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Background The superficial temporal artery (STA) to middle cerebral artery (MCA) bypass is an effective treatment procedure for steno-occlusive severe ischemic disease of the anterior circulation. The formation of an aneurysm at the anastomosis site is a rare complication, and the mechanism underlying this condition and the appropriate treatment strategy, have not yet been established. We describe a case of an unruptured anastomosis aneurysm that was treated by endovascular embolization 7 years after bypass surgery. Case Description A 62-year-old woman presented with slurred speech, with magnetic resonance imaging and angiography showing multiple infarctions in her left cerebral hemisphere and severe stenosis in the left internal carotid artery and left MCA. An STA-MCA anastomosis was performed without neurologic sequelae. Five years later, follow-up magnetic resonance imaging showed that an aneurysm had formed at the MCA side of the anastomosis site. After 2 years, the saccular aneurysm had grown and was embedded in the brain parenchyma. Because the patient had experienced repeated problems with surgical wound healing, an endovascular intervention was performed, achieving obliteration of the aneurysm by coil embolization. Conclusions Endovascular treatment is a feasible and efficacious treatment option for an aneurysm at the anastomosis site of an STA-MCA bypass.

The Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) has provided advice in relation to the Chemical Weapons Convention on assistance and protection. We present the SAB's response to a request from the OPCW Director-General in 2014 for information on the best practices for preventing and treating the health effects from acute, prolonged, and repeated organophosphorus nerve agent (NA) exposure. The report summarises pre- and post-exposure treatments, and developments in decontaminants and adsorbing materials, that at the time of the advice, were available for NAs. The updated information provided could assist medics and emergency responders unfamiliar with treatment and decontamination options related to exposure to NAs. The SAB recommended that developments in research on medical countermeasures and decontaminants for NAs should be monitored by the OPCW, and used in assistance and protection training courses and workshops organised through its capacity building programmes. Fil: Timperley, Christopher M.. Defence Science and Technology Laboratory; Reino Unido Fil: Abdollahi, Mohammad. Tehran University of Medical Sciences; Irán Fil: Al-Amri, Abdullah Saeed. Saudi Basic Industries Corporation; Arabia Saudita Fil: Baulig, Augustin. Secrétariat Général de la Défense Et de la Sécurité Nationale; Francia Fil: Benachour, Djafer. Université Ferhat Abbas Sétif 1; Argelia Fil: Borrett, Veronica. Bai Scientific; Australia. University of Melbourne; Australia Fil: Cariño, Flerida A.. University Of The Philippines Diliman; Filipinas Fil: Geist, Michael. Basf Se; Alemania Fil: Gonzalez, David. Universidad de la República Facultad de Química; Uruguay Fil: Kane, William. Monsanto Company; Estados Unidos Fil: Kovarik, Zrinka. Institut Za Medicinska Istrazivanja I Medicinu Rada; Croacia Fil: Martínez Álvarez, Roberto. Universidad Complutense de Madrid; España Fil: Mourão, Nicia Maria Fusaro. ABIQUIM; Brasil Fil: Neffe, Slawomir. Military University of Technology; Polonia Fil: Raza, Syed K.. Institute of Pesticides Formulation Technology; India Fil: Rubaylo, Valentin. State Scientific Research Institute of Organic Chemistry and Technology; Rusia Fil: Suarez, Alejandra Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Takeuchi, Koji. National Institute of Advanced Industrial Science and Technology; Japón Fil: Tang, Cheng. National Defence University; China Fil: Trifirò, Ferruccio. Universidad de Bologna; Italia Fil: van Straten, Francois Mauritz. South African Nuclear Energy Corporation SOC Ltd.; Sudáfrica Fil: Vanninen, Paula S.. University of Helsinki; Finlandia Fil: Vucinic, Slavica. Vojnomedicinska Akademija; Serbia Fil: Zaitsev, Volodymyr. Pontifícia Universidade Católica do Rio de Janeiro; Brasil. Taras Shevchenko National University Of Kyiv; Ucrania Fil: Zafar Uz Zaman, Muhammad. National Engineering and Scientific Commission; Pakistán Fil: Zina, Mongia Saïd. Université de Tunis El Manar. Faculté Des Sciences de Tunis; Túnez Fil: Holen, Stian. Opcw Scientific Advisory Board Secretary; Países Bajos Fil: Forman, Jonathan E.. Opcw Scientific Advisory Board Secretary And Science Policy Adviser; Países Bajos. Organisation for The Prohibition of Chemical Weapons; Países Bajos Fil: Alwan, Wesam S.. Monash University Victorian College Of Pharmacy; Australia. OPCW Office of Strategy and Policy; Países Bajos Fil: Suri, Vivek. Opcw Office Of Strategy And Policy; Países Bajos

Background Fluorescence image guided surgery (FIGS) with 5-aminolevulinic acid for malignant gliomas improves surgical outcome. One of the problems during FIGS is photobleaching under surgical microscopic white light. A solid laser-based white light source for neurosurgery that we developed does not include light with a wavelength of around 405 nm, which is strongly absorbed by protoporphyrin IX. In the present study, we examined the efficacy of this light source to prevent the photobleaching of protoporphyrin IX-induced fluorescence. Methods Filter papers transfused with protoporphyrin IX solution and a coronally sectioned F98 glioma rat model pretreated with 50 mg/kg 5-aminolevulinic acid were continuously exposed to white light. One group was exposed to conventional xenon-based white light and another group was exposed to laser-based white light. Fluorescence at a wavelength of 635 nm was measured with a radiospectrometer (in vitro study) and the relative fluorescence brightness was also measured in digital images (in vivo study) under excitation from violet blue light emitted from diodes every 5 min. Results and conclusion Estimated time for 50% photobleaching was prolonged about two times in the laser-based white light exposure group compared with that in the xenon-based white light exposure group (9.1/18.7 min). In the brain tumor rat model, it was also prolonged about 2.7 times (15.1/40.7 min). A laser-based white light source may inhibit photobleaching during FIGS for malignant gliomas. This light source for neurosurgical microscopy has the potential to prolong the prognosis of malignant glioma patients.

Modification of graphitic carbon nitride (g-C3N4) with silver metal significantly improved the adsorption capacity and the photocatalytic degradation activity for methyl mercaptan, which is a typical sulfurous compound, under visible light. These improvements were easily obtained by the shear mixing method. The ultrafine crystallites of metallic silver were formed on surface of carbon nitride by shear mixing of HT-g-C3N4 (Hydrothermal treated g-C3N4) in aqueous solution of silver acetate. One atom of the silver captured ca. 0.6 molecule of methyl mercaptan on average, while a silver atom deposited on TiO2 captured only 0.03 molecule. The migration of silver crystallites over the g-C3N4 surface and the formation of silver thin-layer during the adsorption of methyl mercaptan were observed by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). The silver crystallite on g-C3N4 seemed to have higher mobility than that on TiO2 to form the coordination suitable for the adsorption of methyl mercaptan. This coordination of Ag also enhanced the photocatalytic degradation of methyl mercaptan to dimethyl disulfide.

Human-to-human transmission of PA I38 mutant influenza A(H3N2) viruses with reduced baloxavir susceptibility has been reported in Japan. In December 2019, we detected a PA E23K mutant A(H1N1)pdm09 virus from a child without baloxavir treatment. The PA E23K mutant virus exhibited reduced baloxavir susceptibility but remained susceptible to neuraminidase inhibitors. Epidemiological data suggest possible transmission of this PA E23K mutant virus among humans, although its growth capability relative to that of the wild-type virus was reduced. Therefore, baloxavir susceptibility monitoring of influenza viruses is essential.

