selective estrogen-receptor modulator. We have previously demonstrated that E2 inhibits hepatic fibrosis in rat models of hepatic fibrosis and that the actions of E2 are mediated through estrogen receptors (ERs). This study reports on the antiapoptotic role of idoxifene and E2, and the functions of ER subtypes ER-alpha and ER-beta in hepatocytes undergoing oxidative stress. Lipid peroxidation was induced in cultured rat hepatocytes with ferric nitrilotriacetate solution with idoxifene or E2. Oxidative stress-induced early apoptosis was linked to its ability to inhibit not only the expression of Bcl-2 and Bcl-XL but the production of antioxidant enzymes as well and to stimulate Bad expression. Hepatocytes possessed functional ER-beta, but not ER-alpha, to respond directly to idoxifene and E2. Idoxifene and E2 suppressed oxidative stress-induced reactive oxygen species generation and lipid peroxidation, and their antiapoptotic effects on the activation of activator protein-1 and nuclear factor-kappaB, the loss of antioxidant enzyme activity, and Bcl-2 family protein expression in early apoptotic hepatocytes were blocked by the pure ER antagonist ICI 182,780. Our results indicate that idoxifene and E2 could enhance antiapoptotic activity through ER-beta during oxidative damage in hepatocytes.

Animals↗

PubMed2003

Impact of oestrogens on the progression of liver disease.

As of this writing, the most common cause of hepatic fibrosis is chronic hepatitis C virus infection (HCV), the characteristic feature of which is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which in turn activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory stimuli, and produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. It should be noted that estradiol (E2) is a potent endogenous antioxidant. A recent study has shown that hepatic steatosis became evident in an aromatase-deficient mouse and was diminished in animals, after treatment with E2. Our studies showed that E2 suppressed hepatic fibrosis in hepatic fibrosis models, inhibited the activation of activator protein 1 and nuclear factor-kappa B in cultured hepatocytes undergoing oxidative stress, and attenuated HSC activation in primary culture. Recently, variant oestrogen receptors (ERs) were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. We also demonstrated decreased levels of ERs in postmenopausal women and cirrhotic patients of both genders. The actions of E2 are mediated through ER alpha and beta. HSCs have also been found to possess functional ER beta but not ER alpha. A better understanding the basic mechanisms underlying the gender-associated differences observed in the development of hepatic fibrosis would provide valuable information relative to the search for effective antifibrogenic therapies.

Carcinoma, Hepatocellular↗

PubMed2003

Clinical value of the determination of serum guanase activity in patients with chronic hepatitis type C.

The study examines the clinical significance of guanase (GU) measurement in patients with hepatitis C. 688 patients in whom either ALT was abnormal, or in whom HBsAg or HCVAb was detected in the serum, were enrolled into this study. The percentage of cases in which normal ALT while elevated GU was compared among the different disease groups. Then, the percentage of cases with normal ALT but elevated GU was compared between HBV and HCV groups. For the entire population, a significant correlation was observed between ALT and GU (r=0.872). The overall percentage of cases with normal ALT but elevated GU activity was 11.4%. In HCV group, 449 cases had normal ALT. Of these cases, 20.3% had elevated GU, while ALT was normal. Before 1989, no test to check donated blood for HCV antibody was available. However, screening of donated blood for high GU was associated with a reduced incidence of post-transfusion hepatitis. This is probably because following the screening, blood donated by patients with hepatitis C who had normal ALT but elevated GU was rejected. After the introduction of HCV antibody measurement, GU measurement is still useful to reveal the pathophysiological condition in-patients with chronic hepatitis type C.

Alanine Transaminase↗

PubMed2002

Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance.

BACKGROUND: Recently, we have described a drug (cyclophosphamide [CP] plus busulfan [BU])-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers. Using this method, we have investigated whether or not this regimen can prolong the survival of heart allografts and inhibit the development of posttransplant cardiac allograft vasculopathy (CAV). METHODS: The components of the method are intravenous administration of 1 x 108 allogeneic spleen cells on day 0, intraperitoneal injection of 200 mg/kg of CP and 30 mg/kg of BU on day 2, and intravenous injection of T cell-depleted 1 x 107 allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting was performed on day 28. Chimerism in peripheral blood was followed by flow cytometric analysis, and histological analysis was performed at various times after grafting. RESULTS: In a fully major histocompatability complex (MHC)-mismatched combination of B10.D2 (H-2d, IE+)-->B10 (H-2b, IE-), stable, multilineage-mixed chimerism was observed permanently. B10.D2 heart grafts were accepted permanently in a donor-specific manner, and posttransplant CAV did not develop. CONCLUSIONS: These results demonstrated that the drug-induced tolerance recently established by us can regularly induce a long-lasting heart allograft tolerance without development of CAV.

Animals↗

PubMed2002

Hepatic portal venous gas disappearing within 24 hours.

