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Jyh-Seng Wang

Publications and source records attributed to Jyh-Seng Wang.

At least 19 recordsLinked to original sources
PubMed2006

Increased expression of SKP2 and phospho-MAPK/ERK1/2 and decreased expression of p27 during tumor progression of cervical neoplasms.

OBJECTIVE: The objective of this study was to investigate whether the expression of SKP2, p27 and phospho-MAPK/ERK1/2 is associated with the progression of human cervical neoplasia. METHODS: We performed immunohistochemical detection to stain formalin-fixed paraffin-embedded cervical tissues with anti-SKP2 and anti-p27 monoclonal antibodies and anti-phospho-p42/44 MAPK antibody. The study sample included 23 normal cervical epithelium, 25 low-grade squamous intraepithelial lesion (LSIL), 19 high-grade squamous intraepithelial lesion (HSIL), and 31 squamous cell carcinomas (SCC). In addition, 14 frozen cervical biopsies, including 1 normal, 6 HSIL, 2 adenocarcinoma and 5 SCC, and a human cervical cancer cell line (HeLa), were analyzed the expression levels of mRNA and protein of SKP2 and p27 by RT-PCR and Western blot analysis, respectively. RESULTS: The expression of SKP2, p27 and phospho-MAPK/ERK1/2 were strongly associated with cervical neoplastic progression (P<0.0001, P=0.006, P=0.003, respectively; Fisher's Exact Test). In addition, SKP2 expression was positively correlated with phospho-MAPK/ERK1/2 expression (Spearman correlation coefficient=0.480, P=0.0002). The association between SKP2 and phospho-MAPK/ERK1/2 was significant after controlling for the four histologic grades (P=0.038, Mantel-Haenszel test). CONCLUSIONS: These results suggest that expression levels of SKP2, p27 and phospho-MAPK/ERK1/2 may serve as markers for progression in human cervical carcinoma and may also play roles in cervical carcinoma progression and cervical carcinogenesis.

Adenocarcinoma↗
PubMed2006

Association of vitamin D receptor FokI polymorphism with prostate cancer risk, clinicopathological features and recurrence of prostate specific antigen after radical prostatectomy.

To investigate the effect of vitamin D receptor (VDR) FokI polymorphism on susceptibility to prostate cancer and the outcome of the disease in a Taiwanese population, we genotyped a total of 416 prostate cancer patients, 502 age-matched male controls and 189 non age-matched symptomatic benign prostatic hyperplasia. Although we did not find a significant association between VDR FokI genotypes and overall prostate cancer risk, we found that in men aged less than or equal to the median age of 73 years with VDR FokI F allele specifically had an increased risk of prostate cancer with a marginal significant trend (OR, 2.08; 95% CI, 1.00-4.34, p for trend = 0.056). The FF genotype was also highly associated with more aggressive prostate cancer (Gleason score 8-10) (OR, 2.47; 95% CI, 1.20-5.08) than did the Ff and ff genotypes. After adjusting other covariates, we found that in patients who had localized prostate cancer for which a radical prostatectomy was performed (n = 131), the VDR FokI FF genotype was associated with worse prostate-specific antigen (PSA) recurrence-free survival (hazard ratio = 3.25, 95% CI = 1.32-8.00, p = 0.010). Our findings suggest that the VDR FF genotype may increase the risk of early-onset prostate cancer and is associated with more aggressive disease. Furthermore, the VDR polymorphism could be used as a prognostic marker for localized prostate cancer after radical prostatectomy.

Aged↗
PubMed2006

Invasive pulmonary aspergillosis with cerebral abscess in a patient with idiopathic thrombocytopenic purpura.

