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M Ise

Publications and source records attributed to M Ise.

32 records · Page 2Linked to original sources

[Pathological study on the effect of oral adsorbent AST-120 on chronic renal failure in rats].

In order to evaluate the direct or indirect effect of AST-120 on chronic renal failure (CRF) in rats, histological and electron microscopical examinations were performed. A total of 30 Sprague-Dawley rats (aged 11 weeks and weighing 226 to 229 gm) with CRF induced by 5/6 nephrectomy were prepared. Rats were fed by a commercial diet (CE-2, Japan Kurea) and were divided into two groups: A (16 rats) and B (14 rats). AST-120 (5% content) was only administered to group B. After two months, kidneys were removed and prepared for the histological and electron microscopical examinations. On histological examination, group A kidneys showed severe glomerular hyalinization (more than 80%) and frequent crescents, as well as tubulo-interstitial fibrosis and many protein casts. In contrast, segmental glomerular lesions were identified in group B kidneys. Tubulo-interstitium were also well preserved. Furthermore, the ultrastructural findings of group B were milder than that of group A. The preservation of renal tissue in group B revealed the beneficial effect of AST-120 on CRF rats' kidneys. In conclusion, this beneficial effect is provided by the removal of the serum toxic metabolite (uremic toxin) and the precursor substance of the toxin by orally administered AST-120.

Administration, Oral↗

Effect of an oral adsorbent (AST-120) in rats with daunomycin-induced chronic renal failure.

The effect of an oral adsorbent (AST-120) was examined in rats with daunomycin-induced chronic renal failure. Sixteen pairs of daunomycin rats which had similar levels of proteinuria at 4 weeks after being injected with daunomycin were selected. One rat of each pair served as a control and was fed on a standard diet, while the other rats were fed on a diet containing AST-120. The blood creatinine and blood urea nitrogen (BUN) were significantly lower in the rats fed with AST-120 than in the controls. Moreover, the life span of the rats fed with AST-120 was significantly prolonged as compared to that of the control rats. These findings suggest that oral administration of AST-120 may help to prevent rapid deterioration of renal function in experimental chronic renal failure induced by daunomycin in rats.

Administration, Oral↗

Three-quarters nephrectomy in rats as a model of early renal failure.

To produce a compatible model of early renal failure easily, we prepared three-quarters nephrectomized animal. 20 Sprague-Dawley rats were divided into the following two groups: 10 rats which received three-quarters nephrectomy (Nx group), assuming the weight of both kidneys to be equal, and another 10 rats which underwent sham operations (S group). The levels of creatinine clearance in Nx group and S group were 286.5 +/- 33.5 vs. 431.1 +/- 55.9 microliters/min/100 g BW (P less than 0.001) on week 2, and 233.0 +/- 16.7 vs. 562.3 +/- 62.9 microliters/min/100 g BW (P less than 0.001) on week 10, respectively. The indirect and direct systolic blood pressure (SBP) values of Nx group and S group at the 10th week were 154.5 +/- 5.5 vs. 131.1 +/- 3.6 mmHg (P less than 0.01), and 148.2 +/- 4.8 vs. 130.7 +/- 6.6 mmHg (P less than 0.01), respectively. Significant changes in the levels of urinary protein excretion, urinary sodium output, urinary epinephrine, urinary norepinephrine and plasma renin activity between both groups were recognized on the 10th week. The planar area of Nx group was significantly increased as compared to that of S group (11.0 +/- 0.3 vs. 7.2 +/- 0.1 x 10(-3) mm2, P less than 0.001). It is concluded that this model resembles early renal failure in humans because slow progression of renal dysfunction occurred with mild elevation of SBP, and that it is adequate for evaluating the influence of glomerular hypertrophy, resulting in glomerulosclerosis.

Animals↗

[Effect of oral sorbent, AST-120, on serum concentration of indoxyl sulfate in uremic rats].

