Biomedical subjects

H Kosaka

Publications and source records attributed to H Kosaka.

At least 55 records · Page 3Linked to original sources

PubMed1999

Antimutagenic activity of isoflavones from soybean seeds (Glycine max merrill).

Two isoflavones, daidzein (1) and genistein (2), were isolated from soybean hypocotyls. Daidzein and genistein showed a suppressive effect on umu gene expression of the SOS response in Salmonellatyphimurium TA1535/pSK1002 against the mutagen 3-amino-1, 4-dimethyl-5H-pyrido[4,3b]indole (Trp-P-1), which requires liver metabolizing enzymes. Compound 1 suppressed 73% of the SOS-inducing activity at concentrations <0.74 micromol/mL, and the ID(50) value was 0.37 micromol/mL. Compound 2 suppressed 95% of the SOS-inducing activity at concentrations <0.74 micromol/mL, and the ID(50) value was 0.17 micromol/mL. Compounds 1 and 2 were also assayed with the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) and activated Trp-P-1. In addition to the antimutagenic activities of daidzein and genistein against Trp-P-1, frylfuramide and activated Trp-P-1 were assayed by an Ames test using S. typhimurium TA100.

Antimutagenic Agents↗

PubMed1999

Antimutagenic activity of polymethoxyflavonoids from Citrus aurantium.

The methanol extract from Citrus aurantium showed a suppressive effect on umu gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The methanol extract from C. aurantium was successively re-extracted with hexane, dichloromethane, butanol, and water. A dichloromethane fraction showed a suppressive effect. The suppressive compounds in the dichloromethane fraction were isolated by SiO(2) column chromatography and identified as tetra-O-methylscutellarein (1), sinensetin (2), and nobiletin (3) by EI-MS and (1)H- and (13)C NMR spectroscopy. These compounds suppressed the furylfuramide-induced SOS response in the umu test. Gene expression was suppressed 67%, 45%, and 25% at a concentration of 0.6 micromol/mL, respectively. The ID(50) value (50% inhibition dose) of compound 1 was 0. 19 micromol/mL. These compounds were assayed with other mutagens, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver metabolizing enzymes, activated Trp-P-1, and UV irradiation. These compounds showed of all mutagen-induced SOS response in the umu test. In addition, compounds 1-3 exhibited antimutagenic activity in the S. typhimurium TA100 Ames test.

Antimutagenic Agents↗

PubMed1999

Intracoronary administration of adenosine triphosphate increases coronary blood flow and attenuates the severity of myocardial ischemic injury in dogs.

ATP generates nitric oxide (NO) via activation of P2y receptors, and is degraded to adenosine. This study was undertaken to examine whether ATP causes coronary hyperemic flow via purinoceptors-, NO- and adenosine-dependent mechanisms, and attenuates the severity of contractile and metabolic dysfunction in the ischemic myocardium. In the non-ischemic canine hearts, the infusions of ATP into the coronary artery dose-dependently increased coronary blood flow. The levels of adenosine and end-product of NO in coronary venous blood over the arterial blood also increased. This hyperemic flow was partially attenuated by either 8-sulfophenyltheophylline (8SPT) or L(omega)-nitro arginine methyl ester (L-NAME), and completely blocked by the treatment with 8SPT, L-NAME and suramin (SRM). During myocardial ischemia, exogenous ATP increased coronary blood flow, and attenuated myocardial metabolic and contractile dysfunction, which was completely blunted by the treatment with 8SPT, L-NAME and SRM. We conclude that exogenous ATP increases coronary blood flow in the non-ischemic and ischemic myocardium mainly via either NO- or adenosine-dependent mechanisms.

Adenosine Triphosphate↗

PubMed1999

Reaction of neuronal nitric oxide synthase with the nitric oxide spin-trapping agent, iron complexed with N-dithiocarboxysarcosine.

