Biomedical subjects

T Oshima

Publications and source records attributed to T Oshima.

At least 19 recordsLinked to original sources

PubMed2006

Analysis of corneal inflammation induced by cauterisation in CCR2 and MCP-1 knockout mice.

AIM: To elucidate the role of CCR2/MCP-1 in corneal inflammation. METHODS: A cauterisation induced corneal inflammation model was used. The corneas were cauterised with silver nitrate in CCR2 knockout (KO) mice, MCP-1 KO mice, and control mice. Clinical signs such as corneal oedema and opacity were examined 96 hours after cauterisation and the phenotypes of the cells infiltrating the cornea were analysed by flow cytometry. Corneal inflammation in neutrophil depleted mice was also analysed. RESULTS: After cauterisation both CCR2 KO and MCP-1 KO mice showed the same levels of corneal oedema and opacity as control mice. Flow cytometry revealed that in control mice most of the infiltrating cells were neutrophils and macrophages, whereas in both CCR2 KO mice and MCP-1 KO mice, the number of macrophages infiltrating the cornea were markedly reduced. However, prominent infiltrates of neutrophils were still observed in the cornea in CCR2 KO mice and MCP-1 KO mice. The depletion of neutrophils significantly reduced the oedema and opacity induced in the cornea by cauterisation. CONCLUSION: The CCR2 and MCP-1 molecules are not essential for cauterisation induced corneal inflammation. Neutrophils, rather than migrated macrophages, are the final effector cells involved in inducing inflammation in this model.

Animals↗

PubMed2005

Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease.

BACKGROUND: The epidemiology and pathophysiology of non-erosive gastro-oesophageal reflux disease differs from erosive gastro-oesophageal reflux disease. There is a possibility that non-erosive gastro-oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged. AIM: To investigate the efficacy of famotidine and omeprazole in the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro-oesophageal reflux disease. PATIENTS AND METHODS: A randomized, open-label trial was conducted. Fifty-four gastro-oesophageal reflux disease patients were assigned to treatment with famotidine at a dosage of 20 mg twice daily; or omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health Survey and Gastrointestinal Symptom Rating Scale administered at baseline and after 8 weeks of treatment as well as a symptom questionnaire were conducted daily. RESULTS: Short Form-36 revealed that gastro-oesophageal reflux disease has severe impact on health-related quality of life. Thirty-nine subjects (77%) were endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score of non-erosive gastro-oesophageal reflux disease significantly improved in famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no significant change regarding improved heartburn symptoms of non-erosive gastro-oesophageal reflux disease between treatments in the daytime or night-time. CONCLUSION: Famotidine and omeprazole were both effective in improving symptoms of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal reflux disease.

Analysis of Variance↗

PubMed2004

Helicobacter pylori eradication decreases blood neutrophil and monocyte counts.

BACKGROUND: The effect of Helicobacter pylori infection on systemic disorders is not well understood. AIM: The purpose of this study was to elucidate the systemic effects of H. pylori infection by comparing differential counts of leukocytes and platelets in peripheral blood before and after eradication of H. pylori. METHODS: A total of 164 H. pylori-positive patients underwent eradication therapy, and populations of peripheral blood leukocytes and platelets before and 0 (just after therapy), 1, 3 and 12 months after eradication were retrospectively analysed. RESULTS: In the eradicated group (n = 138), blood leukocytes, neutrophils and monocytes decreased significantly after eradication, but there was no significant change in eosinophils, basophils, lymphocytes or platelets. In the non-eradicated group (n = 26), there was no significant change in any studied parameter. With regard to smoking status, although leukocytes and neutrophils did not decrease after eradication in the smoking group, they significantly decreased after eradication in the nonsmoking group. CONCLUSIONS: These findings suggest that: (1) H. pylori infection increases neutrophil and monocyte counts in the peripheral blood, which indicates a significant role of H. pylori infection in systemic disorders; and (2) Smoking may mask the effect of H. pylori eradication on peripheral leukocytes, which would explain the controversy in previous reports concerning H. pylori infection and peripheral leukocytes.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

The relative contributions of each subset of ocular infiltrated cells in experimental choroidal neovascularisation.

