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T Morino

Publications and source records attributed to T Morino.

36 records · Page 2Linked to original sources
PubMed1989

[Subacute toxicity study of miporamicin in rats by twenty-eight-day administration in feed].

A 28-day oral dosage test of miporamicin (MPM), a new macrolide antibiotic, was performed to assess its toxicologic potential in groups of male and female rats receiving the compound in feed. Five graded dosage levels of 0, 3,200, 8,000, 20,000, and 50,000 ppm were employed for treatment with MPM in feed and the treatment period was followed by a 28-day recovery phase observation period. 1. No deaths occurred throughout the course of the experiment. Animals receiving 50,000 ppm developed signs: ruffled hair coat and emaciation, which disappeared following withdrawal of the drug. 2. The MPM-50,000 group displayed depression of weight gain and decrease of feed and water intake during the treatment period. During the posttreatment recovery phase observation period the animals showed recovery in weight gain rate as well as in feed and water intake. 3. The achieved compound dosage was 273 mg/kg/day in males and 288 mg/kg/day in females in the MPM-3,200 group, 721 and 773 mg/kg/day respectively in the MPM-8,000 group, 1,738 and 1,856 mg/kg/day in the MPM-20,000 group, and 3,405 and 3,611 mg/kg/day in the MPM-50,000 group. 4. Hematological examinations revealed low values for RBC, WBC, hematocrit and hemoglobin concentration and decreased platelet counts in the MPM-50,000 group, which were considered to be due to the decreased feed intake. These changes disappeared or abated following withdrawal. 5. Of various serum biochemical parameters assessed, total protein, albumin, glucose and triglycerides showed lowered values in the MPM-50,000 group. All these changes were considered to be attributable to the decreased feed intake. During the ensuing recovery phase observation period, all these parameters showed restoration or abatement in parallel with the recovery in feed intake. 6. Urine analysis disclosed decrease of urine volume, lowered electrolyte concentration and elevation of urine osmolarity in the MPM-20,000 and the MPM-50,000 groups. These changes were considered to be secondary to cecal enlargement which is commonly seen with antibiotic medication, or to the decreased feed and water intake. Following drug withdrawal, all these changes disappeared with the recovery in feed and water intake and abatement of cecal hyperplasia. 7. At terminal necropsy, diminution of body fat and atrophy of the spleen and thymus that correlated with emaciation were noted in the MPM-50,000 group. Dose-related enlargement of the caecum was also noted in the treated groups. All these changes disappeared or abated following withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1989

[Six-month chronic toxicity study of miporamicin in rats].

A six-month oral toxicity test of the new macrolide antibiotic miporamicin (MPM) was carried out in male and female rats receiving the compound in feed at concentrations of 1,280, 3,200, 8,000, or 20,000 ppm. The animals were further observed for recovery for 2 months after the completion of the treatment period. 1. No death occurred at any dosage levels throughout the study period. The only notable signs observed were marginal blepharitis and aging-associated changes that were seen occasionally among the treated and control rats. There were no symptomatic changes of particular note. 2. Body weight, feed intake and water consumption data did not reveal any noticeable change. 3. The achieved test compound intake was 69 mg/kg/day for males and 82 mg/kg/day for females in the MPM-1,280 group, 176 mg/kg/day for males and 207 mg/kg/day for females in the MPM-3,200 group, 436 mg/kg/day for males and 519 mg/kg/day for females in the MPM-8,000 group, and 1,080 mg/kg/day for males and 1,280 mg/kg/day for females in the MPM-20,000 group. 4. No changes attributable to these treatments were noted in the hematological examination or serum biochemical tests. 5. Urinalysis disclosed mild changes with respect to urine volume, urinary electrolyte concentration and osmolarity. Animals recovered from all these changes during the recovery phase observation. 6. At gross pathologic examination a dose-related enlargement of the caecum was observed. The change disappeared or diminished following the 2-month recovery phase observation. 7. Organ weight analysis showed a dose-related increase of weight of the caecum. Animals recovered or abated in this respect during the 2-month recovery phase observation. 8. Histopathologic examination revealed no adverse toxicologic changes other than spontaneous or aging-associated ones. 9. No abnormalities were noted in the liver or in the kidneys as examined by electron microscopy. 10. The maximum non-effective level of MPM thus was estimated to be 20,000 ppm at which no organic damage occurred.

