RESUMEN
The isoprenoid pathway related cascade was assessed in trisomy 21. Membrane Na+, K(+)-ATPase activity, serum magnesium, and ubiquinone were decreased while hydroxy methyl glutaryl CoA (HMG) coenzyme A (CoA) reductase activity, serum digoxin, and dolichol levels were increased in trisomy 21. There were increased levels of tryptophan catabolites--nicotine, strychnine, quinolinic acid, and serotonin--and decreased levels of tyrosine catabolites--dopamine, noradrenaline, and morphine in trisomy 21. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycan (GAG) fractions, and lysosomal enzymes in trisomy 21. Reduced levels of ubiquinone, reduced glutathione, and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in trisomy 21. Hypothalamic digoxin and a disordered isoprenoid pathway are important in the pathogenesis of trisomy 21.
Asunto(s)
Digoxina/sangre , Síndrome de Down/sangre , Hipotálamo/metabolismo , Alcaloides/sangre , Animales , Dolicoles/sangre , Síndrome de Down/metabolismo , Inhibidores Enzimáticos/metabolismo , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Radicales Libres/metabolismo , Hidroximetilglutaril-CoA Reductasas/sangre , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Terpenos/metabolismo , Ubiquinona/sangreRESUMEN
This study assessed the changes in digoxin and some other metabolites of the isoprenoid pathway in metabolic syndrome X presenting with multiple lacunar state. The isoprenoid pathway and digoxin status was also studied for comparison in individuals of differing hemispheric dominance to find out the role of cerebral dominance in the genesis of syndrome X. There was an increase in plasma HMG CoA reductase activity with a consequent increase in serum digoxin, which caused a reduction in RBC membrane Na(+)-K+ ATPase activity. There was an increase in serum tryptophan and its metabolites and a decrease in tyrosine and its metabolites. Serum magnesium was decreased with consequent alteration in the metabolism of glycosaminoglycans and glycolipids. Increase in dolichol, another product of the isoprenoid pathway, resulted in alteration in glycoprotein metabolism. Changes in the composition of membrane glycosaminoglycans, glycoproteins and cholesterol: phospholipid ratio were also observed in this disorder leading to decreased lysosomal stability. Decrease in ubiquinone, another isoprenoid metabolite, resulted in alteration in the free radical generation. Membrane Na(+)-K+ ATPase inhibition due to digoxin, altered membrane structure, increased tryptophan catabolites and decreased tyrosine catabolites can lead to increased intracellular calcium and reduced intracellular magnesium which can account for the symptoms of syndrome X. The biochemical patterns including hyperdigoxinemia observed in syndrome X correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for syndrome X with multiple lacunar state.
Asunto(s)
Demencia por Múltiples Infartos/metabolismo , Digoxina/metabolismo , Dominancia Cerebral/fisiología , Hipotálamo/metabolismo , Angina Microvascular/metabolismo , Análisis de Varianza , Humanos , Masculino , Persona de Mediana Edad , Terpenos/metabolismoRESUMEN
The isoprenoid pathway produces three key metabolites--endogenous digoxin-like factor (EDLF) (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), ubiquinone (free radical scavenger), and dolichol (regulator of glycoconjugate metabolism). The pathway was assessed in peptic ulcer and acid peptic disease and its relation to hemispheric dominance studied. The activity of HMG CoA reductase, serum levels of EDLF, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in acid peptic disease, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. All the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. The pathway was upregulated with increased EDLF synthesis in peptic ulcer disease (PUD). There was increase in tryptophan catabolites and reduction in tyrosine catabolites in these patients. The ubiquinone levels were low and free radical production increased. Dolichol and glycoconjugate levels were increased and lysosomal stability reduced in patients with acid peptic disease (APD). There was increase in cholesterol:phospholipid ratio with decreased glyco conjugate levels in membranes of patients with PUD. Acid peptic disease represents an elevated EDLF state which can modulate gastric acid secretion and the structure of the gastric mucous barrier. It can also lead to persistence of Helicobacter pylori infection. The biochemical pattern obtained in peptic ulcer disease is similar to those obtained in left-handed/right hemispheric chemically dominant individuals. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listen ing test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Peptic ulcer disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
Asunto(s)
