Subcutaneous injection pain with C.E.R.A., a continuous erythropoietin receptor activator,compared with darbepoetin alfa

ABSTRACT

Objective: This study assessed injection site pain following subcutaneous (SC) administration with a continuous erythropoietin receptor activator (C.E.R.A.), compared with darbepoetin alfa in healthy adults.

Methods: In a randomized, placebo-controlled, single-centre, single-blind, three-way crossover study, subjects received one of six treatment sequences (ABC/ACB/BAC/BCA/CBA/CAB) involving SC injection of (A) C.E.R.A. 50?μg, (B) darbepoetin alfa 50?μg, or (C) placebo on days 1, 29, and 57. An initial pilot phase (n = 12) was used to determine the sample size for the confirmatory phase (n = 72), and data were combined for the final analysis (n = 84).

Main outcome measures: The primary endpoint was pain on the 100?mm visual analog scale (VAS) immediately after dosing. Secondary endpoints included VAS at 1 hour after dosing and pain on the six-point verbal rating scale (VRS) immediately and at 1 hour after dosing.

Results: C.E.R.A. was associated with significantly less pain immediately after SC injection compared with darbepoetin alfa: least squares mean VAS 21.5 (95% confidence interval [CI]: 17.5, 25.5) versus 33.4 (95% CI: 28.4, 38.4) (?p < 0.0001). Incidence of pain on the VRS was lower with C.E.R.A. compared with darbepoetin alfa immediately after dosing (?p < 0.0001). One hour after administration, most subjects had no VRS pain. A study limitation is the small sample size and the findings need to be confirmed in a large trial of chronic kidney disease patients.

Conclusions: SC injection with C.E.R.A. is significantly less painful than SC darbepoetin alfa in healthy adults. Treatment of anemia in chronic kidney disease with SC injection of C.E.R.A. may provide a lower pain burden compared with darbepoetin alfa.     

C.E.R.A.: pharmacodynamics,pharmacokinetics and efficacy in patients with chronic kidney disease

C.E.R.A., a continuous erythropoietin receptor activator, has been developed for the treatment of anaemia in patients with chronic kidney disease. Compared with other erythropoiesis-stimulating agents, C.E.R.A. has a unique pharmacological profile, including a longer elimination half-life and slower clearance rate. This allows C.E.R.A. to be administered at extended intervals up to once every month. Phase III clinical trials have shown that C.E.R.A. once every 2 weeks corrects anaemia in erythropoiesis-stimulating agent-naive patients who are on or are not on dialysis, whereas once-monthly C.E.R.A. maintains stable haemoglobin levels when patients are directly converted from more frequent epoetin or darbepoetin alfa administration. C.E.R.A. is well tolerated. This review summarises clinical data on C.E.R.A. and discusses the potential effect of this novel agent on clinical practice.     

A high-throughput test to detect C.E.R.A. doping in blood

C.E.R.A., a continuous erythropoietin receptor activator, is a new third-generation erythropoiesis-stimulating agent (ESA) that has recently been linked with abuse in endurance sports. In order to combat this new form of doping, we examined an enzyme-linked immunosorbent assay (ELISA) designed to detect the presence of C.E.R.A. in serum samples. The performance of the assay was evaluated using a pilot excretion study that involved six subjects receiving C.E.R.A. Validation data demonstrated an excellent reproducibility and ensured the applicability of the assay for anti-doping purposes. To maximize the chances of detecting the drug in serum samples, we propose the use of this specific ELISA test as a high-throughput screening method, combined with a classic isoelectric focusing test as a confirmatory assay. This strategy should make C.E.R.A. abuse relatively easy to detect, thereby preventing the future use of this drug as a doping agent.     

Men and Women Who Attend Al-Anon: Gender Differences in Reasons for Attendance,Health Status and Personal Functioning,and Drinker Characteristics

Although Al-Anon Family Groups (Al-Anon) is the most common source of help for people concerned about someone else's drinking, only 16% of members are men. To identify gender differences, we compared demographics, reasons for attendance, health status, and personal functioning, and drinker characteristics of 174 men and women attending Al-Anon. Men and women were similar in most areas; however, some key differences emerged. Men reported better overall mental health than women, and described some differing concerns and drinker characteristics. With this information, healthcare providers may facilitate men's participation in Al-Anon by addressing their unique concerns and possible barriers to attendance.     

