Metal-based nanoparticles: Promising tools for the management of cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of death worldwide. A search for more effective treatments of CVD is increasingly needed. Major advances in nanotechnology opened new avenues in CVD therapeutics. Owing to their special properties, iron oxide, gold and silver nanoparticles (NPs) could exert various effects in the management and treatment of CVD. The role of iron oxide NPs in the detection and identification of atherosclerotic plaques is receiving increased attention. Moreover, these NPs enhance targeted stem cell delivery, thereby potentiating the regenerative capacity at the injured sites. In addition to their antioxidative and antihypertrophic capacities, gold NPs have also been shown to be useful in the identification of plaques and recognition of inflammatory markers. Contrary to first reports suggestive of their cardio-vasculoprotective role, silver NPs now appear to exert negative effects on the cardiovascular system. Indeed, these NPs appear to negatively modulate inflammation and cholesterol uptake, both of which exacerbate atherosclerosis. Moreover, silver NPs may precipitate bradycardia, conduction block and sudden cardiac death. In this review, we dissect the cellular responses and toxicity profiles of these NPs from various perspectives including cellular and molecular ones.

Integrating Bioinformatics Strategies in Cancer Immunotherapy: Current and Future Perspectives.

For the past few decades, the mechanisms of immune responses to cancer have been exploited extensively and significant attention has been given into utilizing the therapeutic potential of the immune system. Cancer immunotherapy has been established as a promising innovative treatment for many forms of cancer. Immunotherapy has gained its prominence through various strategies, including cancer vaccines, monoclonal antibodies (mAbs), adoptive T cell cancer therapy, and immune checkpoint therapy. However, the full potential of cancer immunotherapy is yet to be attained. Recent studies have identified the use of bioinformatics tools as a viable option to help transform the treatment paradigm of several tumors by providing a therapeutically efficient method of cataloging, predicting and selecting immunotherapeutic targets, which are known bottlenecks in the application of immunotherapy. Herein, we gave an insightful overview of the types of immunotherapy techniques used currently, their mechanisms of action, and discussed some bioinformatics tools and databases applied in the immunotherapy of cancer. This review also provides some future perspectives in the use of bioinformatics tools for immunotherapy.

[Silent myocardial ischemia in diabetics--by treadmill exercise testing].

We examined silent myocardial ischemia in diabetics by treadmill exercise testing. There were 28 diabetic men and 64 diabetic woman without angina, with a mean age of 59 +/- 11 years. Symptom-limited treadmill exercise testing was performed, and we used the electrocardiogram during exercise and immediately after exercise for judgement. ST segment depression was defined as positive if there was at least 0.1 mV of ST depression 80 ms from the J point. It was defined as negative if max heart rate (HR) was more than 80% of target HR and there was no significant ST depression. It was defined as equivocal if there was no significant ST depression but max HR was less than 80% of target HR. In 92 diabetics, 21 patients (23%) showed positive ST depression, 35 (38%) showed negative ST depression, 36 (39%) showed equivocal ST depression. In 56 diabetics exclusive of treadmill equivocal patients, 38% of patients showed positive ST depression. Treadmill positive diabetics had a significantly higher rate of smokers, patients with hypertension, and a higher triglyceride level as compared with treadmill negative diabetics. Coronary arteriography, which was performed in six treadmill positive diabetics, revealed coronary stenosis of more than 75% in four patients.

[Clinical evaluation of coronary artery fistula and coronary artery-cardiac chamber shunt].

Coronary artery fistula and coronary artery-cardiac chamber shunts were observed in 16 cases out of 462 consecutive cases in which coronary angiography was performed. 9 of these cases had coronary artery fistula, 5 of the cases had coronary artery-cardiac chamber shunts. 2 cases had both of these conditions. Coronary artery fistula has a draining vein originating from the coronary artery and an entering vein terminating in the cardiac chamber or the pulmonary artery. Coronary artery-cardiac chamber shunts have no such veins, and contrast material used in the injection phase of coronary angiography escapes directly into the cardiac chamber. 2 cases of coronary artery fistula, 2 cases of coronary artery-cardiac chamber shunts, and 1 case involving the both of these conditions showed positive results in submaximal exercise tolerance tests, and no significant arteriosclerotic changes in the coronary artery. These factors lead us to suggest that coronary artery-cardiac chamber shunts cause cardiac ischemia for the same reason that coronary artery fistula does.

[A case of coronary artery fistula with angina pectoris].

