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1.
Uniformly 14C-ring-labelled tert-butylhydroquinone (TBHQ) was diluted with non-radioactive TBHQ and administered orally (for excretion studies) to Fischer 344 rats. An average of 72.9% and 10.6% of the administered radioactivity was recovered in the urine and faeces, respectively, of male rats, and 77.3% and 8.2% in the urine and faeces, respectively, of female rats in 4 days. No significant sex-related differences were found in either excretion, tissue distribution or urinary metabolites of TBHQ-derived radiolabel. For distribution studies, intraperitoneal doses were administered to female rats, and tissue levels of radiolabel were determined at various times after dosing. The parent compound quickly disappeared from tissue in vivo. The highest concentrations of radiolabel were found in the liver and kidneys. The urinary metabolites consisted of conjugated TBHQ and unidentified polar substance(s).  相似文献   

2.
Duplications of the esophagus or stomach alone are infrequent, and complete foregut duplication has only rarely been described. Most combined esophagogastric duplications present within the first year of life, and if communication with the normal alimentary tract does occur, it does so only either above or below the diaphragm. This report illustrates a case of continuous duplication of the esophagus and stomach with communication to the normal alimentary tract at both proximal and distal ends. Operative management and a review of the literature and embryology are described.  相似文献   

3.
The medial basal hypothalamus of ovariectomized rats was destroyed using a modified Halász knife. Large increases in prolactin secretion were observed 1 and 14 days following the lesions. Long- and short-term lesioned animals were anesthetized with chloral hydrate and treated with various doses of apomorphine (0.05, 0.2, 2, 5 mg/kg). Blood samples were obtained before and 10, 30 and 60 minutes after the injection. Both the 0.05 and 0.2 mg/kg doses caused significantly greater and longer-lasting inhibition of prolactin in long-term than in short-term lesioned animals. Since the MBH was totally destroyed this study suggests that anterior pituitary dopamine receptors involved in the inhibition of prolactin secretion become supersensitive in long-term lesioned rats.  相似文献   

4.
The purpose of this study was to test the hypothesis that vasoconstriction in the mesenteric and renal circulations is greater at both submaximal and maximal exercise intensities with advancing age. Arterial blood pressure, heart rate, and mesenteric, renal, and iliac (hindlimb) artery blood flow velocities were measured before and during graded treadmill exercise in mature (12 mo) and senescent (24 mo) male Fischer 344 rats. During treadmill running at mild, moderate, and maximal exercise intensities (approximately 45, 70, and 100% of maximal oxygen uptake), the increases in arterial pressure were similar in the mature and senescent animals, whereas heart rate rose less in the older group (P < 0.05). Mesenteric and renal flow velocities declined and vascular resistances increased from resting levels in both groups in response to graded exercise; however, the magnitudes of the increases in both mesenteric and renal vascular resistance were significantly augmented in the older rats at the moderate and maximal workloads. Hindlimb blood flow velocity increased and resistance declined from resting levels at each exercise intensity in both groups. In contrast to the visceral and renal adjustments, the magnitudes of the changes in both hindlimb flow and resistance were similar for the two age groups at all exercise intensities. These findings support the hypothesis that mesenteric and renal vasoconstriction is augmented in senescent Fischer 344 rats during exercise at moderate and maximal intensities but not at mild workloads. Despite these regional differences, the maintenance of arterial pressure is not altered at either submaximal or maximal exercise intensities with advancing age.  相似文献   

