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Biomedical subjects

M Uchida

Publications and source records attributed to M Uchida.

At least 199 records · Page 11Linked to original sources

Effect of tauroursodeoxycholic acid on bile flow and calcium excretion in ischemia-reperfusion injury of rat livers.

BACKGROUND/AIMS: Tauroursodeoxycholic acid is known to have a hepatoprotective action in cholestatic disorders. We evaluated whether oral pretreatment with tauroursodeoxycholic acid could protect the liver from ischemia-reperfusion injury, with particular regard to its effect on bile flow and biliary calcium excretion. METHODS: A 1-hour in vivo ischemia-reperfusion model of 70% of the lobes of rat liver was used. Animals were divided into six groups (each group; n = 8); a non-ischemia sham group (CS), a control group without bile acids (CON), and 4 bile acid groups; 10 mg/kg and 50 mg/kg (U10, U50), taurocholic acid 10 mg/kg (CA10) and tauroursodeoxycholic acid 10 mg/kg (CD10). Bile acids were given orally for 7 days before operation. RESULTS: Three hours after reperfusion, oral bile acid pretreatment failed to reduce the hepatic ischemia-reperfusion injury biochemically, but histological improvement was observed in the tauroursodeoxycholic acid groups. After reperfusion, tauroursodeoxycholic acid significantly increased bile flow from the ischemic liver, and also significantly increased serum calcium concentration. Although tauroursodeoxycholic acid did not change biliary calcium concentration, it significantly enhanced total biliary calcium output during reperfusion. CONCLUSION: Thus, tauroursodeoxycholic acid inhibited tissue calcium accumulation and enhanced sinusoidal and biliary calcium output during hepatic ischemia-reperfusion. However, it is still unclear if calcium mobilization is part of the protective mechanisms of tauroursodeoxycholic acid in ischemia-reperfusion injury of the liver.

Analysis of Variance↗

Contribution of brain injury to hypertension following intravenously-administered pancuronium in rats.

Abnormal hypertension sometimes occurs following intravenous administration (i.v.) of pancuronium in patients with brain injury. The present experiment was designed to determine whether brain injury contributes to the hypertensive response of i.v. pancuronium. Forty-six Wister strain rats were studied, of which 39 had induced brain injury at (a) upper pons (b) midbrain (c) thalamus region (excluding hypothalamus) and (d) cerebellum or a combination of these sites. The injury was made by single insertion of a 22 Gauge needle through the skull surface. The quantity of pancuronium solution administered i.v. in each case was 1.0 ml containing either 0.8 mg/kg or 8 mg/kg of pancuronium. Group A (n = 7) had no brain injury and the mean arterial pressure (MAP) did not change following i.v. administration of pancuronium. In Group B (n = 9) (a+b+c, 8.0 mg/kg) MAP rose from 90.9 +/- 15.4 to 102 +/- 22.0 mmHg and in Group C (n = 7) (a+b+c, 0.8 mg/kg) MAP rose from 148.4 +/- 13.3 to 160 +/- 14.4 mmHg. In Group D (n = 5) (b+c, 8.0 mg/kg) MAP remained unchanged. In Group E (n = 5) (a, 8.0 mg/kg) MAP rose from 130.3 +/- 18.7 to 146 +/- 27.6 mmHg and in Group F (n = 6) (a, 0.8 mg/kg) MAP rose from 129.7 +/- 15.6 to 135.8 +/- 13.8 mmHg. In Group G (n = 7) (d, 8.0 mg/kg) MAP remained unchanged. Since the MAP was elevated in only those groups that received injury in the upper pons, we concluded that injury in the upper pons can lead to hypertension following i.v. administration of pancuronium.

Animals↗

Hydroxyl radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study.

We studied the scavenging activity of rebamipide, a novel antipeptic ulcer agent, and seven related compounds against hydroxyl radicals using the electron paramagnetic resonance (EPR) spin trapping technique. 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was used as a spin trapping agent. We estimated the second order rate constant for the reaction between the agents tested and hydroxyl radical at pH 7.8 by kinetic competition studies. All compounds tested scavenged the hydroxyl radicals with a certain relationship between concentration and scavenging efficacy. A structure-scavenging activity relationship was derived from the kinetic evidence available on the formation and inhibition of the DMPO spin adduct EPR signal of hydroxyl radicals (DMPO-OH). Important determinants for scavenging hydroxyl radicals were the 3,4-double bond of the quinolinone ring in conjunction with a 2-oxo function and the carbonyl portion of the amido group in conjunction with a para-chlorobenzoyl function.