AIM: Choroidal neovascularisation (CNV) is a major cause of blindness in adults. The aim of this study was to investigate the role of infiltrating cells in the development of experimental CNV. METHODS: CNV was induced in C57BL/6 (B6) mice by laser photocoagulation (PC). After PC, the numbers of each subset of infiltrated cells were analysed by flow cytometry at multiple time points. Each subset (except for macrophages) was depleted by the specific antibodies in vivo. Thereafter, the area of CNV was compared between the control B6 mice and the specific antibody treated mice 7 days after PC. The CNV formation in neutrophil depleted CC chemokine receptor-2 (CCR2) knockout mice was also examined to minimise the effects of macrophages. RESULTS: In the early phase of CNV formation, a large number of neutrophils and macrophages infiltrated to the eyes. Natural killer (NK) cells and T lymphocytes were barely detected while no B lymphocytes were detected. The CNV areas did not significantly change compared between the control B6 mice and the specific antibody treated mice. However, the neutrophil depleted CCR2KO mice resulted in a reduction of CNV. CONCLUSION: Although lymphocytes and NK cells had little effect on CNV formation, neutrophils partially contributed to CNV in the absence of macrophages.

Animals↗

PubMed2004

Relation between C reactive protein concentrations and coronary microvascular endothelial function.

OBJECTIVE: To determine how C reactive protein (CRP), a sensitive marker of inflammation, is related to coronary endothelial function. DESIGN: Changes in quantitative coronary angiographic findings and Doppler flow velocity measurements in response to locally infused acetylcholine were assessed. SETTING: Tertiary cardiology centre. PATIENTS: 46 patients with angiographically normal coronary arteries were divided into groups with normal (< or = 3 mg/l) or increased (> 3 mg/l) CRP concentrations. INTERVENTIONS: Acetylcholine (3 and 30 microg/min) was infused into the left coronary ostium for two minutes. MAIN OUTCOME MEASURES: Percentage change in diameter of epicardial coronary arteries and coronary blood flow (CBF) in response to acetylcholine; and correlations between these parameters and serum CRP concentrations. RESULTS: 15 patients had increased CRP concentrations. The change in coronary artery diameter induced by acetylcholine infusion was similar between the groups but the increase in CBF induced by acetylcholine was smaller in patients with increased CRP concentrations (54.9% v 139.4% with acetylcholine 30 microg/min, p = 0.0030). Multivariate analysis identified increased CRP concentration as independently associated with attenuated CBF response to acetylcholine at 30 microg/min (p = 0.0078, R2 = 0.434). CONCLUSIONS: These findings suggest that inflammation appears to be associated with impaired coronary endothelial function in resistance but not conduit vessels. The data suggest a close relation between chronic vascular inflammation and endothelial dysfunction in atherosclerosis.

Acetylcholine↗

PubMed2003

A phylogenetic hypothesis for the origin of hiccough.

The occurrence of hiccoughs (hiccups) is very widespread and yet their neuronal origin and physiological significance are still unresolved. Several hypotheses have been proposed. Here we consider a phylogenetic perspective, starting from the concept that the ventilatory central pattern generator of lower vertebrates provides the base upon which central pattern generators of higher vertebrates develop. Hiccoughs are characterized by glottal closure during inspiration and by early development in relation to lung ventilation. They are inhibited when the concentration of inhaled CO(2) is increased and they can be abolished by the drug baclofen (an agonist of the GABA(B) receptor). These properties are shared by ventilatory motor patterns of lower vertebrates, leading to the hypothesis that hiccough is the expression of archaic motor patterns and particularly the motor pattern of gill ventilation in bimodal breathers such as most frogs. A circuit that can generate hiccoughs may persist in mammals because it has permitted the development of pattern generators for other useful functions of the pharynx and chest wall muscles, such as suckling or eupneic breathing.

Animals↗

PubMed2003

Time required to achieve a stable cuff pressure by repeated aspiration of the cuff during anaesthesia with nitrous oxide.

