Biomedical subjects

A Kast

Publications and source records attributed to A Kast.

At least 37 records · Page 2Linked to original sources

PubMed1989

Plantar decubitus ulcers in rats and rabbits.

A high incidence of plantar decubitus ulcers, 35% in males and 22 or 45% in females, respectively, occurred in rats of two carcinogenicity studies independent of the bedding used, hard or soft wood chips. Among rabbits kept in chrome-plated wire cages, about 2-year-old female breeders suffered from the plantar ulcers, but not their male partners of the same age group. The causes of the foot disease appear to be manifold, however, in our cases the lesions could be prevented in both species by housing on a cage floor made from flattened stainless wire.

Animal Husbandry↗

PubMed1988

Corticosterone induction of cleft palate in mice dosed with orciprenaline sulfate.

Orciprenaline sulfate is a beta-adrenoceptor stimulant chemically described as 1-(3,5-dihydroxyphenyl)-1-hydroxy-2-isopropylaminoethane sulfate (Alupent). The drug has broncho-dilating activity and has been developed in numerous countries since 1961. The purpose of these studies was to investigate the teratogenic potential of orciprenaline and its mode of action in pregnant Jcl:ICR mice, when administered during the period of organogenesis and, more systematically, during the critical period of palate formation. Daily doses of 5, 50, and 500 mg/kg were given orally by gavage to mice on days 6-15, 11-13, or on day 12 of gestation. Additional studies were done to evaluate the maternal cardiotoxic action of orciprenaline and its effects on adrenal cortex and endogenous serum corticosterone. Five mg/kg triamcin-olone acetonide, a glucocorticoid, were given subcutaneously as a positive control causing 100% cleft palate. Myocardial necroses occurred in pregnant mice only after 500 mg/kg orciprenaline had been given, and a significant increase in cleft palate occurred if exposure took place during days 11-13 or day 12 of gestation. This increase in cleft palate can be explained by the teratogenic effect of an elevated maternal serum corticosterone level 1 hr after orciprenaline treatment, about three times the control value.

Administration, Oral↗

PubMed1988

Teratogenicity of the antiallergic Sm 857 SE in rats versus rabbits.

Sm 857 SE is an antiallergic drug chemically described as 11-Oxo-11H-pyrido(2,1-b)quinazoline-2-carboxylic acid that has activity against allergic bronchoconstriction in animal models. The purpose of this study was to investigate the teratogenic potential in pregnant rats and rabbits when administered during the critical period of organogenesis. The drug was suspended in aqueous 0.25% carboxymethylcellulose (CMC) solution. Daily doses of 20, 90, or 400 mg/kg were given orally by gavage to rats on days 7 through 17 of gestation and to rabbits on days 6 through 18. Two additional studies were done in rats dosed with 400 mg/kg, and with 90, 200, or 400 mg/kg, respectively. Doses of 20, 90, and 200 mg/kg had no meaningful effects on maternal animals of either species or on their offspring. A dose of 400 mg/kg was maternally toxic in rats as shown by the effects on body weight and food consumption. Among pregnant rabbits, two deaths and three miscarriages occurred at this dose. In rats, 400 mg/kg caused embryonic death, retarded fetal development, and two specific malformations, namely microphthalmia and vertebral-costal defects. A mild teratogenic action of 400 mg/kg also occurred in the first additional study but not in the second one. There was, however, one anophthalmia in a rat fetus of the 90 mg/kg group. In rabbits, no embryotoxic or teratogenic effects were observed. These species differences were explained by the concentration and protein binding in maternal serum as well as by the relatively high concentration of 14C-Sm 857 SE in the rat fetus.

Abnormalities, Drug-Induced↗

PubMed1988

The influence of the hour of the day on the performance of male rats in water multiple T-maze.

The performance of male SD rats in the water multiple T-maze was tested at 2 different times of the day: during the dark phase from 1900 to 2100, the elapsed time between the entry into water and the arrival at ramp was significantly shorter and the number of errors significantly less in comparison with the results of another group of male rats allowed to swim during the light phase from 0700 to 0900. However, only the acceptance of information was retarded, while the keeping of memory remained unaffected.

Animals↗

PubMed1988

The optimum pH of serum alkaline phosphatase after induced cholestasis in the male rat, mouse and rabbit.

