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1.
A tocotrienol (T3) mixture was intragastricaly administered to Sprague-Dawley rats, and the T3 levels in various tissues were measured 0, 4, 8 and 24 hr after the administration. In blood clots, brain, thymus, testes, vice-testes and muscles, T3 homologues were not detected at all. In epididymal adipose, renal adipose, subcutaneous adipose and brown adipose tissues and in the heart, the T3 levels were maintained or increased for 24 hr after the administration. In the serum, liver, mesenteric lymph node, spleen and lungs, the T3 levels were highest 8 hr after the T3 administration. These results suggest that the distribution and metabolism of T3 in the rat vary considerably among different tissues.  相似文献   

2.
1. Rainbow trout (Salmo gairdneri) given a single intraperioneal injection of propanolol (a β-adrenoceptor inhibitor) had plasma triiodothyronine (T3) levels which were significantly (P < 0.01) lower than in control fish 8 hr after the injection, but not after 24hr; thyroxine (T4) levels and T4/T3 ratios were not significantly affected.2. Isoproterenol (a β-adrenoceptor stimulator) had no effect on T4, T3 or T4/T3 ratios.3. A single intraperitorial injection of TSH and prolactin given together induced a significant increase (P < 0.05) in plasma T3 levels 24 hr after the injection.4. TSH and prolactin given to propanol-treated fish caused a further significant increase in T3 levels compared with TSH + prolactin-, TSH-, prolactin-, or solvent-injected groups (P < 0.01).5. The data suggest that the inhibition of peripheral monodeiodination of T4 to T3 by propranolol, well documented in mammals, does not occur in rainbow trout. On the contrary, T3 levels after propranolol administration are increased in conditions where thyroid simulation occurs.  相似文献   

3.
As part of a study of the therapeutic potential of anti-T cell monoclonal antibodies, we studied the biologic effects of 8BE6, a mouse anti-guinea pig (GP) pan-T cell monoclonal antibody, on blood and tissue T cells and on the prototypic T cell-mediated reactions, classic delayed hypersensitivity (DH) and cutaneous basophil hypersensitivity (CBH). 8BE6 reacts to a 68,000 m.w. protein probably homologous with human CD5 (T1) and murine Lyt-1. A single dose of 1.8 to 3.4 mg 8BE6 caused lymphopenia and greater than 90% depletion of 8BE6+ peripheral T cells 1 to 72 hr later, and a significant but lesser decrease of lymphocytes reacting with another pan-T cell monoclonal antibody (p less than 0.02 at 24 hr). Free serum 8BE6 was detected for up to 48 hr after administration. Immunoperoxidase stains of tissue revealed that lymphocytes in lymph nodes and spleen were coated with mouse immunoglobulin 1 hr after antibody treatment and displayed in situ capping. Subsequently, there was a loss of T cells in all tissues (spleen, lymph node, liver, and kidney) except the thymus, with normal 8BE6 antigen staining returning by 72 hr. Areas of induration of DH reactions to PPD were reduced in 8BE6-treated GP, compared with pretreatment reactions in the same GP or in control-treated GP (p less than 0.001 for both). The numbers of infiltrating T cells and fibronectin-receptor-positive macrophages were also reduced. In contrast, 8BE6 had no effect on CBH reactions, as judged by erythema and basophil counts in 1-micron sections, although fewer T cells were found in reaction sites. There were no differences in IgM, fibronectin, or Ia staining between 8BE6-treated GP and controls. In vivo administration of a single dose of anti-T cell monoclonal antibody results in a transient, highly specific depletion of T cell populations in peripheral blood and tissues except the thymus. This treatment inhibits DH but not CBH reactions by systemic and local depletion of T cells.  相似文献   