5.
We examined skeletal and cardiac muscle responses of mature (8 mo) and old (23 mo) male Fischer 344 rats to 14 days of hindlimb suspension. Hexokinase (HK) and citrate synthase (CS) activities and GLUT-4 glucose transporter protein level, which are coregulated in many instances of altered neuromuscular activity, were analyzed in soleus (Sol), plantaris (PI), tibialis anterior (TA), extensor digitorum longus (EDL), and left ventricle. Protein content was significantly (P < 0.05) lower in all four hindlimb muscles after suspension compared with controls in both mature (21-44%) and old (17-43%) rats. Old rats exhibited significantly lower CS activities than mature rats for the Sol, Pl, and TA. HK activities were significantly lower in the old rats for the Pl (19%) and TA (33%), and GLUT-4 levels were lower in the old rats for the TA (38%) and EDL (24%) compared with the mature rats. Old age was also associated with a decrease in CS activity (12%) and an increase in HK activity (14%) in cardiac muscle. CS activities were lower in the Sol (20%) and EDL (18%) muscles from mature suspended rats and in the Sol (25%), Pl (27%), and EDL (25%) muscles from old suspended rats compared with corresponding controls. However, suspension was associated with significantly higher HK activities for all four hindlimb muscles examined, in both old (16-57%) and mature (10-43%) rats, and higher GLUT-4 concentrations in the TA muscles of the old rats (68%) but not the mature rats. These results indicate that old age is associated with decreased CS and HK activities and GLUT-4 protein concentration for several rat hindlimb muscles, and these variables are not coregulated during suspension. Finally, old rat skeletal muscle appears to respond to suspension to a similar or greater degree than mature rat muscle responds.  相似文献   

6.
Potassium bromate (KBrO3) is a rodent carcinogen and a nephro- and neurotoxicant in humans. KBrO3 is used in cosmetics and food products and is a by-product of water disinfection by ozonization. KBrO3 is carcinogenic in the rat kidney, thyroid, and mesothelium and is a renal carcinogen in the male mouse. The present study was designed to investigate the relationship of time and dose to bromate-induced tumors in male Fischer 344 (F344) rats and to provide some insight into the development of these tumors. KBrO3 was dissolved in drinking water at nominal concentrations of 0, 0.02, 0.1, 0.2, and 0.4 g/L and administered to male F344 rats as the sole water source for 12, 26, 52, 78, or 100 wk. Renal cell tumors were present after 52 wk of treatment only in the high-dose group. Mesotheliomas developed after 52 wk of treatment on the tunica vaginalis. Mesotheliomas were present at sites other than the testicle after 78 wk of treatment, indicating that their origin was the testicular tunic. Thyroid follicular tumors were present as early as 26 wk in 1 rat each from the 0.1- and 0.2-g/L groups. The present study can be used as a basis for the determination of dose-time relationships of tumor development for a better understanding of KBrO3-induced cancer.  相似文献   

7.
8.
The rat is a common laboratory animal utilized in a variety of investigations including experimental gerontology. Gerontologic investigations can be compromised when the differences observed when comparing young and old animals are actually differences between normal and disease states. It is of critical interest to know the pathology of the animals being studied and to understand the impact of these disease processes on the parameters being measured. The incidence and average age of occurrence for lesions have been characterized and are reported here for one inbred (Brown Norway) and two hybrid strains (Brown Norway x Fischer 344 and Fischer 344 x Brown Norway) of rat. Total lesion incidence functions as a biomaker of aging for all of the strains examined (p < or = .00001). These three genotypes have significantly lower incidence of several major pathologic processes (including glomerulonephritis, retinal atrophy, and leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized strains. Additionally, the BN and F344 x BN F1 hybrid attain 50% mortality at 130 and 146 weeks of age, respectively, which is significantly greater than the 103 weeks for the F344 rat. It is hoped that access to basic information on these three rat genotypes will increase their utilization by the community of gerontologic scientists.  相似文献   

