[en] Objective: To evaluate the effect of rhIL-11 on apoptosis of bone marrow cells of mice irradiated with 5.5 Gy ⁶⁰Co γ-rays. Methods: At 6, 12, 24 hours and on days 3, 7 after irradiation, apoptosis of bone marrow cells was studied by means of in situ terminal labeling, flow cytometry and DNA electrophoresis. The expressions of P53 and Bcl-2 of bone marrow cells were evaluated by immunocytochemistry. Results: (1) There was a significant descending trend of apoptotic ratio in rhIL-11-treated group 6 and 12 hours after TBI compared with the control group. (2) On day 3, P53 was expressed at a significantly lower level (P<0.01), whereas Bcl-2 at a significantly higher level (P<0.01), in rhIL-11-treated groups than those of the placebo controls, respectively. On day 7, expression of Bcl-2 was still higher in rhIL-11-administered-before-TBI group (P<0.01). Conclusion: rhIL-11 can promote recovery of murine BM cells by protecting them from apoptosis. The effects of rhIL-11 on apoptosis may have close relationship to the modulation of Bcl-2 and P53

[en] Objective: To examine the therapeutic effect of combined administration of rhIL-11 and rhG- CSF on acute radiation syndrome induced with neutron exposure in beagles. Methods: Fourteen male beagles were randomly divided into rhIL-11 + rhG-CSF treatment group (n=7) and the control group (n=7). All the beagles in both groups were whole-body irradiated with neutron of 2.0 Gy (Neutron:gamma rays = 9:1). The animals in the treatment group had been subcutaneously administered daily with rhG-SCF of 10 μg·kg^-1·d^-1 and rhIL-11 of 50 μg·kg^-1·d^-1 for 14 and 21 days, respectively. All the animals were killed on 33 d after the irradiation. Hemogram of peripheral blood, ratios of CD4⁺/CD8⁺ , and formation of bone marrow CFU-E were used to evaluate the therapeutic effect. Results: By 30 days since the neutron exposure, all the beagles were survived in the treatment group, whereas 3 beagles were died in the control group. The counts of white blood cells during the whole period of experiment and the counts of blood platelets during the recovery period were higher in the treatment group than that in the control group. The ratio of CD4⁺/CD8⁺ in the treatment group was 1.24, 1.55, and 2.15 times higher than that in the control group on the first, 21st and 33rd day since neutron exposure, respectively. More formations of CFU-E in bone marrow were observed in the treatment group, 5.25 and 2.3 times more CFU-E were formatted than that in the control group on the first day and 33rd day, respectively. Conclusion The combined administration of rhIL-11 and rhG-CSF significantly improved the recovery of hematopoietic and immunological function of neutron-irradiated beagles. (authors)

[en] Objective: To evaluate the biological effects of Beagle dogs irradiated by γ-rays at different doses. Methods: All Beagle dogs were divided into six groups and were subjected respectively to total-body irradiation (TBI) with a single dose of 6.5, 5.5, 5.0, 4.5, 3, 5 and 2.5 Gy γ-rays delivered by ⁶⁰Co sources at 7.224 x 10^-2 C/kg per minute. The general condition, blood cell counts and bone marrow cell CFC assays were observed. Results: Vomiting occurred at 0.5 to 2 hours after TBI in all groups. In 6.5 Gy group 3/5 dogs had blood-watery stool and 1/5 in 5.5 Gy group had watery stool. Diarrhea occurred in all other animals. Only one dog in 2.5 Gy group survived, all of others died. in order of decreasing irradiation dosage, the average survival time was 5.0, 8.0, 9.3, 9.5, 10.5 and 14.1 days, respectively. Conclusions: According to the clinical symptoms, leukocyte count and survival time of the dogs, the irradiation dose which will induce very severe hematopoietic radiation syndrome in Beagle dogs is 4.5 to 5.0 Gy

[en] We investigated the heat of formation, density, thermal stability, and detonation properties of a series of carbon-oxidized triazole and tetrazole derivatives substituted by -NH₂ and -NO₂ groups using density functional theory. It is found that their properties are associated with the numbers of substituents and substitution positions in the parent ring. The results show that the -NO₂ group is an effective structural unit for enhancing their detonation performance. It also indicates that the substitution positions play a very important role in increasing the heat of formation values of the derivatives. An analysis of impact sensitivity (h₅₀) indicates that incorporating the -NH₂ groups into the parent ring increases their thermal stability. Considering the detonation performance and thermal stability, seven of the designed compounds may be regarded as potential high-energy compounds. These results provide basic information for the molecular design of novel high-energy compounds. (author)

