Surgical correction for sinus venosus atrial septal defect with partial anomalous pulmonary venous connection in a dog.

A 5-year-old male toy poodle was referred for corrective surgery of an atrial septal defect. A sinus venosus-type atrial septal defect (ASD) with partial anomalous venous connection, suspected pulmonary hypertension, and pulmonary edema was confirmed by radiography, echocardiography, and cardiac computed tomography. Thoracic radiographs showed right heart enlargement. Echocardiography revealed right atrial and ventricular dilatation with mild flattening of the interventricular septum. Left-to-right shunt flow through the ASD was observed on color Doppler examination. Surgical correction of the sinus venosus ASD with a partial anomalous pulmonary venous connection was performed under cardiopulmonary bypass. A follow-up evaluation at 1 year after surgery showed resolution of the right-sided volume overload and no evidence of recurrence of ASD. Complications were not observed. Our findings indicate that surgical correction under cardiopulmonary bypass is a valid treatment option for an ASD with a partial anomalous pulmonary venous connection.

Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures.

The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing.

Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the nasal epithelial barrier.

BACKGROUND: Diesel exhaust particles (DEP), traffic-related air pollutants, are considered environmental factors that affect allergic diseases adversely. However, the exact effect of DEP on allergic rhinitis (AR) is unclear. OBJECTIVE: We thought to investigate the effect of DEP on seasonal AR using a mouse model. METHODS: Ragweed-pollen-sensitized mice were nasally challenged with ragweed pollen in the presence or absence of DEP. The frequency of sneezing was evaluated immediately after each nasal challenge. The expression of a tight junction (TJ) protein, zonula occludens-1 (ZO-1), was examined by immunohistochemistry in AR mice. RPMI 2650 cells were used for in vitro examination of paracellular permeability. RESULTS: Mice challenged with ragweed pollen plus DEP showed increased frequency of sneezing compared with mice challenged with pollen alone. Interestingly, intranasal DEP pretreatment before ragweed pollen challenge increased ragweed-pollen-induced sneezing to levels comparable with the co-administration group. In vitro examination revealed that DEP reduced ZO-1 expression in RPMI 2650 cells. In addition, intranasal administration of DEP, but not ragweed pollen, disrupted nasal mucosal TJs in vivo. The effect of a single DEP treatment on ragweed-induced sneezing and ZO-1 expression persisted for at least 4 days and was inversely correlated. Finally, an antioxidant substance, N-acetyl-L-cysteine, inhibited DEP-mediated TJ disruption and exacerbation of sneezing in AR. CONCLUSIONS AND CLINICAL RELEVANCE: DEP disrupts TJs by a reactive oxygen species-mediated pathway, leading to the increased permeability of nasal epithelial cells. This may result in the promotion of allergen delivery into subepithelial tissues contributing to the exacerbation of immediate allergic responses.

Estimation of the congestion area volume in potential living donor remnant livers.

BACKGROUND: Living donor liver transplantation is widely performed in adult patients. One of the problems in this setting is a small-for-size graft, which results in dysfunction and poor prognosis of a transplantation. A right liver graft was devised to overcome this problem; furthermore, inclusion of the middle hepatic vein (MHV) has been suggested to greatly improve recipient outcomes. However, extended right hepatectomy involves a surgical risk for the living donor in terms of congestion of the left paramedian sector. The volume of the venoocclusive region of a living donor liver possibly varies depending on the collateral patterns of veins draining the cranial part of segment 4 (S4). PATIENTS AND METHODS: We were analyzed the normal livers of 50 patients who underwent triphasic contrast-enhanced multidetector row computed tomography during preoperative and postoperative examinations. The patient pathologies consisted of gastric cancer (n = 25), colon cancer (n = 1), or renal cancer (n = 24). We calculated the volume of the entire liver as well as those of the right graft and left remnant lobes for comparison with the drainage volume of each hepatic vein and its branches. RESULTS: On the basis of the anatomic venous drainage of the cranial part of S4 (V4sup), we classified hepatic veins as group A (n = 31), the V4sup joined the left hepatic vein or the MHV distal to the vein draining S8 area (MV8), or group B (n = 19), V4sup joined the MHV proximal to MV8. The mean volume of the congested area was 6.9% in group A and 15.9% in group B. The venoocclusive areas in the remnant livers were estimated to be larger in group B (P < .001). CONCLUSION: The collateral pattern of V4sup and MV8 as well as preoperative volumetric analysis are important for graft selection to decide the line of transection.

Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells.

BACKGROUND AND PURPOSE: The voltage-gated Na(+) channels (Na(v)) and their corresponding current (I(Na)) are involved in several cellular processes, crucial to metastasis of cancer cells. We investigated the effects of eicosapentaenoic (EPA), an omega-3 polyunsaturated fatty acid, on I(Na) and metastatic functions (cell proliferation, endocytosis and invasion) in human and rat prostate cancer cell lines (PC-3 and Mat-LyLu cells). EXPERIMENTAL APPROACH: The whole-cell voltage clamp technique and conventional/quantitative real-time reverse transcriptase polymerase chain reaction analysis were used. The presence of Na(v) proteins was shown by immunohistochemical methods. Alterations in the fatty acid composition of phospholipids after treatment with EPA and metastatic functions were also examined. KEY RESULTS: A transient inward Na(+) current (I(Na)), highly sensitive to tetrodotoxin, and Na(V) proteins were found in these cells. Expression of Na(V)1.6 and Na(V)1.7 transcripts (SCN8A and SCN9A) was predominant in PC-3 cells, while Na(V)1.7 transcript (SCN9A) was the major component in Mat-LyLu cells. Tetrodotoxin or synthetic small interfering RNA targeted for SCN8A and SCN9A inhibited metastatic functions (endocytosis and invasion), but failed to inhibit proliferation in PC-3 cells. Exposure to EPA produced a rapid and concentration-dependent suppression of I(Na). In cells chronically treated (up to 72h) with EPA, the EPA content of cell lipids increased time-dependently, while arachidonic acid content decreased. Treatment of PC-3 cells with EPA decreased levels of mRNA for SCN9A and SCN8A, cell proliferation, invasion and endocytosis. CONCLUSION AND IMPLICATIONS: Treatment with EPA inhibited I(Na) directly and also indirectly, by down-regulation of Na(v) mRNA expression in prostate cancer cells, thus inhibiting their metastatic potential.

Effect of nanoparticles on the male reproductive system of mice.

The effects of nanoparticles toward on the male reproductive system of mice were investigated. Three sizes (14, 56 and 95 nm) of carbon black nanoparticles were intratracheally administered (0.1 mg/mouse for 10 times every week) to ICR male mice to investigate their adverse effects on the reproductive function. The serum testosterone levels were elevated significantly in the 14- and 56-nm carbon nanoparticles-exposed groups. Histological examination showed partial vacuolation of the seminiferous tubules. In addition, the effects of particle number towards the male reproductive system were investigated. The particle number controlled 14-nm nanoparticles-exposed group (14 N group, which has approximately the same particle number per unit volume as the 56-nm nanoparticles) showed fewer effects than did the 56-nm nanoparticles-exposed groups. These results suggest that carbon nanoparticle-exposure has adverse effects on the mouse male reproductive function. Furthermore, the effects of nanoparticles on the male reproductive system depend on particle mass rather than particle number.

CT colonography to detect rectosigmoid involvement in patients with primary ovarian cancer.

INTRODUCTION: We retrospectively evaluated the performance of preoperative computed tomographic (CT) colonography to detect tumor involvement of the rectosigmoid wall and predict the need for rectosigmoid resection in patients with primary ovarian cancer. METHODS: Thirty-three patients with primary ovarian cancer who underwent preoperative CT colonographic examination were evaluated. The images of the examination were analyzed and compared with the subsequent surgical findings. RESULTS: All abnormal findings (malignant infiltration of the rectosigmoid mucosa and extrinsic compression) revealed by conventional colonoscopy were correctly observed as extrinsic compression using CT colonography. The sensitivity, specificity, positive predictive value and negative predictive value of CT colonography for the prediction of rectosigmoid resection were 100%, 64.7%, 72.7%, and 100%, respectively. Though conventional colonoscopic examinations could not be completed in five patients because of the presence of extrinsic stenosis and occlusion at the sigmoid colon, CT colonography enabled the entire large bowel to be examined in these patients. CONCLUSIONS: This preliminary study showed that the CT colonographic examination is feasible and safe. CT colonography seems to have several advantages over conventional colonoscopy for the detection of rectosigmoid involvement in patients with advanced ovarian cancer. For confirmation of the efficacy of CT colonography, further large prospective studies are needed.

Antioxidative role of interleukin-6 in septic lung injury in mice.

