scholarly journals Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Pei-Jyun Liao ◽  
David L. Bolduc ◽  
Thomas B. Elliott ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Marrow Cell ◽  
Total Body Surface Area ◽  
Body Weight Loss ◽  
Cell Depletion ◽  
Photon Radiation ◽  
Whole Body ◽  
Life Threatening ◽  
Radiation Induced ◽  
Total Body

Exposure to ionizing radiation alone (radiation injury, RI) or combined with traumatic tissue injury (radiation combined injury, CI) is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to60Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.

scholarly journals Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Pei-Jyun Liao ◽  
Thomas B. Elliott ◽  
Nikolai V. Gorbunov
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cell ◽  
Tissue Injury ◽  
Marrow Cell ◽  
Total Body Surface Area ◽  
Body Weight Loss ◽  
Cell Depletion ◽  
Photon Radiation ◽  
Whole Body ◽  
Total Body

Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit.

scholarly journals Distinct vascular genomic response of proton and gamma radiation

2018 ◽  
Author(s):  
Ricciotti Emanuela ◽  
Dimitra Sarantopoulou ◽  
Gregory R. Grant ◽  
Jenine K. Sanzari ◽  
Gabriel S. Krigsfeld ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
Dose Response ◽  
Photon Radiation ◽  
Radiation Response ◽  
Whole Body ◽  
Proton Radiation ◽  
Vascular Effects ◽  
Radiation Induced ◽  
Total Body ◽  
Genomic Response

AbstractPurpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge.Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 - 200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.Results.While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes;q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation;p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships.Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

scholarly journals Thrombopoietin Receptor Agonist Mitigates Hematopoietic Radiation Syndrome and Improves Survival after Whole-Body Ionizing Irradiation Followed by Wound Trauma

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Pei-Jun Liao ◽  
Connie Ho ◽  
Nikolai V. Gorbunov ◽  
...  
Keyword(s):  
Wound Healing ◽  
Receptor Agonist ◽  
Tissue Injury ◽  
Body Weight Loss ◽  
Photon Radiation ◽  
Whole Body ◽  
Delayed Wound Healing ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Reduced Water

Ionizing radiation combined with trauma tissue injury (combined injury, CI) results in greater mortality and H-ARS than radiation alone (radiation injury, RI), which includes thrombocytopenia. The aim of this study was to determine whether increases in numbers of thrombocytes would improve survival and mitigate H-ARS after CI. We observed in mice that WBC and platelets remained very low in surviving RI animals that were given 9.5 Gy60Co-γ-photon radiation, whereas only lymphocytes and basophils remained low in surviving CI mice that were irradiated and then given skin wounds. Numbers of RBC and platelets, hemoglobin concentrations, and hematocrit values remained low in surviving RI and CI mice. CI induced 30-day mortality higher than RI. Radiation delayed wound healing by approximately 14 days. Treatment with a thrombopoietin receptor agonist, Alxn4100TPO, after CI improved survival, mitigated body-weight loss, and reduced water consumption. Though this therapy delayed wound-healing rate more than in vehicle groups, it greatly increased numbers of platelets in sham, wounded, RI, and CI mice; it significantly mitigated decreases in WBC, spleen weights, and splenocytes in CI mice and decreases in RBC, hemoglobin, hematocrit values, and splenocytes and splenomegaly in RI mice. The results suggest that Alxn4100TPO is effective in mitigating CI.

scholarly journals Metabolomic Studies of Tissue Injury in Nonhuman Primates Exposed to Gamma-Radiation

2019 ◽  
Vol 20 (13) ◽  
pp. 3360 ◽  
Author(s):  
Amrita K. Cheema ◽  
Khyati Y. Mehta ◽  
Meena U. Rajagopal ◽  
Stephen Y. Wise ◽  
Oluseyi O. Fatanmi ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Radiation Effects ◽  
Nonhuman Primates ◽  
Clinical Symptoms ◽  
Tissue Injury ◽  
Predictive Biomarkers ◽  
Whole Body ◽  
Biomarkers Of Exposure ◽  
Radiation Induced ◽  
Over Time

Exposure to ionizing radiation induces a complex cascade of systemic and tissue-specific responses that lead to functional impairment over time in the surviving population. However, due to the lack of predictive biomarkers of tissue injury, current methods for the management of survivors of radiation exposure episodes involve monitoring of individuals over time for the development of adverse clinical symptoms and death. Herein, we report on changes in metabolomic and lipidomic profiles in multiple tissues of nonhuman primates (NHPs) that were exposed to a single dose of 7.2 Gy whole-body 60Co γ-radiation that either survived or succumbed to radiation toxicities over a 60-day period. This study involved the delineation of the radiation effects in the liver, kidney, jejunum, heart, lung, and spleen. We found robust metabolic changes in the kidney and liver and modest changes in other tissue types at the 60-day time point in a cohort of NHPs. Remarkably, we found significant elevation of long-chain acylcarnitines in animals that were exposed to radiation across multiple tissue types underscoring the role of this class of metabolites as a generic indicator of radiation-induced normal tissue injury. These studies underscore the utility of a metabolomics approach for delineating anticipatory biomarkers of exposure to ionizing radiation.

