富氢水减轻造血干祖细胞的辐射损伤

目的 探讨富氢水对辐射诱导的造血干祖细胞（HSPCs）损伤的保护作用。方法 32只C57BL/6小鼠根据体重分层随机区组法分为健康对照组、富氢水组、照射组、照射+富氢水组,共4组,每组8只。富氢水组和照射+富氢水组小鼠于照射前5 min至照后7 d,每天灌胃给予0.5 ml富氢水,其余小鼠每天灌胃给予0.5 ml蒸馏水,照射组和照射+富氢水组小鼠接受2 Gy的¹³⁷Cs γ射线全身照射。照后15 d取小鼠骨髓,检测骨髓中HSPCs比例、骨髓细胞的克隆形成和移植重建能力、骨髓中LSK细胞的活性氧（ROS）水平和细胞凋亡情况。结果 与照射组相比,照射+富氢水组小鼠骨髓中造血祖细胞和LSK细胞比例升高（t=-4.935、-7.898,P<0.05）,骨髓细胞形成克隆的数目增加（t=5.488,P<0.05）,竞争性骨髓移植后受体小鼠的供体嵌合率升高（t=-12.769,P<0.05）,骨髓中LSK细胞的ROS水平和细胞凋亡比例降低（t=4.380、3.954,P<0.05）。结论 富氢水对2 Gy电离辐射诱导的HSPCs损伤具有一定的保护作用。     

四物汤有效成分配伍组方对电离辐射所致氧化损伤的防护作用

目的 观察四物汤有效成分配伍组方对电离辐射所致人淋巴母细胞AHH-1细胞氧化损伤的辐射防护作用,并初步探讨其作用机制。方法 4.0 Gy ⁶⁰Co γ射线单次照射AHH-1细胞,造成电离辐射损伤。观察不同浓度的四物汤有效成分配伍组方(果糖、阿魏酸、芍药苷、川芎嗪质量比为9 008:53:721:267)对于电离辐射损伤的AHH-1细胞活力、凋亡情况、活性氧(ROS)水平的影响,以及对pGL4-ARE报告基因载体的激活作用。结果 四物汤有效成分配伍组方在10 mg/L的浓度下抗辐射效果最为显著,可以减缓受照AHH-1细胞活力下降(t=-8.152,P<0.05),缓解早期细胞凋亡(t=12.777,P<0.05),降低ROS水平(t=3.465,P<0.05),诱导报告基因pGL4-ARE荧光表达倍数提高(t=-19.752,P<0.05)。结论 四物汤有效成分配伍组方具有体外抗辐射活性,可能通过激活Nrf2-Keap1-ARE抗氧化通路、降低辐射所致氧化损伤,从而发挥辐射防护作用。     

氮氧自由基化合物对60Co γ射线致BALB/c小鼠辐射损伤的防护作用

目的 观察氮氧自由基化合物NHCOCH3-TEMPO对雄性BALB/c小鼠电离辐射损伤的防护效果。方法 将120只雄性BALB/c小鼠按随机数字表法分成4和7 Gy照射组,每组60只,每组再按随机数字表法分成6组,每组10只,分别为生理盐水对照组、生理盐水照射组、低剂量TEMPO照射组、中剂量TEMPO照射组、高剂量TEMPO照射组和阳性对照(WR-2721)组。⁶⁰Co γ射线照射前0.5 h动物腹腔注射防护药物,剂量分别为:WR-2721组200 mg/kg、低、中、高剂量TEMPO组分别为100、200和400 mg/kg、生理盐水对照组和生理盐水照射组给予等量生理盐水。4 Gy全身照射组用于观察小鼠照后8和15 d骨髓有核细胞数、骨髓DNA含量和外周血象的变化;7 Gy全身照射用于观察小鼠照后30 d生存率。结果 4 Gy照射后,TEMPO预处理组小鼠骨髓有核细胞计数、骨髓DNA含量较生理盐水照射组均明显增加(t=2.53~6.13,P<0.05);中剂量TEMPO预处理组小鼠外周血白细胞数较生理盐水照射组明显增加(t=4.34,P<0.05),但外周血红细胞数与生理盐水照射组相比,差异无统计学意义。7 Gy照射后,低剂量TEMPO预处理组小鼠30 d存活率较生理盐水照射组明显增加(χ²=5.934,P<0.05)。结论 氮氧自由基化合物NHCOCH3-TEMPO对雄性BALB/c小鼠γ射线辐射损伤有一定的防护作用。     

阿魏酸对小鼠骨髓造血功能辐射损伤的防护作用

目的 观察阿魏酸对小鼠外周血象和骨髓造血功能辐射损伤的防护作用,初步探讨阿魏酸的抗辐射作用机制。方法 6~8周ICR小鼠96只,随机数表法分为正常对照组、照射模型组、阳性药（408片）治疗组和阿魏酸10、30、90 mg ·kg^-1·d^-1治疗组,每组16只。小鼠初次给药后24 h接受3.5 Gy ⁶⁰Co γ单次全身照射,之后连续7 d给药。其中,每组10只用于观察照射前2 d及照射后3、7、10、15、22 d的外周血象;其余6只用于照射后7 d检测骨髓嗜多染红细胞的微核细胞率、造血祖细胞集落形成能力、以及Thbd和HMGB1蛋白的表达水平。结果 与照射模型组比较,90 mg ·kg^-1 ·d^-1的阿魏酸可有效提高小鼠3.5 Gy照射后3、10、15、22 d的外周血白细胞数（t=2.267、2.399、1.945、2.828,P<0.05）,显著降低骨髓嗜多染红细胞微核细胞率（t=4.013,P<0.05）,明显提高造血祖细胞红细胞集落生成单位（CFU-E）、红细胞爆裂型集落生成单位（BFU-E）和粒-单细胞集落生成单位（CFU-GM）的集落形成能力（t=2.366、2.953、3.115,P<0.05）,并提高骨髓细胞中Thbd和核内HMGB1蛋白表达水平（t=17.75、23.39,P<0.01）。结论 阿魏酸可通过调节Thbd和HMGB1蛋白表达,促进小鼠骨髓造血功能辐射损伤修复,加速外周血象恢复。     

维生素D对不同剂量X射线照射小鼠免疫功能的保护作用

目的 观察维生素D对不同剂量X射线照射小鼠免疫功能的影响。方法 将小鼠采用随机数字表法分为5组:健康对照组、2 Gy和5 Gy照射组、2 Gy+药物(维生素D)组和5 Gy+药物(维生素D)组。给药组小鼠在不同剂量X射线照射后,连续7 d腹腔注射6 IU维生素D[1,25(OH)₂D₃]/g体重,于给药后第8天,5组小鼠均处死。测定小鼠体重、胸腺和脾脏指数,ConA诱导的脾脏T淋巴细胞增殖能力,ELISA法检测脾细胞IL-2的分泌量。结果 与健康对照组相比,2和5 Gy照射组小鼠脾脏T淋巴细胞增殖能力、脾细胞IL-2的分泌量均显著降低(F=36.20、7.13,P<0.05);与2 Gy照射组相比,2 Gy+药物组小鼠胸腺指数、脾脏指数、脾脏T淋巴细胞增殖能力均显著增高(t=-2.54、-2.24、-2.84,P<0.05);与5 Gy照射组相比,5 Gy+药物组小鼠的胸腺指数、脾细胞IL-2的分泌量显著增高(t=-5.02、-2.64,P<0.05)。结论 维生素D能够改善受照小鼠的免疫功能,但随照射剂量增大,改善作用减弱。     

纳米氧化铈对γ射线诱导小鼠免疫系统损伤的影响

目的 研究纳米氧化铈在γ射线诱导小鼠免疫系统损伤中的影响。方法 BALB/c小鼠120只按随机号法分为健康对照、照射、阳性药物与纳米氧化铈100、300和900 mg/kg组,共6组,每组20只。小鼠经3.5 Gy ⁶⁰Co γ射线一次性全身照射,照射前两周至照射后处死前连续口服灌胃给药。流式细胞术检测胸腺淋巴细胞凋亡率、外周血白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）阳性率,二苯基四氮唑溴盐（MTT）法检测自然杀伤细胞（NK）活性。结果 与照射组相比,受照后3 d,纳米氧化铈各剂量组的细胞死亡率均降低,纳米氧化铈300 mg/kg组差异有统计学意义（F=4.50,P<0.05）,纳米氧化铈300 mg/kg组的IFN-γ表达显著增多（t=2.26,P<0.05）;受照后8 d,纳米氧化铈900 mg/kg组的细胞死亡率明显降低（F=4.07,P<0.05）,纳米氧化铈100 mg/kg组细胞早期凋亡率显著下降（F=3.47,P<0.05）,纳米氧化铈300 mg/kg组IFN-γ表达显著增多（t=2.47,P<0.05）,各剂量组IL-2表达均呈降低趋势,但差异无统计学意义（P>0.05）;纳米氧化铈各剂量组和阳性药物组的NK细胞活性均显著升高,差异有统计学意义（t=3.40、5.40、3.40、5.20,P<0.05）。结论 纳米氧化铈在一定程度上降低受照小鼠胸腺淋巴细胞凋亡率和死亡率,促进IFN-γ表达量增高,增强NK细胞活性,可提高机体免疫力,对辐射损伤有一定防护作用。     

亚低温对急性辐射损伤小鼠的保护作用及其机制研究

目的 探讨亚低温对急性辐射损伤小鼠的辐射防护作用及其机制.方法 105只雄性BALB/c小鼠按随机数字表法分为3组,即单纯照射组、亚低温干预组和健康对照组,每组35只.单纯照射组和亚低温干预组小鼠均接受6 Gy ⁶⁰Co γ射线单次全身照射,亚低温干预组在照后即刻进行亚低温干预并维持6 h,观察照后1、3、7、14、21和28 d小鼠外周血白细胞数、骨髓有核细胞计数,骨髓病理组织学变化,照后6和24 h, 检测小鼠血清中丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH-px)和超氧化物歧化酶(SOD)活力,采用流式细胞术检测骨髓细胞周期.结果 与单纯照射组比较,亚低温干预组小鼠外周血白细胞数和骨髓有核细胞数在照后早期较高(t=-2.63、-3.41,P<0.05),且提前1周恢复;同时,小鼠骨髓细胞衰减较晚,恢复较早.受照后6 h与其他组相比,亚低温干预组小鼠血清MDA含量较低(t=3.83,P<0.05),SOD活力较高(t=-6.57,P<0.05),骨髓S期细胞比例较高(t=-4.67,P<0.05),G₂期细胞较低(t=3.04, P<0.05);受照后24 h与其他组相比,亚低温干预组小鼠血清GSH-px活力较高(t=-3.13, P <0.05),骨髓S期细胞比例较单纯照射组降低(t=7.19,P<0.05).结论 照后亚低温干预对急性辐射损伤有较好的保护作用,机制与亚低温可增强机体抗氧化力、抑制骨髓细胞周期进程有关.     

香兰素衍生物VND3207对小鼠骨髓细胞遗传损伤的防护效应研究

目的 研究香兰素衍生物4-羟基-3,5-二甲氧基苯甲醛(VND3207)对γ射线整体照射小鼠骨髓细胞遗传损伤的防护作用。方法 BALB/c小鼠按10、50和100 mg/kg不同剂量灌胃给药,1次/d,连续5 d,最后一次给药后2 h, 2 Gy ⁶⁰Co γ射线照射,照射后48 h观察小鼠骨髓嗜多染红细胞微核、染色体畸变和骨髓有丝分裂指数的改变。结果 不同剂量(10、50和100mg/kg)的VND3207均能有效地降低小鼠骨髓嗜多染红细胞微核率(t=2.40～4.26,P<0.05)和染色体畸变率(t=2.36～3.52,P<0.05),同时提高骨髓有丝分裂指数。药物保护效果与给药剂量呈依赖关系,其中100 mg/kg剂量组的微核率和染色体畸变率与单纯照射组相比,分别降低了65%和50%。结论 VND3207对⁶⁰Co γ射线诱发的小鼠骨髓辐射损伤有良好的保护作用。     

