This action might not be possible to undo. Are you sure you want to continue?
To subscribe, visit alternative-therapies.com
The Assessment of the Energy Metabolism in Patients With Chronic Fatigue Syndrome by Serum Fluorescence Emission
Nina Mikirova, PhD; Joseph Casciari, PhD; Ronald Hunninghake, MD AbSTRACT Context • Chronic fatigue syndrome (CFS) is a debilitating fatigue illness that has unknown etiology and lacks an objective diagnostic marker. Objective • To examine the metabolic component of CFS to determine if practitioners can use serum NAD(P)H concentration measurements to monitor metabolism and fatigue status in patients with CFS. Design • The research team conducted a case-control study, comparing a group of patients who were diagnosed with CFS with a control group of healthy subjects. The team obtained venous blood samples from fasting patients to examine the serum NAD(P)H concentrations. Setting • The study occurred at the Riordan Clinic in Witchita, Kansas. Participants • The study included 44 CFS patients at the Riordan Clinic and 30 healthy control participants. The CFS patients presented a spectrum of symptoms that had existed for at least 6 months: new, unexplained, persistent, or relapsing chronic fatigue that bed rest did not resolve and that was severe enough to reduce daily activity significantly—by 50%—in conjunction with headache, muscle pain, pain in multiple joints, and unrefreshing sleep. In the control group, the research team Mina Mikirova, PhD, is the director of research; Joseph Casciari, PhD, is a consultant; and Ronald Hunninghake, MD, is the chief medical officer, Riordan Clinic, Wichita, Kansas Corresponding author: Nina Mikirova: email@example.com Author Disclosure Statement: The authors declare that they have no competing interests. enrolled subjects without diagnosis of disease or injury. Outcome Measures • The research team determined levels of serum reduced nicotinamide adenine dinucleotides (NADH and NAD[P]H) by measuring serum fluorescence emission at 450 nm. The team then conducted sensitivity and specificity analyses. Results • NAD(P)H concentrations in serum of CFS participants averaged 8.0 ± 1.4 (standard deviation [SD]) nmol/mL, while those in the healthy controls averaged 10.8 ± 0.8 (SD) nmol/mL, a statistically significant difference. Using a cut-off concentration of 9.5 nmol/mL, the research team attained a sensitivity of 0.73 and a specificity of 1.0. An analysis of receiver-operator characteristics yielded an area under the curve of 0.9. The research team compared serum NAD(P)H to several endocrine and metabolic lab parameters. Serum NAD(P)H was directly correlated with serum CoQ10 levels and inversely correlated with urine hydroxyhemopyrrolin-2-one levels. Conclusions • Based on these findings, the research team proposed using serum NAD(P)H, measured as an intrinsic serumfluorescence emission, to monitor metabolism and fatigue status in patients with CFS. Following patients’ NAD(P)H levels over time may aid in selecting therapeutic strategies and monitoring treatment outcomes. (Altern Ther Health Med. 2012;18(1):36-40.) ME, ranging from neurological and endocrine dysfunctions to immunological disorders and infections.5 Possible neurological issues include disruptions in hypothalamic-pituitary-adrenal (HPA) response and neurotransmitters, both of which have been associated with CFS.7-9 Many, but not all, CFS patients have prior exposure to the Epstein-Barr virus (EBV).10-18 Other evidence of an immunological component includes increased numbers of activated T-cells, increased cytokine circulation and T-helper cells, and altered natural killer cell activity in patients with CFS.19-33 A number of recent studies suggests that oxidative stress and alterations in mitochondrial function may contribute to CFS.34 For example, one study linked CFS to reduced carnitine levels,35 an indication of compromised mitochondrial function, but researchers have not observed this linkage elsewhere.36 At present, the underlying mechanism for CFS is not known, which makes finding reliable biomarkers for diagnosing it difficult. Markers under study include altered gene expression profiles in leukocytes.37-41 In particular, researchers have identified 12 genes for which mRNA levels change significantly with CFS comAssessing Energy Metabolism in CFS
