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Biomedical subjects

K Umezu

Publications and source records attributed to K Umezu.

At least 73 records · Page 4Linked to original sources

[Suppressive effect of tritoqualine (TRQ) on the acceleration of fibrosis in the liver].

Liver cirrhosis was induced by consecutive CCl4-treatment of rats (0.5 ml/kg, s.c., 2 times/week) to investigate the effect of TRQ on the acceleration of fibrosis in the liver. An increase of hydroxyproline content in the liver of rats began 12 weeks after the CCl4 treatment and a 1.9-fold increase was observed at week 14 compared with non-CCl4 treated rats. Histamine in the liver increased about 2 times at week 14. Increased numbers of mast cells were seen in the area of proliferated collagen fiber in the liver under microscopic observation, and also a good correlation was recognized between the number of mast cells and the progression of fibrosis. An administration of TRQ to the rats for 2 weeks from week 13 resulted in significant suppression of both the increase in hydroxyproline and histamine in the liver dose-dependently compared with the CCl4 control group. Both progression of collagen and increase in mast cell numbers were also suppressed by TRQ dose-dependently under histopathological observation; at the same time the decrease in mast cells was recognized to correspond to the decrease in hydroxyproline and histamine in the liver. Thus, it was suggested that increased mast cells participated in the biosynthesis of collagen. Though the elevated serum transaminases, alkaline phosphatase and leucine amino peptidase were also suppressed by TRQ administration, the protein biosynthesis activity of the liver and lowered serum total cholesterol were not improved as much as the other parameters. From these results, it was shown that TRQ was especially and remarkably effective in suppressing the acceleration of fibrosis, and one of the pharmacological mechanisms of this action may be ascribed to the inhibitory effect of TRQ on the activation of mast cells by some stimulants.

Animals↗

Suppressive effects of tritoqualine on cell growth and collagen secretion in fibroblasts.

The effects of tritoqualine (TRQ) on established cell lines of fibroblasts, Balb/3T3 and 3T6, were investigated with respect to growth and collagen secretion. TRQ suppressed growth rate in the log phase and inhibited collagen secretion in the stationary phase of both cell lines. However, TRQ was not cytotoxic because of lack of influence on cell maintenance in the stationary phase. These effects of TRQ are thought to be very important as a mechanism of inhibitory action against liver fibrosis in chronic liver injury in rats.

Animals↗

Suppressive effect of tritoqualine on lipid peroxidation and enzyme leakage induced by carbon tetrachloride in rat hepatocytes.

Since tritoqualine (TRQ) is effective in suppressing the increase of serum transaminases in acute hepatic injured rats induced by some hepatotoxins, protection of the hepatocyte membrane is suggested to be one of the pharmacological effects of TRQ. In the present study, we investigated the effects of TRQ on lipid peroxidation and enzyme leakage caused by carbon tetrachloride (CCl4) exposure in isolated hepatocytes and the liver in vivo, compared with vitamin E. The results were as follows: Hepatocytes isolated from TRQ-administered rats showed less enzyme leakage than those from control rats after CCl4 addition. TRQ displayed strong inhibition of lipid peroxidation in isolated hepatocytes. In comparison with vitamin E, TRQ showed almost the same inhibitory action on lipid peroxidation, but a stronger suppression of enzyme leakage. Vitamin E showed a weaker protection from increase of glutamic oxaloacetic transaminase than TRQ, in spite of its stronger inhibition of lipid peroxidation in vivo. From these results, it is suggested that the membrane protecting action of TRQ is partially derived from its suppression of lipid peroxidation, but "another action" may also play an important role in protecting the fragile membrane.

Alanine Transaminase↗

[Concomitant therapy with cefmenoxime and cefsulodin for refractory complicated urinary tract infection (especially caused by Pseudomonas aeruginosa)].