电离辐射对皮肤细胞铁死亡的影响及其抑制剂Ferrostatin-1的防护作用研究

目的 探讨电离辐射对皮肤细胞铁死亡的影响以及铁死亡抑制剂Ferrostatin-1（Fer-1）对受照射皮肤细胞的保护作用及机制。方法 为检测Fer-1对人永生化角质形成细胞（HaCaT）辐照后的影响,按照射与给药方式分为对照组、Fer-1组、单纯照射组、照射+Fer-1组。采用CCK-8法和乳酸脱氢酶（LDH）释放检测X射线照射以及Fer-1处理对HaCaT细胞存活和细胞死亡的影响。采用流式细胞术检测X射线照射以及Fer-1处理后对HaCaT细胞脂质过氧化水平的影响。利用结晶紫染色法检测X射线照射以及Fer-1处理对HaCaT细胞克隆形成能力的影响。Western blot检测X射线照射以及Fer-1处理对铁死亡相关蛋白ACSL4和GPX4表达的影响。结果 单纯照射组经不同剂量的X射线照射后细胞存活率明显降低（t=5.63、8.74,P<0.05）,LDH的释放明显增加（t=3.98、5.08、9.27,P<0.05）,Fer-1能够提高受照射皮肤细胞存活率（t=5.79,P<0.05）,降低LDH的释放量（t=12.36、11.96、18.13、9.96,P<0.05）。单纯照射组经10 Gy的X射线照射后细胞的脂质过氧化水平明显升高（t=9.59,P<0.05）,克隆存活能力明显减弱（t=4.26,P<0.05）,而Fer-1能够降低X射线照射引起的脂质过氧化水平的升高（t=6.48、17.04,P<0.05）,增加受照射皮肤细胞的克隆存活能力（t=3.96,P<0.05）。10 Gy的X射线照射会导致ACSL4表达水平的升高和GPX4的表达水平的降低,而Fer-1的治疗能促进ACSL4和GPX4的表达水平恢复正常（t=5.23、7.16、4.78、8.29、6.43,P<0.05）。结论 铁死亡抑制剂Fer-1在细胞水平上能够通过抑制电离辐射后铁死亡的发生而保护皮肤细胞,为放射性皮肤损伤的防护提供了一种新的策略。     

2 Gy γ射线照射对小鼠调节性T细胞和Th17细胞及其免疫平衡的影响

目的 观察2 Gy γ射线照射对小鼠Treg/Th17免疫平衡的影响。方法 50只C57BL/6雄性小鼠随机数字表法分为对照组和照射组,照射组小鼠接受2 Gy γ射线一次性全身照射(剂量率为164.94 Gy/min),对照组行假照射。于照射后1、3、7、14和28 d检测外周血象的变化;流式细胞仪分析外周血、胸腺及脾脏调节性T细胞(Treg细胞)和脾脏Th17细胞数量的改变。结果 受照后小鼠外周血白细胞总数和淋巴细胞数降低(t=8.89～33.54, P<0.05)。小鼠外周血Treg略有升高;胸腺Treg在照后1、3 d显著高于对照组(t=-6.45和-10.59, P<0.05),至28 d明显低于对照组(t=5.34, P<0.05);脾脏Treg在照后1～14 d显著高于对照组(t=-6.82～-3.89, P<0.05)。脾脏Th17细胞于照后1 d出现显著增高,3 d达到最大值(t=-2.42, P<0.05),较脾脏内Treg增长更为明显。Treg/Th17比值在照后1～14 d降低,差异有统计学意义(t=4.02～8.04, P<0.05),导致Treg/Th17平衡模式向Th17方向明显偏移。结论 Treg/Th17免疫平衡失调在辐射所致免疫功能损伤中可能扮演重要角色。     

Recovery from sublethal damage and potentially lethal damage

Purpose

In order to clarify the biological response of tumor cells to proton beam irradiation, sublethal damage recovery (SLDR) and potentially lethal damage recovery (PLDR) induced after proton beam irradiation at the center of a 10?cm spread-out Bragg peak (SOBP) were compared with those seen after X?ray irradiation.

Methods

Cell survival was determined by a colony assay using EMT6 and human salivary gland tumor (HSG) cells. First, two doses of 4?Gy/GyE (Gray equivalents, GyE) were given at an interfraction interval of 0–6?h. Second, five fractions of 1.6?Gy/GyE were administered at interfraction intervals of 0–5?min. Third, a delayed-plating assay involving cells in plateau-phase cultures was conducted. The cells were plated in plastic dishes immediately or 2–24?h after being irradiated with 8?Gy/GyE of X?rays or proton beams. Furthermore, we investigated the degree of protection from the effects of X?rays or proton beams afforded by the radical scavenger dimethyl sulfoxide to estimate the contribution of the indirect effect of radiation.

