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Biomedical subjects

K Shimpo

Publications and source records attributed to K Shimpo.

At least 37 records · Page 2Linked to original sources
PubMed1985

[Study on toxicity of halopredone acetate. (III). Chronic toxicity study in rats].

Chronic toxicity study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl: Wistar rats. THS-201 was subcutaneously administered to the rat in doses of 0.02, 0.1, 0.5 and 2.5 mg/kg/day, with the periods for administration and recovery being 12 and 2 months, respectively. In the group of THS-201 2.5 mg/kg, the below findings were observed: thinning of lumbar hair, suppression in body weight gain, decrease of food consumption in both sexes and decrease of water consumption in male. The lesions to lymphatic system were indicated by the examinations of hemogram, organ weight and histopathology. A few changes in urinary and biochemical values were seen, and foreign body granuloma was observed in the injected subcutis. After 2 month-recovery period, above-mentioned findings almost disappeared. In the group of THS-201 0.5 mg/kg, some of the changes were noted slightly and disappeared after the recovery period. In the groups of THS-201 0.1 and 0.02 mg/kg, any toxic changes attributable to THS-201 were not observed. It was concluded that the non-toxic dose and the defined toxic dose of THS-201 in this study were 0.1 and 0.5 mg/kg/day, respectively.

Animals↗
PubMed1984

[Chronic toxicity study of AC-1370 sodium, an antibiotics, intravenously administered in rats].

A study on chronic toxicity of AC-1370 sodium (AC) in addition to recovery from its toxicity, was carried out using the rat. AC was administered to the rat through the tail vein in doses of 30, 100, 300 and 1000 mg/kg body weight/day, with the periods for administration and recovery being 26 and 13 weeks, respectively. The results obtained from the present study were as follows. In each group, neither death case nor fatal damage was observed throughout the whole process. In the group of 1000 mg/kg, the below findings were observed in one or both sexes: suppression in increase of body weight, increases in drunk amount of water, urinary volume and urinary excretions of electrolytes, degeneration in renal tubules and several correlated changes, tendency of anemia, changes in serum biochemical tests, and changes in each organ weight. In the group of 300 mg/kg, the above findings were observed slightly in comparison to the group of 1000 mg/kg. In the groups of 100 and 30 mg/kg, any changes suggesting the damages were not observed. In the recovery test, the group of 1000 mg/kg was found to be incompletely restored from the damages, with the partially residual damages being shown. In contrast, the group of 300 mg/kg showed to be almost restored from the damages. These results denotes that the maximal non-toxic dose of AC in this study is 100 mg/kg/day in long-term administration.

Animals↗
PubMed1984

[Effects of intravenous administration of ranitidine hydrochloride to the pregnant rat in organogenesis period].

The effects of ranitidine hydrochloride, a histamine H2-receptor antagonist, on development and general behavior of F1 generation of Crj: CD (SD) rats were examined. Ranitidine hydrochloride was intravenously administered once daily from day 7 to 17 of gestation at dose levels of 5, 15 and 40 mg/kg in base weight respectively. Two-thirds of females were killed on day 20 of gestation to examine the development of fetuses, the remaining females were allowed to litter naturally and the postnatal development of the offsprings was observed. Tachypnea, prone position and transient tremor were observed for approximately 15 from 30 seconds directly after an intravenous administration of ranitidine hydrochloride in the dose of 40 mg/kg, which were probably induced by a rapid fall in blood pressure. During the gestation period, there occurred a slight depression of the maternal body weight gain in the ranitidine-treated groups. At the stage of lactation, the body weights of dams showed slightly lower levels than control and their liver weights of dams were also inclined to decrease in 15 and 40 mg/kg groups. In the observation of the fetuses, there were no significant differences between the control and ranitidine-treated groups concerning fetal growth and development, external, skeletal and internal anomalies in fetuses. In delivery and postpartum observation, no influence of ranitidine administration was observed on the litter size, mortality rate of F1 pups. There was a tendency towards decrease in body weight in males of the ranitidine-treated groups. But no significant changes were observed in general behavior, postnatal development, various functions such as reflex response, learning and reproductive performances of F1 generation. Therefore, it was concluded that ranitidine hydrochloride had no effects on fetal and postnatal development, general behavior and various functions of F1 generation at the dose of 40 mg/kg/day or less.

Abnormalities, Drug-Induced↗
PubMed1984

[Effects of intravenous administration of ranitidine hydrochloride to the female rat in perinatal and postnatal periods].

