- Email: [email protected]
The future of disease prevention
Correspondence / Medical Hypotheses 73 (2009) 854–865
and furnish intestinal microflora; however, they simultaneously reduce the relative intake of tryptophan. Non-fat, 1% and 2% skim milk, at 5.8%, 5.0% and 5.3% Try/LNAA%, respectively, are only 23%, 6% and 12% above the benchmark sorghum (4.7%) and yogurt is below it ( 50%), as previously noted. Whole milk, with a Try/LNAA% of 11.3%, has about twice the tryptophan of the lower-fat milks. Dieticians need to consider the relative tryptophan levels to prevent developmental delays and also to ensure that apparently normal children develop to their full potential. References [1] Coleman M. Serotonin and central nervous system syndromes of childhood: a review. J Autism Child Schizophr 1973;3(1):27–35. [2] Young JG et al. Clinical neurochemistry of autism and associated disorders. J Autism Dev Disord 1982;12(2):147–65. [3] McDougle CJ et al. Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry 1996;53(11):993–1000. [4] Posey DJ et al. The use of selective serotonin reuptake inhibitors in autism and related disorders. J Child Adolesc Psychopharmacol 2006;16(1–2): 181–6. [5] D’Eufemia P et al. Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile autism. Biomed Pharmacother 1995;49(6):288–92. [6] Smith, Quentin R, James Stoll. Blood–brain barrier amino acid transport. In: William M. Pardrige, editor. An introduction to the blood–brain barrier: methodology, biology and pathology. Cambridge University Press; 1998. ISBN 0 521 58124 9 1. [7] USDA National Nutrient Database for Standard Reference, Release 17. [8] Beretich Jr GR. Neurochemical foods. http://www.lulu.com/content/345292. [9] Rajakumar Pellagra K. http://www.emedicine.com/ped/topic1755.htm; updated June 25, 2003 [accessed 13.10.2005].
Guy R. Beretich Agrimmune Inc., 3733 Hobbton Hwy, Clinton, NC 28328, United States Tel.: +1 919 637 7107 E-mail address: [email protected] doi:10.1016/j.mehy.2009.05.001
The future of disease prevention Dear Editor After the Severe Acute Respiratory Syndrome (SARS) and Avian Flu pandemics we see another in the making; Swine Flu. As we take to fighting them with new weaponry we should also be in control of those that are already established. In the near future of immunology, a one-cure-all panacea might evolve. In the cutting edge we foresee memory type lymphocyte transfusion. Mature memory type lymphocytes are known to directly induce and guide the developments of the hematopoietic cells [1]. We propose that these cells be taken from elder individuals, whose immunity has seen them through many a battle with diseases over time, and be transfused in small quantities, sufficient to direct the development of other lymphocytes, into young infants. This, of course, is only after testing for blood group and other compatibilities. These cells can now direct the production of antibodies and other necessary arsenal to combat infectious agents the body was never exposed to. Pooling from various donors with similar compatibility profiles would be the order of the day. Vaccines currently in vogue would become redundant. Mammal trials in this arena would do much justice to the current state of health affairs.
857
Reference [1] Melchers F. From stem cells to lymphocytes. Z Rheumatol 2009 Apr 22 [Epub ahead of print]. PMID: 19384553.
K. Pradyumna Majumdar * Shravan K. Gangula Sravanth Karteek Chelakari Santhosh Reddy Mannem Vishal Gupta Pramod Krishna Majumdar * Research Intern, Borgess Research Institute, Gull Rd., Kalamazoo, MI 49048, USA Tel.: +91 984 437 0234 E-mail address: [email protected] (K.P. Majumdar)
doi:10.1016/j.mehy.2009.04.038
Can adenosine substitute for SAM-e as an adjunct in the treatment of depression?
