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排序方式: 共有69条查询结果,搜索用时 15 毫秒
1.
1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a serotonin type 2 (5-HT2) agonist, elevates plasma corticosterone levels and reduces the cerebral metabolic rate for glucose (rCMRglc) in the hippocampus, a structure which possesses few 5-HT2 receptors but a large number of steroid receptors. To explore the hypothetical interaction between 5-HT and steroid mechanisms in the hippocampus, we measured rCMRglc in intact, adrenalectomized and metyrapone-pretreated rats after saline or DOI administration. Metyrapone pretreatment alone had no significant effect on rCMRglc, but adrenalectomy produced widespread rCMRglc increases in the cortex, hippocampus and monoaminergic brainstem nuclei. In intact rats, DOI 10 mg/kg reduced rCMRglc in limbic areas and increased it in the interanteromedial and paracentral thalamic nuclei. Metyrapone pretreatment and adrenalectomy abolished rCMRglc responses to DOI in hippocampal areas and enhanced those in thalamic nuclei. These results indicate that brain responses to DOI are dependent upon the functional state of the hypothalamus-pituitary-adrenal cortex axis. 相似文献
2.
A paclitaxel-hyaluronan bioconjugate targeting ovarian cancer affords a potent in vivo therapeutic activity. 总被引:1,自引:0,他引:1
Alessandra Banzato Sara Bobisse Maria Rondina Davide Renier Fabio Bettella Giovanni Esposito Luigi Quintieri Laura Meléndez-Alafort Ulderico Mazzi Paola Zanovello Antonio Rosato 《Clinical cancer research》2008,14(11):3598-3606
PURPOSE: This study was designed to evaluate the pharmacologic and biological properties of a paclitaxel-hyaluronan bioconjugate (ONCOFID-P) against IGROV-1 and OVCAR-3 human ovarian cancer xenografts following i.p. administration. EXPERIMENTAL DESIGN: In vitro tumor sensitivity to ONCOFID-P was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas bioconjugate interaction with cells was studied cytofluorimetrically and by confocal microscopy. In vivo toxicity was assessed by a single-dose maximum-tolerated dose, peripheral blood cell count determination and by histologic analysis. Biodistribution of the compound was evaluated with a small animal-dedicated scintigraphy gamma camera following injection of 99mTc-labeled ONCOFID-P. Pharmacokinetic analysis was also carried out. Female severe combined immunodeficiency mice implanted with ovarian cancer cells underwent treatment with ONCOFID-P or free paclitaxel starting from day 7 or 14 after tumor injection, and survivals were compared. RESULTS: ONCOFID-P interacted with CD44, entered cells through a receptor-mediated mechanism, and exerted a concentration-dependent inhibitory effect against tumor cell growth. After i.p. administration, the bioconjugate distributed quite uniformly within the peritoneal cavity, was well-tolerated, and was not associated with local histologic toxicity. Pharmacokinetic studies revealed that blood levels of bioconjugate-derived paclitaxel were much higher and persisted longer than those obtained with the unconjugated free drug. Intraperitoneal treatment of tumor-bearing mice with the bioconjugate revealed that ONCOFID-P exerted a relevant increase in therapeutic activity compared with free drug. CONCLUSIONS: ONCOFID-P significantly improved results obtained with conventional paclitaxel, in terms of in vivo tolerability and therapeutic efficacy; these data strongly support its development for locoregional treatment of ovarian cancer. 相似文献
3.
Welling MM Mongera S Lupetti A Balter HS Bonetto V Mazzi U Pauwels EK Nibbering PH 《Nuclear medicine and biology》2002,29(4):413-422
A technetium-99m-labeled peptide derived from ubiquicidine, further referred to as 99mTc-UBI 29-41, targets bacterial and fungal infections, but not sterile inflammatory processes, in experimental animals. This paper reports on the radiochemical and biological features of this radioactive agent and the importance of the amino acid sequence of UBI 29-41 for imaging of infections.Radiochemical analyses of 99mTc-UBI 29-41 and a radiolabeled scrambled version of this peptide, i.e. 99mTc-Sc-UBI 29-41, revealed that both peptides were labeled rapidly (within 10 min) and effectively with little colloid formation (less than 5% of the total radioactivity) and very little free pertechnetate (or radioactive intermediates) in the preparations containing radiolabeled peptide. Furthermore, association of the peptides with bacteria could be competed with excess unlabeled peptide and this association proved to be temperature-dependent. Based on this in vitro data we concluded that labeling of peptides with 99mTc by this direct method is rapid, efficient, and safe.Scintigraphy demonstrated that radioactivity is rapidly removed from the circulation (half-lifes of UBI 29-41 and Sc-UBI 29-41 were 16 and 21 min, respectively) mainly by renal clearance. Analysis of murine blood revealed that only a small proportion of the intravenously injected 99mTc-peptides is associated with blood cells. Although both radiolabeled peptides accumulated rapidly at sites of infection, the values for 99mTc-UBI 29-41 were higher (P < 0.05) than for 99mTc-Sc-UBI 29-41. Moreover, injection of excess unlabeled UBI 29-41, but not Sc-UBI 29-41, into Staphylococcus aureus-infected mice prior to injection of 99mTc-UBI 29-41 significantly (P < 0.05) reduced the accumulation of this radiopharmaceutical at the site of infection. In addition, we observed significantly (P < 0.01) higher amounts of 99mTc-UBI 29-41 at the site of infection in mice using a carrier-free radiolabeled UBI 29-41 as compared with unpurified preparations containing radiolabeled UBI 29-41. This in vivo data indicates that the amino acid sequence of 99mTc-UBI 29-41 contributes to its accumulation at the site of infection. 相似文献
4.
