- Email: [email protected]
The potential role of nitric oxide metabolites in diagnosing chronic fatigue syndrome
Correspondence [2] Dickinson CJ. Chronic fatigue syndrome. aetiological aspects. Eur J Clin Invest 1997;27(4):257–67. [3] Linde A, Andersson B, Svenson SB, Ahrne H, Carlsson M, Forsberg P, et al. Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome. J Infect Dis 1992;165(6):994–1000. [4] Patarca R, Klimas NG, Lugtendorf S, Antoni M, Fletcher MA. Dysregulated expression of TNF in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. Clin Infect Dis 1994; 18(Suppl. 1):S147–53. [5] Lovell DJ, Bowyer SL, Solinger AM. Interleukin-1 blockade by anakinra improves clinical symptoms in patients with neonatal-onset multisystem inflammatory disease. Arthritis Rheum 2005;52(4):1283–6.
197 Sayed Shahabuddin Hoseini Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Shahriar Gharibzadeh Neuromuscular Systems Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology, Somayyeh, Hafez, Tehran 15875-4413, Iran Tel.: +98 21 6454 2369; fax: +98 21 6649 5655. E-mail address: [email protected].
doi:10.1016/j.mehy.2006.01.041
The potential role of nitric oxide metabolites in diagnosing chronic fatigue syndrome A case of chronic fatigue syndrome (CFS) has a range of symptoms including fatigue, difficult concentration, headache, sore throat, tender lymph nodes, muscle ache, joint ache, abdominal cramp, chest pain, etc. The defining characteristic has repeatedly been reported to be physical and mental fatigue [1]. Sensitization of the central nervous system (CNS) has been suggested to take part of CFS pathophysiology. It is hypothesized recently that a nitric oxide (NO) dependent reduction in inhibitory activity of the CNS and consequent central sensitization accounts for some of the above-mentioned manifestations in CFS patients [2,3]. NO is synthesized from L-arginine by NO synthase. It reacts rapidly with heme. The affinity of heme for NO is 10000 times more than for oxygen. In the absence of oxygen, NO bound to hemoglobin is relatively stable, but in the presence of oxygen it is converted to nitrate and the iron of heme oxidized to methemoglobin. Finally, the nitrates are excreted in the urine [4]. The endogenous NO, which is present in the exhaled air of normal rabbits, guinea pigs, and humans, can be measured by laboratory procedures. In addition, NO production can be assessed in nasal lavage fluid in humans [5]. It is worth noting that the diagnosis of CFS is still difficult because there is no available laboratory test, and therefore it is made largely from symptoms reported by the patient [6].
We suggest that the assessment of urine nitrate, blood methemoglobin, nasal lavage NO, and exhaled NO can be used for diagnosis, severity assessment, evaluating response to treatment and prognosis of the CFS patients. Surely, the sensitivity and specificity of these tests should be evaluated in clinical trials.
References [1] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994; 121(12):953–9. [2] Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. Best Pract Res Clin Rheumatol 2003;17(4):563–74. [3] Nijs J, Van de Velde B, De Meirleir K. Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation? Med Hypotheses 2005;64(3):558–62. [4] Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43(2):109–42. [5] Hirvonen MR, Ruotsalainen M, Roponen M, Hyvarinen A, Husman T, Kosma VM, et al. Nitric oxide and proinflammatory cytokines in nasal lavage fluid associated with symptoms and exposure to moldy building microbes. Am J Respir Crit Care Med 1999;160(6):1943–6. [6] Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramirez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA 2001;286(11):1360–8. Erratum in: JAMA 2002; 287(11):1401.
