AGNP精神科治疗药物监测共识指南：2011

治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从"强烈推荐"到"可能有用"的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的"治疗参考浓度范围"和"剂量相关参考浓度范围"呈现给大家。本共识指南引入了"实验室警戒浓度"的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中获益。

Exposure to ambient air particulate matter and non-alcoholic fatty liver disease

The present study was designed to alert the public opinion and policy makers on the supposed enhancing effects of exposure to ambient air particulate matter with aerodynamic diameters < 2.5 mm (PM 2.5 ) on non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries. For far too long literature data have been fixated on pulmonary diseases and/or cardiovascular disease, as consequence of particulate exposure, ignoring the link between the explosion of obesity with related syndromes such as NAFLD and air pollution, the worst characteristics of nowadays civilization. In order to delineate a clear picture of this major health problem, further studies should investigate whether and at what extent cigarette smoking and exposure to ambient air PM 2.5 impact the natural history of patients with obesity-related NAFLD,i.e. , development of non alcoholic steatohepatitis, disease characterized by a worse prognosis due its progression towards fibrosis and hepatocarcinoma.

Development of an HPLC–UV assay method for the simultaneous quantification of nine antiretroviral agents in the plasma of HIV-infected patients

A new method using high-performance liquid chromatography coupled with ultra violet detection(HPLC–UV)was developed and validated for the simultaneous quantification of atazanavir,dolutegravir,darunavir,efavirenz,etravirine lopinavir,raltegravir,rilpivirine and tipranavir in human plasma.For the first time we reported here the development and validation of an HPLC–UV assay to quantify the frequently administered 9antiretroviral compounds including dolutegravir and rilpivirine.A simple solid phase extraction procedure was applied to 500 μL aliquots of plasma.The chromatographic separation of the drugs and internal standard(quinoxaline) was achieved with a gradient of acetonitrile and sodium acetate buffer on a C_(18) reverse-phase analytical column with a 25 min analytical run time.Calibration curves were optimised according to the therapeutic range of drug concentrations in patients,and the coefficient of determination(r^2) was higher than0.99 for all analytes.Mean intraday and interday precisions(RSD) for all compounds were less than 15.0%,and the mean accuracy(% deviation from nominal concentration) was also found to be less than 15.0%.Extraction recovery range was between 80% and 120% for all drugs analysed.The solid phase extraction and HPLC–UV method enable a specific,sensitive,and reliable simultaneous determination of nine antiretroviral agents in plasma.Good extraction efficiency and low limit of HPLC–UV quantification make this method suitable for use in clinical trials and therapeutic drug monitoring.

POTENTIATION OF BOANMYCIN ANTITUMOR ACTIVITY BY CHEMOTACTIC PEPTIDE

Objective: Chemotactic peptide may interfere with the process of tumor growth, invasion and metastasis by activating and attracting leukocytes containing macrophages. fMLP (CHO-Met-II e-Phe) is one of the chemotactic peptides. Boanmycin (BAM), a single A6 component from the bleomycin complex, is effective against a panel of cancers in clinical trials. This study was set to investigate the antitumor activity of BAM in combination with chemotactic peptide fMLP. Methods: Cytotoxicity of BAM and fMLP to cancer cells was determined by MTT assay. Therapeutic effect was evaluated by using the model of subcutaneously transplanted hepatoma 22 in mice. Results were judged as that a CDI less than 0.85 was considered as synergism and one less than 0.75 as significant synergism. Results: BAM and fMLP showed no synergism in cytotoxicity to cancer cells. In all in vivo experiments, fMLP was administered peritumorally at the dose of 1 mg/mouse; no significant inhibition by fMLP alone on the growth of hepatoma 22 was found. Different settings of BAM and fMLP combination included: (1) BAM, administered peritumorally×3, was started 24 h after tumor inoculation. BAM (0.5 mg/kg) alone and BAM-fMLP combination inhibited the growth of hepatoma 22 by 26.6% and 64.7%, respectively (P<0.05, CDI=0.36) on day 13. (2) BAM, administered ip×3, was started 24 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 14, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed the growth of tumor by 11% and 70.6%, respectively (P<0.05), CDI=0.42). (3) BAM, administered ip×3, was started 96 h after tumor inoculation. The growth of tumor in BAM (1 mg/kg) group was faster than that in BAM-fMLP combination group. On day 13, BAM (1 mg/kg) alone and BAM-fMLP combination suppressed tumor growth by 38.2% and 77.1%, respectively (P<0.05, CDI=0.51). As shown in all in vivo experimental settings, antitumor effect of BAM in combination with fMLP was much more potent than that of BAM alone. Conclusion: This experiment shows that chemotactic peptide fMLP may enhance the antitumor effect of BAM, which indicates that chemotactic modulation may play a positive role in cancer chemotherapy.

