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951.
目的 探讨肺癌的胆碱显像与肺癌组织细胞中胆碱代谢的变化.方法 选取经手术病理证实的18例肺癌患者.术前均进行~(11)C-胆碱PET/CT显像,用目测法和半定量法分析显像结果,术后将取得的肺癌组织及正常肺组织用RT-PCR和Western blot 方法,检测胆碱乙酰基转移酶(ChAT)和胆碱激酶(Chok)基因的表达,分析肺癌的胆碱显像与肺癌组织细胞中胆碱代谢的变化.结果 18例肺癌的PET/CT图像均显示胆碱放射性摄取明显增高,18例肺癌组织细胞中,14例Chok mRNA及蛋白质的表达比正常肺组织升高,9例肺癌组织细胞ChATmRNA及蛋白质表达升高.其中8例Chok及ChAT表达均升高.鳞癌与腺癌对胆碱的平均标准摄取值(SUV)差异无统计学意义.结论 肺癌的胆碱显像有异常增高,其增高因为与肺癌细胞中胆碱代谢的磷酸化途径及乙酰化途径增高有关. 相似文献
952.
María Fernanda Urquiza Inés Carretero Paola Rita Cano Carabajal Rodolfo Agustín Pasqualini María Macarena Felici Rodolfo Sergio Pasqualini Carlos José Quintans 《Journal of assisted reproduction and genetics》2014,31(11):1553-1555
ObjectiveTo report a birth of a healthy girl after long-term oocyte cryopreservation by slow cooling in sodium depleted medium.DesignClinical application.SettingUniversity Affiliated, Private IVF center.PatientA 38-year-old woman received embryos from IVF by intracytoplasmic sperm injection (ICSI) with her own oocytes that were cryopreserved by slow freezing in a low-sodium medium 14 years and 6 months before, when she was 24 years old.Result(s)From six metaphase-II oocytes thawed, two survived, one was fertilized after ICSI and a cleaving embryo was transferred on day 3. A single term pregnancy was achieved, ending with the delivery of a healthy girl.Conclusion(s)Cryopreservation after slow freezing in a sodium depleted medium maintained the developmental competence of oocytes after long-term storage and resulted in a successful live birth. As far as is known, this case represents, up to date, the longest storage period of cryopreserved human oocytes resulting in a live birth. 相似文献
953.
目的探讨高果糖诱发的胰岛素抵抗大鼠认知功能、胆碱乙酰转移酶(choline acetyltransferase,CHAT)活性及胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)的变化及吡格列酮的干预作用。方法从45只Wistar大鼠中随机选取10只作为对照组(NC组);其余35只以10%的果糖水诱发胰岛素抵抗;4周后根据胰岛素抵抗指数(insulin resistance index,IRI)将制作成功的胰岛素抵抗模型大鼠随机分为胰岛素抵抗组(IR组)和吡格列酮组(PIO组)。于干预12周末通过Morris水迷宫实验观察大鼠认知功能改变情况;采用化学比色法测定脑组织内ChAT活性;Western blotting检测脑组织IGF-1的表达;对脑组织切片进行尼氏染色。结果PIO组与IR组逃避潜伏期较NC组明显延长(分别为P〈0.01,P〈0.05),PIO组较IR组明显缩短(P〈0.01);PIO组与IR组ChAT活性较NC组降低(P〈0.01,P〈0.01),PIO组较IR组增强(P〈0.05);PIO组与IR组IGF-1表达较NC组降低(P〈0.01),PIO组IGF-1表达较IR组增加(P〈0.05)。结论吡格列酮对IR模型大鼠的学习记忆功能减退具有改善作用,其机制可能与促进神经元ChAT、IGF-1的表达,维持胆碱能神经功能正常有关。 相似文献
954.