198
Correspondence Shahriar Gharibzadeh Neuromuscular Systems Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
Sayed Shahabuddin Hoseini Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Tel.: +9821 6454 2369; fax: +9821 6649 5655. E-mail address: [email protected].
doi:10.1016/j.mehy.2006.01.040
Some objective facts about the myth of caloric restriction and longevity
A paper just published in this journal [1] on the subject of caloric deprivation exposes ideas in frontal contradiction with a recent article of mine [2]. With the highest respect that all serious and interesting works deserve, I must note that [1] has apparently overlooked some important factors, which results in seriously flawed conclusions. In wild environments, long-term chronic ‘‘undernutrition’’, postulated in [1] for the Homo of 1–2 Myr ago, is impossible: the number of individuals of the affected species would decrease because of lower reproduction rates, greater vulnerability to diseases and predators, and inability to compete for food with more vigorous species. In these conditions, only two short-term issues are possible: either the amount of food available per individual increases, the nutrition becomes adequate again and the population stabilises, or the species disappears. Furthermore, the possible survivors would not necessarily be those with lower metabolic rates. Depending on the circumstances, other qualities may prevail: strength, endurance, polyvalence, intelligence, etc. Inversely, for wild species, sustained demographic growth is associated to a situation of nutritional abundance. In this respect, the success of the Homo genus has been spectacular: it has managed to perform several successive worldwide expansions from tiny spots located mainly in eastern or southern Africa. Furthermore, Homo, and most specially our species Homo Sapiens, has doi:10.1016/j.mehy.2006.01.026
developed specific adaptations to food overabundance, like the custom of investing energy surplus in Pharaonic enterprises since prehistoric times. Unlike any other animal, our genetic emotional profile allows us to enjoy investing our extra energy in a large variety of recreational or spiritual activities, not always directly useful, but at least instructive: sports, games, arts, crafts, familial and social activities, altruistic work, etc. In sum, although our Homo lineage has occasionally known periods of shortage, overall we not only are perfectly adapted to nutritional abundance, but probably depend on it for our evolutionary success. What our species is not prepared for is a massive contamination by psychoactive poisons propagating through the air.
References [1] Amen-Ra N. Humans are evolutionarily adapted to caloric restriction resulting from ecologically dictated dietary deprivation imposed during the Plio–Pleistocene period. Med Hypotheses 2006;66:978–84. [2] Gracia MC. Inflammatory, autoimmune, chronic diseases: Bad diet and physical inactivity are causes or effects? Med Hypotheses 2006;66:939–44.
M.C. Gracia C/Lopez de Aranda 35, 28027 Madrid, Spain E-mail address: [email protected].
197 Sayed Shahabuddin Hoseini Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Shahriar Gharibzadeh Neuromuscular Systems Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology, Somayyeh, Hafez, Tehran 15875-4413, Iran Tel.: +98 21 6454 2369; fax: +98 21 6649 5655. E-mail address: [email protected].
doi:10.1016/j.mehy.2006.01.041
The potential role of nitric oxide metabolites in diagnosing chronic fatigue syndrome A case of chronic fatigue syndrome (CFS) has a range of symptoms including fatigue, difficult concentration, headache, sore throat, tender lymph nodes, muscle ache, joint ache, abdominal cramp, chest pain, etc. The defining characteristic has repeatedly been reported to be physical and mental fatigue [1]. Sensitization of the central nervous system (CNS) has been suggested to take part of CFS pathophysiology. It is hypothesized recently that a nitric oxide (NO) dependent reduction in inhibitory activity of the CNS and consequent central sensitization accounts for some of the above-mentioned manifestations in CFS patients [2,3]. NO is synthesized from L-arginine by NO synthase. It reacts rapidly with heme. The affinity of heme for NO is 10000 times more than for oxygen. In the absence of oxygen, NO bound to hemoglobin is relatively stable, but in the presence of oxygen it is converted to nitrate and the iron of heme oxidized to methemoglobin. Finally, the nitrates are excreted in the urine [4]. The endogenous NO, which is present in the exhaled air of normal rabbits, guinea pigs, and humans, can be measured by laboratory procedures. In addition, NO production can be assessed in nasal lavage fluid in humans [5]. It is worth noting that the diagnosis of CFS is still difficult because there is no available laboratory test, and therefore it is made largely from symptoms reported by the patient [6].