Agonists for EP4 receptor, a prostaglandin E2 receptor subtype, appear to be a promising therapeutic strategy for ulcerative colitis (UC) due to their anti-inflammatory and epithelial regeneration activities. However, the clinical development of orally-available EP4 agonists for mild to moderate UC has not yet been reported. Furthermore, the possibility of an increased risk of colitis-associated cancer (CAC) through direct proliferative effects on epithelial cells via EP4 signaling has not been ruled out. Recently, we identified KAG-308 as an orally-available EP4-selective agonist. Here, we investigated the pharmacological and pharmacokinetic profiles of KAG-308. Then, we compared KAG-308 and sulfasalazine (SASP) for their abilities to prevent colitis and promote mucosal healing in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Finally, the effect of KAG-308 treatment on CAC was evaluated in an azoxymethane (AOM)/DSS-induced CAC mouse model. KAG-308 selectively activated EP4 and potently inhibited tumor necrosis factor-α production in peripheral whole blood and T cells. Oral administration of KAG-308, which showed relatively high bioavailability, suppressed the onset of DSS-induced colitis and promoted histological mucosal healing, while SASP did not. KAG-308 also prevented colorectal carcinogenesis by inhibiting colitis development and consequently decreasing mortality in a CAC model, whereas SASP had marginal effects. In contrast, MF-482, an EP4 antagonist, increased mortality. These results indicated that orally-administered KAG-308 suppressed colitis development and promoted mucosal healing. Moreover, it exhibited preventive effects on colorectal carcinogenesis, and thus may be a new therapeutic strategy for the management of UC that confers a reduced risk of colorectal carcinogenesis.

Prostaglandin E2 not only prevents NSAID-generated small intestinal lesions, but also promotes their healing. The protective effects of prostaglandin E2 are mediated by the activation of EP4 receptors and functionally associated with the stimulation of mucus/fluid secretions and inhibition of intestinal hypermotility, resulting in the suppression of enterobacterial invasion and iNOS up-regulation, which consequently prevents intestinal lesions. Prostaglandin E2 also promotes the healing of intestinal damage by stimulating angiogenesis through the up-regulation of VEGF expression via the activation of EP4 receptors. These findings have contributed to a further understanding of the mechanisms responsible for 'protective' and 'healing-promoting' effects of prostaglandin E2 and the development of new strategies for the prophylactic treatment of NSAID-induced enteropathy.

Aims The present study compared the effects of frequently used anti-platelet drugs, such as clopidogrel, ticlopidine, and cilostazol, on the gastric bleeding and ulcerogenic responses induced by intraluminal perfusion with 25 mM aspirin acidified with 25 mM HCl (acidified ASA) in rats. Main methods The stomach was perfused with acidified ASA at a rate of 0.4 ml/min for 60 min under urethane anesthesia, and gastric bleeding was measured as the concentration of hemoglobin in the luminal perfusate, which was collected every 15 min. Clopidogrel (10–100 mg/kg), ticlopidine (10–300 mg/kg), or cilostazol (3–30 mg/kg) was given p.o. 24 h or 90 min before the perfusion of acidified ASA, respectively. Key findings Perfusion of the stomach with acidified ASA alone led to slight bleeding and lesions in the stomach. The pretreatment with clopidogrel, even though it did not cause bleeding or damage by itself, dose-dependently increased the gastric bleeding and ulcerogenic responses induced by acidified ASA. Ticlopidine also aggravated the severity of damage by increasing gastric bleeding, and the effects of ticlopidine at 300 mg/kg were equivalent to those of clopidogrel at 100 mg/kg. In contrast, cilostazol dose-dependently decreased gastric bleeding and damage in response to acidified ASA. Significance These results demonstrated that clopidogrel and ticlopidine, P2Y12 receptor inhibitors, increased gastric bleeding and ulcerogenic responses to acidified ASA, to the same extent, while cilostazol, a phosphodiesterase III inhibitor, suppressed these responses. Therefore, cilostazol may be safely used in dual anti-platelet therapy combined with ASA, without increasing the risk of gastric bleeding.

Dimethyl methylphosphonate (DMMP) removal by a continuous photocatalytic reaction system at different levels of humidity (RH) was investigated for the purpose of allowing rescue operations at disaster sites over an extended period of time when applied to gas masks or other protective gear. With a high flow rate of air (10 L/min), around 85% of the 0.17 μmol/L DMMP was successfully eliminated by this photocatalytic reaction system regardless of relative humidity. On the other hand, the formation of intermediates on the TiO2 surface indicated that photocatalytic activity was dependent on relative humidity, and during a 5-h test period, the ratio of photocatalytic DMMP conversion reached 74.5% at 100% RH. DMMP adsorption onto the TiO2 surface was found to be quite strong; DMMP removal was observed despite low humidity and dark conditions

Aims We examined changes in the expression of a pro-angiogenic factor, vascular endothelial growth factor (VEGF), and an anti-angiogenic factor, endostatin, as well as matrix metalloproteinase (MMP)-2 and MMP-9 in the rat small intestine after administration of indomethacin and investigated the roles of these factors in the healing of indomethacin-induced small intestinal ulcers. Main methods Male SD rats were given indomethacin (10 mg/kg) p.o. and euthanized at various time points (3–24 h and 2–7 days) after the administration. To impair the healing of these lesions, low-dose of indomethacin (2 mg/kg) was given p.o. once daily for 6 days starting 1 day after ulceration. Levels of VEGF, endostatin, MMP-2 and MMP-9 were determined by Western blotting. Key findings The expression of both VEGF and endostatin was upregulated after the ulceration. Repeated administration of low-dose indomethacin impaired the ulcer healing with a decrease of VEGF expression and a further increase of endostatin expression, resulting in a marked decrease in the ratio of VEGF/endostatin expression. The levels of MMP-2 and MMP-9 were both significantly increased after the ulceration, but these responses were suppressed by the repeated indomethacin treatment. The healing of these ulcers was significantly delayed by the repeated administration of MMP inhibitors such as ARP-101 and SB-3CT. Significance The results confirm the importance of the balance between pro-angiogenic and anti-angiogenic activities in the healing of indomethacin-induced small intestinal damage and further suggest that the increased expression of MMP-2 and MMP-9 is another important factor for ulcer healing in the small intestine.

The specific differences on TiO 2 photocatalytic decomposition rates of vaporized isopropyl methylphosphonofluoridate, sarin (GB), r GB as a real Chemical Warfare Agent (CWA) and vaporized dimethyl methylphosphonate (DMMP), r DMMP as CWA simulant in gas phase have been investigated by Gas chromatography/mass spectrometry (GC/MS) analysis in ambient. The concentration of GB molecules adsorbed at the surface of TiO 2 in the dark, C GB , was 28 times larger than C DMMP in the dark. The r GB was then 3.3 times faster than the r DMMP . The results were explained by taking into account faster hydrolysis of GB molecules at the surface of TiO 2 and the larger diffusion constant of GB in the gas phase than DMMP molecules. The effect of F − adsorption at the surface of TiO 2 as fluoridated surface on the TiO 2 photocatalysis was also studied.

The TiO2 photocatalytic decomposition of ethyl-S-dimethylaminoethyl methylphosphonothiolate (VX) as a real chemical warfare agent (CWA) in liquid phase has been investigated by gas chromatography/mass spectrometry (GC/MS) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. The TiO2 photocatalytic decomposition rate, rVX, was accelerated with increase in alkalinity. The several kinds of by-products such as diisopropylamine, ethyl methylphosphonic acid, oxygenated VX and partially oxidized VX were observed. On the basis of the by-products, the TiO2 photocatalysis were proposed as the P–S, C–N cleavage and oxygenation of VX molecule carried out mainly. The difference between rVX and vaporized dimethyl methylphosphonate (DMMP), rDMMP as CWA simulant was also investigated and the rVX was 30 times faster than the rDMMP. On the basis of the decomposition mechanism of VX and DMMP molecules, the results of the acceleration of rVX in alkaline condition and of the comparison of rVX and rDMMP were also discussed.

