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1.
Objective: To determine whether prior eating behavior characterized by dietary restraint alters responses in energy expenditure and substrate oxidation associated with a short‐term, energy‐restricted diet. Research Methods and Procedures: A repeated‐measures, 3‐day diet‐intervention study of adequate (125 kJ/kg of body weight) or restricted (62.5 kJ/kg) energy intake was conducted with 30 women, 20 to 46 years, BMI 25 to 45 kg/m2, whose prior eating behavior was “restrained” or “unrestrained.” The Eating Inventory (cognitive restraint subscale) was used to measure restrained eating behavior. Energy expenditure and substrate oxidation were measured after a 12‐hour fast and during the first and fourth hours after a standard meal. Plasma glucose, nonesterified fatty acids, and insulin were measured at corresponding times. Body composition was determined by total body electrical conductivity. Results: Resting energy expenditure was not affected by 3 days of energy restriction. Short‐term energy restriction resulted in lower respiratory‐exchange ratios, higher rates of fat oxidation, and lower rates of carbohydrate oxidation. Subjects classified as restrained eaters had higher postprandial respiratory‐exchange ratios and carbohydrate‐oxidation rates compared with unrestrained eaters. Fasting insulin concentrations were lower in restrained eaters. These effects associated with prior eating behavior were independent of the diet intervention. Discussion: Metabolic outcomes associated with a 3‐day energy‐restricted diet (i.e., increased fat oxidation and decreased carbohydrate oxidation) were not affected by prior restrained eating behavior. However, restrained eating behavior was associated with increased carbohydrate oxidation after a mixed meal. This effect of restrained eating behavior may be attributable to increased insulin sensitivity.  相似文献   

2.
Objective: Two studies explored in nonclinical samples variables that may influence meal size assessments. Research Methods and Procedures: In Study 1, the contribution of dietary restraint, weight, depressive symptoms, and gender to ratings on the Food Amount Rating Scale was examined in 153 white women and 121 white men; in Study 2, the contribution of dietary restraint, weight, ethnicity, and ethnic group identification to Food Amount Rating Scale ratings was examined in 67 Asian, 81 Hispanic, and 107 white women. Results: Study 1 indicated that food amounts were rated as larger when rated by male rather than female raters (male rater, mean = 62.37, SD = 1.14; female rater, mean = 59.28, SD = 0.89), for female rather than male targets (male target, mean = 56.16, SD = 0.97; female target, mean = 64.87, SD = 1.02), and by restrained rather than unrestrained eaters (restrained, mean = 63.14, SD = 1.11; unrestrained, mean = 58.69, SD = 0.91). Study 2 indicated that food amounts were rated as larger when rated by restrained eaters (restrained, mean = 67.53, SD = 1.21; unrestrained, mean = 64.99, SD = 1.09), Hispanic women (Asian, mean = 64.59, SD = 1.61; Hispanic, mean = 68.71, SD = 1.30; white, mean = 65.41, SD = 1.34), and underweight women (underweight, mean = 70.38, SD = 1.68; normal weight, mean = 64.52, SD = 0.93; overweight: mean = 64.23, SD = 1.64). Discussion: Food amount judgments may be influenced by personal characteristics. Future research should examine whether variation in food amount judgments is related to dieting behavior, disordered eating, or obesity.  相似文献   

