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Biomedical subjects

I Narama

Publications and source records attributed to I Narama.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Perinatal and postnatal study of trandolapril (RU44570) in rats].

A perinatal and postnatal study was performed in female Sprague-Dawley rats treated orally with trandolapril (RU44570) at dosage levels of 3, 30 and 300 mg/kg/day from day 17 of pregnancy to postpartum day 21. In each group, 24 or 25 pregnant female rats were allowed to litter naturally for the postnatal examination of their offspring. Clinical symptoms and mortality attributable to the administration of RU44570 were not observed in the dams (P). In the 30 and 300 mg/kg group, food consumption was slightly lower than that of the control group during the lactation period, however RU44570 did not affect body weight gain. Incidence of dilatation of renal pelvis with higher value in kidney weight was increased in offspring (F1) in the 30 and 300 mg/kg dosage groups, and water consumption at the same dosage groups was higher than that of the control group. Body weight gain in offspring (F1) was depressed in each treated group and viability of offspring (F1) from postpartum day 0 to day 4 was slightly decreased in the 30 and 300 mg/kg dosage groups comparing with that of the control group. No adverse effects were observed on the other postnatal development of the offspring, such as differentiation, sexual maturation, reflex, motor activity, emotionality, learning ability and reproductive performance. No adverse effects were detected in the second generation offspring (F2). The results suggest that the non-effective dose of RU44570 is 3 mg/kg for dams (P), lower than 3 mg/kg for development in offspring and 300 mg for fetuses (F2), respectively.

Abnormalities, Drug-Induced↗
PubMed1993

[Twelve-month oral toxicity study of trandolapril (RU44570) in rats].

1) The chronic toxicity of (-)-(2S, 3aR, 7aS)-1-[(S)-N-[(S)-1- ethoxycarbonyl-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic++ + acid (trandolapril: RU44570), a novel angiotensin-converting enzyme blocking antihypertensive drug, was assessed in rats by oral administration for 12 months at dosage levels of 0.05, 0.25, 2.50 and 25.00 mg/kg/day, comparing with the control animals received 0.5% methylcellulose solution. Reversibility of the drug-induced changes was also examined by 3 months' withdrawal following the administration period. 2) There was no death or general symptom that was thought to be attributable to the administration of RU44570. 3) The body weight gain was significantly suppressed from 1st week to the end of administration period in male animals of the dosage groups of 2.50 mg/kg or more and from week 1 to 15 of administration in female animals of the 25.00 mg/kg dosage group. During the withdrawal period, the difference of the body weights between these groups and control was reduced and that was never statistically significant. 4) The food consumption generally tended to be lowered in male animals of the dosage groups of 2.50 mg/kg or more throughout the administration period. The values were significantly different from that of control group on almost all measurement points from week 2 to 34 of administration. The difference of the food consumption of these groups from control group tended to be smaller thereafter, although significant difference was seen sporadically. Male animals of the 0.05 and 0.25 mg/kg dosage groups also showed the tendency of decreased food consumption infrequently. There was no constant tendency of fluctuation in the food consumption among the each RU44570 treated group during the withdrawal period. 5) The water consumption increased significantly in male animals of the 25.00 mg/kg dosage group from 1st week to the end of administration period. Male animals of the 2.50 mg/kg dosage group showed similar high value of the water consumption but the degree was lesser than that of 25.00 mg/kg dosage group. Although female animals of the 25.00 mg/kg dosage group showed significantly increased water consumption from week 3 to 4 of administration, they began to show decreasing tendency from approximately week 10 of administration conversely. From week 26 of administration, the water consumption of this group significantly decreased frequently comparing with that of control group. Female animals of the 2.50 mg/kg dosage group showed similar decrease in water consumption from approximately week 26 of administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1993

[Fertility study of trandolapril (RU44570) in rats].

