Recycling of Waste Toner Powder as Adsorbent to Remove Aqueous Heavy Metals.

The removal of Cd2+, Zn2+ and Ni2+ from metal solutions onto waste toner power (WTP) was investigated. The influence of parameters such as pH, contact time, initial metal concentration and adsorbent dosage was studied in batch adsorption experiments. Batch equilibrium experiments showed that the highest removal efficiency for Zn2+ and Cd2+ occurs at pH 7, while pH 5 is the most suitable for Ni2+ removal. The amount of metal removed (mg/g) improved when increasing the initial concentration, and sorption of heavy metals reached equilibrium in 24 h. Metals' uptake increased with increasing adsorbent dosage. The adsorption isotherms of Zn2+, Cd2+ and Ni2+ onto WTP fit the Langmuir better than the Freundlich model with correlation coefficient R2 values ranging from 0.998 to 0.968 and 0.989 to 0.881, respectively. The data showed that the maximum adsorption capacity of heavy metals, amax, ranged from 2.42 to 1.61 mg/g, from 6.22 to 2.01 mg/g and from 3.49 to 2.56 mg/g for Ni2+, Zn2+ and Cd2+, respectively, with the three WTPs used in this study. This adsorbent can potentially be used to remove metal ions from wastewater.

Application of biochar, compost and ZVI nanoparticles for the remediation of As, Cu, Pb and Zn polluted soil.

Here we tested the capacity of zero valent iron nanoparticles (nZVI) combined with two organic amendments, namely, compost and biochar, to immobilize metal(oid)s such as As, Cu, Pb, and Zn. In addition, the effects of the amendments on the development of Brassica juncea L., a plant widely used for phytoremediation purposes, were also examined. To perform the experiments, pots containing polluted soil were treated with nZVI, compost-biochar, or a blend of compost-biochar-nZVI. Metal(oid)s availability and soil properties were evaluated after 15 and 75 days, and the height and weight of the plants were measured to determine development. The compost-biochar amendment showed excellent capacity to immobilize metals, but As availability was considerably increased. However, the addition of nZVI to the mixture corrected this effect considerably. In addition, soil treatment with nZVI alone led to a slight increase in Cu availability, which was not observed for the mixture with organic amendments. With respect to soil properties, the CEC and pH were enhanced by the compost-biochar amendment, thereby favoring plant growth. Nevertheless, the nanoparticles reduced the concentration of available P, which impaired plant growth to a certain extent. In conclusion, Fe-based nanoparticles combined with organic amendments emerge as powerful approaches to remediate soils contaminated by metals and metalloids.

A multi-faceted, environmental forensic characterization of a paradigmatic brownfield polluted by hazardous waste containing Hg, As, PAHs and dioxins.

Hg and As mining-metallurgy plants have severely impacted environmental compartments. La Soterraña site (northern Spain) has been previously studied in this context. However, here we used a novel multi-purpose forensic approach to examine accumulations not only of mining-metallurgical waste (volumes above 80,000 t) but also C&D waste as a repository of pollutants (above 10% of As leached in standard tests) at this site. High Hg and As content in very fine grain-size fractions (up to 100,000 mg/kg of As in metallurgy waste below 10 µm) was significant, as was the predominance of As (III) in metallurgy waste. In addition, GC-MS techniques revealed the predominance of PAHs (secondarily Oxy-PAHs and PCBs), which showed a pyrogenic fingerprint, as determined by molecular ratios. Moreover, toxic organometallics (Hg-aromatics) were detected and metallurgy waste was identified as a source of dioxins and furanes (TEQ close to 30). On the basis of our observations, La Soterraña emerges as one of the most polluted sites in Europe and therefore requires urgent remediation. Our key findings indicate that C&D waste should be considered hazardous. Metallurgy waste, in turn, raises maximum concern given the simultaneous presence of toxic inorganic and organic contaminants.

Industrial waste materials as adsorbents for the removal of As and other toxic elements from an abandoned mine spoil heap leachate: a case study in Asturias.

The purpose of this study is to determine the capacity of four industrial waste materials originate from steelmaking processes and from gas treatment at a thermal power plant to remove As and other contaminants from a leachate from the spoil heap of an abandoned mercury mine. Arsenic removal is faster in the first minutes, then increases only slightly over time reaching equilibrium in 8 hours. As removal efficiency increased with increasing adsorbent concentration. As removal efficiency was found to be 82.7%, 71%, 37.2% and 27.2% for EA, FA, HA and G, respectively, when employing 80 g/dm3 of adsorbent concentration. The main mechanism of As removal appears to be the results show that Hg and Pb are completely removed using low concentrations of adsorbents regardless of the waste material used in the treatment. FA removed more than 82% of other toxic elements such as Ni, Cu and Cd. EA is the most effective byproduct of the four employed in this study for removing pollutants, while G is the least effective. The present study shows it is possible to carry out an efficient and economical treatment of mine leachate using these byproducts.

