肝脏可溶性复合物不同剂量、不同途径移植对肿瘤细胞增殖抑制的体内外实验

目的:肝脏可溶性复合物具有保护肝脏、刺激肝组织再生等生物学活性,观察天然物质肝脏可溶性复合物对肿瘤细胞生长增殖的抑制作用.方法:实验于2006-05/2007-02在四川大学华西医院生物治疗国家重点实验室实验肿瘤研究室完成.①分离人胚胎、成年及新生小鼠肝脏组织,生理盐水清洗、剪碎、筛网过滤,用生理盐水制备混悬液,3 000 r/min离心,收集上清,制备肝脏可溶性复合物.②体外实验:用上述不同来源的肝脏可溶性复合物体外处理肿瘤细胞,四甲基偶氮唑盐比色法测定其对乳腺癌细胞EMT6增殖的影响.③体内实验:观察成年鼠肝脏可溶物质对乳腺癌细胞EMT6体内生长的抑制作用及其对荷瘤鼠生存状况的影响,包括不同给药剂量及不同给药途径两个实验,给药途径包括在接种肿瘤细胞部位的对侧腋下、同侧腋下、腹腔注射及灌胃等.结果:①体外实验显示不同来源的肝脏可溶性复合物能明显抑制肿瘤细胞EMT6增殖率,肿瘤增殖抑制率均显著高于血清白蛋白处理组(P＜0.05),并呈剂量依赖性.②成年鼠肝脏可溶物质8mg/L组抑瘤率高于2,4 mg/L组(P＜0.05),未观察到明显毒副效应.③比较不同给药途径,成年鼠肝脏可溶物质同侧注射组的抑瘤率较其他3组的抑瘤率高(P＜0.05),各成年鼠肝脏可溶物质给予组的体质量增长率比相应生理盐水对照组高(P＜0.05).④与相应生理盐水对照组比较,在同侧腋下注射成年鼠肝脏可溶物质的小鼠生存期明显延长(P＜0.05).结论:肝脏可溶性复合物具有抑制肿瘤细胞生长的作用,并且呈一定的剂量依赖性.不同的给药途径中,在接种肿瘤细胞部位的同侧腋下给药抑瘤效果最好.     

山东泰安地区两个自然村人群血脂状况调查

目的:调查了解山东泰安地区农村人群的血脂水平,为该地区农民心脑血管疾病的预防提供基础数据。方法:实验于2006-06随机选取泰安市两个自然村650人进行健康检查,男270人,女380人,年龄2～88岁。①650人均于早晨空腹采集静脉血3mL,静置凝固后,2h内分离血清,采用全自动生化分析仪常规测定患者血脂指标总胆固醇、三酰甘油水平。②总胆固醇>5.2mmol/L判定为高胆固醇血症,三酰甘油>1.7mmol/L判定为高三酰甘油血症。结果:650人全部完成血样采集与血脂指标检测。①不同性别血脂水平比较:被检人群男性三酰甘油水平显著高于女性[(1.16±1.47),(0.95±0.84)mmol/L,P<0.05];男女总胆固醇水平基本相似(P>0.05)。②不同年龄段血脂水平比较:8人因具体年龄段不祥被排除,剩余642人分为3个年龄段:2～30岁、31～50岁、51～88岁。结果31～50岁人群三酰甘油水平显著高于2～30岁人群[(1.14±1.47),(0.88±0.70)mmol/L,P<0.05],略高于51～88岁人群(P>0.05);51～88岁人群总胆固醇水平>31～50岁人群>2～30岁人群,相邻年龄段间比较差异均有显著性意义(P<0.001)。③各年龄段男女间血脂水平比较:2～30岁人群和51～88岁人群三酰甘油水平性别间差异均无显著性意义(P>0.05),但总胆固醇水平女性均显著高于男性[(2.38±1.47),(1.85±1.26)mmol/L,P<0.05;(4.48±0.92),(4.18±0.76)mmol/L,P0.01]。31～50岁人群男性三酰甘油水平显著高于女性[(1.51±2.06),(0.90±0.80)mmol/L,P<0.01],总胆固醇水平基本相似(P>0.05)。④各年龄段男女高血脂症构成比:31～50岁人群高三酰甘油血症构成比显著高于2～30岁、51～88岁人群(23.1%,5.5%,9.3%,P<0.01);随着年龄增高,各年龄段高胆固醇血症构成比逐渐升高,相邻年龄段间差异均有显著性意义(2.7%,8.6%,15.6%,P<0.01)。31～50岁人群男性高三酰甘油血症、高胆固醇血症的构成比显著高于女性(P<0.01);2～30岁、51～88岁人群男女间高血脂症的构成比基本相似(P>0.05)。结论:①山东泰安地区农村人群高三酰甘油血症,31～50岁年龄段患病率最高;高胆固醇血症患病率随年龄增长逐步上升,提示中年人健康体检尤为重要。②高脂血症应从青少年开始加大预防和保健力度,进行广泛和反复的健康教育,倡导健康的生活方式和生活行为。     

恶性肿瘤淋巴管生成与转移的研究进展

淋巴道转移是肿瘤转移的重要途径,也是判断预后的重要依据. 随着淋巴管生成因子及许多淋巴管特异性标记物的发现,肿瘤新生淋巴管调控与淋巴道转移机制研究得以深入开展. 大量的研究发现,恶性肿瘤和瘤周组织内存在新生的淋巴管,新生的淋巴管密度和淋巴管标记物的表达强度均与淋巴结转移密切相关. 这为揭示恶性肿瘤淋巴道转移机制和开发淋巴管靶向治疗提供了重要的研究途径. 现就近年来肿瘤淋巴管生成与转移的研究进展作一综述.     

