Hepatobiliary and pancreatic: splenic artery aneurysm after liver transplantation.
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Adult↗
Biomedical subjects
M Akahane
Publications and source records attributed to M Akahane.
Bone viability of amputated limbs treated with hypothermia: assessment by evaluation of mRNA levels.
We evaluated rat bone viability using a bone viability index (BVI). To evaluate hypothermic ischaemic bone injury, 21 amputated hind limbs of Fischer rats were preserved at hypothermia (4 degrees C) for 1, 3 and 6 hours. To evaluate hypothermic ischaemia/reperfusion injury, another 28 amputated limbs were transplanted to recipient rats after hypothermic ischaemia for 3 and 6 hours, respectively. Total RNA isolated from each tibia was fractionated by electrophoresis and hybridised with 32P-labelled cDNA of GAPDH, and the radioactivity of intact and degraded GAPDH mRNA measured. BVI was calculated as follows, BVI = [A / (A + B)] x 100, where A and B represent the radioactivities corresponding to intact and degraded GAPDH mRNA bands, respectively. In the hypothermic ischaemic insult group, BVIs were comparable to those of controls. However, in the 3-hour hypothermic ischaemia/reperfusion group, BVI was lower than that of the controls. Likewise, there was a significant difference between the 6-hour ischaemia/reperfusion group and controls. These results showed that bone viability decreased even after just a 3-hour hypothermic ischaemia/reperfusion.
Animals↗
Viability of hypothermic preserved muscle determined by gene expression levels.
We report a muscle viability index (MVI) that reflects mRNA degradation. The viability of hypothermically preserved (48C) rat skeletal muscle was evaluated using this MVI. To evaluate the hypothermic ischaemic insult of the muscle, 21 hind limbs of Fischer rats (three subgroups of seven limbs each) were hypothermically preserved for 1h, 3h and 6h, before harvesting the tibialis anterior muscle. To investigate reperfusion injury after hypothermic preservation, an additional 28 limbs were transplanted to recipient Fischer rats after hypothermic ischaemia for either 3h or 6h. The transplanted muscles were harvested on either day 3 or day 7 after transplantation. Seven fresh muscles were also harvested, and used as controls. In the 3h ischaemia group, the MVIs of both the hypothermic-ischaemia and the ischaemia-reperfusion subgroups were comparable to the controls. Likewise, there were no significant differences between the controls and the 6h hypothermic ischaemia and ischaemia-reperfusion subgroups. These results show that muscle viability is maintained with hypothermic preservation of up to 6h, and after reperfusion. Therefore, in clinical replantations the amputated extremity should be preserved under hypothermic conditions from the time of injury to the time of surgery.
Animals↗
Static scapholunate dissociation diagnosed by scapholunate gap view in wrists with or without distal radius fractures.
This prospective study investigated static scapholunate dissociation (SLD) in wrists associated with distal radius fractures. SLD was detected as a widening of the scapholunate (SL) joint interval by SL gap view. Ninety-six distal radius fractures and 154 normal wrists were investigated by SL gap view, which is better for detecting SLD than the standard posteroanterior (PA) view. Incidences of non-symptomatic SLD detected by SL gap view in normal wrists increased by age. In the young age bracket, incidences of SLD in distal radius fractures were significantly higher than in normal wrists. Our results indicated that in patients younger than 30 years old, SLD in distal radius fractures was a fracture-caused abnormality. In those over 30, ascribing SLD to the fracture was difficult. Close examinations, like arthroscopy and dynamic cineradiography, need to be made in patients with SLD associated with distal radius fractures, especially in those younger than 30.
Adolescent↗
False positive uptake of metaiodobenzylguanidine in hepatocellular carcinoma.
We present the case of a patient who showed increased accumulation of (123)I-metaiodobenzylguanidine (MIBG) in hepatocellular carcinoma, leading to a false presumptive diagnosis of intrahepatic neuroendocrine tumour. The increase in uptake was not seen on images obtained 4 h after tracer injection but was evident on those taken after 24 h, suggesting slower washout from the liver tumour than from non-tumoural liver parenchyma. Our observations indicate that a non-neuroendocrine malignant tumour may exhibit high accumulation of MIBG associated with prolonged retention.