A fertility study was performed in Sprague-Dawley rats treated orally with trandolapril (RU44570) at the dosage levels of 3, 30 and 300 mg/kg/day. The male rats were treated for 63 days before mating and during the mating period. The female rats were treated from 14 days before mating to day 7 of pregnancy. Each 24 male and female rats in the same dosage group were mated and female rats were sacrificed on day 20 of pregnancy for the examination of their fetuses. No abnormal findings were observed in symptom during the administration period, however body weight gain and food consumption in both male and female animals of treated groups were lower than control group. Any adverse effects on reproductive performance were not detected. Numbers of implantations and live fetuses were decreased slightly at 30 and 300 mg/kg dosage group comparing with those of the control group. However, RU44570 did not affect fetal mortality, growth of fetuses, or the incidence of external, visceral or skeletal malformation of the fetuses. From these results, it is suggested that non-effective dose level of RU44570 is lower than 3 mg/kg for general toxicity in parent animals, 300 mg/kg for reproductive ability in parent animals, and 3 mg/kg for development in embryos and fetuses, respectively.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Endocrine cell populations in the pancreas of diabetic WBN/Kob rats.

Numerical changes of insulin-, glucagon- and somatostatin-positive cells in the pancreas of WBN/Kob male rats with spontaneously occurring diabetes were examined. The rats examined were divided into three different age groups: Groups I (12 weeks old) and II (33 weeks old) were clinically prediabetic and group III (60-90 weeks old) was diabetic. Serum glucose value was in the normal range in groups I and II, while it was much higher in group III. B and A cells were markedly decreased in number in groups II and III. In group II, the ratio of B to A cells was normally preserved, though the total endocrine cell number was markedly decreased as compared with that in group I. In group III, the percentage of B cells was decreased significantly. The normal ratio in group II seemed to keep serum glucose within the normal level. In addition to the total endocrine cell reduction, an altered ratio of B and A cells was considered to cause the diabetic condition.

Animals↗
PubMed1992

Estimation of structural changes in the cataractous rat lens using Raman spectroscopy.

For quantitative evaluation of cataract-related changes in lens proteins and lens water, the relative contents of water and SH residues and changes in the microenvironments of aromatic amino acid residues were quantitatively examined in cataract of the rat lens which had been induced by sodium selenite. Using Raman spectroscopy, results were compared with those of age-matched control lenses. The relative contents of water and SH residues decreased with increasing age in normal lenses from 3 to 8 weeks of age. In the cataractous lens, the relative water content increased constantly as compared with that of age-matched controls. The relative SH residue content continued to decline in the cataractous lenses of animals at every age. The microenvironments of tyrosine residues in cataractous lenses also changed progressively.

Animals↗
PubMed1992

[Effect of sex hormones on the onset of diabetic syndrome in WBN/Kob rats].

The effects of sex hormone on diabetic conditions were investigated in WBN/Kob strain rats, i.e., castrated or spayed, hormone-treated, and non-treated rats. The effects of sex hormone on glycosuria, body-weight change, glucose tolerance and histopathology of the pancreas were compared among these animals. There were no abnormal changes in these parameters in the non-treated females and estrogen-treated males. The glycosuria began to be observed from the age of about 30 weeks in the non-treated group and from the age of 52 weeks in the castrated group. In the female animals, this symptom began to appear from the age of 55 weeks in the testosterone-treated group and from the age of 72 weeks in the spayed group. Before the onset of the diabetic symptoms, glucose tolerance was impaired in these animals. Body weights of the castrated and estrogen-treated males were lower than that of the non-treated males, especially in the estrogen-treated males. Those of the spayed and testosterone-treated females were much heavier than that of the non-treated females. Testosterone treatment accelerated body-weight gain in the spayed female animals. Histopathological examination of the pancreas revealed atrophy of the aciner tissue and atrophy and disappearance of the islet cells similar to those of the non-treated WBN/Kob male rats in the castrated males, spayed females and testosterone-treated females. However, these changes were not observed in the non-treated females or estrogen-treated males. These findings suggest that female hormone suppressed the onset of hyperglycemia along with glycosuria and male hormone accelerates the onset of hyperglycemia in the WBN/Kob rats.

Animals↗
PubMed1991

Glomerular lesions in spontaneously occurring diabetic WBN/Kob rats.

