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Biomedical subjects

M Suematsu

Publications and source records attributed to M Suematsu.

At least 145 records · Page 8Linked to original sources
PubMed1991

Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

BACKGROUND: The reductions of myocardial beta-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by beta-receptor blockade. METHODS AND RESULTS: We administered the oral beta-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of beta-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial beta-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial beta-receptor density and attenuated the decrease in the cardiac beta-adrenergic sensitivity that occurred in right heart failure. CONCLUSIONS: Excessive sympathetic stimulation may play an important role in the development of beta-receptor downregulation and beta-adrenergic subsensitivity in right heart failure.

Adenylyl Cyclases↗
PubMed1991

Intralobular heterogeneity of carbon tetrachloride-induced oxidative stress in perfused rat liver visualized by digital imaging fluorescence microscopy.

Spatial and temporal alterations in carbon tetrachloride-induced oxidative stress were studied in perfused hepatic microcirculatory units of the rat by digital imaging microscopic fluorography using dichlorofluorescin diacetate, a hydroperoxide-sensitive fluorogenic probe. The surface of the liver loaded with dichlorofluorescin was microscopically visualized, and the fluorescence of dichlorofluorescin (DCF), a highly fluorescent molecule generated by hydroperoxide-mediated oxidation of dichlorofluorescin, was digitally processed. After completing the experiments, fluorescein-labeled albumin was injected into the perfusate to confirm the state of sinusoidal perfusion and the topography of hepatic microangioarchitecture in the area studied. During transportal infusion of carbon tetrachloride, DCF fluorescence was observed predominantly in the pericentral area and was attenuated by pretreatment with SKF-525A, suggesting the involvement of cytochrome P-450. After peaking at the maximum level, the pericentral DCF fluorescence gradually decreased in parallel to the loss of viability, implicating the causal role of intracellular hydroperoxide formation in hepatocellular injury. In retrogradely perfused liver, in which intralobular O2 gradient was reversed, no significant activation of DCF fluorescence was observed among hepatic lobules. It is therefore conceivable that the zonal heterogeneity of carbon tetrachloride-induced lipid peroxidation may depend on at least two factors, sinusoidal oxygenation and the intralobular distribution of cytochrome P-450. Furthermore, development of the current technique will provide a useful method to investigate the microtopography of oxidative stress in organ microcirculatory units.

Animals↗
PubMed1990

[Relation between localization of gastric mucosal lesions and microvascular disturbance].

Acute gastric mucosal lesions in the rats were produced by intermittent electrical stimuli to a main trunk of the left gastric artery (LGA), right gastroepiploic artery (RGEA) or a posterior branch of the left gastric artery (PLGA). The image processing analysis was applied to determine the relation between distribution of the lesions and perfusion area of the supplying artery to which electrical stimuli were given. Electrical stimuli of 50 Hz, 5 msec, 100 microA was supplied to the artery for 30 sc three times with 10 sec interval. A series of these stimuli was repeated three times. The mucosal blood flow measured with the laser doppler method in each perfusion area was reduced to less than 35% of the control value during the electrical stimuli for 30 sec. After the repeated electrical stimuli to LGA, 85.8 and 95.4% of the mucosal lesions were found in the mean and maximum perfusion area of LGA, respectively. Electrical stimuli to PLGA caused 84.5% and 95.3 of the lesions in the mean and maximum area of PLGA, respectively. Stimuli to RGEA caused 53.4% and 74.1% of the lesions in the mean and maximum perfusion area of RGEA. In the antrum, electrical stimuli to LGA, PLGA or RGEA produced 0%, 5.4% or 5.0% of the mucosal lesions. It is concluded that the corpus mucosal lesions induced by regional ischemia are distributed in the ischemic area.

Animals↗
PubMed1989

Effects of serine protease inhibitors on oxyradical burst from phagocytizing neutrophils--analysis by chemiluminescence counting and its microscopic imaging.

Reaction difference of oxyradical generation and luminol-dependent photoemission of zymosan- and phorbol ester-treated neutrophils were investigated using a conventional photomultiplier and ultrasensitive photonic imaging technique. Zymosan-treated cells released a concentrated photonic burst corresponding to the cellular distribution. In contrast, phorbol ester-treated cells produced a negligible level of photoemission, and the additional application of Ca2+ ionophore enhanced the photonic burst, which was gradually spread out into extracellular space. Serine protease inhibitors did not attenuate PMA-induced chemiluminescence but did attenuate zymosan-induced chemiluminescence. This suggests the involvement of serine protease in the respiratory burst of phagocytizing neutrophils.

