Aided phytostabilisation reduces metal toxicity, improves soil fertility and enhances microbial activity in Cu-rich mine tailings.

(Aided) phytostabilisation has been proposed as a suitable technique to decrease the environmental risks associated with metal(loid)-enriched mine tailings. Field scale evaluations are needed for demonstrating their effectiveness in the medium- to long-term. A field trial was implemented in spring 2011 in Cu-rich mine tailings in the NW of Spain. The tailings were amended with composted municipal solid wastes and planted with Salix spp., Populus nigra L. or Agrostis capillaris L. cv. Highland. Plant growth, nutritive status and metal accumulation, and soil physico- and bio-chemical properties, were monitored over three years (four years for plant growth). The total bacterial community, α- and ß-Proteobacteria, Actinobacteria and Streptomycetaceae were studied by DGGE of 16s rDNA fragments. Compost amendment improved soil properties such as pH, CEC and fertility, and decreased soil Cu availability, leading to the establishment of a healthy vegetation cover. Both compost-amendment and plant root activity stimulated soil enzyme activities and induced important shifts in the bacterial community structure over time. The woody plant, S. viminalis, and the grassy species, A. capillaris, showed the best results in terms of plant growth and biomass production. The beneficial effects of the phytostabilisation process were maintained at least three years after treatment.

Inoculation methods using Rhodococcus erythropolis strain P30 affects bacterial assisted phytoextraction capacity of Nicotiana tabacum.

In this study different bacterial inoculation methods were tested for tobacco plants growing in a mine-soil contaminated with Pb, Zn, and Cd. The inoculation methods evaluated were: seed inoculation, soil inoculation, dual soil inoculation event, and seed+soil inoculation. Each inoculum was added at two bacterial densities (10(6) CFUs mL(-1) and 10(8) CFUs mL(-1)). The objectives were to evaluate whether or not the mode of inoculation or the number of applied microorganisms influences plant response. The most pronounced bacterial-induced effect was found for biomass production, and the soil inoculation treatment (using 10(6) CFUs mL(-1)) led to the highest increase in shoot dry weight yield (up to 45%). Bacterial-induced effects on shoot metal concentrations were less pronounced; although a positive effect was found on shoot Pb concentration when using 10(8) CFUs mL(-1) in the soil inoculation (29% increase) and in the seed+soil inoculation (34% increase). Also shoot Zn concentration increased by 24% after seed inoculation with 10(6) CFUs mL(-1). The best effects on the total metal yield were not correlated with an increasing number of inoculated bacteria. In fact the best results were found after a single soil inoculation using the lower cellular density of 10(6) CFUs mL(-1).

Bioavailability and plant accumulation of heavy metals and phosphorus in agricultural soils amended by long-term application of sewage sludge.

Amendment of agricultural soils with municipal sewage sludges provides a valuable source of plant nutrients and organic matter. Nevertheless, addition of heavy metals and risks of eutrophication continue to be of concern. Metal behaviour in soils and plant uptake are dependent on the nature of the metal, sludge/soil physico-chemical properties and plant species. A pot experiment was carried out to evaluate plant production and heavy metal uptake, soil heavy metal pools and bioavailability, and soil P pools and possible leaching losses, in agricultural soils amended with sewage sludge for at least 10 years (F20) compared to non-amended soils (control). Sewage sludge application increased soil pH, N, Olsen-extractable-P, DOC and exchangeable Ca, Mg and K concentrations. Total and EDTA-extractable soil concentrations of Cu and Zn were also significantly greater in F20, and soil metal (Cu, Mn and Zn) and P fractionation altered. Compared to the control, in F20 relative amounts of acid-extractable (Mn, Zn), reducible (Mn, Zn) and oxidisable (Cu, Zn) metal fractions were greater, and a dominance of inorganic P forms was observed. Analyses of F20 soil solutions highlighted risks of PO4 and Cu leaching. However, despite the observed increases in metal bioavailability sewage sludge applications did not lead to an increase in plant shoot concentrations (in wild plants or crop species). On the contrary, depending on the plant species, Mn and Zn tissue concentrations were within the deficiency level for most plants.

Microbial community structure and activity in trace element-contaminated soils phytomanaged by Gentle Remediation Options (GRO).

