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141.
142.
Conventionally, the dynamics of distribution in the body is evaluated by the so-called distribution half-life (e.g., t1/2, alpha); but then the mean time of the distribution process is underestimated due to the influence of elimination. By contrast, information about the dynamics of distribution contained in drug disposition curves can be extracted by the second and third curve moments, parameters that are related to the variance (VDRT) and skewness (SDRT) of residence time distributions; whereas the equilibrium state characterized by the volume of distribution (Vss), is determined by the mean residence time (MDRT) or the first curve moment. The approach represents a general noncompartmental analysis that is independent of a detailed structural model or a particular disposition function. Two parameters are introduced to characterize the dynamics of drug distribution: (i) the degree of departure of the system from "well-mixed" behavior of instantaneous distribution equilibrium (related to VDRT) and (ii) the mean time until equilibration is achieved (mean equilibration time, MEQT), which additionally depends on SDRT. Both parameters are quantitative measures of the dynamics of distribution and display explicit physical significance in terms of distribution within the corresponding noneliminating system. It is further shown that the so-called "distribution phase" in biexponential disposition curves is related to a monoexponential mixing curve of its corresponding noneliminating system with an equilibration or mixing half-time, t1/2,M = t1/2,alpha (V beta/Vss*), where Vss* denotes the distribution volume of the noneliminating system. The results are applied to mixing and disposition curves measured for acetaminophen in liver-ligated and intact rats, respectively. 相似文献
143.
Subregional topography of capillaries in the dorsal vagal complex of rats: I. Morphometric properties 总被引:1,自引:0,他引:1
S W Shaver J J Pang K M Wall N M Sposito P M Gross 《The Journal of comparative neurology》1991,306(1):73-82
Cytoarchitectonic and neurochemical studies of the dorsal vagal complex in the caudal medulla oblongata of rats indicate the existence of distinct anatomical and functional compartments within its components. We applied morphometric methods to discern whether capillary networks differed quantitatively between subregions and zones of area postrema, nucleus tractus solitarii (NTS), and dorsal motor nucleus of the vagus nerve (DMN) of rats. Analysis of 11 subdivisions of area postrema identified both "true" (range in luminal diameter of 3-7.5 microns) and sinusoidal (luminal diameter greater than 7.5 microns) capillaries that, together, made the capillary density for most of area postrema 75% greater than that found in NTS and DMN (526/mm2 vs about 300/mm2). The rank order of true capillary density in area postrema along its rostracaudal axis was caudal greater than central greater than rostral, whereas the reverse order was true for sinusoidal capillaries. Dorsal (periventricular) and medial zones of area postrema throughout its rostrocaudal axis tended to have higher values for capillary density, volume, surface area, luminal diameter, and pericapillary space volume than lateral or ventral zones bordering NTS. Within 200 microns of obex, the ventral zone of rostral area postrema was distinct, having a relatively sparse capillary density that may indicate morphological specializations limiting blood-tissue communication in this subregion. There were no quantitative differences in capillary dimensions between DMN and three subnuclei of NTS. These studies add to extant evidence that the dorsal vagal complex is differentiated for specific functions. Area postrema, especially, has topographical diversity in its capillary organization that likely corresponds to complex roles in neuroendocrine, autonomic, and chemosensory mechanisms. 相似文献
144.
Theoretical analysis of two models of hepatic drug clearance revealed that one powerful discriminator between them is the effect of changes of hepatic blood flow on either the emergent drug concentration or the availability of a highly extracted compound when operating under linear conditions. Lidocaine (extraction ratio 0.997) was employed in the discriminatory studies. The behavior of this drug under linear conditions (input lidocaine concentrations < 5 mg/ liter) to changes in hepatic blood flow rate (10–16 ml/min per liver) was examined in the perfused rat liver in situpreparation. The steady-state output lidocaine concentration in the blood leaving the liver was predicted better by a well-stirred model than by a parallel tube model. As anticipated, the clearance of a poorly extracted compound, antipyrine (extraction ratio 0.08),was unaltered by changes in hepatic blood flow. These experimental findings, and the data from the literature, point to the acceptance of the well-stirred model, which describes the liver as a well-stirred compartment with the drug in the hepatic venous blood being in equilibrium with that in the liver.Supported in part by National Institutes of Health Grant GM 16496 and the Patent Fund, Graduate Division, University of California, San Francisco.Abstracted in part from a dissertation submitted by K. Sandy Pang to the Graduate Division, University of California, San Francisco, California, in partial fulfillment of the Doctor of Philosophy degree requirements. 相似文献
145.
