Intravenous superoxide dismutase administration reduces contralateral lung injury induced by unilateral lung ischemia and reperfusion in rats through suppression of activity and protein expression of matrix metalloproteases.

BACKGROUND: Ischemia and reperfusion (I/R) of the lungs induces massive superoxide radical production. On the other hand, matrix metalloproteases (MMPs) were shown to play an essential role in I/R-associated lung injury. We aimed to investigate the lung-protective efficacy of intravenous superoxide dismutase (SOD) administration and its relation with MMPs activity in the lungs subsequent to I/R injury. METHODS: Twenty-two male Sprague-Dawley rats were divided into a sham group (n = 6), a unilateral lung I/R group (n = 8), and a SOD-treated lung I/R group (n = 8). Unilateral lung ischemia was conducted by occluding the left lung hilum for 90 min, followed by 5 hours of reperfusion through release of the occlusion. In the SOD-treated group, SOD was administered intravenously during the first hour of reperfusion. We assessed the protein contents in the broncho-alveolar lavage fluid (PCBAL) as a marker for protein permeability and lung wet-to-dry weight ratio (W/D) for lung water content. We also measured levels of lipid peroxidation and MMP activity in the lungs, by tissue malonedealdehyde (MDA) level with the use of enzyme-linked immunoassay, and the gelatin zymography technique, respectively. RESULTS: Forty-eight hours of left-lung I/R significantly increased PCBAL (P < .001), W/D (P < .05), tissue MDA level (P < .05), and MMP-9 and MMP-2 activity. SOD treatment attenuated I/R-induced contralateral lung injury, reducing pulmonary permeability, lipid peroxidation, and MMP activities. CONCLUSIONS: I/R injury of the left lung induced increases in W/D, PCBAL, MDA level, and MMP-9 activity in the right lung. SOD treatment during the first hour of a 5-hour reperfusion protected the lung through suppressing MMP-9 activity and reducing tissue lipid peroxidation.

Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

BACKGROUND: Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. METHODS: Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. RESULTS: Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. CONCLUSIONS: Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils.

Resveratrol alleviates lung ischemia and reperfusion-induced pulmonary capillary injury through modulating pulmonary mitochondrial metabolism.

OBJECTIVE: Lung ischemia and reperfusion (I/R) injury is one of the major causes of postoperative pulmonary dysfunction after cardiopulmonary surgery and thoracic organ transplantation. Recent studies suggest that lung I/R injury may be associated with defects in pulmonary mitochondrial function, in addition to damage from reactive oxygen species. In this study, we examined effects of one lung I/R injury on the other lung, and the protective efficacy of resveratrol on mitochondrial biogenesis in lungs. METHODS: Studies were performed in male Sprague-Dawley rats in 3 groups: sham-operated, lung I/R injury, and treated with resveratrol before lung I/R injury (20 mg/kg/d, orally). Lung ischemia was established by occluding the lung left hilum for 60 minutes, followed by releasing the occlusion and closing the chest. Four days after ischemia, we assessed the lung water content and protein concentration in lung lavage of the nonischemic lung; lung inflammation and pulmonary oxidative stress were assessed by leukocyte counts and tissue content of malondialdehyde (MDA), respectively. The level of mitochondrial biogenesis was determined according to PGC1-α mRNA expression. RESULTS: The left lung I/R injury significantly suppressed right lung PGC1-α mRNA expression, increasing pulmonary oxidative stress, lung water content, and lavage leukocyte count and protein concentration (P < .05). Resveratrol treatment attenuated lung injury as well as increasing PGC1-α mRNA expression. CONCLUSIONS: Resveratrol treatment protects lung against I/R injury through improving mitochondrial biogenesis and reducing oxidative stress and leukocyte infiltration.

Effects of the antioxidants lycium barbarum and ascorbic acid on reperfusion liver injury in rats.

