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71.
Polymer-conjugated bovine pancreatic and seminal ribonucleases inhibit growth of human tumors in nude mice. 总被引:2,自引:0,他引:2
P Poucková M Zadinová D Hlousková J Strohalm D Plocová M Spunda T Olejár M Zitko J Matousek K Ulbrich J Soucek 《Journal of controlled release》2004,95(1):83-92
The hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) was used for RNase A or BS-RNase modification to prevent their degradation in bloodstream or fast elimination. Two PHPMA chains (classic and star-like) were synthesized and their conjugates with both enzymes were tested on the CD-1 nude mice bearing various human tumors. These RNase conjugates injected intravenously or intraperitoneally into the mice bearing melanoma, neuroblastoma or ovarian tumor caused significant reduction of transplanted tumors following ten daily doses of 2.5 and/or 1 mg/kg, respectively, while free RNase A or BS-RNase injected in doses of 10 mg/kg exerted only negligible antitumor activity. Histological examination confirmed potent cytotoxic effect of RNase A conjugates in ovarian tumor. Despite the antitumor activity observed in vivo, the in vitro cytotoxic activity of RNase A conjugates was not pronounced and did not differ from that caused by the free RNase A. The in vitro experiments with 125I-labeled preparations demonstrated that polymer conjugates were internalized by tumor cells very poorly in contrast to the dose-dependent internalization of the wild enzyme preparation. Surprisingly, mice injected with EL-4 leukemic cells, which were preincubated for 4 h with BS-RNase conjugates, exerted significantly prolonged survival compared with the control non-treated mice. It may be supposed that both BS-RNase and RNase A conjugates with PHPMA act after administration in vivo by a mechanism different from that or those occurring under in vitro conditions because in vivo they exert an antitumor action, whereas in vitro, they are ineffective. The experiments proved that RNase A, when conjugated to PHPMA, produced identical aspermatogenic and antitumor effects as BS-RNase conjugated to this polymer and that this preparation may be regarded as a potential anticancer drug. 相似文献
72.
Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge 总被引:3,自引:0,他引:3
Humphries SE; Talmud PJ; Cox C; Sutherland W; Mann J 《QJM : monthly journal of the Association of Physicians》1996,89(9):671-680
We examined the role of common genetic variation in determining the
consistency and magnitude of change in plasma total cholesterol (TC) levels
in response to two separate changes from a high-saturated (SFA) to a
low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of
free-living healthy men and women. Consistent responders were defined as
those whose mean difference in the change in TC was within one SD of the
mean for all participants, and the remainder were defined as variable
responders. DNA was obtained from 55 individuals and genotype determined at
the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T)
and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent
responders, the apoBSP24 allele was significantly more common than in the
17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). No
other polymorphism showed a significant frequency difference between
groups. In the group as a whole, the correlation between the change in TC
level in response to the first and second dietary change was 0.28 (p =
0.05), but those with one or more apoB SP24 alleles and those with the
apoCIII genotype CC had a significantly higher correlation than those with
other genotypes (0.46 (p = 0.05) vs. 0.12 (NS) and 0.31 (p = 0.05) vs. 0.02
(NS), respectively). In the group as a whole, mean response left TC 10%
higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII
genotypes affected the magnitude of this response. However, individuals
with the LPL HindIII genotype H+ H+ had a significantly smaller change in
mean TC in response to diet than those with one or more H- allele (9.3% vs.
14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects the
consistency of response to change in dietary fat content, while variation
at the LPL gene locus affects magnitude of response.
相似文献
73.
74.
A Novel Approach to Increase the Stability of Liposomal Containers via In Prep Coating by Poly[N‐(2‐Hydroxypropyl)Methacrylamide] with Covalently Attached Cholesterol Groups
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Olga V. Zaborova Sergey K. Filippov Petr Chytil Lubomir Kováčik Karel Ulbrich Alexander A. Yaroslavov Tomaš Etrych 《Macromolecular chemistry and physics.》2018,219(7)
Highly stable liposomes are developed by coating phosphatidylcholine liposomes with amphiphilic N‐(2‐hydroxypropyl)methacrylamide copolymer. Two approaches in the preparation of coated liposomes are employed: the copolymer is added during (“in prep”) or after (“ex post”) the liposome formation. The influence of polymer concentration and coating method is evaluated using the cryogenic transmission electron microscopy, dynamic light scattering, and small‐angle X‐ray scattering techniques. The in prep modification significantly increases, up to four weeks, the stability of liposomes against aggregation and makes the liposomal membrane nonpermeable toward an inorganic salt. Such enhanced longevity is attributed to the different structure of in prep coated liposomal membranes. 相似文献
75.
76.
