Chapters authored
Chagas Cardiomyopathy: Role of Sustained Host-Parasite Interaction in Systemic Inflammatory Burden By Rodolfo A Kölliker-Frers, Matilde Otero-Losada, Gabriela Razzitte,
Mariela Calvo, Justo Carbajales and Francisco Capani
The economic and social burden associated with Chagas disease morbidity and mortality is regrettably large in Latin America causing more deaths than does any other parasitic disease. Inflammatory dilated cardiomyopathy is, by far, the most important clinical consequence of Trypanosoma cruzi infection. The insidious persistence of this parasite determines chronic myocarditis progression. The clinical outcome is multifactorial and depends on the particular parasite strain and virulence factors, the infective load and route of infection, the parasite ability to by-pass the protective immune response, the intensity and type of immune response during the acute infective phase, and the host genetic background. From the immunological viewpoint, host control of T. cruzi has been shown to depend on both humoral and cell-mediated adaptive responses and from the innate immune system. In this review, we discuss the most relevant literature conveying information on the relevance of identifying a subset of systemic inflammatory molecules as potential markers of cardiovascular risk morbidity and mortality in patients with Chagas disease. Concurrently, a direct role for the parasite in the perpetuation of myocardial inflammation is substantiated. Ultimately, host-parasite interactions determine the course of the ongoing systemic inflammation and the perpetuation of myocardial inflammation in genetically predisposed patients.
Part of the book: Chagas Disease
Mitochondrial KATP Channel and Dopaminergic Vulnerability Neurons in Parkinson’s Disease By Gesivaldo Santos, Julita Maria Pereira Borges, Marcos Avilla-Rodriguez, Érika Pereira Rubio, Cattiúscia Batista Bromochenkel, Djalma Menezes Oliveira, Jane Lima dos Santos, Rosane Moura Aguiar, Milena Mascarenhas Ferraz, Silvana Batista Gaino, Francisco Capani and George E. Barreto
The motor deficiency control commonly characterizes Parkinson’s disease (PD), resulting in impairment of neuromuscular command, because of basal ganglia nuclei degeneration and late formation of Lewy’s bodies in the remaining dopaminergic (DA) neurons. Motor signals are triggered in high cortical motor areas and go toward the midbrain regions, where the final tuning movement takes place. PD is characterized primarily by the death of dopaminergic neurons in the regions known as substantia nigra compacta (STNc). Mutations in a couple of genes, such as Parkin1 and DJ1, correspond to the usual familial form of the disease, due to its association with oxidative stress and depolarization of mitochondrial membrane. However, this form does not explain the selective pattern of apoptosis between the neuronal dopaminergic areas of midbrain regions. In this chapter, we are putting forward the hypothesis of oxidative stress and mitochondrial changes as the apparent most relevant cause in PD, as well as the neuroprotective role played by Kir6.2, a potassium-ATP channel and calcium voltage-gated v1.3.
Part of the book: Parkinson's Disease and Beyond
Immune-Mediated Inflammation: Human T CD4 Helper Lymphocyte Diversity and Plasticity in Health and Disease By Rodolfo Alberto Kölliker Frers, Matilde Otero-Losada, María Inés Herrera, Sabrina Porta, Vanesa Cosentino, Eduardo Kerzberg, Lucas Udovin and Francisco Capani
The CD4+ T helper (Th) cells have a critical role in organizing the adaptive immune response. The emerging cells of the differentiation after the immune synapse produce helper T cell subpopulations that activate, suppress, or regulate the immune response upon interaction with varying immune cells. There are two main Th cell functional categories: the “effector cells” and the “regulatory T cells.” Classic T helper lymphocytes can also be distinguished by their lineage according to the developmental microenvironment, the expression of cell adhesion-homing receptors, the profile of cytokines they are exposed to, and the involved transcription factors. Traditionally, the CD4+ and CD8+ phenotypes have been considered as helper and cytotoxic/suppressor T lymphocytes, respectively. Currently, the distinction is little rigorous. The immune response is exceedingly complex beyond the classic Th1 and Th2 effector cells’ involvement, and other populations of helper T lymphocytes like the Th17, Tfh, Th22, and Th9 lymphocytes have been phenotypically characterized. These lymphocytes also participate in the pathogenesis of several immune-mediated inflammatory disorders. Here, we revisit and discuss the essential aspects of the state of the art regarding phenotypic diversity and plasticity of TCD4 cells in the T lymphocyte repertoire frame and their potential implication in human inflammatory diseases.
Part of the book: Cells of the Immune System
In Vivo Studies of Protein Misfolding and Neurodegeneration Induced by Metabolic Syndrome Relative to Chronic Cerebral Hypoperfusion: A Critical Review By María I. Herrera, Juan P. Luaces, Lucas D. Udovin, Nicolás Toro-Urrego, Matilde Otero-Losada and Francisco Capani
Metabolic syndrome (MetS) leads to microvascular dysfunction and chronic cerebral hypoperfusion (CCH) in an insidious way. Clinical evidence and several rodent models have contributed to determining the neurodegenerative effect of a sustained decrease in cerebral blood flow (CBF). Protein misfolding and aggregation derived from CCH might account for the establishment of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). However, the complex and multifactorial etiology of cerebrovascular disease demands the combination of experimental models in scientific research. In this sense, the present work aims at summarizing the differential available rodent paradigms for studying the establishment of cognitive decline resulting from protein misfolding induced by MetS in association with CCH. Revising experimental findings in the field will help further basic research on the pathophysiology of cerebrovascular disease and the future testing of protein-remodeling factors as neuroprotective agents for the prevention of cognitive impairment.
Part of the book: Neuroprotection
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