Real-world outcomes of first- and second-generation tyrosine kinase inhibitors first-line in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer: A retrospective observational cohort study.

The sequencing of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) remains a matter of controversy. This cohort study analyzed the overall survival (OS) and progression-free survival (PFS) of afatinib compared with erlotinib and gefitinib first-line. EGFRm+, advanced NSCLC patients treated with either afatinib, erlotinib or gefitinib were retrospectively analyzed. A total of 107 patients were included. There was no statistically significant difference in PFS among the 3 groups. In the ≥ 60 years age group, the afatinib group had longer survival compared to the gefitinib group (p = 0.01). Median OS were 19.1, 22.9, and 35.6 months for gefitinib, erlotinib, and afatinib groups, respectively, with statistical significance between the gefitinib and afatinib groups (p = 0.009). Patients on afatinib also had longer median OS than erlotinib and gefitinib pooled together (35.5 versus 21.4 months; hazard ratio = 0.54, p = 0.016), despite similar median PFS. In conclusion, afatinib is a better choice compared to gefitinib or erlotinib for EGFRm+ patients. The OS obtained with afatinib is just 3 months shorter than osimertinib in the FLAURA trial. Direct comparison studies with osimertinib are still needed to determine optimal sequencing.

Cathelicidin attenuates hyperoxia-induced lung injury by inhibiting oxidative stress in newborn rats.

PURPOSE: High concentrations of oxygen administered to newborn infants with respiratory failure increases oxidant stress and leads to lung injury, characterized by decreased alveolar and capillary development. Cathelicidin belongs to an important group of human antimicrobial peptides that exhibit antioxidant activity; its overexpression reduces hyperoxia-induced oxidative stress. This study evaluated the therapeutic effects of cathelicidin in hyperoxia-induced lung injury in newborn rats. METHODS AND MATERIALS: Sprague Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O2) and then randomly treated with low-dose (4 mg/kg) and high-dose (8 mg/kg) cathelicidin in 0.05 mL of normal saline (NS) administered intraperitoneally on postnatal days 1-6. The following six groups were obtained: RA + NS, RA + low-dose cathelicidin, RA + high-dose cathelicidin, O2 + NS, O2 + low-dose cathelicidin, and O2 + high-dose cathelicidin. Lungs were harvested for Western blot and histological analyses on postnatal day 7. RESULTS: Compared with the RA-reared rats, the hyperoxia-reared rats exhibited significantly lower body weights, higher mean linear intercept (MLI), lung injury score, interleukin-6, and oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression but lower superoxide dismutase 1 (SOD1) and vascular endothelial growth factor (VEGF) protein expression and vascular density. Cathelicidin treatment attenuated hyperoxia-induced lung injury as demonstrated by lower MLI and injury score and higher VEGF expression and vascular density. CONCLUSIONS: Cathelicidin attenuated hyperoxia-induced lung injury and caused a decrease in 8-OHdG and SOD1 protein expression, most likely by inhibiting oxidative stress in the lung.

Residual heart rate variability measures can better differentiate patients with acute myocardial infarction from patients with patent coronary artery.

PURPOSE: It has been shown that the power spectral density (PSD) of heart rate variability (HRV) can be decomposed into a power-law function and a residual PSD (rPSD) with a more prominent high-frequency component than that in traditional PSD. This study investigated whether the residual HRV (rHRV) measures can better discriminate patients with acute myocardial infarction (AMI) from patients with patent coronary artery (PCA) than traditional HRV measures. MATERIALS AND METHODS: The rHRV and HRV measures of 48 patients with AMI and 69 patients with PCA were compared. RESULTS: The high-frequency power of rHRV spectrum was significantly enhanced while the low-frequency and very low-frequency powers of rHRV spectrum were significantly suppressed, as compared to their corresponding traditional HRV spectrum in both groups of patients. The normalized residual high-frequency power (nrHFP = residual high-frequency power/residual total power) was significantly greater than the corresponding normalized high-frequency power in both groups of patients. Between-groups comparison showed that the nrHFP in AMI patients was significantly smaller than that in PCA patients. Receiver operating characteristic curve analysis showed that the nrHFP or nrHFP + normalized residual very low-frequency power (residual very low-frequency power/rTP) had better discrimination capability than the corresponding HRV measures for predicting AMI. CONCLUSIONS: Compared with traditional HRV measures, the rHRV measures can slightly better differentiate AMI patients from PCA patients, especially the nrHFP or nrHFP + normalized residual very low-frequency power.

Optimizing Survival of Patients With Marginally Operable Stage IIIA Non-Small-Cell Lung Cancer Receiving Chemoradiotherapy With or Without Surgery.

BACKGROUND: For marginally operable stage IIIA non-small-cell lung cancer (NSCLC), surgery might not be done as planned after neoadjuvant concurrent chemoradiotherapy (CCRT) for reasons (unresectable or medically inoperable conditions, or patient refusal). This study aims to investigate the outcomes of a phased CCRT protocol established to maximize the operability of marginally operable stage IIIA NSCLC and to care for reassessed inoperable patients, in comparison with continuous-course definitive CCRT. MATERIALS AND METHODS: Forty-seven patients with marginally operable stage IIIA NSCLC receiving CCRT were included. Twenty-eight patients were treated with our phased CCRT protocol, including neoadjuvant CCRT followed by surgery (group A, n = 16) or, for reassessed inoperable patients, maintenance chemotherapy and split-course CCRT boost (group B, n = 12). The other 19 were treated with continuous-course definitive CCRT (group C). Overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: Among all, median OS and PFS were 35.6 and 12.8 months, respectively (median follow-up, 22.3 months). The median OS of group A (not reached) was better than that of group B (34.4 months) and group C (15.2 months) (P = .009). On multivariate analysis, performance status 0 to 1 (hazard ratio [HR], 0.026; P < .001), adenocarcinoma (HR, 0.156; P = .003), and group A (HR, 0.199; P = .033) were independent prognostic factors. The OS of group B (HR, 0.450; 95% confidence interval, 0.118-1.717; P = .243) was not statistically different from that of group C. CONCLUSIONS: For marginally operable stage IIIA NSCLC, our phased CCRT strategy may optimize survival by maximizing operability and maintain an acceptable survival for reassessed inoperable patients by split-course CCRT boost following maintenance chemotherapy.

Tumor-Like Liver Abscess Mimicking Malignancy With Lung Metastases in a Patient With Acute Renal Failure: A Case Report.

The worldwide incidence of Klebsiella pneumoniae liver abscess (KLA) is increasing. It is important to accurately diagnose this life-threatening disease to provide timely and appropriate treatment. Here we report the case of a 38-year-old man with acute renal failure and a tumor-like liver abscess and septic pulmonary embolism. Initially, his clinical symptoms, laboratory tests, and radiological findings presented equivocal results of malignancy with metastases. Fine needle aspiration of liver tumor was performed, which showed purulent material with a culture positive for K pneumoniae. KLA symptoms are atypical, and radiological findings may mimic a malignancy with tumor necrosis. In some circumstances, liver aspiration biopsy may be necessary to confirm the real etiology, leading to prompt and timely treatment. Moreover, we should be alert for the impression of KLA when facing a diabetic patient with liver mass lesion and acute renal failure.

A Case of Solitary Kidney Atrophy Due to Primary Hyperparathyroidism: A Case Report.

Although primary hyperparathyroidism (PHPT) is asymptomatic in most patients, its main clinical manifestation is nephrolithiasis. In general, hypercalcemia would lead to unilateral renal stones, which may become bilateral over time. We present a rare case of a large unilateral asymptomatic ureteral stone in a patient with hypercalcemia secondary to PHPT, which eventually led to renal atrophy.The diagnosis of PHPT should be considered in patients with hypercalcemia and renal stones, as asymptomatic PHPT may result in a devastating renal outcome.

Aerobic capacity and its correlates in patients with ankylosing spondylitis.