ong-lasting disabling fatigue characterizes chronic fatigue syndrome (myalgic encephalomyelitis, myalgic encephalopathy, CFS or CFS/ME). The disease includes nonspecific symptoms such as weakness, malaise, subjective fever, sore throat, lymph node pain, and decreased memory.1-4 No conclusive diagnostic tests exist for CFS. Practitioners diagnose it when debilitating fatigue symptoms of the sort listed above occur in the absence of psychiatric disorders, bipolar disorder, substance abuse, morbid obesity, or any untreated or unresolved disease.5,6 Researchers have investigated many potential causes for CFS/
ALTERNATIVE THERAPIES, jan/feb 2012, VOL. 18, NO. 1
VOL. Riordan Clinic’s laboratory performed all other laboratory tests (hemoglobin. nicotinamide. The study considered values of P < . MATERIALS AND METHOD Participants The present study. in conjunction with other contributing molecules.44 The purpose of the current study was to examine the use of levels of serum nicotinamide adenine dinucleotide phosphate-H (NAD[P]H) as a metabolic marker of fatigue state. Medical doctors of the Riordan Clinic diagnosed CFS patients according to the Centers for Disease Control’s criteria (released in 1994.5 mL sulfuric acid in 50 mL of methanol). pain in multiple joints. followed by reaction with Ehrlich’s acid aldehyde reagent (0. excitation scans 315-340 nm. 3-hydroxyanthranilic acid.1 at the excitation wavelength. in conjunction with correlations between serum NADH and other metabolic and endocrine markers. gov/cfs).05 to be statistically significant.45 Previously. For this test. NO. and an unidentified urine metabolite (CFS symptom marker 2). pyridoxal-5-phosphate. The team ran fluorescence spectra using a SPEX spectrofluorometer (sensitivity 4000:1. subjecting it to analysis without further purification. 4-pyridoxic acid.5 g of p-dimethylaminobenzaldehyde. To subscribe. Mikirova et al. Inc. For estimating the effect of different fluorescence components (proteins and coenzymes) on the native serum fluorescence emission. tyrosine. conducted at the Riordan Clinic in Witchita. and (2) specificity = [true negatives] ÷ [true negatives + false positives]. glutamic acid. Illinois). They diluted all specimens by phosphate buffered saline (PBS). using a ratio of 1:20 to measure the emission in the range of absorption less than 0. http://www. EBV. unexplained. the team separated plasma from whole blood by centrifugation and collected CoQ10 using a lipid extraction procedure. 2. a prior study. The equipment detected CoQ10 at 275 nm absorbance maximum by an ultraviolet detector. and nicotinic acid (all ordered from Sigma. California). β-alanine. Missouri). The team separated the serum from the blood by centrifugation at 3500 rpm for 15 minutes. This preparation yields a chromophore with an absorption maximum of 540 nm. the research team compared the emissions of the different fractions of fluorescent serum biomolecules such as NAD(P)H. 18. which separates the extract on a reversed-phase C-18 column using methanol (66%) and hexane (34%) as a mobile phase (flow rate 1 mL/min and injection volume 50 µL). The research team excluded other clinical conditions that may produce similar symptoms by a thorough evaluation based on the appropriate laboratory findings.42 One study43 made an attempt to monitor alterations in metabolism and homeostasis in CFS patients by measuring urine metabolite