3-Iodobenzylguanidine↗
Discovery of novel N-phenylglycine derivatives as potent and selective beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence.
With a novel assay using isolated ferret detrusor to estimate beta(3)-adrenoceptor agonistic activity, we found that a series of glycine derivatives of ritodrine, a beta(2)-adrenoceptor agonist, are potent beta(3)-adrenoceptor agonists, with excellent selectivity versus beta(1) and beta(2) subtypes. Substitution of halogens in the phenyl ring increased potency and selectivity for the beta(3)-adrenoceptor, and this was dependent upon the position of the halogens. The chlorine-substituted derivatives 3f-i exhibited potent beta(3)-adrenoceptor-mediated relaxation of ferret detrusor (EC(50) = 0.93, 11, 14, and 160 nM) and higher potency at beta(3)-adrenoceptors than at beta(1) or beta(2). The intravenous administration of 3h significantly reduced the urinary bladder pressure in anesthetized male rats (ED(50) = 48 microg/kg) without cardiovascular side effects. This article is the first report of structure-activity relationships (SAR) concerning beta(3)-adrenoceptor agonists as agents for the treatment of urinary frequency and incontinence.
Adrenergic beta-Agonists↗
Viability of ischemia/reperfused muscles in rat: a new evaluation method by RNA degradation.
The rat's skeletal muscle viability was evaluated using the muscle viability index (MVI) which reflects the mRNA degradation. To evaluate ischemic injury of the muscle, 24 hind limbs of Fischer rats (three subgroups of eight rats each) were preserved at normothermia for 1, 3 and 6 h and then tibialis anterior muscle was harvested. To investigate ischemia/reperfusion injury, another 48 limbs were transplanted to recipient Fischer rats after the ischemia at normothermia for 1, 3 and 6 h, respectively. The transplanted muscles were harvested on day 3 and day 7 after transplantation. Eight fresh muscles were also harvested and used as control. Total RNA isolated from each muscle was fractionated by electrophoresis and hybridized with 32P-labelled cDNA of GAPDH, and the radioactivity of intact and degraded GAPDH mRNA was measured. MVI was calculated as follows, MVI = [X/(X + Y)] x 100, where X and Y represent the radioactivities corresponding to intact GAPDH and degraded GAPDH mRNA band, respectively. In 1-h ischemia group, the MVI indices of both ischemic insult and ischemia/reperfusion group were comparable to control. In the 3-h ischemia group, the index of ischemia/reperfused group was comparable to control although the index of ischemic insult group was significantly lower than control. However, in the 6-h ischemia group, both indices of ischemic insult and ischemia/reperfusion group were significantly lower than control. These results show that the muscle damage was detected in ischemia at normothermia even after 3 h. However, this damage was overcome by reperfusion. There was no recovery from damage in muscles that had been preserved for more than 6 h which had resulted in irreversible degeneration. Therefore, in clinical muscle transplantation, one has to transplant the muscle at least within 3-h ischemia.
Animals↗
Beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acid.
In a search for novel analogues of beta(3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure had been incorporated, were synthesised. Compound 1a was found to be a selective beta(3)-AR agonist in functional assays using the ferret detrusor (beta(3)-AR), rat uterus (beta(2)-AR), and rat atrium (beta(1)-AR); beta(3): EC(50)=7.8 nM, beta(2): IC(50)=7,300 nM, beta(1): EC(20)=23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of 1a further improved beta(3)-AR selectivity. In an in vivo study, 1a lowered intrabladder pressure (ED(50)=31 microg/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that 1a and its analogues (1b-e), possess beta(3)-AR agonistic activity in the absence of undesirable beta(1)- or beta(2)-AR mediated actions, and may be useful for clinical treatment and pharmacological studies.
Adrenergic beta-3 Receptor Agonists↗
KRH-594, a new angiotensin AT1 receptor antagonist, prevents end-organ damage in stroke-prone spontaneously hypertensive/Izm rats.