AIM: To evaluate aerobic capacity in patients with ankylosing spondylitis (AS) and determine possible relationships between aerobic capacity, pulmonary function, and disease-related variables. METHOD: Forty-two patients with AS and 42 healthy controls were recruited in the study. Descriptive data, disease-related variables (grip strength, lumbosacral mobility, occiput-to-wall distance, chest expansion, finger-to-floor distance, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Global Score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and hemoglobin), and chest and thoracic spine x-rays were collected in each patient with AS. All subjects took standard pulmonary function and exercise tolerance tests, and forced vital capacity (FVC) and aerobic capacity were recorded. RESULTS: Both aerobic capacity and FVC in patients with AS were significantly lower than those in normal subjects (P < 0.05). AS patients with BASFI scores of < 3 or BASDI scores of < 4 had a higher aerobic capacity. There was significant correlation between aerobic capacity, vital capacity, chest expansion, Schober's test, cervical range of motion, and BASFI in patients with AS. Neither aerobic capacity nor vital capacity correlated with disease duration, ESR, CRP, and hemoglobin. CONCLUSIONS: Significantly reduced aerobic capacity and FVC were observed in patients with AS, and there was significant correlation between aerobic capacity, vital capacity, chest expansion, and BASFI.

Neonatal Hyperoxia Exposure Induces Kidney Fibrosis in Rats.

BACKGROUND: Human and animal studies have demonstrated that neonatal hyperoxia increases oxidative stress and adversely affects glomerular and tubular maturity. This study was undertaken to determine how exposure to neonatal hyperoxia affected kidney morphology and fibrosis and to elucidate the relationship between connective tissue growth factor (CTGF) and collagen expression in rat kidneys. METHODS: Sprague-Dawley rat pups were exposed to either hyperoxia or ambient air. The control groups were maintained in ambient air for 1 week and 3 weeks. The hyperoxia groups were exposed to >95% O2 for 1 week and subsequently placed in an environment of 60% O2 for an additional 2 weeks. The animals were euthanized on Postnatal Day 7 or 21 and the kidneys underwent histological analyses and oxidative stress and total collagen measurements. RESULTS: The rats reared in O2-enriched air exhibited significantly higher tubular injury scores (1.4 ± 0.5 vs. 0.7 ± 0.7 on Day 7; 1.4 ± 0.5 vs. 0.6 ± 0.5 on Day 21), a larger proportion of the cortex occupied by glomeruli (25.5 ± 4.1 vs. 21.3 ± 3.1% on Day 7; 20.1 ± 3.5 vs. 17.1 ± 1.7% on Day 21), larger glomerular sizes (84.7 ± 5.8 vs. 77.5 ± 6.1 µm on Day 7; 88.4 ± 2.9 vs. 84.9 ± 3.1 µm on Day 21), and higher total collagen content (54.1 ± 27.5 vs. 18.3 ± 6.3 µg/mg protein on Day 7; 397.4 ± 32.8 vs. 289.5 ± 80.0 µg/mg protein on Day 21) than did rats reared in ambient air. Immunohistochemical expressions of oxidative stress marker 8-hydroxy-2'-deoxyguanosine and CTGF immunoreactivities were significantly higher in the rats reared in O2-enriched air compared with the rats reared in ambient air on Postnatal Days 7 and 21. CONCLUSION: Neonatal hyperoxia exposure contributes to kidney fibrosis, which is probably caused by activated CTGF expression.

Serum amyloid a as a predictive marker for radiation pneumonitis in lung cancer patients.

PURPOSE: To investigate serum markers associated with radiation pneumonitis (RP) grade ≥3 in patients with lung cancer who were treated with radiation therapy. METHODS AND MATERIALS: Pretreatment serum samples from patients with stage Ib-IV lung cancer who developed RP within 1 year after radiation therapy were analyzed to identify a proteome marker able to stratify patients prone to develop severe RP by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Dosimetric parameters and 3 biological factors were compared. RESULTS: Serum samples from 16 patients (28%) with severe RP (grade 3-4) and 42 patients (72%) with no or mild RP (grade 0-2) were collected for analysis. All patients received a median of 54 Gy (range, 42-70 Gy) of three-dimensional conformal radiation therapy with a mean lung dose (MLD) of 1502 cGy (range, 700-2794 cGy). An m/z peak of 11,480 Da was identified by SELDI-TOF-MS, and serum amyloid A (SAA) was the primary splitter serum marker. The receiver operating characteristic area under the curve of SAA (0.94; 95% confidence interval [CI], 0.87-1.00) was higher than those of C-reactive protein (0.83; 95% CI, 0.72-0.94), interleukin-6 (0.79; 95% CI, 0.65-0.94), and MLD (0.57; 95% CI, 0.37-0.77). The best sensitivity and specificity of combined SAA and MLD for predicting RP were 88.9% and 96.0%, respectively. CONCLUSIONS: Baseline SAA could be used as an auxiliary marker for predicting severe RP. Extreme care should be taken to limit the lung irradiation dose in patients with high SAA.