levels via gas chromatography and mass spectroscopy. To share or copy this article. free T3. please visit copyright. The CFS patients presented a spectrum of symptoms that had existed for at least 6 months: new. The control group consisted of volunteers from the clinic’s staff who had no diagnosis of disease or injury. St Louis. coinciding with the respective absorption and emission of NAD(P)H. muscle pain. Computation of sensitivity and specificity at various NADH cut-offs used the following equations: (1) sensitivity = [true positives] ÷ [true positives + false negatives].0 mL of urine for analysis). Other biochemical Assays The hydroxyhemopyrrolin-2-one (HPL) assay is based on the extraction of pyrroles from urine with chloroform. The study assessed the diagnostic accuracy of coenzyme NAD(P) H levels in terms of true positive (sensitivity) vs true negative (1-specificity) using nonparametric receiver operating characteristics (ROC) analyses). Chicago. After collecting human blood in EDTA-containing tubes. and succinic acid in conjunction with reductions in alanine. presented a 37 ALTERNATIVE THERAPIES.cdc. persistent or relapsing chronic fatigue that bed rest did not resolve and that was severe enough to reduce previous daily activity significantly—by 50%—in conjunction with headache. The team chose excitation-scan wavelengths to exclude protein. Candida albicans) using standard clinical techniques. Serum Fluorescence Emission The research team obtained venous blood samples from fasting participants whom they also asked not to take supplements and medicine for 24 hours before the blood draw. visit alternative-therapies. the team used the HPLC system (Hewlett Packard. L-tryptophan. CFS patients showed increases in amino-hydroxy-n-methylyrrolidine (CFS symptom marker 1). The research team has developed a method of determining NAD(P)H levels based on fluorescence emission of serum at 450 nm. The team measured backAssessing Energy Metabolism in CFS ground curves for the solvent (PBS) and subtracted them from the fluorescence spectra of serum to remove background effects. and emission scans 330-600 nm). kynurinine. and unrefreshing sleep. The team measured standard curves of emission intensity (counts per second) vs the NADH concentration (nmol/mL) to allow conversion of the former to the latter. All participants signed an informed consent that the Riordan Clinic Institutional Review Board approved. To analyze human plasma Q10. 1 .45 The present manuscript details the study’s data on serum NAD(P)H and chronic fatigue. Use ISSN#10786791. aconitic acid. RESULTS Characterization of Serum Fluorescence Emission Irradiation of the serum at wavelengths from 300 nm to 340 nm gave rise to emissions in the 350 nm to 600 nm region. Kansas. a precaution necessary because fluorescence emission from vitamins and drugs can interfere with the assay for serum fluorescence emission. they showed that cancer patients have reduced concentrations of serum NAD(P)H correlating with reported levels of fatigue. Another group has attempted to use the near-infrared spectra of serum to distinguish between CFS patients and healthy people. Pennsylvania).com. jan/feb 2012.46-49 The research team performed curve fitting using Kaleidagraph (Synergy Software. the research team collected random urine samples and added 200 mg to 500 mg of ascorbic acid as a preservative (2. Serum coenzyme Q10 (CoQ10) levels were determined as follows. which produces an intense emission peek at excitation wavelengths around 280 nm. Reading. Santa Clara.This article is protected by copyright. double-grating spectrophotometers. consisted of 44 CFS patients and 30 healthy volunteers. Statistics The research team used the nonparametric Mann-Whitney test to determine the magnitudes of differences between groups (Systat 13.com pared to controls matched for age and gender.
