慢性阻塞性肺疾病分级与血清白蛋白水平相关性研究

目的 了解慢性阻塞性肺疾病(COPD)患者血清白蛋白水平与病情严重度分级的相关性.方法 120例COPD患者按病情严重度分级分为Ⅰ、Ⅱ、Ⅲ、Ⅳ四级,收集患者空腹血清白蛋白,采用微型营养评定表(MNA)、体质量指数(BMI)、血清白蛋白3个营养指标分别对患者进行营养评定,并分析比较.结果 Ⅰ级COPD患者营养良好者、轻度营养不良者和低白蛋白血症者人数分别为34例、6例、1例,Ⅱ级分别为8例、9例、2例,Ⅲ级分别为18例、12例、4例,Ⅳ级分别为7例、13例、6例,营养不良发生率分别为17.1％、57.9％、47.1％和73.1％;COPD严重度分级与血清白蛋白的相关指数为0.251 (P ＜0.05);COPD患者Ⅰ级与Ⅱ、Ⅲ、Ⅳ级间血清白蛋白的相关指数分别为0.273、0.331、0.324(均P＜0.05).结论 COPD严重度分级与血清白蛋白的下降具有相关性,随COPD级别增加血清白蛋白下降越明显.     

The serum level approach to individualization of drug dosage

Summary The importance of individualizing the dosage of potent drugs in order to maximize their therapeutic effectiveness and safety is generally accepted. Whenever possible the dosage of a drug should be titrated directly in each patient against the intensity of its therapeutic or toxic actions. Unfortunately, for many drugs convenient clinical yardsticks of the intensity of their pharmacologic effects are lacking. Determination of the serum concentration of such compounds can help to guide adjustment of dosage during their therapeutic use. By measuring the serum level of drugs one bypasses the largest source of individual differences in doseeffect relationships — the pharmacokinetic variation between subjects. However, the relationship between the serum concentration of a drug and the intensity of its pharmacodynamic action is influenced by many other factors, which must always be considered in interpretation of serum levels. Therapeutic decisions should never be based solely on the serum concentration of a compound, nor can such measurements ever substitute for careful medical observation and judgement.     

Development of transdermal system containing nicotine by using sustained release dosage design

This study was carried out to develop a membrane-controlled transdermal formulation (TF) of nicotine by using sustained release dosage design (SRDD). TFs were prepared with polyethylene membrane as a rate-controlling barrier; a carbomer was used as the gel reservoir with or without propylene glycol (PG). The in vitro target flux (0.0535 mg cm(-2) h(-1)) was calculated according to SRDD calculations. Nicotine permeation through the membrane with or without transfer adhesive was also studied using diffusion cells. Nicotine permeated through membrane (without adhesive) with a flux of 0.0555 mg cm(-2) h(-1) and this value was similar to that of the in vitro target flux. The release from the TFs and from a commercial product (Nicotinell, 52.5 mg 30 cm(-2)) was studied using the FDA paddle method. The nicotine amount was increased from 22.7 to 56.5 mg in gel reservoir, and a plateau was reached beyond 45.4 mg of drug; the system attained the maximum thermodynamic activity with 56.5 mg of nicotine. The release rate from TFs (without adhesive layer) containing PG in the reservoir was very similar to the target release rate (1.07 mg h(-1)). The fluxes of nicotine from Nicotinell and TF containing 45.4 mg of nicotine were close to the in vitro target release rate.     

慢性心力衰竭病人血清肾上腺髓质素2、尿酸水平的变化及意义

目的：本研究探讨了新发现的小分子生物活性肽肾上腺髓质素2和尿酸在慢性心力衰竭（CHF）患者血清中的变化及可能机制。方法： 分为4组：正常对照组,心功能Ⅱ级组、Ⅲ级组、Ⅳ级组, 血清肾上腺髓质素2的观察每组20例,血清尿酸的观察每组40例,临床诊断采用美国纽约心脏病学会（N YHA） 心功能分级标准。采用酶联免疫吸附（ELISA）法测定血清肾上腺髓质素2,采用全自动生化分析仪测定尿酸。结果：（1） 心功能Ⅱ级、Ⅲ级、Ⅳ级组血清肾上腺髓质素2水平明显高于正常对照组（P〈0.01）,心功能Ⅲ级组明显高于Ⅱ级组,心功能Ⅳ级组明显低于Ⅲ级组（P〈0.01）,心功能Ⅱ级组与Ⅳ级组比较无显著性（P〉0.05）;（2）血清尿酸含量随着心功能级别的增高而逐渐升高。结论：肾上腺髓质素2可能参与了心力衰竭病理生理过程及对心功能的调节。尿酸含量能反映心力衰竭程度,可以作为心功能恶化的预测指标。     

