Synthetic Haemostatic Sealants: Effectiveness, Safety, and In Vivo Applications.

Rapid haemostasis during surgery is essential when one wants to reduce the duration of operations, reduce the need for transfusions, and above all when one wants to achieve better patient management. The use of haemostatic agents, sealants, and adhesives improves the haemostatic process by offering several advantages, especially in vascular surgery. These agents vary widely in their mechanism of action, composition, ease of application, adhesion to wet or dry tissue, immunogenicity, and cost. The most used are cyanoacrylate-based glues (Glubran 2) or polysaccharide hydrogel-microsphere powder (AristaTMAH). This work is based on a retrospective study carried out on a sample of patients with different vascular diseases (FAV, pseudoaneurysm, and PICC application) in which two different haemostatic sealants were used. The aim was to assess the safety, the advantages, and the ability of both sealants to activate the haemostatic process at the affected site, also in relation to their chemical-physical characteristics. The obtained results showed that the application of Glubran 2 and AristaTMAH as surgical wound closure systems is effective and safe, as the success achieved was ≥94% on anastomoses of FAV, 100% on stabilization of PICC catheters, and ≤95% on pseudoaneurysms.

Gallic Acid-Based Hydrogels for Phloretin Intestinal Release: A Promising Strategy to Reduce Oxidative Stress in Chronic Diabetes.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia caused by abnormalities in insulin secretion and/or action. In patients with diabetes, complications such as blindness, delayed wound healing, erectile dysfunction, renal failure, heart disease, etc., are generally related to an increase in ROS levels which, when activated, trigger hyperglycemia-induced lesions, inflammation and insulin resistance. In fact, extensive cell damage and death occurs mainly due to the effect that ROS exerts at the level of cellular constituents, causing the deterioration of DNA and peroxidation of proteins and lipids. Furthermore, elevated levels of reactive oxygen species (ROS) and an imbalance of redox levels in diabetic patients produce insulin resistance. These destructive effects can be controlled by the defense network of antioxidants of natural origin such as phloretin and gallic acid. For this reason, the objective of this work was to create a nanocarrier (hydrogel) based on gallic acid containing phloretin to increase the antioxidant effect of the two substances which function as fundamental for reducing the mechanisms linked to oxidative stress in patients suffering from chronic diabetes. Furthermore, since the bioavailability problems of phloretin at the intestinal level are known, this carrier could facilitate its release and absorption. The obtained hydrogel was characterized using Fourier transform infrared spectroscopy (FT-IR). Its degree of swelling (a%) and phloretin release were tested under pH conditions simulating the gastric and intestinal environment (1.2, 6.8 and 7.4). The antioxidant activity, inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a free radical source, was evaluated for four hours. All results showed that gallate hydrogel could be applied for releasing intestinal phloretin and reducing the ROS levels.

Advances in Nanomaterials Based on Cashew Nut Shell Liquid.

Cashew nut shell liquid (CNSL), obtained as a byproduct of the cashew industry, represents an important natural source of phenolic compounds, with important environmental benefits due to the large availability and low cost of the unique renewable starting material, that can be used as an alternative to synthetic substances in many industrial applications. The peculiarity of the functional groups of CNSL components, such as phenolic hydroxyl, the aromatic ring, acid functionality, and unsaturation(s) in the C15 alkyl side chain, permitted the design of interesting nanostructures. Cardanol (CA), anacardic acid (AA), and cardol (CD), opportunely isolated from CNSL, served as building blocks for generating an amazing class of nanomaterials with chemical, physical, and morphological properties that can be tuned in view of their applications, particularly focused on their bioactive properties.

Evaluation of Effective Composite Biosorbents Based on Wood Sawdust and Natural Clay for Heavy Metals Removal from Water.

