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Biomedical subjects

Hirokazu Tsukahara

Publications and source records attributed to Hirokazu Tsukahara.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress.

The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper that generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic antioxidant responses in WD using liver specimens from affected patients showing mild liver damage (group I, n = 3), moderate or greater liver damage (group II, n = 5), and fulminant hepatic failure (group III, n = 5) and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in group II and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-dependent superoxide dismutase (CuZn-SOD), and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase (GPx) activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, Mn-SOD, and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.

Adult↗
PubMed2006

Urinary creatinine excretion and protein/creatinine ratios vary by body size and gender in children.

Urinary protein/creatinine ratio (Up/cr) is a simple measurement for evaluation of proteinuria. However, exact effects of body size and gender on urinary excretion of creatinine and Up/cr remain unknown. We aimed to clarify their effects. Early morning urine samples were collected from 124 children with urinary tract disorders. Urinary hourly excretion of creatinine, Ucr (in milligrams per hour), urinary hourly excretion of protein per body surface area, Up (milligrams per square meter per hour), and Up/cr (milligrams per milligram) were calculated. Effects of gender, age, body height, body weight and body surface area on Ucr and Up/cr were analyzed, respectively, in a multiple linear regression model. Body surface area and gender affected Ucr (r2=0.842, P<0.0001). Ucr adjusted by body surface area increased as body surface area grew with moderate variation. Up/cr showed a close correlation with Up and was affected by body height and gender as well. The regression equation showed that Up/cr values corresponding to the normal upper limit of Up, i.e., 4 mg/m2/h, in boys and girls 170 cm tall were approximately one third of those in children 80 cm tall (0.121 vs 0.043 for boys, 0.132 vs 0.047 for girls). The present study indicates that estimation of Up/cr needs to include consideration of children's body height and gender.

Adolescent↗
PubMed2006

Evaluation of a urinary multi-parameter biomarker set for oxidative stress in children, adolescents and young adults.

The involvement of reactive oxygen species (ROS) and oxidative stress in pediatric diseases is an important concern, but oxidative stress status in healthy young subjects and appropriate methods for its measurement remain unclear. This study evaluated a comprehensive set of urinary biomarkers for oxidative stress in healthy children, adolescents and young adults. Results show that urinary excretion of acrolein-lysine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), nitrite/nitrate and pentosidine were highest in the youngest subjects and decreased to constant levels by early adolescence. Urinary acrolein-lysine, 8-OHdG, nitrite/nitrate and pentosidine showed significant inverse correlations with age, but pyrraline did not change significantly with age. No significant differences in biomarkers were apparent between males and females. Younger subjects grow rapidly and sustain immune activation, and are probably exposed to high concentrations of ROS and nitric oxide. Consequently, they are more vulnerable to oxidation of lipids, proteins, DNA and carbohydrates. Normal reported values in this study are a basis for future studies of disease mechanisms involving oxidative stress and for future trials using antioxidant therapies for oxidative stress-related diseases in the pediatric field.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Urinary oxidative stress markers in young patients with type 1 diabetes.

BACKGROUND: Involvement of oxidative stress in the pathogenesis of diabetic vascular complications has been proposed. However, there are few methods to determine the status of oxidative stress both directly and quantitatively in young patients with type 1 diabetes. METHODS: A total of 27 young patients with type 1 diabetes (mean age +/- SD, 12.6 +/- 4.2 years) with normal renal function and 38 healthy control subjects (13.0 +/- 4.6 years) were investigated. Early morning voiding urine samples were collected. The concentrations of acrolein-lysine adducts, 8-hydroxy-2'-deoxyguanosine (8-OHdG) were determined using competitive enzyme-linked immunosorbent assay, and nitric oxide metabolites were measured using the colorimetric, non-enzymatic assay. RESULTS: Urinary concentrations of 8-OHdG, but not acrolein-lysine adducts and nitric oxide metabolites, were significantly increased in the diabetic group. For diabetic patients, microalbuminuria was significantly correlated with higher concentrations of all three markers. Hemoglobin A(1c) values were significantly correlated with 8-OHdG values. CONCLUSIONS: These findings indicate that increased oxidative stress and the risk of vascular complications may be present at early stages of type 1 diabetes.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Micelles of pulmonary surfactant in human amniotic fluid at term.

