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Chronic Fatigue Syndrome: HELP
Articles from Bangkok
Based on 25 articles published since 2010
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These are the 25 published articles about Fatigue Syndrome, Chronic that originated from Bangkok during 2010-2020.
 
+ Citations + Abstracts
1 Editorial Is a diagnostic blood test for chronic fatigue syndrome on the horizon? 2019

Maes, Michael / Rodriguez, Laura Andres / Morris, Gerwyn. ·Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. · Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. · IMPACT Strategic Research Center, Deakin University, Geelong, Australia. · Group of Psychological Research in Fibromyalgia & Chronic Pain (AGORA), Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain. ·Expert Rev Mol Diagn · Pubmed #31617771.

ABSTRACT: -- No abstract --

2 Review Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities. 2019

Chaves-Filho, Adriano José Maia / Macedo, Danielle S / de Lucena, David Freitas / Maes, Michael. ·Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil. Electronic address: adrianoafilho@hotmail.com. · Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil. Electronic address: daniellesilmacedo@gmail.com. · Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil. Electronic address: daviddelucena@me.com. · Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; IMPACT Strategic Research Center, Deakin University, Geelong, Australia. Electronic address: dr.michaelmaes@hotmail.com. ·Behav Brain Res · Pubmed #31136774.

ABSTRACT: In 2011, it was reviewed that a) there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS; and b) the comorbidity between both disorders may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies, which are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicates that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and especially activated microglia underpin comorbid depression and CFS. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

3 Review Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop? 2019

Morris, Gerwyn / Maes, Michael / Berk, Michael / Puri, Basant K. ·IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, Victoria, Australia. · Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. · Department of Psychiatry, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. · Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia. · Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Victoria, Australia. · Department of Medicine, Imperial College London, Hammersmith Hospital, London, England, W12 0HS, UK. basant.puri@imperial.ac.uk. ·Metab Brain Dis · Pubmed #30758706.

ABSTRACT: A model of the development and progression of chronic fatigue syndrome (myalgic encephalomyelitis), the aetiology of which is currently unknown, is put forward, starting with a consideration of the post-infection role of damage-associated molecular patterns and the development of chronic inflammatory, oxidative and nitrosative stress in genetically predisposed individuals. The consequences are detailed, including the role of increased intestinal permeability and the translocation of commensal antigens into the circulation, and the development of dysautonomia, neuroinflammation, and neurocognitive and neuroimaging abnormalities. Increasing levels of such stress and the switch to immune and metabolic downregulation are detailed next in relation to the advent of hypernitrosylation, impaired mitochondrial performance, immune suppression, cellular hibernation, endotoxin tolerance and sirtuin 1 activation. The role of chronic stress and the development of endotoxin tolerance via indoleamine 2,3-dioxygenase upregulation and the characteristics of neutrophils, monocytes, macrophages and T cells, including regulatory T cells, in endotoxin tolerance are detailed next. Finally, it is shown how the immune and metabolic abnormalities of chronic fatigue syndrome can be explained by endotoxin tolerance, thus completing the model.

4 Review Recognizing the Leaky Gut as a Trans-diagnostic Target for Neuroimmune Disorders Using Clinical Chemistry and Molecular Immunology Assays. 2018

Simeonova, Denitsa / Ivanovska, Mariya / Murdjeva, Mariana / Carvalho, Andre F / Maes, Michael. ·Department of Psychiatry and Medical Psychology, Medical Faculty, Medical University of Plovdiv, Plovdiv, Bulgaria. · Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University of Plovdiv, Plovdiv, Bulgaria. · Department of Psychiatry, University of Toronto, Toronto, ON, Canada. · Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada. · Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. ·Curr Top Med Chem · Pubmed #30430944.

ABSTRACT: BACKGROUND: Increased intestinal permeability with heightened translocation of Gramnegative bacteria, also known as "leaky gut", is associated with the pathophysiology of neuroimmune disorders, such as Major Depressive Disorder (MDD), Chronic Fatigue Syndrome (CSF) and (deficit) schizophrenia, as well as with general medical disorders, including irritable bowel syndrome. This review aims to summarize clinical biochemistry and molecular immunology tests that may aid in the recognition of leaky gut in clinical practice. METHODS: We searched online libraries, including PubMed/MEDLINE, Google Scholar and Scopus, with the key words "diagnosis" or "biomarkers" and "leaky gut", "bacterial translocation", and "intestinal permeability" and focused on papers describing tests that may aid in the clinical recognition of leaky gut. RESULTS: To evaluate tight junction barrier integrity, serum IgG/IgA/IgM responses to occludin and zonulin and IgA responses to actomyosin should be evaluated. The presence of cytotoxic bacterial products in serum can be evaluated using IgA/IgM responses to sonicated samples of common Gram-negative gut commensal bacteria and assays of serum lipopolysaccharides (LPSs) and other bacterial toxins, including cytolethal distenting toxin, subunit B. Major factors associated with increased gut permeability, including gut dysbiosis and yeast overgrowth, use of NSAIDs and alcohol, food hypersensitivities (IgE-mediated), food intolerances (IgG-mediated), small bacterial overgrowth (SIBO), systemic inflammation, psychosocial stressors, some infections (e.g., HIV) and dietary patterns, should be assessed. Stool samples can be used to assay gut dysbiosis, gut inflammation and decreased mucosal defenses using assays of fecal growth of bacteria, yeast and fungi and stool assays of calprotectin, secretory IgA, β-defensin, α- antitrypsin, lysozyme and lactoferrin. Blood and breath tests should be used to exclude common causes of increased gut permeability, namely, food hypersensitivities and intolerances, SIBO, lactose intolerance and fructose malabsorption. DISCUSSION: Here, we propose strategies to recognize "leaky gut" in a clinical setting using the most adequate clinical chemistry and molecular immunology assays.

