Vitamin D3 Attenuates Viral-Induced Inflammation and Fibrotic Responses in Bronchial Smooth Muscle Cells.

Toll-like receptor 3 (TLR3) activation by viral infections plays a key role in promoting inflammatory immune responses that contribute to pulmonary fibrosis in chronic inflammatory respiratory diseases. Vitamin D3 has been shown to be beneficial to patients with asthma and chronic obstructive pulmonary disease (COPD) through its anti-inflammatory and anti-fibrotic properties. Smooth muscle cells are one of the major contributors to airway remodeling in asthma and COPD. We therefore aimed to investigate the effect of vitamin D3 treatment on viral-induced TLR3 responses in Bronchial Smooth Muscle Cells (BSMCs) as a mechanism contributing to pulmonary fibrosis in asthma and COPD. Primary BSMCs from patients with asthma (n=4), COPD (n=4), and healthy control subjects (n=6) were treated with polyinosinic: polycytidylic acid (polyI:C), TLR3 agonist in the presence or absence of vitamin D3 (1,25D3). Here we report the mRNA expression and protein levels of pro-inflammatory and pro-fibrotic markers (IL-6, IFN-ß1, CCL2/MCP-1, fibronectin 1 and type I collagen) among BSMCs groups: asthma, COPD, and healthy controls. We show that at the baseline, prior to polyI:C stimulation, asthma and COPD BSMCs presented increased pro-inflammatory and pro-fibrotic state compared to healthy control subjects, as measured by quantitative PCR and immunoassays (ELISA/Flow Cytometry. Ligation of TLR3 by polyI:C in BSMCs was associated with increased TLR3 mRNA expression, and 1,25D3 treatment significantly reduced its expression. In addition, 1,25D3 decreased the expression of IL-6, IFN-ß1, CCL2, FN1 and COL1A1 induced by polyI:C in BSMCs. The regulatory effect of 1,25D3 treatment on polyI:C-stimulated BSMCs was further confirmed at protein levels. Our findings suggest that vitamin D3 attenuates TLR3 agonist-induced inflammatory and fibrotic responses in BSMCs and support the clinical relevance of vitamin D3 supplementation in patients with viral infections having chronic respiratory diseases, such as asthma and COPD.

Reversal of IL-13-induced inflammation and Ca(2+) sensitivity by resolvin and MAG-DHA in association with ASA in human bronchi.

The aim of this study was to investigate the effects of resolvin D1 (RvD1), as well as the combined treatment of docosahexaenoic acid monoglyceride (MAG-DHA) and acetylsalicylic acid (ASA), on the resolution of inflammation markers and Ca(2+) sensitivity in IL-13-pretreated human bronchi (HB). Tension measurements performed with 300 nM RvD1 largely abolished (50%) the over-reactivity triggered by 10 ng/ml IL-13 pretreatment and reversed hyper Ca(2+) sensitivity. Addition of 300 nM 17(S)-HpDoHE, the metabolic intermediate between DHA and RvD1, displayed similar effects. In the presence of 100 µM ASA (a COX inhibitor), the inhibitory effect of 1 µM MAG-DHA on muscarinic tone was further amplified, but not in the presence of Ibuprofen. Western blot analysis revealed that the combined treatment of MAG-DHA and ASA upregulated GPR-32 expression and downregulated cytosolic TNFα detection, hence preventing IκBα degradation and p65-NFκB phosphorylation. The Ca(2+) sensitivity of HB was also quantified on ß-escin permeabilized preparations. The presence of ASA potentiated the inhibitory effects of MAG-DHA in reducing the Ca(2+) hypersensitivity triggered by IL-13 by decreasing the phosphorylation levels of the PKC-potentiated inhibitor protein-17 regulatory protein (CPI-17). In summary, MAG-DHA combined with ASA, as well as exogenously added RvD1, may represent valuable assets against critical AHR disorder.

