香烟烟雾提取物诱导A-549肺上皮细胞凋亡

目的：探讨香烟烟雾提取物诱导A-549肺上皮细胞凋亡的机制。方法：以不同浓度香烟烟雾提取物作用于A-549肺上皮细胞，用碘化丙啶（PI）及Annexin V-FITC/PI双标记法检测凋亡细胞及坏死细胞。结果：50％、30％、20％、10％及5％浓度的香烟烟雾提取物处理细胞24h后，经细胞早期凋亡检测，细胞凋亡率分别达到0、31．7％、11．9％、1．6％、0．3％，细胞坏死率分别为100％、34．2％、6．2％、1．1％、0．8％。结论：一定浓度香烟烟雾提取物可诱导A-549肺上皮细胞凋亡，凋亡与坏死相伴存在，并呈剂量依赖性。     

胱抑素C等生化指标用于糖尿病肾病肾损害程度的适用性评价

目的 探讨血清胱抑素C（CysC）等生化指标在糖尿病肾病各期诊断中的临床适用性。方法 选取2012年11月—2013年3月于平煤神马医疗集团总医院住院治疗的141例2型糖尿病患者为研究对象,所有病例均采用1999年WHO标准,本实验依据24 h尿微量白蛋白排泄率（UAER）分为：正常白蛋白尿组38例,微量白蛋白尿组42例,少量白蛋白尿组35例,大量白蛋白尿组26例,同期选取46例健康体检者进行对照分析。结果 2型糖尿病肾病早期肾功能损害患者血清CysC、UAER明显高于正常对照组（P〈0.05）;2型糖尿病肾病早期肾功能损害患者血清CysC和UAER检出率比较,差异无统计学意义（P〉0.05）。结论 血清CysC和UAER在2型糖尿病肾病早期肾功能损害患者中的升高均较为灵敏,CysC测定方法简单且结果受年龄、饮食等因素干扰少,值得临床推广应用。     

HPLC法同时测定清开灵注射液中黄芩苷和千层纸素A-7-O-β-d-葡糖醛酸苷的含量

目的:建立同时测定清开灵注射液中黄芩苷和千层纸素A-7-O-β-d-葡糖醛酸苷含量的方法,并比较不同厂家、批号产品中黄芩苷和千层纸素A-7-O-β-d-葡糖醛酸苷的含量差异。方法:采用高效液相色谱法。色谱柱为Agilent ZORBAX SB-C18,流动相为甲醇-0.1%磷酸溶液(梯度洗脱),流速为1.0 ml/min,检测波长为274 nm,柱温为30℃,进样量为10μl。结果:黄芩苷、千层纸素A-7-O-β-d-葡糖醛酸苷检测质量浓度分别在10.1²52.0、1.0252.0、1.0⁶.0μg/ml范围内与各自峰面积积分值呈良好的线性关系(r=0.999 9);精密度、稳定性、重复性试验的RSD≤1.6%;平均加样回收率分别为99.64%、99.03%,RSD分别为2.7%、0.9%(n=6)。不同厂家、批号产品中黄芩苷、千层纸素A-7-O-β-d-葡糖醛酸苷的质量浓度范围分别为4.1516.0μg/ml范围内与各自峰面积积分值呈良好的线性关系(r=0.999 9);精密度、稳定性、重复性试验的RSD≤1.6%;平均加样回收率分别为99.64%、99.03%,RSD分别为2.7%、0.9%(n=6)。不同厂家、批号产品中黄芩苷、千层纸素A-7-O-β-d-葡糖醛酸苷的质量浓度范围分别为4.151⁴.849、0.0974.849、0.097⁰.157 mg/ml。结论:该方法简单、准确、可靠,适用于清开灵注射液的质量控制;不同厂家、批号清开灵注射液中黄芩苷和千层纸素A-7-O-β-d-葡糖醛酸苷的含量存在较大差异。     

Insights from analysis for harmful and potentially harmful constituents (HPHCs) in tobacco products

