Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A two and one-half year old boy with complex congenital heart disease had Howell-Jolly bodies in his blood raising the possibility of the asplenia syndrome. A 99mTc-sulfur colloid liver-spleen scan was reported normal, but the right lobe of the abnormally reversed liver was mistaken for the spleen. The diagnosis of visceral heterotaxy (Ivemark's syndrome) was established after scanning the patient with a new radiopharmaceutical, 99mTechnetium pyridoxylidene glutamate. The agent clearly demonstrated a left-sided gall bladder, and on comparison with the sulfur colloid scan it was established that asplenia was present. Radionuclide imaging with the new generation of hepatobiliary agents is a reliable method to document asplenia and is useful in studying patients with visceral heterotaxy.
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PMID:99mTechnetium pyridoxylidene glutamate imaging in visceral heterotaxy (Ivemark's syndrome). 48 37

For the first time, the GluR-1 subtype of AMPA receptor was identified in the sympathetic nervous system of neonatal swine, an animal model of human development and heart disease. The rationale was to seek evidence of a role ascribed to glutamate in cardiorespiratory regulation in the laboratory rat. The receptor was demonstrated with the avidin-biotin immunoperoxidase technique by using an affinity-purified polyclonal antibody judged to be specific to Glu-R1 in several species. Glu-R1 immunoreactivity was regionally distributed in the thoracic spinal gray, and present intracellularly in neurons and within the surrounding neuropil. Sympathetic preganglionic neurons in the intermediolateral cell column of upper and lower thoracic spinal segments were intensely labeled and surrounded by labeled neuropil. High concentrations of Glu-R1 distinguished laminae II: substantia gelatinosa and the outer region of lamina III. Laminae I and V of the dorsal horn but not IV contained immunolabeled neurons. Arrays of moderately immunoreactive perikarya extended from an intermediate zone of laminae VII to the central gray. Glia and perivascular processes were not labeled, confirming previous observations [Tachibana, M., Wenthold, R.J., Morioka, H., Petralia, R.S., 1994. Light and electron microscopic immunocytochemical localization of AMPA-selective glutamate receptors in the rat spinal cord. J. Comp. Neurol. 344, 431-454]. Neuronal staining patterns corroborated evidence in rats indicating a postsynaptic localization of Glu-R1 associated with plasma membranes and cytoplasmic organelles [Martin, L.J., Blackstone, C.D., Levey, A.I., Huganir, R.L., Price, D.L., 1993. AMPA glutamate receptor subunits are differentially distributed in rat brain. Neuroscience 53, 327-358.; Rubio, M.E., Wenthold, R.J., 1997. Glutamate receptors are selectively targeted to postsynaptic sites in neurons. Neuron 18, 939-950]. Our data predict a role for L-glutamate in postnatal development of cardiorespiratory reflexes in swine.
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PMID:Presence of a non-NMDA glutamate receptor subtype in the sympathetic nervous system of neonatal swine. 986 84

Unlike disorders of other fields of medicine (eg., diabetes, heart disease), schizophrenia has been only marginally impacted by the study of animal models. This gap reflects the incomplete understanding of the causes and mechanisms of schizophrenia and the resulting lack of defined targets for model development. However, prior attempts at modeling in animals the complex symptoms of schizophrenia have given way to more promising component models. This review will address the evolving field of animal models of schizophrenia with a focus on models of errors in neurotransmission, and of psychophysiological deficits, with a concluding discussion of the present and future promise of genetic-based models. Evolving models based on the long-held conceptualization of schizophrenia as being based on errors in neurotransmission are discussed as regards the integration of newer findings implicating alterations in dopamine, glutamate and neurotensin function in the pathophysiology and pharmacotherapy of schizophrenia. The case for the more recent conceptualization of schizophrenia as a core deficit in information processing and stimulus filtering is discussed. Animal behavioral paradigms that model psychophysiologic constructs of stimulus processing deficits related to schizophrenia include prepulse inhibition (PPI), a model of sensorimotor gating, or latent inhibition (LI), a model of salience learning. These models represent both better supported associations with schizophrenia and more productive targets and are providing important new information regarding the psychopharmacology of schizophrenia. Genetic models of schizophrenia are based on the demonstrated heritability of the disorder and more recent pharmacogenetic findings for antipsychotic medications. Genetic-based animal models use behavioral or molecular genetic techniques to manipulate behaviors related to schizophrenia by altering the frequencies of related genes. The future development of increasingly informative animal models of schizophrenia will be dependent on a more complete understanding of schizophrenia, an integration of findings across animal models and refinements in the criteria used to assess model "validity" that better reflect the changing nature and roles of animal models of schizophrenia.
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PMID:The changing roles and targets for animal models of schizophrenia. 1174 40