Enterobacteria play important roles in the pathophysiology of small intestinal injuries induced by nonsteroidal anti-inflammatory drugs (NSAIDs). We investigated the effects of rebamipide, a gastrointestinal mucoprotective drug, on indomethacin-induced small intestinal injuries, intestinal microbiota, and expression levels of α-defensin 5, which is a Paneth cell-specific antimicrobial peptide and is important for the regulation of intestinal microbiota. Indomethacin (10mg/kg) was orally administered to mice after oral administration of rebamipide (100 or 300 mg/kg) or vehicle for 1 week, and the small intestinal injuries were assessed. After oral administration of rebamipide, the small intestinal contents were subjected to terminal restriction fragment length polymorphism (T-RFLP) analysis to assess the intestinal microbiota composition. Further, the expression levels of mRNA and protein for α-defensin 5 in the ileal tissue were determined by real-time reverse transcription-polymerase chain reaction and western blotting analysis, respectively. Rebamipide inhibited indomethacin-induced small intestinal injuries and T-RFLP analysis showed that rebamipide increased the percentage of Lactobacillales and decreased the percentage of Bacteroides and Clostridium than that in vehicle-treated controls. The mice that were treated with rebamipide showed an increase in α-defensin 5 mRNA expression and protein levels in the ileal tissue compared to vehicle-treated control mice. Indomethacin reduced expression of α-defensin 5 mRNA in ileal tissue, while rebamipide reversed expression of α-defensin 5 mRNA. In conclusion, our study results suggest that rebamipide inhibits indomethacin-induced small intestinal injuries, possibly by modulating microbiota in the small intestine by upregulation of α-defensin 5.

We previously proposed that direct cytotoxicity of NSAIDs due to their membrane permeabilization activity, together with their ability to decrease gastric prostaglandin E 2 , contributes to production of gastric lesions. Compared to loxoprofen (LOX), fluoro-loxoprofen (F-LOX) has much lower membrane permeabilization and gastric ulcerogenic activities but similar anti-inflammatory activity. In this study, we examined the mechanism for this low ulcerogenic activity in rats. Compared to LOX, the level of gastric mucosal cell death was lower following administration of F-LOX. However, the gastric level of prostaglandin E 2 was similar in response to treatment with the two NSAIDs. Oral pre-administration of F-LOX conferred protection against the formation of gastric lesions produced by subsequent administration of LOX and orally administered F-LOX resulted in a higher gastric pH value and mucus content. In the presence of a stimulant of gastric acid secretion, the difference in the ulcerogenic activity of F-LOX and LOX was less apparent. Furthermore, an increase in the mucus was observed in gastric cells cultured in the presence of F-LOX in a manner dependent of increase in the cellular level of cAMP. These results suggest that low ulcerogenic activity of F-LOX involves its both low direct cytotoxicity and protective effect against the development of gastric lesions. This protective effect seems to be mediated through an increase in a protective factor (mucus) and a decrease in an aggressive factor (acid).

A number of behavioral studies suggest that infant-directed speech (IDS) plays a more important role in facilitating both: a) speech perception, and b) adult–infant social interactions than does adult-directed speech (ADS), and hence that IDS contributes to subsequent social and language development. However neural substrates that may underlie these IDS functions have not been examined. The present study examined cerebral hemodynamic responses to IDS in 48 infants (4–13 months of age) using near-infrared spectroscopy (NIRS). Japanese sentences uttered by the infants' own mothers and by unfamiliar mothers were used to record activations in temporal and frontal area separately. Increased activations were observed predominantly in infants' left and right temporal areas when they listened to IDS rather than to ADS when both involved voices of their own and unfamiliar mothers. In contrast, significantly greater activations were observed in the frontal area when infants listened to IDS produced by their own mothers, not when IDS arose from unfamiliar mothers. Furthermore, the present results indicate that responses to IDS do vary as a function of the infant's age and the talker familiarity. These findings suggest a differential function for frontal and temporal areas in processing infant-directed speech by the different speakers.

The adsorption and photocatalytic degradation of nerve agent, isopropyl methylphosphonofluoridate, Sarin (GB) as a real Chemical Warfare Agent (CWA) on powdery Titanium dioxide (TiO2) film have been investigated using Gas chromatography/mass spectrometry (GC/MS) analysis in ambient atmosphere. We found that the ability to decontaminate GB molecules on TiO2 photocatalyst can be estimated to be 42 molecules/nm2, indicating that 1 g of TiO2 photocatalyst can decontaminate 3.4 mmol of GB molecules as the limitation value to maintain the photocatalytic activity. We also elucidated a plausible photocatalytic decontamination mechanism of GB at the surface of TiO2 photocatalyst on the basis of the results obtained in this study.

Dipeptidyl peptidase IV (DPP-4) inhibition is a validated therapeutic option for type 2 diabetes, exhibiting multiple antidiabetic effects with little or no risk of hypoglycemia. In our studies involving non-covalent DPP-4 inhibitors, a novel series of quinoline-based inhibitors were designed based on the co-crystal structure of isoquinolone 2 in complex with DPP-4 to target the side chain of Lys554. Synthesis and evaluation of designed compounds revealed 1-[3-(aminomethyl)-4-(4-methylphenyl)-2-(2-methylpropyl)quinolin-6-yl]piperazine-2,5-dione (1) as a potent, selective, and orally active DPP-4 inhibitor (IC₅₀=1.3 nM) with long-lasting ex vivo activity in dogs and excellent antihyperglycemic effects in rats. A docking study of compound 1 revealed a hydrogen-bonding interaction with the side chain of Lys554, suggesting this residue as a potential target site useful for enhancing DPP-4 inhibition.

The design, synthesis, and structure-activity relationships of a new class of potent and orally active non-peptide dipeptidyl peptidase IV (DPP-4) inhibitors, 3-aminomethyl-1,2-dihydro-4-phenyl-1-isoquinolones, are described. We hypothesized that the 4-phenyl group of the isoquinolone occupies the S1 pocket of the enzyme, the 3-aminomethyl group forms an electrostatic interaction with the S2 pocket, and the introduction of a hydrogen bond donor onto the 6- or 7-substituent provides interaction with the hydrophilic region of the enzyme. Based on this hypothesis, intensive research focused on developing new non-peptide DPP-4 inhibitors has been carried out. Among the compounds designed in this study, we identified 2-[(3-aminomethyl-2-(2-methylpropyl)-1-oxo-4-phenyl-1,2-dihydro-6-isoquinolinyl)oxy]acetamide (35a) as a potent, selective, and orally bioavailable DPP-4 inhibitor, which exhibited in vivo efficacy in diabetic model rats. Finally, X-ray crystallography of 35a in a complex with the enzyme validated our hypothesized binding mode and identified Lys554 as a new target-binding site available for DPP-4 inhibitors.

The secretion of HCO(3)(-) in the duodenum is increased by exogenous prostaglandin (PG) E(2) and mucosal acidification, the latter being accompanied by a rise in mucosal PGE(2) content and nitric oxide (NO) release. The stimulatory effect of PGE(2) is mediated intracellularly by both Ca(2+) and 3',5'-adenosine cyclic adenosine monophosphate (cAMP), and this action is inhibited by EP3 and EP4 antagonists. The secretion is also increased by NOR3 (NO donor), and this response is mimicked by dibutyryl 3',5'-cyclic guanosine monophosphate (dbcGMP) and attenuated by indomethacin. Mucosal acidification stimulates HCO(3)(-) secretion with concomitant increases in mucosal PGE(2) production and NO release. The effects on HCO(3)(-) secretion and PGE(2) production are inhibited by indomethacin [nonselective cyclooxygenase (COX) inhibitor] and SC-560 (selective COX-1 inhibitor) but not rofecoxib (selective COX-2 inhibitor). N(G)-nitro-l-arginine methyl ester [l-NAME: nonselective NO synthase (NOS) inhibitor], but not aminoguanidine [selective inducible NOS inhibitor], attenuates the acid-induced HCO(3)(-) secretion and NO release in an l-arginine-sensitive manner. In addition, the response to PGE(2) is potentiated by vinpocetine [phosphodiesterase (PDE) 1 inhibitor] and cilostamide (PDE3 inhibitor), while the response to NOR3 is increased by vinpocetine. We conclude that endogenous PGs and NO are both involved in the local regulation of acid-induced duodenal HCO(3)(-) secretion; COX-1 and constitutive NOS are key enzymes responsible for the production of PGs and NO, respectively; NO stimulates HCO(3)(-) secretion by increasing PG production; PGE(2) stimulates HCO(3)(-) secretion via activation of EP3/EP4 receptors; and both PDE1 and PDE3 are involved in the regulation of duodenal HCO(3)(-) secretion.