A review on the International Patient Decision Aid Standards （IPDAS）： history, development and application

患者决策辅助工具（Patient Decision Aid，PtDA）是基于循证医学与叙事医学理念与方法，在临床实践中促成医患共同决策的重要手段，也是在精准医疗背景下，承载个体化诊疗信息的重要媒介。随着全球医疗卫生保健领域患者决策辅助工具的研究兴趣与工具数量激增，建立统一的质量评价标准，规范其研制流程与后效评价势在必行。本文旨在介绍国际患者决策辅助工具标准（International Patient Decision Aid Standards，IPDAS）的主要内容、发展历程及其应用，为该评价标准在国内的应用提供参考。

异丙酚促进睡眠剥夺恢复

背景:睡眠和全麻在神经生理上某些相似性,使全麻恢复睡眠剥夺后的睡眠平衡成为可能.然而,麻醉对睡眠平衡的作用尚不清楚.为了证实全麻可促使睡眠剥夺后的恢复,作者让大鼠持续24 h不能睡眠后,给以6 h的睡眠或异丙酚麻醉,并比较了两种不同处理后睡眠的特点.

神经精神药理学治疗药物监测共识指南:2017版

治疗药物监测(Therapeutic Drug Monitoring,TDM)通过定量测定和解释血药浓度以优化药物治疗。TDM着眼于药代动力学的个体差异,使个体化药物治疗成为可能。在精神病学和神经病学领域中,有可能明显获益于TDM的主要患者群体包括少年儿童、孕妇、老年患者、智障患者、药物滥用者、涉法精神病患者、已知或怀疑药代动力学异常的患者以及合并躯体疾病影响药代动力学的患者。常规剂量下治疗无效,用药依从性难以判断,药物耐受性不佳,以及可能存在药代动力学方面的药物-药物相互作用等情况都是治疗药物监测的典型指征。然而,只有将TDM充分整合到临床治疗过程中,才能发挥其优化药物治疗的潜在优势。为了向临床医生和实验室提供有效的TDM信息,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了第一版《精神科治疗药物监测指南》。2011年进行了更新之后,现在再次更新。遵循新版指南,可能会改善神经精神药物治疗的效果,加快很多患者的康复,并降低医疗费用。

神经精神药理学治疗药物监测共识指南:2017版

2.2剂量相关参考浓度范围对于TDM结果的解释,除了治疗参考浓度范围外还有另一个浓度范围,即所谓的剂量相关参考浓度范围。治疗参考浓度范围的应用是药效动力学问题,而剂量相关参考浓度范围的运用是药代动力学问题。后者比较的是测得的药物浓度与理论预期药物浓度范围。参照药代动力学研究,优先考虑没有合并用药或药物基因组异常的患者群(“正常”患者),在日维持剂量(Daily maintenance dose,D m)、给药间隔(Dosing interval,d i)、总清除率(Total clearance,CL)和生物利用度(Bioavailability,F)已知情况下,某种药物在某个“正常”患者体内的预期平均稳态浓度(Average steady-state concentration,C av)可通过下面的公式计算。

ADENOSINE REDUCES INTRAOCULAR PRESSURE AND INCREASES OPTIC NERVE HEAD AND CHOROIDAL BLOOD FLOW IN HEALTHY HUMANS

Purpose: There is evidence from a variety of animal studies that the adenosine system plays a role in the control of intraocular pressure (IOP) and ocular blood flow. However, human data on the effect of adenosine on IOP, choroidal and optic nerve blood flow are lacking. Methods: We investigated the effect of stepwise increasing doses of adenosine (10, 20, 40μg/kg/min, 30 min-