5 Review Hypothalamic-Pituitary-Adrenal Hypofunction in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) as a Consequence of Activated Immune-Inflammatory and Oxidative and Nitrosative Pathways. 2017

Morris, Gerwyn / Anderson, George / Maes, Michael. ·Tir Na Nog, Bryn Road seaside 87, Llanelli, Wales, SA152LW, UK. · CRC Scotland & London, Eccleston Square, London, UK. · IMPACT Strategic Research Centre, School of Medicine and Barwon Health, Deakin University, Geelong, VIC, Australia. dr.michaelmaes@hotmail.com. · Health Sciences Postgraduate Program, State University of Londrina, Londrina, Paraná, Brazil. dr.michaelmaes@hotmail.com. · Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com. · Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria. dr.michaelmaes@hotmail.com. ·Mol Neurobiol · Pubmed #27766535.

ABSTRACT: There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). There is also evidence that these neuroimmune diseases are accompanied by hypothalamic-pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline glucocorticoid levels. This paper aims to review the bidirectional communications between immune-inflammatory and O&NS pathways and HPA axis hypoactivity in ME/CFS, considering two possibilities: (a) Activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms, or (b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPA axis hypoactivity. Electronic databases, i.e., PUBMED, Scopus, and Google Scholar, were used as sources for this narrative review by using keywords CFS, ME, cortisol, ACTH, CRH, HPA axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, and O&NS. Findings show that activation of immune-inflammatory and O&NS pathways in ME/CFS are probably not secondary to HPA axis hypoactivity and that activation of these pathways may underpin HPA axis hypofunction in ME/CFS. Mechanistic explanations comprise increased levels of tumor necrosis factor-α, T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-β, elevated levels of nitric oxide, and viral/bacterial-mediated mechanisms. HPA axis hypoactivity in ME/CFS is most likely a consequence and not a cause of a wide variety of activated immune-inflammatory and O&NS pathways in that illness.

6 Review Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome. 2017

Morris, Gerwyn / Berk, Michael / Klein, Hans / Walder, Ken / Galecki, Piotr / Maes, Michael. ·Tir Na Nog, Bryn Road seaside 87, Llanelli, SA152LW, Wales, UK. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 291, Geelong, 3220, Australia. · Orygen Youth Health Research Centre and the Centre of Youth Mental Health, Poplar Road 35, Parkville, 3052, Australia. · The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Royal Parade 30, Parkville, 3052, Australia. · Department of Psychiatry, Royal Melbourne Hospital, University of Melbourne, Level 1 North, Main Block, Parkville, 3052, Australia. · Department of Psychiatry, University of Groningen, UMCG, Groningen, The Netherlands. · Metabolic Research Unit, School of Medicine, Deakin University, Waurn Ponds, Australia. · Department of Adult Psychiatry, Medical University of Lodz, Łódź, Poland. · Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com. · Department of Psychiatry, Faculty of Medicine, State University of Londrina, Londrina, Brazil. dr.michaelmaes@hotmail.com. · Department of Psychiatry, Medical University Plovdiv, Plovdiv, Bulgaria. dr.michaelmaes@hotmail.com. · Revitalis, Waalre, The Netherlands. dr.michaelmaes@hotmail.com. · IMPACT Strategic Research Center, Barwon Health, Deakin University, Geelong, VIC, Australia. dr.michaelmaes@hotmail.com. ·Mol Neurobiol · Pubmed #27339878.

ABSTRACT: Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function. However, in an environment of chronic oxidative and nitrosative stress (O&NS), nitrosylation of crucial cysteine groups within key enzymes of the thioredoxin, glutathione, and pyridoxine systems leads to their inactivation thereby disabling denitrosylation and transnitrosylation and subsequently a state described as "hypernitrosylation." This state leads to the development of pathology in multiple domains such as the inhibition of enzymes of the electron transport chain, decreased mitochondrial function, and altered conformation of proteins and amino acids leading to loss of immune tolerance and development of autoimmunity. Hypernitrosylation also leads to altered function or inactivation of proteins involved in the regulation of apoptosis, autophagy, proteomic degradation, transcription factor activity, immune-inflammatory pathways, energy production, and neural function and survival. Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis. In those disorders, increased bacterial translocation may drive hypernitrosylation and autoimmune responses against nitrosylated proteins.

