人尿提取物抗肿瘤活性研究

目的　研究人尿提取物的抗肿瘤活性。方法　从人尿中提取到一种小肽混合物UAP(uricantitumorpeptides) ,用细胞计数法和MTT法测定UAP对 3种人肿瘤细胞SMMC772 1,MKN4 5和U937生长的抑制作用 ,并对其进行体内实验和急性毒性实验。结果　人尿中的提取物UAP对体外培养的SMMC772 1,MKN4 5和U937细胞具有抑制作用 ,但对人正常白细胞HNL(humannormalleucocyte)无明显抑制作用 ,体内实验表明UAP对小鼠HAC肝癌 ,小鼠LEWIS肺癌和小鼠S180 肉瘤瘤体生长有明显抑制作用。急性毒性试验显示其的毒性作用很低 ,LD50 =2 137 13mg·kg-1。结论　人尿中此种小肽提取物在体外体内实验中均有明显的抑瘤作用     

尿多酸肽对人肝癌细胞Smmu7721体内体外抑制作用

目的 :研究由人尿提取的尿多酸肽 (uroacitide)对人肝癌细胞的体内体外抑制作用。方法 :体外实验 ,以四唑盐(MTT)比色法测定培养板中加入尿多酸肽后 ,人肝癌细胞Smmu772 137℃ 5 %CO2 培养箱培养 72h的生物活性 ;体内抑瘤实验为裸鼠皮下接种人肝癌细胞Smmu 772 1,待肿瘤生长后 ,连续每天ip尿多酸肽 10天 ,观察其抑制作用。结果 :体外实验 ,尿多酸肽剂量为 0 0 3～ 2 0 0mg·mL- 1 ,对人肝癌细胞Smmu 772 1的IC5 0 为 0 35～ 0 49mg·mL- 1 ;体内实验 ,尿多酸肽剂量 5 0 0～ 2 0 0 0mg·kg- 1 ,对裸鼠接种人肝癌细胞Smmu 772 1的抑瘤率在 38 9%～ 6 7 9%。结论 :尿多酸肽对人肝癌细胞Smmu772 1体内体外均有显著的抑制作用。     

人尿胰蛋白酶抑制剂的快速纯化

目的以人尿浓缩物为原料 ,对人尿胰蛋白酶抑制剂的分离纯化技术进行研究。方法利用纯胰蛋白酶作为配体偶联于CNBr Sepharose 4B为亲和载体 ,在不同条件下洗脱亲和蛋白 ,可从粗品溶液中快速分离纯化具有胰蛋白酶抑制活性的两种纯产物。结果层析图谱与SDS PAGE分析表明 ,根据洗脱条件 ,可将有抑制活性的 2 0kD和 40kD蛋白质分离为两个单独组份或混合物。其中 2 0kD组份的抑制活性回收为 35 % ,抑制比活为 3 387U/mg;40kD组份的相应值分别为 5 3 %和 3 116U/mg。混合物的抑制活性回收和抑制比活分别为 89%和 3 0 76U/mg ,再经Su perose 12或Superdex 75凝胶渗透层析 ,分别获得两种组份的纯产物。 结论通过选择性洗脱亲和柱 ,可快速获得高收率、高纯度的人尿胰蛋白酶抑制剂     

人尿激肽原酶治疗急性脑梗死对血压的影响

目的:探讨人尿激肽原酶治疗急性脑梗死对血压产生影响的因素及防范措施.方法:收集人尿激肽原酶对血压影响的临床前研究资料及人尿激肽原酶治疗急性脑梗死Ⅰ-Ⅲ期临床试验的相关报道,结合我院Ⅳ期临床试验观察资料,综合分析该药治疗急性脑梗死过程中对血压的影响.结果:人尿激肽原酶对血压产生影响的因素包括用药速度、浓度及合用ACEI类降压药.结论:人尿激肽原酶用药时严格控制用药速度、浓度、用药前72 h至用药后24 h内禁止合用ACEI类药物.能有效防止低血压的发生.     

人尿中诺氟沙星的毛细管电泳快速分析

目的开发一种快速检测人尿中诺氟沙星（Ｎｏｒｆ）的分析法。方法采用毛细管区带电泳（ＣＺＥ）,硼酸缓冲液,ＤＡＤ紫外检测器,测定冷冻后人尿中的Ｎｏｒｆ。结果Ｎｏｒｆ单剂２００ｍｇ口服后尿药峰浓度出现在４～６ｈ,２４ｈ后仍大于３１３．２μｍｏｌ·Ｌ－１。在２００～３５０ｎｍ有吸收峰,最大吸收峰在２７４ｎｍ处。结论ＣＺＥ法简单、快速,适用于尿药快速检测;一般尿路感染口服Ｎｏｒｆ０．２ｇ,ｂｉｄ似足够。     

人尿促性腺激素生产新工艺研究

报道由绝经期妇女尿中提取、纯化人尿促性腺激素(HMG)的新工艺。尿液经乙酸酸化,Polyer-de-2吸附,10%乙酸铵-40%乙醇冼脱,乙醇沉淀,再经碱性离子交换层析纯化,所得初步纯化产物不含热原,FSH 活性为20 IU/mg,活性回收率为64～69%。     

银杏叶注射液联合人尿激肽原酶对脑梗死患者安全性及疗效观察

目的 观察银杏叶注射液联合人尿激肽原酶对脑梗死患者临床疗效及安全性.方法 急性脑梗死患者60例随机分为两组,对照组:人尿激肽原酶;观察组;银杏叶注射液联合人尿激肽原酶.2组治疗前及治疗后分别观察患者神经功能缺损评分(NIHSS)、血液参数的变化,并进行两组间比较.结果 两组治疗后神经功能缺损评分及血液参数差异均有统计学意义(P<0.05).结论 银杏叶注射液联合人尿激肽原酶治疗急性急性脑梗死安全、疗效显著.     

人尿提取物的抗菌活性研究

人尿中含有多种物质，近年来我国已从人尿提取了表皮生长因子、尿激酶及清蛋白，以及从提取尿激酶后的残液中提取尿胰蛋白酶抑制剂(UTI)和集落刺激因子(CSF)等。本实验室从人尿中分离纯化到小肽混合物，它们的分子量不超过800Da，定名为UAP(uric antibacterial peptides)。通过对UAP抗菌活性的研究，证明UAP具有很高的抗菌活性。     

人尿激肽原酶治疗脑梗死疗效观察

目的：观察人尿激肽原酶（尤瑞克林）对脑梗死的临床疗效。方法：将87例脑梗死患者随机分为治疗组和对照组,治疗2周,治疗前后分别以NIHSS量表评价疗效。结果：两组治疗前NIHSS评分差异无统计学意义（P〉0．05）,两组治疗后NIHSS评分差异有统计学意义（P〈0．05）。治疗组总显效率为84．8％,高于对照组的51．3％（P〈0．01）.结论：尤瑞克林能有效改善脑梗死神经功能缺损。     

人尿激肽原酶治疗急性脑梗死的随机双盲对照试验

目的评价人尿激肽原酶治疗急性颈内动脉系统脑梗死的效果及其安全性。方法采用随机、双盲、3∶1安慰剂平行对照的方法,将患者随机分为治疗组(45例静脉滴注人尿激肽原酶0.15 PNAU、维脑路通注射液200 mg,qd)和对照组(15例静脉滴注安慰剂0.15 PNAU、维脑路通注射液200 mg,qd),疗程21 d;欧洲脑卒中量表(ESS)和Barthel指数(B I)评价神经功能恢复状况。结果治疗组患者治疗后的ESS量表评分和Barthel指数改善情况优于对照组,两者比较有统计学意义(P<0.01),两组均未发生明显不良反应。结论人尿激肽原酶治疗急性颈内动脉系统脑梗死所致的神经功能缺损,其效果及安全性良好。     

Phosphodiesterase (PDE) inhibitors in the treatment of lower urinary tract dysfunction

