Previous studies have shown that neurokinin 1 receptor (NK1R) occurs naturally in human glioblastomas and its stimulation causes cell proliferation. In the present study we show that stimulation of NK1R in human U373 glioblastoma cells by substance P increases Akt phosphorylation by 2.5‐fold, with an EC50 of 57 nM. Blockade of NK1R lowers basal phosphorylation of Akt, indicating the presence of a constitutively active form of NK1R; similar results are seen in U251 MG and DBTRG‐05 glioblastoma cells. Linkage of NK1R to Akt implicates NK1R in apoptosis of glioblastoma cells. Indeed, treatment of serum‐starved U373 cells with substance P reduces apoptosis by 53 ± 1% (p < 0.05), and treatment with NK1R antagonist L‐733,060 increases apoptosis by 64 ± 16% (p < 0.01). Further, the blockade of NK1R in human glioblastoma cells with L‐733,060 causes cleavage of Caspase‐3 and proteolysis of poly (ADP‐ribose) polymerase. Experiments designed to elucidate the mechanism of NK1R‐mediated Akt phosphorylation revealed total involvement of non‐receptor tyrosine kinase Src and phosphatidyl‐3‐kinase, a partial involvement of epidermal growth factor receptor, and no involvement of mitogen‐activated protein/extracellular signal‐related kinase. Taken together, the results of the present study indicate a key role for NK1R in glioblastoma apoptosis.

The efficacy of noninvasive esCCO technology was compared with TDCO in 213 cases. Five hundred eighty-seven datasets comparing esCCO and TDCO showed close correlation and small bias and precision, which were comparable to current arterial waveform analysis technologies.

Cardiac G protein-coupled receptors that function through stimulatory G protein G␣ s , such as ␤ 1 -and ␤ 2 -adrenergic receptors (␤ 1 ARs and ␤ 2 ARs), play a key role in cardiac contractility. Recent data indicate that several G␣ s -coupled receptors in heart also activate G␣ i , including ␤ 2 ARs (but not ␤ 1 ARs). Coupling of cardiac ␤ 2 ARs to G␣ i inhibits adenylyl cyclase and opposes ␤ 1 AR-mediated apoptosis. Dual coupling of ␤ 2 AR to both G␣ s and G␣ i is likely to alter ␤ 2 AR function in disease, such as congestive heart failure in which G␣ i levels are increased. Indeed, heart failure is characterized by reduced responsiveness of ␤ARs. Cardiac ␤AR-responsiveness is also decreased with aging. However, whether age increases cardiac G␣ i has been controversial, with some studies reporting an increase and others reporting no change. The present study examines G␣ i in left ventricular membranes from young and old Fisher 344 rats by employing a comprehensive battery of biochemical assays. Immunoblotting reveals significant increases with age in left ventricular G␣ i2 , but no changes in G␣ i3 , G␣ o , G␣ s , G␤ 1 , or G␤ 2 . Aging also increases ADP-ribosylation of pertussis toxin-sensitive G proteins. Consistent with these results, basal as well as receptor-mediated incorporation of photoaffinity label [ 32 P]azidoanilido-GTP indicates higher amounts of G␣ i2 in older left ventricular membranes. Moreover, both basal and receptor-mediated adenylyl cyclase activities are lower in left ventricular membranes from older rats, and disabling of G␣ i with pertussis toxin increases both basal and receptorstimulated adenylyl cyclase activity. Finally, age produces small but significant increases in muscarinic potency for the inhibition of both ␤ 1 AR-and ␤ 2 ARstimulated adenylyl cyclase activity. The present study establishes that G␣ i2 increases with age and provides data indicating that this increase dampens adenylyl cyclase activity.Cardiac contractility is controlled by several G protein-coupled receptors (GPCRs), 1 such as ␤ 1 -and ␤ 2 -adrenergic receptors (␤ 1 ARs and ␤ 2 ARs), that function through stimulatory GTP-binding regulatory proteins (G␣ s ) and activate adenylyl cyclase (AC). Activation of AC increases the formation of cAMP, which activates cAMP-dependent protein kinase A resulting in the phosphorylation of proteins controlling cardiac excitationcontraction (1). An important recent discovery is that ␤ 2 ARs (but not ␤ 1 ARs) in both rat (2, 3) and human heart (4) also activate G␣ i , a G␣-subunit that inhibits AC (5). We also demonstrated that G␣ i couples to several other G␣ s -coupled receptors in human heart, including receptors for histamine, glucagon, and serotonin (4). Coupling of ␤ 2 AR and other G␣ s -coupled receptors to G␣ i is relevant to cardiac function because inactivation of G␣ i by pertussis toxin (PTX) increases myocyte contractility in rat heart (6) and increases both basal and receptormediated AC activity in human heart (4). In addition to inhibiting AC, the G␣ i pathway in hea...

A new non-invasive continuous cardiac output (esCCO) monitoring system solely utilizing a routine cardiovascular monitor was developed, even though a reference cardiac output (CO) is consistently required. Subsequently, a non-invasive patient information CO calibration together with a new automated exclusion algorithm was implemented in the esCCO system. We evaluated the accuracy and trending ability of the new esCCO system. Either operative or postoperative data of a multicenter study in Japan for evaluation of the accuracy of the original version of esCCO system were used to develop the new esCCO system. A total of 207 patients, mostly cardiac surgical patients, were enrolled in the study. Data were manually reviewed to formulate a new automated exclusion algorithm with enhanced accuracy. Then, a new esCCO system based on a patient information calibration together with the automated exclusion algorithm was developed. CO measured with a new esCCO system was compared with the corresponding intermittent bolus thermodilution CO (ICO) utilizing statistical methods including polar plots analysis. A total of 465 sets of CO data obtained using the new esCCO system were evaluated. The difference in the CO value between the new esCCO and ICO was 0.34 ± 1.50 (SD) L/min (95 % confidence limits of −2.60 to 3.28 L/min). The percentage error was 69.6 %. Polar plots analysis showed that the mean polar angle was −1.6° and radial limits of agreement were ±53.3°. This study demonstrates that the patient information calibration is clinically useful as ICO, but trending ability of the new esCCO system is not clinically acceptable as judged by percentage error and polar plots analysis, even though it’s trending ability is comparable with currently available arterial waveform analysis methods.

Preoperative BNP level is an independent predictor of postoperative AF following OPCAB. Our findings permit us to stratify the risk of AF and to plan prophylactic strategies in high-risk patients.

Electrogastrography analysis suggests that the frequency of gastric contractions during CS was less than that in the postpartum period.

Revascularization of the hypogastric artery often tends to be neglected in aortoiliac reconstructive surgery; however, its incomplete revascularization can result in unfavorable complications such as buttock claudication or necrosis, vascular impotence, and colonic ischemia. Multiple vascular lesions in the abdominal aorta and bilateral iliac arteries were reconstructed using a newly designed double bifurcated graft in five male patients. All five patients demonstrated excellent graft limb patency and postoperative improvement of the ankle-brachial pressure index without any clinical signs of ischemia in regions of the hypogastric artery. Thus, we conclude that an aggressive approach toward hypogastric circulation maintenance is essential in aortoiliac reconstructive surgery. By using this double bifurcated graft, rapid and safe revascularization of the bilateral hypogastric arteries concomitant with the external iliac or femoral arteries can be performed.

Preoperative LV dysfunction is a predictor of severe mitral regurgitation during OPCAB. When poor LV function is suggested, it is necessary to be prepared for further hemodynamic deterioration caused by mitral regurgitation.