Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Ecological Study in the Basque Country,Spain (2000–2011)

Chronic obstructive pulmonary disease (COPD) is a prevalent condition in adults aged ≥40 years characterized by progressive airflow limitation associated with chronic inflammatory response to noxious particles in the airways and lungs. Smoking, genetics, air pollution, nutrition and other factors may influence COPD development. Most hospitalizations and deaths for COPD are caused by its acute exacerbations, which greatly affect the health and quality of life of COPD patients and pose a high burden on health services. The aims of this project were to identify trends, geographic patterns and risk factors for COPD exacerbations, as revealed by hospitalizations and deaths, in the Basque Country, Spain, over a period of 12 years (2000–2011). Hospitalization and mortality rates for COPD were 262 and 18 per 100,000 population, respectively, with clusters around the biggest cities. Hospital mortality was 7.4%. Most hospitalized patients were male (77.4%) and accounted for 72.1% of hospital mortality. Hospitalizations decreased during the study period, except for 50–64 year-old women, peaking significantly. Using a multivariate modeling approach it was shown that hospitalizations were positively correlated with increased atmospheric concentrations of NO₂, CO, PM₁₀, and SO₂, and increased influenza incidence, but were negatively associated with increased temperatures and atmospheric O₃ concentration. COPD exacerbations decreased in the Basque Country during 2000–2011, but not among 50–64-year-old women, reflecting the high smoking prevalence among Spanish women during the 1970–1990s. The main metropolitan areas were those with the highest risk for COPD exacerbations, calling attention to the role of heavy car traffic. Influenza virus, cold temperatures, and increased atmospheric NO₂, CO, PM₁₀, and SO₂ (but decreased O₃) concentrations were identified as potential contributors to the burden of COPD exacerbations in the community. These findings are important for both the understanding of the disease process and in providing potential targets for COPD-reducing initiatives and new avenues for research.     

Koelreuteria Formosana Extract Induces Growth Inhibition and Cell Death in Human Colon Carcinoma Cells via G2/M Arrest and LC3-II Activation-Dependent Autophagy

Autophagy is a self-destructive process that degrades cytoplasmic constituents. In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1 and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited cancer cell proliferation, induced G2/M-phase arrest associated with downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and induced cell death by activating autophagy but did not cause apoptotic cell death. Exposed KFEE cells showed increased levels of acridine orange, autophagic vacuoles, and LC3-II proteins, which are specific autophagic markers. Bcl-2, p-Akt, and p-mTOR levels, which have been implicated in autophagic downregulation, were decreased after KFEE treatment. Autophagy inhibitor 3-methyladenosine and bafilomycin-A1 and genetic silencing of LC3 attenuated KFEE-induced growth inhibition. These findings suggested that KFEE causes cytostatic effect through autophagy. In xenograft studies, oral administration of KFEE had significantly inhibited the tumor growth in nude mice that had received subcutaneous injection of DLD-1 cells. KFEE is a promising candidate in phytochemical-based, mechanistic, and pathway-targeted cancer prevention strategies.     

Multiple Coronary Artery Aneurysms of the Right Coronary Artery in Neonate with Pulmonary Atresia with Intact Ventricular Septum

Pulmonary atresia with intact ventricular septum (PA/IVS) with right ventricular‐dependent coronaries is a rare congenital cardiac anomaly. It has been associated with wide range of considerable anomalies including sinusoids, fistulae, coronary stenosis, or complete atresia. Coronary artery aneurysms in a neonate with PA/IVS have not been described. We report a case of neonate with pulmonary atresia with intact ventricular septum with giant coronary artery aneurysms.     

Early pregnancy induced expression of prostaglandin E2 receptors EP2 and EP4 in the ovine endometrium and regulated by interferon tau through multiple cell signaling pathways

Prostaglandin E2 (PGE₂) plays pleiotropic roles at fetal-maternal interface during establishment of pregnancy. The objectives of the study were to: (i) determine regulation of PGE2 receptors EP1, EP2, EP3, and EP4 in the endometrium during the estrous cycle and early pregnancy; and (ii) understand endometrial epithelial and stromal cell-specific hormonal regulation of EP2 and EP4 in sheep. Results indicate that: (i) early pregnancy induces expression of EP2 and EP4 but not EP1 and EP3 proteins in the endometrium on days 12-16 compared to that of estrous cycle; (ii) intrauterine infusion of interferon tau (IFNT) increases expression of EP2 and EP4 proteins in endometrium; and (iii) IFNT activates distinct epithelial and stromal cell-specific JAK, EGFR, ERK1/2, AKT, or JNK signaling module to regulate expression of EP2 and EP4 proteins in the ovine endometrium. Our results indicate a role for EP2 and EP4-mediated PGE₂ signaling in endometrial functions and establishment of pregnancy in ruminants.     

