Non-steroidal Anti-inflammatory Diclofenac Research Articles

Re-assessment of monoclonal antibodies against diclofenac for their application in the analysis of environmental waters.

The non-steroidal anti-inflammatory drug (NSAID) diclofenac (DCF) is an important environmental contaminant occurring in surface waters all over the world, because, after excretion, it is not adequately removed from wastewater in sewage treatment plants. To be able to monitor this pollutant, highly efficient analytical methods are needed, including immunoassays. In a medical research project, monoclonal antibodies against diclofenac and its metabolites had been produced. Based on this monoclonal anti-DCF antibody, a new indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed and applied for environmental samples. The introduction of a spacer between diclofenac and the carrier protein in the coating conjugate led to higher sensitivity. With a test midpoint of 3 μg L-1 and a measurement range of 1-30 μg L-1, the system is not sensitive enough for direct analysis of surface water. However, this assay is quite robust against matrix influences and can be used for wastewater. Without adjustment of the calibration, organic solvents up to 5%, natural organic matter (NOM) up to 10 mg L-1, humic acids up to 2.5 mg L-1, and salt concentrations up to 6 g L-1 NaCl and 75 mg L-1 CaCl2 are tolerated. The antibody is also stable in a pH range from 3 to 12. Cross-reactivity (CR) of 1% or less was determined for the metabolites 4'-hydroxydiclofenac (4'-OH-DCF), 5-hydroxydiclofenac (5-OH-DCF), DCF lactam, and other NSAIDs. Relevant cross-reactivity occurred only with an amide derivative of DCF, 6-aminohexanoic acid (DCF-Ahx), aceclofenac (ACF) and DCF methyl ester (DCF-Me) with 150%, 61% and 44%, respectively. These substances, however, have not been found in samples. Only DCF-acyl glucuronide with a cross-reactivity of 57% is of some relevance. For the first time, photodegradation products were tested for cross-reactivity. With the ELISA based on this antibody, water samples were analysed. In sewage treatment plant effluents, concentrations in the range of 1.9-5.2 μg L-1 were determined directly, with recoveries compared to HPLC-MS/MS averaging 136%. Concentrations in lakes ranged from 3 to 4.4 ng L-1 and were, after pre-concentration, determined with an average recovery of 100%.

Effects of Ibuprofen and Diclofenac Pre-Treatment on Viability and Apoptosis Processes in Human Dental Pulp Stem Cells

Background and Objectives: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. Materials and Methods: We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro, as well as their effects on the expression of angiogenic growth factors (VEGFA and HGF) and selected genes in apoptosis signalling pathways (BAX, BAK, CASP3, CASP9, and BCL2). Results: Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Conclusions: Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.

Chemoreactomic analysis of acyzole in comparison with zinc derivatives of nonsteroidal anti-inflammatory drugs

Background. Nonsteroidal anti-inflammatory drugs (NSAIDs) are characterized by ulcerogenic effects and used for effective and safe pharmacotherapy of inflammation and pain. The zinc-containing drug acyzole is a promising anti-inflammatory drug that potentially does not have this drawback. Objective: to conduct chemoreactomic modeling of the pharmacological effects of acyzole and zinc derivatives of well-known NSAIDs (diclofenac, nimesulide, ketorolac).Material and methods. The analysis of the pharmacological capabilities of NSAIDs was based on a chemoinformatic approach, i.e. comparing the chemical structure of the studied molecules with the structures of millions of other molecules with established molecular pharmacological properties. The analysis procedure was based on the latest machine learning technologies developed in the theory of topological and metric analysis of feature descriptions.Results. It was shown that acyzole might have an anti-inflammatory effect due to its impact on the activity of cytokines and, partly, on the metabolism of prostaglandins and leuktrienes. The central effects of acyzole are comparable to those of zinc-NSAIDs. The analgesic effect of acyzole may be associated with kinin receptors inhibition, and weak antihistamine and antinociceptin effects. Acizol may also exhibit a gastroprotective effect. It was established that acyzole, to a lesser extent than the reference molecules, negatively affected the metabolism of vitamins and microelements.Conclusion. Chemoreactomic profiling of acyzole indicates prospects for its use as an anti-inflammatory drug.

