P W Stacpoole

Summary

Affiliation: University of Florida
Country: USA

Publications

  1. ncbi request reprint Liquid chromatography-tandem mass spectrometry method for the simultaneous determination of delta-ALA, tyrosine and creatinine in biological fluids
    Natalia M Felitsyn
    Department of Medicine Division of Endocrinology and Metabolism, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Clin Chim Acta 350:219-30. 2004
  2. pmc Clinical pharmacology and toxicology of dichloroacetate
    P W Stacpoole
    Department of Medicine, College of Medicine, University of Florida, Gainesville, USA
    Environ Health Perspect 106:989-94. 1998
  3. ncbi request reprint Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children
    Peter W Stacpoole
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Gainesville, Florida, USA
    Pediatrics 117:1519-31. 2006
  4. ncbi request reprint Teaching hypothesis-oriented thinking to medical students: the University of Florida's clinical investigation program
    P W Stacpoole
    General Clinical Research Center GCRC, J Hillis Miller Health Center, Gainesville, FL 32610, USA
    Acad Med 76:287-92. 2001
  5. ncbi request reprint The pyruvate dehydrogenase complex as a target for gene therapy
    Peter W Stacpoole
    Department of Medicine, Division of Endocrinology and Metabolism, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Curr Gene Ther 3:239-45. 2003
  6. ncbi request reprint Deficiencies of folate and vitamin B(6) exert distinct effects on homocysteine, serine, and methionine kinetics
    G J Cuskelly
    Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida 32611-0307, USA
    Am J Physiol Endocrinol Metab 281:E1182-90. 2001
  7. pmc A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate
    Zongchao Han
    Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida College of Medicine, Gainesville, FL, USA
    Mol Genet Metab 93:381-7. 2008
  8. ncbi request reprint QUICKI does not accurately reflect changes in insulin sensitivity with exercise training
    G E Duncan
    Department of Medicine, University of Florida, Gainesville, Florida 32610, USA
    J Clin Endocrinol Metab 86:4115-9. 2001
  9. ncbi request reprint Primed, constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism
    J F Gregory
    Department of Nutritional Sciences, University of California Berkeley, Berkeley, CA, USA
    Am J Clin Nutr 72:1535-41. 2000
  10. ncbi request reprint Inhibition and recovery of rat hepatic glutathione S-transferase zeta and alteration of tyrosine metabolism following dichloroacetate exposure and withdrawal
    Xu Guo
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, FL 32610, USA
    Drug Metab Dispos 34:36-42. 2006

Collaborators

Detail Information

Publications45

  1. ncbi request reprint Liquid chromatography-tandem mass spectrometry method for the simultaneous determination of delta-ALA, tyrosine and creatinine in biological fluids
    Natalia M Felitsyn
    Department of Medicine Division of Endocrinology and Metabolism, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Clin Chim Acta 350:219-30. 2004
    ..There is currently no facile, sensitive and specific method to measure these analytes simultaneously...
  2. pmc Clinical pharmacology and toxicology of dichloroacetate
    P W Stacpoole
    Department of Medicine, College of Medicine, University of Florida, Gainesville, USA
    Environ Health Perspect 106:989-94. 1998
    ..It remains to be determined whether important differences in its metabolism and toxicology exist in humans between environmentally and clinically relevant doses...
  3. ncbi request reprint Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children
    Peter W Stacpoole
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Gainesville, Florida, USA
    Pediatrics 117:1519-31. 2006
    ..We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease...
  4. ncbi request reprint Teaching hypothesis-oriented thinking to medical students: the University of Florida's clinical investigation program
    P W Stacpoole
    General Clinical Research Center GCRC, J Hillis Miller Health Center, Gainesville, FL 32610, USA
    Acad Med 76:287-92. 2001
    ....
  5. ncbi request reprint The pyruvate dehydrogenase complex as a target for gene therapy
    Peter W Stacpoole
    Department of Medicine, Division of Endocrinology and Metabolism, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Curr Gene Ther 3:239-45. 2003
    ....
