Transesophageal echocardiography of the quadricuspid aortic valve.
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Adult↗
Biomedical subjects
Ferenc Puskas
Publications and source records attributed to Ferenc Puskas.
Cognitive dysfunction after cardiac surgery: revisiting etiology.
Cognitive dysfunction remains a frequent complication of cardiac surgery. Despite many years of research, few preventive strategies and no definitive therapeutic options exist for the management of this troublesome clinical problem. This shortcoming may be secondary to an incomplete understanding of the pathophysiology and etiology of cognitive loss after cardiac surgery; a better understanding of the etiology is essential to finding new therapies. The etiology of cognitive dysfunction after cardiac surgery is multifactorial and includes cerebral microembolization, global cerebral hypoperfusion, systemic and cerebral inflammation, cerebral temperature perturbations, cerebral edema, and possible blood-brain barrier dysfunction, all superimposed on genetic differences in patients that may make them more susceptible to injury or unable to repair from injury once it has occurred. This review expands on these potential etiologies in detailing the evidence for their existence.
Blood-Brain Barrier↗
Apoptosis and mitochondrial dysfunction in lymphocytes of patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is characterized by abnormal activation and cell death signaling within the immune system. Activation, proliferation, or death of cells of the immune system are dependent on controlled reactive oxygen intermediate (ROI) production and ATP synthesis in mitochondria. The mitochondrial transmembrane potential (Delta(Psi)m) reflects the energy stored in the electrochemical gradient across the inner mitochondrial membrane, which in turn is used by F0F1-ATPase to convert adenosine 5'-diphosphate to ATP during oxidative phosphorylation. Mitochondrial hyperpolarization and transient ATP depletion represent early and reversible steps in T-cell activation and apoptosis. By contrast, T lymphocytes of patients with SLE exhibit elevated Delta(Psi)m, that is, persistent mitochondrial hyperpolarization, cytoplasmic alkalinization, increased ROI production, as well as diminished levels of intracellular glutathione and ATP. Oxidative stress affects signaling through the T-cell receptor as well as the activity of redox-sensitive caspases. ATP depletion may be responsible for diminished activation-induced apoptosis and sensitize lupus T cells to necrosis. Mitochondrial dysfunction is identified as a key mechanism in the pathogenesis of SLE.
Adenosine Triphosphate↗
Intrathecal clonidine and severe hypotension after cardiopulmonary bypass.
The use of intrathecal clonidine as an adjunct for the management of chronic pain, intra- and postoperative analgesia is gaining an increase in popularity. However, antinociceptive doses of intrathecal clonidine may produce pronounced hemodynamic side effects, including hypotension and bradycardia. In this report, we present a case of severe hypotension after cardiopulmonary bypass in a patient with intrathecal clonidine infusion. We postulate that the intrathecally administered alpha 2-agonist clonidine reduced our patient's ability to tolerate the hemodynamic lability that is present during the separation from cardiopulmonary bypass by potentially inhibiting sympathetic nervous system activity, renin-angiotensin system, or vasopressin release. The authors report a case of severe hypotension after cardiopulmonary bypass in a patient receiving intrathecal clonidine infusion for chronic neuropathic pain.
Adrenergic alpha-Agonists↗
Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus.
OBJECTIVE: Peripheral blood lymphocytes (PBLs) from systemic lupus erythematosus (SLE) patients exhibit increased spontaneous and diminished activation-induced apoptosis. We tested the hypothesis that key biochemical checkpoints, the mitochondrial transmembrane potential (deltapsim) and production of reactive oxygen intermediates (ROIs), mediate the imbalance of apoptosis in SLE. METHODS: We assessed the deltapsim with potentiometric dyes, measured ROI production with oxidation-sensitive fluorochromes, and monitored cell death by annexin V and propidium iodide staining of lymphocytes, using flow cytometry. Intracellular glutathione levels were measured by high-performance liquid chromatography, while ATP and ADP levels were assessed by the luciferin-luciferase assay. RESULTS: Both deltapsim and ROI production were elevated in the 25 SLE patients compared with the 25 healthy subjects and the 10 rheumatoid arthritis patients. Intracellular glutathione contents were diminished, suggesting increased utilization of reducing equivalents in SLE. H2O2, a precursor of ROIs, increased deltapsim and caused apoptosis in normal PBLs. In contrast, H2O2-induced apoptosis and deltapsim elevation were diminished, particularly in T cells, and the rate of necrotic cell death was increased in patients with SLE. The intracellular ATP content and the ATP:ADP ratio were reduced and correlated with the deltapsim elevation in lupus. CD3:CD28 costimulation led to transient elevation of the deltapsim, followed by ATP depletion, and sensitization of normal PBLs to H2O2-induced necrosis. Depletion of ATP by oligomycin, an inhibitor of F0F1-ATPase, had similar effects. CONCLUSION: T cell activation and apoptosis are mediated by deltapsim elevation and increased ROI production. Mitochondrial hyperpolarization and the resultant ATP depletion sensitize T cells for necrosis, which may significantly contribute to inflammation in patients with SLE.
Adenosine Triphosphate↗
Differential regulation of hydrogen peroxide and Fas-dependent apoptosis pathways by dehydroascorbate, the oxidized form of vitamin C.
Dehydroascorbate (DHA), the oxidized form of vitamin C (ascorbate), enhanced antioxidant defenses of human T cells preferentially importing DHA over ascorbate. In itself, DHA did not affect cytosolic or mitochondrial reactive oxygen intermediate levels as monitored by flow cytometry using oxidation-sensitive fluorescent probes. DHA at 200-1,000 microM stimulated activity of pentose phosphate pathway enzymes glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and transaldolase, elevated intracellular glutathione levels, and inhibited H(2)O(2)-induced changes in mitochondrial transmembrane potential and cell death. With respect to the CD4 antigen, DHA selectively enhanced cell-surface expression of the Fas receptor and increased susceptibility of Jurkat and H9 human T cells to Fas-mediated cell death. The data identify DHA as a selective regulator of H(2)O(2)- and Fas-dependent apoptosis pathways.
Animals↗
Metabolic switches of T-cell activation and apoptosis.
The signaling networks that mediate activation, proliferation, or programmed cell death of T lymphocytes are dependent on complex redox and metabolic pathways. T lymphocytes are primarily activated through the T-cell receptor and co-stimulatory molecules. Although activation results in lymphokine production, proliferation, and clonal expansion, it also increases susceptibility to apoptosis upon crosslinking of cell-surface death receptors or exposure to toxic metabolites. Activation signals are transmitted by receptor-associated protein tyrosine kinases and phosphatases through calcium mobilization to a secondary cascade of kinases, which in turn activate transcription factors initiating cell proliferation and cytokine production. Initiation and activity of cell death-mediating proteases are redox-sensitive and dependent on energy provided by ATP. Mitochondria play crucial roles in providing ATP for T-cell activation through the electron transport chain and oxidative phosphorylation. The mitochondrial transmembrane potential (DeltaPsi(m)) plays a decisive role not only by driving ATP synthesis, but also by controlling reactive oxygen species production and release of cell death-inducing factors. DeltaPsi(m) and reactive oxygen species levels are regulated by the supply of reducing equivalents, glutathione and thioredoxin, as well as NADPH generated in the pentose phosphate pathway. This article identifies redox and metabolic checkpoints controlling activation and survival of T lymphocytes.
Adenosine Triphosphate↗