10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model

We have measured the responses to endurance exercise training on body composition and glucose regulation, as well as cardiovascular and liver structure and function in rats fed a high carbohydrate and high fat (HCHF) diet as a model of human metabolic syndrome. Male Wistar rats (9–10 weeks old) were randomly allocated into corn starch (CS) or HCHF diet groups for 16 weeks; half of each group were exercised on a treadmill for 20, 25, and then 30 min/day, 5 days/week, during the last 8 weeks of the protocol. Metabolic, cardiovascular, and liver parameters were monitored. The HCHF diet induced symptoms of metabolic syndrome, including obesity, dyslipidemia, impaired glucose tolerance, and increased systolic blood pressure associated with the development of cardiovascular remodeling and nonalcoholic steatohepatitis. Exercise in HCHF rats decreased body mass, abdominal fat pads and circumference, blood glucose concentrations, plasma lipid profiles, systolic blood pressure, left ventricular diastolic stiffness, collagen deposition and inflammatory cell infiltration in the left ventricle, improved aortic contractile and relaxation responses, and decreased liver mass and hepatic fat accumulation. This study demonstrates that endurance exercise is effective in this rat model of diet-induced metabolic syndrome in improving body composition and glucose regulation, as well as cardiovascular and liver structure and function.

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Bendamustine Conditioning Alters Host Dendritic Cell Composition and Function

Blood ◽

10.1182/blood-2018-99-117140 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5670-5670

Author(s):

Megan Stanley Molina ◽

Jessica Stokes ◽

Emely Hoffman ◽

Emmanuel Katsanis

Keyword(s):

Flow Cytometry ◽

Total Body Irradiation ◽

Conflicts Of Interest ◽

Host Cells ◽

Differential Effects ◽

Donor Cells ◽

Alternative Agent ◽

Conditioning Regimens ◽

Total Body ◽

And Function

Abstract Background A largely understudied strategy for reducing graft-versus-host disease (GvHD) is the modification of conditioning regimens. We have demonstrated that pre-transplant bendamustine (BEN) used in combination with total body irradiation (TBI) significantly reduces GvHD compared to the more commonly used cyclophosphamide (CY) + TBI. The short half-lives of BEN/CY (<4h), which are given 48h prior to transplant, indicate that these drugs do not directly affect the donor cells. Therefore, the striking improvement in GvHD by substituting CY with BEN must be due to differential effects on the host cells. Conditioned host immune cells diminish over time, but are the majority early after transplant and are able to critically interact with the infused donor cells at the earliest stages of GvHD pathogenesis. Methods Using an MHC-mismatched murine model of bone marrow transplantation (BMT) with C57BL/6 donors into BALB/c recipients (H2Kb into H2Kd), we evaluated the differential effects of BEN conditioning on host dendritic cells (DCs) early after transplant, as compared to CY conditioning. Transplant recipient mice were conditioned with BEN or CY on day -2 pre-BMT, and supplemented with 400cGy of total body irradiation on day -1. On days 1, 3, and 5 post-BMT, splenic pan-DCs were isolated and analyzed by flow cytometry to evaluate host (H2Kb-) DC phenotype and activation state. Further, on day 0 (without BMT), circulating leukocytes and splenic pan-DCs were isolated from conditioned mice and analyzed by flow cytometry, qPCR and allogeneic mixed leukocyte reactions. Results We found that BEN-conditioned pan DCs are less stimulatory of allogeneic T-cells than CY-treated DCs. BEN conditioning significantly alters host DC composition compared to CY conditioning, resulting in a significantly higher frequency and number of host CD8α+ DCs on days 1 and 3 post-BMT. BEN-conditioned CD8α+ DCs also display a highly regulatory phenotype (CD80highCD86low) and have greater suppressive ability compared to CY-conditioned CD8α+ DCs. Analysis of host DCs on day 0 (without BMT) revealed a significantly greater percentage of BEN-conditioned DCs positively expressing the Flt3 receptor compared to CY. Conclusions These findings advocate a potential role of Flt3L-dependent DCs, particularly CD8α+ DCs, in the mechanism by which BEN alters GvHD pathogenesis to limit morbidity and mortality. Thus, BEN may have advantages as an alternative agent to CY for pre-transplant conditioning in allogeneic BMT. Disclosures No relevant conflicts of interest to declare.

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Late toxicity of total body irradiation with bone marrow transplantation in a rat model

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/0360-3016(89)90955-3 ◽

1989 ◽

Vol 16 (6) ◽

pp. 1501-1509 ◽

Cited By ~ 64

Author(s):

John E. Moulder ◽

Brian L. Fish

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Rat Model ◽

Total Body Irradiation ◽

Marrow Transplantation ◽

Late Toxicity ◽

Total Body

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Storage and translocation of integumentary calcium during the moult cycle of the terrestrial isopod Oniscus asellus (L.)

Canadian Journal of Zoology ◽

10.1139/z93-002 ◽

1993 ◽

Vol 71 (1) ◽

pp. 4-10 ◽

Cited By ~ 44

Author(s):

C. G. H. Steel

Keyword(s):

Calcium Content ◽

Structure And Function ◽

The Body ◽

Anterior Region ◽

Moult Cycle ◽

Total Body Calcium ◽

Biphasic Pattern ◽

Calcium Deposits ◽

Total Body ◽

And Function

The calcium content of pieces of integument of standardized size from various regions of the body was measured at all 15 stages of the intermoult cycle. Calcium resorbed from the posterior integument during premoult is stored mainly in the sternal calcium deposits of the anterior region, which contain 20% of total body calcium in late premoult. Earlier arguments that the deposits are not a store of calcium are refuted. These deposits are similar to gastroliths in both structure and function. After posterior ecdysis, calcium in the deposits is resorbed rapidly and employed in calcification of the new posterior exocuticle. Calcium is then resorbed from the general anterior integument within 24 h and may accumulate transiently in the haemolymph. During this period resorption of integumentary calcium and calcification proceed simultaneously in the anterior and posterior regions of the animal. Ecdysis of the anterior region then occurs, and calcium from the haemolymph is employed in calcification of the new anterior exocuticle. Forty-eight percent of intermoult calcium content is conserved. However, both exuviae are eaten and it is argued that further calcium is conserved by resorption from the exuviae within the gut. It is suggested that this calcium, together with dietary calcium, is employed in calcification of the endocuticle after ecdysis. It is proposed that comparable events occur in all crustaceans that conserve calcium, but are rendered especially dramatic in isopods, owing to the unusual biphasic pattern of cuticle secretion.

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