Kazuaki Nishio

Congestive heart failure is associated with the rate of bone loss

Abstract.  Nishio K, Mukae S, Aoki S, Itoh S, Konno N, Ozawa K, Satoh R, Katagiri T (School of Medicine Showa University, Hatanodai, Shinagawa‐ku, Tokyo, Japan). Congestive heart failure is associated with the rate of bone loss. J Intern Med 2003; 253: 439–446.

Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough: A meta-analysis

AIM To evaluate the association between genetic polymorphisms and angiotensin converting enzyme inhibitor (ACEI)-related cough, and the race- or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy. METHODS We conducted a search in PubMed, EMBASE, Cinahl, and the Cochrane Database without language limitation. A database of 11 studies on ACEI-related cough, with detailed information regarding ACE I/D or bradykinin B(2) receptor polymorphisms, was created. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. A subgroup analysis was also performed using ethnicity. RESULTS Six studies were included on ACE I/D polymorphism (398 Caucasians, 723 East Asians), and three studies were included on bradykinin B(2) receptor polymorphism (300 East Asians). The distribution of ACE genotypes showed significant differences in the entire population (P = 0.004) and in East Asians (P = 0.005) but not in Caucasians (P = 0.23). Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR) = 1.49 (1.11-2.02)]. The meta-analysis with a random effects model showed a significant association between ACE allele I/D and ACEI-related cough [random effects (RE) OR = 1.49 (1.11-2.02), P = 0.009] in East Asians, but not in Caucasians [RE OR = 0.90 (0.60-1.35)]. The allelic frequencies of the bradykinin B(2) receptor gene were significantly different [OR = 2.25 (1.42-3.57)]. The distributions of the T/C genotypes of the bradykinin B(2) receptor gene were significantly different (χ(2) = 8.366, P = 0.015). The meta-analyses revealed that there was a significant association between the bradykinin B(2) receptor allele and ACEI-related cough in East Asians [RE OR = 2.29 (1.42-3.69), P = 0.001]. CONCLUSION ACE I/D and Bradykinin B(2) receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians, but a negative association between ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

Comparison of bare metal stent with pioglitazone versus sirolimus-eluting stent for percutaneous coronary intervention in patients with Type 2 diabetes mellitus☆

BACKGROUND Drug-eluting stents (DESs) have been shown to decrease restenosis as compared with bare-metal stents. Recently, thiazolidinediones effectively reduced restenosis and the risk of repeat target vessel revascularization. We conducted a study to compare the performance of a DES with that of a bare-metal stent with pioglitazone in patients with Type 2 diabetes mellitus (DM). METHODS The study was a prospective cohort trial involving 38 Type 2 diabetic patients referred for coronary stenting who were assigned to either the sirolimus-eluting stent (SES) group or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months of follow-up to evaluate in-stent late luminal loss and the percentage of the luminal diameter and the rate of restenosis. We also analyzed major adverse cardiac events (MACE) at 12 months. RESULTS There were no significant differences in glycemic control levels or in lipid levels in the two groups at follow up. The insulin and homeostasis model assessment insulin resistance at follow-up were significantly lower in the pioglitazone group than in the SES group. The percentage of restenosis was similar between the SES group and the pioglitazone group. The incidence of MACE at 1 year tended to be lower in the pioglitazone group than in the SES group. CONCLUSIONS The bare-metal stent with pioglitazone is not inferior to the SES in the present study and is one of therapeutic strategies of percutaneous coronary intervention for patients with DM.

The effect of pioglitazone on nitric oxide synthase in patients with type 2 diabetes mellitus.

The aim of this study was to evaluate the effect of pioglitazone on nitric oxide in patients with type 2 diabetes and coronary artery disease. Twenty-seven patients with coronary artery disease and diabetes mellitus who had received coronary stenting were eligible for the study. They were assigned to the no insulin resistance (NIR) group, the insulin resistance (IR) group, and the pioglitazone group (30 mg once a day). Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), interleukin-6, leptin, and adiponectin were measured. In the pioglitazone group, eNOS, iNOS, and leptin were significantly lower and adiponectin was significantly higher than those in the IR group. Stepwise multiple regression analyses showed that eNOS correlated with TNF-alpha and iNOS correlated with leptin and TNF-alpha. Leptin was the strongest predictor of iNOS. Treatment with pioglitazone significantly reduced eNOS and iNOS by improving adipocytokine levels.

