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Thoracic endovascular aortic repair of the ascending aorta remains challenging. We have reported the case of an 81-year-old woman with ascending aortic injury who underwent a life-saving hybrid repair. The patient had previously undergone extended radical mastectomy and postoperative radiotherapy for breast cancer, which had resulted in a right thoracic wall defect and bone exposure and osteonecrosis of the sternum. Therefore, the ascending aorta was directly compressed by the sternum at the level of the brachiocephalic artery bifurcation, causing persistent bleeding from the thoracic wall. Hybrid zone 0 debranching thoracic endovascular aortic repair with a left subclavian artery inflow was emergently performed and achieved hemostasis.

Background Limited data is available on the use of a polyester graft limb with a helical stent configuration deployed in the external iliac artery (EIA) during endovascular aneurysm repair (EVAR), so we prospectively analyzed the efficacy of the Zenith Spiral-Z limb deployed in the EIA.Methods and Results:Patients undergoing EVAR using a Zenith stent-graft and Spiral-Z limb deployed in the EIA were prospectively registered in 24 Japanese institutions from June 2017 to November 2017. In total, 65 patients (74 limbs) (mean age: 77.1±8.0 years, 87.7% men, mean abdominal aortic aneurysm (AAA) diameter: 51.9±7.2 mm, mean iliac artery aneurysm (IAA) diameter: 38.3±10.0 mm) were registered and followed up. The most common reason for deployment in the EIA was a common IAA (43 limbs, 58.1%), and 8 limbs (10.8%) had a bare nitinol stent placed at the Spiral-Z limb. A total of 61 patients (70 limbs) completed a 24-month follow-up. There were 2 Spiral-Z limb stenoses and 1 occlusion, leading to a primary patency of 95.5% and a secondary patency of 100%, at 24 months. Buttock claudication occurred in 24.3% of the limbs treated at 1 month but decreased to 4.3% at 24 months. Conclusions Our multicenter prospective study showed that Spiral-Z limb deployed in the EIA was associated with satisfactory results and seems to be a durable option, even in the era of iliac branch devices.

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.

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.

Carbocisteine (CCis), a mucoactive agent, is widely used to improve respiratory diseases. This study demonstrated that CCis increases ciliary bend angle (CBA) by 30% and ciliary beat frequency (CBF) by 10% in mouse airway ciliary cells. These increases were induced by an elevation in intracellular pH (pHi; the pHi pathway) and a decrease in the intracellular Cl− concentration ([Cl−]i; the Cl− pathway) stimulated by CCis. The Cl− pathway, which is independent of CO2/HCO3−, increased CBA by 20%. This pathway activated Cl− release via activation of Cl− channels, leading to a decrease in [Cl−]i, and was inhibited by Cl− channel blockers (5-nitro-2-(3-phenylpropylamino) benzoic acid and CFTR(inh)-172). Under the CO2/HCO3−-free condition, the CBA increase stimulated by CCis was mimicked by the Cl−-free NO3− solution. The pHi pathway, which depends on CO2/HCO3−, increased CBF and CBA by 10%. This pathway activated HCO3− entry via Na+/HCO3− cotransport (NBC), leading to a pHi elevation, and was inhibited by 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid. The effects of CCis were not affected by a protein kinase A inhibitor (1 μM PKI-A) or Ca2+-free solution. Thus, CCis decreased [Cl−]i via activation of Cl− channels including CFTR, increasing CBA by 20%, and elevated pHi via NBC activation, increasing CBF and CBA by 10%.