Alanine↗

Direct expression of pig testicular 3 alpha/beta (20 beta)-hydroxysteroid dehydrogenase in Escherichia coli.

The cDNA coding for pig testicular 3 alpha/beta (20 beta)-hydroxysteroid dehydrogenase was expressed in Escherichia coli by placing it under the control of an isopropylthiogalactoside (IPTG) inducible tac promoter. Production of 3 alpha/beta (20 beta)-HSD was demonstrated by Western blotting and by catalytic activity with 5 alpha-dihydrotestosterone as a substrate for 3 alpha/beta-HSD, and progesterone and 17 alpha-hydroxyprogesterone as substrates for 20 beta-HSD in the presence of NADPH. The 3 alpha/beta (20 beta)-HSD enzyme was detected in a soluble fraction of the lysate of E. coli added to IPTG to induce the synthesis of the protein. Its molecular weight was estimated to be 30.5 kDa by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Recombinant 3 alpha/beta (20 beta)-HSD was purified to apparent homogeneity as determined by SDS-PAGE by column chromatography using DEAE-cellulose. The purified enzyme reduced not only steroids but also prostaglandins and other carbonyl compounds including aldehydes, ketones and quinones as demonstrated in native enzymes purified from pig testes. The amino terminus of the purified enzyme was serine which was coded next to the ATG start codon, and the sequence of the amino terminal 24 residues was identical with the coding amino acid in the cDNA; whereas, the amino terminus of the native 3 alpha/beta (20 beta)-HSD was not detected suggesting that the N-terminal amino acid was blocked.

3-Hydroxysteroid Dehydrogenases↗

Percutaneous cryosurgery for renal tumours.

OBJECTIVE: To evaluate the use of percutaneous cryosurgery in the treatment of renal tumours. MATERIALS AND METHODS: A cryoprobe using liquid nitrogen was designed. The tolerance of renal cancer cells to cooling was tested. Freezing tests on two extirpated kidneys involved with hypervascular tumour were performed in water at 40 degrees C. A clinical trial of percutaneous cryosurgery was carried out in two patients with advanced renal carcinoma. RESULTS: The cooling function of the new probe was similar to that of a conventional probe. The tolerance test on renal cancer cells showed that the cooling temperature should be below -20 degrees C to render them necrotic. Freezing tests on two nephrectomized kidneys with hypervascular renal cancer suggested that embolization of the renal artery might be advisable before treatment. The clinical trial in two patients with advanced renal carcinoma showed that the whole kidney, including the tumour, became necrotic and shrunken post-operatively. The patients' Karnofsky performance scale showed a marked improvement 3 months after the operation, but their general condition gradually deteriorated. Patient 1 died 10 months and patient 2 died 5 months after the procedure. CONCLUSION: Percutaneous cryosurgery was performed successfully in two patients with hypervascular renal tumours. Cryo-immunological activity was assumed to have contributed to the temporary improvement in their condition. These results suggest that percutaneous cryosurgery might be useful as minimally invasive treatment in a limited number of patients with advanced renal carcinoma.

Aged↗

Electrophysiologic determinants of ventricular rate in human atrial fibrillation.

INTRODUCTION: The mechanisms of the ventricular response during atrial fibrillation (AF) remain uncertain. The parameters obtained during an electrophysiologic study, including atrial rates during AF, were analyzed to clarify further the determinants of the ventricular rate during AF. METHODS AND RESULTS: Thirty patients without manifest preexcitation in whom AF was induced during electrophysiologic study were divided into two groups. Group 1 consisted of 20 patients (ages 55 +/- 10 years) without a dual AV nodal pathway. Group 2 consisted of 10 patients (ages 53 +/- 13 years) having a dual AV nodal pathway. The correlation coefficient between the mean RR interval during AF (mRR) and the mean intra-atrial potential interval during AF (mff) was positive (0.05 [P < 0.05] in group 1 and 0.37 [P = NS] in group 2). The correlation coefficient of the mRR against the functional refractory periods of the AV node (AVFRP) was 0.73 (P < 0.001) in group 1. The correlation coefficients between mRR and the fast AV nodal pathway functional refractory periods and the slow AV nodal pathway effective refractory periods (SPERP) were 0.58 (P = NS) and 0.7 (P < 0.05) in group 2, respectively. The correlation coefficients between mRR against (mff x AVFRP)1/2 in group 1 and (mff x SPERP)1/2 in group 2 were 0.8 (P < 0.001) and 0.72 (P < 0.05), respectively. CONCLUSIONS: This clinical study did not indicate an inverse relation between the atrial and ventricular rates that had been reported by the previous experimental study. The ventricular rate during AF appeared to be quantitatively related to the atrial rate via AV node function. The importance of the slow pathway in determining the ventricular rate during AF was observed.