Aquaporin-8 is involved in water transport in isolated superficial colonocytes from rat proximal colon 总被引:3,自引:0,他引:3
Laforenza U Cova E Gastaldi G Tritto S Grazioli M LaRusso NF Splinter PL D'Adamo P Tosco M Ventura U 《The Journal of nutrition》2005,135(10):2329-2336
Water is an essential nutrient because it must be introduced from exogenous sources to satisfy metabolic demand. Under physiologic conditions, the colon can absorb and secrete considerable amounts of water even against osmotic gradients, thus helping to maintain the body fluid balance. Here we describe studies on both aquaporin (AQP) expression and function using cells isolated from the superficial and lower crypt regions of the rat proximal colon. The expression of AQP-3, -4, and -8 in isolated colonocytes was determined by semiquantitative RT-PCR and by immunoblotting. The localization of AQP-8 in the colon was evaluated by immunohistochemistry. A stopped-flow light scattering method was used to examine osmotic water movement in isolated colonocytes. Moreover, the contribution of AQP-8 to overall water movement through isolated colonocytes was studied using RNA interference technology. Colonocytes from the proximal colon express AQP-3, -4, and -8 with increasing concentrations from the lower crypt cells toward those on the surface. Osmotic water permeability was higher in surface than in crypt colonocytes (P < 0.05); it was significantly inhibited by the water channel blocker dimethyl sulfoxide, and reversed by beta-mercaptoethanol (P < 0.05). Immunohistochemistry revealed a strong AQP-8 labeling in the apical membrane of the superficial colonocytes. Inhibition of aquaporin-8 expression by small interfering RNA significantly decreased osmotic water permeability (approximately 38%; P < 0.05). Current results indicate that aquaporin-8 may play a major role in water movement through the colon by acting on the apical side of the superficial cells. 相似文献
5.
Freo U Ori C Weiss SR Perini GI 《Journal of neural transmission (Vienna, Austria : 1996)》2005,112(11):1447-1462
Summary. The time course and the relation to dose of locomotor activity and of the regional cerebral metabolic rates for glucose (rCMRglc)
were measured in freely moving Sprague-Dawley rats after intracerebroventricular administration of ovine corticotropin releasing
factor (oCRF). Motor activity was determined using a familiar photocage cell. rCMRglc was measured, using the quantitative
autoradiographic [14C]2-deoxyglucose procedure, in 73 brain regions at 10, 30, 90 and 180 min after administration of oCRF 10 μg and at 90 min
after oCRF 0.1, 1 and 100 μg. oCRF 10 μg increased motor activity in a sustained fashion and increased rCMRglc with different
time courses throughout brain regions. In cerebellar regions rCMRglc increases peaked at 90 min and were sustained up to 180 min.
In non-cerebellar regions rCMRglc increases peaked at 90 min but declined thereafter. At lower doses (0.1 and 1 μg) oCRF increased
rCMRglc in fewer brain regions (1 and 5 regions affected, average increases 1% and 7%) including cerebellar areas and brainstem
sensory nuclei and decreased rCMRglc in medial prefrontal cortex. At the highest dose (100 μg) oCRF induced large and widespread
rCMRglc increases in cerebellar, brainstem, hypothalamic, limbic and neocortical areas (40 brain regions affected, average
increase 32%). The findings indicate that cerebellar areas and brainstem nuclei are highly sensitive to oCRF and may mediate
oCRF autonomic and behavioral effects. 相似文献
6.