Luciano F Schopf José Carlos Fraga Rodrigo Porto Luis A Santos Douglas R Marques Paulo R Sanchez Fabíola S Meyer Jane M Ulbrich 《Journal of pediatric surgery》2018,53(7):1305-1309
Background/purpose
Silicone and metallic stents are not effective in children with tracheobronchial stenosis or tracheomalacia. Herein, we aimed to evaluate the clinical manifestations and histological reaction of rabbit trachea to the presence of a new poly(lactic-co-glycolic acid) with polyisoprene (PLGA/PI) polymer absorbable stent.Methods
Fourteen adult white rabbits (weight, 3.0–3.5 kg) were randomly assigned to three groups: Group I (n = 6): PLGA/PI spiral stent; Group II (n = 6): PLGA/PI fragment; and Group III (n = 2): controls. After a longitudinal incision on three cervical tracheal rings, the stents and fragments were inserted into the trachea and fixed onto the lateral wall with nonabsorbable sutures.Results
The stented group showed significantly more stridor at rest (p = 0.0041), agitation (p = 0.014), and use of accessory muscles (p = 0.0002) and required more emergency endoscopies than the fragment group. Further, it showed significantly more remarkable histological inflammatory damage than the fragment and control groups (p = 0.002).Conclusions
The new PLGA/PI polymeric stent implanted into the trachea of rabbits caused more clinical manifestations and histologically verified inflammatory reaction than the PLGA/PI polymeric fragment. Future studies should be aimed at reducing the stent-wall thickness. 相似文献77.
目的:了解延边地区朝鲜族和汉族居民的脂肪分布特征及其与血压、血脂及血糖的关系。方法:于2006-08-8/17在延边地区九龙和翁声社区随机选择40~60岁朝鲜族和汉族常住居民2378名进行内脏脂肪率和体脂肪率以及血压、血脂、血糖等生化指标的检测。调查以健康体检形式进行,①内脏脂肪和体脂肪率测定采用日本TANITA株式会社生产的BC-600型体成分计测定,并且按其判定标准确定超过标准者[内脏脂肪率≥15%(男)、≥10%(女),体脂肪率(40~59岁)≥23%(男)、≥36%(女),体脂肪率(≥60岁)≥25%(男)、≥37%(女)]。②取清晨空腹(禁食12h)静脉血,采用日立-7600-010全自动生化分析仪测量血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、空腹血糖等指标。③高血压的诊断标准:收缩压≥140mmHg(1mmHg=0.133kPa)及或舒张压≥90mmHg。④血脂异常的诊断标准:总胆固醇≥5.72mmol/L,三酰甘油≥1.7mmol/L,高密度脂蛋白胆固醇<0.90mmol/L(男)、<1.0mmol/L(女)。⑤高血糖的诊断标准:空腹血糖≥6.1mmol/L。结果:①汉族男性的内脏脂肪率和体脂肪率均值分别为(10.51±3.66)%和(22.70±4.85)%,朝鲜族男性分别为(9.16±3.81)%和(20.28±5.02)%,汉族均高于朝鲜族(P<0.01);汉族女性的内脏脂肪率和体脂肪率分别为(6.22±2.27)%和(35.31±5.65)%,朝鲜族女性分别为(5.88±2.19)%和(34.00±5.72)%,汉族均高于朝鲜族(P<0.01)。②汉族男性的内脏脂肪率和体脂肪率超标率分别为12.1%和45.8%,朝鲜族男性分别为7.8%和28.6%,汉族均高于朝鲜族(P<0.05);汉族女性的内脏脂肪率和体脂肪率超标率分别为6.7%和47.9%,朝鲜族女性分别为3.8%和37.3%,汉族均高于朝鲜族(P<0.05)。③Logistic逐步回归分析结果表明,内脏脂肪率与民族、性别、年龄、高血压、高三酰甘油血症和高血糖有密切关系;体脂肪率与民族、性别、高血压、高三酰甘油血症、低高密度脂蛋白血症和高血糖有密切的关系。结论:①延边地区汉族居民内脏脂肪率和体脂肪率平均水平及其超标率明显高于朝鲜族。②内脏脂肪率和体脂肪率均与民族、性别、年龄(体脂肪率除外)、高血压、高三酰甘油血症和高血糖相关。 相似文献
78.
79.
A Ramasamy SE Harrisson MPM Stewart M Midwinter 《Annals of the Royal College of Surgeons of England》2009,91(7):551-558
INTRODUCTION
Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict.PATIENTS AND METHODS
Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq.RESULTS
Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident.CONCLUSIONS
The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons. 相似文献80.
PD Dr. rer. biol. hum. S. Ückert K. Sigl E.S. Waldkirch P. Sandner E. Ulbrich M. Oelke C.G. Stief M.A. Kuczyk 《Der Urologe. Ausg. A》2009,48(7):764-769