Química Encefálica , Digoxina/metabolismo , Dominancia Cerebral , Hipotálamo/metabolismo , Úlcera Péptica/metabolismo , Adenosina Trifosfatasas/metabolismo , Adulto , Cardenólidos , Estudios de Casos y Controles , Colesterol/metabolismo , Pruebas de Audición Dicótica , Digoxina/sangre , Dolicoles/metabolismo , Eritrocitos/metabolismo , Glicoconjugados/metabolismo , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipotálamo/química , Lisosomas/enzimología , Magnesio/metabolismo , Úlcera Péptica/sangre , Fosfolípidos/metabolismo , Saponinas/sangre , Triptófano/metabolismo , Tirosina/metabolismo , Ubiquinona/metabolismoRESUMEN
The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with idiopathic pulmonary fibrosis and in individuals of differing hemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of idiopathic pulmonary fibrosis. All 15 cases of interstitial lung disease were right-handed/left hemispheric dominant by the dichotic listening test. The isoprenoidal metabolites--digoxin, dolichol, and ubiquinone, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, tyrosine/tryptophan catabolic patterns, free radical metabolism, glycoconjugate metabolism, and RBC membrane composition--were assessed in idiopathic pulmonary fibrosis as well as in individuals with differing hemispheric dominance. In patients with idiopathic pulmonary fibrosis 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 patients with idiopathic pulmonary fibrosis. Isoprenoid pathway dysfunction con tributes to the pathogenesis of idiopathic pulmonary fibrosis. The biochemical patterns obtained in interstitial lung disease are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. However, all the patients with interstitial lung 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. Interstitial lung disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
Asunto(s)
Química Encefálica , Digoxina/metabolismo , Dominancia Cerebral , Hipotálamo/metabolismo , Enfermedades Pulmonares/metabolismo , Adenosina Trifosfatasas/metabolismo , Cardenólidos , Estudios de Casos y Controles , Pruebas de Audición Dicótica , Digoxina/sangre , Dolicoles/metabolismo , Radicales Libres/metabolismo , Glicoconjugados/metabolismo , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipotálamo/química , Isoproterenol/metabolismo , Enfermedades Pulmonares/clasificación , Magnesio/metabolismo , Persona de Mediana Edad , Neurotransmisores/metabolismo , Saponinas/sangre , Ubiquinona/metabolismoRESUMEN
The isoprenoid pathway and its metabolites--digoxin, dolichol, and ubiquinone--were assessed in autism. The isoprenoid pathway and digoxin status was also studied for comparison in individuals of differing hemispheric dominance to determine the role of cerebral dominance in the genesis of autism. There was an upregulation of the isoprenoid pathway as evidenced by elevated HMG CoA reductase activity in autism. Digoxin, an endogenous Na+-K+ ATPase inhibitor secreted by the hypothalamus, was found to be elevated and RBC membrane Na+-K+ ATPase activity was found to be reduced in autism. Membrane Na+-K+ ATPase inhibition can result in increased intracellular Ca2+ and reduced magnesium levels. Hypothalamic digoxin can modulate conscious and subliminal perception and its dysfunction may lead to autism. Digoxin can also preferentially upregulate tryptophan transport over tyrosine resulting in increased levels of depolarizing tryptophan catabolites--serotonin, quinolinic acid (NMDA agonist), strychnine (blocks glycinergic inhibitory transmission), and nicotine (promotes dopamine release) and decreased levels of hyperpolarizing tyrosine catabolites--dopamine, noradrenaline, and morphine--contributing to membrane Na+-K+ ATPase inhibition. Increased nicotine levels can produce increased dopaminergic transmission in the presence of low dopamine levels. NMDA excitotoxicity could result from hypomagnesemia induced by membrane Na+-K+ ATPase inhibition and quinolinic acid, an NMDA agonist acting on the NMDA receptor. Hypomagnesemia and increased dolichol level can affect glycoconjugate metabolism and membranogenesis leading on to disordered synaptic connectivity in the limbic allocortex and defective presentation of viral antigens and neuronal antigens contributing to autoimmunity and viral persistence important in the pathogenesis. Membrane Na+-K+ ATPase inhibition can produce immune activation, a component of autoimmunity. Mitochondrial dysfunction consequent to altered calcium/magnesium ratios and reduced ubiquinone levels can result in increased free radical generation and reduced free radical scavenging and defective apoptosis leading to abnormal synaptogenesis. Autism can thus be considered a syndrome of hypothalamic digoxin hypersecretion consequent to an upregulated isoprenoid pathway. The biochemical patterns including hyperdigoxinemia observed in autism correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for autism.
