Antihypertensive effect of total flavone extracts from Puerariae Radix

Aim of the study

To evaluate the antihypertensive effect of total flavone extracts from Puerariae Radix (FEPR). To explore the hemodynamic profiles and pertinent mechanism of the extracts.

Materials and methods

Acute and chronic antihypertensive effects of FEPR were examined in spontaneous hypertensive rats (SHRs) and reno-hypertensive rats (two kidneys one clip model, 2K1C). Anesthetized dogs were used to evaluate the hemodynamic effects of FEPR. The determination of angiotensin converting enzyme (ACE) activity in vitro and plasma renin activity (PRA) and endothelin (ET) in vivo were used to study the pilot mechanism of FEPR. Moreover, the toxicity study of FEPR was evaluated.

Results

FEPR (100, 200 and 400 mg/kg, i.v.) notably reduced the blood pressure of SHRs in a short time period. A two-week administration of FEPR (45, 90 and 180 mg/kg, p.o.) decreased the blood pressure of both 2K1C rats and SHRs. The results of hemodynamic study in anesthetized dogs showed that, left ventricular end systolic pressure and left ventricular dP/dt_max had shown no significant difference between FEPR-treated dogs and those from the control group, while the cerebral blood flow increased significantly in FEPR-treated groups. FEPR significantly inhibited the ACE activities in vitro dose dependently, and inhibited the PRA in vivo, while the content of ET showed no difference in the FEPR treated group comparing with the control group.

Conclusions

FEPR shows significantly blood pressure lowering and cerebral vascular resistance (CVR) decreasing effect, which can partly be explained by the involvement of the Renin-Angiotensin-System (RAS).     

Inhibition of T-cell activation and proliferation by mycophenolic acid in patients awaiting liver transplantation: PK/PD relationships

Mycophenolic acid (MPA) plasma concentrations were reported to be associated with a decrease in T-cell proliferation, and in both IL-2 α-chain (CD25) and transferin receptor (CD71) expression. The aim of this study was to confirm, quantify and model these PK/PD relationships.Full profiles of MPA plasma concentrations, T-cell proliferation, intracytoplasmic IL-2 and TNF-α expression, and both CD71 and CD25 expression were collected over the 12 h after dosing in 10 patients on the waiting list for liver transplantation. Data were analyzed using NONMEM^®.Both CD25 and CD71 expression and T cell proliferation clearly decreased (median of decrease from baseline 62%, 68% and 94%, respectively) with increasing MPA concentrations, in contrast to IL-2 and TNF-α expression. The CD25 and CD71 baseline expression (E₀) and maximum effect (E_max) were correlated with the E₀ and E_max values of T-cell proliferation (r² = 0.509 and r² = 0.622, respectively). The CD25, CD71 expression and T-cell proliferation profiles were adequately fitted using a sigmoid inhibitory E_max model. Low estimated values (≤2 mg/L) for 50% inhibitory MPA concentrations were obtained. This study confirmed a transient MPA concentration-dependent decrease in T-cells expressing CD25 and CD71 and a strong reduction of T-cell proliferation and showed that CD25 and CD71 expression was correlated with T-cell proliferation.     

High incidence of iron depletion and restless leg syndrome (RLS) in regular blood donors: intravenous iron sucrose substitution more effective than oral iron

Background and objectives Iron depletion is common in regular blood donors. The objective of the study was to investigate the frequency and severity of iron depletion in regular blood donors and whether IV iron is more effective than oral to avoid iron depletion and symptoms thereof, especially restless legs syndrome (RLS). Method One hundred and twenty blood donors with at least five previous whole blood donations were randomized to receive either IV iron sucrose (Venofer^®, RenaPharma/Vifor, Uppsala, Sweden), 200 mg, or to 20 × 100 mg of oral iron sulphate (Duroferon^®, GlaxoSmithKline, Stockholm, Sweden), after each blood donation during 1 year. Iron status and RLS incidence and severity were investigated. Results Iron status was generally poor among regular blood donors, especially in women, with a high incidence of iron depletion (> 20%) and RLS (18%). The IV iron group increased storage iron to a greater extent than the oral iron group after 12 months (P = 0·0043). Female donors were more responsive to IV iron sucrose compared to oral iron sulphate, particularly female donors below 50 years of age. RLS severity scores were significantly lower in the IV iron group. The two treatments were safe. Conclusion Iron status is poor in regular blood donors, restless legs syndrome is common, and the routine iron supplementation is insufficient. IV iron sucrose substitutes iron loss in blood donors more efficiently compared with oral iron sulphate, especially in women. Iron substitution to blood donors should be individualized and based on P‐ferritin monitoring.     