Free Radicals↗
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↗
PubMed1988

Luminol-dependent photoemission from single neutrophil stimulated by phorbol ester and calcium ionophore--role of degranulation and myeloperoxidase.

Luminol-dependent photonic burst from phorbol ester-treated single neutrophil was visually investigated by using an ultrasensitive photonic image intensifier microscope. Neutrophils stimulated by phorbol myristate acetate (0.1 microgram/ml) alone produced a negligible level of photonic activities in the presence of luminol (10 micrograms/ml). The additional application of 0.1 microM Ca2+ ionophore A23187 induced explosive changes of photonic burst corresponding to the distribution of neutrophils, and these photonic activities were gradually spread to extracellular space. Sodium azide, which prevents myeloperoxidase activity, inhibited Ca2+ ionophore-induced photonic burst from phorbol ester-treated neutrophil. These findings suggest a prerequisite role of degranulation and myeloperoxidase release in luminol-dependent photoemission from stimulated neutrophils.

Azides↗
PubMed1988

Alterations in gastric mucosal microvascular endothelium in a stressed condition--relevance to gastric ulcerogenesis.

The present paper describes the morphological and functional alterations of the gastric mucosal microvascular endothelium under restraint-stressed condition. On the basis of the direct cholinergic innervation of capillaries and non-muscular venules in the gastric mucosa, these endothelial changes would be caused by the stress-induced overstimulation of the cholinergic nerves and modified by the degranulation of mast cells, contributing to the stress-induced ulcer formation as schematically illustrated in Fig. 10.

Aged↗
PubMed1988

Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease.

Chemiluminescence (CL) analysis of monocytes and polymorphonuclear cells (PMNs) was performed on 13 patients with Crohn's disease (CD) and 10 healthy volunteers. The percentages of monocyte populations in mononuclear cells obtained from the patients with CD were greater than those from the healthy volunteers, but the numbers of PMNs were not different between the two groups. The peak level of phorbol myristate acetate (PMA)-induced CL activity generated by diluted whole blood from the patients with CD was more significantly elevated than that from the healthy volunteers, whereas the peak levels of opsonized zymosan-induced CL activity did not differ between the two groups. In monocytes, the peak levels of both PMA- and opsonized zymosan-induced CL activity were significantly higher in the patients with CD than in the healthy volunteers. CL in PMNs, however, showed no significant difference between CD and controls. It is suggested that monocytes of CD have a large capacity to generate active oxygen species. The present study suggests that excessive active oxygen species released by monocytes and perhaps macrophages may play an important role in formation of the intestinal lesions in CD.

Adult↗
PubMed1988

The effect of ceruletide on tardive dyskinesia: a double-blind placebo-controlled study.

1. In a double-blind placebo-controlled study of 37 patients with tardive dyskinesia, the therapeutic effect of ceruletide was evaluated. 2. The patients were assigned at random to two groups that received either intramuscular injections of 0.8 micrograms/kg of ceruletide or placebo once weekly for 4 weeks. Conventional neuroleptic medication was not changed 3 weeks prior to and throughout the study period. Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale over an 8-week period. 3. Ceruletide had a more pronounced effect on TD than the placebo however, because of the limited number of subjects examined, the difference between the two groups was not significant. Ceruletide was more effective than placebo in patients under 60 years of age (p less than 0.05) and whose antipsychotic medication was mainly butyrophenones. 4. No serious side effect was noted. 5. The findings suggested that ceruletide therapeutically benefits patients with tardive dyskinesia.

Ceruletide↗
PubMed1988

Microcirculatory disturbances in endotoxin-induced disseminated intravascular coagulation. The effects of heparin and gabexate mesilate on locomotive and metabolic changes of neutrophils.