Administration, Oral↗
PubMed1988

[Indications for limited hepatic resection in hepatocellular carcinoma].

Indications for limited hepatic resection in patients with hepatocellular carcinoma were evaluated by retrospective and clinicopathologic analysis of postoperative cases. Particular attention was paid to hepatic functional reserve and long-term prognosis. In our department, in order to estimate the hepatic functional reserve, indocyanine green clearance test (ICG), Child's classification and the oral glucose tolerance test have been applied. For instances, the incidences of hospital deaths were 17% and 19% in cases with an ICG-K value below 0.06 and between 0.06 and 0.08, which were high, compared with 6% and 3% in cases ICG-K values of with 0.08-0.10 and 0.10-0.12. On the other hand, by clinicopathologically analyzing 18 surviving patients or those surviving without recurrence for over 3 years after hepatic resection and 41 cases of small hepatocellular cancer less than 3 cm in diameter, those with capsule formation and without portal tumor invasion, intrahepatic metastasis and capsular invasion had a good long-team prognosis without recurrence even following limited resection. Particularly, patients with a surgical margin of over 1cm between the tumor and cut surface were candidates for long, non-recurrence survival. Form these results, the indications for limited hepatic resection for hepatocellular carcinoma were considered to be on ICG-K value of less than 0.08 in hepatic function and cases without venous invasion and extracapsular tumor invasion. In other cases, it is recommended that limited resection should be followed by multidisciplinary treatment.

Carcinoma, Hepatocellular↗
PubMed1987

[Comparative toxicity study of rokitamycin and josamycin in rats].

A comparative toxicity study on macrolide antibiotics, rokitamycin (TMS-19-Q) and josamycin, was performed in male rats. These drugs were given orally for 1 month at daily doses of 250, 500, 1,000, and 2,000 mg/kg. No animals died in the study. No abnormal symptoms or changes in body weights and food consumption were observed. Results of urinalysis, hematological analysis and biochemical analysis of serum and organ weights were normal except that a dose-dependent hypertrophy of caecum was observed in all dosage groups. Necropsy revealed no notable drug related abnormalities except in caecum of all test groups. Pathological examination found no significant drug-related abnormalities in the test groups. No toxicological signs were detected in the group administered with 2,000 mg/kg of either drug and no difference was found between the 2 drugs.

Animals↗
PubMed1986

[Toxicological studies on isepamicin (HAPA-B). I. Acute toxicity test in the mouse, rat and dog].

Acute toxicity of isepamicin (HAPA-B), a new aminoglycoside antibiotic, in mice, rats and dogs was examined in comparison with amikacin (AMK) and gentamicin (GM). Intravenous LD50 values of HAPA-B were 234 mg/kg in male and 236 mg/kg in female for mice, 489 mg/kg in male and 476 mg/kg in female for rats and 720-864 mg/kg for dogs. Those of AMK were 183 mg/kg in male and 181 mg/kg in female for mice, 420 mg/kg in male and 417 mg/kg in female for rats. Those of GM were 50 mg/kg in male and 47 mg/kg in female for mice, 119 mg/kg in male and 124 mg/kg in female for rats. Intraperitoneal LD50 values of HAPA-B were 2,244 mg/kg in male and 2,272 mg/kg in female for mice, 1,664 mg/kg in male and 1,591 mg/kg in female for rats. Intramuscular LD50 values of HAPA-B were 2,508 mg/kg in male and 2,632 mg/kg in female for mice, 2,088 mg/kg in male and 2,111 mg/kg in female for rats and greater than 1,800 mg/kg for dogs. Those of AMK were 1,247 mg/kg in male and 1,334 mg/kg in female for mice, 2,324 mg/kg in male and 2,244 mg/kg in female for rats. Those of GM were 359 mg/kg in male and 360 mg/kg in female for mice, 559 mg/kg in male and 557 mg/kg in female for rats. Subcutaneous LD50 values of HAPA-B were 3,321 mg/kg in male and 3,320 mg/kg in female for mice, 3,451 mg/kg in male and 3,392 mg/kg in female for rats. Oral LD50 values of HAPA-B were more than 5,000 mg/kg in mice and rats. Ataxia, acratia, dyspnea and convulsions were observed following administration by all routes, except for oral route, of all drugs in mice, rats and dogs. The cause of early death was due to respiratory paralysis which is the typical acute toxic sign of aminoglycoside antibiotics, and that of late death was due to renal injuries. BUN and creatinine values of surviving dogs after day 14 increased after administration by either intravenous or intramuscular routes. Disintegration, necrosis and calcification of epithelial cells of the proximal convoluted tubuli were observed in rats which died during the course of the study, and atrophy, dilatation and eosinophilic degeneration in epithelial cells of the proximal convoluted tubuli and thickening of Bowman's capsule were observed in surviving dogs.

