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Biomedical subjects

I Hayashi

Publications and source records attributed to I Hayashi.

At least 19 recordsLinked to original sources
PubMed2003

Amelioration of hyperalgesia by kinin receptor antagonists or kininogen deficiency in chronic constriction nerve injury in rats.

OBJECTIVE: The present study was designed to examine the involvement of bradykinin in thermal and mechanical hyperalgesia induced by chronic constriction nerve injury (CCI) using B1 and B2 receptor antagonists and mutant kininogen-deficient rats. METHODS: Sprague-Dawley (SD) rats and Brown Norway (B/N-) rats given CCI treatment on day 0, were used as a model of neuropathic pain. Either a kinin B1 antagonist des-Arg9-[Leu8]-bradykinin or the receptor B2 antagonist HOE-140 was constantly infused into the left jugular vein of SD rats on days 15 to 22 after CCI. Vehicle-treated rats and sham-operated rats without nerve injury were also prepared as controls. In all rats, we observed pain behavior, and measured the latency period of paw withdrawal from the thermal stimuli and, with von Frey filaments, the mechanical pain threshold, before surgery and on days 14 and 22 after CCI. B/N-Katholiek rats, which congenitally lack plasma kininogen and release no kinin, were also tested for hyperalgesic parameters. Expression of kinin receptor mRNA in the dorsal root ganglia was detected by RT-PCR. RESULTS: Most of the rats (88%) showed some pain behavior, which was reduced to 67% by a B1 antagonist and to 57% by a B2 antagonist infused between days 15 to 22. Thermal hyperalgesia was significantly reduced from 7.25 +/- 0.41 sec (mean +/- SEM) to 8.36 +/- 0.41 sec in paw withdrawal latency on day 22 by a B1 antagonist and from 7.24 +/- 0.19 sec to 8.23 +/- 0.21 sec by a B2 antagonist (P < 0.05). Mechanical hyperalgesia was also ameliorated from 0.02 +/- 0.007 g force to 0.16 +/- 0.08 g force in pain threshold by a B1 antagonist and from 0.03 +/- 0.007 g force to 0.10 +/- 0.003 g force on day 22 by a B2 antagonist. Moreover, deficient B/N-Katholiek rats showed a low incidence of thermal and mechanical hyperalgesia on day 14. Expression of both B1 and B2 receptor mRNAs was detected in the lumbar dorsal ganglia ipsilateral to the site of the nerve injury. CONCLUSION: These data suggests that kinin were at least partly involved in yielding nociceptor hypersensitivity up to day 14 after CCI. Bradykinin and its B1 and B2 receptors were involved in the maintenance of hyperalgesia.

Animals↗
PubMed2003

Endogenous prostaglandin I2 regulates the neural emergency system through release of calcitonin gene related peptide.