The aim of our study is to develop apparatuses that use TiO 2 for effective decontamination of air contaminated by Sarin gas. We performed photocatalytic decomposition of gaseous dimethyl methylphosphonate (DMMP) by TiO 2 and identified the oxidization products. The high activity of TiO 2 (0.01 g) was observed under UV-light irradiation and high concentration DMMP (33.5 μM) was removed rapidly. On the other hand, DMMP was not decreased under UV-light irradiation without TiO 2 . This indicates that photocatalytic treatment is very effective for the removal of DMMP. Methanol, formaldehyde, formic acid, methyl formate, CO, CO 2 and H 2 O were detected as the primary products. In the gas phase, no highly poisonous substances were detected. In order to examine the performance of photocatalytic activity during long-term reactions, we performed photocatalytic decomposition by repeated-batch reactions using TiO 2 . High photocatalytic activities decreased gradually. Meanwhile, the strong adsorption of TiO 2 against DMMP was observed as photocatalytic activities decreased. During the repeated-batch reactions with the sample scaled up (TiO 2 : 0.1 g), the total amount of removed DMMP reached 968.5 μM by both photocatalytic decomposition and the strong adsorption of TiO 2 . These results suggest the possibility of removing large amounts of DMMP.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin decrease mucosal PGE(2) content by inhibiting cyclooxygenase (COX) activity and produce damage in the small intestine. The development of intestinal lesions induced by indomethacin was accompanied by increases in intestinal motility, enterobacterial invasion, and myeloperoxidase (MPO) as well as inducible nitric oxide synthase (iNOS) activity, together with the up-regulation of COX-2 and iNOS mRNA expression. Neither SC-560, a selective COX-1 inhibitor, nor rofecoxib, a selective COX-2 inhibitor, alone caused intestinal damage, but their combined administration provoked lesions in the small intestine. SC-560, but not rofecoxib, caused intestinal hypermotility, bacterial invasion and the expression of COX-2 as well as iNOS mRNA, yet the iNOS and MPO activity was increased only when rofecoxib was administered together with SC-560. Although SC-560 inhibited PG production, the level of PGE(2) recovered in a rofecoxib-dependent manner. The intestinal hypermotility in response to indomethacin was prevented by both 16,16-dimethyl PGE(2) and atropine but not by ampicillin, yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 as well as the iNOS activity in the intestinal mucosa following indomethacin treatment, thereby preventing the intestinal damage. These results suggest that inhibition of COX-1, despite causing intestinal hypermotility, bacterial invasion and iNOS expression, up-regulates the expression of COX-2, and the PGE(2) derived from COX-2 counteracts the deleterious events caused by COX-1 inhibition and maintains mucosal integrity. These sequences of events explain why intestinal damage occurs when both COX-1 and COX-2 are inhibited.

We examined the expression of aquaporin (AQP)-1 in monolayers of the rat gastric epithelial cell line RGM1 and investigated the roles AQP1 plays in the epithelial restitution during wound healing. A round wound of constant size was produced in the center of a confluent cell monolayer using a rotating silicon tip. The RGM1 cells expressed AQP1 mRNA. Hg(2+) (HgCl(2)), an inhibitor of AQPs, suppressed cell migration during wound repair in a concentration-dependent manner. Likewise, cell migration was also impaired in cells in which AQP1 was knocked down by RNA interference, resulting in a marked delay of wound healing. The AQP1 knockdown RGM1 cells showed a decrease in the formation of membrane protrusions (lamellipodia) at the leading edge of the wound as compared with control RGM1 cells. These results suggest for the first time that AQP1 plays a crucial role in gastric epithelial cell migration during wound healing.

We have discovered that Cu 2+ -loaded TiO 2 films (1.5 μm thick) exhibit a high activity of selective reduction of NO 2 to NO in air under UV light illumination (1 mW cm −2 ). This effect is associated with a reduced NO oxidation to HNO 3 . For an increasing amount of Cu 2+ ions the NO reductions become more stable. Cu 2+ ions are responsible for the high redox property, playing an important role in adsorption of NO 2 /NO 2 − , electron transfer from the TiO 2 to NO 2 /NO 2 − , and recombination center for positive holes.

A deactivating behavior of TiO2 photocatalysts in NO2 oxidation to HNO3 was studied with use of TiO2 nanoparticulate thin films (0.5−1.5 μm thick) under UV light illumination over 10 h. The photocatalytic activity was decreased with accumulation of HNO3 on the TiO2 surface. For thicker TiO2 films, the deactivation rate was found to be slower. The amount of HNO3 trapped on the TiO2 surface was increased and finally saturated, at which the largest amount of HNO3 was proportional to the thickness of the film. On the basis of the results, we concluded that the produced HNO3, inhibiting the reaction as a physical barrier, must be able to diffuse on the TiO2 surface at a rate of at least more than 1.5 μm h−1, and finally distributes homogeneously on the whole film. The maximum density of HNO3 accumulated on the TiO2 surface was estimated to be ∼2 molecules nm−2 under standard conditions. Finally, when the steady state is reached, the photocatalytic activity remained ∼8% of the initial one.

Aims We established a new model of ischemic enteritis in rats and evaluated its usefulness for screening prophylactic drugs. Main methods Male SD rats were used after 18 h of fasting. Under ether anesthesia, the superior mesenteric artery (SMA) was exposed, and a calibrated stenosis was produced by placing a needle on a blood vessel, ligating both the vessel and needle, and then removing the needle from the ligature. Key findings The stenosis caused severe damage on the anti-mesenteric side of the small intestine within 3 days; the severity of the damage increased with the gauge of a needle. No damage occurred in the small intestine following the stenosis with a needle of less than 21 gauge. Multiple hemorrhagic lesions occurred at an incidence of 100% when a 23-gauge needle was used. The development of enteritis was accompanied by enterobacterial invasion in the mucosa, with an up-regulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. The ischemia-induced enteritis was significantly prevented by repeated treatment with aminoguanidine (a selective iNOS inhibitor), L-NAME (a nonselective NOS inhibitor), ampicillin, and aztreonam (a gram-negative bacterium antibiotic), but not vancomycin (a gram-positive bacterium antibiotic). Significance These results showed that a novel model of ischemic enteritis is induced in rats by stenosis of the SMA, this model may be useful for screening drugs against ischemic enteritis, and gram-negative bacteria as well as iNOS/NO are involved in the pathogenesis of enteritis in this model.

We present a method to analyze the photocatalytic oxidation of ethanol (EtOH) in an aqueous TiO 2 suspension by measuring the consumption of dissolved oxygen (DO) as a function of varying EtOH and H 2 O 2 concentrations in the suspension. The consumption of DO was analyzed by means of Langmuir–Hinshelwood (L–H) kinetics. The parameter K D-DO calculated from L–H kinetics, defined as (O 2 consumption rate constant) (O 2 reproduction rate constant) −1 , reflects the adsorption equilibrium of EtOH and the photocatalytic reaction mechanisms. The observed K D-DO values for the photocatalytic oxidation of EtOH reflected to the proposed reaction mechanism measured by HPLC and starch–Iodine methods. By using this DO analysis method, we elucidated the photocatalytic reaction mechanism of EtOH oxidation and discussed the effect of H 2 O 2 as active oxygen species on TiO 2 photocatalysis.

Aims We examined the effect of a prostacyclin (PGI 2 ) analog iloprost on histamine-induced acid secretion and investigated how endogenous PGI 2 mediated the decreased secretory response in the damaged stomach after exposure to taurocholate (TC). Main methods Male C57BL/6 mice, both wild-type (WT) and IP receptor knockout (IP-KO) animals, were used after 18 h of fasting. Under urethane anesthesia, the abdomen was incised, and an acute fistula was provided in the stomach. Key findings Acid secretion in WT and IP-KO mice was similarly and dose-dependently increased by histamine. Iloprost decreased the histamine-stimulated secretion in WT but not IP-KO mice. The inhibitory effect of iloprost in WT mice was totally abrogated by the prior administration of CYN154806, a selective somatostatin SST2 receptor antagonist. On the other hand, the acid secretion in WT mice was decreased after exposure of the stomach to 20 mM TC for 20 min, with an increase in mucosal PGI 2 content, but the decrease was significantly less marked in IP-KO mice. The decreased acid response to TC in WT mice was totally prevented by the prior administration of CYN154806 as well as indomethacin. Somatostatin contents in the stomach were reduced after the administration of iloprost or the mucosal exposure to TC, while the blood levels increased. Significance Somatostatin/SST2 receptors are involved in the decreased acid response of the damaged stomach, in addition to PGI 2 /IP receptors. It is assumed that PGI 2 releases somatostatin from D cells, which in turn decreases acid secretion via the activation of SST2 receptors.

