A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia.

BACKGROUND/PURPOSE: To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial. METHODS: One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7-10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS). RESULTS: The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred. CONCLUSION: Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250.

[Effects of methylprednisolone plus Xuebijing on bleomycin-induced acute exacerbation of pulmonary fibrosis in rats].

OBJECTIVE: To explore the effect of Xuebijing plus methylprednisolone in a rat model of pulmonary fibrosis induced by bleomycin. METHODS: Eighty Wistar rats were randomly divided into 5 groups of control, model control, Xuebijing, methylprednisolone and combined treatment (Xuebijing plus methylprednisolone). Pulmonary fibrosis model was induced by an intra-tracheal injection of bleomycin. The treatment groups were administrated with 4.5 ml · kg(-1) · d(-1) Xuebijing and 4.5 ml · kg(-1) · d(-1) physiologic saline, 4.5 ml · kg(-1) · d(-1) methylprednisolone and 4.5 ml · kg(-1) · d(-1) physiologic saline, or 4.5 ml · kg(-1) · d(-1) methylprednisolone and 4.5 ml · kg(-1) · d(-1) Xuebijing respectively by intraperitoneal injection. And the control and model control groups received 9 ml · kg(-1) · d(-1) physiological saline. The animals were sacrificed at Days 14 and 28 respectively. The degrees of lung inflammation and pulmonary fibrosis were detected by hematoxylin & eosin and Masson staining. The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of transforming growth factor-ß1 (TGF-ß1) in lung tissue was evaluated by immunohistochemical staining. RESULTS: Compared between the combined treatment and model control groups, at Days 14 and 28, the degree of alveolitis ((1.09 ± 0.30) vs (2.03 ± 0.25) and (0.75 ± 0.27) vs (1.78 ± 0.36) ng/L) , the degree of pulmonary fibrosis ((0.91 ± 0.19 )vs (1.34 ± 0.23) and (0.75 ± 0.27) vs (1.78 ± 0.36)) . The expression of TGF-ß1 in lung tissue ((12.11 ± 3.06)% vs (17.70 ± 2.70)% & (10.96 ± 2.53)% vs (16.72 ± 2.20)%). And the serum level of TNF-α ((68.39 ± 9.28) vs (90.94 ± 11.16) ng/L & (67.14 ± 10.88) vs (81.73 ± 7.23) ng/L) all significantly decreased (all P < 0.05). At Day 14, the serum level of IL-6 in the combined treatment group significantly decreased as compared with the model control group ((199 ± 31) vs (250 ± 43)ng/L, P = 0.036). At Day 28, no statistic difference was found ( (192 ± 25) vs (227 ± 24)ng/L, P = 0.058). CONCLUSIONS: The combined treatment of methylprednisolone and Xuebijing is more effective in a rat model of pulmonary fibrosis. And its mechanism is associated with the reduced levels of IL-6 and TNF-α and TGF-ß1 expression in lung tissue.

[The mechanism of airway inflammation in eosinophilic bronchitis and cough variant asthma].

