不同剂量戊酸雌二醇治疗宫腔粘连的临床效果

目的:观察不同剂量戊酸雌二醇治疗宫腔镜术后宫腔粘连的临床效果。方法:选取2013年6月-2015年3月在我院接受宫腔镜手术且术后出现宫腔粘连的患者80例,根据用药剂量不同,将所选患者分为小剂量组和大剂量组,每组40例。小剂量组患者给予戊酸雌二醇3 mg,大剂量组患者给予戊酸雌二醇9 mg治疗。观察并比较两组患者的临床疗效、月经恢复情况及不良反应发生率。结果:大剂量戊酸雌二醇治疗宫腔粘连的临床疗效显著优于小剂量组,差异具有统计学意义(P0.05)。大剂量戊酸雌二醇治疗宫腔粘连,患者术后的月经恢复率高于小剂量组,差异具有统计学意义(P0.05)。两组不良反应的发生率比较,差异无统计学意义(P0.05)。结论:9 mg戊酸雌二醇应用于宫腔镜术后具有较好的效果,能显著降低宫腔粘连发生率。     

Genotoxicity and repair capability of Mus musculus DNA following the oral exposure to Tramadol

Tramadol is an analgesic and psychoactive drug that acts primarily upon the central nervous system where it alters brain function, resulting in temporary changes in perception, mood, consciousness and behavior. The aim of present study was to analyze the genotoxicity and repair capability of DNA after Tramadol exposure in albino mice (Mus musculus). For this purpose, forty mice were divided equally into four groups as; a control group (without drug) and three treatment groups that were treated with three doses of Tramadol as minimum dose group, Intermediate dose group and maximum dose group, corresponding to 25 mg/kg, 50 mg/kg and 75 mg/kg of body weight respectively. The dose was given orally for 15 days. After 15 days peripheral blood was drawn from half mice of each group and subjected to comet assay. While the remaining half mice were given a recovery period of 15 days and same procedure was used for blood collection and comet assay. Significant difference in various comet parameters was observed among control and exposed groups. Maximum damage was observed at highest concentration 75 mg/kg of Tramadol and minimum damage was observed at dose 25 mg/kg of Tramadol, while results of repaired mice group showed that repair capability of Tramadol was minor and recovery of Tramadol required a lot of time. It can be concluded that Tramadol cause genotoxicity that is dose dependent and has low repair capability.     

Dosimetric characteristics of the INTRABEAM ® system with spherical applicators in the presence of air gaps and tissue heterogeneities

The main aim of this study was to investigate the dosimetric characteristics of the INTRABEAM ® system in the presence of air gaps between the surface of applicators (APs) and tumor bed. Additionally, the effect of tissue heterogeneities was another focus. Investigating the dosimetric characteristics of the INTRABEAM® system is essential to deliver the required dose to the tumor bed correctly and reduce the delivered dose to the ribs and lung. Choosing the correct AP size and fitting it to the lumpectomy cavity is essential to remove the effect of air gaps and avoid inaccurate dose delivery. Consequently, the Geant4 toolkit was used to simulate the INTRABEAM ® system with spherical APs of various sizes. The wall effect of the ion chamber (IC) PTW 34013 used in the present study was checked. The simulations were validated in comparison with measurements, and then used to calculate any inaccuracies in dose delivery in the presence of 4- and 10-mm air gaps between the surface of the APs and the tumor bed. Also, the doses received due to tissue heterogeneities were characterized. It turned out that measurements and simulations were approximately in agreement (± 2%) for all sizes of APs. The perturbation factor introduced by the IC due to differences in graphite-coated polyethylene and air as compared to the phantom material was approximately equal to one for all AP. The greatest relative dose delivery difference was observed for an AP with a diameter of 1.5 cm, i.e., 44% and 70% in the presence of 4- and 10-mm air gaps, respectively. In contrast, the lowest relative dose delivery difference was observed for an AP with a diameter of 5 cm, i.e., 24% and 42% in the presence of 4- and 10-mm air gaps, respectively. Increasing APs size showed a decrease in relative dose delivery difference due to the presence of air gaps. In addition, the undesired dose received by the ribs turned out to be higher when a treatment site closer to the ribs was assumed. The undesired dose received by the ribs increased as the AP size increased. The lung dose turned out to be decreased due to the shielding effect of the ribs, small lung density, and long separation distance from the AP surface.     