Aged↗

Repeated hepatic dearterialization for unresectable liver metastases from gastric cancer: review of five cases.

A novel method of repeated hepatic dearterialization was evaluated in five patients with multiple metastases from gastric cancer in both hepatic lobes. After gastrectomy with extensive lymph node dissection (R2/3), all patients underwent implantation of a vascular occluder around the hepatic artery. Cannulation of the hepatic artery was added for later chemotherapy. The hepatic artery was occluded repeatedly for 1 hour twice daily in combination with intrahepatic infusion of anticancer drugs for as long as possible. Three of five patients demonstrated marked tumour regression with unexpectedly long survival (16 months in two patients and one still alive at 15 months). Carcinoembryonic antigen (CEA) levels decreased to almost normal in four patients who had initially high levels. The present experiences seems to indicate that long survival can be hoped for in patients with advanced gastric cancer with unresectable liver metastases.

Aged↗

Acute progressive and extensive metastatic calcifications in a nephrotic patient following chronic hemodialysis.

We report on a 46-year-old female patient with a 5-year history of refractory nephrotic syndrome who rapidly developed extensive metastatic calcifications in lung, bone, blood vessels, skin, uterus and other soft tissues following maintenance hemodialysis. She was admitted for controlling anasarca. On admission, she suffered from severe nephrotic syndrome and chronic renal failure, showing 1.3 g/dl of serum albumin and 4.6 mg/dl of serum creatinine. She received bicarbonate dialysis combined with extracorporeal ultrafiltration to control anasarca. Following hemodialysis, she was treated with alfacalcidol and an increasing dose of calcium carbonate. Although anasarca was controlled, her nephrotic state remained unchanged. After 3 months of dialysis, roentgenograms of the body disclosed multiple metastatic calcifications. At this time, though the calcium-phosphorous product in serum was almost normal, the free calcium index was confirmed to have been high for 4 weeks. We considered that administration of calcium carbonate and alfacalcidol as well as an influx of free calcium from a dialysate resulted in increased serum ionized calcium which may be unable to be bound to serum protein because of lack of total protein, leading to ectopic deposition of calcium and phosphate. Our findings suggested that intensive care is needed to prevent metastatic calcification when uremic patients with severe nephrosis are treated with bicarbonate hemodialysis.

Acute Disease↗

Magnetic resonance angiography in prostatodynia.

Three-dimensional magnetic resonance venography (3D MRV) of the prostate and the pelvic cavity was demonstrated in 8 normal subjects and 12 patients with prostatodynia. In all normal subjects and patients, 3D MRV images were successfully obtained. The deep dorsal vein of the penis sends major branches into the anterior and lateral capsular veins as well as into the internal pudendal vein. In patients with prostatodynia, the anterior and lateral capsular veins were much thicker in diameter than those in normal subjects, suggesting venous congestion. This congestion was also remarkable in the venous plexuses behind the bladder or along the lateral side of the pelvis in patients with prostatodynia. Another characteristic sign of the disease was a narrowing or an interruption of the internal pudendal vein. Prostatodynia is postulated to be caused by intrapelvic venous congestion.

Adult↗

Synthesis of possible metabolites of 1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl)- 4-oxo-3-quinolinecarboxylic acid (Grepafloxacin, OPC-17116).