Asunto(s)
Trastorno Autístico/metabolismo , Digoxina/sangre , Hipotálamo/metabolismo , Adolescente , Niño , Dolicoles/sangre , Femenino , Humanos , Hipotálamo/enzimología , Magnesio/sangre , Masculino , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Triptófano/metabolismo , Tirosina/metabolismo , Ubiquinona/sangreRESUMEN
The isoprenoid pathway including endogenous digoxin was assessed in systemic lupus erythematosis (SLE). All the patients with SLE were right-handed/left hemispheric dominant by the dichotic listening test. This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with SLE and in those with right hemispheric dominance. In this group of patients (i) the tryptophan catabolites were increased and the tyrosine catabolites reduced, (ii) the dolichol and glycoconjugate levels were elevated, (iii) lysosomal stability was reduced, (iv) ubiquinone levels were low and free radical levels increased, and (v) the membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with left hemispheric dominance the reverse patterns were obtained. The biochemical patterns obtained in SLE is similar to those obtained in left-handed/right hemispheric chemically dominant individuals. But all the patients with SLE were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. SLE occurs in right hemispheric chemically dominant individuals, and is a reflection of altered brain function. The role of the isoprenoid pathway in the pathogenesis of SLE and its relation to hemispheric dominance is discussed.
Asunto(s)
Dominancia Cerebral , Hipotálamo/metabolismo , Vasculitis por Lupus del Sistema Nervioso Central/metabolismo , Pruebas de Audición Dicótica , Digoxina/sangre , Dolicoles/sangre , Membrana Eritrocítica/metabolismo , Femenino , Radicales Libres/metabolismo , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Masculino , ATPasa Intercambiadora de Sodio-Potasio/sangre , Triptófano/metabolismo , Tirosina/metabolismo , Ubiquinona/sangreRESUMEN
The isoprenoid pathway produces three key metabolites--endogenous digoxin, dolichol, and ubiquinone. This was assessed in patients with systemic sarcoidosis. All l5 patients with sarcoidosis were right-handed/left hemispheric dominant by the dichotic listening test. The pathway was also studied in normal right hemispheric, left hemispheric, and bihemispheric dominant individuals for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis. In patients with sarcoidosis 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 patients. The neurotransmitter/digoxin-mediated increased intra cellular calcium induced immune activation, ubiquinone deficiency-related mitochondrial dysfunction/free radical generation, and increased dolichol-related altered glycoconjugate metabolism/endogenous self-glycoprotein antigen generation are crucial to the pathogenesis of sarcoidosis. The biochemical patterns obtained in sarcoidosis are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with sarcoidosis were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Sarcoidosis occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.
Asunto(s)
Digoxina/metabolismo , Dominancia Cerebral , Hipotálamo/metabolismo , Sarcoidosis/metabolismo , Adulto , Pruebas de Audición Dicótica , Dolicoles/metabolismo , Femenino , Humanos , Enfermedades Pulmonares/metabolismo , Masculino , Ubiquinona/metabolismoRESUMEN
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.
Asunto(s)
Colitis Ulcerosa/fisiopatología , Enfermedad de Crohn/fisiopatología , Digoxina/sangre , Membrana Eritrocítica/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Adulto , Análisis de Varianza , Dolicoles/sangre , Dominancia Cerebral/fisiología , Inhibidores Enzimáticos/sangre , Glicoproteínas/sangre , Glicosaminoglicanos/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Hipotálamo/metabolismo , Magnesio/sangre , Análisis por Apareamiento , Neurotransmisores/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , Ubiquinona/sangreRESUMEN
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.
