RESUMEN
INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.
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Demencia , Masculino , Femenino , Humanos , Demencia/epidemiología , Prevalencia , Envejecimiento , Pruebas Neuropsicológicas , India/epidemiologíaRESUMEN
The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.
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Disfunción Cognitiva , Demencia , Anciano , Humanos , Envejecimiento , Demencia/genética , Genómica , Estudios Longitudinales , IndiaRESUMEN
The Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI-DAD) is a population-representative, prospective cohort study of late-life cognition and dementia. It is part of an ongoing international research collaboration that aims to measure and understand cognitive impairment and dementia risk by collecting a set of cognitive and neuropsychological assessments and informant reports, referred to as the Harmonized Cognitive Assessment Protocol (HCAP). LASI-DAD provides nationally representative data drawn from a subsample of the ongoing Longitudinal Aging Study in India (LASI). One of LASI-DAD's distinctive features is its rich geriatric assessment, including the collection of venous blood samples and brain imaging data for a subsample of respondents. In this paper, we discuss the methodological considerations of developing and implementing the HCAP protocol in India. The lessons we learned from translating and applying the HCAP protocol in an environment where illiteracy and innumeracy are high will provide important insights to researchers interested in measuring and collecting data on late-life cognition and dementia in developing countries. We further developed an innovative blood management system that enables us to follow the collection, transportation, assay, and storage of samples. Such innovation can benefit other population surveys collecting biomarker data.
Asunto(s)
Envejecimiento , Demencia/diagnóstico , Anciano , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/fisiopatología , Demencia/clasificación , Demencia/genética , Femenino , Humanos , India , Estudios Longitudinales , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Estudios Prospectivos , Factores de RiesgoRESUMEN
The isoprenoid pathway produces three key metabolites-digoxin (membrane sodium-potassium ATPase inhibitor and regulator of intracellular calcium-magnesium ratios), dolichol (regulator of N-glycosylation of proteins) and ubiquinone (free radical scavenger). The pathway was assessed in a rare and specific type of familial basal ganglia calcification described. The family had a coexistence of basal ganglia calcification (six out of 10 cases), schizophrenia, Parkinson's disease, Alzheimer's disease, rheumatoid arthritis, systemic tumours and syndrome X and were all right hemispheric dominant. The isoprenoid pathway was also studied for comparison in right hemispheric dominant, bihemispheric dominant and left hemispheric dominant individuals. The isoprenoid pathway was upregulated with increased digoxin synthesis in familial basal ganglia calcification. Membrane sodium-potassium ATPase inhibition can lead on to increase in intracellular calcium and calcification of the basal ganglia. There was increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was also an increase in dolichol and glycoconjugate levels with reduced lysosomal stability in these patients. The ubiquinone levels were low and free radical levels increased. The cholesterol-phospholipid ratio was increased and glycoconjugate level of the RBC membrane reduced in these group of patients. No significance difference was noted in family members with and without basal ganglia calcification. This findings were correlated with the pathogenesis of syndrome X, immune mediated diseases, degenerations, tumours and psychiatric disorders noted in the familial basal ganglia calcification described. The biochemical patterns obtained in familial basal ganglia calcification correlated with those in right hemispheric dominance.
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Enfermedades de los Ganglios Basales/sangre , Calcinosis/sangre , Membrana Celular/enzimología , Digoxina/metabolismo , Hipotálamo/enzimología , Monosacáridos de Poliisoprenil Fosfato/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Adulto , Anciano , Enfermedades de los Ganglios Basales/enzimología , Enfermedades de los Ganglios Basales/genética , Calcinosis/enzimología , Calcinosis/genética , Corteza Cerebral/enzimología , Corteza Cerebral/fisiopatología , Femenino , Lateralidad Funcional/fisiología , Humanos , Hipotálamo/fisiopatología , Masculino , Persona de Mediana Edad , LinajeRESUMEN
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 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.
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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
This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol and ubiquinone in multiple myeloma. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition and free radical metabolism. There was elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na+ - K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, nicotine, strychnine and quinolinic acid were elevated while tyrosine, dopamine, noradrenaline and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins, cholesterol and phospholipids were reduced. The activity of all free radical scavenging enzymes, concentration of glutathione, iron binding capacity and ceruloplasmin decreased significantly while the concentration of lipid peroxidation products and NO increased. Hyperdigoxinemia related altered intracellular Ca++ mediated oncogene activation, dolichol induced altered glycoconjugate metabolism and ubiquinone deficiency related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical findings reported could be the cause or the consequence of multiple myeloma.
