Control of chromophore symmetry by positional isomerism of peripheral substituents.

The first example of the control of porphyrinoid chromophore symmetry based on the positional isomerism of peripheral substituents has been achieved by preparing tetraazaporphyrins (TAPs) with C(4h), D(2h), C(2v), and C(s) symmetry due to the relative arrangement of peripheral tert-butylamino and cyano groups as push and pull substituents, respectively. The four structural isomers were successfully isolated and characterized by (1)H NMR spectroscopy and X-ray crystallography. The band morphology in the Q-band region varies depending on the molecular symmetry due to the significant perturbation introduced into the chromophore by the push and pull substituents. The C(4h) and C(2v) isomers exhibit a single Q band, whereas the Q bands of the D(2h) and C(s) isomers show a marked splitting. The magnetic circular dichroism spectra indicate that the push-pull TAPs retain the properties of the 16-membered 18π-electron perimeter generally observed for porphyrinoids. Theoretical calculations have demonstrated that the perturbation introduced by the substituents lowers the D(4h) symmetry of the parent TAP π-conjugated system, and this results in significant spectral changes. A novel approach to the fine-tuning of the spectral properties of porphyrinoids based on changes in the chromophore symmetry is described.

ß2-adrenergic receptor haplotype may be associated with susceptibility to desensitization to long-acting ß2-agonists in COPD patients.

PURPOSE: Τhat ß2-adrenergic receptor (ß2AR) haplotypes may play a key role in clinical response to ß2-agonists and haplotype Cys-19Gly16Gln27 (CysGlyGln) is reported to be associated with desensitization of ß2AR to ß-agonists in lymphocytes isolated from patients with asthma and septic shock. We sought to determine whether haplotypic variation of the ß2AR affects the functional outcomes of long-acting ß2-agonist (LABA) treatment for chronic obstructive pulmonary disease (COPD) when used as monotherapy. METHODS: Treatment-naïve patients with COPD (n = 36) were prospectively treated with two kinds of LABA--inhaled salmeterol and transdermal tulobuterol patch--for 12 weeks in crossover study, and changes in pulmonary function data and 6-minute walk distance (6 MWD) were compared between groups stratified by the CysGlyGln. RESULTS: Frequencies of haplotype and diplotype for the CysGlyGln were 0.51 and 0.36, respectively. The individuals homozygous for CysGlyGln showed less improvement in FEV(1), %FEF(25-75 %), and IC/TLC than those with 0 or 1 copy of CysGlyGln after treatment with both LABAs despite initial bronchodilator responses to albuterol being similar in these groups. The response in these parameters was not significantly different between two types of LABA. Overall changes in 6 MWD in individuals with 2 copies of CysGlyGln versus 0 or 1 copy for salmeterol were 2.8 and 11 m, and for tulobuterol were -1.3 and 16 m, respectively. CONCLUSIONS: Homozygous haplotype for the CysGlyGln of ß2AR may be associated with susceptibility to desensitization to LABA in patients with COPD.

Lower incidence of acute respiratory distress syndrome in community-acquired pneumonia patients aged 85 years or older.

UNLABELLED: Clinical variables and laboratory data were compared to elucidate the risk factors associated with the development of ARDS among elderly patients with community-acquired pneumonia (CAP). The predictors for ARDS appeared to differ from the determinants of severity of CAP. ARDS developed less frequently among patients aged>or=85 years. BACKGROUND AND OBJECTIVE: The incidence of and risk factors for ARDS among elderly patients with community-acquired pneumonia (CAP) have not been well characterized. METHODS: The clinical details of 221 consecutive patients aged>or=65 years, who were admitted with CAP during the period April 2006 to June 2008, were investigated by review of patient charts. Clinical variables and laboratory data at admission for CAP were compared between patients with and without ARDS. RESULTS: Eighteen patients (8.1%) developed ARDS 1-5 days after admission. The mortality rate was 44% in patients with ARDS and 10.3% in those without ARDS (P<0.001). The incidence of ARDS was 8.5-20% among patients aged<85 years and 1.1% in patients aged>or=85 years (P<0.001), while overall mortality rates were not significantly different among the age groups. Predictors for the development of ARDS included higher serum levels of CRP and glucose, lower PaO2/fraction of inspired O2 (FiO2), PaCO2 and HCO3-, and the presence of systemic inflammatory response syndrome at admission. ARDS developed less frequently among patients with pneumonia associated with oropharyngeal aspiration (AP). Multivariate analysis indicated that lower age, serum glucose, pre-existence of systemic inflammatory response syndrome and non-oropharyngeal AP were significant risk factors for ARDS. The Pneumonia Severity Index and confusion, urea, respiratory rate, blood pressure, age>or=65 score were not correlated with the incidence of ARDS. CONCLUSIONS: Predictors for ARDS appeared to differ from the determinants of severity of CAP in the elderly. ARDS developed less frequently in patients aged>or=85 years and in those with oropharyngeal AP. It is important to identify subjects at high risk for ARDS upon admission and to observe them closely.

