A DFT study on the adsorption of benzodiazepines to vermiculite surfaces

Widespread use of pharmaceuticals such as benzodiazepines has been resulting over the last decades in the dissemination of residues of these compounds in the environment, and such fact has been raising increasing concern. The generally low efficiencies of conventional wastewater treatment processes for the removal of this type of pollutants demands for the development of alternative or complementary water and wastewater treatment technologies, among which adsorption processes have been gaining popularity, provided that cheap efficient adsorbents are found. Clay materials have been one of the popular choices in this regard. In the present study, quantumchemical calculations have been performed by periodic DFT using the projector augmented-wave (PAW) method to characterize the interactions of two benzodiazepine molecules, alprazolam and diazepam, with a surface of clay mineral, vermiculite. It was observed that both molecules interact strongly with the vermiculite surface, both through a water-bridge binding and by cation-bridge provided by the exchangeable Mg2+ cations of the vermiculite surface. The results point to an interesting potential of vermiculite to be used efficiently as filter medium to remove these pollutants from water and wastewater

A DFT Study on the Adsorption of Benzodiazepines to Clay Surfaces

Benzodiazepines (BDZ) belong to the group of psychiatric substances which act on the central nervous system, having anxiolytic, sedative and hypnotic effects and is one of the most prescribed groups of pharmaceuticals throughout the world. These compounds are not exclusively used for human therapeutics, their prescription is also common in veterinary treatments for anxiolytic and appetite stimulation effects. Nowadays, there are several benzodiazepines under international control for therapeutic use. The widespread use of these compounds doesn’t come without a cost and trace levels of it can now be found disseminated on the environment, what is a matter of ecological concern. In fact, over the last decade, there has been a significant number of studies reporting the occurrence of BDZ in environmental matrices, namely in wastewater treatment plants influents and effluents, surface waters and drinking waters . Some of the more frequently detected BDZ include alprazolam, diazepam, lorazepam and oxazepam . The main reason for the ubiquitous presence of BDZ in the environment is associated not only with the large use but also the generally low efficiency of conventional biological wastewater treatment to remove these pharmaceutical residues. It has been suggested that this inefficiency is due to the halogenated structure of these compounds that significantly reduces their susceptibility to biodegradation . Adsorption processes are the most promising and cheap alternative for removal of these kind of organic xenobiotic from wastewaters. In recent years, inexpensive widely available materials have been investigated for the selection of efficient adsorbents that can make adsorption processes an attractive solution at reasonable costs. Among some of the adsorbents studied, clay-based materials have received some attention due to their interesting properties such as the high cation exchange capacity, swelling properties and high specific surface areas. In particular for the treatment of wastewaters, these materials can overcome the limitations of biological processes, as used in conventional wastewater treatment. A better understanding of the interactions of these organic molecules with clay minerals may thus allow a more judicious selection of materials for water/wastewater treatment filters that present significant enhancements in the removal of BDZ. In this work, electronic structure calculations based on the density functional theory (DFT) are presented on the interaction of two BDZ molecules (diazepam and alprazolam) with a periodic model surface of the vermiculite mineral. Geometry changes of the molecules upon adsorption were compared and the interaction energies with the surfaces were determined for a few different molecular orientations in order to understand the way these molecules interact with the clay surface and the essential factor governing the adsorption processes

Pilot-scale study on the removal of pharmaceuticals by LECA based SSF-constructed wetlands

