Presence Of PAS Research Articles

Structure‐dependent relative toxic potencies of selected pyrrolizidine alkaloids

Pyrrolizidine alkaloids are naturally occurring secondary plant metabolites mainly found in plant families of Asteraceae, Boraginaceae, and Fabaceae. Chemically, Pas consist of a pyrrolizidine core bearing hydroxyl groups, the so‐called necine base, and mono‐ or dicarboxylic necine acids bound to the pyrrolizidine core via ester linkages. 1,2‐unsaturated PAs are hepatotoxic, genotoxic, and carcinogenic due to the highly reactive pyrrolic metabolites formed by cytochrome P450 monooxygenases (CYPs) primarily in the liver. The presence of PAs as frequent contaminants in the wide variety of food and feed products has to be considered a relevant safety issue.Based on the currently available data, the risk assessment of PAs was mainly approached using the two most toxic potent congeners, i.e., lasiocarpine and riddelliine. However, it is well recognized that toxicity is differing significantly between the congeners related to their structural features. The risk of PA‐containing products is indeed overestimated, and a comprehensive risk assessment should take these differences into account.After analyzing the data of many PAs, Merz and Schrenk derived interim Relative Potency (iREP) factors to present the differences in their toxicity between the sub‐groups of PA congeners concerning their structural features. The use of such iREP factors could probably provide a more scientific basis for PA risk assessment until sufficient experimental analysis of the toxicities of individual congeners is applied. To obtain a better understanding of the relationship between structure and toxicity of PA congeners and provide more evidence for further refinement of relative (toxic) potency factors, data of the in vitro cytotoxicity, genotoxicity, and mutagenicity of diverse individual PA congeners (lasiocarpine, monocrotalineφ, retrorsine, senecionine, seneciphyllineφ, echimidineφ, europineφ, heliotrineφ, indicine, and lycopsamine) has been generated in our project supported by Kooperation Phytopharmaka. Among them, lasiocarpine, retrorsine, senecionine, indicine and lycopsamine have been investigated on my part.Cytotoxicity was assessed using the Alamar blue assay in primary rat hepatocytes, HepG2 cells, and the HepG2 (CYP3A4) cell line. In HepG2 cells, none of the selected PAs exhibited cytotoxic effects, probably due to the lack of CYPs. In primary rat hepatocytes as well as in HepG2(CYP3A4) cells, a clear structure dependent cytotoxicity could be demonstrated. The role of CYP450 enzymes in metabolic activation was further confirmed using an inhibition assay. A kinetic assay analyzing 7‐benzyloxyresorufin‐O‐ dealkylation (BROD) was used for measuring the activity of CYP450 enzymes. Furthermore, the utilization of a glutathione‐reductase‐DTNB recycling assay indicated that glutathione might not play a critical role in PA‐induced cytotoxicity. A micronucleus test was used for determining the PA‐induced clastogenic genotoxicity. All selected PA congeners exhibited concentration‐dependent toxicity in the HepG2 (CYP3A4) cells. The relative potencies of PA congeners estimated from Alamar blue assay and micronucleus assay are generally consistent with the following ranking: lasiocarpine > senecionine > seneciphylline > retrorsine > heliotrine (?) echimidine > europine = indicine = lycopsamine = monocrotaline. The relative toxic potencies evaluated based on our findings were not completely consistent with the iREP classification previously reported by Merz and Schrenk. Monocrotaline in both assays exhibited considerably lower toxic potency. Echimidine, however, was more toxic than expected. On the other hand, mutagenicity was measured in Ames fluctuation assay with Salmonella typhimurium strains TA98 and TA100. None of the selected PA congeners up to 300 μM showed mutagenic effects despite metabolic activation with S9‐mix.

"One-pot" preparation of aminated carbon nanotube-modified magnetic nanoparticles and their application to the quantification of phenoxyacetic acid herbicides in cereal and vegetable samples

