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Biomedical subjects

Y Deguchi

Publications and source records attributed to Y Deguchi.

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

Disposition and alpha(1)-adrenoceptor binding characteristics of JTH-601 and its metabolites in rat tissues.

The present study was performed to characterize the disposition and alpha(1)-adrenoceptor binding of JTH-601, a novel alpha(1L)-adrenoceptor antagonist, and its metabolites (beta-D-glucopyranosyl uronic acid, JTH-601-G1; hydrogen sulfate, JTH-601-S1) in the rat prostate and other tissues. JTH-601, JTH-601-G1, and JTH-601-S1 inhibited competitively specific [(3)H]tamsulosin binding in the prostate, submaxillary gland, and spleen of rats in vitro, and the inhibitory effect of JTH-601 was 2. 5 to 6.4 times more potent than that of its metabolites. JTH-601 and its metabolites inhibited dose dependently in vivo specific [(3)H]tamsulosin binding in the particulate fraction of the prostate, aorta, submaxillary gland, and spleen of rats. Compared with that of JTH-601, the in vivo inhibitory effect of JTH-601-G1 was 1.9 to 2. 9 times more potent, and the effect of JTH-601-S1 was 1.3 to 3.2 times less potent. Based on the ratios of ID(50) values, JTH-601 and JTH-601-G1 appeared to be 4.0 to 6.9 times more selective than prazosin as far as the alpha(1)-adrenoceptors in the prostate and submaxillary gland versus the spleen or aorta were concerned. The total radioactivity in rat tissues after i.v. injection of [(3)H]JTH-601-G1 was considerably lower than that of [(3)H]JTH-601. The plasma concentration of [(3)H]JTH-601-G1 at 10 min after i.v. injection in rats was 3 times higher than that of [(3)H]JTH-601, and conversely, the concentration in the prostate was 3 times lower. Although in vivo [(3)H]JTH-601-G1 binding at 10 min was significantly lower than that of [(3)H]JTH-601 in most rat tissues, there was comparable binding between these radioligands in the prostate and vas deferens. Specific binding of [(3)H]JTH-601, at 60 min after i.v. injection compared with that at 10 min, was considerably reduced in rat tissues except the prostate and vas deferens, both of which showed relatively sustained binding. In conclusion, the present study has shown that JTH-601 and its metabolites bind to alpha(1)-adrenoceptors in rat tissues in vivo and that JTH-601-G1 retains the prostatic alpha(1)-adrenoceptor subtype selectivity of its parent compound.

Adrenergic alpha-Antagonists↗
PubMed1999

High serum coenzyme Q10, positively correlated with age, selenium and cholesterol, in Inuit of Greenland. A pilot study.

Greenlanders (Eskimos) have low prevalence of ischaemic heart disease, partly explained by a lower extent of atherosclerosis and a low n-6/n-3 ratio of polyunsaturated fatty acids. As atherosclerosis is also a result of oxidative stress, the total antioxidative readiness could have a substantial impact. From a health survey we chose the subpopulation from the most remote area, where the traditional Greenlandic diet with high intake of sea mammals and fish predominates. The mean (SD) of S-CoQ10 in males was 1.495 (0.529) nmol/ml and 1.421 (0.629) nmol/ml in females, significantly higher (p < 0.001) compared to a Danish population. In a linear multiple regression model the S-CoQ10 level is significantly positively associated with age and S-selenium in males, and S-total cholesterol in females. The high level of CoQ10 in Greenlanders probably reflects diet, since no bioaccumulation takes place, and it could probably be a substantial part of the antioxidative defense.

Adult↗
PubMed1999

Acute health problems among the people engaged in the cleanup of the Nakhodka oil spill.

