Synthesis of novel 3/5(3,5)-(di)nitropaeonol hydrazone derivatives as nematicidal agents.

Eighteen novel 3/5(3,5)-(di)nitropaeonol hydrazone derivatives were prepared, and their structures well characterized by 1H NMR, HRMS, and mp. Due to the steric hindrance, the substituents on the C = N double bond of all hydrazine compounds (except E/Z = 4/1 for IV-1g, IV-1l, IV-2b, and E/Z = 3/2 for IV-1n, IV-3a) adopted E configuration. Among all compounds, four compounds 2, 4, IV-1j, and IV-1n exhibited potent nematicidal activity than their precursor paeonol, especially 5-nitropaeonol (2) and 3,5-dinitropaeonol (4) displayed the most potent nematicidal activity Heterodera glycines in vivo with LC50 values of 32.3307 and 36.7074 mg/L, respectively.

Synthesis of novel 9R/S-acyloxy derivatives of cinchonidine and cinchonine as insecticidal agents.

Endeavor to discover biorational natural products-based insecticides, two series (27) of novel 9R/S-acyloxy derivatives of cinchonidine and cinchonine were prepared and assessed for their insecticidal activity against Mythimna separata in vivo by the leaf-dipping method at 1 mg/mL. Among all the compounds, especially derivatives 6l and 6o exhibited the best insecticidal activity with final mortality rates of 75.0% and 71.4%, respectively. Overall, a free 9-hydroxyl group is not a prerequisite for insecticidal activity and C9-substitution is well tolerated; the configuration of C8/9 position is important for insecticidal activity, and 9S-configuration is optimal; 6'-OCH3 moiety is not necessary, removal of it is also acceptable. [Formula: see text].

Synthesis, anti-oomycete activity, and SAR studies of paeonol derivatives.

Three series of sulfonate derivatives of paeonol were synthesized and screened in vitro for their anti-oomycete activity against P. capsici, respectively. Among all the compounds, 4m displayed the best promising and pronounced anti-oomycete activity against P. capsici than zoxamide, with the EC50 values of 24.51 and 26.87 mg/L, respectively. The results show that acetyl and 4-OCH3 are two necessary groups. The existence of these two sites is closely related to the anti-oomycete activity. Relatively speaking, hydroxyl group is well tolerated, and the results showed that after modification of hydroxyl group with sulfonyl, the anti-oomycete activity was significantly increased. [Formula: see text].

Synthesis of sulfonate derivatives of carvacrol and thymol as anti-oomycetes agents.

Two series of sulfonate derivatives of carvacrol and thymol were synthesized and screened in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of 32 derivatives, five compounds 3a, 4a, 4k, 3n, and 4n exhibited more potent anti-oomycete activity against P. capsici with EC50 values of 66.66, 62.94, 68.65, 61.24, and 52.91 mg/L, respectively. This suggested that introduction of different substitutions at the hydroxyl position of 1/2 could have remarkable effect on anti-oomycete activity. Overall, when R1 = isopropyl and R2 = methyl, the anti-oomycete activities of the compounds were higher than that of the corresponding compounds of R1 = methyl and R2 = isopropyl.[Formula: see text].

Combinatorial Synthesis of A Series of Paeonol-based Phenylsulfonyl hydrazone Derivatives as Insecticidal Agents.