NAD(P)H concentrations in the serum of CFS patients averaged 8. the function of Q10 ultimately is linked to the generation of energy within the cells. L-tryptophan. Relative Frequency Distributions for Concentrations of Reduced Nicotinamide Adenine Dinucleotide (Phosphate) (NAD[P]H) Relative frequency distributions for concentrations of reduced nicotinamide adenine dinucleotide (phosphate) (NAD[P]H) for healthy people (diagonal shading) and patients with chronic fatigue syndrome (CFS) (red shading). NAD(P)H Levels using Fluorescence Emission The research team determined serum NAD(P)H concentrations for 44 participants with CFS and 30 healthy controls. A factor analysis. Pennsylvania) to make calculations.5 would represent no discrimination.8 (SD) nmol/mL.47.45 Figure 1 shows fluorescence emission data for serum in conjunction with the emission of L-tryptophan and NAD(P)H as a function of emission wavelength. free T3 levels were usually normal for CFS patients in this study. Figure 2. The research also compared NAD(P)H concentrations to other endocrine and metabolic parameters. 38 ALTERNATIVE THERAPIES. based on the correlation matrix between all variables given in the table. jan/feb 2012. Comparison of Serum Emissions Tryptophan Serum emission NAD(P)H + tryptophan NAD(P)H Level of Emission (counts/sec) more detailed description of the different fluorescent fractions of serum. An AUC of 1. While some overlap exists between the two groups in the 9 nmol/mL–to–11 nmol/mL range. To subscribe. most of the control participants had NAD(P)H levels above 10 nmol/mL while most participants with CFS had NADH levels below 10 nmol/mL. At a NAD(P)H cut-off of 9.5 nmol/mL. Data are fit to a Gaussian curve (y = M exp (-(x-α)2/β2). 1 . 18. Figure 3 shows the sensitivity and selectivity of NAD(P)H in matching CFS patients to controls.This article is protected by copyright. for example. EBV and Candida antibodies in CFS patients were well beyond the normal range.5. and urine HPL (r = 0. To share or copy this article. At this range of emission wavelengths.05). while an AUC of 0. VOL.9. On average.0 would represent perfect discrimination (between CFS and controls). That study also described the procedure for calculation of the contribution from different fractions of serum at the concentrations that they would have in serum in a total serum emission. State College. and their sum.8 ± 0.73 and the specificity is 1.4 (SD) nmol/mL while those in healthy controls averaged 10. The Table shows how averages for patients with CFS compare to normal ranges for each parameter. As CoQ10 is the component of a complex series of reactions that occur within mitochondria. A ROC analysis (inset in Figure 3) yields an area under the curve (AUC) of 0. DISCUSSION The measurement of fluorescence of NAD(P)H in serum provides a noninvasive assay to estimate metabolism and fatigue levels in CFS patients. In contrast.0.001). the research team used a program of Watkins MW (Ed & Psych Associates.5 nmol/mL. the research team took future readings at the emission wavelength of 450 nm. P < . please visit copyright.45 To isolate NAD(P)H to the largest extent possible. The correlation between the lower level of CoQ10 and lower NAD(P)H signals for patients with CFS suggests lower bioenergetics for them. visit alternative-therapies.com. Figure 2 shows frequency distributions for NAD(P)H concentration in CFS patients and healthy controls. Use ISSN#10786791. the sensitivity is 0. consistent with the idea of an infection component to CFS. The analysis found an inverse correlation between the level of serum emission and the level of HPL in urine.com Figure 1. adding the L-tryptophan and NAD(P)H signals can account for the serum signal. serum CoQ 10 (r = 0.03). NO. P < .0 ± 1. NAD(P)H concentrations were significantly Assessing Energy Metabolism in CFS wavelength Comparison of serum emissions (excitation: 300-340 nm) to those of nicotinamide adenine dinucleotide phosphate-H (NAD[P]H). For ROC analysis. The graphic uses interval widths of 0. demonstrated that the best correlations were between the emission of NAD(P)H. Figure 4 shows distributions of CoQ10 and HPL for high and low levels of NAD(P) H in serum. a statistically significant difference (P < .