OBJECTIVE: Ischemia/reperfusion (I/R) of the rat liver can induce liver injury through mechanisms involving oxidative and nitrosative stresses. In this study we examined the effects of antioxidants Lycium barbarum (LB) and ascorbic acid on I/R-induced liver injury in rats. METHODS: Liver ischemia was induced by clamping the common hepatic artery and portal vein of rats for 40 minutes. Thereafter, flow was restored with reperfusion for 90 minutes. Blood samples collected before ischemia and after reperfusion were analyzed for alanine transaminase (ALT), lactic dehydrogenase (LDH), hydroxyl radical, and nitric oxide (NO) levels. Pharmacologic interventions included administration of ascorbic acid (100 mg/kg, i.p., 1 hour before I/R) or LB, an extract of Gogi berries: 600 mg in 100 mL of drinking water for 2 weeks prior to experimentation. RESULTS: This protocol resulted in elevation of blood concentrations of NO, hydroxyl radical, ALT, and LDH (P < .001) in the I/R-induced liver injury group. Ascorbic acid significantly attenuated the reperfusion liver injury by attenuating hydroxyl radical (P < .01) and NO (P < .05) release. The LB aggravated I/R-induced liver injury by increasing hydroxyl radical release with no effect on NO release. DISCUSSION AND CONCLUSIONS: This I/R protocol resulted in oxidative and nitrosative stress and liver injury. Ascorbic acid showed significant protective effects on reperfusion liver injury by attenuating hydroxyl radical and NO release. In contrast, LB aggravated liver injury by increasing hydroxyl radical release.

Matrix metalloprotease expressions in both reperfusion lung injury and oleic acid lung injury models and the protective effects of ilomastat.

OBJECTIVE: Our aim was to study the expressions of matrix metalloprotease 9 (MMP9) and the effects of the MMP inhibitor Ilomastat in both ischemia/reperfusion (I/R)- and oleic acid (OA)-induced lung injury models. MATERIALS AND METHODS: Real-time polymerase chain reactions and Western blots were used to assess mRNA and protein expressions of MMP9 in lung tissues after I/R or OA lung injury. Ischemia was induced by clamping one branch of the pulmonary artery for 60 minutes and then reperfusing for 120 minutes. In the OA model, lung injury was induced by intravenous infusion of OA (0.1 mL/kg) for 20 minutes and then observation for 6 hours. Lavage leukocyte concentration and wet/dry lung weight ratio were used to assess lung inflammation and injury. Blood samples were collected for assays of hydroxyl radicals and nitric oxide. The MMP inhibitor Ilomastat (100 microg/kg) was administered before I/R and OA infusion. RESULTS: mRNA and protein expressions of MMP9 were significantly increased in both lung injury models. Ilomastat decreased MMP9 mRNA and protein expressions but did not reach statistical significance. Blood concentrations of hydroxyl radicals and nitric oxide, wet/dry lung weight ratios, and lavage leukocyte concentrations were significantly higher in both experimental groups compared with the sham group (P < .001). Ilomastat significantly attenuated the extent of lung inflammation and injury induced by both I/R and OA. CONCLUSION: MMP may play a critical role in the lung injury induced by I/R and OA infusion.

Diagnosis of pyogenic liver abscess by abdominal ultrasonography in the emergency department.

BACKGROUND: Delayed diagnosis of pyogenic liver abscess remains a challenging problem in the emergency department because of the associated high morbidity and mortality. OBJECTIVE: To evaluate the sensitivity of ultrasono-graphy in the diagnosis of pyogenic liver abscess in patients presenting to the emergency department and the factors that may influence this sensitivity. METHODS: A retrospective study was conducted in patients diagnosed with pyogenic liver abscess in the emergency department (ED) of a tertiary care teaching hospital for a period of 5 years. Between May 2001 and April 2006, 268 patients diagnosed with pyogenic liver abscess were evaluated by ultrasonography and/or CT scanning. The age, sex, clinical presentation, location and number of abscesses and the underlying disease of these two groups were compared. RESULTS: Of the 268 patients admitted via the ED who were discharged or died with a diagnosis of pyogenic liver abscess, there was a predominance of men (M/F 173/95) and the mean age was 57.6 years (range 17-90). 38 had false negative findings on ultrasonography (sensitivity 85.8%) and required abdominal CT scanning for definitive diagnosis. In the other 230 cases, ultrasonography alone was sufficient for diagnosis. Location of the abscess in segments 4 and 5 of the liver raised the sensitivity of ultrasound for diagnosis, while location in segment 8 was most associated with delayed diagnosis by ultrasonography. Right costal angle knocking pain was significant for pyogenic liver abscess even if ultrasound was negative. CONCLUSIONS: The size and location of the liver abscess and the underlying comorbid diseases may affect the diagnostic sensitivity of ultrasound for pyogenic liver abscess in clinical practice. A high index of suspicion should be maintained in patients with diabetes mellitus, previous biliary tract intervention or gastrointestinal malignancy. Follow-up CT scanning is recommended if right flank knocking pain is present, even if ultrasonography is non-revealing. A diagnostic protocol for liver abscess may be feasible in the future.

Inducible nitric oxide synthase expressions in different lung injury models and the protective effect of aminoguanidine.