BACKGROUND: We previously reported that endogenous prostaglandin I(2), generated by a mild irritant, sensitised calcitonin gene related peptide (CGRP) containing sensory nerves and facilitated the release of CGRP and gastric mucosal protection against ethanol. Administration of capsaicin also inhibited ethanol induced gastric mucosal injury through immediate release of CGRP from primary sensory neurones, which is termed the neural emergency system. In the present study, we tested whether endogenous prostaglandin I(2) also modulates the cytoprotective action of capsaicin using prostaglandin I receptor knockout mice (IP(-/-)). METHODS: The stomachs of IP(-/-) or their wild-type counterparts (IP(+/+)), anaesthetised with urethane (1.225 g/kg), were doubly cannulated from the oesophageal and duodenal sides, and the gastric mucosa was perfused (1 ml/min) with physiological saline. Perfusate was changed to 50% ethanol alone, or 50% ethanol containing capsaicin (16 approximately 1600 micro M). The injured area was estimated at the end of each perfusion experiment. In some animals, CGRP-(8-37), a CGRP antagonist (0.3 mg/kg), or indomethacin (1 mg/kg) was intravenously injected before perfusion of 50% ethanol containing capsaicin. RESULTS: Capsaicin inhibited the injured area in a dose dependent manner. Fifty per cent ethanol containing capsaicin (480 micro M) immediately increased intragastric levels of CGRP although 50% ethanol alone did not. The protective action of capsaicin (480 micro M) against ethanol was completely abolished by intravenous injection of CGRP-(8-37). Indomethacin also inhibited the protective action of capsaicin, and this was accompanied by reduced levels of intragastric CGRP. Intragastric levels of prostaglandin E(2) were not increased by capsaicin treatment but those of 6-keto-prostaglandin F(1alpha), a metabolite of prostaglandin I(2), were markedly increased. No protective action of capsaicin was observed in IP(-/-) which lacked the ability to increase intragastric CGRP levels in response to ethanol containing capsaicin. The CGRP content of the stomach from untreated IP(-/-) did not differ from those in IP(+/+). Capsaicin (160 micro M) together with intragastric perfusion of beraprost sodium (PGI(2) analogue, 2.5 micro g/ml) showed enhanced protection against ethanol induced injury. This enhanced protection was completely blocked by intravenous injection of CGRP-(8-37). CONCLUSIONS: The present results suggest that endogenous prostaglandin I(2) enhances the protective action of the capsaicin mediated neural emergency system against ethanol induced gastric mucosal injury through enhancement of CGRP release.

6-Ketoprostaglandin F1 alpha↗
PubMed2003

Mitral stenosis due to fibrous tissue overgrowth after mitral valve repair.

We report an extremely rare case of fibrous tissue overgrowth 3 years after mitral valve repair using a mitral annuloplasty ring in a 53-year-old woman who underwent mitral valve replacement for mitral stenosis. Whitish fibrous tissue had overgrown from the ring on the atrial side of the annulus, and had severely reduced the valvular area. However, the motion of the mitral leaflets was not restricted. Considering the presence of concomitant aortitis syndrome, it is strongly suggested that the overgrowth of fibrous tissue was promoted as a reaction to chronic inflammation.

Cardiac Catheterization↗
PubMed2003

[Procedure and problem for short-term outcomes on off-pump coronary artery bypass grafting].

We performed off-pump coronary artery bypass grafting (CABG) in all cases without reoperation case from July, 2002. Advantage of off-pump CABG versus on-pump CABG which is reduced a number of perioperative complication and early patients recovery was previously demonstrated. In our institute, the mean number of grafts per patients was 4.7 +/- 1.3, and the rate of using arterial grafts was 99.5% in all cases without minimally invasive direct coronary artery bypass (MIDCAB). The mean hospital stay after operation was 10.8 +/- 2.8. It was shorted remarkably in comparison with on-pump CABG; 19.4 +/- 6. Furthermore, sever complication was not occurred in any cases after operation though high risk cases were increased. In the early cases, atrial fibrillation complicated frequently (32%), but using after magnesium sulfate it was remarkably decreased (8.4%). On the other-hand, attention is necessary for the infection caused by the increase of high risk patients. Therefore, we used vancomycin (VCM) at these cases from the viewpoint of prevention. Recently, we performed remnant omental transfer for the sever diabetes mellitus case which was used bilateral internal thoracic artery on CABG. It learned to get the early recovery which was necessary for the off-pump CABG by the above additional treatment.

Antibiotic Prophylaxis↗
PubMed2002

Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats.