Gentle remediation options (GRO) are based on the combined use of plants, associated microorganisms and soil amendments, which can potentially restore soil functions and quality. We studied the effects of three GRO (aided-phytostabilisation, in situ stabilisation and phytoexclusion, and aided-phytoextraction) on the soil microbial biomass and respiration, the activities of hydrolase enzymes involved in the biogeochemical cycles of C, N, P, and S, and bacterial community structure of trace element contaminated soils (TECS) from six field trials across Europe. Community structure was studied using denaturing gradient gel electrophoresis (DGGE) fingerprinting of Bacteria, α- and ß-Proteobacteria, Actinobacteria and Streptomycetaceae, and sequencing of DGGE bands characteristic of specific treatments. The number of copies of genes involved in ammonia oxidation and denitrification were determined by qPCR. Phytomanagement increased soil microbial biomass at three sites and respiration at the Biogeco site (France). Enzyme activities were consistently higher in treated soils compared to untreated soils at the Biogeco site. At this site, microbial biomass increased from 696 to 2352 mg ATP kg-1 soil, respiration increased from 7.4 to 40.1 mg C-CO2 kg-1 soil d-1, and enzyme activities were 2-11-fold higher in treated soils compared to untreated soil. Phytomanagement induced shifts in the bacterial community structure at both, the total community and functional group levels, and generally increased the number of copies of genes involved in the N cycle (nirK, nirS, nosZ, and amoA). The influence of the main soil physico-chemical properties and trace element availability were assessed and eventual site-specific effects elucidated. Overall, our results demonstrate that phytomanagement of TECS influences soil biological activity in the long term.

A phytogeochemical study of the Trás-os-Montes region (NE Portugal): possible species for plant-based soil remediation technologies.

Phytoremediation techniques are now considered to be promising alternatives to conventional techniques for the remediation of diffused or moderately contaminated soils. Despite their growing acceptance relatively few plant species have been studied for phytoremediation purposes. Further geobotanical surveys and plant screenings are necessary since these could lead to the identification of additional species with potential value for such applications. Serpentine areas could prove valuable sources of such plants. In this study heavy metal accumulation was determined in the flora associated with ultramafic and non-ultramafic soils of the Trás-os-Montes region of NE Portugal. Study sites were selected to represent a wide range of soil-forming rocks (serpentinized (S), ultrabasic (UB), basic (B) and acid (migmatite, M and schists, SC) rocks) and plant metal accumulation was related to soil metal bioavailability. Nine plant species (representing 7 families) were sampled including the Ni hyperaccumulator Alyssum serpyllifolium subsp. lusitanicum. The greatest metal accumulation, transport (leaf[metal]:root[metal]) and bioaccumulation (leaf[metal]/soil[metal]) was found in four of the non metal-hyperaccumulating species: Cistus ladanifer, Lavandula stoechas, Plantago subulata subsp. radicata and Thymus mastichina. Metal accumulation depended on both the plant species and the edaphic conditions at its provenance. While P. subulata is of less interest due to its low biomass the remaining three species could be of use in phytoremediation technologies such as phytoextraction, and particularly in soils contaminated with Cr, Mn and Zn. These three species are also of economic interest due to their oil and fragrance producing biomass.

Organic amendments for improving biomass production and metal yield of Ni-hyperaccumulating plants.

Ni phytomining is a promising technology for Ni recovery from low-grade ores such as ultramafic soils. Metal-hyperaccumulators are good candidates for phytomining due to their extraordinary capacity for Ni accumulation. However, many of these plants produce a low biomass, which makes the use of agronomic techniques for improving their growth necessary. In this study, the Ni hyperaccumulators Alyssum serpyllifolium ssp. lusitanicum, A. serpyllifolium ssp. malacitanum, Alyssum bertolonii and Noccaea goesingense were evaluated for their Ni phytoextraction efficiency from a Ni-rich serpentine soil. Effects of soil inorganic fertilisation (100:100:125kgNPKha(-1)) and soil organic amendment addition (2.5, 5 or 10% compost) on plant growth and Ni accumulation were determined. All soil treatments greatly improved plant growth, but the highest biomass production was generally found after addition of 2.5 or 5% compost (w/w). The most pronounced beneficial effects were observed for N. goesingense. Total Ni phytoextracted from soils was significantly improved using both soil treatments (inorganic and organic), despite the decrease observed in soil Ni availability and shoot Ni concentrations in compost-amended soils. The most promising results were found using intermediate amount of compost, indicating that these types of organic wastes can be incorporated into phytomining systems.

Structural and functional lability induced by diethyl ether on the sarcoplasmic reticulum membrane.