Studies using in vitro analysis have shown that the interaction between pulmonary surfactant and vernix caseosa could explain the appearance of amniotic fluid turbidity. That phenomenon is interpreted based on the "roll-up" hypothesis. We tested the roll-up hypothesis by examining the presence of micelles of pulmonary surfactant in human amniotic fluid at term. Amniotic fluid samples were collected from each of six healthy pregnant women at term and at 16 wk of gestation. These samples were stained negatively and analyzed using an electron microscope. Ultrastructures present in amniotic fluid were compared with the structure of micelles derived from suspended surfactant TA isolated from bovine lung. Surfactant TA formed spheroidal and rod-shaped micelles 10-70 nm in diameter above the critical micelle concentration. Identical micelle particles were described in human amniotic fluid at term. In addition, surfactant protein B was identified in the micelle fraction of amniotic fluid. However, no micelles were found in human amniotic fluid taken at 16 wk of gestation. Our results support the view that pulmonary surfactant could induce the detachment of vernix caseosa and increase the turbidity of the amniotic fluid.

Amniotic Fluid↗
PubMed2005

Quantification of L-type fatty acid binding protein in the urine of preterm neonates.

We measured urinary excretion of L-type fatty acid binding protein (L-FABP) in preterm neonates on days 1, 5-10, and 25-30 of life. Urinary L-FABP levels (expressed as the ratio to creatinine) in preterm neonates were considerably higher than those of healthy adults. They did not change significantly during the study period. Urinary L-FABP levels showed significant positive correlation with those of urinary N-acetyl-beta-D-glucosaminidase activity on day 1, and with those of 8-hydroxy-2'-deoxyguanosine on days 25-30. These results suggest that L-FABP is expressed in the neonatal kidney. Our results may also point to potential effects of proximal tubular damage and oxidative stress on urinary excretion of L-FABP.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Concentrations of thioredoxin, a redox-regulating protein, in umbilical cord blood and breast milk.

Growing evidence indicates that oxidative stress occurs during the fetal-to-neonatal transition. Such stress plays an important role in the pathogenesis of many neonatal diseases. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced in various cells against oxidative stress and is secreted extracellularly. This study was undertaken to examine the clinical and biological importance of TRX in the perinatal setting. We measured concentrations of TRX in umbilical cord blood and breast milk using a sandwich ELISA. Our study demonstrated that concentrations of TRX in umbilical cord blood were six to seven times higher than those in blood of healthy adults. This study also showed that umbilical concentrations of TRX were correlated significantly with the extent of prematurity of the newborn, and that they were elevated significantly in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. In contrast, concentrations of coenzyme Q(10) and vitamin E in umbilical blood were lower than adult blood levels. Breast milk concentrations of TRX during the early postpartum period were seven to eight times higher than those in blood of lactating women. Those of the coenzyme Q(10) were lower than adult blood levels, while those of vitamin E were comparable to adult blood levels. Our findings suggest that the systemic release of TRX is enhanced at birth, and that early breast milk is a rich source of this protein. Consequent high levels of TRX in newborns may provide a unique protective mechanism that allows the maintenance of redox balance during the fetal-to-neonatal transition.

Adult↗
PubMed2005

Quantitation of glutathione S transferase-pi in the urine of preterm neonates.

BACKGROUND: Glutathione S transferases (GSTs) are widely distributed enzymes found in highly varying amounts in tissues of the human body. The enzyme GST-pi in urine has been used as a marker of renal distal tubular cell damage. The present study was intended to evaluate urinary excretion of GST-pi and its relationship to other renal markers and to the status of oxidative stress in preterm neonates. METHODS: Levels of urinary GST-pi, N-acetyl-beta-glucosaminidase (a marker of proximal tubular damage), albumin (a marker of glomerular damage) and 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and serum creatinine were measured in preterm neonates at 1 and 4 weeks of age. RESULTS: The results showed that urinary excretion of GST-pi is increased in preterm neonates compared with reported values for healthy adults. No significant relationship was detected between urinary GST-pi and other markers for renal function. Urinary GST-pi showed significantly positive correlation with urinary 8-hydroxy-2'-deoxyguanosine at 1 and 4 weeks. Sick neonates treated with supplemental oxygen and mechanical ventilation showed significantly higher levels of GST-pi as well as 8-hydroxy-2'-deoxyguanosine than clinically stable neonates did at 4 weeks. CONCLUSIONS: These results indicate the potential effect of systemic oxidative stress on urinary excretion of GST-pi. Further studies are necessary to explore the effect of oxidative conditions on expression of GST-pi in distal tubules in the human kidney.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Parameters for measurement of oxidative stress in diabetes mellitus: applicability of enzyme-linked immunosorbent assay for clinical evaluation.

