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排序方式: 共有92条查询结果,搜索用时 15 毫秒
1.
PharmacokineticsofintravenouslyadministeredsodiumdichloroacetateinrabbitsGuBin(顾斌);SongLing(宋岭);JiangYongpei(蒋永培);WenAidong(文... 相似文献
2.
《Journal of labelled compounds & radiopharmaceuticals》2005,48(8):597-604
A convenient synthesis of chloramphenicol labelled with carbon‐14 in the dichloroacetyl group at the 1 position is described. It was prepared as part of a 4‐step sequence from [1 ‐ 14C] glycine and the product was purified by preparative HPLC. A radiochemical yield of 47% was obtained based on [1 ‐ 14C] glycine and the product had a specific activity of 0.47 mCi/mmol. The procedure can be employed for the synthesis of high specific activity [14C] chloramphenicol, labelled at 1, 2 or both the positions of dichloroacetyl group. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
3.
Summary Subcutaneous injection of sodium dichloroacetate (1 mg/g body wt every 3 h) in suckling newborn rats caused in 6 h a fall
of 2.5 mmol/l in blood glucose concentrations, and a rise of 2.4 mmol/ l in total blood ketone body levels, but no change
in the high levels of plasma non esterified fatty acids. Glucose utilization, measured after intraperitoneal injection of
D-glucose (2 mg/g body wt), was not increased in newborns injected with dichloroacetate. The hypoglycaemia resulted from a
decrease in gluconeogenic rate, secondarily to a lowering effect of dichloroacetate on blood levels of lactate, pyruvate and
alanine. The hypoglycaemia induced by dichloroacetate was completely reversed by injecting newborn rats with a mixture of
gluconeogenic precursors (lactate, pyruvate and alanine). It is concluded that the high rate of gluconeogenesis observed in
suckling newborn rats in sustained by an increased release of lactate and, to a much smaller extent of pyruvate and alanine,
by peripheral tissues. This probably resulted from the low pyruvate dehydrogenase activity found in peripheral tissues of
the newborn rat. The hyperketonaemia induced by dichloroacetate could result from an increased ketogenesis and/or a decreased
ketone body utilization. 相似文献
4.
目的观察二氯醋酸二异丙胺联合甘草酸二胺治疗慢性乙型肝炎合并脂肪肝的临床疗效。方法将87例慢性乙型肝炎合并脂肪肝患者随机分为两组:联合组42例,用二氯醋酸二异丙胺联合甘草酸二胺治疗;对照组38例,给予甘草酸二胺治疗,疗程均为8周。结果肝功能:治疗前两组比较差异无显著性(P〉0.05);两组治疗后与治疗前比较差异均有显著性(P〈0.05);治疗后两组比较差异亦有显著性(P〈0.05)。TC(总胆固醇)、TG(甘油三脂):治疗前两组比较差异无显著性(P〉0.05),对照组治疗后与治疗前比较差异无显著性(P〉0.05),治疗后联合组与对照组比较差异有显著性(P〈0.05)。结论二氯醋酸二异丙胺联合甘草酸二胺是治疗慢性乙型肝炎合并脂肪肝的有效药物,可改善肝功能,同时有明显降脂作用。 相似文献
5.
6.
Sonal Josan Jae Mo Park Ralph Hurd Yi‐Fen Yen Adolf Pfefferbaum Daniel Spielman Dirk Mayer 《NMR in biomedicine》2013,26(12):1680-1687
Hyperpolarized 13C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl‐coenzyme A (acetyl‐CoA). [1‐13C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in 13C‐bicarbonate production after dichloroacetate (DCA) administration. With [1‐13C]pyruvate, the 13C label is released as 13CO2/13C‐bicarbonate, and, hence, does not allow us to follow the fate of acetyl‐CoA. Pyruvate labeled in the C2 position has been used to track the 13C label into the TCA (tricarboxylic acid) cycle and measure [5‐13C]glutamate as well as study changes in [1‐13C]acetylcarnitine with DCA and dobutamine. This work investigates changes in the metabolic fate of acetyl‐CoA in response to metabolic interventions of DCA‐induced increased PDC flux in the fed and fasted state, and increased cardiac workload with dobutamine in vivo in rat heart at two different pyruvate doses. DCA led to a modest increase in the 13C labeling of [5‐13C]glutamate, and a considerable increase in [1‐13C]acetylcarnitine and [1,3‐13C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2‐13C]lactate, [2‐13C]alanine and [5‐13C]glutamate. The change in glutamate with dobutamine was observed using a high pyruvate dose but not with a low dose. The relative changes in the different metabolic products provide information about the relationship between PDC‐mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways. Using a high dose of pyruvate may provide an improved ability to observe changes in glutamate. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
7.
Vitalba Ruggieri Francesca Agriesti Rosella Scrima Ilaria Laurenzana Donatella Perrone Tiziana Tataranni Carmela Mazzoccoli Lorenzo Lo Muzio Nazzareno Capitanio Claudia Piccoli 《Oncotarget》2015,6(2):1217-1230
Reprogramming of metabolism is a well-established property of cancer cells that is receiving growing attention as potential therapeutic target. Oral squamous cell carcinomas (OSCC) are aggressive and drugs-resistant human tumours displaying wide metabolic heterogeneity depending on their malignant genotype and stage of development. Dichloroacetate (DCA) is a specific inhibitor of the PDH-regulator PDK proved to foster mitochondrial oxidation of pyruvate. In this study we tested comparatively the effects of DCA on three different OSCC-derived cell lines, HSC-2, HSC-3, PE15. Characterization of the three cell lines unveiled for HSC-2 and HSC-3 a glycolysis-reliant metabolism whereas PE15 accomplished an efficient mitochondrial oxidative phosphorylation. DCA treatment of the three OSCC cell lines, at pharmacological concentrations, resulted in stimulation of the respiratory activity and caused a remarkably distinctive pro-apoptotic/cytostatic effect on HSC-2 and HSC-3. This was accompanied with a large remodeling of the mitochondrial network, never documented before, leading to organelle fragmentation and with enhanced production of reactive oxygen species. The data here presented indicate that the therapeutic efficacy of DCA may depend on the specific metabolic profile adopted by the cancer cells with those exhibiting a deficient mitochondrial oxidative phosphorylation resulting more sensitive to the drug treatment. 相似文献
8.