The effects of ranitidine hydrochloride, a histamine H2-receptor antagonist, on delivery, lactation, postnatal development of F1 generation of Crj:CD (SD) rats were examined. Ranitidine hydrochloride was intravenously administered once daily from day 17 of gestation to day 21 after delivery at dose levels of 5, 15 and 40 mg/kg in base weight respectively. All females were allowed to litter naturally, and postnatal development of offsprings was observed. Tachypnea, prone position and transient tremor were observed for approximately one minute directly after an intravenous administration of ranitidine in the dose of 40 mg/kg, which were probably induced by a rapid fall in blood pressure. In delivery and postpartum observation, there occurred no influence of the ranitidine administration on maternal body weight, delivery and lactation. In studies on general behavior of F1 rats, no abnormal changes were observed on postnatal development and various functions such as reflex response and learning. Ranitidine treatment did not affect reproductive performances of F1 generation. A slight inhibition in body weight gain and a slight decrease in average weight of liver were observed in F1 females of 40 mg/kg group, but no other influence attributable to the ranitidine administration was observed on the general state and development of offsprings. In necropsy of offsprings, hydronephrosis, transitional epithelial carcinoma, kinky tail, unilateral absence of testis and epididymis were observed in one case of ranitidine-treated groups. But they were not attributable to administration of ranitidine. In summary, it was concluded that ranitidine hydrochloride had no effects on delivery and lactation of dams, and also on viability, development and various functions of F1 generation at the dose of 40 mg/kg/day or less.

Animals↗
PubMed1983

[Acute toxicity of intrarectally administered (ketoprofen (T10) in rat weanlings].

Acute toxicity of Ketoprofen, a nonsteroidal antiinflammatory analgestic, was studied using rat weanlings. Ketoprofen was intrarectally administered in the form of a mixture with T10, a basic materials for suppositaries. The results obtained were as follows: LD50 of KP was estimated to be 434 mg/kg in male weanlings and 496 mg/kg in female weanlings. These values were about four times higher than those obtained from our previous study (Shimpo et al., 1981) using six-weeks old adult rats of both sexes. The fact indicated that rat weanlings were far tolerant to KP intrarectally administered than young adult rats. Intrarectal administration of KP at high doses, caused death between the second and the seventh day after administration. Gross and histopathological examinations revealed that dead weanlings carried perforative peritonitis with ulcers mainly in jejunum and ileum not in rectum. It was therefore suggested that the ulcer was produced in small intestine by entero-hepatic circulation of KP and finally mortal peritonitis occurred.

Age Factors↗
PubMed1983

[Carcinogenicity study of cholestyramine in rats].

Carcinogenicity study on cholestyramine, an anti-hypercholesterolemic agent, was carried out using Fischer rats by feeding with a normal pellet diet (control) and with three sorts of the pellet diets in which cholestyramine was admixed in the common diet at the rates of 1.25, 2.5 and 5%, respectively. The animals were fed with these diets for 26 months and a normal diet for subsequent 2 months. Some of the male rats fed with the 5% admixed diet revealed a slight growth retardation and occasionally hemorrhagic tendency, without resulting in severe macroscopic and microscopic lesions of the internal organs and in shortening of the mean survival time as compared with that of the control group. The rates of tumor-bearing animals were high in all experimental groups including the control, but the rates were not considered to be drug-related. Incidences of individual tumors were not significantly different each other between cholestyramine-fed groups and control group. Thus, it was not recognized that cholestyramine induced any drug-related specific tumors and an accelerated growth of any tumors.

Animals↗
PubMed1983

[Effects on offsprings induced by oral administration of ranitidine to the female rat in peri- and postnatal periods].

A perinatal and postnatal study was carried out in the Crj:CD (SD) rats orally administered ranitidine hydrochloride, a histamine H2-receptor antagonist, at dose levels of 50, 200, and 800 mg/kg/day as base for a period of time from day 17 of gestation to day 21 after delivery. All pregnant rats were allowed to litter naturally, and the postnatal development of the offsprings was observed. In the 800 mg/kg group, the delivery rate was significantly decreased and offspring mortality during the lactation period showed a tendency to increase as compared with control, but the difference was not significant. No significant differences between the control group and the treated groups were found in postnatal growth and differentiation, behavior and reproductive ability of male and female offsprings.

Administration, Oral↗
PubMed1983

[Chronic toxicity study of ranitidine hydrochloride orally administered in rats].