A water-soluble iron complex with N-dithiocarboxysarcosine (Fe-DTCS) has been developed as an ESR spin-trapping agent for NO and successfully applied to ESR imaging of endogenous NO production in mice. We attempted to measure NO produced by purified neuronal NO synthase (nNOS) by this method, but could not detect NO. We speculated that Fe-DTCS inhibits NOS activity. In fact, it markedly inhibited NOS activity with an IC50 value of 9.7 +/- 0.7 microM in the citrulline-formation assay. DTCS alone did not inhibit the activity. An iron complex with N-methyl-D-glucamine dithiocarbamate, a similar spin-trapping agent for NO, also inhibited the activity, with an IC50 value of 25.1 +/- 2.9 microM. Fe-DTCS suppressed cytochrome c and ferricyanide reductase activities of nNOS, and markedly increased nNOS-mediated NADPH oxidation. Concomitantly, it accelerated oxygen consumption caused by activated nNOS. These results suggest that the ESR spin-trapping agent Fe-DTCS inhibits NO synthesis by interfering with the physiological electron flow from NADPH to nNOS heme iron.

Animals↗

PubMed1999

Hypoxia potentiates ultraviolet A-induced riboflavin cytotoxicity.

Flavins are thought to be important chromophores for chronic photo-induced skin injury, but the mechanism is not well known. We have reported that the primary cytotoxicity remaining in ultraviolet A-irradiated riboflavin solution is attributable to hydrogen peroxide. Because the dermis is more hypoxic than the atmosphere, we investigated the cytotoxicity of riboflavin solution during and after ultraviolet A irradiation under hypoxia. Riboflavin solution showed stronger cytotoxicity during irradiation under hypoxia than under air. Riboflavin solution that had been irradiated under hypoxia at lower ultraviolet A doses showed stronger cytotoxicity and contained more hydrogen peroxide than solution irradiated under air at the same doses. At higher ultraviolet A doses, however, the cytotoxicity and hydrogen peroxide quantity were similar in riboflavin solutions irradiated under different oxygen conditions. The effect of a singlet oxygen quencher, sodium azide, on the induction of cytotoxicity and production of hydrogen peroxide by ultraviolet A irradiation of riboflavin solution was examined. The presence of sodium azide in the solution during ultraviolet A irradiation suppressed the cytotoxicity and hydrogen peroxide production to similar levels at various ultraviolet A doses regardless of oxygen conditions. At the maximum suppression by sodium azide, hydrogen peroxide production decreased to 10% of the unsuppressed production. About 40% of the oxygen molecules of hydrogen peroxide produced was thought to be derived from oxygen dissolved in the riboflavin solution.

Cell Line↗

PubMed1999

Uptake of 10 polar organic solvents during short-term respiration.

Respiratory uptake was investigated for 10 polar organic solvents with high blood/air partition coefficients (lambda(blood/air)): ethyl acetate (lambda(blood/air), 77), methyl iso-butyl ketone (90), methyl acetate (90), methyl propyl ketone (150), acetone (245), iso-pentyl alcohol (381), iso-propyl alcohol (848), methyl alcohol (2590), ethylene glycol monobutyl ether (EGBE, 7970), and propylene glycol monomethyl ether (PGME, 12380). Test-air concentrations (Cinh) were 25 to 200 ppm. Four healthy male volunteers inhaled the test air for 10 min at rest and then room air for 5 min. The percentage of solvent in the end-exhaled air and in the mixed-exhaled air increased after the start of the test-air respiration, and reached a quasi-steady-state level within a few min. The speeds of these increases at the start of the test-air respiration became lower as lambda(blood/air) increased. The mean uptakes (U) for the last five min of the test air respiration were 67.3, 52.9, 60.4, 53.0, 52.6, 63.0, 60.3, 60.8, 79.7, and 81.3%, respectively, for ethyl acetate, methyl iso-butyl ketone, methyl acetate, methyl propyl ketone, acetone, iso-pentyl alcohol, iso-propyl alcohol, methyl alcohol, EGBE and PGME. Thus, U values of the alcohols were higher than those of the ketones and lower than the glycol ethers. The overall view, except for esters, showed that U increased with lambda(water/air) increases. This tendency can be explained by a hypothesis that solvent absorbed in the mucus layer of the respiratory tract is removed by the bronchial blood circulation. U values of ethyl acetate and methyl acetate were higher than those of methyl iso-butyl ketone and methyl propyl ketone, though the lambda(blood/air) values of these esters were nearly equal to those of the ketones. For the respiration of the esters, their metabolites, ethyl alcohol and methyl alcohol, were detected in the exhaled air. The exhalation percentage of the metabolites increased after the start of test-air respiration and reached a quasi-steady-state level of 2 and 3%, respectively, by the 5th min. These data suggest that removal of the solvent via metabolism in the wall tissue of the respiratory tract plays an important role for the esters.