小檗碱对2型糖尿病ICR小鼠模型的治疗作用

目的比较小檗碱及小檗碱与添加剂对2型糖尿病ICR小鼠模型的降糖、降脂效果。方法100只三周龄雄性ICR小鼠随机分为正常组、模型组、小檗碱组、小檗碱加低剂量添加剂组、小檗碱加高剂量添加剂组及二甲双胍组,以高糖高脂加尿链佐菌素诱导小鼠2型糖尿病模型,并分别以小檗碱、小檗碱加低剂量添加剂、小檗碱加高剂量每天灌胃干预治疗6周。检测血糖、血清血脂、肾功指标的变化情况;给药前后做糖耐量胰岛素耐量实验。每周量小鼠体重,动态观察小鼠体重变化。代谢笼中测量小鼠饮食水量变化。结果模型组血糖较普食组显著上升（P〈0.01）,且维持较好;血脂指标CHO、HDL-c、LDL-c均较普食组升高（P〈0.05）;其他各检测生化指标差异不显著。小檗碱组空腹血糖较模型组总体下降趋势明显且维持较好（P〈0.01）;血脂较模型组有降低;糖耐量胰岛素耐量较模型组有改善。二甲双胍组血糖较模型组有下降趋势,血脂较模型组无显著差别。小檗碱加低剂量添加剂组较模型组血糖血脂无显著差别。小檗碱加高剂量添加剂组血糖较模型有下降趋势,血脂较模型组有下降趋势,其他各项生化指标均无差别。结论小檗碱降糖效果优于二甲双胍,小檗碱加低剂量添加剂,小檗碱加高添加剂。     

烹调油烟挥发性有机物对人胚肺成纤维细胞的氧化应激效应研究

目的：探讨烹调油烟挥发性有机物对人胚肺成纤维细胞（HELF）的氧化应激效应。方法：用活性炭采集烹调油烟挥发性有机物（COF VOCs）,通过MTT实验确定COF VOCs暴露对HELF细胞的半数抑制浓度（IC50）;取对数生长期HELF细胞,使其暴露于剂量分别为20、4、0．8μg／mL的COF VOCs,分别于12、24、48h后进行活性氧（ROS）分析、丙二醛（MDA）检测和Comet试验。结果：COF VOCs刺激HELF细胞12、24、48h的IC50分别为104．9、111．9和127．2μg／mL;流式细胞术检测发现细胞胞质和线粒体内ROS平均荧光强度随COF VOCs剂量增加而增高;剂量组MDA水平与阴性对照组相比无统计学差异;剂量组DNA断裂水平与阴性对照组相比,差异有统计学意义;各剂量组引起的细胞ROS、MDA升高和DNA断裂在不同暴露时间之间差别均无统计学意义。结论：在实验剂量水平和暴露时间内,COF VOCs暴露可引起HELF细胞胞质和线粒体内ROS升高、DNA断裂,但并不能引起脂质过氧化损伤。     

An estimate of the magnitude of random errors in the DS86 dosimetry from data on chromosome aberrations and severe epilation

An analysis of the proportion of cells with chromosome aberrations in cultured blood lymphocytes from A-bomb survivors in Hiroshima and Nagasaki reveals that the dose-response relationship using DS86 assigned dose is significantly steeper in the subsample of individuals who reported severe epilation after the bombings than in those who did not report severe epilation. This effect is due either to random errors in the DS86 dose assignments or to individual differences in sensitivity to radiation, or to both. In this paper, working within a class of dosimetry error models, we estimate the magnitude of random dosimetry errors which would be required to account for all of the difference in the observed dose response between people who did and did not report severe epilation under the assumption that random dosimetry error is the only cause of the effect. We conclude that random dosimetry errors in the range 45 to 50% of true dose are necessary to explain completely the difference in dose response between the two epilation groups. We discuss evidence that the contribution of individual differences in radiation sensitivity to the observed epilation effect is likely to be small, so that random dosimetry errors may be the major cause of this effect.     

Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.     

Chiral pharmacokinetics of rac-flurbiprofen and pharmacodynamics of anabolic bone response in the normal rat

The route of administration of the NSAID, flurbiprofen (sq vs. po) resulted in positive and negative results respectively with regard to enhanced cancellous and cortical bone accumulation in the immature rat. This pharmacokinetic study was an effort to understand the pharmacodynamic difference between the two routes of administration observed when the same dose range of drug, given as single daily doses, had been employed in both studies. Conventional chiral pharmacokinetics were evaluated in young rats. A significant difference was observed in the T_max of the active (S)-enantiomer by both administration routes (sq 4 h and po 1 h). The bioavailability, as evaluated by AUCs favored the sq route as expected. The plasma concentrations over 18 h, at steady state, for one po dose group (0.5 mg/kg/day) fell well within the therapeutic window described by the 0.1 and 0.5 mg/kg sq doses which had demonstrated anabolic bone activity. Oral dosing had exhibited no significant bone activity. We conclude that the pharmacodynamic difference between routes of administration cannot be simply explained on a pahrmacokinetic basis. Consequently, experiments detailing the pharmacodynamics and pharmacokinetics of single and multiple dose administration of aryl-propionic acids in normal and osteopenic states need further pharmacologic study. © 1994 Wiley-Liss, Inc.     