We have previously demonstrated the protective role of interleukin (IL)-6 against septic lung injury induced by lipopolysaccharide (LPS) using IL-6 knock-out (-/-) mice. This protection is mediated, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines. In the present study, we addressed whether IL-6 regulates oxidative stress in the lung generated by LPS exposure using IL-6 (-/-) and corresponding wild type (WT) mice. Intraperitoneal LPS (1 mg/kg) challenge induced transcriptional expressions of inducible nitric oxide synthase and heme oxygenase -1 in the lung of mice with both genotypes. In the presence of LPS, these expressions were significantly greater in IL-6 (-/-) than in WT mice. Immunohistochemistry also showed that LPS induced a significant increase in 8-hydroxy-2'-deoxyguanosine formation in the lung as compared to vehicle. Furthermore, the formation was more intense in IL-6 (-/-) than in WT mice in the presence of LPS challenge. In the presence of LPS, lipid peroxidation in the lung was significantly greater in IL-6 (-/-) than in WT mice. These data suggest that the possible mechanisms in which endogenous IL-6 protects against septic lung injury induced by LPS involve, at least in part, its antioxidative properties.

Cacao liquor proanthocyanidins inhibit lung injury induced by diesel exhaust particles.

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 microg/body). Dietary supplementation with 1.0 percent CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules.

Pulmonary exposure to carbon black nanoparticles increases the number of antigen-presenting cells in murine lung.

Particulate matters can enhance antigen-related airway inflammation and immunoglobulin production. The present study was designed to determine the effects of different sizes of nanoparticles on the antigen-presenting cells (APC) in the lung. ICR mice were exposed to vehicle, carbon black (CB) nanoparticles (14 nm or 56 nm), ovalbumin (OVA), or OVA + nanoparticles intratracheally. The expression of major histocompatibility complex (MHC) class II, costimulatory molecules (CD80, CD86, CD11c), and DEC205 (dendritic cell marker), F4/80 (macrophage marker), and CD19 (B-cell marker) in the lung cells was measured by flow cytometry. 14 nm nanoparticles, but not 56 nm nanoparticles, increased the number of the total lung cells. Combination of OVA and 14 nm or 56 nm nanoparticles increased the total lung cells. The expression of MHC class II and/or costimulatory molecules and the number of APC in the lung were increased by 14 nm nanoparticles in the presence or absence of OVA. The increases were more prominent with combination of OVA and 14 nm nanoparticles. 56 nm nanoparticles did not show any significant effects. 14 nm CB nanoparticles can increase the expression of MHC class II and costimulatory molecules and the number of APC in the lung, especially in the presence of antigen, which can result in subsequent antigen-related airway inflammation and immunoglobulin production.

Imaging findings of radiation-induced sarcoma of the head and neck.

We set out to retrospectively review the clinical and imaging features of patients with post-radiation sarcoma, especially in the head and neck region. We reviewed the records of 4194 patients with carcinoma of the head and neck region who had a history of radiation. They had undergone CT and/or MRI. Medical records were reviewed for the primary diagnosis, radiation history and latency period to the development of sarcoma. The patients included four men and two women with a mean age of 64.5 years. The mean latency period for the development of sarcoma was 11.5 years. Primary diagnoses were maxillary carcinoma, nasopharyngeal carcinoma, adenoid cystic carcinoma of the oral floor, tonsilar carcinoma, soft palate carcinoma and tongue carcinoma. Histopathological examinations revealed osteosarcoma, spindle cell sarcoma, chondrosarcoma, malignant peripheral nerve sheath tumour, spindle cell carcinoma and malignant fibrous histiocytoma, respectively. Common findings were a heterogeneous and well-enhanced soft tissue mass and bone destruction. There is at present little or no prospect for the effective prevention of radiation-induced sarcoma of the head and neck. This emphasizes the importance of the earliest possible diagnosis for such patients. The imaging findings are not diagnosis specific, but strict follow-up within the radiation field by CT and MRI and an appreciation of the expected latency period may help to provide the diagnosis. When radiotherapy is performed for head and neck neoplasms, periodic follow-up observations may be necessary for many years.

Candida soluble cell wall beta-D-glucan induces lung inflammation in mice.

