肿节风总黄酮对小鼠肉瘤S_(180)的抑瘤作用

目的观察肿节风总黄酮对小鼠肉瘤S180实体瘤和腹水瘤的作用,为开发高效低毒的抗肿瘤新药提供依据。方法采用动物整体实验方法,观察肿节风总黄酮对S180荷瘤小鼠实体瘤及腹水瘤的抑瘤作用及生命延长率。结果肿节风总黄酮对S180实体瘤的抑瘤率为20.7%～60.1%,对S180腹水瘤的延长率为36.8%。结论肿节风总黄酮有一定的抗肿瘤作用及生命延长率。     

鸡血藤提取物的抗肿瘤作用研究

目的：研究鸡血藤提取物的体内与体外抗肿瘤作用。方法：采用mT法检测鸡血藤提取物对体外培养的5种肿瘤细胞增殖的抑制作用;体内试验采用小鼠实体瘤S180细胞株接种小鼠,建立实体瘤与腹水瘤模型。计算抑瘤率与生命延长率。结果：鸡血藤提取物在5μg／ml-80μg/ml剂量的范围内对5种肿瘤细胞均有抑制作用。体内试验小鼠分另吐灌胃给予20mg/kg、50mg／kg、100mg／kg,能抑制小鼠体内肿瘤增长。也能明显提高腹水瘤小鼠的生命延长率。结论：鸡血藤提取物在体外对不同组织来源的肿瘤细胞增殖有明显的抑制作用;在体内能抑制小鼠体内瘤体生长,明显延长小鼠的生存期。     

极大螺旋藻胞内多糖IPSⅡA对小鼠移植性肿瘤抑制作用的初步研究

目的研究极大螺旋藻胞内多糖IPSⅡA对小鼠S180肉瘤的生长抑制作用。方法建立S180腹水瘤、实体瘤模型，通过不同途径给予IPSⅡA，测定腹水瘤小鼠的生命延长率以及实体瘤小鼠的瘤重、白细胞数、胸腺指数和脾指数。结果IPSⅡA对S180肉瘤有一定的抑制作用，提前给药，抑制作用更显著，而且腹腔注射比灌胃效果更好。结论提前腹腔注射IPSⅡA，能显著延长荷S180腹水瘤小鼠的生存时间，并且抑制S180实体瘤的生长。     

脱氧氟尿苷冻干粉针剂的抗肿瘤作用研究

目的研究脱氧氟尿苷(DFUR)冻干粉针剂(DFURLP)对荷瘤小鼠的抗肿瘤活性.方法以荷瘤小鼠的瘤重和生命延长率为指标,观察药物(300,150,75 mg*kg-1)的抗肿瘤活性.结果DFURLP(300,150 mg*kg-1,iv)对小鼠移植性肉瘤180(S180)、肝瘤实体型(Heps)及子宫肉瘤(U14)的肿瘤生长具有明显的抑制作用(P<0.01),DFURLP(300 mg*kg-1,iv)与DFUR(600 mg*kg-1,ig)作用相近,DFURLP(300,150 mg*kg-1,ip)能显著延长S180,Heps,EAC腹水型小鼠移植瘤的存活天数,而DFUR(300 mg*kg-1,ig)对以上3种腹水瘤无明显延长生命作用.结论DFURLP iv及ip对动物实验性肿瘤具有显著的抑制作用.     

泥蚶提取物-海生素抗肿瘤作用的实验研究

目的:探讨泥蚶提取物 海生素对体外培养的人肺癌、乳癌、胃癌细胞增殖的影响和对小鼠移植性肿 瘤预防治疗的作用。方法:采用MTT法检测海生素(0.5%～2%)对体外培养的人肿瘤细胞增殖的抑制作 用;体内实验则首先尾静脉给予小鼠147,210,300mg·kg-1·d-1的海生素,共3d。然后用小鼠实体瘤S180、 肝癌实体瘤(Heps)和艾氏腹水瘤(EAC)株接种小鼠,接种后继续给药10d,计算抑瘤率和荷瘤小鼠生命延长 率。结果:海生素在0.5%～2%的剂量范围内,对体外培养的3种肿瘤细胞均有抑制作用。其中对肺癌细胞 最明显,且存在量效关系(r=0.974,P<0.01)。体内实验结果显示灌胃给药海生素147～300mg·kg-1剂 量范围内,对接种的S180和肝癌实体瘤(Heps)的抑瘤率分别达到19.34%～65.19%和32.23%～79.53%,对 艾氏腹水瘤(EAC)小鼠的生命延长率为40.54%～57.66%。结论:海生素对体外培养的人肺癌、乳癌和胃癌 肿瘤细胞和对接种的小鼠肿瘤具有明显的抑制作用,且毒副作用小,有可能开发成为一种海洋抗肿瘤药物。     