A comparison of the predicted risks of developing osteosarcoma for dogs exposed to 238PuO2 based on average bone dose or endosteal cell dose.

Dose-response relationships observed in laboratory animals can be used to identify possible human risk factors and may also be used in a quantitative manner when human data are not available. This paper presents an analysis of the dose dependency of osteosarcoma incidence in beagle dogs given a single inhalation exposure to a monodisperse aerosol of 238PuO2. We were particularly interested in comparing the predicted risks that were based on average bone dose with those based on endosteal cell dose and in evaluating the advantages of using a more biologically relevant cell-specific dose in risk estimation. The endosteal cell dose was calculated using the method of Marshall et al. (Health Phys. 35, 91-101, 1978), as extended to account for exposure by inhalation. The relationship between dose and time to tumor was analyzed by the proportional hazards regression model. The probability of developing osteosarcoma was strongly dependent on dose for dogs receiving low doses, but this was not true for dogs receiving high doses. The predicted risk based on endosteal cell dose was not consistently higher or lower than the risk based on average bone dose at various times after exposure, because the relationship between these two doses was not linear with respect to time. Also, as a result of the nonlinear relationship between these two doses, the risk estimated based on endosteal cell dose would not be a fixed factor of that based on the average dose. Random errors in the measured initial lung burden had a relatively large impact on the predicted risk based on endosteal cell dose, and the difference between the estimated risk of developing osteosarcoma based on endosteal cell dose and that based on average bone dose is likely to be within the error margins of the estimated risks.     

不同剂量rhBMP-2/CPC 体内骨诱导活性的比较研究*

目的:对比不同剂量rhBMP-2与多孔CPC复合后的诱导成骨效应,探讨与多孔CPC复合后的rhBMP-2的量效关系.方法:将0.5 mg/ml、1 mg/ml、2 mg/ml、3 mg/ml 4种不同剂量的rhBMP-2与多孔CPC材料复合后,植入36只小鼠双侧股部肌肉内,分别于术后1周、2周及4周取材,通过大体观察、组织学分析、形态计量学分析、荧光双标测定,观察4组诱导成骨情况.结果:植入1周,rhBMP-2与多孔CPC材料复合表现出了较明显的剂量依赖性,含有较多rhBMP-2的材料内诱导形成的骨组织也较多,但骨组织的增加并未随着rhBMP-2剂量的增加而连续递增,2 mg组和3 mg组新生骨组织含量无明显差异(P＞0.05).植入4周,新生骨组织向材料内部生长,但此时的新生骨组织面积较2周增加不显著(P＞0.05).0.5 mg组新生骨组织含量仍处于最低水平,而其它三组之间却无明显差异(P＞0.05).结论:在0.5 mg/ml-2.0 mg/ml剂量范围,与多孔CPC复合的rhBMP-2诱导成骨量与其剂量成正比,最佳剂量为2 mg/ml.     

Mutation induction by different dose rates of gamma rays in radiation-sensitive mutants of mouse leukemia cells

Induction of cell killing and mutation to 6-thioguanine resistance was examined in a radiation-sensitive mutant strain LX830 of mouse leukemia cells following gamma irradiation at dose rates of 30 Gy/h (acute), 20 cGy/h (low dose rate), and 6.2 mGy/h (very low dose rate). LX830 cells were hypersensitive to killing by acute gamma rays. A slight but significant increase was observed in cell survival with decreasing dose rate down to 6.2 mGy/h, where the survival leveled off above certain total doses. The cells were also hypersensitive to mutation induction compared to the wild type. The mutation frequency increased linearly with increasing dose for all dose rates. No significant difference was observed in the frequency of induced mutations versus total dose at the three different dose rates so that the mutation frequency in LX830 cells at 6.2 mGy/h was not significantly different from that for moderate or acute irradiation.     

