Histological changes of various organs in aged SD-JCL rats (author's transl)

Age-related histological changes were studied in various organs from SD-JCL rats reared throughout their lifespan. In aged-male rats examined at 5 to 36 months of age were frequently observed nephropathy, periarteritis, skeletal muscle degeneration, pigmentation of the follicular epithelium in the thyroid, fibrosis of the pancreatic islets, hyperplasia of the parathyroid epithelium, and changes of the acini in the extraorbital lacrymal gland. In aged-female rats sinusoid dilatation of the adrenal, and atrophy of the ovary were also noted. Perilobular fat deposition of the liver, dilatation of the gastric gland and severe hemosiderosis of the spleen were observed similar frequency in the both sexes. The nephropathy and cardiovasculopathy were major factors to cause death for males, while the main cause of death for females was tumors, especially of the mammary and pituitary glands. Enlargement of the parathyroid gland, bone resorption and metastatic calcification in the solf tissues were found in rats with severe nephropathy.     

Diurnal variations in food intake and in lipogenesis in mammary gland and liver of lactating rats.

Despite the hyperphagia, the food intake of the lactating rat showed marked diurnal changes which paralleled those of virgin rats. The major difference was that lactating rats consumed a higher proportion (35%) of their diet during the light period than did virgin rats (14%). The peak rate of lipogenesis in the lactating mammary gland occurred around midnight, and this decreased by 67% to reach a nadir around mid-afternoon; this corresponded with the period of lowest food intake. The diurnal variations in hepatic lipogenesis in lactating rats were much less marked. The changes in hepatic glycogen over 24 h suggest that it acts to supply carbon for lipogenesis during the period of decreased food intake. The activation state of acetyl-CoA carboxylase in mammary gland altered during 24 h, but the changes did not always correlate with alterations in the rate of lipogenesis. The changes in plasma insulin concentration tended to parallel the food intake in the lactating rats, but they did not appear to be sufficient to explain the large alterations in lipogenic rate in the mammary gland.     

Effect of starvation and refeeding on amino acid uptake by mammary gland of the lactating rat. Role of ketone bodies.

Arteriovenous differences of amino acids across the mammary glands of lactating rats are diminished when the rats are starved for 24 h. When 24 h-starved rats were refed for 2 1/2 h, the arteriovenous differences of amino acids returned to values similar to those found in well-fed rats. In order to find a possible explanation for these rapid changes, we tested the effect of ketone bodies on amino acid uptake by the gland. At 5 min after injection of acetoacetate to fed rats, when the total concentration of ketone bodies in blood was similar to that found in starvation, the uptake of amino acids by the mammary gland was similar to that found after starvation, i.e. lower than in fed rats. However, 30 min after administration of acetoacetate, when the arterial concentration of ketone bodies had returned to values similar to those in fed rats, the arteriovenous differences of amino acids were similar to those found in fed rats. We conclude that the changes in blood ketone bodies may be responsible, at least in part, for the changes in amino acid uptake that occur in starvation and in the starvation--refeeding transition.     

Tissue-specific effects of starvation and refeeding on the disposal of oral [1-14C]triolein in the rat during lactation and on removal of litter.

1. The effects of starvation and refeeding on the disposal of oral [14C]triolein between 14CO2 production and 14C-lipid accumulation in tissues of virgin rats, lactating rats and lactating rats with pups removed were studied. 2. Starvation (24 h) increased 14CO2 production in lactating rats and lactating rats with pups removed to values found in virgin rats. This increase was accompanied by decreases in 14C-lipid accumulation in mammary gland and pups of lactating rats and in white and brown adipose tissue of lactating rats with pups removed. 3. Short-term (2 h) refeeding ad libitum decreased 14CO2 production in lactating rats and lactating rats with pups removed, and restored the 14C-lipid accumulation in mammary glands plus pups and in white and brown adipose tissue respectively 4. Insulin deficiency induced with mannoheptulose inhibited the restoration of 14C-lipid accumulation in white adipose tissue on refeeding of lactating rats with pups removed, but did not prevent the restoration of 14C-lipid accumulation in mammary gland. 5. Changes in the activity of lipoprotein lipase in mammary gland and white adipose tissue paralleled the changes in 14C-lipid accumulation in these tissues. 6. It is concluded that 14C-lipid accumulation in mammary gland may not be affected by changes in plasma insulin concentration and that it is less sensitive to starvation than is lipogenesis or lactose synthesis. This has the advantage that the milk lipid content can still be maintained from hepatic very-low-density lipoprotein for a period after withdrawal of food. The major determinant of the disposal of oral 14C-triolein appears to be the total tissue activity of lipoprotein lipase. When this is high in mammary gland (fed lactating rats) or white adipose tissue (fed lactating rats with pups removed), less triacylglycerol is available for the muscle mass and consequently less is oxidized.     

A karyometric and stereologic study of the effects of gonadotrophin and testosterone on the interstitial gland of the testis of intact and endoxan treated rats

Adult male rats were treated daily for 18 days with endoxan in doses of 4 mg/kg of body weight or testosterone in doses 2.5 mg per rat. For the last 5 days of the experiment some of the rats received gonadotrophin injections in doses of 50 I.U. Karyometric and stereologic studies were undertaken on paraffin sections of the testes stained with haematoxylin and eosin. Endoxan treatment decrease the nuclear volume of the Leydig cells and lowers the volume fraction occupied by the interstitial gland in the testis. These changes were accompanied by a decrease in the intensity of reaction for acid phosphatase, non-specific esterases and 3-beta-hydroxy-steroid dehydrogenase. Testosterone injected alone or jointly with endoxan resulted in more pronounced changes than following treatment with endoxan alone. As expected, gonadotrophin injections into intact rats resulted in a marked increase in nuclear volume of the Leydig cells and in the volume fraction of the interstitial gland. This effect of gonadotrophin on the interstitial gland of the rat testis was partially inhibited by endoxan treatment. It follows from these experiments that endoxan impairs the functional activity of the interstitial gland of the rat testes by lowering the endogenous gonadotrophin levels, as well as by direct action on the Leydig cells.     

GLP-1 expression in von Ebner's gland of diabetic rats

GLP-1, a peptidergic endocrine hormone, which associate with appetite control, glucose homeostasis and satiety. It might play an important role in the gustatory system. We tried to investigate the expression of GLP-1 in von Ebner's gland of diabetic and control rats, and the ultrastructure changes on von Ebner's gland of diabetes rats. GLP-1 expression in von Ebner's gland was evaluated by immunohistochemistry. The number of GLP-1 positive cells in diabetic rat von Ebner's gland was significantly higher than that in normal controls. Electron micrographs showed that a series of pathologic changes in von Ebner's gland of diabetes rats. The results suggest that GLP-1 have some effects within the gustatory systems, and elevated von Ebner's gland GLP-1 expression may be one cause of diabetic taste impairment.     

Studies on the toxic effect of cadmium in the rat. I. Testicular changes induced by a single subcutaneous injection of cadmium chloride.

Adult male rats of Wistar strain were subcutaneously injected with a single dose of 0.025 mM CdCl2/kg body weight. The autopsies were performed 2 and 12 weeks post cadmium injection. Experimental animals showed a normal gain of body weight while a marked lowering of the testes weight was observed. The lowering of testes weight of cadmium treated rats occured mainly due to the necrosis of seminiferous tubules, volume of which is markedly lower if compared to intact control rats. After 2 weeks of experiment a marked enlargement of the interstitial gland of the testis occured while after 12 weeks the gland is markedly lower if compared to control rats and to rats studied 2 weeks post cadmium injection. Histochemical reactions for lactic, succinic, alpha-glycerophosphate and 3beta-hydroxy steroid dehydrogenases, NADH tetrazolium reductase, acid phosphatase and nonspecific esterases showed for irreversible necrotic changes of seminiferous tubules of cadmium treated rats while the damage to interstitial gland is only temporary.     

Atrophic change of rat salivary gland during adenovirus-induced hyperleptinemia

Sustained hyperleptinemia in normal rats induced by infusing a recombinant adenovirus containing the rat leptin cDNA (AdCMV-leptin) exhibited a remarkable reduction in food intake (AdCMV-leptin, 9.3 +/- 2.6 vs untreated, 20.6 +/- 1.0 g/day) and ablated body fat without any significant changes in wet weight of liver and left ventricle. In those hyperleptinemic rats, we found a 52% reduction in wet weight of salivary gland compared with that in the pair-fed AdCMV-beta-gal-treated rats, which received a recombinant virus containing the beta-galactosidase gene (AdCMV-beta-gal) and were fed on the same amount of food as had been consumed by the AdCMV-leptin-treated group on the previous day. Microscopic examination with hematoxylin-eosin staining revealed that atrophic change was induced in both serous and mucous gland only in the AdCMV-leptin-treated group, but not in the pair-fed controls. Thus, the atrophic changes in hyperleptinemic rats were due to neither a decrease of food intake nor disuse of the salivary gland related with anorexia. Our data suggested that size of the salivary gland was controlled, at lease in part, by "non-anorexic" effect of leptin.     

Ultrastructural changes in the rat pineal gland after sympathetic denervation. Quantitative study

Ultrastructural changes in the rat pineal gland were studied quantitatively 7 and 60 days after the sympathetic denervation by bilateral excission or decentralization of superior cervical ganglia. The surface occupied by pineal parenchymal cells decreased in rats of experimental groups with respect to the control group. Furthermore, profile areas of the cytoplasm, nucleus and nucleolus of the pinealocytes were also diminished. Cytoplasmic lipid droplets in the pinealocytes were markedly decreased in number and size in experimental rats. As demonstrated by the Kruskal-Wallis H test, statistically significant differences were found between rats of the control and operated groups. Rats treated by superior cervical ganglionectomy or decentralization showed morphological changes indicating a hypofunctional pineal gland, although differences were found between both groups.     

Premature induction of amylase in pancreas and parotid gland of growing rats by dexamethasone.

Studies were made on changes in the contents of alpha-amylase (EC 3.2.1.1) in the pancreas and parotid gland of rats during postnatal development, on the premature induction of this enzyme by hormones and on the existence of specific glucocorticoid receptors in these tissues. The amylase content in the pancreas increased from the 9th day after birth and reached the adult level on the 28th day, its content in the parotid gland increased rapidly from the 16th to the 28th day after birth and then rose more gradually to the adult level. Injection of dexamethasone into rats 6--8 days after birth induced increase in the amylase of the pancreas but not the parotid gland. However, injection of dexamethasone into weanling rats 21--23 days after birth resulted in precocious induction of amylase in both tissues. Specific glucocorticoid receptors were detectable in the parotid gland of rats from 6 days after birth but were almost undetectable in the pancreas until adolescence.     

Effects of diabetes and dietary manipulation on rat parotid gland secretory response to sympathetic nerve stimulation.

1. The effects of streptozotocin-diabetes, bulk-diet, low protein diet (8%) and protein-calorie malnutrition on parotid gland response to sympathetic nerve stimulation were studied in male Wistar rats. 2. Mean body weights were considerably less in diabetic and protein-calorie malnourished rats than in the other groups, but parotid gland weight was reduced only in animals placed on a low-protein diet. 3. Salivary flow rate (microliter/min/g tissue) and total protein output (mg secreted/g tissue) were reduced in diabetic rats. 4. Salivary composition was altered in diabetes and protein-calorie restriction, and the specific changes were unique to each condition. 5. Thus, with the possible exception of gland weight the effects of diabetes on parotid gland structure and function are not related to either hyperphagia or nutritional status.     

Acute effects of endotoxin (lipopolysaccharide) on tissue lipid metabolism in the lactating rat. The role of delivery of intestinal glucose

The aim of this study was to compare the effects of endotoxin on lipid metabolism and, in particular, lipogenesis in virgin and lactating rats. Intraperitoneal administration of bacterial endotoxin (lipopolysaccharide, LPS; 3 mg/kg body wt.) to fed virgin rats caused a 4-fold increase in lipogenic rate in liverin vivo. The stimulatory effect was not seen when glucose (6 mmol) was administered either orally or intraperitoneally to increase the basal rate. In contrast, the rate of lipogenesis in interscapular brown adipose tissue was inhibited, after LPS, and this was relieved by intraperitoneal glucose. In the lactating rat there were no significant changes in hepatic lipogenesis after the administration of endotoxin. However, LPS decreased the lipogenic rate in mammary gland of lactating rats and intraperitoneal glucose administration, but not oral, was able to restore the rate. In both virgin and lactating rats, LPS decreased glucose removal from the intestina tract. In lactating rats, LPS induced a rise in blood concentrations of lactate, and plasma triacylglycerols and non-esterified fatty acids, similar to those in endotoxin-treated virgin rats. The administration of LPS did not decrease the accumulation of radioactivity in lipid in either liver or in mammary gland after injection of³H-oleate. In contrast, LPS decreased the accumulation of radioactivity in mammary gland after injection of²H-chylomicrons and increased it in liver and plasma. These changes were accompanied by a decrease in mammary gland activity of lipoprotein lipase. Intraperitoneal glucose partially reversed these changes in chylomicron disposition. It is concluded that the inhibitory effect of LPS on mammary gland lipogenesis and uptake of exogenous lipid is primarily due to sensitivity of this tissue to the rate of delivery of glucose from the intestine.     