Spatial patterns in the diet of Gyps vultures in India and their implications for conservation

Dietary analyses are particularly useful for developing conservation programmes for species threatened by resource depletion, poisoning and environmental pollution. Gyps vultures in South Asia represent one such case, having undergone a population collapse caused by feeding on carcasses of cattle treated with the non-steroidal anti-inflammatory drug diclofenac. Following a ban on the veterinary use of diclofenac, populations of vultures remain low and mostly concentrated near protected areas. Understanding the role of protected areas in the recovery of these critically endangered species requires analyses of spatial variation in their diet. We used faecal metabarcoding to investigate the spatial variation in the diet of Gyps vultures across four landscapes from sites located inside and outside protected areas. We collected faecal 642 samples, of which 419 yielded adequate molecular data to identify the vulture species and 30 molecular operational taxonomic units corresponding to at least 28 diet species. The diet was dominated by large ungulates and varied across landscapes, protection status and vulture species, with the observed variation largely explained by differential intake of wild and domestic species. Domestic livestock was present in >95 % of the samples from Central, West and North India, but 77 % of the samples had only wild species in South India. This variation was explained by livestock density within 100 km radius of the sampling site. Our results imply that protected areas may not offer a respite from possibility of diclofenac-poisoning across most parts of the country and efforts should continue unabated to remove nephrotoxic drugs from veterinary use.

Long-term dietary exposure to the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen can affect the physiology of common carp (Cyprinus carpio) on multiple levels, even at “environmentally relevant” concentrations

The aim of the study was to evaluate the effects of emerging environmental contaminants, the non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac (DCF) and ibuprofen (IBP), on physiological functions in juvenile common carp (Cyprinus carpio). Fish were exposed for 6 weeks, and for the first time, NSAIDs were administered through diet. Either substance was tested at two concentrations, 20 or 2000 μg/kg, resulting in four different treatments (DCF 20, DCF 2000, IBP 20, IBP 2000). The effects on haematological and biochemical profiles, the biomarkers of oxidative stress, and endocrine disruption were studied, and changes in RNA transcription were also monitored to obtain a comprehensive picture of toxicity. Fish exposure to high concentrations of NSAIDs (DCF 2000, IBP 2000) elicited numerous statistically significant changes (p < 0.05) in the endpoints investigated, with DCF being almost always more efficient than IBP. Compared to control fish, a decrease in total leukocyte count attributed to relative lymphopenia was observed. Plasma concentrations of total proteins, ammonia, and thyroxine, and enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase (ALP) were significantly elevated in either group, as were the activities of certain hepatic antioxidant enzymes (superoxide dismutase, glutathione-S-transferase) in the DCF 2000 group. The transcriptomic profile of selected genes in the tissues of exposed fish was affected as well. Significant changes in plasma total proteins, ammonia, ALT, and ALP, as well as in the transcription of genes related to thyroid function and the antioxidant defense of the organism, were found even in fish exposed to the lower DCF concentration (DCF 20). As it was chosen to match DCF concentrations commonly detected in aquatic invertebrates (i.e., the potential feed source of fish), it can be considered “environmentally relevant”. Future research is necessary to shed more light on the dietary NSAID toxicity to fish.

The radiation- and chemo-sensitizing capacity of diclofenac can be predicted by a decreased lactate metabolism and stress response