THE USE OF SMALL SKIN SURFACE AREAS FOR WHOLE BODY SWEATING ASSESSMENT

1965 ◽  
Vol 43 (6) ◽  
pp. 971-977 ◽  
Author(s):  
Arthur C. Custance
Keyword(s):  
Body Weight ◽  
Body Weight Loss ◽  
Total Body Weight ◽  
Skin Surface ◽  
Moisture Loss ◽  
Whole Body ◽  
Surface Areas ◽  
Short Period ◽  
The Subject ◽  
Total Body

It is possible to obtain a continuous record of the sweating rate of an active subject by monitoring changes in total body weight. However, elaborate equipment is required that is capable of accommodating the treadmill (or other exercising device) as well as the subject. The balance must be rugged enough to withstand the movements of the subject, yet sensitive enough to respond to small changes in weight. It would be a great convenience to be able, instead, to monitor small representative areas of the skin surface with confidence that they faithfully reflect whole body reactions.In this research, moisture loss from a representative area of the skin of the dorsum under a capsule covering 14 sq. cm was measured by an apparatus which automatically altered the flow of dry air to keep the humidity of the effluent constant. In four subjects exercising on a treadmill at 3.5 m.p.h. the correlation coefficient between the area under the curves so obtained and the total body weight loss was very high (more than 0.93), and there was also good correlation after sweating was partially suppressed by atropine. Short-period fluctuations were simultaneous and highly correlated between bilaterally symmetrical areas of skin. It is concluded that moisture loss from a single area of skin can be used to represent changes in the rate and pattern of sweating of the whole body.

scholarly journals Brief Report: Prolonged Intravenous Iron-Dextran Therapy in a Patient with Multiple Hereditary Telangiectasia

Blood ◽  
1969 ◽  
Vol 34 (5) ◽  
pp. 691-695 ◽  
Author(s):  
MILAN CHERNELCH ◽  
HARRY SAUL WINCHELL ◽  
MYRON POLLYCOVE ◽  
THORNTON SARGENT ◽  
NATALIA KUSUBOV
Keyword(s):  
Tissue Injury ◽  
Hemoglobin Concentration ◽  
Intravenous Iron ◽  
Total Iron ◽  
Whole Body ◽  
Iron Dextran ◽  
Time Of Death ◽  
Excess Iron ◽  
Quantitative Measurements ◽  
Total Body

Abstract Quantitative measurements of blood and iron whole body radioiron loss, total body iron, and iron and erythrocyte kinetics are presented in a patient with hereditary hemorrhagic telangiectasia treated with massive quantities of an iron-dextran complex given intravenously. This iron therapy enabled the patient to maintain a hemoglobin concentration of 6 Gm./100 ml. despite the loss of 600-900 ml. of blood per day. Though considerable hemosiderosis was present at the time of death, no apparent tissue injury was present. The excess iron present constituted a very small fraction of the total iron administered, was only slowly mobilizable for hemoglobin synthesis and, consequently, did not obviate the need for continued administration of fresh dextran iron.

scholarly journals Marrow Stromal Cell Infusion Rescues Hematopoiesis in Lethally Irradiated Mice despite Rapid Clearance after Infusion

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Xiaodong Yang ◽  
Ilango Balakrishnan ◽  
Beverly Torok-Storb ◽  
Manoj M. Pillai
Keyword(s):  
Cellular Therapy ◽  
Tissue Injury ◽  
Direct Interaction ◽  
Rt Pcr ◽  
Immune Histochemistry ◽  
Radiation Induced ◽  
Rapid Clearance ◽  
Total Body ◽  
Lethal Irradiation

Marrow stromal cells (MSCs, also termed mesenchymal stem cells) have been proposed as a promising cellular therapy for tissue injury including radiation-induced marrow failure, but evidence for a direct effect is lacking. To assess the effects of MSCs on survival after lethal irradiation, we infused syngeneic MSCs (either as immortalized MSCs clones or primary MSCs) intravenously into wild-type C57/Bl6 mice within 24 hours of lethal total body irradiation (TBI). Mice receiving either of the MSC preparations had significantly improved survival when compared to controls. In vivo imaging, immune histochemistry, and RT-PCR employed to detect MSCs indicated that the infused MSCs were predominantly localized to the lungs and rapidly cleared following infusion. Our results suggest that a single infusion of MSCs can improve survival after otherwise lethal TBI but the effect is not due to a direct interaction with, or contribution to, the damaged marrow by MSCs.

scholarly journals Is it Pemphigus Vulgaris or toxic epidermal necrolysis? A dilemmatic condition to confirm diagnosis