7 Review The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. 2016

Morris, Gerwyn / Berk, Michael / Walder, Ken / Maes, Michael. ·Tir Na Nog, Bryn Road seaside 87, Llanelli, SA15 2LW, Wales, UK. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia. · Orygen, The National Centre of Excellence in Youth Mental Health, Department of Psychiatry and The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Australia. · Centre for Molecular and Medical Research, School of Medicine, Deakin University, Geelong, Australia. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia. dr.michaelmaes@hotmail.com. · Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com. ·Mol Neurobiol · Pubmed #26081141.

ABSTRACT: Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

8 Review The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases. 2016

Morris, Gerwyn / Berk, Michael / Galecki, Piotr / Walder, Ken / Maes, Michael. ·Tir Na Nog, Bryn Road seaside 87, Llanelli, SA152LW, Wales, UK. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 291, Geelong, 3220, Australia. · Orygen Youth Health Research Centre and the Centre of Youth Mental Health, Poplar Road 35, Parkville, 3052, Australia. · The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Royal Parade 30, Parkville, 3052, Australia. · Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, 3052, Australia. · Department of Adult Psychiatry, Medical University of Lodz, Lodz, Poland. · Metabolic Research Unit, Deakin University, Geelong, Australia. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, P.O. Box 291, Geelong, 3220, Australia. dr.michaelmaes@hotmail.com. · Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com. · Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil. dr.michaelmaes@hotmail.com. · Impact Strategic Research Center, Deakin University, Geelong, Australia. dr.michaelmaes@hotmail.com. ·Mol Neurobiol · Pubmed #25598355.

ABSTRACT: Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

9 Review Inflammatory and oxidative and nitrosative stress cascades as new drug targets in myalgic encephalomyelitis and chronic fatigue syndrome. 2013

Maes, Michael. ·Maes Clinics @ TRIA, Piyavate Hospital, Bangkok, Thailand. ·Mod Trends Pharmacopsychiatry · Pubmed #25224898.

ABSTRACT: Myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS) and chronic fatigue (CF) are distinct diagnostic categories with regard to clinical symptoms, severity of illness and biomarkers. Patients with ME and CFS show higher scores on fatigue, neurocognitive disorders, hyperalgesia, autonomic symptoms, postexertional malaise and a subjective feeling of infection than patients with CF. ME is characterized by increased postexertional malaise, a subjective feeling of infection and neurocognitive disorders and is a more severe variant than CFS. Fukuda's 1994 CDC criteria are adequate to make a distinction between patients with ME/CFS and CF, while ME/CFS patients should be subdivided into those with and without postexertional malaise into ME and CFS, respectively. Different interrelated pathophysiological mechanisms play a role in ME/CFS, i.e. (1) inflammation and immune activation, (2) oxidative and nitrosative stress and lowered antioxidant defenses, (3) activation of cell signaling networks, e.g. nuclear factor ĸβ, the 2 9 ,5 9 -oligoadenylate/RNase-L and/or protein kinase R pathway, (4) a transition towards autoimmune reactions, and (5) bacterial translocation. The inflammatory biomarkers are higher in ME/CFS than in CF and higher in ME than in CFS. The above-mentioned pathways may explain the onset of characteristic ME/CFS symptoms, such as fatigue, malaise, autonomic symptoms, hyperalgesia, and neurocognitive symptoms. Different etiological factors may trigger ME/CFS/CF, e.g. viral and bacterial infections, and (auto)immune and inflammatory disorders, while psychosocial and physical stressors act as modulating factors. New pathophysiologically driven drug candidates for ME and CFS are discussed which target the pathways that play a role in ME/CFS.

10 Review Molecular mechanisms underpinning laser printer and photocopier induced symptoms, including chronic fatigue syndrome and respiratory tract hyperresponsiveness: pharmacological treatment with cinnamon and hydrogen. 2013

Lucas, Kurt / Maes, Michael. ·Free Inventor, Sportzenkoppel 54, 22359 Hamburg, Germany. · Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand. ·Neuro Endocrinol Lett · Pubmed #24522022.

