The superoxide anion donor,potassium superoxide,induces pain and inflammation in mice through production of reactive oxygen species and cyclooxygenase-2

It is currently accepted that superoxide anion (O₂ ^•−) is an important mediator in pain and inflammation. The role of superoxide anion in pain and inflammation has been mainly determined indirectly by modulating its production and inactivation. Direct evidence using potassium superoxide (KO₂), a superoxide anion donor, demonstrated that it induced thermal hyperalgesia, as assessed by the Hargreaves method. However, it remains to be determined whether KO₂ is capable of inducing other inflammatory and nociceptive responses attributed to superoxide anion. Therefore, in the present study, we investigated the nociceptive and inflammatory effects of KO₂. The KO₂-induced inflammatory responses evaluated in mice were: mechanical hyperalgesia (electronic version of von Frey filaments), thermal hyperalgesia (hot plate), edema (caliper rule), myeloperoxidase activity (colorimetric assay), overt pain-like behaviors (flinches, time spent licking and writhing score), leukocyte recruitment, oxidative stress, and cyclooxygenase-2 mRNA expression (quantitative PCR). Administration of KO₂ induced mechanical hyperalgesia, thermal hyperalgesia, paw edema, leukocyte recruitment, the writhing response, paw flinching, and paw licking in a dose-dependent manner. KO₂ also induced time-dependent cyclooxygenase-2 mRNA expression in the paw skin. The nociceptive, inflammatory, and oxidative stress components of KO₂-induced responses were responsive to morphine (analgesic opioid), quercetin (antioxidant flavonoid), and/or celecoxib (anti-inflammatory cyclooxygenase-2 inhibitor) treatment. In conclusion, the well-established superoxide anion donor KO₂ is a valuable tool for studying the mechanisms and pharmacological susceptibilities of superoxide anion-triggered nociceptive and inflammatory responses ranging from mechanical and thermal hyperalgesia to overt pain-like behaviors, edema, and leukocyte recruitment.     

鹿茸多肽对微波辐射致小鼠卵巢次级卵泡发育损伤的保护作用

  目的：研究鹿茸多肽(VAP)对微波辐射所致小鼠卵巢次级卵泡发育损伤的保护作用及其机制  方法：将75只8周龄昆明种雌性小鼠,随机分为对照组、微波辐射组(MR组)、MR+低VAP组、MR+中VAP组、MR+高VAP组,每组15只。除对照组外,其余小鼠进行5 mW/cm²强度的微波辐射30天;然后MR+低VAP组、MR+中VAP组、MR+高VAP组腹腔注射VAP 30天,剂量分别为1.5 mg·kg-1·d-1、3 mg·kg-1·d-1和6 mg·kg-1·d-1。观察小鼠卵巢组织中次级卵泡的发育情况,TUNEL法检测小鼠次级卵泡中颗粒细胞的凋亡,免疫组织化学法检测小鼠次级卵泡颗粒细胞中凋亡抑制蛋白Bcl-2 和活化型促凋亡蛋白caspase-3的表达,ELISA法检测小鼠血清中雌激素水平  结果：与MR组比较,高浓度VAP显著提高了小鼠卵巢组织中次级卵泡的发育,改善其组织结构状态,显著减少次级卵泡颗粒细胞的凋亡和活化型促凋亡蛋白caspase-3的表达,升高次级卵泡颗粒细胞中凋亡抑制蛋白Bcl-2的表达和小鼠血清中的雌激素水平  结论：VAP可显著修复微波辐射引起的小鼠卵巢次级卵泡发育损伤,其修复机制可能与减少次级卵泡中颗粒细胞凋亡,促进卵泡雌激素合成和分泌有关。     

How to use nitrates

Nitrates are old drugs, available in many formulations, that are effective in relieving symptoms in various CAD syndromes as well as congestive heart failure. Nitrate tolerance is the major problem limiting nitrate efficacy and use by physicians. Currently, an intermittent dosing strategy is the only practical way to limit the development of tolerance or attenuation of nitrate actions.     

