儿童用含麝香中成药存在问题分析

目的:通过研究儿童用含麝香中成药的药品标准,分析其存在的问题,为儿童用含麝香中成药的合理用药提出建议。方法:对《新编国家中成药》(第2版)中所收载的儿童用含麝香的中成药进行统计,针对其剂型、处方、用法用量等进行分析。结果与结论:儿童用含麝香中成药处方、剂型、用法用量等存在不同程度的问题,有必要对其进行再评价并统一规范完善药品标准的相应项目。     

Lefetamine‐derived designer drugs N‐ethyl‐1,2‐diphenylethylamine (NEDPA) and N‐iso‐propyl‐1,2‐diphenylethylamine (NPDPA): Metabolism and detectability in rat urine using GC‐MS,LC‐MSn and LC‐HR‐MS/MS

N‐Ethyl‐1,2‐diphenylethylamine (NEDPA) and N‐iso‐propyl‐1,2‐diphenylethylamine (NPDPA) are two designer drugs, which were confiscated in Germany in 2008. Lefetamine (N,N‐dimethyl‐1,2‐diphenylethylamine, also named L‐SPA), the pharmaceutical lead of these designer drugs, is a controlled substance in many countries. The aim of the present work was to study the phase I and phase II metabolism of these drugs in rats and to check for their detectability in urine using the authors’ standard urine screening approaches (SUSA). For the elucidation of the metabolism, rat urine samples were worked up with and without enzymatic cleavage, separated and analyzed by gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐high resolution‐tandem mass spectrometry (LC‐HR‐MS/MS). According to the identified metabolites, the following metabolic pathways for NEDPA and NPDPA could be proposed: N‐dealkylation, mono‐ and bis‐hydroxylation of the benzyl ring followed by methylation of one of the two hydroxy groups, combinations of these steps, hydroxylation of the phenyl ring after N‐dealkylation, glucuronidation and sulfation of all hydroxylated metabolites. Application of a 0.3 mg/kg BW dose of NEDPA or NPDPA, corresponding to a common lefetamine single dose, could be monitored in rat urine using the authors’ GC‐MS and LC‐MSⁿ SUSA. However, only the metabolites could be detected, namely N‐deethyl‐NEDPA, N‐deethyl‐hydroxy‐NEDPA, hydroxy‐NEDPA, and hydroxy‐methoxy‐NEDPA or N‐de‐iso‐propyl‐NPDPA, N‐de‐iso‐propyl‐hydroxy‐NPDPA, and hydroxy‐NPDPA. Assuming similar kinetics, an intake of these drugs should also be detectable in human urine. Copyright © 2014 John Wiley & Sons, Ltd.     

Electronic circular dichroism behavior of chiral Phthiobuzone

Phthiobuzone is a bis(thiosemicarbazone) derivative with a single chiral center which has been used as a racemate in the clinical treatment of herpes and trachoma diseases. In this study, its two enantiomers were prepared from chiral amino acids and their absolute configurations were investigated by electronic circular dichroism (ECD) combined with modern quantum-chemical calculations using time-dependent density functional theory. It was found that solvation changed both the conformational distribution and the ECD spectrum of each conformer. The theoretical ECD spectra of the two enantiomers were in good agreement with the experimentally determined spectra of the corresponding isomers in dimethyl sulfoxide. The ECD behavior of the bis(thiosemicarbazone) chromophore in a chiral environment is also discussed. Our results indicate that ECD spectroscopy may be a useful tool for the stereochemical evaluation of chiral drugs.Key words: Electronic circular dichroism, Chiral drugs, Absolute configuration, Time-dependent density functional theory     

Current status of COVID-19 treatment: An opinion review

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development. Several drugs have been used for the management of coronavirus disease 2019 (COVID-19), which has affected many hospitals and health centers worldwide. Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality, as there are very few published randomized clinical trials. Despite this, the literature offers some material for study and reflection. This opinion review attempts to address three burning questions on COVID-19 treatment options. (1) What kind of studies are currently published or ongoing in the treatment of patients with COVID-19? (2) What drugs are currently described in the literature as options of treatment for patients affected by the infection? And (3) Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy? By answering these questions, we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo, and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.     

Genetic polymorphisms in the Toll-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer

Background

Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.

Methods

A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR–RFLP and real-time PCR.

Results

Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 −260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20–10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41–0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).

Conclusions

Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.     

Internet Search and Krokodil in the Russian Federation: An Infoveillance Study

Background

Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States.

Objective

This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed.

Methods

First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries.

Results

In the 6 months preceding CCM sales restrictions, 21 of Russia''s 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study.