Hypofractionated radiotherapy for primary or secondary oligometastatic lung cancer using Tomotherapy.

BACKGROUND: To retrospectively review the outcome of patients with primary or secondary oligometastatic lung cancer, treated with hypofractionated Tomotherapy. METHODS: Between April 2007 and June 2011, a total of 33 patients with oligometastatic intrapulmonary lesions underwent hypofractionated radiotherapy by Tomotherapy along with appropriate systemic therapy. There were 24 primary, and 9 secondary lung cancer cases. The radiation doses ranged from 4.5 to 7.0 Gy per fraction, multiplied by 8-16 fractions. The median dose per fraction was 4.5 Gy (range, 4.5-7.0 Gy), and the median total dose was 49.5 Gy (range, 45-72 Gy). The median estimated biological effective dose at 10 Gy (BED10) was 71.8 Gy (range, 65.3-119.0 Gy), and that at 3 Gy (BED3) was 123.8 Gy (range, 112.5-233.3 Gy). The mean lung dose (MLD) was constrained mainly under 1200 cGy. The median gross tumor volume (GTV) was 27.9 cm3 (range: 2.5-178.1 cm3). RESULTS: The median follow-up period was 25.8 months (range, 3.0-60.7 months). The median overall survival (OS) time was 32.1 months for the 24 primary lung cancer patients, and >40 months for the 9 metastatic lung patients. The median survival time of the patients with extra-pulmonary disease (EPD) was 11.2 months versus >50 months (not reached) in the patients without EPD (p < 0.001). Those patients with smaller GTV (≦27.9 cm3) had a better survival than those with larger GTV (>27.9 cm3): >40 months versus 12.85 months (p = 0.047). The patients with ≦2 lesions had a median survival >40 months, whereas those with ≧3 lesions had 26 months (p = 0.065). The 2-year local control (LC) rate was 94.7%. Only 2 patients (6.1%) developed ≧grade 3 radiation pneumonitis. CONCLUSION: Using Tomotherapy in hypofractionation may be effective for selected primary or secondary lung oligometastatic diseases, without causing significant toxicities. Pulmonary oligometastasis patients without EPD had better survival outcomes than those with EPD. Moreover, GTV is more significant than lesion number in predicting survival.

Maternal nicotine effects on vascular endothelial growth factor expression and morphometry in rat lungs.

AIMS: Maternal smoking during pregnancy may impair pulmonary function in infants, and the exact mechanisms underlying these changes are unknown. We evaluated the effects of maternal nicotine exposure on lung VEGF expression and morphometry during the postnatal period in rats. METHODS AND RESULTS: Timed pregnant Sprague-Dawley rats were injected subcutaneously with nicotine at a dose of 2 mg/kg/day from Day 3 to Day 21 of gestation. A control group was injected with saline. Body weight, lung weight, and lung volume were comparable between control and nicotine-exposed rats. Plasma vascular endothelial growth factor (VEGF) levels and lung VEGF mRNA expression decreased with advancing age, and nicotine exposure insignificantly decreased plasma VEGF levels and lung VEGF mRNA expression, compared with the control rats during the study period. Nicotine exposure caused a significant decrease in vascular endothelial growth factor receptor (VEGFR)-2 mRNA expression, compared with the level of the control rats on Postnatal Day 1. On Postnatal Day 1, nicotine-exposed rats exhibited a significantly lower volume fraction of alveolar airspace and alveolar surface area and a significantly higher alveolar wall volume fraction than did the control rats. CONCLUSIONS: Maternal nicotine exposure during pregnancy decreases VEGF and VEGFR-2 mRNA expression and alters lung structure in the lungs of postnatal rats. Because angiogenesis is vital for alveolarization during normal lung development, these results suggest that decreased VEGF expression might be involved in the structural alterations of the developing lung after exposure to antenatal nicotine.

Activation of the renin-angiotensin system in hyperoxia-induced lung fibrosis in neonatal rats.