Invasive aspergillosis is a devastating infection in immunocompromised hosts. The lung is the most common site of primary infection, and the central nervous system is the most common secondary site of invasive disease. Invasive aspergillosis in autoimmunopathies treated with corticosteroids has rarely been reported in the literature. Herein, we report the case of a 48-year-old female patient with idiopathic thrombocytopenic purpura complicated with fatal invasive pulmonary and cerebral aspergillosis. She had been given 1,016 g intravenous amphotericin B empirically for lung infection during a previous admission. At presentation, she had fever, cough, and shortness of breath for 4 weeks. Chest radiography revealed a huge cavity over the left upper lung field. Bronchoscopic biopsy and culture showed Aspergillus species. She was initially treated with intravenous amphotericin B (0.9 mg/kg/day), and intravenous hydrocortisone for her idiopathic thrombocytopenic purpura. However, deterioration of consciousness occurred 12 days after hospitalization. Computed tomography of the brain showed ring-like cystic mass lesions in the right side basal ganglion. Stereotactic aspiration of the brain revealed Aspergillus species. Her condition exacerbated despite combination treatment with high-dose amphotericin B (1.2 mg/kg/day) and itraconazole (400 mg/day). She died 24 days after admission. This case suggests that treatment with corticosteroids and premature discontinuation of antifungal drugs bear the risk of fatal cerebral involvement in patients with invasive pulmonary aspergillosis.

Amphotericin B↗
PubMed2006

Thermal injury-induced peroxynitrite production and pulmonary inducible nitric oxide synthase expression depend on JNK/AP-1 signaling.

OBJECTIVE: To determine whether burn-induced peroxynitrite production and expression of lung inducible nitric oxide synthase (iNOS), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, CXCR2, macrophage inflammatory protein (MIP)-2, and neutrophil chemokine (KC) are mediated by the c-Jun NH2-terminal kinase (JNK). DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury models in the mice. INTERVENTIONS: In experiment 1, specific pathogen-free C57/BL6 mice were subjected to 30% total body surface area third-degree burn over shaved back. At 0 hr, 2 hrs, 4 hrs, and 6 hrs after burn, lung tissues of those mice were harvested for JNK activity assay, AP-1 DNA-binding activity, and pJNK immunohistochemistry. In experiment 2, a specific JNK inhibitor, SP600125, was given (30 mg/kg intraperitoneally) to mice immediately postburn to suppress the JNK activity. At 8 hrs after burn, blood was assayed for the peroxynitrite-mediated dihydrorhodamine (DHR) 123 oxidation. Lung tissues were harvested for myeloperoxidase (MPO) determination, ICAM-1, VCAM-1, CXCR2, KC, MIP-2, interleukin-1beta, and interleukin-6 messenger RNA expression; iNOS immunohistochemical staining; and histologic studies. Pulmonary microvascular dysfunction was quantified by measuring the extravasations of Evans blue dye. MEASUREMENTS AND MAIN RESULTS: The JNK activity and AP-1 DNA-binding activity of lung tissue significantly increased to a peak at 2 hrs and 4 hrs, respectively, after thermal injury. Immunohistochemical study demonstrated that the increase of the pJNK was mostly from the bronchiole epithelial cells. This increase of MPO activity in lung, blood DHR 123 oxidation level, and lung permeability increased six-fold, nine-fold, and four-fold after burn. SP600125 administration obliterated the thermal injury-induced JNK activity, AP-1 DNA-binding activity, and iNOS expression in lung tissue. SP600125 treatment also significantly decreased MPO activity, blood DHR 123 oxidation, and lung permeability by 54%, 8%, and 47%, respectively, and markedly decreased the thermal injury-induced perivascular and interstitial inflammatory cell infiltration and septum edema. Furthermore, SP600125 abolished thermal injury-induced ICAM-1, VCAM-1, CXCR2, MIP-2, and KC but not interleukin-1beta and interleukin-6 messenger RNA levels of lung tissues. CONCLUSIONS: Thermal injury induces lung tissue JNK activation and AP-1 DNA-binding activity mainly from airway epithelial cells. Thermal injury-induced peroxynitrite production and lung iNOS, ICAM-1, and VCAM-1 expression are mediated by the JNK signaling. JNK inhibition decreases thermal injury-induced lung neutrophil infiltration and subsequently pulmonary hyperpermeability.

Animals↗
PubMed2005

Inhibition of nitric oxide synthase reverses the effect of albumin on lung damage in burn.