AIM: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and pathological improvements generated by correction of the Dmo1 genetic pathway, we produced congenic lines, in which both OLETF Dmo1 alleles are replaced by the F344-derived genome. METHODS: Congenic animals were produced by introgressing F344-derived Dmo1 alleles into the OLETF rat. Congenic animals of the fourth generation (BC4) were intercrossed to obtain F1 animals (BC4:F1). Animals of the next generation, BC4:F2, were used for this study. We used 23 BC4:F2 males harbouring homozygous replacement of the OLETF Dmo1 region with the F344-derived genome. Seven animals with OLETF-derived Dmo1 alleles were used as controls. RESULTS: Dmo1-F344/F344 congenic rats showed significant decreases in body weight, abdominal fat weight, serum triacylglycerols, total cholesterol, food consumption and blood glucose after glucose loading (13%, 39%, 45%, 27%, 18% and 27% respectively; p < 0.05) compared with Dmo1-OLETF/OLETF animals. Furthermore, histopathological analysis of the kidney showed that mesangial sclerosis, hyalin deposits and deposition of PAS-positive substance were significantly lower in Dmo1-F344/F344 animals (p < 0.05). CONCLUSION: Improvements in metabolic parameters and histopathological scores show that correction of the Dmo1 genetic pathway in the diabetic and mildly obese OLETF rat strain produces wide-ranging therapeutic effects. Thus, this pathway might represent a new drug target also applicable to humans.

Animals↗
PubMed2001

Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction.

To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg(-1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg(-1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated.

Animals↗
PubMed2001

Synthetic activity of Sso DNA polymerase Y1, an archaeal DinB-like DNA polymerase, is stimulated by processivity factors proliferating cell nuclear antigen and replication factor C.

DNA replication efficiency is dictated by DNA polymerases (pol) and their associated proteins. The recent discovery of DNA polymerase Y family (DinB/UmuC/RAD30/REV1 superfamily) raises a question of whether the DNA polymerase activities are modified by accessory proteins such as proliferating cell nuclear antigen (PCNA). In fact, the activity of DNA pol IV (DinB) of Escherichia coli is enhanced upon interaction with the beta subunit, the processivity factor of DNA pol III. Here, we report the activity of Sso DNA pol Y1 encoded by the dbh gene of the archaeon Sulfolobus solfataricus is greatly enhanced by the presence of PCNA and replication factor C (RFC). Sso pol Y1 per se was a distributive enzyme but a substantial increase in the processivity was observed on poly(dA)-oligo(dT) in the presence of PCNA (039p or 048p) and RFC. The length of the synthesized DNA product reached at least 200 nucleotides. Sso pol Y1 displayed a higher affinity for DNA compared with pol IV of E. coli, suggesting that the two DNA polymerases have distinct reason(s) to require the processivity factors for efficient DNA synthesis. The abilities of pol Y1 and pol IV to bypass DNA lesions and their sensitive sites to protease are also discussed.

Amino Acid Sequence↗
PubMed2001

Structural and functional studies of MinD ATPase: implications for the molecular recognition of the bacterial cell division apparatus.

Proper placement of the bacterial cell division site requires the site-specific inactivation of other potential division sites. In Escherichia coli, selection of the correct mid-cell site is mediated by the MinC, MinD and MinE proteins. To clarify the functional role of the bacterial cell division inhibitor MinD, which is a membrane-associated ATPase that works as an activator of MinC, we determined the crystal structure of a Pyrococcus furiosus MinD homologue complexed with a substrate analogue, AMPPCP, and with the product ADP at resolutions of 2.7 and 2.0 A, respectively. The structure reveals general similarities to the nitrogenase iron protein, the H-Ras p21 and the RecA-like ATPase domain. Alanine scanning mutational analyses of E.coli MinD were also performed in vivo. The results suggest that the residues around the ATP-binding site are required for the direct interaction with MinC, and that ATP binding and hydrolysis play a role as a molecular switch to control the mechanisms of MinCDE-dependent bacterial cell division.

Adenosine Triphosphatases↗
PubMed2001

Nitric oxide is generated in smooth muscle layer by neurokinin A and counteracts constriction in guinea pig airway.

