Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes.
A series of ethylenediamine platinum(II) complexes connected through semi-rigid chains of 1,2-bis(4-pyridyl)ethane to DNA intercalating subunits (naphthalene, anthracene or phenazine) has been synthesized, and their interactions with calf thymus (CT) DNA have been evaluated by viscometric titrations and equilibrium dialysis experiments. The parent ligands that contain anthracene or phenazine chromophores showed a monointercalative mode of DNA interaction (especially the anthracene derivative), with apparent association constants in the order of 10(4)M(-1). The corresponding platinum(II) complexes bind CT DNA through bisintercalation, as established by the significant increase of DNA contour length inferred from viscosity measurements, and the association constants are in the order of 10(5)M(-1). The naphthalene derivatives, however, exhibit a mixed mode of interaction, which suggests a partial contribution of both intercalation and groove binding for the ligand, and monointercalation in the case of the platinum(II) complex. Competition dialysis experiments carried out on the intercalative compounds have revealed a moderate selectivity towards GC DNA sequences for the derivatives containing the anthracene chromophore.
Platinum(ii) complexes comprising abnormal diimidazolylidene ligands were synthesized from cis-PtMe(2)(DMSO)(2) using microwave-assisted double C-H bond activation. NMR analysis revealed an unusual solvolysis process, induced by coordinating solvents such as DMSO and MeCN, which has not been observed in related normal dicarbene complexes. NMR and IR spectroscopy and crystallographic analysis of the mono-substituted DMSO complex indicate a sulfur-bonding of the DMSO ligand to the platinum(ii) center. Analysis of the DMSO exchange kinetics provided for the first time a quantitative measure of the trans effect of abnormal carbene ligands. The kinetic exchange rate in these bidentate abnormal dicarbene complexes is 0.050(±2) s(-1) and thus similar to analogous platinum(ii) complexes containing phenylpyridine, yet significantly slower than that induced by pyridylidene pyridine. Reaction of the dicarbene platinum(ii) complexes with PhICl(2), Br(2) and I(2) afforded the corresponding platinum(iv) complexes. Linkage isomerism of the Pt(IV)-bound DMSO was observed when the bromination reaction was performed in DMSO solution. Moreover, solvolysis was less pronounced in the platinum(iv) complexes than in the corresponding platinum(ii) analogues.
Human Cumulative Irritation Tests of Common Preservatives Used in Personal Care Products: a Retrospective Analysis of Over 45,000 Subjects
- Toxicological sciences : an official journal of the Society of Toxicology
- Published over 4 years ago
The cumulative irritation test (CIT) is an accepted method used to evaluate the skin irritation potential and safety of individual ingredients and formulas of leave-on skin care and cosmetic compounds. Here we report the results of CITs collected by JOHNSON & JOHNSON Consumer Companies, Inc. (Skillman, NJ), part of an extensive tiered program to evaluate product safety. In the CIT, test formulations were applied to the skin of adults (18-70 years) with no known skin disease or allergies, 3 times per week for 2 weeks using semi-occlusive clinical patches. Preservatives were 1 of up to 16 components of test formulas, and included ethylenediaminetetraacetic acid, diazolidinyl urea, DMDM hydantoin, parabens, isothiazolinone, phenoxyethanol, sorbates, or benzoates. Skin sites were scored after each patch removal using a 5-point scale, with 0 = no visible reaction and 4 = erythema, marked edema, or substantial vesiculation. Scores were reported as percentage of maximal irritation score. Data were analyzed from 1363 CIT studies (over 45,000 subjects). There were no significant differences in percentage of maximal scores between formulas grouped by preservative types (P>0.1). Median score across the entire dataset was 0.44, with most formulas showing none or mild irritation. Although seasonal variations were observed, no correlation was noted between score and preservative concentration. In conclusion, in a large, normal subject dataset, preservatives at typical in-use concentrations did not appear to contribute to skin irritation.
We present the cobalt(III)-mediated interaction between polyhistidine (His)-tagged proteins and nitrilotriacetic acid (NTA)-modified surfaces as a general approach for a permanent, oriented, and specific protein immobilization. In this approach, we first form the well-established Co(2+) -mediated interaction between NTA and His-tagged proteins and subsequently oxidize the Co(2+) center in the complex to Co(3+) . Unlike conventionally used Ni(2+) - or Co(2+) -mediated immobilization, the resulting Co(3+) -mediated immobilization is resistant toward strong ligands, such as imidazole and ethylenediaminetetraacetic acid (EDTA), and washing off over time because of the high thermodynamic and kinetic stability of the Co(3+) complex. This immobilization method is compatible with a wide variety of surface coatings, including silane self-assembled monolayers (SAMs) on glass, thiol SAMs on gold surfaces, and supported lipid bilayers. Furthermore, once the cobalt center has been oxidized, it becomes inert toward reducing agents, specific and unspecific interactions, so that it can be used to orthogonally functionalize surfaces with multiple proteins. Overall, the large number of available His-tagged proteins and materials with NTA groups make the Co(3+) -mediated interaction an attractive and widely applicable platform for protein immobilization.