Administration, Inhalation↗

PubMed1999

Endothelium-derived contracting factor in carotid artery of hypertensive Dahl rats.

The present study is designed to investigate whether acetylcholine (ACh) elicits an endothelium-derived contracting factor (EDCF) and whether it contributes to decreased relaxant response induced by ACh in Dahl rats. Dahl salt-sensitive (DS) and -resistant (DR) rats were fed a 0.4% NaCl or an 8% NaCl diet for 4 weeks. High sodium intake significantly increased blood pressure in DS rats but not in DR rats. The carotid rings were suspended for isometric tension recording. ACh caused an endothelium-dependent contraction in carotid rings from hypertensive DS rats but not from normotensive Dahl rats. Atropine, indomethacin, SQ29548, or ONO-3708 (prostaglandin H(2) [PGH(2)]/thromboxane A(2) [TXA(2)] receptor antagonist) abolished ACh-induced contraction, and OKY-046 (inhibitor of TXA(2) synthetase) partially attenuated the contraction. High sodium intake significantly enhanced contraction evoked by U46619, a PGH(2)/TXA(2) receptor agonist, in both DS and DR rats. In contrast, ACh-induced relaxation was significantly depressed in the rings from hypertensive DS rats, and ONO-3708 partially improved the depressed relaxation. Administration of ONO-8809 (an orally active PGH(2)/TXA(2) receptor antagonist; 30 micrograms per body per day) for 4 weeks neither reduced blood pressure nor improved the depressed ACh-induced relaxation in hypertensive DS rats. These results suggest that ACh causes release of EDCF in carotid rings of hypertensive DS rats, which is likely to be PGH(2) and TXA(2). The EDCF contributed in part to the depressed ACh-induced relaxation.

Acetylcholine↗

PubMed1999

Involvement of superoxide in acute reaction of angiotensin II in mesenteric microcirculation.

Superfusion of angiotensin II (Ang II) ceased blood flow in rat mesenteric microcirculation, however, successive reflow occurred. When nitric oxide synthase inhibitor was present, the stoppage of flow occurred by the lower concentration of Ang II. Superoxide dismutase (SOD) significantly delayed the stoppage by Ang II and restored the successive reflow earlier. The acute reaction between Ang II and mesenteric artery induced immediate superoxide (O(2)(-)) production when observed by a chemiluminescence method using the Cypridina luciferin analog. The acute vascular O(2)(-) production on the addition of Ang II contributed to in vitro vascular contraction as it was significantly attenuated by SOD. The acute superoxide-producing effect is likely to be specific to Ang II because such significant modification by SOD was not observed for norepinephrine.

Angiotensin II↗

PubMed1999

Potassium supplementation increases sodium excretion and nitric oxide production in hypertensive Dahl rats.

The present study was designed to investigate whether antihypertensive and natriuretic effects of K were achieved by elevation of nitric oxide (NO) production in Dahl salt-sensitive (DS) rats. The rats were placed in individual metabolic cage and fed a high sodium diet with or without K supplementation for 4 weeks. K supplementation counteracted the blood-pressure raising effect of NaCl. K supplementation significantly enhanced sodium excretion and reduced sodium retention, increased the urinary nitrite plus nitrate excretion and kidney constitutive NO synthase activity in salt-loaded DS rats. These effect did not occur in the rats fed a low sodium diet with K supplementation. These results suggest that K supplementation attenuates development of hypertension with reduction of sodium retention in salt-loaded DS rats, which is mediated by the recovery of salt-induced NO production mechanism.

