低剂量辐射联合环磷酰胺对肿瘤细胞凋亡、细胞周期以及骨髓增殖的影响

目的　探讨低剂量辐射联合环磷酰胺对小鼠移植肿瘤细胞的凋亡、细胞周期以及骨髓增殖的影响。方法　昆明种雄性小鼠随机分为空白对照组、荷瘤对照组 (假照组 )、低剂量照射组(LDR组 )、CTX化疗组 (CTX组 )和低剂量照射联合化疗组 (LDR CTX组 ) ,左后肢腹股沟皮下接种S180肉瘤细胞 ,接种后第 5 ,8天γ射线全身照射 75mGy ,照射后 36h采用环磷酰胺 (CTX)化疗 ,测量肿瘤大小变化 ,并取肿瘤组织经流式细胞仪分析细胞凋亡、细胞周期 ,取冲洗骨髓组织分析骨髓增殖情况。结果　与假照组相比 ,各处理组肿瘤生长缓慢。LDR组肿瘤细胞凋亡增加 ,CTX组、LDR CTX组G1 期细胞比例明显增加 ,S期细胞比例明显减少 (P <0 0 5 )。与空白对照组相比 ,假照组、低剂量照射组骨髓细胞浓度未见明显变化 ,化疗组 (CTX组、LDR CTX组 )明显减少 (P <0 0 0 1) ;增殖指数 (PI)CTX组、LDR CTX组明显增加 ,LDR CTX组比CTX组高。结论　低剂量辐射联合环磷酰胺可使机体肿瘤细胞G1 期阻滞加剧 ,对肿瘤增殖细胞杀伤作用增强 ,明显提高机体抗肿瘤的作用 ,同时保护机体的骨髓造血机能 ,具有辅助肿瘤化疗的实际临床意义。     

角质细胞生长因子对受照小鼠的遗传保护作用

目的 应用单细胞凝胶电泳（SCGE）和微核实验探讨角质细胞生长因子（KGF）对受照小鼠的遗传保护作用。 方法 将40只C57BL/6J小鼠随机分为空白对照组、照射对照组、KGF低（1 mg/kg）、中（2 mg/kg）、高（4 mg/kg）剂量组5组。KGF的3个给药组于照射前给药,连续3 d分别给予腹腔注射1、2、4 mg/kg的KGF,1次/d。照射对照组腹腔注射磷酸盐缓冲液。给药后,空白对照组给予假照射,其他4组给予7.2 Gy 137Cs γ射线全身一次性照射。应用SCGE和微核实验检测5组小鼠的DNA损伤情况。 结果 与照射对照组相比,KGF低剂量组小鼠的DNA微核率显著降低,中、高剂量组的彗星尾矩、Olive尾矩和微核率均显著降低。 结论 KGF对受照小鼠有显著的遗传保护作用。     

DHEA对放、化疗损伤造血功能保护作用的实验研究

目的：研究17aα-D-高炔雌二醇-3-乙酯（DHEA）对137Csγ射线和环磷酰胺（CTX）所致小鼠造血及免疫功能损伤的保护作用。方法分别用8．0 Gy 137Csγ射线和CTX建立C57BL/6小鼠动物模型,观察DHEA低、中、高3个剂量对两个模型小鼠的造血干细胞脾结节形成细胞（CFU-S）数、外周血WBC、骨髓有核细胞数、脾脏指数的影响。结果 DHEA各组对小鼠137Csγ射线照射所致的外周血WBC、CFU-S数、骨髓有核细胞数的降低具有保护作用,并增大了脾脏指数。DHEA各组对环磷酰胺引起的小鼠WBC、CFU-S数、骨髓有核细胞数降低有抑制作用。结论 DHEA能减轻辐射和环磷酰胺对小鼠造血系统的损伤。     

西咪替丁对急性照射小鼠存活率及造血系统改变的影响

目的 观察西咪替丁对急性照射小鼠存活率及造血系统改变的影响.方法 采用137Cs γ射线全身照射小鼠,两次实验的照射剂量分别为6.0Gy和8.0Gy,剂量率均为1.01Gy/min.每次实验取健康雄性C57BL/6小鼠60只,按体重随机分为空白对照组?模型对照组?阳性药组(523)及33.3?100?300mg/kg西咪替丁组,每组10只.西咪替丁各剂量组于照射前6d灌胃给药,每天1次,照射后5h给药1次;阳性药组于照射前1d灌胃给药1次,照射后5h给药1次.检测8.0Gy照射后30d小鼠存活率,以及6.0Gy照射后30d小鼠外周血象?骨髓DNA含量和骨髓嗜多染红细胞微核率.结果8.0Gy照射后,模型对照组小鼠于第21天全部死亡,西咪替丁低?中?高剂量组30d存活率分别为50%?20%和30%;6.0Gy照射后第30天,与空白对照组比较,各照射组小鼠外周血白细胞明显降低(P<0.01),骨髓嗜多染红细胞微核率明显升高(P<0.05),骨髓DNA含量明显降低(P<0.05);与模型对照组比较,西咪替丁高剂量组外周血白细胞明显升高(P<0.01),西咪替丁各剂量组骨髓DNA含量明显升高(P<0.01,P<0.05),而骨髓嗜多染红细胞微核率明显降低(P<0.01,P<0.05)并趋于正常.结论 西咪替丁能提高急性照射小鼠30d存活率,且对其造血系统有较好的保护作用.     

