Oxidation of 5,15-Dioxaporphyrin: Its Generality and Novelty as an Oxaporphyrin Analogue.

5,15-Dioxaporphyrin (DOP) is a novel meso-oxaporphyrin analogue and exhibits unique 20π-antiaromaticity, unlike its mother congener of 18π-aromatic 5-oxaporphyrin, commonly known as its cationic iron complex called verdohem, which is a key intermediate of heme catabolism. To reveal its reactivities and properties as an oxaporphyrin analogue, the oxidation of tetra-ß-arylated DOP (DOP-Ar4 ) was explored in this study. Stepwise oxidation from the 20π-electron neutral state was achieved, and the corresponding 19π-electron radical cation and 18π-electron dication were characterized. Further oxidation of the 18π-aromatic dication resulted in the formation of a ring-opened dipyrrindione product by hydrolysis. Considering a similar reaction of verdoheme to ring-opened biliverdin in the heme degradation in nature, the current result consolidates the ring-opening reactivity of oxaporphyrinium cation species.

Rational Synthesis of Antiaromatic 5,15-Dioxaporphyrin and Oxidation into ß,ß-Linked Dimers.

5,15-Dioxaporphyrin was synthesized for the first time by a nucleophilic aromatic substitution reaction of a nickel bis(α,α'-dibromodipyrrin) complex with benzaldoxime, followed by an intramolecular annulation of the α-hydroxy-substituted intermediate. This unprecedented molecule is a 20π-electron antiaromatic system, in terms of Hückel's rule of aromaticity, because lone pair electrons of oxygen atoms are incorporated into the 18π-electron conjugated system of the porphyrin. A theoretical analysis based on the gauge-including magnetically induced current method confirmed its antiaromaticity and a dominant inner ring pathway for the ring current. The unique reactivity of 5,15-dioxaporphyrin forming a ß,ß-linked dimer upon oxidation was also revealed.

Cytomegalovirus infection during immunosuppressive therapy for diffuse parenchymal lung disease.

BACKGROUND AND OBJECTIVE: Cytomegalovirus (CMV) infection is a life-threatening condition in patients with diffuse parenchymal lung diseases (DPLDs), who are receiving immunosuppressive therapy. The aim of this study was to describe the clinical features of CMV infection and to propose a strategy for managing CMV infection in patients with DPLD who are receiving immunosuppressive therapy. METHODS: A retrospective longitudinal observational study was performed on 69 patients with DPLDs (39 with acute/subacute onset, 30 with chronic onset) who were receiving immunosuppressive therapy and were positive for CMV pp65 antigen (CMV-pp65Ag) in peripheral blood leukocytes (PBLs). RESULTS: Clinical CMV disease and subclinical CMV antigenaemia developed in 23 and 46 patients, respectively. The cut-off level of CMV-pp65Ag indicating clinical CMV disease, as determined by receiver operator characteristic curve analysis, was 7.5 cells per 5 × 10(4) PBLs. Multivariate analysis revealed that early CMV infection was associated with acute/subacute onset of underlying DPLD and with respiratory dysfunction at the commencement of immunosuppressive therapy. Multivariate analysis also suggested that the acute/subacute onset of underlying DPLD, a CMV-pp65Ag titre of >7.5 cells per 5 × 10(4) PBLs, and C-reactive protein levels ≥ 10 mg/L indicated a poor prognosis. CONCLUSIONS: We recommend that CMV-pp65Ag antigenaemia of >7.5 cells per 5 × 10(4) PBLs in patients with DPLD should be treated with ganciclovir. Patients with lower levels of CMV-pp65Ag antigenaemia should be closely monitored or treated with ganciclovir if the clinical findings suggest a poor prognosis.

[Multidisciplinary assessment of effects, safety and procedure of whole lung lavage for 8 patients with autoimmune pulmonary alveolar proteinosis].

We treated 8 cases of autoimmune pulmonary alveolar proteinosis (APAP) with whole lung lavage (WLL) in our hospital and evaluated the disease severity of APAP before and after WLL, adverse events (AEs) and recurrence-free survival in those cases who improved. In all cases, unilateral WLL was performed in both lungs. The median of total lavage volume in unilateral WLL was 17.9 L, and the median procedure time of unilateral WLL was 105 min. Fever was the most frequently observed AE (87.5% of all procedures). Pulmonary function tests (percentage of predicted value of VC, FEV1 and diffusing capacity of carbon monoxide), serum markers (KL-6, surfactant apoprotein (SP)-D, SP-A and carcinoembryonic antigens), arterial blood gas analyses (PaO2, AaDO2) and disease severity score all significantly improved after WLL. The serum levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody temporarily decreased after unilateral WLL, but returned to previous levels (before WLL) in 7 cases. The radiological findings improved in 6 cases. In the 7 improved cases in whom AaDO2 decreased more than 10 Torr, the median recurrence-free survival of APAP after WLL was 17.5 months. We concluded that WLL is an effective and safe method for the treatment of APAP, and all parameters except for anti GM-CSF antibody are useful to evaluate the effect of WLL.

[A case of tuberculosis pleuritis developing contralateral pleural effusion during anti-tuberculosis chemotherapy, falling into chronic respiratory failure].

The patient was a 74 year-old male presenting right pleural effusion with mild fever. His temperature was 37.0 degrees C. Culture of a pleural biopsy specimen revealed Mycobacterium tuberculosis, although culture of sputum and pleural effusion were negative. Therapy was begun with 300 mg of isoniazid (INH) per day, 600 mg of rifampicin (RFP) per day, and 1200 mg of pyrazinamide (PZA) per day. His temperature improved temporarily. One week after beginning of the therapy he had a fever over 38.0 degrees C. On the 17th day after starting chemotherapy, a chest radiological examination showed left pleural effusion in which numerous lymphocytes were found but Mycobacterium tuberculosis was negative. We assumed that the left pleural effusion was due to a paradoxical reaction to the anti-tuberculosis chemotherapy. After 3 days' discontinuation, the same regimen was resumed with an addition of prednisolone, but bilateral pleural effusion remained and the case finally fell into chronic respiratory failure.