Bentonitic clay and wood sawdust are natural materials widely available in nature at low cost with high heavy metals sorption properties that, in this work, were combined to achieve an effective composite biosorbent with high sorption properties and enhanced mechanical stability. Pine, aspen, and birch wood sawdust, as well as different bentonite clays and different sawdust modification methods (H3PO4 or HCl) were used for preparing new composite biosorbents. A mixture of wood sawdust and bentonite in a ratio of 2:1 was used. All materials were characterized by using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope (SEM) methods and tested for Cu and Ni ions removal from water. The adsorption process for all composite biosorbents was well described from a pseudo-second order kinetic model (R2 > 0.9999) with a very high initial adsorption rate of Cu and Ni ions and a maximum uptake recorded within 2 h. The results have shown that the adsorption capacity depends mainly on the kind of wood and the acid treatment of the wood that enhances the adsorption capacity. At a concentration of 50 mg/L, the biosorbent prepared using birch wood sawdust showed the worst performance, removing barely 30% of Cu and Ni ions, while aspen wood sawdust improved the adsorption of Cu (88.6%) and Ni (52.4%) ions. Finally, composite biosorbent with pine wood sawdust showed the best adsorption be haviour with an efficiency removal of 98.2 and 96.3% of Cu and Ni ions, respectively, making it a good candidate as an inexpensive and effective biosorbent for the removal of heavy metals.

Hyaluronic Acid-Mediated Phenolic Compound Nanodelivery for Cancer Therapy.

Phenolic compounds are bioactive phytochemicals showing a wide range of pharmacological activities, including anti-inflammatory, antioxidant, immunomodulatory, and anticancer effects. Moreover, they are associated with fewer side effects compared to most currently used antitumor drugs. Combinations of phenolic compounds with commonly used drugs have been largely studied as an approach aimed at enhancing the efficacy of anticancer drugs and reducing their deleterious systemic effects. In addition, some of these compounds are reported to reduce tumor cell drug resistance by modulating different signaling pathways. However, often, their application is limited due to their chemical instability, low water solubility, or scarce bioavailability. Nanoformulations, including polyphenols in combination or not with anticancer drugs, represent a suitable strategy to enhance their stability and bioavailability and, thus, improve their therapeutic activity. In recent years, the development of hyaluronic acid-based systems for specific drug delivery to cancer cells has represented a pursued therapeutic strategy. This is related to the fact that this natural polysaccharide binds to the CD44 receptor that is overexpressed in most solid cancers, thus allowing its efficient internalization in tumor cells. Moreover, it is characterized by high biodegradability, biocompatibility, and low toxicity. Here, we will focus on and critically analyze the results obtained in recent studies regarding the use of hyaluronic acid for the targeted delivery of bioactive phenolic compounds to cancer cells of different origins, alone or in combination with drugs.

Polymeric Based Hydrogel Membranes for Biomedical Applications.

The development of biomedical applications is a transdisciplinary field that in recent years has involved researchers from chemistry, pharmacy, medicine, biology, biophysics, and biomechanical engineering. The fabrication of biomedical devices requires the use of biocompatible materials that do not damage living tissues and have some biomechanical characteristics. The use of polymeric membranes, as materials meeting the above-mentioned requirements, has become increasingly popular in recent years, with outstanding results in tissue engineering, for regeneration and replenishment of tissues constituting internal organs, in wound healing dressings, and in the realization of systems for diagnosis and therapy, through the controlled release of active substances. The biomedical application of hydrogel membranes has had little uptake in the past due to the toxicity of cross-linking agents and to the existing limitations regarding gelation under physiological conditions, but now it is proving to be a very promising field This review presents the important technological innovations that the use of membrane hydrogels has promoted, enabling the resolution of recurrent clinical problems, such as post-transplant rejection crises, haemorrhagic crises due to the adhesion of proteins, bacteria, and platelets on biomedical devices in contact with blood, and poor compliance of patients undergoing long-term drug therapies.

Solid Lipid Nanoparticles Hydroquinone-Based for the Treatment of Melanoma: Efficacy and Safety Studies.

Classical melanoma therapy has several side effects that are responsible for a decrease in the final therapeutic efficacy. It is possible that the drug is degraded before reaching the target site and is metabolized by the body itself, resulting in repeated doses being administered throughout the day and a decrease in patient compliance. Drug delivery systems avoid degradation of the active ingredient, improve release kinetics, prevent the drug from being metabolized before reaching the site of action, and improve the safety and efficacy profiles of adjuvant cancer therapy. The solid lipid nanoparticles (SLNs) based on hydroquinone esterified with stearic acid realized in this work represent a chemotherapeutic drug delivery system that is useful in the treatment of melanoma. The starting materials were characterized by FT-IR and 1H-NMR, while the SLNs were characterized by dynamic light scattering. In efficacy studies, their ability to influence anchorage-dependent cell proliferation was tested on COLO-38 human melanoma cells. Furthermore, the expression levels of proteins belonging to apoptotic mechanisms were determined by analyzing the role of SLNs in modulating the expression of p53 and p21WAF1/Cip1. Safety tests were conducted to determine not only the pro-sensitizing potential but also the cytotoxicity of SLNs, and studies were conducted to assess the antioxidant and anti-inflammatory activity of these drug delivery.

Transdermal Delivery of Phloretin by Gallic Acid Microparticles.

Exposure to ultraviolet (UV) radiation causes harmful effects on the skin, such as inflammatory states and photoaging, which depend strictly on the form, amount, and intensity of UV radiation and the type of individual exposed. Fortunately, the skin is endowed with a number of endogenous antioxidants and enzymes crucial in its response to UV radiation damage. However, the aging process and environmental stress can deprive the epidermis of its endogenous antioxidants. Therefore, natural exogenous antioxidants may be able to reduce the severity of UV-induced skin damage and aging. Several plant foods constitute a natural source of various antioxidants. These include gallic acid and phloretin, used in this work. Specifically, polymeric microspheres, useful for the delivery of phloretin, were made from gallic acid, a molecule that has a singular chemical structure with two different functional groups, carboxylic and hydroxyl, capable of providing polymerizable derivatives after esterification. Phloretin is a dihydrochalcone that possesses many biological and pharmacological properties, such as potent antioxidant activity in free radical removal, inhibition of lipid peroxidation, and antiproliferative effects. The obtained particles were characterized by Fourier transform infrared spectroscopy. Antioxidant activity, swelling behavior, phloretin loading efficiency, and transdermal release were also evaluated. The results obtained indicate that the micrometer-sized particles effectively swell, and release the phloretin encapsulated in them within 24 h, and possess antioxidant efficacy comparable to that of free phloretin solution. Therefore, such microspheres could be a viable strategy for the transdermal release of phloretin and subsequent protection from UV-induced skin damage.

Green Synthesis of Iridium Nanoparticles from Winery Waste and Their Catalytic Effectiveness in Water Decontamination.

An environmentally friendly procedure was adopted for the first time to prepare green iridium nanoparticles starting from grape marc extracts. Grape marcs, waste of Negramaro winery production, were subjected to aqueous thermal extraction at different temperatures (45, 65, 80, and 100 °C) and characterized in terms of total phenolic contents, reducing sugars, and antioxidant activity. The results obtained showed an important effect of temperature with higher amounts of polyphenols and reducing sugars and antioxidant activity in the extracts with the increase of temperature. All four extracts were used as starting materials to synthesize different iridium nanoparticles (Ir-NP1, Ir-NP2, Ir-NP3, and Ir-NP4) that were characterized by Uv-Vis spectroscopy, transmission electron microscopy, and dynamic light scattering. TEM analysis revealed the presence of very small particles in all samples with sizes in the range of 3.0-4.5 nm with the presence of a second fraction of larger nanoparticles (7.5-17.0 nm) for Ir-NPs prepared with extracts obtained at higher temperatures (Ir-NP3 and Ir-NP4). Since the wastewater remediation of toxic organic contaminants on catalytic reduction has gained much attention, the application of the prepared Ir-NPs as catalysts towards the reduction of methylene blue (MB), chosen as the organic dye model, was evaluated. The efficient catalytic activity of Ir-NPs in the reduction of MB by NaBH4 was demonstrated and Ir-NP2 was prepared using the extract obtained at 65 °C, showing the best catalytic performance, with a rate constant of 0.527 ± 0.012 min-1 and MB reduction of 96.1% in just six min, with stability for over 10 months.

Green Chemistry Principles for Nano- and Micro-Sized Hydrogel Synthesis.