BACKGROUND: Oxygen toxicity plays an important role in lung injury and may lead to bronchopulmonary dysplasia. We previously demonstrated that hyperoxia activated the renin-angiotensin system (RAS) in cultured human fetal lung fibroblasts. OBJECTIVE: To examine whether the upregulation of RAS components is associated with hyperoxia-induced lung fibrosis in neonatal Sprague-Dawley rats. METHODS: Experimental rat pups were exposed to 1 week of >95% O(2) and a further 2 weeks of 60% O(2). Control pups were exposed to room air over the same periods. Lung tissues were taken for biochemical and histochemical assays on postnatal days 7 and 21. RESULTS: Hyperoxia significantly increased total collagen content and the expression of type I collagen and alpha smooth muscle actin when compared to control rats. RAS components including angiotensinogen, angiotensin-converting enzyme, angiotensin II, and angiotensin II type 1 receptor were significantly upregulated by hyperoxia. The results also demonstrated that only the extracellular signal-regulated kinase (ERK) signaling pathway was activated by hyperoxia exposure. p38 mitogen-activated protein kinase and c-Jun N-terminal kinase were not activated. CONCLUSIONS: Local RAS activation is involved in the pathogenesis of hyperoxia-induced lung fibrosis in neonatal rats. ERK phosphorylation might mediate angiotensin II type 1 receptor activation.

Improving Detection Accuracy of Lung Cancer Serum Proteomic Profiling via Two-Stage Training Process.

BACKGROUND: Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) is a frequently used technique for cancer biomarker research. The specificity of biomarkers detected by SELDI can be influenced by concomitant inflammation. This study aimed to increase detection accuracy using a two-stage analysis process. METHODS: Sera from 118 lung cancer patients, 72 healthy individuals, and 31 patients with inflammatory disease were randomly divided into training and testing groups by 3:2 ratio. In the training group, the traditional method of using SELDI profile analysis to directly distinguish lung cancer patients from sera was used. The two-stage analysis of distinguishing the healthy people and non-healthy patients (1st-stage) and then differentiating cancer patients from inflammatory disease patients (2nd-stage) to minimize the influence of inflammation was validated in the test group. RESULTS: In the test group, the one-stage method had 87.2% sensitivity, 37.5% specificity, and 64.4% accuracy. The two-stage method had lower sensitivity (> 70.1%) but statistically higher specificity (80%) and accuracy (74.7%). The predominantly expressed protein peak at 11480 Da was the primary splitter regardless of one- or two-stage analysis. This peak was suspected to be SAA (Serum Amyloid A) due to the similar m/z countered around this area. This hypothesis was further tested using an SAA ELISA assay. CONCLUSIONS: Inflammatory disease can severely interfere with the detection accuracy of SELDI profiles for lung cancer. Using a two-stage training process will improve the specificity and accuracy of detecting lung cancer.

Upfront gefitinib/erlotinib treatment followed by concomitant radiotherapy for advanced lung cancer: a mono-institutional experience.

BACKGROUND: Upfront tyrosine kinase inhibitor (TKI) has proved effective for selective advanced lung cancer patients in Taiwan. We hypothesized that early integration of radiotherapy during TKI treatment would decrease the chance of drug resistance and prolong progression-free survival (PFS). METHODS: This study included 25 patients with stage IIIb or IV non-squamous cell, non-small cell lung cancer (NSqCLC) who responded to upfront TKI treatment. Multi-target radiotherapy was administered during the TKI treatment course. Tomotherapy comprising a hypofractionated schedule with a dose of 40-50 Gy in 16-20 fractions was used for individual metastatic lesions. RESULTS: The patients' median follow-up duration was 30 months (range, 9-62 months). Of the 23 patients who had stage IV disease, 9 had oligometastases (≤5 gross target volumes) and 14 were in the more advanced stages of the disease. Twelve patients received more than 1 cycle of radiotherapy (median, 3; range, 2-6) with TKI being the only systemic treatment before they were salvaged with chemotherapy. The overall response rate after radiotherapy was 84.0%, and the median PFS was 16 months. The 3-year overall survival rate was 62.5% (95% confidence interval [CI], 39.1-85.8%). Toxicities were generally tolerated but it is necessary to prevent radiation-induced pneumonitis. CONCLUSION: We showed that combined first-line TKI therapy and early multi-target radiotherapy are very effective in selected patients that respond to TKI, when the status of mutations in the epidermal growth factor receptor (EGFR) are not known before the treatment. Our data may aid expansion of the effectiveness of TKI treatment through radiotherapy in Asian patients with stage IV NSqCLC.

