Effects of fractionated radiotherapy on bone blood flow in man

Effects of fractionated irradiation on bone blood flow during and some months after the radiotherapy were measured with a 133Xe washout method from the greater trochanteric regions of human femurs. The results suggest that at low dose levels (CRE from 250 to 1050 reu) the decrease in bone blood flow is small. However, there seems to be a significant decrease in blood flow (about 50%) several months after the irradiation.     

重离子和X射线照射对小鼠骨髓细胞周期分布的影响

目的 研究重离子和X射线全身照射小鼠对骨髓细胞周期分布的影响，为面向生物学对象的重离子治疗提供基础数据。方法用X射线和重离子照射BALB／c小鼠后，24h后制得骨髓细胞，采用PI染色用流式细胞仪测骨髓细胞周期变化。结果照射24h后，X射线照射的各组骨髓细胞周期分布与对照组差异没有统计学意义；重离子照射组与对照组相比，出现G1／G0期和G1／M期阻滞，与相同剂量X射线照射组相比亦出现G1／G0期和G2／M期阻滞。结论 相同剂量的重离子照射较X射线对骨髓细胞的损伤更严重，引发不同的生物学效应。     

Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

Background and purpose

Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation.

Material and methods

Daily fractionated irradiation (5?×?3 Gy/week) was given over 1 (days 0–4) or 3 weeks (days 0–4, 7–11, 14–18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose–effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols.

Results

Transplantation of 6?×?10⁶, but not of 3?×?10⁶ bone marrow stem cells on day ??1, +?4, +?8, +?11 or +?15 significantly increased the ED₅₀ values (dose, at which an ulcer is expected in 50?% of the mice); transplantation on day +?2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day ??1, 2 or +?8 significantly, and on day +?4 marginally increased the ED₅₀ values.

Conclusion

Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation.     

加热复合电离辐射对人骨髓细胞的影响

目的：研究了加热与电离辐射后对人离体骨髓细胞存活率及形态等方面的影响。结果：骨髓细胞存活率随加热时间增加而呈直线下降，温度越高直线斜率越大。在形态学上，骨髓细胞受热后可出现非特异性退行性变化，随着时间的延长，这些变化更加明显。骨髓细胞受单纯Ｘ射线照射后，可见随着照射剂量的增大，细胞存活率明显下降。形态学上单纯３ＧｙＸ射线照射可使少数细胞出现空泡变性，线粒体肿胀，核膜破裂等变化。骨髓细胞受Ｘ射线照射后立即给予４２℃３０分钟的加热使骨髓细胞存活率下降的程度比各自单独作用之和要大（Ｐ＜０．０１）。电镜显示结构破坏明显，细胞支架系统、细胞器均受到破坏，细胞膜、核膜破坏乃至溶解，核浆、细胞浆外溢。     

Radiation damage to the rat spinal cord: the effect of single and fractionated doses of X rays

The tolerance of the rat lumbar spinal cord to single and multiple doses of X irradiation has been studied using paralysis of the hind legs as the endpoint. The paralysis, which has an acute onset progressing from the first symptoms to full paralysis within two to three days, occurs within one year post-irradiation. Dose/effect relationships were estimated at one year. Experiments which were designed to study the effect of varying the overall treatment time between two equal doses of X rays showed that a large amount of recovery from irradiation damage occurred during the first 24 hours after irradiation (D2-D1 at 24 hours was 950 rad). No further recovery took place for another 15 days but at 32 days another wave of recovery seemed to be in progress (D2-D1 at 32 days was 1250 rad). The effect of varying the number of fractions independently of the overall treatment time was investigated. The tolerance of the cord increased rapidly as the number of fractions given in a six-week period was increased from four to 30. The slope of a Strandqvist-type plot of this data was about 0.4. The data for the spinal cord have been compared with similar data for late damage in the mouse lung. The latent period between irradiation and the onset of paralysis was also investigated. At high doses, when the probability of paralysis occurring was great, the latent period was independent of the dose. At lower doses which gave rise to a lower incidence of paralysis, the latent period was inversely related to the dose. A second type of paralysis occurred later than one year after irradiation. This had a very protracted development and occurred in unirradiated as well as irradiated animals.     

Use of impedance plethysmography to continually monitor bone marrow blood flow

Methods for measuring bone-blood flow are often time-consuming, tedious, single-point measurements which require sacrifice of the animal. An impedance plethysmographic technique is described which can be used to quantify temporal bone marrow blood flow changes. Results obtained with the impedance technique compare favorably with the data from simultaneously administered microspheres. Injection of sympathomimetic drugs produced measurable responses: isoproterenol caused a significant increase in bone marrow blood flow within 1 min and levarterenol decreased bone marrow blood flow. Data obtained with impedance plethysmography suggest that the technique is feasible for multiple measurements on the same animal and that the technique can be used to study acute or chronic changes in bone marrow blood flow following various experimental treatments.     