This study demonstrated that PDE1 (phosphodiesterase 1) existing in the ciliary beat frequency (CBF)-regulating metabolon regulates CBF in procaterol-stimulated lung airway ciliary cells of mouse. Procaterol (an β2-agonist) increased the ciliary bend angle (CBA) and CBF via cAMP accumulation in the ciliary cells of mice: interestingly, the time course of CBF increase was slower than that of CBA increase. However, IBMX (3-isobutyl-1-methylxanthine, an inhibitor of PDE) increased CBA and CBF in an identical time course. Lowering an intracellular Ca2+ concentration ([Ca2+]i) caused by switching to an EGTA-containing Ca2+-free solution from normal one elevated the procaterol-induced increasing rate of CBF. These observations suggest that Ca2+-dependent PDE1 controls cAMP-stimulated CBF increase. Either application of 8MmIBMX (8-methoxymethyl-IBMX, a selective PDE1 inhibitor), BAPTA-AM (an intracellular Ca2+ chelator), or calmidazolium (an inhibitior of calmodulin) alone increased CBA and CBF in the lung airway ciliary cells and increased cAMP contents in the isolated lung cells, and like IBMX, each application of the compound made the time courses of CBA and CBF increase stimulated by procaterol identical. The immunoelectron microscopic examinations revealed that PDE1A exists in the space between the nine doublet tubules ring and plasma membrane in the lung airway cilium, where the outer dynein arm (a molecular motor regulating CBF) functions. In conclusion, PDE1A is a key factor slowing the time course of the procaterol-induced increase in CBF via degradation of cAMP in the CBF-regulating metabolon of the mouse lung airway cilia.

A PPARα (peroxisome proliferation activation receptor α) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARα activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARα (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca(2+)-regulated exocytosis) mediated via NO, which was abolished by GW6471, N-PLA, wortmannin, and AKT-inh. The Western blotting revealed that GW7647 phosphorylates NOS1 via phosphorylation of PI3K/Akt in antral mucous cells. The immunofluorescence examinations demonstrated that PPARα existing with NOS1 co-localizes with PI3K and Akt in the cytoplasm of antral mucous cells. ACh alone and AACOCF3, an analogue of arachidonic acid (AA), induced the NOS1 phosphorylation via PI3K/Akt to produce NO, which was inhibited by GW6471. Since AA is a natural ligand for PPARα, ACh stimulates PPARα probably via AA. In conclusion, PPARα activates NOS1 via PI3K/Akt phosphorylation to produce NO in antral mucous cells during ACh stimulation.

Carbocisteine (CCis), a mucoactive agent, is widely used to improve respiratory diseases. This study demonstrated that CCis increases ciliary bend angle (CBA) by 30% and ciliary beat frequency (CBF) by 10% in mouse airway ciliary cells. These increases were induced by an elevation in intracellular pH (pH

This study demonstrated that PDE1 (phosphodiesterase 1) existing in the ciliary beat frequency (CBF)-regulating metabolon regulates CBF in procaterol-stimulated lung airway ciliary cells of mouse. Procaterol (an β

We investigated the effects of microwave irradiation under normothermic conditions on cultured cells. For this study, we developed an irradiation system constituted with semiconductor microwave oscillator (2.45 GHz) and thermos-regulatory applicator, which could irradiate microwaves at varied output powers to maintain the temperature of cultured cells at 37 °C. Seven out of eight types of cultured cells were killed by microwave irradiation, where four were not affected by thermal treatment at 42.5 °C. Since the dielectric properties such as ε’, ε” and tanδ showed similar values at 2.45 GHz among cell types and media, the degree of microwave energy absorbed by cells might be almost the same among cell types. Thus, the vulnerability of cells to microwave irradiation might be different among cell types. In HL-60 cells, which were the most sensitive to microwave irradiation, the viability decreased as irradiation time and irradiation output increased; accordingly, the decrease in viability was correlated to an increase in total joule. However, when a high or low amount of joules per minute was supplied, the correlation between cellular viability and total joules became relatively weak. It is hypothesized that kinds of cancer cells are efficiently killed by respective specific output of microwave under normothermic cellular conditions.

In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca2+-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N5-[imino(propylamino)methyl]-l-ornithine hydrochloride ( N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca2+-regulated exocytosis in antral mucous cells.