Cefmenoxime (2 g) and cefsulodin (1 g) were given twice daily for 5 days by concomitant intravenous drip infusion (mixed infusion) to 135 patients with complicated urinary tract infection (c-UTI) probably caused by Pseudomonas aeruginosa. The clinical efficacy was evaluated according to the criteria proposed by the UTI committee in Japan. Ninety one subjects met the criteria for c-UTI and were evaluable for drug efficacy. P. aeruginosa was detected in 44 cases (including mixed infection with other organisms). The overall efficacy rate was 73% of the 91 cases; 75% of the 44 cases with P. aeruginosa and 70% in the 47 cases without P. aeruginosa infection. As to bacteriological response, the eradication rate was 91% (105/116) for all cases. By organism, the eradication rate for P. aeruginosa, Serratia spp. and Citrobacter spp. were 82 (36/44), 100 (12/12) and 100% (10/10), respectively. The eradication rate for gram-negative rods was 93% (99/107). Twenty-three strains appeared after treatment, and the majority of them (13) were yeast-like organisms. There was only one strain of P. aeruginosa. As for side effects, eruption was found in 2 cases. Cefmenoxime and cefsulodin were administered concomitantly to patients with c-UTI which was suspected to be caused by P. aeruginosa. The high overall efficacy rate of about 70% on the average was obtained regardless of the causative organism and disease state. The eradication rate of as high as about 90% was obtained excluding Enterococcus faecalis. Neither severe side effects nor abnormal laboratory values were found. It appeared, therefore, that this dosage regimen was useful for the treatment of refractory complicated urinary tract infection.

Anti-Infective Agents, Urinary↗

[A case of bladder tumor with brain metastasis].

We report a case of bladder tumor with multiple metastases including the brain. Bladder tumor is the most common malignancy in uroepithelial tumor, but brain metastasis from bladder tumor is extremely rare. Since 1970 only 8 cases have been reported in Japan. The literature was reviewed.

Adult↗

[Pharmacokinetics of cefixime in patients with impaired renal function].

Cefixime (CFIX) was given orally in a single dose of 100 mg to 7 patients with varying degrees of impaired renal function (Ccr 12.0-56.7 ml/min) and serum concentrations and urinary excretion rates were measured with time for the first 24 hours by the bioassay method to investigate in vivo pharmacokinetics of the drug. The results obtained are summarized as follows. The mean peak serum concentration of CFIX in 3 patients with moderately impaired renal function (group I: Ccr greater than or equal to 30-less than 60 ml/min) was 2.04 micrograms/ml at 6 hours after dosing and gradually declined to 0.10 microgram/ml at 24 hours after dosing. The half-life was 4.15 hours. The mean peak serum concentration of CFIX achieved was 2.27 micrograms/ml at 8 hours after dosing in 4 patients with severely impaired renal function (group II: Ccr greater than or equal to 10-less than 30 ml/min) and the concentration of CFIX was 0.99 microgram/ml even after 24 hours. The half-life was prolonged to 11.05 hours. There was no great difference between groups I and II in the first 24-hour urinary excretion rates. However, the first 4-hour urinary excretion accounted for 2.14% of the administered dose of CFIX in group I but only 0.47% in group II. Urinary concentrations of CFIX peaked at 4-6 hours after dosing in both groups, and thereafter gradually decreased in group I. Whereas, they did not decline much in group II until 24 hours after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Change of hepatic histamine content during hepatic fibrosis.