3.
ABSTRACT

Studies have suggested that eating at later times may be a risk factor for being overweight. The aim of this study was to investigate the association of caloric midpoint on the anthropometric profile and calorie and macronutrient intake during the day. The study included 718 Brazilian undergraduate students (20.5 ± 2.9 years old; 67% women). Dietary intake was assessed by 24-h recall and the diurnal variation of calorie consumption was evaluated by caloric midpoint average time at which 50% of daily energy were consumed. Participants were classified into two groups according to caloric midpoint median; early eaters (caloric midpoint ≤ 3:00 pm) or late eaters (caloric midpoint > 3:00 pm). Body weight and waist circumference were measured and body mass index (BMI) was determined. Generalized linear models adjusted for confounding variables were used to determine the association between variables. The late eaters presented higher BMI when compared to early eaters (23.0 kg/m2 ± 0.3 vs. 22.1 kg/m2 ± 0.2, respectively; p = .02). Late eaters reported a higher total daily consumption of energy (p < .001) and proportion consumed after 9:00 pm (p < .001), as well as total daily carbohydrate (p < .001), protein (p < .001), fat (p < .001), saturated fat (p < .001), and cholesterol (p = .04) intake when compared with early eaters. We conclude that concentrating food intake later in the day is associated with higher total energy and macronutrient intake as well as a higher average BMI.  相似文献   

4.
ObjectivesThe derivation of neural crest stem cells (NCSCs) from human pluripotent stem cells (hPSCs) has been commonly induced by WNT activation in combination with dual‐SMAD inhibition.In this study, by fine‐tuning BMP signalling in the conventional dual‐SMAD inhibition, we sought to generate large numbers of NCSCs without WNT activation.Materials and methodsIn the absence of WNT activation, we modulated the level of BMP signalling in the dual‐SMAD inhibition system to identify conditions that efficiently drove the differentiation of hPSCs into NCSCs. We isolated two NCSC populations separately and characterized them in terms of global gene expression profiles and differentiation ability.ResultsOur modified dual‐SMAD inhibition containing a lower dose of BMP inhibitor than that of the conventional dual‐SMAD inhibition drove hPSCs into mainly NCSCs, which consisted of HNK+p75high and HNK+p75low cell populations. We showed that the p75high population formed spherical cell clumps, while the p75low cell population generated a 2D monolayer.We detected substantial differences in gene expression profiles between the two cell groups and showed that both p75high and p75low cells differentiated into mesenchymal stem cells (MSCs), while only p75high cells had the ability to become peripheral neurons.ConclusionsThis study will provide a framework for the generation and isolation of NCSC populations for effective cell therapy for peripheral neuropathies and MSC‐based cell therapy.  相似文献   

5.
ALGER, SHARON A., MARGARET MALONE, JENNIFER CERULLI, STEVEN FEIN, LYN HOWARD. Beneficial effects of pharmacotherapy on weight loss, depressive symptoms, and eating patterns in obese binge eaters and non-binge eaters. Obes Res. Objective: The purpose of this study was to compare the impact of drug therapy on weight loss, Beck Depression Inventory (BDI) scores, and binge eating patterns (BES) between obese binge eaters and non-binge eaters. Research Methods and Procedures: 22 severe binge eaters, 17 moderate binge eaters, and 16 non-binge eaters received phentermine resin 15mg/day and dl-fenfluramine 20mg three times daily over a 6 month period for weight loss. All data are reported as mean±S. Results: The percent weight loss compared to baseline within the 3 groups ranged from 8. 9% to 11. 3% at 3 months and 10. 6% to 14. 9% at 6 months. After 6 months, 73% of the severe binge eaters, 59% of moderate binge eaters and 69% of non-binge eaters had experienced more than 10% weight loss. BDI scores were significantly higher in the severe group at baseline when compared to non-binge eaters (p<0. 006). After 3 and 6 months BDI scores improved in all groups but remained significantly different between the severe and non-binge eaters until the 6-month assessment. BES scores declined in all groups over the 6-month period. Echocardiograms were performed in 35 of 55 subjects following reports of a possible association between fenfluramine and valvular changes. Fifteen (43%) of subjects had no abnormal findings and 20 (57%) had evidence of valvular insufficiency occurring in one or more valves. Seven patients (20%) had significant valve damage according to the DHHS and FDA criteria. Conclusion: After 24 weeks of treatment severe binge eaters improved their eating pattern, depression scores, and achieved weight loss similar to non-binge eaters. These data suggest that pharmacologic intervention for weight loss and subsequent weight maintenance can be as successful in binge eaters as non-binge eaters. A relationship was seen between duration of drug treatment and valvular insufficiency in subjects treated for an average of 52 weeks. These findings validate the FDA requirement for studies of at least 1 year duration to evaluate both the safety and efficacy of pharmacologic treatment for obesity.  相似文献   

6.
摘要 目的:DNA连接酶III(DNA ligase III, Lig3)基因是碱基切除修复通路中的关键基因,在胚胎发育过程中发挥重要作用,通过研究Lig3基因在叶酸代谢障碍状态下的表达情况,探讨其对小鼠胚胎神经发育的影响。方法:采用无特定病原体(specific pathogen free, SPF)级C57BL/6J成年小鼠(8-9周,18-20 g),雌雄1:1合笼,孕鼠随机分为实验组和对照组,孕7.5天实验组腹腔注射4.5 mg/kg体重甲氨蝶呤(Methotrexate, MTX,二氢叶酸还原酶抑制剂)诱导产生叶酸代谢障碍的小鼠神经管畸形(neural tube defects, NTDs)模型,对照组腹腔注射等体积的生理盐水。孕10.5天体视显微镜下观察胎鼠的发育情况。同时利用200 nM的MTX建立叶酸代谢障碍的小鼠神经干细胞模型。在模型建立成功的基础上,应用实时荧光定量聚合酶链反应(Real time quantitative PCR,RT-qPCR)及免疫印迹(Western blot)等方法研究碱基切除修复通路相关基因Lig3的表达水平。结果:4.5 mg/kg 体重MTX处理孕鼠后胎鼠NTDs的发生率为31.1%(19/61),而正常对照组未见胎鼠NTDs的发生。在体视显微镜下可见NTDs胎鼠神经管未闭合,而正常胎鼠发育完好。RT-qPCR检测发现叶酸代谢障碍小鼠NTDs 胚胎神经组织中Lig3 mRNA的表达水平明显低于对照组(P<0.05)。Western blot检测发现,与对照组相比,叶酸代谢障碍NTDs胎鼠神经组织中Lig3蛋白水平明显降低(P<0.05)。同时,在MTX处理的神经干细胞中,Lig3的表达水平明显低于对照组(P<0.05)。对凋亡相关蛋白Cleaved caspase-3进行检测发现MTX处理后的NTDs胎鼠神经组织及细胞模型中其表达均明显增加,表明细胞凋亡增加。结论:在叶酸代谢障碍前提下,Lig3表达降低,DNA修复功能减弱,细胞凋亡增加,导致NTDs的发生,为NTDs及出生缺陷的防控提供新思路。  相似文献   

7.
Background aimsThe characteristics, such as morphologic and phenotypic characteristics and neural transdifferentiation ability, of mesenchymal stromal cells (MSC) derived from different origins have yet to be reported for cases isolated from the same individual.MethodsThe proliferation capacity, secretion ability of neurotrophins (NT) and neural differentiation ability in rat MSC isolated from bone marrow (BMSC) and adipose tissue (ADSC) were compared from the same animal.ResultsThe ADSC had a significantly higher proliferation capacity than BMSC according to cell cycle and cumulative population doubling analyses. The proportion of cells expressing neural markers was greater in differentiated ADSC than in differentiated BMSC. Furthermore, the single neurosphere derived from ADSC showed stronger expansion and differentiation abilities than that derived from BMSC. The findings from Western blot lent further support to the immunocytochemical data. The mRNA and protein levels of nerve growth factor (NGF) and brain-derived growth factor (BDNF) expressed in ADSC were significantly higher than those in BMSC at different stages before and following induction.ConclusionsOur study suggests that the proliferation ability of ADSC is superior to that of BMSC. Furthermore, differentiated ADSC expressed higher percentages of neural markers. As one possible alternative source of BMSC, ADSC may have wide potential for treating central nervous system (CNS) diseases.  相似文献   