Structural and functional changes occurring in sarcoplasmic reticulum vesicles following exposure to low concentrations (5--7%, v/v) of diethyl ether in aqueous media, were studied by electron microscopy and by kinetic measurements of Ca2+ transport and ATPase activity. Electron microscopy of thin sectioned and freeze-fractured sarcoplasmic reticulum vesicles provided detailed resolution of Ca-ATPase amphiphilic molecules displaying 'lollipop' portions on the outer surface of the vesicle, and non-polar moieties penetrating the membrane's hydrophobic interior. This asymmetric disposition of ATPase molecules was disrupted in vesicles exposed to ether and then centrifuged and/or resuspended in aqueous media. Such vesicles had a tendency to undergo fragmentation, and the distribution of ATPase molecules was markedly altered. The continuous fuzzy layer of lollipops became discontinuous, and the intramembranous particles became randomly distributed over both the concave and the convex freeze-fracture membrane faces. Functionally, the vesicles lost their ability to accumulate calcium in the presence of ATP, although high rates of ATPase activity were maintained. Vesicles which were simply exposed to ether, without being subjected to centrifugation and/or homogenization, did not appear altered ultrastructurally, and retained their ability to accumulate calcium. In fact, the enzyme turnover and the maximal levels of calcium uptake were increased. It is concluded that diethyl ether interferes with lipid-lipid and protein-lipid interactions in the sarcoplasmic reticulum vesicle membrane, thereby facilitating molecular motions which may be a limiting factor in the transport mechanism. On the other hand, these weakened interactions permit structural denaturation and loss of the ability to maintain a transmembrane Ca2+ gradient when the vesicles are subjected to mechanical perturbations which are harmless in the absence of ether.

Subcutaneous granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects.

The toxicity, pharmacokinetics, and hematologic effects of granulocyte-macrophage colony-stimulating (GM-CSF) were studied in a phase I/II trial of 16 patients with myelodysplastic syndrome (MDS). The GM-CSF was administered subcutaneously (SC) daily so as to achieve prolonged blood levels and to establish an outpatient treatment regimen. Four dose levels were administered for ten days: 0.3 microgram/kg/d (three patients), 1.0 microgram/kg/d (three), 3.0 micrograms/kg/d (four), and 10.0 micrograms/kg/d (six). The most common toxicities were fever and a flu-like syndrome, which were dose-dependent. The maximum-tolerated dose was 10.0 micrograms/kg/d, which induced severe rigors (two patients), fever greater than 40 degrees C (one), severe bronchospasm (one), and WBC 60,000 (one). In one patient, refractory anemia with excess blasts in transformation (RAEB-T) progressed to acute nonlymphocytic leukemia after two doses of GM-CSF, and the patient died of leukemia that did not respond to chemotherapy. After doses of 3.0 and 10.0 micrograms/kg, serum GM-CSF levels peaked at 3.8 to 6.3 hours, and persisted for 14 and 24 hours, respectively. Circulating granulocytes (neutrophils and bands) increased in a dose-dependent manner, as 11 of 13 patients who received greater than or equal to 1.0 microgram/kg/d responded with a two- to 194-fold increase. Although the neutrophils usually returned to pretreatment levels shortly after stopping GM-CSF, two patients continue to exhibit an elevation of neutrophils for 6 months. Dose-related increases in circulating monocytes and eosinophils were also noted. Transient increases in platelet and reticulocyte counts were observed in two and three patients, respectively. Five of the 16 patients later received maintenance GM-CSF at 3 micrograms/kg/d for 2 to 9 weeks. All showed a dramatic increase in neutrophils after 2 weeks. Thereafter, despite continued therapy, the neutrophil count in four patients declined markedly. In conclusion, GM-CSF is well tolerated by the SC route and induces striking, but usually temporary, improvement in the neutropenia of MDS. Larger prospective phase III trials will determine the duration of hematologic responses and the impact on infection, morbidity, and mortality.

Magnetic resonance imaging of bone marrow in hairy cell leukemia: correlation with clinical response to alpha-interferon.

Five patients with progressive hairy cell leukemia were treated with recombinant alpha 2-interferon and examined prospectively at 3-month intervals using serial bone marrow biopsies and magnetic resonance (MR) imaging. Pretreatment iliac crest marrow biopsies demonstrated hairy cell infiltration involving 30-90% of marrow cellularity. Concurrent pretreatment coronal images of the proximal femurs and pelvis using MR revealed extensive marrow involvement that varied in distribution from patchy to diffuse. At 6 months, all patients had responded to alpha 2-interferon with improvement in peripheral blood counts and decrease in lymphoid infiltration on marrow biopsy to 15-40%. Six-month follow-up MR scans demonstrated decreasing marrow leukemia infiltration and increasing marrow fat. MR bone marrow imaging appears useful in the initial diagnosis of hairy cell leukemia, for monitoring the response to treatment, and possibly for predicting relapse.