Hepatic function was studied by measuring the time courses of several variables in blood and liver using a chronic liver-injury model produced by administering CCl4 consecutively for 12 weeks in rats. A marked increase in liver histamine content occurred after 10 weeks of treatment with CCl4. At weeks 10 and 12, liver histamine levels in the CCl4-treated group were 1.95 and 4.61 times higher, respectively, than in the control group. This change in liver histamine content appeared after that in other variables such as glutamic pyruvic transaminase, alkaline phosphatase, and white blood cells, but it corresponded to a change in liver hydroxyproline. Increased mast cells were seen in fibrotic foci around Glisson's sheath by microscopic morphological observation of the liver 12 weeks after treatment with CCl4. The histamine concentration in plasma tended to decrease after CCl4 treatment, and at week 12 the decrease was statistically significant compared with control. The liver activities of histamine-metabolizing enzymes, histamine-N-methyltransferase and histaminase, decreased to 1/3.4 and 1/6.0 times those of the nontreated group, respectively, 12 weeks after treatment with CCl4, whereas blood histaminase increased about 9.2 times. The increase in histamine content in injured liver was presumedly derived from the increase in mast cells in the inflamed area of the liver; also, the deficiency of histamine-metabolizing enzymes in liver might have caused the high histamine content in the liver. On the other hand, the decrease in plasma histamine concentration might have occurred as a consequence of the enzyme leakage from hepatocytes that accompanied the breakdown of hepatocytes by CCl4 and thus, of the histamine metabolism in blood by the leaked enzymes. The same kind of experiment was performed using a dimethylnitrosamine-induced liver injury model in rats. The increase of hydroxyproline in the liver occurred 11 days after that of histamine content in liver. These results suggest the possibility that increased histamine in the liver may participate in the biosynthesis of collagen.

Animals↗

Prevention of rotavirus infection by oral administration of cow colostrum containing antihumanrotavirus antibody.

After immunizing 8-month pregnant Holstein cows with human rotavirus, Wa strain, cow colostrum containing neutralizing antibody to human rotavirus, designated as Rota colostrum, was obtained. After randomly grouping 13 infants from a single orphanage, 6 infants received 20 ml of Rota colostrum every morning and 7 control infants received 20 ml of market milk. One month later, rotavirus associated diarrhea was observed in 6 of the 7 infants given milk and 1 out of the 6 infants given Rota colostrum. Orally administered Rota colostrum significantly protected infants from diarrhea caused by rotavirus (P less than 0.05). Two out of 5 Rota colostrum recipients who were free from diarrhea showed rises in complement fixation (CF) antibody titer after the rotavirus infection epidemic. Thus, Rota colostrum prevented the outbreak of diarrhea but did not prevent immunological responses to natural rotavirus infection. In the therapeutic trial Rota colostrum had no effect on duration of diarrhea, bowel movements or virus shedding in stool. However, there were no side-effects of Rota colostrum.

Administration, Oral↗

[Prophylactic effect of tritoqualine (TRQ) on the CCl4-induced chronic liver injury model in rats].

Tritoqualine (TRQ) administered at doses of 100 or 200 mg/kg, perorally, had a preventive effect on the liver injury in rats induced by the treatment with CCl4 for 12 weeks consecutively. Rats subjected to this chronic treatment with CCl4 showed a decrease in body weight gain and changes in several serum parameters that are indicators of hepatic function were observed: the increase of transaminases, as a parameter of hepatocyte breakdown; the increase of alkaline phosphatase, as a parameter of biliary system abnormalities, the reduction of prothrombin time, as a marker of protein biosynthesis in the liver; and the change of lipids concentrations, reflecting liver injury. After the administration of TRQ perorally, there was a notable suppression of the increment in leaked enzymes in the serum and a marked improvement of the parameters concerning protein biosynthesis and lipid metabolism in comparison with CCl4 control rats. Marked fibrosis in the liver was observed after CCl4 treatment for 12 weeks, and the collagen content in the liver was 5 times higher than that of control rats. TRQ suppressed the increment in collagen formation and also showed improvement of the decrease of the liver function with regards to protein biosynthesis in CCl4-treated rats. Judging from these results, it was concluded that TRQ had a remarkable protecting action on the liver injury chronically induced by CCl4 treatment and was a effective compound for restoring liver function.

Animals↗

[Therapeutic effect of TRQ on chronic liver injury model in rats induced by CCl4].

