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Biomedical subjects

T Horie

Publications and source records attributed to T Horie.

At least 163 records · Page 9Linked to original sources
PubMed1998

Evaluation of damaged small intestine of mouse following methotrexate administration.

PURPOSE: Methotrexate (MTX) treatment causes damage to the small intestine, resulting in malabsorption and diarrhea. The active and passive transport capacities of the small intestine are decreased by the treatment. The purpose of this study was to evaluate the damage to the small intestine of mice caused by MTX administration by examining the permeability of the paracellular pathway of the small intestinal epithelium. METHODS: MTX was administered orally to male ddY mice once daily for 1-6 days. The permeability of the small intestine to the nonabsorbable markers phenol red (PR) and fluorescein isothiocyanate (FITC) dextrans was examined using everted segments of the intestine. RESULTS: PR and FITC dextran permeation through the small intestine increased significantly in parallel with changes in body weight of the mice, wet weight of the small intestine and chemical composition of the small intestinal epithelium. CONCLUSIONS: In addition to changes in permeation through the transcellular pathway reported previously, this study revealed that MTX treatment disorders the paracellular barrier function of the small intestinal epithelium, resulting in increased permeation of nonabsorbable markers via the paracellular pathway of the small intestinal mucosa. The present approach to the examination of the barrier function of the intestinal epithelium could be of great use in evaluating the damage to the small intestine and malabsorption.

Administration, Oral↗
PubMed1998

Docosahexaenoic acid exhibits a potent protection of small intestine from methotrexate-induced damage in mice.

Oral administration of methotrexate (MTX) to mice causes the damage of small intestine. The permeability of poorly absorbable compound fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) through the small intestine was studied in vitro using everted segments of the small intestine. The permeability of FITC-dextran increased remarkably in the MTX-treated mice and oral administration of docosahexaenoic acid ethyl ester (DHA) protected the small intestine from the increase in the small intestinal permeability induced by the MTX treatment. The MTX treatment decreased retinol concentration in plasma of mice and the coadministration of DHA maintained its concentration to the level of control mice. The present study showed that DHA protected the small intestine of mice from the MTX-induced damage.

Animals↗
PubMed1998

Proinflammatory cytokine-induced and chemical mediator-induced IL-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase-dependent pathway.

The p38 mitogen-activated protein (MAP) kinase is activated in various cells by proinflammatory cytokines and environmental stresses. However, little is known about the role of p38 MAP kinase in proinflammatory cytokine- and chemical mediator-induced cytokine expression in human bronchial epithelial cells (BECs). In this study we examined the role of p38 MAP kinase in IL-8 expression in BECs to clarify the signal transduction pathway regulating IL-8 expression in BECs stimulated with tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, and platelet-activating factor (PAF). We used TNF-alpha, IL-1alpha, and PAF as inducers for the analysis of the signal transduction pathway and determined IL-8 expression in BECs because TNF-alpha, IL-1alpha, and PAF are known to induce cytokine expression in BECs, and these proinflammatory cytokines and PAF are described to have a role in the production of allergic inflammation. The results showed that TNF-alpha, IL-1alpha, and PAF induced tyrosine phosphorylation of p38 MAP kinase in a dose- and time-dependent manner. The specific p38 MAP kinase inhibitor, SB 203580, completely inhibited TNF-alpha-, IL-1alpha-, or PAF-induced IL-8 protein and mRNA expression in BECs. These results indicated that p38 MAP kinase plays an important role in TNF-alpha-, IL-1alpha-, or PAF-activated signaling pathway, which regulates IL-8 expression in BECs. In addition, these results provide new evidence on a strategy for treatment of airway inflammation with the specific p38 MAP kinase inhibitor.

Bronchi↗
PubMed1998

Retinoic acid differentially regulates interleukin-1beta and interleukin-1 receptor antagonist production by human alveolar macrophages.