BACKGROUND AND OBJECTIVE: When the endotracheal tube cuff is repeatedly aspirated to avoid excessive cuff pressure during nitrous oxide anaesthesia, a stable cuff pressure is eventually achieved. We assessed the time required to achieve a stable cuff pressure after repeated cuff deflation. METHODS: During 67% nitrous oxide and oxygen anaesthesia, air-filled cuffs of a standard tracheal tube (Mallinckrodt Hi-Contour) were repeatedly deflated every 30 min for the first 3 or 4 h to inhibit excessive pressure (Groups Def-3 or Def-4, respectively, n = 10 for each); the cuff pressure was monitored for an additional 3 h. In some patients, the study was terminated at 1, 2, 3 and 4 h (n = 6 for each). RESULTS: Cuff pressure in Group Def-3, but not in Group Def-4, > 22 mmHg after stopping cuff aspiration. Intracuff nitrous oxide concentrations increased during repeated cuff deflation and increased further in Group Def-3 during an additional 3 h (from 39.8 +/- 4.7% to 44.3 +/- 3.8%; P < 0.05), whereas intracuff nitrous oxide concentrations at 4 h were not different from those in Group Def-4 at the end of the study (43.7 +/- 4.5% versus 42.3 +/- 4.8%; P = 0.579). CONCLUSIONS: When the air-filled cuff of the standard endotracheal tube is repeatedly deflated every 30 min for 4 h, but not for only 3 h, during nitrous oxide anaesthesia, a stable cuff pressure can be achieved without further deflation of the cuff. Our data also suggest that achieving an equilibrating nitrous oxide concentration in the cuff provides a subsequent stable cuff pressure.

Analysis of Variance↗

PubMed2003

Effects of sevoflurane on cerebral blood flow and cerebral metabolic rate of oxygen in human beings: a comparison with isoflurane.

BACKGROUND AND OBJECTIVE: Isoflurane is commonly used for neurosurgery but the effects of sevoflurane on human cerebral blood flow and cerebral metabolic rate of oxygen have not been fully evaluated. We therefore assessed the effects of sevoflurane and isoflurane on global cerebral blood flow and cerebral metabolic rate of oxygen in patients without noxious stimuli or neurological disorders. METHODS: General anaesthesia was induced with midazolam (0.2 mg kg(-1)) and fentanyl (5 microg kg(-1)) in 20 ASA I patients undergoing knee joint endoscopic surgery. Epidural anaesthesia was also performed to avoid noxious stimuli during surgery. Cerebral blood flow and cerebral arteriovenous oxygen content difference was measured using the Kety-Schmidt method with 15% nitrous oxide as a tracer before and after administration of either sevoflurane or isoflurane (1.5 minimum alveolar concentration, 60 min) and cerebral metabolic rate of oxygen was then calculated. RESULTS: Sevoflurane and isoflurane both increased cerebral blood flow (17%, P < 0.05; 25%, P < 0.05, respectively) and decreased cerebral metabolic rate of oxygen (26%, P < 0.01; 38%, P < 0.01, respectively). There were no significant differences in cerebral blood flow and cerebral metabolic rate of oxygen between sevoflurane and isoflurane. CONCLUSIONS: Sevoflurane and isoflurane similarly increased cerebral blood flow and decreased cerebral metabolic rate of oxygen in human beings anaesthetized with midazolam and fentanyl.

Adult↗

PubMed2003

The protective effect of rebamipide on paracellular permeability of rat gastric epithelial cells.

BACKGROUND: Barrier function in gastric epithelial cells is essential for the gastric defence mechanism against acid back-diffusion into the mucosal layer. Our previous study indicated that trans-epithelial resistance (TER) of rat gastric epithelial cells was rapidly increased when the cells were exposed to acid. This response to acid was diminished by indometacin. AIM: Evaluate the effects of a mucoprotective agent, rebamipide, on the nonsteroidal anti-inflammatory drug (NSAID)-induced increase of gastric epithelial permeability. METHODS: Rat gastric epithelial cells were plated on tissue culture inserts. Cells were exposed to a NSAID (indometacin, 10-7 M). Trans-epithelial permeability was measured by TER and diffusion rate of 14C-mannitol. The effect of rebamipide was evaluated by measuring TER. Endogenous prostaglandin E2 (PGE2) production in culture medium was also measured. RESULTS: Indometacin gradually and significantly decreased TER and increased 14C-manitol permeability. Rebamipide reversed the indometacin-induced changes in epithelial permeability and induced PGE2 synthesis. This induction was blocked by either indometacin or a Cyclooxygenase (COX)-2 specific inhibitor. CONCLUSIONS: COX inhibitors such as indometacin inhibit regulation of epithelial permeability by reducing PGE2. COX-1 has an important role in the gastric defense mechanism. Rebamipide suppressed an indometacin-induced increase in gastric epithelial permeability by increasing PGE2 levels in a COX-2 dependent manner.