BACKGROUND: Early colloid resuscitation in major burn patients has been stopped because of its deteriorating effect on thermal injury-induced vascular hyperpermeability. We hypothesized that inhibition of inducible nitric oxide synthase (iNOS) to stabilize endothelial permeability and to retain colloid solution in the vascular space will reverse its effect on lung damage. STUDY DESIGN: In experiment 1, specific pathogen free rats underwent 35% total-body surface area burn or sham burn and were given equal volumes (7.5 mL/kg) of normal saline or albumin from femoral veins for fluid resuscitation immediately after burn. In experiment 2, S-methylisothiourea (SMT, 7.5 mg/kg, IP) was given immediately after burn to rats from different groups, as in experiment 1. At 8 hours after burn, blood was assayed for peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation, and lung tissues were harvested for myeloperoxidase (MPO) determination and histologic studies. Pulmonary microvascular dysfunction was quantified by measuring the extravasations of Evans blue dye. RESULTS: Blood peroxynitrite level and iNOS expression, MPO activity, permeability, and inflammatory cell infiltration of lungs were significantly induced after thermal injury. Albumin resuscitation after burn without iNOS inhibition enhanced thermal injury-induced lung damage with 10%, 14%, and 5% increases in blood DHR oxidation level, lung MPO activity, and lung permeability, respectively, compared with saline injection. In contrast, burn + SMT rats with albumin injection showed significant, 23%, 37%, and 20%, decreases, respectively, in blood DHR 123 oxidation level, lung MPO activity, and lung permeability compared with burn + SMT + saline rats. CONCLUSIONS: Thermal injury induced lung damage. Restoration of extracellular fluid in early burn shock with albumin markedly augmented the lung neutrophil deposition, lung permeability increase, and blood peroxynitrite level. Inhibition of iNOS before albumin supplementation reversed its damaging effects on thermal injury-induced lung dysfunction to beneficial ones.

Albumins↗
PubMed2005

Increased endothelin 1 expression in adult-onset minimal change nephropathy with acute renal failure.

BACKGROUND: Acute renal failure (ARF) occurs in some adult patients with minimal change nephropathy (MCN). To investigate clinical and pathological factors associated with developing ARF, we compared clinical features and kidney pathological characteristics of endothelin 1 (ET-1) expression in patients with adult-onset MCN with and without ARF. METHODS: The patient population consisted of 53 patients consecutively diagnosed with adult-onset MCN during a 10-year period. Based on creatinine clearance, 25 patients were assigned to the ARF group and 28 patients were assigned to the non-ARF group. RESULTS: Clinical data show that the ARF group had a higher blood pressure, higher serum cholesterol level, and lower serum albumin level than the non-ARF group. Pathological data showed more severe foot-process effacement, interstitial edema, and flattened tubular epithelium in the same group. Greater ET-1 expression was detected in vessels, tubules, and glomeruli of the ARF compared with non-ARF group. The ARF group experienced a lower steroid response rate. However, there was no significant difference in stability of remission to steroid treatment in patients who achieved a remission. CONCLUSION: ARF associated with enhanced kidney ET-1 expression is a reversible complication of MCN that occurs frequently in patients with apparently expanded extracellular fluid. Presumptively, ARF may develop as an amplification of the underlying pathogenesis of MCN involved in enhanced ET-1 expression, which may be superimposed by a transient episode of circulatory insufficiency during diuretic treatment.

Acute Kidney Injury↗
PubMed2005

Correlation of p53 protein accumulation and Bcl-2 overexpression with histopathological features in prostatic cancer.

BACKGROUND AND PURPOSE: p53 mutation and Bcl-2 overexpression is correlated with advanced prostate cancer. This study investigated the correlation of p53 and Bcl-2 immunoreactivity frequency with histopathological features in patients with prostate cancer in Taiwan. METHODS: Primary adenocarcinomas from 125 radical prostatectomy specimens were stained using commercial monoclonal antibodies. Association between immunohistochemical findings and tumor extent, Gleason score and preoperative prostate-specific antigen (PSA) levels were assessed. RESULTS: Abnormal p53 expression was identified in 44 tumors (35.2%) and was correlated with high serum PSA (p=0.022) and advanced disease (p=0.005), but not Gleason score. Ten tumors (8%) expressed Bcl-2. A significant positive association was found between Bcl-2 and PSA (p=0.034). There was no association between p53 and Bcl-2 immunopositivity. CONCLUSIONS: p53 mutation was positively correlated with serum PSA and tumor extent. Overexpression of Bcl-2 was associated with high serum PSA only.