正相HPLC法测定雷公藤药材及其制剂中雷公藤酯甲的含量

目的：建立正相高效液相色谱法对雷公藤药材和雷公藤多苷片中雷公藤酯甲的含量测定方法。方法：采用Alltima Silica色谱柱。流动相：正己烷-异丙醇（95：5）。采用蒸发光散射检测器，漂移管温度：70℃，气流速：1．8L／min。结果：雷公藤酯甲在0．64～3．2μg范围内线性关系良好（r=0．9998），平均回收率为97．98%，RSD=4．31％（n=5）。结论：本方法简便，灵敏，准确，重现性好，可用于雷公藤药材及其制剂的含量测定和质量控制。     

伤寒、甲、乙、丙型副伤寒沙门菌多重荧光PCR方法的评估及临床应用

目的建立和评估多重荧光PCR方法快速鉴定伤寒、甲、乙、丙型副伤寒沙门菌的方法,并应用于临床血培养样品的检测。方法收集留取医院的可疑伤寒患者的血培养标本,用多重实时荧光PCR法和传统分离培养法同时进行分离鉴定,分析比较双盲实验结果,评价多重实时荧光PCR方法的灵敏度、特异度等检测性能指标。结果共检测临床样本538例,多重荧光PCR法检出阳性218例,比传统培养法多检出6例;阴性320例,与传统培养法一致。以传统检测方法为金标准,多重荧光PCR方法的灵敏度为100%,特异度为98.2%。结论建立的多重荧光PCR检测方法操作简便,可快速、特异、灵敏地检测出伤寒、甲、乙、丙型副伤寒沙门菌,可以应用于临床标本的早期快速分型诊断,提升重大传染病的应急处置能力和监测能力。     

交流示波极谱滴定在药物分析中的应用——Ⅱ.用镉滴定二巯基丁二酸钠

In NH₄OH—NH₄Cl buffer solution, disodium dimercaptosuccinate can be directly titrated with standard aqueous solution of CdI₂, using the disappearance of the incision of disodiurn dimercaptosuccinate as the end point. This method is simple and rapid and superior to the official method. The result of determination is in agreement with that of official method.     

The effects of dose, route, and repeated dosing on the disposition and kinetics of tetrabromobisphenol A in male F-344 rats.

Studies were conducted to characterize the metabolic and dispositional fate of (14)C-tetrabromobisphenol A (TBBPA)-a commonly used brominated flame retardant, in male Fischer-344 rats. The percent of dose eliminated as total radioactivity in feces at 72 h following three different single oral doses (2, 20, or 200 mg/kg) of (14)C-TBBPA was 90% or greater for all doses. Most of the dose was eliminated in the first 24 h. At 72 h after administration of the highest dose, the amounts of (14)C found in the tissues were minimal (0.2-0.9%). With repeated daily oral doses (20 mg/kg) for 5 or 10 days, the cumulative percent dose eliminated in the feces was 85.1+/-2.8 and 97.9+/-1.1, respectively. In all studies radioactivity recovered in urine was minimal, <2%. Repeated dosing did not lead to retention in tissues. Following iv administration, feces was also the major route of elimination. Following iv administration of TBBPA, the radiolabel found in the blood decreased rapidly and could be described by a biexponential equation, consistent with a two-compartment model. The key calculated kinetic parameters are terminal elimination half-life (t(1/2)beta)=82 min; area under the blood concentration-time curve from time 0 to infinity (AUC)=1440 mug x min/ml; and apparent clearance (CL)=2.44 ml/min. Although readily absorbed from the gut, systemic bioavailability of TBBPA is low (<2%). It is extensively extracted and metabolized by the liver and the metabolites (glucuronides) exported into the bile. About 50% of an oral dose (20 mg/kg) was found in the bile within 2 h. This extensive extraction and metabolism by the liver greatly limits exposure of internal tissues to TBBPA following oral exposures.     

A randomized controlled trial of Structural Ecosystems Therapy for HIV medication adherence and substance abuse relapse prevention

Background

Substance abuse in women with HIV/AIDS overshadows other priorities, including health care. Substance abuse may cause women to avoid health care systems and not adhere to their medication regimen.

Methods

A randomized controlled trial tested the efficacy of Structural Ecosystems Therapy (SET) relative to a psychoeducational Health Group (HG) in 126 HIV+ women in recovery. SET, a 4-month intervention, focused on building family support for relapse prevention and HIV medication adherence. Over 12-month follow-up, women were assessed for drug use and medication adherence every 2 months; CD4 T-cell count and HIV viral load were assessed every 4 months.

Results

Levels of drug use did not differ by condition. There was a significant difference in curvature of the rates of change in drug use with SET increasing and then decreasing and HG decreasing and then increasing. Women in SET were more likely to increase substance abuse services in response to relapse and separate from drug using household members than were women in HG. These two changes explained the decline in drug use observed within SET between 6 and 12 months. SET showed declines in medication adherence but increases in CD4 T-cell count relative to HG. The increase in CD4 T-cell count in SET was related to increasing proportions of women in SET taking antiretroviral medications.