In recent years, the occurrence and fate of pharmaceutically active compounds (PhACs) in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. Some compounds are just resistant to degradation in the sewage treatment plants (STPs) while others, although suffering partial degradation, still end up in receiving water bodies due to the large inputs received in STPs [1]. Clofibric acid (a metabolite from a series of widely used blood lipids lowering agents), ibuprofen (an anti-inflamatory non-prescription drug) and carbamazepine (an anticonvulsant and mood stabilizing drug) are some of the most frequently found PhACs in environmental monitoring studies [1]. Wastewater treatment by sub-surface flow constructed wetland systems (SSF-CWs) is a low-cost technology that has shown some capacity for removal of several organic xenobiotic pollutants, but fewer studies exist on pharmaceuticals behavior. The aim of the present work was to evaluate the efficiency of a pilot SSF-CW assembled with the plants cattail (Typha spp.) and a clay material (LECA 2/4) as support matrix, for the removal of three pharmaceuticals, namely ibuprofen (IB), carbamazepine (CB) and clofibric acid (CA), from contaminated wastewaters. Four beds were planted with pre-grown cattails (density of 80 plants/m2) and four were left unplanted to be used as controls. Experiments were conducted both in batch and in continuous mode with a flooding rate of 100%. Pharmaceutical concentrations were quantified by HPLC with UV detection at 210 nm (CB), 222 nm (IB) and 230 nm (CA). Solid phase extraction was used for sample pre-concentration whenever the measured pharmaceutical concentrations fell under the limit of quantification of the analytical method. The physico-chemical characterization of the support matrix material, LECA, involved the determination of properties such as pH, point of zero charge, electrical conductivity, apparent porosity, bulk density and hydraulic conductivity. In order to shed some light on the tolerance mechanisms developed by Typha spp. in the presence of these pharmaceuticals, biochemical and physiological parameters were evaluated. Typha spp. showed good tolerance to the presence of CA, CB and IB concentrations of 1 mg L-1, which is a value much higher than those usually reported in wastewaters. LECA alone was able to remove about 90% of the initial amounts of CB and IB in solution, and 50% of CA. IB was very susceptible to microbial degradation and up to 80% of the initial concentration could be removed by the microbial population present in the wastewater used. Overall, the CWS shows a higher removal performance for CA, CB and IB than any of its individual components (plants, support matrix, microorganisms) considered separately. CA proved to be the most resilient compound, which comes in agreement with other published data. However, this system enabled the removal of substantially higher amounts of CA than has previously been reported in other studies. The use of systems of this kind for the removal of pharmaceuticals from wastewaters seems like a promising alternative to the less efficient processes of conventional wastewater treatment

Removal of the Antibiotic Sulfamethoxazole by “Green” Clay Sorbents

Contamination of water resources with pharmaceuticals has been one of the top concerns of environmental sciences in the latest years [1, 2], the matter having received very significant media coverage recently [2, 3]. Antibiotics in particular have been gathering considerable attention and are amongst the most serious worries due to the development of antibiotic resistant bacteria as result of prolonged exposure [1, 2, 3]. In particular, antimicrobials and their metabolites are being detected in significant amounts in water supplies, and although no evidence exists that human health is affected by minute doses of antibiotics over long periods of time, changes have been observed in ecosystem functions [3,4]. In addition to antimicrobial resistance, other effects have been observed such as a delay in cell growth of bacteria, limited denitrification, and shifts in community composition [5]. Sulfamethoxazole (SMX), a broad-spectrum biostatic sulfanilamide, has become a point of interest because of its prevalence in contaminated wastewaters at concentrations correlated to bacterial resistance and genetic mutations in organisms [3,4,5]. Taking into account the widespread use of sulfonamides and their potential environmental effects, there is importance in developing new technologies for removing SMX and similar compounds from points of discharge. In fact, most wastewater treatment plants are inefficient for the removal of most micropollutants, especially hardly biodegradable organic xenobiotics which are present in wastewaters at low concentrations, as these conventional systems were only designed for removing bulk pollutants. Several advanced technologies have been evaluated as options to treat these contaminants, e.g. advanced oxidative processes or membrane filtration, but despite the sometimes high removal efficiencies attained, these technologies are too expensive to be considered as viable solutions on a large scale. Adsorption, alone or as part of a more complex water or wastewater treatment process, has been seen as playing a very important role in the removal of many organic xenobiotic pollutants [6, 7]. In this regard, the choice of adsorbent materials is crucial. However, pollutants removal efficiency is not the sole selection criterion, as the cost of the materials may provide or preclude economic viability of the water/wastewater treatment system. Therefore, the quest for efficient adsorbents that are widely available, and do not require expensive processing in order to be used (thereby allowing lower production costs) is a very important aspect of research aimed to manage this environmental problem. In this work we present the study of sorption properties of clay materials (LECA and vermiculite) for the removal of SMX from water. The dependence of removal efficiencies on the antibiotic initial concentrations, contact time with the adsorbents and other system/environment conditions was assessed. The two clay materials were compared in terms of their more balanced performance towards the removal of the pharmaceutical tested and the materials are suggested as a useful component of a water or wastewater treatment system designed for the removal of this contaminant (and others of similar type). Vermiculite was shown to be more efficient than LECA in the adsorption of the pharmaceutical and the one with faster kinetics. In other to gain a deeper insight into the characteristics that favor the removal of this compound by mineral surfaces, quantum chemical theoretical calculations were performed to illustrate the type of interactions that are responsible for the preferable adsorption of the compound to the vermiculite surface

