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T Endoh

Publications and source records attributed to T Endoh.

At least 19 recordsLinked to original sources
PubMed2000

Characterization of the antinociceptive effects of TRK-820 in the rat.

We have already reported that TRK-820, (-)-17-cyclopropylmethyl-3, 14b-dihydroxy-4, 5a-epoxy-6b-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan hydrochloride, a new selective kappa-opioid receptor agonist, has affinity for kappa-subtype opioid receptors other than the kappa(1)-opioid receptor. It would be of interest to examine whether the different kappa-opioid receptor subtype properties of TRK-820 participate in its antinociceptive action in the inflamed paw test and the formalin test. TRK-820 produced a potent antinociceptive effect, which was inhibited by the selective kappa-opioid receptor antagonist nor-binaltorphimine, but not by the mu-opioid receptor antagonist naloxone in the mechanical paw pressure test. TRK-820 also produced a potent antinociceptive effect in rats with adjuvant-induced arthritis. TRK-820 and morphine, a prototype mu-opioid receptor agonist, were equally effective in inhibiting the nociceptive responses in the arthritic rats and in the normal rats, while ICI-199441, 2-(3, 4-dichlorophenyl)-N-methyl-N-[(1S)-1-phenyl-2-(1-pyrrolidinyl)ethyl]- acetamide, a kappa-opioid receptor agonist, was about 5-fold less potent in the arthritic rats than in the normal rats. In the formalin test TRK-820 had a very similar antinociceptive potency to that of ICI-199441, unlike in the arthritic rats in which TRK-820 was 2.5 times more potent than ICI-199441. It is concluded that TRK-820 produced a potent antinociceptive action via the stimulation of kappa-opioid receptors in rats. TRK-820 has a unique antinociceptive profile different from that of the other kappa-opioid receptor agonists such as ICI-199441 in arthritic rats.

Analgesics, Opioid↗
PubMed1999

The modulatory effect of (+)-TAN-67 on the antinociceptive effects of the nociceptin/orphanin FQ in mice.

To clarify the pharmacological properties of (+)2-Methyl-4aalpha-(3-hydroxyphenyl)-1, 2, 3, 4, 4a, 5, 12, 12aalpha-octahydro-quinolino[2, 3, 3-g]isoquinoline ((+)-TAN-67), the effect of (+)-TAN-67 on the antinociception induced by the intrathecal (i.t.) administration of nociceptin/orphanin FQ was studied in mice using the tail-flick test and the formalin test. I.t. administration of (+)-TAN-67, at doses of 1 to 10 ng, facilitated the tail-flick response in a dose-dependent manner in mice. In addition, i.t. administration of (+)-TAN-67 (1 to 10 ng) in mice produced a marked pain-like aversive responses. I.t. pretreatment with D-Pro(9)-[spiro-gamma-lactam]-Leu(10)-Trp(11)-physalaemin(1-11) (GR82334, 0.1-1.0 nmol), a potent and selective tachykinin NK(1) receptor antagonist, dose-dependently blocked the reduction of the tail-flick response induced by (+)-TAN-67. Furthermore, (+)-TAN-67-induced facilitation of the tail-flick response was abolished in capsaicin-treated mice. On the other hand, (+)-TAN-67-induced flinching responses were dose-dependently and significantly reduced by i.t. pretreatment with GR82334 (0.1-1.0 nmol). The duration of i.t. (+)-TAN-67-induced flinching responses was significantly reduced in capsaicin-treated mice as compared with naive mice. I.t. administration of nociceptin/orphanin FQ (1-10 nmol) dose-dependently increased the tail-flick latency. I.t. administration of nociceptin/orphanin FQ (0.1-1.0 nmol) significantly and dose-dependently reduced the first-phase nociceptive response, but not the second-phase nociceptive response. I.t. pretreatment with (+)-TAN-67 (0.3-3.0 microg) for 30 min dose-dependently attenuated the antinociception induced by i.t. nociceptin (10 nmol) in the tail-flick test. Furthermore, the antinociceptive effect of nociceptin/orphanin FQ (1 nmol, i.t.) on the first-phase response in the formalin test was dose-dependently attenuated by s.c. pretreatment with (+)-TAN-67 (0.3-3.0 microg). (+)-TAN-67 (0.3-3.0 microg, i.t.), by itself, did not facilitate the tail-flick response or produce apparent behavioral changes. It is possible that (+)-TAN-67 has an antagonistic effect on nociceptin/orphanin FQ-induced antinociception.