Human cell membrane oxidative damage induced by single and fractionated doses of ionizing radiation: a fluorescence spectroscopy study

Purpose: To investigate the production and repair of lipid oxidative damage in two human cell lines exposed to acute and fractionated dose of ionizing radiation. Radiation dose was in the range from 0.1 to 44Gy. Materials and Methods: K562 and HL60 human cell lines have been used, 24 and 96 h after seeding. Membrane lipid oxidative damage has been detected by the measurement of the fluorescence decay of 1,6-diphenyl-1,3,5-hexatriene (DPH), its polarization value and the conjugated dienes concentration. The modification of DPH decay has been previously reported to be directly related to the lipid hydroperoxide concentration. Results: A modification of the DPH decay has been observed as a linear function of the logarithm of the radiation dose and only when the irradiation was performed in the presence of oxygen. The amount of the damage is related to the time after the cell medium change. By exposing the cells to fractionated radiation doses for several days (10 cGyday- 1), the oxidative damage has been found to be cumulative. After a single acute dose, evidence of repair of the lipid oxidative damage was not obtained. Conclusions: Following a previously developed method, the membrane damage was attributed to the production of hydroperoxide residues in the lipid acyl chains with the consequence of water penetration into the external portion of the bilayer, from the aqueous environment to the position of hydroperoxides. This damage is not repaired. The results obtained by measuring the DPH fluorescence decay have been compared with those obtained using other current optical and biochemical methods. None of these techniques could detect membrane oxidative damage at doses 10 Gy. Finally, the different sensitivity of 'young' and 'old' cells to the oxidative damage can be related to different cholesterol concentrations.     

洁治术对艇员牙龈血流量和牙龈炎的影响

目的探讨洁治术前后牙龈血流量（GBF）和牙周临床指标的变化。方法选取患有牙龈炎的艇员60例，分为2组，洁治组用牙周洁治治疗，对照组局部用双氧水冲洗，1周后复诊，分别用激光多普勒血流仪测定2组治疗前后的GBF及牙龈指数（GI）、菌斑指数（PLI）和牙石指数（CI），并比较2组的差异。结果洁治后1周时，洁治组GBF、GI、PLI、CI与对照组比较差异有统计学意义（P〈0．01），洁治组GBF较治疗前明显增加，GI、PLI、CI均明显降低（P〈0．01）；对照组GBF和GI有轻度降低，但PLI和CI无明显变化（P〉0．05），牙周洁治术对慢性龈炎的GBF、GI、PLI、CI与增生性龈炎各指数的作用无明显差异。治疗1个月时，洁治组GBF、GI、PLI、CI与1周时无显著性变化。结论洁治术可使艇员GBF明显增加，GI、PLI、CI明显降低，改善微循环，使牙龈炎症减轻，其疗效与调节牙龈微循环有密切关系。该方法疗效好，操作方便，可作为艇员牙龈炎防治的常用方法。     

The effect of small radiation doses: desoxyribonucleic acid (DNA) synthesis and DNA repair by the thymus, spleen and bone marrow cells of rats following fractionated whole-body X-ray irradiation

After three to seven days following to fractionated total body X-ray irradiation (TBI) (four exposures with doses of 0.3 to 5.0 cGy per fraction at intervals of 24 hours), a maximum 50 percent stimulation of the semiconservative DNA synthesis (SDS) of spleen cells was measured in vitro. This was not dependent of the fact if an acute high-dose (400 and/or 800 cGy) unique irradiation was applied after the fractionated TBI at the moment of stimulation. A significant increase of 3H-thymidine incorporation into the DNA of bone marrow and thymus cells was only found when doses of 1.25 cGy per fraction had been used. After fractionated TBI with doses of greater than or equal to 5 cGy per fraction, an increase of DNA synthesis resistant to hydroxyurea ("unprogrammed" DNA synthesis, UDS) was demonstrated in spleen cells. The UV-stimulated UDS decreased proportionately. The sedimentation of thymus, spleen, and bone marrow nucleoids in a neutral saccharose gradient gave no evidence of an increased DNA repair capacity after fractionated TBI. Whereas the SDS stimulation by fractionated TBI with small doses can be explained by a modified proliferation behavior of exposed cells, the UDS behavior of spleen cells after considerably higher radiation doses suggests regenerative processes correlated with an increased number of cells resistant to hydroxyurea and cells presenting an UV repair deficiency. These findings can be considered to be a further proof of the assumed immune-stimulating effect of small radiation doses.     