4.
Some alterations in lipid metabolism in mice were observed by the intraperitoneal injection of endotoxin from Salmonella typhimurium. The content of serum triglyceride increased markedly in poisoned mice 16-24 hr postintoxication. The level of free fatty acid (FFA) in the serum of endotoxin-administered mice decreased in inverse proportion to an increase in the injected dose of endotoxin. The electrophoretic analysis of the serum lipoprotein on cellulose acetate membrane showed that pre beta-lipoprotein increased markedly and that FFA fraction in the poisoned mice sera disappeared 18 hr postintoxication. The activity of hormone-sensitive lipase in adipose tissue was elevated appreciably 2 hr after injection, but decreased more significantly after 18 hr than that in fasted control mice. On the other hand, the activity of lipoprotein lipase decreased in the post-heparin serum and adipose tissue 3 hr postintoxication, and decreased significantly after 16 hr. There were no significant differences between changes in the formation of active glycerol (alpha-GP) and in the activity of alpha glycerophosphate dehydrogenase (alpha-GPDH) in the mice liver with or without administration of endotoxin, and after 16 hr levels of both hepatic alpha-GP content and alpha-GPDH activity in poisoned mice showed a tendency to be slightly lower than those in fasted control mice.  相似文献   

5.
Quantitative autoradiographic techniques demonstrate that chronic alcohol administration causes a decrease in [3H]-glutamate binding to hippocampal N-methyl-D-aspartate (NMDA) receptors. A 14% decrease in [3H]-glutamate binding in the hippocampal CA1 region is seen both in the rat after five days of ethanol administration and in postmortem hippocampal tissues from alcoholics. In the rat, 24 hr ethanol withdrawal values are intermediate between control and alcohol binding levels. There was no significant effect of ethanol on [3H]-glutamate binding in the cortex or caudate.  相似文献   

6.
n-3 polyunsaturated fatty acids (n-3 PUFA) might regulate metabolism by lowering endocannabinoid levels. We examined time-dependent changes in adipose tissue levels of endocannabinoids as well as in parameters of glucose homeostasis induced by n-3 PUFA in dietary-obese mice, and compared these results with the effect of n-3 PUFA intervention in type 2 diabetic (T2DM) subjects. Male C57BL/6J mice were fed for 8, 16 or 24?weeks a high-fat diet alone (cHF) or supplemented with n-3 PUFA (cHF?+?F). Overweight/obese, T2DM patients on metformin therapy were given for 24?weeks corn oil (Placebo; 5?g/day) or n-3 PUFA concentrate as above (Omega-3; 5?g/day). Endocannabinoids were measured by liquid chromatography-tandem mass-spectrometry. Compared to cHF-fed controls, the cHF?+?F mice consistently reduced 2-arachidonoylglycerol (up to ~2-fold at week 24) and anandamide (~2-fold) in adipose tissue, while the levels of endocannabinoid-related anti-inflammatory molecules N-eicosapentaenoyl ethanolamine (EPEA) and N-docosahexaenoyl ethanolamine (DHEA) increased more than ~10-fold and ~8-fold, respectively. At week 24, the cHF?+?F mice improved glucose tolerance and fasting blood glucose, the latter being positively correlated with adipose 2-arachidonoylglycerol levels only in obese cHF-fed controls, like fasting insulin and HOMA-IR. In the patients, n-3 PUFA failed to reduce 2-arachidonoylglycerol and anandamide levels in adipose tissue and serum, but they increased both adipose tissue and serum levels of EPEA and DHEA. In conclusion, the inability of n-3 PUFA to reduce adipose tissue and serum levels of classical endocannabinoids might contribute to a lack of beneficial effects of these lipids on glucose homeostasis in T2DM patients.  相似文献   

7.
Carbohydrate metabolic disorders were investigated by means of enzyme activities in mice (ddYS) injected intraperitoneally with endotoxin from Salmonella typhimurium. The mice exhibited hyperglycemia 2 hr after administration of endotoxin and hypoglycemia at 18 hr. Activity of hepatic phosphorylase in the endotoxin-poisoned mice at 2 hr was slightly higher than that in the control mice, whereas the level of this activity was not significantly different from that in the controls after 18 hr. Glucose-6-phosphatase activity in the poisoned mice increased by 2 hr after injection, but decreased by 18 hr. The blood lactate level in the poisoned mice transiently decreased until 3 hr after injection, but the mice exhibited a marked lactacidemia by 8–24 hr. The time course of lactate dehydrogenase (LDH) activity in various tissues was examined in mice injected with endotoxin. The activity of hepatic LDH declined to about two-thirds of that of the control mice after 16 hr, and was restored to the normal level by 48 hr. LDH in the cardiac muscle was markedly activated (by about 37%) in the early period (3–6 hr) after administration of endotoxin, and this activity gradually declined. However, the activity of LDH in the skeletal muscle showed a tendency similar to the rise and fall of the levels of blood lactate, and was restored to the normal value at 72 hr after injection. On the other hand, the serum LDH activity in the poisoned mice increased about 1.75-fold by 16 hr after injection. Mice injected with endotoxin exhibited a leakage of the isozymes LDH 3 and 5, but the origin of the leakage is uncertain. Similar elevation in the activities of transaminases (GPT and GOT) and malate dehydrogenase was found in the mouse serum at 16 hr after injection of endotoxin.  相似文献   