The combination of two agents with different but complementary mechanisms of action is a logical approach for treating patients with type 2 diabetes. Thus, we evaluated chronic combination therapy with alogliptin, a highly selective dipeptidyl peptidase-4 inhibitor that enhances the action of incretins, and pioglitazone, a thiazolidinedione that improves peripheral and hepatic insulin sensitivity. Studies were designed to investigate the chronic metabolic and pancreatic effects of alogliptin (0.03%) plus pioglitazone (0.003%) combination treatment in obese ob/ob mice. After 4-5 weeks of treatment, alogliptin significantly increased plasma active glucagon-like peptide-1 levels up to 4.1-fold and decreased plasma glucagon up to 25%, whereas pioglitazone significantly increased plasma adiponectin up to 1.3-fold. Combination treatment exhibited a complementary effect, increasing plasma insulin levels by 3.2-fold (alogliptin alone, 1.6-fold; pioglitazone alone, 1.5-fold) and decreasing glycosylated hemoglobin by 2.3% (alogliptin alone, 1.0%; pioglitazone alone, 1.5%), and non-fasting and fasting plasma glucose by 37% and 62% (alogliptin alone, 17% and 24%; pioglitazone alone, 30% and 45%), respectively. Combination treatment also decreased plasma triglycerides by 67% and non-esterified fatty acids by 25% (alogliptin alone, 24% and 11%; pioglitazone alone, 54% and 8%). Moreover, combination treatment increased pancreatic insulin content by 2.2-fold (alogliptin alone, 1.3-fold; pioglitazone alone, 1.6-fold), with no significant changes in body weight. These results indicate that combination treatment with alogliptin and pioglitazone improved glycemic control, lipid profiles and increased pancreatic insulin content in ob/ob mice by preventing incretin inactivation and improving insulin resistance. These results provide a strong argument for using alogliptin in combination with pioglitazone.

Aims We investigate the role of nitric oxide (NO) in the hypersecretion of acid and pepsinogen induced by stomach distension. Main method The rat stomach was distended by instillation of saline through an acute fistula under urethane anesthesia. Key findings Both secretions of acid and pepsinogen were increased by the distension depending on the volume of saline introduced, and responses were attenuated by bilateral cervical vagotomy or prior administration of atropine. N G -nitro- l -arginine methyl ester (L-NAME) had a dual effect on these responses, causing an increase in the acid response and a decrease in the pepsin response, both in an l -arginine-sensitive manner. Distension of the stomach increased the luminal NO release; this response was suppressed by vagotomy and L-NAME. Intragastric application of FK409, a NO donor, dose-dependently increased pepsinogen secretion while decreasing acid secretion in the stomach without distension. However, serosal application of both FK409 and 8-bromo-guanosine cyclic 3′, 5′-monophosphate (8-Br-cGMP) stimulated the secretion of pepsinogen in isolated mouse stomachs in vitro . The stimulatory effect of FK409 on pepsinogen secretion was totally abolished by LY83583, a guanylate cyclase inhibitor. Significance Distension of the stomach increases both acid and pepsinogen secretion through a vagal–cholinergic pathway in addition to the luminal release of NO, and NO affects these responses in opposite ways, suppressing the acid response while enhancing the pepsin response, both mediated by a guanylate cyclase/cGMP pathway.

Intravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients, but it also enhances the generation of hydroxyl radicals. Previously we demonstrated that IVIR increases oxidized serum albumin levels in HD patients. However, the effect of IVIR frequencies on the oxidative stress has never been studied before. Therefore, we compared the two IVIR schedules recommended by the Japanese Society for Dialysis Therapy guideline 2004 by measuring oxidized albumin in chronic HD patients.Twenty-two HD patients were divided into two IVIR protocol groups (group I: 40 mg of iron 3 times a week for 4 weeks, group II: 40 mg of iron once a week for 3 months). These protocols differ in IVIR frequency, but receive the same amount of iron (total 520 mg). We compared these two regimens by determining the levels of hemoglobin, serum ferritin, advanced oxidation protein products (AOPP), and oxidized albumin at 0, 4, 8, 12, 16, and 20 weeks.Both patient groups resulted in a similar and significant increase in hemoglobin levels, whereas group I markedly induced AOPP and oxidation of serum albumin than group II at 4 weeks (P0.05). AOPP and oxidation of serum albumin was also gradually declined by 20 weeks, while the oxidized albumin and AOPP in group II was not significantly changed during the entire experimental period. Transferrin saturation and serum ferritin levels were also increased in group I compared with group II at 4 weeks (P0.001). In addition, we found a strong positive correlation between oxidized albumin and serum ferritin levels (r=0.615, P0.05), suggesting the possibility that the accumulation of iron stores has a causative role in the progression of oxidative stress in HD patients treated with IVIR.The results of this study indicate that lower frequency IVIR protocol is recommended to reduce IVIR-induced oxidative stress in HD patients.

Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes by increasing plasma active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide levels. However, the effects of chronic DPP-4 inhibition on in vivo beta-cell function are poorly characterized. We thus evaluated the chronic effects of the DPP-4 inhibitor alogliptin benzoate (formerly SYR-322) on metabolic control and beta-cell function in obese diabetic ob/ob mice. Alogliptin (0.002%, 0.01%, or 0.03%) was administered in the diet to ob/ob mice for 2 days to determine effects on plasma DPP-4 activity and active GLP-1 levels and for 4 weeks to determine chronic effects on metabolic control and beta-cell function. After 2 days, alogliptin dose-dependently inhibited DPP-4 activity by 28–82% and increased active GLP-1 by 3.2–6.4-fold. After 4 weeks, alogliptin dose-dependently decreased glycosylated hemoglobin by 0.4–0.9%, plasma glucose by 7–28% and plasma triglycerides by 24–51%, increased plasma insulin by 1.5–2.0-fold, and decreased plasma glucagon by 23–26%, with neutral effects on body weight and food consumption. In addition, after drug washout, alogliptin (0.03% dose) increased early-phase insulin secretion by 2.4-fold and improved oral meal tolerance (25% decrease in glucose area under the concentration–time curve), despite the lack of measurable plasma DPP-4 inhibition. Importantly, alogliptin also increased pancreatic insulin content up to 2.5-fold, and induced intense insulin staining of islets, suggestive of improved beta-cell function. In conclusion, chronic treatment with alogliptin improved glycemic control, decreased triglycerides, and improved beta-cell function in ob/ob mice, and may exhibit similar effects in patients with type 2 diabetes.

The gastric mucosa maintains structural integrity and function despite continuous exposure to noxious factors, including 0.1 mol/L HCl and pepsin, that are capable of digesting tissue. Under normal conditions, mucosal integrity is maintained by defense mechanisms, which include preepithelial factors (mucus-bicarbonate-phospholipid "barrier"), an epithelial "barrier" (surface epithelial cells connected by tight junctions and generating bicarbonate, mucus, phospholipids, trefoil peptides, prostaglandins (PGs), and heat shock proteins), continuous cell renewal accomplished by proliferation of progenitor cells (regulated by growth factors, PGE(2) and survivin), continuous blood flow through mucosal microvessels, an endothelial "barrier," sensory innervation, and generation of PGs and nitric oxide. Mucosal injury may occur when noxious factors "overwhelm" an intact mucosal defense or when the mucosal defense is impaired. We review basic components of gastric mucosal defense and discuss conditions in which mucosal injury is directly related to impairment in mucosal defense, focusing on disorders with important clinical sequelae: nonsteroidal anti-inflammatory drug (NSAID)-associated injury, which is primarily related to inhibition of cyclooxygenase (COX)-mediated PG synthesis, and stress-related mucosal disease (SRMD), which occurs with local ischemia. The annual incidence of NSAID-associated upper gastrointestinal (GI) complications such as bleeding is approximately 1%-1.5%; and reductions in these complications have been demonstrated with misoprostol, proton pump inhibitors (PPIs) (only documented in high-risk patients), and COX-2 selective inhibitors. Clinically significant bleeding from SRMD is relatively uncommon with modern intensive care. Pharmacologic therapy with antisecretory drugs may be used in high-risk patients (eg, mechanical ventilationor=48 hours), although the absolute risk reduction is small, and a decrease in mortality is not documented.

