The involuntary dual control systems of the autonomic nervous system (ANS) in the bladder of awake spontaneously hypertensive rats (SHRs) were investigated through simultaneous registrations of intravesical and intraabdominal pressures to observe detrusor overactivity (DO) objectively as a core symptom of an overactive bladder. SHRs (n = 6) showed the features of overactive bladder syndrome during urodynamic study, especially DO during the filling phase. After injection of the nonselective sympathetic blocking agent labetalol, DO disappeared in 3 of 6 SHRs (50%). DO frequency decreased from 0.98 ± 0.22 min(-1) to 0.28 ± 0.19 min(-1)(p < 0.01), and DO pressure decreased from 3.82 ± 0.57 cm H(2)O to 1.90 ± 0.86 cm H(2)O (p < 0.05). This suggests that the DO originating from the overactive parasympathetic nervous system is attenuated by the nonselective blocking of the sympathetic nervous system. The detailed mechanism behind this result is still not known, but parasympathetic overactivity seems to require overactive sympathetic nervous system activity in a kind of balance between these two systems. These findings are consistent with recent clinical findings suggesting that patients with idiopathic overactive bladder may have ANS dysfunction, particularly a sympathetic dysfunction. The search for newer and better drugs than the current anticholinergic drugs as the mainstay for overactive bladder will be fueled by our research on these sympathetic mechanisms. Further studies of this principle are required.

The dynamics of NO rebinding in hemoglobin (Hb) was directly observed using femtosecond mid-IR spectroscopy after photodeligation of NO from HbNO in D2O at 283 K. Time-resolved spectra of bound NO appeared to have a single feature peaked at 1616 cm-1 but were much better described by two Gaussians with equal intensities but different rebinding kinetics, where the feature at 1617 cm-1 rebinds faster than the one at 1614 cm-1. It is possible that the two bands each correspond to one of two subunit constituents of the tetrameric Hb. Transient absorption spectra of photodeligated NO revealed three evolving bands near 1858 cm-1 and their red-shifted replicas. The red-shifted replicas arise from photodeligated NO in the vibrationally excited v = 1 state. More than 10% of the NO was dissociated into the vibrationally excited v = 1 state when photolyzed by a 580-nm pulse. The three absorption bands for the deligated NO could be attributed to three NO sites in or near the heme pocket. The kinetics of the three transient bands for the deligated NO, as well as the recovery of the bound NO population, was most consistent with a kinetics scheme that incorporates time-dependent rebinding from one site that rapidly equilibrates with the other two sites. The time dependence results from a time-dependent rebinding barrier due to conformational relaxation of protein after deligation. By assigning each absorption band to a site in the heme pocket of Hb, a pathway for rebinding of NO to Hb was proposed.

This review covers the construction of drug-like 2<em>H</em>-benzopyrans and related libraries using solid-phase parallel synthesis. In this context, the preparation of substituted benzopyrans such as mono-, di- and trisubstituted benzopyran derivatives and additional ring-fused benzopyrans such as benzopyranoisoxazoles, benzopyranopyrazoles, six-membered ring-fused benzopyrans, and polycyclic benzopyrans are highlighted.

Background:It was recently reported that the transcription factor Forkhead box P3 (FoxP3) is expressed not only in regulatory T cells (Tregs) but also in cancer cells. The aim of this study was to clarify the clinical significance of FoxP3 expression in gastric carcinoma.Methods:We performed immunohistochemical staining of FoxP3 to examine the association of FoxP3 expression with clinicopathological features of 194 patients with gastric cancer who underwent surgical resection from 2000 to 2010. We also investigated the immunosuppressive function of FoxP3 using gastric cancer cell lines.Results:Immunohistochemical staining indicated FoxP3-positive cells within tumour tissue including both Tregs and tumour cells. Forkhead box P3-positive tumour cells were observed in 79.3% of signet ring cell carcinoma patients, and the expression of FoxP3 showed a significant correlation with lymph node metastasis. We showed that transforming growth factor-β augmented FoxP3 mRNA expression in cell lines derived from signet ring cell carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown.Conclusion:Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma.

In this Letter, we first investigated the barrier protective effects of eckol and its derivatives against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. Data showed that eckol (1) and dieckol (2) inhibited lipopolysaccharide (LPS)-mediated barrier disruption and transendothelial migration of leukocytes to human endothelial cells. Eckol (1) also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Interestingly, the barrier protective effects of dieckol (2) were better than those of eckol (1) and hydroxyl groups in dieckol (2) positively regulate protective effects.

The epithalamic lateral nucleus of the habenula (LHb) plays a key role in regulating firing of dopamine and serotonin neurons in the midbrain and is thereby involved in various cognitive and affective behaviors. It is not yet clear, however, from where the LHb receives cognitive and affective information relevant to its regulation of the midbrain monoaminergic systems. The prefrontal cortex would be among the ideal sources. Here, using anterograde and retrograde tracer injections in the rat brain, we characterized the topography of the corticohabenular projections. Following injections of cholera toxin subunit B into the LHb, retrogradely labeled neurons were produced in the anterior insular, cingulate, prelimbic and infralimbic cortices. Consistent with this retrograde tracing, injections of biotinylated dextran amine (BDA) into these cortical regions labeled robust terminals in the LHb. Our quantification of the BDA-impregnated varicosities revealed that projections from the anterior insula terminated mainly in the intersection regions of the lateral and ventral two-thirds of the LHb, while projections from the cingulate cortex terminated mainly in the lateral two-thirds of the LHb. By comparison, BDA-labeled terminals originating from the medial prefrontal regions were contained mainly in the medial plus ventral one-third of LHb. Based on these data, we hypothesize that LHb provides a link for conveying cognitive and affective information from prefrontal and insular regions to the midbrain monoaminergic centers.