Analgesics↗
PubMed1999

Fragility of the electron transport chain and superoxide generation in mitochondria of the liver graft after cold ischemia.

BACKGROUND: After cold ischemia, electrons transferred in the electron transport chain may leak out of the mitochondria in proportion to the deterioration of mitochondrial oxidative phosphorylation. This seems to be one major cause of the lipid peroxidation that occurs mainly in the hepatocytes at reperfusion in liver transplantation. To examine this hypothesis, we investigated superoxide generation and the amount of oxidative phosphorylation in the mitochondria isolated from rat livers after cold preservation. METHODS: Rat liver was preserved in University of Wisconsin solution at 4 degrees C for 24 hr. The mitochondrial fraction was prepared, and the amount of ATP synthesis and superoxide generation was investigated. Superoxide generation in the electron transport chain of submitochondrial particles was also measured by a chemiluminescence recorder. RESULTS: The amount of ATP synthesis was significantly decreased after 12 hr of cold preservation. In the whole mitochondria, superoxide production in the presence of succinate was approximately 1/2000 to 1/3000 less than that observed in the submitochondrial particles at any determination point, and superoxide production was not affected by cold preservation. In the presence of antimycin A, superoxide production in the mitochondria after 18 hr of preservation increased significantly. CONCLUSION: These results indicate that the electron transfer in the complex III of the mitochondrial membrane becomes leaky after long periods of cold ischemia, but that leakage of superoxide anion did not increase, although the mitochondrial respiratory phosphorylation was deteriorated. We conclude that superoxide through the mitochondrial membrane cannot cause lipid peroxidation in hepatocytes at reperfusion even after a long period of cold ischemia.

Adenosine Triphosphate↗
PubMed1999

Inhibition of calcium channels by neurokinin receptor and signal transduction in hamster submandibular ganglion cells.

Both substance P (SP) and neurokinin A (NKA) are known as neurotransmitters of the submandibular ganglion (SMG) neurons. SP released from collaterals of the sensory nerves also regulates the excitability of SMG neurons. It has recently been shown that neurokinins (NK) inhibit calcium channels in various neurons. In this study, the effects of NK on voltage-dependent calcium channel current (I(Ca)) in SMG cells were investigated using the whole-cell patch-clamp recording method. NK-1 receptor agonist and SP caused inhibition of I(Ca) in SMG cells in a dose-dependent manner. NK-1 receptor agonist inhibited L-, N- and P/Q-type I(Ca) components. GDP-beta-S included in the pipette solution reduced the NK-1 receptor agonist-induced inhibition of I(Ca). In addition, NK-1 receptor agonist-induced inhibition of I(Ca) was reduced by stimulation of protein kinase C (PKC) but not cyclic AMP-dependent protein kinase (PKA). The results provided evidence for a signal transduction pathway in which calcium channel inhibition by NK receptors required activation of G-protein and PKC-affected step phosphorylation in SMG neurons.

Animals↗
PubMed1999

Tachykinin-induced responses via neurokinin-1 and -3 receptors in hamster submandibular ganglion neurones.