Adenocarcinoma↗
PubMed2004

Hypertonic saline-enhanced postburn gut barrier failure is reversed by inducible nitric oxide synthase inhibition.

OBJECTIVE: To determine whether inhibition of inducible nitric oxide synthase to stabilize endothelial permeability and to retain hypertonic saline in the vascular space will ameliorate burn-induced gut barrier dysfunction. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury models in the rat. INTERVENTIONS: In experiment 1, specific pathogen free rats underwent 3% total body surface area burn or sham burn and were given 7.5 mL/kg hypertonic saline (7.5% NaCl), 7.5 mg/kg saline, or 50 mL/kg saline (nearly equal sodium load with hypertonic saline) in the right femoral vein for 15 mins for fluid resuscitation at 0, 4, or 8 hrs after burn. In experiment 2, S-methylisothiourea (7.5 mg/kg, intraperitoneally), a specific inducible nitric oxide synthase inhibitor, was given immediately after burn to rats from different groups as in experiment 1. At 24 hrs after burn, the intestinal mucosa was assayed for myeloperoxidase activity and lipid peroxidation, the distribution of fluorescein isothiocyanate-dextran across the lumen of the small intestine was determined, and bacterial translocation to the mesenteric lymph nodes and ileum histology were also examined. MEASUREMENTS AND MAIN RESULTS: Burn induced significant increases in intestinal mucosa inducible nitric oxide synthase expression, myeloperoxidase activity, lipid peroxidation, intestinal permeability, bacterial translocation to mesenteric lymph nodes, and villi sloughing in rats. Hypertonic saline administration at 0 or 4 hrs after burn worsened intestinal mucosa lipid peroxidation, neutrophil sequestration, intestinal permeability, and villi sloughing compared with those of burn + 7.5 mg/kg saline and burn + 50 mL/kg saline rats. To the contrary, burn + S-methylisothiourea rats with hypertonic saline injection at 4 or 8 hrs after burn showed an improvement of gut barrier function compared with burn + S-methylisothiourea + 7.5 mg/kg saline and burn + S-methylisothiourea + 50 mL/kg saline rats. Administration of hypertonic saline at 8 hrs after burn and S-methylisothiourea injection also significantly attenuated the bacterial translocation to mesenteric lymph nodes and villi sloughing. CONCLUSIONS: Using hypertonic saline as a resuscitation fluid in early burn shock markedly augmented the thermal injury-induced intestinal mucosa neutrophil deposition, lipid peroxidation, and intestinal hyperpermeability. Inhibition of inducible nitric oxide synthase not only significantly attenuated neutrophil deposition and mucosa lipid peroxidation but also reversed the deteriorating effects of hypertonic saline on thermal injury-induced gut barrier dysfunction and bacterial translocation.

Animals↗
PubMed2004

Inducible nitric oxide synthase inhibitor reverses exacerbating effects of hypertonic saline on lung injury in burn.

