Cigarette Smoking as a Risk Factor of Coronary Artery Disease and its Effects on Platelet Function

It has been well established that cigarette smoking is a powerful risk factor for coronary artery disease. A number of epidemiologic studies have shown a strong association between cigarette smoking and atherosclerosis, myocardial infarction and death from coronary artery disease. In addition to active smoking, passive smoking can also carry a risk of coronary artery disease. Although the detailed mechanism through which cigarette smoking is associated with cardiovascular disease has not yet been clarified, it is suggested that cigarette smoking is related to thrombogenesis, as well as atherogenesis, and blood platelet behavior is thought to be prominent among the proposed mechanisms involved in atherogenesis and thrombogenesis. The following is a review of evidence that cigarette smoking affects platelet function

Postprandial hyperglycemia as an etiological factor in vascular failure

Postprandial hyperglycemia is characterized by hyperglycemic spikes that induce endothelial dysfunction, inflammatory reactions and oxidative stress, which may lead to progression of atherosclerosis and occurrence of cardiovascular events. Emerging data indicate that postprandial hyperglycemia or even impaired glucose tolerance may predispose to progression of atherosclerosis and cardiovascular events. There is evidence that postprandial hyperglycemia, but not fasting hyperglycemia, independently predicts the occurrence of cardiovascular events. We proposed a concept of 'vascular failure' as a comprehensive syndrome of vascular dysfunction extending from risk factors to advanced atherosclerotic disease. Postprandial hyperglycemia is therefore one of the very important pathophysiological states contributing to vascular failure. Accordingly, controlling postprandial hyperglycemia should be the focus of future clinical investigation as a potential target for preventing vascular failure

N-Myc-activated microRNAs Inhibit Protein Synthesis of RUNX1 and RUNX3 in Neuroblastoma Cell Lines

　RUNX1 and RUNX3 are master transcription factors in sensory neuron lineage specifications. Protein levels of such developmental regulators are tightly controlled during carcinogenesis, in order to block differentiation and drive proliferation. Here we report that neuroblastoma specific microRNAs inhibit protein syntheses of RUNX1 and RUNX3 through 3’UTR sequences. Computational prediction identified two putative binding sequences for N-Myc-activated microRNAs both in RUNX1 and RUNX3 3’UTRs. Streptavidin RNA aptamer-tagged 3’UTR sequences pulled down miR-17, miR-18a, miR-19a, miR-20a or miR-130a from neuroblastoma cell lysate. 3’UTR target protection from N-Myc-activated microRNAs increased protein synthesis of RUNX1 or RUNX3 and induced differentiation in neuroblastoma cell lines. Together, protein levels of RUNX1 and RUNX3 are post-transcriptionally regulated by N-Myc-activated microRNAs, highlighting the mutual negative feedback between N-Myc oncogene and RUNX3 tumor suppressor in neuroblastoma

Postprandial endothelial dysfunction in subjects with new-onset type 2 diabetes: an acarbose and nateglinide comparative study

<p>Abstract</p> <p>Background</p> <p>Postprandial hyperglycemia is believed to affect vascular endothelial function. The aim of our study was to compare the effects of acarbose and nateglinide on postprandial endothelial dysfunction.</p> <p>Methods</p> <p>We recruited a total of 30 patients with newly diagnosed type 2 diabetes (19 men and 11 women, age 67.8 ± 7.3 years). Patients were randomly assigned to 3 groups receiving either 300 mg/day acarbose, 270 mg/day nateglinide, or no medication. A cookie test (consisting of 75 g carbohydrate, 25 g butter fat, and 7 g protein for a total of 553 kcal) was performed as dietary tolerance testing. During the cookie test, glucose and insulin levels were determined at 0, 30, 60, and 120 min after load. In addition, endothelial function was assessed by % flow-mediated dilation (FMD) of the brachial artery at 0 and 120 min after cookie load.</p> <p>Results</p> <p>Postprandial glucose and insulin levels were similar in the 3 groups. Postprandial endothelial dysfunction was similar in the 3 groups before treatment. After 12 weeks of intervention, postprandial FMD was significantly improved in the acarbose group compared with the control group (6.8 ± 1.3% vs 5.2 ± 1.1%, p = 0.0022). Area under the curve (AUC) for insulin response was significantly increased in the nateglinide and control groups; however, no significant change was observed in the acarbose group.</p> <p>Conclusions</p> <p>Our results suggest that acarbose improves postprandial endothelial function by improvement of postprandial hyperglycemia, independent of postprandial hyperinsulinemia. Acarbose may thus have more beneficial effects on postprandial endothelial function in patients with type 2 diabetes than nateglinide.</p