The growing demand for drug carriers and green-technology-based tissue engineering materials has enabled the fabrication of different types of micro- and nano-assemblies. Hydrogels are a type of material that have been extensively investigated in recent decades. Their physical and chemical properties, such as hydrophilicity, resemblance to living systems, swelling ability and modifiability, make them suitable to be exploited for many pharmaceutical and bioengineering applications. This review deals with a brief account of green-manufactured hydrogels, their characteristics, preparations, importance in the field of green biomedical technology and their future perspectives. Only hydrogels based on biopolymers, and primarily on polysaccharides, are considered. Particular attention is given to the processes of extracting such biopolymers from natural sources and the various emerging problems for their processing, such as solubility. Hydrogels are catalogued according to the main biopolymer on which they are based and, for each type, the chemical reactions and the processes that enable their assembly are identified. The economic and environmental sustainability of these processes are commented on. The possibility of large-scale processing in the production of the investigated hydrogels are framed in the context of an economy aimed at waste reduction and resource recycling.

Expanded Polytetrafluoroethylene Membranes for Vascular Stent Coating: Manufacturing, Biomedical and Surgical Applications, Innovations and Case Reports.

Coated stents are defined as innovative stents surrounded by a thin polymer membrane based on polytetrafluoroethylene (PTFE)useful in the treatment of numerous vascular pathologies. Endovascular methodology involves the use of such devices to restore blood flow in small-, medium- and large-calibre arteries, both centrally and peripherally. These membranes cross the stent struts and act as a physical barrier to block the growth of intimal tissue in the lumen, preventing so-called intimal hyperplasia and late stent thrombosis. PTFE for vascular applications is known as expanded polytetrafluoroethylene (e-PTFE) and it can be rolled up to form a thin multilayer membrane expandable by 4 to 5 times its original diameter. This membrane plays an important role in initiating the restenotic process because wrapped graft stent could be used as the treatment option for trauma devices during emergency situations and to treat a number of pathological vascular disease. In this review, we will investigate the multidisciplinary techniques used for the production of e-PTFE membranes, the advantages and disadvantages of their use, the innovations and the results in biomedical and surgery field when used to cover graft stents.

Raclopride-Molecularly Imprinted Polymers: A Promising Technology for Selective [11C]Raclopride Purification.

In this work, we developed a novel approach to purify [11C]Raclopride ([11C]RAC), an important positron emission tomography radiotracer, based on tailored shape-recognition polymers, with the aim to substitute single-pass HPLC purification with an in-flow trap & release process. Molecular imprinting technology (MIT) applied to solid phase extraction (MISPE) was investigated to develop a setting able to selectively extract [11C]RAC in a mixture containing a high amount of its precursor, (S)-O-Des-Methyl-Raclopride (DM-RAC). Two imprinted polymers selective for unlabeled RAC and DM-RAC were synthesized through a radical polymerization at 65 °C using methacrylic acid and trimethylolpropane trimethacrylate in the presence of template molecule (RAC or DM-RAC). The prepared polymer was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy and tested in MISPE experiments. The polymers were used in testing conditions, revealing a high retention capacity of RAC-MISPE to retain RAC either in the presence of similar concentrations of RAC and DM-RAC precursor (96.9%, RSD 6.6%) and in the presence of a large excess of precursor (90%, RSD 4.6%) in the loading solution. Starting from these promising results, preliminary studies for selective purification of [11C]Raclopride using this RAC-MISPE were performed and, while generally confirming the selectivity capacity of the polymer, revealed challenging applicability to the current synthetic process, mainly due to high backpressures and long elution times.

Disposable Molecularly Imprinted Polymer-Modified Screen-Printed Electrodes for Rapid Electrochemical Detection of l-Kynurenine in Human Urine.

