生草乌及配伍诃子的整合TK-TD模型研究

目的:应用整合的毒物代谢动力学(TK)-毒物效应动力学(TD)模型作为一种新的定量框架来评估生草乌引起的异常心率(HR)合并QT间期变化.初步应用于探讨草乌诃子1∶1、1∶3、3∶1配伍后的TK-TD拟合,进一步研究诃子草乌配伍减毒存效可能的机制.方法:建立TK-TD结构模型和原假设H0:Σ=S,采用Amos 24...     

Association of Pre- and Post-Donation Renal Function with Midterm Estimated Glomerular Filtration Rate in Living Kidney Donors: A Retrospective Study

PurposeThe estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR_6m) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to investigate the incidence of eGFR_6m <60 mL/min/1.73 m² (eGFR_6m <60) and identify the risk factors that can predict the occurrence of eGFR_6m <60 in living kidney donors.Materials and MethodsLiving kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR_6m <60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR_6m <60 occurrence were determined using the Youden index.ResultsThe eGFR_6m <60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2_pre) (≥0.39 mg/dL) increased the risk of eGFR_6m <60. The addition of ΔCr2_pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR_6m <60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 [95% confidence interval (CI), 0.863–0.908] vs. 0.862 (95% CI, 0.838–0.887), p<0.001}.ConclusionThe incidence of eGFR_6m <60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2_pre were associated with the occurrence of eGFR_6m <60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2_pre showed the highest predictive power for eGFR_6m <60.     

Comparison of the effects of 2-deoxyglucose and immobilization on secretion and synthesis rate of catecholamines in the adrenal gland: a microdialysis study in conscious rats

Using microdialysis, extracellular 3,4-dihydroxyphenylalanine (DOPA), noradrenaline (NA) and adrenaline (AD) concentrations in the adrenal gland were monitored in conscious rats during and after 60 min of immobilization (IMM) as well as after injection of 500 mg kg^-1 2-deoxyglucose (2-DG). IMM produced a rapid and transient increase in secretion of AD (20-fold), NA (13-fold) and DOPA (3.6-fold). This was accompanied by an increase in blood pressure (+ 18 mmHg) and heart rate (- 146 b. p.m.). Repeated exposure to IMM (daily 60 min, for 5 days) had no influence on either catecholamine secretion of haemodynamic profiles, indicating the lack of habituation to stressful conditions. Unlike IMM, the stress of 2-DG-induced centralneuroglucopenia stimulated the release of AD without affecting NA secretion. AD levels peaked (5.1-fold increase) 4&60 min after 2-DG injection and then slowly declined. 2-DG induced no changes in blood pressure but reduced the heart rate (-48 b. p.m.). In separate experiments, steady-state dialysate DOPA levels, reached during continuous infusion of decarboxylase inhibitor NSD 1015 into adrenal gland tissue through the dialysis probe, served as an index of adrenomedullary tyrosine hydroxylase (TH) activity. IMM evoked a marked increase in TH activity (DOPA formation increased 2.7-fold), which remained elevated 60 min after the cessation of stress when AD and NA secretion had already fallen to baseline. After 2-DG, despite significant hormonal response, adrenal TH activity was unchanged. These results give clear evidence that IMM and 2-DG-induced neuroglucopenia may be considered as two different types of stressful stimuli.     