有效萃取是分析复杂样品中苯氧羧酸类除草剂(PAs)残留的关键步骤。为此,该文利用“一锅法”水热技术快速、简便地制备了氨基碳纳米管功能化磁性纳米粒子(NH2-CNTs@M)并作为磁固相萃取(MSPE)的萃取介质,用于萃取谷物和蔬菜样品中痕量PAs。研究利用多种手段对NH2-CNTs@M的形貌、尺寸、磁性性质等进行了表征,结果表明Fe3O4的粒径、氨基化碳纳米管的直径以及NH2-CNTs@M的磁饱和值分别为30 nm、40 nm和44.2 emu/g。详细考察了制备条件和萃取参数对NH2-CNTs@M/MSPE萃取性能的影响,结果表明,NH2-CNTs@M/MSPE可通过π-π、疏水和氢键作用有效富集目标化合物,最佳萃取条件如下:吸附剂用量为30 mg,解吸溶剂为含2.0%(v/v)甲酸的乙腈溶液,吸附时间和解吸时间分别为8.0 min和3.0 min,基底pH值为6.0,不调节基底的离子强度。将NH2-CNTs@M/MSPE与高效液相色谱-二极管阵列检测技术(HPLC-DAD)联用,建立了谷物和蔬菜中PAs的灵敏检测方法。谷物和蔬菜基质中苯氧羧酸类除草剂的检出限(LOD, S/N=3)分别为0.32~1.6 μg/kg和0.53~1.6 μg/kg,定量限(LOQ, S/N=10)分别为0.94~4.8 μg/kg和1.6~4.8 μg/kg。在两种实际样品中不同浓度下的加标回收率分别为73.1%~112%和72.3%~113%。与现有方法相比,所建方法具有萃取速度快、灵敏度高和环境友好等特点。

Incidence and risk factors for post-penetrating keratoplasty glaucoma.

Purpose:To carry out a prospective study to analyze the incidence and various preoperative, intraoperative, and postoperative risk factors for the development of PPKG.Methods:A total of 207 patients were analyzed prospectively, who were operated for penetrating keratoplasty (PK) in a tertiary eye care hospital between the time period of August 1, 2017 and February 28, 2018 and were followed up till the sixth month. Each patient was analyzed at every visit to determine the factors responsible for post-keratoplasty glaucoma.Results:Out of 207 eyes, post-PK glaucoma developed in 84 cases, which yielded an incidence of 41%. Incidence of PPKG (Post PK glaucoma) in various conditions was as follows: in repeat PK 62%, in perforated corneal ulcer 33%, in nonperforated corneal ulcer 29%, in corneal scar including adherent leukoma 37.2%, and in pseudophakic bullous keratopathy and aphakic bullous keratopathy, 14% and 80%, respectively. In age- and sex-adjusted multivariate analysis, the significant risk factors were age (P-value- 0.006), presence of PAS (P-value 0.001), and fellow eye glaucoma (P-value 0.04). Aphakia and combined surgery were not found to be significantConclusion:Our study recommends a meticulous examination of the fellow eye to assess the presence of glaucoma as it can increase the suspicion of glaucoma in the eye to be operated. The presence of PAS and age are important risk factors for developing PPKG. The risk of developing PPKG increases exponentially as the number of risk factors increases, but the presence of more than three risk factors does not add to the development of PPKG.

Fact or Fiction, It Is Time for a Verdict on Vasculogenic Mimicry?

The term vasculogenic mimicry (VM) refers to the capacity of certain cancer cells to form fluid-conducting structures within a tumor in an endothelial cell (EC)-free manner. Ever since its first report by Maniotis in 1999, the existence of VM has been an extremely contentious issue. The overwhelming consensus of the literature suggests that VM is frequently observed in highly aggressive tumors and correlates to lower patient survival. While the presence of VM in vivo in animal and patient tumors are claimed upon the strong positive staining for glycoproteins (Periodic Acid Schiff, PAS), it is by no means universally accepted. More controversial still is the existence of an in vitro model of VM that principally divides the scientific community. Original reports demonstrated that channels or tubes occur in cancer cell monolayers in vitro when cultured in matrigel and that these structures may support fluid movement. However, several years later many papers emerged stating that connections formed between cancer cells grown on matrigel represented VM. We speculate that this became accepted by the cancer research community and now the vast majority of the scientific literature reports both presence and mechanisms of VM based on intercellular connections, not the presence of fluid conducting tubes. In this opinion paper, we call upon evidence from an exhaustive review of the literature and original data to argue that the majority of in vitro studies presented as VM do not correspond to this phenomenon. Furthermore, we raise doubts on the validity of concluding the presence of VM in patient samples and animal models based solely on the presence of PAS+ staining. We outline the requirement for new biomarkers of VM and present criteria by which VM should be defined in vitro and in vivo.

Commentaries on health services research

Commentaries on health services research

Hybrid polarizing solids for pure hyperpolarized liquids through dissolution dynamic nuclear polarization.

