AstraZeneca ChAdOx1-S COVID-19 Vaccine Can Be Safely Administered in Patients with EDTA Allergy

Background: Immediate hypersensitivity reactions to COVID-19 vaccines have been postulated to be linked to their excipients, such as polyethylene glycol (PEG) in Pfizer Comirnaty, or polysorbate 80 and ethylenediaminetetracetic acid (EDTA) in AstraZeneca ChAdOx1-S [recombinant] (Vaxzevria). These excipients are potentially found in a range of other products, including injectable and oral medications as well as intravenous radiocontrast media (RCM) and various cosmetic products.Currently patients with proven excipient allergy may be advised to avoid a COVID-19 vaccine containing that excipient and/or potentially cross-reactive excipients. We present two cases of previously confirmed EDTA anaphylaxis, who had negative Vaxzevria vaccine in-vivo testing and subsequently tolerated the vaccine.Case 1: A patient with history of anaphylaxis to RCM and local anaesthetics (LA) had positive intradermal test (IDT) to EDTA nine years earlier. Skin testing to Vaxzeria vaccine (up to 1:10 IDT), Comirnaty vaccine (up to 1:10 IDT) and EDTA 0.3mg/mL IDT were negative. However, following EDTA 3mg/ml IDT, he developed immediate generalised urticaria without anaphylaxis. Basophil activation testing was negative to disodium EDTA, Vaxzevria and Cominarty vaccines. Given the negative in-vitro and in-vivo testing to Vaxzevria vaccine, he proceeded to Vaxzevria immunisation and tolerated both doses.Case 2: A patient with history of anaphylaxis to RCM had positive skin testing to EDTA and RCM containing EDTA six years earlier. Following referral to COVID19 vaccine clinic, Vaxzevria vaccine (1:10 IDT) and Cominarty vaccine (1:10 IDT) were negative whilst EDTA was positive at 0.3mg/mL IDT. He subsequently tolerated both Vaxzevria vaccinations.Conclusion: Excipient allergy does not necessarily preclude a patient from receiving a vaccine containing that excipient. Allergy testing can help identify excipient-allergic patients who may still tolerate vaccination, which is important in situations where COVID-19 vaccination options are limited.

Zinc(II) binding on human wild-type ISCU and Met140 variants modulates Fe-S complex activity

ABSTRACTThe human de novo iron-sulfur (Fe-S) assembly complex consists of the cysteine desulfurase NFS1, accessory protein ISD11, scaffold protein ISCU, and allosteric activator frataxin (FXN). FXN has been shown to bind the NFS1-ISD11-ISCU complex (SDU), to activate the desulfurase activity and thus Fe-S cluster biosynthesis. Conversely, in the absence of FXN, the NFS1-ISD11 (SD) complex was reported to be inhibited by the binding of recombinant ISCU. Here, we show that recombinant ISCU binds zinc(II) ion, and that the presence of zinc in as-isolated ISCU has impacts on the SDU desulfurase activity as measured by sulfide production. Indeed, the removal of this zinc(II) ion from ISCU causes a moderate but significant increase in activity compared to SD alone, and FXN can activate both zinc-depleted and zinc-bound forms of ISCU complexed to SD. Recent yeast studies have reported a substitution on the yeast ISCU orthologue Isu, at position Met141 (Met140 in human numbering of precursor protein) to Ile, Leu, Val, or Cys that could bypass the requirement of FXN for Fe-S cluster assembly and cell viability. Using recombinant human proteins, we report no significant differences in the biochemical and biophysical properties observed between wild-type and variants M140I, M140 L, and M140 V of ISCU. Importantly, in the absence of FXN, ISCU variants behaved like wild-type and did not stimulate the desulfurase activity of the SD complex. This study therefore identifies an important regulatory role for ISCU-bound zinc in modulation of the human Fe-S assembly system in vitro but no ‘FXN bypass’ effect on mutations at position Met140 in human ISCU.ABBREVIATIONSACPacyl carrier transfer proteinBLIbiolayer interferometryBSAbovine serum albuminCDcircular dichroismDMPDNN-dimethyl-p-phenylenediamineDSFdifferential scanning fluorimetryDTTdithiothreitol; EDTA, ethylenediaminetetracetic acidFe-Siron sulfurFRDAFriedreich’s ataxiaFXNfrataxinHEPES4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidIPTGisopropyl β-D-1-thiogalactopyranosidePLPpyridoxal 5′-phosphateSDprotein complex composed of NFS 1 and ISD11SDUprotein complex composed of NFS 1, ISD11ISCUSDUF, protein complex composed of NFS 1, ISD11, ISCU, and frataxinTCAtrichloroacetic acidTCEPtris(2-carboxyethyl) phosphineTristris(hydroxymethyl)aminomethane

