scholarly journals The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 3167 ◽  
Author(s):  
Richard Lobb ◽  
Gregory Jacobson ◽  
Ray Cursons ◽  
Michael Jameson
Keyword(s):  
Blood Cells ◽  
Mononuclear Cells ◽  
Malignant Cells ◽  
Cancer Treatments ◽  
Peripheral Blood Mononuclear ◽  
Normal Cells ◽  
Anticancer Properties ◽  
Methylseleninic Acid ◽  
Mononuclear Blood Cells

Selenium, a trace element with anticancer properties, can reduce harmful toxicities of chemotherapy and radiotherapy without compromising efficacy. However, the dose-response relationship in normal versus malignant human cells is unclear. We evaluated how methylseleninic acid (MSA) modulates the toxicity and efficacy of chemotherapy and radiation on malignant and non-malignant human mononuclear blood cells in vitro. We specifically investigated its effects on endoplasmic reticulum stress induction, intracellular glutathione concentration, DNA damage and viability of peripheral blood mononuclear cells and THP1 monocytic leukaemia cells in response to radiation, cytosine arabinoside or doxorubicin chemotherapy. MSA, at lower concentrations, induced protective responses in normal cells but cytotoxic effects in malignant cells, alone and in conjunction with chemotherapy or radiation. However, in normal cells higher concentrations of MSA were directly toxic and increased the cytotoxicity of radiation but not chemotherapy. In malignant cells higher MSA concentrations were generally more effective in combination with cancer treatments. Thus, optimal MSA concentrations differed between normal and malignant cells and treatments. This work supports clinical reports that selenium can significantly reduce dose-limiting toxicities of anticancer therapies and potentially improve efficacy of anticancer treatments. The optimal selenium compound and dose is not yet determined.

scholarly journals Early suppression of peripheral mononuclear blood cells in sepsis in response to stimulation with cytomegalovirus, OKT3, and pokeweed mitogen

2019 ◽  
Vol 127 (6) ◽  
pp. 1539-1547
Author(s):  
N. M. Malewicz ◽  
K. Walstein ◽  
T. Heine ◽  
A. Engler ◽  
A. Bick ◽  
...  
Keyword(s):  
Blood Cells ◽  
Time Course ◽  
Mononuclear Cells ◽  
Pokeweed Mitogen ◽  
Acquired Immunity ◽  
Peripheral Blood Mononuclear ◽  
Icu Admission ◽  
Early Sepsis ◽  
Mononuclear Blood Cells

Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [ days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with sepsis ( n = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV ( P = 0.01), OKT3 ( P = 0.02), and PWM ( P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ. HLA-DRA expression was also significantly decreased in patients with sepsis at all time points ( P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as HLA-DRA expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis. NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.

Human Erythroblasts Generated in Vitro Remain Functional with a Normal Karyotype 8 Years after Cryopreservation: Implications for Ex Vivo Generated Erythroid Transfusion Products.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2303-2303 ◽  
Author(s):  
Massimo Sanchez ◽  
Amanda Leblanc ◽  
Annalisa Mancini ◽  
Francesca Masiello ◽  
Valentina Tirelli ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Genomic Rearrangements ◽  
Multicolor Fish ◽  
Peripheral Blood Mononuclear ◽  
Differentiation Potential ◽  
Blood Mononuclear Cells