Several disorders of the human upper and lower urinary tract, such as urinary stone disease, lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) and detrusor overactivity, can be therapeutically addressed by influencing the function of the smooth musculature of the ureter, prostate or urinary bladder, respectively. In order to ensure a drug effect without significant adverse events, a certain degree of tissue selectivity is mandatory. The treatment of said conditions aims to focus on orally available drugs acting via intracellular signalling pathways. Specifically, the cyclic nucleotide monophosphate cyclic GMP represents an important mediator in the control of the outflow region (bladder, urethra). The use of phosphodiesterase (PDE) inhibitors, such as sildenafil, tadalafil, vardenafil, avanafil or udenafil, known to restrain the degradation of the second messenger cyclic GMP, offers great opportunities in the treatment of lower urinary tract dysfunction. PDE inhibitors are regarded as efficacious, have a rapid onset of action and favourable effect-to-side-effect ratio. The role of PDE5 inhibitors in the treatment of BPH/LUTS and the overactive bladder has already been addressed in randomized, double-blind, placebo-controlled trials, as well as preliminary open-label studies enrolling either several hundreds or only 20 patients. The purpose of this review is to focus on the potential use and clinical significance of PDE inhibitors in the treatment of storage and voiding dysfunctions of the lower urinary tract. The strategy of modulating the activity of PDE isoenzymes might represent a novel approach in patients with lower urinary tract dysfunction (LUTD).     

A physiologically based model for the ingestion of chromium(III) and chromium(VI) by humans.

A physiologically based model of human chromium kinetics has been developed, based on an existing physiologically based model of human body and bone growth (O'Flaherty, 1993, Toxicol. Appl. Pharmacol. 118, 16-29; 1995a, Toxicol. Appl. Pharmacol. 131, 297-308; 2000, Toxicol. Sci. 55, 171-18) and an existing physiologically based model of chromium kinetics in rats (O'Flaherty, 1996, Toxicol. Appl. Pharmacol. 138, 54-64). Key features of the adapted model, specific to chromium, include differential absorption of Cr(VI) and Cr(III), rapid reduction of Cr(VI) to Cr(III) in all body fluids and tissues, modest incorporation of chromium into bone, and concentration-dependent urinary clearance consistent with parallel renal processes that conserve chromium efficiently at ambient exposure levels. The model does not include a physiologic lung compartment, but it can be used to estimate an upper limit on pulmonary absorption of inhaled chromium. The model was calibrated against blood and urine chromium concentration data from a group of controlled studies in which adult human volunteers drank solutions generally containing up to 10 mg/day of soluble inorganic salts of either Cr(III) (chromic chloride, CrCl(3)) or Cr(VI) (potassium dichromate, K(2)Cr(2)O(7)) (Finley et al., 1997, Toxicol. Appl. Pharmacol. 142, 151-159; Kerger et al., 1996, Toxicol. Appl. Pharmacol. 141, 145-158; Paustenbach et al., 1996, J. Toxicol. Environ. Health 49, 453-461). In one of the studies, in which the chromium was ingested in orange juice, urinary clearance was observed to be more rapid than when inorganic chromium was ingested. Chromium kinetics were shown not to be dependent on the oxidation state of the administered chromium except in respect to the amount absorbed at these ambient and moderate-to-high exposures. The fraction absorbed from administered Cr(VI) compounds was highly variable and was presumably strongly dependent on the degree of reduction in the gastrointestinal tract, that is, on the amount and nature of the stomach contents at the time of Cr(VI) ingestion. The physiologically based model is applicable to both single-dose oral studies and chronic oral exposure, in that it adequately reproduced the time dependence of blood plasma concentrations and rates of urinary chromium excretion in one of the subjects who, in a separate experiment, ingested daily 4 mg of an inorganic Cr(VI) salt in 5 subdivided doses of 0.8 mg each for a total of 17 days. The high degree of variability of fractional absorption of Cr(VI) from the gastrointestinal tract leads to uncertainty in the assignment of a meaningful value to this parameter as applied to single Cr(VI) doses. To model chronic oral chromium exposure at ambient or moderately above-ambient levels, the physiologically based model in its present form should be usable with urinary clearance set to a constant value of 1-2 liters/day and the gastrointestinal absorption rate constants set at 0.25/day for Cr(III) and 2.5/day for Cr(VI). The model code is given in full in the Appendix.     