Bioactivity of cell wall component(s) of fungi has not been fully elucidated, especially in vivo. We isolated Candida soluble beta-D-glucan (CSBG) from Candida albicans (C. albicans). We investigated the effects of airway exposure to CSBG on the immune systems in the airways in mice. CSBG exposure induced neutrophilic and eosinophilic inflammation in the lung, which was concomitant with the increased local expression of proinflammatory cytokines including tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, macrophage inflammatory protein -1alpha, macrophage chemoattractant protein -1, RANTES (regulated on activation and normal T cells expressed and secreted), and eotaxin. The lung inflammation with enhanced expression of proinflammatory proteins caused by CSBG was directly related to its structure, since structurally degraded products of CSBG by formic acid induced negligible responses in the lung. CSBG enhanced nuclear localization of phosphorylated signal transducer and activator of transcription (STAT)-6 in the lung. These results suggest that airway exposure to CSBG induces lung inflammation, at least partly, via the enhanced expression of proinflammatory cytokines and the activation of STAT-6 pathway, and can be a proper murine model for fungal lung inflammation.

Induction of osteoclast-like cells derived from the synovial lavage fluids of patients with temporomandibular joint disorders.

OBJECTIVE: Although biochemical studies have examined the synovial fluid (SF) of patients with temporomandibular joint (TMJ) disorders (TMDs), the details of the molecular mechanism of bone destruction and remodeling remain unknown. In this study, we induced and characterized osteoclast-like cells from the SF of patients with TMD and investigated the participation of these cells in the pathogenesis of TMD. METHODS: We collected SF cells from patients with TMD after a pumping procedure, cultured osteoclast-like cells, and examined their characteristics, including osteoclast markers and bone resorption activities. In addition, we obtained fibroblastic cells from the SF of TMD patients by continuous sub-culturing. Using these fibroblastic cells, we examined fibroblast markers using immunocytochemical staining and analyzed the receptor activator of nuclear-factor-kappaB ligand (RANKL) mRNA levels. Detection of soluble form of RANKL (sRANKL) in the SF was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Osteoclast-like cells were induced from the SF cells of patients with TMD by adding recombinant human (rh) macrophage colony stimulating factor (M-CSF) and either 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] or prostaglandin E2 (PGE2). These multinucleated giant cells were positive for tartrate-resistant acid phosphatase (TRAP) and had the ability to absorb bone. The fibroblastic cells from the SF of TMD patients were positive for fibroblast markers and RANKL mRNA was up-regulated. Detection of sRANKL in SF of patient group was significantly higher than control group. CONCLUSION: The results suggest that the joint-infiltrating SF cells from TMD patients play important roles in the pathogenesis of these disorders, which is characterized by progressive bone destruction or remodeling.

Murine strain differences in 8-hydroxy-deoxyguanosine formation in hepatic DNA induced by oxidized lard and dietary oils.

Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8-oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two murine strains fed with oxidized lard and dietary oils may be associated with the different mRNA levels in the DNA repair enzymes because the mRNA levels in the DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.

Elk-1 associates with the mitochondrial permeability transition pore complex in neurons.

The nuclear transcription factor E-26-like protein 1 (Elk-1) is thought to impact neuronal differentiation [Sharrocks, A. D. (2001) Nat. Rev. Mol. Cell Biol. 2, 827-837], cell proliferation [Sharrocks, A. D. (2002) Biochem. Soc. Trans. 30, 1-9], tumorigenesis [Chai, Y. L., Chipitsyna, G., Cui, J., Liao, B., Liu, S., Aysola, K., Yezdani, M., Reddy, E. S. P. & Rao, V. N. (2001) Oncogene 20, 1357-1367], and apoptosis [Shao, N., Chai, Y., Cui, J., Wang, N., Aysola, K., Reddy, E. S. P. & Rao, V. N. (1998) Oncogene 17, 527-532]. In addition to its nuclear localization, Elk-1 is found throughout the cytoplasm, including localization in neuronal dendrites [Sgambato, V., Vanhoutte, P., Pages, C., Rogard, M., Hipskind, R., Besson, M. J. & Caboche, J. (1998) J. Neurosci. 18, 214-226], raising the possibility that Elk-1 may have alternative extranuclear functions in neurons. Using coimmunoprecipitation and reciprocal coimmunoprecipitation from adult rat brain, we found an association between Elk-1 protein and the mitochondrial permeability transition pore complex (PTP), a structure involved in both apoptotic and necrotic cell death. Electron microscopy in adult rat brain sections confirmed this association with mitochondria. Elk-1 was also identified from purified mitochondrial fractions by using Western blotting, and Elk-1 increased its association with mitochondria following proapoptotic stimuli. Consistent with a role for Elk-1 in neuron viability, overexpression of Elk-1 in primary neurons decreased cell viability, whereas Elk-1 siRNA-mediated knockdown increased cell viability. This decrease in viability induced by Elk-1 overexpression was blocked with application of a PTP inhibitor. These results show an association of the nuclear transcription factor Elk-1 with the mitochondrial PTP and suggest an additional extranuclear function for Elk-1 in neurons.