Alanine↗

PubMed2003

Expression of junctional proteins in human platelets.

Platelets play a major role in thrombosis and hemostasis by binding the sub-endothelial matrix at sites of injury, but also participate in vascular pathologies such as atherosclerosis. Recently, junctional proteins like PECAM-I and JAM-family members have been recovered from platelets, therefore we examined what other junctional molecules may be present in platelets. We observed immunoreactivity for APC (147 kD), beta-catenin (92 kD), E-cadherin (120 and 84 kD) and occludin (70-85 kD) by western blotting. Additionally, beta-catenin, pan-reactive cadherins, E-cadherin and occludin were seen to partition with the triton insoluble cytoskeleton in platelets. These proteins were also found in a megakaryocyte (platelet precursor) line, MEG-01. Our data suggest that conventional junctional molecules are expressed in platelets and could possibly participate in aggregation, clot formation and wound healing.

Adenomatous Polyposis Coli Protein↗

PubMed2002

TNF-alpha -induced endothelial cell adhesion molecule expression is cytochrome P-450 monooxygenase dependent.

It is strongly suspected that cytokine-induced gene expression in inflammation is oxidant mediated; however, the intracellular sources of signaling oxidants remain controversial. In inflammatory bowel disease (IBD) proinflammatory cytokines, such as TNF-alpha, trigger gene expression of endothelial adhesion molecules including mucosal addressin cell adhesion molecule-1 (MAdCAM-1). MAdCAM-1 plays an essential role in gut inflammation by governing the infiltration of leukocytes into the intestine. Several groups suggest that endothelial-derived reduced NADP (NADPH) oxidase produces signaling oxidants that control the expression of adhesion molecules (E-selectin, ICAM-1, VCAM-1). In addition to NADPH oxidase, cytochrome P-450 (CYP450) monooxygenases have also been shown to trigger cytokine responses. We found that in high endothelial venular cells (SVEC4-10), multiple inhibitors of CYP450 monooxygenases (SKF-525a, ketoconazole, troleandomycin, itraconazole) attenuated TNF-alpha induction of MAdCAM-1, whereas NADPH oxidase inhibition (PR-39) did not. Conversely, E-selectin, ICAM-1, and VCAM-1 induction requires both NADPH oxidase and CYP450-derived oxidants. We show here that MAdCAM-1 induction may depend exclusively on CYP450-derived oxidants, suggesting that CYP450 blockers might represent a possible novel therapeutic treatment for human IBD.

Animals↗

PubMed2002

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗

PubMed2002

Polynitroxylated starch/TPL attenuates cachexia and increased epithelial permeability associated with TNBS colitis.