  6. ncbi request reprint Deficiencies of folate and vitamin B(6) exert distinct effects on homocysteine, serine, and methionine kinetics
    G J Cuskelly
    Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida 32611-0307, USA
    Am J Physiol Endocrinol Metab 281:E1182-90. 2001
    ..85, P = 0.0015). Rates of homocysteine remethylation and serine synthesis were inversely correlated (r = -0.89, P < 0.001). These studies demonstrate distinctly different metabolic consequences of vitamin B(6) and folate deficiencies...
  7. pmc A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate
    Zongchao Han
    Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida College of Medicine, Gainesville, FL, USA
    Mol Genet Metab 93:381-7. 2008
    ..These data suggest that a combined gene delivery and pharmacological approach may hold promise for the treatment of PDH deficiency...
  8. ncbi request reprint QUICKI does not accurately reflect changes in insulin sensitivity with exercise training
    G E Duncan
    Department of Medicine, University of Florida, Gainesville, Florida 32610, USA
    J Clin Endocrinol Metab 86:4115-9. 2001
    ..e. QUICKI) at estimating basal insulin sensitivity in nondiabetic adults. However, QUICKI does not accurately reflect exercise-induced changes in insulin sensitivity within individual subjects...
  9. ncbi request reprint Primed, constant infusion with [2H3]serine allows in vivo kinetic measurement of serine turnover, homocysteine remethylation, and transsulfuration processes in human one-carbon metabolism
    J F Gregory
    Department of Nutritional Sciences, University of California Berkeley, Berkeley, CA, USA
    Am J Clin Nutr 72:1535-41. 2000
    ..One-carbon metabolism involves both mitochondrial and cytosolic forms of folate-dependent enzymes in mammalian cells, but few in vivo data exist to characterize the biochemical processes involved...
  10. ncbi request reprint Inhibition and recovery of rat hepatic glutathione S-transferase zeta and alteration of tyrosine metabolism following dichloroacetate exposure and withdrawal
    Xu Guo
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, FL 32610, USA
    Drug Metab Dispos 34:36-42. 2006
    ..The liver/body weight ratio increased in the high-dose group after 8 weeks of DCA. These studies demonstrate that short-term administration of DCA inhibits rat liver GSTz across the wide concentration range to which humans are exposed...
  11. ncbi request reprint Methylphenidate does not improve cognitive function in healthy sleep-deprived young adults
    Christopher L Bray
    University of Florida College of Medicine, Gainesville, FL 32610 1042, USA
    J Investig Med 52:192-201. 2004
    ..Abuse of methylphenidate, a treatment of attention-deficit/hyperactivity disorder, is reported to be increasing among students for the purpose of improving cognition...
  12. ncbi request reprint Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency
    Kristen Berendzen
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida College of Medicine, P O Box 10226, Gainesville, FL 32610, USA
    Mitochondrion 6:126-35. 2006
    ..A controlled trial is needed to determine the definitive role of DCA in the management of this devastating disease...
  13. ncbi request reprint Magnetic resonance spectroscopic investigation of mitochondrial fuel metabolism and energetics in cultured human fibroblasts: effects of pyruvate dehydrogenase complex deficiency and dichloroacetate
    Nicholas E Simpson
    Department of Medicine, Division of Endocrinology and Metabolism, University of Florida, Gainesville, FL 32610, USA
    Mol Genet Metab 89:97-105. 2006
    ..This study demonstrates that NMR spectroscopy provides insight into biochemical consequences of PDC deficiency and the mechanism of putative therapeutic agents...
  14. pmc Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate
    Peter W Stacpoole
    Department of Medicine, General Clinical Research Center, JHMHC, Gainesville, FL 32610 0226, USA
    Pediatrics 121:e1223-8. 2008
    ..The purpose of this research was to report results on long-term administration of dichloroacetate in 36 children with congenital lactic acidosis who participated previously in a controlled trial of this drug...
  15. pmc Role of dichloroacetate in the treatment of genetic mitochondrial diseases
    Peter W Stacpoole
    Department of Medicine, Division of Endocrinology and Metabolism, College of Medicine, University of Florida, Gainesville, FL 32610 0226, USA
    Adv Drug Deliv Rev 60:1478-87. 2008
    ..Recent in vitro data indicate that a combined DCA and gene therapy approach may also hold promise for the treatment of this devastating condition...