Mechanism in the pathogenesis of acute respiratory distress syndrome which is the clinical feature of pulmonary involvement in retinoic acid (RA) syndrome has been investigated. Pulmonary infiltration of matured neutrophils and leukemic cells is thought to be associated with the pathogenesis of pulmonary involvement in RA syndrome; however. Little is known about the mechanism in pulmonary infiltration of these cells. In the present study, we examined the effect of RA on IL-1beta and IL-1ra production by human alveolar macrophages in order to clarify the mechanism in pulmonary infiltration of neutrophils, since IL-1 has been shown to initiate neutrophil recruitment into the lung through up-regulated expression of adhesion molecules on vascular endothelium. RA enhanced IL-1beta and inhibited IL-1ra production by 4beta phorbol 12beta-myristate-13alpha acetate (PMA)- and lipopolysaccharide (LPS)-stimulated human alveolar macrophages. These results show that RA differentially regulates IL-1beta and IL-1ra production by alveolar macrophages and indicate that an imbalanced production between IL-1beta and IL-1ra may contribute to initiating neutrophil recruitment into the lung through up-regulated expression of adhesion molecules.

Adult↗
PubMed1998

Trimethadione metabolism and microsomal monooxygenases in untreated and phenobarbital-treated rhesus monkeys.

The contribution of induced cytochrome P450 (P450) isozymes (CMLa; CYP2B, CMLb; CYP2A and CMLc; CYP3A) and related enzymes to trimethadione (TMO) metabolism in phenobarbital-treated rhesus monkey were investigated. The animals received a single dose of TMO (4 mg kg-1) and plasma samples were withdrawn before this administration and again at 0.08, 0.25, 0.5, 1 and 2 h later. Phenobarbital-treatment (20 mg kg-1 day-1 for 3 days; i.p.) significantly increased the plasma dimethadione (DMO)/TMO ratios at 0.08, 0.5, 1 and 2 h one's appropriate controls. Phenobarbital treatment also increased the P450 content (1.7-fold) and activity of aniline p-hydroxylase (1.3-fold), p-nitroanisole O-demethylase (1.8-fold) and benzphetamine N-demethylase (2.3-fold). The content of CMLa, CMLb and CMLc were increased about 12.8, 2.3 and 2.7-fold by phenobarbital pretreatment, respectively. The activity of TMO N-demethylation was inhibited by anti-P450 CMLa and anti-P450 CMLb. However, the anti-P450 CMLc antibody had no effect on this activity in liver microsomes. The results of both in vivo and in vitro studies of the effects of phenobarbital treatment on TMO metabolism indicate that these effects may be attributed to the induction of CMLa. These findings suggest that plasma DMO/TMO ratio in a single blood sampling after TMO administration is very useful for determination the degree of hepatic induction in clinical study.

Aniline Hydroxylase↗
PubMed1998

Hypocalcemic induced increase in creatine kinase in rats.

Calcium plays an important role in various myopathies. We report on an animal model with increased plasma creatine kinase (CK) resulting from hypocalcemia that will provide clues for studying human hypocalcemic myopathy. Male Wistar rats were pair-fed either a control or a calcium- and vitamin D3-deficient diet for 1, 2, 3, 4, or 5-6 weeks after weaning (3 weeks old). In the deficient diet-fed rats, plasma creatine kinase was increased and was accompanied by marked hypocalcemia. The omission of calcium and vitamin D3 from the diet for 1 or 2 weeks was enough to cause increased plasma creatine kinase; the creatine kinase ratio of deficient diet-fed rats to controls was 4.84 (1,777 IU L(-1)/367 IU L(-1)), and the calcium ion ratio was 0.41 (1.8 mg dL(-1)/4.4 mg dL(-1)) after 2 weeks. These values returned to control levels on treatment of the rats with the control diet and 1alpha-OH-vitamin D3 for 1 week.

Animals↗
PubMed1998

N-acetylcysteine inhibits IL-1 alpha-induced IL-8 secretion by bronchial epithelial cells.

The protective effects of N-acetylcysteine (NAC) have been documented in experimental and clinical acute lung injury. However, the effect of NAC on the secretion of interleukin-8-(IL-8), which is an important mediator of the pathogenesis of acute lung injury through the recruitment of neutrophils, has not been determined. In the present study, therefore, we examined the effect of NAC on IL-8 secretion by IL-1 alpha-stimulated bronchial epithelial cells. NAC inhibited IL-8 secretion by bronchial epithelial cells in a dose-dependent manner. In addition, the structurally unrelated antioxidants, butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC) also effectively inhibited secretion. These results indicated that an antioxidant-sensitive mechanism might be involved in inhibition of IL-8 secretion by IL-1 alpha-stimulated bronchial epithelial cells. The protective effects of NAC on acute lung injury have been suggested to be due to scavenging reactive oxygen intermediates (ROIs) and stimulation of glutathione synthesis. In addition to this, our results may provide an alternative explanation for the efficacy of NAC on acute lung injury.