Administration, Oral↗
PubMed1986

[Toxicological studies on isepamicin (HAPA-B). II. Intramuscular subacute toxicity test in the rat].

Subacute toxicity in the rat of isepamicin (HAPA-B), a new aminoglycoside antibiotic, was examined in comparison with amikacin (AMK). Daily doses of 12.5, 25, 100 and 300 mg/kg of HAPA-B or 25 and 100 mg/kg of AMK were injected intramuscularly for 28 days. No animal died and there were no changes in general symptoms except for hemorrhage at injection sites of both drugs. Decreases in body weight gain and food consumption were observed in males and females in the HAPA-B 300 mg/kg dose group. Water consumption was increased in males in the HAPA-B 300 mg/kg and AMK 100 mg/kg dose groups. Elevations of serum creatinine and/or BUN in males and females were occasionally observed in the HAPA-B 300 mg/kg and AMK 100 mg/kg dose groups, and elevation of GOT, which seemed to be due to muscle injuries, was occasionally observed in a no dose-dependent manner with either drug. Increases in kidney and caecum weights of males and females in the HAPA-B 100, 300 mg/kg and AMK 25, 100 mg/kg dose groups and increases in adrenal relative-weights in males and females in the HAPA-B 300 mg/kg dose group were observed. At necropsy, discoloration and enlargement of the kidney were observed in a dose-dependent manner at or above 100 mg/kg with either drug. Histopathological findings indicated degeneration and necrosis in epithelial cells of the proximal convolute tubuli and thickening of basement membrane. Electron microscopic findings indicated an increase in number of large lysosomes containing myeloid bodies in the epithelial cells of the proximal convolute tubuli with both drugs. The above results suggest that HAPA-B has renal toxicity like other aminoglycoside antibiotics but its toxicity was lower than AMK. The non-toxic dose of HAPA-B in this test was 12.5 mg/kg.

Amikacin↗
PubMed1986

[Toxicological studies on isepamicin (HAPA-B). IV. Intramuscular subacute toxicity test in the dog].

The subacute toxicity in the dog of isepamicin (HAPA-B), a new aminoglycoside antibiotic, was studied in comparison with amikacin (AMK). HAPA-B at dose levels of 6.25, 25 and 100 mg/kg/day and AMK at dose levels of 25 and 100 mg/kg/day were given intramuscularly for 30 days. Only one female dog in the AMK 100 mg/kg dose group died on day 29. The activities of urinary NAG and gamma-GTP increased dose-relatedly in dogs in the 25 and 100 mg/kg dose groups of either drug. Discoloration and/or enlargement of the kidneys were observed in dogs at 100 mg/kg of either drug. Hemorrhage and/or edema at the injection sites were observed in dogs in the 25 and 100 mg/kg dose groups of either drug. Increases of absolute and relative kidney weights were observed in the AMK 100 mg/kg group. An increase of relative kidney weights was also observed in the HAPA-B 100 mg/kg group. In microscopic observations, various histopathological changes of renal tubules and tubular epithelium were observed dose-relatedly in the 25 and 100 mg/kg groups of both drugs. At a dose of 25 mg/kg, there was no significant difference of the incidence and severity of these renal changes between HAPA-B and AMK groups. Desquamation and necrosis of the renal tubular epithelium were observed only in the AMK 100 mg/kg group. The necrosis in these changes was considered to be one of the severest possible changes in renal tubules, hence the renal toxicity of HAPA-B was judged to be milder than that of AMK at the dose level of 100 mg/kg. The non-toxic dose of HAPA-B in this study was estimated to be 6.25 mg/kg.

Amikacin↗
PubMed1986

[Toxicological studies on isepamicin (HAPA-B). VII. Chronic intramuscular test in the rat].

