1.
Hypothalamic digoxin, cerebral chemical dominance, and regulation of gastrointestinal/hepatic function.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(1):75-105
Abstract
The role of the isoprenoid pathway in gastrointestinal and hepatic diseases, and its relation to hemispheric dominance, was assessed in this study. The following parameters were measured in patients with (i) acid peptic disease, (ii) ulcerative colitis, (iii) gallstones, (iv) cryptogenic cirrhosis liver, (v) Reye's syndrome, (vi) mesenteric artery occlusion, (vii) irritable bowel syndrome, and (viii) in individuals with right hemispheric, left hemispheric, and bihemispheric dominance: 1. plasma HMG CoA reductase, digoxin, dolichol, ubiquinone, and magnesium levels; 2. tryptophan/tyrosine catabolic patterns; 3. free radical metabolism; 4. glycoconjugate metabolism; and 5. membrane composition. In patients with gastrointestinal and hepatic disease there were elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. The RBC membrane Na(+)-K+ ATPase activity and serum magnesium were decreased. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites in the serum. There was an increase in cholesterol: phospholipid ratio and a reduction in the glycoconjugate level of RBC membrane in these groups of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. An upregulated isoprenoid pathway and hyperdigoxinemia is characteristic of gastrointestinal and hepatic disease and in right hemispheric chemical dominance. Right hemispheric chemical dominance is important in deciding the predisposition to gastrointestinal and hepatic disease.
2.
Central role of hypothalamic digoxin in conscious perception, neuroimmunoendocrine integration, and coordination of cellular function: relation to hemispheric dominance.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2002;(6):705-39
Abstract
Alteration in the isoprenoid metabolites--digoxin, ubiquinone, and dolichol--have been reported in neuronal degeneration (Parkinson's disease), oncogenesis (central nervous system glioma), functional neuropsychiatric disorders (schizophrenia and epilepsy), and immune-mediated disorders (multiple sclerosis). The coexistence of these disorders has been documented in literature and a central dysfunction related to digoxin and the isoprenoid pathway may underlie all these disorders. A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome X, rheumatoid arthritis, and epilepsy has been described. The psychological behavioral patterns of the family were: creativity and high IQ, hypersexual behavior, reduced appetite and eating behavior, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less bonding and affectionate behavior, and left handedness/right hemispheric dominance. Digoxin, an endogenous Na(+)-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and red blood cell (RBC) membrane Na(+)-K+ ATPase activity was found to be reduced in all the disorders and in the indexed family studied. Hypothalamic digoxin can modulate conscious perception and its dysfunction may lead to schizophrenia. Digoxin can also preferentially upregulate tryptophan transport over tyrosine, resulting in increased levels of depolarizng tryptophan catabolites, serotonin, quinolinic acid, strychnine, and nicotine, and decreased levels of hyperpolarizing tyrosine catabolites, dopamine, noradrenaline, and morphine, contributing to membrane Na(+)-K+ ATPase inhibition in all the above disorders and the indexed family. Digoxin-induced membrane Na(+)-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced Mg2+ levels, leading on to glutamate excitotoxicity, oncogene activation, and immune activation. Digoxin-induced altered Ca2+/Mg2+ ratios, reduced ubiquinone, and increased dolichol can affect glycoconjugate metabolism, membrane formation and structure, and mitochondrial function, leading to the diverse disorders described above, including those in the indexed family. The isoprenoid pathway and neurotransmitter patterns were compared in right-handed/LH dominant and left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated hydroxymethylglutarylcoenzyme A reductase activity, with increased serum digoxin and dolichol levels. The serum ubiquinone, serum Mg2+ and RBC Na(+)-K+ ATPase activity were reduced in left-handed/RH dominant individuals. The left-handed/RH dominant individuals compared to right-handed/LH dominant individuals had elevated levels of serum tryptophan, quinolinic acid, serotonin, nicotine, and strychnine. The levels of tyrosine, dopamine, noradrenaline, and morphine were low in left-handed/RH dominant compared to right-handed/LH dominant individuals. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and coordinate the functions of various cellular organelles.