Investigation of thiol-disulphide balance in patients with acute urticaria and chronic spontaneous urticaria

Background: Thiol–disulphide balance plays a major role in health and diseases. This balance may be disrupted by various diseases. We aimed to determine status of the effect of thiol–disulphide balance in urticaria.

Objectives: We aimed to investigate the thiol–disulphide balance in patients with acute urticaria (AUP) and chronic spontaneous urticaria (CSU).

Methods: Study included 53 AUP and 47 healthy controls plus 57 patients with chronic spontaneous urticaria (CSUP) and 57 healthy controls. Levels of native thiols, disulphides and total thiols were evaluated in plasma using a new and automated spectrophotometric method. Ratios of disulphides/total thiols, disulphides/native thiols and native thiols/total thiols were calculated.

Results: For AU, there was no statistical difference compared to control group in levels of native thiols, disulphides and total thiols. For CSU, however, there was an increase in levels of native thiols, disulphides and total thiols and the ratio of thiol/disulphide in favour of disulphide.

Conclusion: Thiol–disulphide balance was not affected by AU but shifted towards to disulphide in CSU indicating the presence of oxidative stress (OS).     

Trusting and misleading. Parents’ and children’s communication and negotiation about alcohol as described by teenagers

Background: Typically, research on parents’ and children’s interactions around alcohol issues focuses on how parenting styles and parents’ examples affect teenager’s drinking habits. In this paper, we approach the theme from the youngsters’ perspective. We ask how teenagers describe the interaction on alcohol-related issues with their parents and how they would like their parents to act during these interactions.

Data and methods: The article applies the concept of trust, which is seen as a feature connecting all kinds of communities, and especially families. We pay attention to whether alcohol issues challenge trustful relations and give rise to contradictions and complications in the interactions between parents and children.

Results: The analysis shows the ways how trust is maintained and challenged in teenagers? accounts of communication regarding alcohol with their parents. It also shows that although trust is tested in several ways, it is essential for teenagers. Even though teenagers tell how they can mislead their parents by using strategies that challenge trust, they nevertheless highlight the importance of trusting ties with parents. Teenagers do not exclude their parents from alcohol-related discussion but expect rules, communication and authority from them. Our data suggest that teenagers also want to protect their parents from disappointments caused by their own actions.

Conclusions: A trusting parent–child relationship, based on dialog rather than opposition, seems to play a significant role in guiding teenagers’ alcohol-related attitudes and practices.     

我院住院患者质子泵抑制剂的使用分析

目的分析我院2015年住院患者质子泵抑制剂(proton pump inhibitor,PPI)的使用情况。方法对我院2015年住院患者PPI的品种、销售量、消耗金额、用药频度(DDDs)和日均费用(DDC)等情况进行统计分析。结果我院PPI品种DDDs排序前3位的为雷贝拉唑肠溶胶囊、注射用奥美拉唑和注射用泮托拉唑;销售金额排序前3位的为注射用兰索拉唑、注射用奥美拉唑和注射用泮托拉唑;以雷贝拉唑肠溶胶囊序号比值>1的情况最为突出,其余大多数药品的序号比值为1;住院患者使用PPI病例数占首位的为消化内科;DDDs占首位的为心血管内科。结论 PPI在我院临床使用基本合理,但存在无适应证使用、盲目预防性使用等不合理现象,特别是外科;医院应加强对PPI使用的监管,促进合理用药。     

Study on the metabolism of 5,6-methylenedioxy-2-aminoindane (MDAI) in rats: identification of urinary metabolites

1.?5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs.

2.?Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20?mg MDAI.HCl/kg body weight. The urine of rats was collected within 24?h after dosing for analyses by HPLC-ESI-HRMS and GC/MS.

3.?The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged.

4.?Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane.

5.?Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards.     

Use of a semi-physiological pharmacokinetic model to investigate the influence of itraconazole on tacrolimus absorption,distribution and metabolism in mice

1.?The aim of this study was to investigate the influence of itraconazole (ITCZ) on tacrolimus absorption, distribution and metabolism by developing a semi-physiological pharmacokinetic model of tacrolimus in mice.

