Candida-Related Immune Response Inflammatory Syndrome Treated With Adjuvant Corticosteroids And Review Of The Pediatric Literature (original) (raw)
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Candida spp. and Oxidative Stress Response in Innate Immune Cells
2010
In this work the oxidative burst of the innate immune system in response to Candida albicans infection was investigated. The clinical spectrum of the human opportunistic pathogen C. albicans ranges from mucocutaneous infections to systemic life-threatening diseases in immunocompromised patients. One of the immediate early responses of cells of the innate immune system on encountering microbial pathogens is the production of reactive oxygen species (ROS) by phagocytes. ROS play important roles in inflammatory reactions by destroying invading pathogens. However, overproduction of ROS may also cause endothelial damage, and excessive inflammation. Previous studies have shown that zymosan, a cell wall preparation of Saccharomyces cerevisiae, as well as C. albicans in the yeast form, strongly induce ROS in macrophages. The C. albicans genome harbours six superoxide dismutases (SOD1-6) involved in ROS degradation; SOD1 to SOD3 are intracellular and SOD4 to SOD6 are located in the cell wall...
Immune Dysfunction, Cytokine Disruption, and Stromal Changes in Myelodysplastic Syndrome: A Review
Cells
Myelodysplastic syndromes (MDS) are myeloid neoplasms characterized by bone marrow dysfunction and increased risk of transformation to leukemia. MDS represent complex and diverse diseases that evolve from malignant hematopoietic stem cells and involve not only the proliferation of malignant cells but also the dysfunction of normal bone marrow. Specifically, the marrow microenvironment—both hematopoietic and stromal components—is disrupted in MDS. While microenvironmental disruption has been described in human MDS and murine models of the disease, only a few current treatments target the microenvironment, including the immune system. In this review, we will examine current evidence supporting three key interdependent pillars of microenvironmental alteration in MDS—immune dysfunction, cytokine skewing, and stromal changes. Understanding the molecular changes seen in these diseases has been, and will continue to be, foundational to developing effective novel treatments that prevent dis...
Blood research, 2016
Immune thrombocytopenia (ITP) is the most common cause of acquired childhood thrombocytopenia and is characterized by increased immune-mediated destruction of circulating thrombocytes. Oxidative damage may be involved in ITP pathogenesis; paraoxonase (PON) and arylesterase (ARE) enzymes are closely associated with the cellular antioxidant system. We investigated the effect of short-term high-dose methylprednisolone (HDMP) treatment on the total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and PON and ARE enzymatic activity in children with acute ITP. Thirty children with acute ITP constituted the study group and 30 healthy children constituted the control group. Children with acute ITP were treated with HDMP: 30 mg/kg for 3 days, then 20 mg/kg for 4 days. The TOS, TAC, OSI, PON, and ARE levels were determined before and after 7 days of HDMP treatment. The TAC level (P<0.001), and PON (P<0.001) and ARE (P=0.001) activities were lower and...
Bone marrow oxidative stress and specific antioxidant signatures in myelodysplastic syndromes
Blood Advances, 2019
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders with an inherent tendency for transformation in secondary acute myeloid leukemia. This study focused on the redox metabolism of bone marrow (BM) cells from 97 patients compared with 25 healthy controls. The level of reactive oxygen species (ROS) was quantified by flow cytometry in BM cell subsets as well as the expression level of 28 transcripts encoding for major enzymes involved in the antioxidant cellular response. Our results highlight increased ROS levels in BM nonlymphoid cells and especially in primitive CD34posCD38low progenitor cells. Moreover, we identified a specific antioxidant signature, dubbed “antioxidogram,” for the different MDS subgroups or secondary acute myeloblastic leukemia (sAML). Our results suggest that progression from MDS toward sAML could be characterized by 3 successive molecular steps: (1) overexpression of enzymes reducing proteic disulfide bonds (MDS with <5% BM...
Free Radical Research, 2015
Beyond the disorders recognized as mitochondrial diseases, abnormalities in function and/or ultrastructure of mitochondria have been reported in several unrelated pathologies. These encompass ageing, malformations, and a number of genetic or acquired diseases, as diabetes and cardiologic, haematologic, organ-specific (e.g., eye or liver), neurologic and psychiatric, autoimmune, and dermatologic disorders. The mechanistic grounds for mitochondrial dysfunction (MDF) along with the occurrence of oxidative stress (OS) have been investigated within the pathogenesis of individual disorders or in groups of interrelated disorders. We attempt to review broad-ranging pathologies that involve mitochondrial-specific deficiencies or rely on cytosol-derived prooxidant states or on autoimmune-induced mitochondrial damage. The established knowledge in these subjects warrants studies aimed at elucidating several open questions that are highlighted in the present review. The relevance of OS and MDF in different pathologies may establish the grounds for chemoprevention trials aimed at compensating OS/MDF by means of antioxidants and mitochondrial nutrients.
