Biomedical subjects

S Kawazoe

Publications and source records attributed to S Kawazoe.

At least 19 recordsLinked to original sources

PubMed2001

Novel malonamide derivatives as alpha v beta 3 antagonists. Syntheses and evaluation of 3-(3-indolin-1-yl-3-oxopropanoyl)aminopropanoic acids on vitronectin interaction with alpha v beta 3.

In attempt to find novel integrin alphavbeta3 antagonists, we selected SC65811 and its guanidine analogue (1) as lead compounds. Modification of the glycine part of SC65811 led to a new series of malonamide derivatives that exhibited alphavbeta3 inhibitory activity. Among them, (R,S)-3-[3-[6-(3-benzylureido)indolin-1-yl]-3-oxopropanoylamino]-3- (pyridin-3-yl)propanoic acid (43a) showed not only potent activity with an IC50 value of 3.0 nM but also good selectivity for alphavbeta3 relative to alphaIIbbeta3, alpha5beta1, and alphavbeta5 with IC50 values of 19,000, 11,000, and 14 nM, respectively. Furthermore, optimization of 43a led to the most potent alphavbeta3 antagonist, (R,S)-3-(3-[6-[(4,5-dihydro-1H-imidazol-2-yl)amino]indolin-1-yl]-3-oxopropanoylamino)-3-(quinolin-3-yl)propanoic acid (431) with an IC50 value of 0.42 nM. The synthesis and the structure-activity relationships of these malonamide derivatives are presented.

Aniline Compounds↗

PubMed2000

Evidence for the involvement of N-methylthiourea, a ring cleavage metabolite, in the hepatotoxicity of methimazole in glutathione-depleted mice: structure-toxicity and metabolic studies.

In mice depleted of GSH by treatment with buthionine sulfoximine (BSO), methimazole (2-mercapto-1-methylimidazole, MMI) causes liver injury characterized by centrilobular necrosis of hepatocytes and an increase in serum alanine transaminase (SALT) activity. MMI requires metabolic activation by both P450 monooxygenase and flavin-containing monooxygenase (FMO) before it produces the hepatotoxicity. MMI and its analogues were examined for the ability to increase SALT activity in GSH-depleted mice. Saturation of the C-4,5 double bond in MMI resulted in a complete loss of hepatotoxicity. Similarly, ring fusion of a benzene nucleus to the C-4,5 double bond, forming 2-mercapto-1-methylbenzimidazole, abolished the toxic potency. As for MMI, 2-mercapto-1,4,5-trimethylimidazole, and 2-mercapto-1-methyl-4, 5-di-n-propylimidazole, the toxic potency decreased with the increasing bulk of the 4- and 5-alkyl substituents. Furthermore, methylation of the thiol group of MMI totally reduced its toxicity. These structural requirements and the known toxicity of thiono-sulfur compounds led us to the hypothesis that MMI would undergo epoxidation of the C-4,5 double bond by P450 enzymes and, after being hydrolyzed, the resulting epoxide would be then decomposed to form N-methylthiourea, a proximate toxicant. Before N-methylthiourea would produce toxicity, it would be further biotransformed to its S-oxidized metabolites mainly by FMO. Evidence for this hypothesis was provided by the facts that N-methylthiourea and glyoxal as the accompanying fragment were identified as urinary metabolites in mice treated with MMI and that N-methylthiourea caused a marked increase in SALT activity when administered to mice in combination with BSO.

Animals↗

PubMed2000

[Hepatotoxicity induction in mice after acute DL-lactic acid intake].