BackgroundAn enhanced aerobic glycolysis (“Warburg effect”) associated with an increase in lactic acid in the tumor microenvironment contributes to tumor aggressiveness and resistance to radiation and chemotherapy. We investigated the radiation- and chemo-sensitizing effects of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac in different cancer cell types.MethodsThe effects of a non-lethal concentration of diclofenac was investigated on c-MYC and Lactate Dehydrogenase (LDH) protein expression/activity and the Heat shock Protein (HSP)/stress response in human colorectal (LS174T, LoVo), lung (A549), breast (MDA-MB-231) and pancreatic (COLO357) carcinoma cells. Radiation- and chemo-sensitization of diclofenac was determined using clonogenic cell survival assays and a murine xenograft tumor model.ResultsA non-lethal concentration of diclofenac decreases c-MYC protein expression and LDH activity, reduces cytosolic Heat Shock Factor 1 (HSF1), Hsp70 and Hsp27 levels and membrane Hsp70 positivity in LS174T and LoVo colorectal cancer cells, but not in A549 lung carcinoma cells, MDA-MB-231 breast cancer cells and COLO357 pancreatic adenocarcinoma cells. The impaired lactate metabolism and stress response in diclofenac-sensitive colorectal cancer cells was associated with a significantly increased sensitivity to radiation and 5Fluorouracil in vitro, and in a human colorectal cancer xenograft mouse model diclofenac causes radiosensitization.ConclusionThese findings suggest that a decrease in the LDH activity and/or stress response upon diclofenac treatment predicts its radiation/chemo-sensitizing capacity.

Recent trends in populations of Critically Endangered Gyps vultures in India

Summary This paper reports results from the eighth of a series of road transect surveys of Gyps vultures conducted across northern, central, western, and north-eastern India since the early 1990s. Populations of the White-rumped Vulture Gyps bengalensis, Indian Vulture G. indicus, and Slender-billed Vulture G. tenuirostris declined rapidly, beginning in the mid-1990s. The principal cause of the declines was poisoning due to widespread veterinary use of the non-steroidal anti-inflammatory drug (NSAID) diclofenac on cattle. The results of the current survey suggest that, while populations of all three species of vulture remain at a low level with no signs of recovery, they appear to have been approximately stable since veterinary use of diclofenac was banned in the mid-2000s. Population trends in India, where the illegal use of diclofenac and legal use of other toxic NSAIDs continues, are compared with more positive trends in Nepal, where the veterinary use of toxic NSAIDs appears to have been reduced to a low level.

Fibromyalgia Animal Models Using Intermittent Cold and Psychological Stress.

Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain and other frequent symptoms such as fatigue, sleep disturbance, cognitive impairment, and mood disorder. Based on the view that intermittent stress would be the most probable etiology for FM, intermittent cold- and intermittent psychological stress-induced generalized pain (ICGP and IPGP) models in mice have been developed and validated as FM-like pain models in terms of the patho-physiological and pharmacotherapeutic features that are shared with clinical versions. Both models show long-lasting and generalized pain and female-predominant sex differences after gonadectomy. Like many other neuropathic pain models, ICGP and IPGP were abolished in lysophosphatidic acid receptor 1 (LPAR1) knock-out mice or by LPAR1 antagonist treatments, although deciding the clinical importance of this mechanism depends on waiting for the development of a clinically available LPAR1 antagonist. On the other hand, the nonsteroidal anti-inflammatory drug diclofenac with morphine did not suppress hyperalgesia in these models, and this is consistent with the clinical findings. Pharmacological studies suggest that the lack of morphine analgesia is associated with opioid tolerance upon the stress-induced release of endorphins and subsequent counterbalance through anti-opioid NMDA receptor mechanisms. Regarding pharmacotherapy, hyperalgesia in both models was suppressed by pregabalin and duloxetine, which have been approved for FM treatment in clinic. Notably, repeated treatments with mirtazapine, an α2 adrenergic receptor antagonist-type antidepressant, and donepezil, a drug for treating Alzheimer's disease, showed potent therapeutic actions in these models. However, the pharmacotherapeutic treatment should be carried out 3 months after stress, which is stated in the FM guideline, and many preclinical studies, such as those analyzing molecular and cellular mechanisms, as well as additional evidence using different animal models, are required. Thus, the ICGP and IPGP models have the potential to help discover and characterize new therapeutic medicines that might be used for the radical treatment of FM, although there are several limitations to be overcome.

Retrospective evaluation of the incidence of gastrointestinal bleeding in dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs.