The use of hypertonic saline (HTS) resuscitation in major trauma patients is still controversial. The objective of this study is to determine if inhibition of inducible nitric oxide synthase (iNOS) to stabilize the endothelial permeability and to retain HTS in the vascular space will reverse its exacerbating effect on burn-induced lung damage. In Experiment 1, specific pathogen-free (SPF) rats underwent 35% total body surface area (TBSA) burn and were resuscitated with 7.5 mL/kg HTS (7.5% NaCl), 7.5 mL/kg saline, or 50 mL/kg saline (nearly equal sodium load as HTS) via femoral veins for 15 min immediately after the burn. In Experiment 2, S-methylisothiourea (SMT) (7.5 mg/kg, i.p.) was given immediately after the burn to rats from the different groups of Experiment 1. At 8 h after the burn, the permeability and myeloperoxidase (MPO) activity of lung tissues were determined, and plasma samples were assayed for peroxynitrite levels. Burn significantly induced lung MPO activity, lung permeability, and blood dihydrorhodamine 123 (DHR 123) oxidation in rats. HTS administration after burn significantly increased the blood DHR 123 oxidation level, lung MPO activity, lung permeability, and inflammatory cell infiltration in comparison with those of burn plus 7.5 mg/kg saline and burn plus 50 mL/kg saline rats. In contrast, burn plus SMT rats with HTS injection showed significant 54%, 11%, and 35% decreases in blood DHR 123 oxidation level, lung MPO activity, and lung permeability, respectively, in comparison with burn plus SMT plus 7.5 mg/kg saline rats. In conclusion, restoration of extracellular fluid in early burn shock with HTS supplementation significantly exacerbates burn-induced lung neutrophil deposition, lung hyperpermeability, and blood peroxynitrite production. Inhibition of iNOS before HTS supplementation reverses the deteriorating effects of HTS on thermal injury-induced lung damage to beneficial ones. Using HTS in thermal injury resuscitation without the inhibition of iNOS is dangerous.

Animals↗
PubMed2004

E-cadherin expression in prostate adenocarcinomas in Chinese and its pathological correlates.

INTRODUCTION: We examined the E-cadherin expression in prostate adenocarcinomas in Chinese to correlate this immunohistochemical marker with histopathological features. MATERIALS AND METHODS: Primary adenocarcinomas from 122 radical prostatectomy specimens were stained using anti-E-cadherin (HECD-1) antibody. The association of E-cadherin expression with serum prostate-specific antigen (PSA), pathological stage and Gleason score was assessed by Kendall's tau-b test. RESULTS: Aberrant E-cadherin expression was identified in 79 tumors (64.8%). Abnormal E-cadherin expression did not correlate to serum PSA (p = 0.802), tumor stage (p = 0.684) and Gleason score (p = 0.385). CONCLUSIONS: The frequency of aberrant E-cadherin expression was higher in prostate adenocarcinomas of Chinese as compared to that reported in Caucasians. No association with pathological stage, Gleason score and serum PSA was identified.

Adenocarcinoma↗
PubMed2004

Primary Sjögren's syndrome complicated with cryoglobulinemic glomerulonephritis, myocarditis, and multi-organ involvement.

Glomerulonephritis in primary Sjögren's syndrome is rarely reported. Cryoglobulinemic glomerulonephritis with the presence of cryoglobulin deposition in the glomerular capillary lumen in primary Sjögren's syndrome is extremely rare. A 51-year-old woman with primary Sjögren's syndrome for > 10 years complained of fever, hypertension, and proteinuria. In addition, novel manifestations, including myocarditis with heart failure, pericardial effusion, and polyneuropathy (sensory motor neuropathy) were also noted. Cryoglobulinemia test was positive, and kidney biopsy results were consistent with cryoglobulinemic glomerulonephritis. There were no symptoms associated with systemic lupus erythematosus or other connective tissue disease. Treatment with monthly methylprednisolone and cyclophosphamide pulse therapy for 6 months resulted in resolution of proteinuria, heart failure, and neurologic symptoms.

Cryoglobulinemia↗
PubMed2004

Retroperitoneal enteric duplication cyst.

Enteric duplication cysts (EDCs) can occur in any portion of the alimentary tract, but are most commonly associated with the small bowel and esophagus. Retroperitoneal location is really unusual. This 19-year-old female was in excellent health, but a week's abdominal pain made her search for a doctor's help. After the detailed examination, surgical intervention was performed under the impression of cystic tumor of the retroperitoneum. A retroperitoneal cystic tumor, 13.0 x 8.0 x 3.5 cm in size, without any communication with the alimentary tract was noted during the operation. Finally, EDC was diagnosed after the pathologic examination of this resected cystic lesion. To our knowledge, there have been only 6 reported cases of EDC of the retroperitoneum in the English literature. This report concerns the seventh case of retroperitoneal EDC, in an adolescent, with different clinical presentation and histopathologic findings from the previous ones.