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Radicales Libres/metabolismo , Mieloma Múltiple/metabolismo , Transducción de Señal , Terpenos/metabolismo , Triptófano/metabolismo , Tirosina/metabolismo , Calcio/farmacología , Digoxina/sangre , Dolicoles/sangre , Membrana Eritrocítica/enzimología , Glicoconjugados/metabolismo , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Persona de Mediana Edad , Mieloma Múltiple/patología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Ubiquinona/metabolismoRESUMEN
The human hypothalamus synthesis an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin-mediated model for quantal perception of geomagnetic fields is proposed. External geomagnetic fields can produce membrane Na(+)-K(+) ATPase inhibition. The inhibition of Na(+)-K(+) ATPase can contribute to increase in intracellular calcium and decrease in magnesium, which can result in (1) defective neurotransmitter transport mechanism, (2) neuronal degeneration and apoptosis, (3) mitochondrial dysfunction, (4) defective golgi body function and protein processing dysfunction, (5) immune dysfunction and oncogenesis. Geomagnetic fields can thus regulate cellular function and contributing to the pathogenesis of disease.
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Digoxina/metabolismo , Enfermedad/etiología , Campos Electromagnéticos , Hipotálamo/metabolismo , Apoptosis , Aparato de Golgi/metabolismo , Humanos , Sistema Inmunológico , Mitocondrias/metabolismo , Neuronas/patología , Neurotransmisores/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidoresRESUMEN
A family with a high prevalence of Parkinson's disease, schizophrenia, neoplasms, syndrome-X, rheumatoid arthritis and epilepsy has been described. The psychological behavioural patterns of the family were as follows--creativity and high IQ, hypersexual behaviour, reduced appetite and eating behaviour, insomnia and reduced sleep patterns, increased tendency for spirituality, increased tendency for addiction, less of bonding and affectionate behaviour and left handedness. 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 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 depolarising tryptophan catabolites - serotonin, quinolinic acid, strychnine and nicotine and decreased levels of hyperpolarising 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 Ca(2+) and reduced Mg(++) levels leading to glutamate excitotoxicity, oncogene activation and immune activation. Digoxin induced altered Ca(++)/Mg(++) 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/left hemispheric dominant and left-handed/right hemispheric dominant individuals. The biochemical patterns in the indexed family and the diverse disorders studied correlated with those obtained in right hemispheric dominance. The hyperdigoxinemic state indicates right hemispheric dominance. Hypothalamic digoxin can thus function as the master conductor of the neuroimmunoendocrine orchestra and co-ordinate the functions of various cellular organelles.
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Digoxina/metabolismo , Hipotálamo/patología , Neuronas/patología , Enfermedad , Salud de la Familia , Femenino , Radicales Libres , Lateralidad Funcional , Humanos , Lisosomas/metabolismo , Masculino , Trastornos Mentales/metabolismo , Linaje , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Triptófano/metabolismo , Tirosina/metabolismoRESUMEN
The case report of a family with coexistence of hypotension, recurrent respiratory infection, motor tics, obsessive-compulsive disorder (OCD), 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 and less tendency toward spirituality. They did not have insomnia, but they did display tendency toward increased somnolence. No addictive behavior was observed. The family demonstrated a high level of bonding and affectionate behavior, and they were less creative, with an average intelligence quotient (IQ). There was a total absence of vascular thrombosis, systemic neoplasms and neuronal degeneration in the indexed family. All members of the indexed family were left hemispheric dominant. The levels of serum digoxin, HMG-CoA reductase activity, and dolichol were found to be decreased in the members of the indexed family, with a corresponding increase in red blood cell (RBC) Na(+)-K+ ATPase activity, serum ubiquinone and magnesium levels. There was increase in tyrosine catabolites and a reduction in tryptophan catabolites in the serum. The total and individual glycosaminoglycan fractions, carbohydrate residues of glycoproteins, activity of glycosaminoglycans (GAG) degrading enzymes, and glycohydrolases were decreased in the serum. The concentration of RBC membrane total GAG and carbohydrate residues of glycoproteins increased, while the cholesterol: phospholipid ratio of the 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.
Asunto(s)
Química Encefálica/fisiología , Digoxina/metabolismo , Salud de la Familia , Enfermedades Hipotalámicas/metabolismo , Índice de Masa Corporal , Trastorno Depresivo Mayor , Dolicoles/metabolismo , Dominancia Cerebral , Eritrocitos/fisiología , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipertensión , Enfermedades Hipotalámicas/complicaciones , Enfermedades Hipotalámicas/genética , Enfermedades Hipotalámicas/fisiopatología , Masculino , Trastorno Obsesivo Compulsivo/etiología , Osteoporosis , Trastornos Respiratorios/etiología , Disfunciones Sexuales Fisiológicas/etiología , ATPasa Intercambiadora de Sodio-Potasio , Tics , Triptófano/metabolismo , Tirosina/metabolismoRESUMEN
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.