Jannet F. Lewis Michelle Dacosta Thomas Wargowich Peter Stacpoole 《Clinical cardiology》1998,21(12):888-892
Background: Conventional approaches to management of congestive heart failure (CHF) rely on drugs that increase myocardial contractility or reduce ventricular afterload. These approaches often improve cardiac symptoms and survival, but may be associated with significant deleterious effects. An alternative approach is to enhance myocardial energy production. Dichloroacetate (DCA) stimulates pyruvate dehydrogenase activity and accelerates aerobic glucose, pyruvate, and lactate metabolism in myocardial cells. These alterations would be expected to improve myocardial function. Hypothesis: The purpose of the investigation was to assess the efficacy of DCA in patients with left ventricular systolic dysfunction and to examine the mechanism by which improvement occurs. Methods: A total of 25 patients (16 men, 9 women; age range 31-72 years, mean 59) with CHF and ejection fraction ≤40% received an intravenous infusion of 50 mg/kg DCA over 15 min. Indices of systolic and diastolic function were obtained by two-dimensional and Doppler echocardiography performed at baseline, 30 min, and 60 min following completion of DCA infusion. Results: Baseline ventricular ejection fraction was 27.3 ± 9.1%; 17 patients (68%) had nonischemic cardiomyopathy. Heart rate increased after DCA infusion from 73.9 ± 14.5 to 79.2 ± 14.9 beats/min at 60 min; p = 0.02. Left ventricular diastolic and systolic volumes increased at 30 min compared with baseline (248.7 ± 98.1 vs. 259.6 ± 99.6; p = 0.04, and 180.1 ± 80.4 vs. 192.2 ± 84.9; p = 0.002, respectively), but stroke volume (49.2 ± 19.1 vs. 48.9 ± 18.1; p = 0.9) and ejection fraction (27.3 ± 9.1 vs. 25.7 ± 9.8; p = 0.2) were un changed. Indices of diastolic function were also unchanged. Conclusion: Dichloroacetate infusion in patients with CHF is not associated with improvement in noninvasively assesse left ventricular function. 相似文献
9.
Seiji Kimura Noriyuki Ohtuki Atuo Nezu Miyabi Tanaka Saoko Takeshita 《Brain & development》1997,19(8):535-540
We administered sodium dichloroacetate (DCA), which reduces the circulating lactate and pyruvate concentrations by stimulating the activity of the pyruvate dehydrogenase complex (PDHC), to three children with mitochondrial encephalomyelopathy. Significant clinical, biochemical and radiologic improvements were obtained following DCA therapy (approximately 30 mg/kg per day, divided into three doses). All three patients had non-pyruvate dehydrogenase complex (PDHC) deficiencies: two exhibited Leigh syndrome (complex I deficiency and unknown etiology), and one abnormal myelination (multienzyme deficiency), demonstrated on magnetic resonance imaging (MRI). The lactic and pyruvic acid concentrations in serum and cerebrospinal fluid (CSF) were decreased significantly by the oral DCA treatment. The lactic acid peak on MR spectroscopy also markedly decreased in parallel with the CSF level. In addition, the brain lesions observed on MRI were improved in all patients. No exacerbation was observed in any of the patients, who have been followed-up more than 21 months following the DCA therapy. These results suggest that DCA therapy should be considered in all patients with a mitochondria-related enzyme deficiency. 相似文献
10.
E. Naito M. Ito I. Yokota T. Saijo J. Matsuda Y. Kuroda 《European journal of pediatrics》1998,157(8):648-652
Lactic acidaemia is sometimes associated with a defect of the pyruvate dehydrogenase complex (PDHC), catalysing the thiamine-dependent
decarboxylation of pyruvate. The activity of PDHC for different thiamine pyrophosphate (TPP) concentrations was determined
in 13 patients with lactic acidaemia, clinically responsive to thiamine treatment in order to assess the role of PDHC in the
aetiology of thiamine-responsive lactic acidaemia. Culture of lymphoblastoid cells and skin fibroblasts and muscle biopsies
were performed in these 13 patients. The activity of PDHC to sodium dichloroacetate (DCA), known as the activator of PDHC,
was also examined. Three groups were identified according to PDHC activity. Group 1 (two patients) displayed very low PDHC
activity, which was not increased by DCA. This PDHC activity increased at high TPP concentrations. Group 2 (five patients)
displayed below normal PDHC activity at low TPP concentrations, increased by DCA. This PDHC activity became normal at high
TPP concentrations. PDHC deficiency in these patients of groups 1 and 2 was due to a decreased affinity of PDHC for TPP. Group
3 included six patients with normal PDHC activity at low as well as high TPP concentrations. This PDHC activity was increased
by DCA.
Conclusion High concentrations of TPP may be required for maximal activity of PDHC in some patients with lactic acidaemia. The assay
of PDHC activity, performed at a low concentration of TPP (1 × 10−4 mM) allows selection of patients with thiamine-responsive lactic acidaemia.
Received: 21 January 1997 / Accepted: 3 March 1998 相似文献