Two-week administration of rivaroxaban resolved left atrial thrombus

AbstractAn 89-year-old man visited our hospital complaining of palpitation. Electrocardiography showed atrial fibrillation, and transthoracic echocardiography demonstrated a mobile thrombus of 28.6mm×20.8mm in the left atrium. Administration of a direct factor Xa inhibitor rivaroxaban (10mg/day) was started. The thrombus reduced its size and disappeared completely 2 weeks after the commencement of rivaroxaban treatment. To our knowledge, this is the first case report that rivaroxaban successfully dissolved left atrial thrombus during a short period. Rivaroxaban might have a potential, not only to prevent de novo thrombus formation, but also to dissolve established thrombi by direct inhibition of free and thrombus-associated factor Xa.<Learning objective: The incidence of nonvalvular atrial fibrillation is increasing, and left atrial thrombus is the major cause of cardiogenic thrombo-embolism that we need to prevent. Recently, novel oral anticoagulants have been developed. The effects of these agents on intracardiac thrombus resolution have not been fully elucidated. Data from a large cohort study would be required to assess efficacy of novel oral anticoagulants for thrombus resolution.

Influence of organic fertilizer on rhizome yield and α-tocopherol content of Codonopsis lanceolata

Codonopsis lanceolata (Sieb. et Zucc.) Trautv. is a valuable wild vegetable in East Asian countries, especially Korea. We investigated effects of organic fertilizer application on rhizome yield and quality under Andosol soil conditions in the AFC field of Shinshu University. Commercial barnyard manure, which was fermented with crushed bark and beef cattle dung, and Japanese oak leaf mold were applied at the rates of 0, 5, 10, 15, and 20 g m-2. Barnyard manure increased the fresh weight yield of rhizomes but decreased the DL-α-tocopherol (vitamin E) content. The rhizome yield was drastically influenced by the C/N ratio of the soil from the surface to 30 cm below ground level that was controlled by the application ratio of barnyard manure to leaf mold. Total N, soluble P, exchangeable K, Ca, and Mg did not significantly affect the rhizome yield. There was a significant negative correlation between the rhizome fresh weight and vitamin E content at harvest time. The highest vitamin E content of 9-10 mg 100 g-1 dry matter was obtained at a leaf mold application rate of 10 g m-1. Nitrogen supply from the soil to plants primarily influenced the yield and quality of rhizomes as vegetables or drugs. The vitamin E content under a higher soil C/N ratio was the highest among commercial vegetables available in common Japanese food markets.Article信州大学農学部AFC報告 10: 1-7(2012)departmental bulletin pape

Methylglyoxal attenuates isoproterenol-induced increase in uncoupling protein 1 expression through activation of JNK signaling pathway in beige adipocytes

Methylglyoxal (MG) is a metabolite derived from glycolysis whose levels in the blood and tissues of patients with diabetes are higher than those of healthy individuals, suggesting that MG is associated with the development of diabetic complications. However, it remains unknown whether high levels of MG are a cause or consequence of diabetes. Here, we show that MG negatively affects the expression of uncoupling protein 1 (UCP1), which is involved in thermogenesis and the regulation of systemic metabolism. Decreased Ucp1 expression is associated with obesity and type 2 diabetes. We found that MG attenuated the increase in Ucp1 expression following treatment with isoproterenol in beige adipocytes. However, MG did not affect protein kinase A signaling, the core coordinator of isoproterenol-induced Ucp1 expression. Instead, MG activated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases. We found that JNK inhibition, but not p38, recovered isoproterenol-stimulated Ucp1 expression under MG treatment. Altogether, these results suggest an inhibitory role of MG on the thermogenic function of beige adipocytes through the JNK signaling pathway