Investigations of the mechanisms involved in the onset and progression of diabetes have recently confronted the role of reactive oxygen species (ROS) and oxidative stress. Prolonged exposure to hyperglycemic conditions induces nonenzymatic glycation of protein via the so-called Maillard reaction, resulting in Schiff-base products and Amadori products that engender ROS production. These processes initiate and exacerbate micro- and macrovascular complications in diabetes. Increased oxidative stress is induced by excessive ROS production and inadequate antioxidant defenses. Recently, oxidative stress status markers have been associated directly with the severity and prognosis of diabetes. To examine oxidative stress, reliable and high-throughput methods are needed to examine large numbers of clinical samples. The emerging availability of enzyme-linked immunosorbent assay (ELISA) for oxidative stress status markers allows its application to assessment of various pathophysiologic conditions, including diabetes. This review outlines the recent achievements of ELISA application for clinical studies elucidating oxidative stress. It introduces the potential applicability of ELISA for investigating oxidative stress in diabetes.

Animals↗
PubMed2005

[Current status of redox markers in immunological and inflammatory diseases].

Overloads of reactive oxygen species (ROS), including superoxide, hydrogen peroxide and hydroxyl radical, that exceed the capacity of antioxidant systems induce oxidative stress in the body. Accumulating evidence suggests that ROS play a critical role in the pathogenesis of immunological and inflammatory diseases. Excessive exposure to ROS is the hallmark of oxidative stress and leads to damage of lipids, proteins and nucleic acids. Recently, specific redox (i.e., reduction/oxidation) biomarkers for oxidative damage and antioxidant defenses have been introduced into the field of clinical and laboratory medicine. This brief review discusses the rapidly accruing data linking oxidative events as critical participants in immunological and inflammatory diseases, including atopic dermatitis, bronchial asthma, systemic inflammatory response syndrome and diabetes mellitus. Data from our recent clinical and experimental studies are presented. Studies evaluating the efficacy of antioxidant substances in the prevention and treatment of the diseases are reviewed, and suggestions are made for the direction of future studies.

Biomarkers↗
PubMed2004

Marked renal damage in a child with hydronephrosis infected by Trichosporon asahii.

We describe a case of urinary infection caused by Trichosporon asahii, which drastically aggravated renal function in a left hydronephrotic kidney. Previous implantation of a nephrostomy tube and a ureteral J-stent and administration of broad-spectrum antibiotics seemed to have predisposed the non-granulocytopenic child to the urinary fungal infection.

Child↗
PubMed2004

Effects of antioxidants and NO on TNF-alpha-induced adhesion molecule expression in human pulmonary microvascular endothelial cells.

Pro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium. Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-alpha signaling and upregulate gene expression. We therefore evaluated the effects of pyrrolidine dithiocarbamate (PDTC; 0.1 mM) and spermine NONOate (Sper-NO; 1 mM) on adhesion molecule expression and nuclear factor kappa B (NF-kappaB) activation induced by TNF-alpha (10 ng/ml) in cultured human pulmonary microvascular endothelial cells (PMVEC). Treatment of cells with TNF-alpha for 4 h significantly induced the surface expression of E-selectin and ICAM-1. Treatment with TNF-alpha for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and VCAM-1. The upregulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. 8-Bromo-cyclic GMP (1 mM) had no such effect, suggesting that the NO donor's effect was non-cGMP-dependent. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-kappaB induced by TNF-alpha for 2 h were decreased significantly by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had little inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-alpha. Treatment with TNF-alpha for 4 h enhanced HL-60 leukocyte adhesion to human PMVEC, the effect of which was inhibited significantly by pretreatment with PDTC or Sper-NO. These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-kappaB. Although our in vitro results cannot be directly extrapolated to the in vivo situation, they suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung.

Antioxidants↗
PubMed2004

Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-kappaB activation in human dermal microvascular endothelial cells.

Cell adhesion molecules expressed on endothelial cells in inflamed skin appear to be controlled by the actions of cytokines and reactive oxygen species. However, molecular mechanisms of the expression of adhesion molecules during skin inflammation are currently not well understood. To evaluate the role of antioxidants and nitric oxide in modulating inflammatory processes in the skin, we examined the effects of pyrrolidine dithiocarbamate (PDTC, 0.1 mM) and spermine NONOate (Sper-NO, 1 mM) on adhesion molecule expression and nuclear factor kappa B (NF-kappaB) activation induced by TNF-alpha (10 ng/ml) in cultured human dermal microvascular endothelial cells (HDMEC). Treatment of cells with TNF-alpha for 4 h significantly induced the surface expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1). Treatment with TNF-alpha for 8 h significantly induced the surface expression of E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). The up-regulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-kappaB induced by TNF-alpha for 2 h were significantly decreased by the above two pretreatments. N-acetylcysteine (10 mM) and S-nitroso-N-acetylpenicillamine (1 mM) had no significant inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-alpha. These findings indicate that both cell surface and mRNA expression of adhesion molecules in HDMEC induced by TNF-alpha are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-kappaB. These results suggest a potential therapeutic approach using antioxidant agents or nitric oxide pathway modulators in the treatment of inflammatory skin diseases.

Antioxidants↗