Effects of activated protein C on ventilator-induced lung injury in rats.

BACKGROUND: Mechanical ventilation with a high tidal volume (VT) increases lung and systemic plasminogen activator inhibitor (PAI)-1 levels and alveolar fibrin deposition. Activated protein C (APC) may decrease PAI activity in endothelial cell-conditioned medium and thus enhance fibrinolysis. OBJECTIVES: The aims of this study were to test the hypothesis that APC can neutralize PAI-1 activity and improve lung function in an animal model of ventilator-induced lung injury. METHODS: Rats were ventilated with a high-volume zero positive end-expiratory pressure (PEEP; HVZP) protocol by a volume-cycled ventilator for 2 h at a VT of 30 ml/kg, a respiratory rate of 25 breaths/min, and an FiO(2) of 0.21. Fifteen minutes before ventilation, the rats received intravenous APC (250 microg/kg, HVZP+APC group) or normal saline (vehicle; HVZP group). Another group that received no ventilation served as the control group. RESULTS: Levels of arterial blood gas tension were comparable between the two ventilation groups throughout the study period. Rats treated with the HVZP protocol exhibited significantly higher total protein and macrophage inflammatory protein-2 concentrations in bronchoalveolar lavage fluid (BALF) and higher lung PAI-1 mRNA expression and plasma active PAI-1 levels than did the control group. Administration of APC tended to reduce the BALF protein content and systemic PAI-1 activity but did not improve the lung histology in the HVZP+APC group. Plasma levels of D-dimers were comparable among the three study groups. CONCLUSIONS: These results suggest that APC administered at a higher dosage might improve lung function by reducing alveolar protein leakage and systemic coagulation.

Potent suppressive effects of 3-O-methylquercetin 5,7,3',4'-O-tetraacetate on ovalbumin-induced airway hyperresponsiveness.

We investigated the suppressive effects of 3-O-methylquercetin 5,7,3',4'- O-tetraacetate (QMTA), a more-potent phosphodiesterase (PDE)3/4 inhibitor than quercetin 3-O-methyl ether (3-MQ), which has been reported to have the potential for treating asthma, against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR). The IC50 value of QMTA for PDE3 was significantly less than that for PDE4. According to the Lineweaver-Burk analysis, QMTA (1-10 microM) competitively inhibited PDE3 and PDE4 activities. The Ki values were 0.9+/-0.3 (n=5) and 3.9+/-0.5 (n=5) microM, respectively, which significantly differed from each other, suggesting that QMTA has higher affinity for PDE3 than for PDE4. QMTA (3-10 microM) concentration-dependently relaxed the baseline level, and significantly inhibited cumulative OVA (10-100 microg/mL)-induced contractions in isolated sensitized guinea pig trachealis suggesting that QMTA has bronchodilator and inhibiting effects on mast cell degranulation. After the secondary challenge, the AHR was measured in unrestrained OVA-sensitized mice, with nebulized methacholine (MCh, 6.25-50 mg/mL), by barometric plethysmography using a whole-body plethysmograph. In the present results, QMTA (3-10 micromol/kg, I. P.) dose-dependently attenuated the enhanced pause (Penh) value induced by MCh (25-50 mg/mL). QMTA (3-10 micromol/kg, I. P.) also significantly inhibited total inflammatory cells, macrophages, neutrophils, lymphocytes, and eosinophils in BALF after determination of Penh values. It also significantly suppressed the release of interleukin (IL)-2, IL-4, IL-5, IFN-gamma, and TNF-alpha, with the exception that 3 micromol/kg QMTA did not suppress the releases of IL-5. QMTA even at 1 micromol/kg significantly inhibited eosinophils, IL-2, and TNF-alpha. In conclusion, our results strongly suggest that QMTA has greater potential than 3-MQ for the treatment of asthma.

Angiotensin-converting enzyme inhibitor captopril attenuates ventilator-induced lung injury in rats.

