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I Narama

Publications and source records attributed to I Narama.

At least 73 records · Page 4Linked to original sources

[Reproduction study of propiverine hydrochloride (2)--teratological study in rats by oral administration].

A teratogenicity study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day to dams from day 7 to day 17 of pregnancy. Twenty two or twenty three female rats in each group were sacrificed on day 21 of pregnancy for examination of their fetuses, and thirteen female rats were allowed to deliver for the postnatal examination of their offspring. In dams, the dose of 50 mg/kg caused toxic signs consisting of mydriasis, salivation and rale, body weight loss in the early stage of administration, and reduced food intake and increased water intake. The dose of 10 mg/kg caused rale, very slight suppression of body weight gain and slight reduction of food intake. Body weight of the fetuses was decreased very slightly in the 50 mg/kg group. However, embryonal or fetal mortality and incidences of external, visceral or skeletal anomalies were not increased. In offspring, P-4 had no adverse effect on the postnatal development such as viability, growth, differentiation, emotionality, learning ability or reproductive performance. The results suggest that the non-effective dose level of P-4 is 2 mg/kg/day in maternal animals, 10 mg/kg/day in fetuses and 50 mg/kg/day in offspring.

Abnormalities, Drug-Induced↗

[Reproduction study of propiverine hydrochloride (3)--teratological study in rabbits by oral administration].

A teratogenicity study was performed in New Zealand white rabbits by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2.4, 12 and 60 mg/kg/day to dams from day 6 to day 18 of pregnancy. Thirteen or fifteen pregnant rabbits in each group were sacrificed on day 29 of pregnancy for examination of their fetuses. In dams, the dose of 60 mg/kg caused mydriasis, body weight loss or decreased body weight gain and reduced food and water intakes. Autopsy and weighing of organ weight revealed no evidence due to drug administration in any group. There were no significant differences in embryo-fetal mortality, fetal body weight, or incidences of external, visceral or skeletal anomalies and skeletal variation between treated and control animals. The compound had no lethal effects on the embryos and no growth-inhibiting or teratogenic effects on the fetuses. The results suggest that the non-effective dose level of P-4 is 12 mg/kg/day in maternal animals and 60 mg/kg/day in fetuses.

Abnormalities, Drug-Induced↗

[Reproduction study of propiverine hydrochloride (4)--perinatal and postnatal study in rats by oral administration].

A perinatal and postnatal study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day to dams from day 17 of pregnancy to day 21 after delivery. Twenty two or twenty four dams in each group were allowed to deliver for the postnatal examination of their offspring. In dams, the dose of 50mg/kg caused toxic signs consisting of mydriasis, salivation and rale. One dam of this group showed piloerection, low body temperature, blanching of extremity and auricle, and emaciation associated with marked prolongation of delivery. Body weight gain of the dams was retarded in the 50 mg/kg group throughout the administration period. Food and water intakes were reduced in the 50mg/kg group. In gross pathology of the dam that showed prolonged delivery, the spleen and thymus were moderately or severely atrophied and the adrenal was moderately enlarged. The viability index of the offspring on day 4 was reduced in the 50mg/kg group. Body weight of pups slightly decreased in the 50mg/kg group during sucking and rearing periods. Absolute weights of some organs of the three-week aged offspring were reduced due to attributable depression of body weight gain. However, P-4 had no adverse effect on the postnatal development such as emotionality, motor activity, learning ability or reproductive performance. The results suggest that the non-effective dose level of P-4 is 10mg/kg/day in maternal animals and offspring.

Administration, Oral↗

[Retinal degeneration in the WBN/Kob rat].

Spontaneous, retinal degeneration in the WBN/Kob rat, a new diabetic strain, was examined by behavior pattern, electroretinogram (ERG) and histopathology. Histopathological evidence of retinal degeneration was first detected at about 30 weeks of age in male and female rats. The earliest change in the retina was loss of rads and cones, and the inner layer was gradually involved. The retina showed marked atrophy in the thinned inner plexiform layer and a decreased number of ganglionic cells by 90 weeks. Severe retinal change was observed in almost all rats over 90 weeks old. Prior to the onset of histological change, the ERG showed prominent change. Amplitude of a- and b-waves began to be reduced at 17 weeks and was non-recordable at 32 weeks. This retinal abnormality was thought to be hereditary, but further investigation is needed to clarify the relationship between the genetic background of this change and diabetes.

