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Biomedical subjects

E Sasaki

Publications and source records attributed to E Sasaki.

At least 37 records · Page 2Linked to original sources
PubMed2000

Therapeutic effect of melatonin on carbon tetrachloride-induced acute liver injury in rats.

The therapeutic effect of melatonin on acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). Melatonin (10, 50, or 100 mg/kg body weight [BW]) was intraperitoneally administered to male Wistar rats 6 hr after intraperitoneal injection of CCl4 (1.6 g/kg BW) at which time an apparent liver injury occurred. This post-melatonin administration dose dependently prevented the progression of liver injury at 24 hr after CCl4 injection, judging from the levels of serum transaminases, indices of liver cell damage. Rats injected with CCl4 alone showed an increase in liver lipid peroxide (LPO) content and a decrease in liver reduced glutathione content at 6 and 24 hr after the injection. The post-melatonin administration dose dependently ameliorated both changes found at 24 hr after CCl4 injection. Rats injected with CCl4 alone showed an increase in liver triglyceride (TG) content and decreases in serum TG concentration and liver tryptophan 2,3-dioxygenase (TDO) activity, a marker of the inhibition of liver protein synthesis by CCl4, at 6 and 24 hr after the injection, and also a decrease in serum albumin concentration at 24 hr. The changes in serum TG, albumin concentration, liver TG content, and TDO activity found at 24 hr after CCl4 injection were not ameliorated by the post-administration of melatonin. The same administration of melatonin dose dependently reduced liver LPO content in CCl4-untreated rats. These results indicate that melatonin exerts a therapeutic effect on CCl4-induced acute liver injury in rats, possibly through its antioxidant action.

Animals↗
PubMed2000

Effects of macrophage colony-stimulating factor (M-CSF) on anti-fungal activity of mononuclear phagocytes against Trichosporon asahii.

Trichosporon asahii is an emerging opportunistic pathogen in immunocompromised patients. Little is known about the mechanisms of host defence against T. asahii. We investigated the fungicidal activity of human peripheral blood monocytes and murine peritoneal macrophages against T. asahii isolates, and the effects of M-CSF on the anti-fungal activity of mononuclear phagocytes. We also established a neutropenic mouse model of disseminated trichosporonosis with T. asahii. M-CSF enhanced the phagocytic fungicidal activity of mononuclear cells, and infected mice treated with human M-CSF at 10 x 106 U/kg showed a significant improvement in survival rate, with fewer fungal colony counts in the lung compared with control mice. Mice treated with human M-CSF showed higher concentrations of tumour necrosis factor-alpha (TNF-alpha) in the lung and plasma compared with control mice. The survival rate was significantly reduced in mice treated with anti-mouse TNF-alpha. Our results showed that M-CSF enhanced the fungicidal activity of mononuclear phagocytes partly by production of TNF-alpha, and suggest that the administration of M-CSF to patients with disseminated trichosporonosis may be a useful adjunct to conventional anti-microbial therapy and prophylaxis.

Animals↗
PubMed2000

TAS-301 blocks receptor-operated calcium influx and inhibits rat vascular smooth muscle cell proliferation induced by basic fibroblast growth factor and platelet-derived growth factor.

The purpose of this study was to determine the effect of a recently synthesized drug, TAS-301 [3-bis(4-methoxyphenyl)methylene-2-indolinone], on vascular smooth muscle cell (VSMC) proliferation and the intracellular signal transduction pathways involved in VSMC proliferation. In an in vitro assay, TAS-301 inhibited the proliferation of rat VSMCs stimulated by platelet-derived growth factor (PDGF)-BB, basic fibroblast growth factor, or 2% fetal bovine serum in a concentration-dependent manner. TAS-301 dose-dependently inhibited the PDGF-induced Ca2+ influx; the concentration for the inhibition of Ca2+ influx was nearly identical to that for inhibition of VSMC proliferation. The Ca2+ influx induced by PDGF was also attenuated by NiCl2 but not by nifedipine, suggesting that PDGF-induced Ca2+ influx would be mediated by some non-voltage-dependent mechanisms. Furthermore, TAS-301 inhibited PDGF-induced activation of protein kinase C (PKC) and the phorbol 12-myristate 13-acetate-mediated induction of activator protein 1 (AP-1) in a concentration-dependent manner. These findings indicate that TAS-301 inhibited the proliferation of VSMCs by blocking voltage-independent Ca2+ influx and downstream signals such as the Ca2+/PKC signaling pathway, leading to AP-1 induction.