Different effects of thiazolidinediones on target vessel revascularization with bare metal stents: a meta-analysis

OBJECTIVE Thiazolidinediones (TZDs) are used in patients with Type 2 diabetes mellitus, but evidence is mixed regarding the influence of medications of this class on target vessel revascularization. The aim of this meta-analysis is to evaluate the effect of TZDs on repeat target vessel revascularization following percutaneous coronary intervention. RESEARCH DESIGN AND METHODS We searched Medline, EMBASE, Cinahl, and the Cochrane Database from earliest available date through December 2007. Criteria for inclusion in our meta-analysis included the use of randomized control trial and the availability of target vessel revascularization. Relative risks (RRs) with 95% confidence intervals (CIs) of target vessel revascularization (TVR) and restenosis were estimated using a fixed-effects meta-analysis of seven randomized controlled trials (n=347, including 178 receiving pioglitazone and 169 receiving rosiglitazone). RESULTS One hundred seventy-eight patients were treated with pioglitazone, and 169 were treated with rosiglitazone. Pioglitazone is associated with a significantly lower risk of target vessel revascularization or restenosis (TVR: n=37/96 vs. 7/94; RR, 5.91; 95% CI, 3.00-11.7; P<.0001, restenosis: n=42/96 vs. 8/94; RR, 6.48; 95% CI, 3.37-12.4; P<.0001). Rosiglitazone had no effect on target vessel revascularization (n=56/131 vs. 51/124; RR, 1.11; 95% CI, 0.63-1.96; P=.793). CONCLUSIONS Pioglitazone is associated with a significantly decreased risk of target vessel revascularization, but rosiglitazone does not reduce the risk of target vessel revascularization following percutaneous coronary intervention.

Interferon related pericarditis: Review

AIM To conduct a review of “interferon related pericarditis”. METHODS We searched MEDLINE, EMBASE, Cinahl, and the Cochrane Database from the earliest available date through September 2016. A search strategy using the Medical Subject Headings and text keywords “interferon” and ”pericarditis” were used. RESULTS Nine case reports were eligible for the present study. Six of 8 cases were women and the mean age was 43.8 ± 13.8 years with chronic hepatitis C in 6 cases, malignant melanoma in 2 cases and chronic myelogenous leukemia in 1 case. The patients complained of chest pain in 6 cases, dyspnea in 5 cases and edema in 2 cases. Pericardial friction rub was heard in 3 of 9 cases. Congestive heart failure occurred in 3 of 9 cases. Two mechanisms for pericarditis were demonstrated, one is autoimmune included lupus like syndrome in 2 cases and the other is cardio toxicity in 4 cases. Treatment of interferon related pericarditis is discontinuation of Interferon treatment. Four of 9 cases were treated with prednisone and 4 with nonsteroidal anti-inflammatory drugs. CONCLUSION Interferon related pericarditis still remains uncertain. Treatment of interferon related pericarditis rests mainly on early recognition and drug discontinuation. Interferon related pericarditis was treated with steroid and/or nonsteroidal anti-inflammatory drugs.

Three-year clinical outcome in type 2 diabetic patients with drug-eluting stents versus bare-metal stents with pioglitazone.