Abstract The safety and adequacy of the blood supply is threatened by natural disasters, social and political events, epidemics, and emerging infections. During shortages, frozen blood is used to supplement the blood supply. Current regulations allow red blood cells to be stored frozen up to ten years; however, the shelf-life of such products is limited once blood is thawed. Cultured human erythroid cells derived in vitro from either fresh or cryopreserved CD34+ cells or peripheral blood mononuclear cells potentially represent an alternative source of erythrocytes for transfusion. However, it is unknown if normal erythroid cells undergoing ex-vivo expansion with growth factors will remain functional or develop genetic rearrangements in culture making them unsuitable for transfusion. We have compared the proliferative and differentiation potential of human erythroblasts obtained in culture from the peripheral blood mononuclear cells (PBMC) of adult donors. This analysis included freshly expanded erythroblasts as well as erythroblasts cryopreserved and stored for short (1 month) and long (8 years) periods. PBMC from four volunteer blood donors were prepared using gradient-density centrifugation and cryopreserved in DMSO in June 2000. One months later, 2x107 PBMC from one of the donors were thawed and cultured under conditions that allow massive ex vivo generation of erythroblasts (HEMA culture, Migliaccio et al Blood Cells Mol Dis2002;28:169-80). These cultures were stimulated with recombinant hSCF (50ng/mL), hGM-CSF (1ng/ml), hIL3 (1U/mL), hEPO (1U/mL) and contained dexamethasone and estradiol (each 10−6 M). Twenty million PBMC from the three additional donors were thawed and cultured under HEMA conditions in 2008. In all the three cases, the day 9 cultures contained an average of 10x107 cells, 95% of which were erythroid by CD36 and CD235a staining. These day 9 cells were either cultured for 4 additional days or cryopreserved (>10 individual vials per donor containing 5x106 each). Cells were subcultured and maintained either under HEMA conditions (to assess their proliferation ability) or stimulated with EPO alone (5U/ mL) (to assess maturation). In May 2008, aliquots of the erythroblasts obtained from all donors were thawed and cultured again and amplification and differentiation potential of the freshly expanded and thawed cells were compared. Cells thawed after few months or 8 years of cryopreservation gave similar results and the data were pooled. The viability of the erythroblasts after thawing was 60–70%. After 4 days under HEMA conditions, both freshly expanded and cryopreserved erythroblasts doubled in numbers and retained an immature erythroid phenotype (CD36highCD235alow). On the other hand, in cultures containing EPO alone, the erythroblasts remained constant in number but progressed to a mature CD36posCD235ahigh phenotype. The results are summarized in the following table: Proliferation and Maturation Profile of Fresh and Cryopreserved Human Erythroblasts Fold Increase Phenotype CD36highCD235alow CD36highCD235ahigh Fresh cells HEMA culture 2 53% 40% EPO alone 1 15% 80% Thawed Cells HEMA culture 2 46% 36% EPO alone 1 5% 90% The eight-years cryopreserved erythroblasts expanded in culture were also cytogenetically evaluated. Karyotype and multicolor FISH analyses demonstrated a normal 46,XY karyotype with no obvious genomic rearrangements. To determine whether cells carried any known in utero leukemic genomic rearrangements, interphase FISH studies were performed for TEL/ETV6-AML1, MLL, 5q31 (EGR1) and 7q31 loci. In 800 evaluated interphase nuclei, all loci were present in disomy. This data indicates that human erythroblasts obtained in culture can be efficiently cryopreserved, remain functional in culture and do not acquire chromosomal abnormalities detectable by multicolor FISH analysis. These observations suggest that cultured erythroblasts should be further evaluated to determine if they represent a more suitable long term storage product than cryopreserved mature red blood cells.

scholarly journals Influence of Flavonoids on the Cytotoxic Activity of Mononuclear Blood Cells in Model Tests

2019 ◽  
Vol 7 (12) ◽  
pp. 1900-1904 ◽  
Author(s):  
Liudmila Ivanovna Babaskina ◽  
Tatiana Mikhailovna Litvinova ◽  
Dmitrii Vladimirovich Babaskin ◽  
Mikhail Valentinovich Kiselevsky ◽  
Olga Vladimirovna Savinova ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Blood Cells ◽  
Cytotoxic Effect ◽  
Mononuclear Cells ◽  
Tumour Cells ◽  
Immunomodulatory Activity ◽  
Target Cells ◽  
Killer Activity ◽  
Mononuclear Blood Cells

BACKGROUND: The spread of phytocomplex application and justification of its selective effects on tumour cells (mainly due to the presence of flavonoids) require research of its cytotoxic and immunomodulatory activity. AIM: The goal was to study the direct cytotoxic effect of the phytocomplex and its modulating effect on the cytotoxic activity of the donor's mononuclear blood cells in in vitro experiments. METHODS: The phytocomplex was a dry extract from marsh cinquefoil, creeping alfalfa and common hop; its main active ingredients were flavonoids. Transplantable monolayer cultures of lung adenocarcinoma, colorectal cancer, erythroblastic leukaemia, and fibroblasts were used as target cells. The cytotoxic activity was assessed using a cytotoxic test based on the selective ability to live cells to reduce MTT (3-[4, 5-dimethyltriazol-2-yl]-2, 5 diphenyltetrazolium bromide) to formazan in mitochondria. Quantitative determination of formazan was performed using spectrophotometry. RESULTS: A direct cytotoxic effect of the phytocomplex in concentrations of at least 2.5 mg/ml on tumour cells has been established. Its modulating effect on the cytotoxic activity of mononuclear blood cells at a concentration of 0.05 mg/ml was shown. The phytocomplex in doses of 0.25 and 0.5 mg/ml increased the killer activity of the mononuclear cells in a diseased person's blood, but did not affect these blood cells in a healthy donor. Incubation of lymphocytes with a phytocomplex for 24 hours increased the cytotoxic activity of mononuclear cells by 20-25%. CONCLUSION: The direct cytotoxic effect of the phytocomplex and its modulating effect on the cytotoxic activity of mononuclear blood cells in model experiments in vitro have been established.

