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[(Pro)insulin biosynthesis of isolated islands of Langerhans in the sand rat and Wistar rat].

Sand rats develop a diabetes-like syndrome, connected with temporary hyperinsulinism, when fed a rat laboratory chow diet. The conversion of proinsulin to insulin is not disturbed in these animals. Sand rat islets do not secrete newly synthesized (pro) insulin preferentially. Time course and glucose response of [3H]-leucine incorporation are different between islets of sand rats and Wistar rats.

Animals

Diet, liver function and dimethylhydrazine-induced gastrointestinal tumours in male Wistar rats.

Male Wistar rats fed a normal laboratory pelleted diet, when treated s.c. with 1,2-dimethylhydrazine (DMH) 10 mg/kg/wk survived the 24-week experiment, showed no signs of chemical toxicity or macroscopic liver damage, and developed mainly large-bowel tumours. Conversely, male Wistar rats treated with 20 mg/kg/wk DMH did not survive the full term of the experiment and developed ascites, pleural effusions and nodular livers. They also developed more small-bowel tumours than large-bowel tumours. The relationship between the predominant site of tumour development and dosage of DMH was highly significant.Male Wistar rats fed with an all-liquid diet (Vivonex) and treated with 20 mg/kg/wk DMH behaved quite differently both in terms of survival and site of tumour development. These rats survived the full term of the experiment, showed no signs of chemical toxicity, experienced minimal liver damage and developed predominantly large-bowel tumours. The protection afforded by the all-liquid diet against DMH toxicity and small-bowel tumour induction was statistically highly significant.A series of blood tests with special reference to liver function confirmed the highly significant degree of protection against liver damage afforded by the all-liquid diet.Sections of liver from treated rats were examined, and a simple pathological scoring system was devised which showed a highly significant difference in liver histology between standard diet and liquid-diet rats treated with 20 mg/kg/wk DMH.The results strongly suggest an association between severity of liver damage from DMH and the subsequent development of small-bowel tumours. The all-liquid diet protected rats from liver damage and these rats developed significantly fewer small-bowel tumours.

Animal Feed

Bilirubin UDP-glucuronyltransferase activity of wistar rat kidney.

Wistar rat kidneys have been shown to possess a bilirubin glucuronyltransferase (BGT) activity capable of conjugating about 3/5 of the total pool of unconjugated bilirubin within 48 h of being grafted to Gunn rat hosts. Bilirubin conjugated by the kidney is taken up by the liver and excreted in the bile. Except when the bile duct is ligated, no conjugated bilirubin appears in the plasma or urine. Renal BGT activity is about 1/20th of the hepatic activity on a weight basis in Wistar rats. The Gunn rat's hyperbilirubinemia probably causes an induction of the renal enzyme since its activity doubles in 48 h.

Animals

Mesotheliomas induced by sterigmatocystin in Wistar rats.

Male Wistar rats were given repeated injections of sterigmatocystin (stg) and related compounds into the peritoneal cavity once a week for 23 weeks. Only stg alone produced mesothelioma in 20 of 40 rats given a total dose of 20 approximately 25 mg, while no mesotheliomas were found in rats injected O-acetyl-stg (AcO-stg) and dihydro-stg. There were two histological types in the mesothelioma induced by stg; the epithelioid and mesenchymal types. There was little loose connective tissue between the epithelioid cell tumors, whereas abundant dense collagen fibers were found between the cell nests of the mesenchymal cell types of mesothelioma. The hepatocellular carcinomas were found in a rat treated with stg and in five animals given AcO-stg. The fact that mesotheliomas could be induced in high incidence by direct intraperitoneal application of stg suggests a potent carcinogenicity of stg. Although both dihydro-stg and stg formed fine needle-like crystals when injected into the peritoneal cavity, dihydro-stg could not produce any mesothelioma. Dihydro-stg, reduction product of stg, has no double bond in the terminal furan ring. Therefore, the carcinogenicity of stg may be related more closely with the presence of a double bond in the terminal furan ring of stg than the physical form in the peritoneal cavity. AcO-stg may easily be absorbed from the peritoneum, so that it could not persist in the peritoneium for sufficient duration for carcinogenesis.

