Diabetic hyperglycemia is typically accompanied by various protein modifications, indicating hyperglycemic glucotoxicity. Overactivation of poly [adenosine diphosphate (ADP)-ribose] polymerase 1 (PARP-1) has been implicated in the pathogenesis of oxidative stress-related diseases including diabetes and its complications. Furthermore, obesity and diabetes are known to be associated with a substantial risk of chronic liver disease. We have previously reported that thiamine supplementation prevented obesity and diabetes-related liver disease. As a step forward, in the present study, we focus on hepatic ADP-ribosylation that reflects PARP-1 activation and an increased oxidative stress condition. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were randomly divided into the following groups: thiamine-supplemented and unsupplemented control groups. The thiamine-supplemented group received 2 g of thiamine/L of drinking water for 33 weeks. ADP-ribosylated protein expression was analyzed in the livers of OLETF rats using Western blotting. Moreover, the fasting blood glucose level was measured in these rats. The obese diabetic OLETF rats exhibited high ADP-ribosylated protein expression in the liver. Interestingly, hepatic ADP-ribosylated protein expression and fasting blood glucose levels were lower in the thiamine-supplemented OLETF group than in the control OLETF group. These results suggest that thiamine supplementation attenuates oxidative stress by inhibiting hepatic ADP-ribosylation in OLETF rats. The beneficial effect of high-dose thiamine on oxidative stress-related diseases could be attributed to its inhibitory effect on PARP-1 activation, in addition to its role as a coenzyme. Furthermore, we found that thiamine supplementation prevented fasting hyperglycemia, suggesting that high-dose thiamine modifies the hepatic glucose metabolism and obesity-induced hepatic insulin resistance.
We encountered two cases expressing excessive daytime sleepiness (EDS) and manifesting two or more sleep‐onset rapid eye movement (REM) periods in the multiple sleep latency test. Unbearable daytime sleepiness occurred abruptly, which usually led to short‐lasting naps, after which the patients felt refreshed. The EDS was successfully reduced by treatment with methylphenidate. In spite of these features similar to narcolepsy, these cases of REM hypersomnia did not present cataplexy or other auxiliary symptoms of narcolepsy, and, furthermore, the class‐II human leukocyte antigen DR2 appeared to be negative.
The patient was a 66-year-old woman. She underwent central venous port insertion as part of postoperative adjuvant chemotherapy for sigmoid colon cancer. At the beginning of the 2 cycle, she experienced discomfort in the neck, and computed tomography was performed. As a result, catheter deviation and a thrombus in the internal jugular vein were observed. It was considered that breast displacement due to gravity caused the catheter deviation and that the position of the tip of the catheter deviating to immediately above the venous valve caused thrombus formation. We examined the factors that may cause catheter deviation.
Abstract The present study examined whether the activities of the rostral basal forebrain neurons alter the activities of the orexin (also known as hypocretin) neurons in the tuberal part of the hypothalamus in rats. We performed microdialysis perfusion of the ventromedial portion of the rostral basal forebrain with the GABA A receptor agonist muscimol to inhibit focally the neuronal activities in the rostral basal forebrain. Then, we monitored sleep/wake behaviour and investigated the pattern of activities of orexin neurons by examining the expression of FOS as an indicator of cellular activation. Bilateral perfusion with muscimol (5, 15, and 50 µ m ) produced a dose‐dependent decrease in the amount of sleep. This perfusion with muscimol at 50 µ m produced FOS‐like immunoreactivity in 37% of the orexin neurons located in the tuberal part of the hypothalamus, whereas the FOS‐like immunoreactivity was sparse in orexin neurons of the sleeping control rats ( P = 0.001 by Mann–Whitney U‐test). Unilateral perfusion with muscimol (50 µ m ) also suppressed sleep. In this case, FOS‐like immunoreactivity was seen in 40% of the orexin neurons on the side ipsilateral to the perfusion site but only in 10% of orexin neurons on the contralateral side ( P = 0.018 by Wilcoxon signed rank test). These functional data suggested that a sleep‐generating element in the ventromedial part of the rostral basal forebrain provides an inhibitory influence on the activities of the orexin neurons in the tuberal part of the hypothalamus.