To report the incidence of gastrointestinal (GI) bleeding and associated risk factors in a population of dogs receiving ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs). Medical records of dogs prescribed ophthalmic NSAIDs (cases), dogs receiving systemic NSAIDs alone and dogs receiving systemic prednisone alone (controls). Data were collected retrospectively from the medical records of 204 dogs prescribed ophthalmic NSAIDs (diclofenac, ketorolac, or flurbiprofen), which were subdivided based on if they received any concurrent systemic NSAIDs or glucocorticoids, 136 dogs receiving a systemic NSAID (carprofen or meloxicam) alone, and 151 dogs receiving a systemic glucocorticoid (prednisone) alone at a referral hospital from 2015 to 2019. Gastrointestinal bleeds developed in 8/79 (10.1%) of topical NSAID-only cases, 10/136 (7.4%) of systemic NSAID controls, and 14/151 (9.3%) of systemic glucocorticoid controls, with no significant difference between the three groups (p = .6103). There were no significant differences in GI bleed rates between cases treated with ketorolac, diclofenac, or flurbiprofen (p = .160), although severe GI bleeding was only seen in ketorolac-treated dogs. Presence of a known concurrent risk factor for GI bleeding was significantly associated with the development of GI bleed in dogs on ophthalmic NSAIDs (p = .032). Dogs treated with ophthalmic NSAIDs developed GI bleeding at a frequency comparable to dogs receiving systemic NSAIDs or systemic glucocorticoids alone, suggesting that dogs receiving ophthalmic NSAIDs may be at increased risk of GI bleeding.

Vaginal Vault Infiltration With Bupivacaine for Postoperative Pain Control After Total Laparoscopic Hysterectomy: A Randomized Control Trial

ABSTRACT A viable alternative to total abdominal hysterectomy is total laparoscopic hysterectomy (TLH), which offers abdominal route advantages for women in need of total hysterectomy for benign diseases. Fewer complications, faster recovery, and less pain are ensured by laparoscopy, although this method is not entirely devoid of pain. Reports from various authors indicate that up to 80% of laparoscopic surgery patients require opioid analgesia, which could increase hospital-stay duration and delay mobilization/recovery. Because of these statistics, opioid analgesic usages ought to be minimized, for the aforementioned reasons and also to prevent additional adverse effects. This study was performed to evaluate efficacy of reducing postoperative pain by infiltration of bupivacaine, a long-acting anesthetic agent, into the vaginal vault after TLH. This study was a randomized control trial designed as a 2-arm double-blinded study conducted at a North-Indian Apical Center in the Department of Obstetrics and Gynecology. After written informed consent from all patients, computer-generated randomization software placed them in 1 of 2 groups: group 1, the intervention group (received the infiltration of bupivacaine in the vaginal vault following TLH), or group 2 (the control group). The inclusion criteria were a uterine size of ≤12 weeks' pregnancy and patients requiring TLH with or without bilateral salpingo-oophorectomy for uterine size and benign conditions. Exclusion criteria were contraindication to any medication used by the study, presence of malignancy, history of multiple surgeries, and history of inflammatory disease. Postoperative pain outcome measured in both groups at 1, 3, 6, 12, and 24 hours via a visual analog score was the primary outcome. The secondary outcome was the need for rescue analgesia. A complete profile of each patient was created, using eligibility criteria, body mass index, and demographic profile, and a complete gynecological and physical examination was performed, along with preoperative investigations for fitness to general anesthesia. Per standard protocol, general anesthesia was administered for all surgeries. After vault closure, a fine-tipped aspiration needle was used to administer 10 mL of bupivacaine, which was infiltrated laparoscopically at 2 different locations, approximately 2–4 cm apart. The control group omitted this step. In the first 24 hours after operation, pain was treated using 1 g intravenous paracetamol every 6 hours. For the next 5 days, patients were given nonsteroidal anti-inflammatory drugs (diclofenac) 3 times daily for 5 days. Participants scaled their pain using the visual analog scale (VAS) score at the 1, 2, 6, 12, and 24 hours intervals postsurgery. Scores greater than 4 initiated the distribution of tramadol 50 mg intramuscular. Also recorded were the uterine weight, the operative time, complications, and the amount of operative bleeding. Group 1 patients exhibited VAS scores of less than 4 at 1 hour postsurgery (100%), 3 hours postsurgery (100%), 6 hours postsurgery (97%), 12 hours postsurgery (96.7%), and 24 hours postsurgery (36.7%). The control group VAS scores of less than 4 for the respective times were as follows: 1 hour (93%), 3 hours (86.6%), 6 hours (30%), 12 hours (10%), and 24 hours (3.3%). From these data, it is clear that the infiltration with a local analgesia was effective in reducing postoperative pain. Overall, a feasible and safe option for postoperative pain relief is vaginal cuff infiltration with local anesthetic. A significant increase in the number of women experiencing minimal postoperative pain for 24 hours after laparoscopic hysterectomy took place due to infiltration of the vaginal vault with 10 mL of 0.25% bupivacaine (with no complications). Furthermore, this method reduces requirements of additional opioid/analgesia usage. The beneficial use of local vault infiltration with bupivacaine after TLH within the first 24 postoperative hours is highlighted by this study.