Glomerular lesions in WBN/Kob male rats with spontaneous diabetes were examined histopathologically. The glomerulopathy caused by diabetes was compared with lesions in chronic progressive nephropathy of non-diabetic SD and F344 male aged rats. Diffuse and global thickening of the mesangial area was observed only in WBN/Kob rats and showed a statistically significant correlation with serum glucose concentrations. Therefore, it suggested that the mesangial thickening was a result of hyperglycaemia. Fibrin cap-like lesions were seen in both WBN/Kob and non-diabetic SD or F344 male rats. The severity of these lesions was closely related to that of chronic progressive nephropathy and, therefore, the fibrin cap-like lesions were considered to be due to the chronic progressive nephropathy.

Age Factors↗
PubMed1991

[Biochemical and histopathological studies on a mouse brain ischemic model induced by bilateral carotid artery occlusion: comparison with the carbon monoxide inhalation method and other ischemic or anoxic models].

Bilateral occlusion of the carotid arteries (BCAO) killed 52% of the male ddY mice (N = 86) and 77% of the ICR mice (N = 96) within 10 min, and the mean survival time of the ddY strain recorded for the 10 min was significantly longer than the time of the ICR strain. Among animals that survived longer than 1 hr after BCAO, some (5 of ddY and 3 of ICR) were able to survive for more than 24 hr. All of the neurobehavioral and histopathological signs developed by BCAO and in most cases followed by death were found to be also inducible by unilateral occlusion alone, although this was in a small fraction of mice. The brain levels of ATP, glucose and acetylcholine significantly decreased in mice that died within 10 min after BCAO, while none of these changes were detectable in mice surviving BCAO for 1 hr, just as in mice that died by carbon monoxide or ether inhalation. The results obtained herein indicate that mice may not be homogeneous in the functional level of the collateral route of blood supply to the brain tissue and/or in the sensitivity toward the ischemia-inducible lethality.

Acetylcholine↗
PubMed1991

Prevalence of antibodies to five selected zoonosis agents in monkeys.

The prevalence of antibodies against 5 zoonosis agents was determined in serum samples of 443 breeding monkeys. Of the monkeys, 296 were bred or kept for a long time at R institute, and the remaining 147 were newly imported from the Philippines and kept at S institute for quarantine. Antibodies to simian virus 40 were highly prevalent at 89.1% among monkeys of R institute, whereas no antibody could be detected in those of S institute. Antibodies to Chlamydia psittaci and Yersinia pseudotuberculosis were detected in 14.4 and 11.6% at R institute, and in 9.0 and 3.5% at S institute, respectively, evidencing a significant difference (P less than 0.05) between those of the two institutes for both agents. Antibodies to Toxoplasma gondii and Leptospira interrogans were found in 3.6 and 2.9% of the overall, respectively, showing no difference in positive rates in relation to breeding place. Even in cases positive to the latter 4 zoonosis agents, the antibody titers were low. The results obtained suggest that all zoonoses tested do not seem to be so serious diseases among monkeys at the present time except simian virus 40 infection, which is highly prevalent among breeding monkeys in Japan.

Animals↗
PubMed1990

Glycogen accumulation in the renal tubular cells of spontaneously occurring diabetic WBN/Kob rats.

Cytoplasmic and nuclear accumulation of glycogen granules in the kidney cells of 72 male WBN/Kob rats with a long-term diabetic condition was studied histologically and by electron microscopy. The incidence and degree of the accumulation showed good correlation with the blood glucose concentration. In the kidneys, there was evidence of two types of lesion, cytoplasmic glycogen accumulation in the distal convoluted tubules and nuclear accumulation in the ascending thick segment of Henle's loops. Electron microscopically, the cytoplasmic glycogen accumulation was often associated with an increased number of lysosomal bodies containing lamellar bodies. Glycogen bodies, the halo of which was thought to be identical with that of nuclear bodies, were frequently observed in the nuclei containing the glycogen granules. These morphological and topographical differences between the two types of lesion were considered suggestive of different pathogenetic mechanisms for glycogen accumulation in the kidney cells.

Animals↗
PubMed1990

Histopathology of spontaneous panarteritis in beagle dogs.