Grepafloxacin (1-cyclopropyl-1,4-dihydro-6-fluoro-5-methyl-7-(3-methyl-1-piperazinyl )-4-oxo-3-quinoline-carboxylic acid, OPC-17116) (1) exhibits potent and broad-spectrum in vitro and in vivo antibacterial activity. In order to identify the structures of the metabolites of grepafloxacin, 17 possible metabolites were prepared. Among them, 6 compounds were found to be actual metabolites (2a, b, 4a, b and 6a, b) of grepafloxacin in rats, dogs and/or humans. The antibacterial activities of these metabolites were found to be weaker than that of grepafloxacin.

Animals↗

Synthesis of 4-(phenylamino)quinoline-3-carboxamides as a novel class of gastric H+/K+-ATPase inhibitors.

In search for inhibitors of gastric H+/K+-ATPase, 4-(phenylamino)quinoline-3-carboxamides were synthesized and evaluated for antisecretory activity against histamine-induced gastric acid secretion in rats. These compounds were synthesized by condensation of aniline derivatives with N-substituted 4-chloroquinoline-3-carboxamides, which were obtained from treatment of 4(1H)-quinolinone-3-carboxylic acid with thionyl chloride. Most of the compounds inhibited histamine-induced gastric acid secretion in rats. Among them, N-allyl-4-(2-ethylphenylamino)quinoline-3-carboxamide (4h) was the most potent inhibitor and had the best profile as a candidate antiulcer agent. This compound showed reversible, K+-competitive gastric H+/K+-ATPase inhibitory activity.

Animals↗

[Direct expression of the pig testicular 3 alpha/beta(20 beta)- hydroxysteroid dehydrogenase cDNA using baculovirus expression system].

The direct expression of the pig testicular 3 alpha/beta(20 beta)- hydroxysteroid dehydrogenase (HSD) cDNA using a baculovirus expression system was investigated. A minimum essential cDNA containing the coding region of 3 alpha/beta(20 beta)-HSD was amplified by polymerase chain reaction (PCR) to extend the DNA linker including the Bam HI restriction site in the both ends of the cDNA. As the template, 3 alpha/beta(20 beta)-HSD cDNA, pBS 52, which was subcloned to Bluescript II was used. The PCR fragment was ligated to Bam HI-cut transfer plasmid (pBlueBac III). Recombinant transfer plasmid (pBlueBac-20 beta) constructed was cotransfected into Spodoptera frugiperda Sf-9 cells with the baculovirus. After transfection, the recombinant virus was detected by the plaque assay with color selection. The expression of 3 alpha/beta(20 beta)-HSD cDNA was detected by Western blotting and enzyme assay. The expressed protein showed the same molecular weight and immunochemical cross-reaction to the native enzyme. Furthermore, it had 3-keto reductase activity of 3 alpha/beta(20 beta)-HSD for 5 alpha-dihydrotestosterone and 20-keto reductase activity for 17 alpha-hydroxyprogesterone in the presence of NADPH.

3-Hydroxysteroid Dehydrogenases↗

[Therapeutic effect of IGN-2098, a new antiulcer drug (H2-antagonist), in the ulcer diminishing period against acetic acid-induced gastric ulcer in rats].

The effects of IGN-2098 on the healing process of acetic acid-induced gastric ulcer was investigated in comparison with the other histamine H2-receptor antagonists, famotidine and roxatidine acetate HCl, in rats. Ulcer was induced by the injection of acetic acid solution (20%, 0.05 ml). From the 4th day to 17th day after the ulcer induction, drugs were orally administered twice a day. On the 18th day after the ulcer induction, rats were sacrificed to measure the ulcer index macroscopically and to take pictures of the stomachs. Judging from the photographs, the prominence of ulcer the edge was graded into 4 classes, which showed a significant correlation with the histological amount of connective tissue at the ulcer edge. All drugs accelerated the healing of the ulcer, and the effect of IGN-2098 was the most remarkable. In addition, IGN-2098-treatment exhibited more marked inhibition against the prominence of the ulcer edge as compared with the control group. Based on these results, it is concluded that IGN-2098 may be a useful drug for the clinical treatment of ulcer and that the healing acceleration by IGN-2098 without prominence of the ulcer edge may induce no relapse of the ulcer after healing.

Acetates↗

Inhibitory effect of phosphorylated oligosaccharides prepared from potato starch on the formation of calcium phosphate.

