scholarly journals Gamma-Tocotrienol, A Radiation Countermeasure, Reverses Proteomic Changes In Serum Following Total-Body Gamma Irradiation In Mice

2021 ◽  
Author(s):  
Elliot Rosen ◽  
Oluseyi Fatanmi ◽  
Stephen Y. Wise ◽  
V. Ashutosh Rao ◽  
Vijay K. Singh
Keyword(s):  
Gamma Irradiation ◽  
Immune Cell ◽  
Serum Proteins ◽  
Complement C3 ◽  
High Dose ◽  
Cell Trafficking ◽  
Associated Proteins ◽  
High Doses ◽  
Significant Expression ◽  
Total Body

Abstract Radiological incidents or terrorist attacks would likely expose civilians and military personnel to high doses of ionizing radiation, leading to the development of acute radiation syndrome (ARS). While the effects and symptoms of high dose radiation exposure have been established, prophylactic treatments and methods for determining the extent of exposure remain limited. We examined the effectiveness of prophylactic administration of a developmental radiation countermeasure, g-tocotrienol (GT3), in a total-body irradiation (TBI) mouse model. CD2F1 mice received GT3 24 h prior to 11 Gy cobalt-60 gamma-irradiation, a supralethal dose for this strain. Two-dimensional differential in-gel electrophoresis was followed by mass spectrometry and Ingenuity Pathway Analysis (IPA). Analysis revealed a change in expression of 18 proteins in response to TBI, and these changes were reversed with prophylactic treatment of GT3. IPA revealed a network of associated proteins involved in cellular movement, immune cell trafficking, and inflammatory response. Of particular interest, significant expression changes in beta-2-glycoprotein 1, alpha-1-acid glycoprotein 1, alpha-2-macroglobulin, complement C3, mannose-binding protein C, and major urinary protein 6 were noted after TBI and reversed with GT3 treatment. This study reports the network and specific serum proteins which could be translated as biomarkers of both radiation injury and protection by radiation countermeasures.

scholarly journals Effect of gamma-irradiation on the properties of aluminum dihydrogen triphosphate

2017 ◽  
Vol 82 (10) ◽  
pp. 1111-1121 ◽  
Author(s):  
Weiqiang Song ◽  
Qinghuan Song ◽  
Longchao Wu ◽  
Lantao Yang
Keyword(s):  
Thermal Analysis ◽  
Corrosion Resistance ◽  
Gamma Irradiation ◽  
Electrochemical Impedance ◽  
Dose Range ◽  
Xrd Analysis ◽  
High Dose ◽  
Crystal Transition ◽  
Steel Panels ◽  
High Doses

The effect of gamma irradiation on the properties of aluminum dihydrogen triphosphate (ADTP) in the dose range of 0 to 150 kGy was studied by X-ray diffraction (XRD) analysis, thermal analysis, acid?base titration, electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). Although the XRD and SEM results indicated that there were no significant effects on the crystal structure and the surface morphology of ADTP, thermal analysis revealed that the crystal transition of Al(PO3)3 from Type-B to Type-A did not occur at a high temperature in irradiated ADTP. EIS results showed that high-dose gamma irradiation (100 kGy and 150 kGy, 60Co) improved the corrosion inhibition ability of ADTP on tinplate steel. SEM was used to investigate the surface of tinplate steel panels after immersion in ADTP extracts for 69 h, and revealed that many slices were formed on the surface. The slices were attributed to the formation of Fe2P3O10. Inter-slice gaps may be the reason for the lower corrosion resistance of ADTP compared with the resistance of some toxic pigments containing lead and chromium. Overall, high doses of gamma irradiation improved the corrosion resistance of ADTP.

scholarly journals Understanding the mechanisms of glutamine action in critically ill patients

2010 ◽  
Vol 82 (2) ◽  
pp. 417-430 ◽  
Author(s):  
Gisele P. Oliveira ◽  
Cristina M. Dias ◽  
Paolo Pelosi ◽  
Patricia R.M. Rocco
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Cell Function ◽  
Immune Cell ◽  
Experimental Studies ◽  
High Dose ◽  
Neutrophil Accumulation ◽  
Metabolic Functions ◽  
Heat Shock Protein Expression ◽  
High Doses

Glutamine (Gln) is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor)-kB activation, a balance between pro- and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day) demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.

scholarly journals DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment

Blood ◽  
1995 ◽  
Vol 86 (11) ◽  
pp. 4376-4381 ◽  
Author(s):  
C Yu ◽  
R Storb ◽  
B Mathey ◽  
HJ Deeg ◽  
FG Schuening ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Lethal Dose ◽  
High Dose ◽  
Starting Dose ◽  
High Doses ◽  
Total Body ◽  
Mixed Chimeras ◽  
Long Term Survivors ◽  
Additional Therapy

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.