1. In the present study, we examined whether KRH-594, a new angiotensin AT1 receptor antagonist, would stop the progression of renal failure and end-organ damage and improve the survival rate in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. Oral administration of KRH-594 (3 and 10 mg/kg per day) for 11 weeks significantly reduced systolic blood pressure, urinary total protein, blood urea nitrogen, serum creatinine and urinary N-acetyl glucosaminidase and increased creatinine clearance in SHRSP/Izm. 3. In a histological study, KRH-594 (3 and 10 mg/kg per day) significantly improved the glomerulosclerosis, basophilic change and hyalin cast of tubules, proliferation of afferent arterioles and interlobular artery wall scores of the kidney and the cardiac fibrosis scores of the heart in SHRSP/Izm. KRH-594 (3 and 10 mg/kg per day) also significantly inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day) prevented death in SHRSP/Izm during the examination period. 5. These results suggest that KRH-594 improves hypertensive complications, such as renal failure, cardiac hypertrophy and thickening of the artery wall, and prevents death in salt-loaded SHRSP/Izm.
Angiotensin Receptor Antagonists↗
Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats.
1. In the present study, we investigated the prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by either single (15 Gy) or repeated (8.6 Gy x3 days) X-ray irradiation in rats. Pilocarpine hydrochloride was administered orally 90 min before each irradiation session. Then, 7 days later, salivary volume, amylase activity and protein concentration in the saliva secreted from the right parotid gland were measured before and after a subsequent administration of pilocarpine hydrochloride (intraduodenal). 2. In irradiated no-pretreatment rats, irradiation induced a significant reduction in both spontaneous and pilocarpine hydrochloride-stimulated secretion (both total salivary volume and flow rate), regardless of the protocol used for X-ray exposure. In irradiated, pilocarpine hydrochloride-pretreated rats, salivary secretion was increased after stimulation by pilocarpine hydrochloride (intraduodenal) to a degree that depended on the pretreatment dose of pilocarpine hydrochloride (p.o.) in both xerostomia models. 3. There were no differences in amylase or protein concentrations between irradiated rats pretreated with pilocarpine hydrochloride and irradiated no-pretreatment control rats. 4. A decrease in the weight of the parotid gland was observed in rats exposed to either the single dose or repeated irradiation protocols. Changes in the submandibular gland were less marked than those in the parotid gland. These changes in gland weight were not affected by pilocarpine hydrochloride pretreatment. 5. The responsiveness of the parotid gland to subsequent stimulation with pilocarpine hydrochloride was apparently preserved in both xerostomia models by pretreatment with pilocarpine hydrochloride, which itself increased salivary secretion. This suggests that pilocarpine hydrochloride may exert functional protective effects against xerostomia that occurs following irradiation therapy through a stimulation of salivary secretion.
Animals↗
Viability of ischemia/reperfused bone determined at the gene expression level.
Rat bone viability was evaluated, using a bone viability index (BVI) that reflects mRNA degradation. To evaluate ischemic injury of the bone, 28 amputated hind limbs of Fischer rats (ischemic insult group: four subgroups, each containing seven limbs) were preserved at normothermia for 1, 3, 6 and 9 hr and the tibiae were harvested. To investigate ischemia/reperfusion injury, another 42 amputated limbs were transplanted to recipient Fischer rats after ischemia at normothermia for 1, 3 and 6 hr, respectively. The tibiae from the transplanted limbs were harvested on day 3 and day 7 after the transplantation (ischemia/reperfusion group). Seven fresh tibiae were also harvested and used as controls (control group). The total RNA isolated from the tibia of each group was fractionated by electrophoresis and hybridized with 32P-labelled cDNA of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the radioactivity of intact and degraded GAPDH mRNA was measured. BVI was calculated as follows: BVI = [A/(A + B)] x 100, where A and B represent the radioactivities corresponding to the intact GAPDH and degraded GAPDH mRNA band, respectively. In the 1-hr and 3-hr ischemia groups, the BVIs of the ischemia/reperfused group were comparable to those of controls, although the indexes of the ischemic insult group were significantly lower than controls. However, in the 6-hr ischemia group, indexes of both the ischemic insult and ischemia/reperfusion groups were significantly lower than controls. These results demonstrated that bone damage was detected with ischemia at normothermia even after 1 hr; however, this tissue damage was overcome by reperfusion. There was no recovery from damage in bones that had been preserved for more than 6 hr, resulting in irreversible degeneration. Therefore, in clinical vascularized bone grafts, it appears that transplantation should be done within a 3-hr ischemic period for it to be successful.