To determine if the Nakhodka oil spill and subsequent cleanup efforts had any health effects on the residents along the oil-contaminated coast, we investigated the health status of Anto residents who resided nearest to the coast where the bow ran aground. Two hundred eighty-two men and women involved in the cleanup activities between January 7 and January 20 were interviewed and examined by public health nurses to determine whether they suffered physical symptoms after exposure to the oil spill. Urine examinations for hydrocarbon toxicological markers were performed on 97 residents. The average number of days worked on cleanup activities was 4.7 days for men and 4.3 for women. Seventeen percent of the subjects had worked on cleanup activities for more than 10 days. Protective equipment was used against direct exposure to oil during the cleanup jobs and consisted of gloves used by almost 100% of the subjects and masks used by 87.1% of women and by only 35.4% of men. Glasses were worn by less than 30% of the subjects. Many symptoms emerged after the beginning of cleanup activities. The principal symptoms included low back pain and leg pain, headache, and symptoms of eyes and throat. Among the subjects undergoing urine tests, only three people showed a higher level of hippuric acid, although they returned to normal in the second examination. Accordingly, the exposure to the oil and the subsequent cleanup efforts were suggested to inflict acute health problems on local residents.

Acute Disease↗
PubMed1999

Brain receptor binding characteristics and pharmacokinetics of JTP-2942, a novel thyrotropin-releasing hormone (TRH) analogue.

JTP-2942 competed with [3H]-Me-TRH for the binding sites in rat brain in vitro, and its inhibitory effect was approximately 17 times less potent than TRH, as shown by Ki values of 673 and 39.7 nM, respectively. Both JTP-2942 and TRH significantly increased apparent dissociation constant (Kd values) for brain [3H]-Me-TRH binding. Intravenous injection of JTP-2942 (0.3-3 mg/kg) and TRH (3 and 10 mg/kg) produced a significant reduction of [3H]-Me-TRH binding sites (Bmax values) in rat brain. Although the decrease by TRH was maximal 10 min after the injection and declined rapidly with time, the decrease by JTP-2942 (1 and 3 mg/kg) tended to be maximal at 30 min later and it lasted until 120 min. The intravenous injection of JTP-2942 was at least 3 times more potent than that of TRH in decreasing Bmax values for brain [3H]-Me-TRH binding. Plasma concentration of JTP-2942 (0.3-3 mg/kg) after intravenous injection in rats rose with the increase of dose, and it peaked immediately after the injection, thereafter decreasing with t1/2 of 19.3-29.9 min. It is concluded that JTP-2942, compared to TRH, may exert fairly potent and sustained occupation of brain TRH receptors under in vivo condition. Thus, JTP-2942 could be clinically useful for the treatment of CNS disorders.

Animals↗
PubMed1999

Comparative study on pharmacokinetics and in vivo alpha1-adrenoceptor binding of [3H]tamsulosin and [3H]prazosin in rats.

The plasma concentration, total radioactivity and in vivo alpha1-adrenoceptor binding in rat tissues after intravenous (i.v.) injection of [3H]tamsulosin were measured and they were compared with those obtained after the injection of [3H]prazosin. The plasma concentration of [3H]tamsulosin was consistently higher than that of [3H]prazosin, with 1.4 times greater areas under the curve (AUC(0-infinity)) of plasma concentration. As there was a significantly lower value of apparent volume of central compartment (Vd(c)) and distribution volume at steady state (Vd(ss)) for [3H]tamsulosin than [3H]prazosin with little difference in elimination rate constant (beta), the higher concentration of [3H]tamsulosin in plasma might be associated mainly with the smaller volume of distribution. The ratio of total radioactivity in tissues to the plasma unbound concentration of [3H]tamsulosin after i.v. injection of the ligand was consistently lower than that of [3H]prazosin. These observations suggest that [3H]tamsulosin is distributed in rat tissues in a more limited manner than [3H]prazosin. A significantly lower level of in vivo specific binding of [3H]tamsulosin than [3H]prazosin was observed in the spleen, heart and liver. Further, the apparent dissociation constant (Kd) and maximal number of binding sites (Bmax) for in vivo specific [3H]tamsulosin binding were considerably lower than those for [3H]prazosin binding. Therefore, these findings suggest that [3H]tamsulosin labels preferentially a subpopulation of the alpha1-adrenoceptor sites in rat tissues labeled by [3H]prazosin. In conclusion, the present study has shown that there is a significant difference in the pharmacokinetics and in vivo alpha1-adrenoceptor binding characteristics between tamsulosin and prazosin.

Adrenergic alpha-Antagonists↗
PubMed1999

In vivo measurement by [3H]Tamsulosin of alpha1 adrenoceptors in rat tissues in relation to the pharmacokinetics.

