排序方式: 共有67条查询结果,搜索用时 15 毫秒
51.
Despite successful use of the ketogenic diet (KD) for the treatment of drug-resistant epilepsy, its mechanism of action is unclear. After KD-feeding, increased plasma D-beta-hydroxybutyrate (BHB) levels appear to be important for protection against seizures. We hypothesized that the KD leads to metabolic changes in the brain, which are reflected in the hippocampal extracellular fluid (hECF). CD1 mice were fed control or KD for 2-3 weeks since weaning. In vivo microdialysis of hECF was used to measure the levels of glucose, lactate, as well as BHB under basal conditions and during 30 min stimulation with 60 mM K(+), which was retrodialysed. The hECF BHB concentration in KD-fed mice was determined as 43.4±10.1 μM using the zero-flow method and 50.7±5.5 μM based on in vitro recovery. The total BHB concentration in brain homogenate from KD-fed mice was 180 nmol/g. The intracellular BHB concentration is therefore estimated to be about 3-fold higher than the extracellular level, which suggests that BHB in adolescent mouse brains may not be quickly metabolized. The basal hECF glucose concentration was 30% lower in KD-fed mice, indicating that glucose may be less important as an energy source. Lactate levels were similar in control and KD-fed mice. High potassium stimulation elevated lactate by 3-3.5-fold and decreased glucose by 40-50% in both diet groups, consistent with similar anaerobic and aerobic metabolism in both diet groups during high hippocampal activity. Overall, these data (1) defined the BHB concentration in the hippocampal extracellular fluid in KD-fed mice and (2) showed lower glucose metabolism compared to control diet-fed mice. This work will now enable other researchers to mimic the hippocampal extracellular environment in experiments aimed at deciphering the mechanisms of the KD. 相似文献
52.
Haihong Jin Giovanni Cianchetta Arokiasamy Devasagayaraj Kunjian Gu Brett Marinelli Lakshman Samala Sheldon Scott Terry Stouch Ashok Tunoori Ying Wang Yi Zang Chengmin Zhang S. David Kimball Alan J. Main Zhi-Ming Ding Weimei Sun Qi Yang Xiang-Qing Yu David R. Powell Alan Wilson Zhi-Cai Shi 《Bioorganic & medicinal chemistry letters》2009,19(17):5229-5232
Tryptophan hydroxylase (TPH) is a key enzyme in the synthesis of serotonin. As a neurotransmitter, serotonin plays important physiological roles both peripherally and centrally. Here we describe the discovery of substituted triazines as a novel class of tryptophan hydroxylase inhibitors. This class of TPH inhibitors can selectively reduce serotonin levels in murine intestine after oral administration without affecting levels in the brain. These TPH inhibitors may provide novel treatments for gastrointestinal disorders associated with dysregulation of the serotonergic system, such as chemotherapy-induced emesis and irritable bowel syndrome. 相似文献
53.
Variam Ullas Jeankumar Manoj Chandran Ganesh Samala Mallika Alvala Pulla Venkat Koushik Perumal Yogeeswari Elena G. Salina Dharmarajan Sriram 《Bioorganic & medicinal chemistry letters》2012,22(24):7414-7417
Twenty eight 5-nitrothiazole derivatives were synthesized and evaluated for in vitro activities against Mycobacterium tuberculosis (MTB), cytotoxicity against HEK 293T. Among the compounds, 5-nitro-N-(5-nitrothiazol-2-yl)furan-2-carboxamide (20) was found to be the most active compound in vitro with MICs of 5.48 μM against log-phase culture of MTB and also non-toxic up to 100 μM. 相似文献
54.
Singh SK Vobbalareddy S Shivaramakrishna S Krishnamraju A Rajjak SA Casturi SR Akhila V Rao YK 《Bioorganic & medicinal chemistry letters》2004,14(7):1683-1688
The effect of methanesulfonamide (MeSO(2)NH) group on COX-2 inhibitory activity of 1,5-diarylpyrazole is described. While this group being at position-4 of the N(1)-phenyl ring was found to be ineffective, its installation at position-4 of the C-5 phenyl ring offered several potent and selective inhibitors of COX-2 with IC(50) as low as 30 nM. 相似文献
55.
Eduardo?M?Del Aguila Marcio?B?Dutra Joab?T?Silva Vania?MF?PaschoalinEmail author 《BMC molecular biology》2005,6(1):9
Background
Preparation of RNA free from DNA is a critical step before performing RT-PCR assay. Total RNA isolated from several sources, including those obtained from Saccharomyces cerevisiae, using routine methodologies are frequently contaminated with DNA, which can give rise to amplification products that mimic the amplicons expected from the RNA target. 相似文献56.
Eduardo?S?SilvaEmail author Gerard?J?Schoone Celia?MF?Gontijo Reginaldo?P?Brazil Raquel?S?Pacheco Henk?DFH?Schallig 《Kinetoplastid biology and disease》2005,4(1):4
Background
The direct agglutination test (DAT) has proved to be a very important sero-diagnostic tool combining high levels of intrinsic validity and ease of performance. Otherwise, fast agglutination screening test (FAST) utilises only one serum dilution making the test very suitable for the screening of large populations. 相似文献57.
58.
59.
Margarida Cepa Georgina Correia-da-Silva Elisiário J Tavares da Silva Fernanda MF Roleira Margarida Borges Natércia A Teixeira 《BMC cell biology》2008,9(1):41
Background
Aromatase, the cytochrome P-450 enzyme (CYP19) responsible for estrogen biosynthesis, is an important target for the treatment of estrogen-dependent breast cancer. In fact, the use of synthetic aromatase inhibitors (AI), which induce suppression of estrogen synthesis, has shown to be an effective alternative to the classical tamoxifen for the treatment of postmenopausal patients with ER-positive breast cancer. New AIs obtained, in our laboratory, by modification of the A and D-rings of the natural substrate of aromatase, compounds 3a and 4a, showed previously to efficiently suppress aromatase activity in placental microsomes. In the present study we have investigated the effects of these compounds on cell proliferation, cell cycle progression and induction of cell death using the estrogen-dependent human breast cancer cell line stably transfected with the aromatase gene, MCF-7 aro cells. 相似文献60.