PURPOSE Endovascular aneurysm repair (EVAR) is a minimally invasive treatment that is becoming standard in abdominal aortic aneurysm treatment. We examine the risk factors of death by comparing the short-term results of abdominal aortic aneurysm by open surgical repair with EVAR. METHODS We performed elective abdominal aortic aneurysm treatment on 122 cases during the period from January 2008 to December 2009. Seventy one cases were treated with open surgical repair while 51 cases were treated with EVAR. RESULTS Compared to the open surgical repair group, the EVAR group was significantly older and had a higher complication rate and past laparotomy rates. No significant difference in hospital deaths was observed between the two groups. Two deaths with thromboembolism due to shaggy aorta were observed in the EVAR group. Two cases in the open surgical repair group developed postoperative myocardial infarction and one death was observed. Both patients underwent coronary artery treatment using drug eluting stents (DES) prior to surgery. CONCLUSION Shaggy aorta has a high possibility of causing thromboembolism and EVAR should not be performed unless there is a considerable reason. In cases in which coronary artery treatment is performed with DES in recent days, EVAR is more preferable.

Objective: The choice of cannulation site for the treatment of acute Stanford type A aortic dissection is much debated. We believe that central cannulation is quick to perform, easy to use, and safe to manage acute type A aortic dissection. Materials and Methods: We retrospectively investigated 26 cases of acute aortic dissection performed using two different central cannulation methods between April 2011 and March 2012. Direct ascending aortic cannulation was performed using the Seldinger technique in 20 patients, and transapical ascending aortic cannulation was performed in six patients in whom puncture was difficult. Results: Patients were 21–86 years old (mean age, 67 years). The surgical techniques used to treat aortic dissection were hemiarch repair in 21 patients and total arch replacement in 5 patients. The mean length of surgery was 393 min. One death (3.8%) was attributed to intestinal ischemia. Conclusion: During surgery for acute aortic dissection, central cannulation using either transapical or direct puncture can be performed quickly and safely, and satisfactory short-term outcomes can be obtained. Because acute aortic dissection can present with various conditions, there is no single perfect surgical or cannulation method; therefore, the choice of surgical procedure should be individualized for each patient.

In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca2+-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, N2-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 Ca2+-regulated exocytosis. PDE2 may prevent antral mucous cells from excessive mucin secretion caused by the cAMP accumulation.

A PPARα (peroxisome proliferation activation receptor α) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARα activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARα (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca(2+)-regulated exocytosis) mediated via NO, which was abolished by GW6471, N-PLA, wortmannin, and AKT-inh. The Western blotting revealed that GW7647 phosphorylates NOS1 via phosphorylation of PI3K/Akt in antral mucous cells. The immunofluorescence examinations demonstrated that PPARα existing with NOS1 co-localizes with PI3K and Akt in the cytoplasm of antral mucous cells. ACh alone and AACOCF3, an analogue of arachidonic acid (AA), induced the NOS1 phosphorylation via PI3K/Akt to produce NO, which was inhibited by GW6471. Since AA is a natural ligand for PPARα, ACh stimulates PPARα probably via AA. In conclusion, PPARα activates NOS1 via PI3K/Akt phosphorylation to produce NO in antral mucous cells during ACh stimulation.

We describe a case of re-endovascular aortic repair after endovascular aortic repair for acute type B aortic dissection, complicated by visceral, renal, and leg malperfusion. We performed endovascular aortic repair to cover the primary entry tear at the distal thoracic aortic arch in a 62-year-old male with visceral, renal, and leg malperfusion, after 4 days of conservative therapy. After the first operation, the pressure differential between upper and lower limbs disappeared. However, bilateral leg ischemia appeared at postoperative day 2. CT showed that the true lumen was severely compressed again by a thrombosed false lumen and two re-entries appeared at the level of the proximal celiac artery and infra-renal abdominal artery, respectively. The distal edge of the stent graft was intact with no new stent graft-induced entry. We once again performed endovascular aortic repair by means of thoracic and abdominal stent grafts covering the re-entry tears at the level of proximal celiac artery and infra-renal abdominal artery. After the procedure, the leg ischemia, renal ischemia and mesenteric ischemia improved, and the patient was transferred back to the local hospital without paraplegia.