Animals↗

PubMed1998

The peripheral deletion of autoreactive CD8+ T cells induced by cross-presentation of self-antigens involves signaling through CD95 (Fas, Apo-1).

Recently, we demonstrated that major histocompatibility complex class I-restricted cross-presentation of exogenous self-antigens can induce peripheral T cell tolerance by deletion of autoreactive CD8+ T cells. In these studies, naive ovalbumin (OVA)-specific CD8+ T cells from the transgenic line OT-I were injected into transgenic mice expressing membrane-bound OVA (mOVA) under the control of the rat insulin promoter (RIP) in pancreatic islets, kidney proximal tubules, and the thymus. Cross-presentation of tissue-derived OVA in the renal and pancreatic lymph nodes resulted in activation, proliferation, and then the deletion of OT-I cells. In this report, we investigated the molecular mechanisms underlying this form of T cell deletion. OT-I mice were crossed to tumor necrosis factor receptor 2 (TNFR2) knockout mice and to CD95 (Fas, Apo-1) deficient mutant lpr mice. Wild-type and TNFR2-deficient OT-I cells were activated and then deleted when transferred into RIP-mOVA mice, whereas CD95-deficient OT-I cells were not susceptible to deletion by cross-presentation. Furthermore, cross-presentation led to upregulation of the CD95 molecule on the surface of wild-type OT-I cells in vivo, consistent with the idea that this is linked to rendering autoreactive T cells susceptible to CD95-mediated signaling. This study represents the first evidence that CD95 is involved in the deletion of autoreactive CD8+ T cells in the whole animal.

Animals↗

PubMed1998

Organ and development related difference in tissue norepinephrine concentrations in Dahl rats.

To determine organ and development related differences in tissue norepinephrine concentration (tNE) in Dahl salt-sensitive (S) and -resistant (R) rats, we measured the tNE of 16 organs, including the heart (left ventricle), kidney, cerebrum, brain stem, stomach, jejunum, ileum, colon, spleen, pancreas, liver, aorta, lung, bone, salivary gland, and muscle, at 1, 3, 5, 7, 9, 11 weeks old. Large differences were found in tNE among the organs of both S and R rats, ranging from 4.0 +/- 1.1 ng/g tissue (the bone of S rats) to 1234.8 +/- 32.5 ng/g tissue (the salivary gland of R rats). tNE in R rats increased development-dependently in 12 of 16 organs, but did not significantly change in the other three organs, and decreased in the bone. On the other hand, the development-dependent increase in tNE was suppressed in S rats, and the tNE values of S rats were significantly lower than those of R rats in 14 of 16 organs. To eliminate the baroreflexive effects on tNE, another group of 5-week-old S and R rats were subjected to sinoaortic denervation (SAD) or the sham operation. The tNE was measured in 10 organs in these animals at 9 weeks old. SAD did not alter the tNE in most of the organs in both S and R rats. There was no significant differences in mean arterial pressure (MAP) between S and R rats with baroreceptor intact at 9 weeks old. SAD slightly but significantly increased MAP in S rats, whereas not in R rats. There was no significant differences in plasma NE concentration (pNE) between S and R rats with the baroreceptor intact. SAD did not alter pNE in S or R rats. These results demonstrate that variations of the tNE were dependent on the organ and development. Many organs of S rats had lower tNE than those of R rats. The developmental-dependent increases in tNE in S rats were suppressed, compared with those in R rats. These tNE behaviors in S rats may not be related to blood pressure or baroreflex sensitivity, but might be involved in an abnormal sympathetic nerve activity.

Animals↗

PubMed1998

Role of endogenous endothelin in the development of graft arteriosclerosis in rat cardiac allografts: antiproliferative effects of bosentan, a nonselective endothelin receptor antagonist.

