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.

Evaluation of Rational Use of Antiretrovirals before the Dolutegravir Transition in Kinshasa, Democratic Republic of Congo

Background: The ultimate goal of AntiRetroViral Treatments (ART) is to achieve complete immune restoration and lasting viral suppression in the infected patient. In order to ensure the efficacy, safety and accessibility of antiretroviral drugs (ARVs), it is recommended that they should be prescribed according to national guidelines;which are evolving with the various recommendations of the World Health Organization (WHO) and the arrival of newer, more effective and safer molecules. Objective: The objective of this study was to assess the rational use of Antiretrovirals in patients treated in Kinshasa before the use of Dolutegravir within the national program in order to assess the correct use of these molecules. Methods: This work is a descriptive cross-sectional study to assess the rational use of first-line ARVs among People Living with HIV (PLHIV) in different Centers of Treatment (ATCs) in Kinshasa before the introduction of Dolutegravir. The records of patients on ARVs were randomly and rationally selected in 12 different ATCs for HIV in Kinshasa according to three centers per district in the period from June to September 2018. Information on use and consumption of ARVs, compliance with guidelines, change of therapeutic combination as well as their reasons were consulted for the present study. Results: 507 files of PLHIV were collected in the various ATCs. 274 (54.1%) were from female patients. The most represented age group was 26 to 35 years with 192 patients (37.9%). The mean duration of first-line treatment for all patients included was 16.30 ± 5.85 months. The most widely used combination of ARVs overall was TDF + 3TC + EFV at 45.4%. 305 (60.2%) PLHIV kept the same first-line treatment molecule throughout the treatment period with an average treatment duration of 12.9 ± 2.77 months. The most common combination found in this population was TDF + 3TC + EFV (69.2%). 202 (39.8%) PLHIV changed treatment molecule yet respecting the first-line combinations. The average duration of treatment for those who changed molecules was 21.43 ± 7.25 months. Before the change, 112 (55.5%) of these patients were using the ZDV + 3TC + EFV combination. After switching, 105 (52%) of the patients used the TDF + 3TC + NVP combination. The first reason for changing molecules was its unavailability (53.3%) in the ATCs. Conclusion: Although some banned molecules are still available in some treatment centers, the guidelines on first-line treatments are respected in different centers in Kinshasa.

Drug-induced liver injury:Is it somehow foreseeable?

The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.

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.

Three-dimensional bio-printing: A new frontier in oncology research

Current research in oncology deploys methods that rely principally on two-dimensional(2D) mono-cell cultures and animal models.Although these methodologies have led to significant advancement in the development of novel experimental therapeutic agents with promising anticancer activity in the laboratory, clinicians still struggle to manage cancer in the clinical setting.The disappointing translational success is attributable mainly to poor representation and recreation of the cancer microenvironment present in human neoplasia.Threedimensional(3D) bio-printed models could help to simulate this micro-environment, with recent bio-printing of live human cells demonstrating that effective in vitro replication is achievable.This literature review outlines up-to-date advancements and developments in the use of 3D bio-printed models currently being used in oncology research.These innovative advancements in 3D bio-printing open up a new frontier for oncology research and could herald an era of progressive clinical cancer therapeutics.

Serum Bcl-2 concentrations in overweight-obese subjects with nonalcoholic fatty liver disease

AIM： To shed some light on the relationship between anti-apoptotic serum Bcl-2 concentrations and metabolic status, anthropometric parameters, inflammation indi- ces, and non-alcoholic fatty liver disease severity were investigated in 43 young individuals with fatty liver （FL） and 41 with nonalcoholic steatohepatitis （NASH）. METHODS： Circulating levels of Bcl-2 were detected in 84 patients with ultrasonographic findings of ＂bright liver＂ and/or hyper-transaminasemia of unknown origin and/or increase in T-glutamyl-transpeptidase （T-GT） strictly in the absence of other acute or chronic liver disease, whose age was not advanced, who gave consent to liver biopsy and were then divided on the basis of the histological results into two groups （43 with FL and 41 with NASH）. Twenty lean subjects, apparently healthy and young, were chosen as controls.RESULTS： Serum Bcl-2 concentrations were significantly higher in the FL group than in the NASH group. Insulin resistance and γ-GT activity were significantly higher in NASH subjects. Apoptotic hepatocytes were significantly more numerous in NASH patients. NASH patients presented with larger spleens and augmented C-reactive protein （CRP） concentrations than healthy subjects. Steatosis grade at histology was similar in both NASH and FL populations. The number of apoptotic cells was significantly related to anti-apoptotic Bcl-2 protein values in FL patients. Bcl-2 serum levels positively correlated to body mass index （BMI） values （P ~ 0.0001） but not to age of the population. Triglycerides/HDL ratio correlated well to waist circumference in males （P = 0.0008）. γ-GT activity was associated with homeostatic metabolic assessment （HOMA） （P = 0.0003） and with serum ferritin （P = 0.02）. Bcl-2 concentrations were not related to either spleen size or CRP values. NASH patients pre- sented a weak negative correlation between Iobular inflammation and Bcl-2 levels. A prediction by low values of serum Bcl-2 towards a greater presence of metabolically unhealthy overweight/obese patients （MUOs） was evidenced. HOMA, BMI and uric acid, in that sequence, best predicted serum Bcl-2 concentrations. CONCLUSION： IvlUOs could be detected by Bcl-2 levels. By favoring the life span of hepatocytes, and enhancing triglyceride formation, the anti-apoptotic process inhibits free fatty acids toxicity in FL.

Spleen:A new role ffoorr an old player?

The spleen could be considered a neglected organ.To date,it has been deemed an ancillary organ in portal hypertension or an organ localization in lymphoproliferative diseases,even though it has had significant attention in infectious diseases for some time.Now,it is thought to be central in regulating the immune system,a metabolic asset and involved in endocrine function with regard to nonalcoholic fatty liver disease.The main mechanisms involved in this complex network will be critically discussed in this article.

老年人使用镇静催眠药、抗抑郁剂和苯二氮（艹卓）类药物显著增加跌倒风险

跌倒是一种常见的老年科综合征，在老年人中发生率较高，对生活质量和残疾有重大影响，多种因素导致发生跌倒的风险。药代动力学和药效学方面年龄相关性改变，以及健康逐渐衰退，使老年人尤其容易发生药物副作用，包括跌倒。如果危险因素可以容易地被识别、改变，并且最好能够被避免的话，那么这些危险因素在临床实践中的意义就最为重要。药物使用通常满足这些标准。

为规范处方行为开个处方——一些医学生并不具备熟练开处方的能力

每年的这个时候，新分配来的医生上岗了，老的担心又出现了——他们受过良好的培训了吗？特别令人担忧的是：他们在临床药物治疗和开处方方面是否受过合格的培训？我们认为培训未必合格。