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D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease 总被引:6,自引:0,他引:6 下载免费PDF全文
Tieu K Perier C Caspersen C Teismann P Wu DC Yan SD Naini A Vila M Jackson-Lewis V Ramasamy R Przedborski S 《The Journal of clinical investigation》2003,112(6):892-901
Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of the nigrostriatal dopaminergic neurons accompanied by a deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes dopaminergic neurodegeneration and a mitochondrial deficit reminiscent of PD. Here we show that the infusion of the ketone body d-beta-hydroxybutyrate (DbetaHB) in mice confers partial protection against dopaminergic neurodegeneration and motor deficits induced by MPTP. These effects appear to be mediated by a complex II-dependent mechanism that leads to improved mitochondrial respiration and ATP production. Because of the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier, DbetaHB may be a novel neuroprotective therapy for PD. 相似文献
115.
Hodgkin's disease and mycosis fungoides are only rarely reported to occur in the same individual. The authors report a patient who initially presented with Hodgkin's disease but later died with massive visceral mycosis fungoides. This sequence of events is unique in the world's reported lymphoma experience. 相似文献
116.
A 42-year-old woman with an 18-year history of suprasellar tumor, treated by repeated radiation therapy and surgery, was found to have both a craniopharyngioma and subependymoma of the third ventricle. The case is unique in that well documented subependymomas have not been reported in this location. Furthermore, only a few cases of subependymoma have been reported to be accompanied by a primary tumor of the central nervous system other than an ependymoma. Potential causative factors for this seemingly reactive subependymoma are briefly discussed. 相似文献
117.
Clostridial septicemia complicating the course of leukemia 总被引:2,自引:0,他引:2
J G Caya S G Farmer P S Ritch N J Wollenberg T M Tieu H W Oechler M Spivey 《Cancer》1986,57(10):2045-2048
The authors report an analysis of 47 leukemia patients (including 9 from our own medical center) whose courses were complicated by 48 episodes of clostridial septicemia. There were 36 adults and 11 children; acute myelogenous leukemia and acute lymphoblastic leukemia accounted for 61.7% and 14.9% of cases, respectively. All patients for whom remission status was known were in leukemic relapse. Fever was a presenting complaint in at least 36 patients whereas neutropenia, thrombocytopenia, and gastrointestinal lesions were noted in 100%, 90.9%, and 87.9%, respectively, of the patients for whom information on these parameters was available. Overall mortality from clostridial septicemia was 78%; none of the children and none of the patients with intravascular hemolysis survived. Overall, antibiotic therapy resulted in a 40% survival rate. However, among patients receiving beta lactam and/or chloramphenicol therapy, 57% survived their episode of clostridial septicemia. Prompt initiation of appropriate antimicrobial therapy offers the best chance of survival in leukemia patients with clostridial septicemia. 相似文献
118.
Goodarzi MO Taylor KD Guo X Quiñones MJ Cui J Li X Hang T Yang H Holmes E Hsueh WA Olefsky J Rotter JI 《Diabetes》2005,54(4):1222-1227
The rising prevalence of the insulin resistance syndrome in our society necessitates a better understanding of the genetic determinants of all aspects of insulin action and metabolism. We evaluated the heritability of insulin sensitivity and the metabolic clearance rate of insulin (MCRI) as quantified by the euglycemic-hyperinsulinemic clamp in 403 Mexican Americans. We tested the candidate gene AMP deaminase 1 (AMPD1) for association with insulin-related traits because it codes for an enzyme that has the potential to influence multiple aspects of insulin pharmacodynamics. By converting AMP to inosine monophosphate, AMPD1 plays a major role in regulating cellular AMP levels; AMP activates AMP kinase, an enzyme that modulates cellular energy and insulin action. We determined that nine AMPD1 single nucleotide polymorphisms (SNPs) defined two haplotype blocks. Insulin clearance was found to have a higher heritability (h(2) = 0.58) than fasting insulin (h(2) = 0.38) or insulin sensitivity (h(2) = 0.44). The MCRI was associated with AMPD1 SNPs and haplotypes. Insulin clearance is a highly heritable trait, and specific haplotypes within the AMPD1 gene, which encodes a skeletal muscle-specific protein, are associated with variation in insulin clearance. We postulated that the processes of insulin action and insulin clearance in skeletal muscle are highly regulated and that AMPD1 function may play an important role in these phenomena. 相似文献
119.
Tarantal AF Laughlin LS Dieter J Tieu J Hendrickx AG Overstreet JW Lasley BL 《Early pregnancy : biology and medicine : the official journal of the Society for the Investigation of Early Pregnancy》1997,3(4):281-290
The goal of these studies was to correlate sonographic evidence of pregnancy during the peri-implantation period with the timing of the rise in monkey chorionic gonadotropin (mCG) as measured with an enzyme-linked immunosorbent assay. Animals were time-mated at mid-cycle, and ultrasound examinations were performed on postovulation days 12-15 (n = 77). Pregnancy was sonographically identified in 48 of 77 animals (62.3%), of which 28 had correlative ultrasound/endocrine data collected. For these animals, blood samples were obtained on postovulation days 12-15 for mCG assay. Pregnancy was identified by ultrasound on postovulation days 12 (6/28; 21.4%), 13 (6/28; 21.4%), 14 (8/28; 28.6%) or 15 (8/28; 28.6%). Seven of the 28 (25.0%) were found to have mCG levels consistent with pregnancy (> or = 1 ng/ml) on the same day as ultrasound confirmation, 12 of 28 (42.9%) were sonographically detected as pregnant 1 (n = 6), 2 (n = 3) or 3 (n = 3) days earlier than by mCG, and nine of 28 (32.1%) were found to have elevated mCG levels 1 (n = 7), 2 (n = 1) or 3 (n = 1) days earlier than ultrasound confirmation of pregnancy. The results of these studies have demonstrated (1) the utility of anatomical and endocrine techniques for detecting pregnancy approximately 3 days after the onset of implantation, and (2) the variation in the timing of implantation and the rise in circulating mCG in individual animals. 相似文献