The antidepressant effects of S-adenosylmethionine (SAM-e) have been known for many years, and researchers generally regard SAM-e as being effective as an adjunctive or even standalone treatment for major depression [2]. The assumption has generally been that SAM-e produces antidepressant effects by serving as a cofactor for methyltransferase enzymes [2], but the true mechanisms underlying the antidepressant effects of SAM-e are still unknown. Renshaw et al. [15] proposed that increases in adenosine (Ado), a major metabolite of SAM-e, or its nucleotides, may mediate the antidepressant effects of SAM-e [15]. Ado monophosphate (AMP), Ado diphosphate (ADP), and Ado triphosphate (ATP) comprise the ‘‘adenylate pool,” meaning AMP + ADP + ATP. Researchers have found that Ado can produce antidepressant effects in animal models of depression, and those effects seem to be mediated by changes in a variety of neurotransmitter systems [6–10]. In various types of cultured cells or tissues, exogenous SAM-e has been shown to increase the overall, tissue adenylate pool [4,16] or the concentrations of intracellular adenosine [4,14,18], ATP [4,13,14], or cAMP [17]. SAM-e increases Ado formation by serving as a cofactor for numerous methyltransferase enzymes [2], and the S-adenosylhomocysteine (SAH) formed as a product of those transmethylations can then be hydrolyzed, by SAH hydrolase (SAHH), to Ado and homocysteine [2]. The increases in the intracellular concentrations of Ado or its nucleotides would then be expected to equilibrate with and buffer or increase the pools of extracellular Ado or its nucleotides, leading to the activation of Ado receptors [14]. In many cases, researchers have noted that these elevations in Ado or its nucleotides are at least partially responsible for the protective effects of SAM-e against ischemia-induced damage to tissues or for other cellular effects of SAM-e [4,17,19]. Researchers have also frequently found that the effects of SAM-e can be mimicked by Ado [16,18] or blocked by Ado receptor antagonists [3,14,17–19]. The use of oral AMP or ATP disodium as an alternative to the use of SAM-e might be advantageous, given that the bioavailability of oral SAM-e has been shown to be extremely low [20]. Yang et al. [20] found that the relative bioavailability of a 1000-mg dose of oral SAM-e, expressed as AUC(oral)/AUC(intravenous) over 24 h,
and furnish intestinal microflora; however, they simultaneously reduce the relative intake of tryptophan. Non-fat, 1% and 2% skim milk, at 5.8%, 5.0% and 5.3% Try/LNAA%, respectively, are only 23%, 6% and 12% above the benchmark sorghum (4.7%) and yogurt is below it ( 50%), as previously noted. Whole milk, with a Try/LNAA% of 11.3%, has about twice the tryptophan of the lower-fat milks. Dieticians need to consider the relative tryptophan levels to prevent developmental delays and also to ensure that apparently normal children develop to their full potential. References [1] Coleman M. Serotonin and central nervous system syndromes of childhood: a review. J Autism Child Schizophr 1973;3(1):27–35. [2] Young JG et al. Clinical neurochemistry of autism and associated disorders. J Autism Dev Disord 1982;12(2):147–65. [3] McDougle CJ et al. Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry 1996;53(11):993–1000. [4] Posey DJ et al. The use of selective serotonin reuptake inhibitors in autism and related disorders. J Child Adolesc Psychopharmacol 2006;16(1–2): 181–6. [5] D’Eufemia P et al. Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile autism. Biomed Pharmacother 1995;49(6):288–92. [6] Smith, Quentin R, James Stoll. Blood–brain barrier amino acid transport. In: William M. Pardrige, editor. An introduction to the blood–brain barrier: methodology, biology and pathology. Cambridge University Press; 1998. ISBN 0 521 58124 9 1. [7] USDA National Nutrient Database for Standard Reference, Release 17. [8] Beretich Jr GR. Neurochemical foods. http://www.lulu.com/content/345292. [9] Rajakumar Pellagra K. http://www.emedicine.com/ped/topic1755.htm; updated June 25, 2003 [accessed 13.10.2005].