Results

In both the first and second experiments, SLDR was more suppressed after proton beam irradiation than after X?ray irradiation. In the third experiment, there was no difference in PLDR between the proton beam and X?ray irradiation conditions. The degree of protection tended to be higher after X?ray irradiation than after proton beam irradiation.

Conclusion

Compared with that seen after X?ray irradiation, SLDR might take place to a lesser extent after proton beam irradiation at the center of a 10?cm SOBP, while the extent of PLDR does not differ significantly between these two conditions.

     

Temozolomide-induced liver damage

Background

Temozolomide (TMZ) is an alkylating agent used in chemoradiotherapy and adjuvant chemotherapy regimens for treatment of newly diagnosed or recurrent glioblastoma. In Germany alone, 900,000 daily doses of the drug are prescribed each year. Therefore, all severe side effects of TMZ, even those rarely observed, are relevant to radiotherapists.

Materials and methods

We report a case of severe drug-induced toxic hepatitis that developed during chemoradiotherapy with TMZ in a patient with glioblastoma multiforme.

Results

Transaminase elevation was observed after 5 weeks of TMZ treatment, followed by severe jaundice symptoms which only subsided 2 months later. These findings were consistent with diagnosis of the mixed hepatic/cholestatic type of drug-induced toxic hepatitis. Due to the early termination of treatment, no life-threatening complications occurred in our patient. However, rare reports of encephalopathy and fatality as complications of TMZ therapy can be found in the literature.

Conclusion

When using TMZ for treatment of glioblastoma, monitoring of liver enzyme levels should be performed twice weekly to prevent fatal toxic hepatitis. In the case of any drug-induced hepatitis, TMZ must be discontinued immediately.

Zusammenfassung

Temozolomid (TMZ) ist als Alkylanz Bestandteil der Radiochemotherapie und der adjuvanten Chemotherapie zur Behandlung neu diagnostizierter und rezidivierender Glioblastome. Allein in Deutschland werden jährlich 90.000 Tagesdosen verordnet. Daher sind auch seltene gravierende Nebenwirkungen für Strahlentherapeuten relevant.

Material und Methoden

Wir berichten von einer Patientin mit Glioblastoma multiforme, die während der Radiochemotherapie mit TMZ eine medikamentös-toxische Hepatitis entwickelte.

Ergebnisse

In der 5. Behandlungswoche kam es zum Anstieg der Transaminasen und nachfolgend zu einem Ikterus, der sich erst nach 2 Monaten zurückbildete, was dem Bild der hepatitisch-cholestatischen Mischform der medikamentös-toxischen Hepatitis entspricht. Wesentliche Komplikationen ergaben sich nicht. In der Literatur sind vereinzelt enzephalopathische und fatale Verläufe beschrieben.

Schlussfolgerung

Bei der Behandlung mit TMZ ist eine 2-mal wöchentliche Kontrolle der Leberenzyme und Cholestaseparameter erforderlich, um fatale Verläufe einer toxischen Hepatitis zu vermeiden.     

A case of generalized hypoxic brain damage following traumatic brain damage

In forensic autopsy cases, transient brain hypoxia can be induced by cardiac arrest, hypovolemic shock, and other conditions with severe circulatory failure. Although cortical laminar necrosis in watershed areas between territories of the major cerebral arteries is occasionally seen, cases with global hypoxic damage to the brain is rare, because patients with irreversible severe brain damage rarely survive for more than a few days. In this report we describe autopsy results for an injury victim who survived unconscious for approximately 4 weeks after admission. Macroscopic thinning of the gray matter and uniformly cheesecake-like cloudy changes in white matter were observed. Microscopically, cortical laminar necrosis was observed in all lobes of the cerebrum, and massive gliosis was diffused throughout the white matter. We speculate that traumatic brain damage, continuous hypoxemia, and many other factors induced these characteristic pathological changes during the long time interval from brain damage to death.     