Role of Plasma Amino Acids and Urinary Organic Acids in Diagnosis of Mitochondrial Diseases in Children

BackgroundDiagnostic difficulty in mitochondrial diseases (MD) results not only from the wide spectrum of symptoms and signs but also from the absence of a reliable screening or diagnostic biomarker.AimTo investigate the likelihood of MD in patients with symptoms and signs impressive of MD through quantitative measurement of plasma amino acids, and urinary organic acids.MethodsTwenty patients with symptoms and signs suggestive of MD were further evaluated by quantitative plasma amino acids and urinary organic acids assay and neuroimaging.ResultsPlasma amino acid results revealed elevation of alanine in 11, glycine in five, and proline in two patients. Abnormal urinary organic acid analysis was present in six patients; increased urinary lactate (20%), dicarboxylicaciduria (15%), and urinary ketone bodies (10%). Upon enrollment our patients scored as possible MD according to the MD scoring system. At the end of the study, five patients still scored as possible MD, eight patients as probable MD, and seven patients as definite MD. All patients with definite MD had elevated serum lactate. In three patients, elevated urinary lactate was the only abnormality. Alanine was elevated in all patients with definite MD, whereas proline was elevated in only one. Magnetic resonance imaging of the brain showed atrophic changes in one patient and bilateral basal ganglia hyperintensity in another.ConclusionUrinary organic acids and quantitative plasma amino acids can help in the diagnosis of MD, especially when the economic burden and absence of specialized centers limits the diagnosis.     

类弹性蛋白多肽黏膜下注射在内镜黏膜下剥离术中的应用研究

目的 研究类弹性蛋白多肽(ELP)作为一种黏膜下注射制剂在内镜黏膜下剥离术(ESD)中的应用,比较不同质量浓度的ELP在ESD中的应用,并对其有效性和安全性进行评估.方法 40只新西兰大白兔随机分为2组(n=20).第1组观察不同注射液分离组织的有效性.依据不同质量浓度的ELP(0.05、0.025、0.012 5、0.005 g/ml)及对照组(甘油果糖)随机分为5个亚组(n=4),切取胃组织,在胃窦或胃体处分别注射不同质量浓度的ELP和甘油果糖2ml,观察并记录药物注射后0、5、10、30 min局部黏膜隆起高度及黏膜表面的改变.第2组测量不同注射液的注射压力.亚组分组同第1组,使用注射器/压力计组件分别测量2ml不同质量浓度ELP和甘油果糖的注射压力.结果 注射药物后30 min内,0.05、0.025 g/ml ELP维持黏膜隆起高度均大于甘油果糖,差异具有统计学意义(P＜0.05);0.012 5 g/ml ELP维持黏膜隆起高度与甘油果糖相比,差异无统计学意义(P＞0.05);0.005 g/ml ELP维持黏膜隆起高度小于甘油果糖,且差异具有统计学意义(P＜0.05).同时,注射压力与浓度相关,2 ml ELP(0.05、0.025、0.012 5、0.005 yml)和甘油果糖注射后的平均注射压力分别为(332±36)、(223±24)、(174±22)、(142±19)、(269±17)kPa,0.025 g/ml ELP注射压力小于甘油果糖,差异有统计学意义(P＜0.05).结论 ELP是一种安全有效的新型黏膜下注射制剂,推荐ESD术中注射ELP的最适质量浓度为0.025 g/ml.     

The identification of a volume‐regulated anion channel: an amazing Odyssey

The volume‐regulated anion channel (VRAC) plays a pivotal role in cell volume regulation in essentially all cell types studied. Additionally, VRAC appears to contribute importantly to a wide range of other cellular functions and pathological events, including cell motility, cell proliferation, apoptosis and excitotoxic glutamate release in stroke. Although biophysically, pharmacologically and functionally thoroughly described, VRAC has until very recently remained a genetic orphan. The search for the molecular identity of VRAC has been long and has yielded multiple potential candidates, all of which eventually turned out to have properties not fully compatible with those of VRAC. Recently, two groups have independently identified the protein leucine‐rich repeats containing 8A (LRRC8A), belonging to family of proteins (LRRC8A–E) distantly related to pannexins, as the likely pore‐forming subunit of VRAC. In this brief review, we summarize the history of the discovery of VRAC, outline its basic biophysical and pharmacological properties, link these to several cellular functions in which VRAC appears to play important roles, and sketch the amazing search for the molecular identity of this channel. Finally, we describe properties of the LRRC8 proteins, highlight some features of the LRRC8A knockout mouse and discuss the impact of the discovery of LRRC8 as VRAC on future research.     