9.
Myocyte apoptosis increases with age in Fischer 344 rats, but the multiple molecular events implicated in this phenomenon remain to be identified. Several defects involving Ca2+ homeostasis, pH, and the expression of p53 and genes of the Bcl-2 protein family may contribute to the activation of myocyte death. Therefore, changes in intracellular pH, cytosolic Ca2+, DNase I and DNase II were measured in myocytes isolated by enzymatic digestion from rats of different ages. Moreover, the expression of p53, Bcl-2 and Bax in these cells was determined. Measurements of intracellular pH by BCECF fluorescence at 3, 12 and 24 months showed that this parameter did not change with age: 3 months, 7.20+/-0.05; 12 months, 7.21+/-0.07; 24 months, 7.18+/-0.09. In contrast, diastolic Ca2+ determined by the Fura 2-AM method increased progressively from 99.8+/-1.9 nm at 3 months to 136.3+/-9.6 nm at 24 months (P<0.001). Concurrently, DNase I activity evaluated by plasmid digestion assay in myocytes increased 3.2-fold from 3 to 24 months (P<0.02). Conversely, pH-dependent-DNase II remained essentially constant with age. Western blotting performed on ventricular myocytes did not detect significant changes in p53, Bax and Bcl-2 proteins with age. Similarly, immunocytochemically, the fraction of myocytes labeled by p53, Bax and Bcl-2 did not change from 3 to 24 months. In conclusion, myocyte aging is characterized by an increase in diastolic calcium which may activate DNase I triggering apoptosis, independently from the expression of p53, Bax and Bcl-2 in the cells.  相似文献   

10.
Localization of age-related deficits in the cerebellar beta adrenergic signal transduction cascade were investigated electrophysiologically using forskolin (FORSK) and adenosine-3',5'-cyclic monophosphothioate Sp-isomer (Sp-cAMPS) applied via pressure ejection from extracellular multibarreled glass electrodes to activate the transduction cascade. In young rats, 100 microM FORSK activated AC, and 100 microM Sp-cAMPS activated protein kinase A; thus, both increased GABAergic inhibition of Purkinje cell firing. In aged rats, however, 100 microM FORSK was unable to increase GABAergic inhibition of Purkinje cell firing. In addition, 1 mM 7 beta-decacetyl-7 beta-(gamma-N-methylpiperazino)butyryl-forskolin, an analog of FORSK, was also unable to increase GABAergic inhibition in aged rats. In contrast, Sp-cAMPS was able to increase GABAergic inhibition in aged rats, but higher doses were required than in young rats, Isoproterenol (ISO), a beta adrenergic agonist, was ineffective in increasing GABAergic inhibition of Purkinje firing in aged rats when tested alone, but ISO was effective in increasing Purkinje cell inhibition when ISO was tested with Sp-cAMPS. The results of this experiment indicate that one age-related deficit in the cerebellar beta adrenergic system occurs at the level of protein kinase A activation.  相似文献   

11.
The potential oncogenic effects of isopropanol, a widely used solvent, were investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm. Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were terminated during Weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to a recovery group and did not receive any further exposure following Week 53 but were retained until the core group of animals was euthanized. Transient signs of narcosis were observed for both mice and rats during exposure to 2500 and 5000 ppm and following exposure for mice from the 5000-ppm group. Increased mortality (100% versus 82% for controls) and a decreased mean survival time (577 days versus 631 days for controls) were noted for male rats from the 5000-ppm group. Increases in body weight and/or body weight gain were typically observed for both sexes of mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis and urine chemistry changes indicative of impaired kidney function (i.e., decreased osmolality and increased total protein, volume, and glucose) were noted for male rats from the 2500-ppm group as well as for male and female rats from the 5000-ppm group. At the interim euthanasia, a concentration-related increase in testes weight (absolute and relative as a percentage of body and brain weight) was observed for male rats. Concentration-related increases in absolute and relative liver weight (as a percentage of body weight) were observed for male and female mice. In addition, increased absolute and/or relative (as a percentage of body and brain weight) liver and kidney weights were observed for male and/or female rats from the 2500- and 5000-ppm groups. At necropsy, an increased incidence of seminal vesicle enlargement was observed grossly for male mice from the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions noted for mice included an increased incidence of ectasia of the seminal vesicles for male mice from the 2500- and 5000-ppm groups, minimal renal tubular proteinosis for male and female mice from all isopropanol groups, and renal tubular dilation for female mice from the 5000-ppm group. A number of nonneoplastic lesions were observed for male and female rats from the 2500- and 5000-ppm groups, with the most significant lesions being observed in the kidney and associated with chronic renal disease. The lesions noted with increased severity and/or frequency included mineralization, tubular dilation, glomerulosclerosis, interstitial nephritis, interstitial fibrosis, hydronephrosis, and transitional cell hyperplasia. The only tumor type increased in incidence during the study was interstitial cell adenomas of the testes in male rats. However, the increase in these adenomas was not believed to be exposure-related due to an unusually low incidence observed for the control group. There were no increased frequencies of neoplastic lesions noted for male or female mice or for female rats from any isopropanol exposure group. Chronic renal disease was attributed to be the main cause of death for male and female rats from the 5000-ppm group and was also considered to account for much of the mortality observed for male rats from the 2500-ppm group. In conclusion, the no-observed-effect level (NOEL) for toxic effects for both rats and mice was 500 ppm. The NOEL for oncogenicity effects for both mice and rats was determined to be greater than 5000 ppm.  相似文献   