Acetylcysteine↗
PubMed1998

Spontaneous chemiluminescence production, lipid peroxidation, and covalent binding in rat hepatocytes exposed to acetaminophen.

Spontaneous chemiluminescence associated with the cell injury was observed in the isolated rat hepatocyte suspension during acetaminophen (APAP) metabolism, indicating the occurrence of oxidative stress. APAP apparently affected the hepatocytes in various manners. APAP, at low concentrations (1-2 mM), damaged the hepatocytes due to lipid peroxidation provoked during APAP metabolism, while at high concentrations (5-50 mM), APAP protected the hepatocytes due to a chemical antioxidant effect of the unmetabolized APAP that remained in the medium because of the saturation of APAP metabolism. The covalent binding of APAP to the hepatocytes increased with APAP concentration up to 50 mM without loss of cell viability. When an overdose of APAP was administered to rats, the APAP plasma concentration was around 1-3 mM, which corresponded to the concentration range where lipid peroxidation occurred in the isolated hepatocytes. Thus, it seems likely that lipid peroxidation contributes to the APAP-induced hepatotoxicity in the early stage of the toxic process.

Acetaminophen↗
PubMed1998

Correlation of plasma monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1alpha (MIP-1alpha) levels with disease activity and clinical course of sarcoidosis.

MCP-1 and MIP-1alpha exhibit chemotactic activity toward macrophages/monocytes and induce the production of inflammatory cytokines affecting granuloma formation. Up-regulated expression of MCP-1 and MIP-1alpha in the affected organ of sarcoidosis has been shown; however, the relationship between their plasma levels and the clinical course of this disease has not been determined. In the present study we measured plasma MCP-1 and MIP-1alpha levels in 26 patients with active sarcoidosis by ELISA in order to assess the state of MCP-1 and MIP-1alpha in this disease. Most patients in this study (21/26) had clinical evidence of extrathoracic disease in addition to pulmonary involvement. In addition, a high proportion of patients (n = 15) showed spontaneous remission of disease, whereas five patients showed no spontaneous remission and six patients were treated with corticosteroids over the 2-year period of study. At the time of diagnosis, both plasma MCP-1 and MIP-1alpha levels in patients with active sarcoidosis were significantly higher than in the normal controls. The levels of these cytokines in patients with extrathoracic disease were compatible with those in patients without extrathoracic disease. A longitudinal evaluation of plasma MCP-1 and MIP-1alpha levels showed that the changes in both cytokines were closely related to the clinical course of sarcoidosis. These results suggest that plasma MCP-1 and MIP-1alpha may be useful parameters for monitoring the clinical course of sarcoidosis. In addition, plasma MCP-1 and MIP-1alpha may reflect subclinical evidence of extrathoracic sarcoidosis and may play a role in initiating monocyte migration into the tissue.

Adult↗
PubMed1998

Changes in the enzymatic activities of beagle liver during maturation as assessed both in vitro and in vivo.

1. We have examined changes in caffeine and trimethadione (TMO) metabolism in vivo, agents which are used as probe drugs. In this study the total body clearance (Cl) of caffeine and TMO was low 1 week after birth (week 1), increased rapidly from week 3, peaked and then decreased gradually until reaching the level for the mature, adult dog. The elimination half-life (t1/2) of caffeine and TMO was prolonged during week 1; however, it then gradually became shorter. Gradually it became longer and reached the level for the adult dog. The apparent volume of distribution (Vd) of caffeine did not change throughout the study. However, the Vd of TMO was only high during week 1. 2. The in vitro changes in a variety of typical substrates for seven different cytochrome P450 (CYP) isozymes were examined. In this study three different patterns of metabolism can be identified: (1) activity is low immediately after birth, increases, peaks and then decreases to the adult dog level (p-nitroanisole; CYP1A1, caffeine; CYP1A2, benzphetamine; CYP3A/2B(?), aniline; 2E1 and TMO; CYP2C9/2E1/3A4); (2) activity generally increases rapidly soon after birth, continues to increase, peaks and then gradually decreases to the adult level (phenytoin; CYP2C9); and (3) activity is high (about the same level as the adult) immediately after birth, decreases and then gradually increases to the adult level (erythromycin; CYP3A4/5). 3. The results of these in vivo and in vitro studies suggest that changes in enzyme activity are due to differences in P450 isoenzymes during development.

