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)

Ten to twelve million people irregularly distributed mainly through extensive rural areas of Latin America are afflicted by American trypanosomiasis (Chagas disease). Trypanosoma cruzi is the etiological agent, and it is naturally transmitted to humans by hematophagous hemiptera of Triatominae sub-family. These hemiptera feed by biting and usually defecate in the area near the puncture wound. Mucous membranes of breaks in the continuity of skin serve as passage ways for the parasite present in the excrement of the bug. Acute and chronic forms of American trypanosomiasis occur. Nervous system involvement in the acute form may give rise to meningoencephalitis. Central and/or peripheral signs of nervous system involvement can occur in the chronic form. Neuronal depopulation due to cell destruction by direct parasitism during the acute stage of the disease is the main pathogenetic way pointed out to explain chronic forms of nervous system involvement. Chronic Chagas cardiopathy usually produces mural thrombi. Fragments of thrombus situated in the left ventricle may become detached and migrate with the bloodstream to cause embolic phenomena in distant vessels--as in brain vessels--thus causing embolic cerebrovascular insults. Data on clinical and experimental studies are critically analysed.
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PMID:[American trypanosomiasis (Chagas disease) and the nervous system]. 314 93

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

Neuronal activity plays a pivotal role in shaping neuronal wiring. We investigated the role of neuronal activity in the formation of interhemispheric (callosal) axon projections in neonatal mouse visual cortex. Axonal labeling with enhanced green fluorescent protein (GFP) was used to demonstrate spatially organized pattern of callosal projections: GFP-labeled callosal axons from one hemisphere projected densely to a narrowly restricted region at the border between areas 17 and 18 in the contralateral hemisphere, in which they terminated in layers 1-3 and 5. This region- and layer-specific innervation pattern developed by postnatal day 15 (P15). To explore the role of neuronal activity of presynaptic and postsynaptic neurons in callosal connection development, an inwardly rectifying potassium channel, Kir2.1, was expressed in callosal projection neurons and their target postsynaptic neurons. Kir2.1 overexpression reduced the firing rate of cortical neurons. Kir2.1 overexpression in callosal projection neurons disturbed the growth of axons and their arbors that normally occurs between P7 and P13, whereas that in postsynaptic neurons had limited effect on the pattern of presynaptic callosal axon innervation. In addition, exogenous expression of a gain-of-function Kir2.1 mutant channel found in patients with a familial heart disease caused severe deficits in callosal axon projections. These results suggest that projection neuron activity plays a crucial role in interhemispheric connection development and that enhanced Kir2.1 activity can affect cortical wiring.
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PMID:Evidence for activity-dependent cortical wiring: formation of interhemispheric connections in neonatal mouse visual cortex requires projection neuron activity. 1792 33

A large body of evidence indicates that sporadic Alzheimer's disease (AD) is a vascular disorder with neurodegenerative consequences and needs to be treated and managed as such. Epidemiologic studies of vascular risk factors, together with preclinical detection tools for AD are proof of concept that cerebral hypoperfusion is one of the earliest pathological signs in the development of cognitive failure. Vascular risk factors involving heart disease and stroke in the elderly individual who already possesses a dwindling cerebrovascular reserve due to advancing age contribute to further decline in cerebral blood flow (CBF) resulting in unrelenting brain hypoperfusion. Brain hypoperfusion, in turn, can reach a critically attained threshold of cerebral hypoperfusion (CATCH) giving rise to a neuronal energy crisis via reduced ATP synthesis. The ensuing metabolic energy crisis initially carves up ischemic-sensitive neurons in the hippocampus and posterior parietal cortex setting up cognitive meltdown and progressive neurodegenerative and atrophic changes in the brain. Neuronal energy compromise accelerates oxidative stress, excess production of reactive oxygen species, aberrant protein synthesis, ionic membrane pump dysfunction, signal transduction impairment, neurotransmitter failure, abnormal processing of amyloid precursor protein resulting in beta-amyloid deposition and axonal microtubule disruption from tau hyperphosphorylation. The high energy metabolic changes leading to oxidative stress and cellular hypometabolism precede clinical expression of AD. Regional CBF measurements using neuroimaging techniques can predict AD preclinically at the mild cognitive impairment stage or even before any clinical manifestation of dementia is expressed. Clinical diagnostic assessment of elderly persons who could develop or already present with memory complaints can prevent, reverse or slow down AD development. Although pathologic aging is the subject of thousands of studies, the question of why the elderly (and not younger people) succumb to AD has not been adequately addressed. The explanation(s) as to why vascular risk factors, for example, can trigger AD or vascular dementia usually in the elderly and not the young should provide vital clues in the search for a strategically effective dementia treatment. This review offers inductive hypothetical darts relative to that critical question.
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PMID:Pathophysiology of neuronal energy crisis in Alzheimer's disease. 1832 69

Protein kinase C (PKC) is a family of enzymes whose members transduce a large variety of cellular signals instigated by the receptor-mediated hydrolysis of membrane phospholipids. While PKC has been widely implicated in the pathology of diseases affecting all areas of physiology including cancer, diabetes, and heart disease-it was discovered, and initially characterized, in the brain. PKC plays a key role in controlling the balance between cell survival and cell death. Its loss of function is generally associated with cancer, whereas its enhanced activity is associated with neurodegeneration. This review presents an overview of signaling by diacylglycerol (DG)-dependent PKC isozymes in the brain, and focuses on the role of the Ca2+-sensitive conventional PKC isozymes in neurodegeneration.
Neuronal Signal 2017 Apr
PMID:Conventional protein kinase C in the brain: 40 years later. 3271 76