Electronic substituent effect on the conformation of a phenylalanine-incorporated cyclic peptide.

The Phe-incorporated cyclic peptide [cyclo(-Phe1-oxazoline2-d-Val3-thiazole4-Ile5-oxazoline6-d-Val7-thiazole8-)] is in a conformational equilibrium between square and folded forms in solution. In the folded form, a CH⋯π interaction between the Phe1 aromatic ring and the Oxz2 methyl group is observed. We endeavored to control the local conformation and thus modulate the CH⋯π interaction and flexibility of the Phe1 side chain by controlling the electronic substituent effects at the 4-position of the aromatic ring of the Phe1 residue. The effect of the 4-substituent on the global conformation was indicated by the linear relationship between the conformational free energies (ΔGo) determined through NMR-based quantification and the Hammett constants (σ). Electron-donating substituents, which had relatively strong CH⋯π interactions, promoted peptide folding by restraining the loss in entropy. Local control by the 4-substituent effects suggested that the Phe side chain exerts an entropic influence on the folding of these cyclic peptides.

Primary Pulmonary Angiosarcoma Presenting with Hemoptysis and Ground-Glass Opacity: A Case Report and Literature Review.

Angiosarcoma originates from the vascular endothelium and accounts for only 1-2% of all sarcomatous malignancies. The skin is one of the most common primary sites. However, primary pulmonary angiosarcoma is rare, and only 31 cases of primary pulmonary angiosarcoma have been reported. A 79-year-old Japanese female developed bloody sputum, and chest X-ray and chest computed tomography (CT) showed consolidation with ground-glass opacity (GGO) on the right middle and lower lung fields. The bronchoscopic findings demonstrated bleeding from the right B(4) and B(5), and bronchial arterial embolization was subsequently performed. However, the CT findings demonstrated new pulmonary nodules with GGO in the left lung, and she presented with hemosputum and a progression of anemia. Right hemothorax also occurred, and surgical lung resection was performed to control the bleeding. The pathological analysis of the resected lung revealed the focal growth of atypical alveolar epithelioid-like cells that were positive for CD31 and negative for epithelial membrane antigen, and these atypical cells were replacing the endothelium of the pulmonary artery. Based on these findings, the patient was diagnosed with pulmonary angiosarcoma, which might originate from the endothelium of the pulmonary artery. No abnormal findings were observed except for the pulmonary involvement on systemic CT scanning. However, the patient passed away due to respiratory failure with compression of the brainstem caused by brain metastasis three months after the first visit. Early surgical resection is the important treatment for patients with angiosarcoma. In addition, we review the literature reporting the patients with primary pulmonary angiosarcoma.

Incidence and outcome of lung involvement in IgG4-related autoimmune pancreatitis.

We evaluated the incidence and outcome of lung involvement in 35 patients with autoimmune pancreatitis (AIP). Our results indicate that lung involvement is commonly observed in AIP (40%). In addition, corticosteroid treatment improved the lung lesions and appeared to reduce the probability of relapse compared with pancreatic lesions (0% vs 36%). This is the first report to assess the long-term outcome of lung involvement in AIP (52 ± 33 months).

Possible familial case of Birt-Hogg-Dubé syndrome complicated with lung cancer: A possible link between these two disease entities.

A 65-year-old Japanese woman was introduced to our hospital for an examination of multiple pulmonary cystic lesions and a pulmonary nodule in the left lower lobe. She had a smoking history of 25 pack-years, and her two younger brothers had suffered from pneumothorax; one of them additionally had lung cancer with pulmonary multiple cystic lesions. A surgical biopsy specimen obtained from her left lower lobe revealed adenocarcinoma surrounded by a single epithelial layer that was covered with collagen fibers. The pathological features were compatible with the findings of the cystic lesions in the patients with Birt-Hogg-Dubé syndrome (BHDS). A diagnosis of BHDS was eventually made according to the detection of a folliculin gene mutation. This is the first report of a possible familial case of BHDS complicated with primary lung cancer. We herein reviewed the previously reported cases of BHDS with lung cancer and other tumors and discussed a potential mechanism of tumorigenesis and carcinogenesis in the lung in the patients with BHDS.

Possible role of anaerobes in the pathogenesis of nontuberculous mycobacterial infection.