Rats were treated with CCl4 for 12 weeks to induce chronic liver injury. An administration of tritoqualine (TRQ) to rats was begun 3 weeks after the first CCl4 treatment, and the therapeutic effect of TRQ on this model was investigated. On the 12th week after CCl4 treatment, a marked increase in content of hydroxyproline and histamine in the liver was found. In addition, increased fibrosis around Glisson's sheath was observed under microscopic observation. The increase in these biochemical parameters was suppressed significantly in the rats administered TRQ at doses of 25-100 mg/kg. The histopathological observation demonstrated the suppression of the formation of pseudolobules with fibrinogenesis in the liver of TRQ administered rats. In addition, there was a noticeable improvement in the activity of the liver protein synthesis in the TRQ administered rats when the parameters that represented the hepatic functions were measured. Glutamic oxaloacetic transaminase in the serum of TRQ-administered rats also decreased significantly, compared with the CCl4 treated control rats. From these results, TRQ was shown to exhibit a marked therapeutic effect on liver damage accompanied by chronically accelerated fibrosis in rats which have been treated with CCl4 for 12 weeks.

Alanine Transaminase↗

[Effect of tritoqualine on liver regeneration after partial hepatectomy in rats].

Effect of tritoqualine (TRQ) on liver regeneration after partial hepatectomy in normal rats and chronically injured rats treated with carbon tetrachloride (CCl4) for 12 weeks were investigated by the measurement of serum and liver biochemical parameters concerning the hepatic function. The results are as follows: 1) In normal rats, the liver regeneration rate after partial hepatectomy was increased dose-dependently with the administration of TRQ for 7 days after the operation. TRQ improved BSP retention rate which was decreased after partial hepatectomy. In addition, protein synthetic activity in the liver microsomes prepared from TRQ-administered rats was higher than that prepared from control rats, and the contents of serum total protein, serum albumin and liver protein were also higher in TRQ-administered rats. 2) In the rats treated with CCl4 for 12 weeks, the liver regeneration rate after partial hepatectomy was increased dose-dependently with the administration of TRQ for 6 days. TRQ also improved the contents of serum total protein, serum albumin and liver protein. Though the amount of collagen in the liver chronically injured by CCl4 increased more than twice compared with that in the normal liver, the amount of collagen in the regenerating liver of CCl4-treated rats whose liver regeneration was accelerated by TRQ was not different from that in the normal liver. These results suggest that TRQ has the effect of improving the various hepatic functions through the activation of the protein synthesis in hepatocytes.

Animals↗

Inhibitory effect of tritoqualine (TRQ) on histamine release from mast cells.

Tritoqualine (TRQ), used clinically as an antiallergic drug, did not inhibit histidine decarboxylase activity (HDC, EC. 4.1.1.22.) partially purified from fetal rats and the enzymes prepared from mastocytoma P-815 cells. However, TRQ inhibited the histamine release from rat peritoneal mast cells induced by compound 48/80 and ATP. TRQ was also effective in inhibiting antigen-induced histamine release in rat mast cells sensitized actively or passively by the homologous anti-DNP-Ascaris antibody. Preincubation of cultured mastocytoma P-815 cells in a medium including TRQ inhibited non-cytotoxically the histamine release of mastocytoma cells induced by compound 48/80, and the effect of TRQ became more marked with lengthening of the culture period in the presence of TRQ. It was concluded from these results that one of the main actions of TRQ as an antiallergic drug was not the inhibitory action on HDC, but might be ascribed to its inhibitory effect on histamine release from mast cells.

Animals↗

[Comparative studies of the efficacy, safety and usefulness of S6472, cefaclor and cephalexin on complicated urinary tract infection by the double-blind method].