l-Kynurenine (l-Kyn) is an endogenous metabolite produced in the catabolic route of l-Tryptophan (l-Trp), and it is a potential biomarker of several immunological disorders. Thus, the development of a fast and cheap technology for the specific detection of l-Kyn in biological fluids is of great relevance, especially considering its recent correlation with SARS-CoV-2 disease progression. Herein, a disposable screen-printed electrode based on a molecularly imprinted polymer (MIP) has been constructed: the o-Phenylenediamine monomer, in the presence of l-Kyn as a template with a molar ratio of monomer/template of 1/4, has been electropolymerized on the surface of a screen-printed carbon electrode (SPCE). The optimized kyn-MIP-SPCE has been characterized via cyclic voltammetry (CV), using [Fe(CN)6)]3-/4- as a redox probe and a scanning electron microscopy (SEM) technique. After the optimization of various experimental parameters, such as the number of CV electropolymerization cycles, urine pretreatment, electrochemical measurement method and incubation period, l-Kyn has been detected in standard solutions via square wave voltammetry (SWV) with a linear range between 10 and 100 µM (R2 = 0.9924). The MIP-SPCE device allowed l-Kyn detection in human urine in a linear range of 10-1000 µM (R2 = 0.9902) with LOD and LOQ values of 1.5 and 5 µM, respectively. Finally, a high selectivity factor α (5.1) was calculated for l-Kyn toward l-Trp. Moreover, the Imprinting Factor obtained for l-Kyn was about seventeen times higher than the IF calculated for l-Trp. The developed disposable sensing system demonstrated its potential application in the biomedical field.

Green Aspects in Molecularly Imprinted Polymers by Biomass Waste Utilization.

Molecular Imprinting Polymer (MIP) technology is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. In the last decades, MIP technology has gained much attention from the scientific world as summarized in several reviews with this topic. Furthermore, green synthesis in chemistry is nowadays one of the essential aspects to be taken into consideration in the development of novel products. In accordance with this feature, the MIP community more recently devoted considerable research and development efforts on eco-friendly processes. Among other materials, biomass waste, which is a big environmental problem because most of it is discarded, can represent a potential sustainable alternative source in green synthesis, which can be addressed to the production of high-value carbon-based materials with different applications. This review aims to focus and explore in detail the recent progress in the use of biomass waste for imprinted polymers preparation. Specifically, different types of biomass waste in MIP preparation will be exploited: chitosan, cellulose, activated carbon, carbon dots, cyclodextrins, and waste extracts, describing the approaches used in the synthesis of MIPs combined with biomass waste derivatives.

Directional Immobilization of Proteins on Gold Nanoparticles Is Essential for Their Biological Activity: Leptin as a Case Study.

Gold nanomaterials hold great potential for biomedical applications. While this field is evolving rapidly, little attention has been paid to precise nanoparticle design and functionalization. Here, we show that when using proteins as targeting moieties, it is fundamental to immobilize them directionally to preserve their biological activity. Using full-length leptin as a case study, we have developed two alternative conjugation strategies for protein immobilization based on either a site-selective or a nonselective derivatization approach. We show that only nanoparticles with leptin immobilized site-selectively fully retain the ability to interact with the cognate leptin receptor. These results demonstrate the importance of a specified molecular design when preparing nanoparticles labeled with proteins.

Response surface methodology approach for the preparation of a molecularly imprinted polymer for solid-phase extraction of fenoxycarb pesticide in mussels.

The aim of this work was to develop an efficient method for the selective extraction and analysis of fenoxycarb, a carbamate pesticide, in mussel samples using a molecularly imprinted solid-phase extraction device. The optimization of molecularly imprinted polymer synthesis was performed using the experimental design under the response surface methodology approach. A fast rebinding study and Freundlich isotherm adsorption were carried out to calculate binding capacity B, site number n, and affinity constant Kf . The optimum molecularly imprinted polymer was successfully used as sorbent of a solid-phase extraction cartridge for the determination of fenoxycarb in real mussel samples. The range of linearity was 0.3-30 mg/L with a correlation coefficient of 0.991. The limit of detection was 0.247 mg/kg. The recovery of fenoxycarb extracted from mussel samples of Mediterranean sea was 97% (n = 3) with relative standard deviation between 6 and 7% proving the reliability of the developed method.

Gold Nanoparticles Functionalized with RGD-Semipeptides: A Simple yet Highly Effective Targeting System for αV ß3 Integrins.