Metal extraction by Alyssum serpyllifolium ssp. lusitanicum on mine-spoil soils from Spain.

The efficiency of Alyssum serpyllifolium ssp. lusitanicum (Brassicaceae) for use in phytoextraction of polymetallic contaminated soils was evaluated. A. serpyllifolium was grown on two mine-spoil soils (MS1 and MS2): MS1 is contaminated with Cr (283 mg kg(-1)) and MS2 is moderately contaminated with Cr (263 mg kg(-1)), Cu (264 mg kg(-1)), Pb (1433 mg kg(-1)) and Zn (377 mg kg(-1)). Soils were limed to about pH 6.0 (MS1/Ca and MS2/Ca) or limed and amended with NPK fertilisers (MS1/NPK and MS2/NPK). Biomass was reduced on MS2/Ca due to Cu phytotoxicity. Fertilisation increased biomass by 10-fold on MS1/NPK, but root growth was reduced by 7-fold compared with MS1/Ca. Plants accumulated Mn, Ni and Zn in shoots, and both metal content and transportation were generally greater in MS2 than in MS1. Zinc bioaccumulation factors (BF, shoot([metal])/soil([metal])) were significantly greater in MS2 than in MS1. However, metal yields were greatest in plants grown on MS1/NPK. Concentrations of EDTA-, NH(4)Cl- and Mehlich 3 (M3)-extractable Mn and Zn were greater after plant growth. Concentrations of M3-extractable Cr, Ni, Pb and Zn were increased at the rhizosphere. Sequential extractions showed changes in the metal distribution among different soil fractions after growth. This could reflect the buffering capacity of these soils or the plants' ability to mobilise metals from less plant-available soil pools. Results suggest that A. serpyllifolium could be suitable for phytoextraction uses in polymetallic-contaminated soils, provided Cu concentrations were not phytotoxic. However, further optimisation of growth and metal extraction are required.

Prediction of CD4 count from CD4 percentage: experience from three laboratories.

OBJECTIVE: CD4 counts have been used to monitor progression of disease in HIV infection as criteria for initiation of therapy, and to stratify and follow patients in clinical trials. Recently, the Centers for Disease Control and Prevention (CDC) has made CD4 counts part of the classification of HIV disease. Because a CD4 percentage may be the only laboratory information available, this study was initiated to determine whether the correlation between CD4 percentages and CD4 counts is sufficiently high to enable these measures to be substituted for each other. DESIGN, SETTING AND PATIENTS: One thousand consecutive CD4 measurements from the University of Washington (UW) were used to create a model that was tested using datasets of 1000 CD4 measurements each from Maryland Medical Laboratories (MML) and Rush-Presbyterian-St Luke's Medical Center (Rush). The patients were not selected for age, sex, risk group or treatment. All patients from MML and Rush were known to be HIV-positive, while the HIV status of all UW patients was unknown. RESULTS: The model predicted that a patient with a CD4 percentage > or = 14% would have a CD4 count > or = 200 x 10(6)/l(if CD4 percentage of 14% was used, 9% of patients would have a CD4 count > or = 200 x 10(6)/l), and a patient with a CD4 percentage > or = 27% would have a CD4 count > or = 500 x 10(6)/l(if CD4 percentage of 27% was used, 17% of patients would have a CD4 count > or = 500 x 10(6)/l). CONCLUSIONS: These CD4 percentage correlations may be useful when a white blood cell and lymphocyte count are not available to calculate the CD4 count.

Myasthenia gravis associated with T helper cell lymphoma.

A case of myasthenia gravis (MG) associated with a T helper cell lymphoma is reported. Treatment of the lymphoma led to resolution of the MG. This and other cases of hematologic tumors associated with MG suggest that immunoregulatory abnormalities may underlie the production of antibodies directed against the acetylcholine receptor.

Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit.