IFN-α对体外培养CML-DC功能、表达- 趋化因子及其受体的影响

为了研究α干扰素(IFN-α)对慢性粒细胞白血病(CML)来源的树突状细胞(DC)分泌趋化因子、表达趋化因子受体及其功能的影响,取13例CML慢性期患者骨髓单个核细胞,在小牛血清培养体系中诱导培养CML来源的DC,以rhSCF、rhFlt3L作为扩增体系的细胞因子,加入rhGMCSF、rhTNFα、rhIL4,加或不加rhIFN-α诱导DC的生成,培养2周后流式细胞术检测培养细胞的免疫表型,ELISA法检测培养上清液中CMLDC分泌MIP3-β的含量,MTT法检测CMLDC刺激健康人外周血T淋巴细胞增殖能力。结果表明:IFN-α组培养所获DC表面CD86、CD83、CD40、MHCⅠ类分子、CCR7的表达均高于对照组(P<0.01);IFN-α组诱导培养的CMLDC表达MIP3β较对照组明显增高(P<0.01);IFN-α组诱导培养的CMLDC刺激异体T淋巴细胞增殖的能力较对照组明显增强(P<0.01)。结论:IFN-α可能部分通过纠正CMLDC的免疫表型以加速CMLDC的成熟,增强CMLDC的功能。     

Involvement of hypothalamic PI3K–STAT3 signalling in regulating appetite suppression mediated by amphetamine

BACKGROUND AND PURPOSE

Appetite suppression induced by amphetamine has been attributed to its inhibition of neuropeptide Y (NPY) neurons and activation of pro-opiomelanocortin (POMC) neurons in the hypothalamus. This study examined whether STAT3 was involved in these actions of amphetamine.

EXPERIMENTAL APPROACH

Rats were given amphetamine daily for 4 days. Changes in the expression of NPY, POMC, melanocortin MC₃ receptors, PI3K and STAT3 in the hypothalamus were assessed by RT-PCR and Western blotting. Antisense oligonucleotides to STAT3 were also used.

KEY RESULTS

Expression of NPY decreased with a maximum effect day 2 of amphetamine treatment. Expression of POMC, MC₃ receptors, PI3K and STAT3 increased with a maximum response on day 2. Moreover, phosphorylation of STAT3 and its DNA binding activity increased and was expressed in a similar pattern. Infusion (i.c.v.) of STAT3 antisense at 60 min before amphetamine treatment, partly blocked amphetamine-induced anorexia and modulated expression of NPY, POMC, MC₃ receptors and PI3K, indicating the involvement of STAT3 in amphetamine-treated rats.

CONCLUSIONS AND IMPLICATIONS

Hypothalamic PI3K–STAT3 signalling participated in the regulation of NPY- and POMC-mediated appetite suppression. These findings may contribute to a better understanding of anorectic drugs.     

Crystallization Behavior and Mechanical Properties of Poly(ε-caprolactone) Reinforced with Barium Sulfate Submicron Particles

Poly(ε-caprolactone) (PCL) was mixed with submicron particles of barium sulfate to obtain biodegradable radiopaque composites. X-ray images comparing with aluminum samples show that 15 wt.% barium sulfate (BaSO₄) is sufficient to present radiopacity. Thermal studies by differential scanning calorimetry (DSC) show a statistically significant increase in PCL degree of crystallinity from 46% to 52% for 25 wt.% BaSO₄. Non-isothermal crystallization tests were performed at different cooling rates to evaluate crystallization kinetics. The nucleation effect of BaSO₄ was found to change the morphology and quantity of the primary crystals of PCL, which was also corroborated by the use of a polarized light optical microscope (PLOM). These results fit well with Avrami–Ozawa–Jeziorny model and show a secondary crystallization that contributes to an increase in crystal fraction with internal structure reorganization. The addition of barium sulfate particles in composite formulations with PCL improves stiffness but not strength for all compositions due to possible cavitation effects induced by debonding of reinforcement interphase.