Animals↗
Radiological findings of accidental radiation injury of the fingers: a case report.
This case report describes the medical follow-up of a 46-y-old (at the time of exposure) man who in 1971 accidentally exposed the fingers of his right hand to gamma-ray radiation from an iridium source that was used for nondestructive testing [estimated radiation dose: 26 Gy to 90 Gy (2,600 rad to 9,000 rad)]. No prominent acute injury was detected except for leukocytopenia (800 mm(-3)) and thrombocytopenia (15,000 mm(-3)). Three years later, the first, second, and third fingers presented repeated infection and started to develop contracture. Twenty-two years after exposure, he underwent amputation of the first and second fingers, and a toe graft was done. Radiological examinations prior to and following the operation revealed atrophic change of the finger bones and arterial injuries. Angiographic findings coincided with the region and extent of radiation injury of the fingers, which indicates that arterial damage is involved in the development of this chronic disorder.
Angiography↗
Relaxant effects of isoproterenol and selective beta3-adrenoceptor agonists on normal, low compliant and hyperreflexic human bladders.
PURPOSE: We compared the relaxant effects of the stimulation of beta-adrenoceptors with isoproterenol and of drugs selective for beta-adrenoceptor subtypes in detrusor preparations from patients with normal and neurogenic bladder, respectively. MATERIALS AND METHODS: We studied in vitro preparations of a cystometrically normal, low compliant and hyperreflexic bladder from 45, 26 and 7 patients, respectively. RESULTS: Isoproterenol relaxed concentration dependently and with the same potency as detrusor preparations obtained from normal and neurogenic bladders. In 37 normal detrusor, 25 low compliant and 7 hyperreflexic cases pD2 values were 6.36, 6. 25 and 6.38, respectively. Maximal relaxation did not differ significantly among the 3 groups (about 80% of 10-5 M. forskolin induced relaxation). Neither the beta1-/beta2-adrenoceptor agonist dobutamine nor the beta2-adrenoceptor agonist procaterol produced any significant relaxation of preparations from the 3 groups at a concentration of up to 10-5 M. At a concentration of 10-4 M. the preparations were relaxed but neither of these effects reached a maximum. BRL37344A and CL316243, selective beta3-adrenoceptor agonists and CGP-12177A (a selective beta3-adrenoceptor partial agonist and beta1-/beta2-adrenoceptor antagonist) relaxed detrusor preparations from the normal, low compliant and hyperreflexic groups when applied at concentrations greater than 10-6 M. For each agonist the pD2 value did not differ significantly among the 3 groups. CONCLUSIONS: beta-adrenoceptor stimulation is an effective way of relaxing the human detrusor and the effect is similar in normal and neurogenic bladders. A major portion of the relaxant effect of isoproterenol is mediated via beta3-adrenoceptor stimulation. Clinical trials may reveal whether this method is useful for treating bladder overactivity.
Adrenergic beta-Agonists↗
Plasma digoxin concentration in dogs with mitral regurgitation.
Fifteen and eight mature beagles, without (normal group) and with experimental mitral regurgitation (MR group), respectively, were given 0.02 mg/kg/day digoxin powder for 10 days orally. The optimum time for sample collection after administration of digoxin was observed to be 8-18 hr and 10-22 hr in the normal and MR groups, respectively. In both groups, a stable concentration was reached after 3-5 days of treatment. No differences in plasma level were observed between sexes. The optimum concentration of digoxin was attained at an earlier stage than has been previously reported for both dogs and humans.
Animals↗
Pharmacological characterization of KUR-1246, a selective uterine relaxant.
