1.
Hypothalamic digoxin, hemispheric chemical dominance, and chronic bronchitis emphysema.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(9):1241-58
Abstract
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). This was assessed in patients with chronic bronchitis emphysema. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find the role of hemispheric dominance in the pathogenesis of chronic bronchitis emphysema. All the 15 patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. In patients with chronic bronchitis emphysema 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 cholesterol:phospholipid ratio and a reduction in glycoconjugate levels of RBC membrane in patients with chronic bronchitis emphysema. The same biochemical patterns were obtained in individuals with right hemispheric dominance. Endogenous digoxin by activating the calcineurin signal transduction pathway of T-cell can contribute to immune activation in chronic bronchitis emphysema. Increased free radical generation can also lead to immune activation. Endogenous synthesis of nicotine can contribute to the pathogenesis of the disease. Altered glycoconjugate metabolism and membranogenesis can lead to defective lysosomal stability contributing to the disease process by increased release of lysosomal proteases. The role of an endogenous digoxin and hemispheric dominance in the pathogenesis of chronic bronchitis emphysema and in the regulation of lung structure/function is discussed. The biochemical patterns obtained in chronic bronchitis emphysema is similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Chronic bronchitis emphysema occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance can play a role in the regulation of lung function and structure.
2.
Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(9):1221-40
Abstract
The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. It was considered pertinent to assess the pathway in inflammatory bowel disease (ulcerative colitis and regional ileitis). Since endogenous digoxin can regulate neurotransmitter transport, the pathway and the related cascade were also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. All the patients with inflammatory bowel disease were right-handed/left hemispheric dominant by the dichotic listening test. The following parameters were measured in patients with inflammatory bowel disease and in individuals with differing hemispheric 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 and RBC membrane Na+-K+ ATPase activity. Statistical analysis was done by ANOVA. In patients with inflammatory bowel disease 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 cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Inflammatory bowel disease is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to immune activation, defective glycoprotein bowel antigen presentation, and autoimmunity and a schizophreniform psychosis important in its pathogenesis. The biochemical patterns obtained in inflammatory bowel disease is similar to those obtained in left-handed/right hemispheric dominant individuals by the dichotic listening test. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Inflammatory bowel disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
3.
Endogenous hypodigoxinemia-related immune deficiency syndrome.
Kurup, RK, Kurup, PA
The International journal of neuroscience. 2003;(9):1287-303
Abstract
The isoprenoid pathway produces three key metabolites--digoxin (membrane Na+-K+ ATPase inhibitor, regulator of neurotransmitter transport, and an immunomodulatory agent), dolichol (a regulator of N-glycosylation of proteins), and ubiquinone (a free radical scavenger). The pathway was assessed in acute rheumatic fever patients with recurrent streptococcal infections, and who were also studied for differences in right and left hemispheric dominance. The isoprenoid pathway was downregulated with decreased digoxin synthesis in these patients and in those with left hemispheric chemical dominance. The tryptophan catabolites were decreased and the tyrosine catabolites increased. In these groups of patients the dolichol and glycoconjugate levels were reduced and lysosomal stability was increased. The ubiquinone levels were elevated and free radical levels decreased in these patients. The membrane cholesterol:phospholipid ratios were decreased and membrane glycoconjugates increased. On the other hand in right hemispheric chemical dominance the reverse patterns and hyperdigoxinemia with an upregulated isoprenoid pathway were noticed. The role of the isoprenoid pathway in the pathogenesis of acute rheumatic fever and recurrent streptococcal infections and its relation to hemispheric chemical dominance is discussed.
4.
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.