The Forefront for Novel Therapeutic Agents Based on the Pathophysiology of Lower Urinary Tract Dysfunction: Pathophysiology of Voiding Dysfunction and Pharmacological Therapy

Normal lower urinary tract function consists of voiding and storage. During voiding, the pontine micturition reflex center orders the sacral parasympathetic nucleus to increase parasympathetic activity, resulting in urinary bladder detrusor contraction via activation of post-synaptic muscarinic receptors (M2/3) and in the relaxation of both urethral and prostatic smooth muscle by nitric oxide (NO). In addition, the rhabdosphincter relaxes by inhibition of the pudendal nucleus at the sacral portion. During the storage phase, increase in sympathetic activity relaxes the urinary bladder via activation of post-synaptic β³-receptors and in the contraction of both urethral and prostatic smooth muscles via α¹-adrenoceptor. Many factors influence voiding function, including lower urinary tract disorders (benign prostatic hyperplasia in males, urethral stricture) and neurological disorders (central and peripheral). Theories of pharmacotherapy for voiding dysfunction are 1) increase detrusor contractility and 2) decrease urethral resistance. The former includes agonists for muscarinic receptors and cholinesterase inhibitor; and the latter includes α¹-adrenoceptor antagonists, NO donors, benzodiazepines, baclofen, dantrolene, and boturinum toxin.     

尿红细胞MCV与RDW测定鉴别血尿来源的性质

目的探讨尿红细胞平均体积（MCV）与红细胞体积分布宽度（RDW）测定在血尿来源诊断中的价值。方法应用SYsmex XE-2100血细胞分析仪测定4O例。肾小球性血尿患者与36例非肾小球性血尿患者的MCV与RDW。结果’肾小球性血尿MCV明显低于非。肾小球性血尿,有显著性差异。肾小球性血尿的RDW明显高于非肾小球性血尿,有显著性差异。结论使用血细胞分析仪测定尿中红细胞MCV及RDW对血尿来源诊断有一定的价值。     

Human tachykinin NK2 receptor: a comparative study of the colon and urinary bladder

1. The present study compared the binding and functional characteristics of tachykinin NK2 receptors in human detrusor muscle with those in human colon circular muscle. 2. In radioligand binding studies, similar KD values were observed for tachykinin NK2 receptor radioligands [125I]-neurokinin (NK) A, [125I]-[Lys5,Tyr(I2)7,MeLeu9,Nle10,]NKA(4-10) and [3H]-SR48968 in both human colon circular muscle (0.28-1.1 nmol/L) and human bladder detrusor (0.49-0.91 nmol/L), suggesting binding was primarily to tachykinin NK2 receptors. Receptor capacity (Bmax) was greater in colon compared with detrusor muscle. 3. In functional studies of isolated smooth muscle contraction, there was an excellent positive correlation between human bladder detrusor and colon circular muscle with respect to in vitro contractile potency (r = 0.97) and maximum responses (r = 0.98) to tachykinins, selective tachykinin receptor ligands and l-Ala-substituted NKA(4-10) analogues. 4. Species differences between the human and rat tachykinin NK2 receptors were apparent as observed by a low correlation for potency (r = 0.77) and efficacy (r = 0.32) of l-Ala-substituted analogues in isolated smooth muscle contractile studies. 5. Minor differences observed in the affinity and potency of NK2 receptor agonists between colon and bladder are dependent on the tissue of interest, the receptor-effector coupling and the presence of other tachykinin receptors. Overall, the NK2 receptors of human colon and urinary bladder smooth muscle appear pharmacologically identical.     