Diseases of the heart are the No. 1 killer in industrialized countries. Brain injury can develop as a result of cerebral ischemia-reperfusion due to stroke (brain attack) and other cardiovascular diseases. Learning about the disease is the best way to reduce disability and death. We present here whether gene repair activities are associated with neuronal death in an ischemia-reperfusion model that simulates stroke in male Long-Evans rats. This experimental stroke model is known to induce necrosis in the ischemic cortex. Cerebral ischemia causes overactivation of membrane receptors and accumulation of extracellur glutamate and intracellular calcium, which activates neuronal nitric oxide synthase, causing damage to lipids, proteins, and nucleic acids, and reduces energy sources with consequent functional deterioration, leading to cell death. Restoration processes normally repair genes with few errors. However, ischemia elevates oxidative DNA lesions despite these repair mechanisms. These episodes concurrently occur with the induction of immediate-early genes that critically activate other late genes in the signal transduction pathway. Damage, repair, and transcription of the c-FOS gene are presented here as examples, because Fos peptide, one of the components of activator protein 1, activates nerve growth factor and repair mechanisms. The results of our studies show that treatments with 7-nitroindazole, a specific inhibitor of nitric oxide synthase known to attenuate nitric oxide, oxidative DNA lesions, and necrosis, increase intact c-fos mRNA levels after stroke. This suggests that the accuracy of gene expression could be accounted for the recovery of cellular function after cerebral injury.
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PMID:Ischemia-reperfusion-related repair deficit after oxidative stress: implications of faulty transcripts in neuronal sensitivity after brain injury. 1256 81

We used proton magnetic resonance spectroscopy to study 11 children (age < 8 years) with congenital heart disease undergoing cardiopulmonary bypass to determine whether low (10 +/- 4; n = 6) vs high (20 +/- 4; n = 5) perfusate hematocrits during bypass resulted in changes in brain metabolites which correlate with neurologic injury. Long and short echo time single voxel magnetic resonance spectroscopy in occipital gray matter and neurologic assessment were performed preoperatively and 2 and 5 days postoperatively. We also determined whether prolonged periods at low flow rates during bypass affected spectroscopy variables. We found no significant differences in metabolite ratios between the low vs high hematocrit groups or the lower vs higher flow rate groups (repeated measures analysis of variance of observation ranks converted to normal scores). However, our study was limited by statistical power due to the small sample size, therefore no conclusions could be made. Additional studies involving a greater number of patients are necessary. In all 11 children, magnetic resonance spectroscopy detected a significant decrease in brain N-acetyl-aspartate, and increases in myoinositol and glutamate/glutamine after surgery (Quade test) demonstrating that magnetic resonance spectroscopy is sensitive in detecting subtle postoperative changes in brain metabolites.
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PMID:Serial proton magnetic resonance spectroscopy of the brain in children undergoing cardiac surgery. 1458 Jun 52

The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 microl centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P < 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia.
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PMID:In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus. 1609 7