BACKGROUND: The purpose of this study was to determine whether endothelin-1 (ET-1) contributes to the development of graft arteriosclerosis and whether the orally active nonpeptide endothelin receptor antagonist bosentan, which blocks both ETA and ETB receptors, can protect against this pathologic damage. METHODS AND RESULTS: Recipient male Lewis rats were divided into three groups; group 1 received heterotopic heart transplantations from Lewis donors and groups 2 and 3 received transplantations from Brown-Norway donors; group 3 recipients also received bosentan orally at the dose of 20 mg/kg per day for 120 days. All recipients were given cyclosporine and were euthanized at examination 120 days after transplantation. Plasma ET-1 levels were significantly higher in group 2 than in group 1 (6.99+/-0.91 and 4.15+/-.83 pg/mL, respectively). Strong ET-1 immunoreactivity was seen in both the thickened neointima and the media of the coronary arteries in group 2 but not in group 1. The mean ratio of the coronary luminal area to the total vascular area in group 2 (19.0+/-11.7%) was significantly lower than that in group 1 (34.2+/-9.9%) and was significantly increased in group 3 (33.2+/-9.2%). CONCLUSIONS: These results show that local upregulation of ET-1, mainly in the thickened neointima and the media of the coronary arteries, may play an important role in the pathogenesis of graft arteriosclerosis by stimulating ETA receptors, ETB receptors, or both. Orally active bosentan might be a useful agent for the clinical prevention of graft arteriosclerosis.

Actins↗

PubMed1998

Sinoaortic denervation produces sodium retention in Dahl salt-sensitive rats.

The role of the arterial baroafferent signals in sodium (Na) homeostasis was examined in salt-sensitive rats. Sodium balances, water balances, and systolic arterial pressure (SAP) were measured for 3 weeks in sinoaortic denervated (SAD) or sham denervated (Sham) Dahl salt-sensitive (S) and salt-resistant (R) rats fed a standard-salt diet (0.4% NaCl). In R rats, there was no significant difference in Na balance, water balance, or SAP between the SAD and Sham animals. In the S rats, urinary Na excretion was suppressed in the SAD but not in the Sham animals, resulting in Na retention. SAD significantly increased SAP and mean arterial pressure. High salt challenge (8% NaCl diet) markedly increased SAP and Na and water balances in both S-SAD and S-Sham rats. However, no significant difference was found in SAP or cumulative Na and water balances between S-SAD and S-Sham rats. These results suggest that the baroafferent signals may have some role on the regulation of Na balance in salt-sensitive animals under a standard-salt condition, although a high-salt load masked the baroafferent-dependent sodium excretion.

Animals↗

PubMed1998

The gain of the hepatorenal reflex in anesthetized dogs.

To determine the overall gain of the hepatorenal reflex, hypertonic NaCl solutions were infused into the portal vein or inferior vena cava of anesthetized dogs at a rate of 0.01 ml/kg/min for 30 min and the urinary Na excretion measured. Infusion of 2.25% NaCl into either the portal vein or inferior vena cava had no effect. Portal infusion of 4.5% or 9% NaCl produced an increase of 36 +/- 16 or 40 +/- 17 microeq/kg/30 min, respectively, while inferior vena caval infusion had no effect. With 13.5% NaCl infusion, a significant increase in the natriuretic response was seen with portal venous infusion, with no significant difference between portal venous and inferior vena caval infusion. Thus, the difference in the natriuretic response between portal venous and inferior vena caval infusion was dependent on the degree of input; when an appropriate input was given, natriuresis was induced only by portal venous infusion, probably mediated by the hepatorenal reflex. The gain of the hepatorenal reflex was calculated from the output divided by the input. When 4.5% or 9% NaCl was infused into the portal vein, the 2-h gain of the hepatorenal reflex was 0.38 +/- 0.15 or 0.34 +/- 0.14, respectively.

Animals↗

PubMed1998

Increase in experimental pulmonary metastasis in mice by L-arginine under inhibition of nitric oxide production by NG-nitro-L-arginine methyl ester.