New biobased chitosan/polyvinyl alcohol/graphene oxide derivatives for the removal of pharmaceutical compounds from aqueous mixtures

The main scope of this study is synthesis, characterization and implementation of new bio-based chitosan derivatives for the removal by adsorption of pharmaceutical mixtures from aqueous matrices. Six different materials of chitosan/polyvinyl alcohol were synthesized using an increasing quantity of graphene oxide and reduced graphene oxide (0.05%, 0.1% and 0.2%). A combination of different groups of pharmaceuticals was used as a model pollutant. Within this context, four non-steroidal anti-inflammatory drugs (diclofenac, ibuprofen, ketoprofen, paracetamol), one anti-epileptic (carbamazepine) and two antihypertensives (valsartan and irbesartan) were selected. The highest adsorption capacity was exhibited by the composites with the highest concentration of GO and rGO (0.2%), while the pollutants that presented the highest adsorption removal were valsartan and diclofenac. The adsorption process was appeared to be finished after 3 h for all compounds of the studied mixture (well-fitted to pseudo-2nd order model). The results indicated that the Langmuir model offered better match for the experimental data, while the adsorption capacity of adsorbents increased with the rise of the temperature. Overall, the highest adsorption capacities achieved at pH 10 (55 °C). Desorption was accomplished by using different aqueous eluents (with pH 2–10) and organic solvents. FTIR, SEM, EDS techniques were used to characterize the composition and morphology, and for the compounds detection the UHPLC system was used.

Circulating miR-222-3p is associated with ankylosing spondylitis development and predicts therapeutic efficacy of nonsteroidal anti-inflammatory drugs.

Ankylosing spondylitis (AS) is a chronic rheumatic disease, and some microRNAs (miRNAs) in AS have been identified. This study aimed to measure miR-222-3p expression in AS patients, investigate the association of miR-222-3p with AS disease activity, and explore the clinical value of miR-222-3p in diagnosing AS and predicting therapeutic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on AS patients. This study included 96 patients with AS, 58 patients with rheumatoid arthritis (RA), and 90 healthy controls. miR-222-3p expression was detected by reverse-transcription quantitative polymerase chain reaction (PCR). The ability of miR-222-3p to discriminate between different groups was evaluated by receiver operating characteristic analysis. The predictive value of miR-222-3p on the efficacy of NSAID treatment for AS was assessed by logistic regression analysis. AS patients treated with oral NSAIDs diclofenac sodium were divided into response (n = 76) and no-response (n = 20) groups after 16 weeks of treatment. miR-222-3p in AS patients was higher than that in healthy subjects and RA patients. miR-222-3p had high diagnostic value in distinguishing patients with AS from RA patients and healthy controls. miR-222-3p, increased in active AS patients, had the ability to screen active AS patients from inactive AS patients. miR-222-3p was decreased in the response group, and had high accuracy in predicting the therapeutic efficiency of NSAIDs. The findings indicate that increased miR-222-3p in AS patients may function as a diagnostic biomarker for AS, and predictive biomarker for the therapeutic efficacy of NSAIDs in patients with AS. In addition, miR-222-3p is associated with AS disease activity.