阿多拉扶正霖对钴辐射诱发小鼠骨髓嗜多染红细胞微核的影响

目的 观察小鼠受钴(~(60)Co)γ射线照射前后,分别口服阿多拉扶正霖(ADL)冲剂,对诱发骨髓嗜多染红细胞微核的影响。方法 将昆明种小鼠随机分成对照组、~(60)Coγ射线照射A组、ADL预防组、~(60)Coγ射线照射B组和ADL治疗组,每组16只,雌雄各半。以ADL 6g/kg体重每天灌胃1次,连续8天。ADL预防组与A组于第9天照射,第10天处死;ADL治疗组与B组于第1天照射,第10天处死。~(60)Coγ射线照射剂量为2.0Gy,全身1次照射。小鼠处死后制作骨髓片,常规染色与计数。结果 无论是ADL预防组还是治疗组,微核率均比相应的~(60)Coγ射线照射组低,有非常显著性差异(P<0.01),两个~(60)Coγ射线照射组之间和两个ADL组之间,差异均不显著(P>0.05)。结论 ADL可在短期内恢复由~(60)Coγ射线造成的小鼠骨髓嗜多染红细胞微核率的上升,提示ADL有抗辐射损伤的作用。     

流式细胞仪检测γ射线照射后小鼠骨髓嗜多染红细胞微核率的研究

目的应用流式细胞仪检测γ射线照射后小鼠骨髓嗜多染红细胞微核率,建立本实验室快速检测微核率的自动化实验方法。方法将48只雄性BALB/c小鼠随机分为4个照射剂量组,分别给予60Coγ射线一次性全身照射00、.51、和2Gy,于照射后24、48h取骨髓标本,每个剂量和每个时间点均为6只小鼠。采用流式细胞术检测受照小鼠骨髓嗜多染红细胞微核率,以传统显微镜检微核的方法作为对照。结果流式细胞术及显微镜检方法检测的小鼠骨髓嗜多染红细胞微核率均呈良好的剂量依赖性及时间依赖性,并且两种方法的检测结果呈显著正相关(r=0.987,P<0.01)。流式细胞仪检测速度为人工阅片的40倍以上,且能够避免人工镜检人员阅片的主观性,检测结果更为客观。结论采用流式细胞仪检测小鼠骨髓红细胞微核较传统的人工显微镜检测,更加简便、易行、快速,检测结果准确、可信、客观,适用于大规模核辐射伤员的高通量快速生物剂量诊断。     

低水平电离辐射的抗肿瘤转移作用及临床应用前景初探

经低剂量Ｘ射线照射后，荷瘤小鼠肺转移结节明显减少；与低剂量环磷酰胺（ＣＹ）合用后也可使荷瘤小鼠的肺转移结节减少。对小鼠体内免疫功能检测研究表明：小鼠脾脏细胞（ＮＫ）活性，ＬＡＫ活性以及对白细胞介素－２（ＩＬ－２）的反应性均显著增强；当与低剂量ＣＹ合用时，上述抗肿瘤免疫功能也提高，可见低水平照射能通过有效地激活体内抗肿瘤免疫功能而具有显著的抗转移效果，它为探讨低水平电离辐射临床应用可能性提供了较为可靠的实验依据。     

白藜芦醇促进γ射线照射小鼠造血系统损伤修复的作用

目的观察白藜芦醇对60Coγ射线照射小鼠造血系统损伤修复的影响。方法 ICR小鼠随机分成5组,即正常对照组、照射对照组以及白藜芦醇50、100、200 mg.kg-1照射组,照射前3 d灌服给药,每天1次。除正常对照组外,所有小鼠60Co射线全身5.5 Gy辐照1次,照射后第7天小鼠取骨髓细胞和脾脏,对骨髓单个核细胞和脾集落形成单位进行计数,测定骨髓细胞DNA含量和细胞周期。结果与正常对照组比较,照射对照组小鼠骨髓单个核细胞数和骨髓细胞DNA含量显著降低（P〈0.05）,脾集落形成单位数和S和G2/M期细胞百分率显著增多（P〈0.05）;与照射对照组比较,白藜芦醇100、200 mg.kg-1照射组小鼠照射骨髓单个核细胞数、骨髓细胞DNA含量、脾集落形成单位数和S和G2/M期细胞百分率显著增多（P〈0.05）,白藜芦醇50 mg.kg-1照射组有增多趋势。结论白藜芦醇可以促进60Coγ射线照射小鼠造血系统损伤的恢复,防护效果与给药剂量相关。     

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。     

中子和γ射线照射对小鼠骨髓造血细胞死亡方式的探讨

目的探讨中子和γ射线照射后小鼠骨髓造血细胞的死亡方式及其意义。方法采用不同剂量中子和^60Coγ射线全身照射350只BALB／c小鼠，通过光镜、电镜、流式细胞术、原位末端标记和DNA凝胶电泳等观察造血细胞凋亡与坏死情况。结果中子照射后小鼠骨髓中坏死和凋亡的造血细胞均明显增多，5．5Gy组以坏死为主；而γ射线照射后则以凋亡为主，且呈剂量相关性。凋亡的细胞表现为核染色质浓缩、边移，呈半月型、环状或不规则状，凋亡小体形成，电泳下见DNA梯状图谱。坏死的细胞表现为核肿胀、溶解，线粒体膜、核膜等膜性结构破坏。结论2．5～5．5Gy中子及5．5～12Gy γ射线照射可使骨髓造血细胞死亡方式不同：中子照射见凋亡与坏死并存，5．5Gy组以坏死为主；而γ射线照射则以凋亡为主。     

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.

     

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.     

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.     

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.     

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。     

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.