Induction of a specific (LM) protein in the submandibular gland of the rat by repeated amputation of the lower incisor teeth

Chronic administration of the beta-adrenergic agonist isoproterenol (IPR) leads to marked hyperplastic/hypertrophic enlargements of the parotid and submandibular glands in rats and mice with concomitant changes in the composition of both the glands and the saliva. Conspicuous among the alterations of the submandibular saliva is the appearance of a 13,000 Mr protein, termed LM (large mobile) protein. Repeated amputation of the lower incisor teeth also causes enlargements of the major salivary glands in rats. In this study, we have compared the enlargements of submandibular glands of rats produced by IPR administration or teeth amputation with respect to the relative levels of the LM protein in gland extracts and saliva. Administration of IPR-HCl (40 mg/kg) twice daily for 5 days or amputation of the lower incisor teeth 3 times a week for 3 weeks resulted in a 2.2-fold increase in the weight of the submandibular gland. Amputation for one week led to a 1.4-fold increase in gland weight. Double immunodiffusion in agar antibodies against the purified LM protein gave a single precipitin line with gland extracts and saliva of IPR-treated and teeth-amputated rats, indicating immunological identity of the reacting antigens. No precipitin lines were seen with gland extracts or saliva of untreated rats. Immunoblots of pooled saliva obtained from IPR-treated or teeth-amputated rats revealed a single protein band of the same electrophoretic mobility in SDS-polyacrylamide gels when stained using anti-LM antibodies. The relative concentrations of LM protein in gland extracts and saliva were measured by a solid-phase enzyme-linked immunoabsorption assay using antibodies against the purified LM protein.(ABSTRACT TRUNCATED AT 250 WORDS)     

Potential therapeutic effects of induced pluripotent stem cells on induced salivary gland cancer in experimental rats

Salivary gland neoplasms exhibit complex histopathology in a variety of tumor types and treatment options depend largely on the stage of the cancer. Induced pluripotent stem cells (iPS) have been investigated for treating induced salivary gland cancer and for restoring salivary gland function. We investigated iPS treatment for salivary gland cancer both in vitro and in vivo. For our study in vitro, we re-programmed human skin fibroblasts to form iPS cells using a plasmid containing Oct4, Sox2, L-MYC and LIN28. For our study in vivo, we used 30 white male albino rats divided into the following groups of 10: group 1 (control): rats were injected with phosphate-buffered saline (PBS), group 2 induced squamous cell carcinoma (SCC): rat submandibular glands were injected with squamous carcinoma cells (SCC), group 3 (induced SCC/iPS): SCC treated rats treated with 5 × 106 iPS cells. Submandibular glands from rats of all groups were examined histologically and real time PCR was performed for amylase, and COX I and COX II gene expression. We confirmed that submandibular gland specimens included tumor tissue before starting treatment with iPS. iPS treated cases exhibited regeneration of salivary glands, although minor degenerative and vascularization changes remained. The acinar cells regained their proper organization, but continued to exhibit abnormal activity including hyperchromatism. iPS cells may be useful for treating salivary gland carcinomas.     

Body, heart, thyroid gland and skeletal muscle weight changes in rats with altered thyroid status

In the present paper we describe changes of anatomical parameters in inbred Lewis strain rats, namely their body weight, body weight gain per week, absolute and relative heart, thyroid gland and skeletal muscle weights, that are assumed to reflect experimentally altered thyroid status. The hyperthyroid state was induced by DL-thyroxine or Na 3,3',5-triiodo-L-thyronine, while methimazole was employed for inducing hypothyroidism. We have found that when compared to euthyroid rats, hypothyroidism resulted in a significantly lower body weight gain, absolute and relative heart weight and, in contrast, in a significant increase of absolute and relative thyroid gland weight. On the other hand, hyperthyroidism led to a significant increase of absolute and relative heart weight and to a significant reduction of absolute and relative thyroid gland weight. However, the body mass was not significantly altered in hyperthyroidism as compared with euthyroid rats. We conclude that our protocol leads to chronic hyper- or hypothyroidism as demonstrated by body, heart and thyroid gland weight changes. These anatomical data can thus be utilized as supplemental criteria for the assessment of the thyroid state of experimental rats.     

Chronic sialodacryoadenitis virus (SDAV) infection in athymic rats.