BACKGROUND: Plant secondary metabolites play an essential role in the discovery of novel insecticide due to their unique sources and potential target sites. Paeonol, the main phenolic components in Moutan Cortex, is recognized as a safe and potent botanical insecticide to many insects. The structural modification of paeonol in this study into phenylsulfonylhydrazone derivatives is proved an effective approach for the development of novel insecticides, those derivatives being more toxic than paeonol. However, there have been no reports on the insecticidal activity of paeonol-based phenylsulfonylhydrazone derivatives in controlling Mythimna separata. METHODS: We have been working to discover biorational natural products-based insecticides. Twelve novel paeonol-based phenylsulfonylhydrazone derivatives have been successfully prepared by structural modification of paeonol, and the insecticidal activity against M. separata by the leafdipping method at the concentration of 1 mg/mL has been evaluated. RESULTS: Insecticidal activity revealed that out of 12 title compounds, derivatives 5c and 5f displayed the best against M. separate with the FMR both of 53.6% than toosendanin (FMR = 50.0%). CONCLUSION: The results suggested that for the paeonol-based phenylsulfonylhydrazone series derivatives, the proper substituent of arylsulfonyl R at the hydroxyl position of paeonol was very important for their insecticidal activity. These preliminary results will pave the way for further modification of paeonol in the development of potential new insecticides.

Synthesis of sulfonate derivatives of maltol and their biological activity against Phytophthora capsici and Bursaphelenchus xylophilus in vitro.

Sixteen sulfonate derivatives of maltol were synthesized and screened in vitro for their anti-oomycete and nematicidal activity against Phytophthora capsici and Bursaphelenchus xylophilus, respectively. Among all the compounds, 3e, 3m, and 3p exhibited the most promising and pronounced anti-oomycete activity against P. capsici than zoxamide, and the EC50 values of 25.42, 18.44, 23.69, and 27.99 mg/L, respectively; compounds 3e, 3m, 3n, and 3p exhibited potent nematicidal activity with LC50 values ranging from 1 to 2 mg/L, especially 3m and 3n showed the best promising and pronounced nematicidal activity, with LC50 values of 1.1762 and 1.2384 mg/L, respectively. [Formula: see text].

Synthesis and insecticidal activity of sulfonate derivatives of sesamol against Mythimna separata in vivo.

A series of sulfonate derivatives of sesamol were synthesized and evaluated for their insecticidal activity against a crop-threatening agricultural pest, the pre-third-instar larvae of Mythimna separata in vivo. Among all the target compounds, compounds 3b, 3g, 3h, and 3p exhibited more promising insecticidal activity than sesamol and toosendanin, and the final mortality rates (FMRs) of 3b, 3g, 3h, 3p, 1, and toosendanin were 60.7%/60.7%/67.9%/53.6%/32.1%/50.0%, respectively. Especially compound 3h exhibited the most potent insecticidal activity with FMRs of 67.9%. This suggested that a 4-fluorophenylsulfonyl group introduced at the hydroxyl position of sesamol was necessary for obtaining the most potent compound.[Formula: see text].

Controlled synthesis of N, N-dimethylarylsulfonamide derivatives as nematicidal agents.

Gramine can be intelligently and efficiently supplied with N, N-dimethylamino group and then reacted with the corresponding sulfonyl chlorides to synthesize N, N-dimethylarylsulfonamides. We herein designed and controlled synthesis of N, N-dimethylarylsulfonamide derivatives, and first reported the results of the nematicidal activity of 15 title compounds 3a-o against Meloidogyne incongnita in vitro, respectively. Among all of the title derivatives, compounds 3a, 3c, 3k, and 3o exhibited potent nematicidal activity with median lethal concentration (LC50) values ranging from 0.22 to 0.26 mg/L. Most noteworthy, N, N-dimethyl-4-methoxyphenylsulfonamide (3c) and N, N-dimethyl-8-quinolinesulfonamide (3o) showed the best promising and pronounced nematicidal activity, with LC50 values of 0.2381 and 0.2259 mg/L, respectively.

Stereoselective synthesis of 4ß-acyloxypodophyllotoxin derivatives as insecticidal agents.

As our ongoing work on research of natural-product-based insecticidal agents, some 4α/ß-acyloxypodophyllotoxin derivatives were synthesized, and were evaluated against the pre-third-instar larvae of B. mori, A. dissimilis and M. separate in vivo at the concentration of 1 mg ml-1, respectively. Among all derivatives, compounds 2 g, h and 4c, d showed more promising insecticidal activities than their precursors - podophyllotoxin and epipodophyllotoxin. Furthermore, derivatives 2 g, h and 4c, d exhibited more relative amicable activities than their precursors - podophyllotoxin and epipodophyllotoxin. This results indicated that 4ß-acyloxy moiety in the podophyllotoxin derivatives was significant for obtaining the more potent compounds.