To objectively evaluated the usefulness of the standard formulation of cefaclor (CCL) and the long-acting formulation of cefaclor (S6472) in noncatheterized complicated urinary tract infection (UTI), a double-blind comparison study was carried out using cephalexin (CEX) as a control. Patients were orally treated with either 500 mg of CCL 3 times/day, 750 mg of S6472 2 times/day, or 500 mg of CEX 4 times/day for 14 days. Overall clinical effect was evaluated on days 5 and 14 in accordance with the UTI therapeutic evaluation standard, with check for recurrence on day 21. There was no demographic difference between the groups. There was no difference in the effective rate on day 5 among the 3 treatment groups: 58.1% in S6472 group, 66.0% in CCL group and 61.9% in CEX group. Nor on day 14, was there any significant difference in the effective rate among the 3 groups: 70.8% in S6472 group, 63.4% in CCL group and 61.8% in CEX group. Stratification analyses (by UTI group, infection site, in- or out-patient, time of starting treatment, pretreatment severity of pyuria, total number of bacteria before treatment) revealed no significant difference among the 3 groups. Therapeutic effect evaluated by physicians in charge was not significantly different among the 3 groups on day 5 or day 14. In terms of overall therapeutic effect, all 3 products were very effective in patients infected with sensitive bacteria: On day 5, 85.4% in S6472 group, 84.4% in CCL group, and 83.7% in CEX group. There was no significant difference among the 3 groups on either day. The incidence of side effects was not significantly different among the 3 groups: 4 out of 129 patients treated with S6472 (3.1%), 2 of 131 treated with CCL (1.5%) and 2 of 128 with CEX (1.6%). Clinical laboratory tests revealed 4 abnormal findings in 4 patients treated with S6472, 6 findings in 4 treated with CCL, and 4 findings in 2 treated with CEX, showing no significant difference in incidence among the 3 groups. Both side effects and abnormal clinical laboratory findings were mild and reversible. Physicians in charge judged the usefulness of the 3 drugs on days 5 and 14, taking efficacy and safety into consideration. Significant difference was not observed. The presence of recurrence was examined 7 days after drug withdrawal in patients regarded as remarkable responders to 14-day treatment by overall therapeutic effect evaluation.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

[Fundamental and clinical studies on S6472 (a new prolonged acting preparation of cefaclor) in the urological field].

Fundamental and clinical studies on S6472, a new prolonged acting preparation of cefaclor, were performed and the following results were obtained. Serum level and urinary excretion. 750 mg of S6472, 500 mg of cefaclor (CCL) and 500 mg of cephalexin (CEX) were orally administered in 6 healthy adult volunteers by the cross over method to measure serum level and urinary excretion. The serum level-time curve of S6472 showed 2 peaks at 1 and 6 hours after administration. The peak serum level of S6472 was 4.2 micrograms/ml and 2.9 micrograms/ml, respectively, 1 and 6 hours after administration. The peak serum level of CCL and CEX was 5.8 micrograms/ml and 12.1 micrograms/ml, respectively, 2 hours after administration. The urine level-time curve of S6472 also showed 2 peaks at 0-2 and 4-6 hours after administration and the peak urine level was 1,320 micrograms/ml and 994 micrograms/ml, respectively, 0-2 and 4-6 hours after administration. The peak urine level of CCL was 1,337 micrograms/ml, 0-2 hours after administration and that of CEX was 2,079 micrograms/ml, 2-4 hours. The mean urinary excretion of S6472, CCL and CEX was 56%, 69% and 94% of dose at 12 hours after administration. Clinical evaluation. S6472 was tried in 200 cases of various urinary tract infections. For one group of 85 cases with acute uncomplicated cystitis, clinical effects were evaluated as excellent in 40 cases, moderate in 42 cases and poor in 3 cases, and the overall clinical effectiveness rate was 96.5%. For another group of 68 cases with complicated urinary tract infection, clinical effects were evaluated as excellent in 9 cases, moderate in 27 cases and poor in 32 cases, and the overall clinical effectiveness rate was 52.9%. Side effects. Side effects were observed in 7 cases with diarrhea, epigastralgia, stomatitis, eruption and facial swelling. Administration of S6472 was discontinued in 2 cases, but in 7 cases all symptoms were transient.