OBJECTIVE: Our aim was to study the expression of inducible nitric oxide synthase (iNOS) in 2 experimental models: (1) ischemia/reperfusion (I/R) of the lung tissues and (2) oleic acid infusion. The protective effect of an iNOS inhibitor, aminoguanidine, was evaluated in these 2 injury models. MATERIALS AND METHODS: Real-time polymerase chain reactions and Western blots were used to assess the mRNA and protein expressions of iNOS in lung tissues after applying 2 injury models. In the I/R model, ischemia was induced by clamping one branch of the pulmonary artery for 60 minutes and then reperfusing for 120 minutes. In the bone fracture model, lung injury was induced by intravenous (IV) infusion of oleic acid (0.1 mL/kg); analysis was performed 6 hours after injury. Blood samples were collected for the assay of 3 inflammatory parameters: tumor necrosis factor alpha, hydroxyl radicals, and nitric oxide (NO). The wet/dry lung weight ratio was used as a parameter reflecting the lung injury level. RESULTS: mRNA and protein expressions of iNOS were significantly increased in these 2 lung injury models compared with the controls. Blood concentrations of TNFalpha, hydroxyl radicals, NO, and wet/dry lung weight ratio were also significantly higher in the 2 experimental groups than in the sham-treated group. The iNOS inhibitor aminoguanidine (20 mg/kg) significantly attenuated the lung injury induced by these challenges. CONCLUSIONS: Reperfusion of the ischemic lung tissues or IV infusion of oleic acid can both induce lung injury by activating systemic inflammatory responses and inducing iNOS expression. Administration of aminoguanidine can significantly attenuate the injury, suggesting that iNOS expression may play a critical role in the lung injury induced in these 2 models.

Severe acute respiratory syndrome in Taiwan: analysis of epidemiological characteristics in 29 cases.

OBJECTIVES: To describe the clinical characteristics and outcomes of patients with severe acute respiratory syndrome (SARS). METHODS: Between March 28 and June 30 '2003, 29 patients with probable SARS seen at Shin Kong Wu Ho-Su Memorial Hospital, Taipei, were analysed. RESULTS: Presenting symptoms included fever (100%), cough (69.0%), chills or rigor (62.1%), and shortness of breath (41.4%). Mean days to defervescence were 6.8+/-2.9 days, but fever recurred in 15 patients (51.7%) at 10.9+/-3.4 days. Common laboratory features included lymphopenia (72.4%), thrombocytopenia (34.5%) and elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) (93.1, 62.1, 44.8%, respectively). All patients except one had initial abnormal chest radiographs and 20 (69.0%) had radiological worsening at 7.5+/-2.6 days. Nine patients (31.0%) subsequently required mechanical ventilation with four deaths (13.8%). Most patients with clinical deterioration responded to pulse corticosteroid therapy (14 out of 17) but six complicated with nosocomial infections. The risk factors associated with severe disease were presence of diarrhoea, high peak LDH and CRP, high AST and creatine kinase on admission and high peak values. CONCLUSIONS: Prudent corticosteroid use, vigilant microbiological surveillance and appropriate antibiotics coverage are the key to successful treatment.

In vitro insulin-like growth factor-I, growth hormone, and insulin resistance occurs in symptomatic human immunodeficiency virus-1-infected children.

Poor growth is a common feature of symptomatic children (Centers for Disease Control stage P2) infected with human immunodeficiency virus-1 (HIV-1). However, several previous studies have failed to show any relationship between serum hormone levels and poor growth. To assess the roles of hormone deficiency and hormone resistance in the development of poor growth in HIV-1-infected children, we studied six asymptomatic Centers for Disease Control stage P1 [height SD score = 0.01 +/- 1.0 (mean +/- SD)], 10 P2 (height SD score = -2.0 +/- 1.0), and six short, normal children (height SD score = -2.4 +/- 1.2). Mean weight:height SD scores were similar in all three groups, suggesting that gross nutritional status did not differ between groups. There were no significant differences between groups with respect to mean plasma levels of IGF-I, thyroid hormones, TSH, and cortisol. As an index of hormone sensitivity, we quantified in vitro colony formation of erythroid progenitor cells, isolated from peripheral blood of study subjects, in response to IGF-I, growth hormone (GH), and insulin. P2 subjects had a quantitative mean reduction in erythroid progenitor cells colony formation in response to IGF-I of 32% compared with P1 subjects (p = 0.001 by analysis of variance) and 21% compared with controls (p = 0.006); in response to GH of 21% compared with controls (p = 0.015); and in response to insulin of 35% compared with P1 subjects (p = 0.038) and 34% compared with controls (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)