OBJECTIVE: To explore the characteristics of airway inflammatory cells, cytokines and inflammatory mediators in eosinophilic bronchitis (EB) and cough variant asthma (CVA) patients and to elucidate the underlying mechanism of distinct airway inflammation between EB and CVA. METHODS: This study included 15 patients with EB (EB group), 15 patients with cough variant asthma (CVA, CVA group), 14 patients with bronchial asthma (asthma group) and 14 healthy controls (healthy group). Percentage of eosinophils (EOS) in sputum induced by hypertonic saline was detected by FACS. The percentage of CD(69)(+) EOS stimulated by interleukin-5 (IL-5) and interferon γ (IFN-γ) was also detected by FACS. The expression of leukotriene C4 synthase (LTC4S) and prostaglandin-endoperoxide synthase-2 (PTGS2) mRNA in sputum was measured by real-time PCR and the concentration of leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) in sputum was measured by ELISA. RESULTS: The percentage of EOS in induced sputum was 15.8 ± 3.2 (EB group), 13.0 ± 2.7 (CVA group) and 11.6 ± 4.5 (asthma group), respectively, which were significantly higher than 1.0 ± 0.4 in the healthy group. The difference was significant and the t value was 16.31, 15.23 and 14.21 respectively (P < 0.05). After stimulated by IL-5 and IFN-γ, the percentage of CD(69)(+) EOS in induced sputum was 1.5 ± 0.4 and 1.5 ± 0.5 (EB group), 1.4 ± 0.4 and 1.4 ± 0.3 (CVA group) and 1.42 ± 0.72 and 1.37 ± 0.46 (asthma group) respectively. There was no statistical significance between these 3 groups, but when compared with 0.4 ± 0.2 and 0.4 ± 0.1 in healthy group, the difference was significant (P < 0.05). The expression of IL-5 mRNA and protein in induced sputum of EB group, CVA group and asthma group were higher than the healthy group and the difference was all statistically different (P < 0.05), but there was no statistical significance between EB group, CVA group and asthma group. The expression of IFN-γ mRNA and protein in induced sputum of each group was not different when compared with healthy group (P > 0.05). The concentration of PGE2 in induced sputum of EB group was(839 ± 69) ng/L, which was higher than (33 ± 8) ng/L of CVA group, (25 ± 6) ng/L of asthma group and (24 ± 8) ng/L of healthy group (all P < 0.01). There was no statistical difference between CVA group, asthma group and healthy group. The expression of PTGS2 in induced sputum of EB group increased significantly; when compared with CVA group, asthma group and healthy group, the difference was significant (all P < 0.01). The concentration of LTC4 in induced sputum of EB group, CVA group and asthma group was all higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA of EB group, CVA group and asthma group was also higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA and LTC4 in the EB group was higher than that in the CVA group and the asthma group (P < 0.05). The value of LTC4/PGE2 in the CVA group and the asthma group was higher than that in the EB group (t = 8.7 and 13.1, P < 0.05). CONCLUSION: These data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and CVA (or asthma) may be due to the results of differences in PGE(2) production and an imbalance between the production of bronchoconstrictor LTC(4) and bronchoprotective PGE(2) lipid mediators.

Ku80 is differentially expressed in human lung carcinomas and upregulated in response to irradiation in mice.

Based on the role of Ku80 in mediating radiation-induced DNA repair, we investigated Ku80 expression in human lung cancers of different pathological types and evaluated the effect of radiotherapy on Ku80 expression levels in a mouse model. We used immunohistochemistry and real-time PCR to determine Ku80 protein and mRNA levels, respectively. We inoculated nude mice with A549 cells and subjected the tumor-bearing mice to varying doses of irradiation. Lung carcinoma tissue exhibited higher Ku80 mRNA and protein levels when compared with normal tissue. Among the tumor subtypes, lung adenocarcinoma and lung squamous carcinoma showed higher levels of Ku80 protein and mRNA, compared with small-cell lung carcinoma. There was a dose-dependent and time-dependent increase in Ku80 mRNA levels in nude mice that were inoculated with A549 cells and exposed to varying doses of irradiation. Ku80 may play an important role in the DNA damage response pathway. Higher Ku80 levels in lung squamous carcinoma and adenocarcinoma may explain their lower radiosensitivity when compared with small-cell lung carcinoma. Ku80 expression levels could be useful in predicting radiosensitivity of lung tumors and inhibition of Ku80 may be an interesting target to improve radiosensitivity in lung cancer patients.

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.

[Expression of aquaporins and its significance in human pulmonary adenocarcinoma cell line SPC-A-1].

BACKGROUND: To investigate the expression of aquaporins in human pulmonary adenocarcinoma cell line SPC-A-1. METHODS: The expressions of aquaporin 1, aquaporin 3, aquaporin 4, and aquaporin 5 in mRNA level and their locations were determined in cell line SPC-A-1 respectively by RT-PCR and immunohistochemistry. RESULTS: The immunohistochemical stain showed aquaporin 3 and aquaporin 5 located on the membrane of SPC-A-1 cell, but no positive stain of aquaporin 1 and aquaporin 4 was observed. Both aquaporin 3 and aquaporin 5 mRNA expressed in SPC-A-1 cell line, and the expression level of aquaporin 5 mRNA was significantly higher than that of aquaporin 3 mRNA ( P < 0.01). Aquaporin 1 and aquaporin 4 mRNA did not express in SPC-A-1 cell line. CONCLUSIONS: Aquaporin 3 and aquaporin 5 express in SPC-A-1 cell, and their roles in water transport of SPC-A-1 cell should be further investigated.