scholarly journals The association gene polymorphisms with risk of cancer in long-term «low-dose» y-irradiation exposure

2009 ◽  
Vol 7 (4) ◽  
pp. 23-33 ◽  
Author(s):  
Nikolay V Litvjakov ◽  
Maksim B Freydin ◽  
Ravil M Takhauov ◽  
Alena M Ageeva ◽  
Natalia M Volkova ◽  
...  

The association of 13 biallelic polymorphisms of genes hOGG1 977C > G, XPD1 2251A > C, XPG1 3310G > C, XRCC1:580C> T, 839G >A, 1196G>A GSTT1 («+»/«-»), GSTM1 («+»/«-»), CYP2C19 681G> A, NOS3: -665C>T, 774С> T, 894G > T, VNTRint4 with risk of development of malignant new growths (MNG) in conditions of "low-dose" ionizing irradiation was investigated. In 1 group of irradiated patients of malignant new growths there are 96 persons, in 2 group of non-irradiated patients of MNG - 135 persons, in 3 control group - 148 healthy irradiated workers of the Siberian Group of Chemical Enterprises. By means of procedure FDR it is shown that only polymorphic variants of gene CYP2C19681G* are authentically associated with risk of occurrence of MNG against an irradiation. 1 genotype consisting of a combination of 5 polymorphic loci is selected. Frequency of occurrence of this genotype in 1 group makes 16,9 % (14/83), in 2 group - 1,0 % (1/100), in 3 group - 0,84 % (1/119). At its carriers in conditions of low-dose irradiation more than in 20 times the risk of occurrence of MNG (OR between 1 and 3 groups (95 % CI) = 24,14 (3,21-502,64) increases; p = 0,0000581, taking into account the correction of Bonferroni р = 0,01046).

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alberto Benazzo ◽  
Ara Cho ◽  
Anna Nechay ◽  
Stefan Schwarz ◽  
Florian Frommlet ◽  
...  

Abstract Background Long-term outcomes of lung transplantation are severely affected by comorbidities and development of chronic rejection. Among the comorbidities, kidney insufficiency is one of the most frequent and it is mainly caused by the cumulative effect of calcineurin inhibitors (CNIs). Currently, the most used immunosuppression protocols worldwide include induction therapy and a triple-drug maintenance immunosuppression, with one calcineurin inhibitor, one anti-proliferative drug, and steroids. Our center has pioneered the use of alemtuzumab as induction therapy, showing promising results in terms of short- and long-term outcomes. The use of alemtuzumab followed by a low-dose double drug maintenance immunosuppression, in fact, led to better kidney function along with excellent results in terms of acute rejection, chronic lung allograft dysfunction, and survival (Benazzo et al., PLoS One 14(1):e0210443, 2019). The hypothesis driving the proposed clinical trial is that de novo introduction of low-dose everolimus early after transplantation could further improve kidney function via a further reduction of tacrolimus. Based on evidences from kidney transplantation, moreover, alemtuzumab induction therapy followed by a low-dose everolimus and low-dose tacrolimus may have a permissive action on regulatory immune cells thus stimulating allograft acceptance. Methods A randomized prospective clinical trial has been set up to answer the research hypothesis. One hundred ten patients will be randomized in two groups. Treatment group will receive the new maintenance immunosuppression protocol based on low-dose tacrolimus and low-dose everolimus and the control group will receive our standard immunosuppression protocol. Both groups will receive alemtuzumab induction therapy. The primary endpoint of the study is to analyze the effect of the new low-dose immunosuppression protocol on kidney function in terms of eGFR change. The study will have a duration of 24 months from the time of randomization. Immunomodulatory status of the patients will be assessed with flow cytometry and gene expression analysis. Discussion For the first time in the field of lung transplantation, this trial proposes the combined use of significantly reduced tacrolimus and everolimus after alemtuzumab induction. The new protocol may have a twofold advantage: (1) further reduction of nephrotoxic tacrolimus and (2) permissive influence on regulatory cells development with further reduction of rejection episodes. Trial registration EUDRACT Nr 2018-001680-24. Registered on 15 May 2018