呋喃妥因肠溶微囊体外溶出试验及人体内生物利用度研究

本文考察了呋喃妥因肠溶微囊的体外溶出行为,用尿药法研究了其人体内的生物利用度并与市售肠溶片进行比较。体外溶出试验结果表明呋喃妥因肠溶微囊于人工胃液中药物释放降低,人工肠液中快速释放。肠溶微囊人体内生物利用度明显高于市售片。     

Pharmacokinetics of Once-a-Month Injectable Microspheres of Leuprolide Acetate

The pharmacokinetic parameters of leuprolide acetate, a potent analogue of LH-RH, were determined in rats and dogs after i.v. and s.c. dosing with leuprolide solution. The effective human dose of once-a-month injectable microspheres of leuprolide was estimated to be about 3.2 to 8.1 mg analogue/month using these parameters. After microsphere injection at three different doses in rat serum leuprolide concentrations were sustained for over 4 weeks, and the AUCs and mean serum levels were linearly correlated with the dose. The serum levels and urinary excretion of the analogue in rats after repeated s.c. injection of the microspheres every 4 weeks exhibited similar profiles after each injection; no changes of the absorption and excretion of the analogue after the repeated injection could be demonstrated. The serum levels of the analogue metabolite (M-I) were 21% of the intact form 3 hr after injection of the microspheres but very low at the steady state after 1 to 4 weeks.     

尿糖、尿微量白蛋白联合检验对糖尿病早期肾损伤的诊断作用分析

目的探究尿糖、尿微量白蛋白联合检验对糖尿病早期肾损伤的诊断价值。方法选取42例糖尿病早期肾损伤患者作为观察组, 42例糖尿病非肾损伤患者作为对照组, 42例健康体检患者作为健康组。检测对比三组尿糖、尿微量白蛋白水平,统计尿糖单独检验、尿微量白蛋白单独检验及尿糖、尿微量白蛋白联合检验的诊断结果。对比尿糖单独检验、尿微量白蛋白单独检验及尿糖、尿微量白蛋白联合检验的敏感性、特异性及准确率。结果观察组尿糖、尿微量白蛋白水平分别为(3.38±0.45)mmol/L、(36.53±6.15)mg/L;对照组尿糖、尿微量白蛋白水平分别为(2.91±0.36)mmol/L、(24.85±4.73)mg/L;健康组尿糖、尿微量白蛋白水平分别为(1.15±0.28)mmol/L、(14.13±2.84)mg/L;观察组尿糖、尿微量白蛋白水平均显著高于对照组和健康组,对照组显著高于健康组,差异有统计学意义(P<0.05)。尿糖单独检验检出阳性72例,阴性54例;尿微量白蛋白单独检验检出阳性34例,阴性92例;尿糖、尿微量白蛋白联合检验检出阳性40例,阴性86例;病理结果显示:阳性42例,阴性84例。尿微量白蛋白单独检验及尿糖、尿微量白蛋白联合检验的特异性、准确率显著高于尿糖单独检验,尿糖、尿微量白蛋白联合检验的敏感性、准确率显著高于尿微量白蛋白单独检验,差异有统计学意义(P<0.05)。结论尿糖、尿微量白蛋白是糖尿病早期肾损伤的重要指标,尿糖、尿微量白蛋白联合检验诊断糖尿病早期肾损伤效果良好,显著优于单独检验,宜于临床推广。     

Cholinergic Innervation of the Human Urethra and Urinary Bladder: A histochemical study and review of methodology.

Abstract The present work gives a survey of the various methods for the histochemical demonstration of cholinergic nervous structures. The theoretical background and the specificity and sensitivity of the various methods are compared. It is concluded that the histochemical localization of the cholinergic transmitter metabolizing enzyme acetylcholine esterase still probably is the best method, giving a fairly good reflection of the distribution of cholinergic nerves. In comparison with the Falck and Hillarp technique for the demonstration of adrenergic nerves this method is much less specific and sensitive. The present work describes a rich supply of cholinergic nerves in the human urethra and urinary bladder in comparison with the scanty adrenergic innervation. Various functional aspects of the cholinergic innervation are discussed.