BACKGROUND AND OBJECTIVE: Recent advances in cultivation-independent molecular biological modalities for detecting bacterial species have indicated that several bacterial species may play a role in the pathogenesis of certain infectious diseases. The aim of this study was to evaluate the role of bacterial flora in the pathogenesis of nontuberculous mycobacteriosis (NTM) using a bacterial floral analysis of bronchoalveolar lavage fluid (BALF) with 16S rRNA gene sequencing in patients with bronchiectasis. METHODS: Fifty-eight patients with bronchiectasis evaluated using chest computed tomography were enrolled. BALF obtained from the most affected lung lesions was evaluated using culture and culture-independent methodologies. Approximately 600 bp of the bacterial 16S rRNA gene (E341F-E907R) was amplified via polymerase chain reaction using universal primers, and clone libraries were constructed. Nucleotide sequences of 96 randomly chosen clones for each specimen were determined, and the homology was searched using a basic local alignment search tool to determine the bacterial phylotypes and their proportions (bacterial floral analysis) in each specimen. RESULTS: Twenty-nine patients with bronchiectasis were diagnosed with NTM based on culture-based methods using Ogawa medium. The molecular method showed a significantly high rate of anaerobes among the patients with NTM compared with that observed in the bronchiectasis patients without NTM. In addition, findings of collapse/consolidation were significantly related to the proportion of Prevotella species in the BALF samples determined using the molecular method (P < 0.001). CONCLUSION: Given the results of the present study, anaerobes may play an important role in the pathogenesis of bronchiectasis in patients with NTM.

A rare case of paragonimiasis miyazakii with lung involvement diagnosed 7 years after infection: A case report and literature review.

We report a rare case of pulmonary paragonimiasis caused by Paragonimus miyazakii that showed pulmonary manifestations and a long-term clinical course after infection. A 45-year-old Japanese male developed cough and dyspnea in 2004 and was diagnosed with eosinophilic pneumonia. He had been treated with low-dose oral corticosteroid for 7 years. He recalled that he had consumed a large amount of raw freshwater crab (Geothelphusa dehaani) several weeks before he had been admitted for the first time, and that had been the only occasion when he had eaten this meat. The patient was referred to our hospital due to persistent hemoptysis, and his chest computed tomography scan showed pulmonary nodules and cavities, and his serum total IgE level was elevated. Bronchoscopy was performed, and ova were detected in the bronchoalveolar lavage fluid. The morphological examination of the ova and immunoserological examination yielded typical findings of P. miyazakii. Treatment with praziquantel improved his chest radiographic findings and a decrease of serum total IgE, as well as the values of immunoserological examination for P. miyazakii. The clinical course of this patient indicated that he had been infected with P. miyazakii for 7 years at least, which is unusual for paragonimiasis miyazakii.

Evaluation of a rapid immunochromatographic ODK0501 assay for detecting Streptococcus pneumoniae antigens in the sputum of pneumonia patients with positive S. pneumoniae urinary antigens.

BACKGROUND: A novel, rapid and noninvasive test (ODK0501, RAPIRUN(®)Streptococcus pneumoniae) uses polyclonal antibodies to detect C polysaccharide of S. pneumoniae derived from sputum samples using an immunochromatographic assay. We evaluated its usefulness in Japanese patients with pneumonia who exhibited positive urinary antigen tests for S. pneumoniae (BinaxNOW(®)S. pneumoniae). PATIENTS AND METHODS: Forty adult patients with pneumonia treated between May 2011 and August 2013 were enrolled. Bacterial cultures, Gram staining and ODK0501 assays of sputum as well as urinary antigen tests for S. pneumoniae using urine samples obtained from the same patients were performed upon admission, the fourth day after starting antimicrobial treatment and at the end of the antimicrobial treatment. RESULTS: Twenty-seven of the 40 patients were positive for ODK0501, while a negative result for ODK0501 was associated with low-quality sputum samples according to the Geckler classification of sputum. The sensitivity and specificity of the ODK0501 assay in the 40 patients were 90.9% and 61.1%, respectively, based on the culture results. The results obtained with this kit were more favorable than those observed on Gram staining. The ODK0501 assay also showed a rapid reaction to the disappearance of S. pneumoniae in the sputum samples, while approximately 80% of the patients exhibited persistent positive results on the urinary antigen detection tests at the end of treatment. CONCLUSIONS: The ODK0501 test is a noninvasive, rapid and accurate tool for diagnosing respiratory infections caused by S. pneumoniae, although good quality sputum must be obtained prior to adequate treatment with antibiotics.

[A case of lung adenocarcinoma with uncontrollable myocardial metastasis and pericardial effusion].