Animals

The B-vitamin group and the activity of hepatic microsomal mixed-function oxidases of the growing Wistar rat.

1. Male Wistar rats were given isoenergetic, semi-synthetic diets deficient in thiamin, riboflavin, pyridoxine or all the B-vitamins. 2. In rats given these deficient diets the 'sleeping time' induced with pentobarbital (PB) and the 'paralysis time' with zoxazolamine (Zz) were prolonged. 3. The tolerance effect against both drugs was nearly independent of the levels of B-vitamins in the diets. 4. In preparations from vitamin-B deficient animals the activities of the following hepatic microsomal enzymes were reduced: the aliphatic hydroxylase of PB, the aromatic hydroxylases of aniline (EC 1.14.14.1) and of Zz, the N-demethylase of aminopyrine, the UDP glucuronyltransferase (EC 2.4.1.17) of p-nitrophenol. The reactions most influenced were those of 'type-1' substrates, particularly those involving the hydroxylases. 5. The effects observed were caused mainly by deficiency of riboflavin and to a lesser extent of thiamin or pyridoxine.

Animals

Transplantation of chemically induced gastric cancer in Wistar rats.

Seven of 35 male Wistar rats developed well-differentiated adenocarcinoma of the glandular stomach on combined treatment with N-methyl-N'-nitro-N-nitro soguanidine and 4-nitroquinolin 1-oxide. One of the tumors was successfully transplanted into newborn Wistar rats by subcutaneous inoculation. The latent period after inoculation was less than one month and the growth of the transplanted tumor was slow throughout 10 transplant generations. The tumor appeared nodular or cystic in subcutaneous tissues of rats and often caused ulceration of the skin. The histology of transplanted tumors was very similar to that of the primary tumor. Metastasis to both lungs was observed in one rat of the first transplant generation.

4-Nitroquinoline-1-oxide

Biosynthesis of somatostatin in pancreatic islets of Wistar rats.

Pancreatic islets of Wistar rats were isolated by collagenase digestion and incubated with [3H]-L-phenylalanine. Using a specific somatostatin antiserum radioactivity was found in the antibody-antigen-complex. The radioactivity was displaced by unlabelled somatostatin. These findings give the first evidence for the biosynthesis of somatostatin or somatostatin-like peptides in mammalian pancreatic islets.

Animals

Frequency of hydronephrosis in Wistar rats.

Kidneys from 1806 Wistar rats were examined grossly for hydronephrosis and ureteral dilation. Hydronephrosis was seen more often on the right side (11%) than the left (0.3%). Overall frequency of hydronephrosis in males (181/1305) was greater than in females (23/501), and the frequency was statistically greater in male rats aged 5,6,8 and 9 weeks than in age-matched females.

Animals

Biochemical studies on the mechanism of difference in the renal toxicity of 5-hydroxy-L-tryptophan between Sprague Dawley and Wistar rats.

The biochemical mechanisms of the renal toxicity of 5-hydroxy-L-tryptophan to rats were studied using Wistar and Sprague Dawley rats, which had different LD50 values. When the amino acid was injected intraperitoneally, Wistar rats, which had a low LD50 value of 5-hydroxy-L-tryptophan, excreted larger amonts of serotonin and smaller amounts of 5-hydroxyindole acetic acid into the urine than Spraque Dawley rats, which had a high LD50 value. The activity of renal aromatic L-amino acid decarboxylase was higher in Wistar rats than in Sprague Dawley rats, while the activity of renal aromatic amino acid transaminase was in an opposite relationship. The activity of renal monoamine oxidase was almost the same in both strains and the activity of renal UDP glucuronyltransferase in Wistar rats was higher than in Sprague Dawley rats. Since the renal damage caused in rats by 5-hydroxy-L-tryptophan was very similar to that caused by serotonin, the amine formed from the administered amino acid was thought to be an important factor for the renal necroses, and difference in serotonin formation from the administered precursor amino acid may be one of the important factors leading to the difference in LD50 values in the two strains of rats.