8.
Food consumption in stressful situations vary as a function of individual difference factors (e.g., emotional vs. non-emotional eating), and may be related to hormonal responses elicited by the stressful event. These hormonal responses may be tied to specific emotions elicited by the stressful event. The present investigation examined the emotional and hormonal (cortisol, ghrelin) responses of high and low emotional eaters following a laboratory stressor (Trier Social Stress Test; TSST). Women (n = 48) either high or low in emotional eating status were tested in a TSST or served as controls during which blood samples were taken for analysis of cortisol and ghrelin, both of which have been implicated in eating and in response to stressors. The TSST promoted elevated cortisol levels, being somewhat more pronounced in emotional than in non-emotional eaters. Both shame and anger were provoked by the TSST, and although both these emotions were correlated with cortisol levels, only anger significantly mediated the relationship between the stressor and cortisol levels. As well, baseline ghrelin levels in low emotional eaters exceeded that of high emotional eaters, and increased moderately in response to the stressor situation, irrespective of emotional eating status. Interestingly, when provided with food, ghrelin levels declined in the non-emotional eaters, but not in emotional eaters. The possibility is offered that the lack of a decline of ghrelin in emotional eaters may sustain eating in these individuals.  相似文献   

9.
Objective: To examine breakfast consumption in subjects maintaining a weight loss in the National Weight Control Registry (NWCR). Research Methods and Procedures: A cross-sectional study in which 2959 subjects in the NWCR completed demographic and weight history questionnaires as well as questions about their current breakfast consumption. All subjects had maintained a weight loss of at least 13.6 kg (30 lb) for at least 1 year; on average these subjects had lost 32 kg and kept it off for 6 years. Results: A large proportion of NWCR subjects (2313 or 78%) reported regularly eating breakfast every day of the week. Only 114 subjects (4%) reported never eating breakfast. There was no difference in reported energy intake between breakfast eaters and non-eaters, but breakfast eaters reported slightly more physical activity than non-breakfast eaters (p = 0.05). Discussion: Eating breakfast is a characteristic common to successful weight loss maintainers and may be a factor in their success.  相似文献   

10.
Background aimsMetastasis to different organs is the major cause of death in breast cancer patients. The poor clinical prognosis and lack of successful treatments for metastatic breast cancer patients demand the development of new tumor-selective therapies. Thus, it is necessary to develop treatments capable of releasing therapeutic agents to both primary tumors and metastases that avoid toxic side effects in normal tissue, and neural stem cells are an attractive vehicle for tracking tumor cells and delivering anti-cancer agents. The authorspreviously demonstrated that a soluble form of growth arrest specific 1 (GAS1) inhibits the growth of triple-negative breast tumors and glioblastoma.MethodsIn this study, the authors engineered ReNcell CX (EMD Millipore, Temecula, CA, USA) neural progenitor cells to express truncated GAS1 (tGAS1) under a tetracycline/on inducible system using lentiviral vectors.ResultsHere the authors show that treatment with ReNcell-tGAS1 in combination with tetracycline decreased primary tumor growth and inhibited the formation of metastases in tumor-bearing mice by diminishing the phosphorylation of AKT and ERK1/2 in orthotopic mammary gland tumors. Moreover, the authors observed that ReNcell-tGAS1 prolonged the survival of 4T1 tumor-bearing mice.ConclusionsThese data suggest that the delivery of tGAS1 by ReNcell cells could be an effective adjuvant for the treatment of triple-negative breast cancer.  相似文献   