The inhibitory effect of phosphorylated oligosaccharides, which were prepared from potato starch, on the formation of calcium phosphate in vitro were investigated. Phosphorylated oligosaccharides from potato were fractionated by ion-exchange chromatography into two fractions, PO-1 and PO-2. Fraction PO-1 was composed of maltotriose, maltotetraose, and maltopentaose to which one phosphate group was attached. Fraction PO-2 was predominantly composed of maltopentaose and maltohexaose to which at least two phosphate groups were attached. The average degree of polymerization of dephosphorylated PO-1 and PO-2 was evaluated to be 4.02 and 5.82, respectively. Fraction PO-2 was the main component having an inhibitory effect on calcium phosphate formation. In addition, among the phosphorylated monosaccharides, glucose-1,6-diphosphate and fructose-1,6-diphosphate were more effective inhibitors of the formation of calcium phosphate than glucose-6-phosphate and fructose-6-phosphate. These results suggest that the strength of the inhibitory effect might depend on the number of phosphate groups attached to each sugar molecule.

Calcium↗

Renal dysfunction in multiple myeloma.

This study aims to determine the clinical factors that may affect renal function and patient survival in 82 multiple myeloma patients. The patients were divided into 3 groups according to their renal function during the initial 8 weeks after diagnosis: Group I, 54 patients with serum creatinine (S-Cr) < 177 mumol/L; Group II, 11 with S-Cr > or = 177 mumol/L and receiving no dialysis; Group III, 17 undergoing dialysis treatment. Clinical status at diagnosis, subsequent renal function and patient survival were compared. Bence Jones proteinuria (BJP) was found in all patients in Groups II and III, compared to 67% of patients in Group I (p < 0.05, I vs II or III). Hypercalcemia, hyperuricemia and intravenous administration of contrast medium, together with BJP each constituted independent risk factors of renal dysfunction. The incidence of hypercalcemia in Group II was significantly higher than in the other 2 groups. Patient survival was 26.8 +/- 23.7 months in Group I, 8.1 +/- 10.3 in II and 12.1 +/- 16.6 in III (p < 0.05, I vs II or III). Renal function and patient survival depended on the initial renal function. Renal function was likely compromised in the presence of BJP.

Female↗

[Efficacy of repeated hepatic dearterialization combined with intra-arterial infusion chemotherapy for unresectable tumors of the liver].

In the present study, repeated hepatic dearterialization combined with intra-arterial infusion chemotherapy was performed in patients with unresectable tumors of the liver. Of 36 patients, 16 had primary liver tumors (13 hepatocellular carcinomas and 3 cholangiocellular carcinomas), while 20 had metastatic tumors (7 gastric carcinomas, 10 colon carcinomas, 2 pancreatic carcinomas, and 1 gastric carcinoid). A significantly better survival outcome was found in those with intra-arterial infusion chemotherapy and those without cirrhosis. In the HCC cases, those with the therapy tended to show a better survival as compared with the natural history. Remarkable tumor regression was found in four (67%) of six patients with metastases of gastric cancer.

Aged↗

Cirrhotic livers can tolerate 30 minutes ischaemia at normal environmental temperature.

OBJECTIVE: To find out the safe time limit for Pringle's manoeuvre (compression of the hepatic artery and portal vein in the gastrohepatic omentum to halt bleeding) under normal environmental conditions for limited resection of cirrhotic livers. DESIGN: Prospective open study. SETTING: University hospital, Japan. SUBJECTS: Pringle's manoeuvre was used in 73 consecutive patients with hepatocellular carcinoma and cirrhosis (Child's classification: A = 44, B = 24, and C = 5), and in 20 patients it was not used (Child's classification: A = 11, B = 5, and C = 4). INTERVENTIONS: Limited hepatic resections were done with the duration of Pringle's manoeuvre ranging from 5 to 41 minutes. 15 patients simultaneously underwent 17 other abdominal operations. MAIN OUTCOME MEASURES: Child's classification, blood loss during operation, and duration of hepatic ischaemia. RESULTS: The morbidity and mortality with Pringle's manoeuvre were 1 (2%) and 0 in Child's A cirrhosis, 7 (29%) and 2 (8%) in Child's B cirrhosis, and 2 (40%) and 1 (20%) in Child's C cirrhosis. The higher rates in class B and C patients were ascribed to the amount of blood loss rather than to Pringle's manoeuvre. CONCLUSION: Pringle's manoeuvre can be used safely for up to 30 minutes during limited resection of the cirrhotic liver.

Adult↗