川芎嗪对慢性心力衰竭患者血清NT-proBNP水平影响的研究

目的探讨川芎嗪对慢性心力衰竭(CHF)患者氨基末端脑钠肽前体(NT-proBNP)水平的影响。方法将52例CHF患者随机分为治疗组27例和对照组25例。对照组仅予以常规治疗;治疗组在对照组治疗基础上加用川芎嗪治疗,疗程均为14d。2组治疗前、后分别采血检测并比较血清NT-proBNP水平。结果 2组治疗后NT-proBNP水平低于本组治疗前,且治疗组低于对照组,差异均有统计学意义(P<0.05和P<0.01)。结论 CHF患者血清NT-proBNP水平明显增高,在常规治疗基础上加用川芎嗪治疗可进一步降低心力衰竭患者血清NT-proBNP水平。     

Effects of serum from patients with chronic renal failure on rat hepatic cytochrome P450

1. In humans, chronic renal failure (CRF) is associated with decreased hepatic drug metabolism, particularly that mediated by the cytochrome P450 (P450). The mechanisms remain poorly understood. The present study aimed to investigate the effects of the serum of patients with CRF on liver P450, and to evaluate whether renal replacement therapies (dialysis or transplantation) impede the inhibition of CRF serum on P450. 2. Rat hepatocytes were incubated for 24 h with serum from patients with severe CRF and from controls to measure (1) P450 level, (2) protein expression and mRNA levels of P450 isoforms and (3) metabolic activities of CYP3A and CYP1A. Similar experiments were performed with serum of patients once on chronic hemodialysis and after kidney transplantation. 3. In rat hepatocytes incubated for 24 h with serum from patients with CRF, P450 level and protein expression, as well as mRNA levels of P450 isoforms (CYP1A2, 2C6, 2C11, 2D1/2D2, 3A2 and 4A1/4A3), were decreased by more than 45% (P<0.001) compared to control serum, while the levels of CYP2E1 were not modified. CYP3A and CYP1A activities were decreased by 51 and 59% (P<0.001), respectively. The inhibitory effect of serum obtained from patients before first dialysis was similar after 1 or 6 months on chronic hemodialysis but was lost after successful kidney transplantation. In CRF serum, the fraction containing proteins between 10 and 15 kDa decreases P450. 4. Human uremic serum contains mediator(s) that decreases rat hepatic P450 activity and expression secondary to reduced gene expression. The inhibitory effect of serum persists even after initiation of dialysis, but disappears after normalization of renal function following kidney transplantation.     

培哚普利对慢性充血性心力衰竭病人血清地高辛浓度和肾功能的影响

目的 :探讨培哚普利对慢性充血性心力衰竭 (CCHF)病人血清地高辛和肾功能的影响。方法 :32例心功能Ⅲ～Ⅳ级的CCHF病人给地高辛0 .2 5mg ,po ,qd× 1wk ,继而地高辛剂量改为 0 .12 5～ 0 .2 5mg ,po ,qd× 4wk ;给地高辛wk 1末后开始给培哚普利 2～ 4mg ,po ,qd× 4wk。结果 :培哚普利治疗前、治疗wk 2末和wk 4末其血清地高辛浓度分别为 ( 1.14±s 0 .13) ,( 1.2 3± 0 .0 6)和 ( 1.2 3±0 .12 )nmol·L- 1,治疗前后差异无显著意义 (P >0 .0 5) ;血钾上升 ,但在正常范围 ;血尿素氮、肌酐、尿酸和 β2 微球蛋白均略有下降 ,纠正肌酐清除率至wk 4末有显著升高 (P <0 .0 1)。结论 :培哚普利能改善CCHF病人的肾功能 ,不增加地高辛的浓度     