Alanine Transaminase↗
PubMed1998

Species differences and mechanism of the epimerization of a new MAO-A inhibitor.

1. (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl-2-oxazolidinone (E2011) has two chiral centers in its structure. In vivo optical inversion of the hydroxy group at one of the chiral centers converts E2011 to a diastereoisomer (ER-20593). Pharmacokinetic parameters of E2011 and ER-20593 were determined after administration of E2011 to rat at 10 mg/kg, and the plasma concentration ratios of E2011 to ER-20593 were almost constant after Tmax of the plasma concentrations. 2. E2011 and ER-20593 were separately administered orally to six species in addition to rat, and the species differences in both directions of epimerization (i.e. from E2011 to ER-20593 and from ER-20593 to E2011) were studied by measuring the plasma concentrations of both compounds. In mouse, guinea pig, dog, and squirrel monkey, the epimerization of E2011 to ER-20593 did not occur, but the epimerization of ER-20593 to E2011 did. In rat, pig and rhesus monkey, the inversion of E2011 to ER-20593 occurred, but the ratios of this inversion were smaller than those for the inversion in the opposite direction. E2011 underwent about 15% inversion to ER-20593 in rat, which was the largest inversion in the seven species examined. 3. To study the mechanism of the epimerization, deuterium-labelled E2011 and ER-20593 (created by substituting the proton at the chiral center of the parent compounds for deuterium) were orally administered (separately) to rat and dog, and the concentration ratios and molecular weights of E2011 and ER-20593 in the plasma were determined by hplc and FAB(+)-mass spectrometry respectively. The results indicated that the major mechanism of the epimerization was oxidation to the carbonyl form followed by reduction to the original epimer and/or the other epimer. 4. The carbonyl form of E2011 (CO-E2011) was reduced to E2011 and ER-20593 (alcohol forms) by liver cytosol and microsomes from rat and dog in vitro with NADH or NADPH. The resultant epimeric ratios (E2011:ER-20593) were consistent with the in vivo results in rat and dog. 5. In conclusion, species differences in the epimerization of E2011 would result from product stereoselectivity of the reductase activity with the carbonyl intermediate.

Administration, Oral↗
PubMed1998

Expression of cytochrome P450 3A4 in foveolar epithelium with intestinal metaplasia of the human stomach.

The expression of cytochrome P450 3A4 (CYP3A4) in the foveolar epithelium of the human stomach with intestinal metaplasia was studied using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR). CYP3A4 was immunohistochemically detected in the foveolar epithelium with intestinal metaplasia, but was not detected in foveolar epithelium without intestinal metaplasia, in the pyloric gland or in the fundic gland of the stomach. Western blotting and RT-PCR demonstrated that CYP3A4 protein and mRNA were expressed in the liver and pyloric gland mucosa with intestinal metaplasia, but not in the fundic gland mucosa without intestinal metaplasia. Possible roles of CYP expression in the gastric mucosa with intestinal metaplasia in human stomach carcinogenesis are briefly discussed.

Cytochrome P-450 CYP3A↗
PubMed1998

Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats.