11.
Random asymmetry, that is the coexistence of left‐ and right‐sided (or ‐handed) individuals within a population, is a particular case of natural variation; what triggers and maintains such dimorphisms remains unknown in most cases. Here, we report a field‐based cage experiment in the scale‐eating Tanganyikan cichlid Perissodus microlepis, which occurs in two morphs in nature: left‐skewed and right‐skewed individuals with respect to mouth orientation. Using underwater cages stocked with scale‐eaters and natural prey fish, we first confirm that, under semi‐natural conditions, left‐skewed scale‐eaters preferentially attack the right flank of their prey, whereas right‐skewed individuals feed predominantly from the left side. We then demonstrate that scale‐eaters have a higher probability for successful attacks when kept in dimorphic experimental populations (left‐ and right‐skewed morphs together) as compared to monomorphic populations (left‐ or right‐skewed morphs), most likely because prey fishes fail to accustom to strikes from both sides. The significantly increased probability for attacks appears to be the selective agent responsible for the evolution and maintenance of mouth dimorphism in P. microlepis, lending further support to the hypothesis that negative frequency‐dependent selection is the stabilizing force balancing the mouth dimorphism at quasi‐equal ratios in scale‐eating cichlids.  相似文献   

12.
Abstract

The experimental objectives were to verify whether a qualitative measure of creep feed consumption using a dye was related to performance, and associate this with teat order. Indigo carmine (5 g/kg) was added to a starter diet between days 12 and 31 (weaning) of lactation. On days 19, 23, 27 and 31, faeces from each piglet were assessed for colouration. Each piglet was categorized as a ‘good’, ‘moderate’ or ‘small/non’ eater of feed. There were no differences in pre-weaning growth rate between categories. Piglets classed as ‘good’ or ‘moderate’ eaters in lactation grew fastest (p = 0.009) in the first three days after weaning, but between days 4 and 7, the highest growth rate occurred in ‘moderate’ eaters. ‘Small/non' eaters grew slower (p < 0.01) between weaning and 28 days after weaning. Piglets drinking milk from anterior teats were heavier at weaning (p < 0.001) and for the first 14 days after weaning (p = 0.104) compared to piglets sucking posterior teats. Data from this study demonstrated that creep feed intake of piglets could qualitatively be assessed using indigo carmine, and that this categorization was related to performance in the immediate post-weaning period.  相似文献   

13.
目的 最近在金纳米粒子(AuNPs)表面重构抗体片段的天然构象和功能的研究表明分子构象工程的可行性。本质上,分子构象工程就是要像蛋白质折叠一样,通过精确控制柔性非功能分子的构象使其产生新功能。本文在铂纳米粒子(PtNPs)表面重构抗体互补决定簇区(CDR)片段的天然构象和功能,旨在探索分子构象工程的普适性及揭示蛋白质结构-功能机制。方法 本文将抗溶菌酶抗体(cAB-lys3)中的CDR3片段(在单独存在时没有稳定构象和功能)通过两个Pt-S键偶联到PtNPs表面。CDR片段的天然构象和功能的恢复通过它对溶菌酶活性的抑制来表征。结果 通过多肽密度优化和表面聚乙二醇修饰,制得基于PtNPs的抗溶菌酶人工抗体(简称铂抗体)。溶菌酶活性测试结果表明,铂抗体可以特异性结合溶菌酶并显著抑制其活性。结论 本文第一次在PtNPs表面重构了蛋白质片段的天然构象并恢复了其功能,证明分子构象工程可作为一种通用方法制备基于纳米粒子的人工蛋白质。  相似文献   

14.
Background/ObjectivesIn vitro studies have shown that dengue virus (DENV) can thwart the actions of interferon (IFN)-α/β and prevent the development of an antiviral state in infected cells. Clinical studies looking at gene expression in patients with severe dengue show a reduced expression of interferon stimulated genes compared to patients with dengue fever. Interestingly, there are conflicting reports as to the ability of DENV or other flaviviruses to inhibit IFN-α/β signaling.ConclusionsThe ability of DENVs to inhibit IFN-α/β signaling is conserved. Although some variation in the inhibition was observed, the moderate differences may be difficult to correlate with clinical outcomes. DENVs were unable to inhibit pSTAT1 in NHP cell lines, but their ability to inhibit pSTAT1 in primary Rhesus macaque dendritic cells suggests that this may be a cell specific phenomena or due to the transformed nature of the cell lines.  相似文献   

