Effects of Systemic or Topical Administration of Sodium Selenite on Early Radiation Effects in Mouse Oral Mucosa

PURPOSE: To quantify the effect of sodium selenite (selenium) on radiation-induced oral mucositis (mouse) after subcutaneous or topical administration. MATERIAL AND METHODS: Mucosal ulceration of the lower epithelium of mouse tongue was analyzed. Selenium (5 mug) was applied subcutaneously (s.c.) or locally, 60 min or 30 min prior to irradiation, respectively. In combination with single-dose irradiation, a single selenium application was given. With daily fractionated irradiation (3 Gy/fraction) for 1 week (days 0-4), selenium was administered at all 5 days of irradiation. With ten fractions over 2 weeks, selenium was applied in week 1, week 2, or both. All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. RESULTS: In a single-dose control experiment, the ED(50) (dose after which ulcer induction is expected in 50% of the mice) was 12.9 +/- 1.6 Gy. Selenium increased the ED(50) to 17.7 +/- 2.6 Gy (s.c.; p = 0.0003) and 16.3 +/- 3.0 Gy (local; p = 0.0104). The ED(50) for test irradiation after 5 x 3 Gy was 7.4 +/- 2.2 Gy. Subcutaneous administration of selenium resulted in an ED(50) of 11.5 +/- 2.0 Gy (p = 0.0015), local application yielded an ED(50) of 10.0 +/- 2.1 Gy (p = 0.0284). The ED(50) for test irradiation after 10 x 3 Gy/2 weeks was 8.0 +/- 1.7 Gy. Subcutaneous or local administration of selenium in week 1 yielded a significant increase in ED(50) to 10.5 +/- 1.0 Gy (p = 0.0069) and 10.7 +/- 1.0 Gy (p = 0.0039), respectively. By clear contrast, selenium administration in week 2 had no significant effect. Administration in both weeks resulted in an ED(50) of 9.1 +/- 2.0 Gy (s.c.; p = 0.2747) and 9.7 +/- 1.4 Gy (local; p = 0.0541). CONCLUSION: Administration of sodium selenite during clinically relevant fractionated irradiation protocols has a significant effect during the initial treatment phase, i.e., week 1 in the mouse. Therefore, in clinical radiotherapy, the latent time to manifestation of confluent mucositis may be significantly prolonged, and hence the burden for the patient clearly reduced by selenium.     

Comparison of the Intraperitoneal,Retroorbital and per Oral Routes for F-18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

Purpose

We compared alternative routes for ¹⁸F-fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice.

Materials and Methods

CRL-1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c-nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9 mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection.

Results

There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans.

Conclusion

RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.     

广东高本底地区居民外周血淋巴细胞姐妹染色单体互换观察

调查组检查15～16岁的正常男女青年学生126人, 平均SCE值为12.9±76.37/细胞。0.28/染色体; 对照组检查了同年龄组的男女青年学生124人, 平均SCE值为11.05±6.4/细胞, 0.24/染色体。两组SCE值具有统计学差异, 考虑可能与慢性小剂量长期内外照射机体内产生过氧阴离子基团(O₂^-)或辐射后细胞体产生其它辐射产物, 致使DNA损伤、染色体断裂, SCE增加及调查组居民体内²²⁶Ra, ²²⁸Th和发锰含量较对照组明显增高等有关。对照组SCE本底值较高则可能是细胞培养过程中受到较长肘同的自然光照, BrdU光分解增多所致。     

Effects of Ionizing Radiation on Artificial (Planar) Lipid Membranes. I. Radiation Inactivation of the Ion Channel Gramicidin A

Summary

The ion channel formed by the pentadecapeptide gramicidin A in planar lipid membranes is extremely sensitive to ionizing radiation. The membrane conductance may drop by several orders of magnitude under appropriate experimental conditions (low pH and presence of oxygen). The radiation sensitivity is strongly reduced for gramicidin M^?. This analogue has the four tryptophan residues replaced by phenylalanines. Experiments performed in the presence of various radical scavengers suggest that the inactivation of the channel is due to a combined action of OH and of HO₂ radicals at the tryptophan residues.

The shape of the inactivation curves following continuous radiolysis or pulse radiolysis were found to be in fair agreement with a simple model which assumes that the damage of a single tryptophan residue is sufficient for channel inactivation. The conductance of inactivated channels could not be resolved within the experimental accuracy. This is contrary to photolysis of gramicidin channels found by Busath and Waldbilling (1983), where a broad distribution of low conductance states was observed. The inactivation by radiolysis seems to represent an ‘all-or-none-process’ of the channel conductance.     