Asunto(s)
Bronquitis Crónica/fisiopatología , Digoxina/sangre , Enfisema/fisiopatología , Membrana Eritrocítica/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Análisis de Varianza , Dolicoles/sangre , Dominancia Cerebral/fisiología , Inhibidores Enzimáticos/sangre , Glicoproteínas/sangre , Glicosaminoglicanos/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Hipotálamo/metabolismo , Magnesio/sangre , Análisis por Apareamiento , Persona de Mediana Edad , Neurotransmisores/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , Ubiquinona/sangreRESUMEN
The isoprenoid pathway produces four key metabolites important in cellular function--digoxin (endogenous membrane Na(+)-K+ ATPase inhibitor), dolichol (important in N-glycosylation of proteins), ubiquinone (free-radical scavenger), and cholesterol (component of cellular membranes). This study assessed the changes in the isoprenoid pathway and the consequences of its dysfunction in Parkinson's disease (PD). There was an elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol levels, and a reduction in serum magnesium, RBC membrane Na(+)-K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine, and quinolinic acid were elevated, while tyrosine, morphine, dopamine, and noradrenaline were decreased. The total serum glycosaminoglycans (GAG) and glycosaminoglycan fractions (except chondroitin sulphates and hyaluronic acid), the activity of GAG degrading enzymes, carbohydrate residues of serum glycoproteins, the activity of glycohydrolase-beta galactosidase, and serum glycolipids were elevated. HDL cholesterol was reduced and free fatty acids increased. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins and cholesterol were reduced, while phospholipid was increased. The activity of all serum free-radical scavenging enzymes, concentration of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin decreased significantly in PD, while the concentration of serum lipid peroxidation products and nitric oxide increased. A dysfunctional isoprenoid pathway and related cascade are important in the pathogenesis of Parkinson's disease. A hypothalamic digoxin mediated model for Parkinson's disease is also postulated.
Asunto(s)
Digoxina/sangre , Hipotálamo/metabolismo , Enfermedad de Parkinson/sangre , Anciano , Dolicoles/sangre , Inhibidores Enzimáticos/sangre , Eritrocitos/metabolismo , Femenino , Glicoconjugados/sangre , Glicosaminoglicanos/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Modelos Biológicos , Neuronas/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Triptófano/sangre , Tirosina/sangre , Ubiquinona/sangreRESUMEN
The isoprenoid path way produces endogenous digoxin, a substance that can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in individuals with chronic insomnia. The patterns were compared in those with right hemispheric and left hemispheric dominance. The activity of HMG GoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in individuals with chronic insomnia and in individuals with differing hemispheric dominance. Digoxin synthesis was increased with upregulated tryptophan catabolism (increased levels of serotonin, strychnine, and nicotine), and downregulated tyrosine catabolism (decreased levels of dopamine, noradrenaline, and morphine) in those with chronic insomnia and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism (decreased levels of serotonin, strychnine, and nicotine) and upregulated tyrosine catabolism (increased levels of dopamine, noradrenaline, and morphine) in those with normal sleep patterns and left hemispheric chemical dominance. Hypothalamic digoxin plays a central role in the regulation of sleep behavior. Hemispheric chemical dominance in relation to digoxin status is also crucial.
Asunto(s)
Digoxina/sangre , Dominancia Cerebral/fisiología , Hipotálamo/metabolismo , Magnesio/sangre , Trastornos del Inicio y del Mantenimiento del Sueño/metabolismo , Adulto , Inhibidores Enzimáticos/sangre , Eritrocitos/metabolismo , Femenino , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Fosfatos de Poliisoprenilo/metabolismo , Sueño/fisiología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Tirosina/sangreRESUMEN
The isoprenoid pathway produces three key metabolites--endogenous digoxin (modulate tryptophan/tyrosine transport), dolichol (important in N-glycosylation of proteins), and ubiquinone (free radical scavenger). It was considered pertinent to assess the pathway in alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. 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. In the patient group 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, as well as reduced endogenous morphine synthesis from tyrosine. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. Alcoholic cirrhosis, alcoholic addiction, and acquired hepatocerebral degeneration are associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to NMDA excitotoxicity and altered connective tissue/lipid metabolism important in its pathogenesis. Endogenous morphine deficiency plays a role in alcoholic addiction. The same biochemical patterns were obtained in those with right hemispheric chemical dominance. Alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration occur in right hemispheric, chemically dominant individuals.