Animals↗
PubMed2000

Inhibitory effect of TAS-301, a new synthesized constrictive remodeling regulator, on renarrowing after balloon overstretch injury of porcine coronary artery.

The purpose of this study was to determine the efficacy and the possible mechanism of action of a recently synthesized drug, TAS-301 [3-bis(4-methoxyphenyl)methylene-2-indolinone], on stenosis after balloon overstretch injury of porcine arteries. We measured the diameter of vessels by angiography and conducted histological analysis. The oral administration of TAS-301 kept dilated the angiographic luminal diameter of injured segment 4 weeks after overstretch injury and reduced calculated stenosis ratio in a dose-dependent manner, significantly reducing it at doses of 30 and 100 mg/kg. Histopathological analysis showed that TAS-301 significantly reduced the adventitial area at doses of 30 and 100 mg/kg with moderate reduction of the neointimal area, resulting in the larger residual lumen. In an in vitro assay, TAS-301 dose dependently inhibited the proliferation of adventitial fibroblasts stimulated by basic fibroblast growth factor or transforming growth factor-beta(1). In addition, the drug reduced adventitial fibroblast-mediated three-dimensional collagen gel contraction. These findings indicate that TAS-301, the first compound developed for targeting the constrictive remodeling, showed a high inhibitory potency on coronary artery stenosis of micropigs after injury, mainly due to inhibition of adventitial fibroblast proliferation and of the contractile ability of myofibroblasts. Our results suggest the strong possibility that TAS-301 may be efficacious for prevention of restenosis after angioplasty and the need to examine the therapeutic usefulness of this drug in clinical trials.

Angioplasty, Balloon, Coronary↗
PubMed1999

Change in hepatic antioxidant defense system with liver injury development in rats with a single alpha-naphthylisothiocyanate intoxication.

The change in hepatic antioxidant defense system with the development of alpha-naphthylisothiocyanate (ANIT)-induced liver injury was examined in rats injected once with the toxicant (75 mg/kg body weight). Liver injury with cholestasis did not occur 12 h after ANIT injection, but appeared at 24 h, progressed at 48 h, and recovered at 72 h, judging from the serum levels of marker enzymes and components. Liver lipid peroxide content increased 12 h after ANIT injection and further increased 24 and 48 h, but this increase was attenuated at 72 h. Liver superoxide dismutase and catalase activities decreased 24 and 48 h, respectively, after ANIT injection, although the catalase activity increased at 12 h, but these decreases were attenuated at 72 h. Liver Se-glutathione peroxidase activity remained unchanged 24, 48, and 72 h after ANIT injection, although the activity increased at 12 h. Liver reduced glutathione content increased 24 h after ANIT injection, but the increase was reduced time dependently thereafter. Liver ascorbic acid content increased 12 h after ANIT injection and further increased at 24 h, but the increase was reduced time dependently thereafter. These results indicate that the change in hepatic antioxidant defense system occurs before and with the development of ANIT-induced liver injury in rats, and suggest that the reduction of hepatic antioxidant defense system mediated by SOD and catalase could contribute to the liver injury development through an enhancement of hepatic lipid peroxidation.

1-Naphthylisothiocyanate↗
PubMed1999

Preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on the development of stress-induced acute gastric mucosal lesions in rats.

The preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15), a traditional Chinese herbal medicine for the therapies of gastric ulcers and gastritis, on the development of stress-induced acute gastric mucosal lesions was examined in rats with water immersion restraint (WIR) stress. Simultaneous p.o. administration of TJ-15 at a dose of 20, 100 or 250 mg/kg prevented dose-dependently gastric mucosal lesion development in rats subjected to WIR stress over a 6-h period. In the gastric mucosa of rats with WIR stress alone, lipid peroxide concentration and xanthine oxidase (XOD) and myeloperoxidase--an index of neutrophil infiltration--activities increased with lesion development, while nonprotein SH concentration decreased. The simultaneous administration of TJ-15 attenuated all these changes with gastric mucosal lesion development in a dose-dependent manner. These results indicate that simultaneously administered TJ-15 exerts a preventive effect on the development of WIR stress-induced acute gastric lesions in rats, and suggest that the preventive effect of TJ-15 could be due to its preventive actions on enhanced sulfhydryl oxidation and lipid peroxidation via oxygen free radicals generated by the xanthine-xanthine oxidase system and infiltrated neutrophils in the gastric mucosa and on neutrophil infiltration into the tissue.

Animals↗
PubMed1999

An association between lipid peroxidation and alpha-naphthylisothiocyanate-induced liver injury in rats.

An association between lipid peroxidation and alpha-naphthylisothiocyanate (ANIT)-induced liver injury was examined in rats injected once with the toxicant (75 mg/kg body weight). The severity of liver injury was estimated 12, 24, 48, and 72 h after ANIT injection. Liver injury appeared 24 h after ANIT injection, progressed at 48 h, and recovered at 72 h, judging from the serum levels of marker enzymes and components. Serum lipid peroxide (LPO) concentration increased 24 h after ANIT injection and further increased at 48 h, but this increase was attenuated at 72 h. In contrast, liver LPO content increased 12 h after ANIT injection and further increased 24 and 48 h, but this increase was attenuated at 72 h. Similarly, myeloperoxidase (MPO) activity, an index of neutrophil infiltration, in the liver tissue increased 12 h after ANIT injection and further increased at 24 and 48 h, but this increase was attenuated at 72 h. Either serum LPO concentration or liver LPO content was significantly correlated with liver MPO activity (r = 0.661 for serum LPO concentration; r = 0.585 for liver LPO content). These results suggest that lipid peroxidation might be associated with ANIT-induced liver injury in rats and that this lipid peroxidation might occur via oxygen radicals derived from neutrophils infiltrated into the liver tissue of ANIT-intoxicated rats.

1-Naphthylisothiocyanate↗
PubMed1999

Predictability of dielectric properties for ischemic injury of the skeletal muscle before reperfusion.

OBJECTIVE: The purpose of this study is to assess whether or not dielectric properties could predict the severity of ischemic injury of the skeletal muscle before reperfusion to prevent the myonephropathic metabolic syndrome (MNMS). METHODS: Japanese White rabbits were anesthetized and their hind limbs were subjected to 0, 2, 4, and 6 h of ischemia and then 10 h of reperfusion (n = 4, 5, 6, and 6). Dielectric properties of the gastrocnemius muscle were measured and tan delta(m) and D were calculated from them. To assess ischemic injury, we also measured (a) creatine phosphate kinase (CPK) and aldolase, (b) spectrophotometric assay of triphenyltetrazolium chloride assay, and (c) histological evaluation by H & E staining, 10 h after reperfusion. RESULTS: The tan delta(m) increased and D decreased significantly compared with those in preischemia (P < 0.01). The tan delta(m) value just before reperfusion significantly correlated positively with the maximum value of CPK (CPK(max)) or the maximum value of aldolase (ALD(max)) (r = 0.73, 0.69) and negatively with %TTC (r = 0.66). The D value just prior to reperfusion significantly correlated negatively with CPK(max) and ALD(max) (r = 0.81, 0.86) and positively with %TTC (r = 0.79) after reperfusion, respectively. Histologically, skeletal muscle necrosis was detected in 11 out of 12 skeletal muscles with tan delta(m) values which were 3.70 or more and 11 out of 14 muscles with D values which were 1.47 or less. CONCLUSION: The severity of skeletal muscle ischemic injury can be evaluated before reperfusion by measuring the dielectric properties during ischemia.