BioNanoScience
In this paper, we report results of the study of immune parameters with the assessment of regulatory and effector subpopulations of lymphocytes and monocytes with candidiasis in children with chronic somatic diseases (secondary pyelonephritis and obstructive diseases of the upper gastrointestinal tract). Candidiasis was diagnosed by the rising level of circulating Candida albicans mannan antigen and culture mycological research. It was found that the persistence of fungi is associated with differentiated regulatory changes in the structure of subpopulations of lymphocytes and monocytes with preferential increase of immunosuppressive cells (CD4+ CD25+hi, CD3+CD16/56+, CD3−CD8+, CD3+4−8−) amid reduction of effector subpopulations of lymphocytes and antigen presenting cells associated with Th1 immune response profile.
Frontiers in Cell and Developmental Biology, 2021
Oxidative stress has been implicated in the development of several types of cancer, including myelodysplastic syndromes (MDS), as well as in the resistance to treatment. In this work, we assessed the potential of oxidative stress parameters to predict the response to erythropoiesis-stimulating agents (ESAs) in lower-risk MDS patients. To this end, we analyzed the systemic levels of reactive species (peroxides and NO), antioxidant defenses (uric acid, vitamin E, vitamin A, GSH, GSSG, TAS, as well as GPX and GR activities], and oxidative damage (8-OH-dG and MDA) in 66 MDS patients, from those 44 have been treated with ESA. We also calculated the peroxides/TAS and NO/TAS ratios and analyzed the gene expression of levels of the redox regulators, NFE2L2 and KEAP1. We found that patients that respond to ESA treatment showed lower levels of plasma peroxides (p < 0.001), cellular GSH (p < 0.001), and cellular GR activity (p = 0.001) when compared to patients who did not respond to ESA...
Leukemia Research, 1996
Extensive apoptosis or programmed cell death (PCD) of both hematopoietic (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysplastic syndromes (MDS) cancels the high birth-rate resulting in ineffective hematopoiesis and has been demonstrated as the probable basis for peripheral cytopenias in MDS by our group. It is proposed that factors present in the microenvironment are inducing apoptosis in all the cells whether stromal or parenchymal. To investigate this hypothesis further, bone marrow biopsies from 46 MDS patients and eight normal individuals were examined for the presence of three cytokines, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β) and granulocyte macrophage-colony stimulating factor (GM-CSF) and one cellular component, macrophages, by the use of monoclonal antibodies immunohistochemically. Results showed the presence of TNF-α and TGF-β in and cases of MDS respectively, while only 15 cases showed the presence of GM-CSF. Further a significant direct relationship was found between the degree of TNF-α and the incidence of PCD (p = 0.0015). Patients who showed high PCD also had an elevated TNF-α level. Thus, the expression of high amounts of TNF-α and TGF-β and low amounts of the viability factor GM-CSF may be responsible for the high incidence of PCD leading to ineffective hematopoiesis in MDS. Future studies will be directed at attempting to reverse the lesion in MDS by using anti-TNF-α drugs such as pentoxifylline.
Experimental Hematology, 2000
Objectives. To determine the relation of apoptosis and clonal proliferation in the bone marrow (BM) to the effectiveness of a therapeutic protocol described to downmodulate monokine activity in patients with myelodysplastic syndromes (MDS). Materials and Methods. Prior to protocol therapy, BM stroma was cultivated and selected CD34 ϩ cells were studied in stroma and cytokine-dependent clonogenic assays. The TUNEL assay was used to establish the degree of apoptosis occurring in the marrow and CD34 ϩ population. The effectiveness of oral ciproloxacin 500 mg b.i.d., pentoxifylline 800 mg t.i.d., and dexamathasone 4 mg t.i.d. (CPD) antiinflammatory therapy was correlated with the intensity of cell apoptosis and proliferation of BM progenitor cells. Results. Seventeen patients were studied. Twelve patients (10 transfusion dependent) received therapy for a median of 99 days (range 49-284). Toxicity caused four patients to discontinue the drug combination. Six patients fulfilled response criteria. Four patients became transfusion independent, and 50% reduction in the need for blood transfusions was noted in one patient. Blood parameters of one untransfused patient increased by Ͼ 30%. Blood count remained unsupported in three patients, even at a median of 12 months after trial discontinuation. Apoptosis of marrow cells and selected CD34 ϩ progenitors was detected in a median of 49.5% (range 3.6%-90%) and 10.6% (range 3.6%-100%; p Ͻ 0.01), respectively. In patients who responded to therapy, the median apoptosis rate in the bone marrow population was 71%, in contrast to the nonresponder's rate of 13% (p ϭ 0.002). Overall clonogenic growth of selected precursors corresponded significantly with response to CPD protocol (p ϭ 0.004). Conclusions. In some patients with MDS, ineffective hematopoiesis is related to high apoptotic index despite proliferation of the CD34 ϩ precursors. These patients seem to benefit from CPD cytokine modulatory therapeutic strategy.
The Role of Oxidative Stress in Children with Acute and Chronic Immune Thrombocytopenic Purpura
2018
Primary immune thrombocytopenia, previously referred to as idiopathic thrombocytopenic purpura (ITP) is an immune-mediated acquired disorder characterized by mucocutaneous bleeding and isolated thrombocytopenia below 100,000/uL in the absence of any specific cause of the thrombocytopenia [1]. It is further classified according to its duration since diagnosis as follows; newly diagnosed (<3 months), persistent (3-12 months) and chronic (>12 months) [2]. Platelets coated with antibodies are phagocytized by macrophages homing in the reticuloendothelial Abstract