AIMS The aim of this study was to examine outcome subsequent to implantation of bare-metal stents (BMS) with pioglitazone, which are novel insulin-sensitizing agents, and drug-eluting stents (DES) in patients with diabetes. METHODS AND RESULTS A total of 139 consecutive Type 2 diabetic patients treated with stent were followed up for 3 years. Data on death, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis were ascertained from January 2003 to January 2006. Eighty-nine patients were treated with a BMS with pioglitazone, and 50 patients were treated with a DES. The incidence of MI was 1.1% in the BMS with pioglitazone group, 4.0% in the DES group [relative risk RR):0.52; 95% CI: 0.10-2.56]. The incidence of TLR was 22.5% in the BMS with pioglitazone group, 28.0% in the DES group (RR 0.89; 95% CI: 0.65-1.22). The incidence of stent thrombosis was 1.0% in the BMS with pioglitazone group, 4.0% in the DES group (RR 0.52; 95% CI: 0.10-2.56). Overall 3-year mortality was similar in the two groups (RR 0.77; 95% CI: 0.34-1.74). CONCLUSIONS During 3 years of follow-up, patients treated with BMS with pioglitazone had similar risks of death, TLR, MI, and stent thrombosis compared with patients treated with DES.

Oxygen Consumption and Mitochondrial Membrane Potential in Postischemic Myocardium

Oxygen consumption may be disproportionately high relative to contractile function in postischemic reperfused myocardium. The study reported in this chapter investigated the mechanism of the dissociation between oxygen consumption and contractile function in postischemic reperfused myocardium using isolated rat hearts. Mitochondrial dysfunction secondary to increased calcium uptake has been implicated as an important mediator of reperfusion injury in the heart. In postischemic, isovolumic, antegrate-perfused rat hearts, the myocardial oxygen consumption rate (MVO2) and contractile function were studied in relation to mitochondrial function. Left ventricular pressure, coronary blood flow, and oxygen consumption were determined. Mitochondrial respiration and the mitochondrial membrane potential were measured by polarography and flow cytometry, respectively. To examine the role of mitochondrial calcium uptake in ischemia reperfusion injury, isolated rat hearts perfused with ruthenium red, which inhibits calcium uptake by mitochondria, were compared to control perfused hearts. After stabilization, hearts were subjected to 60 minutes of no-flow ischemia, followed by 60 minutes of reperfusion. At 15 minutes after the onset of reperfusion, there was poor recovery of left ventricular developed pressure to 64% of the control level, but myocardial oxygen consumption was increased to 134% of control. The addition of 2.5 μM ruthenium red to the perfusate resulted in a decrease of myocardial oxygen consumption. The oxygen consumption rate in state 3 of mitochondria decreased similarly following reperfusion in control and ruthenium red hearts. The mitochondrial membrane potential was reduced to 89% (logarithmic scale) after 15 minutes of reperfusion and then returned to preischemic level. These data suggest that the dissociation between oxygen consumption and contractile function following early reperfusion is partly caused by the repair of intracellular damage resulting from calcium accumulation to mitochondria.

Production of Hydrogen Peroxide During Hypoxia-Reoxygenation in Isolated Myocytes

Active oxygen species, including hydrogen peroxide (H2O2), have been implicated in myocardial reperfusion injury. Recently, spin-trap agents and biochemical techniques applied to intact hearts have shown that H2O2 is generated by leukocytes, by endothelial cells, and by mitochondria in myocytes. In this study, we used electron microscopy and the cerium (Ce) method to histologically investigate H2O2 formation during hypoxia—reoxygenation and its toxic effects on myocardium. This Ce method involves the formation of an electron-dense precipitate when H2O2 reacts with cerium chloride (CeCl3). Single myocytes were obtained from rat hearts by the collagenase method. Isolated myocytes were reoxygenated for 15 minutes after 30 minutes of hypoxia. Digitonin and CeCl3, were added to make cell membranes permeable and to detect intracellular H2O2 by electron microscopy. In the control group, the ultrastructure was well preserved and no dense deposits were found in myocytes. However, in the hypoxia—reoxygenation group, precipitates, which were cerium—H2O2 reaction products, were found along swollen mitochondria. Moreover, in the hypoxia-reoxygenation group, cell viability was reduced to 72% of control. These results indicate that H2O2 is generated by mitochondria and that its relese into cytosol may lead to myocyte death during hypoxia—reperfusion.