DL-Lactic acid and its salts are added to food as acidulants, pH control agents, leavening agents, nutrient supplements and seasonings. However, the basic data concerning the safety and toxicity of these compounds are insufficient. In this article, we examined induction of hepatotoxicity and nephrotoxicity in mice after acute intake of DL-lactic acid. Body weight change, serum glutamic pyruvic transaminase (SGPT) activity, serum urea nitrogen (SUN) concentration, liver and kidney weights, and renal lipid peroxide level could not be affected significantly in mice at 4 h after intraperitoneal administration of DL-lactic acid at 1.2 mmol/kg, indicating no induction of toxicity in the liver and kidney. In contrast, at 20 h after the treatment, SGPT activity, liver weight and lipid peroxide level were enhanced significantly, suggesting induction of hepatotoxicity. However, SUN concentration, kidney weight and lipid peroxide level could not be affected significantly at 20 h after the treatment, indicating no induction of nephrotoxicity.

Administration, Oral↗

PubMed2000

[In vivo toxicity, lipid peroxide lowering, and glutathione, ascorbic acid and copper elevation induced in mouse liver by low dose of oxine-copper, a fungicide].

While oxine-copper (OxCu) is generally used as an agricultural fungicide and induces a harmful effect on ecosystems, little information is available regarding a toxic effect of OxCu on mammals. In this article, we examined in vivo induction of toxicity and change of levels of glutathione and ascorbic acid, major biological antioxidants, lipid peroxide and copper (Cu) in liver and kidney 4 h and 24 h after intraperitoneal administration of OxCu at a low dose (0.05 mmol/kg) to mice. Increased hepatic ascorbic acid and Cu levels were found at 4 h after the treatment. In addition, body weight change was lowered and serum glutamic pyruvic transaminase activity was elevated significantly compared to control at 24 h after the treatment, suggesting induction of systemic and hepatic toxicity respectively. These were accompanied by lowered lipid peroxide level and enhanced glutathione, ascorbic acid and Cu levels in the mouse liver. On the other hand, OxCu induced no elevation in serum urea nitrogen concentration 4 h and 24 h after the treatment, suggesting no induction of nephrotoxicity, accompanied by no change in renal lipid peroxide, glutathione, ascorbic acid and Cu levels. These results suggest that hepatic Cu elevation may induce hepatotoxicity and no renal Cu elevation may lead to no induction of nephrotoxicity after the treatment with OxCu.

Animals↗

PubMed2000

[In vivo toxicity, and glutathione, ascorbic acid and copper level changes induced in mouse liver and kidney by copper(II) gluconate, a nutrient supplement].

While copper(II) gluconate (CuGL) is generally used as a nutrient supplement for infant foods and as an oral deodorant, little information is available regarding a toxic effect of CuGL on mammals. In this article, we examined in vivo induction of toxicity and change of level of glutathione and ascorbic acid, major biological antioxidants, lipid peroxide and copper (Cu) in liver and kidney 4 h after single intraperitoneal administration of CuGL at 0.05 and 0.10 mmol/kg to mice. Serum glutamic pyruvic transaminase (SGPT) activity, an indicator of hepatotoxicity, significantly increased compared to control in proportion to doses of CuGL. Hepatic level of glutathione measured as nonprotein sulfhydryl was not proportional to CuGL doses, but enhanced after dosing of 0.05 mmol/kg and lowered by 0.10 mmol/kg. Like SGPT activity, serum urea nitrogen (SUN) concentration, an indicator of nephrotoxicity, significantly increased in proportion to doses of CuGL. Renal glutathione level was not different from control after dosing of 0.05 mmol/kg and lowered by 0.10 mmol/kg. In both organs, relative organ weight and lipid peroxide level were not affected by the treatment with CuGL; ascorbic acid level was elevated after dosing of 0.05 mmol/kg and was not different from control after treatment with 0.10 mmol/kg; like SGPT activity and SUN concentration, Cu level significantly increased in proportion to doses of CuGL. These results suggest that in the liver and kidney after the treatment with CuGL Cu accumulated may induce toxicity, leading to level changes of glutathione and ascorbic acid and to no induction of oxidative damage.

Animals↗

PubMed2000

Direct evidence for in vivo hydroxyl radical generation in blood of mice after acute chromium(VI) intake: electron spin resonance spin-trapping investigation.