Intravenous adenosine (adenoscan) versus exercise in the noninvasive assessment of coronary artery disease by SPECT

Fifteen patients at a mean age of 58 underwent adenosine and maximal exercise thallium SPECT imaging. All scans were performed 1 week apart and within 4 weeks of cardiac catheterization. SPECT imaging was performed after the infusion of 140 micrograms/kg/min of adenosine for 6 minutes. Mean heart rate increment during adenosine administration was 67 +/- 3.7 to 77 +/- 4.1. Mean blood pressure was 136 +/- 7.2 to 135 +/- 6.2 systolic and 78 +/- 1.8 to 68 +/- 2.6 diastolic. No adverse hemodynamic effects were observed. There were no changes in PR or QRS in intervals. Five stress ECGs were ischemic. No ST changes were observed with adenosine. Although 68% of the patients had symptoms of flushing, light-headedness, and dizziness during adenosine infusion, symptoms resolved within 1 minute of dosage adjustment or termination of the infusion in all but one patient, who required theophylline. Sensitivity for coronary artery detection was 77% and specificity 100%. Concordance between adenoscans and exercise thallium scintigraphy was high (13/15 = 87%). In two patients, there were minor scintigraphic differences. The authors conclude that adenosine is a sensitive, specific, and safe alternative to exercise testing in patients referred for thallium imaging and may be preferable to dipyridamole.     

Radiation chemistry of d(TpApCpG) in oxygenated solution

The radiation chemistry of the DNA tetranucleoside triphosphate d(TpApCpG) was investigated. The tetramer was X-irradiated in oxygenated aqueous solution and the various products separated by high-performance liquid chromatography. The principal modifications of the tetramer were analysed intact using nuclear magnetic resonance (NMR) spectroscopy and in some instances also by fast atom bombardment (FAB) mass spectrometry. The principal radiation-induced lesions of d(TpApCpG) were found to be a formamido modification derived from the thymine base, two stereoisomeric forms of a 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine modification derived from the cytosine base and an 8-hydroxyguanine modification.     

犬烧伤休克早期延迟输液对肺功能的影响

目的：探讨烧伤休克后立即和延迟输液对肺功能的影响。方法：４３只犬被随机分为四组，①正常对照组，②立即输液组，③延迟输液组，④不输液组。除正常对照组外，所有犬都造成５０％Ⅲ度体表烧伤。血气分析、ＣＯ、ＦＡＰ等在伤后０．５、２、６、１２、１８、２４、３６、４８小时观测。所有犬除不输液组外，伤后按Ｐａｒｋｌａｎｄ公式静脉补液。结果：正常对照组和立即输液组伤后ＰａＯ２、ＰａＣＯ２、ＣＯ、ＦＡＰ等无明显变化。不输液组所有犬伤后１２小时内死于烧伤休克，但ＰａＯ２、ＰａＣＯ２无明显变化。延迟输液组所有犬显示严重休克，低氧血症，呼吸性碱中毒，代谢性酸中毒，血ＳＯＤ明显降低，肺ＭＤＡ和肺水量明显增加，同正常对照组和立即输液组比较，其中８６．７％的犬死于烧伤休克。结论：延迟输液组肺功能不全，除了烧伤休克和烧伤本身影响外，与延迟输液引起再灌注损害，产生氧自由基导致脂质过氧化和肺毛细血管通透性增加，加重肺水肿，从而影响肺功能有关。     

Radiation dose distributions in normal tissue adjacent to tumors containing (131)I or (90)Y: the potential for toxicity.

Given the relatively large tumor-absorbed doses reported for patients receiving radionuclide therapy, particularly radioimmunotherapy, and the relatively long pathlength of the nonpenetrating emissions of some radionuclides being used for these therapies, there exists the possibility of large absorbed doses to tissues adjacent to, surrounded by, or surrounding these tumors. Because tumors can occur adjacent to critical organs or tissues, such as arteries, nerves, pericardium, and the walls of the organs of the gastrointestinal tract, large absorbed doses to these normal tissues can lead to acute complications. METHODS: In this study, the Monte Carlo radiation transport code MCNP4b was used to simulate the deposition of energy from emissions of 2 radionuclides of interest, (131)I and (90)Y, to assess the possible magnitude of the absorbed doses in tissues adjacent to tumors. Mathematic models were constructed to simulate situations that might occur, such as tumor wrapped around a small cylinder (e.g., a nerve or artery), tumor against a tissue (e.g., the pericardium or wall of any gastrointestinal tract organ), and tumor surrounded by any soft tissue. Tumor masses of 10, 20, and 40 g were used in each model. Depth dose distributions were calculated using Monte Carlo simulations of the radiation transport in these geometric models. RESULTS: For tissues close to tumors containing (90)Y, the absorbed dose ranged from 24% of the absorbed dose in the tumor, for the case of tissues 1 mm from the tumor, to 103% of the absorbed dose in the tumor, for the case of small structures such as nerves or arteries surrounded by tumor. For tissues close to tumors containing (131)I, the absorbed dose ranged from 4% of the absorbed dose in the tumor, for the case of tissues 1 mm from the tumor, to 46% of the absorbed dose in the tumor, for the case of small structures such as nerves or arteries surrounded by tumor. CONCLUSION: This study showed that when absorbed doses to tumors are large, the absorbed dose to adjacent tissues can also be large, potentially causing unexpected toxicities.     