ABSTRACT: Emissions of laser printers and photocopiers (LP&P) may be associated with health problems. The aim of this review is to describe the clinical picture that is triggered by exposure to LP&P and the molecular mechanisms underpinning the symptoms. Exposure to LP&P to vulnerable subjects may cause a symptom complex consisting of 1) irritation and hyperresponsiveness of the upper and lower respiratory tract; and 2) chronic fatigue (syndrome, CFS). Symptoms occur within hours after L&P exposure and may last for some days or become chronic with exacerbations following LP&P exposure. Substances that can be found in toners or are generated during the printing process are Silica nanoparticles, Titanium Dioxide nanoparticles, Carbon Black, metals, ozone, volatile organic compounds (VOC), etc. The latter may generate oxidative and nitrosative stress (O&NS), damage-associated molecular patterns molecules, pulmonary and systemic inflammation, and modulate Toll Like Receptor 4 (TRL4)‑related mechanisms. It is concluded that LP&P emissions may cause activation of the TLR4 Radical Cycle and thus be associated with the onset of chronic inflammatory and O&NS illnesses, such as CFS, in some vulnerable individuals. Cinnamon, an antagonist of the TLR4 complex, and Hydrogen, a potent antiinflammatory and oxygen radical scavenger, may have efficacy treating LP&P-induced illness.

11 Review An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways. 2011

Maes, Michael. ·Maes Clinics @ TRIA, 998 Rimklongsamsen Road, Bangkok 10310, Thailand. dr.michaelmaes@hotmail.com ·Prog Neuropsychopharmacol Biol Psychiatry · Pubmed #20609377.

ABSTRACT: There is a significant 'comorbidity' between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2'-5' oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS. Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways. Depression and ME/CFS are not 'comorbid' disorders, but should be regarded as 'co-associated disorders' that are clinical manifestations of shared pathways.

12 Review Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways. 2010

Maes, Michael / Twisk, Frank N M. ·Maes Clinics @ TRIA, Piyavate Hospital, Bangkok, Thailand. crc.mh@telenet.be ·BMC Med · Pubmed #20550693.

ABSTRACT: BACKGROUND: In a recently published paper, Harvey and Wessely put forward a 'biopsychosocial' explanatory model for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is proposed to be applicable to (chronic) fatigue even when apparent medical causes are present. METHODS: Here, we review the model proposed by Harvey and Wessely, which is the rationale for behaviourally oriented interventions, such as cognitive behaviour therapy (CBT) and graded exercise therapy (GET), and compare this model with a biological model, in which inflammatory, immune, oxidative and nitrosative (IO&NS) pathways are key elements. DISCUSSION: Although human and animal studies have established that the pathophysiology of ME/CFS includes IO&NS pathways, these abnormalities are not included in the model proposed by Harvey and Wessely. Activation of IO&NS pathways is known to induce fatigue and somatic (F&S) symptoms and can be induced or maintained by viral and bacterial infections, physical and psychosocial stressors, or organic disorders such as (auto)immune disorders. Studies have shown that ME/CFS and major depression are both clinical manifestations of shared IO&NS pathways, and that both disorders can be discriminated by specific symptoms and unshared or differentiating pathways. Interventions with CBT/GET are potentially harmful for many patients with ME/CFS, since the underlying pathophysiological abnormalities may be intensified by physical stressors. CONCLUSIONS: In contrast to Harvey and Wessely's (bio)psychosocial model for ME/CFS a bio(psychosocial) model based upon IO&NS abnormalities is likely more appropriate to this complex disorder. In clinical practice, we suggest physicians should also explore the IO&NS pathophysiology by applying laboratory tests that examine the pathways involved.

13 Article International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact of air pollution on patients with AR: Current knowledge and future strategies. 2020

Naclerio, Robert / Ansotegui, Ignacio J / Bousquet, Jean / Canonica, G Walter / D'Amato, Gennaro / Rosario, Nelson / Pawankar, Ruby / Peden, David / Bergmann, Karl-Christian / Bielory, Leonard / Caraballo, Luis / Cecchi, Lorenzo / Cepeda, S Alfonso M / Chong Neto, Herberto José / Galán, Carmen / Gonzalez Diaz, Sandra N / Idriss, Samar / Popov, Todor / Ramon, German D / Ridolo, Erminia / Rottem, Menachem / Songnuan, Wisuwat / Rouadi, Philip. ·Johns Hopkins School of Medicine, Baltimore, MD, USA. · Department of Allergy & Immunology, Hospital Quironsalud Bizkaia- Bilbao, Spain. · INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, France. · University Versailles St-Quentin-en-Yvelines, France. · Allergy-Centre-Charité, Charité-Universita¨tsmedizin Berlin, Berlin, Germany. · Humanitas University & Research Hospital, Milano, Italy. · Division of Respiratory and Allergic Diseases, High Specialty Hospital A. Cardarelli, Napoli, Italy; School of Specialization in Respiratory Diseases University Federico II Naples, Italy. · Pediatric Respiratory Medicine Division, Complexo Hospital de Clinicas, UFPR, Curitiba, Brazil. · Dept. of Pediatrics, Nippon Medical School, Tokyo, Japan. · UNC Center for Environmental Medicine, Asthma, and Lung Biology; Division of Allergy, Immunology and Rheumatology, Dpt. of Pediatrics UNS School of Medicine, USA. · Medicine & Ophthalmology Hackensack Meridian School of Medicine at Seton Hall University Nutley, New Jersey, USA. · Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia. · Centre de Bioclimatology, University de Florence, Florence, Italy. · SOS Allergy and Immunology, Prato - USL Toscana Centro, Italy. · Fundación Hospital Universitario Metropolitano de Barranquilla, Barranquilla, Colombia. · Federal University of Paraná, Brazil. · Department of Botany, Ecology and Plant Physiology, University of Córdoba, Spain. · San Francisco Centro de Especialistas Médicos Monterrey NL, Mexico. · Department of Otolaryngology- Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon. · Alexander's University Hospital Clinic of Allergy & Asthma, Bulgaria. · Alergia e Inmunología, Hospital Italiano Regional del Sur, Bahía Blanca-Buenos Aires, Argentina. · Department of Clinical and Experimental Medicine, Università; di Parma, Parma, Italy. · Allergy Asthma and Immunology, Emek Medical Center, Afula, Israel. · Rappaport Faculty of Medicine Technion, Israel Institute of Technology, Haifa, Israel. · Department of Plant Science, Faculty of Science, Mahidol University, Bangkok, Thailand. · Systems Biology of Diseases Research Unit, Faculty of Science, Mahidol University, Bangkok, Thailand. ·World Allergy Organ J · Pubmed #32256939.