Chronic toxicity of ranitidine hydrochloride, a new histamine H2-receptor antagonist, was studied using Sprague Dawley rats. Ranitidine was administered orally at dose levels of 30, 100, 300 and 1000 mg/kg/day for 26 or 53 weeks. In the 1000 mg/kg/day group, ten of 31 females died showing acute toxic signs. In the survived animals of this dose group, changes were observed, such as salivation, depression of body weight gain, increase in water consumption, increase in urinary Na and K excretion, increase in serum albumin content, increase in weights of the liver, kidneys and heart. Main histopathological findings were as follows: centrolobular or midzonal fat deposition in liver, increase in s-ER in hepatocytes, increase in foamy cells in lung and some slight degenerative changes occasionally seen in renal tubules. In the 300 mg/kg/day group, the changes similar to those in the 1000 mg/kg/day group were observed, however, the degree of these changes was more moderate. All of the above-mentioned findings were demonstrated to be reversible in recovery period for 8 weeks. In the 100 and 30 mg/kg/day groups, no remarkable changes were observed in both sexes. It was concluded that the maximum nontoxic dose of ranitidine hydrochloride was 100 mg/kg/day in male and female rats.

Administration, Oral↗
PubMed1983

[Fertility study on ranitidine hydrochloride in rats].

A fertility study was carried out in Crj: CD (SD) rats orally administered ranitidine hydrochloride, a histamine H2-receptor antagonist, at dose levels of 50, 200 and 800 mg/kg/day in base weight. Male rats were treated from 60 days before mating until the completion of mating. Female rats were administered ranitidine hydrochloride from 14 days prior to mating up to day 7 of gestation. All pregnant females were sacrificed on day 20 of gestation and all fetuses were examined for abnormalities. Temporary salivation was noted in rats of both sexes given 800 mg/kg/day of ranitidine and in the male rat group given 200 mg/kg/day. No abnormal signs were seen in mating or fertility in the rats treated with ranitidine. No external, internal and skeletal anomalies attributable to ranitidine hydrochloride were observed in the fetuses. It was concluded that ranitidine hydrochloride has no harmful effect on mating, fertilization, implantation, or embryonic development.

Administration, Oral↗
PubMed1982

[Carcinogenicity study of cholestyramine in mice].

Carcinogenicity study of cholestyramine, an anti-hypercholesterolemic agent, was carried out by feeding B6C3F1 mice of both sexes with the pellet diet in which cholestyramine was admixed at the rates of 1.25, 2.5 and 5%. The animals were fed on the drug-admixed diet for 18 months and on a normal diet for subsequent 3 months. After 32 weeks the mortality of male mice began to increase in the 5% cholestyramine group and the number of dead or moribund mice increased markedly after 60 weeks. Hemorrhage recognized in pleural cavity, heart and other organs, was suggested to be the main cause of death. Some kinds of tumors occurred in each group, but the tumor-incidences seen in mice of 1.25 and 2.5% cholestyramine groups were similar to those in mice of the control group and the occurrence of the specific tumor or an acceleration of tumor-development by feeding cholestyramine were not observed. Furthermore, the tumor-incidence in mice fed on the 5% cholestyramine diet was less than that in mice of the other three groups.

Animals↗
PubMed1981

[Acute toxicity of ketoprofen intrarectally administered in rats, with special reference to histopathological changes (author's transl)].

Acute toxicity was studied on Ketoprofen, one of the non-steroidal antiinflammatory analgesics, using SPF rats. Ketoprofen was intrarectally administered in three forms such as pure powder (KP), KP suspension in CMC solution (KP-CMC) and a mixture of KP with powdered basic materials of capsule (KP-T10). The results obtained were as follows:1. LD50 values of terms of KP were 84 mg/kg in male rats and 122 mg/kg in female rats when KP-CMC was administered intrarectally, and 117 mg/kg in male and 92 mg/kg in female when KP-T10 was administered intrarectally., while peroral administration of KP-CMC showed LD50 values of 68 mg/kg in males and 78 mg/kg in females in terms of KP. 2. Major toxic signs of KP were ulceration on small intestines and peritonitis. Degeneration of hepathocytes and decrease in thymus lymphocytes were also observed. 3. Minimum lethal dose of KP-T10 was slightly higher than that of KP-CMC.

Administration, Oral↗
PubMed1981

[Toxicological study on the anorectal irritation and systemic organ toxicity evoked by long-term intrarectal administration of ketoprofen in rabbits (author's transl)].

Ketoprofen (KP) was administered intrarectally and perorally to rabbits weighing approximately 3 kg of both sexes for a period of 13 weeks, in order to study the anorectal irritation and chronic systemic organ toxicity of KP which was capsulated with the soft T10 capsule for rectal administration and with a hard capsule for peroral administration. Doses of capsulated drugs for one animal were 9.0 mg and 4.5 mg in terms of KP. All animals treated by these dose levels survived without showing any abnormal symptoms. Intrarectal administration of KP-T10 did not produce any mucosal lesions in digestive tracts, while peroral administration of KP with hard capsule induced ulcers in cecum or anus, and congestion in small intestines in a small number of cases. No pathological change was recognized in organs except for digestive tracts in all cases by autopsy. From the above results, it can be seen that the suppository of KP capsulated by the soft T10 does not show any irritating effect on anorectal mucosa and has no toxic effect on all organs systemically. Then, a suppository of KP-T10 can be used more harmlessly than the peroral capsulated KP.