Halothane-dependent release of intracellular Ca2+ in blood cells in malignant hyperthermia

1990 ◽  
Vol 258 (3) ◽  
pp. C495-C503 ◽  
Author(s):  
A. Klip ◽  
G. B. Mills ◽  
B. A. Britt ◽  
M. E. Elliott
Keyword(s):  
Malignant Hyperthermia ◽  
Blood Cells ◽  
Mononuclear Cells ◽  
Cytosolic Calcium ◽  
Tetraacetic Acid ◽  
Peripheral Blood Mononuclear ◽  
Normal Cells ◽  
Normal Individuals ◽  
Normal Humans ◽  
In Cells

The concentration of ionized cytosolic calcium [( Ca2+]i) was determined in peripheral blood mononuclear cells from normal and malignant hyperthermia (MH)-susceptible humans and pigs, using the fluorescent Ca2+ indicator indo-1. [Ca2+]i was slightly but significantly elevated in cells from MH human cells relative to normal cells (198 +/- 18 nM, n = 15, and 146 +/- 14 nM, n = 11, respectively, P less than 0.05). Anesthetic concentrations of halothane in the cell suspension resulted in a rapid increase in [Ca2+]i in cells from both normal and MH humans or pigs. The increases (delta) were more pronounced in cells from MH subjects than from normal individuals (delta at 5.7 mM halothane: 245 +/- 53 vs. 57 +/- 11 nM, respectively) and from MH than from normal pigs (delta of 241 +/- 63 vs. 53 +/- 27 nM, respectively). Removal of extracellular Ca2+ obliterated the delta[Ca2+]i caused by halothane in cells from normal humans or pigs but only decreased by about half the delta[Ca2+]i in cells from MH humans or pigs. In 1,2-bis-(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)-loaded cells, in the absence of extracellular Ca2+, halothane failed to increase [Ca2+]i. This suggests that buffering Cai2+ with BAPTA precludes detection of release of Ca2+ from intracellular stores, explaining the previous observations made with quin2, a highly chelating Ca2+ indicator. It is concluded that clinical concentrations of halothane allow influx of Ca2+ in cells from both normal and MH-susceptible individuals but release Ca2+ from intracellular stores selectively in cells from the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Study of the IL-4 and IL-4δ2 interaction with the IL-4R receptors of the I and II types in silico and the effect on the functional activity of mononuclear cells in vitro

2010 ◽  
Vol 9 (3) ◽  
pp. 51-56
Author(s):  
K. V. Goremykin ◽  
A. N. Silkov ◽  
B. V. Shilov ◽  
V. Yu. Serebrov ◽  
A. E. Sazonov ◽  
...  
Keyword(s):  
Blood Cells ◽  
Proliferative Activity ◽  
Mononuclear Cells ◽  
Splice Form ◽  
Antagonistic Effects ◽  
Computer Methods ◽  
Full Form ◽  
Alternatively Spliced ◽  
Mononuclear Blood Cells

Alternatively spliced interleukins are very actively studied over the last years. Splice form of IL-4 — IL-4δ2 has antagonistic effects to its full form on proliferative activity of human mononuclear blood cells and their IL-6 production. Antagonistic effects between IL-4 and IL-4δ2 were confirmed and explained in this study due to combination of biochemical and computer methods.

Preliminary Report of In vitro and In vivo Effectiveness of Dornase Alfa on SARS-CoV-2 Infection (Preprint)

2020 ◽  
Author(s):  
Hacer Kuzu Okur ◽  
Koray Yalcin ◽  
Cihan Tastan ◽  
Sevda Demir ◽  
Bulut Yurtsever ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Tract ◽  
Mononuclear Cells ◽  
Multiple Organ ◽  
Peripheral Blood Mononuclear ◽  
Dornase Alfa ◽  
Tract Infections ◽  
Adult Peripheral Blood

UNSTRUCTURED Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). Coronavirus disease 2019 (COVID-19) pandemic affected more than two million people over the world, resulting in unprecedented health, social and economic crises. The COVID-19, viral pneumonia that progresses to ARDS and even multiple organ failure, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High blood neutrophil levels are an early indicator of SARS-CoV-2 infection and predict severe respiratory diseases. A similar mucus structure is detected in COVID-19 patients due to the accumulation of excessive NET in the lungs. Here, we show our preliminary results with dornase alfa that may have an in-vitro anti-viral effect against SARS-CoV-2 infection in a bovine kidney cell line, MDBK without drug toxicity on healthy adult peripheral blood mononuclear cells. In this preliminary study, we also showed that dornase alfa can promote clearance of NET formation in both an in-vitro and three COVID-19 cases who showed clinical improvement in radiological analysis (2-of-3 cases), oxygen saturation (SpO2), respiratory rate, disappearing of dyspnea and coughing.

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