Removal of pharmaceuticals in constructed wetlands using Typha and LECA. A pilot-scale study.

An ever-increasing number of xenobiotic compounds are getting detected in environmental samples worldwide. Serious concern about the contamination of water resources and drinking water supplies has aroused from the prevalence of pharmaceutical residues in the aquatic ecosystems. Some pharmaceuticals such as ibuprofen, carbamazepine and clofibric acid are frequently detected in waters [1]. These compounds are generally quantified at low concentrations (at the ng/L or mg/L range) but, due to their persistence in the environment and to potentially cumulative effects in the organisms, studies have shown that these compounds can have some damaging effects on the aquatic ecosystems [1]. Several xenobiotic organic compounds have already been removed from contaminated waters using constructed wetlands (CW) where the processes occurring in natural wetlands can be optimized in engineered man-made ecosystems, specifically designed for wastewater treatment. Among several physico-chemical phenomena, sorption by the support matrix plays an important role in the contaminant removal mechanisms. It is important to select a matrix with a high sorption capacity, which will depend on the physico-chemical properties of the material chosen. Previous studies have shown that expanded clay (LECA) is capable to remove, by sorption, this type of substances from water [2]. CWs also take advantage of the ability of plants to adsorb, uptake and concentrate pollutants, as well as to release root exudates that enhance compound biotransformation and degradation. Wetland species such as the cattail (Typha spp.) have already been tested and found suitable for the removal of several organic compounds from wastewaters, being commonly used in CWs [3]. The aim of the present work was to evaluate the efficiency of a subsurface flow constructed wetland assembled with the plants Typha spp. and LECA as support matrix, for the removal of three pharmaceuticals, namely ibuprofen, carbamazepine and clofibric acid, from contaminated waters

Sorption behavior of granular matrices for application in pharmaceutical removal by SSF constructed wetlands

In recent years, the occurrence and fate of pharmaceutically active compounds (PhACs) in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. Clofibric acid, ibuprofen and carbamazepine are some of the most frequently found PhACs in environmental monitoring studies. Some xenobiotics have already been successfully removed from contaminated waters using constructed wetlands (CW). Depuration of wastewaters in CWs is achieved by the concerted action between plant rhizomes, microorganisms and matrix component. CWs efficiency can be significantly improved by careful selection of the matrix, plants and microorganism used. Among several physico-chemical phenomena, sorption by the matrix plays an important role in the PhACs removal mechanism. It is important to select a matrix with a high sorption capacity, which depends on the physico-chemical properties of the material chosen. Previous studies carried out by the authors showed that expanded clay (LECA) presents a high sorptive affinity by clofibric acid [1]. The aim of the present work was to evaluate the capacity of LECA to remove other PhACs, namely ibuprofen and carbamazepine, and compare the results obtained with these pharmaceuticals with those obtained previously with clofibric acid. In addition, other materials were tested for the removal of clofibric acid and the results were compared with those obtained with LECA. The ultimate objective of this work will be to optimize the performance of this component in the overall performance of a constructed wetlands system designed for the removal of PhACs from wastewaters

Using clay materials to remove pharmaceuticals from waters

Pharmaceutical active compounds (PhACs) have an important role in the treatment and prevention of disease in both human and animals. Ingested drugs are only partially absorbed by the organisms and studies have shown that the excreted compounds are only partially removed in the sewage treatment plants (STPs) [1]. Contaminated effluents are being released from the STPs and trace amounts of PhACs have been detected in wastewaters, surface and groundwaters worldwide [1]. Acidic pharmaceuticals like diclofenac, ibuprofen and clofibric acid are some of the most frequently detected compounds [1]. The concentrations detected are low (ng/L - μg/L) but, due to the very nature of these compounds, studies have shown damaging effects on the aquatic ecosystems [1]. Several different processed natural materials can be used as filter media in water and wastewater treatment systems. Some of these materials can additionally present functions which extend beyond the simple process of filtration. Their surface areas can constitute a support for microbial population growth in biofilters as well as support matrix for the development of macrophytes in sub-surface flow constructed wetland systems (SSF-CWS) [2] which are increasingly being used in sewage tertiary treatment. The efficiency of these biological systems in the removal of xenobiotics can be significantly enhanced by a greater capability of the support matrix to retain contaminants by sorption phenomena, ionic exchange or other physico-chemical processes [2]. The aim of the present work was to evaluate the efficiency of two different materials namely, Light Expanded Clay Aggregates [LECA] (in two different particle sizes) and sand, for the removal from water of three acidic PhACs, clofibric acid, diclofenac and ibuprofen. In addition, relationships were established between the compounds removal efficiencies and the physico-chemical properties of each material. A series of batch essays were carried out to study the sorption capacities of the different materials for the 3 chemical compounds. The influence of some experimental conditions, such as the contact time, the initial PhACs concentrations (1 mg/L up to 50 mg/L) and LECA particle size, were investigated. The media were sterilized before use in order to minimize any microbial development on the matrix and experiments were conducted in the dark to avoid any photocatalytic degradation reactions. The mineralogical composition of the materials was determined by X-ray diffraction and some physico-chemical properties were characterized. Samples of the contaminants’ aqueous solutions were collected over a range of contact times with the support matrix and the remaining concentrations in solution were determined by UV/Vis spectrophotometry. The results show that LECA has a good sorption capacity for acidic compounds. In contrast, sand does not exhibit any sorption capacity for any of the compounds tested. Not surprisingly, LECA with smaller particle sizes show higher efficiencies that larger grade LECA, due to a larger available surface area. However, the use of these smaller particle media at upper scales may present problems with hydraulic conductivities. From the results obtained, it can be concluded that expanded clay presents important advantages as a CWS support matrix or as a filter medium, because it has a good sorption capacity, a pH buffer capacity and an excellent control of hydraulic permeability. On the other hand, sand does not exhibit any sorption capacity that might enhance the performance of filters and CWS in the treatment of water contaminated with this type of contaminants

Removing pharmaceutical residues from contaminated wastewaters using expanded clay aggregates

Pharmaceutical compounds (PhCs) are ingested in large quantities by humans in treatment and prevention of disease, but they are only partially absorbed by the organisms being excreted together with their metabolites. The sewage treatment plants (STP) are only able to partially remove some of these compounds and, despite the low concentrations present in the wastewaters (ng-μg/L), these xenobiotics can still pose a serious threat to the aquatic environments. Sub-surface flow constructed wetland systems (SSF-CWS) are biological systems used in wastewater treatment, and clay materials can be used as support matrices for these systems. Clay materials act not only as filters but they also can potentially remove organic pollutants due to its sorption properties. In this study a processed clay material, light expanded clay aggregates (LECA), was tested for their sorption capacity towards three widespread water polluting pharmaceuticals, namely clofibric acid (CA), ibuprofen (IB) and carbamazepine (CB). Sorption assays were done with aqueous solutions of the individual compounds and with their mixture at different concentrations from 1.0 to 50.0 mg L-1. The sorptive properties of LECA were also investigated using wastewater spiked with a mixture of the three compounds at the same concentrations tested for the aqueous solutions. Reversed phase HPLC with UV-Vis detection at 210, 222 and 227 nm for CB, IB and CA respectively was used to measure the compounds concentrations. For the single-compound solutions the HPLC analyses were performed in isocratic mode with a mobile phase composed by 75:25 acetonitrile:water with 0.1% (v/v) phosphoric acid. For the solutions containing the three compounds, the separation was performed using the same elution solvents and a gradient program. The total run time was 8 minutes, the flow rate was 1.0 mL min-1 and the injection volume was 20 µL. Calibration curves were constructed for standard solutions of CB, IB and CA individually, as well as solutions containing the three mixed compounds. The average areas of the compounds’ peaks were plotted against the standards concentrations resulting in linear correlations with R2 equal to or higher than 0.999 in every calibration curve. Whenever the measured concentrations were below the method’s LOQs of 0.27 mg L-1, 0.39 mg L-1 and 0.13 mg L-1 for CB, IB and CA respectively, the samples were pre-concentrated on LiChrolut® RP-18. All data were analyzed by the analysis of variance method (ANOVA, single factor) at different significance levels. Results for the individual compounds in aqueous solutions have shown that LECA presents higher removal rates for IB and CB (44 – 92% and 60 – 95% respectively) whereas for CA the removal rates are moderate but still significant (30– 58%). In any case, and for all the studied compounds, the % removal decreased with the increasing load, the lower % removal still correspond to increasing absolute amounts sorbed. When the three compounds are put simultaneously in contact with LECA there are evidences of competitive sorption among the studied compounds, with CB being the less affected compound of the three. When all the compounds were dissolved in wastewater, there was a slight loss of removal efficiency, probably due to an increased solubility in the aqueous media owing to the organic matter present in the wastewater or to competitive sorption effects. Considering the hydraulic and physico-chemical properties of LECA which make this material suitable for constructed wetlands applications, its sorption properties evidenced in this work make it especially interesting for applications aiming at the removal of this kind of pollutants from wastewaters

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE)

Introduction Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord which causes motor and sensory disturbance and limited recovery in 50% of patients. Standard treatment is steroids, and patients with more severe disease appear to respond to plasma exchange (PLEX). Intravenous immunoglobulin (IVIG) has also been used as an adjunct to steroids, but evidence is lacking. We propose the first randomised control trial in adults and children, to determine the benefit of additional treatment with IVIG. Methods and analysis 170 adults and children aged over 1 year with acute first episode TM or neuromyelitis optica (with myelitis) will be recruited over a 2.5-year period and followed up for 12 months. Participants randomised to the control arm will receive standard therapy of intravenous methylprednisolone (IVMP). The intervention arm will receive the above standard therapy, plus additional IVIG. Primary outcome will be a 2-point improvement on the American Spinal Injury Association (ASIA) Impairment scale at 6 months postrandomisation by blinded assessors. Additional secondary and tertiary outcome measures will be collected: ASIA motor and sensory scales, Kurtzke expanded disability status scale, International Spinal Cord Injury (SCI) Bladder/Bowel Data Set, Client Services Receipt Index, Pediatric Quality of Life Inventory, EQ-5D, SCI Pain and SCI Quality of Life Data Sets. Biological samples will be biobanked for future studies. After 6-months' follow-up of the first 52 recruited patients futility analysis will be carried out. Health economics analysis will be performed to calculate cost-effectiveness. After 6 months’ recruitment futility analysis will be performed