Both substance P and neurokinin A are known as neurotransmitters of the submandibular ganglion cell. In this study, the effects of neurokinin (NK) receptor-subtype agonists on hamster submandibular ganglion cells were investigated using the whole-cell patch-clamp technique. Membrane currents evoked by a ramp pulse from +50 to -100 mV (-150 mV/1000 msec) were compared in both the absence and presence of NK receptor agonist. The NK-1 receptor agonist [Sar9, Met (O2)11]-substance P, the NK-2 receptor agonist [Ala5, beta-Ala8]-alpha-neurokinin fragment 4-10, and the NK-3 receptor agonist senktide were used. The three agonists dose-dependently increased the amplitude of the inward current with a reversal potential near 0 mV. Their rank order was NK-1 = NK-3 > NK-2. Even when the external solution was replaced with Cs+ or N-methyl-D-glucamine+ instead of Na+, the NK receptor agonists also increased the amplitude of the inward current. Thus, NK-1 and NK-3 receptors are apparently coupled with non-selective cation channels in submandibular ganglion cells.

Animals↗
PubMed1999

Potent antinociceptive effects of TRK-820, a novel kappa-opioid receptor agonist.

TRK-820, a new type of 4,5-epoxymorphinan derivative, was investigated in vivo for antinociceptive activities and its selectivity on various opioid receptors in mice. TRK-820 given s.c. or p.o. was found to be 351- and 796-fold more potent than U50,488H with acetic acid-induced abdominal constriction test. The duration of the antinociceptive effect produced by TRK-820 was longer than that produced by mu-opioid receptor agonist morphine or other kappa-opioid receptor agonists. In addition, with four other antinociceptive assays, low temperature hot plate (51 degrees C), thermal tail flick, mechanical tail pressure and tail pinch tests, TRK-820 was also found to be 68- to 328-fold more potent than U-50488H, and 41- to 349-fold more potent than morphine in producing antinociception, as comparing the weight of the different compound. However, TRK-820 was less active in inhibiting the high temperature (55 degrees C) hot plate response. The antinociceptive effects produced by TRK-820 were inhibited by nor-BNI, but not by naloxone or naltrindole (NTI) with the abdominal constriction test, indicating that the antinociception is selectively mediated by the stimulation of kappa-, but not mu- or delta-opioid receptors. Co-administration of TRK-820 with morphine slightly enhanced the antinociception induced by morphine in the mouse hot plate test. On the other hand, pentazocine significantly reduced the morphine-induced antinociception. TRK-820 produced sedation at doses, which are much higher than the doses for producing antinociception. These results indicate that the potent antinociception induced by TRK-820 is mediated via the stimulation of kappa-, but not mu- or delta-opiod receptors.

Administration, Oral↗
PubMed1999

Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis.

BACKGROUND/AIMS: Blood concentration levels of alpha-fetoprotein like the Lens culinaris agglutinin-reactive fraction (AFP-L3) are a useful marker for predicting the long-term prognosis of hepatocellular carcinoma. This study investigated the relationship between serum AFP-L3 and various imaging modalities. METHODS: Sixty-three patients with small hepatocellular carcinomas < or = 2 cm in diameter were studied. Serum AFP-L3 concentrations were measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting and expressed as % AFP-L3 (the percent of AFP-L3 as total AFP). A clinical "cutoff level" of 10% was used in this study to indicate the presence of hepatocellular carcinoma. Selective hepatic intraarterial digital subtraction angiography (DSA), ultrasonographic angiography with carbon dioxide microbubbles (USAG), and computed tomography during arterial portography (CTAP) were performed to evaluate the hemodynamics of hepatic nodules. RESULTS: Fourteen (22.2%) of the 63 patients were positive for % AFP-L3. The % AFP-L3 levels (n=45, 4.4%) of patients with hypervascular tumors were significantly higher than those (n=15, 0.0%) of patients with isovascular or hypovascular tumors as determined by USAG (p=0.0061). The % AFP-L3 levels (n=53, 4.4%) of patients with a negative portal blood supply were significantly higher than the % AFP-L3 levels (n=7, 0.0%) of patients with a positive portal blood supply as determined by CTAP (p=0.0140). The % AFP-L3 levels of patients with tumors with a long doubling time (DT) were significantly lower than for patients with tumors with a short DT (p=0.0176). CONCLUSION: AFP-L3 is a positive indicator which may be more specific for small advanced hepatocellular carcinoma.