  16. pmc The dichloroacetate dilemma: environmental hazard versus therapeutic goldmine--both or neither?
    Peter W Stacpoole
    Department of Medicine, Division of Endocrinology and Metabolism, College of Medicine, University of Florida, Gainesville, Florida 32610, USA
    Environ Health Perspect 119:155-8. 2011
    ..Thus, DCA holds an almost unique position at the interface between environmental science and allopathic medicine...
  17. ncbi request reprint Exercise training, without weight loss, increases insulin sensitivity and postheparin plasma lipase activity in previously sedentary adults
    Glen E Duncan
    Department of Medicine, University of Florida, Gainesville, Florida 32610 0226, USA
    Diabetes Care 26:557-62. 2003
    ..To determine the effects of exercise, without weight loss, on insulin sensitivity (S(I)), postheparin plasma lipase activity (PHPL), intravenous fat clearance rate (K(2)), and fasting lipids in sedentary adults...
  18. ncbi request reprint Renal manifestations of congenital lactic acidosis
    Richard E Neiberger
    Department of Pediatrics, Division of Nephrology, and the General Clinical Research Center, University of Florida, Gainesville, FL, USA
    Am J Kidney Dis 39:12-23. 2002
    ....
  19. ncbi request reprint Pharmacokinetics and metabolism of [14C]dichloroacetate in male Sprague-Dawley rats. Identification of glycine conjugates, including hippurate, as urinary metabolites of dichloroacetate
    M O James
    Departments of Medicinal Chemistry and Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL 32610 0485, USA
    Drug Metab Dispos 26:1134-43. 1998
    ....
  20. ncbi request reprint Gene therapy for pyruvate dehydrogenase E1alpha deficiency using recombinant adeno-associated virus 2 (rAAV2) vectors
    Renius Owen
    Department of Pediatrics, the General Clinical Research Center, University of Florida, Gainesville, Florida 32610, USA
    Mol Ther 6:394-9. 2002
    ..These studies provide the basis for future efforts to develop a recombinant AAV (rAAV)-based gene therapy approach for the correction of PDC deficiency...
  21. pmc Development of optimized AAV3 serotype vectors: mechanism of high-efficiency transduction of human liver cancer cells
    B Cheng
    Division of Cellular and Molecular Therapy, Departments of Pediatics and Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610 3633, USA
    Gene Ther 19:375-84. 2012
    ..The optimized tyrosine-mutant AAV3 serotype vectors containing proapoptotic genes should prove useful for the potential gene therapy of human liver cancers...
  22. pmc Down-regulation of expression of rat pyruvate dehydrogenase E1alpha gene by self-complementary adeno-associated virus-mediated small interfering RNA delivery
    Zongchao Han
    Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Mitochondrion 7:253-9. 2007
    ..Thus, scAAV siRNA-mediated knockdown of PDHA1 gene expression provides a strategy that may be applied to create a useful animal model of PDC deficiency...
  23. ncbi request reprint Pharmacologic or genetic ablation of maleylacetoacetate isomerase increases levels of toxic tyrosine catabolites in rodents
    Chandramohan V Ammini
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
    Biochem Pharmacol 66:2029-38. 2003
    ..These results demonstrate that pharmacologic or genetic ablation of MAAI cause potentially toxic concentrations of tyrosine intermediates to accumulate in mice and perhaps in other species...
  24. ncbi request reprint Peripheral neuropathy in genetic mitochondrial diseases
    David E Stickler
    Department of Neurology, University of Florida, Gainesville, Florida, USA
    Pediatr Neurol 34:127-31. 2006
    ....
  25. ncbi request reprint Efficacy of dichloroacetate as a lactate-lowering drug
    Peter W Stacpoole
    Department of Medicine Division of Endocrinology and Metabolism, Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, USA
    J Clin Pharmacol 43:683-91. 2003
    ..Recent clinical studies of acquired lactic acidosis suggest that DCA could be rapidly effective in reducing this risk factor of mortality in patients with mild hyperlactatemeia...
  26. pmc Age-dependent kinetics and metabolism of dichloroacetate: possible relevance to toxicity
    Albert L Shroads
    Departments of Medicine, University of Florida Colleges of Medicine and Pharmacy, University of Florida, Gainesville, Florida, USA
    J Pharmacol Exp Ther 324:1163-71. 2008
    ..We conclude that age is an important variable in the in vivo metabolism and elimination of DCA and that it may account, in part, for the neurotoxicity of this compound in humans and other species...