The optimum pH of serum alkaline phosphatase (alk. P., EC 3.1.3.1) was investigated in adult male rats, mice and rabbits after fasting or after the induction of cholestasis by a single oral dose of 200 mg/kg alpha-naphthylisothiocyanate (ANIT). The nature of serum alk.P. was also studied with the inhibitory effects of three L-amino acids (L-phenylalanine, L-homoarginine and L-cystine) and by electrophoresis. In the rat, fasting as well as ANIT-treatment shifted the optimum pH of alk.P. from 9.4 to 10.0 due to a decrease in intestinal isoenzymes or due to newly appeared liver isoenzymes, while no shifting occurred in mouse and rabbit.

1-Naphthylisothiocyanate↗

PubMed1988

Circadian rhythm of liver parameters (cellular structures, mitotic activity, glycogen and lipids in liver and serum) during three consecutive cycles in phenobarbital-treated rats.

The circadian rhythm of gastric content, serum alkaline phosphatase (alk.P.), serum lipids, body weight (wt), relative (rel.) liver wt, cellular structures (by light- and electron-microscopy), mitotic activity of hepatocytes, glycogen content, protein and lipids in liver was studied in 180 male Sprague-Dawley rats orally treated at 0830-1030 with 50 mg/kg phenobarbital (PB) for 7 days. Thereafter, five PB-treated males and five controls each were studied at 4-hr intervals at 0600, 1000, 1400, 1800, 2200 and 0200 on 3 consecutive days. The lighting schedule in the colony was 12:12 = light/dark (light from 0600 to 1800). Following the rhythm of gastric emptying, the rel. liver wt showed a clear circadian rhythm with a peak at 0800. The rel. liver wt was raised in PB-treated rats at all times of the day. The circadian rhythm of cellular structures was closely related to the hepatic glycogen content which exhibited a clear rhythm with the peak also at 0800, but lowered values were found in PB-treated rats. The mitotic activity of hepatocytes was significantly increased in PB-treated rats but displayed the same circadian rhythm as controls with peaks at noon and troughs at midnight. The well-known hypertrophy of the smooth endoplasmic reticulum in PB-treated rats was not found at 0600, but was fully developed at 1400 and 2200. PB-treatment increased significantly the liver content of cholesterol, triglycerides and phospholipids. Liver cholesterol showed a clear circadian rhythm with peaks at 1800. No rhythm of liver protein, triglycerides and phospholipids was observed. In serum, levels of cholesterol were significantly elevated, those of triglycerides and alk.P. significantly lowered, while those of phospholipids were not affected by the treatment. The three serum lipids, alk.P. and beta-lipoprotein exhibited a clear circadian rhythm, while serum glucose and non-esterified fatty acids did not.

Animals↗

PubMed1987

Circadian rhythm of the liver of male rats dosed with phenobarbital--I. Organ weight, cellular structures, glycogen contents and mitotic activity.

The circadian rhythm of the liver, namely organ weight, cellular structures (by light-microscopy), glycogen content (by periodic acid-Schiff (PAS) reaction) and mitotic activity, was studied in 166 male Sprague-Dawley rats orally treated daily at 0800-0900 with 70 (study 1) or 50 (study 2) mg/kg phenobarbital (PB) for 7 days. Thereafter, eight (study 1) or five (study 2) rats each were studied at 4-hr intervals at 1000, 1400, 1800, 2200, 0200, 0600 and 1000 through till the following day. The lighting schedule in the colony was 12:12, light:dark (light from 0600 to 1800). The liver weight was raised in PB-treated rats at all times of the day compared to controls and showed a distinct circadian rhythm with a peak at 1000 and a minimum at 2200 in PB-treated rats and the controls. The circadian rhythm of cellular structures was closely related to the hepatic glycogen content which was in good agreement with the controls, but at 1400 and 1800 the glycogen particles were more distinctly diminished in the enlarged centrilobular hepatocytes of PB-treated rats. The mitotic activity of hepatocytes was markedly increased in rats treated with PB but showed the same circadian rhythm as controls with a peak at 1000.

Animals↗

PubMed1987

Circadian rhythm of the liver of male rats pre-treated with phenobarbital--II. Hexobarbital sleeping time and lipids content in liver and serum.