Cytokines are potentially useful biomarkers of sepsis and other inflammatory conditions. Many cytokines can be released by leukocytes and platelets after sampling. The sampling and processing techniques are consequently critically important to measure the in vivo levels. We therefore examined the effects of four different anticoagulants, EDTA, citrate, lepirudin, heparin compared to serum, on the levels of 27 different cytokines. The effects of storage temperature, freezing and thawing on the plasma cytokines were examined. Cytokines were analysed using a multiplex immunoassay. The cytokine levels in serum were significantly higher compared with plasma, consistent with release of cytokines in vitro during coagulation. In general, the lowest values for all cytokines were found in EDTA samples, stored on crushed ice, centrifuged within 4h and thereafter stored at -80°C. MCP-1 and MIP-1β levels were highest in heparin plasma and storage of blood for up to 4h at room temperature significantly increased the interleukin (IL)-2, IL-6, IL-8, IFN-γ and GM-CSF levels in EDTA plasma, indicating post-sampling release. In contrast, the IP-10 levels were unaffected by sample storage at both temperatures. Our results indicate that the cytokines were more stable in plasma than in whole blood after sampling. Thus, cytokines should be analysed in EDTA plasma samples stored on ice and centrifuged within 4h. Based on these data, the reference ranges of 27 cytokines in EDTA plasma in 162 healthy human donors were calculated.
HbA1c is used in forensic toxicology to identify undiagnosed diabetes mellitus (DM) and those with poor glycemic control prior to death. HbA1c is typically measured in whole blood collected in tubes containing ethylenediaminetetraacetic acid (EDTA). The effect of other additives, including sodium fluoride (NaF), is unclear. Furthermore, the assessment of short- and long-term stability of HbA1c has produced conflicting results. In this study, we collected paired postmortem blood samples in EDTA and NaF tubes (n = 142) to assess their comparability for HbA1c measurement. Stability was assessed by measuring HbA1c at baseline, 2, 3, and 4 weeks postcollection (stored at 4°C) and at 2, 4, 6, and 12 months postcollection (stored at -20°C). We found no significant difference in HbA1c between the two preservatives at any of the time points indicating NaF is a suitable preservative for HbA1c measurement. We also determined that DM status, postmortem interval, and decomposition had no effect on stability.
Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial
- JAMA : the journal of the American Medical Association
- Published almost 7 years ago
Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy.
We describe the synthesis of a catenane that consists of two triply entwined 114-membered rings, a molecular link. The woven scaffold is a hexameric circular helicate generated by the assembly of six tris(bipyridine) ligands with six iron(II) cations, with the size of the helicate promoted by the use of sulfate counterions. The structure of the ligand extension directs subsequent covalent capture of the catenane by ring-closing olefin metathesis. Confirmation of the Star of David topology (two rings, six crossings) is provided by NMR spectroscopy, mass spectrometry and X-ray crystallography. Extraction of the iron(II) ions with tetrasodium ethylenediaminetetraacetate affords the wholly organic molecular link. The self-assembly of interwoven circular frameworks of controlled size, and their subsequent closure by multiple directed covalent bond-forming reactions, provides a powerful strategy for the synthesis of molecular topologies of ever-increasing complexity.
An automated, droplet-flow microfluidic system explores and optimizes Pd-catalyzed Suzuki-Miyaura cross-coupling reactions. A smart optimal DoE-based algorithm is implemented to increase the turnover number and yield of the catalytic system considering both discrete variables-palladacycle and ligand-and continuous variables-temperature, time, and loading-simultaneously. The use of feedback allows for experiments to be run with catalysts and under conditions more likely to produce an optimum; consequently complex reaction optimizations are completed within 96 experiments. Response surfaces predicting reaction performance near the optima are generated and validated. From the screening results, shared attributes of successful precatalysts are identified, leading to improved understanding of the influence of ligand selection upon transmetalation and oxidative addition in the reaction mechanism. Dialkylbiarylphosphine, trialkylphosphine, and bidentate ligands are assessed.