Studies of long-term continuous irradiations using daily doses ranging from 0.07 to 0.30 Gy on the B lymphoid system of the rat

The effects of a continuous exposure to cobalt gamma rays administered to rats at a daily dose of 0, 0.07, 0.12, 0.20 or 0.30 Gy for a period of up to 90 or 135 days, have been observed on their B lymphocyte populations and on their immunoglobulin serum levels. The effects increase with the daily dose and the duration of irradiation. At a daily dose of 0.07 Gy, no clear effect was observed. The depletion was almost negligible after 30 days at a daily dose of 0.12 Gy, but visible after all other doses and durations. However, a clear difference in susceptibility was observed between the marginal zone B compartment and the follicular one, the former being much more affected by the radiation than the second.     

On the differential responsiveness of males and females in the micronucleus assay

The primary question asked was whether the increased sensitivity of female mice to the induction of micronuclei by ethyl methanesulphonate, compared to males, would vanish if the doses were adjusted for any difference in the LD50 between the sexes. The second question was whether the frequency of micronuclei after 4 daily treatments would differ from 2 daily treatments. We measured the LD50 in the two sexes separately and found the female value to be lower. We also repeated the micronucleus measurements in each sex separately. At any given dose expressed in mg/kg the response in females was greater than in males. This was still true when the dose was expressed as a fraction of the LD50, but the difference was reduced. The uncertainty in the LD50 measurements was such that there may be no meaningful difference between males and females when the dose is expressed in this way. The 2-day and 4-day results differed very little for ethyl methanesulphonate, but were quite different for the positive control, dimethylbenz[a]anthracene, being higher at 4 days than at 2 days. We argue that the results of our experiments, which confirm the results of others, demonstrate the advisability of using both sexes in the assay.     

烹调油烟挥发性有机物对人胚肺二倍体成纤维细胞活性氧水平的影响

目的：研究烹调油烟挥发性有机物（COFVOCs）对人胚肺二倍体成纤维细胞（HEIF）活性氧（ROS）水平的影响。方法：用活性炭采集烹调油烟挥发性有机物,对HELF进行染毒,采用MTT试验测得半数抑制浓度（IC50）,设计剂量和暴露时间,设立添加和不添加维生素C组,以2′,7′-二氯双氢荧光素二乙酸酯（DCFH-DA）和双氢罗丹明123（DHR123）进行标记,通过流式细胞术检测细胞ROS水平。结果：COFVOCs刺激HELF12、24、48h的IC50分别是104．9、111．9和127．2μg／mL;HEIF胞质内ROS平均荧光强度随COFVOCs剂量增加而增高;线粒体内ROS24、48h暴露于0．8、4μg／mL剂量与阴性对照组相比有统计学差异;维生素C预处理后,ROS平均荧光强度较未预处理时均有所降低,100μg／mL剂量组前后差异有统计学意义。结论：COFVOCs可引起HELF内ROS水平升高,维生素C对细胞的ROS升高有一定的抑制作用。     

Resistance to reinfection in rats induced by irradiated metacercariae of Clonorchis sinensis

A study was made to observe the association between the resistance to reinfection induced by irradiated metacercariae (MC) of Clonorchis sinensis and antigen specific Th1- and Th2-type cytokine productions in rats. Rats were infected with 20 MC of C. sinensis, previously exposed to a single dose of gamma irradiation, which varied from 0 to 100 Gy. All of them, single dose of 12 Gy showed higher IgG antibody titer with lowest worm recovery. Thus, 50 MC were used to challenge infection in rats previously infected with 20 MC irradiated at 12 Gy and the highest resistance to challenge infection was observed. The results of lymphocyte proliferation with specific antigen, ES Ag were shown no difference of proliferative responses as compared with primary and challenge infection at 12 Gy irradiation dose. In the case of cytokines production were observed that interferon (IFN-gamma) and interlukin (IL-2) were significantly enhanced, while IL-4 and IL-10 was almost unchanged to make comparison between primary and secondary infection at 12 Gy irradiation dose. In conclusion, the single dose of 12 Gy could be adopted for induction of the highest resistance to challenge infection. Up-regulation of Th1 type cytokines, IFN-gamma and IL-2 may be affected to develop vaccine by irradiated MC.     

Analyzing the performance of ArcCHECK diode array detector for VMAT plan

Aim

The aim of this study is to evaluate performance of ArcCHECK diode array detector for the volumetric modulated arc therapy (VMAT) patient specific quality assurance (QA). VMAT patient specific QA results were correlated with ion chamber measurement. Dose response of the ArcCHECK detector was studied.

Background

VMAT delivery technique improves the dose distribution. It is complex in nature and requires proper QA before its clinical implementation. ArcCHECK is a novel three dimensional dosimetry system.

Materials and methods

Twelve retrospective VMAT plans were calculated on ArcCHECK phantom. Point dose and dose map were measured simultaneously with ion chamber (IC-15) and ArcCHECK diode array detector, respectively. These measurements were compared with their respective TPS calculated values.