2.?Mice were randomly divided into four groups, namely control group (CG, taking 3?mg kg^?1 tacrolimus only), low-dose group (LDG, taking tacrolimus with 12.5?mg kg^?1 ITCZ), medium-dose group (MDG, taking tacrolimus with 25?mg kg^?1 ITCZ) and high-dose group (HDG, taking tacrolimus with 50?mg kg^?1 ITCZ).

3.?Liver clearance (CL_li) decreased significantly (**p?<?0.01) in LDG (35.3%), MDG (45.2%) and HDG (58.7%) mice compared to CG mice. With respect to gut clearance (CL_gu), significant (**p?<?0.01) decrease was also revealed in LDG (35.9%), MDG (50.2%) and HDG (64.6%) mice. A significant (**p?<?0.01) higher tacrolimus brain-to-blood partition coefficient (K_t,br) was found in MDG (25.3%) and HDG (55.9%) mice than in CG mice. Moreover, a significant (*p?<?0.05) increase (16.3%) was found in the absorption rate constant (K_a) in HDG mice compared to CG mice. There was a significant (**p?<?0.01) association between ITCZ dose and the change in CL_gu (ΔCL_gu, r=??0.790), the change in CL_li (ΔCL_li, r=??0.787) and the change in K_t,br (ΔK_t,br, r?=?0.727), while the association between ITCZ dose and the change in K_a (ΔK_a) was not significant (p?>?0.05).

4.?These findings could be useful in predicting the efficacy and toxicity of tacrolimus, and drug–drug interaction of ITCZ and tarcolimus in human.     

Screening of drug metabolizing enzymes for fusidic acid and its interactions with isoform-selective substrates in vitro

1.?Fusidic acid (FA) is widely used for the treatment of infections of sensitive osteomyelitis or skin and soft tissue caused by bacteria. However, the role of cytochrome P450s (CYPs) in the metabolism of FA is unclear. In the present study, we screened the main CYPs for the metabolism of FA and studied its interactions with isoform-selective substrates in vitro.

2.?The main CYP450s were screened according to the inhibitory effect of specific inhibitors on the metabolism of FA in human liver microsomes (HLMs) or recombinant CYP isoforms. Enzyme kinetic parameters including K_i, K_i′, V_max, and IC₅₀ were calculated to determine the potential of FA to affect CYP-mediated metabolism of isoform-selective substrates.

3.?FA metabolism rate was inhibited by 49.8% and 83.1% under CYP2D6, CYP3A4 selective inhibitors in HLMs. In recombinant experiment, the inhibitory effects on FA metabolism were 83.3% for CYP2D6 and 58.9% for CYP3A4, respectively. FA showed inhibition on CYP2D6 and CYP3A4 with K_is of 13.9 and 38.6?μM, respectively. Other CYP isoforms including CYP1A2, CYP2A6, CYP2C9, CYP2E1, and CYP2C19 showed minimal or no effect on the metabolism of FA.

4.?FA was primarily metabolized by CYP2D6 and CYP3A4 and showed a noncompetitive inhibition on CYP2D6 and a mixed competitive inhibition on CYP3A4. Drug–drug interactions between FA and other chemicals, especially with substrates of CYP2D6 and CYP3A4, are phenomena that clinicians need to be aware of and cautious about.     

Interaction between the photosensitizer lumichrome and human serum albumin: effect of excipients

Lumichrome (Lc) is a photodegradation product of riboflavin that can be used as a photosensitizer (PS) in antibacterial photodynamic therapy (aPDT). The binding of Lc with plasma proteins such as human serum albumin (HSA) could affect its efficiency as PS. Excipients are necessary to prepare stable formulations to be used in aPDT and they may affect the PS-HSA binding. Hydroxypropyl (HP)-α, β, γ-cyclodextrin (CD), polyethylene glycol 400 (PEG400) and Pluronic^® F-127 (PF127) were selected as model excipients in this study. The intrinsic HSA fluorescence quenching and absorption and fluorescence spectroscopy were used to evaluate the Lc-HSA interaction in the absence and presence of excipients. Nano-differential scanning calorimetry (DSC) was used to determine the effect of excipients on HSA. The photostability of the samples was also evaluated. The combined results showed a modest interaction between Lc and HSA which was reduced mainly by HPβCD. No major alterations of the HSA nano-DSC thermogram were observed after addition of excipients. HSA did enhance Lc photodegradation. The presence of PF127 did also induce photochemical destabilization of Lc independent of HSA. In conclusion, HPαCD, HPγCD and PEG400 seemed to be the excipients more suitable for use in topical preparations containing Lc.     