Animals↗
PubMed1999

Preventive effect of melatonin on the progression of carbon tetrachloride-induced acute liver injury in rats.

We examined the preventive effect of melatonin on the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rats. In rats injected with CCl4 (1.0 ml/kg body weight), liver injury appeared 6 h after the injection and progressed at 24 h. This liver injury progression was prevented by treatment with melatonin (50 or 100 mg/kg body weight), which was conducted 6 h after CCl4 injection. An increase in liver lipid peroxide content and a decrease in liver reduced glutathione content occurred with the liver injury progression. These changes were prevented by the post-treatment of melatonin (50 or 100 mg/kg body weight). These results indicate that melatonin can prevent the progression of CCl4-induced acute liver injury through its antioxidant action.

Animals↗
PubMed1999

Effect of albumin administration on L-tryptophan levels in the serum and tissues of rats with puromycin aminonucleoside-induced nephrosis.

We examined the effect of albumin administration on L-tryptophan (Trp) levels in the serum and tissues of rats with puromycin aminonucleoside (PAN)-induced nephrosis. PNA-injected rats showed increased urinary protein and serum non-esterified fatty acids levels and decreased serum albumin level at 8 days after the injection. The nephrotic rats showed a decrease in total serum Trp level and increases in free serum Trp and liver and kidney Trp levels but no change in urinary Trp level. At 5 min after intravenous injection of bovine serum albumin, the nephrotic rats had serum albumin concentration similar to the level of non-nephrotic rats and showed a recovery of decreased total serum Trp with the reduction of increased free serum Trp and liver Trp.

Animals↗
PubMed1999

Contribution of serum albumin to the transport of orally administered L-tryptophan into liver of rats with L-tryptophan depletion.

The role of serum albumin in the transport of orally administered L-tryptophan (Trp) into rat tissues was examined using analbuminemic and Sprague-Dawley (SD) rats with and without alpha-methyl-DL-tryptophan (AMT)-induced Trp depletion. Trp was orally administered to rats 16 h after AMT or 0.85% NaCl administration, when liver tryptophan 2,3-dioxygenase and protein synthetic activities in AMT-treated rats were similar to those of 0.85% NaCl-treated rats. After oral Trp administration, regardless of the presence or absence of Trp depletion, free serum Trp concentrations were similar in the analbuminemic and SD rats, while total serum Trp concentrations were lower in analbuminemic rats than in SD rats. Although liver, brain, and muscle Trp concentrations after oral Trp administration under Trp depletion were lower in analbuminemic rats than in SD rats, the ratio of the liver Trp concentration in analbuminemic rats to that in SD rats was smaller than that of the brain or muscle Trp concentration. These results suggest that variations in serum albumin levels could affect the transport of orally administered Trp into the liver of rats with Trp depletion.

Administration, Oral↗
PubMed1999

Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis.

Cryptococcus neoformans causes infection in individuals with defective T cell function, such as AIDS, as well as without underlying disease. It has been suggested that humoral as well as cellular immunity might play an important role in the immune response to C. neoformans infection. We have recently shown, using immunoblotting, that the 70-kD hsp family of C. neoformans was the major target molecule of the humoral response in murine pulmonary cryptococcosis. In this study we also used immunoblotting to define the antibody responses in the sera of 24 patients with pulmonary cryptococcosis: 21 proven and three suspected diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%) patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (< or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients positive for anti-hsp70 antibody showed high titres in the Eiken latex agglutination test for the detection of serum cryptococcal antigen. Our results indicate that the 70-kD hsp family from C. neoformans appears to be a major target molecule of the humoral response, not only in murine pulmonary cryptococcosis, but also in human patients with pulmonary cryptococcosis.