It has been reported that several bronchoconstrictors generate nitric oxide (NO), counteracting bronchoconstriction, and removal of bronchial epithelia reduces NO production. However, it has not been elucidated whether neurokinin A (NKA), a potent bronchoconstrictor liberated from nerve terminals, generates NO. Specific questions in this study were (1) does NKA also generate NO, (2) does NO counteract NKA-induced bronchoconstriction, and (3) does the NO generation require bronchial epithelial cells? In an in vivo study exogenous as well as endogenous (capsaicin-induced) NKA increased airway opening pressure (P(ao)) and the exhaled NO level, and both were inhibited by an antagonist selective for NK(2) receptor (a receptor for NKA), SR48968. The exhaled NO level became negligible with an inhibitor of NO synthase (NOS) type 1-3 (N(G)-nitro-L-arginine methyl ester, L-NAME) with increased P(ao), but not with a NOS type 2 inhibitor. In an in vitro study, NKA increased the nitrite/nitrate level in superfused fluid of tracheal segments. Removing smooth muscle reduced nitrite/nitrate in the fluid to negligible levels, while the level was unchanged with removal of the epithelia. Pretreatment with l-NAME enhanced the tension of epithelia-removed tracheal segments. These findings indicate that (1) NKA generates NO, (2) NO counteracts NKA-induced bronchoconstriction, and (3) NKA activates NOS in the muscle layer, independently of bronchial epithelia.

Airway Resistance↗
PubMed2001

Aortic and mitral valve replacement in a patient with acute febrile neutrophilic dermatosis (Sweet's syndrome): report of a case.

A 29-year-old woman was admitted to our hospital with severe orthopnea, fever, and acute dermatosis. She had a 5-year history of episodic acute neutrophilic dermatosis and peripheral leukocytosis following a high fever, which were symptoms consistent with a diagnosis of Sweet's syndrome. Echocardiography revealed remarkable dysfunction of the left ventricle due to severe aortic regurgitation, which had not been present at a previous admission when mild mitral regurgitation was detected. The aortic and mitral valves were replaced with prosthetic valves on an emergency basis. The leaflets of the aortic valve were very thin and appeared fragile. The anterior leaflet of the mitral valve showed severe prolapse due to the torn chordae and hypoplasia of the posterior strut chordae. Her postoperative course was uneventful. Microscopic examination revealed fibrosal degeneration and the infiltration of lymphocytes and macrophages into both heart valves. This may be the first case report of valvulitis and Sweet's syndrome occurring simultaneously.

Adult↗
PubMed2001

Survey of antibiotic resistance in Pseudomonas aeruginosa by The Tokyo Johoku Association of Pseudomonas Studies.

Pseudomonas aeruginosa resistance (minimum inhibitory concentration [MIC], > or =16 microg/ml defined as resistant) to meropenem, imipenem, panipenem, piperacillin, ceftazidime, cefozopran, cefoperazone, sulbactam/cefoperazone, amikacin, and tobramycin, as well as cross-resistance profiles, were investigated in P. aeruginosa strains isolated at eight hospitals in the Johoku area, Tokyo, during November 1998. Overall, 8.3% of isolates were imipenem-resistant and 4.6% were ceftazidime-resistant. However, the incidence of antibiotic-resistant P. aeruginosa was distinctly different at each hospital. P. aeruginosa resistance to imipenem ranged from (MIC) 1 to 64 microg/ml (MIC90 32 microg/ml), and its resistance to ceftazidime ranged from 2 to more than 128 microg/ml (MIC90, 64 microg/ml). Meropenem (MIC range, < or =0.25 to 16 microg/ml) was more active than panipenem (MIC range, 2 to 64 microg/ml). Cefozopran was more active than piperacillin, cefoperazone, or sulbactam/cefoperazone, but many strains were resistant to cefoperazone (17/57). Our analysis found cross-resistance to many beta-lactams, but the degree of cross-resistance was very variable.

Anti-Bacterial Agents↗
PubMed2001

Coronary artery bypass grafting in patients on chronic hemodialysis: surgical outcome in diabetic nephropathy versus nondiabetic nephropathy patients.

