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Biomedical subjects

I Kurose

Publications and source records attributed to I Kurose.

At least 91 records · Page 5Linked to original sources
PubMed1993

Inhibition of nitric oxide production. Mechanisms of vascular albumin leakage.

The mechanisms by which nitric oxide modulates microvascular albumin exchange were investigated by monitoring leukocyte-endothelial cell adhesion and fluorescein isothiocyanate-albumin leakage in rat mesenteric venules exposed to NG-nitro-L-arginine methyl ester (L-NAME). L-NAME elicited an initial rapid increase followed by a slower rate of albumin accumulation in the interstitial space. The initial phase of albumin leakage preceded the L-NAME-induced leukocyte adherence and emigration, whereas the magnitude of the albumin leakage observed in the later phase of L-NAME exposure was highly correlated with the number of adherent and emigrated leukocytes in the same segment of venule. Monoclonal antibodies (MAbs) directed against adhesion molecules CD11/CD18, ICAM-1, or P-selectin, but not a nonbinding MAb, attenuated the albumin leakage induced by L-NAME. WEB2086, a platelet activating factor antagonist, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) reduced the leukocyte adherence and emigration as well as the increased albumin leakage. Only 8-br-cGMP and the P-selectin MAb attenuated the platelet-leukocyte aggregation elicited by L-NAME. Phalloidin, which promotes endothelial junctional integrity, inhibited both the early and late phases of albumin leakage. Overall, these findings suggest that the increased albumin leakage observed in postcapillary venules after inhibition of nitric oxide production involves a mechanism that includes a role for cGMP, platelet activating factor, leukocyte-endothelial cell adhesion, and the endothelial cell cytoskeleton.

Albumins↗
PubMed1993

Nitric oxide mediates vasoactive effects of endothelin-3 on rat mesenteric microvascular beds in vivo.

In order to clarify whether the vasoactive effects of endothelin-3 (ET-3) on microvessels are associated with the endothelium-derived relaxing factor (EDRF) in vivo, the authors examined the effects of L-NG-monomethyl arginine (L-NMMA), an analog of L-arginine, on low-dose ET-3 induced hemodynamic changes in the mesenteric microcirculation of male Wistar rats. The intravital observation revealed that ET-3 100 pM induced a remarkable and periodic vasoconstriction in arterioles, and the constriction was sustained for approximately fifteen minutes. No remarkable change was observed in the microvessels after the superfusion of 1 pM ET-3. Superfusion of 1 pM ET-3 with 100 microM L-NMMA elicited the vasoconstriction in arterioles, and the arteriolar diameter recovered to the control level within ten minutes in spite of continuing the superfusion. The vasoconstriction induced by low-dose ET-3 with L-NMMA was suppressed by the additional superfusion of 200 microM L-arginine. The present study suggests that the recovery of arteriolar diameter after the ET-3-induced constriction may be mediated by nitric oxide at least in the early phase.

Animals↗
PubMed1993

Nitric oxide mediates lipopolysaccharide-induced alteration of mitochondrial function in cultured hepatocytes and isolated perfused liver.

The influence of endogenous nitric oxide, which is generated by stimulation with lipopolysaccharide, on the mitochondrial energization of rat hepatocytes was investigated in vitro and ex vivo. Using a fluorescence microscope equipped with a silicon intensifier target camera, we visualized fluorescence of rhodamine-123, a mitochondrial energization-sensitive fluorescence probe, in individual hepatocytes and measured the fluorescence intensity with a digital imaging processor. Although addition of Kupffer cells or lipopolysaccharide in a range of 0.1 to 1.0 microgram/ml caused no significant alteration in the fluorescence in hepatocytes, Kupffer cells plus 1.0 microgram/ml lipopolysaccharide reduced fluorescence intensity in the cocultured hepatocytes. The alteration of rhodamine-123 fluorescence in the hepatocytes induced by lipopolysaccharide-activated Kupffer cells was significantly inhibited by the addition of NG-monomethyl-L-arginine, a selective inhibitor of nitric oxide synthesis. The transportal infusion of lipopolysaccharide also decreased rhodamine-123 fluorescence in perfused rat liver. The decrease was significantly enhanced in the pericentral regions. Autofluorescence of NADH was elicited by continuous infusion of lipopolysaccharide; this reaction was also enhanced in the pericentral regions. We showed the main site of uptake of infused lipopolysaccharide in the hepatic lobule to be in the periportal regions with fluorescein isothiocyanate-labeled lipopolysaccharide. Our results indicate that the inhibition of mitochondrial energization occurs mainly in pericentral regions, which are distant from the lipopolysaccharide uptake site. The continuous administration of NG-monomethyl-L-arginine significantly attenuated the lipopolysaccharide-induced decrease in rhodamine-123 fluorescence and increase of the NADH contents of the hepatic lobule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Visualization of oxidative processes at the cellular level during neutrophil-mediated cytotoxicity against a human hepatoma cell line, HCC-M.