12.
The exact nature of the saccharoid fraction (non-glucose reducing substances) in human blood is not known. The saccharoid fraction is increased in diabetic patients and a direct relationship exists to the height of the blood sugar. Some of the constituents of the saccharoid fraction, namely, glutathione, glucuronic acid and organic phosphate are significantly increased in diabetic patients. Fructose diphosphate and ATP are increased in the patients treated with oral hypoglycemic drugs. The known constituents of the saccharoid fraction which were determined accounted only for about 48% in normal and 36% in diabetic patients. The reduced contribution of these compounds to the saccharoid fraction in diabetic patients indicates that the nature of the saccharoid fraction may be different in diabetic patients.  相似文献   

13.
Delayed, attenuated, or absence of the proestrous LH surge occurs in aging rats. To assess how aging affects the positive feedback action of 17 beta-estradiol (E2) on the pituitary, we determined the responsiveness of rat pituitary cells to GnRH and the secretagogues affecting intracellular signal transduction mechanisms in the presence or absence of E2. We also correlated the LH response to pituitary LH content. Anterior pituitaries excised from ovariectomized Sprague-Dawley rats, either young (3-4 months) or old (19-20 months), were enzymatically dispersed and then pretreated with or without E2 (0.6 nM) for 48 h, followed by incubation for 3 h with or without various secretagogues. The secretagogues included GnRH (1 and 10 nM), veratridine (increases Ca2+ influx; 5 and 10 microM), and phorbol 12-myristate 13-acetate (a protein kinase-C activator; 10 and 100 nM). LH in media and cells were measured by RIA and expressed on the basis of cellular DNA. GnRH, veratridine, and phorbol 12-myristate 13-acetate at all doses stimulated (P < 0.01) LH release in cells from both young and old rats. E2 stimulated (P < 0.05 to P < 0.01) all secretagogue-induced LH release in cells from both young and old rats, but only basal LH release (P < 0.05) in cells from young rats. The magnitude of both basal and secretagogue-induced LH release in either the presence or absence of E2 was smaller (P < 0.01) in cells from old than in those from young rats. The initial cellular LH was lower (P < 0.01) in cells from old than in those from young rats. The LH-releasing ability (expressed as a percentage of total cellular LH) of cells from old rats was identical (P > 0.05) to that of cells from young rats under all conditions studied. These results suggest that the reduced magnitude of LH release by cells from old rats may be attributed to reduced cellular LH, rather than to impaired estrogen feedback or impaired signal transduction mechanisms. It remains to be determined whether LH biosynthesis per cell and/or the number of gonadotropes decrease with age.  相似文献   

14.
Acute sodium depletion in rats leads to dramatic increases in intake of hypertonic NaCl solutions, a behavior known as sodium appetite. The importance of signals conveyed by the chorda tympani (ChT) nerve to the expression of sodium appetite is unclear. The effects of bilateral ChT transection were examined on the short- and long-term response to sodium depletion in Wistar and Fischer 344 (F344) rat strains, because Wistar rats normally display a NaCl preference in the absence of need whereas F344 rats avoid NaCl. In both strains, sodium appetite after ChT transection and treatment with the diuretic furosemide was delayed and blunted or eliminated. The results suggest that signals conveyed by the ChT nerve are important in the expression of a sodium appetite. Effects on F344 rats are particularly interesting because ChT transection surgery appears to have opposite effects on NaCl intake depending on whether F344 rats are sodium replete or deplete. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