BACKGROUND: The presence of diabetes mellitus adversely affects the late survival of patients undergoing coronary artery bypass grafting (CABG). The purpose of this study is to clarify the role of diabetic nephropathy on outcomes of a group of patients on chronic hemodialysis undergoing CABG. METHODS: Between April 1984 and July 1999, 45 patients on chronic hemodialysis underwent CABG. Forty-three had conventional CABG and 2 had off-pump CABG. There were 37 males and 8 females, and the mean age was 57 years (43 to 76 years). Twenty-one patients had diabetic nephropathy (group D) and 24 had nondiabetic nephropathy (group ND). Early and late results were determined in both groups. RESULTS: Early outcome was not significantly different between the groups. There was no hospital mortality, stroke, or requirement for prolonged mechanical ventilation (>24 hours) in either group. No patients in group D, and only 1 (4.2%) in group ND had low cardiac output syndrome. The difference in the incidence of arrhythmias (23.8% in group D and 25% in group ND), wound infections (9.5% in group D and 8.3% in group ND), and delayed tamponade (5% in group D and 12.5% in group ND) was not statistically significant. However, late results differed significantly between the two groups. Actuarial survival (Kaplan-Meier) at 5 and 9 years was 22.9% and 11.5% in group D and 89.1% and 45.7% in group ND (p = 0.01), respectively. Similarly, the cardiac event-free rate at the same intervals was 50.4% and 0% for group D and 100% and 65.8% for group ND (p = 0.001), respectively. CONCLUSIONS: Using present technology, CABG can be done in patients on chronic hemodialysis with acceptable early mortality and morbidity. Late results in patients with diabetic nephropathy on hemodialysis are not as favorable as their nondiabetic cohort.

Aged↗
PubMed2001

Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain.

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Alleles↗
PubMed2001

Proinflammatory characteristics of a nonpeptide bradykinin mimic, FR190997, in vivo.

1. Proinflammatory potency of the nonpeptide bradykinin (BK) B(2) receptor agonist FR190997 (8-[2,6-dichloro-3-[N-[(E)-4-(N-methylcarbamoyl)cinnamidoacetyl]-N-methylamino]benzyloxy]-2-methyl-4-(2-pyridylmethoxy)quinoline) was investigated. 2. Intradermal injection of FR190997 (0.03 - 3 nmol site(-1)) into dorsal skin of rats increased vascular permeability in a dose-dependent manner. The effect was less than that of BK, but it was long-acting and was inhibited by treatment with FR173657 (3 mg kg(-1), p.o.). Captopril (10 mg kg(-1), i.p.) did not enhance the plasma extravasation by FR190997 (0.3 nmol site(-1)) in the presence of soybean trypsin inhibitor (SBTI, 30 microg site(-1)). 3. Subcutaneous injection of FR190997 (3 nmol site(-1)) into the hindpaw of mice markedly induced paw swelling. The oedema lasted up to 3 h after the injection. Administration of indomethacin or NS-398 (10 mg kg(-1), i.p.) significantly reduced it at 3 h after the injection. 4. Simultaneous i.p. injection of prostaglandin (PG) E(2) (1 nmol site(-1)) or beraprost sodium (0.5 nmol site(-1)) with FR190997 (5 nmol site(-1)) greatly enhanced frequency of writhing reactions in mice. 5. FR190997 (0.3 - 30 nmol kg(-1), i.v.) showed less increase in airway opening pressure (Pao) in the guinea-pig after i.v. injection. Furthermore, FR190997 (0.03 - 30 nmol) resulted in a very weak contraction of tracheal ring strips and lung parenchymal sections in vitro. 6. In mice sponge implants, topical application of FR190997 increased angiogenesis and granulation with enhanced expressions of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) mRNAs. 7. These results indicate that FR190997 has proinflammatory long-lasting characteristics and it might be 'a stable tool' for studying the role of BK B(2) receptor in vivo.

Animals↗
PubMed2001

Adaptive cytoprotection mediated by prostaglandin I(2) is attributable to sensitization of CRGP-containing sensory nerves.