Antegrade central perfusion for acute Stanford type A aortic dissection prevents malperfusion and retrograde cerebral embolism during cardiopulmonary bypass. Prompt establishment of antegrade perfusion via the ascending aorta may improve surgical results of type A dissections, especially in situations of hemodynamic instability. Thus, we evaluated the safety and efficacy of cannulation of the dissected ascending aorta in acute type A dissection.We reviewed the medical charts of patients undergoing repair of acute ascending aortic dissection (n = 52) from April 2010 to April 2013. Cannulation was accomplished in 29 patients via the ascending aorta (central) and in 23 patients via the femoral or axillary artery (peripheral). The ascending aorta was routinely cannulated using Seldinger technique under epiaortic ultrasound guidance. Comorbidities, mortality, complications, and durations of hospital stays were compared for the groups.In all cases, routine cannulation of the ascending aorta was safely performed with no resultant malperfusion or thromboembolism. Mean operative duration, cardiopulmonary bypass time, intubation time, and intensive care unit stay were significantly shorter in the central group. Two patients (6.8 %) in the central group died compared with four patients (17.3 %) in the peripheral group (P = 0.005).Antegrade central perfusion via the ascending aorta, a simple and safe technique that enables rapid establishment of antegrade systemic perfusion, was as safe as peripheral cannulation in patients with type A acute aortic dissection.
In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca 2+ -regulated exocytosis, consisting of an initial peak that declines rapidly (initial transient phase) followed by a second slower decline (late phase) lasting during ACh stimulation. The addition of 8-bromo-cGMP (8-BrcGMP) enhanced the initial phase, which was inhibited by the protein kinase G (PKG) inhibitor guanosine 3′,5′-cyclic monophosphorothoiate, β-phenyl-1, N 2 -etheno-8-bromo, Rp-isomer, sodium salt (Rp-8-BrPETcGMPS, 100 nM). However, Rp-8-BrPETcGMPS produced a delayed, but transient, increase in the exocytotic frequency during the late phase that was abolished by a protein kinase A (PKA) inhibitor (PKI-amide), suggesting that Rp-8-BrPETcGMPS accumulates cAMP. The cGMP-dependent phosphodiesterase 2 (PDE2), which degrades cAMP, may exist in antral mucous cells. The PDE2 inhibitor BAY-60-7550 (250 nM) mimicked the effect of Rp-8-BrPETcGMPS on ACh-stimulated exocytosis. Measurement of the cGMP and cAMP contents in antral mucosae revealed that ACh stimulates the accumulation of cGMP and that BAY-60-7550 accumulates cAMP similarly to Rp-8-BrPETcGMPS during ACh stimulation. Analyses of Western blot and immunohistochemistry demonstrated that PDE2A exists in antral mucous cells. In conclusion, Rp-8-BrPETcGMPS accumulates cAMP by inhibiting PDE2 in ACh-stimulated antral mucous cells, leading to the delayed, but transient, increase in the frequency of Ca 2+ -regulated exocytosis. PDE2 may prevent antral mucous cells from excessive mucin secretion caused by the cAMP accumulation.
The reason why this paper deals with GTO behavior mainly is that the reverse bias safety operating area (SOA) of GTO is narrower than the ones of GCT and IEGT. On the development of large-capacity GTO converter, it is important to evaluate the performance of snubber circuit. This paper is concerned with the spike voltage VDSP during turning-off a GTO, and deals with the design and evaluation of stray inductance for snubber circuit, and shows investigation for transient forward voltage of snubber diode. Especially, the method is described that estimates stray inductance from aspect of snubber circuit structure by electromagnetic field analysis before making prototype. The experimental results of spike voltage VDSP are in approximate agreement with the estimated results. Therefore, investigations on this paper are proper and applicable. The same manner of evaluation is also appropriate to IEGT application, and the development of IEGT converter is easier than in GTO converter because of the gate resistor adjustment for di/dt of main current and a wider SOA.
The case was a 32-year-old man. Blalock-Taussig shunt was performed at five months-old for tetralogy of Fallot, and intracardiac repair was performed at four years-old. He was admitted with a diagnosis of infective endocarditis. Preoperative echocardiography showed vegetations on the mitral valve and severe mitral regurgitation. Severe right heart pressure load findings, pulmonary valve stenosis and regurgitation, and residual ventricular septal defect were also observed. The surgery included mitral valve repair, reconstruction of the right ventricular outflow tract, pulmonary valve replacement, and closure of the ventricular septal defect. The postoperative course was favorable. The cause of mitral regurgitation was an abnormal chordae tendineae attached to the interventricular septum and valve destruction by infective endocarditis.