ERC/mesothelin as a marker for chemotherapeutic response in patients with mesothelioma.

BACKGROUND: It has been recently reported that soluble mesothelin-related protein (SMRP), serum mesothelin, and osteopontin (OPN) are considered as relevant biomarkers for the diagnosis of mesothelioma. The aim of this study was to investigate whether serum N-ERC/mesothelin, an NH3-terminal fragment of mesothelin, and plasma OPN reflect chemotherapeutic effect in patients with mesothelioma. MATERIALS AND METHODS: Serum N-ERC/mesothelin and plasma osteopontin were determined with a sandwich enzyme-linked immunosorbent assay (ELISA) system. RESULTS: The average N-ERC ratio, determined by dividing the N-ERC levels following chemotherapy by those prior to chemotherapy, in the partial response (PR) group was significantly lower than that of the stable disease (SD)/progressive disease (PD) group. In contrast, the average OPN ratio, determined by dividing the OPN levels following chemotherapy by those prior to chemotherapy, in the PR group was not statistically different from that of the SD/PD group. CONCLUSION: N-ERC/mesothelin is considered as relevant in monitoring chemotherapeutic response in patients with mesothelioma.

[Evaluation of clinical effectiveness of Pazufloxacin Mesilate in acute exacerbation of chronic respiratory diseases].

Patients with chronic respiratory disease have increased susceptibility to infection, because of impairment of the local immunologic defense mechanism in the airway system, which often results in acute exacerbation. Acute exacerbation of chronic respiratory disease is one of the most important predictors of increased morbidity and mortality, and thus the management in the acute phase is essential for better prognosis. Although the clinical guidelines for the management of respiratory tract infections published by the Japanese Respiratory Society recommend administering fluoroquinolones intravenously in case of hospitalized patients, the clinical evidence is still limited. In this study, we evaluated the efficacy of Pazufloxacin Mesilate (PZFX). an intravenous fluoroquinolone. in patients with chronic respiratory diseases complicated with acute exacerbation caused by acute respiratory infections. As a result, 16 out of 18 cases were successfully treated with PZFX. No adverse event was observed during this study. These results may support the validity of administering intravenous fluoroquinolone in hospitalized patients with acute exacerbation caused by infections, as recommended by the Japanese Respiratory Society.

[A patient with pleural thickening of sarcoidosis].

We report a 51-year-old woman with characteristic pleural involvement of sarcoidosis. Video-assisted thoracoscopic examination identified diffuse pleural thickening in the right lung, which coincided in distribution with parenchymal reticular shadows demonstrated with high-resolution thoracic CT scan. Biopsied specimens revealed epithelioid cell granuloma with noncaseating necrosis and multi-nucleated giant cells in the parenchymal lung tissue. Infiltration of inflammatory cells was demonstrated in the thickened pleural tissue, but no typical sarcoid lesion. This pleural lesion was considered as pleural involvement of sarcoidosis, since deterioration of the pleural thickening was accompanied with progression of a parenchymal sarcoid lesion during the period of two months after biopsy. Video-assisted thoracoscopy and high-resolution CT scan both supported the diagnosis of sarcoidosis with pleural involvement.

Bronchial reversibility with a short-acting ß2-agonist predicts the FEV1 response to administration of a long-acting ß2-agonist with inhaled corticosteroids in patients with bronchial asthma.

A long-acting ß2-agonist (LABA) combined with an inhaled corticosteroid (ICS) is frequently prescribed as initial therapy in steroid-naïve asthma patients because of its effective control of symptoms and improvement of pulmonary function. However, it is unclear which patients will be responsive to LABAs and whether bronchial responsiveness to LABAs is similar to that to short-acting ß2-agonists (SABAs) in a clinical setting. Therefore, the goal of the present study was to compare the changes in spirometric parameters after SABA (salbutamol) inhalation to those after 1-month LABA/ICS (salmeterol/fluticasone propionate) therapy. Spirometric changes were evaluated as absolute values, as the percentage of predicted normal values and as the percentage of baseline values after salbutamol inhalation or 1-month LABA/ICS therapy in 45 patients with asthma. Compared to SABA inhalation, LABA/ICS therapy produced significant improvements in forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), forced expiratory flow at 50% of vital capacity expired (FEF50%) from baseline (expressed as the percentage predicted) in all patients. FEV1 and the FEV1/forced vital capacity (FVC) ratio after SABA or LABA/ICS therapy were inversely related to the corresponding baseline values. Analysis of spirometric changes after SABA inhalation showed that FEV1 was the best among spirometric parameters, such as PEF, correlated with responsiveness to LABA/ICS therapy. Reversibility of FEV1 with SABA inhalation predicts the spirometric response to LABA/ICS as initial therapy in patients with bronchial asthma. LABA/ICS therapy had a greater effect on bronchial reversibility in asthmatic patients, compared to SABA inhalation. This suggested that evaluation of bronchial reversibility after LABA/ICS therapy would be superior to that after SABA inhalation.