Asunto(s)
Alcoholismo/metabolismo , Digoxina/sangre , Degeneración Hepatolenticular/metabolismo , Hipotálamo/metabolismo , Cirrosis Hepática Alcohólica/metabolismo , Adulto , Análisis de Varianza , Colesterol/sangre , Susceptibilidad a Enfermedades , Dolicoles/sangre , Dominancia Cerebral/fisiología , Inhibidores Enzimáticos/sangre , Eritrocitos/metabolismo , Femenino , Glicoconjugados/sangre , Glicosaminoglicanos/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Masculino , Proteínas de la Membrana/metabolismo , Neurotransmisores/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Triptófano/sangre , Tirosina/sangre , Tirosina/metabolismo , Ubiquinona/sangreRESUMEN
The human hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor, digoxin, which regulates neuronal transmission. The digoxin status and neurotransmitter patterns were studied in creative and non-creative individuals, as well as in individuals with differing hemispheric dominance, in order to find out the role of cerebral dominance in this respect. The activity of HMG CoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in creative/non-creative individuals, and in individuals with differing hemispheric dominance. In creative individuals there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in creative individuals correlated with right hemispheric dominance. In non-creative individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in non-creative individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to creative tendency.
Asunto(s)
Creatividad , Digoxina/sangre , Dominancia Cerebral/fisiología , Hipotálamo/metabolismo , Adulto , Inhibidores Enzimáticos/sangre , Eritrocitos/metabolismo , Femenino , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Magnesio/sangre , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Neurotransmisores/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Tirosina/sangre , Tirosina/metabolismoRESUMEN
The isoprenoid pathway produces three key metabolites--endogenous digoxin (modulate tryptophan/tyrosine transport), dolichol (important in N -glycosylation of proteins), and ubiquinone (free radical scavenger). It was considered pertinent to assess the pathway in alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Since endogenous digoxin can regulate neurotransmitter transport, the pathway was also assessed in individuals with differing hemispheric dominance to find out the role of hemispheric dominance in its pathogenesis. In the patient group 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 as reduced endogenous morphine synthesis from tyrosine. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate level of RBC membrane in these groups of patients. The same patterns were obtained in individuals with right hemispheric chemical dominance. Alcoholic cirrhosis, alcoholic addiction, and acquired hepatocerebral degeneration are associated with an upregulated isoprenoid pathway and elevated digoxin secretion from the hypothalamus. This can contribute to NMDA excitotoxicity and altered connective tissue/lipid metabolism important in its pathogenesis. Endogenous morphine deficiency plays a role in alcoholic addiction. Alcoholic cirrhosis, addiction, and acquired hepato -cerebral degeneration occur in right hemispheric chemically dominant individuals. Ninety percent of the patients with alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration were right-handed and left hemispheric dominant by the dichotic listening test. However, their biochemical patterns were similar to those obtained in right hemispheric chemical dominance. Hemispheric chemical dominance is a different entity and has no correlation with handedness or the dichotic listening test.
Asunto(s)
Alcoholismo/metabolismo , Digoxina/sangre , Dominancia Cerebral/fisiología , Degeneración Hepatolenticular/metabolismo , Hipotálamo/metabolismo , Cirrosis Hepática Alcohólica/metabolismo , Adulto , Alcoholismo/patología , Análisis de Varianza , Degeneración Hepatolenticular/patología , Humanos , Hipotálamo/patología , Cirrosis Hepática Alcohólica/patología , Persona de Mediana Edad , Telencéfalo/metabolismo , Telencéfalo/patologíaRESUMEN
The isoprenoid pathway produces an endogenous membrane Na+-K+ ATPase inhibitor, digoxin, which can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in eating disorders. The patterns were compared in those with right hemispheric and left hemispheric dominance. The serum HMG CoA reductase activity, RBC membrane Na+-K+ ATPase activity, serum digoxin, magnesium, tryptophan catabolites (serotonin, quinolinic acid, strychnine, and nicotine), and tyrosine catabolites (morphine, dopamine, and noradrenaline) were measured in anorexia nervosa, bulimia nervosa, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. Digoxin synthesis was increased with upregulated tryptophan catabolism and downregulated tyrosine catabolism in those with anorexia nervosa and right hemispheric chemical dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism and upregulated tyrosine catabolism in those with bulimia nervosa and left hemispheric chemical dominance. The membrane Na+-K+ ATPase activity and serum magnesium were decreased in anorexia nervosa and right hemispheric chemical dominance while they were increased in bulimia nervosa and left hemispheric chemical dominance. Hypothalamic digoxin and hemispheric chemical dominance play a central role in the regulation of eating behavior. Anorexia nervosa represents the right hemispheric chemically dominant/hyperdigoxinemic state and bulimia nervosa the left hemispheric chemically dominant/hypodigoxinemic state.