8.
9.
The objective of the present study was to investigate the effect of the time of administration of androgen, during the neonatal period, on the development of masculine copulatory behavior in female rats. In addition, the influence of androgen, administered neonatally, on the development of penile reflexes and cytoplasmic androgen receptor levels in the hypothalamic-preoptic area (HPOA) was examined. Female rats were injected with 0.5 mg testosterone propionate (TP) at either 1, 8, or 24 hr after birth and again 24 hr after the first injection. Fifty percent of the females treated with TP at 1 and 8 hr after birth displayed the ejaculatory response when tested in adulthood. In contrast, 93 and 87.5% of oil-treated males and females, respectively, which were androgenized at 24 hr after birth exhibited this response. The results indicate that a considerable amount of masculinization occurs postnatally in the rat. However, none of the androgenized females displayed any penile reflexes even when tested following the display of an ejaculatory response. HPOA androgen receptor levels were somewhat higher in the oil-treated females than in males but were not correlated with the ability to exhibit ejaculation patterns.  相似文献   

10.
Female European eels, Anguilla anguilla, were given a single intra-arterial injection via a catheter of cortisol hemisuccinate at doses ranging from 3.5 to 35 micrograms (15 to 150 micrograms/kg body wt), yielding mean plasma cortisol levels of 87-410 ng/ml 2 hr after injection. Cortisol treatment (17.5 and 35 micrograms) significantly decreased plasma levels of thyroxine (T4) and triiodothyronine (T3) within 24 hr relative to those in control fish. Cortisol treatment (35 micrograms) appeared to increase the clearance rate of 125I-T3 from plasma and the proportionate uptake of radioactivity in certain tissues after injection of 125I-T3. Cortisol treatment had no apparent effect on the plasma clearance of 125I-T4 or tissue distribution of radioactivity after injection of 125I-T4.  相似文献   

11.
Spleen cultures prepared from mice injected 24 hr earlier with 2 × 106?2 × 108 sRBC and challenged in vitro with sRBC produced 10 times more anti-sRBC IgM PFC than cultures prepared from uninjected mice. The effect was specific for the particular species of foreign RBC injected in vivo. In vitro responses to TNP were also increased in spleen cultures prepared from animals injected 24 or 12 hr earlier with carrier RBC alone, directly implicating carrier-specific T cells in this process. Similar enhancements of PFC formation occurred in cultures prepared from mice which had been injected with sRBC 24 and 48 hr earlier, but which were exposed to lethal irradiation at 1 hr after injection of antigen, if their spleens were shielded extracorporeally during irradiation. This finding indicated that in vivo recruitment of antigen-reactive extrasplenic X-ray-sensitive cells from the circulating lymphocyte pool by the spleen could not account for the observed enhancement.Proliferation in the spleen of antigen-reactive T cells, commencing 12–20 hr after the administration of antigen, was demonstrated by the tritiated thymidine pulse technique. An 8-hr hot-pulse given to spleen cell cultures from normal animals at 20 hr after in vitro challenge with antigen did not affect the rate of generation of IgM-producing cells; however, administration of a similar pulse to cultures which were initiated at 12 or at 20 hr after the in vivo injection of sRBC eliminated the enhanced generation of PFC and delayed the in vitro response to sRBC by 24 hr.Spleen cell cultures were prepared from mice which had been injected in vivo with sRBC at 12, 20, and 70 hr earlier, and 8- to 10-hr hot pulses were given immediately after initiation of the cultures. The cultures were then challenged with sRBC-TNP; antibody responses to TNP were greatly reduced in hot-pulsed cultures prepared from mice injected in vivo with carrier RBC at 12 or 20 hr prior to initiation of the cultures. In contrast, antibody responses to TNP observed in hot-pulsed cultures prepared from mice which had been injected with carrier RBC at 70 hr prior to initiation of the cultures were generally similar to those of nonpulsed 70 hr control cultures. This result suggests that the onset of T helper cell proliferation begins within 12–20 hr after injection of antigen, but subsides in vivo within 70 hr. By that time, the antigen-reactive T cells have already differentiated to perform their helper function.In spite of the triggering of T-cell proliferation during the first 24 hr after injection of antigen, spleen cell cultures prepared from mice which had been injected 24 hr earlier in vivo with 2 × 108 sRBC produced only minimal numbers of anti-sRBC PFC if no antigen was added to the cultures. The presence of unprocessed antigen thus appears to be a requirement for B-cell proliferation in vitro, even after T-cell division has been triggered. This finding is consistent with earlier suggestions that the function of “helper” T cells may not be limited to passive transport of antigenic determinants to B cells. Evidence is also presented to support the contention that the antigen-reactive T cell involved in this process may have to undergo cell division in order to develop “helper” capacity.  相似文献   