Two cases with solitary pulmonary nodule due to non-tuberculous mycobacterial infection showing intense 18F-fluorodeoxyglucose uptake on positron emission tomography scan.

We report an 81-year-old man and a 65-year-old woman with a solitary pulmonary nodule (SPN) due to infection with non-tuberculous mycobacteria (NTM). In each case, the nodule showed a high (18)F-fluorodeoxyglucose (FDG) uptake with the maximum standardized uptake values (SUV) of 13.2 and 4.8 on positron emission tomography (PET) imaging, respectively. Both cases required partial lung resection for confirmation of the histological diagnosis. A review of six reported patients with SPN due to NTM infections showed that the SUV of FDG was more than 4.0 in the nodules of all cases. Positive results on FDG-PET should be interpreted cautiously when evaluating SPN, especially in patients having predisposing factors for NTM infections.

A retrospective analysis of clinical outcomes of patients older than or equal to 80 years with small cell lung cancer.

INTRODUCTION: The optimal treatment for patients older than 80 years with small cell lung cancer (SCLC) is unknown. METHODS: A retrospective chart review was conducted for 45 patients aged 80 years or older with SCLC, and therapeutic indices and toxicities of anticancer treatment were compared with those of 38 patients aged 70 to 79 years. Subgroup analyses according to the levels of performance status (PS) and comorbidity were also performed. RESULTS: Twenty-four (53%) of the 45 patients underwent combination chemotherapy and/or thoracic radiotherapy, which resulted in significant survival benefit compared with those left untreated (p < 0.01). The main reasons for not administrating anticancer treatments were advanced age (>85 years), poor PS, and severe comorbidities. The average total chemotherapy dose delivered was 60% of the intended protocol dose. Median survival time and 1-year survival of the treated patients were 13.0 months and 57% for limited disease and 10.3 months and 40% for extensive disease, respectively. Despite a lower chemotherapy dose being administered, survival indices were similar to those of patients aged 70 to 79 years. Survival benefit was observed even in the treated patients with PS 2 to 3 or a moderate degree of comorbidity compared with those left untreated. The frequency of grade 3 to 4 hematologic toxicities was not significantly different between the two age groups. CONCLUSIONS: The standard chemotherapy regimen with or without thoracic radiotherapy seems to be feasible for patients older than 80 years with SCLC, even for those with PS 2 to 3 and/or moderate comorbidity, although frequent dose adjustment is necessary.

Curcumin suppresses increased bone resorption by inhibiting osteoclastogenesis in rats with streptozotocin-induced diabetes.

Curcumin is a potent inhibitor of the transcription factor activator protein-1 which plays an essential role in osteoclastogenesis. However, the effects of curcumin on bone metabolism have not been clarified in vivo. We reported herein the inhibitory effects of curcumin on the stimulated osteoclastic activity in insulin-dependent diabetes mellitus using rats with streptozotocin-induced diabetes. A dietary supplement of curcumin reversed the increase in levels of activity and mRNA of tartrate-resistant acid phosphatase (TRAP) and cathepsin K to control values. A histochemical analysis showed that the increase in TRAP-positive cells in the distal femur of the diabetic rats was reduced to the control level by the supplement. These results suggested that curcumin reduced diabetes-stimulated bone resorptive activity and the number of osteoclasts. When bone marrow cells were cultured with macrophage colony stimulating factor and receptor activator NF-kappaB ligand (RANKL), the increased activity to form TRAP-positive multinucleated cells and the increased levels of mRNA and protein of c-fos and c-jun in the cultured cells from diabetic rats decreased to control levels in the curcumin-supplemented rats. Similarly, the increased expression of c-fos and c-jun in the distal femur of the diabetic rats was significantly reduced by the supplement. These results suggested that curcumin suppressed the increased bone resorptive activity through the prevention of osteoclastogenesis associated with inhibition of the expression of c-fos and c-jun in the diabetic rats.

Pulmonary paragonimiasis with coincidental malignant mesothelioma.

A 72-year-old man patient was referred to our institution for evaluation and treatment of right pleural effusion. Eosinophilic pleural effusion and peripheral eosinophilia were identified during the course of hospitalization. Pulmonary paragonimiasis was confirmed by the presence of paragonimus-specific IgG antibodies for Paragonimus (P.) westermani and P. miyazakii in his serum. Although Praziquantel, a highly effective agent for the treatment of lung flukes was repeatedly administered, the pleural effusion did not subside and the patient's condition gradually deteriorated until his death due to circulatory insufficiency. Postmortem examination revealed malignant mesothelioma of the sarcomatous type encasing the right lung and heart. Cardiac involvement accompanied with old and recent-onset myocardial ischemic changes resulted in death of this patient. Here, we report a very rare case of malignant mesothelioma with a concomitant infection of parasitic lung fluke.