[en] Objective: To observe the curative effect of rhSCF or rhSCF+rhG-SCF-mobilized peripheral blood stem cells (PBSC) on 7.0 Gy γ ray-irradiated rhesus monkeys. Methods: Fifteen healthy adult rhesus monkeys were divided into placebo control, rhSCF-mobilized, and rhSCF + rhG-CSF-mobilized groups. The two mobilized groups received rhSCF 50 μg·kg^-1·d^-1 for 3 days, then the rhSCF + rhG-CSF-mobilized group was further administered rhG-CSF 10μg·kg^-1·d^-1 for 5 successive days. The placebo control group was given 0.9% sodium chloride at the same volume per kilogram. At day 0 of the irradiation, PBSCs were collected from all subjects. 3-4 hrs after irradiation, all animals received autologous PBSC infusion. Results: rhSCF + rhG-CSF-mobilized PBSC accelerated the recovery of platelet and WBC counts, compared with rhSCF-mobilized PBSC, in which only higher platelet counts were observed. Bone marrow karyocyte culture demonstrated that only rhSCF + rhG-SCF-mobilized PBSC stimulated bone marrow karyocytes to form more CFU-GM, CFU-Mix, and CFU-MK. Histopathological study showed that there were more hematopoietic cells and less fat cells in the bone marrow of mobilized groups than in that of the placebo control group. Conclusion: The infusion of rhSCF or rhSCF+rhG-CSF-mobilized PBSC improves the hematopoietic recovery in 7.0 Gy γ ray irradiated rhesus monkeys. Two cytokine mobilization can get better effects

[en] Objective: The author describes the therapeutic effect of recombinant human interleukin-11 (rhIL-11) administered at different times on acute radiation sickness in monkeys. Methods: Rhesus monkeys irradiated with 3.0 Gy ⁶⁰Co γ rays were divided into 3 groups. One group was the control administered with vehicle, the second one was subjected to administer rhIL-11 on days 0-13 after TBI (60 μg·kg^-1·d^-1, sc) and the third one to administer rhIL-11 on days 13-26 after TBI at the same doses. Results: The early treated group had higher platelet nadirs compared with that of the other two. The duration of platelet and leukocyte numbers below 50% of their baseline values shortened significantly in animals treated with rhIL-11, especially in the early treated group. During the first week after irradiation, the early treated group had lower erythrocyte count compared with the control, but it began to rise at day 19 after irradiation. Semi-solid bone marrow cell culture demonstrated that rhIL-11 could stimulate bone marrow cells to form more CFU-MK, CFU-Mix, CFU-E, BFU-E and CFU-GM in vitro. The authors also got the same results in histopathological observation. Conclusion: rhIL-11 administered at different times can not only accelerate the haematopoietic recovery of acute radiation sickness in rhesus monkeys, but also result in better therapeutic effect when administered earlier

[en] Objective: To investigate the mechanism of treatment of granulocyte colony-stimulating factor (rhG-CSF), recombinant human interleukin-11 (rhIL-11) and recombinant human interleukin-2 (rhIL-2) on hematopoietic injuries induced by 4.5 Gy ⁶⁰Co γ-ray irradiation in beagles, and to provide experimental evidence for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS). Methods: Sixteen beagle dogs were given 4.5 Gy ⁶⁰Co γ-ray total body irradiation (TBI), then randomly assigned into irradiation control group, supportive care group or cytokines + supportive care (abbreviated as cytokines) group. In addition to supportive care, rhG-CSF, rhIL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group. The percentage of CD34 + cells, cell cycle and apoptosis of nucleated cells in peripheral blood were examined by Flow cytometry. Results: After 4.5 Gy ⁶⁰Co γ-ray irradiation, the CD34 + cells in peripheral blood declined obviously (61.3% and 52.1% of baseline for irradiation control and supportive care group separately). The cell proportion of nucleated cells in G₀/G₁ phase was increased notably notably (99.27% and 99.49% respectively). The rate of apoptosis (26.93% and 21.29% separately) and necrosis (3.27% and 4.14%, respectively) of nucleated cells were elevated significantly when compared with values before irradiation (P<0.05) 1 d post irradiation. When beagles were treated with cytokines and supportive care, the CD34 + cells in peripheral blood were markedly increased (135.6% of baseline). The effect of G₀/G₁ phase blockage of nucleated cells became more serious (99.71%). The rate of apoptosis (5.66%) and necrosis (1.60%) of nucleated cells were significantly lower than that of irradiation control and supportive care groups 1 d after exposure. Conclusions: Cytokines maybe mobilize CD34 + cells in bone marrow to peripheral blood, indce cell block at G₀/G₁ phase and reduce apoptosis, and eventually cure hematopoietic injuries induced by irradiation. (authors)