ABSTRACT: Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking.

14 Article Attenuation of autoimmune responses to oxidative specific epitopes, but not nitroso-adducts, is associated with a better clinical outcome in Myalgic Encephalomyelitis/chronic fatigue syndrome. 2014

Maes, Michael / Leunis, Jean-Claude. ·Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand. · Laboratoire Ategis, Brussels, Belgium. ·Neuro Endocrinol Lett · Pubmed #25617880.

ABSTRACT: OBJECTIVES: There is evidence that inflammatory, oxidative and nitrosative stress (IO&NS) pathways participate in the pathophysiology of a subgroup of patients with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Increased IgM-related autoimmune responses to oxidative specific epitopes (OSEs), including malondialdehyde (MDA), oleic acid and phosphatidyl inositol (Pi), and nitroso-(NO)-adducts, including NO-tryptophan (NOW), NO-arginine and NO-cysteinyl, are frequently observed in ME/CFS. Autoimmune responses in ME/CFS may be driven by increased bacterial translocation as measured by IgM and IgA responses to LPS of gram negative bacteria. METHODS: The aim of this study is to examine whether IgM responses to OSEs and NO-adducts are related to a better outcome as measured by the Fibromyalgia and Fatigue Rating Scale (FF). 76 ME/CFS patients with initially abnormal autoimmune responses were treated with care-as-usual, including nutraceuticals with anti-IO&NS effects (NAIOS), such as L-carnitine, coenzyme Q10, taurine + lipoic acid, with or without curcumine + quercitine or N-acetyl-cysteine, zinc + glutamine. RESULTS: We found that use of these NAIOS was associated with highly significant reductions in initially increased IgM-mediated autoimmune responses to OSEs and NO-adducts. A greater reduction in autoimmune responses to OSEs during intake of these NAIOS was associated with a lower FF score. Reductions in IgM responses to oleic acid, MDA and Pi, but not in any of the NO-adducts, were associated with reductions in severity of illness. These associations remained significant after adjusting for possible effects of increased bacterial translocation (leaky gut). CONCLUSIONS: Our results show that autoimmune responses to OSEs are involved in the pathophysiology of ME/CFS and that these pathways are a new drug target in a subgroup of ME/CFS patients. Although hypernitrosylation and nitrosative stress play a role in ME/CFS, reductions in these pathways are not associated with lowered severity of illness. Randomized controlled trials with NAIOS should be carried out in the subgroup of ME/CFS patients with initially increased autoimmune responses to OSEs.

15 Article Evidence for the existence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) with and without abdominal discomfort (irritable bowel) syndrome. 2014

Maes, Michael / Leunis, Jean-Claude / Geffard, Michel / Berk, Michael. ·Maes Clinics @ TRIA, Bangkok, Thailand, Thailand. · Laboratory Ategis, Wavre, Belgium. · Association Institute for Research and Development in Human Pathology and Therapy, Talence, France. · Department of Psychiatry, Deakin University, Geelong, Australia. ·Neuro Endocrinol Lett · Pubmed #25433843.