Human neutrophil-mediated oxidative processes against a human hepatoma cell line, HCC-M, was visualized at the cellular level by using a silicon-intensified target camera and subsequently processing with a computer-assisted digital-imaging processor. Neutrophils were activated by a streptococcal preparation, OK-432. A hydroperoxide-sensitive tracer, dichlorofluorescein diacetate, was loaded in HCC-M and temporal and spatial changes of lipid peroxides in this cell after addition of stimulated neutrophils were analyzed. The luminol-dependent chemiluminescence activity of neutrophils was significantly enhanced and continued for at least 2 hr by stimulation with OK-432, and its activity was shown to be accumulated at the site where a neutrophil attached with HCC-M. The intensity of dichlorofluorescein fluorescence in HCC-M rapidly increased after adding stimulated neutrophils, and their reaction was significantly attenuated by superoxide dismutase. The number of non-viable cells was increased as the dichlorofluorescein fluorescence increase. It is suggested that oxidative stress may play an important role in neutrophil-mediated tumor-cell damage.

Carcinoma, Hepatocellular↗
PubMed1992

Tissue-type plasminogen activator of colonic mucosa in ulcerative colitis. Evidence of endothelium-derived fibrinolytic activation.

Microvascular endothelial alterations are thought to be a crucial step for development of hemorrhagic changes in various pathological states. In this study, we determined the activity and amount of tissue-type plasminogen activator (t-PA) in the biopsy specimens from sigmoid colon of patients with ulcerative colitis to evaluate endothelial alterations and vascular changes of permeability. The results of this investigation revealed that mucosal amount of t-PA in the active stage of ulcerative colitis was two- to threefold higher than in healthy controls, while t-PA levels in plasma samples showed no remarkable differences among the groups. Increased t-PA activity appeared to correlate well to the degree of inflammation of colonic mucosa, and t-PA amount was still increased in the inactive stage. The present study indicates that t-PA determination in colonic biopsy specimens may be useful for the evaluation of clinical activity of ulcerative colitis in terms of the mucosal microvascular endothelial changes.

Adult↗
PubMed1992

Role of platelet activating factor on the fibrinolytic activation in the pathogenesis of gastric mucosal damage induced by endothelin-1.

We have examined the hypothesis that the release of tissue type plasminogen activator may play a prominent role in endothelin induced gastric mucosal injury. We determined tissue type plasminogen activator activity in the regional blood sample and the concentration of platelet activating factor in the gastric mucosa after the administration of endothelin-1 in a range of 50-500 pmol/kg into the left gastric artery of male Wistar rats. Endothelin-1 increased the tissue type plasminogen activator release and platelet activating factor formation, and induced subsequent gastric mucosal haemorrhagic change in a dose dependent manner. In addition CV-6209, a selective platelet activating factor blocker, attenuated the activation of regional tissue type plasminogen activator and the development of mucosal damage induced by endothelin-1. The results of this study showed that tissue type plasminogen activator activation may play an important role in the pathogenesis of endothelin induced mucosal injury of rat stomach, and suggest that the platelet activating factor may be involved in the process of regional fibrinolytic activation induced by endothelin-1.

Animals↗
PubMed1992

Intestinal microcirculatory changes during fat absorption and the effect of cholecystokinin inhibitor.

The major objective of this study was to estimate how microvascular changes occur in the intestinal segment in relation to fat absorption and also to assess the role played by cholecystokinin (CCK) in fat-induced intestinal hyperemia. A 12-cm loop of rat middle small intestine was exposed to a 120-min infusion of oleic acid micelle solution containing [14C]oleic acid. Time-course changes of vascular diameter and red blood cell (RBC) velocity of submucosal arterioles, venules, and periglandular and muscular capillaries were determined simultaneously in their different order of branching by using intravital microscopy equipped with a high-speed video camera system. Lymphatic transport of oleic acid was also monitored by collecting lymph from intestinal lymphatics. The instillation of micelle produced significant dilatation of submucosal arterioles and venules and significant increase in RBC velocity in submucosal microvessels and periglandular capillaries at 15 to 30 min after the fat instillation. This corresponds well to the appearance of [14C]oleic acid in intestinal lymph. This microvascular dilatation and RBC velocity increase continued throughout the exposure to fat and started to attenuate 30 min after restoration to saline infusion. There was also heterogeneity in microvascular responses among different orders of branches to fat administration, and RBC velocity increase was not observed in muscular capillaries. Local intra-arterial infusion of CCK inhibitor, loxiglumide (CR 1505, 10 mg.kg-1.h-1), significantly attenuated both fat-induced microvascular dilatation and RBC velocity increase but not the fat absorptive function. Our results indicate that CCK plays a significant role in intestinal hyperemia induced by fat absorption. However, CCK-mediated intestinal microvascular change was not a prerequisite for fat absorption.