Hyperpolarization of substrates for magnetic resonance spectroscopy (MRS) and imaging (MRI) by dissolution dynamic nuclear polarization (D-DNP) usually involves saturating the ESR transitions of polarizing agents (PAs; e.g., persistent radicals embedded in frozen glassy matrices). This approach has shown enormous potential to achieve greatly enhanced nuclear spin polarization, but the presence of PAs and/or glassing agents in the sample after dissolution can raise concerns for in vivo MRI applications, such as perturbing molecular interactions, and may induce the erosion of hyperpolarization in spectroscopy and MRI. We show that D-DNP can be performed efficiently with hybrid polarizing solids (HYPSOs) with 2,2,6,6-tetramethyl-piperidine-1-oxyl radicals incorporated in a mesostructured silica material and homogeneously distributed along its pore channels. The powder is wetted with a solution containing molecules of interest (for example, metabolites for MRS or MRI) to fill the pore channels (incipient wetness impregnation), and DNP is performed at low temperatures in a very efficient manner. This approach allows high polarization without the need for glass-forming agents and is applicable to a broad range of substrates, including peptides and metabolites. During dissolution, HYPSO is physically retained by simple filtration in the cryostat of the DNP polarizer, and a pure hyperpolarized solution is collected within a few seconds. The resulting solution contains the pure substrate, is free from any paramagnetic or other pollutants, and is ready for in vivo infusion.

Effects of p-Aminosalicylic acid on the neurotoxicity of manganese on the dopaminergic innervation of the cilia of the lateral cells of the gill of the bivalve mollusc, Crassostrea virginica

The lateral cilia of the gill of Crassostrea virginica are controlled by a dopaminergic–serotonergic innervation. Dopamine is the neurotransmitter causing cilio-inhibition. High levels of manganese are neurotoxic to people, causing Manganism, a Parkinson-like disease. Clinical interventions for Manganism have not been very successful. Recently, p-Aminosalicylic acid (PAS) was reported as an effective treatment of severe Manganism in humans; however, its mechanism of action is unknown. Previously, we reported that manganese treatments caused disruption of the dopaminergic innervation of gill of C. virginica. Here we compared the effects of manganese on gill innervation in the presence of PAS, EDTA or Acetylsalicylic acid (ASA), and examined whether co-treating animals with PAS could block the deleterious effects of manganese on the oyster's dopaminergic innervation of the gill. Beating rates of the lateral cilia of the gill were measured by stroboscopic microscopy. Pre-treating gill preparations with PAS or EDTA blocked the neurotoxic effects of manganese, while ASA did not. In other experiments, animals exposed to three day treatments with manganese produced a dose dependent impairment of the dopaminergic, cilio-inhibitory system, which was decreased by co-treatment with PAS. The study shows that PAS protects the animal against neurotoxic effects of manganese and the mechanism of action of PAS in alleviating Manganism is more likely related to its chelating abilities than its anti-inflammatory actions.

Beneficiation of diasporic-bauxite ore by selective flocculation with a polyacrylate flocculant

Beneficiation of a diasporic-bauxite ore by selective flocculation with sodium polyacrylate (PAS) was studied. Flocculation behaviors of diaspore, kaolinite, illite and pyrophyllite in the presence of PAS were also investigated by sedimentation tests. PAS shows good selectivity for the flocculation separation of diaspore from silicates in the range of pH 8–12. A concentrate with Al 2O 3/SiO 2 ratio 8.9 and the recovery of Al 2O 3 87.0% was obtained from a diasporic-bauxite ore with Al 2O 3/SiO 2 ratio 5.7 with the addition of sodium carbonate 5 kg/t and PAS 7 g/t. Micro-photogram, zeta potential and FTIR measurements were then performed to study the mechanisms. It was observed that the zeta potentials of diaspore shifted to negative value strongly and the isoelectric point (IEP) of diaspore was also changed from about pH 6–4, and the flocs of diaspore were larger and denser than that of kaolinite in the presence of PAS. A new band at 1640 cm −1 was found in the infrared spectrum of the diaspore after interaction with PAS, and this new band matched the characteristic peak at 1624 cm −1 in the infrared spectrum of the reaction products of PAS and AlCl 3. The adsorption of PAS on diaspore is concluded to be chemisorption caused by the chemical reaction between carboxylate group and the exposed Al sites on diaspore surface.

The plasminogen activator/plasmin system.

proteases and inhibitors has been shown to be under the control of hormones and growth factors. Plasminogen activators (PAs) and their inhibitors (PAIs) are thought to be key participants in the balance ofproteolytic and antiproteolytic activities that regulates matrix turnover. This article summarizes the evidence that supports this contention, discusses the role ofPAspecific cell surface binding sites, and also draws attention to a number of instances in which the presence ofPAs cannot be reconciled with an exclusive function in ECM degradation.

Drug‐Induced Malabsorption of Vitamin B12

The present paper describes dialysis tests of rat stomach and bowel extract to show the effect of PAS on the various stages of vitamin B12 absorption. According to the results, PAS does not inhibit the formation of IF nor interfere with the binding of vitamin B12 to the IF that has formed. Nor does PAS inhibit origination of the “releasing factor” in the wall of the rat intestine. The “releasing factor” releases B12 from the IF complex also in the presence of PAS. This finding supports the view that the PAS‐induced malabsorption of vitamin B12 is based on inhibition of the enzyme system by means of which B12 normally penetrates the bowel wall.