Two patients with bepridil-induced interstitial pneumonia.

Two patients developed bepridil-induced interstitial pneumonia during treatment of arrhythmia. The first patient was a 69-year-old man who received bepridil to maintain sinus rhythm in atrial fibrillation and who developed dyspnea on the 20th day after administration. The second patient was a 72-year-old man who received bepridil for paroxysmal atrial fibrillation and who developed dyspnea on the 60th day after administration. They were diagnosed with interstitial pneumonia on the basis of physical and imaging findings. The first patient was discharged after steroid pulse therapy, and the second patient after improvement of physical and imaging findings when bepridil was discontinued. Although a limited number of cases of bepridil-induced interstitial pneumonia have been reported, the disorder should be kept in mind as an important adverse reaction when breathlessness or dyspnea develops during administration of the drug.

A first trial in the clinical application of photodynamic therapy for the prevention of restenosis after coronary-stent placement.

BACKGROUND AND OBJECTIVES: The aim of this clinical study was to evaluate the safety of local delivery of a photosensitizer followed by photodynamic therapy (PDT), to determine its effectiveness in reducing in-stent restenosis. STUDY DESIGN/PATIENTS AND METHODS: Porfimer sodium was administered via a local delivery catheter to five coronary-stent implanted lesions followed by irradiation with a pulse laser. Coronary angiography (CAG) was performed at the baseline, after the procedure and at a 6-month follow-up. RESULTS: By the 18-month clinical follow-up, no adverse events such as photodermatosis, or myocardial ischemia had occurred. At the follow-up, no coronary embolization, dissection, or aneurysmal dilatation was observed in the CAG. In-stent diameter stenosis, late loss, and loss index were 19.16+/-8.20%, 0.37+/-0.18 mm, and 0.19+/-0.12, respectively. No in-stent restenosis was observed. CONCLUSIONS: This study suggests that PDT, with local delivery of Porfimer sodium, is safe and may be a feasible technique in preventing in-stent restenosis.

Cerivastatin-induced apoptosis of human aortic smooth muscle cells through partial inhibition of basal activation of extracellular signal-regulated kinases.

BACKGROUND: The beneficial effects of cerivastatin including hypolipidemic properties have been demonstrated to involve nonlipid as well as lipid mechanisms. In the present study, we examined the mechanisms underlying cerivastatin-induced growth inhibition of human aortic smooth muscle (ASM) cells. METHODS: Human ASM cells were cultured in 96-well plates with or without cerivastatin in the presence or absence of mitogen-activated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase MEK1/MEK 2 inhibitor PD98059. Cell growth was assessed by colorimetric quantitation of NADH, and cell viability was determined by trypan blue dye exclusion method. The induction of apoptosis was determined by propidium iodide (PI) staining method using flow cytometer. The activation of ERKs or c-Jun N-terminal kinases (JNKs) was determined by Western blotting using antibodies (Abs) specific for phospho-ERKs or phospho-JNKs. RESULTS: Treatment of the ASM cells with cerivastatin prevented cell growth in a concentration-dependent manner through at least induction of apoptosis. The cerivastatin-induced apoptosis was reversed by coincubation with isoprenoid [mevalonate, geranylgeranyl pyrophosphate (GGPP), and farnesyl pyrophosphate (FPP)] suggesting a role for isoprenoid in the cerivastatin-induced apoptosis. The cerivastatin cooperated with a MEK1/MEK2 inhibitor PD98059 to induce apoptosis, which appeared to correlate with down-regulation of ERK activation (phospho-ERKs expression) induced by the combination. CONCLUSION: Cerivastatin-induced blockade of ERK activation in ASM cells might result in growth inhibition including apoptosis, which might explain some aspects of the beneficial effects of cerivastatin on coronary artery disease.