To determine if reported reductions of regional cerebral metabolic rates for glucose (rCMRglc) induced by the 5-HT agent metachlorophenylpiperazine (MCPP) (2.5 mg/kg) are due to a presynaptic action, 3-month old Fischer-344 rats were given parachloroamphetamine (PCA), a serotonin neurotoxin, and rCMRglc was measured 1 or 3 weeks later with the quantitative autoradiographic [14C]2-deoxyglucose procedure in 74 brain regions after administering saline, MCPP or other drugs. PCA alone increased rCMRglc significantly only in the raphe nuclei and in visual structures (visual cortex, lateral geniculate, superior colliculus). MCPP alone reduced rCMRglc in 75% of the regions studied. In PCA-lesioned rats, metabolic responses to MCPP 2.5 mg/kg were virtually abolished and rCMRglc was increased in interanteromedial and centrolateral thalamic nuclei. rCMRglc responses to quipazine, a postsynaptic serotonin agonist, and to arecoline and bromocriptine, cholinergic and dopaminergic agonists, were unchanged by PCA-pretreatment. Selective abolition by PCA of the metabolic response to MCPP confirms that MCPP, at the dose studied, reduces rCMRglc in the forebrain via a presynaptic mechanism and that postsynaptic serotonergic function is not altered by PCA. 相似文献
7.
The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats after administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective serotonergic 5-HT2 agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]2-deoxyglucose technique, in 75 brain regions at 5, 15, 30, 60 and 90 min after administration of DOI 10 mg/kg i.p., and at 15 min after DOI 2.5, 25 or 50 mg/kg i.p. In non-hippocampal regions, peak effects were observed at 15-30 min, when rCMRglc in 12% of the regions was significantly different from control. In hippocampal regions rCMRglc effects peaked at 30 min (average rCMRglc reduction 21%) and were sustained for at least 60 min. Higher doses of DOI reduced rCMRglc in most prosencephalic regions (25 mg/kg, 35% of all regions studied; 50 mg/kg, 32%), where 5-HT2 receptors are present in high density. These data suggest that selective 5-HT2 receptor stimulation leads to rCMRglc reduction in areas with high densities of 5-HT2 receptors. 相似文献
8.
9.
Ulderico Freo Pietro Pietrini Gilberto Pizzolato Maura Furey-Kurkjian Antonio Merico Susanna Ruggero Mauro Dam Leontino Battistin 《Brain research》1995,677(2):213
In this study we compared the effects of the anxiolytic buspirone on behavior and regional cerebral metabolic rates for glucose (rCMRglc) with those of the reference serotonin (5-HT)1A agonist 8-hydroxy-2(di-N-propylamino)tetralin (DPAT). Behavioral effects were assessed by scoring the 5-HT syndrome. rCMRglc was measured in 56 brain regions by using the quantitative autoradiographic [14C]2-deoxyglucose technique, at 10 min after i.p. injection of DPAT (1 mg/kg) or buspirone (0.4, 4 and 40 mg/kg) in awake male Fischer-344 rats. Whereas DPAT produced an intense 5-HT syndrome, buspirone had no behavioral effect. A low dose (0.4 mg/kg) of buspirone reduced rCMRglc in 18 brain areas (32%), more markedly in limbic areas and raphe nuclei. These were the only rCMRglc effects buspirone had in common with the potent 5-HT1A agonist DPAT and suggest that low dose buspirone activates preferentially 5-HT1A receptors. Hence, this receptor subtype may mediate buspirone functional effects on the limbic system and, given the role of these brain areas in mood control, possibly buspirone therapeutic actions. High doses (4 and 40 mg/kg) of buspirone produced widespread rCMRglc decreases in 46 (82%) and 44 (79%) of the areas studied and increased rCMRglc in one brain area, the lateral habenula, that was not affected by DPAT or a low dose of buspirone. The topographic distribution and direction of rCMRglc changes by high doses of buspirone differ from those produced by the 5-HT1A agonist DPAT. Instead these changes resemble the rCMRglc effects of dopaminergic D2 antagonists like haloperidol and are consistent with some pharmacological and binding properties of buspirone. In summary, this study suggests that buspirone produces dual, dose-dependent rCMRglc effects: (i) at a low dose rCMRglc reductions in limbic areas and raphe nuclei, probably due to preferential activation of 5-HT1A receptors, and (ii) at higher doses widespread rCMRglc reductions along with a rCMRglc increase in the lateral habenula resulting from dopamine D2 receptor blockade. 相似文献
10.
Sciarra A Autran Gomez AM Gentilucci A Parente U Salciccia S Gentile V Di Silverio F 《European urology》2007,52(2):597-599
A 69-yr-old man with bilateral and metastatic renal cell carcinoma developed progressive disease after interleukin-2 and interferon therapy. He was submitted to radical left nephrectomy, right nephron-sparing surgery, and bone metastasis removal, followed by therapy with sorafenib. At 12-mo follow-up there was a significant improvement in patient performance status and no evidence of clinical progression. 相似文献