These correlations are instructive because all three variables can be thought of as metabolic markers. y axis.8 1.0 ± 0. VOL.8 ± 1.4 ± 0. hematocrit. unstable hemoglobin.49-51 HPL is from a subclass of monopyrroles. on the other hand. NO.43 which the researchers based on a comparison of the CFS urinary marker 1 with neuroactive drug 3-amino-1-hydroxypyrrolidin-2-one (which alters 39 ALTERNATIVE THERAPIES. the analysis of the metabolites excreted in urine of CFS patents demonstrated that the best moleAssessing Energy Metabolism in CFS Laboratory test parameters and NAD(P)H concentrations for patients with CFS (mean ± standard deviation [SD] given) compared with normal ranges. It is likely that decreases in serum NAD(P)H and CoQ10 both indicate lower bioenergetics in CFS patients’ cells. etc) but do correlate with CoQ10 (positive correlation) and urine HPL (negative correlation). Lines represent medians. HPL. sensitivity) for the data set. NAD(P)H.5 12.2 20 ± 24 Low-Normal 9. Abbreviations: NAD(P)H. Comparison of the Average Test Values With Normal Rangea Parameter NAD(P)H (nm) Free T3 (pg/mL) Q10 (µg/mL) EBV early IgG (AU) Candida IgG (EU) Candida IgM (EU) Candida IgA (EU) Hemoglobin HPL (µg/dL) a CFS Mean (SD) 8.8 ± 1.2 1. chronic fatigue syndrome. please visit copyright.com.com Figure 3. 18.5 16 10 lower in CFS patients compared to healthy controls. To share or copy this article. Curve fits are to a sigmoid (y = α + (β – α)/(1 + (x/γ)τ).6 50 ± 54 33 ± 18 22 ± 11 28 ± 18 13.3 0 0 0 0 12 0 High-Normal 12. The insert represents an ROC curve (x axis.3 3.1 20 12. Table. well-known for biotoxicity. visit alternative-therapies. 1 – specificity. The structure of this metabolite is similar to the HPL metabolite in urine that the current study measured in CFS patients. Abbreviations: CFS. receiver operating characteristic.43 According to this study. In the case of NADH. the normal range is ±2 SD from the control group’s mean. hydroxyhemopyrrolin-2-one. and elevated HPL excretion classically is associated with emotional stress. white blood cell counts.0 nmol/ml. The study. CoQ10 is essential for adenosine-5’-triphosphate production. reduced nicotinamide adenine dinucleotide (phosphate).4 2. NAD(P)H concentrations determined from serum fluorescence did not correlate with typical complete blood-count parameters (red blood cell [RBC] counts. and boxes represent first to third quartile. jan/feb 2012.This article is protected by copyright. Since heme is tightly coupled to neuronal metabolic activity. hemoglobin. ROC. EBV.4 1. Sensitivity (Detection of Positives) and Specificity (Nondetection of Negatives) Figure 4. hydroxyhemopyrrolin-2-one. ROC analysis demonstrated the sensitivity and specificity of using NAD(P)H levels to distinguish between CFS and control groups. and RBC hemolysis). and it exists in mitochondria in quantities 10-fold greater than those of other redox components. cule for separation of this state was aminohydro-N-methylpyrrolidine (referred as CFS urinary marker 1).5 12. HPL.4 3. Epstein-Barr virus. heme depression may decrease neuronal activity.51 Urine HPL may result from aberrations in porphyrin metabolism (as in conditions such as iron deficiency. To subscribe. Distributions of Coenzyme Q10 and Hydroxyhemopyrrolin-2-one for high and low levels of NAD(P)H in serum CoQ10 (ug/mL) or log HPL (ug/dL) CoQ10 (NAD[P]H < 9) CoQ10 (NAD[P]H > 9) HPL (NAD[P]H < 9) HPL (NAD[P]H > 9) Distributions of coenzyme Q10 and HPL in subjects with serum NAD(P)H concentrations above or below 9. This figure plots sensitivity (detection of positives) and specificity (nondetection of negatives) against the NAD(P)H concentration cut-off (nmol/ mL). Use ISSN#10786791. moreover. nicotinamide adenine dinucleotide phosphate-H. A study by McGregor et al found measurements for metabolites in the urine of CFS patients that support the current study’s data. reduced nicotinamide adenine dinucleotide (phosphate). is often elevated in patients with mental illness. 1 . Abbreviations: HPL. NAD(P)H.