计数时间窗位置对SPECT测定肾小球滤过率的影响

目的 观察计数时间窗位置对SPECT测定肾小球滤过率(GFR)的影响。 方法 以231名北京地区健康居民为研究对象,分别采用双血浆法和^99mTc-DTPA肾动态显像法测定GFR(GFR_dt和GFR_Gates)。在以血流灌注相峰值点时间(峰时)为新时间原点的时间-计数率曲线上依次移动时间窗,于25个时间点上提取计数,并分别计算各点上的GFR_Gates。分析不同药物累积相峰时GFR_Gates与GFR_dt的相关性。 结果 ①左右肾脏血流灌注相峰时均值分别为(19.69±5.20)s和(20.29±5.19)s,基本呈正态分布。②肾滤过累积相峰时均值为(166.19±50.22)s,呈偏态分布,频数峰为132 s。③时间窗位于累积相峰值区时GFR_Gates达到最大,在峰值两侧,GFR_Gates均减小。④时间窗位于累积相峰值左侧上升区时,GFR_Gates与GFR_dt的相关系数随时间窗后移而增加;当后移到时间窗内含有部分峰值区段时,相关系数增速变缓;随着时间窗与峰值区段的重叠增加,相关系数达拐点,随后开始减小。 结论 在以肾血流灌注相峰时为原点的时间-计数率曲线上,提取86~145 s时间窗计数,可获得受时间影响较小的GFR。     

高龄心力衰竭患者静息心率与心功能预后的相关性分析

目的探讨高龄心力衰竭患者入院时静息心率与其心功能预后的相关性。方法统计79例高龄慢性心力衰竭(CHF)患者,在循证医学标准治疗的基础上,对其入院时的静息心率与其出院时及随访后的心功能及预后进行相关性分析。结果高龄组(≥80岁)入院时的静息心率与出院时的疗效(相关系数-0.385;P=0.000)、随访疗效(相关系数-0.351;P=0.002)显著负相关;与总死亡率(相关系数0.247;P=0.028)显著正相关;而本研究中老年组(<80岁)相关性不明显。总体样本分析显示:全组CHF患者入院时的静息心率与出院时的疗效(相关系数-0.163;P=0.017)、随访疗效(相关系数-0.161;P=0.019)呈负相关;与总死亡率(相关系数0.162;P=0.018)显著正相关。结论老年心力衰竭患者尤其是高龄老人心力衰竭患者的静息心率越快,其治疗效果越差,死亡率越高。     

Effects of ambient particulate matter on peak expiratory flow rates and respiratory symptoms of asthmatics during Asian dust periods in Korea

OBJECTIVE: Dust generating events frequently produce ambient dust particles that are less than 10 microm in diameter, and these have been linked to adverse effects in the general population. However, the evidence linking these particles to adverse effects on the airways of asthmatic individuals is limited. The objective of this study was to investigate the possible adverse effects of Asian dust events on the respiratory functions and symptoms of subjects with bronchial asthma. METHODOLOGY: From March to June 2002, individuals were enrolled who had been diagnosed as having asthma by bronchial challenge or by their bronchodilator response. The patients were divided into three groups according to asthma severity: mild, moderate and severe. Patients with other major disease states were excluded. Patients completed twice-daily diaries monitoring PEF, respiratory symptoms, and daily activities. The daily and hourly mean levels of particulate matter <10 microm in diameter (PM(10)), as well as nitrogen dioxide (NO(2)), sulphur dioxide (SO(2)), ozone (O(3)) and carbon monoxide (CO) were measured at 10 monitoring sites in Incheon, Korea. RESULTS: Dust events occurred 14 times during the study period. On dusty days there were increased levels of PM(10), decreased levels of NO(2) and SO(2), and no change in the CO levels, compared to the levels on control days. An increase in PM(10) concentration was associated with increases in PEF variability of >20% (P<0.05), more night-time symptoms (P<0.05), and a decrease in the mean PEF (P<0.05), calculated by longitudinal data analysis. In contrast, there was no association between the PM(10) levels and bronchodilator inhaler use or daytime respiratory symptoms. Using a general additive Poisson regression model, a borderline association was noted between PM(10) and respiratory symptoms, with a relative risk of 1.05 (95% confidence interval (CI), 0.99--1.17). There was no association between the PM(10) concentrations and PEF measurements, with PEF variability of >20% between the morning and evening values and a relative risk of 1.05 (95% CI, 0.89--1.24) in all subjects. CONCLUSIONS: This study provides evidence that Asian dust events are impacting on the respiratory symptoms of subjects with bronchial asthma, and ambient air pollution, particularly elevated PM(10), might be one of the aggravating factors.