2013 ◽  
Vol 16 (1) ◽  
pp. 45-54 ◽  
Author(s):  
M. Gajęcka

AbstractCompanion animals, including bitches, may be exposed to zearalenone (ZEN) toxins that are often present in feed, and ZEN intoxication may lead to ovarian dysfunction. This study involved evaluation of the degree of ZEN-induced hypo stimulation of ovary by determination of proliferative and apoptotic indices and description of the ultra-structural organization of ovarian follicles in pre-pubertal bitches subjected to experimental, long-term exposure to low-dose ZEN mycotoxicosis. The experiment involved 30 clinically healthy, immature Beagle bitches aged approximately 70 days with initial average body weight of 8 kg, randomly divided into three groups of 10 animals each: two experimental groups (EI and EII) and a control group (C). Over a period of 42 days, ZEN was administered per os to EI animals at a dose of 50 μg/kg BW, and to EII bitches at a dose of 75 μg/kg BW. Control group animals were fed placebo containing no ZEN for 42 days. Analytical samples of the mycotoxin were administered daily in gelatin capsules before morning feeding. All the bitches were subjected to ovario-hysterectomy at the end of the experiment. Proliferation index (PCNA method) and apoptotic index (TUNEL test) values were determined by immune-histological analyses. The median for apoptotic index was determined at 13.45 for group EI, 17.84 for group EII, and 8.59 for group C. The median for proliferation index was determined at 35.25 for group EII, 42.44 for group EI, and 70.60 for group C. The results of ultra-structural examinations of the ovaries revealed that experimental, ZEN-induced hyperestrogenism enhanced apoptosis and lowered the proliferative ability of follicular cells what contributed to organelle destruction in pre-pubertal bitches. The changes observed were particularly advanced in EII animals, which were administered a higher dose of ZEN.


1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ana Carolina Lupepsa ◽  
Paula Vargas-Sanchez ◽  
Marcella Goetz Moro ◽  
Leomar Emanuel Almeida Mecca ◽  
Marcela Claudino ◽  
...  

Abstract Background Several drugs are capable of promoting changes in bone metabolism. The aim of this study was to evaluate the effect of long-term low-dose aspirin (LDA) therapy on implant osseointegration. Methods Male Wistar rats were divided into 4 groups (n = 8/group) according to oral gavage solution received prior (42 days) to the implant surgery on the tibia. The control group was treated with saline solution for 7 (CG-7) and 28 (CG-28) days. The use of low-dose aspirin was performed in AG groups (6.75 mg/kg of aspirin) for 7 (AG-7) and 28 (AG-28) days. After experimental periods, histomorphometric evaluation of bone-to-implant contact (BIC) and the bone area between threads (BABT) was performed. Results Reduced BIC values were detected in AG-7 (62.8% ± 17.1) group compared to AG-28 (91.9% ± 5.4), CG-7 (82.7% ± 15.2), and CG-28 (89.9% ± 9.7). BABT evaluation revealed lower values in AG-7 (70.9% ± 15.2) compared to AG-28 (95.4% ± 3.7) and CG-28 (87.1% ± 10.2) groups. Conclusions The treatment with low doses of aspirin promoted a discrete inhibitory effect in the early stages (7 days) of repair after implant placement, specifically in the bone deposition. However, these effects were not detected in the late stages (28 days), considering BIC and BABT parameters.


2020 ◽  
Vol 9 (3) ◽  
pp. 249-262
Author(s):  
Xiaochang Liu ◽  
Zheng Liu ◽  
Duo Wang ◽  
Yang Han ◽  
Sai Hu ◽  
...  

Abstract Whole-body exposure to low-dose radiation due to diagnostic imaging procedures, occupational hazards and radiation accidents is a source of concern. In this study, we analyzed the effects of single and long-term low-dose irradiation on the immune system. Male Balb/c mice received a single whole-body dose of irradiation (0.01, 0.05, 0.2, 0.5 or 1 Gy). For long-term irradiation, mice were irradiated 10 times (total dose of 0.2, 0.5 or 1 Gy) over a period of 6 weeks. Two days after single or long-term irradiation, the numbers of splenic macrophages, natural killer cells and dendritic cells were reduced, and the spleen organ coefficient was decreased. At 2 Days after long-term low-dose irradiation, the number of white blood cells in the peripheral blood of the mice decreased. Between 7 and 14 Days after long-term low-dose irradiation, the number of immune cells in the thymus and spleen began to increase and then stabilized. Th1/Th2 cytokines and reactive oxygen species-related proteins first decreased and then increased to a plateau. Our results show a significant difference in the effects of single and long-term low-dose irradiation on the immune system.