Anti-inflammatory effect of triterpenoic Acids of Eriobotrya japonica (Thunb.) Lindl. Leaf on rat model of chronic bronchitis.

This study was designed to investigate the anti-inflammatory effect of Triterpenoic Acids from Eriobotrya japonica (Thunb.) Lindl. (TAL) on chronic bronchitis (CB) in rats. CB model was established by combination of Bacillus Calmette-Guerin (BCG, 5 mg/kg, injected through the caudal vein) and lipopolysaccharide (LPS, 1 g/L, injected through endotracheal intubation). Rats with CB model were treated with TAL (50, 150 and 450 mg/kg) for 3 weeks. The leukocytes in bronchoalveolar lavage fluid (BALF) were counted after Wright staining, the levels of cytokine tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-8, and IL-10 in the supernatants of lung homogenate were assessed by enzyme-linked immunosorbent assay (ELISA), and the protein expression of nuclear factor kappaB (NF-kappaB) and intercellular adhesion molecule-1 (ICAM-1) on bronchial epithelium were tested by immunohistochemical staining. As compared to the normal and sham groups, the total number of leukocyte, the differential counts of neutrophils and alveolar macrophage (AM) in BALF, the levels of TNF-alpha and IL-8 in the supernatants of lung homogenate, and the expression of NF-kappaB and ICAM-1 on bronchial epithelium in CB rats were significantly increased, while the level of IL-10 was decreased. TAL (50, 150 and 450 mg/kg) attenuated these alterations in model CB rats, which indicates that TAL has anti-inflammatory effect in the rats with CB.

The effect of Bach's magnificat on emotions, immune, and endocrine parameters during physiotherapy treatment of patients with infectious lung conditions.

The purpose of this study was to determine the effect of Bach's Magnificat on emotions, immune, and endocrine parameters in patients of specific infectious lung conditions. Participants (N = 40; 9 men & 31 women) ranging in age from 40 to 75 participated in the study. Patients were randomly allocated to an experimental and control group. During a 3-day period the experimental group received physiotherapy with the selected music, while the control group only received physiotherapy. ANOVA statistics indicate significant changes in the following parameters: POMS-scale, CD4+:CD8+ ratio, cortisol, and cortisol:DHEA ratio. The intervention of music demonstrates communication between the mind and body.

[Effects of the zhikuofang on the inflammation and cytostatics of the airway model of bronchiectasis].

OBJECTIVE: To explore the effects of Zhikuofang, a TCM prescription, and Ofloxacin on the inflammation and cytostatics of the airway model of bronchiectasis. METHOD: The airway model of bronchiectasis (AMB) was set up and infused with Ps. Aeruginosa. A comparison between the effects of Zhikuofang and Of loxacin on the AMB was made. RESULT: Zhikuofang is better than Ofloxacin in following aspects: lowering the density of inflammation cells in blood, decreasing the volume of tracheal secretion and inhibiting the cytostatics (IL-8 and TNF-alpha) of the trachea tissue, but Ofloxacin is more effective in diminishing the amount of bacteria in trachea flushing liquor. There was no marked difference between them in their histopathy effects on the trachea. CONCLUSION: Zhikuofang probably plays antiphlogistic and bacteriostatic effects by inhibiting the IL-8 and TNF-alpha, resisting secretion, decreasing the inflammation cells and resisting inflammation of trachea.

Pharmacokinetic/pharmacodynamic predictors of time to clinical resolution in patients with acute bacterial exacerbations of chronic bronchitis treated with a fluoroquinolone.