15.
Three batches comprised of 48 young adult Fischer female rats each were subjected to total-body irradiation with 50 rads modified fission neutrons, or were given 600 rads 137Cs gamma-rays, or served as unirradiated controls. On the day following exposure, one-half of each batch was grafted with a single anterior pituitary gland beneath the left kidney capsule. The animals were observed for mammary neoplasia and all those that died during the experiment were autopsied. The experiment was terminated 538 +/- 13 days after irradiation when all neutron-irradiated, pituitary-grafted animals had one or more mammary tumors. Only 2 of the 23 untreated rats that survived until termination of the experiment developed mammary fibroadenomas, and none had mammary carcinomas. The incidence of fibroadenomas was increased, and a single carcinoma was found, in unirradiated rats with pituitary grafts. Irradiation alone caused an increase in the incidence of mammary fibroadenomas and the appearance of carcinomas. Fibroadenomas were markedly increased by the addition of pituitary grafts to irradiation. Carcinoma incidence was less markedly affected. The neutron dose of 50 rads was slightly more effective in inducing mammary neoplasms than the 600-rad dose of gamma-rays.  相似文献   

16.
To investigate possible gender- and age-associated changes of the hypothalamic-pituitary-thyroid (HPT) axis at baseline and during stress, we studied healthy young (3-month) and old (23-month) female 344/N Fischer rats at the basal state and after 2 h of immobilization (IMMO), in parallel to age-matched male rats. At baseline, there were no major differences on HPT axis functions between young female and male animals. Old age was associated with impaired central thyroid function in both genders, albeit to a much lesser extent in females than in males. Plasma prolactin (PRL) levels were similar in young females and males but were higher in old females than males. IMMO inhibited HPT axis functions in both genders in young, but not old animals. Thus, plasma TSH and hypothalamic TRH mRNA levels were decreased by IMMO in young, but not in old rats of both genders. IMMO increased plasma PRL in young and old males, but did not have any effect in young and old females. In summary, these data indicate that age and gender exert diverse effects on HPT axis functions at baseline and after stress.  相似文献   

17.
In post-partum lactating rats, sucking by the young was associated with high prolactin release and maintenance of lactation but severe inhibition of LH and FSH release and suspension of oestrous cycles. Shortly after the pups were removed on day 22 post partum LH and FSH release returned to normal and oestrous cycles resumed. Twice-daily injections of ergocornine methanesulphonate (ERG) into mothers beginning at 5 or 7 days post partum, resulted in sustained inhibition of prolactin release and diminished mild secretion. By frequent exchange of pups between control and ERG-treated mothers, it was possible to maintain vigorous sucking and almost normal pup growth despite low serum prolactin levels and diminished lactation. In these rats, serum levels of LH remained low during 11 or more days of treatment with ERG, but serum FSH was consistently higher than in untreated control mothers. After 11 or more days of ERG treatment, most rats showed a return to normal LH and FSH release and resumption of oestrous cycles. These results suggest (a) that the sucking stimulus rather than high prolactin levels in the circulation is mainly responsible for inhibition of LH and FSH release during the first 11 days post partum, (b) that the sucking stimulus acts to increase prolactin and inhibit LH release by separate hypothalamic mechanisms, and (c) that administration of ERG results in diminished prolactin release and lactation, and in increased release of FSH and subsequently of LH with earlier resumption of oestrous cycles.  相似文献   