AIMS: To examine the effects of oestradiol and testosterone on the early carcinogenic changes expressed in rat liver from the diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF), partial hepatectomy (PH) model of hepatocarcinogenesis. METHODS: Preneoplastic liver lesions were evaluated using immunohistochemical analysis of glutathione-S-transferase placental form (GST-P) expression; oestrogen and androgen receptor levels were measured by radioimmunoassay. RESULTS: Oestradiol administration to non-castrated DEN-AAF-PH treated males resulted in a decrease in the area of GST-P positive foci, while testosterone increased the serum oestradiol level and reduced the area. In males, castration alone and castration with oestradiol replacement significantly reduced the GST-P positive area, and increased the hepatic oestrogen receptor level. In DEN-AAF-PH treated females, castration with testosterone replacement was associated with a significant increase in the GST-P positive area and the hepatic androgen receptor level. CONCLUSION: These findings suggest that exogenous and endogenous oestradiol can suppress chemical hepatocarcinogenesis. It appears that oestrogen receptors may be involved in the inhibition of malignant transformation of preneoplastic liver cells, while androgens and androgen receptors are involved in hepatocarcinogenesis.

2-Acetylaminofluorene↗
PubMed1998

Left coronary artery-left ventricle fistula with right coronary artery spasm.

A 72-year-old woman was admitted to our hospital for evaluation of chest pain. Coronary angiography showed a left coronary artery-left ventricle fistula. An acetylcholine provocation test induced vasoconstriction of the right but not the left coronary artery. Her chest pain was not relieved by combined therapy with isosorbide dinitrate, diltiazem and nicorandil. Because of the coronary spasm, beta-blockers could not be used. However, her chest pain was relieved after the administration of a minor tranquilizer. Thus, the patient's chest pain was unlikely to be associated with either the fistula or the coronary spasm.

Acetylcholine↗
PubMed1998

Acute effects of nasal continuous positive airway pressure on 24-hour blood pressure and catecholamines in patients with obstructive sleep apnea.

To assess the acute effects of nasal continuous positive airway pressure (CPAP) on the 24-hour blood pressure and the secretion of catecholamines in urine and plasma, we investigated the changes in the 24-hour blood pressure and urinary and plasma concentrations of epinephrine (E) and norepinephrine (NE) in 26 men with obstructive sleep apnea (OSA) with and without nasal CPAP. Nasal CPAP resulted in significant decreases in the daytime diastolic pressure (from 86 +/-16 mmHg to 83+/-12 mmHg), the nighttime diastolic pressure (from 81+/-12 mmHg to 77+/-9 mmHg) and the nighttime systolic pressures (from 125+/-15 mmHg to 120+/-10 mmHg). There was no significant difference between patients with and without CPAP in the daytime or nighttime urinary E level, but patients who received CPAP showed a significant decrease in daytime urinary NE level (from 156+/-112 microg/14h to 119+/-101 microg/14h) and nighttime urinary NE level (from 143+/-91 microg/10h to 112+/-65 microg/10h). The morning plasma level of NE also decreased (from 371+/-181 pg/ml to 273 +/-148 pg/ml) in patients who received nasal CPAP (p<0.02), but the plasma level of E remained unchanged. There were no correlations between PSG parameters and the reductions in blood pressure and the catecholamine levels induced by nasal CPAP. These findings suggest that OSA contributes, at least in part, to the development of systemic hypertension by increasing sympathetic nervous activity.

Biomarkers↗
PubMed1998

Kimura's disease associated with bronchial asthma presenting eosinophilia and hyperimmunoglobulinemia E which were attenuated by suplatast tosilate (IPD-1151T).

A 29-year-old man developed atopic bronchial asthma in association with eosinophilia and hyperimmunoglobulinemia E (hyper-IgE). A biopsy specimen from an inguinal lymph node showed changes consistent with Kimura's disease. IPD-1151T (suplatast tosilate), an anti-allergy drug, attenuated eosinophilia and hyper-IgE as well as the serum level of eosinophil cationic protein (ECP). The drug, however, did not affect the positivity for specific IgE antibodies against common allergens or the bronchial hyperresponsiveness to acetylcholine. Interleukin (IL)-2, IL-4, IL-5, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha were measured to be undetectable in serum before or during therapy. However, the expressions of mRNAs for IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha in peripheral blood T-lymphocytes and the expression of IL-5 mRNA in peripheral blood eosinophils were detected before and during therapy, which were unchanged by therapy with IPD-1151T. The present results suggest that different mechanisms other than the predominance of type 2 helper (T(H2))-like T-lymphocytes may underlie Kimura's disease and atopic bronchial asthma regarding the findings of eosinophilia and hyper-IgE, which could be modulated by IPD-1151T.

Adult↗