Forty nine subjects with acute bacterial exacerbations of chronic bronchitis (ABECB) treated with grepafloxacin were evaluated for parameters predictive of clinical outcome. Signs and symptoms associated with ABECB were serially collected and evaluated for changes. Coughs per day, sputum volume and the percentage of sputum neutrophils were associated with clinical outcome. A by groups analysis, based on clinical success was performed using Cox regression analysis to determine factors associated with time to clinical success and time to reduction in sputum volume, coughs per day and sputum neutrophil percent. Factors evaluated included AUIC (AUC/MIC), isolate species, years and type of underlying lung disease, alcohol use, smoking history and number of ABECB within the previous 12 months. AUIC<276 (mg h/l)/mg/l (P<0.03) and or the presence of mild bronchiectasis (P<0.01) were associated with longer time to clinical success. In addition a relationship was found between AUIC>212 (mg h/l)/mg/l (P<0.01) and AUIC>576 (mg h/l)/mg/l (P<0.02) and decreasing days to sputum volume reduction and coughs per day, respectively. A diagnosis of mild bronchiectasis prolonged the time to reduce coughs per day (P<0.03) and neutrophil percentage (P<0.01). Patients with mild bronchiectasis were found to have an increase in the time to clinical success, coughs per day improvement and sputum neutrophil percent improvement. AUIC is an important PK/PD parameter predictive of successful outcome in ABECB, even in subjects with mild bronchiectasis. Grepafloxicin has been withdrawn from sale since these studies were carried out. This work is published to illustrate the relationship between pharmacodynamics and clinical efficacy and the use of AUIC as a valuable predictive parameter for fluoroquinolones.

[Chronic obstructive pulmonary disease patients undergoing home oxygen therapy: a study of clinical parameters, nutritional status and ambulatory capacity]. / Patients BPCO sous oxygénothérapie à domicile: étude des paramètres cliniques, de l'état nutritionnel et de la capacité de déambulation.

AIM OF THE STUDY: The aim of the study was to document the nutritional status and the calorie demands of patients suffering from severe chronic airflow obstruction (BPCO) who were on continuous domiciliary oxygen therapy (OCD) and to correlate this information with the clinical picture, the severity of the respiratory disease and the daily distance walked, this to be measured in a prospective manner. PATIENTS AND METHODS: Fifty clinically stable patients with chronic airflow obstruction on continuous oxygen therapy for 33 months (range 4-106) in whom the following measures were made at home: pulmonary function, maximal static inspiratory and expiratory pressure (PIMAX and PEMAX), strength of hand, grip, the mean distance walked daily (wearing a pedometer for one week), body mass index (IMC), and the body composition by electrical bio-impedence and calorie requirements. RESULTS: Thirty four per cent of patients presented with an excessive body mass (IMC > 27 kg/m2), 42 per cent had normal nutrition (IMC 20-27 kg/m2) and 24 per cent were malnourished (IMC < 20 kg/m2). Malnourished patients had, in a statistically significant manner, airflow obstruction of greater severity and a lower oxygen saturation and a PEMAX as well as a lower daily distance compared to over weight subjects. However, their net calorie requirements were markedly higher (39 +/- 5 Kcal/kg/j) compared to patients having normal weight (29 +/- 11 kcal/kg/j) or excess weight (25 +/- 8 kcal/kg/j). From the clinical standpoint no malnourished patient fulfilled the clinical criteria of chronic bronchitis. By contrast 61 per cent of subjects with normal nutrition and 94 per cent of subjects with excessive weight were chronic bronchitics. CONCLUSION: In the group of patients with severe airflow obstruction on domiciliary oxygen, 25 per cent were malnourished and this was in spite of netly increased calorie consumption which is superior to their theoretical need. This suggests that the solution of increasing supplements to their dietary requirements would be a difficult to realise. These subjects presented also with a more marked ventilatory handicap and a clinical picture characterised by the absence of the classical signs of chronic bronchitis.

Intraluminal inflammation in the airways of patients with chronic bronchitis after treatment with Ambroxol.

