Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease.
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.
Kurup
Ravi Kumar
RK
Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India. kvgnair@satyam.net.in
Kurup
Parameswara Achutha
PA
D000328:Adult; D000704:Analysis of Variance; D003093:Colitis, Ulcerative / Q000503:physiopathology*; D003424:Crohn Disease / Q000503:physiopathology*; D004077:Digoxin / Q000097:blood*; D004286:Dolichols / Q000097:blood; D004292:Dominance, Cerebral / Q000502:physiology; D004791:Enzyme Inhibitors / Q000097:blood; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood; D006025:Glycosaminoglycans / Q000097:blood; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism; D008274:Magnesium / Q000097:blood; D016555:Matched-Pair Analysis; D018377:Neurotransmitter Agents / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014451:Ubiquinone / Q000097:blood
D004286:Dolichols; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D006025:Glycosaminoglycans; D018377:Neurotransmitter Agents; D011106:Polyisoprenyl Phosphates; D014451:Ubiquinone; D004077:Digoxin; D006903:Hydroxymethylglutaryl CoA Reductases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium