Angiotensin type 1 receptor blocker reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice

The interactions between the renin-angiotensin system and neovascularization in atherosclerotic plaque development are unclear. We investigated the effects of angiotensin II type 1 receptor antagonism in the pathogenesis of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice with a special focus on plaque neovascularization. ApoE(-/-) mice fed a high-fat diet were randomly assigned to 1 of 2 groups and administered vehicle or olmesartan for 12 weeks. Quantification of plaque areas at the aortic root and in the thoracic and abdominal aorta revealed that, in all 3 of the regions, olmesartan reduced intimal neovessel density and the mRNA levels of toll-like receptor (TLR) 2 and TLR4. Olmesartan increased the levels of collagen and elastin, reduced the level of macrophages in the aortic root, and reduced the mRNA and the activity of matrix metalloproteinase (MMP) 2 in aortic roots and thoracic aortas. Aortic ring assay revealed that olmesartan-treated ApoE(-/-) mice had a markedly lower angiogenic response than that of untreated ApoE(-/-) mice. Bone marrow-derived endothelial progenitor cell-like c-Kit(+) cells from olmesartan-treated ApoE(-/-) mice showed marked impairment of cellular functions and lower expression of TLR2/TLR4 and MMP-2 compared with those of untreated controls. MMP-2 deficiency reduced intimal neovessel density and atherosclerotic lesion formation. Olmesartan and small-interfering RNA targeting TLR2 reduced the levels of TLR2, and MMP-2 mRNA induced angiotensin II in cultured endothelial cells. Angiotensin II type 1 receptor antagonism appears to inhibit intimal neovascularization in ApoE(-/-) mice, partly by reducing TLR2/TLR4-mediated inflammatory action and MMP activation, thus decreasing atherosclerotic plaque growth and increasing plaque instability.     

Comparison of three-year clinical outcomes after sirolimus-eluting stent implantation among insulin-treated diabetic, non-insulin-treated diabetic, and non-diabetic patients from j-Cypher registry

The purpose of the present study was to evaluate the 3-year clinical outcomes after percutaneous coronary intervention with sirolimus-eluting stents in patients with insulin-treated diabetes mellitus (DM-insulin) and those with non-insulin-treated DM (DM-non-insulin) compared to patients without DM. Of 10,778 consecutive patients treated exclusively with sirolimus-eluting stents in the j-Cypher registry, we identified 996 patients with DM-insulin, 3,404 with DM-non-insulin, and 6,378 without DM. Compared to the non-DM group, the adjusted risk of a serious cardiovascular event (composite of all-cause death, myocardial infarction, and stroke) was significantly greater in the DM-insulin group (hazard ratio 1.12, 95% confidence interval [CI] 1.03 to 1.23; p = 0.01), but not in the DM-non-insulin group (hazard ratio 1.02, 95% CI 0.96 to 1.09; p = 0.47). The adjusted risk of target lesion revascularization was significantly greater in both the DM-insulin group (odds ratio 1.52, 95% CI 1.19 to 1.92; p = 0.0006) and the DM-non-insulin group (odds ratio 1.24, 95% CI 1.05 to 1.45; p = 0.009). In conclusion, a diabetes-associated excess risk of target lesion revascularization was found, regardless of insulin use in this large, real-world study of Japanese patients with sirolimus-eluting stent implantation. However, regarding serious cardiovascular events, an excess risk was seen only in the DM-insulin group. The risk of serious cardiovascular events was similar between the DM-non-insulin and non-DM groups.     