  27. ncbi request reprint Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate
    Minghong Jia
    General Clinical Research Center, University of Florida, 1600 Archer Road, Gainesville, Florida 32610, USA
    J Clin Pharmacol 46:1449-59. 2006
    ..Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health...
  28. ncbi request reprint A GC-MS/MS method for the quantitative analysis of low levels of the tyrosine metabolites maleylacetone, succinylacetone, and the tyrosine metabolism inhibitor dichloroacetate in biological fluids and tissues
    Melissa D Zolodz
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 837:125-32. 2006
    ..To increase sensitivity, analytes were extracted from liver, urine, plasma and cultured nerve cells before and after dosing with DCA, derivatized to their pentafluorobenzyl esters, and analyzed via GC-MS/MS...
  29. ncbi request reprint Unified gas chromatographic-mass spectrometric method for quantitating tyrosine metabolites in urine and plasma
    Albert L Shroads
    Division of Endocrinology and Metabolism, Department of Medicine, University of Florida, Gainesville, FL 32610, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 808:153-61. 2004
    ..Thus far, the method has been successfully applied in the analysis of over 5000 urine and plasma samples from humans and rodents...
  30. pmc The heme precursor delta-aminolevulinate blocks peripheral myelin formation
    Natalia Felitsyn
    Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610 0244, USA
    J Neurochem 106:2068-79. 2008
    ..These results suggest that the neuropathic effects of delta-ALA are attributable, at least in part, to its pro-oxidant properties which damage myelinating Schwann cells...
  31. ncbi request reprint Methylenetetrahydrofolate reductase 677C->T polymorphism and folate status affect one-carbon incorporation into human DNA deoxynucleosides
    Eoin P Quinlivan
    Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, College of Medicine, University of Florida, Gainesville, FL 32611, USA
    J Nutr 135:389-96. 2005
    ..These findings support the feasibility of further assessment of factors affecting deoxynucleotide synthesis and DNA methylation in human 1-carbon metabolism...
  32. ncbi request reprint Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1 subunit
    Zongchao Han
    Department of Pediatrics, Division of Cellular and Molecular Therapy, Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA
    J Biol Chem 283:237-43. 2008
    ..They also provide a novel mechanism accounting for congenital deficiency of the PDH complex and perhaps other inborn errors of metabolism...
  33. ncbi request reprint Effects of alginate encapsulation on mitochondrial activity
    J Oca-Cossio
    Department of Medicine, Division of Endocrinology, University of Florida, Gainesville, FL 32610 0226, USA
    J Mater Sci Mater Med 16:521-4. 2005
    ..The results show that alginate encapsulation of fibroblasts does not affect the glucose consumption, the mitochondrial integrity, or the mitochondrial mass during 21 days of in vitro culture...
  34. ncbi request reprint Homocysteine synthesis is elevated but total remethylation is unchanged by the methylenetetrahydrofolate reductase 677C->T polymorphism and by dietary folate restriction in young women
    Steven R Davis
    Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, College of Medicine, University of Florida, Gainesville 32611 0370, USA
    J Nutr 135:1045-50. 2005
    ..In conclusion, elevated homocysteine synthesis is a cause of mild hyperhomocysteinemia in women with marginal folate status, particularly those with the MTHFR 677 T/T genotype...
  35. pmc AAV3-mediated transfer and expression of the pyruvate dehydrogenase E1 alpha subunit gene causes metabolic remodeling and apoptosis of human liver cancer cells
    Lyudmyla G Glushakova
    Department of Medicine, Division of Endocrinology and Metabolism, College of Medicine, University of Florida, FL, USA
    Mol Genet Metab 98:289-99. 2009
    ..These data indicate that molecular targeting of mitochondrial oxidative metabolism in liver cancer cells by AAV3-mediated delivery of pda1 holds promise as a novel and effective therapeutic approach for human hepatic tumors...