Asunto(s)
Digoxina/metabolismo , Dominancia Cerebral/fisiología , Conducta Alimentaria/fisiología , Trastornos de Alimentación y de la Ingestión de Alimentos/metabolismo , Hipotálamo/metabolismo , Adulto , Análisis de Varianza , Anorexia Nerviosa/metabolismo , Anorexia Nerviosa/fisiopatología , Bulimia/metabolismo , Bulimia/fisiopatología , Conducta Alimentaria/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Femenino , Humanos , Hipotálamo/fisiología , Hipotálamo/fisiopatologíaRESUMEN
The isoprenoid pathway produces three key metabolites--digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), dolichol (regulator of N-glycosylation of proteins), and ubiquinone (free radical scavenger). The isoprenoid pathway was assessed in patients with bronchial asthma. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find out the role of hemispheric dominance in the pathogenesis of bronchial asthma. The pathway was upregulated with increase in digoxin synthesis in bronchial asthma. There was an increase in tryptophan catabolites and a reduction in tyrosine catabolites in patients with bronchial asthma. The ubiquinone levels were low and lipid peroxidation increased in these patients. There was increase in dolichol and glycoconjugate levels and reduction in lysosomal stability in these patients. The cholesterol:phospholipid ratio was increased and glycoconjugate levels were reduced in the membranes of these patients. The patterns noticed in bronchial asthma were similar to those in patients with right hemispheric chemical dominance. Bronchial asthma occurs in right hemispheric chemically dominant individuals. Ninety percent of the patients with bronchial asthma were right-handed and left hemispheric dominant by the dichotic listening test. But their biochemical patterns were similar to those obtained in right hemispheric chemical dominance. Hemispheric chemical dominance is a different entity and has no correlation with handedness or the dichotic listening test.
Asunto(s)
Asma/etiología , Asma/metabolismo , Digoxina/metabolismo , Dominancia Cerebral/fisiología , Hipotálamo/metabolismo , Adulto , Análisis de Varianza , Asma/fisiopatología , Radicales Libres/metabolismo , Humanos , Hipotálamo/fisiopatologíaRESUMEN
The isoprenoid pathway produces endogenous digoxin which can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in individuals with differing family bonding patterns. The patterns were compared in those with right hemispheric and left hemispheric dominance. Digoxin synthesis was increased with upregulated tryptophan catabolism (increased levels of serotonin, strychnine and nicotine) and down regulated tyrosine catabolism (decreased levels of dopamine, noradrenaline and morphine) in those with reduced family bonding and right hemispheric chemical dominance. Digoxin synthesis was reduced with down regulated tryptophan catabolism (decreased levels of serotonin, strychnine and nicotine) and upregulated tyrosine catabolism (increased levels of dopamine, noradrenaline and morphine) in those with increased family bonding and left hemispheric chemical dominance. Hypothalamic digoxin plays a central role in the regulation of family bonding behavior. Hemispheric chemical dominance in relation to digoxin status is also crucial.