Free radicals play an important role in the initiation and progression of inflammatory bowel disease (IBD). Therefore, the reduction or elimination of adverse oxidant effects can provide novel therapy for IBD. Here, the antioxidant capacity and protective effects of a new class of chemically modified hetastarch (polynitroxyl starch, or PNS) plus 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol or TPL) (PNS/TPL) were assessed in a model of colitis. The superoxide scavenging capacity of PNS/TPL-that is, the inhibition of the reduction of cytochrome c in the presence of xanthine/xanthine oxidase (X/XO)-was evaluated in vitro. The effects of PNS/TPL on X/XO-induced neutrophil endothelial adhesion in vitro were investigated. Also, this study tested the protection produced by PNS/TPL in a mouse model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. PNS/TPL was given intravenously immediately before (< 30 min) and intraperitoneally at 24 and 72 hr after TNBS induction. The body weight and survival rate of the mice were checked daily. Colonic mucosal damage was assessed on the 7th day by measuring intestinal permeability to Evans blue (EB) in vivo. The ability of PNS to reoxidize bioreduced TPL was documented by whole-body electron paramagnetic resonance (EPR) detection. We found that PNS or TPL exhibits superoxide dismutase (SOD)-like activity, with approximately 2% of SOD activity occurring on a molar basis. The endothelial-neutrophil adherence induced by X/XO was significantly inhibited by PNS/TPL but not by TPL alone. PNS/TPL protected against cachexia and mortality, both usually induced by TNBS. Epithelial permeability was increased significantly in TNBS mice but was ameliorated by the administration of PNS/TPL. In conclusion, PNS/TPL may be beneficial in the treatment or prevention of IBD through its antioxidant effects, which inhibit oxidant-mediated leukocyte adhesion and injury to endothelial cells.

Adult↗

PubMed2002

Effects of propofol on cerebral blood flow and the metabolic rate of oxygen in humans.

BACKGROUND: Effects of propofol on human cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and blood flow-metabolism coupling have not been fully evaluated. We therefore assessed the effects of propofol on total-CBF and CMRO2 in patients without noxious stimuli and neurologic disorders. METHODS: General anesthesia was induced with midazolam (0.2 mg/kg) and fentanyl (5 microg/kg) in 10 patients (ASA physical status I) undergoing knee joint endoscopic surgery. Epidural anesthesia was also performed to avoid noxious stimuli during surgery. Cerebral blood flow (CBF) and cerebral arteriovenous oxygen content difference (a-vDO2) was measured using the Kety-Schmidt method with 15% N2O as a tracer before and after propofol infusion (6 mg/kg/h for 40 min), and the CMRO2 was also calculated. RESULTS: CBF decreased following propofol infusion from 34.4 ml/100 g/min (range 28.4-52.0) to 30.0 ml/100 g/min (range 20.2-42.4) (P=0.04). Although there was no significant change in a-vDO2, CMRO2 decreased following propofol infusion from 2.7 ml/100 g/min (range 2.2-4.3) to 2.2 ml/100 g/min (range 1.4-3.0) (P=0.04). There was a strong linear correlation between CBF and CMRO2 (r=0.90). CONCLUSION: Propofol proportionally decreased CBF and CMRO2 without affecting a-vDO2 in humans, suggesting that normal cerebral circulation and metabolism are maintained.

Adult↗

PubMed2002

Maintenance of stable cuff pressure in the Brandt tracheal tube during anaesthesia with nitrous oxide.

BACKGROUND: The Brandt tracheal tube keeps cuff pressure constant during anaesthesia, but the mechanisms have not been examined. We assessed volume, pressure and gas concentration in the cuff and pilot balloon using the Brandt system. METHODS: The pressure in an air-filled cuff of the Brandt system (Mallinckrodt Brandt tracheal tube, n = 60) was recorded during anaesthesia with 67% nitrous oxide; gas volume and concentration in cuffs and balloons were measured for up to 12 h from the start of anaesthesia. The volume change of each gas was calculated to assess its contribution to the cuff pressure. We also measured cuff compliance in vitro. RESULTS: Cuff pressure increased slightly during anaesthesia (P < 0.05). The nitrous oxide concentration increased to 47.7 (8.2)% (mean (SD)) in the cuff and to 2.2 (0.9)% in the pilot balloon. The nitrous oxide volume in the cuff and pilot balloon increased by approximately 2 ml during the first 4 h of anaesthesia. The carbon dioxide volume increased slightly, and nitrogen and oxygen did not change significantly. The compliance of the Brandt tube cuff was six times greater than that of a standard tube cuff (Mallinckrodt Hi-Contour tracheal tube). CONCLUSIONS: The Brandt tracheal tube maintains stable cuff pressure during nitrous oxide anaesthesia because of a highly compliant balloon. The concentration gradient of nitrous oxide between the cuff and pilot balloon also contributes to the stable-cuff pressure because the high nitrous oxide concentration in the cuff reduces nitrous oxide influx.

