Silver-Catalyzed Efficient Synthesis of Oxindoles and Pyrroloindolines via α-Aminoalkylation of N-Arylacrylamides with Amino Acid Derivatives.

α-Aminoalkylation of N-arylacrylamides with amino acid derivatives was achieved by silver-catalysis in moderate to high yields. The reaction provides an efficient strategy for the synthesis of functionalized oxindoles, and is suitable for a wide range of N-arylacrylamides and amino acids, both of which are inexpensive and readily available. The oxindoles obtained were readily transformed into densely functionalized pyrroloindolines by deprotection and cyclization in one pot.

Effect of 12-month rehabilitation with low loading program on chronic respiratory disease.

[Purpose] The purpose of this study was to examine the effect of 12-month rehabilitation with low loading program on chronic respiratory disease. [Subjects and Methods] Twelve patients with chronic respiratory disease participated in this study, in which the effect of long-term rehabilitation for 12 months was assessed. Nine patients had chronic obstructive pulmonary disease, two had asthma, and one had interstitial pneumonia. In all patients, symptoms, lower-extremity strength, walking distance, activities of daily living, and quality of life were investigated to examine the effect of respiratory rehabilitation. [Results] After 12 months, the isometric knee extension strength and weight-bearing index both showed a significant increase. [Conclusion] The findings of this study suggested that improvement in lower-limb muscle strength can be achieved through long-term intervention, and indicated the validity of repetitive standing and walking exercises.

Prevalence of childhood asthma in Ulaanbaatar, Mongolia in 2009.

BACKGROUND: Bronchial asthma is a common but important chronic disease in children in all over the world. To take measures against prevalence of childhood asthma, many researchers have surveyed the actual statuses of childhood asthma in developed countries, but in most Asia-Pacific developing countries including Mongolia such surveys have never been sufficiently conducted until now. We have thought that this survey, though performed in 2009, will give important and meaningful information even now in taking measures to prevent prevailing bronchial asthma in children in Mongolia or the countries under similar statuses. METHODS: The asthma prevalence and patient background information in Mongolian children aged 6-7 living in Ulaanbaatar were examined using a written questionnaire modified for their parents from that prepared by the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: The estimated prevalence of asthma in Mongolian children was 20.9%. The following 3 risk factors were found to be related to asthma: (1) having allergic rhinitis symptoms, (2) mothers' smoking, and (3) history of severe respiratory infection before 1-year-old. CONCLUSIONS: The asthma prevalence in Mongolian children was higher than that in the world and Asia-Pacific countries reported by ISAAC. The higher prevalence was probably attributable to households' (especially mothers) smoking in draft-free houses designed for the cold area and severe air-pollution due to rapid industrialization and urbanization in Mongolia. Smoking prohibition in the mother (including family members) and a reduction of exposure to air pollutants are urgently needed to prevent developing childhood asthma.

Prevalence of asthma and allergic rhinitis among adult population in Ulaanbaatar, Mongolia.

BACKGROUND: Mongolia is changing lifestyle, unhealthy habits, increase of air pollution, increasing life expectancy have led to an up rise of chronic respiratory diseases. Over 10 years ago, the prevalence of asthma and allergic rhinoconjunctivitis in Mongolia were in the lower range reported from previous studies. OBJECTIVE: The main aim of the survey is to know the prevalence of asthma and allergic rhinitis among adult population of Ulaanbaatar city, Mongolia and their risk factors. METHODS: Total of approximately 1,200 adults aged 20 years and over were planned to be randomly selected. The questionnaire was developed on the basis of WHO Protocol for Assessment of Prevalence of Major Respiratory Diseases and modified by local risk factors assessment and by other international survey approach including Global Initiative for Asthma and European Community Respiratory Health Survey. RESULTS: Prevalence of current wheezer in all age group was 15.7% (95% CI: 14.7-16.8). Age and sex segregated distribution of current wheezer were defined among male and female and prevalence was 14.5% (95% CI: 13.3-16.2) in male and female 16.6% (95% CI: 15.2-18.3) respectively. Prevalence of diagnosed asthma among adults was 4.7% (95% CI: 4.3-5.6) in all age group, 3% (95% CI: 2.4-3.7) in male and 6.8% (95% CI: 5.8-7.9) in female. Prevalence of rhinoconjunctivitis was 14.6% in all age group. 28.4% out of subjects with allergic rhinitis has current asthma, while 11.6% of subjects without allergic rhinitis has asthma (p < 0.01). CONCLUSION: The prevalence of asthma increased for one decade in Ulaanbaatar. Prevalence of diagnosed asthma is approximately 5% and current wheezer is approximately 15% in adults of population, which is close to other Asia and European countries. Allergic rhinitis is a risk factor for asthma.