Muscle Thickness of Anterior Mid-Thigh in Hospitalized Patients : Comparison of Supine and Standing Postures

Objectives: To compare the magnitude changes in muscle thickness (MTH) of the anterior mid-thigh between the supine and standing postures.Design: Experimental.Setting: University hospital laboratory.Participants: Inpatients (N=283) between the ages of 29 and 93 years (193 men, 90 women) with cardiovascular disease who volunteered for this study.Interventions: Not applicable.Main Outcome Measures: MTH of the anterior mid-thigh was measured with a 10 MHz ultrasound probe while the participants stood or lay supine in a relaxed position with their arms extended and by their sides.Results: Age and percentage of body fat were greater (P<.01) in women than in men (74.3±12.3 vs 67.7±12.1y and 32.6±10.3% vs 27.4±7.4%, respectively), but standing height, body weight, and body mass index were greater (P<.01) in men than in women (164.9±6.3 vs 149.1±7.5 cm, 65.4±12.7 vs 49.5±11.1 kg, and 23.8±3.9 vs 22.1±4.4 kg/㎡, respectively). Correlations were found between the standing posture and supine position in the anterior-mid thigh MTH for both men (r=0.85; P<.01) and women (r=0.82; P<.01). In the anterior-mid thigh for men and women, MTH was greater in the standing posture (3.7±1.0 vs 2.5±0.7 cm) than in supine position (3.1±0.8 vs 2.1±0.7 cm) (both P<.01).Conclusions: In this study, MTH of the anterior mid-thigh during prolonged hospitalization was approximately 16% higher in men than in women regardless of posture, and was approximately 32% higher in standing posture than in the supine position regardless of sex

Analysis of Infant Microbiota Composition and the Relationship With Breast Milk Components in the Asian Elephant (Elephas Maximus) at the Zoo

The prevention of diseases through health control is essential at zoos. Here, we investigated the gut microbiota formation during infancy in an Asian elephant and compared the composition between infant and mother. Besides, we analyzed the components of breast milk and examined the correlation with the infant gut microbiota. Analysis revealed the gut microbiota of the infant contained high amount of Lactobacillales and its diversity was relatively low compared to that of the mother. We found several milk components, showed a positive correlation with the change of Lactobacillales. The present study revealed the mechanism of gut microbiota formation during infancy in an Asian elephant and provides important insights into the health control of Asian elephants in zoos

Flow Cytometric Analysis of Ca2+-Induced Membrane Permeability Transition of Isolated Rat Liver Mitochondria

The membrane permeability transition (MPT) of mitochondria plays an important role in the mechanism of apoptotic cell death in various cells. Classic type MPT is induced by Ca2+ in the presence of inorganic phosphate and respiratory substrate, and is characterized by various events including generation of reactive oxygen species (ROS), membrane depolarization, swelling, release of Ca2+ and high sensitivity to cyclosporine A. However, the sequence of these events and the effect of antioxidants on their events remain obscure. Flow cytometry is a convenient method to investigate the order of events among various functions occurring in MPT using a limited amount of mitochondria (200 µl of 0.02 mg protein/ml) without contamination by other organelles. Flow cytometric analysis revealed that Ca2+ sequentially induced ROS generation, depolarization, swelling and Ca2+ release in mitochondria by a cyclosporine A-inhibitable mechanism. These results were supported by the finding that Ca2+-induced MPT was inhibited by antioxidants, such as glutathione and N-acetylcysteine. It was also revealed that various inhibitors of Ca2+-induced phospholipase A2 suppressed all of the events associated with Ca2+-induced MPT. These results suggested that ROS generation and phospholipase A2 activation by Ca2+ underlie the mechanism of the initiation of MPT