Adult↗
PubMed1999

Elevated levels of beta-chemokines in bronchoalveolar lavage fluid (BALF) of individuals infected with human T lymphotropic virus type-1 (HTLV-1).

Pulmonary complications are known to develop in HTLV-1 carriers, including T lymphocytic alveolitis, and increased IL-2 receptor alpha (CD25)-bearing T cells have been found in BALF. Several chemokines may contribute to accumulation of T lymphocytes in the lungs of HTLV-1 carriers. Here, we compared the distribution of T lymphocyte subsets and beta-chemokines, such as macrophage inflammatory peptide-1alpha (MIP-1alpha), regulated on activation normal T expressed and secreted (RANTES), and macrophage chemoattractant protein-1 (MCP-1), in BALF and peripheral blood between HTLV-1 carriers and non-infected healthy normal subjects. Flow cytometric analysis with MoAbs to cell surface antigens was used to identify T lymphocyte subsets in BALF samples from HTLV-1 carriers (n = 13) and non-infected healthy controls (n = 10). The levels of different beta-chemokines were estimated by ELISA. High percentages of CD3+ cells, CD3 expressing HLA-DR antigen and CD3+CD25+ cells were detected in BALF of HTLV-1 carriers compared with non-infected controls. The concentration of MIP-1alpha in BALF of patients was significantly higher than in non-infected healthy controls and correlated well with the percentage of CD3+CD25+ cells. The level of RANTES in BALF was also significantly high in HTLV-1 carriers, but did not correlate with the percentage of CD3+CD25+ cells. On the other hand, the level of MCP-1 in BALF of HTLV-1 carriers was not different from that of controls. Our results suggest a possible interaction between activated T cells bearing CD25 and beta-chemokines, especially MIP-1alpha, which may contribute to the pulmonary involvement in HTLV-1 carriers.

Adult↗
PubMed1999

The use of otherwise redundant skin to provide nasal lining in the reconstruction of full-thickness alar defects by nasolabial flap repair.

The use of otherwise redundant nasolabial flap skin is described for lining in reconstruction of full-thickness alar defects. The techniques have been successfully used to reconstruct full-thickness alar defects in four patients. The overall procedure has the advantage of providing well-vascularised tissue of appropriate colour, texture and thickness for external skin and nasal lining in one-stage reconstruction.

Aged↗
PubMed1999

Experimental vascular graft using small-caliber fascia-wrapped fibrocollagenous tube: short-term evaluation.

This study was undertaken to evaluate the application of autogenous fascia as a framework for a fibrocollagen tube for small-caliber vascular prostheses in Japanese white rabbits (n = 15). The fascia, measuring 10 x 40 mm, was harvested from the dorsal fascia and was carefully wrapped around a silicone rod of 1.5 mm in diameter. Then, the fascia-wrapped silicone rod was implanted into a subcutaneous pocket on the medial thigh. Four weeks later, the fascia-wrapped silicone rod was removed from the subcutaneous pocket. The rod was removed from the material, and the fascia-wrapped fibrocollagen tube was treated to make it antithrombogenic. Subsequently, the 1.5 x 10-mm fascia-wrapped tube was prepared as an arterial conduit. Using microvascular techniques, the tube was interposed into the divided femoral artery. Eleven of 15 grafts maintained patency over the follow-up period and no aneurysmal formation was found at any graft site. Microscopically, there was an ingrowth of endothelium with fibroblast proliferation from each end of the recipient vessel at 2 weeks after interposition; however, no neointima was found to line the center of the conduit. At 5 weeks after interposition, the neointimal growth rate was 70 percent. There was an ingrowth of endothelium with fibroblast proliferation from each end onto the entire internal surface of the conduit at 8 weeks after interposition. Further study is required before any long-term conclusions can be drawn.

Animals↗
PubMed1999

In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans.

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.

Animals↗