5-Hydroxytryptophan

Palatal shelf elevation in the Wistar rat fetus.

Palatogenesis in the Wistar rat fetus was studied macroscopically, microscopically, ultrastructurally and experimentally between days 13 and 19. The developmental ages of the fetuses were calculated from the smear age of the litter adjusted for individual variations in crown-rump lengths. Palatal shelf elevation occurs at day 16.4 +/- 0.1. Experimentally induced shelf elevation in freshly delivered fetuses was sluggish at day 14, but by day 16.3 it occurred in less than 1 second. Both shelf elevation and shelf fusion begin anteriorly where the shelves show a marked convexity of their margins, and proceed posteriorly. The extreme posterior part of each shelf (future soft palate) is horizontal from the beginning. The matrix of the shelf mesenchyme (especially in the region of the anterior convexities) shows an increasing accumulation of mucopolysaccharides from day 14 to day 16.3 and becomes increasingly oedematous. The shelf attachment to the main maxillary process is progressively undercut by epithelial invagination, producing a fulcrum for shelf elevation. The maxillary and palatine osteogenic blastemata are present at the base of the shelf prior to elevation and rapidly invade the shelves after the event. The elevated palatal shelves fuse with the nasal septum anteriorly, but posteriorly the palate is not attached to the septum. The posterior septum at first has a free lower edge, but then it develops lateral flanges which fuse with corresponding bulges on the lateral nasal walls. In this way two sphenoethmoidal recesses are formed above the fused flanges, while a common nasal passage is formed above the palate, roofed anteriorly by the septal flanges and posteriorly by the cranial base. The space needed to create (simultaneous with shelf elevation) the common nasal passage is made available by flattening of the tongue and protrusion of its tip out of the oral cavity--this protrusion being facilitated by the sloping bulge of the primary palate and nasal septum. Many existing theories of shelf elevation are inconsistent with these observations. It was concluded that shelf elevation occurs very rapidly at a rather precise developmental stage and that turgor (due to binding of water to mucopolysaccharides) is the intrinsic force which elevates the shelves, a force which at 16.4 days reaches a threshold level enabling the shelves to force their way up and over the intervening tongue.

Animals

[Histotopochemical and electronmicroscopical investigations of Wistar-rats with streptozotocin diabetes (author's transl)].

15 streptozotocin-diabetic wistar rats (an application of a single dose of 64 mg/kg body weight streptozotocin) and a control group of 12 wistar rats with a healthy metabolism have been examined. The majority of B-cells was largely degranulated, insulin was hardly or not to be found with histochemical methods. The A- and B-cells of 11 test animals showed pathological findings: Karyolysis, the dissolution of cell membranes and the decay of cytoplasm which are criteria of necrosis. Besides a round-cell infiltration could be found as a symptom of insulitis. The B-cells showed only single granula under the electron microscope. The endoplasmatic reticulum was only poorly developed and with hardly any ribosomes. There were only very little mitochondria and no GOLGI's apparatus. The cell membrane was smooth and not enlarged by microvilli. Emiocytosis-figures were missing. No changes of nuclei could be noticed. The findings on organelles correlate well with the microscopical results. The exocrine parenchyma contained regions showing the decay of the lobule structure as well as of single acini. The acinus cells were in necrosis. The connective tissue was obviously increased. There were regions in the stroma with a round-cell infiltration as found with a pancreatitis. Both these and the results discussed from our literature show that streptozotocin does not only affect the B-cells of the islets of LANGERHANS, but also the exocrine pancreas and other organs.

Animals

Comparison of the activities of some dehydrogenases in the juxtaglomerular complex of kidneys of Wistar rats and desert rats (Meriones unguiculati).