Indoxyl sulfate is a metabolite of tryptophan. Indole is synthesized in intestine from tryptophan by intestinal bacteria. The absorbed indole is converted to indoxyl sulfate through indoxyl in liver. Serum concentration of indoxyl sulfate is markedly increased as an inhibitor of drug-binding in uremic patients as compared with healthy subjects. Since indoxyl sulfate is bound to serum albumin, it cannot be removed efficiently by hemodialysis, and it tends to accumulate in uremic serum. To determine if oral sorbent, AST-120, could adsorb indole in intestine and then decrease serum concentration of indoxyl sulfate, it was administered to nephrectomized uremic rats. Serum concentration of indoxyl sulfate was markedly decreased in uremic rats fed with oral sorbent as compared with control uremic rats. However, serum concentrations of creatinine and urea nitrogen were not significantly decreased in the uremic rats fed with oral sorbent as compared with the control uremic rats. Serum concentration of tryptophan was not decreased but rather increased in the uremic rats fed with oral sorbent as compared with the control uremic rats. Concentration of indoxyl sulfate in bile of a uremic rat was much lower than that in the uremic serum, suggesting that the adsorption of indoxyl sulfate in intestine is not a major mechanism of decreasing the serum concentration of indoxyl sulfate. These results demonstrate that oral sorbent, AST-120, can decrease serum concentration of indoxyl sulfate in uremia due to adsorption of indole in intestine.

Administration, Oral↗

Osseous changes and abnormalities of mineral metabolism in daunomycin rats.

We examined whether daunomycin rats could be used as an experimental model of human chronic renal failure in terms of their osseous changes and mineral metabolism. The daunomycin rats revealed hyperphosphatemia and osteodystrophic bone changes. In this respect, they were similar to human chronic renal failure. A high calcium level was found in the daunomycin rats at first due to the effect of the daunomycin injection, but later there was a lower calcium level than in the control rats due to chronic renal failure. We conclude that daunomycin rats can be successfully used as an experimental model of chronic renal failure from the standpoint of their osseous changes and mineral metabolism.

Animals↗

[The effects of oral adsorbent (AST-120) in the experimental model of chronic renal failure--pathophysiological study on renal function, glomerular hypertrophy, mesangial function and glomerular histology].

Oral adsorbent (AST-120) reduces blood levels of urea and creatinine in experimental studies. It has also been shown to retard the progression of chronic renal failure in clinical studies. In the present study, the effect of AST-120 was examined in the rat model of subtotal nephrectomy (sNPX). This experimental model of chronic renal failure is characterized by glomerular hyperfunction, glomerular hypertrophy, increased mesangial trapment of macromolecules and subsequent glomerular sclerosis. We report the effect of AST-120 on glomerular hyperfunction, glomerular hypertrophy and mesangial trapment of macromolecules in the early stage and glomerular function and histology in the late stage of the rat model of sNPX. From 2 days after sNPX, rats were fed regular rat chow with (AST group: AST) or without (control) AST-120. At 2 weeks, iron dextran (ID) was injected intravenously. Three days after the injection, mesangial trapment of ID was largely ameliorated in AST when compared with control (p less than 0.02). The value of mean planar area of glomerulus (PAmean) in AST was significantly lower than that in control (p less than 0.05). At 2 and 9 weeks, the values of GFR and RPF in AST were all statistically higher than those in control. At 9 weeks, whereas average glomerular sclerosis index (SI: 0-4 scale) was 1.07 in control, significantly lower SI (0.57) was noted in AST (p less than 0.05). Thus, AST-120 has effects on glomerular hypertrophy, increased mesangial trapment of macromoleculus and finally the progression of chronic renal failure in the rat model of sNPX. The effects are not through reducing glomerular hyperfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

[Daunomycin rats. Second Report. Is it possible to use daunomycin rats as an experimental model of chronic renal failure?].

