Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-26T11:05:46.884Z Has data issue: false hasContentIssue false
  • English
  • Français

Hypothalamic digoxin, hemispheric chemical dominance and sarcoidosis

Published online by Cambridge University Press:  24 June 2014

A. Ravi Kumar  and
Parameswara Achutha Kurup
A. Ravi Kumar
Affiliation:
Department of Neurology, Medical College
Parameswara Achutha Kurup*
Affiliation:
Metabolic Disorders Research Centre, Trivandrum, Kerala, India
*
Dr P. A. Kurup, Gouri Sadan,T.C.4/1525, North of Cliff House, Kattu Road, Kowdiar PO, Trivandrum, Kerala, India. Tel: 0471-2541607; Fax: 91-0471-2550782; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background/aims:

The isoprenoid pathway produces three key metabolites: endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). The role of the isoprenoid pathway in the pathogenesis of sarcoidosis in relation to hemispheric dominance was studied.

Methods:

The isoprenoid pathway-related cascade was assessed in patients with systemic sarcoidosis with pulmonary involvement. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis.

Results:

In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol:phospholipid ratio and a reduction in the glycoconjugate level of red blood cell (RBC) membrane in this group of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. In individuals with left hemispheric dominance the patterns were reversed.

Conclusions:

Endogenous digoxin, by activating the calcineurin signal transduction pathway of T cells, can contribute to immune activation in sarcoidosis. An altered glycoconjugate metabolism can lead to the generation of endogenous self-glycoprotein antigens in the lung as well as other tissues. Increased free radical generation can also lead to immune activation. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of sarcoidosis in relation to right hemispheric chemical dominance is discussed. All the patients with sarcoidosis were right-handed/left hemispheric dominant according to the dichotic listening test, but their biochemical patterns were suggestive of right hemispheric chemical dominance. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.

Keywords

digoxinhemispheric chemical dominancehypothalamusisoprenoidsarcoidosis
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 16 , Issue 3 , June 2004 , pp. 160 - 168
Copyright
Copyright © 2004 Blackwell Munksgaard