Animals↗

[Effect of gonadectomy on the onset of diabetic syndrome in the female WBN/Kob rats].

Almost all the male animals of WBN/Kob rat strain show the diabetic syndrome whereas none of the female animals develop such diseased conditions even at elder age. We investigated the effect of sex hormones on the onset of diabetic syndrome of this rat strain by comparing the results of body weight gain and various clinical tests such as glucose tolerance, serum biochemistry and histopathology of spayed female rats with those of non-treated and sham-operated female animals kept until 88-week-old. Non-treated and sham-operated female animals had shown no abnormal result even at 88-week-old. Spayed female animals began to reveal glucosuria associated with polydipsia and polyuria from 72-week-old, and gradually developed emaciation and cataract. Increased body weight gain, impaired glucose tolerance and lasting hyperglycemia were observed prior to the onset of the symptoms. Pancreatic changes consisted of atrophy of acinar tissue and atrophy or disappearance of islet tissue attributable to clinical data also were detected in spayed female animals. These diabetic syndrome and pancreatic change were analogous to those of aged male WBN/Kob rats but the onset of spayed females was delayed and less severe. Present results suggest that female sex hormones are protective from the onset of diabetic syndrome of WBN/Kob rats.

Animals↗

[Six-month chronic intravenous toxicity study of cefodizime sodium in dogs].

The chronic intravenous toxicity of cefodizime sodium (THR-221) was studied in beagle dogs. Groups of 6 males and 6 females were treated with THR-221 at doses of 0 (saline), 200, 400, 800 and 1600 mg/kg/day for 6 months. The THR-221 related symptoms were vomiting, excessive drinking behavior and salivation. The paleness of the visible mucosa and discoloration of vascular color by funduscopy due to systemic anemia were observed in one animal each of 800 and 1600 mg/kg/day groups. Body weight was depressed transiently or continuously in a few animals of 400-1600 mg/kg/day groups. The hematological, serum chemical and urinalysis findings in a few animals of 400-1600 mg/kg/day groups revealed decreases in RBC count, PCV and hemoglobin, an increase in reticulocyte count, a decrease in WBC count, a decrease in platelet count, slight increase in TP, and albumin, a decrease in AlP, and an increase in urinary Na. Light microscopically, deposition of hemosiderin and increased extramedullary hematopoiesis in the liver and spleen, and deposition of fibroid substance in the white pulp of the spleen and diffuse fibrosis in the bone marrows were detected in a few animals of 800 and 1600 mg/kg/day groups. Electron microscopically, no significant toxic changes were observed. The maximum nontoxic doses of THR-221 are estimated as 200 mg/kg/day in male and less than 200 mg/kg/day in female.

Anemia↗

Relationship between cellular morphology and immunocytological findings of spontaneous pituitary tumours in the aged rat.

A total of 339 spontaneous pituitary tumours from 284 aged rats were studied by light microscopy. Based on the cellular morphology in preparations stained by haematoxylin and eosin, tumour cells were classified into 4 types: granular; agranular small; agranular large polygonal; and agranular large slender cells. Eight tumours consisted of mixed neoplastic masses of 2 types of cells. A total of 85 cases representative for each tumour type was used for special staining and immunocytochemistry. All tumours of the granular cell type and some tumours of the agranular large polygonal cell type had granules which stained red by azocarmine and were positive for prolactin. All agranular small cell type tumours were also positive for prolactin and agranular slender cell type tumours were positive for adrenocorticotropic hormone. Only tumours of the agranular large polygonal cell type gave an indefinite or negative reaction for all the various pituitary hormones. These results indicate a relatively good correlation between the cellular morphology and the immunocytochemistry of spontaneous pituitary tumours in aged rats.