Aged↗
PubMed1999

Ceftizoxime-induced hemolysis due to immune complexes: case report and determination of the epitope responsible for immune complex-mediated hemolysis.

BACKGROUND: Several occurrences of immune complex-mediated, cephalosporin-induced intravascular hemolysis have been reported. This report describes the first case of hemolytic anemia caused by an immune-complex mechanism associated with ceftizoxime and delineates the epitope responsible for hemolysis. CASE REPORT: The patient's serum was tested for antibody that reacted with five penicillins and 30 cephems (all types of cephalosporins) by using protocols to detect drug-adsorption and immune-complex mechanisms. The patient's antibody that formed immune complexes with ceftizoxime reacted with 10 of 30 cephems. These 10 drugs were classified as oxime-type cephalosporins, which have a common structural formula consisting of [(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetoamido] at the C7 position on 7-aminocephalosporinic acid with or without substitution at the C3 position. CONCLUSION: The patient's antibody recognized a common structure in 10 oxime-type cephalosporins, and immune complexes formed by the antibody specifically or nonspecifically bound to red cell membranes. Therefore, when intermittent antibiotic therapy is required, as in this case, care should be taken in antibiotic selection to avoid drug-induced hemolytic anemia. In addition, when this type of hemolysis is observed, tests for antibody that reacts by adsorption and immune-complex mechanisms should be performed against penicillins and cephems to select antibiotics not showing a cross-reaction.

Adsorption↗
PubMed1999

Simultaneous amplification of Bordetella repeated insertion sequences and toxin promoter region gene by polymerase chain reaction.

A polymerase chain reaction was devised to simultaneously detect repeated insertion sequences and the pertussis toxin promoter gene for the diagnostic identification of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. The sensitivity of this method was sufficient to detect one B. pertussis organism using the following cycles and temperatures: 95 degrees C for 15 min, followed by 32 amplification cycles (1 min at 95 degrees C, 1 min at 66 degrees C, 1 min at 72 degrees C), and finally 5 min at 72 degrees C. Using the primers as a combined set did not affect sensitivity, but required an increased temperature for optimal annealing compared with a single-sequence assay. As nasopharyngeal aspirate and swab materials sometimes contain hemoglobin, we also tested the inhibitory effect of hemoglobin on this assay, which was inhibited completely when using DNA extracts from samples containing hemoglobin at a final concentration >0.015 g/L: this inhibition was reversed by addition of bovine serum albumin to the buffer. Our assay shows promising sensitivity and specificity for clinical use.

Bordetella Infections↗
PubMed1999

[Significance and effects of intraperitoneal cisplatin administration for ovarian cancer].

We studied the efficacy and safety of combination chemotherapy in which a high-dose platinum agent was administered intraperitoneally (i.p.) plus intravenously (i.v.) to 22 patients with stage III ovarian cancer. The chemotherapy consisted of etoposide (i.p.), cisplatin (i.p.), and carboplatin (i.v.). Each course was repeated every 4 weeks and a maximum of 5 courses was given in the 6 months following the initial surgery. As a control, 13 patients received different chemotherapy (CAP etc.) in which cisplatin, cyclophosphamide and doxorubicin pirarubicin hydrochloride were administered. The mean (SD) total dose of cisplatin in the patient group group (790.6 +/- 317.0 mg/m2) over the 6 months was significantly higher than in the control group (377.2 +/- 215.1 mg/m2). The overall response rate (CR + PR) 6 months after the completion (95.5%) was significantly higher in the study patients than in the control group (53.1%). The 1, 3, 5-year survival rates were significantly higher in the EPJ group (91.0, 59.0, 42.1%) than in the control group (53.8, 15.4, 15.4%). There was no significant difference in renal toxicity or bone marrow suppression (leukopenia and thrombocytopenia) between the two groups. EPJ therapy allowed an increased dose of cisplatin in the treatment of ovarian cancer without enhancing renal toxicity, resulting in higher response and survival rates. This study demonstrated that this therapy is an effective and well-tolerated regimen.