饮酒对飞行人员红细胞变形性的影响

目的探讨饮酒对飞行人员血液粘度和红细胞变形性的影响。方法３５例飞行人员于６：００空腹抽静脉血进行血液流变学检测；于当日１８：００吃饭时饮３８度白酒１００ｍｌ～１５０ｍｌ，于次日６：００空腹再次抽静脉血进行血液流变学检测，并与饮酒前的血液流变学结果进行自身对照。结果饮酒后次日晨全血高切粘度（２００ｓ－１）及红细胞刚性指数显著增高（Ｐ＜０．０５）。结论饮酒可使红细胞变形性显著降低，血粘度升高，导致脑及全身器官微循环灌注障碍，可能影响到飞行质量和安全     

自体外周血干细胞联合自体骨髓移植与单纯自体骨髓移植后造血功能重建的比较

目的 :比较自体外周血干细胞联合自体骨髓移植 (APBSCT ABMT)与单纯自体骨髓移植 (ABMT)后造血功能重建及有关临床指标。方法 :以 10例APBSCT ABMT及 10例ABMT病人作为研究对象。结果 :移植后APBSCT ABMT组与ABMT组白细胞 >1.0× 10 9·L 1、中性粒细胞 >0 .5× 10 9·L 1和血小板 >5 0× 10 9·L 1的中位数时间分别为 10、11、13d和 15、17、2 0d(均为P <0 .0 5 )。输血浆量及血小板量APBSCT ABMT组明显较ABMT组为少 (P <0 .0 1)。伊米配能使用率ABMT组明显高于APBSCT ABMT组 (P <0 .0 1)。出血发生率及程度两组均有显著差异 (P <0 .0 5 )。住层流病房时间APBSCT ABMT组明显较ABMT组短 (P <0 .0 1)。但血红蛋白下降程度两组无显著差异 (P >0 .0 5 )。结论 :APBSCT ABMT可加快造血功能重建速度 ,并降低严重感染和出血的发生率 ,减少血液成分输注及抗生素的使用 ,缩短住院时间 ,同时可利用骨髓进行体外净化 ,因此仍不失为一种治疗恶性肿瘤的有效手段。     

Hyperemic peripheral red marrow in a patient with sickle cell anemia demonstrated on Tc-99m labeled red blood cell venography

A 25-year-old gravid woman, homozygous for sickle cell anemia, with a history of recent deep venous thrombosis, was examined using Tc-99m labeled red blood cell venography for recurrent thrombosis. Although negative for thrombus, the study presented an unusual incidental finding: the patient's peripheral bone marrow was hyperemic in a distribution consistent with peripheral red bone marrow expansion. Such a pattern has not been documented before using this technique. This report supports other literature that has demonstrated hyperemia of peripheral red bone marrow in other hemolytic anemias. This finding may ultimately define an additional role of scintigraphy in assessing the pathophysiologic status of the sickle cell patient.     

骨髓间充质干细胞对大鼠皮肤损伤促愈作用的研究

目的：研究骨髓间充质干细胞（MSCs)对大鼠皮肤损伤所发挥的促愈作用。从而为临床皮肤损伤修复提供新的种子细胞来源。方法：体外培养扩增雄性Wistar大鼠的骨髓MSCs，选择雌性Wistar大鼠30只制作皮肤损伤模型，并随机分为MSCs-胶原膜组（接种细胞胶原膜组，A组），单纯胶原膜组（B组）和自然愈合组（对照组，C组），每组10只。采用创面大体观察、组织学检查和透射电镜等方法观察创面愈合情况，并结合原位杂交方法判定创面愈合过程中是否存在植入细胞。结果：伤后7，14d,3组中任何两组之间创口收缩率比较，差异均有非常显著性意义（P＜0．01），其顺序为A组＞B组＞C组；组织学检查显示，A组肉芽组织含量明显多于B、C组；电镜检查显示，A组受损皮肤接近正常；原位杂交结果表明，移植后7，21，27d,A组均可检测到雌性Wistar大鼠受损皮肤真皮层有雄性大鼠sry基因的表达。结论：MSCs可对皮肤损伤发挥明显的促愈作用。     

Effect of exercise conditioning on red blood cell volume and erythropoietin concentration in the beagle dog

To determine if endurance conditioning has a stimulating effect on red blood cell and erythropoietin production, we exercised five beagle dogs on a motor-driven treadmill for 1 hour per day, 5 days per week, for 6 weeks at a speed near their maximal capability. Three additional beagles were kept in cages and served as nonconditioned controls. Endurance conditioning in these dogs produced no increase in red blood cell mass, serum erythropoietin concentration, or any other blood cell index measured. We conclude that this type of exercise conditioning does not produce the necessary stimulus for an increase in erythropoiesis.