Conclusions

Illicit drug use data are generally regarded as difficult to obtain through traditional survey methods. Our analysis suggests it is plausible that Yandex search behavior served as a proxy for patterns of krokodil production and use during the date range we investigated. More generally, this study demonstrates the application of novel methods recently used by policy makers to both monitor illicit drug use and influence drug policy decision making.     

长期使用抗癫药物对发育期大鼠脑的影响

目的探讨长期使用抗癫药（AEDs）对发育期大鼠脑的影响,在细胞及分子水平上观察AEDs影响认知功能的机制。方法将生后7 d的Wistar大鼠234只任意分为13组：4种AEDs［苯巴比妥（PB）,丙戊酸（VPA）,拉莫三嗪（LTG）,托吡酯（TPM）］分别分为高、中、低剂量组和对照组,每组18只大鼠。PB 80、 40、20 mg·kg-1和VPA 200、100、50 mg·kg-1分别溶于超纯水腹腔注射每日1次共21 d,LTG 80、40、20 mg·kg-1和TPM 80、40、20 mg·kg-1分别溶于1％纤维素钠灌胃每日1次共21 d,对照组予相同体积1％纤维素钠灌胃每日1次共21 d。从第22天始每组6只大鼠断头取脑,用Annexin-V FITC/PI双标检测细胞凋亡,用实时定量PCR检测脑源性神经营养因子（BDNF）和神经营养物质-3（NT-3）mRNA的表达;余12只大鼠过量麻醉后灌注固定,分别用于BrdU染色和Timm's染色。 结果①4种AEDs均会造成幼鼠脑重减轻,其中VPA高、中、低剂量组大鼠脑重降低最明显,VPA高剂量组导致脑重降低15％。②4种AEDs均引起神经细胞凋亡的增加,其阈值分别为：PB 20 mg·kg-1, VPA 50mg·kg-1, LTG 80 mg·kg-1,TPM 40 mg·kg-1。③实时定量PCR结果显示,4种AEDs可导致海马区BDNF和NT-3 mRNA表达的减少,其阈值分别为PB 40 mg·kg-1、VPA 100 mg·kg-1、LTG 80 mg·kg-1、TPM 40 mg·kg-1。VPA和LTG低剂量组可引起海马齿状回和门区BrdU标记的细胞数增加。Timm's染色结果显示4种AEDs CA3区和颗粒细胞上层Timm评分与对照组比较差异均无统计学意义(P>0.05)。 结论长期使用AEDs会对发育期大脑造成损害,不同AEDs可引起大脑细胞凋亡增加和海马区神经营养物质表达减少,其阈值有所不同,这可能是造成认知损害的机制之一。VPA和LTG会造成神经发生增加,但不伴有明显的苔藓纤维发芽。     

An Overview on Biologic Medications and Their Possible Role in Apical Periodontitis

Introduction

Apical periodontitis (AP) is the expression of a deficient balance between infection and the host immune response.

Methods

If reducing the bacterial load from the root canal and preventing its reinfection may lead to clinical success, then the integrity of the nonspecific immune system has a relevant influence on the outcome of endodontic treatment.

Results

Compromised immune systems and/or genetic alterations of the host's response may as well play an important role on the development, progression, and healing of AP. Thus, immunomodulatory drugs might have the potential to influence both the severity of AP and the outcome of endodontic treatment. Biologic medications are a new class of drugs of monoclonal antibodies or fusion proteins that include fragments of a peculiar cytokine receptor. Specific inflammatory molecules or cells, such as tumor necrosis factor, interleukins, and T or B cells, are the selective targets of these drugs. They modulate the altered immune response and perform an important role in the short-term treatment of chronic inflammatory diseases such as rheumatoid arthritis, refractory Crohn disease, or ulcerative colitis. Despite the clinical positive outcomes and their widespread use, the consequences of administering biologic medications on the development of the dental diseases have not been adequately investigated.

Conclusions

The aim of this review was to give an overview of biologic medications, their composition, their mechanisms of action, and their possible implications on endodontic and other dental diseases.     

Perianesthesia Implications and Considerations for Drug-Induced QT Interval Prolongation

Prolongation of the QT interval can predispose patients to fatal arrhythmias such as torsade de pointes. While arrhythmias can occur spontaneously in patients with a genetic predisposition, drugs such as ondansetron and droperidol, which are frequently used in the perioperative period, have been implicated in the prolongation of the QT interval. As the list of medications that cause QT prolongation grows, anesthesia providers and perioperative nurses must be informed regarding the importance of the QT interval. This article reviews the physiology and measurement of the QT interval, the risk factors of QT prolongation, the mechanism of drug-induced QT prolongation, and perioperative considerations for patient care.