Although it is assumed from in vitro experiments that the hydroxyl radical (*OH) may be responsible for chromium(VI) toxicity/carcinogenicity, no electron spin resonance (ESR) evidence for the generation of *OH in vivo has been reported. In this study, we have employed an ESR spin-trapping technique with 5,5-dimethylpyrroline-N-oxide (DMPO), a selective *OH trap, to detect *OH in blood. The ESR spectrum of spin adduct observed in the blood of mice given 4.8 mmol Cr(VI)/kg body weight exhibited the 1:2:2:1 intensity pattern of a quartet with a hyperfine coupling constant A(N) = A(H) = 14.81 G and g-value = 2.0067. The concentration of the spin adduct detected in the blood was 7.37 microM. The adduct production was inhibited by the addition of specific *OH scavengers such as sodium benzoate and methional to the blood. The results indicate that the spin adduct is nitroxide produced by the reaction of *OH with DMPO. This is the first report of ESR evidence for the in vivo generation of *OH in mammals by Cr(VI).

Aldehydes↗

PubMed2000

In vivo singlet-oxygen generation in blood of chromium(VI)-treated mice: an electron spin resonance spin-trapping study.

Although it is assumed from in vitro experiments that the generation of reactive oxygen species such as the singlet oxygen (1O2), the hydroxyl radical, and the superoxide anion are responsible for chromium(VI) toxicity/carcinogenicity, no electron spin resonance (ESR) evidence for the generation of 1O2 in vivo has been reported. In this study, we have employed an ESR spin-trapping technique with 2,2,6,6-tetramethyl-4-piperidone (TMPD), a specific 1O2 trap, to detect 1O2 in blood. The ESR spectrum of the spin adduct observed in the blood of mice given 4.8 mmol Cr(VI)/kg body weight exhibited the 1:1:1 intensity pattern of three lines with a hyperfine coupling constant A(N) = 16.08 G and a g-value = 2.0066. The concentration of spin adduct detected in the blood was 1.46 microM (0.1% of total Cr concentration). The adduct production was inhibited by the addition of specific 1O2 scavengers such as 1,4-diazabicyclo[2.2.2]octane and sodium azide to the blood. The results indicate that the spin adduct is nitroxide produced by the reaction of 1O2 with TMPD. This is the first report of ESR evidence for the in vivo generation of 1O2 in mammals by Cr(VI).

Animals↗

PubMed2000

[A case of percutaneous and transpapillary placements of expandable metallic stents in a patient with cholangiocarcinoma at the hilum of the liver].

A 76-year-old woman was admitted with obstructive jaundice. US and MR cholangiopancreatography (MRCP) revealed an inoperative cholangiocarcinoma, 3 cm in diameter at the hilum of the liver, the obstruction of the hepatic duct bifurcation and the separation of bilateral hepatic bile ducts. Percutaneous transhepatic biliary drainage (PTBD) was performed from bilateral hepatic bile ducts. The right PTBD tube was spontaneously extubated. We could not succeed in performing internal biliary drainage across the hilar malignant stricture from a left hepatic bile duct, because of bad angulation. Transpapillary insertion into the common bile duct (CBD) was extremely difficult due to the collapse of the CBD. Endoscopic sphincterotomy (EST) after precutting method was performed. Although we performed the ballooned dilatation of malignant stricture and the insertion of a self-expandable metallic stent (EMS) into a right hepatic bile duct transpapillary. After dilatation of the hilar malignant stricture by the initial EMS, we inserted a guidewire into the CBD through the wire mesh of a stent from the left PTBD tube. We could insert the second EMS from a left hepatic bile duct to the CBD transhepatically, using a dilator and a dilating balloon. Finally, we performed the ballooned dilatation from bilateral hepatic bile ducts to the CBD transpapillary. She was discharged after bilateral internal biliary drainages, successfully.

Aged↗

PubMed1999

[An extremely elderly patient with choledocholithiasis and many complications].