正确应用损害控制性剖腹术

损害控制策略是提高腹部创伤救治成功率的关键环节之一,有助于改善面临低体温、酸中毒和凝血功能障碍的危重患者的预后。首先是通过短时间的剖腹手术紧急控制出血和污染,然后在ICU继续积极复苏,在致命性三联征纠正后再进行确定性手术处理。     

Apophyseal damage in adolescent athlete

The increasing demands on the adolescent athlete in high performance sports puts high biomechanical stress on the growing structures of the active and passive locomotor system. The "growing factor" itself increases stretching forces on tendon insertions, which are often overloaded when a physical demanding sport is performed additionally. The apophysis is an ossification nucleus near the tendon insertion, which appears before the growing age resumes and these apophysis finally fuses with the adjacent bone. The tensile forces from vigorous sports activity leads to a chronic or acute avulsion of the ossifying tendon insertion. The radiological appearance of this apophyseal damage with ossification and osteolytic processes is sometimes difficult with respect to differential diagnoses. Apophyseal impairment is associated with pain, tenderness to palpation and decreased muscle function. If it is not diagnosed and treated properly it can lead to end of career in many adolescent athletes.     

Fluorescence of radiation-induced tissue damage

Purpose: The aim of this study was evaluating changes in the photosensitizer fluorescence in vivo in the radiation-induced damage area in comparison of intact areas with a simultaneous assessment of changes both in blood parameters and in histological data.

Materials and methods: The study was conducted in white outbred SHK mice (n?=?21). Their right hindlimbs were irradiated with a dose of 25?Gy after the intraperitoneal injections of photosensitizer ‘Photosens’. Fluorescence intensity was traced in vivo by a laser diagnostic system for seven weeks. Simultaneously, histological examination of the damaged areas and blood tests were performed.

Results: An increased intensity of the laser-induced fluorescence of the photosensitizer ‘Photosens’ in the damaged areas, compared to the intact symmetrical ones was observed. Laboratory blood tests and histological examination showed changes that may indicate the occurrence of inflammation.

Conclusion: Enhanced intensity of the exogenous fluorescence of the photosensitizer in the radiation-induced inflammation of noncancerous tissues was observed. The obtained results may potentially affect an interpretation of the results of intraoperative tumors navigation that have been previously irradiated and can be used for selection of an individualized dose fractionation algorithm in radiology.     

对"损伤控制性外科"的理解

"损伤控制性外科(damage control surgery)"理念从20世纪90年代开始[1]逐渐在文献中出现,应用面也越来越广.凡以手术作为治疗手段之一的专科都引入了这一理念,且将范围由创伤处理扩展至非创伤疾患的处理[2],可见这一理念有着很高的理论价值,也有着十分有效的实用价值.     

Exercise-induced muscle damage and adaptation

Novel, unaccustomed exercise has been shown to result in temporary, repairable skeletal muscle damage. After exhaustive endurance exercise, muscle damage can be produced by metabolic disturbances associated with ischaemia. Extensive disruption of muscle fibres also occurs after relatively short term eccentric exercise where high mechanical forces are generated. Biopsies taken after repetitive eccentric muscle actions have revealed broadening, streaming and, at times, total disruption of Z-discs. Muscles that develop active tension eccentrically also become sore, lose inherent force-producing capability, and show a marked release of muscle proteins into the circulation. Because creatine kinase (CK) is found almost exclusively in muscle tissue, it is the most common plasma marker of muscle damage. Despite the universal use of CK as a marker, several factors with regard to efflux and clearance remain unexplained. Also the large intersubject variability in response to exercise complicates its interpretation. Damage progresses in the postexercise period before tissues are repaired. However, the mechanism to explain exercise-induced muscle damage and repair is not well defined. Among the factors that may influence the damage and repair processes are calcium, lysosomes, connective tissue, free radicals, energy sources, and cytoskeletal and myofibrillar proteins. Physical conditioning results in an adaptation such that all indicators of damage are reduced following repeated bouts of exercise. Recently, investigators have suggested that the prophylactic effect of training may be due to performance of a single initial exercise bout. Following a second bout of exercise performed 1 to 6 weeks after the first bout, there is a reduction in morphological alterations and performance decrements and a profoundly reduced elevation in plasma CK levels. Several hypotheses have been presented to explain the repeated bout or rapid training effect. Stress-susceptible fibres may be eliminated or susceptible areas within a fibre may undergo necrosis and then regenerate. These regenerated fibres, along with adaptations in the connective tissue, may provide greater resistance to further insult.