Conclusion

The results of the trial were mixed. Women in SET did not show better drug use or medication adherence outcomes, but did show improvement in CD4 T-cell count and theoretical mechanisms of action on drug relapse.     

Evaluation of Antimicrobial Activity of Some Endemic Verbascum., Sideritis., and Stachys. Species from Turkey

Abstract

Methanol extracts obtained from endemic Verbascum pseudoholotrichum. Hub.-Mor., Verbascum cymigerum. Hub.-Mor., Verbascum cholorostegium. Bornm. & Murb., Verbascum linguifolium. Hub.-Mor., Verbascum pellitum. Hub.-Mor., Sideritis brevidens. P.H. Davis, Sideritis cilicica. Boiss. & Bal., Sideritis vuralii. H. Duman & Baser, Stachys aleurites. Boiss. & Heldr., and Stachys pinardii. Boiss. have been investigated for their antimicrobial activity. Antimicrobial activity was determined with Escherichia coli. ATCC 11230, Staphylococcus aureus. ATCC 6538P, Klebsiella pneumoniae. UC57, Pseudomonas aeruginosa. ATCC 27853, Proteus vulgaris. ATCC 8427, Bacillus cereus. ATCC 7064, Mycobacterium smegmatis. CCM 2067, Listeria monocytogenes. ATCC 15313, Micrococcus luteus. CCM 169, Candida albicans. ATCC 10231, Rhodotorula rubra. DSM 70403, and Kluyveromyces fragilis. ATCC 8608 by the disk diffusion method. Verbascum. L. extracts had strong antimicrobial activity against Gram-positive bacteria and yeast cultures. The extracts of Stachys. L. were effective only against bacteria. The extracts of Sideritis. L. demonstrated antimicrobial effects against the bacteria and the yeast cultures used in this study.     

NEURAI NETWORKS IN Q.S.A.R STUDIES:Estimation and prediction of The anticonvuisant activities of thirty-eight cinnamamides

Neural Networks(NN) Method was used to study The structure-activity relationship(S.A.R) of cinnamamide derivatives. The relationship between biological activity(P.C) and thosc parameters such as the partition coefficients(log p octanol/water) of the compounds Hammett δ constants and steric parameter(M.R) of cinnamamides were investigated by the modified backpropagation (MBP) Neural Netwoks. The biological activity of cinnamamides derivatives thus estimated and predicted 100% fit with MLP Method. The resalts obtined by the developed MBPNN Method Seem to be better than those by Multivariate linear regression(MLR). The neural Networks Method might therefore be regarded as an excellent and effective chemometric Modelling technique for estim ating and predicting biological cativity on basic Q.S.A.R studies.     

美国高等教育专业认证的出现及其背景

美国高等教育专业认证是美国高等教育认证体系中的重要组成部分，它保证了高等院校专业教育的质量和学术水平并促进其提高。美国高等教育专业认证出现于20世纪初期，以当时美国高等教育的数量增长、专业学院的发展、院校认证逐渐完善等为背景，并形成了自己的特点。     

NEURAI NETWORKS IN Q. S. A. R STUDIES:Estimation and prediction of The anticonvuisant activities of thirty─eight cinnamamides

ltheory1.lprincipleoftheModifiedback-pr0pagation(MBP){'j1.2AIgorithmInthispapper.UsesM.B.PalgorithSupervisedLearn-ing.LeaningSignalC0nsists0ffeed-forwardandbackpropa-gati0n(Fig3).Alqorithm:lISigmoidfunctiony(x)=deIConnectionW',andQ,NInputtraimlngpattenSampleX,.andd:,,ftCalclate(coant)rea1ityValue0foatputY.VregulateWeightW,,W,,(l l)=W,,(l) V8.,01j-outputlayer:6'=y,(lwy,)(d,wy,)v.j-hiddenlayer:3j=O,(l-O,)=3kWjkkkisj(n l)layern0de.bN$O###At4oMBackto4StepContinuediterationuntilerr…     

泰山沙参中水溶性多糖的提取工艺研究及其含量测定

目的优化泰山沙参中水溶性多糖的提取工艺并测定其含量。方法以多糖的提取含量为评价指标,采用回流提取法,通过正交实验研究不同浓度乙醇、提取次数、提取时间、料液比对多糖提取量的影响,并筛选出最佳提取条件。结果80%浓度的乙醇、料液比1:20、提取1次、提取4h为泰山沙参中多糖的最佳提取条件;多糖的含量为22.04%,平均回收率为99.38%,RSD为5.09%。结论本方法简便、迅速,泰山沙参中多糖含量丰富,为泰山沙参在临床用药中的安全性和有效性提供科学依据。