Adrenocorticotropic Hormone↗

A serological survey of simian virus 40 in monkeys.

A serological survey of simian virus 40 (SV 40) was conducted by an immune adherence hemagglutination (IAHA) test in breeding monkeys. Of a total of 356 monkeys tested, 168 (47.2%) were seropositive. All 168 seropositive monkeys were detected from 224 monkeys which were bred or kept in Japan for a long time. In contrast, none of the 132 monkeys which were newly imported from Southeast Asia was seropositive. If a comparison was made in the same breeding place, the positive rate of 80.4% (111/138) of Japanese monkeys was significantly (P less than 0.01) higher than the 59.5% (25/42) among rhesus monkeys. The positive rate and the IAHA titers were higher in older age group (greater than 5 years) but similar in male and female. These results indicated that SV 40 was highly prevalent among breeding monkeys in Japan.

Animals↗

Microfilarial granulomas in the spleens of wild-caught cynomolgus monkeys (Macaca fascicularis).

Splenic nodules from 38 cynomolgus monkeys (Macaca fascicularis) which were captured in Malaysia and Indonesia were studied histologically. The lesions were characterized by well-circumscribed focal fibrosis, accumulation of eosinophils and histiocytes, hemorrhage or hemosiderosis, and loss of normal splenic architecture. Small arteries in the lesion frequently had intimal thickening and narrowing of the lumen in addition to the presence of microfilariae. Microfilariae were also seen in the extravascular area of the lesion, and were occasionally engulfed by multinucleated giant cells. The splenic lesion was thought to have been initiated by incomplete infarction caused by intimal thickening and microfilarial occupation of the small arteries.

Animals↗

A new diabetic strain of rat (WBN/Kob).

A new, spontaneously occurring diabetic syndrome has been observed in the aged males of an inbred strain of Wistar rats, WBN/Kob. The main clinical sign, glycosuria, was first detected at about 60 weeks of age, and thereafter some animals developed hyperlipidaemia and gradual emaciation. Prior to the onset of glucosuria, male rats showed impaired glucose tolerance after a glucose load at 21 weeks of age. The histopathologic lesions of the pancreas in the diabetic males consisted of multifocal fibrosis, decreased in number and size of islets and atrophy of exocrine tissue. Multifocal inflammatory foci of varying stages were the main pancreatic lesion in prediabetic male rats. This inflammatory change was detected even in 12-week-old rats and tended to occur around the islets. Therefore focal fibrosis and the decrease in the number and size of islets were considered to result from post-inflammatory scarring. The maturity-onset of this syndrome and the impaired glucose tolerance in younger animals suggested that diabetes mellitus of this rat strain is insulin-independent type II. However, the histological lesions of the pancreas were somewhat different from previous reports of both type I and II diabetes mellitus in man and animals.

Animals↗

[A simplified method for detection of visual abnormality in rats on reproduction study: the critical intensity of illumination and the effect of dark-adaptation].

A newly designed Y-shaped box was previously reported by authors to be useful for a screening test of visual abnormality in rats because of easy numerization and statistical analysis of the results. In the present paper, the relationship between the intensity of illumination and the negative phototaxic response were examined. The total selection rate for the dark area (total time of selecting dark area/total trials) of non-treated rats under 30 lux illumination was 98% and identical wit the result of those under 1600 lux. The selecting rates of non-treated rats under the illumination of 15, 10, 7.5, 5 and 1.25 lux were 95, 93, 89, 82 and 67%, respectively. On the other hand those of dark-adapted rats one hour under 15, 7.5 and 5 lux showed 98, 95 and 92%, respectively. From these results, the critical intensities of illumination-unaffected selection rate for darkness in non-treated and dark-adapted rats were estimated at 30 and 15 lux, respectively. There was an obvious effect of dark-adaptation on the visual ability of rats. The selection rate of eyelid-sutured rats under 30 lux was 52%, an approximate theoretical value of true blindness, but it was 85% under 1600 lux. It is suggested that a more exact detection of visual abnormality would be possible under the critical intensity of illumination-unaffected selection rate for darkness.

Animals↗