15.
When the titre of juvenile hormone III in female Leptinotarsa decemlineata was elevated by the implantation of supernumerary corpora allata or by the injection of the hormone, the rate of endogenous hormone production by the host glands was significantly restrained, as determined by the short-term in vitro radiochemical assay. From denervation studies, it is suggested that during phases of elevated juvenile hormone titre, the corpus allatum activity is regulated via humoral as well as neural factors requiring intact nerve connections. Restrainment of gland activity appears to be mainly via the neural pathway. Isolated corpora allata were not influenced by 10?5 M juvenile hormone III added to the incubation medium in vitro.Studies with farnesenic acid revealed that the final two enzymatic steps in the biosynthetic pathway of juvenile hormone are also diminished during prolonged neural inhibition of the corpora allata.20-Hydroxyecdysone and precocene II had no apparent effect on the corpus allatum activity of Leptinotarsa decemlineata.  相似文献   

16.
Objective: This study evaluated gastric bypass surgery outcomes according to presurgical binge eating severity. Research Methods and Procedures: Adult patients completed assessment questionnaires including the Short Form‐36, Gormally Binge Eating Scale (BES), and Beck Depression Inventory (BDI) before and 12 months after surgery. Results: One hundred nine patients (18 men, 91 women) were recruited. Based on their baseline BES scores, patients were non‐ [n = 52 (48%)], moderate [n = 31 (28%)], or severe [n = 26 (24%)] binge eaters. Although the percentage of excess weight loss was greatest after 12 months in the severe binge eaters, the difference among groups was not significant. Severe binge eaters had higher baseline BDI scores than either non‐ or moderate binge eaters (p = 0.001). After surgery, BDI scores declined significantly in all groups from the baseline scores but remained higher postoperatively in the severe binge eaters (p = 0.018). BES scores declined significantly (p = 0.000) after surgery within all groups. There was no difference in the Short Form‐36 physical component summary scores at baseline among groups. Mental component summary scores were significantly lower in the severe binge eaters (p = 0.001). After surgery, there was no difference among groups in either physical or mental component summary scores. Discussion: In conclusion, data from the present study suggest that patients have similar outcomes in terms of improved depression scores, binge eating behavior, and health‐related quality of life regardless of their binge eating severity before surgery. Patients with the most severe binge eating behavior before surgery showed the most improvement when assessed 12 months after surgery.  相似文献   

17.
Background aimsTraumatic injuries of the central nervous system cause damage and degeneration of specific cell populations with subsequent functional loss. Cell transplantation is a strategy to treat such injuries by replacing lost or damaged cell populations. Many kinds of cells are considered candidates for intraspinal transplantation. Human neural precursor cells (hNPC) derived from post-mortem fetal tissue are easy to isolate and expand, and are capable of producing large numbers of neuronal and glial cells. After transplantation into the nervous system, hNPC produce mature neural phenotypes and permit functional improvement in some models of neurodegenerative disease. In this study, we aimed to elucidate the therapeutic effect of different neuronal and glial progenitor populations of hNPC on locomotor and sensory functions of spinal cord-injured (SCI) ratsMethodsDifferent populations of progenitor cells were obtained from hNPC by cell sorting and neural induction, resulting in cell cultures that were NCAM+ A2B5+, NCAM+ A2B5? or A2B5+ NG2+. These different cell populations were then tested for efficacy in repair of the injured spinal cord by transplantation into rats with SCIResultsThe A2B5+ NG2+ population of hNPC significantly improved locomotor and sensory (hindlimb) functional recovery of SCI rats. Importantly, no abnormal pain responses were observed in the forelimbs following transplantationConclusionsThis treatment approach can improve functional recovery after SCI without causing allodynia. Further studies will be conducted to investigate the ability of A2B5+ NG2+ cells to survive, differentiate and integrate in the injured spinal cord.  相似文献   