Animals↗
PubMed1992

Helicobacter pylori-associated ammonia production enhances neutrophil-dependent gastric mucosal cell injury.

The role of neutrophil and its chlorinated oxidant were investigated in Helicobacter pylori-induced gastric mucosal injury in vitro. Luminol-dependent chemiluminescence (ChL) was used to detect neutrophil-derived oxidants. ChL activity was significantly elevated when neutrophils were incubated in H. pylori, indicating that H. pylori actually elicits oxidative burst of neutrophils. To assess whether H. pylori-activated neutrophils exert the cytotoxicity for gastric mucosal cells, rabbit gastric mucosal cell was monolayered in culture wells and labeled with a fluorescence dye, 2',7'-bis(2-carboxyethyl)-5(6)carboxy-fluorescein, which is retained in the intracellular space as long as the cell membrane is intact. Labeled cells were coincubated with neutrophils and H. pylori. We inferred from the cytotoxicity index (specific %cytotoxicity), which was calculated from fluorometrical measurements of supernatant and lysate, that the mucosal cells were significantly damaged by H. pylori-activated neutrophils. This injury was largely attenuated by eliminating urea from the incubation mixture or by acetohydroxamic acid, a potent urease inhibitor. Additionally, the scavengers of neutrophil-derived oxidants, including taurine, methionine, and catalase, also attenuated this injury. Cultured mucosal cells that were exposed to the solution containing monochloramine (an oxidant yielded by reaction of hypochlorous acid and ammonia) were highly damaged compared with cells exposed to hypochlorous acid or hydrogen peroxide at physiological concentrations. These data suggest that H. pylori-activated neutrophils promote gastric mucosal cell injury and that monochloramine plays a unique and important role in this process.

Ammonia↗
PubMed1992

Quantitative analysis of mesenteric microcirculatory disturbances induced by autonomic nervous irritation.

In this study, we have demonstrated that repeated electrical stimuli to the artery of the mesenteric pedicle can produce mesenteric microcirculatory disturbance by autonomic nervous irritation in rats. The parameters to demonstrate microcirculatory damage were observed and quantitatively analyzed using the intravital microscopy after electrical stimulation for 40 minutes. The blood flow of arterioles and venules in the mesentery showed ischemia-reperfusion pattern during the repeated electrical stimulations. The diameter of arterioles did not show significant change, while RBC velocity of arterioles was significantly decreased at 30 min after the irritation. The RBC velocity in venules was decreased from the early period to about 20%. But this values were not significantly dropped during the later observation period, suggesting the formation of short circuit flow by passing the collapsed capillary beds. The number of rolling WBC in the venules was notably increased at the time immediately after irritation, and thereafter the number of rolling WBC number was rather reduced. The number of sticking WBC in venules was time-dependently increased and reached its maximum at 30 min. When permeability of venular wall was determined by the injection of pontamine sky blue, significant increase in permeability was already shown immediately after irritation, suggesting that the integrity of microvascular wall was disturbed in this early period. The permeated area expanded thereafter in parallel with the increase in sticking WBC number. From these observations, it is suggested that endothelial cell damage and following leukocyte-endothelium interaction induced by autonomic nerve irritation appear to be an important factor in microcirculatory disturbances.

Animals↗
PubMed1991

Involvement of superoxide anion and platelet-activating factor in increased tissue-type plasminogen activator during rat gastric microvascular damages.