Chronic toxicity in the rat of isepamicin (HAPA-B), a new aminoglycoside antibiotic, was examined in comparison with amikacin (AMK). Daily doses of 3.125, 6.25, 25 and 100 mg/kg of HAPA-B or 25 and 100 mg/kg of AMK were injected intramuscularly for 6 months, and recovery test was carried out for 2 months after discontinuing the drug. No animal died and there were no changes in general symptoms except for hemorrhage of injection sites of both drugs. Decreases in body weight gain and food consumption were observed in 100 mg/kg dose group of either drug. Water consumption was markedly increased in males of the AMK 100 mg/kg dose group during administration and recovery periods. Decreases in erythrocytes, hematocrit and hemoglobin were observed in 100 mg/kg dose group of either drug. These decreases seemed to be due to renal injury. An increase in the number of platelets was also observed. This was likely caused by the hemorrhage at injection sites. These changes persisted into the recovery period. Elevation of BUN was observed in the 100 mg/kg dose group of either drug. Its value in the AMK 100 mg/kg dose group was markedly higher than that in the HAPA-B 100 mg/kg dose group and did not decrease back to the normal values even during the recovery period. An increase of urine volume and a decrease of urine specific gravity were observed in males in the 100 mg/kg group of either drug. Furthermore, NAG was elevated in a dose-dependent manner from 25 mg/kg with both drugs. The weight of kidney increased dose-relatedly and significantly in groups administered with 25 mg/kg or more of either drug and weight of caecum increased dose-relatedly and significantly in groups administered with 6.25 mg/kg or more of HAPA-B or 25 mg/kg or more of AMK. Discoloration and enlargement of the kidney occurred in a dose-dependent manner as observed by necropsy. Eosinophilic granular degeneration, swelling, fatty degeneration, necrosis, calcification in the epithelial cells of the proximal convoluted tubuli, and thickenings of Bowman'S capsule and tubular basement membrane were observed at 25 and 100 mg/kg dose groups of either drug. In recovery periods, after the necrosis disappeared, calcification and regeneration were observed in epithelial cells. Electron microscopic findings showed an increase in the number of large lysosomes containing myeloid bodies in the epithelial cells of the proximal convolute tubuli with either drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Amikacin↗
PubMed1985

Construction and characterization of a cosmid of Streptomyces lividans.

We constructed a plasmid pR4C1 in which a DNA fragment containing the cohesive ends of an actinophage, R4 was inserted into the ClaI site of plasmid pIJ365. The plasmid pR4C1 was packaged efficiently into R4 phage particles in vivo and therefore transferred by transduction. Southern hybridization analysis of DNA from pR4C1-transducing R4 phage particles indicated that the plasmid DNA was encapsidated as head-to-tail concatemers with the cohesive ends in the termini. We designated the pR4C1 plasmid a cosmid, following the termination of Collins and Hohn (1978).

Bacteriophages↗
PubMed1981

[Subacute toxicity and recovery tests of mequitazine in beagle dogs (author's transl)].

Subacute toxicity and recovery tests of Mequitazine, a new phenothiazine ;type anti-histamine agent, were carried out using each 20 male and female dogs. The drugs was administered orally in doses of 0, 1, 5 and 25 mg/kg day for 14 weeks. Recovery test was carried out for following 4 weeks. As a result, transient decrease of the body weights and somnolences were observed in both male and female dogs given 25 mg/kg. In a female dog given 25 mg/kg, extrapyramidal reaction accompanied with tremors and muscle stiffenings was observed. But no dead animals were observed throughout experimental period. Vomitings, mydriasis and loss of appetite were observed with the dose-responsiveness, but these symptoms were reduced after 1-2 weeks administration. No abnormal changes were observed in hematological, serum biochemical, and other examinations. In histopathological examinations, slights changes were observed in liver, kidneys, mesenteric lymph nodes, palpebra and conjunctival membrane. But these changes were reversible in recovery period. From these results, it was suggested that the maximum non-effective and maximum safety doses were 1 mg/kg/day and 5 mg/kg/day, respectively.

Animals↗
PubMed1976

Urinary kallikrein and plasma renin during the reversal of renovascular hypertension in rats.

1. Urinary kallikrein, sodium, potassium and water excretion, and plasma renin activity were measured before and during the reversal of experimental hypertension produced by unclamping the renal artery in rats. 2. Kallikrein excretion decreased significantly after unclamping, suggesting that it does not play a significant role in the reversal of hypertension. 3. A decrease in plasma renin activity coupled with a slight increase of sodium excretion was observed, indicating that these might participate in the reversal of hypertension.

Animals↗