Adult↗
PubMed1998

Prevention by inhibitors of arachidonic acid cascade of liver carcinogenesis, cirrhosis and oxidative DNA damage caused by a choline-deficient, L-amino acid-defined diet in rats.

Effects of inhibitors of arachidonic acid (AA) cascade on the development of fatty liver, cirrhosis, glutathione S-transferase placental form (GST-P)-positive preneoplastic nodules, neoplastic nodules and generation of 8-hydroxydeoxyguanosine (8-OHdG), caused by a choline-deficient, L-amino acid-defined (CDAA) diet, were examined in Fischer 344 male rats by feeding CDAA diet supplemented with the inhibitors for 12 and 30 weeks. None of the inhibitors affected fatty liver. Among cyclooxygenase (COX) inhibitors, an irreversibly acting acetylsalicylic acid and a long-acting piroxicam, and to a much lesser extent the short-acting ibuprofen but not indomethacin, inhibited the development of cirrhosis, GST-P-positive and neoplastic nodules and generation of 8-OHdG. A phospholipase A2 inhibitor p-bromophenacylbromide (BPB) also exerted similar but lesser extent of inhibitory effects. Lipoxygenase inhibitors quercetin and nordihydroguiaretic acid inhibited GST-P-positive nodules but not cirrhosis or 8-OHdG. Present results suggest that perturbed AA cascade, particularly augmented COX pathway, might play key roles in the causation of liver lesions in the CDAA diet model.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

The regulating manner of opioid receptors on distinct types of calcium channels in hamster submandibular ganglion cells.

It is well known that opioids produce inhibitory effects on neuronal activity and on synaptic transmission at most synapses. In this study, we have investigated the effects of opioids on the low voltage- and high voltage-activated calcium channels in acutely dissociated submandibular ganglion (SMG) neurons, using the whole-cell configuration of the patch-clamp technique. The kappa-opioid-receptor agonist U-50488H, the delta-opioid-receptor agonist [D-Pen 2,5]-enkephalin and the mu-opioid-receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin inhibited L-, N- and P/Q-type calcium-current components in a dose-dependent manner at 10 nM-1 microM, respectively, but not the T-type calcium current. These inhibitory effects were antagonized by naloxone (1 microM). The results showed that three types of opioid receptors regulate the L-, N- and P/Q-types of calcium channels, respectively, but not the T-type, in SMG neurones.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1998

Rational drug design and synthesis of a highly selective nonpeptide delta-opioid agonist, (4aS*,12aR*)-4a-(3-hydroxyphenyl)-2-methyl- 1,2,3,4,4a,5,12,12a-octahydropyrido[3,4-b]acridine (TAN-67).

We designed highly selective non-peptide agonists for the delta-opioid receptor. On the basis of the "message-address" concept in this field and the accessory site hypothesis, a novel class of heterocycle-fused octahydroisoquinoline derivatives were synthesized. One of these compounds [(4aS*,12aR*)-4a-(3-hydroxyphenyl)-2-methyl-1,2,3,4,4a,5,12, 12a -octahydropyrido[3,4-b]acridine, TAN-67 (2)] showed high selectivity for the delta-opioid receptor (Ki = 1.12 nM) in guinea-pig cerebrum with a 2070-fold lower affinity for the mu-opioid receptor and a 1600-fold lower affinity for the kappa-opioid receptor. TAN-67 was a potent delta-opioid receptor agonist with an IC50 value of 6.61 nM in the mouse vas deferens assay that was reversed by naltrindole (NTI) (Ke = 0.21). Moreover, TAN-67 was shown to have antinociceptive activity following subcutaneous administration in the mouse acetic acid abdominal constriction assay that was antagonized by NTI (delta 1- and delta 2-antagonist) and 7-benzylidinenaltrexone (delta 1-antagonist), but not by naltriben (delta 2-antagonist). This systemically applicable non-peptide agonist will be useful for elucidating the pharmacological properties of the delta-opioid receptor.