Hepatic portal venous gas (HPVG) was detected by CT in a 64-year-old woman who suddenly complained of lower abdominal pain. However, the abdominal symptoms disappeared rapidly, and lower gastrointestinal endoscopy indicated only terminal ileitis. Conservative treatment alone was performed, and HPVG completely disappeared approximately 18 hours later. The use of CT proved to be useful for following the course of HPVG.

Embolism, Air↗

PubMed2002

Protective effect of estradiol on hepatocytic oxidative damage.

AIM: To examine the protective effect of estradiol on the cultured hepatocytes under oxidative stress. METHODS: Hepatocytes of rat were isolated by using perfusion method, and oxidative stress was induced by a serum-free medium and FeNTA. MDA level was determined with TBA method. Cell damage was assessed by LDH assay. Apoptosis of hepatocytes was assessed with cytoflowmetric analysis. Expression of Bcl-xl in cultured hepatocytes was detected by Western blot. The radical-scavenging activity of estradiol was valued by its ability to scavenge the stable free radical of DDPH. RESULTS: Oxidative stress increased LDH from 168 +/- 25 x 10(-6)IU.cell(-1) to 780 +/- 62 x 10(-6)IU.cell(-1) and MDA(from 0.28 +/- 0.07 x 10(-6)nmol.cell(-1) to 1.35 +/- 0.12 x 10(-6)nmol.cell(-1)) levels in cultured hepatocyte, and estradiol inhibited both LDH and MDA production in a dose dependent manner. In the presence of estradiol 10(-6)mol.L(-1), 10( -7 )mol.L(-1) and 10(-8)mol.L(-1),the LDH levels are 410 +/- 53 x 10(-6)IU.cell(-1) (P<0.01 vs oxidative group), 530 +/- 37 X 10(-6)IU.cell(-1 ) (P<0.01 vs oxidative group), 687+/-42 x 10(-6)IU.cell(-1) (P<0.05 vs oxidative group) respectively, and the MDA level are 0.71+/-0.12 x 10(-6)nmol.cell(-1) (P<0.01 vs oxidative group),0.97+/-0.11 x 10(-6)nmol.cell(-1 )(P<0.01 vs oxidative group) and 1.27+/-0.19 x 10(-6)nmol.cell(-1) respectively. Estradiol suppressed apoptosis of hepatocytes induced by oxidative stress, administration of estradiol(10(-6)mol/L)decreased the apoptotic rate of hepatocytes under oxidative stress from 18.6 +/- 1.2% to 6.5 +/-2.5%, P<0.01. Bcl-xl expression was related to the degree of liver cell damage due to oxidative stress, and estradiol showed a protective action. CONCLUSION: Estradiol protects hepatocytes from oxidative damage by means of its antioxidant activity.

Animals↗

PubMed2002

Study of the causes of higher mortality rates from chronic liver diseases in Tokushima Prefecture.

Mortality rates from chronic liver diseases (CLD) such as liver cirrhosis and hepatocellular carcinoma have been reported to be higher in Tokushima prefecture, although its causes remain unclear. To clarify the causes of CLD in Tokushima prefecture, we evaluated the positive rates of HBs antigen and anti-HCV antibody and the mortality rates from CLD in patients with liver diseases and blood donors after dividing the entire Tokushima prefecture into 8 district boundaries of health centers. In addition, to evaluate the causes of the higher frequency of CLD and the relationship between the development of CLD and viruses, medical examinations were performed in 2 mountain villages in Tokushima prefecture where the drift of population was limited and the mortality rates from CLD differed from each other. As a result, it was found that HCV infection was the major cause of the higher mortality rates from CLD in Tokushima prefecture. Although there were marked regional differences in the mortality rates from CLD, they were mainly due to different rates of HCV infection.

Adult↗

PubMed2002

Interferon-alpha enhances biological defense activities against oxidative stress in cultured rat hepatocytes and hepatic stellate cells.

Oxidative stress has been implicated as a cause of hepatic fibrosis, and hepatic stellate cells (HSCs), which are the most important collagen-producing cell types, have been reported to be activated by lipid peroxidation products. Antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) provide a defense system that plays a critical role in protecting the cell from free radical damage, particularly lipid peroxidation. To elucidate the antioxidant activity of interferon-alpha (IFN-alpha), the effects of IFN-alpha on rat hepatocytes undergoing oxidative stress and HSCs in primary culture as well as isolated rat liver mitochondria were examined. IFN-alpha was observed to dose-dependently increase the immunoreactive protein levels of copper, zinc-and manganese-dependent SOD as well as the enzyme activities of GPx, and decrease the lipid peroxidation product levels and oxidative burst both in stressed hepatocytes and activated HSCs; GPx activities, however, were not detected in the latter cells. IFN-alpha also inhibited HSC activation and lipid peroxidation in liver mitochondria. These findings suggest that IFN-alpha may enhance biological defense activities against oxidative stress and function as a potent fibrosuppressant by protecting hepatocytes and hepatic stellate cells from lipid peroxidation in vivo.

Actins↗