Krüppel-like factor 17 inhibits urokinase plasminogen activator gene expression to suppress cell invasion through the Src/p38/ MAPK signaling pathway in human lung adenocarcionma.

Krüppel-like factor 17 (KLF17) has been reported to be involved in invasion and metastasis suppression in lung cancer, but the molecular mechanisms underlying the anti-invasion and anti-metastasis roles of KLF17 in lung cancer are not fully illustrated. Here, we showed that KLF17 inhibited the invasion of A549 and H322 cells; the anti-invasion effect of KLF17 was associated with the suppression of urokinase plasminogen activator (uPA/PLAU) expression. KLF17 can bind with the promoter of uPA and inhibit its expression. Enforced expression of uPA abrogated the anti-invasion effect of KLF17 in A549 and H322 cells. In addition, immunohistochemistry staining showed that the protein expression of KLF17 was negatively correlated with that of uPA in archived samples from patients with lymph node metastasis of lung adenocarcinoma (rho = -0.62, P = 0.01). The mutually exclusive expression of KLF17 with uPA could predict lymph node metastasis for lung adenocarcinoma (AUC = 0.758, P = 0.005). Enforced expression of KLF17 inhibited the expression of phosphorylated Src and phosphorylated p38/MAPK in A549 and H322 cells. The invasiveness of the cells were suppressed by treating with sb203580 (p38/MAPK inhibitor) or HY-13805 (PP2, Src inhibitor). furthermore, p38/MAPK inhibition could block the KLF17-induced reduction of p-p38/MAPK and uPA, and Src inhibition enhanced the KLF17-induced suppression of p-Src and uPA in A549 and H322 cells. In conclusion, our study indicated that KLF17 suppressed the uPA-mediated invasion of lung adenocarcinoma. The Src and p38/MAPK signaling pathways were suggested as mediators of KLF17-induced uPA inhibition, thus providing evidence that KLF17 might be a potential anti-invasion candidate for lung adenocarcinoma.

Leukemia inhibitory factor in the neuroimmune communication pathways in allergic asthma.

In the pathogenesis of asthma, central sensitization is suggested to be an important neural mechanism, and neurotrophins and cytokines are likely to be the major mediators in the neuroimmune communication pathways of asthma. However, their impact on the central nervous system in allergic asthma remains unclear. We hypothesize that central neurogenic inflammation develops in the pathogenesis of allergic asthma, and nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are important mediators in its development. An asthma model of rats was established by sensitization and challenged with ovalbumin (OVA). For further confirmation of the role of LIF in neurogenic inflammation, a subgroup was pretreated with intraperitoneally (i.p.) LIF antibody before OVA challenge. The levels of LIF and NGF were measured with reverse transcription and polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry stain in lung tissue, airway-specific dorsal root ganglia (DRG, C7-T5) and brain stem of asthmatic rats, anti-LIF pretreated rats and controls. A significantly increased number of LIF- and NGF-immunoreactive cells were detected in lung tissue, DRG and the brain stem of asthmatic rats. In the asthma group a significantly increase level of mRNA encoding LIF and NGF in lung tissue was detected, but not in DRG and the brain stem. Pretreatment with LIF antibody decreased the level of LIF and NGF in all tissues. LIF is an important mediator in the crosstalk between nerve and immune systems. Our study demonstrate that the increased level of LIF and NGF in DRG and brain stem may be not based on result from de novo synthesis, but rather on result from retrograde nerve transport or passage across the blood-brain-barrier.

[The prevalence and risk factors of bronchiectasis in residents aged 40 years old and above in seven cities in China].