Adult↗

PubMed2001

Complement plays an important role in gastric mucosal damage induced by ischemia-reperfusion in rats.

Ischemia-reperfusion (I/R) of stomach causes gastric mucosal injury. Complement can also cause tissue damage, however its role in gastric I/R injury has not been thoroughly investigated. We evaluated the effect of complement suppression in reducing damage to the gastric epithelium caused by local I/R. Local gastric ischemia was induced by clamping the left gastric artery. The blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. 51Cr-EDTA clearance increased shortly after reperfusion with peak values at 10 min. Intraperitoneal administration of cobra venom factor (CVF; 50 units) prior to I/R, which reduced the serum complement value (CH50) to an undetectable level, remarkably suppressed the 51Cr-EDTA clearance following reperfusion. A monocarboxylic acid derivative of K-76 (K-76 COOH) reduced the CH50 by more than 30% (100 mg/kg) and 60% (200 mg/kg). Rats pretreated with K-76 significantly attenuated the increase in 51Cr-EDTA clearance produced by I/R. These results suggest that complement inhibitor could be used to protect gastric mucosal injury induced by local I/R stress.

Animals↗

PubMed2001

Complete genome sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7.

The complete genomic sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain7 which optimally grows at 80 degrees C, at low pH, and under aerobic conditions, has been determined by the whole genome shotgun method with slight modifications. The genomic size was 2,694,756 bp long and the G + C content was 32.8%. The following RNA-coding genes were identified: a single 16S-23S rRNA cluster, one 5S rRNA gene and 46 tRNA genes (including 24 intron-containing tRNA genes). The repetitive sequences identified were SR-type repetitive sequences, long dispersed-type repetitive sequences and Tn-like repetitive elements. The genome contained 2826 potential protein-coding regions (open reading frames, ORFs). By similarity search against public databases, 911 (32.2%) ORFs were related to functional assigned genes, 921 (32.6%) were related to conserved ORFs of unknown function, 145 (5.1%) contained some motifs, and remaining 849 (30.0%) did not show any significant similarity to the registered sequences. The ORFs with functional assignments included the candidate genes involved in sulfide metabolism, the TCA cycle and the respiratory chain. Sequence comparison provided evidence suggesting the integration of plasmid, rearrangement of genomic structure, and duplication of genomic regions that may be responsible for the larger genomic size of the S. tokodaii strain7 genome. The genome contained eukaryote-type genes which were not identified in other archaea and lacked the CCA sequence in the tRNA genes. The result suggests that this strain is closer to eukaryotes among the archaea strains so far sequenced. The data presented in this paper are also available on the internet homepage (http://www.bio.nite.go.jp/E-home/genome_list-e.html/).

Archaeal Proteins↗

PubMed2001

TNF-alpha induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide.

BACKGROUND: MAdCAM-1 is an adhesion molecule expressed in Peyer's patches and lymphoid tissues which is mobilized by cytokines like TNF-alpha and is a major determinant of lymphocyte trafficking to the gut in human inflammatory bowel disease (IBD). It has been suggested that both reactive oxygen and nitrogen metabolites participate in regulating adhesion molecule expression in response to TNF-alpha. METHODS: To examine how exogenous and endogenous sources of NO modulate MAdCAM-1 induction by TNF-alpha, we pre-treated mouse lymphatic endothelial cells with either long or short acting NO donors prior to TNF-alpha-stimulation, and measured MAdCAM-1 induction at 24 h. RESULTS AND DISCUSSION: DETA-NO, a long-acting NO donor, and SperNO, a rapid releasing NO donor both inhibited TNF-alpha-stimulated MAdCAM-1 expression in a concentration dependent manner. Both NO donors also reduced a4b7-dependent lymphocyte endothelial adhesion. Inhibition of endogenous NO production by either L-NAME, a non-selective NOS inhibitor, or by 1400 w, a selective iNOS inhibitor failed to induce, or potentiate TNF-alpha regulated MAdCAM-1 expression. CONCLUSIONS: Exogenous NO donors may be beneficial in the treatment of IBD, while endogenous nitric oxide synthases may be less effective in controlling adhesion molecule expression in response to cytokines.

Amidines↗