A total of 20 commercial cigarette and 16 commercial smokeless tobacco products were assayed for 96 compounds listed as harmful and potentially harmful constituents (HPHCs) by the US Food and Drug Administration. For each product, a single lot was used for all testing. Both International Organization for Standardization and Health Canada smoking regimens were used for cigarette testing. For those HPHCs detected, measured levels were consistent with levels reported in the literature, however substantial assay variability (measured as average relative standard deviation) was found for most results. Using an abbreviated list of HPHCs, statistically significant differences for most of these HPHCs occurred when results were obtained 4–6 months apart (i.e., temporal variability). The assay variability and temporal variability demonstrate the need for standardized analytical methods with defined repeatability and reproducibility for each HPHC using certified reference standards. Temporal variability also means that simple conventional comparisons, such as two-sample t-tests, are inappropriate for comparing products tested at different points in time from the same laboratory or from different laboratories. Until capable laboratories use standardized assays with established repeatability, reproducibility, and certified reference standards, the resulting HPHC data will be unreliable for product comparisons or other decision making in regulatory science.     

Workplace Interventions and Vaccination-Related Attitudes Associated With Influenza Vaccination Coverage Among Healthcare Personnel Working in Long-Term Care Facilities, 2015‒2016 Influenza Season

ObjectivesInfluenza vaccination of healthcare personnel working in long-term care (LTC) facilities can reduce influenza-related morbidity and mortality among healthcare personnel and among resident populations who are at increased risk for complications from influenza and who may respond poorly to vaccination. The objective of this study was to investigate workplace interventions and healthcare personnel vaccination-related attitudes associated with higher influenza vaccination coverage among healthcare personnel working in LTC facilities.Setting and participantsData were obtained from an online survey of healthcare personnel conducted in April 2016 among a nonprobability sample of 2258 healthcare personnel recruited from 2 preexisting national opt-in Internet panels. Respondents were asked about influenza vaccination status, workplace vaccination policies and interventions, and their attitudes toward vaccination. Analyses were restricted to the 332 healthcare personnel who worked in nursing homes, assisted living facilities, or other LTC facilities.MeasuresLogistic regression models were used to assess the independent associations between each workplace intervention and higher influenza vaccination coverage compared with referent levels, controlling for occupation, age, and race/ethnicity. Prevalence ratios were calculated under the assumption of simple random sampling.ResultsApproximately 77% of healthcare personnel working in LTC facilities reported receiving influenza vaccination in the 2015?2016 influenza season. Influenza vaccination was independently associated with an employer vaccination requirement (prevalence ratio (PR) [95% confidence interval] = 1.28 [1.11, 1.47]), being offered free onsite vaccination (PR = 1.20 [1.04, 1.39]), and employers publicizing vaccination coverage level to employees (PR = 1.24 [1.09, 1.41]). Vaccination was most highly associated with a combination of 3 or more workplace interventions. Most healthcare personnel working in LTC facilities reported positive attitudes toward the safety and effectiveness of influenza vaccination.Conclusions/ImplicationsImplementing employer vaccination interventions in LTC facilities, including employer vaccination requirements and free on-site influenza vaccination that is actively promoted, could increase influenza vaccination among healthcare personnel.     

长白山蝮蛇蛇毒的提取分离

应用ＤＥＡＥ葡聚糖凝佼Ａ－５０对蝮蛇蛇毒进行柱层析分析得到十三个蛋白峰，其有效组份为凝血酶样酶（精氨酸酯）分布在６、７、８峰，并对该组酶的活性进行初步探讨。     

Phase I/pharmacokinetic study of CCI-779 in patients with recurrent malignant glioma on enzyme-inducing antiepileptic drugs

OBJECTIVES: CCI-779 is an ester of the immunosuppressive agent sirolimus (rapamycin) that causes cell-cycle arrest at G1 via inhibition of key signaling pathways resulting in inhibition of RNA translation. Antitumor activity has been demonstrated using cell lines and animal models of malignant glioma. Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs) can have altered metabolism of drugs like CCI-779 that are metabolized through the hepatic cytochrome P450 enzyme system. The objectives of this study were to determine the pharmacokinetic profile and the maximum tolerated dose of CCI-779 in patients with recurrent malignant gliioma taking EIAEDs. STUDY DESIGN: The starting dose of CCI-779 was 250 mg intravenously (IV) administered weekly on a continuous basis. Standard dose escalation was performed until the maximum tolerated dose was established. Toxicity was assessed using the National Cancer Institute common toxicity criteria. RESULTS: Two of 6 patients treated at the second dose level of 330 mg sustained a dose-limiting toxicity: grade III stomatitis, grade 3 hypercholesterolemia, or grade 4 hypertriglyceridemia. The maximum tolerated dose was reached at 250 mg IV. Pharmacokinetic profiles were similar to those previously described, but the area under the whole blood concentration-time curve of rapamycin was 1.6 fold lower for patients on EIAEDs. CONCLUSIONS: The recommended phase II dose of CCI 779 for patients on enzyme-inducing antiepileptic drugs is 250 mg IV weekly. A phase II study is ongoing to determine the efficacy of this agent.     