NSAIDs damage the small intestine as well as the stomach as adverse effects. We previously reported that the gastric ulcerogenic response to NSAIDs was markedly increased in arthritic rats. The present study was designed to examine the intestinal ulcerogenic property of indomethacin in adjuvant-induced arthritic rats in comparison with normal animals. Arthritis was induced in male Dark Agouti rats by injection of Freund's complete adjuvant into the right hindfoot. Two weeks later, indomethacin was given orally and the intestine was examined for lesions at several time points after indomethacin. Indomethacin produced intestinal lesions in both normal and arthritic rats, but in the latter, the ulcerogenic response occurred much earlier and the severity was markedly enhanced. Aminoguanidine, an inhibitor of iNOS, significantly suppressed the damage, yet the efficacy differed in normal and arthritic rats, depending on the dose schedule; the effect of post-administration (6 h after) was greater than that of pre-administration (0.5 h before) in normal rats, whereas that of post-administration was less than that of pre-administration in arthritic rats. The expression of iNOS and TLR4 in the intestine was enhanced in arthritic rats as compared with normal rats. These results suggest that the intestinal ulcerogenic response to indomethacin is markedly aggravated in arthritic rats. Notably, the onset of the ulceration was much earlier in arthritic rats than normal rats. These phenomena may be accounted for by the upregulation of iNOS/NO through the increased expression of TLR4 in the small intestine of arthritic rats.

We investigated the involvement of prostaglandin E (PGE) receptor subtype EP3 in the regulatory mechanism of duodenal HCO 3 − secretion in rats. A proximal duodenal loop or a chambered stomach was perfused with saline, and HCO 3 − secretion was measured using a pH-stat method and by adding 2 mM HCl. Mucosal acidification was achieved through 10 min of exposure to 10 mM HCl in the duodenum or 100 mM HCl in the stomach. Various EP agonists or the EP4 antagonist were given i.v., while the EP1 or EP3 antagonist was given s.c. or i.d., respectively. Sulprostone (EP1/EP3 agonists) stimulated duodenal HCO 3 − secretion in a dose-dependent manner, and this response was inhibited by AE5-599 (EP3 antagonist) but not AE3-208 (EP4 antagonist). AE1-329 (EP4 agonist) also increased duodenal HCO 3 − secretion, and this action was inhibited by AE3-208 but not AE5-599. The response to PGE 2 or acidification in the duodenum was partially attenuated by AE5-599 or AE3-208 alone but completely abolished by the combined administration. Duodenal damage caused by mucosal perfusion with 150 mM HCl for 4 h was worsened by pretreatment with AE5-599 and AE3-208 as well as indomethacin and further aggravated by co-administration of these antagonists. Neither the EP3 nor EP4 antagonist had any effect on the gastric response induced by PGE 2 or acidification. These results clearly demonstrate the involvement of EP3 receptors, in addition to EP4 receptors, in the regulation of duodenal HCO 3 − secretion as well as the maintenance of the mucosal integrity of the duodenum against acid injury.

Un barreau photocatalytique de type guide d'onde consistant en un tube de verre, recouvert a l'exterieur de TiO 2 transparent et contenant a l'interieur un barreau guide d'onde optique, a ete concu et ses performances etudiees. Une eau polluee modele contenant 100 ppm de toluene ou de phenol dans un becher de 500 ml a ete utilisee. La performance du photoreacteur a ete evaluee en etudiant la vitesse d'elimination des polluants dans l'eau sous photo-irradiation. Un barreau acrylique de 6 mm de diametre et de 50 mm de longueur a ete utilise comme guide d'onde de la lumiere. Une de ses extremites a ete depolie ou comporte un filet de vis dans le but d'augmenter la diffusion de la lumiere. Le tube de verre a ete recouvert de couches de TiO 2 de quatre epaisseurs differentes, preparees par la methode dite de dip-coating. Les barreaux photocatalytiques de type guide d'onde permettent d'eliminer efficacement le toluene et le phenol avec une quantite totale d'especes intermediaires faible.

Deposition of ultrafine particle of silver on titanium dioxide (TiO2) significantly improved the photocatalytic activity for degradation of gaseous sulfur compounds, such as hydrogen sulfide (H2S) and methylmercaptan (CH3SH). The silver-deposited photocatalytic filter (Ag-PCF) was prepared by coating TiO2 powder on the porous ceramics substrate and successively depositing nano-sized silver particles on TiO2 by means of photodeposition method. The photocatalytic degradation rates of hydrogen sulfide and methylmercaptan by Ag-PCF were 7 times and 14 times larger, respectively, than those by conventional photocatalytic filter. The sulfur atom of hydrogen sulfide was oxidized into sulfate ion, which was accumulated on the filter. However, the degradation rate did not decline in the experimental period. The deposited silver seems to act as a co-catalyst that enhances the photocatalytic oxidation of sulfur compounds.

Photocatalytic degradation of volatile organic compounds (VOCs) with Pt-loaded TiO 2 was analyzed at elevated temperatures in the laboratory experiments (40–190 °C) and in the field experiments (30–230 °C). The temperature of catalyst coated on the sunlight receiver was easily elevated to around 200 °C by parabolic trough concentrator (1 m × 1 m). When gaseous toluene (15 ppm) or acetaldehyde (400 ppm) was passed through the reactor, 79% of toluene or 93% of acetaldehyde was removed continuously. In the similar condition, bare TiO 2 was rapidly deactivated by the formation of byproducts. The combination of sunlight concentrator and Pt–TiO 2 catalyst exhibited the enhancement of complete degradation of VOCs, the inhibition of deactivation, and the reactivation of photocatalyst. The contributions of photocatalytic and catalytic activities of Pt–TiO 2 were analyzed by using UV lamp and electric heater. Acetaldehyde is thermocatalytically degraded by photodeposited Pt on TiO 2 at 70–190 °C without UV irradiation, however the UV irradiation is necessary for the complete oxidation of acetaldehyde into CO 2 . It is inferred that the degradation of VOCs is enhanced by the combined effect of Pt thermocatalyst and Pt–TiO 2 photocatalyst.

The effects of heme oxygenase (HO) inhibitors, zinc-protoporphyrin-IX (ZnPP-IX), and tin protoporphyrin-IX (SnPP-IX) and their interactions with L-arginine/nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways were investigated in postoperative ileus in rats. Intestinal transit was measured as Evans blue migration after skin incision, laparotomy or laparotomy plus gut evisceration and handling. Laparotomy and small intestinal manipulations increased blood plasma nitrites/nitrates level 1.88-fold. Nu-nitro-L-arginine methyl ester, indomethacin, a selective COX-1 blocker (resveratrol) and COX-2 antagonists (nimesulide, DuP-697, NS-398) reversed the additional inhibitory effects of gut manipulation subsequent to laparotomy. In contrast, N-(3-(aminomethyl)benzyl)acetamidine or S-methylisothiourea highly selective inducible NOS blockers, remained ineffective. ZnPP-IX and SnPP-IX overturned the effects of laparotomy on dye propulsion, but were only partially effective after laparotomy and gut handling attenuating the additional inhibitory influences of gut manipulation, the intestinal transit reaching 89.21%, 92.87%, 53.46%, and 48.56% of respective controls transit. Salutary effects of L-NAME, ZnPP-IX, and SnPP-IX were dose-dependent, L-arginine or hemin (HO substrate) sensitive. Administration of indomethacin and resveratrol subsequent to SnPP-IX reversed the inhibitory effects of laparotomy and manipulation, amounting to 93.91% and 87.43% of controls. On the other hand, L-NAME injected after SnPP-IX abolished the salutary effects of the latter, study dye migration reached 25.18% of control rat. Therefore we demonstrated that nitric oxide, carbon monoxide, and prostanoids play a role in the pathogenesis of postoperative ileus albeit in different mechanisms. Laparotomy stimulated HO activity, whereas gut manipulation led to an excessive constitutive NOS stimulation accompanied by augmented prostanoid synthesis by COX-1. Unaffected synthesis of either NO or CO enables a return of gastrointestinal transit during postoperative period, whereas a pharmacological blockade of two complementary metabolic pathways provides a most effective measure against postoperative ileus development.