ABSTRACT: BACKGROUND: There is evidence that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is accompanied by gastro-intestinal symptoms; and IgA and IgM responses directed against lipopolysaccharides (LPS) of commensal bacteria, indicating bacterial translocation. METHODS: This study was carried out to examine gastro-intestinal symptoms in subjects with ME/CFS versus those with chronic fatigue (CF). The two groups were dissected by dichotomizing those fulfilling and not fulfilling Fukuda's critera. In these groups, we examined the association between gastro-intestinal symptoms and the IgA and IgM responses directed against commensal bacteria. RESULTS: Using cluster analysis performed on gastro-intestinal symptoms we delineated that the cluster analysis-generated diagnosis of abdominal discomfort syndrome (ADS) was significantly higher in subjects with ME/CFS (59.6%) than in those with CF (17.7%). The diagnosis of ADS was strongly associated with the diagnosis of irritable bowel syndrome (IBS). There is evidence that ME/CFS consists of two subgroups, i.e. ME/CFS with and without ADS. Factor analysis showed four factors, i.e. 1) inflammation-hyperalgesia; 2) fatigue-malaise; 3) gastro-intestinal symptoms/ADS; and 4) neurocognitive symptoms. The IgA and IgM responses to LPS of commensal bacteria were significantly higher in ME/CFS patients with ADS than in those without ADS. CONCLUSIONS: The findings show that ADS is a characteristic of a subset of patients with ME/CFS and that increased bacterial translocation (leaky gut) is associated with ADS symptoms. This study has defined a pathway phenotype, i.e bacterial translocation, that is related to ME/CFS and ADS/IBS and that may drive systemic inflammatory processes.

16 Article Oxidative and Nitrosative Stress and Immune-Inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS). 2014

Morris, Gerwyn / Maes, Michael. ·Tir Na Nog, Pembrey, Llanelli, UK. · Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand ; Department of Psychiatry, Deakin University, Geelong, Australia. ·Curr Neuropharmacol · Pubmed #24669210.

ABSTRACT: Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease.

17 Article In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation. 2013

Maes, Michael / Ringel, Karl / Kubera, Marta / Anderson, George / Morris, Gerwyn / Galecki, Piotr / Geffard, Michel. ·Maes Clinics @ TRIA, Bangkok, Thailand. dr.michaelmaes@hotmail.com ·J Affect Disord · Pubmed #23664637.

ABSTRACT: BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation. METHODS: We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale). RESULTS: The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise. DISCUSSION: The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder.

18 Article Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. 2012

Maes, Michael / Twisk, Frank N M / Ringel, Karl. ·Maes Clinics, TRIA, Bangkok, Thailand. dr.michaelmaes @ hotmail.com ·Psychother Psychosom · Pubmed #22832503.

ABSTRACT: BACKGROUND: Depression is an inflammatory disorder while many authors declare myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to be a functional disorder. The aim of the present study is to compare inflammatory and cell-mediated immune (CMI) responses between depression and ME/CFS. METHODS: We measured two proinflammatory cytokines (PICs) in plasma, interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), with enzyme-linked immunosorbent assays, and serum neopterin with a radioimmunoassay in controls, ME/CFS and depressive patients. RESULTS: Plasma PICs were significantly higher in ME/CFS than in depression and higher in both patient groups than in controls. Increased PIC levels in depression were attributable to the presence of fatigue and physio-somatic symptoms. Serum neopterin did not differ significantly between depression and ME/CFS but was higher in both patient groups than in controls. The significant positive correlations between neopterin and either IL-1 or TNF-α were significantly greater in depression than in ME/CFS. CONCLUSIONS: Since PICs cause depression-like behaviors and fatigue/malaise, we suggest that inflammation may play a role in the pathophysiology of ME/CFS and depression. Increased neopterin also seems to contribute to the pathophysiology of both disorders. This study has detected a shared 'pathway phenotype', i.e. disorders in inflammatory and CMI pathways, which underpins both ME/CFS and depression and, therefore, may explain the co-occurrence of both disorders. ME/CFS and depression are discriminated from each other by increased PICs in ME/CFS and differences in the immune cell communication networks.

19 Article IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression. 2012

Maes, Michael / Mihaylova, Ivana / Kubera, Marta / Leunis, Jean-Claude / Twisk, Frank N M / Geffard, Michel. ·Maes Clinics @ TRIA, Piyavate Hospital, 998 Rimklongsamsen Road, Bangkok, 10310, Thailand. dr.michaelmaes@hotmail.com ·Metab Brain Dis · Pubmed #22614823.

ABSTRACT: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and depression are considered to be neuro-immune disorders (Maes and Twisk, BMC Medicine 8:35, 2010). There is also evidence that depression and ME/CFS are accompanied by oxidative and nitrosative stress (O&NS) and by increased autoantibodies to a number of self-epitopes some of which have become immunogenic due to damage by O&NS. The aim of this study is to examine IgM-mediated autoimmune responses to different self-epitopes in ME/CFS versus depression. We examined serum IgM antibodies to three anchorage molecules (palmitic and myristic acid and S-farnesyl-L-cysteine); acetylcholine; and conjugated NO-modified adducts in 26 patients with major depression; 16 patients with ME/CFS, 15 with chronic fatigue; and 17 normal controls. Severity of fatigue and physio-somatic (F&S) symptoms was measured with the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale. Serum IgM antibodies to the three anchorage molecules and NO-phenylalanine were significantly higher in ME/CFS than in depression. The autoimmune responses to oxidatively, but not nitrosatively, modified self-epitopes were significantly higher in ME/CFS than in depression and were associated with F&S symptoms. The autoimmune activity directed against conjugated acetylcholine did not differ significantly between ME/CFS and depression, but was greater in the patients than controls. Partially overlapping pathways, i.e. increased IgM antibodies to a multitude of neo-epitopes, underpin both ME/CFS and depression, while greater autoimmune responses directed against anchorage molecules and oxidatively modified neo-epitopes discriminate patients with ME/CFS from those with depression. These autoimmune responses directed against neoantigenic determinants may play a role in the dysregulation of key cellular functions in both disorders, e.g. intracellular signal transduction, cellular differentiation and apoptosis, but their impact may be more important in ME/CFS than in depression.