小鼠钟基因Period2(Per2)抑制乳腺癌细胞生长的研究

目的 研究小鼠节律基因Period2（Per2）对小鼠乳腺癌细胞（EMT6）的生长抑制及诱导凋亡的作用。方法 将pcDNA3．1（＋）-Per2转导入EMT6细胞内,同时设立转染空质粒pcDNA3．1（＋）入细胞的对照组。以RT-PCR、Western blot、流式细胞技术来检测Per2基因和蛋白的表达;采用MTT、细胞生长曲线、细胞平板集落形成实验检测Per2过表达后对小鼠乳腺癌细胞的生长抑制作用;通过流式细胞技术、DNA梯形带、hochst33258荧光染色和电镜技术检测nr2过表达后对小鼠乳腺癌细胞凋亡的影响。结果 小鼠节律基因nr2过表达抑制EMT6细胞的生长和增殖,诱导细胞凋亡率增加。结论 本研究发现小鼠节律基因Per2可能通过使EMT6细胞阻滞于G1期,并诱导细胞凋亡来实现对该肿瘤细胞的生长抑制作用。     

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.     

Intravenous glycoprotein IIb/IIIa inhibitor (tirofiban) followed by intra-arterial urokinase and mechanical thrombolysis in stroke

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate preliminarily the efficacy and safety of intravenous tirofiban combined with intra-arterial pharmacologic and mechanical thrombolysis in patients with stroke. METHODS: Twenty-one consecutive patients with an acute ischemic stroke due to major cerebral arteries occlusion and a National Institutes of Health Stroke Scale [NIHSS] score > or = 18 were treated with an intravenous bolus of tirofiban and heparin followed by intra-arterial administration of urokinase coupled with mechanical thrombolysis. RESULTS: Thirteen patients had an anterior circulation stroke (T-siphon internal carotid artery [ICA] = 7; middle cerebral artery [MCA] = 6), 6 patients a posterior circulation stroke, and 2 patients an anterior plus posterior circulation stroke (left ICA or M1 tract of MCA plus basilar artery occlusions). Mean NIHSS score on admission was 21 (range, 18-27). Immediate recanalization was successful (thrombolysis in myocardial infarction [TIMI] 2-3) in 17 of 21 patients. The following day, 14 of 19 patients improved substantially and complete vessel patency (TIMI 3-4) was confirmed by digital subtraction angiography. Intracranial bleeding occurred in 5 of 21 patients (3 symptomatic cerebral hemorrhages and 2 subarachnoid hemorrhages) and was fatal in the case of 3 patients. At discharge, the mean NIHSS was 5.4 (range, 0-25). Overall, at 3-month follow-up the functional outcome was favorable (modified Rankin Scale score = 0-2) in 13 of 21 (62%) patients. Death (including all causes) at 90 days occurred in 6 of 21 (28%) cases. CONCLUSIONS: The combination of intravenous tirofiban with intra-arterial urokinase and mechanical thrombolysis may be successful in reestablishing vessel patency and result in a good functional outcome in patients with major cerebral arteries occlusions.     

辣椒素对微波辐射所致小鼠血液系统损伤的保护作用

目的研究辣椒素对微波辐射所致小鼠血液系统损伤的保护作用。方法将小鼠随机分为3组:对照组;辐射组,用频率为2450 MHz、功率密度为65 mW/cm2的微波辐射,连续3 d,每天8 h;辣椒素组,在与辐射组相同的辐射下每天2次辣椒素灌胃,浓度为2.5 g/L,体积为0.2 mL。检测小鼠的红细胞(RBC)计数、嗜多染红细胞微核率、血清超氧化物歧化酶(SOD)与促红细胞生成素(EPO)。结果辐射组微核率升高,SOD,EPO降低,辣椒素组微核率下降至正常,EPO明显上升,RBC计数也明显上升,同时SOD也回升至正常。结论辣椒素对微波所致小鼠血液系统损伤有保护作用,其机制可能与辣椒素的抗氧化作用和促进EPO分泌有关。     

Radiation therapy of the renal tumor in children (author's transl)

Close cooperation of pediatric surgeons and pediatric oncologists with radiotherapists, using coordinated treatment schedules conformable to the stage of the disease, and combining tumor nephrectomy, postoperative irradiation and the treatment with AMD and Vincristine, has increased the 3-year survival rate from 27% (13 of 49) up to 67% (14 of 21) for children with Wilm's tumor.     

Effects of Gamma Radiation on the Fertility of the Common Cattle Grub,Hypoderma Lineatum (de Villers)

Summary

At 9–13 days after collection from the backs of cattle as larvae, or 6–8 days before heel flies emerged, pupae of the common cattle grub, Hypoderma lineatum (de Villers), were exposed to 1000, 2500, 5000, or 7500 roentgens of gamma radiation from a ⁶⁰Co source. Flies from irradiated pupae were mated with those from non-irradiated pupae to determine fertility of the treated individuals. At 5000 and 7500 roentgens both sexes were completely sterilized; at 2500 r females were completely sterilized and males exhibited reduced fertility.