Medicina ◽  
2010 ◽  
Vol 46 (3) ◽  
pp. 204
Author(s):  
Marina Aunapuu ◽  
Andres Arend ◽  
Mai Ots ◽  
Mara Pilmane

Cell proliferation and apoptosis in the remnant rat kidney after treatment with lowdose irradiation was investigated. Material and methods. In the first group (n=9), adult male Wistar rats underwent 5/6 nephrectomy (NPX); in the second group (n=9), NPX was combined with low-dose irradiation. Rats without surgery and irradiation formed the control group (n=9). Results. Hypertension and proteinuria induced by NPX were decreased by 3-Gy irradiation. The 5/6 NPX rats showed a dramatic increase in proliferating and apoptotic cells in the glomeruli and in the distal tubules at week 2, which was significantly decreased by low-dose irradiation. Conclusion. The data demonstrate that low-dose irradiation is a factor slowing the process of chronic renal injury.


1995 ◽  
Vol 25 (2) ◽  
pp. 287A ◽  
Author(s):  
Ron Waksman ◽  
Keith A. Robinson ◽  
Ian R. Crocker ◽  
Michael B. Gravanis ◽  
Gustavo D. Cipolla ◽  
...  

1981 ◽  
Vol 4 (3) ◽  
pp. 142-145 ◽  
Author(s):  
L. Uziel ◽  
A. Agostoni ◽  
E. Pirovano ◽  
A. Pesenti ◽  
A. Pelizzola ◽  
...  

PGI2 plus very low dose of heparin was infused in 6 lambs connected for long term extracorporeal circulation with a membrane lung. Hemodynamic and hemostasis parameters were compared to those of a control group treated only with standard doses of heparin. PGI2 efficacy in inhibiting platelet aggregation and platelet fall was confirmed. A small platelet release, measured as antiheparin activity, was observed during all the by-pass, but did not influence platelet capacity of recovering when PGI2 effect dissolved. Heparin needed resulted less than a quarter of the quantity used for the control group. In our experimental conditions the hemodynamic changes were mainly limited to a decrease in diastolic blood pressure.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Kun Li ◽  
YiShui Chen ◽  
XiaoLiang Li ◽  
ShuJie Lei ◽  
QingFeng Chen ◽  
...  

Objective.The aim of the study is to estimate the immune function through cytokine profiles in sera of uranium mines.Methods.Antibody arrays were used to detect 50 cytokines in sera of uranium miners. Miners who had continuously worked underground for <5 years were treated as control group and those who worked for⩾5 years as experimental group.Results.Of 28 measurable cytokines, the release of IL-1α, IL-1RI, IL-15, IL-3, and IP-10 were significantly upregulated in the experimental group, and no cytokine was found significantly downregulated. Other proinflammatory cytokines such as IFN-γ, IL-10, IL-6, and TNFαlevels were slightly upregulated in the experimental group. With adjustment to age, BMI, and cigarette smoking, IL-1αand IL-3 levels increased significantly with underground time.Conclusion.Alteration of cytokine profiles in this study may indicate persistent inflammatory responses in uranium miners exposed to long-term low doses radiation.


2014 ◽  
Vol 133 (1) ◽  
pp. 124-128 ◽  
Author(s):  
Banhe Din ◽  
Xingwen Wang ◽  
Yuye Shi ◽  
Yufeng Li

Background: To tackle the problems associated with high-dose dexamethasone (HD-DXM) in patients with immune thrombocytopenia (ITP). Aim: To compare the efficacy of HD-DXM with or without low-dose dexamethasone maintenance in untreated ITP patients. Results: Dexamethasone (40 mg/day) was given in 4-day pulses every 14 days for 3 cycles in 61 patients with ITP. Among them, 30 cases were given dexamethasone (0.035 mg/kg per day) for maintenance between pulsed HD-DXM and after 3 HD-DXM courses (HD-DXM-M group) and another 31 cases did not receive dexamethasone maintenance (HD-DXM-nM group). The control group comprised the patients who received prednisone (prednisone group). The following results were obtained: (1) at the end of the 3rd cycle, the overall response rate (ORR) was higher in the HD-DXM group than in the prednisone group; (2) the ORR of the HD-DXM group peaked after the 3rd cycle; (3) the ORR after each course was higher in the HD-DXM-M group than in the HD-DXM-nM group; (4) in the 12th month after HD-DXM discontinuation, the relapse rate of the HD-DXM-M group was lower than that of the other groups (prednisone and HD-DXM-nM). Conclusion: Treatment with 3 cycles of HD-DXM pulses with low-dose dexamethasone maintenance is an effective method for untreated ITP.


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