氯化两面针碱体外和体内的抗肿瘤作用

目的观察氯化两面针碱(NC)的抗肿瘤作用。方法采用MTT法观察NC体外对肿瘤细胞存活的影响。移植性S180肉瘤模型小鼠,ip给予NC,每天1次,共10d,测瘤重,计算抑瘤率,并在电镜下观察移植瘤细胞的超微结构。腹水型H22肝癌模型小鼠,sc给予NC,每天1次,共10d,观察小鼠的存活时间,计算生命延长率。结果体外给予NC0.625,1.25,2.5,5.0和10.0mg·L-1可浓度依赖性地降低人鼻咽癌细胞CNE1、人肺癌细胞SPC-A-1和人乳腺癌细胞MDA-MB-231等9种肿瘤细胞的存活率,作用48h平均IC50为(3.33±0.28)mg·L-1。体内给予NC2.5,5.0和10.0mg·kg-1对小鼠S180肉瘤的抑瘤率分别为1.95%,27.3%和42.9%,对腹水型H22肝癌小鼠的生命延长率分别为35.7%,71.4%和85.7%。电镜下可见NC10.0mg·kg-1组S180移植瘤细胞核染色质浓缩并边缘化,核碎裂,胞浆空泡化明显。结论NC体内外应用均具有明显的抗肿瘤作用。     

鸦胆子提取物对S180 小鼠抗肿瘤作用的实验研究

目的研究鸦胆子提取物对小鼠移植性肿瘤S180的抑制作用。方法建立小鼠腋下S180实体瘤模型,观察不同剂量鸦胆子提取物对小鼠抑瘤率及对免疫器官的影响;建立小鼠S180腹水瘤模型,观察不同剂量鸦胆子提取物对小鼠生存期的影响。结果鸦胆子提取物中、高剂量能明显抑制S180实体瘤的生长（P〈O．05）;抑瘤率分别为20．4％和24．6％。鸦胆子提取物低、中剂量可以延长S180腹水瘤小鼠的生存期（P〈O．05）,延长率为21％和18．5％。结论鸦胆子提取物有一定抗肿瘤的作用。     

海生素注射液抗肿瘤作用的实验研究

目的 :研究海生素的抗肿瘤效果。方法 :采用小鼠移植性实体瘤S180 、艾氏腹水瘤 (EAC)和肝癌实体瘤 (Heps)模型的抑瘤试验 ,尾静脉给予小鼠不同剂量的海生素 ,计算抑瘤率和荷瘤小鼠生命延长率。结果 :海生素在 4 90～ 10 0 0mg·kg- 1·d- 1剂量范围内对小鼠S180 和Heps的抑瘤率分别达到 4 1.10 %～ 4 9.0 8%和 36 .2 9%～ 4 9.19% ,对EAC小鼠的生命延长率为 2 2 .93%～ 6 9.98%。结论 :海生素对荷瘤小鼠具有明显的抑瘤作用 ,在有效治疗肿瘤的同时对小鼠体重无明显影响。     