Gas-phase catalytic and photocatalytic decomposition of ozone (O 3 ) was investigated using TiO 2 and Pt-loaded TiO 2 (Pt/TiO 2 ) at room temperature and atmospheric pressure. The nominal weight loading of Pt was less than 1 wt.%. Results of this study indicate that both the overall conversion of O 3 to O 2 and other products with UV irradiation and without UV irradiation (dark reaction) can be improved by using Pt-loaded TiO 2 . Photocatalytic conversion of O 3 on pure TiO 2 decreased with increasing water vapor. In contrast, Pt/TiO 2 was active for the decomposition of ozone under the humidity condition at room temperature.

The photocatalytic degradation of acetaldehyde by metal-photodeposited TiO 2 was analyzed at room temperature and elevated temperatures. In the humid condition, the acetaldehyde degradation rate of Pt–TiO 2 was larger than that of pure TiO 2 , however, the degradation rate of Pd or Ag–TiO 2 was smaller. The degradation rate of metal-deposited TiO 2 depended on the oxidation state of metal, which also influenced the signal intensities of O 2 − and Ti 3+ in electron spin resonance (ESR) spectrum recorded at 77 K. By elevating temperature from 40 to 130 °C, the acetaldehyde degradation rate and the CO 2 production rate of Pt–TiO 2 were increased by the aid of metal Pt. Acetaldehyde is also thermocatalytically degraded by photodeposited Pt on TiO 2 at 70–190 °C without UV irradiation, however the UV irradiation is necessary for complete mineralization of acetaldehyde. The mineralization of acetaldehyde is considered to be enhanced by the partial oxidation of acetaldehyde by Pt thermocatalyst and the oxidation of intermediates into CO 2 by TiO 2 photocatalyst.

Ellagic acid (EA), a naturally occurring plant phenol, has the antioxidant and anti-inflammatory activities. In the present study, we examined the effect of EA contained in microspheres on the ulcerative colitis induced experimentally in rats by dextran sulfate sodium (DSS). Experimental colitis was induced in male Fisher 344 rats by daily treatment with 3% DSS solution in drinking water for 7 days. EA of microspheres (mcEA: 1 approximately 10 mg/kg as EA contents) was administered p.o. twice daily for 6 days. In a preliminary study, we found that these microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileo-cecal junction and distributed to the terminal ileum and the colon. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substances (TBARS) were measured on 7th day after the onset of DSS treatment. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of MPO activity and TBARS as well as the decreases of body weight gain and colon length. Administration of mcEA reduced the severity of DSS-induced colitis in a dose-dependent manner, and a significant effect was observed at 10 mg/kg, the ED50 being 2.3 mg/kg. This mcEA treatment also significantly mitigated changes in various biochemical parameters in the colonic mucosa induced by DSS. Although plain EA (without using microspheres) was also effective in reducing the severity of DSS-induced colitis, this effect was much less potent as compared with that of mcEA; the ED50 was about 15 times higher than that of mcEA. In addition, a significant effect on DSS-induced colitis was also obtained by intra-rectal administration of superoxide dismutase, an anti-oxidative agent. These results suggest that EA prevents the ulcerative colitis induced by DSS, probably by radical scavenging and/or anti-oxidative actions. The microspheres used in this study may be useful for delivering an orally administered drug specifically to the colon.

We examined the effect of ellagic acid (EA), one of the polyphenols that are abundantly contained in whisky as a nonalcoholic component, on gastric lesions induced by ammonia plus ischemia or ischemia/reperfusion in rats, in relation to the antioxidative system. Under urethane anesthesia, a rat stomach was mounted in an ex vivo chamber, and the following two experiments were performed; 1) a stomach was made ischemic (1.5 ml/100 g body weight) for 20 min, followed by reperfusion for 15 min in the presence of 100 mM HCl; 2) a stomach was made ischemic by bleeding from the carotid artery (1 ml/100 g body weight), followed by intragastric application of ammonia (NH4OH: 120 mM). EA (0.1-10 mg/ml) was applied in the chamber 30 min before the onset of ischemia. Gastric potential difference (PD) and mucosal blood flow (GMBF) were measured before, during and after 20 min of ischemia. Ischemia/reperfusion caused a profound drop in GMBF followed by a return, and resulted in hemorrhagic lesions in the stomach in the presence of 100 mM HCI. These lesions were dose-dependently prevented by EA with suppression of lipid peroxidation but no effect on GMBF, and the effect at 6 mg/ml was almost equivalent to that of superoxide dismutase (SOD: 15000 unit/kg/hr) infused i.v. during a test-period. On the other hand, application of NH4OH to the ischemic stomach produced a marked reduction in PD, resulting in severe hemorrhagic lesions. These changes were prevented with both EA and SOD. In addition, EA had a potent scavenging action against monochloramine in vitro. These results suggest that EA exhibits gastric protective action against gastric lesions induced by NH4OH or reperfusion in the ischemic stomach, probably due to its anti-oxidative activity. This property of EA partly explains the less damaging effect of whisky in the stomach and may be useful as the prophylactic for Helicobacter pylori-associated gastritis.

TiO 2 thin film photocatalysts coated onto glass plates were prepared by thermal decomposition of tetraisopropyl orthotitanate with a dip coating process using α-terpineol as a highly viscous solvent. Two types of ligands, polyethylene glycol 600 and (ethoxyethoxy)ethanol were added to the dip-coating solution as the stabilizer of titanium alkoxide. TiO 2 thin films were obtained after calcination at 450°C for 1 h. The film thickness obtained with a single dipping was proportional to the viscosity of the dip coating solutions. The thin films obtained were transparent with a thickness of 1 μm. The crystal form of the films was anatase alone. The thin films were formed with aggregated nano-sized TiO 2 single crystals (7–15 nm), and the size of TiO 2 crystals became smaller for the polymer-added systems. The photocatalytic activity of the TiO 2 thin films, as evaluated by the photooxidation of NO (1 ppm) in dry air, was as high as our previous TiO 2 thin films prepared by the sol–gel method.

Vinyl chloride monomer (VCM; CH 2 CHCl) was photocatalytically mineralized on TiO 2 (anatase and rutile) and ZnO at room temperature. The VCM decomposition rate was larger in the order of anatase>rutile>ZnO. VCM was decomposed into CO 2 , CO, HCl and long-lived intermediates (formic acid and monochloroacetyl chloride), which were further decomposed into CO 2 and H 2 O; more than 99.5% of carbon atoms in VCM were changed to CO or CO 2 by UV irradiation on TiO 2 (P25) within 360 min. Formic acid was also formed in the photocatalytic decomposition of ethylene on the TiO 2 pretreated with VCM. Cl − ions adsorbed on TiO 2 participated in the decomposition of VCM or ethylene and enhanced the formation of formic acid and CO.