[en] Objective: To explore the clotting mechanism in beagles irradiated by 4.5 Gy γ-rays after treatment with supportive care, or supportive care and combined cytokines. Methods: Sixteen beagles were divided into irradiation control group, Supportive care group and combined cytokines treatment group. Platelet aggregation test, thrombelastography (TEG) and the time measurement were analyzed in vitro. Results: In irradiation group and supportive care group, the platelet aggregation rates in beagles were decreased markedly and the k value of TEG was increased 7 d post-irradiation, while those indexes in combined cytokines treatment group changed little. At 14 d post-irradiation, each parameter of TEG in irradiated group changed obviously. The values of r, k, r + k and M were elevated significantly, clotting time and the maximum coagulation time of thrombus delayed, the Ma value was decreased markedly, and the maximum elasticity amplitude of thrombus was diminished. All parameters in combined cytokines treatment group were better than those in supportive care group. The thrombin time was prolonged obviously in irradiated group 14 d post-irradiation, while the thrombin time was the longest at 2-3 weeks post irradiation in supportive care group and combined cytokines treatment group (P>0.05). Conclusions: Cytokines could improve the platelet aggregation and the blood clotting functions of beagles suffering from acute radiation sickness. (authors)

[en] Objective: To explore the mechanisms of cytokines on acute radiation disease in irradiation beagles. Methods: The sera of beagles irradiated with 4.5 Gy γ-rays with cytokines treatment was collected at different time points post irradiation. The two-dimensional gel electrophoresis (2-DE) was differentially expressed proteins with significance, and the amino acid sequences should be determined. Results: High resolution 2-DE gel map was obtained. There were six differentially expressed proteins in sera of irradiated beagles at different time points. Four protein spots were successfully identified by MS. A significant spot was identified as serum amyloid A (SAA) by HD-MS, with relative molecular mass of 13 077 and isoelectric point of 6.26. Expression of SAA was not found 1 d pre-irradiation and 36 d post-irradiation, but increased slightly 1 d (0.2166) and significantly 14 d post-irradiation (0.4577). Conclusions: The expression of serum amyloid A was consistent with the process of acute radiation injury, which might indicate the turnover of the disease. (authors)

[en] Objective: To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy ⁶⁰Co γ-rays irradiation in beagles, and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS). Methods: 16 beagles were given 4.5 Gy ⁶⁰Co γ-rays total body irradiation, and then randomly assigned into irradiation control group, supportive care group and cytokines group. In addition to supportive care, recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human interleukin-11 (rhIL-11) and recombinant human interleukin-2 (rhIL-2) were administered subcutaneouly to dogs in cytokines group. Peripheral blood hemogram was examined once every two days. Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation. Conventional histopathological sections sternum were prepared to observe the histomorphology changes. Results: After irradiation, the population of all kinds of cells in peripheral blood declined sharply. WBC nadir was elevated (1.04 x 10⁹ /L, but 0.28 x 10⁹ /L and 0.68 x 10⁹ /L for the irradiation control group and the supportive care group separately), the duration of thrombocytopenia was shortened (24 days, but 33 days for the supportive care group) and red blood cell counts were maintained in the range of normal values after cytokines treatment in combination. The colony forming efficiency of haemopoietic stem cells (HSCs) in bone marrow and peripheral blood decreased obviously 1 d post irradiation, but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment. Hematopoietic cells disappeared in bone marrow of animals in irradiation control group, but hematopoietic functions were recovered after cytokines were administrated. Conclusions: RhG-CSF, rhIL-11 and rhIL-2 used in combination could elevate WBC nadir, accelerate the recovery of leukocytes, platelets and red blood cells and promote the proliferation, differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation, eventually restore the hematopoietic function. Hence, combination of rhG-CSF, rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS. (authors)