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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 three key metabolites: i) digoxin (a membrane sodium-potassium ATPase inhibitor which can regulate intracellular calcium/magnesium ratios), ii) dolichol (which regulates N-glycosylation of proteins), and iii) ubiquinone (a free radical scavenger), all of which are important in bone and joint metabolism. The pathway was assessed in senile osteoporosis, spondylosis, and osteoarthritis. Digoxin could possibly play a role in the genesis of cerebral dominance because it can regulate multiple neurotransmitter systems. The pathway was also assessed in individuals of differing hemispheric dominance for comparison and to find out the role of cerebral dominance in the pathogenesis of these diseases. The plasma/serum-activity of HMG CoA reductase, magnesium, digoxin, dolichol, ubiquinone, and tryptophan/tyrosine catabolic patterns, as well as RBC Na(+)-K+ ATPase activity, were measured in the above mentioned groups. The glycoconjugate metabolism, free radical metabolism, and membrane composition were also studied. The pathway was upregulated with increased digoxin synthesis in patients with spondylosis and osteoarthritis. In this group of patients, the glycoconjugate levels and dolichol levels were increased and lysosomal stability reduced. The ubiquinone levels were low and free radicals increased in spondylosis and osteoarthritis. On the other hand, in senile osteoporosis, the isoprenoid pathway was downregulated and digoxin synthesis reduced. The glycoconjugate and dolichol levels were low and lysosomal stability increased. The ubiquinone levels were increased and free radical production increased in senile osteoporosis. The significance of these changes in the pathogenesis of osteoarthritis, spondylosis, and osteoporosis is discussed. The hyperdigoxinemic state is seen in osteoarthritis and spondylosis and in right hemispheric dominance. The hypodigoxinemic state is seen in left hemispheric dominance and senile osteoporosis. Hemispheric dominance plays a crucial role in deciding the predisposition to bone and joint diseases. Right hemispheric chemical dominance predisposes to spondylosis and osteoarthritis. Left hemispheric chemical dominance predisposes to osteoporosis.
Asunto(s)
Digoxina/metabolismo , Dominancia Cerebral , Hipotálamo/metabolismo , Osteoartritis/metabolismo , Osteoporosis/metabolismo , Osteofitosis Vertebral/metabolismo , Digoxina/sangre , Dolicoles/sangre , Eritrocitos/metabolismo , Femenino , Radicales Libres/metabolismo , Glicoconjugados/sangre , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Lisosomas/enzimología , Magnesio/sangre , Masculino , Análisis por Apareamiento , Osteoartritis/sangre , Osteoporosis/sangre , ATPasa Intercambiadora de Sodio-Potasio/sangre , Osteofitosis Vertebral/sangre , Ubiquinona/sangreRESUMEN
The isoprenoid pathway was assessed in atheistic and spiritually inclined individuals. The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has a correlation with spiritual and atheistic tendency. HMG CoA reductase activity, serum digoxin, RBC membrane Na(+)-K+ ATPase activity, serum magnesium, and tyrosine/tryptophan catabolic patterns were assessed in spiritual/atheistic individuals and in those differing hemispheric dominance. In spiritually-inclined 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 spiritually-inclined individuals correlated with right hemispheric chemical dominance. In atheistic individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolities (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in atheistic individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to spirituality or atheism.
Asunto(s)
Digoxina/metabolismo , Dominancia Cerebral/fisiología , Hipotálamo/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Espiritualidad , Adulto , Análisis de Varianza , Digoxina/sangre , Membrana Eritrocítica/enzimología , Femenino , Humanos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Magnesio/sangre , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Fosfatos de Poliisoprenilo/metabolismo , Distribución Aleatoria , Triptófano/metabolismo , Tirosina/metabolismo , Ubiquinona/sangreRESUMEN
BACKGROUND/AIMS: This study assessed the changes in the isoprenoid pathway and its metabolites in seizure disorder (ILAE classification - I generalized - idiopathic generalized epilepsy with age-related onset - epilepsy with generalized tonic clonic seizures on awakening) and the metabolic cascade produced by isoprenoid pathway dysregulation. METHODS: The following parameters were assessed in seizure disorder: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugates metabolism and red blood cell (RBC) membrane composition. RESULTS: There was elevation in plasma HMG-CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na-K+ ATPase activity, serum magnesium and ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine and quinolinic acid were elevated while tyrosine, dopamine, morphine and norepinephrine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions (except dermatan sulfate), the activity of glycosaminoglycans (GAG) degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. Total serum cholesterol, LDL cholesterol and free fatty acids were increased while HDL cholesterol and triglycerides were unaltered. The concentration of membrane hexose, fucose, cholesterol and phospholipids in the RBC membrane decreased significantly but the total RBC membrane GAG was unaltered. CONCLUSIONS: Epileptogenesis could be due to a dysfunctional isoprenoidal pathway and paroxysmal hypothalamic digoxin hypersecretion.