Poisoned baits pose a threat to vultures in Nepal

Poisoning is the greatest threat to vultures globally. Asia’s vultures were driven to near extinction through poisoning by the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Since the ban on the veterinary use of diclofenac in Nepal in 2006, there has been a partial recovery of vulture populations in the country. However, other threats are emerging, including other vulture-toxic NSAIDs, as well as other forms of unintentional poisoning. The use of poison baits, whereby animal carcasses are laced with poison to target carnivores, often results in the collateral deaths of vultures. Here, we summarize the data on the number of such poisoning incidents, and the number of vultures killed, between 2011 and 2023. A total of 224 vultures of seven species were found dead at 22 poisoning incidents across the country. Himalayan griffons accounted for over half of the fatalities (n = 108), along with 93 White-rumped vultures and small numbers of four other species. We recommend that conservationists raise the awareness of this issue with local stakeholders, and try to devise mitigation measures to reduce the threat of poisoning to vulture population.

Impact of hemoglobin A1c level on the association between non-steroidal anti-inflammatory drug use and cardiovascular events in patients with type 2 diabetes: A population-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) should be used cautiously in patients with type 2 diabetes. We examined whether the cardiovascular risks associated with NSAID use depended on HbA1c level in patients with type 2 diabetes. We conducted a population-based cohort study of all adult Danes with a first-time HbA1c measurement ≥48 mmol/mol during 2012-2020 (n = 103 308). We used information on sex, age, comorbidity burden, and drug use to calculate time-varying inverse probability of treatment weights. After applying these weights in a pooled logistic regression, we estimated hazard ratios (HRs) of the association between use of NSAIDs (ibuprofen, naproxen, or diclofenac) and cardiovascular events (a composite of myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, and all-cause death). We stratified all analyses by HbA1c level (<53 or ≥53 mmol/mol). For ibuprofen use, the HR of a cardiovascular event was 1.53 (95% confidence interval [CI]: 1.34-1.75) in patients with HbA1c <53 and 1.24 (95% CI: 1.00-1.53) in patients with HbA1c ≥53 mmol/mol. For naproxen use, the HR was 1.14 (95% CI: 0.59-2.21) in patients with HbA1c <53 and 1.30 (95% CI: 0.49-3.49) in patients with HbA1c ≥53 mmol/mol. For diclofenac use, the HR was 2.40 (95% CI: 1.62-3.56) in patients with HbA1c <53 and 2.89 (95% CI: 1.65-5.04) in patients with HbA1c ≥53 mmol/mol. In patients with type 2 diabetes, glycemic dysregulation did not affect the cardiovascular risk associated with NSAID use.

Effective bioremediation of clarithromycin and diclofenac in wastewater by microbes and Arundo donax L

Bioremediation of pharmaceuticals has gained large research efforts, but there is still a need to improve the performance of bioremediation systems by selecting effective organisms. In this study, we characterized the capability to remove clarithromycin (CLA) and diclofenac (DCF) by the bacterium Streptomyces rochei, and the fungi Phanerochaete chrysosporium and Trametes versicolor. The macrolide antibiotic CLA and the non-steroid anti-inflammatory DCF were selected because these are two of the most frequently detected drugs in water bodies. Growth and content of the PhCs and a DCF metabolite (MET) by the energy crop Arundo donax L. were also evaluated under hydroponic conditions. The removal rate (RR) by S. rochei increased from 24 to 40% at 10 and 100 µg CLA L−1, respectively, averaged over incubation times. At 144 h, the RR by P. chrysosporium was 84%, while by T. versicolor was 70 and 45% at 10 and 100 CLA µg L−1. The RR by S. rochei did not exceed 30% at 1 mg DCF L−1 and reached 60% at 10 mg DCF L−1, whereas approached 95% and 63% by P. chrysosporium and T. versicolor, respectively, at both doses. Root biomass and length of A. donax were strongly affected at 100 µg CLA L−1. CLA concentration in roots and shoots increased with the increase of the dose and translocation factor (TF) was about 1. DCF severely affected both shoot fresh weight and root length at the highest dose and concentration in roots and shoots increased with the increase of the dose. DCF concentrations were 16–19 times higher in roots than in shoots, and TF was about 0.1. MET was detected only in roots and its proportion over the parent compound decreased with the increase of the DCF dose. This study highlights the potential contribution of A. donax and the tested microbial inoculants for improving the effectiveness of bioremediation systems for CLA and DCF removal.