We suggest that the assessment of urine nitrate, blood methemoglobin, nasal lavage NO, and exhaled NO can be used for diagnosis, severity assessment, evaluating response to treatment and prognosis of the CFS patients. Surely, the sensitivity and specificity of these tests should be evaluated in clinical trials.
References [1] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994; 121(12):953–9. [2] Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. Best Pract Res Clin Rheumatol 2003;17(4):563–74. [3] Nijs J, Van de Velde B, De Meirleir K. Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation? Med Hypotheses 2005;64(3):558–62. [4] Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43(2):109–42. [5] Hirvonen MR, Ruotsalainen M, Roponen M, Hyvarinen A, Husman T, Kosma VM, et al. Nitric oxide and proinflammatory cytokines in nasal lavage fluid associated with symptoms and exposure to moldy building microbes. Am J Respir Crit Care Med 1999;160(6):1943–6. [6] Whiting P, Bagnall AM, Sowden AJ, Cornell JE, Mulrow CD, Ramirez G. Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. JAMA 2001;286(11):1360–8. Erratum in: JAMA 2002; 287(11):1401.
198
Correspondence Shahriar Gharibzadeh Neuromuscular Systems Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
Sayed Shahabuddin Hoseini Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran Tel.: +9821 6454 2369; fax: +9821 6649 5655. E-mail address: [email protected].
doi:10.1016/j.mehy.2006.01.040
Some objective facts about the myth of caloric restriction and longevity
A paper just published in this journal [1] on the subject of caloric deprivation exposes ideas in frontal contradiction with a recent article of mine [2]. With the highest respect that all serious and interesting works deserve, I must note that [1] has apparently overlooked some important factors, which results in seriously flawed conclusions. In wild environments, long-term chronic ‘‘undernutrition’’, postulated in [1] for the Homo of 1–2 Myr ago, is impossible: the number of individuals of the affected species would decrease because of lower reproduction rates, greater vulnerability to diseases and predators, and inability to compete for food with more vigorous species. In these conditions, only two short-term issues are possible: either the amount of food available per individual increases, the nutrition becomes adequate again and the population stabilises, or the species disappears. Furthermore, the possible survivors would not necessarily be those with lower metabolic rates. Depending on the circumstances, other qualities may prevail: strength, endurance, polyvalence, intelligence, etc. Inversely, for wild species, sustained demographic growth is associated to a situation of nutritional abundance. In this respect, the success of the Homo genus has been spectacular: it has managed to perform several successive worldwide expansions from tiny spots located mainly in eastern or southern Africa. Furthermore, Homo, and most specially our species Homo Sapiens, has doi:10.1016/j.mehy.2006.01.026
developed specific adaptations to food overabundance, like the custom of investing energy surplus in Pharaonic enterprises since prehistoric times. Unlike any other animal, our genetic emotional profile allows us to enjoy investing our extra energy in a large variety of recreational or spiritual activities, not always directly useful, but at least instructive: sports, games, arts, crafts, familial and social activities, altruistic work, etc. In sum, although our Homo lineage has occasionally known periods of shortage, overall we not only are perfectly adapted to nutritional abundance, but probably depend on it for our evolutionary success. What our species is not prepared for is a massive contamination by psychoactive poisons propagating through the air.
References [1] Amen-Ra N. Humans are evolutionarily adapted to caloric restriction resulting from ecologically dictated dietary deprivation imposed during the Plio–Pleistocene period. Med Hypotheses 2006;66:978–84. [2] Gracia MC. Inflammatory, autoimmune, chronic diseases: Bad diet and physical inactivity are causes or effects? Med Hypotheses 2006;66:939–44.
M.C. Gracia C/Lopez de Aranda 35, 28027 Madrid, Spain E-mail address: [email protected].