Effect of mosapride on glycemic control and gastric emptying in type 2 diabetes mellitus patients with gastropathy

Delay of gastric emptying is one of the factors responsible for unfavorable glycemic control. We investigated the possible effects of mosapride, a digestive tract prokinetic agent, on glycemic control in diabetic patients complicated with gastropathy. Enrolled were 36 type II diabetic patients presenting with mild digestive tract symptoms. They were given mosapride 15 mg per day for 6 months. Seventeen cases were subjected to gastric emptying test according to marker method (administration of a capsule containing 20 pieces of radiopaque marker during breakfast, followed by abdominal X-ray imaging 3 and 5 h later). In 18 cases, HbA(1C) was improved by more than 0.3% for 6 months, whereby these 18 cases were defined as the improvement group. The remaining 18 cases were defined as the non-improvement group. In the gastric emptying study, basal number of the residual markers before administration of mosapride was determined 3 and 5 h later to show 18.3+/-1.8 and 7.6+/-5.1, respectively, in the improvement group while after administration, they were reduced down to 11.2+/-5.1 and 1.4+/-2.5, respectively. In sharp contrast, the basal counterparts in the non-improvement group were 19.1+/-1.5, and 16.4+/-3.4, respectively, whereas administration failed to reduce the number of the residual markers and they remained to be as high as 19.0+/-1.4 and 11.1+/-6.4, respectively. Gastric motility in the improvement group was much more improved by mosapride administration relative to those in the non-improvement group. Mosapride might elicit improvement in the glycemic control in the patients with diabetic gastropathy.     

Progressive nature of paroxysmal atrial fibrillation. Observations from a 14-year follow-up study.

BACKGROUND: Atrial fibrillation (AF) is believed to occur first as paroxysmal, then be gradually perpetuated, and finally become chronic as the end result. However, this presumed clinical course has not been well confirmed. METHODS AND RESULTS: The clinical course of recurrent paroxysmal AF (PAF) from its onset was examined in 171 patients (mean follow-up period: 14.1+/-8.1 years). This study population consisted of patients with no structural heart disease (n=88), ischemic heart disease (n=28), dilated or hypertrophic cardiomyopathy (n=17), valvular heart disease (n=35) or other cardiac diseases. The mean age at the onset of AF was 58.3 +/-11.8 years old. During the mean follow-up period of 14.1 years, PAF eventually developed into its chronic form in 132 patients under conventional antiarrhythmic therapy (77.2%, 5.5% of patients per year). The independent factors for early development into chronic AF were aging (hazard ratio (HR) 1.27 per 10 years, 95% confidence interval (CI) 1.06-1.47)), dilated left atrium (HR 1.39 per 10 mm, 95% CI 1.11-1.69), myocardial infarction (HR 2.33, 95% CI 1.13-4.81), and valvular diseases (HR 2.29, 95% CI 1.22-4.30). CONCLUSIONS: The present long-term observations definitely and quantitatively revealed the progressive nature of PAF.     

Identification of lipomatous metaplasia in old infarcted myocardium by cardiovascular magnetic resonance and computed tomography

Epididymitis, as an unusual side-effect of amiodarone use, in a patient with dilated cardiomyopathy is reported along with a pertinent literature review. The diagnosis was one of exclusion after the patient received several regimens of antimicrobials and was only established after a dose reduction of the amiodarone regimen. Cardiologists should be aware of this rare but existing side effect of amiodarone, in order promptly intervene with dose adjustment or discontinuation of amiodarone and to avoid prolonged use of unnecessary antimicrobial regimens.     

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).     

Combined use of electrosurgical incisions and balloon dilatation for the treatment of refractory postoperative pyloric stenosis

BACKGROUND: Drug therapy plus balloon dilatation without gastroscopic incision does not always relieve postoperative pyloric stenosis. METHODS: Five patients with postoperative pyloric stenosis whose symptoms did not improve with drug therapy and balloon dilatation underwent a combination of gastroscopic incision and balloon dilatation. Two or 3 small radial incisions were made in the stenotic muscle of the pylorus electrosurgically at gastroscopy. Then the stenotic muscle layer was loosened and split bluntly along the incisions with balloon dilatation for 15 to 20 minutes. One week later, the combination procedure or balloon dilatation alone was repeated to prevent restenosis. RESULTS: In the 5 patients, the stenosis was improved with the combination therapy. No complications were observed. CONCLUSIONS: Combined use of gastroscopic incision and balloon dilatation may be considered for patients with refractory pyloric stenosis caused by surgical truncal vagotomy.