Neutrophil-mediated oxidative stress on the rat mesenteric microcirculation was studied in the experimental model of endotoxin-induced disseminated intravascular coagulation (DIC) by using an intravital fluorescent technique and luminol-dependent chemiluminescence (ChL) analysis. Leukocytes sticking to the venules were visualized by the injection of acridine orange, a fluorochrome tracer which shows high affinity to white cells. Endotoxin (E coli, O-111B4, Difco, USA) was infused intravenously at a dose of 2 mg/kg/hr. After starting the infusion of endotoxin, the number of sticking cells were gradually increased on the venular endothelium followed by a transient neutropenia. In order to investigate the distribution of infused endotoxin in the microvasculature, FITC-labeled endotoxin (Sigma, USA) was used. After administration of FITC-endotoxin, multiple patches of fluorescence along the venular walls were observed, while no fluorescent conjugates were found at the sticking neutrophils and along the arteriolar walls. ChL activities of neutrophils were also dramatically elevated, which may reflect the enhanced ability to generate oxyradical species. To investigate the inhibitory effects of heparin sodium and gabexate mesilate which was a synthetic protease inhibitor on locomotive and metabolic changes of neutrophils induced by endotoxemia, both agents were administered prior to endotoxin infusion. Gabexate mesilate attenuated these changes, but heparin sodium did not show any improving effects. It was concluded that endotoxin primarily affects the venular endothelial cells, resulting in the activation of neutrophils. Gabexate mesilate was more likely to attenuate neutrophil-mediated oxidative stress on microvasculature in endotoxin-induced DIC than heparin sodium.

Animals↗
PubMed1988

5-lipoxygenase inhibitor (AA-861) attenuates neutrophil-mediated oxidative stress on the venular endothelium in endotoxemia.

Neutrophil-mediated oxidative stress on the rat mesenteric microcirculation was studied in the experimental model of endotoxin-induced disseminated intravascular coagulation (DIC) by using an intravital fluorescent microscope equipped with a Silicon Intensifier Target Image Tube camera and luminol-dependent chemiluminescence (ChL) analysis. Leukocytes adhering to the venules were visualized by the injection of acridine orange, a fluorochrome tracer which shows high affinity to white cells. Endotoxin (E. coli, O-111 B4) was administered intravenously at a dose of 2 mg/kg/hour. After starting the infusion of endotoxin, the number of adherent cells gradually increased in the venular endothelium and was followed by a transient neutropenia. ChL activities from neutrophils were also significantly elevated, which may reflect the enhanced ability to generate oxygen-radicals. To elucidate the role of 5-lipoxygenase products in the locomotive and metabolic changes of neutrophils, the effects of AA-861, a specific inhibitor of 5-lipoxygenase was tested. In addition prednisolone and indomethacin were evaluated. AA-861 and prednisolone reduced neutropenia, leukocyte adhesion to the venular walls and ChL activities from neutrophils. It was concluded that 5-lipoxygenase may modulate neutrophil-mediated oxidative stress on microvasculature in endotoxin-induced DIC.

Acridine Orange↗
PubMed1987

Real-time visualization of oxyradical burst from single neutrophil by using ultrasensitive video intensifier microscopy.

Dynamics of oxyradical burst from single human neutrophils stimulated by opsonized zymosan was visualized by using an ultrasensitive video intensifier microscopy in the presence of chemiluminescence probe. Luminol-dependent photonic burst activities were clearly corresponding to the distribution of zymosan-treated neutrophils. Heterogeneity of photon-bursting period and the maximum photonic intensity among reactive cells was demonstrated. This may reflect functional heterogeneity of the ability to release oxyradicals among neutrophils.

Free Radicals↗
PubMed1987

Increased lymphocyte transport by lipid absorption in rat mesenteric lymphatics.

The effect of olive oil administration on lymphocyte transport through mesenteric lymphatics was examined to see the possible involvement of nutritional absorption in lymphocyte traffic from the intestinal mucosa. After the olive oil administration to rats, remarkable increase in lymphocyte flux was observed within 2 h in lymph samples collected from rats with lymphatic fistula. The use of a high-speed microscopic video system made it possible to analyze accurately the lymphocyte transport in rapid movement that could not be detected by any of the ordinary video systems. The direct observation of mesenteric collecting lymphatics by this system showed an increment of lymphocyte transport from the intestinal mucosa by lipid absorption in 2 h. The contraction frequency of intestinal collecting lymphatics was also enhanced by olive oil administration. The densitometric analysis on video image was applied to estimate the extent of lipid absorption. The combination of a high-speed video system and the densitometric analysis revealed that the increase in lymphocyte flux occurred before lipid absorption reached its maximum and also demonstrated that the lymphocyte transport returned to control levels under the maximal absorptive condition. The results suggest that the fat absorption could be an important factor influencing the lymphocyte transport in the lymphatic system of intestine.

Absorption↗