目的评价经尿道前列腺汽化(TUVP)和开放性手术对老年前列腺增生(BPH)患者术后性功能的影响.方法分别统计分析经尿道前列腺汽化组(TUVP组)、耻骨上经膀胱前列腺切除组(SPP组)和耻骨后保留尿道前列腺切除组(Madigan组)术后6个月、1 2个月勃起障碍(ED)与逆行射精(RE)的发生率.结果术后6个月ED的发生率在TUVP组(n=52)、SPP组(n=46)、Madigan组(n=32)分别为1 3.4%(7/52)、1 5.2%(7/46)、1 2.5%(4/32),术后12个月ED的发生率分别为11.5%(6/52)、1 5.2%(7/46)、1 2.5%(4/32),术后6个月、1 2个月RE的发生率在TUVP组、SPP组、Madigan组分别为46.2%(24/5 2)、39.1%(1 8/46)、9.3%(3/32).结论TUVP与传统开放性手术SPP及Madigan手术相比较对勃起障碍的影响无统计学差异(p>0.05),但逆行射精的发生率较Madigan手术组高,提示对术后射精功能有较大影响. 相似文献
146.
目的描述并分析传染性非典型肺炎的临床表现及心肌酶学改变。方法采集并分析了23例传染性非典型肺炎患者的临床表现及心肌酶学资料,分析死亡组及存活组出现心肌酶升高的比例的差异。结果患者具有肺炎症状体征,还出现心肌酶的升高。CKMB升高的比例存活组为44.4%,死亡组为80.0%,LDH1升高的比例存活组为22.2%,死亡组为80.0%。心肌酶升高的比例死亡组高于存活组,差异具有显著性意义。结论传染性非典型肺炎存在心肌损伤。 相似文献
147.
反义技术是近20年来发展的一种全新的药物设计方法。本文就近几年来反义寡核苷酸在化学修饰方面,包括骨架修饰、糖环修饰、碱基修饰等的最新发展进行了综述。 相似文献
148.
TGF-β和IGF表达异常与滋养层相关疾病关系的研究 总被引:1,自引:0,他引:1
目的:探讨转化生长因子(TGF-β)和胰岛素样生长因子(IGF)等与滋养层侵入调节密切相关的细胞因子在胎盘绒毛组织中的表达,及与葡萄胎、先兆子痫等滋养层细胞相关妊娠疾病病理机制的关系。方法:采用半定量逆转录多聚酶链反应(RT-PCR)检测方法,分别以正常早孕绒毛和正常足月(自然分娩或剖宫产)胎盘绒毛组织为对照,观察葡萄胎组织与先兆子痫足月胎盘绒毛组织中TGF-β和IGF的表达。结果:5种胎盘绒毛组织中均可检测到IGF-I mRNA的表达,且先兆子痫足月胎盘绒毛组织中IGF-I的表达量明显低于正常足月胎盘绒毛组织,而葡萄胎组织中IGF-I的表达略高于正常早孕绒毛。在3种足月胎盘绒毛组织中可检测到IGF-ⅡmRNA的表达,但相互之间无明显差异。葡萄胎组织中IGF-Ⅱ的表达低于早孕绒毛。5种胎盘绒毛组织中均有TGF-β3的表达,而TGF-β1和TGF-β2的表达并未检测到。在表达量上,葡萄胎组织中TGF-β3的表达明显高于正常早孕绒毛组织,先兆子痫胎盘绒毛组织中TGF-β3的表达强于足月自然分娩的正常胎盘绒毛组织,而剖宫产胎盘绒毛组织中,TGF-β3的表达亦相对较强。结论:TGF-β3和IGF-I在胎盘绒毛组织中的表达变化,可能和葡萄胎、先兆子痫等与滋养层密切相关的妊娠疾病的发生有关。 相似文献
149.
150.
目的 减少外周静脉化疗引起的静脉炎及药物外渗性损伤。方法 对46例锁骨下静脉置管化疗病人进行了护理观察。结果 接受锁骨下静脉置管的患者均完成了3周期化疗,导管保留时间最长为186天,无并发症发生。结论 应用中心静脉导管,一次置管可完成多程化疗,治疗方便,尤其适用于多程化疗及恶液质病人的支持治疗。 相似文献