甲氧基聚乙二醇-聚乳酸胶束载体对丝裂霉素的抑瘤活性及局部组织损伤的影响

目的探讨甲氧基聚乙二醇-聚乳酸(mPEG-PLA)胶束是否可以提高丝裂霉素(MMC)的抗肿瘤活性及降低MMC的局部组织损伤作用。方法采用腹腔种植方法分别制备昆明小鼠肉瘤180(S180)实体瘤模型及H22肝癌腹水瘤模型,每个模型小鼠均分为模型组(生理盐水0.1ml·kg-1),mPEG-PLA组,MCC1mg·kg-1组,胶束MMC2,6和18mg·kg-1组。分别观察S180实体瘤的抑瘤率及H22腹水瘤的生命延长率。BALB/C小鼠分别右后肢im给予生理盐水组(正常对照),mPEG-PLA,胶束MMC0.02,0.04,0.08,0.1,0.16,0.2和0.4mg·kg-1组,MMC0.02,0.04,0.08,0.1,0.16,0.2和0.4mg·kg-1组,观察小鼠局部组织损伤情况。结果在S180实体瘤模型上,mPEG-PLA无肿瘤抑制作用;MMC1mg·kg-1的肿瘤抑制率为34.8%,胶束MMC2,6和18mg·kg-1的肿瘤抑制率分别为31.23%,51.8%,66.8%,胶束MMC6和18mg·kg-1的肿瘤抑制率明显高于MMC组(P<0.01)。在H22腹水癌模型上,mPEG-PLA对肿瘤小鼠的生命延长率无影响;MMC1mg·kg-1的生命延长率为123.4%,胶束MMC2,6和18mg·kg-1的生命延长率分别为76.6%,171.0%和206.5%,胶束MMC2mg·kg-1组生命延长率显著低于MMC组(P<0.01),但高于模型组(P<0.01),胶束MMC6和18mg·kg-1的生命延长率明显好于MMC组(P<0.05)。在组织损伤模型上,胶束MMC组损伤发生时间和损伤面积明显低于相同剂量的MMC组(P<0.05)。结论 mPEG-PLA胶束能够提高MMC体内抗肿瘤作用,降低MMC的毒性作用。     

胡桃楸提取物的抗肿瘤作用

目的探讨胡桃楸提取物SH体内外抗肿瘤活性。方法体外实验应用MTT法检测SH对人宫颈癌细胞株HeLa、小鼠腹水型肝癌细胞株Hca-F的增殖抑制作用;体内实验应用小鼠S180实体瘤动物模型,通过对荷瘤小鼠体质量以及抑瘤率的影响,评价SH不同剂量(4.5、9.0、18.0 mg·kg-1)以及与化疗药物环磷酰胺(cyclophosphamide,CTX)联合用药对S180肉瘤的生长抑制作用。结果体外实验表明,SH可以显著抑制HeLa、Hca-F肿瘤细胞的增殖;体内实验表明,SH具有明显的抑瘤作用,中、高剂量组(9、18 mg·kg-1)的抑瘤率分别为25.9%和35.3%,与CTX联合用药时,能够提高CTX的抑瘤率,中、高剂量组(9+10 mg·kg-1、18+10 mg·kg-1)抑瘤作用呈现相加作用。结论胡桃楸提取物SH,在体外能够明显抑制HeLa、Hca-F肿瘤细胞的增殖,在体内能够抑制荷瘤小鼠S180肉瘤生长,提示胡桃楸提取物SH具有一定的抗肿瘤活性。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Hyperkalaemia in patients in hospital

A survey of all laboratory blood specimens with a plasma potassium concentration greater than or equal to 5.5 mmol/L was conducted over a three month period. Of 331 specimens with hyperkalaemia, 71 were excluded because the specimens was haemolysed, old or contaminated. The laboratory served a population of 348,561 and during this time measured the plasma potassium on 25,016 occasions. Sixty-six outpatients and 20 neonates were not evaluated. The survey was undertaken on 86 of 102 inpatients (46 males), 48 of whom were over 66 years of age. Fifty-seven patients were admitted under a medical service and 29 under a surgical service. Fifty-nine had a single episode of hyperkalaemia. Thirty-two underwent a surgical procedure. The commonest contributing factor was impaired renal function which was present in 71 (83%) patients. Although a definitive causative role for drugs could be identified in only five patients, in 52 (60%) patients drugs were a contributing factor (potassium supplements 24, ACE inhibitors 16, nonsteroidal antiinflammatory drugs 12). Thirty-five of the 86 (41%) patients died during their hospital admission. Nineteen of the 35 deaths occurred within three days of the hyperkalaemia being recorded. A normal plasma potassium was eventually documented in 50 of the 86 patients. Of the remaining 36 patients, 25 (69%) subsequently died. In general the treatment of patients with hyperkalaemia focused on identifying and treating the underlying cause. Hyperkalaemia must always be considered seriously and regard given to the overall clinical status of the patient, with particular attention to drug therapy, renal and cardiac function, acid base status and the possibility of sepsis.     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.