Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells

Airway epithelial cells are the first targets of environmental stimuli and local cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis factor (TNF) in triggering IL-8 release has been documented previously. In this study, IL-8 mRNA and protein expression were examined in cultured human bronchial epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the presence of dexamethasone, budesonide, and fluticasone. Budesonide and fluticasone were 10-fold more potent than dexamethasone. The protein kinase C (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study shows that PKC signal pathway seems to be involved in the pyocyanin-mediated upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells. These findings suggest that a vicious cycle perpetuating inflammation may exist in the biologic milieu of bronchiectatic patients infected with Pseudomonas aeruginosa due to the production of pyocyanin. The priming action of pyocyanin appears to be blocked by glucocorticoids, thus providing in vitro data in support of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.     

Nurturing the “self” in health professions education

The shift in the way how health care is delivered from exclusive (disciplinary) to a more collective and inclusive (interprofessional) has recently been gaining traction in health care. The need for this shift is even magnified when the health care system face unprecedented challenges that single expertise is no more enough. The promise of transformative power of collaboration in health care suggests that collective intelligence achieves tasks more effectively than a single expertise could achieve.     

Clinical Value of Ciliary Assessment inBronchiectasis

Although ciliary dysfunction and numerous ultrastructural defects have been described, and these could be etiologically important in the development of bronchiectasis, their correlation with relevant clinical parameters have not been systematically evaluated. We have prospectively evaluated the prevalence and clinical significance of ciliary beat frequency and ultrastructural defects of nasal respiratory mucosa obtained from 152 stable patients with idiopathic bronchiectasis (100F, 57.7±15.2 yrs) and 127 control subjects (58F, 56.0±24.2 yrs). Bronchiectasis patients had significantly slower ciliary beat frequency (p < 0.05), and a greater percent of patients had central and peripheral microtubular defects (OR 14.4, 95% CI 5.6-36.8), namely, extra peripheral microtubules, “9+1”, “8+2”, and compound cilia (p < 0.05), but not microtubular disarrangement, extra matrix or ciliary tail abnormalities (p > 0.05), than controls. Bronchiectasis patients also had a greater proportion of cilia with any ultrastructural microtubular defects, compound cilia, and ciliary tails than controls (p < 0.05). Ciliary beat frequency did not correlate with clinically relevant parameters (p > 0.05). However, the percent of cilia with central, but not peripheral, microtubular defects correlated with 24 h sputum volume (r = 0.40, p = 0.001, and r = −0.04, p = 0.70, respectively) and FEV₁ (r = −0.24, p = 0.01, and r = 0.00, p =0.99 respectively). Our results strongly suggest a pathogenic role for central microtubular defects in the development of idiopathic bronchiectasis.     

颌骨骨肉瘤中p~(27)的表达及意义

目的 :分析细胞周期素依赖激酶抑制物 (CKI)p2 7蛋白在颌骨骨肉瘤的表达及意义。方法 :采用免疫组织化学ABC法检测p2 7蛋白在 2 0例颌骨骨肉瘤和 8例骨软骨瘤中的表达。结果 :2 0 % (4 2 0 )的骨肉瘤中p2 7呈阳性表达 ,87 5 % (7 8)的骨软骨瘤呈p2 7阳性 ,阳性表达率与骨肉瘤相比有显著性差异 (p <0 0 5 )。结论 :p2 7在颌骨骨肉瘤中低表达并可作为骨肉瘤发生和发展过程中的一个抑癌基因标志物     

Induction of apoptosis by hexamethylene bisacetamide is p53-dependent associated with telomerase activity but not with terminal differentiation

The present study investigated the relationships amongst apoptosis, terminal differentiation and telomerase activity in human colon carcinoma cells. We found that hexamethylene bisacetamide (HMBA) induced apoptosis in human colon carcinoma LoVo cells harbouring wild-type p53 but not in SW1116 cells harbouring mutant p53. HMBA reduced telomerase activity in both colon carcinoma cells but it did not induce differentiation in the colon carcinoma cells. Taken together, our results suggest that HMBA can induce apoptosis via a p53-dependent pathway, but apoptosis and terminal differentiation may be separately regulated in LoVo cells. Inhibition of telomerase activity may activate apoptosis through a p53-dependent mechanism.     

Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide-derived prooxidants

BACKGROUND: Recently, considerable attention has been focused on dietary and medicinal phytochemicals that inhibit, reverse, or retard diseases caused by oxidative and inflammatory processes. Green tea polyphenols have both antioxidant and antiinflammatory properties. OBJECTIVE: We examined the effects of green tea polyphenols in carbon tetrachloride-treated mice, a model of liver injury in which oxidant stress and cytokine production are intimately linked. We tested the effect of a pure form of epigallocatechin gallate (EGCG), the major polyphenol in green tea, in mice treated with carbon tetrachloride. DESIGN: Eight-week-old ICR mice were administered 20 microL/CCl(4) kg dissolved in olive oil. Two different doses of EGCG, 50 and 75 mg/kg, were tested. Control mice were treated with saline and olive oil. We analyzed liver histopathology, lipid peroxidation, and messenger RNA and protein concentrations of inducible nitric oxide synthase. Additionally, nitric oxide-generated radicals were assessed by electron paramagnetic resonance spectroscopy, and protein concentrations were measured by immunohistochemistry and Western blot analysis. RESULTS: Carbon tetrachloride administration caused an intense degree of liver necrosis associated with increases in lipid peroxidation, inducible nitric oxide synthase messenger RNA and protein, nitrotyrosine, and nitric oxide radicals. EGCG administration led to a dose-dependent decrease in all of the histologic and biochemical variables of liver injury observed in the carbon tetrachloride-treated mice. CONCLUSIONS: Green tea polyphenols reduce the severity of liver injury in association with lower concentrations of lipid peroxidation and proinflammatory nitric oxide-generated mediators. Green tea polyphenols can be a useful supplement in the treatment of liver disease and should be considered for liver conditions in which proinflammatory and oxidant stress responses are dominant.     

颅神经嵴细胞向成骨细胞表型分化的诱导实验

目的：观察颅神经嵴细胞（CNCC）在体外是否可以向成骨细胞表型进行诱导分化。方法：用标准的无血清培养液和含10^-8mol/L地塞米松、50mg/L左旋抗坏血酸和10mmol/L β－磷酸甘油钠的矿化诱导培养液对CNCC进行培养。15d后取两组细胞用于实验，观察两组间细胞形态，群体倍增时间、活力细胞数、碱性磷酸酶的活性和OC的含量等方面的变化。结果：诱导后的CNCC形态由成纤维样转变为多角形，细胞群体倍增时间延长，细胞活力数减少，碱性磷酸酶的活性和OC的含量升高。结论：CNCC在特定的矿化诱导培养液中，可以向成骨细胞表型分化。     

Exhaled Nitric Oxide: The Effects of Age, Gender and Body Size

Since little is known of the effects of age, gender, and body size on exhaled nitric oxide (NO) production, we have conducted a prospective study to examine these factors in a healthy nonsmoking women (mean age +/- SD 47.7 +/- 15.8, range 20-79 years). Exhaled NO was measured by an automatic chemiluminescence analyzer (Sievers NO Analyser 280) at steady expiration. Men had significantly higher exhaled NO levels than women (p = 0.001). Although exhaled NO levels did not correlate with age (r = 0.12, p = 0.17), it correlated significantly with height (r = 0.23, p = 0.02), weight (r = 0.34, p     

S-allylmercaptocysteine reduces carbon tetrachloride-induced hepatic oxidative stress and necroinflammation via nuclear factor kappa B-dependent pathways in mice

Purpose  

To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl₄)-induced acute hepatotoxicity in the mouse model.