12.
《Life sciences》1996,58(7):PL119-PL122
The distribution of the putative anti-addictive substance ibogaine was measured in plasma, brain, kidney, liver and fat after ip and sc administration in rats. One hr after ip dosing (40 mg/kg), drug levels ranged from 106 ng/ml (plasma) to 11,308 ng/g (fat), with significantly higher values after sc administration of the same dose. Drug levels were 10–20 fold lower 12 hr after the same dose. These results suggest that: 1) ibogaine is subject to a substantial “first pass” effect after ip dosing, demonstrated by higher drug levels following the sc route, 2) ibogaine shows a large accumulation in adipose tissue, consistent with its lipophilic nature, and 3) persistence of the drug in fat may contribute to a long duration of action.  相似文献   

13.
Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K(3) combination, both alkaline DNase (DNase I) and acid DNase (DNase II) activities were detected in cryosections with a histochemical lead nitrate technique. Alkaline DNase activity appeared 1 hr after vitamin administration, decreased slightly until 2 hr, and disappeared by 8 hr after treatment. Acid DNase activity appeared 2 hr after vitamin administration, reached its highest levels between 4 and 8 hr, and maintained its activity 24 hr after treatment. Methyl green staining indicated that DNase expression was accompanied by a decrease in DNA content of the tumor cells. Microscopic examination of 1-microm sections of the tumors indicated that DNase reactivation and the subsequent degradation of DNA induced multiple forms of tumor cell death, including apoptosis and necrosis. The primary form of vitamin-induced tumor cell death was autoschizis, which is characterized by membrane damage and the progressive loss of cytoplasm through a series of self-excisions. These self-excisions typically continue until the perikaryon consists of an apparently intact nucleus surrounded by a thin rim of cytoplasm that contains damaged organelles.  相似文献   

14.
Time-dependent changes of theanine (gamma-glutamylethylamide) and other amino acids in various tissues of rats were investigated during the 24 hrs after theanine administration. When theanine (4 g/kg of body weight) was intragastrically administered to rats, the concentrations of theanine in the serum, liver and brain were significantly increased 1 hr after its administration, and thereafter gradually decreased, but reached the maximum level in the brain after 5 hrs. Theanine in these tissues had completely disappeared 24 hrs after its administration. In contrast, the administration of theanine resulted in the concentrations of theanine, urea, ethylamine and glutamic acid in the urine being significantly enhanced. These results suggest that theanine might be degraded via glutamic acid.  相似文献   