Acetic Acid↗
PubMed1998

Matrix metalloproteinase matrilysin (MMP-7) participates in the progression of human gastric and esophageal cancers.

Matrilysin is one of matrix metalloproteinases, which is supposed to have a specific role in tumor progression. Expression of matrilysin was investigated in gastric and esophageal cancers by an immunohistochemical examination. Matrilysin was expressed in all esophageal squamous cell carcinomas (13/13) and in the majority of gastric adenocarcinomas (31/35, 89%). The positive staining was observed in tumor cells of cancerous tissues. In gastric cancers, there were significant statistical correlations between matrilysin expression at the invasive front and nodal metastasis or advanced stage. These results suggest that overexpression of matrilysin has an important role in the progression of upper gastrointestinal cancers.

Disease Progression↗
PubMed1998

Actions of calcitonin gene-related peptide on a population of submandibular ganglion cells.

In this study, we analyzed the effect of alpha-calcitonin gene-related peptide (CGRP) on the neurons of hamster submandibular ganglion (SMG). CGRP induced a small slow-depolarization accompanied with an increase in input resistance in about 60% of tested cells. CGRP enhanced durations of their Ca2+ spikes. The Ca2+ spikes were subdivided into two subgroups according to duration short duration within 1 sec and long duration of more than 1 sec. Forskolin, an activator of adenylate cyclase, mimicked the effects of CGRP. These data indicated that the effects of CGRP on SMG cells were mediated via the intracellular cyclic AMP signalling system. The effect of CGRP on the voltage-activated Ca2+ currents was characterized by enhancement of both transient and sustained components. The enhancement was greater in the transient component than in the sustained component. The subgroups of the Ca2+ spike may indicate differences in mechanism accelerating transmitter release and may reflect distinct functional roles of two different populations of SMG cells.

Afferent Pathways↗
PubMed1998

Substance P-induced depolarization accompanied by a decrease in membrane input resistance in the hamster submandibular ganglion cell.

We described in a previous paper (Bull Tokyo dent Coll 33: 33-35, 1992) that the submandibular ganglion cells (SMG) of hamster responded to substance P (SP) with a depolarization, which could be divided into three subtypes according to the change in membrane input resistance (Rm) during depolarization: depolarizations accompanied by either an increase or a decrease in Rm, and without change in Rm. In this study, the generation mechanism of the SP-induced depolarization accompanied by a decrease in Rm was investigated using the current-clamp technique. The result showed that cation channels coupled with NK-1 receptors on SMG cells were involved in generation of the SP-depolarization, and that the main charge carrier was the sodium ion.

Animals↗
PubMed1998

Tachykinin-depolarizations mediated by neurokinin-3 receptors in the hamster submandibular ganglion cells.

In the majority of autonomic ganglia, the responses to tachykinins such as substance P, neurokinin A and neurokinin B are primarily mediated by neurokinin-3 (NK-3) receptors. Neurokinin B (NK-B) and senktide are known as an endogenous tachykinin and the related peptide selective for NK-3 receptor. In this study, the generation mechanism of NK-3 receptor agonist-induced response in the hamster submandibular ganglion (SMG) cells was investigated using the current-clamp technique. The SMG cells responded to the NK-3 receptor agonists with two types of depolarizations accompanied by either a decrease or an increase in membrane input resistance. The results showed that K+ channels alone or the combination of K+ and nonselective cation channels coupled with NK-3 receptors on the SMG cells were involved in generation of the NKB- and senktide-depolarizations.

Animals↗