The circadian rhythm of hexobarbital sleeping time and lipids content in liver and serum were studied in 226 male Sprague-Dawley rats pretreated daily at 0800-0900 with 70 mg/kg (study 1 or 3) or 50 mg/kg (study 2) phenobarbital (PB) orally for 7 days. Thereafter, eight (study 1) or five (study 2 and 3) rats each were studied at 4-hr intervals at 1000, 1400, 1800, 2200, 0200, 0600 and 1000 through the following day. The lighting schedule in the colony was 12:12 +/- light:dark (light from 0600 to 1800). The hexobarbital sleeping times of PB-pretreated rats were generally shortened compared to the controls and no circadian rhythm was observed. PB-treatment increased slightly the liver content of cholesterol, and significantly that of triglycerides and phospholipids. Liver cholesterol and phospholipids showed circadian rhythms with peaks during the dark phase. No circadian rhythm of liver triglycerides existed. In serum, levels of triglycerides and phospholipids were slightly lowered by PB-treatment, while levels of cholesterol and beta-lipoprotein were not influenced. Serum values did not exhibit circadian rhythms.

Animals↗

PubMed1986

Cytoplasmic vacuolation of pancreatic beta cells of rats after oral administration of a derivative of isoquinoline.

beta cells in islets of Langerhans were studied in Sprague-Dawley rats dosed by gavage with 0 (control), 75, 150, 250 or 300 mg/kg body wt/day S-H 966 BS [1-(1-oxido-4-thiomorpholino)-3-(1-piperazinyl)], an isoquinoline derivative. All doses caused a significant and dose-dependent increase in serum glucose (diabetes mellitus). At 250 mg/kg, degranulation of beta cells was discovered after 1 day and vacuole formation after 2 days. Ultrastructural alterations compared well with that seen after treatment with cyproheptadine and other structurally related compounds. The vacuolation of beta cells was fully developed following 6 weeks of daily treatment, when a dose-dependent elevation of blood glucose was first observed. The effects were more severe in males than in females. Lesions were reversible within 6 weeks except at 300 mg/kg in males.

Alkaline Phosphatase↗

PubMed1986

Litter parameters and spontaneous abnormalities in Himalayan rabbits.

A joint study was undertaken in three testing facilities to evaluate cumulative background data of Himalayan rabbits. All litters were derived from control does. The conception rate was high (84.0-95.1%) but the average numbers of corpora lutea (7.9-8.7), implantation sites (6.5-7.5) and viable fetuses (5.8-6.9) were somewhat lower than that of most other strains of rabbit. Altogether 90 malformed fetuses (1.12%) and 425 fetuses with variations (5.27%) occurred among 8,060 virable fetuses.

Animals↗

PubMed1986

Experiences with the identification of small rodents.

Own experiences with the identification of mice and rats using ear tags, ear punching, toe clipping (for newborns only) and ear tattooing are given and compared with methods presented in literature. By far, ear tattooing by the newly developed pincers is the most suitable method for marking adult rodents for life. Tattooing is easy to apply, easy to read and not harmful to the animals. For newborn pups on day 4 p. p., the s. c. injection of India ink into the palm of paw is recommended.

Animal Identification Systems↗

PubMed1986

Reversible pulmonary changes in rats dosed intravenously with imidazoles.

Pulmonary changes were studied in Sprague-Dawley-rats dosed intravenously with various dosages around the LD 50 in acute studies, and with 0 (control), 0.001, 0.01 and 0.1 mg/kg b. wt./day St 91-Cl or with 0, 1, 5 and 25 mg/kg b. wt./day St 600-Cl for 4 weeks in subacute studies. Doses of 0.01 mg/kg St 91-Cl and 1 mg/kg St 600-Cl were well tolerated. At higher doses, both compounds caused acute pulmonary congestion, edema and bleeding. The acute changes obviously occurred after each single i.v. injection, and were followed by an intensive hemosiderosis of alveolar macrophages. All findings were reversible. No pulmonary changes were observed in oral subacute studies with both compounds.

Animals↗

PubMed1985

Cardiac effects of fenoterol hydrobromide on newborn versus adult rats.