Evolution of asthma concept and effect of current asthma management guidelines.

Concept of asthma has changed from symptom-complex or airway hypersensitivity to airway inflammation and airway remodeling. Based on this concept asthma management guidelines (JGL) has been developed in Japan. Death from asthma has decreased drastically since the publication of the guidelines, although it is still high in elderly population. Further works are expected for "zero-death" from asthma and for tighter control of airway inflammation and resultant airway remodeling.

A case of eosinophilic pneumonia successfully treated with suplatast tosilate alone.

We report a case of eosinophilic pneumonia that was successfully treated with suplatast tosilate. A 72-year-old woman with hypertension and diabetes, who did not smoke and did not have pets, consulted a physician with the chief complaints of cough, sputum, and slight fever. Chest X-ray films revealed a permeation shadow in the bilateral upper lobes. She visited a hospital because her symptoms did not improve. Pulmonary tuberculosis was suspected because of an elevated inflammatory reaction, and anti-tuberculosis treatment was started. Afterwards, eosinophilia appeared in the peripheral blood. Although daily drugs (nicardipine hydrochloride, pentoxifylline, and ticlopidine hydrochloride) were stopped, eosinophilia did not improve and was detected in a sputum sample. She was diagnosed with pulmonary infiltration with eosinophilia syndrome and hospitalized. Physical examination revealed neither rhonchus nor cardiac murmurs on auscultation. Laboratory findings showed a leukocyte count of 21,300/microl, with eosinophils accounting for 66.3% of cells. A diagnosis of eosinophilic pneumonia was made after a lung biopsy specimen was examined under a bronchial fiberscope. After suspension of anti-tuberculosis drugs and administration of suplatast tosilate 300 mg/day for 4 weeks, symptoms subsided, eosinophilia improved to within normal ranges, eosinophils in sputum disappeared, and the permeation shadow disappeared on chest X-ray films.

Serum markers in interstitial pneumonia with and without Pneumocystis jirovecii colonization: a prospective study.

BACKGROUND: In patients with chronic respiratory disease, Pneumocystis jirovecii (P. jirovecii) colonization is observed, and may influence disease progression and systemic inflammation. Pneumocystis pneumonia causes interstitial changes, so making a diagnosis of PCP in patients who have interstitial pneumonia (IP) with P. jirovecii colonization is sometimes difficult based on radiography. METHODS: This study investigated the prevalence of P. jirovecii colonization in IP patients and assessed pulmonary injury due to P. jirovecii colonization by measurement of serum markers (KL-6, SP-A, SP-D, and (1-->3) beta-D-glucan (beta-D-glucan)) and the peripheral lymphocyte counts, prospectively. A total of 75 patients with idiopathic pulmonary fibrosis (n = 29), collagen vascular-related interstitial pneumonia (n = 19), chronic bronchitis or pneumonia (n = 20), and Pneumocystis pneumonia (n = 7) were enrolled in this prospective study. P. jirovecii DNA was detected in sputum samples, while serum markers and the lymphocyte count were measured in the peripheral blood. RESULTS: IP patients (idiopathic pulmonary fibrosis and collagen vascular-related IP) who received oral corticosteroids had a high prevalence of P. jirovecii colonization (23.3%). In IP patients, oral corticosteroid therapy was a significant risk factor for P. jirovecii colonization (P < 0.05). Serum markers did not show differences between IP patients with and without P. jirovecii colonization. The beta-D-glucan level and lymphocyte count differed between patients with Pneumocystis pneumonia or P. jirovecii colonization. CONCLUSION: Serum levels of KL-6, SP-A, SP-D, and beta-D-glucan were not useful for detecting P. jirovecii colonization in IP patients. However, the serum beta-D-glucan level and lymphocyte count were useful for distinguishing P. jirovecii colonization from pneumocystis pneumonia in IP patients.

[Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

BACKGROUND: In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. AIM: In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. METHOD: Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. RESULT: The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. DISCUSSION: We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

Interleukin-10 regulates transforming growth factor-beta signaling in cultured human bronchial epithelial cells.

BACKGROUND: The basic pathological features of bronchial asthma can be explained on the basis of chronic airway inflammation, involving inflammatory cells such as T cells (particularly type 2 helper T, Th2, cells) and mast cells, and airway remodeling. Many aspects of airway remodeling remain unclear at the molecular level. Recent attention has focused on the role of transforming growth factor (TGF)-beta, a fibrogenic cytokine, in airway remodeling. Currently available evidence suggests that airway remodeling is caused by an imbalance in regulatory mechanisms mediated by Smads, a family of signal-transducing molecules. OBJECTIVES: We studied the effects of the Th2 cytokines interleukin (IL)-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the regulatory cytokine IL-10 on the expression of inhibitory Smad7 protein in bronchial epithelial cells. METHODS: Real-time reverse-transcriptase polymerase chain reaction was employed. RESULTS: Stimulation with IL-10 upregulated the expression of Smad7 compared with control. Neither IL-5 nor GM-CSF induced Smad7 expression. Smad7 expression was upregulated by IL-10 plus either IL-5 or GM-CSF. IL-10 inhibited the expression of TGF-beta-inducible early gene, which is known to downregulate Smad7 expression. CONCLUSIONS: Our results suggest that IL-10 acts as a regulatory cytokine in the inhibition of airway inflammation.

Prospective survey on safety evaluation of injectable methylxanthines in Japan.

BACKGROUND: Injectable methylxanthines are useful drugs in the treatment of asthma. The Asthma Prevention and Management Guidelines (JGL) that are followed in Japan recommend the use of sustained-release theophylline to control the disease and use of injectable methylxanthines to alleviate symptoms. In contrast, the guidelines followed in the west do not promote theophylline use due to safety concerns, and the use of injectable methylxanthines in particular are not recommended. We thus conducted a study on adult patients with bronchial asthma or chronic obstructive pulmonary disease treated with theophylline and injectable methylxanthines in Japan in order to assess the safety of these drugs. METHODS: 876 patients were surveyed at 55 medical institutions by the Committee on the Safety of Sustained-Release Theophylline and Injectable Methylxanthines (CST) of the Committee for Asthma Prevention and Management Guidelines of the Japanese Society of Allergology (JSA). 682 of the patients were evaluated for safety. RESULTS: Adverse reactions including facial flushing, palpitations, headache, tinnitus, diaphoresis, nausea, vomiting and tachycardia were reported by only 2 (0.29%) of the 682 patients, but none of these were serious. CONCLUSIONS: The results confirm that injectable methylxanthines are safe, when used in accordance with the JGL.

A prospective survey on safety of sustained-release theophylline in treatment of asthma and COPD.

BACKGROUND: Theophylline is a useful drug for the treatment of asthma. The Asthma Prevention and Management Guidelines (JGL) recommend use of sustained-release theophylline products as controllers and of injectable aminophylline products as relievers. The Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention, the NHLB/WHP Workshop Report 1995 (GINA, 1995) and guidelines in Western countries recommend sustained-release theophylline, but not as positively as in the JGL. The aim of this survey was to determine the occurrence of serious adverse reactions. METHODS: The survey was conducted in 66 institutions staffed by physicians certified by the Japanese Society of Allergology (JSA). The target diseases were asthma and COPD including chronic bronchitis and pulmonary emphysema, which are indications for use of sustained-release theophylline products in Japan. RESULTS: 3,921 patients were included in the safety evaluation. No serious adverse reactions were observed among the patients in this survey, although 54 patients (1.38%) exhibited non-serious adverse reactions. The incidence of adverse reactions was found to be high in patients who had begun use of sustained-release theophylline products at the time of registration in this survey, and in patients who were concomitantly taking macrolide antibiotics. CONCLUSIONS: The present survey demonstrates that sustained-release theophylline is safe, as long as used appropriately, although adverse reactions tend to develop early after initiation of administration.