南非成人社区获得性肺炎管理指南

在南非,由于社区获得性肺炎(community-acquired pneumonia,CAP)的疾病负担增加以及抗菌药物耐药率(antimicrobial resistance,AMR)升高,需要规范抗菌药物处方的标准,因而改善CAP患者的管理水平尤其重要。本指南旨在为临床医生提供CAP患者管理的推荐性建议。对临床医生来说,本次更新纳入了CAP患者管理的重要进展和争议。

EFFECT OF NIMODIPINE ON OCULAR BLOOD FLOW AND COLOR CONTRAST SENSITIVITY IN PATIENTS WITH NOR-MAL TENSION GLAUCOMA

Background: To investigate the effects of oral nimodipine on ocular hemodynamic parameters and color contrast sensitivity in patients with normal tension glaucoma (NTG). Methods: The study was performed in 14 consecutive NTG patients in a randomized placebo controlled double-masked cross-over design. The effects or oral nimodipine (60 mg) or placebo on ocular and systemic hemodynamic parameters and color contrast

Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats:Molecular study

BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.

Review on the management of cardiovascular risk factors in the elderly

Cardiovascular risk factors(CVRF)are very prevalent in the elderly population and in addition to predisposing to cardiovascular disease they are related to functional decline,which limits the quality of life in this population.The objective of this work is to offer a review of the current evidence in the management of CVRF in the elderly population.The search strategy was executed in PubMed,Clinicalstrials.org and Embase,to search for clinical trials,observational cohort or cross-sectional studies,reviews,and clinical practice guidelines focused or including elderly population.The results provided were refined after reading the title and abstract,as well as elimination of duplicates,and were finally identified and assessed following the GRADE methodology.A total of 136 studies were obtained for all predefined risk factors,such as sedentary lifestyle,smoking,obesity and metabolic syndrome,hypertension,diabetes mellitus,dyslipidemia and alcohol.We described the results of the studies identified and assessed according to their methodological quality in different recommendation sections:diagnostic and prevention,intervention,or treatment in the elderly population.As the main limitation to the results of this review,there is the lack of quality studies whose target population is elderly patients.This issue limits the recommendations that can be made in this population.Due to this reason,comprehensive geriatric assessment seems the best tool currently available to implement the most appropriate treatment plans based on the baseline situation and comorbidity of each elderly patient.

The Effect of Balanced Hypocaloric Diet on the Anthropometric and Basic Metabolic Indicators in Infertile Women with Gluteofemoral Obesity

Purpose: To evaluate the effect of balanced hypocaloric diet therapy on the anthropometric and basic metabolic indicators in obese women with infertility. Methods: The follow up interventional clinical study included 23 infertile women in reproductive age with grade I gluteofemoral obesity. All patients have prescribed a balanced hypocaloric diet (1200 kcal/day), underwent exercise and behavioral therapy. Before and after 12-month treatment, an anthropometric study was conducted, determining the level of metabolic and hormonal indicators. Results: The total final number of study participants was 20 patients. A decrease in body weight was achieved in 87% of patients from 4 to 24 kg, on the average, by 10.58 ± 5.70 kg, there was also a decrease in BMI from 32.53 ± 1.40 to 28.55 ± 2.50 kg/m2 (p 0.001). The decrease in body weight was accompanied by a statistically significant decrease in leptin levels (p 0.001), E1 (p = 0.049), E2 (p = 0.032), fasting glucose (p 0.001), HOMA-IR (p = 0.002), cholesterol (p < 0.001), TG (p = 0.004), LDL-C (p = 0.001), atherogenic index of plasma (p <0.001) and an increase in progesterone levels (p = 0.030). Ovulatory menstrual cycles were resumed in all women (p = 0.007) and pregnancy occurred within a year in 1 patient. Conclusion: The implementation of a hypocaloric diet for 12 months in infertile women with first-degree obesity helps to normalize metabolic and hormonal indicators, reduces body weight and restores ovulatory menstrual cycle in all patients.