Effective and selective targeting of the αV ß3 integrin subtype is of high relevance in cancer research for the development of therapeutic systems with improved efficacy and of diagnostic imaging probes. We report here a new class of highly selective, αV ß3 -targeted gold nanoparticles (AuNPs), which carry cyclic 4-aminoproline-RGD semipeptides (cAmpRGD) as the targeting moiety immobilized at low surface density on the poly(ethylene glycol) (PEG)-based nanoparticle coating. We show that these nanoparticles are potent inhibitors of the integrin-mediated melanoma tumor cell adhesion to vitronectin and are selectively internalized via receptor-mediated endocytosis. Furthermore, we have developed bifunctional cAmpRGD-functionalized AuNPs by conjugation of a fluorophore (FAM or TAMRA) to a separate set of reactive groups on the PEG-based coating. These bifunctional AuNPs not only recapitulate the binding properties of cAmpRGD-AuNPs but also can be visualized via confocal laser microscopy, allowing direct observation of nanoparticle internalization. The peculiar molecular design of these nanoparticles and their precisely defined architecture at the molecular level accounts for their selective integrin binding with very low nonspecific background.

Urinary l-kynurenine quantification and selective extraction through a molecularly imprinted solid-phase extraction device.

l-Kynurenine is an endogenous metabolite generated by the catabolic pathway of l-tryptophan and it could be a potential biomarker to test the efficacy of several checkpoint inhibitors that have already reached the clinical trials in the antitumor therapy. Thus, a molecularly imprinted polymer specific for the recognition of this metabolite was synthesized and used as innovative system in solid-phase extraction technique for the specific extraction and quantification of l-kynurenine in human urine. The off-line system was firstly tested on l-kynurenine standard solutions, allowing recoveries up to 97.7% (relative standard deviation = 2.2%) and then applied to fortified and deproteinated human urine samples, where a recovery of 84.1% (relative standard deviation = 3.1%) was obtained. The method was validated and it revealed a good linearity in the range of 0.157-20 µg/mL (r2  = 0.9992). The optimized procedure demonstrated a good feasibility on biological samples, allowing a ready quantification of l-kynurenine in the human urine, where the metabolite was found at a very low concentration (0.80 µg/mL). The extraction system developed could attract attention of pharmaceutical industries for l-kynurenine production as potential drug in the treatment of autoimmune disorders through its extraction and purification from biological matrixes.

A New Ion-Imprinted Chitosan-Based Membrane with an Azo-Derivative Ligand for the Efficient Removal of Pd(II).

Herein, we described the synthesis of a novel ion-imprinted membrane for the detection of palladium(II) prepared through the glutaraldehyde crosslinking of chitosan with a 4-[(4-Hydroxy)phenylazo]benzenesulfonic acid ligand trapped into the membrane. The imprinting technology was used to improve adsorption capacity and adsorption selectivity, and was combined with some advantages of the developed membrane, such as low cost and ease of preparation, water-friendly synthesis, and high biocompatible chitosan material. The membranes were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Spectrometry (EDS). The results obtained showed a high swelling ratio with a maximum value of 16.4 (1640%) at pH 4 with a strong pH dependence. Batch rebinding experiments gave a maximum adsorption capacity of 101.6 mg of Pd(II) per gram of imprinted membrane. The Pd(II) adsorption behavior was well-described by a Langmuir model with a theoretical maximum adsorption capacity of 93.48 mg g-1, similar to the experimental one. Finally, a selectivity study versus Ag(I), Pb(II), and Fe(III) ions demonstrated a good selectivity of chitosan-imprinted membrane towards Pd(II).

Molecularly Imprinted Composite Membranes for Selective Detection of 2-Deoxyadenosine in Urine Samples.

An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. In this work, a novel molecularly imprinted polymer composite membrane (MIM) was synthesized and employed for the selective detection in urine samples of 2-deoxyadenosine (2-dA), an important tumoral marker. By thermal polymerization, the 2-dA-MIM was cross-linked on the surface of a polyvinylidene-difluoride (PVDF) membrane. By characterization techniques, the linking of the imprinted polymer on the surface of the membrane was found. Batch-wise guest binding experiments confirmed the absorption capacity of the synthesized membrane towards the template molecule. Subsequently, a time-course of 2-dA retention on membrane was performed and the best minimum time (30 min) to bind the molecule was established. HPLC analysis was also performed to carry out a rapid detection of target molecule in urine sample with a recovery capacity of 85%. The experiments indicated that the MIM was highly selective and can be used for revealing the presence of 2-dA in urine samples.