Ambroxol is a mucus-modifying drug with a known ability to stimulate surfactant secretion and inhibit, in vitro, the production of proinflammatory cytokines, neutrophil chemotaxis, and Na+ absorption by the airway epithelium. In dogs inhaling ozone, bronchial hyperreactivity can be inhibited by aerosolized Ambroxol. To verify the possibility of producing anti-inflammatory effects in a clinically relevant condition, 20 patients with chronic bronchitis, randomly divided into two balanced matched groups, were submitted to a 14 day trial with Ambroxol, 150 mg.day-1, or placebo, according to a double-blind design. A bronchoalveolar lavage (BAL) was performed the day before starting treatment (T0) and at the 14th day (T14). The analysis of the cellular and soluble (total proteins, albumin, immunoglobulin G and A (IgG and IgA)) BAL components demonstrated no clear modifications. In particular, neutrophil values from the bronchial aliquot showed a large dispersion, with no significant differences (Ambroxol: T0 = 13.7 +/- 5.2%, T14 = 14.0 +/- 6.8%; placebo: T0 = 3.6 +/- 1.1%, T14 = 5.5 +/- 2.2%). We found a nonsignificant increase of phospholipids in BAL supernatants from Ambroxol-treated patients (2.5 +/- 1.9 vs 3.0 +/- 1.9 micrograms.mg-1 of protein); whilst in the placebo group data before and after treatment were superimposable (2.2 +/- 1.5 vs 2.3 +/- 1.9 micrograms.mg-1 of protein). In conclusion, we have failed to demonstrate that conventional treatment with oral Ambroxol can modify surfactant and BAL cell populations in the airways of patients with chronic bronchitis.

[Energy metabolic changes in the cardiorespiratory system of patients with chronic bronchitis under the action of galvanization and dalargin electrophoresis on the area of the chest cavity]. / Izmenenie énergoobmena kardiorespiratornoi sistemy bol'nykh khronicheskim bronkhitom pod vozdeistviem gal'vanizatsii i élektroforezom dalargina na oblast' grudnoi kletki.

Galvanization and dalargin electrophoresis were examined for effects on external respiration, hemodynamics and oxygen-related energy metabolism of cardiorespiratory system of chronic bronchitis patients. Universal stress-limiting mechanism of these procedures, correcting cardiorespiratory function is based on more effective utilization of energy resources for support of self-cleaning activity of the body.

[Effect of antibiotics on the absorption of basic nutrients]. / Vliianie antibiotikov na vsasyvanie osnovnykh pitatel'nykh veshchestv.

The impact of tetracycline, gentamicin, streptomycin, erythromycin, oxacillin, benzylpenicillin and sulfanilamides on the absorption function of the small intestine was studied in 79 patients with chronic bronchitis. The drugs were shown to mainly inhibit fat absorption: on the average, by 87 per cent in all the patients treated with tetracycline, on the average, by 89 and 36 per cent in 80-70 per cent of the patients treated with gentamicin and streptomycin, respectively, and, on the average by 26 and 16 per cent in 20-25 per cent of the patients treated with erythromycin and oxacillin, respectively. The absorption of protein decreased, on the average, by 23-74 per cent in all the patients treated with tetracycline, gentamicin and streptomycin. As for the other drugs, they had, on the average no significant effect on protein absorption. The absorption of carbohydrates (d-xylose) significantly decreased under the effect of these three drugs (by 21, 34 and 36 per cent, respectively). The analysis revealed a relation of absorption function to the presence and degree of intestinal dysbacteriosis.

[Fluctuating currents in the combined therapy of inflammatory lung diseases]. / Fliuktuiruiushchie toki v kompleksnoi terapii pri vospalitel'nykh zabolevaniiakh legkikh.

An experimental and clinical trial was performed to evaluate effectiveness of fluctuating currents in the treatment of pulmonary inflammation. A positive effect was registered in the currents use to manage chronic bronchitis. The optimal regimen has been developed.

Effects of qing-fei-tang on the airway inflammation and clearance.

