Macromolecular DNA-damage in murine and human leukemic and lymphoid cells after in vitro exposure to ASTA Z 7557 (INN mafosfamide)

Summary Cyclophosphamide (CPA) is widely used against leukemic and lymphoproliferative diseases, but in vitro studies on response to this agent so far have been limited to instable derivatives with poor galenic properties. ASTA Z 7557 is a newly synthesized activated cyclophosphamide that circumvents the need for hepatic activation and has good stability. The critical cytotoxic lesions after exposure to bifunctional alkylating agents presumably are DNA interstrand crosslinks (ISC). We have, therefore, examined the formation and apparent removal of ISC after in vitro treatment with ASTA Z 7557 by use of the highly sensitive alkaline elution technique. Survival of murine L1210 cells was determined after 1 hour in vitro exposure with a D 37 value of 5.7 g/ml (from the initial shoulder part of the survival curve) and a Do value of 1.5 g/ml (from the exponential part of the curve). Previous labelling of L1210 cells by ¹²⁵IUdR simplified the alkaline elution procedure but there was some cytotoxicity of the radiochemical itself with a reduction of cloning efficiency from 77% to 61 %. The maximum of ISC was observed at 6 h after initiation of treatment with much of the damage apparently removed at 24 h. The simultaneous presence of DNA single strand breaks (SSB), however, confounds the analysis of DNA damage at 24 h and early cytolysis and unaided death of human lymphocytes often preclude the analysis of macromolecular damage at this time. Human peripheral blood cells isolated from patients with leukemic or lymphoproliferative diseases showed a remarkable heterogeneity with regard to the formation of ISC at 3 h. Thus, analysis of macromolecular damage may become an additional prognostic factor for response to CPA beyond the morphologic classification of these diseases.     

Maintain levels of nicotine but reduce other smoke constituents: A formula for “less-hazardous” cigarettes?

Twenty-two volunteers who smoked more than 20 cigarettes with "high" nicotine yields (0.8 to 1.2 mg) per day participated in an 8-week study designed to test the hypothesis that smoking cigarettes with a constant level of nicotine but reduced deliveries of tar, carbon monoxide, and hydrogen cyanide leads to a decrease in smoke absorption. All subjects smoked their usual high-nicotine brand for the first 3 weeks (P1), and the absorption of smoke constituents was determined from levels of thiocyanate and cotinine in saliva and serum, levels of carbon monoxide in expired air, and levels of carboxyhemoglobin in the blood. During the final 5 weeks (P2), the treatment group (16 subjects) switched to the "light" version of their usual brands (similar yields of nicotine but with reduced yields of tar, carbon monoxide, and hydrogen cyanide); the control group (6 subjects) smoked their usual brands for the duration of the study. Average levels of cotinine for the subjects who switched during P2 were not significantly different from those of the control group as was expected. Slight reductions were noted in average expired-air carbon monoxide levels, blood carboxyhemoglobin, and saliva thiocyanate, but these reductions were smaller than anticipated based on brand characteristics. The results suggest that the ratio of smoke constituents is different when individuals, rather than machines, smoke cigarettes. Yields determined under subject-defined conditions are necessary in order to properly evaluate the role of nicotine in the design of "less-hazardous" cigarettes.     

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity rhegmatogenous retinal detachment

The hyperosmolarity response of the ocular standing potential was recorded in unilateral rhegmatogenous retinal detachment (8 eyes) and in the fellow healthy eye (8 eyes). The hyperosmolarity response was greatly suppressed (M-4 SD: M and SD indicate respectively the mean and the standard deviation in normal subjects) in all affected eyes (p < 0.005), and slightly abnormal in 2 fellow eyes. The L/D ratio was normal in 2 affected eyes and in all fellow eyes. The hyperosmolarity response in the affected eyes was still greatly suppressed 14 months after successful surgical treatment.     

Neighborhood social environments,healthy resources,and adult diabetes: Accounting for activity space exposures

This study broadens contextual environments to include adults’ activity spaces—inside and outside the residential neighborhood—to examine how contextual exposures shape type 2 diabetes risk. We use novel longitudinal data from the Los Angeles Family and Neighborhood Survey, construct time-weighted exposure measures of adults’ social-structural and healthy resource environments, and execute random effects logistic models predicting the probability of being diabetic. Results indicate that residential and activity space exposures are independently associated with adult diabetes, and that residential and activity space healthy resources combine to influence diabetes risk in synergistic ways. Living in more socioeconomically advantaged neighborhoods reduces diabetes risk, particularly when spending time in activity spaces with greater access to recreational facilities. Moreover, healthier activity space environments may compensate for living in neighborhoods devoid of healthy food options to lessen diabetes risk. Adopting an activity space framework can inform multilevel interventions aimed at alleviating type 2 diabetes and other chronic ailments.     