A 73-year-old Japanese man visited a local hospital due to palpitations and dyspnea. He was diagnosed as having lung cancer (adenocarcinoma, cT1aN2M1b (BRA), stage Ⅳ), but he did not want to receive any anticancer medications, and was simply being observed. Several months later, he was referred to our hospital due to exacerbation of the dyspnea. His chest computed tomography revealed massive pericardial effusion, therefore he was diagnosed as having cardiac tamponade due to carcinomatous pericarditis and was immediately hospitalized. Upon admission, pericardial fenestration was firstly applied in order to drain pericardial effusion, and intraoperative cardiac findings showed suspicion of myocardial and pericardial metastasis. Immediately after the pericardiotomy, he suffered from cardiac arrest caused by shock. In lung cancer patients with pericardial effusion, even though it is rare, myocardial metastasis in addition to carcinomatous pericarditis and pericardial metastasis should be kept in mind.

[Efficacy and safety of azithromycin infusion in patients with mild or moderate community-acquired pneumonia].

Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

[Efficacy and safety of levofloxacin in patients with nursing and healthcare-associated pneumonia].

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.

[Evaluation of the antiemetic effect of aprepitant in lung cancer patients receiving carboplatin-based chemotherapy using the Functional Living Index-Emesis questionnaire].

In the present study, we evaluated the antiemetic effect of aprepitant in combination with 5-hydroxytryptophan(5-HT3) receptor antagonist and dexamethasone for chemotherapy-induced emesis and nausea in lung cancer patients treated with carboplatin-based systemic chemotherapy using the Functional Living Index-Emesis, an emesis- and nausea-specific quality of life(QOL)questionnaire. Patients experiencing emesis and/or nausea during and/or after previous courses of carboplatin-based chemotherapy received aprepitant in the following treatment cycle with the same anti-cancer agent. Emesis- and nausea-specific QOL aspects were significantly improved with the addition of aprepitant to the existing regimen containing dexamethasone and 5-HT3 receptor antagonist. Our result suggests that combined antiemetic treatment with aprepitant, dexamethasone, and 5-HT3 receptor antagonist is more effective in lung cancer patients receiving carboplatin-based systemic chemotherapy than dexamethasone and 5-HT3 receptor antagonist alone.

Real-world effects of two inhaled corticosteroid/long-acting ß2-agonist combinations in the treatment of asthma.

OBJECTIVE: There are several inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) combinations currently used to treat asthmatic patients, but the differences in the clinical effects of these ICS/LABAs are currently unknown. We herein evaluated the effects of two currently available ICS/LABA combinations in a real-world setting. METHODS: A fluticasone propionate/salmeterol combined Discus inhaler (FP/SM; 250/50 µg bid) was switched to a budesonide/formoterol Turbuhaler inhaler (BUD/FM; 160/4.5 µg two inhalations bid) and FP/SM (500/50 µg bid) was also switched to BUD/FM (160/4.5 µg four inhalations bid) in symptomatic asthmatic patients treated with FP/SM over 20 years of age. RESULTS: Sixty patients were enrolled in this study, and the scores of the asthma control test (ACT) and asthma control questionnaire-5 item version (ACQ5) were significantly improved 4 and 8 weeks after the switch to ICS/LABA treatments, and well-controlled asthma (ACQ5 score <0.75) and good control (ACT score >20) was achieved in 54 (90%) and 40 (66.7%) patients, respectively, at 8 weeks. The spirometric analysis revealed significant improvements of the values of the peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) after switching from FP/SM to BUD/FM, and significantly improved small airway impairments ([Formula: see text]50 and [Formula: see text]25) were observed in patients treated with high-dose ICS/LABA. These subjective and objective improvements were also seen in patients aged over 65 years old. CONCLUSION: These data demonstrated that changing the combined ICS/LABA inhaler from FP/SM to BUD/FM can lead to more effective management of symptomatic patients with asthma, especially in patients treated with high-dose ICS/LABA.

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with multiple thin-walled pulmonary cysts: a case report and review of the literature.

We herein report a rare case of pulmonary mucosa-associated lymphoid tissue (p-MALT) lymphoma with multiple cystic lesions. A previously healthy 58-year-old Japanese woman visited our hospital for an evaluation of abnormal chest computed tomography (CT) findings. Chest CT revealed multiple cystic lesions in both lungs, and she was diagnosed as having p-MALT lymphoma based on the pathological findings. The patient had no underlying autoimmune diseases. She has not received any chemotherapy and has been stable for two years. This case suggests that, although rare, the possibility of p-MALT lymphoma should be considered in patients with multiple cystic lung diseases.

Incidence and outcomes of bepridil-induced interstitial pneumonia.