We hypothesized that lung inflammation and parenchymal apoptosis in ventilator-induced lung injury (VILI) are related to ANG II and assessed the ability of the angiotensin-converting enzyme inhibitor captopril to attenuate VILI in rats. Adult male Sprague-Dawley rats were randomized to receive two ventilation strategies for 2 h: 1) tidal volume of 40 ml/kg, respiratory rate of 25 breaths/min, and inspiratory O2 fraction of 0.21 [high-volume, 0 positive end-expiratory pressure (HVZP) group] and 2) injection of captopril (100 mg/kg ip) 30 min before HVZP ventilation (HVZP+CAP group). Another group, which did not receive ventilation, served as the control. Mean arterial pressure was significantly lower in the HVZP+CAP group than in the HVZP group at 2 h of ventilation. Total protein levels were significantly higher in bronchoalveolar lavage fluid (BALF) recovered from HVZP-ventilated rats than from controls. BALF macrophage inflammatory protein-2 and lung ANG II were significantly higher in the HVZP group than in the control and HVZP+CAP groups. Lung ANG II levels correlated positively with BALF protein and macrophage inflammatory protein-2. The number of apoptotic airway and alveolar wall cells was significantly higher in the HVZP and HVZP+CAP groups than in the control group and significantly lower in the HVZP+CAP group than in the HVZP group. These results suggest that the efficiency of captopril to attenuate VILI is related to reduction of inflammatory cytokines and inhibition of apoptosis and indicate that VILI is partly mediated by the local angiotensin system.

Cytologic diagnosis of a metastatic oligodendroglioma in a pleural effusion. A case report.

BACKGROUND: Extraneural metastasis of oligodendroglioma is extremely rare and is diagnosed primarily by biopsy or autopsy and very occasionally by fine needle cytologic examination. We report a case of metastatic oligodendroglioma diagnosed by cytologic examination of a pleural effusion. Such a diagnosis has not been reported before. CASE: A 64-year-old woman developed anemia and bilateral pleural effusion 7 years after an operation for an oligodendroglioma over the left frontal lobe. Cytologic examination of the pleural effusion showed aggregates of atypical polygonal cells containing round, hyperchromatic nuclei and scanty, granular cytoplasm in Liu's and Papanicolaou stain and cell blocks. Immunohistochemical staining of the tumor cells revealed a positive reaction for antibodies to glial fibrillary acidic protein, S-100 and Olig2. Pleural biopsy confirmed the cytologic diagnosis of pleural effusion. A pathologic fracture of the right humeral and femoral bones was noted 1 month later, and the specimen also showed infiltrating oligodendroglioma cells in bone tissue. CONCLUSION: To the best of our knowledge, this is the first metastatic oligodendroglioma diagnosed by pleural cytology. Fine needle cytology can provide a reliable and rapid way to detect an extracranial metastatic oligodendroglioma in different organs.

Mechanisms of suppression of nitric oxide production by 3-O-methylquercetin in RAW 264.7 cells.

Rhamnus nakaharai Hayata (Rhamnaceae) is used as a folk medicine in Taiwan for treating constipation, inflammation, tumors, and asthma. 3-O-Methylquercetin (3-MQ), a main constituent of the plant, has been reported to have potential for use in the treatment of asthma. The mechanisms of anti-inflammation of 3-MQ are still unclear. Nitric oxide (NO) production induced by lipopolysaccharide (LPS) through iNOS expression in RAW 264.7 cells, a mouse macrophage cell line, may reflect the degree of inflammation and may provide a measure for assessing the effect of drugs on the inflammatory process. Therefore, we were interested in investigating the mechanisms of suppression of NO production by 3-MQ in RAW 264.7 cells. 3-MQ (1-10 microM) concentration-dependently inhibited LPS (100 ng/mL)-induced NO production in RAW 264.7 cells. The IC(50) value was calculated to be 4.23 microM. 3-MQ (1-10 microM) significantly and concentration-dependently inhibited LPS (100 ng/mL)-induced iNOS protein and mRNA expressions in cells. The IC(50) values were calculated to be 4.36 and 6.53 microM, respectively. There was no significant difference among these three IC(50) values of 3-MQ. In conclusion, 3-MQ may exert its anti-inflammatory effect through the inhibition of iNOS DNA transcription.