The toxicity of fenoterol hydrobromide, a beta-adrenoceptor stimulant, was studied in newborn and adult SD-rats dosed with 0 (control), 2.5, 75 and 600 mg/kg/day by gavage for 35 days. 600 mg/kg was lethal for both age groups: newborn rats died either from gastro-intestinal disorders during the lactation period or from underweight and cachexia immediately after weaning. Adult rats which died from 600 mg/kg showed extended myocardial scars. No substance-related myocardial lesions were observed in newborn rats killed terminally, whereas adult rats had a dose-dependent increase in heart weights, at 600 mg/kg also extended myocardial scars.

Aging↗

PubMed1983

Hair embolism in lungs of rat and rabbit caused by intravenous injection.

Among 1422 Sprague-Dawley rats treated daily for 28 consecutive days by i.v. injection, 144 animals (10.1%) showed particles of hair in thrombi at the site of injection. 381 rats (26.8%) had pulmonary emboli with fragments of hair and skin in arterial thrombi or in giant cell granulomas. 6 weeks after cessation of treatment lesions were still found in lungs from 5 of 90 rats (5.6%) allowed to recover. After the experimental administration of 0.75 ml/100 g body wt of a hair suspension (3000 hair particles/ml) to rats, there was no influence on phagocytosis whether endogenous or foreign hairs were injected. In 8 of 64 Himalayan rabbits (12.5%) given 28 injections each into ear veins pulmonary embolism was observed.

Animals↗

PubMed1982

Decrease of carbon tetrachloride liver toxicity in rats given dipyridamole.

The influence of Dipyridamole on acute hepatotoxicity has been studied in male SD-JCL rats doses with carbon tetrachloride. High single oral doses of Dipyridamole lowered the serum enzyme activity and reduced significantly the area % of hepatic necrosis and hydropic degeneration, but not of steatosis. Dipyridamole was effective from 1 hr before through 6 hrs after the oral administration of CCl4. Doses below 1,000 mg/kg Dipyridamole were less effective. No delay in the onset of CCl4-induced liver damages was observed. Dipyridamole was also effective when CCl4 toxicity was enhanced by isopropanol.

1-Propanol↗

PubMed1982

Repairability of drug-induced "wavy ribs" in rat offspring.

The development and repairability of "wavy ribs" were studied in offspring from dams of rat strain SD-JCL dosed with fenoterol, a beta-adrenoceptor stimulant. The incidence of "wavy ribs" was high at 1000 mg/kg/d. The critical administration period for the development of "wavy ribs" was from day 13 through 17 of gestation. Firstly, a delay of ossification in the middle of the ribs was seen on day 17. Thereafter, the middle part of the ribs began to curve and the curves were calcified until the end of gestation. Decreases of alkaline phosphatase and total protein were observed on day 20 in blood of fetuses showing "wavy ribs". The "wavy ribs" gradually disappeared until weaning. The effect of fenoterol could be partially blocked by the action of a beta-adrenoceptor blocker.

Abnormalities, Drug-Induced↗

PubMed1982

Teratology study with orciprenaline sulfate in rabbits.

Orciprenaline sulfate (Alupent), a beta-adrenoceptor stimulant, was studied for adverse effects on pregnant rabbits and their fetuses. Himalayan rabbits (Kawanishi) were dosed orally at 0 (control), 5, 25 and 50 mg/kg/d from gestation day 6 through 18. 15 does were used per group. No distinct influences of orciprenaline sulfate on litter parameters and no teratogenic effect was observed including the "maximum tolerated dose" of 50 mg/kg.

Animals↗

PubMed1981

The effect of fasting on oral acute toxicity of drugs in rats and mice.

The oral acute toxicity of 3 beta-adrenoceptor stimulants, 2 beta-adrenoceptor blockers, and 2 anti-gastric ulcer drugs was studied in 8-week old, SD-JCL rats and ICR-JCL mice, fasted overnight for 17-20 hours. The results were compared with those from rats and mice allowed to feed normally. The order of the fed:fasted ratio of LD50 values in rats was pirenzepin less than propantheline less than pindolol less than salbutamol less than orciprenaline less than fenoterol less than bunitrolol, and was in the range 1.3-4.7. The increased toxicity in fasted animals was considered to be related to acceleration in gastric emptying and intestinal absorption, but not to a general change in the condition of the test system or a decrease in the detoxification ability of the liver because after intraperitoneal administration acute toxicity was similar in fed and fasted rats.

Adrenergic beta-Agonists↗