Investigational drugs targeting the prostaglandin E2 signaling pathway for the treatment of inflammatory pain

Introduction: Non-steroidal anti-inflammatory drugs (NSAID) are the most commonly used drugs for the treatment of pain, inflammation and fever. Although they are effective for a huge number of users, their analgesic properties are not sufficient for several patients and the occurrence of side effects still constitutes a big challenge during long term therapy.

Areas covered: This review gives an overview about the first and second generations of NSAIDs (COX1/2 non-selective, COX-2 selective), and their main side effects which gave still an urgent need for safer drugs and for the establishment of novel treatment strategies (improved safety, tolerability, patient convenience). The current developments of a possible third generation NSAID class comprise changes in the formulation of already approved drugs, combination therapies, dual cyclooxygenase-lipoxygenase inhibitors, NO- and H₂S-releasing NSAIDs, prostaglandin synthase inhibitors and EP receptor modulators, respectively. Literature search has been done with PubMed NCBI.

Expert opinion: Currently, there is no newly developed drug that is superior to the already approved selective and non-selective NSAIDs. Several novel approaches show promising analgesic efficacy but side effects are still an important problem. Solutions might be constituted by combination therapies allowing administration of lower drug doses or by individualized therapies targeting molecules apart from COX, respectively.     

氟比洛芬酯注射液对食管癌术后止痛泵用药剂量及凝血功能的影响

目的探究氟比洛芬酯注射液对食管癌术后患者止痛效果、止痛泵用量及不良反应情况的影响。方法选取2014年2月~2015年8月在该院就诊的食管癌患者98例,将患者随机均分为治疗组及对照组,每组49例,对照组给予常规术后自控止痛泵进行止痛处理并辅以常规术后治疗护理措施;治疗组在此基础上加用小剂量氟比洛芬酯注射液。观察比较2组患者术后即刻及术后36h的各项指数及镇痛效果总满意度。结果术前2组患者的心率(HR)、收缩压(SAP)、血氧饱和度(SaO2)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、血小板计数(PLT)、呼吸抑制、恶心、腹痛及大便潜血阳性例数比较,差异无统计学意义(P>0.05);术后36h治疗组患者的HR、SAP及SaO2明显高于对照组,治疗组患者的呼吸抑制及恶心例数明显少于对照组(P<0.05);治疗组患者术后治疗过程中的主动镇痛次数7.85±1.47次、用药量107.53±12.72mL、ICU留观时间18.54±2.67h及咳痰不畅例数(3,6.12%)明显低于对照组9.31±2.89次、115.37±15.29mL、20.47±3.53h、11(22.45%)(P<0.05);治疗组患者镇痛总满意度(47,95.92%)明显高于对照组(41,83.67%)(P<0.05)。结论小剂量应用氟比洛芬酯注射液可明显促进患者术后呼吸系统功能恢复,降低镇痛泵用药量及不良反应发生率,且无明显凝血指标异常等不良反应。     

The impact of the health-care sector on national economies in selected European countries

Policy-makers face pressures to improve lives and safeguard public finances sustainably. In this analysis, we estimate the economic importance of the health-care sector in 19 European national economies.We use input–output tables for the year 2010 and sectoral data to estimate a set of multipliers: simple, total, truncated, type I and type II multipliers for output, income, value-added, employment and import multiplier.The analysis reveals similarities in the economic importance of the health-care sector for the national economies of the observed countries. Results suggest prevailing positive effects on national economies (value-added, employment and household income) when spending on health-care sector products and services increases, especially in comparison to the effects of increases in spending in other sectors. The importance of the health-care sector is connected to countries’ levels of development; the benefits are especially promising in countries with lower levels of gross domestic product (GDP) per capita, where changes in the health-care sector have a larger impact on employment in the national economy than similar changes in more developed countries. The health-care sector therefore can play an important role as an instrument of economic policy.