van der Meer JW. Functional capacity evaluations of persons with chronic fatigue immune dysfunction syndrome. in cancer). 1996. Doria A. Morgan R. Biochem Biophys Res Commun. Vernon SD. Lasko TA. 17. J Immunol. Mikirova NA. 2007. McClish DK. Orthomolecular Psychiatry: Treatment of Schizophrenia. Working Group of the Royal Australasian College of Physicians. Manian FA. Holgate S. J Orthomol Med. 2003. Kitani T. Spectroscopic diagnosis of chronic fatigue syndrome by visible and near-infrared spectroscopy in serum samples. et al. Bleijenberg G. Galama JM.49(4):327-337. et al.23(3):327-337. Barrows DM.33(6):16601661. Amital H. Butt HL. Saiki T. 2005. Caligiuri M. J Med Virol. Zhou XH. Botta GA.139(10):3306-3313. Vernon SD. 1996. In these cancer patients. Tanaka M. Soetekouw PM. 2007. Wagner D. Bertoni G. Immunologic abnormalities associated with chronic fatigue syndrome. Vázquez Rodríguez JJ. NMDA receptor antagonists that bind to the strychnine-insensitive glycine site and inhibit NMDA-induced Ca2+ fluxes and [3H]GABA release. Wessely S. 46.7:81. et al. 2009. Rajeevan M. Circulation.933:185-200. Behav Brain Funct. 29. concluded that compounds with this structure may change the neuron metabolism or receptor function and may alter excitatory/inhibitory neurotransmission. Clin Diagn Lab Immunol. Levy JA. 2006. 48. Mangano TJ. 34. San Francisco. Zou KH. 42. Pellett PE.This article is protected by copyright.5(5):e10817. J Clin Microbiol. Kurata T. Colle R. Mawle AC. Hoboken. fatigue is one of the debilitating side effects of cancer and its treatment. Serum level of carnitine in chronic fatigue syndrome: clinical correlates. et al. Reeves WC.14(2):40-60. Hickie I. An Med Interna. Cytokines and chronic fatigue syndrome. 2000. but the etiology was different. Black JB. 35. 3. Patarca R. 14. Isr Med Assoc J. 16. Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case control study. Levy JA.38(7):587-590. Pérez Martín A. Kuratsune H. Unger ER. Huang LC. clinical. To share or copy this article. 1987. Mauri L. Plioplys AV. Ponzio NM. Miller RJ. Evidence of inflammatory immune signaling in chronic fatigue syndrome: a pilot study of gene expression in peripheral blood. Lennette ET. Following patients’ NAD(P)H levels over time may aid in selecting therapeutic strategies and monitoring treatment outcomes.28(6):1403-1410. Lin JM. Meiners BA.7:46. 22. J Transl Med. Clin Exp Allergy. Maher KJ. Microbiol Immunol. Reeves WC. Normal carnitine level in patients with chronic fatigue syndrome. Richards SC. Antibody responses to EpsteinBarr virus. 1990. 2005.55(2):79-90. Ann N Y Acad Sci. In: Jason LA. Riordan HD. Clin Infect Dis. 2002. Aspler AL. 36. Maher K. Clin Infect Dis. 50. 7. Dimulescu IM. jan/feb 2012. 41. 2005. Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. J Biomed Inform. Reeves WC. 40. PLoS ONE. et al. Immunological aspects of chronic fatigue syndrome. et al. Landay AL.20(5):1390-1392. Nisenbaum R. 2003.8(4):287-291.10(1):3-7.18(4):193-199. Bolshin C. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. please visit copyright. visit alternative-therapies. McGregor NR. Fletcher MA. Stamey FR. Statistical Methods in Diagnostic Medicine. Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26.31(1):48-52. Chronic fatigue syndrome: characteristics and possible causes for its pathogenesis.23(5):238-244. diagnosis and treatment. NJ: John Wiley & Sons. Dis Markers.338(8769):707-712. 