Results

The ion chamber measurements are in good agreement with TPS calculated doses. Mean difference between them is 0.50% with standard deviation of 0.51%. Concordance correlation coefficient (CCC) obtained for ion chamber measurements is 0.9996. These results demonstrate a strong correlation between the absolute dose predicted by our TPS and the measured dose. The CCC between ArcCHECK doses and TPS predictions on the CAX was found to be 0.9978. In gamma analysis of dose map, the mean passing rate was 98.53% for 3% dose difference and 3 mm distance to agreement.

Conclusions

The VMAT patient specific QA with an ion chamber and ArcCHECK phantom are consistent with the TPS calculated dose. Statistically good agreement was observed between ArcCHECK measured and TPS calculated. Hence, it can be used for routine VMAT QA.     

Interinstar susceptibility of the fall webworm,Hyphantria cunea,to its nucleopolyhedrosis and granulosis viruses

Comparative interinstar susceptibility of the fall webworm, Hyphantria cunea, to granulosis and nucleopolyhedrosis viruses was quantitated. As the larvae matured, susceptibility to either baculovirus preparation decreased. Mortality data converted to a dose per milligram body weight basis demonstrated that this decrease in susceptibility was only in part due to the difference in weight of the larvae tested. Lethal time data showed that incubation time for either baculovirus was dependent on the age of the larvae and the dose of virus assayed. A difference in interinstar susceptibility was observed between the granulosis virus and nucleopolyhedrosis virus.     

Radiosensitivity of murine and human melanoma cells: a comparative study with different models

The in vitro radiosensitivity of one murine melanoma cell line (Cloudman S91 CCL 53.1) and three human melanoma cell strains (C8146C, C8161, and R83-4) were studied. Cells were irradiated by single dose X-rays and plated either in agar or on plastic. The survival curves were fitted by the single-hit multitarget, two-hit multitarget, and quadratic models. Multiple comparisons of the residual sum of squares suggested that the two-hit model was clearly inferior to the single-hit and quadratic models. No statistically significant difference was suggested for either the single-hit or quadratic models. Furthermore, on examination of the differences in correlations between the observed and predicted values, the residual plots (observed minus predicted over dose) failed to suggest a clear advantage of either the single-hit multitarget or the quadratic models. Either model could be recommended for analysis of in vitro radiation data.     

乙烯利对青春期大鼠睾丸组织病理及生精细胞凋亡的影响

目的:探讨乙烯利对青春期大鼠睾丸组织病理及生精细胞凋亡的影响。方法:青春期雄性25日龄SD大鼠,分别以乙烯利浓度为2000 mg/kg、1000 mg/kg、500 mg/kg和生理盐水连续灌胃14和21天,分别取睾丸固定、包埋,以HE染色、末端转移酶标记技术(TUNE法)光镜观察睾丸的组织形态学变化、检测生精细胞凋亡情况。结果:低剂量组较对照组相比生精小管萎缩,生精细胞排列紊乱;中剂量和高剂量组较低剂量组相比,生精小管更加萎缩,生精细胞排列明显紊乱;接触乙烯利14天后高剂量组生精细胞凋亡指数与低剂量、对照组相比具有显著统计学差异(P0.01);高剂量与中剂量组相比无统计学差异(P0.05);中剂量和低剂量与对照组相比有显著统计学差异(P0.01);接触乙烯利21天后各组间比较均具有显著性差异(P0.01)。结论:乙烯利可导致大鼠生精细胞凋亡增加,生精能力下降,这可能是导致青年不育的原因之一。     

Effect of spleen extracts on the immune response in chickens to Ancylostoma caninum larvae

Spleen extracts from WLH chickens nonsensitized and sensitized by repeated infections of Ancylostoma caninum larvae were injected separately into isologous recipients. Extracts from donors infected with repeated high dose (250 + 250 + 500) and low dose (125 + 125 + 250) of larvae induced a significant acquired protective immune response when compared to controls which received normal extracts. No significant difference was observed between the two experimental groups. The filariform Ancylostoma caninum larvae which can cause cutaneous larva migrans in man are found to be carried by a variety of paratenic hosts. Several studies from this lab have shown that the white leg horn (WLH) chicken successfully sustains and also responds immunologically to this parasite. The present authors have also shown that extracts of bursae of Fabricius and spleens of immunized chickens can induce immunity in syngeneic recipients. Here an attempt has been made to investigate whether repeatedly sensitized extracts of A. caninum infected chickens can cause expulsion of a challenge dose from the recipients.