  36. ncbi request reprint MALDI-linear ion trap microprobe MS/MS studies of the effects of dichloroacetate on lipid content of nerve tissue
    Rachelle R Landgraf
    Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA
    Anal Chem 79:8170-5. 2007
    ..A marked decrease is observed in the intensity of lipid ions in spinal cord and sciatic nerve tissues from rats exposed to DCA. The results also demonstrate the rapid, sensitive, and semiquantitative capabilities of this method...
  37. ncbi request reprint Tracer-derived total and folate-dependent homocysteine remethylation and synthesis rates in humans indicate that serine is the main one-carbon donor
    Steven R Davis
    Food Science and Human Nutrition Department, Institute of Food and Agricultural Science, University of Florida, Gainesville, Florida 32611 0370, USA
    Am J Physiol Endocrinol Metab 286:E272-9. 2004
    ..Our dual-tracer procedure is well suited to measure the effects of nutrient deficiencies, genetic polymorphisms, and other metabolic perturbations on homocysteine synthesis and total and folate-dependent homocysteine remethylation...
  38. ncbi request reprint Dichloroacetate causes reversible demyelination in vitro: potential mechanism for its neuropathic effect
    Natalia Felitsyn
    Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, Florida 32610 024, USA
    J Neurochem 100:429-36. 2007
    ..These results demonstrate that DCA induces a reversible inhibition of myelin-related proteins that may account, at least in part, for its clinical peripheral neuropathic effects...
  39. ncbi request reprint Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets
    Brian S Fuehrlein
    Department of Medicine, College of Medicine, University of Florida, Gainesville, Florida 32610, USA
    J Clin Endocrinol Metab 89:1641-5. 2004
    ..Thus, a POLY KD may be superior to a classical SAT KD for chronic administration...
  40. ncbi request reprint Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women
    Steven R Davis
    Food Science andHuman Nutrition Department, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611 0370, USA
    J Nutr 136:373-8. 2006
    ..These data indicate that glutathione homeostasis is altered by dietary vitamin B-6 deficiency and appears to be unrelated to cysteine flux under conditions of minimal amino acid intake as evaluated in this study...
  41. ncbi request reprint The methylenetetrahydrofolate reductase 677C->T polymorphism and dietary folate restriction affect plasma one-carbon metabolites and red blood cell folate concentrations and distribution in women
    Steven R Davis
    Food Science and Human Nutrition Department, Institute of Food and Agricultural Sciences, College of Medicine, University of Florida, Gainesville, FL 32611 0370, USA
    J Nutr 135:1040-4. 2005
    ....
  42. ncbi request reprint Evaluation of dichloroacetate treatment in a murine model of hereditary tyrosinemia type 1
    Chantale Langlois
    Laboratory of Cellular and Developmental Genetics, CREFSIP, Department of Medicine, University Laval, Que, Canada G1K 7P4
    Biochem Pharmacol 71:1648-61. 2006
    ..Thus the failure of DCA treatment in FAH(-/-) mice seems to be attributed to the residual MAAI activity, high enough to lead to FAA accumulation and HT1 phenotype...
  43. ncbi request reprint Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children
    Tsiri Agbenyega
    Department of Physiology, University of Science and Technology, School of Medical Sciences, Departments of Child Health and Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana
    J Clin Pharmacol 43:386-96. 2003
    ..DCA significantly reduces the concentration of blood lactate, an independent predictor of mortality in malaria. Its prospective evaluation in affecting mortality in this disorder appears warranted...
  44. ncbi request reprint A prospective comparison of malaria with other severe diseases in African children: prognosis and optimization of management
    Tim Planche
    Department of Cellular and Molecular Medicine Infectious Diseases, St George s Hospital Medical School, London, United Kingdom
    Clin Infect Dis 37:890-7. 2003
    ..77). Predictors of mortality in children with malaria differ from those for other severe illnesses and reflect differences in underlying pathophysiological processes...
  45. ncbi request reprint Effects of exercise on emerging and traditional cardiovascular risk factors
    Glen E Duncan
    Department of Epidemiology, Nutritional Sciences Program, University of Washington, Seattle, WA 98195, USA
    Prev Med 39:894-902. 2004
    ..insulin and aerobic fitness) are improved with exercise; however, few studies have addressed the potential for training to modify emerging cardiovascular disease risk factors such as homocysteine and high-sensitivity C-reactive protein...