亚胺培南或美罗培南联合利福平降低不动杆菌防耐药突变浓度的体外研究

目的在体外探讨亚胺培南(IMP)和美罗培南(MER)单用及其分别与利福平(RFP)联用对不动杆菌的防耐药突变浓度(MPC)的影响,为防止细菌耐药的产生提供理论依据。方法采用琼脂二倍稀释法,测定IMP或MER与RFP在体外单独以及联合应用的最低抑菌浓度(MIC)、计算部分抑菌浓度(FIC)指数。用肉汤法富集浓度为1010CFU/ml不动杆菌,采用琼脂平板二倍稀释法测定IMP和MER单药以及分别与RFP联用时对16株临床分离不动杆菌的MPC,并计算相应的选择指数(SI)。结果 IMP或MER分别与RFP联合应用后均以无关作用为主,未见拮抗作用,存在一定比例协同作用。IMP和MER单用对上述16株不动杆菌的SI均为16～128;分别与RFP联合使用SI均下降为1～32,联合用药较单独用药SI下降2～32倍。结论 IMP或MER分别与RFP联合使用均可降低其单用对不动杆菌的MPC,缩小MSW,防止耐药突变菌的产生。     

不同补铁方式治疗维持性血液透析患者肾性贫血42例

目的 观察口服补铁与静脉补铁两种方式对维持性血液透析患者肾性贫血的疗效.方法 选取维持性血液透析患者42例,随机分为两组,每组21例,对照组采用重组人促红细胞生成素+口服补充铁剂(力蜚能),治疗组(Ⅱ组)采用重组人促红细胞生成素+静脉补充铁剂(蔗糖铁).两组均行常规血液透析,2次/周,使用重组人促红细胞生成素治疗,试验时间均为12周.结果 与治疗前相比,治疗后两组患者的血红蛋白、红细胞比积、铁蛋白、转铁蛋白饱和度水平均有升高(P<0.05);治疗后各指标治疗组与对照组比较,均有统计学意义(P<0.05).结论 补铁能有效改善维持性血液透析患者的贫血状态,静脉补铁优于1:7服补铁.     

核磁共振法定量测定氢溴酸东莨菪碱的绝对含量

目的:建立测定氢溴酸东莨菪碱绝对含量的核磁共振定量法(简称QNMR)。方法:采用Avance DRX 500型核磁共振谱仪,zg30脉冲序列在恒温25℃下获取1H NMR谱。以对苯二酚为内标,同时测定了氢溴酸东莨菪碱及未知杂质(乙醇)的含量。结果:分别以δ2.63及δ2.82氢溴酸东莨菪碱中的峰及对苯二酚的δ6.63的单峰作为定量峰,含量分别为91.56%与91.50%;分别以δ3.47及δ1.02乙醇中的峰及对苯二酚的δ6.63的单峰作为定量峰,含量分别为3.86%与3.80%。重复性试验的RSD为0.25%(n=5)。结论:采用核磁定量的方法,准确快捷的测定了氢溴酸东莨菪碱的绝对含量,并同时对其中的未知杂质进行了定性与定量,是对标准物质绝对含量测定的一种良好的补充方法。     

Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology

Exposure to childhood trauma may induce persistent changes in Hypothalamic-Pituitary-Adrenal (HPA)-axis functioning even in the absence of current psychopathology. Because previous studies did not systematically exclude subjects with lifetime psychiatric morbidity, prevalent psychopathology may have confounded the association. In this study we investigated whether women exposed to childhood trauma, but without a history of psychiatric disorders, show alterations in HPA-axis functioning. We included 10 women exposed to significant childhood trauma and 12 non-exposed women. All women were between 29 and 64 years old, mentally and physically healthy, and without current or lifetime psychopathology. HPA-axis functioning was assessed as 1) basal activity with salivary cortisol patterns over 8 time points on two consecutive sampling days and 2) plasma cortisol and adrenocorticotropic hormone (ACTH) reactivity over 7 time points after the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) challenge test. Basal salivary cortisol output did not differ between trauma-exposed compared to non-exposed women. Significantly blunted plasma cortisol and ACTH responses in response to dex/CRH administration were found in the trauma-exposed compared to the non-exposed women (F(1,20) = 5.08, p = 0.04 and F(1,20) = 5.23, p = 0.03 respectively). Adjusting for age, body mass index (BMI), oral contraceptive use, and menopausal status, somewhat weakened the associations for cortisol as well as ACTH (F(1,16) = 3.30, p = 0.09) and F(1,16) = 2.17, p = 0.16 respectively), but for cortisol absolute differences in point estimates were largely unaffected. Although basal cortisol patterns were similar in the two groups, exposure to childhood trauma seemed to be related to a blunted HPA-axis reactivity in women who were free of current or lifetime psychopathology.     

蔗糖铁注射液联合红细胞生成素治疗肾性贫血的临床观察

目的 观察蔗糖铁注射液联合红细胞生成素治疗伴有缺铁的维持性血液透析肾性贫血患者疗效及安全性.方法 选取尿毒症维持性血液透析患者46例,按随机数字表法分为治疗组(26例)和对照组(20例).治疗组采用静脉滴注蔗糖铁100 mg,每周2次,总量达1000 mg改为100 mg,每周1次;对照组采用口服乳酸亚铁0.2 g,每日3次.红细胞生成素的使用剂量和方法两组相同,总疗程均为10周.结果 经治疗后治疗组患者血红蛋白、红细胞压积、血清铁蛋白水平与对照组比较差异有统计学意义(P<0.05).结论 蔗糖铁联合红细胞生成素治疗肾性贫血疗效优于口服铁剂联合红细胞生成素治疗.不良反应发生率更低,可作为肾性贫血患者长期补铁的方法之一.     