Intracellular calcium is a powerful secondary messenger that affects a number of calcium sensors, including calpain, a Ca2+-dependent cysteine protease, and calcineurin, a Ca2+/calmodulin-dependent protein phosphatase. Maintenance of low basal levels of intracellular calcium allows for the tightly regulated physiological activation of these proteins, which is crucial to a wide variety of cellular processes, such as fertilization, proliferation, development, learning, and memory. Deregulation of calpain and calcineurin has been implicated in the pathogenesis of several disorders, including hypertension, heart disease, diabetes, cerebral ischemia, and Alzheimer's disease. Recent studies have demonstrated an interplay between calpain and calcineurin, in which calpain can directly regulate calcineurin activity through proteolysis in glutamate-stimulated neurons in culture and in vivo. The calpain-mediated proteolytic cleavage of calcineurin increases phosphatase activity, which promotes caspase-mediated neuronal cell death. Thus, the activation of the calpain-calcineurin pathway could contribute to calcium-dependent disorders, especially those associated with Alzheimer's disease and myocardial hypertrophy. Here, we focus briefly on recent advances in revealing the structural and functional properties of these 2 calcium-activated proteins, as well as on the interplay between the 2, in an effort to understand how calpain-calcineurin signaling may relate to the pathogenesis of calcium- dependent disorders.
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PMID:Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder. 1759 48

Epilepsy is the most common neurological disorder, approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Furthermore, the evidence from the last 10 years suggests that melatonin has an important role in the epileptogenesis process and influences the cardiovascular system as well. The positive effect of melatonin has been demonstrated against different convulsive stimuli in several rodents, including seizures induced by pentylenetetrazole kainate, glutamate, maximal electrical shock and electrically kindled stimulation of amygdala. Clinical studies have also demonstrated a positive role of melatonin on the seizure frequency in children and reduced spiking activity and seizure frequency in patients with intractable epilepsy. In the rat hearts, studies in vivo and in vitro using pharmacological concentrations of melatonin confirmed an anti-arrhythmic effect of this hormone and studies in humans have been shown that chronic heart disease patients have significantly lower melatonin levels in their blood stream than do normal individuals. Thus, caution should be taken in generalization of these findings to epileptic population. Moreover, it is important to note that when dealing with intractable epilepsy that do not respond to any conventional treatment, the additional of melatonin may be evaluated. Taken together, in this paper we suggested a possible relationship between cardiac abnormalities, melatonin and SUDEP.
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PMID:Cardiovascular protective effect of melatonin in sudden unexpected death in epilepsy: a hypothesis. 1768 75

The Krebs cycle plays a fundamental role in cardiac energy production and is often implicated in the energetic imbalance characteristic of heart disease. In this study, we measured Krebs cycle flux in real time in perfused rat hearts using hyperpolarized magnetic resonance spectroscopy (MRS). [2-(13)C]Pyruvate was hyperpolarized and infused into isolated perfused hearts in both healthy and postischemic metabolic states. We followed the enzymatic conversion of pyruvate to lactate, acetylcarnitine, citrate, and glutamate with 1 s temporal resolution. The appearance of (13)C-labeled glutamate was delayed compared with that of other metabolites, indicating that Krebs cycle flux can be measured directly. The production of (13)C-labeled citrate and glutamate was decreased postischemia, as opposed to lactate, which was significantly elevated. These results showed that the control and fluxes of the Krebs cycle in heart disease can be studied using hyperpolarized [2-(13)C]pyruvate.
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PMID:Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. 1932 59

Patients with cardiac disease can develop two types of malnutrition: cardiac cachexia, which appears in chronic congestive heart failure, and malnutrition due to the complications of cardiac surgery or any other type of surgery in patients with heart disease. Early enteral nutrition should be attempted if the oral route cannot be used. When cardiac function is severely compromised, enteral nutrition is feasible, but supplementation with parenteral nutrition is sometimes required. Sustained hyperglycemia in the first 24 hours in patients admitted for acute coronary syndrome, whether diabetic or not, is a poor prognostic factor for 30-day mortality. In critically-ill cardiac patients with stable hemodynamic failure, nutritional support of 20-25 kcal/kg/day is effective in maintaining adequate nutritional status. Protein intake should be 1.2*-1.5 g/kg/day. Routine polymeric or high protein formulae should be used, according to the patient's prior nutritional status, with sodium and volume restriction according to the patient's clinical situation. The major energy source for myocytes is glutamine, through conversion to glutamate, which also protects the myocardial cell from ischemia in critical situations. Administration of 1 g/ day of omega-3 (EPA+DHA) in the form of fish oil can prevent sudden death in the treatment of acute coronary syndrome and can also help to reduce hospital admission for cardiovascular events in patients with chronic heart failure.
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PMID:[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): cardiac patient]. 2230 60


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