Qing-Fei-Tang, a Chinese blended medicine, inhibited the release of slow reacting substance of anaphylaxis (SRS-A) from passively sensitized guinea pig lung after antigen challenge. Qing-Fei-Tang also suppressed the chemiluminescence of oxygen radicals when healthy human leukocytes were stimulated by opsonized zymosan. In rabbits, Qing-Fei-Tang increased the output volume and fatty acid contents in respiratory tract fluid. In the bronchitic rabbits, 6 weeks administration of Qing-Fei-Tang restored the decreased amount of saturated fatty acid in the sputa, and histological examinations revealed an amelioration of the inflammation of lung tissues. In pigeons, Qing-Fei-Tang facilitated tracheal mucociliary transport. Accordingly, Qing-Fei-Tang seems to exert effectiveness via its multiple mechanisms.

[Immunocorrecting properties and effect on the phosphorus-calcium metabolism of oxidevit (1 alpha-hydroxyvitamin D3)]. / Immunokorrigiruiushchie svoistva i vliianie na fosforno-kal'tsievyi obmen oksidevita (1 alpha-hydroksivitamina D3).

Effect of oxidevite (I alpha-hydroxyvitamin D3) on the patterns of immunity system and metabolism of calcium and phosphorus were studied in 45 patients with chronic bronchitis, which, were treated with the drug at doses of 2 or 4 micrograms during 1 or 2 weeks. Specific patterns of calcium and phosphorus metabolism were altered in the patients depending on dose of the drug and duration of the course treatment. The dose of 4 micrograms per a day within 2 weeks was excessive. All the immunity patterns studied involving amount of total and rosette-forming cells, T-lymphocyte helpers and T-lymphocyte suppressors, B lymphocytes, were normalized independently on the initial level of these patterns: the elevated values decreased, the decreased values-increased. The normal values of the immunity patterns studied were not altered during the oxidevite treatment course. Content of blood inorganic phosphorus correlated with leukocytes dynamics.

Ciprofloxacin in acute exacerbations of chronic bronchitis.

Thirty four patients with acute purulent exacerbations of chronic bronchitis were treated with 500 mg ciprofloxacin twice daily, orally, for ten days. The short-term response rate was 97% (cure 70.6%, improvement 26.4%) and failure 3%; the long-term response rate (six months follow-up) was 73.5%. Predominant initial pathogens were Haemophilus influenzae and Streptococcus pneumoniae, mostly in pure cultures. All sputum cultures except those with Str. pneumoniae became negative on the third day of treatment. Apart from a slower clearance of pneumococci from the sputum there were no significant differences in responses between pneumococcal and Haemophilus infections during and after therapy. Peak serum levels at 2 h after administration were 3.8 +/- 1.7 mg/l, half life was 3 h; peak sputum levels at 4 h were 1.3 +/- 0.95 mg/l. The serum-sputum penetration was 49.7% measured by AUC values. Mild adverse gastrointestinal effects were noticed in five patients.

[Glycolytic metabolism during muscular excerise in chronic broncho-pulmonary disease without hypoxemia (author's transl)]. / Metabolisme glycolytique pendent l'exercice musculaire dans les broncho-pneumopathies chroniques non-hypoxémiques

Maximum oxygen uptake (VO2 max) was measured in 11 chronic bronchitics without heart failure or hypoxemia at rest and during maximal work load, using a triangular type of excerise with increasing power (30 W/3 min). Glycolysis was studied in these patients during rectangular exercises lasting 10 minutes, in which power was increased by steps from an average value of 45 % to 72 and 94 % of VO2 max. The metabolic response of lactate in blood is similar to normal, during the limited performances of these patients.

[Aminochlorthenoxycycline levels in experimental acute inflammation of the respiratory tree]. / Ricerche sulla distribuzione dell'aminoclortenoxiciclina nell'infiammazione sperimentale acuta dell'albero respiratorio.

A special technique used to obtain acute respiratory inflammation in the rabbit produced a considerable increase in expectorate by comparison with the controls. Bronchial, lung and blood aminochlorthenoxycycline levels were much higher than in the controls, showing that this antibiotic has a marked affinity for inflamed lung tissue.