Evidence of γ-Tocotrienol as an Apoptosis-Inducing,Invasion-Suppressing,and Chemotherapy Drug-Sensitizing Agent in Human Melanoma Cells

To date, the most effective cure for metastatic melanoma remains the surgical resection of the primary tumor. Recently, tocotrienol-rich-fraction has shown antiproliferative effect on cancer cells. To elucidate this anticancer property in malignant melanoma, this study aimed, first, to identify the most potent isomer for eliminating melanoma cells and second to decipher the molecular pathway responsible for its activity. Results showed that the inhibitory effect of gamma-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of procaspases and the accumulation of sub-G1 cell population. Examination of the prosurvival genes revealed that the gamma-tocotrienol-induced cell death was associated with suppression of NF-kappaB, EGF-R, and Id family proteins. Meanwhile, gamma-tocotrienol treatment also resulted in induction of JNK signaling pathway, and inhibition of JNK activity by selective inhibitor was able to partially block the effect of gamma-tocotrienol. Interestingly, gamma-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and gamma-catenin expression, which was associated with suppression of cell invasion capability. Furthermore, synergistic effect was observed when cells were cotreated with gamma-tocotrienol and chemotherapy drugs. Together, our results demonstrated for the first time the anti-invasion and chemonsensitization effect of gamma-tocotrienol against human malignant melanoma cells.     

A pilot methodology study for the photographic assessment of post‐inflammatory hyperpigmentation in patients treated with tretinoin

Background Post‐inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour. Aims A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual‐controlled methodology study that consisted of a photographic assessment protocol with facial mapping. Materials and methods The study was based on a secondary analysis of a phase 4, community‐based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III–V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation. Results Despite the small number of subjects evaluated (n = 25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ = 0.84). Conclusion Further study with a larger population is recommended to validate the accuracy of this method.     

Resurgence of bedbugs in southern France: a local problem or the tip of the iceberg?

Background Bedbugs (Cimex lectularius) have been feeding on sleeping human beings since prehistory. In Europe, bed bugs were common and endemic until World War II when improved body and home hygiene, and widespread use of insecticides led to almost complete eradication. Current evidence indicates that bedbugs are making a comeback in Europe, USA, Canada and Australia. In our practice in Southern France, we observed several cases within a period of only 1 year. Objectives Based on this experience, we conducted an epidemiological study to evaluate the status of bedbugs in France. Methods During summer 2009, we mailed a short questionnaire to all hospital professors in the CEDEF (Collège des Enseignants de Dermatologie de France) asking four questions: number of suspected diagnosis of bedbugs in the year 2009, and number of certain positive diagnosis, difficulties in treatment, use of a pest control professional for treatment, and finally personal opinion on actual incidence of bedbugs, compared with past years. Results Of the 84 questionnaires sent, there were only 26 responses despite two reminders. The responses were predominantly southern France, probably as a result of intensive immigration and increased travel and trade. Difficulties encountered during diagnosis and treatment are also mentioned. Utilizing the services of entomological experts and pest control professionals is essential. Conclusions France has the same experience regarding the resurgence of bedbugs as several European countries, USA, Canada and Australia, especially the southern regions. This emerging health problem has to be known by dermatologists. A national programme has been launched in France to assess actual incidence and study C. lectularius‐ related diseases.     

Diagnostic value of simultaneous non-invasive continuous,ambulatory finger blood pressure and electrocardiogram monitoring in a patient with hypertrophic obstructive cardiomyopathy

BACKGROUND: The pathophysiology of hypertrophic obstructive cardiomyopathy (HOCM) is complex and heterogeneous, and it may be difficult to disentangle the various pathophysiologic properties leading to complaints. OBJECTIVES: To elucidate the sequence of acute pathophysiologic changes leading to complaints in a patient with HOCM. METHODS: Cardiopres measurements [the combination of non-invasive, continuous finger artery blood pressure monitoring, and three-lead electrocardiogram (ECG) recordings] were performed during physiologic, supine exercise--before and after replacement of metoprolol by verapamil. Within 24 h of the Cardiopres measurement standard Doppler echocardiography was performed. Finger artery pressure wave was analysed using Beatscope software (BMI-TNO, Amsterdam, The Netherlands), ST analysis was performed with H-Scribe (Mortara Instrument, Bilt, The Netherlands). RESULTS: Exercise under metoprolol: finger BP decreased from 130/65 mmHg to 90/60 mmHg, heart rate increased from 65 bpm to 100 bpm and ST analysis revealed significant ST depression in all leads. The occurrence of ST depression preceded the hypotension. Echocardiography showed a dynamic gradient of 70 mmHg. Exercise under verapamil: the patient had less complaints, BP increased from 125/60 mmHg to 165/65 mmHg, heart rate increased from 75 bpm to 107 bpm and ST analysis showed no ST depression > 1 mm. Echocardiography showed no change. CONCLUSIONS: The use of the Cardiopres during a physiological stimulus showed improvement in exercise capacity in a patient with HOCM, while the standard test, stress-echocardiography, showed no correlation with clinical status. The Cardiopres is a useful diagnostic and research tool, allowing non-invasive, ambulatory monitoring of blood pressure and ECG changes.