BACKGROUND: The incidence of bepridil-induced pulmonary toxicity, such as interstitial pneumonia, is still unknown. The aim of the present study was to evaluate the incidence of bepridil-induced pulmonary toxicity. METHODS AND RESULTS: A total of 253 patients treated with bepridil between January 2009 and January 2011 were retrospectively evaluated. Eight out of the 222 evaluable patients (male/female: 5/3, age range: 64-97 years, average age: 80.5 years, median age: 81.0 years) showed bepridil-induced pulmonary toxicity. CONCLUSIONS: The incidence of bepridil-induced pulmonary toxicity was 3.60% in our study population.

[Efficacy and safety of moxifloxacin in patients with nursing and healthcare-associated pneumonia].

Moxifloxacin (MFLX) is a respiratory quinolone, and is effective against not only Gram-positive and negative bacteria but also anaerobes. There has been no prospective studies evaluating the efficacy and safety of MFLX in patients with nursing and healthcare-associated pneumonia (NHCAP). Therefore, we assessed the efficacy and safety of MFLX in patients with NHCAP. NHCAP patients with mild and moderate severity assessed by the A-DROP system in community-acquired pneumonia guideline proposed by Japan Respiratory Society visited our hospitals from April 2011 to March 2012. Clinical symptoms, chest X-ray films and/or computed tomography, peripheral white and red blood cell and platelet counts, serum CRP, AST, ALT, BUN, creatinine were evaluated. Forty patients were eventually evaluated, and average age was 74.1 years old, male/female were 21/19, 92.5% (37/40) of them had one or more comorbidities. Median duration of MFLX administration was 7.1 days (4-15 days). The efficacy of MFLX in all patients was 87.5% (35/40). The efficacies in each age group were 87.9% (aged over 65 years old), 85.7% (aged under 64 years old), and in each pneumonia severity group by the A-DROP system were 91.7% (mild), 85.7% (moderate). Diarrhea and swelling of the breast were observed in one patient (2.5%) after starting MFLX administration. Mild elevated transaminases were observed in three patients (7.5%), and mild renal dysfunction was observed in two patients (5.0%). All abnormally increased levels of transaminases and serum creatinine were recovered after a cessation of MFLX. MFLX is effective and safe in patients with NHCAP.

[A case of rhabdomyolysis caused by saw palmetto of healthy foods].

An 82-year-old man visited our hospital when he developed a fever of over 38 degrees C after having consumed 5 types of health foods. He had previously been treated for chronic obstructive pulmonary disease, hypertension and hyperuricemia. Blood examination on admission revealed renal dysfunction, marked elevation of C-reactive protein, and an elevated level of serum creatine kinase. According to the laboratory data and his clinical history, rhabdomyolysis complicated by acute renal failure was suspected, but his condition improved and his fever was reduced with fluid infusion. As a drug lymphocyte stimulation test was positive for only saw palmetto in the 5 health foods, we diagnosed the case as rhabdomyolysis induced by saw palmetto. We believe that this is the first case of a health food being the cause of rhabdomyolysis.

[A case of localized malignant pleural mesothelioma].

A 74-year-old man was referred to our hospital for examination of an abnormal chest shadow. A chest computed tomography (CT) scan revealed a 5-cm mass attached to the pleura involving the right upper lobe, and a nodule in the right middle lobe. Transbronchial lung biopsy was performed twice, but no definitive diagnosis was achieved. 18-fluorodeoxyglucose positron emission tomography showed abnormal uptake in the chest lesion. Chemotherapy was initiated for advanced-stage lung cancer, but was not effective. Histopathologic and immunohistochemical examinations after CT-guided needle biopsy revealed malignant mesothelioma. The tumor cells were positive for calretinin and thrombomodulin, and negative for CEA, TTF-1, and SP-A. There was local tumor invasion and metastasis in the lung and brain, without diffuse pleural spread. This is a rare and important case of localized malignant mesothelioma pathologically confirmed by biopsy.

Calcitonin gene-related peptide stimulates proliferation of alveolar epithelial cells.