2008.38(5):404-415. Lancet. Redox Rep. Josephs SF. Jessop C. BMC Med. In addition. The discovery of kryptopyrrole and its importance in diagnosis of biochemical imbalances in schizophrenia and in criminal behavior. Vreken P. 20. Klimas NG. Chronic fatigue syndrome is associated with diminished intracellular perforin. Brain Behav Immun.9(4):747-52. Intervirology. 43. 44. Fear D. NO. 1 Assessing Energy Metabolism in CFS . Chronic fatigue syndrome.18(Suppl 1):S136-S141. 2011. Eur J Pharmacol.38(5):269-273. Dobbins JG. Fukuda K. Peakman M. Roberts TK. Pearlman T. Lin E.1995. Chronic fatigue syndrome—a clinically empirical approach to its definition and study. Dunstan RH. REFERENCES 1. 1994. 53. 1995. Yamaguchi K. Roberts TK. Fennel PA. 47. Mikhaylova SV. Clin Infect Dis. and epidemiologic data to characterize chronic fatigue syndrome. 21. Mawle AC. López Rodríguez M. 2005. Hoffer A. Izquierdo Martínez M. Eur J Pharmacol. Detection of energy metabolism level in cancer patients by fluorescence emission from serum. 2010. 2008. 2000.160(2):221-236. Yamanishi K. Shoenfeld Y. 2002.121(12):953-959. Nisenbaum R. 2002.115:654-657. et al. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. For cancer patients who complain of fatigue and exhaustion. Obuchowski NA. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample.33(10):1450-1456.166(3):393-400. Natelson BH. and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response? Clin Infect Dis.9(Suppl 1):S1. Taylor RR. 4. Ann Intern Med. Tachibana Y. England: Royal College of General Practitioners.19(3):448-453. Shaw EJ. Clin Infect Dis. Ohno-Machado L. Am J Occup Ther. Broderick G. VOL. 1995. Lancet. Utility of the blood for gene expression profiling and biomarker discovery in chronic fatigue syndrome. Ngonga GK. 1989. Mizuno K. Yamaguti K. BMC Psychiatry. Biochem Mol Med. et al. herpes simplex virus types 1 and 2. Walch WJ. J Psychosom Res. et al. McGregor NR. 2003. Lorusso L. Discerning the mauve factor. Identification of marker genes for differential diagnosis of chronic fatigue syndrome. Landay AL. Barclay W. Immunologic abnormalities of chronic fatigue syndrome. Butt HL. 1995. Fennis JF. Vercoulen JH. Reeves WC.53). The chronic fatigue syndrome: a comprehensive approach to its definition and study. Harris KM. Immunology. et al. Plioplys S. 25. Kryptopyrrole in molecular psychiatry. 49. Mirandola P. Henry N. Fujimura SF. Wevers RA. 18. Amital D. Sakudo A. Clinical practice guidelines—2002. Chronic fatigue syndrome: a review.com neurotransmitter activity and HPA axis52.17(3):1256-1265. eds. 52. Med J Aust. Simultaneous measurement of antibodies to Epstein-Barr virus. Pauling L.32(3):132-138. Kith P. et al. the team’s previous studies demonstrated that medical practitioners can use the same procedure for the evaluation of the level of fatigue in other pathological conditions (eg. Chronic fatigue syndrome: aetiology. up-regulated in the leucocytes of chronic fatigue syndrome patients. Part 1. London. Powell R. Fletcher MA. 2008. et al. Fletcher MA. 2008. 1995. HA-966 acts at a modulatory glycine site to inhibit N-methyl-D-aspartate-evoked neurotransmitter release. 2003:124-151. Fletcher MA. Autoimmun Rev. Whistler T. 2000.337(8753):1346-1347. 32.18(1):9-24. 1973:146-178. Keith RA.com. Iwine DG. Gene expression in peripheral blood mononuclear cells from patients with chronic fatigue syndrome. 