Intracanal Irrigating Solutions Prior to Calcium Hydroxide Medication and Its Effects on Root Dentin Strength

The aim of this study was to assess the effects of intracanal irrigation with sodium hypochlorite (NaOCl) and ethylenediaminetetracetic acid (EDTA) prior to calcium hydroxide medication on the compressive strength of root dentin. Forty-eight roots with single and straight canals were instrumented with a crown-down technique using Flexofile files and Gates Glidden burs, under 0.9% sodium chloride (NaCl) irrigation. Root canals were randomly separated into 4 groups (n=12), according to the irrigating solution: Control Group, 0.9% NaCl; GroupNaOCl, 1% NaOCl; GroupEDTA, 17% EDTA; and GroupEDTA+NaOCl, 17% EDTA and 1% NaOCl. Solutions remained for 40 min, renewed every 10 min, except for GroupEDTA+NaOCl, where the solutions were alternated every 10 min. Canals were dried and filled with calcium hydroxide paste, and radiographed. Each canal was sealed and stored at 37 °C for 30 days. After this period, the roots were cut 1 mm below the cementoenamel junction and 6 mm apically from this point in order to obtain 6 mm-long cylinders. The compressive test was conducted with a crosshead speed of 1 mm/min. The means (±SD) (MPa) of compressive strength were: Control Group, 151.23±94.36; GroupNaOCl, 167.50±57.25; GroupEDTA, 108.79±99.88; GroupEDTA+NaOCl, 60.12±92.10. Significant statistical differences among groups were found (ANOVA and Tukey, a=5%, p=0.02). Control Group and GroupNaOCl showed higher means of compressive strength than GroupEDTA+NaOCl. Intracanal irrigation with 17% EDTA and 1% NaOCl produced a significant reduction of dentin compressive strength 30 days after medication with calcium hydroxide.

Enhanced Phytoextraction of Cadmium and Zinc Using Rapeseed

In a green house pot experiment, the effects of three amendments, sulphur (S), ammonium sulphate ((NH4)2SO4) and ethylenediaminetetracetic acid (EDTA) were tested for phytoextraction of Cd and Zn by rapeseed (Brassica napus L.). Elemental sulphur was applied as 20.00, 60.00, and 120.00 mg.kg−1 soil. EDTA was tested at a dose of 585.00 mg.kg−1 soil, and (NH4)2SO4) at a rate of 0.23 mg.kg−1 soil. All treatments received a base fertilization (Hogland) before sowing. Plants were harvested after 51 days of growth and shoot dry matter and soil samples were analysed for metal contents. All amendments caused a significant increase in Cd and Zn contents in plant shoots of all treatments than control treatment. Further, EDTA was most effective for extraction metals concentrations in shoot biomass but the plants showed significant signs of toxicity and yield were severely depressed. The addition of sulfur favorably influenced plant biomass production. The fertilized ammonium sulfate treatment resulted in the highest phytoextraction of Cd and Zn and the amounts of these metals accumulated in plant shoot exceeded by a factor of 4 and 3 respectively. Finally, Brassica napus could be used for soil remediation keeping its other uses which will make the contaminated site income generating source for the farmers.

Fabrication of Bi-2212 Films on Ag Substrate by Dip-Coating Method

In this study, Bi2Sr2CaCu2Ox (Bi-2212) thick films on Ag substrate were fabricated using the dip-coating method. Firstly, the Bi-2212 powders were prepared by Sol-Gel process. Metal nitrates were used as starting materials and ethylenediaminetetracetic acid (EDTA) was used as chelating agent. Secondly, the resulting powders were used as solute, and polyvinyl butyral (PVB) was used as solvent to prepare suspension via stirring and ultrasonic vibration. Then the suspension was dip-coated on Ag substrate. After heat treatments, the phase compositions of the samples were characterized using the XRD. The microstructure was observed using SEM. Experimental results show that the sintering temperature strongly influence the phase formation of Bi–2212.

Separation of Ga(III) from Cu(II), Ni(II) and Zn(II) in aqueous solution using synthetic polymeric resins

Poly (acrylamide-acrylic acid-dimethylaminoethylmethacrylate), p(AM-AA-DMAEM) and Poly(acrylamide-acrylic acid)-ethylenediaminetetracetic acid disodium, p(AM-AA)-EDTANa2 were prepared by gamma radiation-induced template polymerization technique and used for the separation of Ga (III) from Cu (II), Ni (II), and Zn (II) in aqueous media. The effect of pH and contact time on the separation process was studied. The optimum pH value for the separation process is 3–3.5. The result shows that Ga (III) is first extracted while Cu (II), Ni (II) and Zn(II) are slightly extracted at this pH value. The recovery of metals using HCl, HNO3 and H2SO4 has been studied. The resins may be regenerated using 2M HCl solutions.