We have previously reported that daunomycin rats can be used as an experimental model of chronic renal failure. We have since studied whether the result were reproducible by repeating the experiment. In this experiment we used larger numbers of rats and many more parameters of investigation compared with the previous experiment. The period of observation was extended to 42 weeks. Twenty-one female Wistar rats were given an injection of 12 mg/Kg of daunomycin into the jugular vein by the one-shot method. Ten control rats were injected with physiological saline. Eighteen daunomycin rats developed chronic renal failure within the observation period. Renal failure was confirmed by the levels of BUN and creatinine, the uremic peak 2a and the pathological findings. One rat died from a tumor and another rat died from thrombosis of the descending aorta. In only one rat was not at the level defined as chronic renal failure, although it was impaired even in this case. There was a correlation between the lifespan of the daunomycin rats and the amount of urine protein at 4 weeks. Rats with heavy proteinuria at 4 weeks died of uremia at an early age. There was a variety of evidence of daunomycin damage when rats were autopsied, not only in the renal glomeruli but also in the pancreas, liver and spleen. Some parts of the pancreas and liver showed vacuolated cells. We supposed that these various changes of many internal organs of daunomycin rats were secondary changes for chronic renal failure. We reconfirmed that daunomycin rats can be used as an experimental model of chronic renal failure.

Animals↗

The clinical features of spasms in patients with a cervical cord injury.

A study concerning subjective symptoms of spasms which occur during 24 hours was carried out in 13 quadriplegic patients. All had spasms. Tonic and clonic spasms occurred involving their limbs and trunk. Extensor spasms occurred more often in the lower limbs than in the upper limbs. The duration of spasms was 8 seconds on average and the frequency was 15 times on average per day. The spasms which were severe tended to last longer in duration and were more frequent in occurrence. No spasms occurred without a trigger. The activities in daily living were interfered with by spasms in most patients. Most of these activities also triggered spasms.

Activities of Daily Living↗

[Effect of oral-adsorbent (AST-120) in chronic renal failure (CRF) in rats].

The progression of renal failure has been suggested to be altered by dietary manipulation of protein based on the presumption that the progressive nature of CRF may be caused by the vicious cycle driven by some toxic metabolite uncleared by failing kidney. We studied 29 female Sprague-Dawley rats aged 12 weeks weighing 226 to 290 gm subjected to a 5/6 nephrectomy. 2 days after, group C (16 rats) were given a commercially prepared diet (CE-2, Japan Kurea). While group A (13 rats) were given the same diet and 5% AST-120. Initial serum creatinine of both group was 2.2 mg/dl. After 9 weeks, all surviving rats were sacrificed for evaluation of renal histology. During the observation period, survival rate, Ccr, urinary creatinine and urea excretion were significantly better in group A rats. Result also showed a better weight increase with concomitant increase in protein catabolic rate in group A rats. These result showed the beneficial effect of AST-120 in uremic rats in terms of survival rate and delaying the progression of CRF despite the presence of increased protein catabolic rate. Based on this study, one way of preventing the progression of renal failure is through removal of some toxic metabolite in the gastrointestinal tract by the use of oral adsorbent as exemplified by AST-120.

Age Factors↗

Digital nerve grafts in replanted digits.

In most cases where digits have been amputated by avulsion and the digital nerve extensively injured, primary nerve suture cannot be performed. For such a digit when replanted, secondary nerve grafting was done under the operating microscope using a lateral femoral cutaneous nerve. Two years after operation, two-point discrimination of these cases proved to be 10.5 mm on average. And in the case of the transplanted three strand cable graft, using a lateral femoral cutaneous nerve yielded the most favourable results. The replacement was superior to the side receiving primary crushed nerve suture. Sensory nerve action potentials indicate that the regenerated nerve does not necessarily mature sufficiently. The recovery of sensitivity even to this degree however was sufficient for the replanted digits to be useful in all cases.

Action Potentials↗