2008 ◽  
Vol 20 (3) ◽  
Author(s):  
E Fitriana Sari ◽  
Titiek Setyowati
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Total Body Surface Area ◽  
Pemphigus Vulgaris ◽  
Hypersensitive Reaction ◽  
Oral Medicine ◽  
Medicine Department ◽  
Histological Features ◽  
Clinical Appearance ◽  
Life Threatening ◽  
Total Body

Pemphigus Vulgaris and Toxic Epidermal Necrolysis both are life threatening diseases. Pemphigus Vulgaris is a mucocutaneous autoimmune disease while Toxic Epidermal Necrolysis is cutaneous drug hypersensitive reaction. It supposes to be easy to distinguish one another, but confusion happens when the clinical appearance is atypical. We report a case which becomes dilemmatic because of some clinical and histological features can be a manifestation from pemphigus vulgaris or toxic epidermal necrolysis. The patient was under supervision by both Oral Medicine Department and Dermatology and Venereal Department. The ulcerative, erosive and sloughing lesion in oral mucosa has been treated successfully by administrating Prednisone 60 mg/ day for almost two months. Epidermal sloughing of more than 10% of total body surface area due to epidermolysis was treated with Methylprednisolone within two months and the epidermolysis is resolved.

scholarly journals Mitigation of radiation-induced gastro-intestinal injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kavya Venkateswaran ◽  
Anju Shrivastava ◽  
Paban K. Agrawala ◽  
Ashok K. Prasad ◽  
Sagolsem Chandrika Devi ◽  
...  
Keyword(s):  
Intestinal Injury ◽  
Epithelial Regeneration ◽  
Cycle Arrest ◽  
Survival Pathways ◽  
Life Threatening ◽  
Important Regulator ◽  
Radiation Induced ◽  
Total Body ◽  
Underlying Mechanisms ◽  
Stimulation Of

Abstract Radiation-induced intestinal injury (RIII) constitutes a crucial clinical element of acute radiation syndrome with life-threatening implications posing challenges in devising effective medical countermeasures. Herein, we report the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to mitigate RIII following total-body irradiation (TBI) in C57BL/6 mice and underlying mechanisms. Administration of DAMTC 24 hours post TBI facilitated structural reconstitution and restoration of functional absorption linked to alleviation of radiation-induced apoptotic death of intestinal crypt progenitor/stem (ICPS) and villus stromal cells through induction of Bcl-2 family-mediated anti-apoptotic signalling. Reduction in TBI-induced DNA damage accumulation coupled with inhibition of cell cycle arrest through stimulation of anti-p53- and anti-p21-dependent synergistic signalling protected ICPS cells from radiation injury. Enhanced proliferation of crypt stem cells, induction of anti-oxidant defence, subjugation of TBI-induced lipid peroxidation and phenotypic polarization of intestinal macrophages to anti-inflammatory M2 class underlie amelioration of RIII. Stimulation of multiple mitigative signalling processes by DAMTC appeared to be associated with enhanced protein acetylation, an important regulator of cellular responses to radiation damage. Our findings establish the mitigative potential of DAMTC against RIII by hyper-acetylation-mediated epigenetic regulation, which triggers axes of anti-apoptotic and pro-survival pathways, enabling proliferation and maintenance of ICPS cells leading to epithelial regeneration.

Effects of varied air velocity on sweating and evaporative rates during exercise

1992 ◽  
Vol 73 (6) ◽  
pp. 2668-2674 ◽  
Author(s):  
W. C. Adams ◽  
G. W. Mack ◽  
G. W. Langhans ◽  
E. R. Nadel
Keyword(s):  
Sweat Rate ◽  
Body Weight Loss ◽  
Cycle Ergometer ◽  
Body Core Temperature ◽  
Whole Body ◽  
Air Velocity ◽  
Sweat Loss ◽  
Ergometer Exercise ◽  
Sweat Production ◽  
Total Body

This study was designed to determine the extent to which changes in the evaporative power of the environment (Emax) affect sweating and evaporative rates. Six male subjects undertook four 60-min bouts of cycle ergometer exercise at 56% maximal O2 uptake (VO2max).Emax was varied by differences in ambient temperature and airflow; two exercise bouts took place at 24 degrees C and two at 35 degrees C, with air velocity at < 0.2 and 3.0 m/s in both. Total sweat production was estimated from body weight loss, whereas whole body evaporative rate was measured continuously from a Potter beam balance. Body core temperature was measured continuously from a thermocouple in the esophagus (T(es)), with mean skin temperature (Tsk) computed each minute from thermocouples at eight sites. Total body sweat loss was significantly greater (P < 0.05) in the 0.2- than in the 3.0-m/s condition at both 24 and 35 degrees C. Tsk was higher (P < 0.05) in the still-air conditions at both temperatures, but final T(es) was significantly higher (P < 0.05) in still air only in the 35 degrees C environment. Thus the reduced Emax in still air caused a greater heat storage, thereby stimulating a greater total sweat loss. However, in part because of reduced skin wettedness, the slope of the sweat rate-to-T(es) relation at 35 degrees C in the 3.0-m/s condition was 118% that at 0.2 m/s (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

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