As we have previously reported, intraperitoneal injections of NG-nitro-L-arginine methyl ester [L-NAME; a competitive inhibitor of nitric oxide (NO) synthase] before and after the injection of B16 melanoma cells through a tail vein increased experimental pulmonary metastasis, while simultaneous injections of L-arginine (a substrate of NO synthase) at a 20-fold higher dose synergistically increased pulmonary metastasis. Our present study was intended to elucidate the mechanisms by which L-NAME alone or together with L-arginine increases metastasis. Injections of L-NAME decreased the serum concentration of nitrite plus nitrate (metabolites of NO) by about 50%, which was not reversed by simultaneous injections of L-arginine. Injections of L-NAME also decreased the diameter of arterioles and venules by 20-30%, while simultaneous injections of L-arginine did not show any significant effect. When collagen- or ADP-induced platelet aggregation was examined using platelet-rich plasma, injections of L-NAME showed little effects on platelet aggregation, while simultaneous injections of L-arginine rather suppressed platelet aggregation. B16 melanoma cells produced NO in culture, and L-NAME (0.2 mM) decreased NO production without effects on viability. Our results suggest that the increased experimental pulmonary metastasis induced by L-NAME can be ascribed partly to the contraction of arterioles and venules, which is induced by the inhibition of endogenous NO production by L-NAME, and that the synergistic effect of L-arginine on metastasis is related to the inhibition of endogenous NO production through unknown mechanisms.

Animals↗

PubMed1998

Cross-presentation of self antigens to CD8+ T cells: the balance between tolerance and autoimmunity.

Upon encounter with foreign antigen, tissue-associated antigen-presenting cells (APCs) migrate to draining lymph nodes to prime specific T cells. Using the transgenic RIP-mOVA model, we recently demonstrated that self antigens derived from peripheral tissues are constitutively transported to draining lymph nodes, and can be presented in association with MHC class I molecules by a bone marrow-derived APC population. This form of class I-restricted presentation of exogenous antigen has been referred to as cross-presentation and can induce activation and proliferation of antigen-specific CD8+ T cells. In the absence of CD4+ T cell help, activation of CD8+ T cells is inefficient, and cross-presentation leads to peripheral deletion of autoreactive CD8+ T cells, acting as a mechanism to maintain self-tolerance. If CD4+ T cell help is available, CD8+ T cell responses to self antigens can be rendered immunogenic, leading to autoreactive responses. Whether autoimmunity results from such responses also depends on the tissue location of the antigen. In RIP-mOVA mice, which express the model antigen mOVA (a membrane-bound form of ovalbumin) in the pancreatic beta cells and kidney proximal tubules, OVA-specific CD8+ T cells, activated by cross-presentation, infiltrated the pancreas and caused B cell destruction. Interestingly, however, these cells did not infiltrate the kidney, suggesting that proximal tubular cells are to some extent protected from immune destruction. Analysis of the role of antigen concentration indicates that high doses were required for efficient cross-presentation, suggesting that this pathway is directed towards immune responses to high-dose antigens, such as may be present during viral infection.

Animals↗

PubMed1998

Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium.

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3 microg/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidaprilat or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrite) concentrations of coronary venous blood were markedly increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either imidaprilat or cilazaprilat in the low constant coronary blood flow condition. It is concluded that ACE inhibitors can increase cardiac NO levels via the accumulation of bradykinin in the ischemic myocardium.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Cellular expression of inducible nitric oxide synthase following rat cortical incision and its suppression by hydroxyl radical scavenger, 1,2-bis(nicotinamido)propane.

Cellular expression of an inducible isoform of nitric oxide synthase (iNOS) was studied immunohistochemically 1,3 and 7 days following rat cortical incision. The induction of iNOS was demonstrated almost exclusively in the macrophages accumulated within the incision cavity on day 3. They were significantly reduced in number by the treatment with 1,2-bis(nicotinamido)propane (P < 0.01), suggesting the involvement of hydroxyl radicals in the macrophage activation after cortical injury.

Animals↗