Effect of Diclofenac Concentration on Activated Sludge Conditions in a Biological Wastewater Treatment Plant

Significant quantities of pharmaceutical substances enter biological wastewater treatment plants, where they interact with activated sludge microorganisms. An example of a pharmaceutical commonly used is the non-steroidal anti-inflammatory drug diclofenac (DCF). The presence of high concentrations of DCF in wastewater can disrupt nutrient removal processes, which are highly sensitive to external environmental factors. This paper discusses the effect of high DCF concentrations (1.04 mg/dm3–12.5 mg/dm3; 0.25 mg/gTS–3.0 mg/gTS) on the efficiency of nitrifying, denitrifying and phosphate-accumulating organisms in the wastewater treatment cycle. The condition of the activated sludge was assessed on the basis of the oxygen and nitrogen uptake rates values and the ability to biologically remove phosphorus compounds from the wastewater. The effect of DCF on the ability of methane-forming bacteria to produce biogas in the anaerobic digester was also investigated. None of the biochemical reactions of activated sludge were inhibited at applied DCF concentrations. A 33% reduction in biogas production was observed at a DCF dose of 0.0391 mg/gTS. Slight deviations from the typical course of biochemical transformation of ammonium compounds were recorded at a DCF concentration of 3 mg/gTS of sludge. However, in the concentration range studied, no negative effect of DCF, on the operation of the activated sludge, was found.

Therapeutic Strategies to Prevent the Recurrence of Nasal Polyps after Surgical Treatment: An Update and In Vitro Study on Growth Inhibition of Fibroblasts.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis, which is typically characterized by a Type 2 inflammatory reaction, comorbidities and high rates of nasal polyp recurrence, causing severe impact on quality of life. Nasal polyp recurrence rates, defined as the number of patients undergoing revision endoscopic sinus surgery, are 20% within a 5 year period after surgery. The cornerstone of CRSwNP management consists of anti-inflammatory treatment with local corticosteroids. We performed a literature review regarding the therapeutic strategies used to prevent nasal polyp recurrence after surgical treatment. Finally, we report an in vitro study evaluating the efficacy of lysine-acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (ketoprofen and diclofenac) on the proliferation of fibroblasts, obtained from nasal polyp tissue samples. Our study demonstrates that diclofenac, even more so than lysine-acetylsalicylic acid, significantly inhibits fibroblast proliferation and could be considered a valid therapeutic strategy in preventing CRSwNP recurrence.