15.
The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one (I), a potent inhibitor of cholesterol synthesis with marked hypocholesteremic activity, has been studied in a nonhuman primate. A mixture of [2,4-3H]-I and [4-14C]-cholesterol was administered to a male baboon in the form of a feedball. Blood was samples at 4, 8, 12, 16, and 24 hr. Detailed analyses of the plasma lipids indicated very rapid absorption of I (relative to cholesterol) and metabolism to cholesterol, cholesteryl esters, and esters of I. The labeled cholesterol was characterized by chromatographic techniques and by purification by way of its dibromide derivative. The levels of 3H in plasma associated with I, esters of I, cholesterol, and cholesteryl esters each showed a different time course. By 24 hr after the administration of [2,4-3H]-I, most of the 3H in plasma was associated with cholesterol and cholesteryl esters. The levels of total 3H and 14C in plasma at various times after the administration of the mixture of [2,4-3H]-I and [4-14C]-cholesterol differed markedly with 3H showing a maximum value at 4 hr and 14C showing a maximum value at 24 hr.  相似文献   

16.
In vitro modulation of human T lymphocyte surface differentiation antigens T3, T8, and T4, by their respective monoclonal antibodies, was studied as a function of donor age. Kinetic studies performed on lymphocytes from young adults indicated that modulation is dependent on concentration of antibody used and duration of culture. OKT3 modulates T3 rapidly (maximum at less than 24 hr) and relatively completely (79% at the highest concentration of antibody used). By 48 hr, regeneration of the T3 antigen is apparent. T8 modulation by OKT8 is slower (continued modulation at 48 hr) and less complete than is T3 modulation by OKT3. OKT4 does not modulate the T4 antigen. In elderly individuals modulation of T3 by OKT3 is preserved whereas modulation of T8 by OKT8 is significantly reduced (24 +/- 8% at 48 hr vs 53 +/- 4% for young controls). These observations document further age-related changes in properties of human T suppressor cells.  相似文献   

17.
Numerous clinical studies have reported that ingestion of chocolate reduces the risk of metabolic syndrome. However, the mechanisms by which this occurs remain unclear. In this murine study, the metabolic-enhancing activity of a 10 mg/kg mixture of flavan-3-ol fraction derived from cocoa (FL) was compared with the same single dose of (-)-epicatechin (EC). Resting energy expenditure (REE) was significantly increased in mice treated with the FL versus the group administered the distilled water vehicle (Cont) during periods of ad libitum feeding and fasting. Mice were euthanized under the effect of anesthesia 2, 5, and 20 hr after treatment with FL or Cont while subsequently fasting. The mRNA levels of the uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in brown adipose tissue (BAT) were significantly increased 2 hr after administration of FL. UCP-3 and PGC-1α in the gastrocnemius were significantly increased 2 and 5 hr after administration of the FL. The concentrations of phosphorylated AMP-activated protein kinase (AMPK) 1α were found to be significant in the gastrocnemius of mice 2 and 5 hr after ingesting FL. However, these changes were not observed following treatment with EC. Plasma was collected for measurement of catecholamine levels in other animals euthanized by decapitation 2 and 4 hr after their respective group treatment. Plasma adrenaline level was significantly elevated 2 hr after treatment with FL; however, this change was not observed following the administration of EC alone. The present results indicated that FL significantly enhanced systemic energy expenditure, as evidenced by an accompanying increase in the type of gene expression responsible for thermogenesis and lipolysis, whereas EC exhibited this less robustly or effectively. It was suggested the possible interaction between thermogenic and lipolytic effects and the increase in plasma catecholamine concentrations after administration of a single oral dose of FL.  相似文献   