It was very difficult to treat a 90-year-old woman for choledocholithiasis with acute obstructive suppurative cholangitis, gallbladder perforation, and a pool of bile in the right perirenal spase. Extracorporeal shockwave lithotripsy (ESWL) was performed after emergency percutaneous transhepatic biliary drainage (PTBD), but we could not perform lithotripsy successfully because of large and hard stones. Although Endoscopic sphincterotomy (EST) was performed using an ultratome by rendezvous method. Lithotripsy was finally successful, after three times endoscopic mechanical lithotripsy (EML) and procedure using an endotriptor for basket impaction. It is very important in advanced aged patients that endoscopic treatment should be performed step by step.

Aged↗

PubMed1997

[An elderly case of post-bulbar Dieulafoy's ulcer].

The case is a 79-year-old man who came to our hospital with melena as chief complaint. Emergency endoscopy showed spurting bleeding from a small ulcer. We diagnosed as Post-Bulbar Dieulafoy's ulcer and performed hemostatic procedure with hemostatic clips. The forth endoscopy (7 days after admission) showed fresh clot and oozing bleeding after the third hemostatic clipping. Although we performed hemostatic procedure with the injection therapy of hypertonic saline epinephrine solution (HSE). The effective hemostatic procedure is discussed with reference to some related literature.

Aged↗

PubMed1995

Sealing ability of thermoplasticized gutta-percha fill techniques as assessed by a new method of determining apical leakage.

One hundred fifty-nine extracted single-rooted maxillary human teeth were instrumented and randomly divided into nine groups of 17 teeth each and 6 control teeth. Experimental groups were obturated with Thermafil, Obtura II, Ultrafil Regular Set gutta-percha, and Ultrafil Firm Set gutta-percha, each with or without root canal sealer. A control group was obturated using the lateral condensation technique and sealer. Teeth were immersed in a resorcinol-formaldehyde resin for 5 days at 4 degrees C, and the resin was allowed to polymerize completely for 4 days at room temperature. Teeth were then sectioned horizontally at 1.5, 2.5, and 3.5 mm from the anatomical apex, and examined under a stereomicroscope at x25 magnification. The resin filled the spaces in the gap between the canal wall and the gutta-percha and this was measured at each of the three levels. The ratio of the area of the resin to the total area of the canal was obtained as the mean leakage area. The results showed no significant difference in the mean leakage area at the same level for the different obturation materials. However, the leakage was significantly less for all materials when root canal sealer was used.

Chi-Square Distribution↗

PubMed1993

Changes in cell proliferative activity in granulation tissue invading the root canal.

Root canal models were implanted in rats in order to investigate histologically the movement of granulation tissue invading apical canals and dead spaces and changes in cell proliferative activity as indicated by 3H-thymidine. The models were prepared to have 1, 2, and 3 mm apical canals, with and without dead spaces, to simulate preparations short of the apex and obturation to several levels. After 12 wks implantation of the models without dead spaces, granulation tissue invading 1 mm apical canals did not degenerate and cell proliferative activity remained high. However, tissue invading the 2 and 3 mm apical canals tended to be necrotic and cell proliferative activity was decreased. In the models with dead spaces, the tissue in the 1 and 2 mm apical canals developed and invaded the dead spaces, and still possessed proliferative activity 12 wks after implantation. In contrast, the tissue in the 3 mm apical canals did not invade the dead spaces, even after 12 wks, and no proliferative activity was observed.

Animals↗

PubMed1992

Sex difference in the nephrotoxicity of thiabendazole in mice depleted of glutathione by treatment with DL-buthionine sulphoximine.

In ICR mice depleted of glutathione (GSH) by treatment with DL-buthionine sulphoximine (BSO), males were much more susceptible to thiabendazole (TBZ) nephrotoxicity than females. The nephrotoxicity was indicated by increases in relative kidney weight and serum urea nitrogen (SUN) concentration and by a decrease in renal GSH concentration at 24 hr after TBZ administration. The susceptibility of males to TBZ-induced nephrotoxicity was completely eliminated by pretreatment with oestradiol (OD). Castration of male mice also reduced, though not completely, their susceptibility to TBZ nephrotoxicity. In females pretreated with testosterone (TS), the nephrotoxic effect of TBZ was increased to an extent comparable with that in males.