20 Article Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data. 2012

Maes, Michael / Twisk, Frank N M / Johnson, Cort. ·Maes Clinics @ TRIA, Piyavate Hospital, 998 Rimklongsamsen Road, Bangkok 10310, Thailand. dr.michaelmaes@hotmail.com ·Psychiatry Res · Pubmed #22521895.

ABSTRACT: There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories. Fukuda's criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda's criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, and lysozyme, and serum neopterin were employed as external validating criteria. Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. "malaise-sickness" and "malaise-hyperalgesia". Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM).

21 Article Evidence for inflammation and activation of cell-mediated immunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): increased interleukin-1, tumor necrosis factor-α, PMN-elastase, lysozyme and neopterin. 2012

Maes, Michael / Twisk, Frank N M / Kubera, Marta / Ringel, Karl. ·Maes Clinics @ TRIA, Bangkok, Thailand. dr.michaelmaes@hotmail.com ·J Affect Disord · Pubmed #21975140.

ABSTRACT: BACKGROUND: There is evidence that inflammatory pathways and cell-mediated immunity (CMI) play an important role in the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Activation of inflammatory and CMI pathways, including increased levels of cytokines, is known to induce fatigue and somatic symptoms. Given the broad spectrum inflammatory state in ME/CFS, the aim of this study was to examine whether inflammatory and CMI biomarkers are increased in individuals with ME/CFS. METHODS: In this study we therefore measured plasma interleukin-(IL)1, tumor necrosis factor (TNF)α, and PMN-elastase, and serum neopterin and lysozyme in 107 patients with ME/CFS, 37 patients with chronic fatigue (CF), and 20 normal controls. The severity of ME/CFS was measured with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. RESULTS: Serum IL-1, TNFα, neopterin and lysozyme are significantly higher in patients with ME/CFS than in controls and CF patients. Plasma PMN-elastase is significantly higher in patients with ME/CFS than in controls and CF patients and higher in the latter than in controls. Increased IL-1 and TNFα are significantly correlated with fatigue, sadness, autonomic symptoms, and a flu-like malaise; neopterin is correlated with fatigue, autonomic symptoms, and a flu-like malaise; and increased PMN-elastase is correlated with concentration difficulties, failing memory and a subjective experience of infection. CONCLUSIONS: The findings show that ME/CFS is characterized by low-grade inflammation and activation of CMI. The results suggest that characteristic symptoms of ME/CFS, such as fatigue, autonomic symptoms and a flu-like malaise, may be caused by inflammatory mediators, e.g. IL-1 and TNFα.

22 Article Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome. 2012

Maes, Michael / Twisk, Frank N M / Kubera, Marta / Ringel, Karl / Leunis, Jean-Claude / Geffard, Michel. ·Maes Clinics @ TRIA, Bangkok, Thailand. dr.michaelmaes@hotmail.com ·J Affect Disord · Pubmed #21967891.

ABSTRACT: BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is accompanied by a) systemic IgA/IgM responses against the lipopolysaccharides (LPS) of commensal bacteria; b) inflammation, e.g. increased plasma interleukin-(IL)1 and tumor necrosis factor (TNF)α; and c) activation of cell-mediated immunity (CMI), as demonstrated by increased neopterin. METHODS: To study the relationships between the IgA/IgM responses to the LPS of microbiota, inflammation, CMI and the symptoms of ME/CFS we measured the IgA/IgM responses to the LPS of 6 different enterobacteria, serum IL-1, TNFα, neopterin, and elastase in 128 patients with ME/CFS and chronic fatigue (CF). Severity of symptoms was assessed by the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. RESULTS: Serum IL-1, TNFα, neopterin and elastase are significantly higher in patients with ME/CFS than in CF patients. There are significant and positive associations between the IgA responses to LPS and serum IL-1, TNFα, neopterin and elastase. Patients with an abnormally high IgA response show increased serum IL-1, TNFα and neopterin levels, and higher ratings on irritable bowel syndrome (IBS) than subjects with a normal IgA response. Serum IL-1, TNFα and neopterin are significantly related to fatigue, a flu-like malaise, autonomic symptoms, neurocognitive disorders, sadness and irritability. CONCLUSIONS: The findings show that increased IgA responses to commensal bacteria in ME/CFS are associated with inflammation and CMI activation, which are associated with symptom severity. It is concluded that increased translocation of commensal bacteria may be responsible for the disease activity in some ME/CFS patients.