慢性乙型肝炎患者血清TGF-β1水平与肝纤维化的关系

目的:探讨慢性乙型肝炎(CHB)患者血消转化生长因子-β1(TGF-β1)在肝纤维化不同阶段的表达情况及其对肝纤维化诊断的价值.方法:采用酶联免疫吸附法(ELASA)检测32例CHB患者血清TGF-β1水平,放射免疫法(RIA)检测血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原氮基端肽(PⅢNP)、Ⅳ型胶原(CⅣ)水平,32例患者均进行肝组织活硷,分析TGF-β1与肝组织纤维化程度分期和炎症活动度分级的关系以及与HA、LN、pⅢNP、CⅣ四项指标的相关性.结果:(1)CHB患者TGF-β1水平明显高于正常对照组(P<0.01),随肝纤维化程度的加重而升高(P<0.01),TGF-β1变化趋势与HA、LN、pⅢNP、CⅣ均呈正相关(P<0.01).(2)按炎症活动度(G)分组,TGF-β1在G1～G4组水平明显高于G0组(P<0.01),但组间两两比较差异无显著性(P>0.05).结论:血清TGF-β1表达水平与CHB患者肝纤维化程度密切相关,不受肝组织炎症程度的影响,在早期肝纤维化的敏感性高于HA、LN、PⅢNp、CⅣ.可作为早期肝纤维化     

Disposition of azapropazone in chronic renal and hepatic failure

Summary The disposition of azapropazone 600 mg i.v. was investigated in 6 healthy subjects, 13 patients with cirrhosis and 8 patients with renal failure. In healthy subjects the elimination half-life was 12.2±2.1 h (mean ± SD), the volume of distribution 10.6±3.31 and the total clearance was 597±135 ml·h^–1. Renal clearance accounted for about 62% of the total clearance. The free fraction of azapropazone in the plasma was 0.0045±0.0006. The patients with cirrhosis were divided into Group I with modest and Group II with severe impairment of liver function. In Group I the total clearance of azapropazone was not significantly different from that in healthy subjects. There was a 2.5-fold increase in its free fraction in plasma, and a reduction in the free drug clearance to about half that in healthy subjects. In Group II patients total clearance was reduced to about 20% of normal. This was partly due to reduced non-renal clearance but mainly to impaired renal clearance of azapropazone. The diminished renal clearance was considered at least in part to represent a drug-induced impairment of renal function, as there was a concomitant reduction in creatinine clearance. The free fraction of azapropazone in the plasma was markedly enhanced (>0.02), and simultaneously, free drug clearance was drastically reduced, to about 2% of that in healthy subjects. In patients with renal failure the total clearance was diminished, depending on the degree of impairment of kidney function. Anephric patients were estimated to have about one third of the total clearance in normal subjects. The free fraction of azapropazone in the plasma was increased in 4 of the 8 patients. It is concluded that patients with cirrhosis and modest impairment of liver function may require about half the normal dose of azapropazone, since free drug clearance is reduced by about 50%. Patients with severe impairment of liver function are expected to be highly susceptible to dose-related side effects, since the pronounced increase in the free fraction in plasma and the decreases in renal and non-renal clearance lead to marked reduction in free drug clearance and so to accumulation of free drug in the body. In patients with renal failure the dose of azapropazone should be reduced according to the degree of impairment of kidney function and plasma protein binding of the drug.     

新型冠状病毒肺炎患者血清白蛋白水平与患者病情的相关分析

目的:探讨新型冠状病毒肺炎（coronavirus disease 2019,COVID-19）患者血清白蛋白水平与患者病情的关系。方法:回顾性分析2020年1月23日至3月5日期间福建省福州肺科医院出院的70例COVID-19患者临床资料,按血清白蛋白水平将患者分为正常白蛋白组（43例）和低蛋白血症组（27例）。统计...     

清肾颗粒对腺嘌呤所致慢性肾功能衰竭大鼠血清甲状旁腺素的影响

目的观察清肾颗粒对慢性肾功能衰竭大鼠血清甲状旁腺素水平的干预作用。方法将腺嘌呤摄入量按每日300 mg.kg-1体重给予,制作慢性肾功能衰竭动物模型。用清肾颗粒(每ml含生药0.5 g)治疗,用保肾康(6 g.L-1)作对照。检测大鼠血清甲状旁腺素、肌酐、尿素氮和24 h尿蛋白定量及肾脏病理改变。结果造模各组大鼠上述指标和正常组相比明显增加(P<0.001)。治疗后上述指标和模型组相比明显减少(P<0.001)。结论清肾颗粒可显著降低CRF大鼠血清上述指标,其效果优于保肾康。