Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease

There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gall-stone formation and mitigate biliary pain in gall-stone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gall-bladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 × 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05±0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94±0.27 versus 0.93±0.32 mg/ml) or total protein (5.8±0.9 versus 6.4±1.3 mg/ml), cholesterol saturation (1.3±0.2 versus 1.5±0.2), or nucleation time (2.0±3.0 versus 1.5±2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9±0.6 versus 5.6±1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content. Since mucus glycoproteins are major determinants of bile viscosity, an alteration in mucin macromolecular composition may conceivably cause the indomethacin-induced decrease in biliary viscosity and explain the beneficial effects of nonsteroidal anti-inflammatory drugs in gallstone disease

The psychogenesis of peptic ulcer

Thesis (M.D.)--Boston Universit

Xenopus: An alternative model system for identifying muco-active agents

The airway epithelium in human plays a central role as the first line of defense against environmental contaminants. Most respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, and respiratory infections, disturb normal muco-ciliary functions by stimulating the hypersecretion of mucus. Several muco-active agents have been used to treat hypersecretion symptoms in patients. Current muco-active reagents control mucus secretion by modulating either airway inflammation, cholinergic parasympathetic nerve activities or by reducing the viscosity by cleaving crosslinking in mucin and digesting DNAs in mucus. However, none of the current medication regulates mucus secretion by directly targeting airway goblet cells. The major hurdle for screening potential muco-active agents that directly affect the goblet cells, is the unavailability of in vivo model systems suitable for high-throughput screening. In this study, we developed a high-throughput in vivo model system for identifying muco-active reagents using Xenopus laevis embryos. We tested mucus secretion under various conditions and developed a screening strategy to identify potential muco-regulators. Using this novel screening technique, we identified narasin as a potential muco-regulator. Narasin treatment of developing Xenopus embryos significantly reduced mucus secretion. Furthermore, the human lung epithelial cell line, Calu-3, responded similarly to narasin treatment, validating our technique for discovering muco-active reagent

臨床所見および検査成績からのスコアーによる喘息分類の特徴

Twenty six patients with bronchial asthma was classified by clinical symptoms and singns (clinical diagnosis), and the classification by clinical diagnosis was compared with the classification by a score calculated from clinical findings and examinations (score diagnosis). 1. Of 12 subjects with type Ia classified by clinical diagnosis, 8 cases with 0 to 49 ml/day of expectoration were evaluated as type Ia by score diagnosis. While four type Ia cases with 50 to 99ml/day of expectoration were calssified as type Ib by score diagnosis. The increased incidence of eosinophils in bronchoalveolar lavage fluid (BALF) of these four cases was similar to the incidence in type Ib cases with hypersecretion. 2. All of 6 subjects with type Ib by clinical diagnosis were estimated as type Ib by score diagnosis. 3. Of 8 cases with type II by clinical diagnosis, 7 cases were assessed as type II by score diagnosis. One case with type II by clinical diagnosis and with the score of 10 points was evaluated as questionable type II by score diagnosis.気管支喘息36例を対象に,臨床病態による喘息の分類（臨床診断）を試み,この分類と臨床所見および臨床検査より求めたスコアーによる分類（スコアー分類）との比較検討を行った｡1.臨床分類でIa.単純性気管支攣縮型と診断された12症例のうち,1日喀痰量0-49mlの8症例は,スコアー分類では同様にIa.型と分類された｡一方,1日喀痰量50-99mlの4症例はスコアー分類ではIb.型（気管支攣縮+過分泌型）と分類された｡これら4症例のBALF中好酸球増多はIb.型に類似した病態であった｡2.臨床診断によりIb.型に分類された6症例はいずれもスコアー診断でもIb.型と分類された｡3.臨床診断によりII.型（細気管支閉塞型）と分類された8症例のうち,7症例はスコアー診断でもII.型と分類されたが,1症例はスコアー10でII.型の診断基準に合わず,questionable II.型と診断された

Obesity and Asthma: Adiponectin Receptor 1 (Adipo R1) and Adiponectin Receptor 2 (Adipo R2) are expressed by normal human bronchial epithelial (NHBE) cells at air-liquid interface (ALI) and expression changes with IL-13 stimulation