The present study was undertaken to simultaneously measure alpha1 adrenoceptors in rat tissues by [3H]tamsulosin in vivo. In vivo specific [3H]tamsulosin binding was observed in the prostate, vas deferens, aorta, submaxillary gland, spleen, heart, lung, and kidney after i.v. injection of the ligand but not in the cerebral cortex and liver. Specific [3H]tamsulosin binding in the kidney, lung, heart, and spleen was greatest at 3 min after i.v. injection and declined rapidly with the disappearance of [3H]tamsulosin from the plasma. On the other hand, [3H]tamsulosin binding in the prostate and aorta peaked at 10 to 60 min after i.v. injection, and a considerable level of specific binding in both tissues persisted up to 240 min. The most sustained binding of [3H]tamsulosin occurred in the submaxillary gland. In vivo specific [3H]tamsulosin binding in rat tissues was effectively inhibited by the coinjection of low doses of unlabeled tamsulosin, prazosin, and terazosin with the radioligand but not by relatively high doses of yohimbine and propranolol. Based on estimated ID50 values, in vivo inhibitory effect of tamsulosin compared with prazosin was 5 to 14 times greater in rat tissues except the spleen, which showed 1.6 times less potent than prazosin. From ratios of ID50 (spleen) to ID50 (submaxillary gland) or ID50 (prostate), tamsulosin was 9 and 19 times, respectively, greater than prazosin in selectivity of alpha1 adrenoceptors in the submaxillary gland and prostate versus the spleen, respectively, suggesting that tamsulosin binds to alpha1A subtype with higher affinity than alpha1B subtype in vivo. The present study suggests that [3H]tamsulosin is a useful radioligand for in vivo measurement of alpha1 adrenoceptors in rat tissues.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1998

Ex vivo occupancy by tamsulosin of alpha1-adrenoceptors in rat tissues in relation to the plasma concentration.

At 0.5-12 h after oral administration of tamsulosin (2.3 micromol/kg) in rats, there was a significant decrease in specific [3H]prazosin binding in the prostate as compared to the control value. The greater decrease occurred in the submaxillary gland. The effect of tamsulosin was mainly due to a marked reduction of [3H]prazosin binding sites (Bmax) rather than to an increase in the dissociation constant (Kd). In contrast, there was only a slight decrease or no change in the [3H]prazosin binding in the spleen, heart, and cerebral cortex of tamsulosin-administered rats at 0.5-12 h. Oral administration of terazosin (21.7 micromol/kg) significantly increased Kd values for [3H]prazosin binding with little effect on Bmax values in the rat prostate at 3 and 6 h. The greater increases in Kd values were observed in the submaxillary gland, spleen and heart at 0.5-12 h. Terazosin had a slight effect on Kd values for the cerebral cortical [3H]prazosin binding. Tamsulosin was absorbed rapidly after oral administration at a dose of 2.3 micromol/kg in rats, and at 6 h, plasma concentration decreased markedly to approximately one-twentieth of the 0.5 h peak level. alpha1-Adrenoceptor occupancy was estimated as a percentage of decrease in Bmax values for [3H]prazosin binding in tissues of tamsulosin-treated rats compared with control rats. The alpha1-adrenoceptor occupancy by tamsulosin in the prostate and submaxillary gland occurred rapidly in parallel with the rise in plasma concentration of tamsulosin, and lasted for over 12 h despite the marked decrease in plasma concentration. Consequently, it is suggested that tamsulosin produces more selective and sustained occupancy in vivo of alpha1-adrenoceptors in the submaxillary gland and prostate of rats than in other tissues.

Administration, Oral↗
PubMed1997

Inhibition of brain cyclooxygenase-2 activity and the antipyretic action of nimesulide.

The antipyretic action and the mechanism of action of 4-nitro-2-phenoxymethanesulfonanilide (nimesulide), a new nonsteroidal antiinflammatory drug, were investigated in yeast-induced febrile rats. Yeast-injected rats developed marked fever and exhibited an approximately 7-fold increase in brain levels of prostaglandin E2 and an approximately 2-fold increase in the expression of cyclooxygenase-2 mRNA despite an almost unchanged expression of cyclooxygenase-1 mRNA. Nimesulide produced a dose dependent antipyretic action, which was stronger than that of indomethacin and ibuprofen, and decreased dose dependently the increased brain prostaglandin E2 levels, whereas it did not influence the expression of cyclooxygenase-2 mRNA. It inhibited markedly the enhanced brain cyclooxygenase activity, primarily cyclooxygenase-2, in vivo and dose dependently increased brain cyclooxygenase activity in vitro. These results suggest that the marked antipyretic action of nimesulide is primarily mediated through the selective inhibition of the activity of brain cyclooxygenase-2 induced under febrile conditions.