安氏隐孢子虫卵囊分离纯化方法研究

目的 建立获取纯净的安氏隐孢子虫卵囊外培养模型。方法研究改进分离纯化安氏隐孢子虫卵囊的方法,采用蒸馏水稀释Sheather’s蔗糖溶液配制不同密度的蔗糖溶液,比较不同稀释比的Sheather’s蔗糖溶液漂浮卵囊的效果,并首次比较了蒸馏水和PBS稀释的Sheather’s蔗糖溶液分离纯化卵囊的活性,将两种方法分离纯化的卵囊37℃水浴1h进行脱囊率比较。结果2：1蔗糖溶液（2体积Sheather’s蔗糖溶液与1体积的蒸馏水）分离奶牛粪样中卵囊效果最好。漂浮三次即可获得大量卵囊,回收率为83．70％,三次漂浮的卵囊总数较Sheather’s蔗糖溶液高57．53％。蔗糖溶液多梯度密度纯化法纯化后的卵囊杂质较少,回收率为47．52％。蒸馏水稀释的蔗糖溶液分离纯化卵囊脱囊率为87．87％,PBS稀释的蔗糖溶液分离纯化卵囊的脱囊率为84．71％,差异无统计学意义P〉0.05）。结论2：1蔗糖溶液适用于分离安氏隐孢子虫卵囊,且用蒸馏水代替PBS稀释Sheather’s蔗糖溶分离纯化隐孢子虫卵囊其活性不受影响。可用于体外培养研究。     

蔗糖铁联合促红细胞生成素治疗老年糖尿病患者慢性心衰合并贫血

目的探讨蔗糖铁联合促红细胞生成素(EPO)治疗老年糖尿病患者慢性心功能不全(CHF)合并贫血的疗效和安全性。方法2006年1月-2008年8月,解放军第四一一医院肾内科共收治36例慢性心功能不全合并贫血老年糖尿病患者;其中男性21例,女性15例;年龄均>65岁,平均(74.2±5.8)岁;血红蛋白(Hb)均<120g/L。所有患者均静脉予以蔗糖铁(200mg/个月),皮下注射EPO(3000U/次,2次/周)治疗,共12个月。治疗前及治疗第6、12个月观测纽约心脏病协会(NYHA)心功能评分、左室射血分数(LVEF)、直视模拟标度尺(VAS)评分、Hb变化及不良反应发生情况并进行对比分析。结果到治疗第12个月,Hb从治疗前的(99.1±14.2)g/L上升至(128.0±12.5)g/L;NYHA分级从(3.9±1.3)级降至(2.7±0.4)级;LVEF从(31.6%±14.1%)上升至(41.0%±12.9%);VAS从(8.4±1.6)降至(2.6±1.9),以上各指标前后对比差异均有统计学意义(P<0.05)。治疗前后收缩压(SBP)、舒张压(DBP)、血肌酐(Scr)无明显改变。无药物不良反应及并发...     

卡马西平血清样品的稳定性考察

目的考察卡马西平血清样品不同保存条件对血清药物浓度的影响。方法取癫痫患者血清样品,在取血当时、室温（28±3）℃保存1d、2d、3d或冷藏（4±1）℃保存1d、3d、7d后,用荧光偏振免疫法（FPIA）测定血清卡马西平浓度并进行比较,考察其稳定性。结果室温保存1d、2d、3d或冰箱冷藏保存1d、3d、7d的血清测定结果均与取血当时测定结果无统计学差异。结论卡马西平血清样品在室温下可稳定保存三天、冷藏条件下可稳定保存七天。     

蔗糖铁对中度贫血的透析患者的治疗作用

目的（1）了解口服铁剂时肾脏替代治疗患者贫血情况;（2）静脉蔗糖铁治疗对中度贫血患者的治疗效果及副作用观察。方法我院透析中心规律透析的尿毒症患者134例,血液透析患者104例,腹膜透析30例。患者均常规叶酸及正规促红细胞生成素使用．统计口服铁剂时患者贫血情况。将中度贫血的部分患者行蔗糖铁静脉注射治疗,观察治疗前后患者血清铁、铁蛋白、血红蛋白、红细胞压积、肝功能等指标并观察蔗糖铁的临床副作用。结果134例肾脏替代治疗患者中经口服铁剂HB达110g以上者占18％,轻度贫血占17％．中度贫血占44％。重度贫血占21％。中度贫血患者经静脉注射蔗糖铁治疗后血清铁、铁蛋白、血红蛋白（HB）、红细胞压积（HCT）较口服时均有明显升高。总有效率达88％。患者使用蔗糖铁过程中血压脉搏呼吸体温等生命体征无明显变化．肝功能无明显改变,无一例出现过敏反应等严重副作用。结论（1）肾脏替代治疗患者口服铁剂以中重度贫血为主．患者血红蛋白达标率低：（2）静脉用蔗糖铁治疗中度肾性贫血安全有效。     