Anal Canal↗
PubMed1981

[On the chronic toxicity of labetalol (AH-5158); a combined alpha-and beta-adrenoceptor-blocking agent (author's transl)].

Chronic toxicity and recovery tests of labetalol hydrochloride, alpha-and beta-adrenoceptor blocking agent, were carried out using male and female Wistar strain rats. The drug was orally administered at 50, 100 or 200 mg/kg/day for 9 months. In all the drug-treated groups, increase in salivation was observed from immediately after to 15 minutes after dosing through treatment period. Suppression of body weight gain was observed in male rats in the 200 mg/kg/day group. Food comsumption tended to be higher in all the drug-treated groups than in the control group. Similar trend was seen also in water comsumption, and increase in urine volume was noted in the groups treated with 100 and 200 mg/kg/day. In the serum biochemical examination, dose-dependent elevation in potassium level was noted in all drug-treated groups, but the values were within the range of physiological variation. In the 100 and 200 mg/kg/day groups, an increase was observed in the absolute heart weight and in its relative weight against body weight. Major abnormalities found in histopathological findings were; swelling of parenchymatous cells in liver and kidney, swelling of fibers and swelling or proliferation of interstitial cells in cardiac and skeletal muscles, and congestion in spleen. No notable abnormality was found in any examination item in the recovery test.

Animals↗
PubMed1980

[On the subacute toxicity of labetalol (AH5158): a combined alpha-and beta-adrenoceptor blocking agent (author's transl)].

Subacute toxicity and recovery tests of labetalol hydrochloride, alpha- and beta-adrenoceptor blocking agent, were carried out using male and female Wistar strain rats. The drug was orally administered at 50, 150, 450 or 1000 mg/kg/day for 1 month. In all the drug-treated groups, increase in salivation was observed from immediately to 15 minutes after dosing through the treatment period. Eight of the 10 males and 9 of the 10 females in the group treated with 1000 mg/kg/day died of intoxication. Suppression of body weight gain was observed in male rats in the 450 and 1000 mg/kg/day groups and in female rats in the 1000 mg/kg/day group. In the 150 mg/kg/day and higher dose groups, water consumption showed a tendency to increase as compared with that of control group. Increase in urine volume was observed in female rats in the 450 mg/kg/day group. In the serum biochemical examination, slight elevation in potassium levels was noted in the 150 and 450 mg/kg/day groups. In histopathological findings, some abnormalities were found in the groups treated at 150 mg/kg/day and higher. Major abnormalities found in organs were; congestion and hypremia of various organs due to vasodilation, swelling of parenchymatous cells in liver and kidneys, and loose arrangement and change in the thickness of muscle fibers in cardiac and skeletal muscles. None of these abnormal findings was found in any examination in recovery tests.

Animals↗
PubMed1978

[On the acute toxicity of labetalol (AH-5158), a combined alpha-and-beta-adrenoceptor-blocking agent (author's transl)].

Acute toxicity studies in labetalol were performed using mice, rats and rabbits, An oral administration of labetalol produced an increase in salivary secretion due to local irritation. Death followed convulsions by large doses of labetalol. Pathological examinations suggested that the cause of death by labetalol was circulatory disturbances due to the damage of heart muscles and a subsequent respiratory paralysis. Parenteral LD50 showed almost the same values among mice (50 mg/kg iv, 117 mg/kg ip), rats (66 mg/kg iv, 115 mg/kg ip) and rabbits (43 mg/kg iv). However, species difference was seen in oral LD50 values which were enormously large as compared with iv LD50 values.

Administration, Oral↗
PubMed1975

[On the toxicity of CT-1341 evoked by long-term administration. I. Subacute toxicity of the intravenous anesthetic, CT-1341 in rats (author's transl)].

CT-1341, an intravenous anesthetic was given in various daily doses in rats for a period of one month to test the subacute toxicity. The drug was administered intraperitoneally in rats. Rats tolerated to daily administration of CT-1341 at doses of less than 1.8 ml/kg without showing other particular toxic signs than anesthesia. Main pathological findings were swelling of cells in the liver and renal tubules, and perivascular cuffing in lungs. No severe patho-histological changes were observed in any organs. Mortal cases were seen in the group of rats, in which CT-1341 was given in a daily dose of 5.4 ml/kg. A paralysis of respiratory center was suggested to be cause of death, because no severe patho-histological changes were observed in any organs of mortal rats. Survivals of this group showed no particular symptom except anesthesia, but an inhibition of the growth curve was seen in male rats only.

Alfaxalone Alfadolone Mixture↗