Spontaneous focal panarteritis was noted in small and medium-sized arteries including extramural and intramural coronary arteries, and arteries in bone marrow, leptomeninges of spinal cord, meninges of medulla oblongata and tunica albuginea of epididymis of 17 out of 925 beagle dogs used for various toxicity studies. The arterial lesion consisted of varying inflammatory processes in all of the arterial wall and was characterized by intimal fibrinoid necrosis in acute cases and intimal fibrous thickening in chronic cases with varying population of inflammatory infiltrates in the arterial wall. The infiltrates included plasma cells, lymphocytes, macrophages and neutrophils. Periarterial inflammatory cells of the affected arteries showed positive reactions to IgG or IgM. Morphological similarities between spontaneous and drug-induced arterial lesions might confuse the evaluation for vascular toxicity of various chemicals. Therefore, detailed description of the morphology and distribution of spontaneous arterial lesions in the beagle dogs seems to be important for the pathological basis on safety assessment.

Animals↗
PubMed1990

Superficial eosinophilic gastritis in laboratory beagle dogs attributable probably to diet.

Stomach tissues from 222 beagle dogs, which were used for toxicological studies, were examined histopathologically. Out of 190 dogs fed the same diet, 185 had gastric lesions, whereas all of 32 dogs fed another diet were free from them. The gastric lesions were noted as an accumulation of eosinophils, infiltration of inflammatory cells including lymphocytes, plasma cells and histiocytes in the gastric lamina propria, formation of foreign body type multinucleated giant cells, focal desquamation and papillary proliferation of mucosal epithelium. The lesions were confined to the superficial layer of the antral and pyloric mucosa, and neither desmoplasia nor clinical signs were seen. Multinucleated giant cells often contained amphophilic foreign bodies of varying appearance with inconsistent reaction for periodic acid-Schiff (PAS), but no definite causal agents were detected.

Animals↗
PubMed1989

Peripheral motor neuropathy in spontaneously diabetic WBN/Kob rats: a morphometric and electron microscopic study.

The morphology and function of peripheral motor nerves of WBN/Kob rats of the newly identified strain with late onset and long-lasting diabetes were studied in comparison with those of nondiabetic age-matched rats. The most conspicuous and frequent change seen by electron microscopy in the diabetic rats was myelinopathy, initiated by vesicle formation in granular material accumulated in the myelin lamella. Initial changes developed into myelin blebbing or distention, demyelination and remyelination. A decreased population of nerve fibers in diabetic rats of advanced age suggested that the final stage of these changes was neuronal loss resulting from complete destruction of the neurons. The myelinopathy was consistently more frequent and conspicuous in diabetic rats than in age-matched nondiabetic rats, but the difference was not significant in rats of over 28 months old, because of the age-dependent increase of the change in older rats. The conduction velocity was significantly less in diabetic rats than in age-matched nondiabetic animals at 20 months but not at 28 months of age, because at the older age nondiabetic rats also showed a reduced conduction velocity. These findings showed that male WBN/Kob rats develop diabetic motor neuropathy, but that the essential changes in diabetic neuropathy are indistinguishable morphologically and functionally from those in age-dependent neuropathy.

Animals↗
PubMed1989

Accumulation of pigment granules in lacrymal gland epithelium in practolol-treated beagle dogs.

A 6-month oral toxicity test of practolol was carried out in beagle dogs as a reference control for a newly developed beta blocker. No significant drug-induced changes were detected in any animals by various ophthalmological examinations such as ERG, tear flow, lysozymal activity in tears, etc. However, an unusual pathological change was detected in the lacrymal gland of all five dogs treated with practolol and not in control animals. Macroscopically, the lacrymal glands assumed a blackish brown to deep black colour on both the outside and the cut surface. Microscopically, fine, dark-brown pigment granules were present in the apical and supra-nuclear portion of the cytoplasm of predominantly serosal type epithelial cells. These pigments reacted positively to Schmorl's method for lipofuscin, but gave a negative PAS reaction for polysaccharide, Prussian blue for iron and Ziehl-Neelsen method for ceroid pigment. They were detected as membrane-bound electron-dense bodies by electron microscopy. Similar pigments were also deposited in the cytoplasm of the apocrine sweat gland. Although the mechanism of the accumulation of these granules is far from clear, concentration of practolol in the lacrymal gland is considered to be very closely related to the presence of these granules. A possible mechanism for ocular toxicity by practolol, involving this change, is discussed.