23 Article Adrenal histoplasmosis: a case series and review of the literature. 2011

Larbcharoensub, Noppadol / Boonsakan, Paisarn / Aroonroch, Rangsima / Rochanawutanon, Mana / Nitiyanant, Prawat / Phongkitkarun, Sith / Poonvutikul, Sirapat / Watcharananan, Siriorn Paritpokee / Ngarmukos, Chardpraorn. ·Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Noppadol_l@hotmail.com ·Southeast Asian J Trop Med Public Health · Pubmed #22299474.

ABSTRACT: Adrenal histoplasmosis is an uncommon mycotic disease typically caused by Histoplasma capsulatum. The objective was to determine the clinicopathological findings in adrenal histoplasmosis. Pathological records were searched from the database at the Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University from 1993 to 2008 for cases of adrenal histoplasmosis. The keywords were "histoplasmosis" and "adrenal gland". Adrenal histoplasmosis was diagnosed by histopathology and Gomori-Grocott methenamine silver staining. Histoplasma capsulatum was confirmed by tissue culture and/or serology. The authors report seven cases of adrenal histoplasmosis in immunocompetent patients. The mean age at diagnosis was 67 years. All patients presented as chronic fatigue syndrome. The onset of symptoms ranged from one to three months. Addison's disease was found in adrenal histoplasmosis in one case (14.3%). The computed tomography revealed adrenal nodules measuring 1.2 to 7.8 cm in diameter. The histopathology showed granulomatous inflammation with caseous necrosis. Culture of adrenal tissue from two patients revealed Histoplasma capsulatum. Serum Histoplasma antibodies were positive in four cases. A cure was accomplished in 6 out of 7 cases (85.7%). The patients were followed up for 2.5 to 16.5 years.

24 Article Lower whole blood glutathione peroxidase (GPX) activity in depression, but not in myalgic encephalomyelitis / chronic fatigue syndrome: another pathway that may be associated with coronary artery disease and neuroprogression in depression. 2011

Maes, Michael / Mihaylova, Ivanka / Kubera, Marta / Uytterhoeven, Marc / Vrydags, Nicolas / Bosmans, Eugene. ·Piyavate Hospital, Bangkok, Thailand, Thailand. dr.michaelmaes@hotmail.com ·Neuro Endocrinol Lett · Pubmed #21552194.

ABSTRACT: BACKGROUND: Major depression and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are two disorders accompanied by an upregulation of the inflammatory and oxidative and nitrosative (IO&NS) pathways and a decreased antioxidant status. Moreover, depression is accompanied by disorders in inflammatory and neuroprogressive (IN-PRO) pathways. METHODS: This study examines whole blood glutathione peroxidase (GPX) in depression and in ME/CFS; GPX is an enzyme that reduces hydroperoxides by oxidizing glutathione and consequently protects the cells from oxidative damage. Blood was sampled in 39 patients with depression, 40 patients with ME/CFS and 24 normal volunteers. Whole blood was analysed for GPX activity using the Ransel assay (Randox). Severity of illness was measured by means of the Hamilton Depression Rating Scale (HDRS) and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF scale). RESULTS: We found that whole blood GPX activity was significantly (p=0.001) lower in depressed patients than in normal controls and that there were no significant differences between ME/CFS and controls. In depression and ME/CFS, there were significant and inverse relationships between GPX activity and the FF items, depressed mood and autonomic symptoms. In depression, there were significant and negative correlations between whole blood GPX and the HDRS score and autonomic symptoms. DISCUSSION: The results show that lowered whole blood GPX activity contributes to the lowered antioxidant status in depression. Since GPX activity is a predictor of neuroprogression and coronary artery disease (CAD), lowered GPX activity in depression contributes to the IN-PRO pathways and the comorbidity between depression and CAD. Our results suggest that patients with depression would benefit from Ebselen or a supplementation with glutathione, N-Acetyl-l-Cysteine and selenium.

25 Article Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). 2011

Maes, Michael / Kubera, Marta / Uytterhoeven, Marc / Vrydags, Nicolas / Bosmans, Eugene. ·Maes Clinics@TRIA, Bangkok, Thailand. dr.michaelmaes@hotmail.com ·Med Sci Monit · Pubmed #21455120.

ABSTRACT: BACKGROUND: There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress. MATERIAL/METHODS: Blood was collected from 56 patients with ME/CFS and 37 normal volunteers. Severity of ME/CFS was measured using the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. RESULTS: Plasma peroxide concentrations were significantly higher in patients with ME/CFS than in normal controls. There was a trend towards significantly higher serum oxLDL antibodies in ME/CFS than in controls. Both biomarkers contributed significantly in discriminating between patients with ME/CFS and normal controls. Plasma peroxide and serum oxLDL antibody levels were both significantly related to one of the FF symptoms. CONCLUSIONS: The results show that ME/CFS is characterized by increased oxidative stress.