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

James, DG.Sarcoidosis and Other Granulomatous Disorders. New York: Marcel Dekker, 1994. Google Scholar
Christoforidis, GA, Spickler, EM, Recio, MV, Mehta, BM.MR of CNS sarcoidosis: correlation of imaging featurers to clinical symptoms and response to treatment. Am J Neuroradiol, 1999;20/4: 655–669.Google Scholar
Venet, A.Enhanced alveolar macrophage-mediated antigen-induced T-lymphocyte proliferation in sarcoidosis. J Clin Invest 1985;75: 293.CrossRefGoogle ScholarPubMed
Johns, Cj, Michele, Tm.The clinical management of sarcoidosis. A 50 year experience of the Johns Hopkins Hospital. Medicine 1999;78: 65–111.CrossRefGoogle ScholarPubMed
Geschwind, N, Behan, P.Left handedness association with immune diseases, migraine, and developmental learning disorders. Proc Natl Acad Sci USA 1982;79: 5097–5100.CrossRefGoogle Scholar
Goldstein, JL, Brown, MS.Regulation of the mevalonate pathway. Nature 1990;343: 425–430.CrossRefGoogle ScholarPubMed
Tamura, H, Shimoyama, S, Sunaga, Y.Digoxin like immunoreactive substance in urine of patients with mucocutaneous lymphnode syndrome. Angiology 1992;10: 856–865. CrossRefGoogle Scholar
Hisaka, A, Kasamatu, S, Takenaga, N.Absorption of a novel prodrug DOPA. Drug-Metabolism Disposal 1990;18: 621–625. Google ScholarPubMed
Felton, D, Cohen, N, Ader, R.Psychoneuroimmunology. New York: Academic Press, 1991. Google Scholar
Martin, R, McFarland, HG.Editorial. Ann Neurol 1995;38: 1–2. Google Scholar
Rao, AV, Ramakrishnan, S.Estimation of HMG CoA reductase activity. Clin Chem 1975;21: 1523–1528.CrossRefGoogle Scholar
Wallach, DFh, Kamath, VB.Methods in Enzymology. New York: Academic Press, 1966. Google Scholar
Arun, P, Ravi Kumar, A, Leelamma, S, Kurup, PA.Identification and estimation of endogenous digoxin in biological fluids and tissues by TLC and HPLC. Indian J Biochem Biophys 1998;35: 308–312.Google ScholarPubMed
Palmer, DN, Maureen, AA, Robert, DJ.Separation of some neutral lipids by normal phase high performance liquid chromatography on cyanopropyl column. Anal Chem 1984;140: 315–319. Google ScholarPubMed
Price, WJ.Spectrochemical Analysis by Atomic Absorption. New York: John Wiley, 1985. Google Scholar
Bloxam, LD, Warren, Wh.Error in the determination of tryptophan by the method of Denkala and Dewey. A revised procedure. Anal Biochem 1974;60: 621–625.CrossRefGoogle Scholar
Wong, PWK, O'Flynn, ME, Inouye, R.Flourimetric method for tyrosine. Clin Chem 1964;10: 1098–1100.CrossRefGoogle Scholar
Curzon, G, Green, AR.Rapid method for the determination of 5-hydroxy tryptophan and 5-hydroxy indoleacetic acid in certain regions of rat brain. Br J Pharmacol 1970;39: 653–655.CrossRefGoogle Scholar
Well-Malherbe. Methods of Biochemical Analysis. New York: InterScience, 1971. Google Scholar
Arun, P, Ravi Kumar, A, Leelamma, S, Kurup, PA.Endogenous alkaloids in the brain of rats loaded with tyrosine/tryptophan in the serum of patients of neurodegenerative and psychiatric disorders. Ind J Med Res 1998;107: 231–238. Google Scholar
Manoj, AJ, Kurup, PA.Changes in the glycosaminoglycans and glycoproteins in the rat brain during protein calorie malnutrition. J Clin Biochem Nutr 1998;25: 149–157. Google Scholar
Lowenstein, JM.Methods in Enzymology. New York: Academic Press, 1969. Google Scholar
Zilversmits, DB, Davis, AK.Estimation of phospholipids. J Lab Clin Med 1950;35: 100–110. Google Scholar
Kakkar, P, Das, B, Viswanathan, PN.A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 1984;21: 130–132.Google Scholar
Maehly, AC, Chance, B.The assay of catalase and peroxidase. Meth Biochem Anal 1954;2: 357. CrossRefGoogle Scholar
Paglia, DE, Valentine, WN.Studies on quantitative and qualitative characterisation of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70: 158–169.Google ScholarPubMed
Bergmeyer, HV.Methods of Enzymatic Analysis. New York: Academic Press, 1978. Google Scholar
Will, ED.Lipid peroxide formation in microsomes – general consideration. Biochem J 1969;113: 315.CrossRefGoogle Scholar
O'Brien, PJ.Estimation of conjugated dienes and hydroperoxide. Can J Biochem 1969;47: 485–492.CrossRefGoogle Scholar
Beutler, E, Duran, O, Kelley, BM.Modified procedure for the estimation reduced glutathione. J Lab Clin Med 1963;61: 882.Google Scholar
Jyothi, JK.Investigations on Metabolic Derangement in Coronary Artery Disease and Neurodegenerative Disorders. Trivandrum: University of Kerala Press, 1998. Google Scholar
Haga, H.Effects of dietary magnesium supplementation on diurnal variation of BP and plasma sodium-potassium ATPase activity in essential hypertension. Jpn Heart J 1992;33: 785–798.CrossRefGoogle Scholar
Finkel, Th.T-cell development and transmembrane signalling. Changing biological responses through a unchanging receptor. Immunol Today 1991;12: 79–86.CrossRefGoogle ScholarPubMed
Ashkenazi, A, Dixit, VM.Death receptors signalling and modulation. Science 1998;281: 1305–1308.CrossRefGoogle ScholarPubMed
Wyllie, Elaine. Treatment of epilepsy: Principles and Practice, 2nd edn. Baltimore: William & Wilkins, 1996. Google Scholar
Brown, RR, Ozaki, Y, Datta, SP, Borden, EC, Sondel, PM, Malone, DG.Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. Rev Adv Exp Med Biol 1991;294: 425–435. CrossRefGoogle ScholarPubMed
Saito, K, Crowley, JS, Markey, SP, Heyes, MP.A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. J Biol Chem 1993;268: 15496–15503.CrossRefGoogle ScholarPubMed
Stefano, GB, Scharrer, B.Endogenous morphine and related opiates, a new class of chemical messengers. Adv Neuroimmunol 1994;4: 57–67.CrossRefGoogle ScholarPubMed
Robinson, BWS.Gamma interferon is spontaneously released by alveolar macrophages and lung T-lymphocytes in patients with pulmonary sarcoidosis. J Clin Invest 1985;75: 1488–1495.CrossRefGoogle ScholarPubMed
Jaya, P, Kurup, PA.Effect of magnesium deficiency on the metabolism of glycosaminoglycans in rats. J Biosci 1986;10: 487–497. CrossRefGoogle Scholar
Linstinsky, JL, Siegal, GP, Listinsky, MC.Alpha- L-Fucose a potentially critical molecule in pathologic processes including neoplasia. Am J Clin Pathol 1998;110: 425–440.CrossRefGoogle Scholar
Ploegh, HL.Viral strategies for immune evasion. Science 1998;280: 248–253.CrossRefGoogle ScholarPubMed
Feinman, RM, Sawyer, J, Hardin, J, Tricot, G.Cytogenetics and molecular genetics in multiple myeloma. Hematology-Oncol Clinics North Am 1997;11: 1–21. CrossRefGoogle ScholarPubMed
Wiedemann, C, Cockcroft, S.Vesicular transport. Nature 1998;394: 426–428.CrossRefGoogle ScholarPubMed
Green, RD, Reed, JC.Mitochondria and apoptosis. Science 1998;281: 1309–1316.CrossRefGoogle ScholarPubMed