The aim of the present study was to evaluate the efficacy and beta 2-adrenoceptor (AR) selectivity of KUR-1246, a new uterine relaxant. Inhibition of spontaneous or drug-induced uterine contractions by KUR-1246 was evaluated in pregnant rats and rabbits by an organ bath method or by a balloon method. The selectivity of KUR-1246 was assessed simultaneously in organs isolated from late-pregnant rats. The affinity of KUR-1246 for human beta 1-, beta 2-, and beta 3-ARs was determined using two radioligands. KUR-1246 suppressed both spontaneous and drug-induced contractions in isolated uteri, the rank order of potency being isoproterenol > KUR-1246 > terbutaline > ritodrine. ICI-118551 (selective beta 2-AR antagonist) competitively antagonized the KUR-1246-induced inhibition of spontaneous uterine contractions, but CGP-20712A (selective beta 1-AR antagonist) and SR-58894A (selective beta 3-AR antagonist) did not. All beta-AR agonists tested produced significant inhibition of spontaneous uterine contractions in vivo: ED(30) value for KUR-1246 was 0.13 microg/kg/min, a potency about 6 times and 400 times greater than that of terbutaline and ritodrine, respectively. In contrast, the positive chronotropic effect was minimal in KUR-1246-treated rats. KUR-1246 displaced radioligand binding to beta 1-, beta 2-, and beta 3-ARs, the pK(i) values being 5.75 +/- 0.03, 7.59 +/- 0.08, and 4.75 +/- 0.03 for beta 1-, beta 2-, and beta 3-ARs, respectively. For the selectivity of KUR-1246 for human beta 2-AR, we obtained values of 39.2 ([IC(50) for beta 1-AR]/[IC(50) for beta 2-AR]) and 198.2 ([IC(50) for beta 3-AR]/[IC(50) for beta 2-AR]), indicating an apparently higher affinity for human beta 2-AR than for other beta-AR subtypes. The present study clearly demonstrated that KUR-1246 is a more selective beta 2-AR agonist than the drugs presently used for relaxing uterine muscle.
Acetamides↗
[Transcatheter arterial chemoembolization using autologous blood clot for the treatment of hepatocellular carcinoma: long-term results of treatment and prognostic factors].
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Blood Coagulation↗
Characterization of beta-adrenoceptor subtypes in the ferret urinary bladder in vitro and in vivo.
In the present study, the beta-adrenoceptor subtypes distributed in the detrusor of the ferret were investigated in functional experiments in vitro and in vivo using a variety of beta-adrenoceptor agonists and antagonists. All the beta-adrenoceptor agonists tested relaxed the isolated detrusor strip, the rank order of potency being (+/-)-(R*, R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]phenoxy]- acetic acid sodium (BRL 37344A)>(+/-)-4-(3-t-butylamino-2-hydroxypropoxy) benzimidazol-2-one (CGP-12177A), isoprenaline and (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate (CL 316,243)>dobutamine and procaterol. In antagonist experiment, 3-(2-allylphenoxy)-1-[(1S)-1,2, 3,4-tetrahydro-naphth-1-ylamino]-(2S)-2-propanol hydrochloride (SR 58894A), but neither 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidaz ole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate (CGP-20712A) nor erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylaminob utan-2-ol hydrochloride (ICI-118,551), caused a rightward shift of the concentration-relaxation curve for isoprenaline. In in vivo experiments, isoprenaline and CL 316,243 each reduced bladder pressure in a dose-dependent manner. CL 316,243 was the only drug that did not produce any significant influences on blood pressure and heart rate at doses that reduced bladder pressure. The present functional study provides the first evidence that relaxation of the ferret detrusor by beta-adrenoceptor activation is mediated mainly via the beta(3)-adrenoceptor, as in the human detrusor.
Adrenergic beta-Agonists↗
Three-dimensional computed tomography for reoperative minimally invasive coronary artery bypass.
We have been using three-dimensional computed tomography (3-D CT) in reoperative coronary artery bypass grafting performed by using a minimally invasive approach. Preoperative 3-D CT scanning can provide beneficial anatomical information about old patent grafts as well as the internal thoracic artery. Thus a mini-thoracotomy can be created at an optimal site, leaving the old graft untouched, and the length of the harvested internal thoracic artery, necessary for the bypass, can be assessed using this new modality.
Coronary Artery Bypass↗