木贼对大鼠心功能的影响

目的：研究木贼对心脏功能的影响。方法：建立新式离体作功心脏模型。用上海产SJ-42型四道生理记录仪测定生理参数左室收缩压（LVSP）、左室内压上升速率最大值（dP/dtmax)、左室舒张期末压（LVEDP）、左室内压下降速率最大值（-dP/dtmax)、冠脉流量（CF）、心率（HR）和心电图（ECG）。结果：经过适当剂量木贼药液灌注后的离体作功心脏与用药前自身对照比较,LVSP、dP/dtmax、-dp/dtmax、CF增大,而HR变慢,经随机区组方差分析,均有显著差异。结论：木贼有增强心脏收缩与舒张功能,有增加冠脉流量和减慢心率的作用。     

白屈菜总生物碱止咳平喘作用实验研究

目的：观察白屈菜总生物碱的止咳平喘作用。方法：昆明种小鼠和豚鼠,均ig给予白屈菜总生物碱5,10,20mg.kg^-1,经小鼠氨水引咳实验,豚鼠枸橼酸引咳实验,豚鼠组织胺引喘实验,观察用药前后引咳潜伏期,3min内的咳嗽次数和豚鼠的引喘潜伏期及发生抽搐跌倒的动物数。结果：白屈菜总生物碱可明显地延长小鼠引咳潜伏期,减少咳嗽次数,延长豚鼠的引喘潜伏期,减少抽搐跌倒的动物数,与对照组比较差异显著（P＜0．01）,结论：白屈菜总生物碱有明显的止咳平喘作用。     

自发性高血压大鼠应用卡托普利加左旋精氨酸、牛磺酸的实验研究

目的：为研究左旋精氨酸、牛磺酸、卡托普利三药合用对自发性高血压大鼠的血压、血脂以及同同型半胱氨酸的影响。方法：用酶法测血脂,用高效液相色谱法测血浆HCY,在大鼠清醒状态下,测鼠尾的尾动脉收缩压,观察两组自发性高血压大鼠（卡托普利单用组,左旋精氨酸＋牛磺酸＋卡托普利三药合用组）在用药前后各指标的变化。结果：①经过四周药物治疗,合用组血压下隆比卡托普利组明显（P＜0.01）。②卡托普利组血脂无降低（P＞0.05）。合用组TC和TG均降低,（P＜0.005)。③两组HCY均下降。用药前,大鼠血压高低与血浆HCY的浓度无相关性（P＞0.05）,用药后,血压的下降与血浆HCY浓度的变化无相关性（P＞0.05）。结论：①卡托普利与有氨酸、牛磺酸合用对血压、血脂的控制比单用卡托普利。②血压的下降与同型半胱氨酸的下降无相关性（P＞0.05）。     

体内外自由基形成的研究及意义

目的研究体内外自由基的形成及意义。方法用TBA-醋酸法检测正常人血清,血浆,胸腹腔渗、漏出液,各细胞提取物及服用西洋参前后的血浆和经过氧化处理后的正常人、糖尿病、高血压、冠心病患者的血清及食用油脂、相应烟雾冷凝油的过氧化脂质(LPO)含量。结果各细胞均有自由基反应,以血小板为最高。血清LPO明显高于血浆(P<0.001),胸腹腔渗出液LPO明显高于漏出液(P<0.001),过氧化处理后的糖尿病、高血压、冠心病患者血清的LPO明显高于过氧化处理后的正常人血清LPO(P<0.001);油脂质量越高,LPO含量越低,相应的烟雾冷凝油的LPO是食用油脂的14.3～35.6倍。结论生物、化学和物理因素均可引起脂质过氧化,不管何种因素所致的脂质过氧化,其反应过程及其产物LPO对生物体都有严重的损害作用。     

射干和马齿苋对46株绿脓杆菌体外抑菌试验的研究

目的 :探讨射干、马齿苋对绿脓杆菌 ( PA)的体外抑菌作用。方法 :取射干、马齿苋水煎剂对4 6株PA进行 MIC试验 ,统计 MIC50 和 MIC90 。结果 :射干水煎剂对 PA MIC范围为 31.2 5～ 3.90 g/ L,MIC50 为 7.81g/ L,MIC90 为 15.62 g/ L;马齿苋水煎剂对 PA MIC范围为 31.2 5～ 7.81g/ L,MIC50 为15.62 g/ L,MIC90 为 31.2 5g/ L。结论 :射干、马齿苋于体外对绿脓杆菌有较强抑制作用。     

白桦叶的二苯基庚烷类化合物

目的：对白桦叶的化学成分做系统研究,以更好的开发利用我国的植物资源。方法采用硅胶柱、凝胶柱及制备薄层色谱法进行了分离,通过波谱技术（^ＨＮＭＲ,^１３ＣＮＭＲ,^１Ｈ－^１ＨＣＯＳＹ,ＨＭＱＣ,ＨＭＢＣ,ＮＯＥＳＹ）进行结构鉴定。结果：分离鉴定了４种二苯基庚烷类化合物,槭木素丁（１）,氧杂二苯庚烯（Ⅱ）,１７－甲基－１５－甲氧基－７－７氧代槭木素丁 (Ⅲ）,槭木素十一（Ⅳ）,结论：化合物Ⅲ,Ⅳ均首次从本种植物中分离得以,并纠正了化合物Ⅲ的碳谱数据归属。