Efficacy and safety of a ready-to-drink bowel preparation for colonoscopy: a randomized, controlled, non-inferiority trial.

BACKGROUND: We performed a randomized, controlled, assessor-blinded, multicenter, non-inferiority (NI) study to compare the safety and efficacy of a ready-to-drink formulation of sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) with a powder formulation (P/MC powder) for oral solution. METHODS: Eligible participants (adults undergoing elective colonoscopy) were randomized 1:1 to split-dose SPMC oral solution or P/MC powder. The primary efficacy endpoint assessed overall colon-cleansing quality with the Aronchick Scale (AS), and the key secondary efficacy endpoint rated quality of right colon cleansing with the Boston Bowel Preparation Scale (BBPS). Assessments were performed by a treatment-blinded endoscopist. Tolerability was assessed using the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events and laboratory evaluations. RESULTS: The study included 901 participants: 448 for SPMC oral solution; 453 for P/MC powder. SPMC oral solution demonstrated non-inferiority to P/MC powder {87.7% (393/448) responders versus 81.5% (369/453) responders [difference (95% confidence interval): 6.3% (1.8, 10.9)]}. The key secondary efficacy objective assessing the right colon was also met. According to the prespecified hierarchical testing, after meeting the primary and key secondary objectives, SPMC oral solution was tested for superiority to P/MC powder for the primary endpoint (p = 0.0067). SPMC oral solution was well tolerated. Most common adverse events were nausea (3.1% versus 2.9%), headache (2.7% versus 3.1%), hypermagnesemia (2.0% versus 5.1%), and vomiting (1.3% versus 0.7%) for SPMC oral solution and P/MC powder, respectively. CONCLUSIONS: Ready-to-drink SPMC oral solution showed superior efficacy of overall colon cleansing compared with P/MC powder, with similar safety and tolerability.[ClinicalTrials.gov identifier: NCT03017235.].

Treatment of mining waste leachate by the adsorption process using spent coffee grounds.

The removal of heavy metals from mining waste leachate by spent coffee grounds has been investigated. In synthetic solutions, metal uptake was studied in batch adsorption experiments as a function of pH, contact time, initial metal concentration, adsorbent concentration, particle size, and the effect of co-ions (Na, K, Ca, Mg, Cu, Cd, Ni, Zn). Results showed that adsorption was significantly affected by pH, showing the highest affinity within a pH range of 5-7. Sorption of heavy metals reached equilibrium in 3 h. Removal percentages of metals ions increased with increasing dosage. Particle size did not have a significant influence on metal uptake. The adsorption of heavy metals was found to fit Langmuir and Freundlich isotherms. Maximum Zn, Cd and Ni uptake values were calculated as 10.22, 5.96 and 7.51 mg/g, respectively, using unwashed coffee grounds (UCG) as the adsorbent and 5.36, 4.28 and 4.37 mg/g when employing washed coffee grounds as the adsorbent. The presence of co-ions inhibited the uptake of heavy metals, divalent ions having a more negative effect than monovalent ions. The results obtained in the experiments with mining waste leachate showed that UCG is effective in removing heavy metals.

Successful sulfur recovery in low sulfurate compounds obtained from the zinc industry: Evaporation-condensation method.

The improvement of an evaporation-condensation method allows for successful recovery of elemental sulfur from sulfide concentrates from the zinc industry. Elemental sulfur can be obtained with this method in samples with a low (60%) sulfur content. The effects of heating temperature between 150°C and 250°C and heating time up to 120min on the recovery of sulfur are also studied. Elemental sulfur obtained in this way is of high purity and therefore, there is no need for further purification. The treatment of these industrial residues would help removing sulfur from the environment.

Suppression of glomerulonephritis in lupus-prone NZB × NZW mice by RN486, a selective inhibitor of Bruton's tyrosine kinase.