18.
Ecological diversity has been reported for killer whales (Orcinus orca) throughout the North Atlantic but patterns of prey specialization have remained poorly understood. We quantify interindividual dietary variations in killer whales (n = 38) sampled throughout the year in 2017–2018 in northern Norway using stable isotopic nitrogen (δ15N: 15N/14N) and carbon (δ13C: 13C/12C) ratios. A Gaussian mixture model assigned sampled individuals to three differentiated clusters, characterized by disparate nonoverlapping isotopic niches, that were consistent with predatory field observations: seal‐eaters, herring‐eaters, and lumpfish‐eaters. Seal‐eaters showed higher δ15N values (mean ± SD: 12.6 ± 0.3‰, range = 12.3–13.2‰, n = 10) compared to herring‐eaters (mean ± SD: 11.7 ± 0.2‰, range = 11.4–11.9‰, n = 19) and lumpfish‐eaters (mean ± SD: 11.6 ± 0.2‰, range = 11.3–11.9, n = 9). Elevated δ15N values for seal‐eaters, regardless of sampling season, confirmed feeding at high trophic levels throughout the year. However, a wide isotopic niche and low measured δ15N values in the seal‐eaters, compared to that of whales that would eat solely seals (δN‐measured = 12.6 vs. δN‐expected = 15.5), indicated a diverse diet that includes both fish and mammal prey. A narrow niche for killer whales sampled at herring and lumpfish seasonal grounds supported seasonal prey specialization reflective of local peaks in prey abundance for the two fish‐eating groups. Our results, thus, show differences in prey specialization within this killer whale population in Norway and that the episodic observations of killer whales feeding on prey other than fish are a consistent behavior, as reflected in different isotopic niches between seal and fish‐eating individuals.  相似文献   

19.
The synthesis and the biological evaluation of pyrano[3,2-e]indoles and their reaction intermediates are described. The compounds prepared were evaluated for their inhibition of NO production, antioxidant activity and also for their ability to inhibit in vitro the growth of four human tumor cell lines: large lung carcinoma (COR-L23), alveolar basal epithelial carcinoma (A549), amelanotic melanoma (C32) and melanoma (A375). The two reaction intermediates, 5a and 5b, showed the highest inhibition of NO production in murine monocytic macrophage (IC50?=?1.1?μM and IC50?=?2.3 μM respectively). Compound 5a was the most active against melanotic melanoma (IC50?=?11.8?μM) while the other compounds exhibited weak cytotoxicity with IC50 values >50?μM on all cell lines.  相似文献   

20.
目的:探讨下丘脑催产素(OXT)对大鼠摄食和胃动力的影响及调控机制。方法:采用荧光金逆行追踪结合免疫组化实验,观察大鼠视上核(SON)与弓状核(ARC)之间的神经通路;采用核团置管术观察ARC微量注射OXT对大鼠摄食的影响;采用单极电刺激观察电刺激SON对大鼠胃运动的影响及ARC微量注射OXT对大鼠胃运动和胃排空的影响。结果:荧光金逆行追踪结合免疫组化实验显示大鼠SON与ARC之间存在神经通路;ARC微量注射OXT大鼠0-2 h、0-3 h和0-4 h摄食量显著下降,OXT受体拮抗剂阿托西班可完全阻断OXT的抑制摄食作用,注射OXT和缩胆囊素(CCK)受体拮抗剂MK-329混合液后,OXT对大鼠摄食的抑制作用被部分阻断;电刺激SON,大鼠胃运动幅度和频率显著增强,预先向ARC内微量注射阿托西班后再电刺激SON,电刺激SON对胃运动的促进作用进一步增强;ARC微量注射OXT后,大鼠胃运动幅度和频率显著降低,阿托西班可完全阻断OXT对胃运动幅度和频率的抑制作用,MK-329可部分阻断OXT对胃运动幅度和频率的抑制作用;ARC微量注射OTX后,大鼠胃排空率显著降低,阿托西班可完全阻断OXT对胃排空的抑制作用,MK-329可部分阻断OXT对胃排空的抑制作用。结论:SON-ARC内具有OXT神经通路,且该通路由CCK介导。  相似文献   

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