Analysis of the volume of fluid (VOF) method for the simulation of the mucus clearance process with CFD

The clearance of mucus through coughing is a complex, multiphase process, which is affected principally by mucus viscosity and airflow velocity; however, it is also critically affected by the thickness of the two layers of mucus—the serous and gel layers—and oscillation level. The present study examines the effects of the latter parameters more closely. To do so, the mucus clearance process is simulated with a transient 3D volume of fluid (VOF) multiphase model in ANSYS Fluent. The model includes mucus’ bilayer properties and a wide range of boundary conditions were tested. The model was analysed in both a straight tube and a realistic trachea. Ultimately, the model was able to both capture air-mucus interface wave evolution and predict the overall behaviour of the clearance process. The results were consistent with experimental clearance data and numerical airflow simulations, which indicates our methodology is appropriate for future studies. Ultimately, the mere presence of the serous layer was found to increase mucus clearance by more than 15 percent. An oscillating flow enhanced clearance by up to 5 percent. Interestingly, interface wave steepness was found to be inversely correlated with mucus thickness, but directly with mucus velocity, which suggests it will be an interesting parameter for further study.     

Cyclic AMP signaling contributes to neural plasticity and hyperexcitability in AH sensory neurons following intestinal Trichinella spiralis-induced inflammation

Trichinella spiralis infection causes hyperexcitability in enteric after-hyperpolarising (AH) sensory neurons that is mimicked by neural, immune or inflammatory mediators known to stimulate adenylyl cyclase (AC)/cyclic 3',5'-adenosine monophosphate (cAMP) signaling. The hypothesis was tested that ongoing modulation and sustained amplification in the AC/cAMP/phosphorylated cAMP related element binding protrein (pCREB) signaling pathway contributes to hyperexcitability and neuronal plasticity in gut sensory neurons after nematode infection. Electrophysiological, immunological, molecular biological or immunochemical studies were done in T. spiralis-infected guinea-pigs (8000 larvae or saline) after acute-inflammation (7 days) or 35 days p.i., after intestinal clearance. Acute-inflammation caused AH-cell hyperexcitability and elevated mucosal and neural tissue levels of myeloperoxidase, mast cell tryptase, prostaglandin E2, leukotrine B4, lipid peroxidation, nitric oxide and gelatinase; lower level inflammation persisted 35 days p.i. Acute exposure to blockers of AC, histamine, cyclooxygenase or leukotriene pathways suppressed AH-cell hyperexcitability in a reversible manner. Basal cAMP responses or those evoked by forskolin (FSK), Ro-20-1724, histamine or substance P in isolated myenteric ganglia were augmented after T. spiralis infection; up-regulation also occurred in AC expression and AC-immunoreactivity in calbindin (AH) neurons. The cAMP-dependent slow excitatory synaptic transmission-like responses to histamine (mast cell mediator) or substance P (neurotransmitter) acting via G-protein coupled receptors (GPCR) in AH neurons were augmented by up to 2.5-fold after T. spiralis infection. FSK, histamine, substance P or T. spiralis acute infection caused a 5- to 30-fold increase in cAMP-dependent nuclear CREB phosphorylation in isolated ganglia or calbindin (AH) neurons. AC and CREB phosphorylation remained elevated 35 days p.i.. Ongoing immune activation, AC up-regulation, enhanced phosphodiesterase IV activity and facilitation of the GPCR-AC/cAMP/pCREB signaling pathway contributes to T. spiralis-induced neuronal plasticity and AH-cell hyperexcitability. This may be relevant in gut nematode infections and inflammatory bowel diseases, and is a potential therapeutic target.     

Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study

Background

Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough.

Methods

Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms.

Results

Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV₁% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV₁% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033).

Conclusion

Productive cough and decreasing FEV₁ were each associated with MMP-9 in COPD, and decreasing FEV₁ remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.     