Ting Hu Ruth E. Bailey Stephen W. Morrall Marilyn J. Aardema Lesley A. Stanley Julie A. Skare 《Toxicology letters》2009
To address the provision of the 7th Amendment to the EU Cosmetics Directive banning the use of in vivo genotoxicity assays for testing cosmetic ingredients in 2009, the 3D EpiDerm™ reconstructed human skin micronucleus assay has been developed. To further characterise the EpiDerm™ tissue for potential use in genotoxicity testing, we have evaluated the dermal penetration and metabolism of two hair dye ingredients, p-aminophenol (PAP) and p-phenylenediamine (PPD) in this reconstructed epidermis model. When EpiDerm™ tissue was topically exposed to PAP or PPD for 30 min (typical for a hair dye exposure), the majority (80–>90%) of PAP or PPD was excluded from skin tissue and removed by rinsing. After a 23.5 h recovery period, the PAP fraction that did penetrate was completely N-acetylated to acetaminophen (APAP). Similarly, 30 min topical application of PPD resulted in the formation of the N-mono- and N,N′-diacetylated metabolites of PPD. These results are consistent with published data on the dermal metabolism of these compounds from other in vitro systems as well as from in vivo studies. When tissue was exposed topically (PAP) or via the culture media (PPD) for 24 h, there was good batch-to-batch and donor-to-donor reproducibility in the penetration and metabolism of PAP and PPD. Overall, the results demonstrate that these two aromatic amines are biotransformed in 3D EpiDerm™ tissue via N-acetylation. Characterising the metabolic capability of EpiDerm™ tissue is important for the evaluation of this model for use in genotoxicity testing. 相似文献
955.
Tauheed Ishrat Md Nasrul Hoda M. Badruzzaman Khan Seema Yousuf Muzamil Ahmad Mohd. Moshahid Khan Ajmal Ahmad Fakhrul Islam 《European neuropsychopharmacology》2009,19(9):636-647
Recent evidence indicates that curcumin (CUR), the principal curcuminoid of turmeric, exhibits antioxidant potential and protects the brain against various oxidative stressors. The aim of the present study was to examine the modulating impacts of CUR against cognitive deficits and oxidative damage in intracerebroventricular–streptozotocin (ICV–STZ) infused rats. Rats were injected bilaterally with ICV–STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with CUR (80 mg/kg) for three weeks. After two weeks of ICV–STZ infusion, rats were tested for cognitive performance using passive avoidance and water maze tasks and then sacrificed for biochemical and histopathological assays. ICV–STZ rats showed significant cognitive deficits, which were significantly improved by CUR supplementation. CUR supplementation significantly augmented increased 4-hydroxynonenal (4-HNE) and malonaldehyde (MDA), thiobarbituric reactive substances (TBARS), hydrogen peroxide (H2O2), protein carbonyl (PC) and oxidized glutathione (GSSG); decreased levels of reduced glutathione (GSH) and its dependent enzymes (Glutathione peroxidase [GPx] and glutathione reductase [GR]) in the hippocampus and cerebral cortex; and increased choline acetyltransferase (ChAT) activity in the hippocampus of ICV–STZ rats. The study suggests that CUR is effective in preventing cognitive deficits, and might be beneficial for the treatment of sporadic dementia of Alzheimer's type (SDAT). 相似文献
956.
Amit Kumar Mehta Naveen Arora Shailendra Nath Gaur Bhanu Pratap Singh 《Regulatory toxicology and pharmacology : RTP》2009,54(3):282-286
Studies suggest that choline has potential to be used as a dietary supplement and a drug for immune inflammatory diseases like asthma and rhinitis. But there are apprehensions regarding adverse effects of choline when given orally in high doses. To address this knowledge gap, toxicity assessment of choline chloride was carried out by intranasal (i.n.), oral and intraperitoneal (i.p.) routes in Balb/c mice for 28 days. Body weight, food and water consumption of mice were recorded daily. Hematology and clinical chemistry were assessed to check hepatocellular functions and morphological alterations of the cells. Splenocyte counts were analysed for evaluating cellular immunity. Liver function test was performed by assaying different enzyme systems in serum such as, urea, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Body weight, food and water consumption did not differ between mice treated with choline and the saline control group. Hematologic and biochemical variables were not affected with any increase in serum toxicity marker enzymes indicating normal liver functioning. Choline administration did not affect total cholesterol and high density lipoprotein levels as compared to their respective controls. Urea and blood urea nitrogen levels in choline treated mice were not different than controls. Creatinine level was, however, higher than control in i.p. treatment group, but other parameters were normal. In conclusion, the repeated consumption of choline chloride via i.n. and oral or i.p. routes did not cause toxicity in mice in the toxicological endpoints examined. 相似文献
957.
958.