OBJECTIVE: To investigate the prevalence and risk factors of bronchiectasis in urban city of China. METHODS: A cross-sectional survey was conducted in 17 urban areas in Beijing, Shanghai, Tianjin, Chongqing cities, and Guangdong, Liaoning, Shanxi provinces. In this study, urban population-based cluster samples were randomly selected from each city/province. In the selected city communities, all residents at least 40 years old were recruited, interviewed with questionnaires and tested with spirometry. Each participant was asked whether he/she was ever diagnosed as bronchiectasis by physician, whether had symptoms of respiratory diseases and possible risk factors, etc. RESULT: Data of 10 811 participants was enrolled for analysis, with a response rate of 75.4% (10 811/14 337). The overall prevalence of physician-diagnosed bronchiectasis was 1.2% (135/10 811), with 1.5% (65/4382) in male and 1.1% (70/6429) in female, without statistical difference in gender (χ² = 3.289, P = 0.070). Prevalence of bronchiectasis increased with age (χ² = 31.029, P < 0.001). There were no statistical significances in crude prevalences of bronchiectasis among cities (χ² = 10.572, P = 0.103), while there was a significant difference among cities after adjustment with confounders (Wald value = 22.116, P = 0.001), by using logistic regression analysis. Logistic regression analysis showed, bronchiectasis was significantly associated with elder ( ≥ 70 years vs 40-49 years; OR = 4.11, 95% CI 2.29-7.36), the family history of respiratory diseases (having two subjects with respiratory diseases in family vs no suffered relatives; OR = 2.04, 95% CI 1.06-3.94), respiratory infection during childhood (suffering two kinds of respiratory diseases vs never; OR = 4.89, 95% CI 2.03-11.81), exposure to coal (OR = 2.30, 95% CI 1.17-4.52), chronic pharyngitis (OR = 3.96, 95% CI 1.38-11.40) and pulmonary tuberculosis (OR = 3.07, 95% CI 1.89-4.98), heart diseases (OR = 1.64, 95% CI 1.11-2.42) and lung cancer(OR = 18.61, 95% CI 7.67-45.18). CONCLUSION: The prevalence of bronchiectasis in population aged 40 years old and above in urban area in China is high and associated with multiple factors such as age, family history of respiratory diseases, respiratory infection during childhood, exposure to coal, chronic pharyngitis, pulmonary tuberculosis, heart diseases, lung cancer and so on.

Asymptomatic patients of chronic obstructive pulmonary disease in China.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China. METHODS: A multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents (over 40 years old) were interviewed with a standardized questionnaire and spirometry. Post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic, personal and exposure variables were collected and analyzed. RESULTS: Among the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The age, sex, body mass index (BMI), rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group. Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P < 0.001) than symptomatic group. More asymptomatic patients were underdiagnosed (91.9% vs. 54.3%, P < 0.001) than symptomatic patients. CONCLUSIONS: This large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.

Transfer of the beta-tubulin gene of Botrytis cinerea with resistance to carbendazim into Fusarium graminearum.

BACKGROUND: Resistance to carbendazim and other benzimidazole fungicides in Botrytis cinerea (Pers. ex Fr.) and most other fungi is usually conferred by mutation(s) in a single chromosomal beta-tubulin gene, often with several allelic mutations. In Fusarium graminearum Schwade, however, carbendazim resistance is not associated with a mutation in the corresponding beta-tubulin gene. RESULTS: The beta-tubulin gene conferring carbendazim resistance in B. cinerea was cloned and connected with two homologous arms of the beta-tubulin gene of F. graminearum by using a double-joint polymerase chain reaction (PCR). This fragment was transferred into F. graminearum via homologous double crossover at the site where the beta-tubulin gene of F. graminearum is normally located (the beta-tubulin gene of F. graminearum had been deleted). The transformants were confirmed and tested for their sensitivity to carbendazim. CONCLUSION: The beta-tubulin gene conferring carbendazim resistance in B. cinerea could not express this resistance in F. graminearum, as transformants were still very sensitive to carbendazim.