Animals↗
PubMed1989

[One-year chronic oral toxicity study of propiverine hydrochloride in dogs followed by one-month recovery].

The chronic oral toxicity of propiverine hydrochloride (P-4), a new anti-pollakiuria agent, was studied in beagle dogs. Groups of 6 males and 6 females were treated with P-4 at doses of 0, 0.3, 1, 3, 9 mg/kg/day for one year and thereafter 2 animals of both sexes in each group were placed on withdrawal for one month. During administration and recovery period, no death occurred in any dosed animals. As a toxic sign, only the frequency of vomiting was increased in animals of 1, 3 and 9 mg/kg/day groups. Body weight, food and water consumption were not affected by the P-4 administration. In serum chemical examinations, gamma-GTP activity was increased in both sexes of 9 mg/kg/day group at 6 month of administration. Further decrease in total and free cholesterol, triglyceride and phospholipid, increase in GPT activity were detected in some animals of 9 mg/kg/day group at 12 month of administration. In addition decreasing tendency in levels of albumin was noted in males of 9 mg/kg/day group at 9 and 12 month of administration. And also, a gradual increase in total protein level and a gradual decrease in alkaline phosphatase activity were seen in control group, but in females or males of 9 mg/kg/day group, those changes were mild. Urine pH rised slightly in females of 3 mg/kg/day group and in both sexes of 9 mg/kg/day group. No specific findings attributable to P-4 treatment were detected in ECG, heart rate, funduscopy, hematology, fecal occult blood test and necropsy. The absolute and/or relative liver weight in males of 3 and 9 mg/kg/day groups were significantly increased. Light-microscopically, the hypertrophy of hepatocytes characterized by homogenization and enlargement of cytoplasmic space, and concentric inclusions in hepatocytic cytoplasm were detected in both sexes of 3 and 9 mg/kg/day groups. Corresponding to these microscopical findings, the following changes were observed electron-microscopically, the proliferation of smooth surfaced endoplasmic reticulum in hepatocytes in both sexes of 1, 3 and 9 mg/kg/day groups, lamellar bodies in hepatocytes in females of 3 mg/kg/day group, and in both sexes of 9 mg/kg/day group, and annulate lamellae in hepatocytes were detected in one female of 9 mg/kg/day group. After the recovery period, the above mentioned abnormalities were markedly attenuated or disappeared except the changes in hepatocytes. From these results, it seemed that 9 mg/kg/day of P-4 might be safety dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1989

[Reproduction study of propiverine hydrochloride (1)--fertility study in rats by oral administration].

A fertility 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. Male rats were treated for 9 weeks before mating and following 4 weeks including mating period. Female rats were administered the test substance from 2 weeks before mating to day 7 of pregnancy. The females were sacrificed on day 21 of pregnancy for examination of their fetuses. Toxic signs consisted of mydriasis, salivation and rale were observed in both male and female animals at the dose of 50 mg/kg group and in male animals at the dose of 10 mg/kg group. Body weight gain was supressed and food intake was decreased in the 50 mg/kg group throughout the administration period. Water intake of the 50 mg/kg group was decreased temporarily at the early stage of administration period, although increased thereafter. Autopsy revealed the enlargement of the liver with yellow-brownish coloration in one male rat at the 50 mg/kg group. Fertility and reproductive ability in both sexes were not affected by administration of P-4. There was no lethal effect and no growth-inhibiting or teratogenic effects on the embryos and the fetuses. The results suggest that the non-effective dose level of P-4 was 2 and 10 mg/kg/day for general toxicity in male and female parent animals respectively, 50 mg/kg/day for reproductive ability in parent animals and in embryos and fetuses.

Abnormalities, Drug-Induced↗