Bombi Lee Bong-Jun Sur Jeong-Jun Han Insop Shim Song Her Hye-Jung Lee Dae-Hyun Hahm 《Progress in neuro-psychopharmacology & biological psychiatry》2010
The ameliorating effect of phosphatidylserine (PS) isolated from krill (KR-PS) on the learning and memory deficits associated with normal aging in rats was investigated, as compared with soybean PS (SOY-PS). Rats were orally administered with KR-PS (20, 50 mg kg−1) and SOY-PS (50 mg kg−1) daily, for 7 days, 30 min before behavioral assessment using the Morris water maze (MWM). Changes in the cholinergic system were examined by measuring choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunoreactivity in the hippocampus. The daily administration of KR-PS produced a significant improvement in the escape latency for finding the platform in the MWM, as compared with SOY-PS. Consistent with the behavioral results, KR-PS treatments significantly alleviated age-associated losses of cholinergic immunoreactivity, and muscarinic acetylcholine receptor type 1 (mAChR-M1) and choline transporter (CHT) mRNA expression in the hippocampus. These findings demonstrate that KR-PS showed significant neuroprotective activity against the neuronal and cognitive impairments that occur with normal aging in rats; comparable results were obtained with SOY-PS. These data indicate that oral administration of PS derived from marine life could substitute for bovine cerebral cortex PS (BC-PS) as therapy for the improvement of diminished memory function in elderly people. 相似文献
959.
Korman SH 《Molecular genetics and metabolism》2006,89(4):289-299
Three inborn errors have been identified in the pathway of isoleucine degradation. Deficiency of beta-ketothiolase (beta-KT, also known as T2, mitochondrial acetoacetyl-CoA thiolase and acetyl-CoA acetyltransferase 1) is a well-described disorder which presents with acute episodic ketoacidosis. In contrast, short/branched-chain acyl-CoA dehydrogenase (SBCAD) and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiencies are recently described and relatively rare defects which present with predominantly neurological manifestations, although acute metabolic decompensation may occur in the early newborn period. Careful examination of urine organic acids is required for identification and differential diagnosis of these disorders, with awareness that the abnormalities may be subtle and variable. Tandem MS analysis of acylcarnitines may reveal elevated C5 (SBCAD) or C5:1 and/or OH-C5 species (MHBD and beta-KT deficiencies) but the abnormalities are non-diagnostic and may be intermittent or absent. Confirmation of diagnosis is therefore advisable by specific enzyme assay and/or mutation analysis of the ACAT1 (beta-KT), ACADSB (SBCAD) or HADH2 (MHBD) genes. The latter is located on the X chromosome, accounting for the milder clinical phenotype in females. If beta-KT deficiency is diagnosed early and treated by fasting avoidance and modest protein restriction, ketoacidosis episodes can be prevented and the prognosis is excellent. The role of treatment in SBCAD deficiency remains unclear pending further delineation of its clinical phenotype and pathogenicity, particularly regarding asymptomatic individuals detected by expanded newborn screening. The ineffectiveness of isoleucine restriction in MHBD deficiency is consistent with the additional roles of this multifunctional enzyme in sex steroid and neurosteroid metabolism and its interaction with amyloid-beta peptide. 相似文献
960.
Down syndrome (DS) is the leading cause of genetically-defined intellectual disability and congenital birth defects. Despite being one of the first genetic diseases identified, only recently, thanks to the phenotypic analysis of DS mouse genetic models, we have begun to understand how trisomy may impact cognitive function. Cognitive disabilities in DS appear to result mainly from two pathological processes: neurogenesis impairment and Alzheimer-like degeneration. In DS brain, suboptimal network architecture and altered synaptic communication arising from neurodevelopmental impairment are key determinants of cognitive defects. Hypocellularity and hypoplasia start at early developmental stages and likely depend upon impaired proliferation of neuronal precursors, resulting in reduction of numbers of neurons and synaptic contacts. The impairment of neuronal precursor proliferation extends to adult neurogenesis and may affect learning and memory. Neurodegenerative mechanisms also contribute to DS cognitive impairment. Early onset Alzheimer disease occurs with extremely high incidence in DS patients and is causally-related to overexpression of β-amyloid precursor protein (βAPP), which is one of the triplicated genes in DS. In this review, we will survey the available findings on neurodevelopmental and neurodegenerative changes occurring in DS throughout life. Moreover, we will discuss the potential mechanisms by which defects in neurogenesis and neurodegenerative processes lead to altered formation of neural circuits and impair cognitive function, in connection with findings on pharmacological treatments of potential benefit for DS. 相似文献