Analgesics, Non-Narcotic↗
PubMed1997

Brain pharmacokinetics and in vivo receptor binding of 1,4-dihydropyridine calcium channel antagonists.

Brain pharmacokinetics of 1,4-dihydropyridine (DHP) calcium channel antagonists and their in vivo receptor binding in mice were characterized. The area under the concentration vs time curve (AUCbrain) for [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 in mouse brain after intravenous injection was higher than that for [3H]amlodipine. Brain/plasma concentration ratios (AUCbrain/AUCplasm) for [3H]nimodipine and [3H]PN 200-110 were 3 to 5 times higher than those for [ H]nifedipine and [3H]amlodipine. Further, brain/heart concentration ratios (AUCbrain/AUCheart) for [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 were about 20 times higher than the ratio for [3H]amlodipine. A significant amount of specific binding in particulate fractions of mouse brain was detected in vivo by intravenous injection of [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 but not [3H]amlodipine. These data suggest that [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 are more extensively taken up into brain from plasma than [3H]amlodipine and bind to the receptor sites in brain parenchymal cells in a significant amount in vivo. In conclusion, the present simultaneous measurement of pharmacokinetics and in vivo receptor binding in mouse brain suggests an usefulness of calcium channel antagonists such as nimodipine in the pharmacotherapy of brain diseases.

Animals↗
PubMed1997

Production of amylase by the intestinal microflora in cultured freshwater fish.

The amylase-producing ability of the intestinal microflora in cultured specimens of ayu, carp, channel catfish, Japanese eel and tilapia was determined. Mean viable counts of aerobes and anaerobes ranged from 1.1 x 10(6) to 3.7 x 10(8) cfu g-1 and from 1.3 x 10(3) to 1.6 x 10(8) cfu g-1, respectively. Aeromonas spp. and Bacteroidaceae were predominant in four to five fish species. Of 206 strains examined, 65 (31.6%) produced > or = 0.01 U amylase ml-1. The percentage of producers differed among families and genera of bacteria and fish species. While 56% of the anaerobes produced amylase, only 20% of the aerobes did. More than 50% of Aeromonas, Bacteroidaceae and Clostridium strains produced amylase efficiently while Acinetobacter, coryneforms, Enterobacteriaceae, Moraxella, Plesiomonas and Streptococcus strains did not. High amylase production (> or = 0.05 U ml-1) was found in 12 strains, 11 from Aeromonas and one Pseudomonas. The percentage of high amylase producers in Japanese eel was lower than the other four fish (2-30%). These results strongly suggest that the amylase produced by the intestinal microflora play an important role in the digestion of starch in freshwater fish to some extent.

Amylases↗
PubMed1997

Vibrio sp. strain NM 10, isolated from the intestine of a Japanese coastal fish, has an inhibitory effect against Pasteurella piscicida.

Vibrio sp. strain NM 10 with an inhibitory activity against Pasteurella piscicida K-III was isolated from the intestine of a spotnape ponyfish (Leiognathus nuchalis). This bacterium efficiently produced an antibacterial substance after growth at 20 degrees C for 24 h on 1/5 PYBG agar prepared with 50% seawater at pHs of 7.5 to 9.0. The antibacterial substance was heat labile and proteinaceous, with a molecular mass of less than 5 kDa, possibly a bacteriocin or a bacteriocin-like substance.

Animals↗
PubMed1997

Direct effect of inorganic mercury on citrate uptake by isolated rat renal brush border membrane vesicles.