The authors compared the enzyme histochemical activities of some dehydrogenases in the macula densa, the Goormaghtigh cells and the epithelioid (or juxtaglomerular cells in the kidneys of desert rodents (Mongolian Gerbils) with those of the Wistar rats. The macula cells (Table 1), which in the Wistar rats are clearly distinct from the non specific epithelial cells of the distal convolution, show, in the desert rats, noticeable fluctuations. Their enzyme histochemical reactions are often weaker than those of the distal convolution cells, with the exception of the NAD-tetrazolium-reductase activity. The Goormaghtigh cells (Table 2) in the kidneys of the Meriones have a much larger enzymatic spectrum than in the Wistar rats. Here also, we find functional variations in the examined desert species. In the epithelioid cells (Table 3) we observed a somewhat weaker enzymatic activity in the Meriones. These cells contain no secretion granules, this making their diagnosis difficult.

Animals

Electronmicroscopy studies on the exocrine pancreas of Wistar-Rats following treatment with Streptozotocin.

In Wistar rats the intraveneous injection of streptozotocin (65 mg/kg body weight) caused a permanent hyperglycemia. After 5 days there were lesions in the exocrine parenchyme of the pancreas and its nerve fibers. Pathological changes were found in cytoplasm, cell membrane, nucleus and all other cell organelles, too. The zymogen granules remaining after extensive degranulation may disintegrate in two different ways: 1. Shrinking of the granules and formation of a hale between granule membrane and core, the electronic density of which is decreased; indistinct demonstrability of the granule membrane and finally its decomposition. 2. Shrinking of the granules, decrease of the electron density and either homogeneous or mainly peripheral arrangement of the disintegrated material of the granules; irregular shape of the granules and splitting of their membranes.

Animals

[Blood count, leukocyte alkaline phosphatase activity, and blood sugar levels in Wistar rats as a function of the reaction type (level of higher nervous activity) of the animal].

The corpuscular blood composition, ALP activity and glucose level of 20 E+ and 20 E- adult male Wistar rats were measured without stress. We wanted to find differences due to the specific reaction type--emotive/non-emotive--of the animals. E+ animals had higher counts of small erythrocytes and a higher total number of leucocytes than E- rats. When the compositions of the blood of several inbred strains were compared, the composition of the red blood, total number of leucocytes and lymphocytes of E- -Wistar rats and E- -Sprague-Dawley rats were most similar. Differences in the activity of the ALP and in the glucose levels we found are similar to those in literature on this topic. When measured in a condition of inactivity the lower glucose values of E+ Wistar rats correspond to the excretion of smaller amounts of urinary catecholamines. Our findings, as well as those mentioned in the literature, confirm the assumption that the reaction type--which corresponds to the type of higher nervous activity--influences all functions of the organism including the composition of the blood.

Alkaline Phosphatase

Resistance of a substrain of Wistar rats to salt hypertension.

Male rats of the Wistar substrain, in which 2/3 nephrectomy was performed, did not develop hypertension when placed on a high salt intake, while rats of the Long-Evans substrain become hypertensive under the same conditions. The described substrain of Wistar rats represents a useful experimental model for studying the mechanism of resistance to the hypertensive stimulus of salt overload.

Animals

Experimental Candida-induced denture stomatitis in the Wistar rat.

An experimental model of yeast-induced denture stomatitis has been set up in the rat by inoculating Candida albicans on the fitting side of a maxillary acrylic plate retained by an orthodontic band around the incisors. Thirty-eight Wistar rats were used in two series of experiments with an observation period of 2 weeks. In each of the series there were one control and three experimental groups. Control rats were left untreated, while rats of the experimental groups wore either uninoculated or inoculated plates, or had their palatal mucosa smeared with the yeast. For cytologic examination the palate was scraped in Series I and the fitting side of the plate in Series II. After 1 week a generalized simple inflammation had developed in the palate of most animals of the experimental groups. It was most severe and persistent in rats with inoculated plates. Histologic signs of inflammation and hyphal formation were also most pronounced in this group. Hyphae did not invade the epithelium. Except for an initial loss of body weight, which was restored by day 10 or 12, the rats tolerated their plates. The Wistar rat seems to be well suited for experimental studies on denture stomatitis.

Animals