OBJECTIVE: Bruton's tyrosine kinase (BTK) plays a critical role in B cell development and function. We recently described a selective BTK inhibitor, RN486, that blocks B cell receptor (BCR) and Fcγ receptor signaling and is efficacious in animal models of arthritis. The aim of this study was to examine the potential efficacy of BTK in systemic lupus erythematosus (SLE), using an NZB × NZW mouse model of spontaneous SLE. METHODS: Mice received RN486 or its vehicle (administered in chow) at a final concentration of 30 mg/kg for 8 weeks, starting at 32 weeks of age. RESULTS: The administration of RN486 completely stopped disease progression, as determined by histologic and functional analyses of glomerular nephritis. The efficacy was associated with striking inhibition of B cell activation, as demonstrated by a significant reduction in CD69 expression in response to BCR crosslinking. RN486 markedly reduced the secretion of IgG anti-double-stranded DNA (anti-dsDNA) secretion, as determined by enzyme-linked immunosorbent and enzyme-linked immunospot assays. Flow cytometric analysis demonstrated depletion of CD138(high) B220(low) plasma cells in the spleen. RN486 inhibited secretion of IgG anti-dsDNA but not IgM anti-dsDNA, suggesting that pharmacologic blockade of BTK resembles the reported transgenic expression of low levels of endogenous BTK in B cells. In addition, RN486 may also impact the effector function of autoantibodies, as evidenced by a significant reduction in immune complex-mediated activation of human monocytes in vitro and down-regulation of the expression of macrophage-related and interferon-inducible genes in both the kidneys and spleens of treated mice. CONCLUSION: Collectively, our data suggest that BTK inhibitors may simultaneously target autoantibody-producing and effector cells in SLE, thus constituting a promising therapeutic alternative for this disease.

Synthesis of three commercial products from Bayer electrofilter powders.

Electrofilter powders, a by-product of the Bayer process for the production of alumina from bauxite, were leached with sulphuric acid to dissolve gibbsite and transition aluminas, thus obtaining a commercial aluminium sulphate solution and a solid residue. This residue is treated again under more drastic conditions with sulphuric acidic in a furnace at a higher temperature, is then leached with water and filtered, a small amount of solid remaining (alpha-alumina). The liquid is a highly acidic aluminium sulphate solution which does not fulfil commercial grade specifications; the liquor is accordingly treated with potassium hydroxide or ammonium hydroxide to obtain potassium or ammonium alum. Experimental tests were conducted to investigate the synthesis of alum by crystallization. The effects on alum formation of various operating conditions, including the amount of potassium or ammonium hydroxide, temperature and seed alum dosage, were examined. The crystallization process was found to be quite effective in obtaining alum.

Design, synthesis, and structure-activity relationship of novel CCR2 antagonists.

A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog 59 was found to posses potent antagonistic activity.

Conformational studies of 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists leading to new spirocyclic antagonists.

In an effort to shed light on the active binding conformation of our 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists, we prepared several conformationally constrained analogs resulting from backbone cyclization. Evaluation of CCR2 binding affinities for these analogs gave insight into the optimal relative positions of the piperidine and benzylamide moieties while simultaneously leading to the discovery of a new, potent lead type based upon a spirocyclic acetal scaffold.

Potent heteroarylpiperidine and carboxyphenylpiperidine 1-alkyl-cyclopentane carboxamide CCR2 antagonists.

This report describes replacement of the 4-(4-fluorophenyl)piperidine moiety in our CCR2 antagonists with 4-heteroaryl piperidine and 4-(carboxyphenyl)-piperidine subunits. Some of the resulting analogs retained potency in our CCR2 binding assay and had improved selectivity versus the I(Kr) channel; poor selectivity against I(Kr) had been a liability of earlier analogs in this series.

CCR5 blockade modulates inflammation and alloimmunity in primates.

Pharmacologic antagonism of CCR5, a chemokine receptor expressed on macrophages and activated T cells, is an effective antiviral therapy in patients with macrophage-tropic HIV infection, but its efficacy in modulating inflammation and immunity is only just beginning to be investigated. In this regard, the recruitment of CCR5-bearing cells into clinical allografts is a hallmark of acute rejection and may anticipate chronic rejection, whereas conventionally immunosuppressed renal transplant patients homozygous for a nonfunctional Delta32 CCR5 receptor rarely exhibit late graft loss. Therefore, we explored the effects of a potent, highly selective CCR5 antagonist, Merck's compound 167 (CMPD 167), in an established cynomolgus monkey cardiac allograft model. Although perioperative stress responses (fever, diminished activity) and the recruitment of CCR5-bearing leukocytes into the graft were markedly attenuated, anti-CCR5 monotherapy only marginally prolonged allograft survival. In contrast, relative to cyclosporine A monotherapy, CMPD 167 with cyclosporine A delayed alloantibody production, suppressed cardiac allograft vasculopathy, and tended to further prolong graft survival. CCR5 therefore represents an attractive therapeutic target for attenuating postsurgical stress responses and favorably modulating pathogenic alloimmunity in primates, including man.

3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2.