Occupational exposure to mercury has long been associated with renal proximal injury and an increased incidence of proteinuria, as has such exposure to cadmium. Renal citrate excretion is very important with respect to acid-base balance since the metabolism of citrate generates three bicarbonate ions. In this study, we exposed isolated rat renal brush border membrane vesicles (BBMV) to mercury (Hg2+) and examined their citrate uptake characteristics. BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration method. The preincubation of BBMV with 0.5 and 2 mM HgCl2 for 1 min significantly inhibited citrate uptake compared with that of BBMV without Hg preincubation. The analysis of the time course of citrate uptake during a 30-min preincubation of BBMV with 0.1 mM Hg2+ also revealed a significant reduction in the uptake compared with that of the control BBMV without preincubation. These findings indicate that the preincubation of BBMV with mercury results in a time- and concentration-dependent inhibition of citrate uptake.

Animals↗
PubMed1997

Evaluation of the polymerase chain reaction method for identification of Vibrio vulnificus isolated from marine environments.

The polymerase chain reaction (PCR) method for identification of Vibrio vulnificus in the marine environment was evaluated by comparing it to both the conventional and DNA-DNA hybridization methods. Of 13,325 isolates obtained from seawater and sediment samples, and oyster and goby specimens collected from the coastal waters of Tokyo Bay, Japan, only 61 isolates were identified as V. vulnificus on the basis of phenotypic characteristics and the amplification of the cytotoxin-hemolysin gene by the PCR method. All 61 isolates were further confirmed to be V. vulnificus by a DNA-DNA hybridization method and the API 20E system although they were divided into 13 groups on the basis of their API 20E profiles. These results strongly suggest that the PCR method is useful for identification of this organism.

Animals↗
PubMed1997

Quantitative evaluation of brain distribution and blood-brain barrier efflux transport of probenecid in rats by microdialysis: possible involvement of the monocarboxylic acid transport system.

This study was performed to evaluate quantitatively the brain distribution and the efflux transport across the blood-brain barrier of probenecid, using in vivo microdialysis and in situ brain perfusion techniques. The brain interstitial fluid (ISF)-to-plasma cerebrospinal fluid (CSF)-to-plasma and brain tissue-to-plasma unbound concentration ratios of probenecid at steady state were less than unity, which suggests restricted distribution in the brain. An uphill concentration gradient from ISF to plasma and a downhill concentration gradient from CSF to ISF were observed. Kinetic analysis revealed that the efflux clearance from brain ISF to plasma (0.0373 ml/min/g brain) was significantly greater than the influx clearance from plasma to brain (0.00733 ml/min/g brain). The ratio of the ISF concentration (Cisf) to the plasma unbound concentration (Cp,f) of probenecid was increased 2- to 3-fold by salicylate (3.7 mM) and benzoate (3.6 mM), which are accepted as substrates of the monocarboxylic acid transport system, compared with the same ratio for the control. In addition, the ratio Cisf/Cp,f was increased by treatment with N-ethylmaleimide, a sulfhydryl-modifying agent, whereas p-aminohippuric acid and choline did not produce increasing effects on Cisf/Cp,f. These data suggest that the restricted distribution of probenecid in the brain may be ascribed to efficient efflux from the brain ISF, which may be regulated by the monocarboxylic acid transport system at a relatively high ISF concentration.

Animals↗
PubMed1996

Interaction between enoxacin, a new antimicrobial, and nimesulide, a new non-steroidal anti-inflammatory agent in mice.

Convulsions induced by the combination of enoxacin, a new antimicrobial, and nonsteroidal anti-inflammatory drugs including nimesulide, ketoprofen, pranoprofen and loxoprofen sodium, were investigated in mice. The oral administration of nimesulide alone induced clonic convulsions at more than 300 mg/kg. The oral administration of ketoprofen, pranoprofen or loxoprofen sodium induced no convulsion up to 1000 mg/kg, 500 mg/kg and 600 mg/kg, respectively, and that of enoxacin induced no convulsion at more than 5000 mg/kg. The combination of nimesulide at 200 mg/kg and enoxacin at 400 mg/kg induced no convulsion. In contrast, the combination of enoxacin at 100 mg/kg and either ketoprofen at 125 mg/kg or pranoprofen at 500 mg/kg induced clonic convulsions, while that of enoxacin at 400 mg/kg and loxoprofen sodium at 600 mg/kg induced no convulsion. These results suggest that the combination of nimesulide and enoxacin may possibly induce few or less convulsions in the clinical setting.

Animals↗