Seventy-two rabbits were separated into groups to receive no drug, subcutaneous verapamil, metoprolol, hydralazine, metoprolol and hydralazine, or oral verapamil in 1 of 3 doses daily for 10 weeks. They also received a high-cholesterol diet and had serum triglyceride, cholesterol, and verapamil levels measured twice during the study. Blood pressure (BP), heart rate and weight were measured every 10 days. Approximately 60% of the rabbits given verapamil had detectable levels of the drug in their serum. This group had significantly less severe atherosclerosis in their aortas at the time they were killed, even though they had significantly higher cholesterol levels than the other groups. This group also did not have different BP than the other groups (except for the subcutaneous verapamil group). Thus, protection from atherosclerosis by verapamil in the cholesterol-fed rabbit is not the result of lowering of BP.

CD7+ acute non-lymphocytic leukemia: evidence for an early multipotential progenitor.

Nineteen of 71 (26%) cases of acute myelogenous leukemia (AML) were found to express CD7, a cell surface marker found early during T lineage differentiation. These myeloid leukemias often expressed other lymphoid markers and frequently had rearranged T-cell receptor beta and immunoglobulin heavy chain genes. We propose that in CD7+ AML, the malignant transformation occurred in a CD7+ progenitor cell. CD7+ myeloid leukemic precursors may be capable of limited differentiation with loss of CD7 during the initial phase of the disease, but this capacity may diminish during the course of treatment such that CD7 expression persists.

Oligoclonal immunoglobulin heavy chain gene rearrangement in a childhood immunoblastic lymphoma. Presentation as a polyphenotypic atypical lymphoproliferative reaction.

The authors describe a diagnostically difficult case of childhood lymphoma that presented as an atypical polyphenotypic lymphoproliferative reaction. Initial immunophenotyping revealed the presence of IgG, IgA, kappa, and lambda within the neoplastic lymphocytes. The patient had circulating plasmacytoid lymphocytes and a polyclonal hypergammaglobulinemia. The patient died of widespread immunoblastic lymphoma in two months. Postmortem tumor DNA showed a oligoclonal pattern of immunoglobulin heavy chain gene rearrangement. Blots for T-cell receptor beta-chain rearrangement showed germline bands. Epstein-Barr virus DNA was present within tumor cells, but there was no history of prior immunosuppression or serologic evidence of Epstein-Barr virus infection. The apparent polyclonal nature of the immunoproliferation delayed the institution of chemotherapy.

Interference of recombinant soluble CD4 immunoglobulin G in flow cytometric measurement of CD4+ lymphocytes.

Recombinant soluble CD4 covalently linked to an immunoglobulin G heavy chain (rCD4-IgG) was evaluated clinically for the treatment of human immunodeficiency virus infection. The interference of rCD4-IgG with the measurement of peripheral blood CD4 lymphocytes by whole-blood lysis flow cytometric analysis was investigated using three commercial monoclonal antibody reagents. Addition of rCD4-IgG resulted in an artifactual decrease in measured CD4 number at rCD4-IgG levels of greater than or equal to 1 micrograms/mL; the threshold for this decrease was dependent on the concentration of monoclonal antibody in the commercial preparation used for the measurement of CD4. This artifactual decrease in CD4 cell count was observed in two patients who received rCD4-IgG intravenously. The apparent decrease in CD4 count was eliminated with the use of a single phosphate-buffered saline wash step before the addition of monoclonal antibody. rCD4-IgG can bind to anti-CD4 antibody and lower the measured CD4 cell count in vitro; this interference can be eliminated by a single or a double wash step and is necessary when using the whole-blood lysis flow cytometric technique of enumerating CD4 lymphocytes in patients receiving rCD4-immunoglobulin G.

Secondary T-cell lymphoproliferation after marrow transplantation.

Secondary lymphoproliferative syndromes in immunosuppressed patients have been characterized as polyclonal or monoclonal B-lineage disorders nearly always associated with Epstein-Barr virus (EBV) infection. The authors now report three patients with a distinctly different lymphoproliferative syndrome. Two patients with common acute lymphoblastic leukemia antigen (CALLA) (CD10)-positive acute lymphoblastic leukemia and one patient with acute myelogenous leukemia, respectively, received high-dose chemoradiotherapy followed by marrow transplantation from either an HLA-identical sibling or HLA-mismatched parent. All three patients developed severe graft-versus-host disease (GVHD), requiring immunosuppressive treatment with corticosteroids. A secondary malignant T-cell lymphoproliferation occurred 2, 21, and 43 months, respectively, after marrow transplantation. In all three cases the lymphoid cells expressed T-cell surface antigens and were morphologically and immunophenotypically distinct from the malignant cells present before transplantation. One tumor was of host cell origin, one was probably of donor origin, and the tumor origin in the third case could not be determined. The authors were unable to find any evidence for EBV, human T-cell lymphotropic virus type I or II, human immunodeficiency virus, or human herpesvirus 6.