18.
Increasing evidence supports the notion that there are significant differences in the health effects of diets enriched in saturated, as opposed to monounsaturated or polyunsaturated fat. However, the current understanding of how these types of fat differ in their handling by relevant tissues is incomplete. To examine the effects of fat type and nutritional status on the metabolic fate of dietary fat, we administered (14)C-labeled oleic, linolenic, or stearic acid with a small liquid meal to male Sprague-Dawley rats previously fasted for 15 h (fasted) or previously fed ad libitum (fed). (14)CO(2) production was measured for 8 h after tracer administration. The (14)C content of gastrointestinal tract, serum, liver, skeletal muscle (soleus, lateral, and medial gastrocnemius), and adipose tissue (omental, retroperitoneal, and epididymal) was measured at six time points (2, 4, 8, 24, and 48 h and 10 days) after tracer administration. Plasma levels of glucose, insulin, and triglyceride were also measured. Oxidation of stearic acid was significantly less than that of either linolenic or oleic acid in both the fed and fasted states. This reduction was in part explained by a greater retention of stearic acid within skeletal muscle and liver. Oxidation of oleate and stearate were significantly lower in the fed state than in the fasted state. In the fasted state, liver and skeletal muscle were quantitatively more important than adipose tissue in the uptake of dietary fat tracers during the immediate postprandial period. In contrast, adipose tissue was quantitatively more important than skeletal muscle or liver in the fed state. The movement of carbons derived from dietary fat between tissues is a complex time-dependent process, which varies in response to the type of fat ingested and the metabolic state of the organism.  相似文献   

19.
Smoak IW 《Teratology》2002,65(1):19-25
BACKGROUND: Tolbutamide is a sulfonylurea oral hypoglycemic agent widely used for the treatment of non insulin-dependent diabetes mellitus. Tolbutamide produces dysmorphogenesis in rodent embryos and becomes concentrated in the embryonic heart after maternal oral dosing. Tolbutamide increases glucose metabolism in extra-pancreatic adult tissues, but this has not previously been examined in embryonic heart. METHODS: CD-1 mouse embryos were exposed on GD 9.5 to tolbutamide (0, 100, 250, or 500 microg/ml) for 6, 12, or 24 hr in whole-embryo culture. Isolated hearts were evaluated for (3)H-2DG uptake and conversion of (14)C-glucose to (14)C-lactate. Glut-1, HKI, and GRP78 protein levels were determined by Western analysis, and Glut-1 mRNA was measured by RT-PCR. RESULTS: Cardiac (3)H-2DG uptake increased after exposure to 500 microg/ml tolbutamide for 6 hr, and 100, 250, or 500 microg/ml tolbutamide for 24 hr, compared to controls. Glycolysis increased after exposure to 500 microg/ml tolbutamide for 6 or 24 hr compared to controls. Glut-1 protein levels increased in hearts exposed to 500 microg/ml tolbutamide for 12 or 24 hr, and Glut-1 mRNA increased in hearts exposed to 500 microg/ml tolbutamide for 24 hr compared to controls. HKI protein levels increased in hearts exposed to 500 microg/ml tolbutamide for 6 hr, but not 12 or 24 hr. There was no effect on GRP78 protein levels in hearts exposed to tolbutamide for 6, 12, or 24 hr. CONCLUSIONS: Tolbutamide stimulates glucose uptake and metabolism in the embryonic heart, as occurs in adult extra-pancreatic tissues. Glut-1 and HKI, but not GRP78, are likely involved in tolbutamide-induced cardiac dysmorphogenesis.  相似文献   

20.
In order to evaluate the possible role of prostaglandins in pituitary prolactin (PRL) secretion, PRL was serially measured following perphenazine (Trilafon) ingestion in 8 men before and after 5 days of indomethacin administration. Since estrogens have been shown to modulate prolactin secretion in man, serum steroids including estrone (E1), estradiol (E2), progesterone (P) and testosterone (T) were measured before and after indomethacin ingestion. Serum E1, P and T levels were similar during the pre- and post-indomethacin study periods: 56 +/- 4 (1 SEM) vs 48 +/- 5 pg/ml, 298 +/- 28 vs 315 +/- 32 pg/ml, and 8.1 +/- 0.7 vs 8.6 +/- 0.7 ng/ml, respectively. Serum E2 levels were slightly, but significantly, lower following indomethacin treatment at 30 +/- 3 vs 37 +/- 3 pg/ml (p less than .01). Basal serum PRL concentrations were unaffected by indomethacin administration (9 +/- 3 pre- vs 8 +/- 2 ng/ml post-drug treatment). Integrated perphenazine-induced PRL responses were likewise similar during the 2 study periods: 101 +/- 16 ng . hr/ml during the control period and 104 +/- 14 ng . hr/ml following indomethacin. Thus, short-term indomethacin treatment had no effect on basal or perphenazine-stimulated PRL secretion in men.  相似文献   

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