27. Chronic fatigue syndrome: clinical condition associated with immune activation. Murray C. Di Luca D. HHV-6 reactivation in chronic fatigue syndrome. Zou KH.3:19. Ferrari D.142(3):505-511. Komaroff AL. 19. suggesting anemia as a cause. Integration of gene expression. The research team recommends future studies with more participants and with participants being followed over time. Lewith G. Neuropsychobiology.10(1):79-82. 1995. Hsu SY. Gómez Cerezo J. CA: WH Freeman and Company. 2003. Swanink CM. Klimas NG. Klimas NG. Balachandran N. 6. 1991.21(6):1386-1389. Am J Psychiatry. Preliminary determinations of a molecular basis to chronic fatigue syndrome. Ricevuti G. Kawai T. 2002. Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome. 2001. Tajima S. Barker E. 40 ALTERNATIVE THERAPIES. Kobayashi T. 8.176(Suppl):S23-S56. 9. CONCLUSION As a result of the current study. 37. 2006.4:44. 13. Yamanishi K. 12.50(1):25-30. Seroepidemiology of chronic fatigue syndrome: a case-control study. reduced NAD(P)H correlated with reduced RBC counts and hemoglobin. Lyall M. Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay. Evidence for the presence of immune dysfunction in chronic fatigue syndrome. eds. To subscribe. Identification of novel expressed sequences. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.57(2):73-80. NY: Wiley & Sons.45 For cancer patients. 33. human herpesvirus 6. A comparison of classification methods for predicting Chronic Fatigue Syndrome based on genetic data. International Chronic Fatigue Syndrome Study Group. J Orthomol Med. New York. the research team proposes that medical doctors can use serum NAD(P)H concentration measurements to evaluate and monitor fatigue level and metabolic slowdown in CFS patients.58(8):826-832. NeuroImage. Reynolds IJ.14(9-10):599-607. Zebbes M. The chronic fatigue syndrome and its diagnosis in internal medicine [article in Spanish]. Capelli E. In: Hawkins D. Audhya T. 39. Fadem MB. Sharpe MC. Maher K. Afari N. 18. Bhagwat JG.345(4):1513-1516.57(1):20-24. 38. Morita K. Buchwald D. Behav Brain Funct. Sairenji T. Vernon SD. J Clin Microbiol. 30. O’Malley AJ. Stewart JA. Yamaguti K. et al. Lindh G. Salvato FR. 24. Watanabe Y. Clin Exp Immunol. Bassi N. Unger ER. McGinnis WR. The use of receiver operating characteristic curves in biomedical informatics.172(1):9-17. Straus SE. 1995. 26. Avellaneda Fernández A. Handbook of Chronic Fatigue. 2009. 15. et al. Kuratsune H. Baker R. 1989. A systematic review and critical evaluation of the immunology of chronic fatigue syndrome. Dunstan RH. 2. Richards RS. J Transl Med. Use ISSN#10786791. Altern Ther Health Med. 1994. Klineberg IJ. Autonomic nervous alterations associated with daily level of fatigue. Turnbull N. Buchwald D. 28.5(1):35-41. human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome. Ashley RL. 2003. Buchwald D. Almond J. Mol Med. 10. Dobbins JG. Ren J. Kaushik N. 51. 1991. Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome. Haghighi MH. Kuratsune H. Zeng XR. Neth J Med. Cassai E. the research team found that the level of NAD(P)H in serum was lower than the normal range. 2002. Yalcin S. J Clin Pathol. 23. Ikuta K. 2009. 31. 45. 1994. 5. Raison CL. Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Barbado Hernández F. Komaroff A. 2009. Zorzenon M. 1994.1(1):10. Rillema P. 11. Nisenbaum R. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy) in Adults and Children.
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue listening from where you left off, or restart the preview.