咳嗽变异性哮喘（CVA）与小气道功能相关性分析

目的：探讨咳嗽变异性哮喘（CVA）患者小气道功能检查对其诊断,治疗的意义。方法：对254例以慢性咳嗽为主的患者行肺功能检查并行支气管激发试验,回顾性分析小气道病变及气道高反应性检查结果与咳嗽变异性哮喘（CVA）的相关性。结果：有小气道功能障碍者接受吸入乙酰甲胆碱激发试验,气道反应性明显增高。有小气道功能障碍确诊咳嗽变异性哮喘（CVA）组起始阻力、反应阈值及阻力上升度与非哮喘组相比差异有统计学意义（P〈0.01）。结论：检查小气道功能障碍有助于哮喘的诊断,治疗及预后随访。     

Biofeedback and Cognitive Coping in the Treatment of Pediatric Habit Cough

Habit cough is a persistent ‘barking’ cough that does not have a medical basis. The current study evaluated a biofeedback approach using skin temperature feedback with a family focus in the treatment of an 11-year-old girl diagnosed with habit cough. Treatment consisted of six, one hour sessions with the family for part of the session and then individually with the girl. Individual treatment involved skin-temperature biofeedback to teach relaxation during the coughing episodes. The girl was cough free at the end of the sixth session and remained cough free at the end of a one and two year follow-ups. The use of a single case baseline design demonstrated the reduction of coughing and increase in extracurricular activity. It is, noteworthy that the girl demonstrated a significant ability to increase skin temperature during treatment and when asked to try to control her cough.     

Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model

Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii‐specific serum antibodies might play an important role in protection. Immuno‐proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA‐like protein of B. holmesii. An aBH vaccine prepared from a BipA‐like protein‐deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA‐like protein plays an important role in the protective efficacy of aBH vaccine.     

Identification and characterization of a brilliant yellow pigment produced by Bordetella pertussis

Culture supernatants of Bordetella pertussis are a brilliant yellow; however, the structure and biological role of the responsible pigment have not been investigated. In this study, a brilliant yellow‐colored fraction was extracted from culture supernatants of B. pertussis and analyzed by HPLC. UV–visible spectral analysis and mass spectrometry identified the brilliant yellow pigment as riboflavin. Riboflavin production was high in lag and early log phases and riboflavin was found to enhance growth of B. pertussis in low‐density cultures. Riboflavin production is not regulated by the BvgAS system. In addition, it was found that other Bordetella species, such as B. parapertussis , B. holmesii and B. bronchiseptica, also release riboflavin into their culture supernatants. This is the first report that B. pertussis secrets riboflavin to the extracellular space and that riboflavin may promote its growth. The mechanism may be associated with pathogenesis of B. pertussis .

     

CFD transient simulation of the cough clearance process using an Eulerian wall film model

In this study, a cough cycle is reproduced using a computational methodology. The Eulerian wall film approach is proposed to simulate airway mucus flow during a cough. The reproduced airway domain is based on realistic geometry from the literature and captures the deformation of flexible tissue. To quantify the overall performance of this complex phenomenon, cough efficiency (CE) was calculated, which provided an easily reproducible measurement parameter for the cough clearance process. Moreover, the effect of mucus layer thickness was examined. The relationship between the CE and the mucus viscosity was quantified using reductions from 20 to 80%. Finally, predictions of CE values based on healthy person inputs were compared with values obtained from patients with different respiratory diseases, including chronic obstructive pulmonary disease (COPD) and respiratory muscle weakness (RMW). It was observed that CE was reduced by 50% in patients with COPD compared with that of a healthy person. On average, CE was reduced in patients with RMW to 10% of the average value of a healthy person.     

七个中药复方对小鼠止咳化痰作用的对比实验

目的为了筛选出防治猪呼吸道疾病综合征(PRDC)有效的中药复方制剂,对七个具有止咳化痰作用的中药复方制剂进行了对比实验。方法以小鼠为实验动物,用右美沙芬、氯化铵作阳性药,生理盐水作空白对照,采用浓氨水引咳法和气管段酚红分泌法,对七个中药复方制剂的止咳化痰作用进行了观测。结果方7、方5可显著延长小鼠的咳嗽潜伏期(P0.05),减少5 min内的咳嗽次数(P0.05),除方4组外,其他中药组的气管酚红排泌量显著低于对照组(P0.05),并且方7、方5和氯化铵组小鼠的酚红排泌量显著低于其他处理组(P0.05)。结论七个中药复方组中,方5、方7的止咳化痰作用最显著,可在进一步实验研究后,作为PRDC的治疗药物。     

组织培养暗紫贝母的药理作用

以组织培养的暗紫贝母为材料,野生暗紫贝母为对照,用不同溶剂提取,得４个化学组人 生物碱部分,总皂甙部分,水溶性部分和脂溶性部分,并以生药粉为阳性对照进行药效学试验。结果表明：组培贝母与野生贝母有相似的止咳、祛痰作用;总皂甙部分与总生物碱部分均为川贝有效活性成分,ｔ得之间无显著性差异;经ＴＬＣ是乌头总生物碱部分与总皂甙部分无化学成分重叠。