ABSTRACT
A family with coexistence of hypotension, recurrent respiratory infection, motor tics, obsessive compulsive disorder, major depressive disorder, early onset osteoporosis, low body mass index, bulimia nervosa and healthy aging with longevity is described. The family members had hyposexual behavior, less tendency for spirituality, had no insomnia but a tendency towards increased somnolence, no addictive behaviour, had more bonding and affectionate behavior and were less creative with an average IQ. There was no vascular thrombosis, systemic neoplasm and neuronal degeneration in the index family. All members of the family were left hemispheric dominant. The level of serum digoxin, HMG CoA reductase activity and dolichol was found to be decreased in all with a corresponding increase in RBC Na(+)-K(+) ATPase activity and serum ubiquinone magnesium level. There was increase in tyrosine catabolites and a reduction in tryptophan catabolites in serum. Total and individual glycosaminoglycan fractions, carbohydrate residues of glycoproteins, glycolipids, activity of GAG degrading enzymes and glycohydrolases were decreased in serum. The concentration of RBC membrane total GAG and carbohydrate residues of glycoproteins increased while cholesterol : phospholipid ratio of membrane decreased. The activity of free radical scavenging enzymes were increased while the concentration of free radicals decreased significantly. The same biochemical patterns were observed in left hemispheric dominance as opposed to right hemispheric dominance. The significance of these findings in the pathogenesis of these disorders is discussed.
Subject(s)
Cardenolides , Depressive Disorder, Major/genetics , Digoxin/blood , Dolichols/metabolism , Dominance, Cerebral , Family Health , Female , Humans , Hydroxymethylglutaryl CoA Reductases/metabolism , Male , Obsessive-Compulsive Disorder/genetics , Pedigree , Saponins/blood , Sodium-Potassium-Exchanging ATPase/metabolism , Ubiquinone/metabolismABSTRACT
BACKGROUND: The isoprenoid pathway was assessed and compared in patients of lone atrial fibrillation with embolic stroke as well as in patients with right hemispheric, left hemispheric and bihemispheric dominance to determine the role of hemispheric dominance in its pathogenesis. METHODS AND RESULTS: The activities of hydroxyl methyl glutaryl-CoA reductase and RBC sodium-potasium ATPase as well as serum levels of plasma magnesium, digoxin, dolichol and ubiquinone were measured. The tyrosine/tryptophan catabolic patterns, glycoconjugate metabolism, free radical metabolism and RBC membrane composition were also assessed. In patients with lone atrial fibrillation with embolic stroke, 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: and an increase in the cholesterol: phospholipid ratio with a reduction in the glycoconjugate levels of the RBC membrane. The same biochemical patterns were obtained in individuals with right hemispheric dominance whereas the patterns were reversed in patients with left hemispheric dominance. CONCLUSIONS: Lone atrial fibrillation with embolic stroke is associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This occurs in right hemisphere-dominant individuals.
Subject(s)
Aged , Atrial Fibrillation/complications , Digoxin/metabolism , Dolichols/metabolism , Female , Functional Laterality , Humans , Intracranial Embolism/complications , Magnesium/metabolism , Male , Middle Aged , Polyisoprenyl Phosphate Monosaccharides/metabolism , Prognosis , Sensitivity and Specificity , Sodium-Potassium-Exchanging ATPase/metabolism , Ubiquinone/metabolismABSTRACT
Endothelial cell proliferation and differentiation into blood capillaries (i.e., angiogenesis) are essential for growth and development, wound healing, osetogenesis, etc. But abnormal angiogenesis during tumor progression could lead to serious consequences. Angiogenesis is a complex biochemical process, and is often difficult to study the molecular mechanism in vivo due to interference by multitude of factors. Here, I present a non-transformed capillary endothelial cell line as a model which has been extensively characterized morphologically and biochemically to study the fundamentals of the angiogenic process. Studies completed in our laboratory also evidenced that expression of Glc3Man9GlcNAc2-PP-Dol is intricately connected with the balance between the cellular proliferation and apoptosis during angiogenesis.