A series of low molecular weight antagonists of both the human and murine CC chemokine receptor 2, containing a 1-alkyl-3-(3-methyl-4-spiroindenylpiperidine)-substituted cyclopentanecarboxamide, is described. A SAR study of the C(1) substituent revealed that short, branched alkyl groups such as isopropyl, isobutyl, or cyclopropyl are optimal for both human and murine CCR2 binding activity.

Discovery of 3-piperidinyl-1-cyclopentanecarboxamide as a novel scaffold for highly potent CC chemokine receptor 2 antagonists.

Introduction of ring restrictions to a linear aminobutyramide CC chemokine receptor 2 (CCR2) antagonist lead (2) led to the discovery of a 1,3-disubstituted cyclopentane scaffold with enhanced hCCR2 receptor binding and antagonist activity. (1S,3R)-N-[3,5-Bis(trifluoromethyl)benzyl]-1-methyl-3-[(1R,3'R)-methyl-1'H-spiro[indene-1,4'-piperidin]-1'-yl]cyclopentanecarboxamide (16) had IC50 of 1.3 nM (binding) and 0.45 nM (functional chemotaxis) against hCCR2. It also showed activity against the mouse CCR2 receptor with an IC50 of 130 nM. Compound 16 is selective against other chemokine receptors, including CCR5 ( approximately 500-fold).

Diaryl substituted pyrazoles as potent CCR2 receptor antagonists.

We have identified and synthesized a series of diaryl substituted pyrazoles as potent antagonists of the chemokine receptor subtype 2. Structure-activity relationship studies directed toward improving the potency led to the discovery of 23 (IC50 = 6 nM).

Novel, orally bioavailable gamma-aminoamide CC chemokine receptor 2 (CCR2) antagonists.

Through modification of a screening hit we have discovered a structurally distinct new lead, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-(4-fluorophenyl)-4-(4-phenylpiperidin-1-yl)butanamide (11), which has subsequently served as the departure point for an ongoing program targeting CCR2 antagonists. Optimization of 11 leading to antagonists 26 and 37 is described. Antagonist 26 was shown to have good oral bioavailability in rats. Antagonist 37 had a CCR2 IC50 of 59 nM and excellent potency in a functional assay measuring inhibition of MCP-1 induced monocyte chemotaxis (IC50 of 41 nM).

Discovery of 3,5-bis(trifluoromethyl)benzyl L-arylglycinamide based potent CCR2 antagonists.

Systematic modification of a screening lead yielded a class of potent glycinamide based CCR2 antagonists. The best compound (55, (2S)-N-[3,5-bis(trifluoromethyl)benzyl]-2-{[2-(1-piperidinyl)ethyl]amino}-2-(3-thienyl)acetamide) displayed good binding affinity (IC50=30 and 39 nM) toward human monocytes and CHO cell expressing human CCR2b, respectively. Functionally, it blocked MCP-1 (CCL2)-induced calcium mobilization (IC50=50 nM) and chemotaxis mediated through the CCR2 receptor (9.6 nM). It is selective against other chemokine receptors tested.

Leukotriene B4 strongly increases monocyte chemoattractant protein-1 in human monocytes.

OBJECTIVE: Leukotriene B4 (LTB4), a product of the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism, has been implicated in atherosclerosis. However, the molecular mechanisms for the atherogenic effect of LTB4 are not well understood. This study is to determine candidate mechanisms. METHOD AND RESULTS: Primary human monocytes were treated with LTB4 and the supernatant was analyzed for cytokine/chemokine production by an immuno-protein array. This analysis revealed a strong increase of the monocyte chemoattractant protein-1 (MCP-1), a proinflammatory cytokine. Follow-up analyses with MCP-1 enzyme-linked immunosorbent assay (for quantitation of MCP-1 protein) and real-time polymerase chain reaction (PCR) (for MCP-1 mRNA) demonstrated that LTB4 strongly induced expression of MCP-1 protein and mRNA in a time-dependent and dose-dependent fashion. This induction was effectively abolished by CP-105,696, an antagonist for the LTB4 receptor BLT1. Selective inhibitors of ERK1/2 or JNK MAPK effectively blocked the LTB4-induced MCP-1 production. Furthermore, LTB4 increased NF-[kappa]B DNA binding activity, which was blocked by CP-105,696. CONCLUSIONS: LTB4 strongly induces MCP-1 production in primary human monocytes. This induction is mediated through the BLT1 pathway increasing MCP-1 transcription. Activation of ERK1/2 or JNK MAPK is essential for this induction. The NF-[kappa]B activation may be involved in LTB4-increased MCP-1 expression. The LTB4-induced MCP-1 in human monocytes may play a critical role in the atherogenicity of LTB4.