Ghrelin is a physiological regulator of insulin release in pancreatic islets and glucose homeostasis

Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach as the endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R). Circulating ghrelin is produced predominantly in the oxyntic mucosa of stomach. Ghrelin potently stimulates GH release and feeding, and exhibits positive cardiovascular effects, suggesting a possible clinical application. Low plasma ghrelin levels are associated with elevated fasting insulin levels and insulin resistance, suggesting both physiological and pathophysiological roles for ghrelin in glucose metabolism. Here, we review the physiological role of ghrelin in the regulation of insulin release and glucose metabolism, and a potential therapeutic avenue to treat type 2 diabetes by manipulating ghrelin and/or its signaling. Ghrelin inhibits insulin release in mice, rats and humans. The signal transduction mechanisms of ghrelin in islet β-cells are distinct from those utilized in GH-releasing and/or GHS-R-expressing cells. Ghrelin is expressed in pancreatic islets and released into pancreatic microcirculations. Pharmacological and genetic blockades of islet-derived ghrelin markedly augment glucose-induced insulin release in vitro. In high-fat diet-induced mildly obese mice, ghrelin-deficiency enhances insulin release and prevents impaired glucose tolerance. Thus, manipulation of insulinostatic function of ghrelin — GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand, providing a potential therapeutic application to prevent type 2 diabetes.     

Concentrations and correlations for eight metals in human liver

This study was undertaken to determine concentrations for eight metals in human liver and investigate correlations among these metals as well as subject age. Autopsy specimens from 32 males, ranging from 38–88 years of age, were analyzed for calcium (Ca), cadmium (Cd), copper (Cu), iron (Fe), mercury (Hg), magnesium (Mg), lead (Pb), and zinc (Zn). Respective mean concentrations were 49.6, 2.1, 4.9, 318.7, 0.72, 135.2, 0.19, and 53.4 μg/g wet wt., and 209.2, 8.8, 20.6, 1342.2, 0.81, 569.4, 3.1 and 228.8 μg/g dry wt. Variables, including age and metal concentrations, were subjected to simple and multiple correlation analysis. Four metal pairs Zn-Cd, Fe-Pb, Mg-Hg, and Mg-Zn gave significant positive correlations. Age and Cu correlated negatively. Multiple correlations were found for Mg with Hg and Zn, Pb with Fe and age, Pb with Fe and Cu, and Zn with Mg and Cd. Results are discussed within the context of relevant literature.     

Prevalence and concentrations of new designer stimulants,synthetic opioids,benzodiazepines, and hallucinogens in postmortem hair samples: A 13-year retrospective study

Hair samples are frequently analyzed in order to characterize consumption patterns of drugs. However, the interpretation of new psychoactive substance (NPS) findings in hair remains difficult because of lacking data for comparison. In this study, selected postmortem hair samples (n = 1203) from 2008 to 2020 were reanalyzed for synthetic cathinones, piperazines, phenethylamines, hallucinogens, benzodiazepines and opioids to evaluate prevalence data and concentration ranges. Hair samples were extracted using a two-step extraction procedure and analyzed using a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Overall NPSs were detected in 381 cases (31.6%). Many cases were tested positive for more than one NPS in the same time span. A variety of NPS with a large range of concentrations was observed. For better comparability and interpretation of positive cases in routine work, quantitation data for 13 NPS were calculated as percentiles. The most frequently detected NPS in this study were N-ethylamphetamine, α-pyrrolidinovalerophenone, mephedrone, benzedrone, metamfepramone, and 4-fluoroamphetamine. In conclusion, a high prevalence of these drugs was observed from postmortem hair samples. The results show a growing use of many different NPSs by mainly young drug-using adults. Consequently, NPS screening procedures should be included in forensic toxicology. Our quantitative data may support other toxicologists in their assessment of NPS hair concentrations.