A case of coronary artery fistula with myocardial ischemia is reported. A 57-year-old-man was admitted to our hospital complaining of anterior chest pain on exertion. Submaximal Treadmill exercise showed the depression of ST segment in leads II, III, aVF, V5 and V6. 75% stenosis of right coronary artery (segment 2) and congenital coronary artery fistula originating from both the right and left coronary arteries were demonstrated by the coronary arteriography. One abnormal artery was originated from proximal portion of the right coronary artery (segment 1) and entered the pulmonary artery trunk. Another one was originated from proximal portion of the left coronary artery and terminated in angiomatous plexus which then communicated with the pulmonary artery trunk. We speculate that myocardial ischemia resulted from decreased right coronary blood flow due to coronary steal and proximal organic stenosis of right coronary artery. Recently, the reviews of coronary artery fistula are increasing, but coronary artery fistula with myocardial ischemia is relatively rare. This case was followed with medical therapy, because antianginal agents were effective. Operative coronary ligation may be necessary, if he has angina or high output heart failure during follow-up.

[Diagnosis and estimation of mitral regurgitation by two-dimensional pulsed Doppler echocardiography].

The sensitivity and specificity of detecting and estimating mitral regurgitation were assessed by two-dimensional pulsed Doppler echocardiography (PDE) for 85 patients, aged 17 to 79 years. Mitral regurgitation was clinically diagnosed in 10 patients, and confirmed by angiography in 60 patients. Using real time two-dimensional images and M-mode displays, the sample volumes were taken at 36 sites, including the mitral ostium, the left atrium, and the left ventricular inflow tract. Doppler signals were analyzed by the FFT method and the diagnosis of mitral regurgitation was based on the systolic turbulence with a wide range of velocities greater than +/- 1 KHz. The results obtained were as follows: In 61 of 70 cases with mitral regurgitation, distinctly abnormal systolic Doppler signals were detected at the mitral ostium or within the left atrium, which were not recorded in the other 15 cases without angiocardiographically documented mitral regurgitation. The signals had either unidirectional or bidirectional wide frequency-band patterns, which were thought to indicate the systolic turbulence caused by mitral regurgitation, because these were occasionally recorded beyond the second heart sound, and increased with the administration of methoxamine and diminished after the inhalation of amyl nitrite. When mitral regurgitation was graded I degree, II degree, III degree and IV degree based on Sellers' classification, a PDE sensitivity for detecting mitral regurgitation was 78.1, 89.5, 100 and 100%, respectively. When approaches were divided by the parasternal long-axis, parasternal short-axis and apical long-axis, a PDE sensitivity was 80.0, 74.2, and 70.0%, respectively. The PDE was highly sensitive in diagnosing mitral regurgitation due to rheumatic valvular disease, mitral valve prolapse or ruptured chordae tendineae (sensitivity 100%), but it was less sensitive in ischemic heart disease, dilated cardiomyopathy or hypertrophic cardiomyopathy. Nine cases in which mitral regurgitation was missed by PDE, mitral regurgitation was mild (seven cases: Sellers I degree, two cases: Sellers II degree). No false positives were found. The overall sensitivity of the PDE was 87.1%, with a specificity of 100%, a diagnostic accuracy of 89.4%, and a predictive value of 100%. By displaying the distribution of systolic turbulence on parasternal or apical long-axis image (flow mapping), the direction and the extent of the regurgitant flow in the left atrium were clearly visualized. The localization of the regurgitant flow at the mitral ostium was visualized in parasternal short-axis images by the flow mapping method.(ABSTRACT TRUNCATED AT 400 WORDS)

[Echocardiographic evaluation of cardiac involvement in patients with chronic alcoholism].

Since chronic alcoholics may accompany with asymmetric septal hypertrophy (ASH), the purpose of this study was to find the difference in cardiac function of such cases from the patients with hypertrophic cardiomyopathy. Ninety-seven alcoholic patients (59 non-cirrhotics and 38 cirrhotics) were examined by non-invasive methods including two-dimensional echocardiography and dye dilution method, and these data were compared with those of 16 normal subjects and 26 patients with hypertrophic cardiomyopathy. The results were as follows: Interventricular septal thickness of more than 12 mm was observed in 25.4% of the non-cirrhotics and 28.9% of the cirrhotics. Furthermore, ASH was present in 23.7% of the former and 18.4% of the latter, when ASH was defined as the septal to posterior wall ratio greater than 1.3 with the interventricular septal thickness greater than or equal to 12 mm. In 66.7% of the chronic alcoholics with ASH, hypertrophy was predominantly located in the septum, however 53.8% of the patients with hypertrophic cardiomyopathy had ASH in association with the thickened left ventricular posterior wall. In 21 chronic alcoholics with ASH, ejection indices such as ejection fraction and mean VCF were moderately increased, although scattered widely, as compared with those of the normal subjects. Latent reduced ventricular function compensated by sympathetic overactivity was postulated based on left ventricular performance maintained normally as indicated by a decrease of end-systolic wall stress. Several possible factors including hypertension, catecholamine and metabolic abnormalities were analyzed to explain the genesis of ASH in chronic alcoholics, but the true etiology remained unknown. In conclusion, ASH associated with chronic alcoholism is a type characteristic of alcoholic cardiomyopathy, and seems to belong to a clinical entity different from hypertrophic cardiomyopathy from a standpoint of clinical symptoms, age and the pattern of left ventricular hypertrophy.