Adult↗

[Studies on antibiotics distribution in the post-operative cavity].

In 17 post-operative patients, serum and operation cavity exudate levels after 2 g administration of various cephems (CZX, LMOX, CTX, and CPZ) by one hour drip infusion were evaluated. Drug concentration in exudate (actual levels) was corrected by using an equation for the purpose of excluding blood contamination. After 2 hours from the start of infusion, theoretical levels generally were similar to actual levels. CZX: Peak exudate level was 38.9 micrograms/ml at 4 hours. Maximum exudate level/maximum serum level (E/S) was 0.31. LMOX: Peak in exudate was 41.4 micrograms/ml at 4 hours. E/S was 0.59. CTX: Exudate peak level was 30.8 micrograms/ml at 2 hours, and E/S was 0.53. CPZ: Peak level in exudate was 74.0 micrograms/ml at 4 hours. E/S was 0.36. Generally, peaks occurred at 4 hours (3 hours later than serum peaks), and their range was between 30 and 80 micrograms/ml. At 8 hours, drug levels in exudate were 10 approximately 60 micrograms/ml, and they were higher than the corresponding serum level at that time.

Adult↗

[Ectopic ureter without urinary incontinence despite ureteric orifice in the vestibulum: report of one case].

UNLABELLED: This is one case of ectopic ureter which lacked urinary incontinence despite ureteric orifice in the vestibulum. CASE: A 20-year-old woman complained of miction pain. On examination, we found a small orifice in the vestibulum. DIP revealed slight hydronephrosis in the left contracted kidney and normal pyelogram in the right kidney. On cystoscopy, the bilateral ureteral orifices were normal, but we found the head of a catheter placed in the orifice of the vestibulum was passing under the mucosa of the bladder. The abnormal lumen was recognized by introducing an opaque medium through a catheter placed into the orifice of the vestibulum. The diagnosis was an abnormal left ureteral ectopic opening into the vestibulum with left complete duplication of renal pelvis and ureter. Left heminephro-ureterectomy was performed. Some discussions about the ectopic ureteral orifice without incontinence were conducted.

Adult↗

A rare case of adenocarcinoma of bladder following augmentation enterocystoplasty.

This is a report of a case of poorly differentiated adenocarcinoma found 20 years after bladder augmentation ileoplasty. The origin of this tumor was proved to be the ileal part of bladder augmentation. Autopsy revealed metastatic lesions in the stoma (sigmoid conduit), lungs, liver, left femur, adrenal glands and lymph nodes. A review of the literature revealed only one other such case. This is a rare case of adenocarcinoma in the ileal part of bladder augmentation.

Adenocarcinoma↗

Treatment of multiple sclerosis with anti-measles cow colostrum.

Previous virological and immunological studies have suggested that multiple sclerosis (MS) is an auto-immune disease triggered by a virus infection. In order to inhibit the growth of measles virus in the patient's jejunum, we obtained an IgA-rich cow colostrum containing anti-measles lactoglobulin resistant to proteases. This colostrum was orally administered to patients with MS to investigate its effect on the course of the disease. Measles-positive antibody colostrum was orally administered every morning to 15 patients with MS at a daily dosage of 100 ml for 30 days. Similarly, measles-negative antibody (less than 8) control colostrum was orally administered to 5 patients. As a clinical assessment, disability scores developed by the International Federation of Multiple Sclerosis Societies were used. As a result, of 7 high NT titre (512-5120) anti-measles colostrum recipients 5 patients improved and 2 remained unchanged. Among 8 low NT titre (8-32) anti-measles colostrum recipients 5 patients improved and 3 remained unchanged. However, of 5 negative NT titre (less than 8) colostrum recipients 2 patients remained unchanged and 3 worsened. No side-effects were observed in colostrum recipients. These findings suggest the efficacy of orally administered anti-measles colostrum in improving the condition of MS patients (P less than 0.05).

Adolescent↗