Sialodacryoadenitis virus (SDAV) was detected in athymic rats subcutaneously implanted with human tumor cell lines. Clinical signs included sneezing, dyspnea, weight loss and death. Necropsy revealed both upper and lower respiratory tract disease from which Staphylococcus aureus, Pasteurella pneumotropica and Pseudomonas aeruginosa were recovered. Histopathological changes consisted of suppurative rhinitis and bronchopneumonia. Lesions characteristic of SDAV infection were found in lacrimal and salivary glands, and viral antigens were detected in the salivary glands and respiratory tract by immunohistochemistry. Submaxillary salivary gland. Harderian gland and lung homogenates from affected athymic rats were inoculated intranasally into euthymic rats as a rat antibody production test. All euthymic rats seroconverted to SDAV. Seroconversion to SDAV was demonstrated in consecutive pairs of sentinel euthymic rats housed for 6 months with infected athymic rats. Inoculation of supernatants of the original tumor cell lines into euthymic rats did not result in seroconversion. The source of the virus was not determined. In this study, spontaneously acquired SDAV infection persisted for at least 6 months in athymic rats.     

Relationship of biochemical and morphological changes in rat thyroid and proton spin-relaxation of the tissue water.

The effect was studied of biochemical and morphological changes induced by antithyroid substances (PTU, C10(-4)) on proton spin-relaxation properties of rat thyroid gland. It was found that thyroid stimulated by PTU (0.05%) or C10(-4) (1.0%) exhibit marked morphological changes (hyperplasia and epithelial hypertrophy) with alteration of the soluble iodoprotein pattern (content and composition.). Both relaxation times spin-lattice (T1) and spin-spin (T2) were increasing with the lenght of treatment with antithyroid drugs. Reversibility of the process was noted in accordance with biochemical and morphological data. The relaxation rate (formula: see text) for thyroid tissue water was in positive correlation with the suluble protein concentration and particularly with the TG content in the gland. There was no difference in relaxation times between normal thyroid and gland of rats treated chronically with excess iodide. The observed difference in T1 between normal glands and glands of PTU,-C10(-4)--treated rats was comparable with that found in cases of human thyroid cancer. This finding is of importance when the diagnostic potential of NMR in the detection of malignancy is considered. In conclusion, a strong correlation was found between microstructural and biochemical changes of the thyroid gland and proton magnetic relaxation of tissue water. The striking difference between the proton spin-relaxation times in normal and in goiter thyroid glands of rats suggests that pulsed NMR spectroscopy could be a method for evaluation of some disturbances in thyroid gland.     

Morphological study of the neurosecretory hypothalamo-hypophyseal system and thyroid gland in intestinal carcinogenesis]

Pathomorphology of the neurosecretory hypothalamo-hypophyseal system and the thyroid gland of 150 rats of both sexes was investigated in intestinal carcinogenesis induced by 1.2-dimethyl hydrazine. Inhibition of the neurosecretory activity of paraventricular and supraoptical nuclei as well as atrophic changes in th: thyroid gland were found to be associated with the latent period of carcinogenesis. The arising of the intestinal tumor is accompanied by hypertrophy of neurons and their nuclei, by a decrease in the neurosecretory substance content and the thyroid gland tendency to return to normal. The tumor spreading provoked neuron hypertrophy and the reduction of the neurosecretory substance as well and pronounced atrophic changes in the thyroid gland.     

离乳大鼠假性性早熟模型的建立及对雌活性物质的应答

以雌激素含量明确的避孕药物作诱导剂观察了其对离乳Wistsar大鼠性成熟的影响,结果显示在给予避孕药后体重、乳腺、阴门、阴道上皮细胞、卵巢、子宫均发生类似人体假性性早熟变化,而肾上腺、脑垂体、甲状腺等与对照组比较均未见明显差异。     

Maternal stress induces adult reduced REM sleep and melatonin level

We have previously reported that neonatal maternal deprivation (MD) resulted in a decrease of total sleep and an increase of orexin A in adult rats. Now, we characterized features of sleep, activity, and melatonin levels in rats neonatally treated with MD and control (MC) procedures. Adult male Sprague-Dawley rats were treated with either MD or MC procedures for 10 days starting at postnatal day 4. At 3 months of age, sleep was recorded for 48 h in one set of MD and MC rats, while another set of MD and MC rats was measured for locomotor activity (under LD = 12:12). Melatonin levels in the blood, pineal gland, and hypothalamus were measured as well as clock protein level in the hypothalamus. Compared to the MC rats, REM sleep in the MD rats was significantly reduced in the light periods but not in the dark periods. Both quiet wake and total wake in the MD rats were significantly increased during the light period compared to the MC rats. The weight of the pineal gland of the MD rats was significantly smaller than in MC rats. Melatonin levels of the MD group were significantly reduced in the pineal gland and hypothalamus compared to the MC group. No significant difference was identified between groups in the expression of the clock protein in the hypothalamus. Neonatal MD resulted in reduced REM sleep and melatonin levels, without changes of circadian cycle of locomotor activity and levels of clock protein.