Diclofenac exhibits cytotoxic activity associated with metabolic alterations and p53 induction in ESCC cell lines and decreases ESCC tumor burden in vivo.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive forms of human malignancy, often displaying limited therapeutic response. Here, we examine the non-steroidal anti-inflammatory drug diclofenac (DCF) as a novel therapeutic agent in ESCC using complementary in vitro and in vivo models. DCF selectively reduced viability of human ESCC cell lines TE11, KYSE150, and KYSE410 as compared with normal primary or immortalized esophageal keratinocytes. Apoptosis and altered cell cycle profiles were documented in DCF-treated TE11 and KYSE 150. In DCF-treated TE11, RNA-Sequencing identified differentially expressed genes and Ingenuity Pathway Analysis predicted alterations in pathways associated with cellular metabolism and p53 signaling. Downregulation of proteins associated with glycolysis was documented in DCF-treated TE11 and KYSE150. In response to DCF, TE11 cells further displayed reduced levels of ATP, pyruvate, and lactate. Evidence of mitochondrial depolarization and superoxide production was induced by DCF in TE11 and KYSE150. In DCF-treated TE11, the superoxide scavenger MitoTempo improved viability, supporting a role for mitochondrial reactive oxygen species in DCF-mediated toxicity. DCF treatment resulted in increased expression of p53 in TE11 and KYSE150. p53 was further identified as a mediator of DCF-mediated toxicity in TE11 as genetic depletion of p53 partially limited apoptosis in response to DCF. Consistent with the anticancer activity of DCF in vitro, the drug significantly decreased tumor burdene in syngeneic ESCC xenograft tumors and 4-nitroquinoline 1-oxide-mediated ESCC lesions in vivo. These preclinical findings identify DCF as an experimental therapeutic that should be explored further in ESCC.

Trimethoprim - Sulfamethoxazole Induced Sweet Syndrome: A Case Report

Sweet syndrome (SS) also called as acute febrile neutrophilic dermatosis, is a rare inflammatory infectious skin reaction characterized clinically by tender, erythematous papules or plaque commonly appearing on the upper limbs, trunk, and head and neck. It is usually accompanied by fever and an elevation in the erythrocyte sedimentation rate (ESR), C- reactive protein. SS is classically triggered by infections, inflammatory bowel disease, pregnancy, malignancy or due to the administration of an associated drugs. Drug induce sweet syndrome (DISS) an uncommon subtype of SS. Drugs like antiepileptics like carbamazepine, diazepam, antibiotics like trimethoprim-sulfamethoxazole (TMP-SMX), minocycline, nitrofurantoin, norfloxacin, ofloxacin, contraceptives, non-steroidal anti-inflammatory drugs (NSAIDS) (celecoxib and diclofenac) and granulocyte – colony stimulating factor are the most common culprit. In this case, the patient was presented with oedematous and pustular eruption of nose with a rapid extension to the face, neck, upper trunk and the limbs which developed after taking TMP-SMX for 10 days accompanied with fever (42ºC) and cough. Laboratory test disclosed elevated WBC with notable increase in polymorphonuclear cells ,elevation of ESR (96mm/h), C-reactive protein (85ng/l, normal &lt;5) and α-2-globulin (10g/l, normal &lt;8). All these presentations clearly indicated that the patient is having DISS as per Walker and Cohen criteria for SS. TMP-SMX was discontinued upon which the lesions started to disappear. Clinical pharmacist must be more aware about the usage of TMP-SMX especially in immune compromised patients. Keywords: Drug induced sweet syndrome, Trimethoprim-sulfamethoxazole, Neutrophilic infiltration, Corticosteroids, oedematous papules,

Iron(III) Complexes with Non-Steroidal Anti-Inflammatory Drugs: Structure, Antioxidant and Anticholinergic Activity, and Interaction with Biomolecules

One the main research goals of bioinorganic chemists is the synthesis of novel coordination compounds possessing biological potency. Within this context, three novel iron(III) complexes with the non-steroidal anti-inflammatory drugs diflunisal and diclofenac in the presence or absence of the nitrogen donors 1,10-phenanthroline or pyridine were isolated and characterized by diverse techniques. The complexes were evaluated for their ability to scavenge in vitro free radicals such as hydroxyl, 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals, revealing their selective potency towards hydroxyl radicals. The in vitro inhibitory activity of the complexes towards the enzymes acetylcholinesterase and butyrylcholinesterase was evaluated, and their potential to achieve neuroprotection appeared promising. The interaction of the complexes with calf-thymus DNA was examined in vitro, revealing their ability to intercalate in-between DNA nucleobases. The affinity of the complexes for serum albumins was evaluated in vitro and revealed their tight and reversible binding.