The role of tissue-type plasminogen activator (t-PA) was investigated in the gastric ulcer formation induced by microvascular derangement. The rat stomach was exposed and repeated electrical stimuli (irritation) were applied on the small arterial wall close to the lesser curvature to induce mucosal ischemia followed by hyperemia. The t-PA activity in the regional blood of the stomach was significantly elevated as early as 5 min after the irritation. Immunohistochemical study using anti-t-PA monoclonal antibody revealed that t-PA was detectable in the endothelial cells of capillaries and collecting venules, suggesting the involvement of endothelium-mediated fibrinolytic activity in the irritation-induced ulcer formation. Pretreatment of SOD or allopurinol significantly attenuated the irritation-induced t-PA activation, suggesting that the t-PA activity was modulated by xanthine oxidase-associated superoxide anions. CV-6209, a selective antagonist of platelet-activating factor (PAF), also prevented the activation of t-PA as well as ulcer formation, providing a concept that PAF may be associated with the local fibrinolytic activation which may cause hemorrhagic changes in the gastric mucosal microvasculature. The present study supports the hypothesis that increased t-PA activity may reflect the microvascular endothelial damages caused by vasomotor derangement and suggests that oxygen-derived free radicals may participate in the regulation of endothelium-derived fibrinolytic activities in the mucosal microvasculature.

Animals↗
PubMed1991

Kupffer cell-mediated oxidative stress on colon cancer cell line visualized by digital imaging fluorescence microscopy.

Temporal and spatial changes of lipid peroxides in a cultured colon cancer cell line, Colo-205 cells, were investigated after culturing with Kupffer cells by using 2',7'-dichlorofluorescein diacetate and a digital imaging processor equipped with an inverted microscope. By this method, we successfully visualized the alteration of lipid peroxides in the individual cancer cell. Without any prior activation, Kupffer cells isolated from an intact rat liver caused rapid increase in the intensity of dichlorofluorescein in tumor cells in a time-dependent manner. The increase of the fluorescent intensity was significantly attenuated by pretreatment with superoxide dismutase. In ex vivo study using isolated perfused rat liver, dichlorofluorescein-preloaded cancer cells, which were transportally injected, were found to adhere to hepatic sinusoids and then to enhance their fluorescence. The present study suggested that the resident Kupffer cell-derived oxidative stress participates in the cytotoxic process against cancer cells by inducing intracellular lipid peroxidation. It may be sustained that Kupffer cells play a role in the host defence mechanisms against the liver metastasis of colon cancer cells.

Animals↗
PubMed1991

Involvement of platelet-activating factor in endothelin-induced vascular smooth muscle cell contraction.

This study was designed to elucidate the participation of platelet-activating factor (PAF) in endothelin-induced vascular constriction in vivo and in vitro. The microvascular hemodynamic changes in rat mesentery induced by the superfusion of endothelin-1 (ET-1) were visualized through an intravital microscopic system. It was revealed in vivo that ET-1 in a range of 100 fM-10 pM caused a sustained arteriolar constriction in a dose-dependent manner. Pretreatment with CV-6209, a selective PAF antagonist, significantly attenuated the constrictive change in arterioles. Changes of intracellular Ca2+ mobilization after treatment with ET-1 were investigated in vitro using a cell line (A-10 cell) derived from rat arterial smooth muscle cells. ET-1 caused a prompt rise in the fura-2-associated fluorescence intensity in the individual A-10 cell and it fell to a lower plateau level that was still higher than the baseline value. CV-6209-pretreated cells did not show the rapid-phase mobilization of Ca2+, but showed the slow late phase of Ca2+ activation. The present study demonstrates that PAF may be involved in endothelin-induced microvascular constriction by mediating the mobilization of Ca2+ in vascular smooth muscle cells.

Animals↗
PubMed1991

Microcirculatory disturbance in indomethacin-induced intestinal ulcer.

Participation of microcirculatory disturbances, especially the role of 5-lipoxygenase products from neutrophils, was investigated in indomethacin (Indo)-induced ulcers of rat small intestine. After Indo treatment (20 mg/kg) in rats, small erosions appeared at 6 h and longitudinal ulcers developed 12 h later. At 6 and 12 h after Indo treatment, severe microcirculatory disturbances were observed under an intravital fluorescence microscope. Significant delay in the clearance and patchy pooling of injected fluorescein isothiocyanate-bovine serum albumin with sludge and stasis were observed in archade vessels of villi of Indo-treated rats. Increased numbers of sticking leukocytes were also detected along submucosal venules in these rats after the infusion of acridine orange. When regional venous blood was collected from the mesentery, a marked increase in neutrophil number and their increased production of oxygen-derived free radicals as determined by chemiluminescence assay were demonstrated at 6 h after Indo treatment. There was also a significant increase in myeloperoxidase activity of the intestinal mucosa at 6 and 12 h after Indo treatment, suggesting a significant neutrophil accumulation at this time. AA-861, a selective inhibitor of 5-lipoxygenase (80 mg/kg), attenuated these microcirculatory changes and neutrophil accumulation in the intestinal mucosa. AA-861 also significantly prevented the formation of intestinal ulcers induced by Indo. However, Indo-induced ulcer formation and leukocyte accumulation in submucosal venules were not attenuated by the treatment of Ono-1078, a potent antagonist of sulfidopeptide leukotrienes. From these observations, it is considered that microcirculatory disturbances, especially leukocyte accumulation and 5-lipoxygenase products, possibly leukotriene B4, may be involved in the development of Indo-induced intestinal ulcer.