Idiopathic myelofibrosis in blast transformation with 4;12 and 5;12 translocations and a 7q deletion.

A case of a patient who developed a leukemic transformation following an 8.5-year history of idiopathic myelofibrosis (IMF) with myeloid metaplasia is presented. Surface marker analysis identified the blast cells as myeloid in lineage. The karyotype of unstimulated peripheral blood cells was 46,XY,t(4;12)(q26;15),t(5;12)(q13;q24),del(7)(q22). In the literature, the 7q- has a minor association with IMF, and the t(5;12) translocation has been reported in one case of acute nonlymphocytic leukemia, but neither the t(4;12) nor the combination of these three abnormalities has been reported in IMF.

Analysis of T-cell receptor gene rearrangement in lymph nodes of patients with mycosis fungoides. Prognostic implications.

OBJECTIVE: To determine the prognostic value of analyzing lymph node (LN) DNA from patients with mycosis fungoides for the presence of a monoclonal T-cell population. DESIGN: Inception cohort study. SETTING: A tertiary care referral center in Seattle, Wash. PATIENTS: Fifty-five uniformly staged patients with the diagnosis of mycosis fungoides and who had a lymph node biopsy, 21 with clinically abnormal nodes and 34 with normal nodes. MAIN OUTCOME MEASURES: Lymph nodes were evaluated by Southern blot analysis for T-cell receptor beta-chain (TCRB) gene rearrangement and by histopathologic examination for the LN classification using the National Cancer Institute system. Patients were observed clinically for a mean (+/- SD) of 4.7 +/- 3.4 years. RESULTS: Patients with detectable TCRB gene rearrangement in lymph node DNA had an increased likelihood of a poor clinical outcome and a decreased probability of survival (P < .001 for both) compared with patients with the TCRB germline. Although patients with clinically enlarged nodes were more likely to have the TCRB gene rearranged, those with normal nodes and the TCRB gene rearranged also had a poor clinical outcome and a decreased probability of survival. Similar to those with the TCRB gene rearranged, most patients with advanced histopathologic changes (LN3 and LN4) had a poor prognosis. The presence of a rearranged TCRB gene, however, correctly predicted some patients with intermediate LN scores (LN2) who had a poor clinical outcome. CONCLUSIONS: Detection of a monoclonal T-cell population, as demonstrated by a rearranged TCRB gene on Southern blot analysis, in LNs of patients with mycosis fungoides is predictive of a poor clinical outcome and a reduced probability of survival. Lymph node TCRB gene analysis provides additional prognostic information for patients with mycosis fungoides with intermediate LN histopathology.

Parkinson's disease as multifactorial oxidative neurodegeneration: implications for integrative management.

Parkinson's disease (PD) is the most common movement pathology, severely afflicting dopaminergic neurons within the substantia nigra (SN) along with non-dopaminergic, extra-nigral projection bundles that control circuits for sensory, associative, premotor, and motor pathways. Clinical, experimental, microanatomic, and biochemical evidence suggests PD involves multifactorial, oxidative neurodegeneration, and that levodopa therapy adds to the oxidative burden. The SN is uniquely vulnerable to oxidative damage, having high content of oxidizable dopamine, neuromelanin, polyunsaturated fatty acids, and iron, and relatively low antioxidant complement with high metabolic rate. Oxidative phosphorylation abnormalities impair energetics in the SN mitochondria, also intensifying oxygen free radical generation. These pro-oxidative factors combine within the SN dopaminergic neurons to create extreme vulnerability to oxidative challenge. Epidemiologic studies and long-term tracking of victims of MPTP (1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine) poisoning, suggest oxidative stress compounded by exogenous toxins may trigger the neurodegenerative progression of PD. Rational, integrative management of PD requires: (1) dietary revision, especially to lower calories; (2) rebalancing of essential fatty acid intake away from pro-inflammatory and toward anti-inflammatory prostaglandins; (3) aggressive repletion of glutathione and other nutrient antioxidants and cofactors; (4) energy nutrients acetyl L-carnitine, coenzyme Q10, NADH, and the membrane phospholipid phosphatidylserine (PS), (5) chelation as necessary for heavy metals; and (6) liver P450 detoxification support.