Obesity is recognized as an important risk factor for the development of many chronic diseases such as hypertension, Type 2 diabetes mellitus (T2DM) cardiovascular disease, cancer, renal disease, neurologic dysfunction, metabolic syndrome and asthma (3, 4). Circulating serum adiponectin levels in obese asthmatics have been reported to be low. Therefore, we aimed to investigate the role of adiponectin in a mucus hypersecretion model and hypothesized that adiponectin would decrease IL-13 induced MUC5AC expression from differentiated NHBE cells and that increasing concentrations of IL-13 would cause a decrease in Adipo R1 and Adipo R2 expression. MUC5AC expression with exposure to adiponectin was not significant. However, mRNA expression of Adipo R1 and Adipo R2 was significantly decreased by stimulation of IL-13 for acute (24 hours) and chronic (14 days) exposure. Therefore, the obese state and specifically IL-13 concentration could play a role in Adipo R1 and Adipo R2 expression within NHBE cells

(-)-Epigallocatechin-3-gallate Reduces Cigarette Smoke-Induced Airway Neutrophilic Inflammation and Mucin Hypersecretion in Rats

published_or_final_versio

Airway surface dehydration aggravates cigarette smoke-induced hallmarks of COPD in mice

Introduction: Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. Objective: We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC). Methods: βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Results: Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. Conclusions: We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD

温泉療法による気管支喘息に対する年間薬剤費の削減

Costs of drugs used for the treatment for 1 year were compared before and after spa therapy in 16 patients with asthma in relation to disease severity. Asthma severity was classified as : stage 1 (intermittent), 2 (mild persistent), 3(moderate persistent), and 4(severe persistent). 1. The total cost of drugs used for each pa-tient for 1 year clearty decreased in all groups. The % decrease of the costs of drugs in each group was 27.2% in patients with stage 1, 43.5% in those with stage 2 and 34.1% in those with stage 3-4 (mean 34.5% ). The reduction of the cost of bronchodilators was predominant in patients with stage 3-4, and the decrease in the cost of corticosteroids predominant in those with stage 2. The reduction of costs of antiallertgics, mucolytics, and antibiotics was predominant in patients with stage 2 and stage 3-4. The % reduction in the cost of corticostroids was remarkable in patients with stage 2. The % decrease in the costs of mucolytics and antibiotics was predomi-nant in patients with stage 2 and stage 3-4. The results obtained here suggest that the costs of drugs used for asthmatics could be reduced by long-term spa therapy, and the reduction of the costs was larger as asthma stage became more severe.気管支喘息16例を対象に,治療のために要した年間薬剤費が温泉療法により削減可能であるのかどうかについて,国際ガイドラインの重症度分類(stageト4)別に若干の検討を加えた｡1.年間の総薬剤費は重症度別の全てのグループにおいて明らかに減少した.2.その削減率は,ステージ1で27.2%,ステージ2で43.5%,ステージ3-4で34.1%であり,その平均は34.5%であった｡3.気管支拡張剤の薬剤費の減少はステージ3-4で高度であり,副腎皮質ホルモンの薬剤費の減少はステージ2で著明であった｡また,抗アレルギー薬,去痩薬,抗生物質などの薬剤費の削減は,ステージ2および3-4で高度であった｡4.削減率では,去壊薬,抗生物質の削減率が,2および3-4で著明であった｡ 以上の結果より,温泉療法により,気管支喘息の治療に必要な薬剤費は削減可能であること,そして,温泉療法による薬剤費の削減は職息の重症度が高い症例でより高度であることが示唆された

Pathogenesis of chronic obstructive pulmonary disease

The current paradigm for the pathogenesis of chronic obstructive pulmonary disease is that chronic airflow limitation results from an abnormal inflammatory response to inhaled particles and gases in the lung. Airspace inflammation appears to be different in susceptible smokers and involves a predominance of CD8(+) T lymphocytes, neutrophils, and macrophages. Studies have characterized inflammation in the peripheral airspaces in different stages of disease severity. Two other processes have received considerable research attention. The first is a protease–antiprotease imbalance, which has been linked to the pathogenesis of emphysema. However, the hypothesis of an increased protease burden associated with functional inhibition of antiproteases has been difficult to prove and is now considered an oversimplification. The second process, oxidative stress, has a role in many of the pathogenic processes of chronic obstructive pulmonary disease and may be one mechanism that enhances the inflammatory response. In addition, it has been proposed that the development of emphysema may involve alveolar cell loss through apoptosis. This mechanism may involve the vascular endothelial growth factor pathway and oxidative stress