The phlorotannins (phloroglucinol, eckol, and dieckol) are active compounds found in Eisenia bicyclis, and have been widely investigated for their antioxidant, anti-tumor, and anti-cancer activities. In this study, we investigated the protective effects of these phlorotannins against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice treated by high mobility group box 1 protein (HMGB1), and the signaling pathways involved. The protective activities of the phlorotannins were determined by measuring permeability, leukocyte adhesion and migration, and the activations of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that the phlorotannins inhibited; lipopolysaccharide (LPS)-induced HMGB1 release, HMGB1-mediated barrier disruption, the expressions of cell adhesion molecules (CAMs), and the adhesion/transendothelial migration of leukocytes to human endothelial cells. The phlorotannins also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that the hydroxyl groups on dieckol positively regulated these vascular barrier protective effects. Collectively, these results suggest that phloroglucinol, eckol, and dieckol protect vascular barrier integrity by inhibiting hyperpermeability, the expressions of CAMs, and the adhesion and migration of leukocytes, which confirms their potential usefulnesses for the treatment of vascular inflammatory diseases.

The conventional acoustic nonlinear technique to evaluate the contact acoustic nonlinearity (CAN) at solid-solid contact interfaces (e.g., closed cracks), which uses the through-transmission of normally incident bulk waves, is limited in that access to both the inner and outer surfaces of structures for attaching pulsing and receiving transducers is difficult. The angle beam incidence and reflection technique, where both the pulsing and receiving transducers are located on the same side of the target, may allow the above problem to be overcome. However, in the angle incidence technique, mode-conversion at the contact interfaces as well as the normal and tangential interface stiffness should be taken into account. Based on the linear and nonlinear contact stiffness, we propose a theoretical model for the reflection of an ultrasonic wave angularly incident on contact interfaces. In addition, the magnitude of the CAN-induced second harmonic wave in the reflected ultrasonic wave is predicted. Experimental results obtained for the contact interfaces of A16061-T6 alloy specimens at various loading pressures showed good agreement with theoretical predictions. Such agreement proves the validity of the suggested oblique incidence model.

A large-scale survey was conducted to investigate the infection status of fresh water fishes with Clonorchis sinensis metacercariae (CsMc) in 3 wide regions, which were tentatively divided by latitudinal levels of the Korean peninsula. A total of 4,071 freshwater fishes were collected from 3 regions, i.e., northern (Gangwon-do: 1,543 fish), middle (Chungcheongbuk-do and Gyeongsangbuk-do: 1,167 fish), and southern areas (Jeollanam-do, Ulsan-si, and Gyeongsangnam-do: 1,361 fish). Each fish was examined by the artificial digestion method from 2003 to 2010. In northern areas, only 11 (0.7%) fish of 2 species, Pungtungia herzi and Squalidus japonicus coreanus from Hantan-gang, Cheolwon-gun, Gangwon-do were infected with av. 2.6 CsMc. In middle areas, 149 (12.8%) fish were infected with av. 164 CsMc. In southern areas, 538 (39.5%) fish were infected with av. 159 CsMc. In the analysis of endemicity in 3 regions with an index fish, P. herzi, 9 (6.2%) of 146 P. herzi from northern areas were infected with av. 2.8 CsMc. In middle areas, 34 (31.8%) of 107 P. herzi were infected with av. 215 CsMc, and in southern areas, 158 (92.9%) of 170 P. herzi were infected with av. 409 CsMc. From these results, it has been confirmed that the infection status of fish with CsMc is obviously different among the 3 latitudinal regions of the Korean peninsula with higher prevalence and burden in southern regions.

AIMS Oxidative stress is involved in the pathogenesis of asthma, and peroxiredoxins (PRDX) may be critical in controlling intracellular oxidative stress. The aim of this study was to evaluate expressions of PRDX and their hyperoxidized forms in asthmatic individuals. MAIN METHODS The levels of expression of PRDX1, PRDX2, PRDX3, and PRDX6 and their hyperoxidized forms (PRDX-SO(3)) were measured in PBMCs from asthma patients and control subjects. In addition, cells from these subjects were treated with hydrogen peroxide (H(2)O(2)) and their intracellular concentrations of reactive oxygen species (ROS) were measured. KEY FINDINGS The ratios of hyperoxidized to total PRDX (PRDX-SO(3/)PRDX) in PBMCs were significantly higher in asthma patients than in normal subjects and were correlated with disease severity, with the highest ratio seen in patients with severe asthma. Furthermore, H(2)O(2) treatment of PBMCs, particularly lymphocytes, increased intracellular ROS concentrations with greater and more persistent increases observed in cells from asthmatic than from control subjects. SIGNIFICANCE Hyperoxidation of PRDX may serve as a biomarker of asthma severity and may predict enhanced susceptibility to oxidative stress load in PBMCs of asthmatics.