18.
Tamoxifen, an antiestrogen used in the treatment of breast cancer, was assessed for carcinogenic potential in the two-stage model of experimental hepatocarcinogenesis. Groups of female Fisher F344 rats were initiated with a non-necrogenic, subcarcinogenic dose of diethylnitrosamine (DEN; 10 mg/kg, po) and fed tamoxifen at a concentration of 250 mg per kg of AIN-76A diet for 6 or 15 months. The livers of these animals exhibited an increase in size and number of altered hepatic foci compared with those animals which were initiated with DEN but not exposed to tamoxifen. This finding indicates that tamoxifen may have a carcinogenic potential in the rat liver. After 6 months of treatment, neoplastic nodules were observed in 3/8 rats in the DEN-initiated, tamoxifen-treated group. In the initiated group provided with tamoxifen for 15 months, neoplastic nodules were observed in 7/8 rats and hepatocellular carcinomas in 3/8 rats. The serum level of tamoxifen in these rats was 200-300 ng/ml. The ratio of tamoxifen, 4-hydroxy tamoxifen, and N-desmethyl tamoxifen was 1:0.1:0.5-1 in the serum. When adjusted for age-related weight increases, the serum and liver levels of tamoxifen and its N-desmethyl metabolite did not change over the 15 months. In the rat liver, the level of tamoxifen and its N-desmethyl metabolite was 10-29 micrograms/g liver after 6 or 15 months of chronic dietary administration. The ratio of tamoxifen:4-hydroxy tamoxifen:N-desmethyl tamoxifen was 1:0.1.3-3.3 in the liver. Therefore, the liver had 20- to 30-fold more tamoxifen and 4-hydroxy tamoxifen and at least 100-fold more N-desmethyl tamoxifen than the serum (assuming 1 gram of tissue is equivalent to 1 ml of serum). These results indicate that tamoxifen is a promoting agent for the rat liver at serum levels found in patients given the usual therapeutic course of tamoxifen. The high concentrations of tamoxifen attained in the rat liver indicate that actions other than its known estrogenicity for liver could contribute to its promoting action. In addition, these results indicate that the pharmacodynamic differences in tamoxifen metabolism in rats and humans and at low versus high doses should be determined. Thus, the therapeutic indications for tamoxifen should be balanced by the potential risk it may present as a promoting agent in mammalian liver.  相似文献   

19.
The effect of voluntary exercise on maximal oxygen uptake (VO2 max) was studied in young female Fischer 344 rats. After 10 weeks of wheel-running training, the absolute VO2 max and VO2 max relative to body mass increased without a decline in body mass. The running speed eliciting VO2 max, heart and soleus muscle mass, and succinate dehydrogenase (SDH) activity in the soleus muscle also increased. These results suggest that voluntary exercise is an effective means of increasing the aerobic exercise capacity of young female Fischer 344 rats.  相似文献   

20.
It is known that there are large temperature elevations in proximity to air bubbles during US (ultrasound) heating. The existence of tiny air bubbles in the target tissue may enhance the temperature elevation in US hyperthermia. To examine this hypothesis, phantom tissue experiments using an US contrast agent consisting of tiny air bubbles surrounded by a 5% (w/v) human albumin shell (Alb) were performed. As a phantom tissue, a 2 cm cube of beef was used. The phantom tissue was heated with or without the US contrast agent by an US hyperthermia device for 3 min. The heating device was operated at 1.5 MHz with the US intensity of 0.9 W/cm2. Physiological saline solution, iodized oil, and ethanol were used for control experiments. The effect of multiple needle punctures to the beef phantom was also examined. The temperature elevation rate (TER) was defined as the ratio of temperature elevation by heating with Alb or control materials to the temperature elevation by US heating alone. The TER of Alb was 1.7, whereas the TERs of the control materials and of the multiple needle punctures were approximately 1. The administration of Alb significantly increased the temperature in US hyperthermia. In addition, the heating efficiency of Alb was compared to the effect of an increase in the US intensity. Phantom tissue was heated at various US intensities. When the US intensity was increased from 0.9 to 1.8 W/cm2, the temperature elevated by approximately 1.7-fold. Thus, the effect of the administration of Alb was almost equivalent to the effect of increase in US power intensities from 0.9 to 1.8 W/cm2 in the present experimental settings. The results suggest that the US contrast agent can be a potential enhancer in US hyperthermia.  相似文献   

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