Tumorigenesis in High-Dose Total Body Irradiated Rhesus Monkeys--A Life Span Study

2003 ◽  
Vol 31 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Carel F. Hollander ◽  
Chris Zurcher ◽  
Johan J. Broerse
Keyword(s):  
Life Span ◽  
Rhesus Monkeys ◽  
High Dose ◽  
Life Span Study ◽  
Total Body

The Influence of Serotonin on Clot Retraction and the Thrombelastogram

1958 ◽  
Vol 02 (01/02) ◽  
pp. 111-124 ◽  
Author(s):  
E Deutsch ◽  
K Martiny
Keyword(s):  
Human Plasma ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Specific Effect ◽  
High Dose ◽  
Clot Retraction ◽  
Platelet Counts ◽  
Essential Value ◽  
High Doses ◽  
Free Plasma

Summary1. Normal platelets are necessary for induction of normal clot retraction.2. Serotonin does not induce retraction in human platelet-free plasma-clots or enhance clot firmness as measured in the coagulogram.3. Serotonin does not improve clot retraction or firmness in plasma clots with sub-optimal platelet counts.4. Methylserotonin inhibits clot retraction of platelet-rich plasma to a certain extent in moderate doses, whereas, high doses are ineffective. BOL 148 has a similar, but less significant action. There is a possibility that these effects are specific antiserotonin-effects.5. LSD 25 was ineffective in all concentrations used.6. Largactil and reserpin inhibit retraction in high doses. There seems to be a non specific effect caused by the high dose.7. Reserpine does not release a retraction-inducing agent from the platelets, which could be detected in the centrifuged platelet-free plasma used for the incubation.8. Serotonin does not replace the retraction-cofactor of Hartert, or the dialyzable factor of Lüscher in synthetic clotting substrates.9. Serotonin is of no essential value in inducing normal retraction of human plasma clots.

New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Cancer Therapy ◽  
Immune Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumour Microenvironment ◽  
Immune Checkpoints ◽  
Tumour Regression ◽  
Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

The Therapeutic Potential of Chemokines in the Treatment of Chemotherapy- Induced Peripheral Neuropathy

2020 ◽  
Vol 21 (3) ◽  
pp. 288-301 ◽  
Author(s):  
Lin Zhou ◽  
Luyao Ao ◽  
Yunyi Yan ◽  
Wanting Li ◽  
Anqi Ye ◽  
...  
Keyword(s):  
Nervous System ◽  
Neuropathic Pain ◽  
Immune System ◽  
Peripheral Neuropathy ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Chemotherapeutic Agents ◽  
Cell Trafficking ◽  
Mediated Communication ◽  
Novel Therapeutic Strategies

Background: Some of the current challenges and complications of cancer therapy are chemotherapy- induced peripheral neuropathy (CIPN) and the neuropathic pain that are associated with this condition. Many major chemotherapeutic agents can cause neurotoxicity, significantly modulate the immune system and are always accompanied by various adverse effects. Recent evidence suggests that cross-talk occurs between the nervous system and the immune system during treatment with chemotherapeutic agents; thus, an emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN, as demonstrated by the upregulation of chemokines. Chemokines were originally identified as regulators of peripheral immune cell trafficking, and chemokines are also expressed on neurons and glial cells in the central nervous system. Objective: In this review, we collected evidence demonstrating that chemokines are potential mediators and contributors to pain signalling in CIPN. The expression of chemokines and their receptors, such as CX3CL1/CX3CR1, CCL2/CCR2, CXCL1/CXCR2, CXCL12/CXCR4 and CCL3/CCR5, is altered in the pathological conditions of CIPN, and chemokine receptor antagonists attenuate neuropathic pain behaviour. Conclusion: By understanding the mechanisms of chemokine-mediated communication, we may reveal chemokine targets that can be used as novel therapeutic strategies for the treatment of CIPN.

Influence of β-D-mannuronic acid, as a new member of non-steroidal anti-inflammatory drugs family, on expression pattern of chemokines and their receptors in rheumatoid arthritis

2019 ◽  
Vol 16 ◽  
Author(s):  
Mona Aslani ◽  
Arman Ahmadzadeh ◽  
Zahra Aghazadeh ◽  
Majid Zaki-Dizaji ◽  
Laleh Sharifi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mrna Expression ◽  
Surface Expression ◽  
Phase Iii ◽  
Cell Surface Expression ◽  
Optimum Dose ◽  
High Dose ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
High Doses

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.

scholarly journals Immune Monitoring during Therapy Reveals Activitory and Regulatory Immune Responses in High-Risk Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2096
Author(s):  
Celina L. Szanto ◽  
Annelisa M. Cornel ◽  
Sara M. Tamminga ◽  
Eveline M. Delemarre ◽  
Coco C. H. de Koning ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Nk Cells ◽  
Immune Cell ◽  
High Dose Chemotherapy ◽  
Immune Monitoring ◽  
High Dose ◽  
Effector Cells ◽  
Gm Csf ◽  
Immune Cell Subsets

Despite intensive treatment, including consolidation immunotherapy (IT), prognosis of high-risk neuroblastoma (HR-NBL) is poor. Immune status of patients over the course of treatment, and thus immunological features potentially explaining therapy efficacy, are largely unknown. In this study, the dynamics of immune cell subsets and their function were explored in 25 HR-NBL patients at diagnosis, during induction chemotherapy, before high-dose chemotherapy, and during IT. The dynamics of immune cells varied largely between patients. IL-2- and GM-CSF-containing IT cycles resulted in significant expansion of effector cells (NK-cells in IL-2 cycles, neutrophils and monocytes in GM-CSF cycles). Nonetheless, the cytotoxic phenotype of NK-cells was majorly disturbed at the start of IT, and both IL-2 and GM-CSF IT cycles induced preferential expansion of suppressive regulatory T-cells. Interestingly, proliferative capacity of purified patient T-cells was impaired at diagnosis as well as during therapy. This study indicates the presence of both immune-enhancing as well as regulatory responses in HR-NBL patients during (immuno)therapy. Especially the double-edged effects observed in IL-2-containing IT cycles are interesting, as this potentially explains the absence of clinical benefit of IL-2 addition to IT cycles. This suggests that there is a need to combine anti-GD2 with more specific immune-enhancing strategies to improve IT outcome in HR-NBL.

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