[Current status of prevention and management of chronic obstructive pulmonary disease in rural area in China].

OBJECTIVE: To investigate the current status of prevalence, prevention and management of chronic obstructive pulmonary disease (COPD) in rural area in China. METHODS: A cross-sectional survey of COPD was conducted in Beijing city, Shanghai city, Guangdong province, Liaoning province, Tianjin city, Chongqing province and Shanxi province. A population-based cluster sample was randomly selected from each rural area. In the selected community, all residents at least 40 years old were recruited, and interviewed with a modified standardized questionnaire from the international burden of obstructive lung diseases (BOLD) study. All participants were tested with spirometry. Those with airflow limitation were performed on post-bronchodilator spirometry. The post-bronchodilator a ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) less than 70% was defined as the diagnostic criteria of COPD. RESULTS: (1) Data of 9434 participants was valid for analysis, with a valid response rate of 83.6%; the prevalence of COPD in rural was 8.8% (830/9434), 12.8% in male and 5.4% in female. (2) The percentage of smoking and the exposure to biomass smoke in rural was 43.0% (4059/9434) and 83.1% (7835/9434) respectively; cigarettes cessation rate was 17.5%; only 12.4% (502/4059) of smokers had received advice to quit smoking. (3) Among COPD patients, only 30.0% (249/830) had ever been diagnosed as COPD, bronchitis, emphysema, or asthma, 2.4% (20/830) had ever received spirometric tests, and 74.5% were current smokers; only 7.9% (50/634) COPD patients in stage two or over had received regular drug treatment. CONCLUSION: There was high prevalence and poor prevention and management for COPD in rural areas. Therefore, an enforced prevention and management for COPD are urgent.

[The quality of life of patients with chronic obstructive pulmonary disease and correlated factors].

OBJECTIVE: To evaluate the quality of life (QOL) of patients with chronic obstructive pulmonary disease (COPD) and correlated factors. METHODS: Data of 20 245 patients with COPD were collected from the cross-sectional survey of COPD, which was conducted between 2002 and 2004 in urban and rural areas of Beijing, Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shanxi for residents aged over 40 years old. The recruited populations were interviewed with questionnaire and tested for spirometry. The quality of life was assessed with 12-item short-form health survey questionnaire (SF-12). Those with less than 70% of post-bronchodilator FEV(1)/FVC were identified as having COPD. The differences between groups in SF-12 scores converted by rank were compared using general linear model. Stepwise multiple linear regressions were conducted to study the main determinants of QOL. RESULTS: Compared to subjects without COPD, those with COPD had impaired QOL (56 +/- 7 vs. 57 +/- 6 in mental component scores, F = 4.442, P < 0.05; 46 +/- 9 vs. 50 +/- 6 in physical component scores, F = 453.960, P < 0.05). Among COPD patients, the mental component score was associated with scores of dyspnea, BMI, comorbidities, sex and living areas, while the physical component score was associated with scores of dyspnea, severity of COPD, comorbidities, exposure to dusts/gases/fumes, sex, age, educational level and previous diagnosis of respiratory diseases (all P < 0.05). CONCLUSIONS: The QOL in patients with COPD was impaired and associated with scores of dyspnea, severity of COPD, comorbidities and BMI. Improvement of dyspnea, nutritional support, prevention of comorbidities and keeping away from risk factors may improve the QOL in COPD patients.

[A study on the correlation of body mass index with chronic obstructive pulmonary disease and quality of life].