Fasciola hepatica: development of monoclonal antibodies and their use to characterize a glycocalyx antigen in migrating flukes

Summary Using mice harbouring early Fasciola hepatica infections, six monoclonal antibodies were prepared against a tegumental antigen present in T1 granules and glycocalyx of flukes. Blocking tests indicated that all monoclonals bound the same T1 epitope (or epitopes in close proximity on the antigen molecule), but this was not the determinant recognized by sheep and cattle. Localization of antibody binding at light and electron microscope levels showed that T1-type antigen also occurred in metacercarial tegument and in glycocalyx of gut cells and excretory ducts in juvenile and adult flukes. This indicates that the natural host-antibody response to F. hepatica may be to one antigen early in the infection. Protein A-gold labelling of monoclonal treated fluke sections revealed that the epitope was probably a polypeptide, unmodified by glycosylation in Golgi bodies. When isolated by immunoadsorption and separated electrophoreti-cally under reducing conditions T1-type antigen was found to consist of a polypeptide mol. wt. 50000, possibly linked to smaller entities mol. wt. 25–40 000. Tissue-specific variations in the antigen molecule might be conferred by linkage of different polypeptides or carbohydrate side-chains to an antigenic core polypeptide. A component of T1-type antigen was found to have mol. wt. of 25000, possibly resembling a polypeptide of mol. wt. 24000 from Schistosoma mansoni tegument.     

Elastin-like polypeptides and their applications in anticancer drug delivery systems: a review

Abstract

Elastin-like polypeptides (ELPs) are large molecular weight biopolymers. They have been widely studied as macromolecular carriers for targeted delivery of drugs. The aim of the present article is to review the available information on ELPs (including our recent investigations), their properties, drug delivery applications to tumor sites and future perspectives. This review also provides information on the use of short synthetic ELPs for making ELP-drug conjugates, for targeted delivery of anticancer drugs. In the present review we also focus on the point that short ELPs can also be used for targeting anticancer drugs to tumor sites as they behave similar to long ELPs regarding their capacity to undergo inverse temperature transition (ITT) behavior.     

Volatile organic compounds from fungi isolated after hurricane katrina induce developmental defects and apoptosis in a Drosophila melanogaster model

In previous work, our laboratory developed a Drosophila model for studying the adverse effects of fungal volatile organic compounds (VOCs) emitted by growing cultures of molds. In this report, we have extended these studies and compared the toxic effects of fungal VOCs emitted from living cultures of four molds isolated after Hurricane Katrina from a flooded home in New Orleans. Strains of Aspergillus, Mucor, Penicillium, and Trichoderma were grown with wild‐type larvae and the toxic effects of volatile products on the developmental stages of Drosophila larvae were evaluated. Furthermore, heterozygous mutants of Drosophila carrying the apoptotic genes, reaper and dronc, were used to assess the role of apoptosis in fungal VOCs mediated toxicity. Third‐instar larvae of Drosophila carrying these apoptotic genes were exposed to fungal VOCs emitted from growing mold cultures for 10 days. The larval strains carrying apoptopic genes survived longer than the control wild type larvae; moreover, of those that survived, heterozygous reaper and dronc strains progressed to pupae and adult phases more rapidly, suggesting that fungal VOCs may induce apoptotic changes in flies. These data lend support to the use of Drosophila as an inexpensive and genetically versatile toxicological model to investigate the mechanistic basis for some of the human illnesses/symptoms associated with exposure to mold‐contaminated indoor air, especially after hurricanes. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 614–620, 2015.