Mechanochemically activated doxorubicin nanoparticles in combination with 40 MHz frequency irradiation on A-549 lung carcinoma cells

Targeting of mechanochemically activated doxorubicin (MA DOXO) nanoparticles, conventional doxorubicin, and electromagnetic irradiation (EMI) at A-549 lung carcinoma cells in vitro was investigated. Conventional DOXO was micronized using an input energy of 20 W/g for 5 min resulting in positively charged MA DOXO particles 10 times smaller than conventional DOXO. Mechanochemical activation gives rise to additional free quinone radicals. High performance liquid chromatograph analyses demonstrate that conventional and MA DOXO are quantitatively similar. Tumor cells were exposed to 40 MHz electromagnetic irradiation at a power density of 2 W/cm². The lethal dose LD₅₀ values of MA DOXO were 5 times greater than conventional doxorubicin. MA DOXO in combination with EMI at 37°C demonstrates improved drug delivery to A-549 human lung carcinoma and greater cell kill than does conventional DOXO.     

Antitumor Effects due to Irreversible Stoppage of Tumor Tissue Blood Flow: Evaluation of a Novel Combretastatin A-4 Derivative, AC7700

The relation between tumor tissue blood flow (tBF) reduction and antitumor effects was investigated. Changes in tBF of normal tissues (liver, kidney cortex, bone marrow and brain cortex) and tumors (Yoshida sarcoma subline, LY80 and Sato lung carcinoma, SLC) due to i.v. administration of AC7700 (1, 3, 10 mg/kg), one of the combretastatin A-4 derivatives, were measured with the hydrogen clearance method. The change in blood flow in tumor microfoci was also observed directly using a rat transparent chamber. Chemotherapy against the solid tumors (LY80, SLC) was performed by administering AC7700 7 times at intervals of 3 days and the effect on the tumor growth, the histological effect, the effect on lymph node metastasis and the survival rate were investigated. Tumor tBF showed a dose-dependent response to AC7700. Although tumor tBF decreased markedly at a dose of 1 mg/kg, it tended to recover partly within several hours. At 10 mg/kg, however, tumor tBF completely stopped within approximately 30 min and never recovered in many regions. The irreversible stoppage of tumor tBF was observed in large s.c. tumors and in microfoci as well. On the other hand, in normal tissues, tBF changes due to AC7700 were not uniform. In the liver, although tBF decreased by approximately 50% at 10 mg/kg AC7700, it recovered within 8 h. In the brain, although the mean maximum reduction was 35%, the blood flow recovered to the original level within 24 h. The blood flow in the kidney cortex did not change at all. In the bone marrow, tBF decreased by approximately 80%. Generally, the blood flow reduction in normal tissues tended to be reversible. The effect on tumor growth and the histological effect were also dependent on the dose of AC7700. The tumor growth was markedly inhibited by 10 mg/kg AC7700 and extensive necrosis was induced. Lymph node metastases were significantly inhibited and survival was prolonged significantly. In the control group, all 8 SLC tumor-bearing rats died of cancer, the presence of which was verified by gross and microscopic evaluation, within 45 days after tumor implantation. On the other hand, in the treated group, 2 of 8 rats recovered completely and survived. No obvious side effects such as body weight loss, anemia or diarrhea were observed at the dose used in this experiment. From these results, we conclude that strong antitumor effects are obtained by stopping tumor tBF irreversibly and by shutting off the nutritional supply into tumor tissue. AC7700 has been demonstrated to be a promising anticancer compound which has such an action.