Animals↗
PubMed1991

Ischemic bowel necrosis induced by endothelin-1: an experimental model in rats.

Local intra-arterial administration of endothelin-1 induced small intestinal mucosal damage in rats in a dose-dependent manner. A remarkable decrease in mucosal blood flow (15% of control values) was observed by a laser Doppler flowmetry 10 min after injection of endothelin-1 (1 nmol/kg). Endothelin-1 at this dose induced significant hemorrhagic and necrotic lesions in the small intestinal mucosa 30 min after the injection. Decreased mucosal blood flow was attenuated to some extent by the pretreatment with platelet-activating factor (PAF) inhibitor, CV-6209, superoxide dismutase plus catalase or the calcium antagonist, nicorandil. All these inhibitors significantly prevented the endothelin-1-induced ischemic necrotic damage in the small intestine. These results suggest a potential role of endothelin-1 in the pathogenesis of ischemic bowel diseases in clinical situations and also the possibility that PAF and oxygen-derived free radicals may be involved as secondary mediators in endothelin-induced intestinal tissue damage.

Animals↗
PubMed1989

In vivo visualization of oxyradical-dependent photoemission during endothelium-granulocyte interaction in microvascular beds treated with platelet-activating factor.

Oxyradical-dependent chemiluminescence from granulocytes sticking to venular endothelium was successfully visualized in rat mesenteric microvascular beds treated with platelet-activating factor (PAF). Intravital photonic image intensifier microscopy revealed that topical application of PAF-acether (100 nM) caused remarkable granulocyte adherence on endothelial walls and the subsequent activation of a luminol-dependent photonic burst. Chemilumigenic sites clearly corresponded to the spatial distribution of sticking cells in post-capillary venules. The present findings thus serve as the first demonstration of an intravital oxidative burst of granulocytes on venular endothelium in PAF-induced microcirculatory disturbances.

Animals↗
PubMed1989

Prolylhydroxylase and collagenase activities in the healing of acetic acid-induced gastric ulcers in rats and the effects of cimetidine and elcatonin.

We examined the changes in prolylhydroxylase (PH) and interstitial collagenase (CA) activities in the healing of acetic acid-induced gastric ulcers in rats. Gastric ulcers were induced by subserosal injection of acetic acid, and confirmed by endoscopy on the third day. At the acute stage of ulceration, PH activity was not high but CA activity was increased. At the healing stage, PH activity was increased but CA activity gradually decreased to a normal level. Cimetidine did not effect PH activity but tended to increase CA activity in the healing. On the contrary, elcatonin increased PH activity but had little effect on CA activity. The above enzymes seems to be indispensable in the healing of gastric ulcers and effects of antiulcer agents on these enzymes must be considered.

Acetates↗
PubMedDate not supplied

Fluorographic study on the oxidative stress in the process of gastric mucosal injury: attenuating effect of vitamin E.

In vivo oxidative change was visualized in the gastric mucosa of rats and the alteration was analysed by using a fluorescence microscope equipped with a digital imaging processor during the development of mucosal damage. Dichlorofluorescein (DCF)-associated fluorescence increased after the repeated electrical stimulation on the gastric artery (irritation), suggesting the occurrence of lipid peroxidation. The increase was enhanced in the mid-zone of two adjacent collecting venules. Allopurinol attenuated the oxidative stress in mucosa, showing the involvement of xanthine oxidase. Luminol-dependent chemiluminescence value in the blood taken from gastric vein was elevated by the irritation, suggesting that leucocyte-generated oxygen radicals also participate in this oxidative process. alpha-Tocopherol attenuated both the DCF activation and the increase in chemiluminescence value and prevented gastric mucosal injury. The present results suggest that alpha-tocopherol may be useful for the prevention of oxidative alteration in gastric mucosa.

Allopurinol↗