BACKGROUND: Alveolar epithelial cells are known as progenitor cells for the restoration from the damage in the lung. Calcitonin gene-related peptide (CGRP) has been reported to play an important role in the proliferation of various types of epithelial and endothelial cells. We investigated the effects of CGRP on the proliferation of alveolar epithelial cells in vitro and in vivo. METHODS: A549 cells were cultured in Dulbecco Modified Eagle Medium with 5% fatal bovin serum for 24 hours, then CGRP was added in vitro. The proliferation of DNA synthesis was measured using 5-bromo-2-deoxyuridine, an analog of thymidine, by enzyme-linked immunosorbent assay.As one intracellular response to CGRP, we examined activation of p44/42- extracellular signal-regulated kinase (ERK) pathway by adding CGRP, using western blotting method.Recombinant adenovirus encoding nuclear-targeted-human beta-CGRP (rhCGRP) was administered into Male Wister rat (n = 5, 10 weeks old) lungs by intratracheal instillation in vivo. 7 days after the administration of CGRP, rat lungs were harvested and histological findings and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) were evaluated to examine cell proliferation. RESULTS: In vitro study, CGRP increased the proliferation of A549 cells in a dose and time dependent manner. CGRP8-37 (inhibitor of CGRP receptor) decreased CGRP induced proliferation of DNA synthesis. Phosphorylation of ERK pathway was observed within 15 minutes and peaked in one hour. U0126 (inhibitor of ERK pathway) decreased CGRP induced proliferation of DNA synthesis.In vivo study, histological examination of the lung indicated proliferation of alveolar epithelial cells in the rhCGRP-treated group and the nuclei of alveolar epithelial cells were positive for PCNA immunostaining. CONCLUSION: In this study, we conclude that CGRP stimulates proliferation of human alveolar epithelial cells in vivo and in vitro.

Differential expression of EC-SOD, Mn-SOD and CuZn-SOD in rat lung exposed to crystalline silica.

Superoxide dismutases (SODs) are antioxidant enzymes that catalyze the dismutation of superoxide into hydrogen peroxide. There are 3 kinds of isozymes: extracellular superoxide dismutase (EC-SOD), manganese-containing superoxide dismutase (Mn-SOD) and copper- and zinc-containing superoxide dismutase (CuZn-SOD). To examine the expression of SOD isozymes in lungs injured by crystalline silica, we intratracheally instilled male Wistar rats with 2 mg (8 mg/kg) of crystalline silica and investigated the mRNA, protein level and distribution of SOD isozymes in the rat lungs using RT-PCR, western blot analysis and immunostaining, respectively at from 3 d to 180 d of recovery following the exposure. EC-SOD mRNA levels significantly increased from 3 d to 90 d and the EC-SOD protein level was significantly higher after 90 and 180 d recovery in the crystalline silica exposed groups than in the control groups. Mn-SOD increased in silica treated rat lungs at both mRNA and protein levels, peaking at 30 d post-exposure. CuZn-SOD mRNA levels were decreased at 3, 7 and 30 d, and CuZn-SOD protein levels were also significantly lower than the control group at 90 and 180 d recovery. There was prominent EC-SOD immunostaining mainly in the plasma and alveolar macrophages and strong Mn-SOD staining in alveolar macrophages and interstitial cells of the proximal and distal portions of the alveolar duct following crystalline silica exposure. There was less CuZn-SOD staining in epithelial cells at terminal bronchioles in the crystalline silica-exposed group. These findings suggest that these SOD isozymes may be related to lung injury induced by crystalline silica.

Calcitonin gene-related peptide (CGRP) as hazard marker for lung injury induced by dusts.

Calcitonin gene-related peptide (CGRP), which has a function as a growth factor of epithelial cells, is thought to play a role in pulmonary epithelium repair. In order to establish whether or not CGRP is associated with repair in lung damaged by dust, we examined gene expression of CGRP in the lungs of animal models exposed to different dusts. Male Wistar rats were administered 2 mg of crystalline silica, crocidolite, potassium octatitanate whisker (PT-1), and silicon carbide whisker (SiCW) suspended in saline by a single intratracheal instillation and were sacrificed at 3 d, 1 wk, 1 mo, 3 mo, and 6 mo of recovery time. Pathological findings of advanced pulmonary fibrosis were present in the rats exposed to crystalline silica and crocidolite through the experiment, whereas findings of mild or reversible pulmonary fibrosis were present in those exposed to SiCW and PT-1. The expression of CGRP in rat lung was observed by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme immunometric assay (EIA). In RT-PCR, CGRP gene expression was decreased at the interval of 3 d and 1 wk in the case of crystalline silica and crocidolite; on the other hand, it was increased at 3 d and 1 wk in SiCW and at 3 d, 1 wk, and 3 mo in PT-1-exposed rats. CGRP protein level in lungs exposed to PT-1 and SiCW was also higher than that to silica and crocidolite at 3 d of recovery time. These data suggest that CGRP is associated with repair in lung damaged by different dusts, and that CGRP could be used as a sensitive biomarker to indicate the pathogenicity of dusts.