OBJECTIVE: To investigate the correlation between body mass index (BMI) and chronic obstructive pulmonary disease (COPD), based on a cross-sectional COPD survey conducted in Beijing, Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shaanxi of China between 2002-2004. METHODS: A multi-stage stratification cluster sampling strategy was used in this cross-sectional survey, and 20,245 subjects (8705 males and 11,540 females) aged 40 years or older were recruited, interviewed with a questionnaire, measured for height and weight, and tested with spirometry. 1668 subjects with post-bronchodilator FEV1/FVC less than 70% were identified as having COPD after other known causes of airflow limitation were excluded. Analysis on relationship between COPD and BMI was performed in 1668 COPD and 18 577 non-COPD subjects. RESULTS: Compared with non-COPD subjects, BMI was significantly lower in COPD patients [(22.7+/-3.5) vs (24.1+/-3.4) kg/m2, F=158.31, P<0.01]; BMI was also significantly lower in smokers than in non-smokers [(23.6+/-3.4) vs (24.2+/-3.5) kg/m2, F=49.10, P<0.01]. And an addictive interaction to BMI between COPD and smoking was observed (F=6.03, P<0.05). BMI decreased with the increase of the stage of COPD (F=45.6, P<0.01), with a negative relationship (r=-0.08, P<0.01). Lower BMI was significantly associated with increased risk of COPD (chi2=102.68, P<0.01). Compared with subjects with normal BMI (BMI=24.0-27.9 kg/m2), those with lower BMI (BMI<18.5 kg/m2) were more likely to have COPD [adjusted OR=2.12 (95% CI 1.73-2.59)], while those with higher BMI (BMI=24.0-27.9 kg/m2) and obesity (BMI>or=28.0 kg/m2) were less likely to have COPD [adjusted OR=0.67 (95% CI 0.59-0.76); and 0.60 [(95% CI 0.49-0.73), respectively]. Moreover, there was an interaction to COPD between smoking and BMI (chi2=4.73, P<0.05). Compared with COPD patients with normal BMI, the quality of life in those with lower BMI was impaired (55+/-8 vs 57+/-6 in mental scores of SF-12, F=2.96, P<0.05; 42+/-10 vs 46+/-9 in physical scores of SF-12, F=4.21, P<0.01), and their dyspnea scores were higher (1.4+/-1.5 vs 1.1+/-1.3, chi2=14.32, P<0.01). CONCLUSION: Lower BMI was strongly associated with COPD, possibly as a risk factor for COPD independent of smoking, and a potential predictor for COPD severity.

[Theophylline in the treatment of chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study].

OBJECTIVE: To observe the benefits and safety of low-dose, slow-release oral theophylline for long-term treatment of stable chronic obstructive pulmonary disease (COPD). METHODS: This was a randomized, parallel-group, double-blind, placebo-controlled trial. Slow-release theophylline (200 mg/d) twice daily or placebo (matching theophylline) was randomly given to 110 patients with stable COPD in the rural area of Shaoguan, Guangdong Province, for one year. Efficacy measures were spirometry and exacerbations, quality of life, dyspnea scores, satisfaction with treatments and adverse effects. Comparison of benefits was performed using superiority test. RESULTS: Of 110 patients, 85 (42 subjects in theophylline group and 43 subjects in placebo group) completed the study. An analysis for intention-to-treat (ITT) individuals showed that individuals with the treatment of theophylline experienced statistically fewer numbers [(0.8 +/- 1.2) times/year, (1.7 +/- 2.6) times/year, Z = -1.674, P = 0.047] and days of exacerbations [(4.6 +/- 7.9) d, (12.5 +/- 22.8) d, Z = -1.699, P = 0.045] in comparison to subjects receiving placebo, that patients receiving theophylline were less likely than the placebo group to experience moderate exacerbations [(0.4 +/- 1.0) times/year, (1.0 +/- 1.8) times/year, Z = -2.136, P = 0.017], and that more individuals satisfied with treatments in the theophylline group than the placebo group (n = 16, 3, Z = -2.198, P = 0.014), and that statistically greater improvement in pre-bronchodilators FEV(1) [(0.006 +/- 0.180) L, (-0.053 +/- 0.169) L, t = 1.789, P = 0.038] were found in the theophylline group in comparison to the placebo group. The similar results were observed in an analysis for per-protocol (PP) subjects. Statistical improvement on quality of life was observed in the PP subjects of theophylline group than in placebo group (-28 +/- 20, -20 +/- 23, F = 2.893, P = 0.047). Time to the first exacerbation in patients receiving theophylline was also delayed in comparison to placebo (365 d, 276 d, chi(2) = 3.880, P = 0.049). But no statistical difference was found between the two groups in post-bronchodilators FEV(1) in both ITT and PP subjects (t = -0.012, P = 0.495 and t = 0.040, P = 0.484 respectively). Drug-related adverse events (8.8%) such as insomnia, palpitation, stomach discomforts or stomachache, and headache were observed in the theophylline group. CONCLUSION: Slow-released oral theophylline (200 mg/d) may be beneficial and safe in long-term treatment of stable COPD in rural area.