Guy R. Beretich Agrimmune Inc., 3733 Hobbton Hwy, Clinton, NC 28328, United States Tel.: +1 919 637 7107 E-mail address: [email protected] doi:10.1016/j.mehy.2009.05.001
The future of disease prevention Dear Editor After the Severe Acute Respiratory Syndrome (SARS) and Avian Flu pandemics we see another in the making; Swine Flu. As we take to fighting them with new weaponry we should also be in control of those that are already established. In the near future of immunology, a one-cure-all panacea might evolve. In the cutting edge we foresee memory type lymphocyte transfusion. Mature memory type lymphocytes are known to directly induce and guide the developments of the hematopoietic cells [1]. We propose that these cells be taken from elder individuals, whose immunity has seen them through many a battle with diseases over time, and be transfused in small quantities, sufficient to direct the development of other lymphocytes, into young infants. This, of course, is only after testing for blood group and other compatibilities. These cells can now direct the production of antibodies and other necessary arsenal to combat infectious agents the body was never exposed to. Pooling from various donors with similar compatibility profiles would be the order of the day. Vaccines currently in vogue would become redundant. Mammal trials in this arena would do much justice to the current state of health affairs.
857
Reference [1] Melchers F. From stem cells to lymphocytes. Z Rheumatol 2009 Apr 22 [Epub ahead of print]. PMID: 19384553.
K. Pradyumna Majumdar * Shravan K. Gangula Sravanth Karteek Chelakari Santhosh Reddy Mannem Vishal Gupta Pramod Krishna Majumdar * Research Intern, Borgess Research Institute, Gull Rd., Kalamazoo, MI 49048, USA Tel.: +91 984 437 0234 E-mail address: [email protected] (K.P. Majumdar)
doi:10.1016/j.mehy.2009.04.038
Can adenosine substitute for SAM-e as an adjunct in the treatment of depression?
The antidepressant effects of S-adenosylmethionine (SAM-e) have been known for many years, and researchers generally regard SAM-e as being effective as an adjunctive or even standalone treatment for major depression [2]. The assumption has generally been that SAM-e produces antidepressant effects by serving as a cofactor for methyltransferase enzymes [2], but the true mechanisms underlying the antidepressant effects of SAM-e are still unknown. Renshaw et al. [15] proposed that increases in adenosine (Ado), a major metabolite of SAM-e, or its nucleotides, may mediate the antidepressant effects of SAM-e [15]. Ado monophosphate (AMP), Ado diphosphate (ADP), and Ado triphosphate (ATP) comprise the ‘‘adenylate pool,” meaning AMP + ADP + ATP. Researchers have found that Ado can produce antidepressant effects in animal models of depression, and those effects seem to be mediated by changes in a variety of neurotransmitter systems [6–10]. In various types of cultured cells or tissues, exogenous SAM-e has been shown to increase the overall, tissue adenylate pool [4,16] or the concentrations of intracellular adenosine [4,14,18], ATP [4,13,14], or cAMP [17]. SAM-e increases Ado formation by serving as a cofactor for numerous methyltransferase enzymes [2], and the S-adenosylhomocysteine (SAH) formed as a product of those transmethylations can then be hydrolyzed, by SAH hydrolase (SAHH), to Ado and homocysteine [2]. The increases in the intracellular concentrations of Ado or its nucleotides would then be expected to equilibrate with and buffer or increase the pools of extracellular Ado or its nucleotides, leading to the activation of Ado receptors [14]. In many cases, researchers have noted that these elevations in Ado or its nucleotides are at least partially responsible for the protective effects of SAM-e against ischemia-induced damage to tissues or for other cellular effects of SAM-e [4,17,19]. Researchers have also frequently found that the effects of SAM-e can be mimicked by Ado [16,18] or blocked by Ado receptor antagonists [3,14,17–19]. The use of oral AMP or ATP disodium as an alternative to the use of SAM-e might be advantageous, given that the bioavailability of oral SAM-e has been shown to be extremely low [20]. Yang et al. [20] found that the relative bioavailability of a 1000-mg dose of oral SAM-e, expressed as AUC(oral)/AUC(intravenous) over 24 h,