Gender-specific association between iron status and the history of attempted suicide: implications for gender paradox of suicide behaviors

PURPOSE: Iron deficiency (ID) has been linked with high impulsivity, and an increased risk of ID was reported among suicide attempters. We hypothesized that poor iron status might be prevalent among suicide attempters, who have high impulsivity. METHODS: As a part of the third National Health and Nutrition Examination Survey (1988-1994), a set of iron indices were measured in 2598 men and 2975 women aged 17-39 years, who completed a mental disorder diagnostic interview. RESULTS: Using non-attempters as reference within each gender, we observed a gender-dependent association between poor iron status and the history of attempted suicide. For male attempters (n=74), the prevalence ratios (PR) of abnormal serum ferritin, serum iron and protoporphyrin were 18.3 (95%CI=3.3-101.7), 3.2 (1.1-9.4) and 5.4(1.8-15.6). In contrast, the PR of abnormal serum ferritin for female attempters (n=217) was 0.3 (0.1-0.6). The hematological indices did not differ significantly between attempters and non-attempters among either men or women. Compared with non-attempters, male attempters were prone to a higher odds [17.5 (4.2-72.4)] while female attempters to a lower odds [0.6 (0.3-1.1)] of ID. CONCLUSION: These data suggest new opportunities for exploring biological bases of gender paradox of suicidal behaviors and a novel way to enhance therapeutic and preventive interventions against suicide.     

不同给药方法补铁对肾性贫血维持性治疗的疗效比较

目的:通过比较静脉用蔗糖铁和口服琥珀酸亚铁(速力菲)在肾性贫血患者维持性补铁治疗中的疗效及不良反应,探讨对功能性缺铁的后续补铁途径、安全性和方法。方法:28例维持性血液透析患者随机分为蔗糖铁组和速力菲组。蔗糖铁组14例,蔗糖铁100mg静脉推注每周一次;速力菲组14例,口服琥珀酸亚铁200mg每日3次。两组患者均联合应用促红细胞生成素(EPO),治疗过程中根据患者病情调整EPO用量。结果:治疗4周后,蔗糖铁组Hb、Hct明显高于速力菲组(P<0.05);治疗8周后,蔗糖铁组Hb、Hct、SF和TSAT均明显高于速力菲组(P<0.05);治疗12周后速力菲组SF和TSAT较前明显下降(P<0.05);而蔗糖铁组TSAT在维持性治疗12周后较前亦有所下降(P<0.05)。各组Ret与用药前均无明显差异(P>0.05)。速力菲组在治疗后期为了达到Hb和Hct目标值逐渐增加EPO用量,而蔗糖铁组在治疗过程中随着Hb和Hct的升高却减少了EPO用量。不良反应发生率蔗糖铁组低于速力菲组(P<0.05)。结论:在血透患者贫血的维持性治疗中,静脉注射蔗糖铁较口服速力菲能更有效并安全地维持血透病人的Hb水平及相对稳定体内的铁储...     

Screening of a polar extract of Paeonia rockii: composition and antioxidant and antifungal activities

Ethnopharmacological relevance

The genus Paeonia (Paeoniaceae), is one of the most important source of crude drugs in traditional Chinese medicine and investigation on many species is large. Up to now studies on Paeonia rockii, one of the eight species recognized in the section Moutan, are very limited.

Aim of the study

This research aimed to investigate the composition of Paeonia rockii roots and to evaluate the in vitro free-radical scavenging and antifungal activities of a polar extract (PPR) and its major constituents.

Materials and methods

PPR was obtained from defatted dried roots of Paeonia rockii using MeOH as extraction solvent. Its n-BuOH soluble portion (PPR-B) was purified by Sephadex LH-20 followed by RP-HPLC to give nineteen compounds belonging to the classes polyphenols, monoterpenes and triterpenes. Their structure were spectrally characterized (UV, 1D and 2D NMR, MS). The polyphenols content of PPR and PPR-B was examined by the Folin-Ciocalteau colorimetric assay and HPLC method. Both extracts (PPR and PPR-B) and their major constituents were tested for the free-radical scavenging activity by DPPH-test, and for the antifungal activity by three methods (micro-broth dilution method, XTT assay and Candida albicans morphological analysis).

Results

5-Butylhydroxy-γ-lactone (1), and ethyl-arabinopyranoside (2) have been isolated for the first time as naturally occurring compounds and taxifolin (3) was reported for the first time in Paeonia spp. Nine polyphenols, four monoterpenes and three triterpenes were also identified. Both the extracts PPR and PPR-B had high polyphenol content, and high concentration of gallic acid derivatives and paeoniflorin, chemotaxonomic characteristic markers of the genus. PPR, gallic acid and methyl-gallate displayed high potency in scavenging free-radicals (DPPH test, EC₅₀ 13.3, 1.2, 1.9 μg/ml, respectively). Both the extracts and gallic acid individually showed an interesting antifungal property (MIC₅₀ at 24 h 25, 0.9 and 30 μg/ml, respectively) and notably, a combination of paeoniflorin/gallic acid (MIC₅₀ = 0.5 + 20 μg/ml, respectively) was more active than the single compound in inhibiting Candida growth.

Conclusion

The polar methanolic extract (PPR), its n-BuOH soluble fraction and constituents of Paeonia rockii were extensively investigated. Both extracts and some of their compounds have the ability to scavenge free-radicals and to inhibit Candida albicans growth.     

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.