Reactivation of antigen-induced arthritis in mice by oral administration of lipopolysaccharide.

We examined whether oral administration of lipopolysaccharide (LPS) from Escherichia coli reactivated antigen-induced arthritis (AIA) in mice that is one of models of human rheumatoid arthritis. To induce AIA, mice were immunized by subcutaneous injection of ovalbumin (OVA) emulsified with complete Freund's adjuvant into the base of the tail (day 0) followed by intraarticular injection of OVA on day 21. To investigate the ability of LPS to reactivate AIA, varying doses of LPS were p.o. administered 48 h after the challenge injection. The results showed that administration of LPS was followed by reactivation of AIA in a dose-related fashion. The reactivation of AIA by LPS was associated with increases in interferon-gamma, interleukin-1beta and tumour necrosis factor-alpha. Polymyxin B sulfate given immediately before administration of LPS suppressed the reactivation of AIA. These findings suggest that LPS from intestinal bacteria may play a role in the reactivation of joint inflammation in which immune responses to pathogenic antigens are involved.

Liver carcinogenesis and formation of 8-hydroxy-deoxyguanosine in C3H/HeN mice by oxidized dietary oils containing carcinogenic dicarbonyl compounds.

Oxidized dietary oils (lard, soybean oil, and sardine oil) were orally administered to C3H/HeN male mice. After 6 months, benign hepatocellular adenoma was observed in the mice treated with all three oxidized dietary oils. After 12 months, malignant hepatocellular carcinoma and hepatoblastoma were observed in addition to the benign tumor. Oxidized sardine oil caused the highest tumor incidence (35%) and malignant tumors (27.5%) among the oxidized dietary oils tested. Mice treated with oxidized lard and sardine oil exhibited a significant increase of 8-OH-dG in the livers. The amounts of 8-OH-dG found in the mice treated with oxidized sardine oil correlated with the rates of tumor incidence. After 6 months, mRNA decreased in the case of oxidized lard and sardine oil, whereas it increased in the case of oxidized soybean oil, either in 8-oxoguanine-DNA glycosylase (OGG1) or in 8-oxo-dGTPase. On the other hand, there was no appreciable change in mRNA, in either OGG1 or 8-oxo-dGTPase, after 12 months. Oxidized sardine oil contained the highest level of malonaldehyde (MA) (713+/-91.1 nmol/g) and glyoxal (33.3+/-5.2 nmol/g) among three oxidized oils. The malignant tumor incidence correlated with the high level of MA and glyoxal found in the dietary oils tested.

Increased urinary 15-F2t-isoprostane concentrations in patients with non-ischaemic congestive heart failure: a marker of oxidative stress.

OBJECTIVE: To investigate a novel marker of oxidative stress in patients with congestive heart failure (CHF). PATIENTS: 15 patients with mild CHF, 15 patients with severe CHF with acute exacerbation, and 15 control subjects. MAIN OUTCOME MEASURES: Measurement of urinary 15-F2t-isoprostane, plasma brain natriuretic peptide (BNP), serum interleukin 6 (IL-6), and serum thrombomodulin concentrations. In patients with severe CHF, samples were taken at admission and 4, 7, and 14 days after admission. RESULTS: Urinary 15-F2t-isoprostane, plasma BNP, and serum IL-6 concentrations in patients with severe CHF were significantly higher than those in control subjects or in patients with mild CHF. However, concentrations of serum thrombomodulin, a marker of endothelial damage, were not different between patients with CHF and control subjects. In addition, urinary 15-F2t-isoprostane, plasma BNP, and serum IL-6 concentrations in patients with severe CHF gradually decreased in proportion to the severity of CHF during hospitalisation. Interestingly, urinary 15-F2t-isoprostane concentrations significantly correlated with plasma BNP concentrations and serum IL-6 concentrations, but not with serum thrombomodulin concentrations. CONCLUSIONS: Urinary 15-F2t-isoprostane concentrations increased in proportion to the severity of CHF in patients. This may be caused by increased 15-F2t-isoprostane production. These findings suggest that urinary 15-F2t-isoprostane may be a marker of morbidity as well as oxidative stress in patients with CHF.