BACKGROUND & AIMS: The phenomenon by which the gastric mucosa is protected in response to mild irritants has been called adaptive cytoprotection, a mechanism believed to be related to production of endogenous prostaglandins (PGs). We tested whether PGs generated by mild irritant prevent injury through the release of calcitonin gene-related peptide (CGRP) from the sensory nerves using prostanoid receptor-knockout mice. METHODS: The stomach was doubly cannulated and perfused with 1 mol/L NaCl or 50% ethanol. CGRP levels in the perfusate were determined by enzyme immunoassay, and the injured area was estimated at the end of perfusion. RESULTS: Preperfusion with mildly hypertonic saline (1 mol/L NaCl) increased generation of gastric PGE(2) and PGI(2) and reduced ethanol-induced mucosal damage. Exposure of ethanol after 1 mol/L NaCl increased intragastric CGRP levels from 166 +/- 27 to 713 +/- 55 pg/2 min (n = 4, P < 0.05), and the protective action of 1 mol/L NaCl was inhibited by indomethacin treatment. CGRP antagonist blocked 1 mol/L NaCl-induced protective effect. Intragastric perfusion of 50% ethanol after administration of PGI(2), but not of PGE(2), increased CGRP levels. Application of 1 mol/L NaCl to IP receptor-knockout mice (IP(-/-)) did not elicit the protective effects seen in the wild-type on ethanol-induced gastric mucosal lesions. Protective effect of 1 mol/L NaCl was observed in EP3 receptor-knockout mice (EP3(-/-)). CGRP level during ethanol perfusion was not increased in IP(-/-) but was increased in EP3(-/-) and wild-type counterparts after preperfusion of 1 mol/L NaCl. CONCLUSIONS: These results indicate that the endogenous PGI(2) generated by 1 mol/L NaCl may have a protective role in gastric mucosal injury through enhancement of CGRP release from gastric mucosa. This mechanism may explain the adaptive cytoprotection observed after treatment with mild irritants.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Relationships among facial type, buccolingual molar inclination, and cortical bone thickness of the mandible.

The purpose of this study was to evaluate the relationships between different facial types, and both the buccolingual molar inclination and cortical bone thickness of the mandible. The material consisted of 31 dry skulls of modern Japanese males from the Museum of the University of Tokyo. They all demonstrated normal occlusion with minimal dental discrepancy, and without crossbite or facial asymmetry. The buccolingual inclination of the second molar (M2) in the long-faced subjects was significantly smaller than the same dimension in the average- and short-faced subjects. It was found that the teeth of long-faced subjects were more lingually inclined than those of the short-faced subjects. The cortical bone thickness of the first molar (M1) and M2 sections was thicker in short-faced subjects than in average- and long-faced subjects. The results of this study provide evidence that a significant, but complex relationship exists between structures of the mandibular body and facial types. The morphological features that relate to masticatory function and facial types are associated with the cortical bone thickness of the mandibular body, and the buccolingual inclination of the first and second molars.

Adolescent↗
PubMed2001

[Endogenous prostaglandins and angiogenesis].

Angiogenesis is a process involved in several physiological events including embryonic development, female reproductive cycle placentation and wound repair. It also plays a part in various pathological conditions such as tumor growth, diabetic retinopathy and rheumatoid arthritis. Angiogenesis is a very complex multistep process involving a variety of biologically active substances, among which are the prostaglandins (PGs), which can induce several growth factors and proliferation of endothelial cells in vitro and in vivo. Angiogenesis is reportedly enhanced by prostaglandins (PGs). We investigated whether or not COX-2 mediated angiogenesis in chronic and proliferate granuloma. In rat sponge implants, angiogenesis was gradually developed over a 14-day experimental period as granuloma formed. In sponge granuloma, mRNA of COX-1 was constitutively expressed, whereas that of COX-2 was increased with neovascularization in parallel with the increased expression of vascular endothelial growth factor (VEGF). bFGF-stimulated angiogenesis was inhibited by indomethacin or a selective COX-2 inhibitor, NS-398. These results suggested that endogenous PGs generated through COX-2 may enhance the neovascularization in sponge granuloma by increased expression of VEGF and that a COX-2 inhibitor would facilitate the management of conditions involving angiogenesis.

Animals↗