Adult↗
PubMed2004

Solitary fibrous tumor of the orbit.

The occurrence of solitary fibrous tumor in the orbit is rare. The following is a report on the case of a 24-year-old man presented with painless, progressive proptosis of the right eye for the duration of 1 year. Computed tomography and magnetic resonance imaging demonstrated a well-circumscribed soft tissue mass with gadolinium enhancement located in the superomedial aspect of the right orbit. The patient underwent complete tumor removal through a right fronto-orbital approach, with a pathological diagnosis of solitary fibrous tumor. Postoperatively, the patient was symptom-free. From review of the literature on orbital solitary fibrous tumor, emphasis should be placed on complete tumor resection and continuous follow-up monitoring of the tumor.

Adult↗
PubMed2004

Primary appendiceal lymphoma presenting as perforated acute appendicitis.

Acute perforated appendicitis is a very rare initial presentation of appendiceal lymphoma. A case of primary lymphoma of the appendix in a 42-year-old female is reported here. The symptom was pain in the right lower quadrant of the abdomen. Surgical intervention was performed under clinical diagnosis of acute appendicitis. Grossly, the resected appendix was gangrenous and perforated. Light microscopy revealed transmural infiltration by diffuse large B-cell lymphoma with angioinvasion and tumor necrosis, resulting in perforated acute suppurative appendicitis. To the best of our knowledge, only 4 cases of well-documented primary diffuse large B-cell lymphoma of appendix have been reported in the world literature.

Acute Disease↗
PubMed2003

Reversal of the effect of albumin on gut barrier function in burn by the inhibition of inducible isoform of nitric oxide synthase.

HYPOTHESIS: The use of albumin in the early resuscitation formula after major burn has been forbidden because of its damaging effect on the gut barrier function. We hypothesize that inhibition of the inducible isoform of nitric oxide synthase to stabilize endothelial permeability and to retain albumin in the vascular space will ameliorate the major trauma-induced gut barrier dysfunction. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: In experiment 1, specific pathogen-free rats undergoing 35% total body surface area burn or sham burn were given equal volumes (7.5 mL/kg) of isotonic sodium chloride solution or albumin from femoral veins for fluid resuscitation at 0, 4, or 8 hours after burn. In experiment 2, intraperitoneal S-methylisothiourea sulfate (7.5 mg/kg) was given immediately after burn to rats from different groups, as in experiment 1 (SMT groups). At 24 hours after burn, the intestinal mucosa was assayed for myeloperoxidase activity as an index for neutrophil sequestration, the distribution of fluorescein isothiocyanate-dextran across the lumen of small intestine was determined to evaluate the intestinal permeability, and bacterial translocation (BT) to the mesenteric lymph nodes (MLNs) and histological findings in the ileum were also examined. RESULTS: Compared with sham burn, burn induced significant increases in intestinal mucosa myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi sloughing in rats. Albumin administration at 0 or 4 hours after burn enhanced the increases in neutrophil sequestration, permeability, and villi sloughing compared with saline injection at the same times. In contrast, injection of albumin in the burn-SMT group did not aggravate these changes in intestinal myeloperoxidase activity, intestinal permeability, BT to the MLNs, and villi edema. Burn-SMT rats with albumin injections at 4 or 8 hours after burn showed significant 35% and 52% decreases, respectively, in intestinal permeability compared with burn-SMT-saline rats. Use of albumin at 8 hours after burn in combination with S-methylisothiourea significantly attenuated BT to the MLNs and reduced villi edema. CONCLUSIONS: Early albumin resuscitation aggravated the burn-induced gut damage. Albumin administration and inhibition of the inducible isoform of nitric oxide synthase in combination decreased burn-induced gut barrier dysfunction and reversed the damaging effect of albumin on gut barrier function and decreased BT.

Albumins↗
PubMed2003

Orbital hemangiopericytoma--a case report.