Caffeic acid phenethyl ester ameliorates cerebral infarction in rats subjected to focal cerebral ischemia.

The effects of caffeic acid phenethyl ester (CAPE), an antioxidant derived from propolis, on the infarct volume elicited by focal cerebral ischemia were studied on Long-Evans rats. Cerebral infarction was induced by microsurgical procedures with ligation of the right middle cerebral artery (MCA) and clipping of bilateral common carotid arteries (CCA) for 60 min. The rats were sacrificed 24 h later and serial brain slices of 2 mm thickness were taken and stained for the measurement of infarct area. CAPE was administered intravenously 15 min before MCA occlusion. Pretreatment of CAPE (0.1, 1 and 10 microg/kg) significantly reduced the total infarct volume from 169.6 +/- 14.5 mm3 (control) to 61.0 +/- 24.1 mm3 (0.1 microg/kg CAPE), 47.4 +/- 9.1 mm3 (1 microg/kg CAPE), and 42.4 +/- 8.7 mm3 (10 microg/kg CAPE), respectively. Plasma nitric oxide (NO) content was significantly increased in rats subjected to focal cerebral ischemia. It is concluded that CAPE possesses neuroprotective properties in focal cerebral ischemia injury in rats possibly through its antioxidant effect and/or via the upregulation of NO production.

[The risk factors for chronic obstructive pulmonary disease in females in Chinese rural areas].

OBJECTIVE: To explore the risk factors for chronic obstructive pulmonary disease (COPD) in females in Chinese rural areas. METHODS: Based on a national multi-center, population-based and cross-sectional survey on prevalence of COPD in seven provinces/cities of China, an analysis on the risk factors for the rural females was conducted in six areas, e.g. Beijing, Shanghai, Guangdong, Liaoning, Tianjin and Shanxi. In the national survey, for each area, one rural and one urban cluster samples were randomly selected using a multi-stage strategy. Residents who were 40 years old or older were interviewed with questionnaires and tested with spirometry. The post-bronchodilators forced expired volume in one second to forced vital capacity ratio (FEV(1)/FVC) x 100% < 70% was used as diagnostic criteria of COPD. RESULTS: The average prevalence of COPD in females in the six Chinese rural areas was 5.4%. The prevalence varied with risk factor exposure among different areas, and the prevalence in Guangdong province was the highest among all areas. Logistic regression model was conducted, and statistical association of COPD was found with a family history of respiratory diseases (OR = 2.46, 95% CI = 1.86 - 3.26), frequent coughing during childhood (frequent coughing vs never coughing: OR = 3.93, 95% CI = 2.02 - 7.63), lower body mass index (lower body mass index vs normal body mass index: OR = 2.20, 95% CI = 1.47 - 3.29), age (70 years or older vs 40 - 49 years: OR = 8.98, 95% CI = 5.90 - 13.67), smoking (OR = 1.68, 95% CI = 1.20 - 2.35), exposure to occupational dusts (OR = 1.45, 95% CI = 1.07 - 1.96), worse ventilation in kitchen room (OR = 1.47, 95% CI = 1.06 - 2.03) and lower educational level (OR = 2.19, 95% CI = 1.38 - 3.46). CONCLUSION: The prevalence of COPD in females in rural areas was associated with multiple factors and prevention of COPD for Chinese women in rural areas is warranted.