Asunto(s)
Digoxina/metabolismo , Dominancia Cerebral/fisiología , Apego a Objetos , Saponinas/metabolismo , Adulto , Cardenólidos , Catecolaminas/metabolismo , Membrana Eritrocítica/enzimología , Familia , Femenino , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipotálamo/metabolismo , Magnesio/sangre , Masculino , Persona de Mediana Edad , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Tirosina/metabolismoRESUMEN
The isoprenoid pathway including endogenous digoxin was assessed in Creutzfeldt-Jakob Disease (CJD). This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with CJD and in those with right hemispheric chemical dominance. In this group of patients (i) the tryptophan catabolites were increased and the tyrosine catabolites reduced, (ii) the dolichol and glycoconjugate levels were elevated, (iii) lysosomal stability was reduced, (iv) ubiquinone levels were low and free radical levels increased, and (v) the membrane cholesterol:phospholipid ratios were increased and membrane glyco conjugates reduced. On the other hand, in patients with left hemispheric chemical dominance, the reverse patterns were obtained. The role of the isoprenoid pathway in the pathogenesis of CJD and its relation to hemispheric chemical dominance is discussed.
Asunto(s)
Síndrome de Creutzfeldt-Jakob/fisiopatología , Digoxina/sangre , Dominancia Cerebral/fisiología , Membrana Eritrocítica/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Química Encefálica/fisiología , Dolicoles/sangre , Inhibidores Enzimáticos/sangre , Radicales Libres/sangre , Glicoproteínas/sangre , Glicosaminoglicanos/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Hipotálamo/metabolismo , Peroxidación de Lípido/fisiología , Lisosomas/metabolismo , Magnesio/sangre , Análisis por Apareamiento , Modelos Biológicos , Modelos Neurológicos , Neurotransmisores/metabolismo , Fosfatos de Poliisoprenilo/metabolismo , Triptófano/metabolismo , Tirosina/metabolismo , Ubiquinona/sangreRESUMEN
The isoprenoid pathway produces endogenous digoxin, a substance that can regulate neurotransmitter and amino acid transport. Digoxin synthesis and neurotransmitter patterns were assessed in individuals with differing family bonding patterns. The family bonding patterns were assessed by the FACES scale--family adaptability and cohesiveness evaluation scale. The criteria given in the handbook for the 16 PF--16 personality factors questionnaire by Cattell, Eber, and Tatsouke--was also chosen for assessing the individual personality aspect of family bonding after suitable modification. The patterns were compared in those with right hemispheric and left hemispheric dominance. Digoxin synthesis was increased with upregulated tryptophan catabolism (increased levels of serotonin, strychnine, and nicotine) and downregulated tyrosine catabolism (decreased levels of dopamine, noradrenaline, and morphine) in those with reduced family bonding and right hemispheric dominance. Digoxin synthesis was reduced with downregulated tryptophan catabolism (decreased levels of serotonin, strychnine, and nicotine) and upregulated tyrosine catabolism (increased levels of dopamine, noradrenaline, and morphine) in those with increased family bonding and left hemispheric chemical dominance. Hypothalamic digoxin plays a central role in the regulation of family bonding behavior. Hemispheric chemical dominance in relation to digoxin status is also crucial in this respect.
Asunto(s)
Digoxina/sangre , Dominancia Cerebral/fisiología , Membrana Eritrocítica/metabolismo , Hipotálamo/metabolismo , Apego a Objetos , Saponinas/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Adulto , Catecolaminas/metabolismo , Dolicoles/sangre , Inhibidores Enzimáticos/sangre , Relaciones Familiares , Femenino , Glicoproteínas/sangre , Glicosaminoglicanos/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Magnesio/sangre , Masculino , Persona de Mediana Edad , Fosfatos de Poliisoprenilo/metabolismo , Tirosina/metabolismo , Ubiquinona/sangreRESUMEN
The study assessed the biochemical differences between right hemispheric dominant and left hemispheric dominant individuals. The HMG CoA reductase activity, isoprenoid metabolites--serum digoxin--serum magnesium, and RBC membrane Na+-K+ ATPase activity were also studied. The results showed that right hemispheric chemically dominant individuals had increased (i) HMG CoA reductase activity, elevated digoxin levels, (ii) reduced RBC membrane Na+-K+ ATPase activity and serum magnesium levels. Left hemispheric chemically dominant individuals had the opposite patterns. Right hemispheric chemical dominance represents a hyperdigoxinemic/hypomagnesemic state with membrane sodium-potassium ATPase inhibition. Left hemispheric chemical dominance represents the reverse pattern with hypodigoxinemia/hypermagnesemia and membrane sodium-potassium ATPase stimulation. Cerebral chemical dominance can regulate calcium/magnesium metabolism.