The beating cilia play a key role in lung mucociliary transport. The ciliary beating frequency (CBF) and ciliary bend amplitude (CBA) of isolated mouse bronchiolar ciliary cells were measured using a light microscope equipped with a high-speed camera (500 Hz). Procaterol (aβ(2)-agonist) increased CBA and CBF in a dose dependent manner via cAMP. The time course of CBA increase is distinct from that of CBF increase: procaterol at 10 nM first increased CBA and then CBF. Moreover, 10 pM procaterol increased CBA, not CBF, whereas 10 nM procaterol increased both CBA and CBF. Concentration-response studies of procaterol demonstrated that the CBA curve was shifted to a lower concentration than the CBF curve, which suggests that CBA regulation is different from CBF regulation. Measurements of microbead movements on the bronchiole of lung slices revealed that 10 pM procaterol increased the rate of ciliary transport by 37% and 10 nM procaterol increased it by 70%. In conclusion, we have shown that increased CBA is of particular importance for increasing the bronchiolar ciliary transport rate, although CBF also plays a role in increasing it.

Rhodamine B hydrazide can be used to detect hydroxyl radicals in plant cells. RBH was easily inserted into plant cells without any pretreatment, and specifically reacted with intracellular hydroxyl radicals produced by antimycin A. RBH will be a powerful tool for detecting hydroxyl radicals in plant cells.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

The purpose of this study was to investigate the minimum effective dose of recombinant canine interferon-gamma (rCaIFN-gamma) for the treatment of dogs with atopic dermatitis (AD). Thirty-four dogs with AD from 17 animal hospitals in Japan were administered half or one-fifth of the approved rCaIFN-gamma dose of 10 000 units/kg, three times a week for 4 weeks, followed by once weekly for an additional 4 weeks. Pruritus, excoriation, erythema and alopecia were evaluated and scored by the investigators on weeks 2, 4, 6, 8 and 12. The efficacy rate (number of excellent cases + number of good cases/total number of cases) at week 8 in the 2000 units/kg group was 36.4% for pruritus, 36.4% for excoriation, 45.5% for erythema and 36.4% for alopecia. In contrast, in the 5000 units/kg group, the efficacy rate was 64.3% for pruritus, 57.1% for excoriation, 78.6% for erythema and 78.6% for alopecia. The efficacy rate of the 5000 units/kg group was high for all signs evaluated and comparable to that of the 10 000 units/kg group reported in a previous study. The results of this study showed that 2000 units/kg of rCaIFN-gamma is less effective than 5000 units/kg to treat dogs with AD, and the efficacy of the 5000 units/kg dose is comparable to that of 10 000 units/kg at week 8.

The present study examined the expression pattern of FOS in the hypothalamic peptide neurons during the sleep-dominant state induced by an adenosine A2A receptor agonist. The control rats, those that received the microdialysis-perfusion of their ventral striatum with artificial cerebrospinal fluid in the dark-active phase, spent 24% of the 90-min period prior to sacrifice in non-rapid eye movement (non-REM) sleep and 2.3% of that in REM sleep. These rats exhibited FOS, a transcription factor, in 21% of their orexin neurons and in 1.0% of their melanin-concentrating hormone (MCH) neurons in the perifornical/lateral hypothalamic areas. However, the rats perfused with 50 microM CGS21680, an adenosine A2A receptor agonist, spent 60% of the 90-min period prior to sacrifice in non-REM sleep and 11% of that in REM sleep. These rats exhibited FOS in 1.7% of their orexin neurons and FOS in 0.5% of their MCH neurons. When the sleep-dominant state was disturbed by mild stimulation and the rats were kept in the sleepy state by treatment with a sleep-inducing dose of CGS21680, the rats exhibited FOS in 13.3% of their orexin neurons, which percentage was about half of that for the control rats. These results suggest that the sleep-promoting process induced by this adenosine A2A receptor agonist was associated with a decline in the activity of orexin neurons. MCH neurons are not likely to change their activities during this sleep-promoting process.

Unilateral microdialysis-perfusion of the preoptic area with 50 microM muscimol decreased the sleep period of rats to less than 3% of the baseline value over a 90 min period before death (p = 0.018 by Wilcoxon signed-rank test). These rats showed the expression of FOS in 36% of the orexin neurons located in the perifornical/lateral hypothalamic areas on the side ipsilateral to the perfusion site, but in only 3% of the orexin neurons on the side contralateral to it (p = 0.018 by Wilcoxon signed-rank test). These results suggest that subpopulations of the preoptic neurons give an inhibitory tone to the activities of the orexin neurons in the perifornical/lateral hypothalamic areas.

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 GABAA 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 micro m) produced a dose-dependent decrease in the amount of sleep. This perfusion with muscimol at 50 micro 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 micro 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.

It has been hypothesized that glutamatergic neurotransmission is related to the therapeutic effect of antipsychotic drugs. To test this hypothesis, we measured by use of the Western blot technique the polypeptide levels of NMDA receptor subunits, that is, NMDAR1, 2A, 2B, and 2C, in several regions of the rat brain after chronic treatment with haloperidol (HPD) or clozapine (CLZ). Each rat was intraperitoneally injected with HPD or CLZ at 10:00 h daily for 14 days. The brain regions examined were frontal cortex, striatum, nucleus accumbens, hippocampus, and cerebellum. Decreases in the polypeptide level of NMDAR2B were seen in hippocampus (but not in other brain regions) following the treatment with HPD or CLZ. Altered levels in NMDAR1-, 2A-, and 2C were not detected in any brain regions examined. We infer that an alteration in NMDAR2B in hippocampus is related to therapeutic effects of antipsychotic drugs.

In antral mucous cells, acetylcholine (ACh, 1 μM) activates Ca(2+)-regulated exocytosis, consisting of a peak in exocytotic events that declines rapidly (initial phase) followed by a second slower decline (late phase) lasting during ACh stimulation. GW7647 [a peroxisome proliferation activation receptor α (PPARα) agonist] enhanced the ACh-stimulated initial phase, and GW6471 (a PPARα antagonist) abolished the GW7647-induced enhancement. However, GW6471 produced the delayed, but transient, increase in the ACh-stimulated late phase, and it also decreased the initial phase and produced the delayed increase in the late phase during stimulation with ACh alone. A similar delayed increase in the ACh-stimulated late phase is induced by an inhibitor of the PKG, Rp8BrPETcGMPS, suggesting that GW6471 inhibits cGMP accumulation. An inhibitor of nitric oxide synthase 1 (NOS1), N(5)-[imino(propylamino)methyl]-L-ornithine hydrochloride (N-PLA), also abolished the GW7647-induced-enhancement of ACh-stimulated initial phase but produced the delayed increase in the late phase. However, in the presence of N-PLA, an NO donor or 8BrcGMP enhanced the ACh-stimulated initial phase and abolished the delayed increase in the late phase. Moreover, GW7647 and ACh stimulated NO production and cGMP accumulation in antral mucosae, which was inhibited by GW6471 or N-PLA. Western blotting and immunohistochemistry revealed that NOS1 and PPARα colocalize in antral mucous cells. In conclusion, during ACh stimulation, a PPARα autocrine mechanism, which accumulates NO via NOS1 leading to cGMP accumulation, modulates the Ca(2+)-regulated exocytosis in antral mucous cells.

We describe a case of type-2 bronchial artery endoleak after endovascular aortic repair of Kommerell diverticulum (KD) involving right-sided aortic arch and aberrant left subclavian artery (LSA). A 68-year-old woman underwent an endovascular repair of KD with an aberrant LSA in our hospital. Follow-up computed tomography (CT) at 6 months after the procedure showed an endoleak. Digital subtraction angiography revealed a type-2 endoleak from a bronchial artery, but no type-1 or type-2 endoleak from the aberrant left subclavian artery. We performed coil embolization of the KD and the left subclavian artery. The endoleak disappeared in the postoperative CT.

Hypocretins/orexins are neuropeptides implicated in sleep regulation and the sleep disorder narcolepsy. In order to examine how hypocretin activity fluctuates across 24 h with respect to the sleep-wake cycle, we measured changes in extracellular hypocretin-1 levels in the lateral hypothalamus and medial thalamus of freely moving rats with simultaneous sleep recordings. Hypocretin levels exhibited a robust diurnal fluctuation; levels slowly increased during the dark period (active phase), and decreased during the light period (rest phase). Levels were not correlated with the amount of wake or sleep in each period. Although an acute 4-h light-shift did not alter hypocretin levels, 6-h sleep deprivation significantly increased hypocretin release during the forced-wake period. Hypocretin activity is, thus, likely to build up during wakefulness and decline with the occurrence of sleep. These findings, together with the fact that a difficulty in maintaining wakefulness during the daytime is one of the primary symptoms of hypocretin-deficient narcolepsy, suggest that hypocretin activity may be critical in opposing sleep propensity during periods of prolonged wakefulness.

The present study has demonstrated that the sleep-promoting potency of 2-[p-(2-carboxyethyl)phenethylamino]-5′-N-ethylcarboxamido adenosine (CGS21680), a selective agonist for the adenosine A2A receptor, varies depending on the location of the administration. CGS21680 was continuously administered to rats through a chronically implanted cannula for 6 h during their active phase. The tip of the cannula was located in the subarachnoid space or the brain ventricle neighbouring the established brain areas implicated in the regulation of sleep–wake phenomena, i.e. rostral basal forebrain, medial preoptic area, lateral preoptic area, posterior hypothalamus, and dorsal tegmentum of the pons and medulla. At an infusion rate of 2.0 pmol/min, the magnitude of increase in non-rapid eye movement sleep varied from 14 min (a 15% increase) to 96 min (a 103% increase), and those of rapid eye movement sleep varied from 6 min (a 40% increase) to 28 min (a 264% increase) from the respective baseline values. The largest increases in both types of sleep occurred when CGS21680 was administered to the subarachnoid space underlying the rostral basal forebrain. These findings were interpreted to mean that the major, if not the only, site responsible for the CGS21680-inducing sleep was located in or near the rostral basal forebrain. This interpretation was supported by the findings that the administration of CGS21680 to the rostral basal forebrain produced predominant expression of Fos within the shell of the nucleus accumbens and the medial portion of the olfactory tubercle, and that the microdialysis perfusion of CGS21680 into the shell of the nucleus accumbens also exhibited a sleep-promoting effect.

We examined the sleep-modulatory effects of four adenosine agonists, namely, (1) 2-(4-(2-carboxyethyl)phenylethylamino)adenosine-5'-N-ethylcarbo xamideadenosine (CGS21680), a highly selective adenosine A2A receptor agonist; (2) 2-(4-(2-(2-aminoethylaminocarbonyl)ethyl)phenylethylamino)-5 '-N-ethylcarboxamidoadenosine (APEC), a selective adenosine A2A receptor agonist; (3) 5'-N-ethylcarboxamidoadenosine (NECA), a nonselective adenosine A1/A2 receptor agonist, and (4) N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist. Each agonist was administered in the subarachnoid space underlying the rostral basal forebrain of rats through chronically implanted cannulae at the rate of 0.02, 0.2, 2.0, 12.0, or 20.0 pmol/min over a 6-h period starting from 2300 h, which period is the active phase of the animals. CGS21680, APEC, and NECA produced significant increases in the total amounts of non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep after at least one dose within the range of administration rates. CPA did not produce any significant increase in the total amount of either type of sleep at any of the above administration rates, but instead suppressed REM sleep at the administration rates of 12.0 and 20.0 pmol/min. These results indicate that the activities of adenosine A2A receptors are crucially involved in the promotion of sleep.

It has been hypothesized that glutamatergic neurons play an important role in clinical manifestations of schizophrenia and that the therapeutic effect of antipsychotic drugs is related to glutamatergic neurotransmission. To elucidate the effect of antipsychotic drugs on glutamatergic transmission, we examined gene expressions of NMDA receptor subunits Rl, R2A, R2B and R2C in the whole brains of rats after acute and chronic administrations of haloperidol and sulphide, using the Northern blot technique. The levels of NMDAR2B mRNAs decreased after the acute administration of haloperidol, but showed no change after the chronic administration. The levels of NMDAR2A and R2B mRNAs decreased after the acute administration of sulpiride, whereas the levels of R2A and R2B increased following the chronic administration. Neither haloperidol nor sulpiride influenced NMDAR1 mRNA levels. These data support differential expression of NMDA receptor subunits in rats upon treatment with haloperidol and sulpiride. The results imply that NMDAR2 subunits may be crucial in the regulation and modification of antipsychotic drugs.