A 50-year-old male presented with progressive proptosis in the right eye for 10 years. Decreased visual acuity to hand-motion level was also noted. Orbital computed tomography revealed a large homogenously enhanced mass lesion in the right retrobulbar region with optic nerve compression. The remainder of the ocular examination was normal, except for right mature cataract. The tumor was completely removed through lateral orbitotomy. Histologic findings showed a picture of hemangiopericytoma. One month after cataract extraction and intraocular lens implantation in the right eye, the patient had restored vision. Through 2 years' follow-up, no more orbital tumor was noted. Orbital hemangiopericytoma may have potentially malignant behavior, and a high local recurrence rate if incompletely excised. Complete, intact removal prevents tumor recurrence and provides a good result.

Hemangiopericytoma↗
PubMed2003

Peroxynitrite is an important mediator in thermal injury-induced lung damage.

OBJECTIVE: Intestinal ischemia and reperfusion injury was known to cause postinjury multiple organ failure by neutrophil and unclear nonneutrophil factors. Peroxynitrite formed by the rapid reaction between superoxide and nitric oxide, is a toxic substance that contributes to tissue injury in a number of biological systems. In this study, the role of nitric oxide and neutrophils on lung damage after burn was investigated. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Thermal injury models in the rat. INTERVENTIONS: In experiment 1, specific pathogen-free Sprague-Dawley rats underwent 35% total body surface area burn. At 4, 8, 16, and 24 hrs after burn, intestinal mucosa and lung tissue were harvested for myeloperoxidase (MPO) assay, blood was collected for measurement of peroxynitrite-mediated oxidation of dihydrorhodamine 123, and pulmonary microvascular dysfunction was quantified by measuring the extravasation of Evans blue dye. In experiment 2, polymorphonuclear granulocyte antibody (0.12 mL/100 g administered intraperitoneally 16 hrs before burn), S-methylisothiourea (7.5 mg/kg, intraperitoneally, immediately after burn), a specific inducible nitric oxide synthase inhibitor, and sterile saline (15 mL/kg, intraperitoneally, immediately after burn) were given to different groups of thermally injured animals individually. The plasma dihydrorhodamine 123 oxidation level, intestinal and lung MPO activity, lung permeability, and lung histology were evaluated at 8 hrs after burn. The cellular localization of nitrotyrosine, a marker for peroxynitrite reactivity, was also examined by immunostaining. In experiment 3, 3-morpholinosydnonimine (10 mM, intraperitoneally), a peroxynitrite donor, was given to nonburned rats to examine the peroxynitrite effect on lung inducible nitric oxide synthase expression. MEASUREMENTS AND MAIN RESULTS: The level of MPO activity in intestine and lung, blood dihydrorhodamine 123 oxidation, and lung permeability were increased up to 2-fold, 2.5-fold, 2-fold, and 2-fold of normal, respectively, at 8 hrs after burn. S-methylisothiourea injection significantly decreased (p <.05) 31% of the lung MPO activity, 41% of the blood peroxynitrite level, 54% of the lung permeability, and the lung peroxynitrite production in burned rats. Polymorphonuclear granulocyte antibody pretreatment significantly decreased 60% of the intestinal MPO, 92% of the blood peroxynitrite level, and 56% the lung MPO activity in burned rats, but the lung permeability was only slightly decreased by polymorphonuclear granulocyte antibody pretreatment. Furthermore, 3-morpholinosydnonimine increased the lung inducible nitric oxide synthase messenger RNA levels. CONCLUSIONS: Thermal injury induces blood dihydrorhodamine 123 oxidation, intestinal and lung neutrophil deposition, lung nitrotyrosine production, and lung damage. Both specific inhibition of inducible nitric oxide synthase and polymorphonuclear granulocyte antibody pretreatment decrease blood dihydrorhodamine 123 oxidation and intestinal and lung neutrophil deposition, but only inducible nitric oxide synthase inhibition with S-methylisothiourea reduces lung peroxynitrite production and thermal injury-induced lung damage. Nitric oxide and the ensuing peroxynitrite production in lung play a more important role than neutrophil in contributing to thermal injury-induced lung damage.

Animals↗