Selected Aspects of Camel Immune System and Immune Responses

The camel economy is of considerable importance for arid countries. In the last decade, studies about camel immune system and immune responses have recorded increasing interest. However, drawing a comprehensive picture of the camel immune system remains far from reached. A major part of this review is to cover the studies of the primary and secondary immune organs and the markers of the camel immune cells and certain lymphoid tissues. At the same time, immune responses to different diseases and the nature of effective immunity were included, with an emphasis on the most important zoonotic diseases in camels such as MERS CoV;brucellosis. New findings on the diversity mechanisms of camel immunoglobulin genes were addressed. However, detail of the mechanism of MHC-restricted cellular immunity and the mechanism of B lymphocyte activation in camels await further attention. Interestingly, the gross and the histological structure of the lymphoid tissues of the camel’s thymus, tonsils, and peyer’s patches have indicated significant differences from other animals in terms of structure and function. The most peculiar CD expression, such as LPAM-I, MAdCAM-1 and CX3CR1, in certain camel cells and tissues refers to possible extraordinary mechanisms of immune hemostasis in camel in comparison to other ruminants. The widely applied immunodiagnostic techniques to control camel diseases and to assist in improving the camel resistance were considered. Extensive studies of the camel immune system were greatly hampered by lack of specific reagents to camel markers and low funds in the field of camel immunology.

Validation of a liquid chromatographic method for the pharmaceutical quality control of products containing elacridar

Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein.Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs.Currently,a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted.This also necessitates the availability of an analytical method for its quality control.A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient.The analytical method was validated for linearity,accuracy,precision,selectivity,carry-over,stability of stock and reference solutions,stability of the final extract,stability-indicating capability and impurity testing.We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed.Therefore,sample solutions with elacridar must be protected from light.

Herlyn-Werner-Wunderlich Syndrome Presenting with Abdominal Pain: A Case Report

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital anomaly characterized by triad of uterus didelphys, obstructed hemi vagina, and ipsilateral renal agenesis. The most common presentation is abdominal pain, dysmenorrhea, and abdominal mass secondary to hemi-hematometrocolpos. We report an emergency presentation of this syndrome during the pandemic of COVID-19 in Qatif Central Hospital, Saudi Arabia, April 2020. An 11-year-old Saudi girl presented to the emergency room with three months history of cyclical lower abdominal pain. The pain was progressive, continuous and not relieved by analgesics. Abdominal examination revealed a tender abdominal mass mainly in the left iliac fossa, Ultrasound evaluation showed two uterine bodies. The left uterus was distended with complex fluid. Pelvic MRI findings consistent with Herlyn-Werner-Wunderlich (HWW) syndrome were found with uterine didelphys and left sided hematometra resulting from obstructed hemi-vagina and ipsilateral agenesis of the left kidney. Resection of the vaginal septum and drainage of hematometra was done. The patient recovered with normal cyclical menstruation. Cyclical or continuous lower abdominal pain with or without amenorrhea is the usual presentation of HWW syndrome during adolescence. Diagnosis is made by ultrasonography and MRI. Early diagnosis and accurate management can provide pain relief, prevent future complications, and preserve fertility.

Revaluation of Clopidogrel:Let the Data Speak for Themselves

Clopidogrel was believed to be superior to aspirin by the well-known CAPRIE trial.However,no other large clinical trials demonstrated the same results,but all focused on the combination use of clopidogrel with aspirin,and combination therapy in CREDO was called the 'Emperor’s New Clothes'.However,no one overturned the results of these clinical trials by quantitatively analyzing them.We reviewed ten large-scale clinical trials about clopidogrel.On the basis of results of CAPRIE,CREDO and CHARISMA trials,we re-estimated their minimal sample sizes and their powers by three well-established statistical methodologies.From the results of CAPRIE,we inferred that the minimal sample size should be 85 086 or 84 968 but its power was only 30.70%.A huge gap existed.The same was also true of CREDO and CHARISMA trials.Moreover,in CAPRIE trial,0 was included in the 95% confidence interval and 1 was included in the 95% confidence interval for the relative risk.There were some paradoxical data in CAPRIE trial.We are led to conclude that the results in CAPRIE,CREDO,and from the subgroup analysis in CHARISMA trials were questionable.These results failed to demonstrate that clopidogrel was superior to aspirin or that clopidogrel used in combination with aspirin was better than aspirin alone.The cost-effectiveness analyses by some previous studies were not reliable.