Body temperature dependency in gastric functional responses to baclofen, a GABA B agonist, such as acid secretion, mucosal blood flow (GMBF) and motor activity, was examined in urethane-anesthetized rats under normal (37±1 °C) and hypothermic (31±1 °C) conditions. A rat stomach was mounted in an ex-vivo chamber, perfused with saline, and the acid secretion was measured using a pH-stat method, simultaneously with GMBF by a laser Doppler flowmeter. Gastric motility was measured using a miniature balloon as intraluminal pressure recordings. Intravenous administration of baclofen significantly increased acid secretion at the doses > 0.3 mg/kg under hypothermic conditions, yet it caused a significant stimulation only at doses >10 mg/kg under normothermic conditions. The increases in gastric motility and GMBF were similarly induced by baclofen, irrespective of whether the animals were subjected to normothermic or hypothermic conditions. These functional responses to baclofen under hypothermic conditions were totally attenuated by either bilateral vagotomy or atropine (3 mg/kg, s.c.). Baclofen at a lower dose (1 mg/kg i.v.) significantly increased the acid secretion even under normothermic conditions when the animals were subjected to chemical deafferenation of capsaicin-sensitive neurons or pretreatment with intracisternal injection of CGRP 8-37 (30 ng/rat). These results suggest that 1) gastric effects of baclofen are dependent on body temperature in stimulating acid secretion but not GMBF or motor activity, 2) the acid stimulatory action of baclofen is enhanced under hypothermic conditions, and 3) the suppression of baclofen-induced acid response under normothermic conditions may be related to capsaicin-sensitive afferent neuronal activity, probably mediated by central release of CGRP.

Gastrointestinal ulcerogenic effect of indomethacin is causally related with an endogenous prostaglandin (PG) deficiency, yet the detailed mechanism remains unknown. We examined the effect of various PGE analogues specific to EP receptor subtypes on these lesions in rats and mice, and investigated which EP receptor subtype is involved in the protective action of PGE(2). Fasted or non-fasted animals were given indomethacin s.c. at 35 mg/kg for induction of gastric lesions or 10-30 mg/kg for intestinal lesions, and they were killed 4 or 24 h later, respectively. Various EP agonists were given i.v. 10 min before indomethacin. Indomethacin caused hemorrhagic lesions in both the stomach and intestine. Prior administration of 16,16-dimethyl PGE(2) (dmPGE(2)) prevented the development of damage in both tissues, and the effect in the stomach was mimicked by 17-phenyl PGE2 (EP1), while that in the small intestine was reproduced by ONO-NT-012 (EP3) and ONO-AE-329 (EP4). Butaprost (EP2) did not have any effect on either gastric or intestinal lesions induced by indomethacin. Similar to the findings in rats, indomethacin caused gastric and intestinal lesions in both wild-type and knockout mice lacking EP1 or EP3 receptors. However, the protective action of dmPGE(2) in the stomach was observed in wild-type and EP3 receptor knockout mice but not in mice lacking EP1 receptors, while that in the intestine was observed in EP1 knockout as well as wild-type mice but not in the animals lacking EP3 receptors. These results suggest that indomethacin produced damage in the stomach and intestine in a PGE(2)-sensitive manner, and exogenous PGE(2) prevents gastric and intestinal ulcerogenic response to indomethacin through different EP receptor subtypes; the protection in the stomach is mediated by EP1 receptors, while that in the intestine mediated by EP3/EP4 receptors.

Nizatidine, a histamine H(2)-antagonist, is known to inhibit acetylcholinesterase (AChE) activity and is used clinically as a gastroprokinetic agent as well as the anti-ulcer agent. We examined whether or not nizatidine stimulates duodenal HCO(3)(-) secretion in rats through vagal-cholinergic mechanisms by inhibiting AChE activity. Under pentobarbital anesthesia, a proximal duodenal loop was perfused with saline, and the HCO(3)(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Nizatidine, neostigmine, carbachol, famotidine or ranitidine was administered i.v. as a single injection. Intravenous administration of nizatidine (3-30 mg/kg) dose-dependently increased the HCO(3)(-) secretion, and the effect at 10 mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg. The HCO(3)(-) stimulatory action of nizatidine was observed at the doses that inhibited the histamine-induced acid secretion and enhanced gastric motility. This effect was mimicked by neostigmine (0.03 mg/kg) and significantly attenuated by bilateral vagotomy and pretreatment with atropine but not indomethacin. The IC(50) of nizatidine for AChE of rat erythrocytes was 1.4 x 10(-6) M, about 12 times higher than that of neostigmine. Ranitidine showed the anti-AchE activity and increased duodenal HCO(3)(-) secretion, similar to nizatidine, whereas famotidine had any influence on neither AChE activity nor the HCO(3)(-) secretion. On the other hand, duodenal damage induced by acid perfusion (100 mM HCl for 4 h) in the presence of indomethacin was significantly prevented by nizatidine and neostigmine, at the doses that increased the HCO(3)(-) secretion. These results suggest that nizatidine increases HCO(3)(-) secretion in the rat duodenum, mediated by vagal-cholinergic mechanism, the action being associated with the anti-AChE activity of this agent.

In the present study, we investigated a protective role of constitutively occurred nitric oxide (NO) against indomethacin-induced intestinal lesions in rats. Indomethacin (10 mg/kg) was given s.c. to animals without fasting, and the intestinal mucosa was examined for lesions 24 h later. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was given s.c. 0.5 h before or 6 hr after indomethacin, while the NO donor (±)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexnamine (NOR-3) was given s.c. 0.5 h before indomethacin. Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility and bacterial translocation. These lesions were markedly prevented or worsened, respectively, by later or prior administration of L-NAME (20 mg/kg), in a L-arginine-sensitive manner. The worsening effect of L-NAME (5–20 mg/kg) on these lesions was dose-dependently observed in association with further enhancement of the bacterial translocation and intestinal hypermotility following indomethacin. By contrast, prior administration of NOR-3 (1–6 mg/kg) dose-dependently prevented the development of intestinal lesions, together with suppression of the bacterial translocation and intestinal hypermotility in response to indomethacin. On the other hand, both indomethacin and L-NAME decreased intestinal mucus and fluid (water) secretion in the small intestine, while NOR-3 increased these secretions. These results suggest that (1) NO occurred constitutively exerts a protective action against indomethacin-induced intestinal ulceration, and (2) this effect is related with prevention of bacterial translocation, the process functionally associated with increase of mucus and fluid secretions as well as inhibition of intestinal hypermotility.

The photocatalytic activity for NO removal under an oxidative atmosphere has been studied over commercial TiO 2 and plasma-treated TiO 2 powders. By the plasma treatment, the photocatalytic activity for NO removal appeared in the visible light region up to 600 nm without a decrease in the ultraviolet light activity. It was found that the NO was removed as nitrate (NO 3 − ) by photocatalytic oxidation over the TiO 2 powders, where NO 3 − was accumulated. No difference in the crystal structure, the crystallinity, and the specific surface area was observed between the raw TiO 2 and the plasma-treated TiO 2 photocatalysts. In electron spin resonance (ESR) measurements, a sharp signal at g =2.004, which was identified as the electrons trapped on oxygen vacancies, was detected only for plasma-treated TiO 2 under visible light irradiation. The saturated intensity of the ESR signal at g =2.004 was proportional to the removal percentage of nitrogen oxides, suggesting that the number of trapped electrons determined the activity for the photocatalytic oxidation of NO to NO 3 − . The appearance of the visible light activity in the plasma-treated TiO 2 photocatalyst was ascribed to the newly formed oxygen vacancy state between the valence and the conduction bands in the TiO 2 band structure.

Nitrous oxide (N 2 O) was photocatalytically decomposed on Ag-photodeposited TiO 2 in the presence of methanol vapor. The N 2 O decomposition activity of Ag-photodeposited TiO 2 was much higher than that of Ag-loaded TiO 2 prepared by deposition–precipitation or impregnation methods. The difference in the N 2 O decomposition activity between the preparation methods was discussed in terms of the surface conditions observed by transmittance electron microscopy and X-ray photoelectron spectroscopy. The N 2 O decomposition activity depended on the amount of photodeposited Ag, and the TiO 2 loaded with only 0.16 wt% Ag has revealed the highest level of activity. Highly dispersed Ag + ions prepared by photodeposition were effective for the photocatalytic decomposition of N 2 O. In the deposition–precipitation or impregnation methods, Ag + ions aggregated to form Ag particles and the N 2 O decomposition activity of these catalysts showed a low level of efficiency. Nitrogen of N 2 O was reduced into N 2 gas, whereas oxygen was released as CO or CO 2 by the reaction with methanol or its derivatives.