Animals↗

PubMed1992

Sealing ability of Thermafil with and without sealer.

The purpose of this study was to evaluate the apical sealing ability of root canals filled using three obturating techniques. Sixteen maxillary first molars were obturated with Thermafil, 16 with Thermafil and a ZOE sealer, and 16 with laterally condensed gutta-percha. Two canal instrumentation methods were used, conventional step-back preparation with K-Flex files and traditional instrumentation combining reaming with reamers and filing with K-Flex files. Following obturation, the teeth were prepared for evaluation of the seal using India ink and a Profile Projector. The depth of penetration of the dye was statistically evaluated for each of the three roots with an analysis of variance. For sealing ability, there was no significant difference at the p < 0.05 level between the conventional step-back preparation and the traditional instrumentation technique. However, a significant difference was present at the p < 0.05 level for the obturation techniques. The mean linear dye penetration for the Thermafil technique was greater than that for lateral condensation.

Dental Leakage↗

PubMed1991

Method of Harvesting the Crude Drug Based on Distribution of Alkaloids in the Hook and in the Stem with Hook of Uncaria rhynchophylla1.

The distribution of the content of the pharmacologically active oxindole alkaloids in the hook and in the stem of the crude drug "Cho-to-ko" (dried stem with hooks of UNCARIA RHYNCHOPHYLLA) prepared from the cultivated plants were investigated. The total oxindole alkaloid content of the stem was similar to that of the hook portion. It was also found that the area closest to the hook showed a slightly higher alkaloid content than the hook, and that the content of the oxindole alkaloid tended to decrease as the distance from the hook increased. Therefore, the presence of the hook does not affect the quality of the crude drug as far as the oxindole alkaloid content is concerned.

Journal Article↗

PubMed1989

Systemic distribution of 14C-labeled formaldehyde applied in the root canal following pulpectomy.

The systemic distribution of 14C-labeled formaldehyde which had been placed in the root canals of the canines of cats following pulpectomies was studied using liquid scintillation counting and wholebody autoradiographic technique. Radioactive 14C which had been placed in the canals was found in the plasma 30 min after the root canal procedure. The recovery of systemic 14C radioactivity increased with time. In addition, it seemed that approximately 3% of the dose placed in the teeth was excreted in the urine within 36 h. Whole-body autoradiograms indicated extensive concentration of 14C radioactivity in tissues other than those analyzed with the liquid scintillation technique.

Animals↗

PubMed1988

Stimulatory effects of neuronally released norepinephrine on renin release from rat kidney cortical slices.

Stimulatory effects of extracellular high K+ in the presence of nifedipine (NIF) on renin release (RR) from kidney cortical slices were investigated. The stimulation was suppressed either by propranolol or by metoprolol but not by prazosin. High K+ plus NIF-induced increase in RR was attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in Ca2+-free buffer or in medium containing divalent cations such as Cd2+, Co2+ and Mn2+. These alterations in RR correlated with 3H-efflux from the slices preloaded with 3H-norepinephrine. We conclude that the high K+ plus NIF-induced increase in RR from the slices is mediated by norepinephrine (NE) derived from renal sympathetic nerves and that this neuronally released NE stimulates RR via the activation of beta-adrenoceptors.

Animals↗

PubMed1988

Stimulatory effects of neuronally released norepinephrine on renin release in vitro.

Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. We found that the decreased response of renin release from rat kidney cortical slices in high potassium solution (20-80 mM) changed to a strikingly increased one in the presence of nifedipine at doses over 10(-6) M. We then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd2+, Co2+, and Mn2+ (0.1-3.0 mM) blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in 3H efflux from the slices preloaded with [3H]norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of beta-adrenoceptors.

Animals↗