Hypothalamic digoxin, hemispheric chemical dominance, and oncogenesis: evidence from multiple myeloma.
This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol, and ubiquinone in multiple myeloma. The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find out the rote of cerebral dominance in the genesis of multiple myeloma and neoplasms. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition, and free radical metabolism--in multiple myeloma, as well as in individuals of differing hemispheric dominance. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol, and a reduction in RBC membrane Na(+)-K+ ATPase activity, serum ubiquinone, and magnesium levels. Serum tryptophan, serotonin, nicotine, strychnine, and quinolinic acid were elevated, while tyrosine, dopamine, noradrenaline, and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins, cholesterol, and phospholipids were reduced. The activity of all free-radical scavenging enzymes, concentration of glutathione, iron binding capacity, and ceruloplasmin decreased significantly, while the concentration of lipid peroxidation products and nitric oxide increased. Hyperdigoxinemia-related altered intracellular Ca++/Mg++ ratios mediated oncogene activation, dolichol-induced altered glycoconjugate metabolism, and ubiquinone deficiency-related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical patterns obtained in multiple myeloma are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with multiple myeloma were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Multiple myeloma occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
Kurup
Ravi Kumar
RK
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India.
Kurup
Paramesware Achutha
PA
D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004077:Digoxin / Q000378:metabolism*; D004286:Dolichols / Q000097:blood; D004292:Dominance, Cerebral; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000097:blood; D006001:Glycoconjugates / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007545:Isoproterenol / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000097:blood; D011897:Random Allocation; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D016166:Free Radical Scavengers; D006001:Glycoconjugates; D018377:Neurotransmitter Agents; D014451:Ubiquinone; D004077:Digoxin; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol