Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury.

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.

Self-reported gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs in female students with dysmenorrhoea at Makerere University: prevalence, discontinuation and associated factors. a cross sectional study.

BACKGROUND: Primary dysmenorrhoea occurs in up to 50% of menstruating females. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used therapeutic remedies for dysmenorrhoea in Uganda. However, NSAIDs are associated with a 3-5 fold increase in the risk of gastrointestinal (GI) adverse drug effects. OBJECTIVES: We aimed to determine the prevalence and associated factors of self-reported NSAID-related GI adverse effects in female students who use NSAIDs in managing dysmenorrhoea-associated pain at Makerere University. DESIGN: A cross-sectional study. SETTING: Makerere University's main campus, situated North of Kampala, Uganda. PARTICIPANTS: 314 female students pursuing an undergraduate programme at Makerere University and residing in different halls of residence and hostels. OUTCOMES: Social demographic data, menstrual history and treatment data. RESULTS: Overall, 314 valid responses were received from female students with a median age of 22 years (IQR: 18-29 years). The median age at menarche was 13 years (IQR: 9-18 years). 41% (n=129/314) of the respondents had used medication for dysmenorrhoea and 32% (n=41/129) of whom reported NSAID-associated GI adverse effects with nausea being the most frequently reported (44%, n=18/41)Factors independently associated with GI adverse effects were: age at menarche (p=0.026), duration of menstruation (p=0.030) and use of ibuprofen (p=0.005). Females taking ibuprofen for dysmenorrhoea were about four times as likely to have NSAID-associated GI adverse effects (adjusted OR 3.87, 95% CI 1.51 to 9.91) than those who did not receive ibuprofen. Logistic regression was used to determine factors associated with self-reported adverse effects of NSAIDs among the female students. A p<0.05 was considered statistically significant. CONCLUSION: We found a considerably high prevalence of NSAID-related GI adverse effects driven by factors such as age at menarche and ibuprofen use.

[Current challenges for therapy of comorbid patients: a new look at celecoxib. A review].

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.

Design of double-core-shell structural materials for the extraction of non-steroidal anti-inflammatory drugs.

In this work, core-shell material with a special structure was designed and applied in solid-phase extraction (SPE) for non-steroidal anti-inflammatory drugs (NSAIDs) combined with high-performance liquid chromatography. Based on the advantages of core-shell ZIF-8@ZIF-67 (Zeolite imidazole ester framework materials [ZIFs]), effective derivatization treatment was carried out to partially vulcanize the original ZIFs, resulting in a special and new double-core-shell structural material CoS/ZIF-67/ZnS/ZIF-8 (ZIFs@ZnS@CoS) with porous surface and center hollow. The multiple forces caused by the rich chemical structure, the large specific surface area caused by the special pore structure, and the effective protection of the ZIFs core by sulfide shell make the designed material have higher extraction efficiency and longer service life, compared with ZIF-8@ZIF-67 and ZIF-8. At the same time, the established analytical method for non-steroidal drugs had a high recovery rate (98.93%-102.10%), low detection limit (0.11-0.27 µg/L), and wide linear range (1-200 µg/L) within a good correlation coefficient R2 (0.9978-0.9993). Satisfactory results were also obtained from the extraction of NSAIDs from the Yellow River water samples. These results indicate that the designed double-core-shell structure material can effectively exert its structural advantages and become a promising extraction material.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.

Demonstrating antibiotic stewardship while diagnosing and treating bilateral pseudoseptic arthritis: a case report.

INTRODUCTION: Although viscosupplementation is a commonly used treatment for osteoarthritis and is widely regarded as a safe treatment option, it is associated with the rare complication of pseudoseptic arthritis. Most existing case reports that cite this rare complication employed the use of early broad-spectrum antibiotics. CASE PRESENTATION: In this case report, we present a 61-year-old African American female patient who presented with bilateral knee pseudoseptic arthritis in the setting of viscosupplementation. She presented 3 days after bilateral viscosupplementation injections with bilateral knee swelling, discomfort, and pain with micromotion. Her white blood cell count (WBC) was 12.83 (4.5-11 normal), her C-reactive protein (CRP) level was 159 mg/L (0-10 normal), and her erythrocyte sedimentation rate (ESR) was 79 mm/hour (0-40 normal). Her left knee aspirate yielded 38,580 WBC with a negative gram stain and negative cultures. Her right knee aspirate yielded 29,670 WBC with a negative gram stain and negative cultures. Through the utilization of careful clinical monitoring, ice therapy, and non-steroidal inflammatory medication, we were able to successfully treat this patient while maintaining proper antibiotic stewardship. CONCLUSION: Pseudoseptic arthritis in the setting of viscosupplementation can be adequately treated and monitored without the use of antibiotics.

ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy. RESULTS: The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s. CONCLUSION: In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.

Evaluation of antimicrobial and non-steroidal anti-inflammatory treatments for BRD on health and welfare in fattening bulls: a cross-sectional study.

Our study aimed to evaluate the effect of different treatments for BRD on health and welfare in fattening bulls. A total of 264 bulls were enrolled. Welfare was assessed on day 2 (T0) and day 15 (T1) after arrival. A decrease in the welfare level was observed from T0 to T1. All bulls were inspected clinically at T0 and T1 revealing an increase of skin lesions and lameness in T1. In both periods, a high incidence of respiratory disease was observed. A prevalence of 79.55% and 95.45% of Mycoplasma bovis using RT-PCR and culture at T0 and T1 respectively was observed. Blood samples were collected for haematology at T0 and T1. At T0, 36 animals were individually treated for BRD with an antimicrobial (IT), 54 received a metaphylactic treatment with tulathromycin (M), 150 received a metaphylactic treatment with tulathromycin plus a second antimicrobial (M + IT) whereas 24 were considered healthy and therefore not treated (NT). Additionally, 128 were treated with a non-steroid anti-inflammatory (NSAID). Neutrophils of M + IT were significantly higher than groups NT and M and the lymphocytes of M + IT were significantly lower than that of IT. White blood cells, neutrophils and N/L ratio of animals treated with an NSAID was significantly higher than that not treated. Lung inspection of 172 bulls at the abattoir indicated that 92.43% presented at least one lung lesion. A statistically significant effect of the NSAID treatment on the lung lesions was observed. Our findings indicate that BRD was a major welfare and health concern and evidence the difficulties of antimicrobial treatment of M. bovis.

Recent clinical practice guidelines for the management of low back pain: a global comparison.

BACKGROUND: Low back pain (LBP) is a significant health problem worldwide, with a lifetime prevalence of 84% in the general adult population. To rationalise the management of LBP, clinical practice guidelines (CPGs) have been issued in various countries around the world. This study aims to identify and compare the recommendations of recent CPGs for the management of LBP across the world. METHODS: MEDLINE, EMBASE, CINAHL, PEDro, and major guideline databases were searched from 2017 to 2022 to identify CPGs. CPGs focusing on information regarding the management and/or treatment of non-specific LBP were considered eligible. The quality of included guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: Our analysis identified a total of 22 CPGs that met the inclusion criteria, and were of middle and high methodological quality as assessed by the AGREE II tool. The guidelines exhibited heterogeneity in their recommendations, particularly in the approach to different stages of LBP. For acute LBP, the guidelines recommended the use of non-steroidal anti-inflammatory drugs (NSAIDs), therapeutic exercise, staying active, and spinal manipulation. For subacute LBP, the guidelines recommended the use of NSAIDs, therapeutic exercise, staying active, and spinal manipulation. For chronic LBP, the guidelines recommended therapeutic exercise, the use of NSAIDs, spinal manipulation, and acupuncture. CONCLUSIONS: Current CPGs provide recommendations for almost all major aspects of the management of LBP, but there is marked heterogeneity between them. Some recommendations lack clarity and overlap with other treatments within the guidelines.

Association between regulator inspection and ratings on primary care prescribing: an observational study in England 2014 to 2019.

BACKGROUND: Healthcare regulators in many countries undertake inspections of healthcare providers and publish inspection outcomes with the intention of improving quality of care. Comprehensive inspections of general practices in England by the Care Quality Commission began for the first time in 2014. It is assumed that inspection and rating will raise standards and improve care, but the presence and extent of any improvements is unknown. We aim to determine if practice inspection ratings are associated with past performance on prescribing indicators and if prescribing behaviour changes following inspection. METHODS: Longitudinal study using a dataset of 6771 general practices in England. Practice inspection date and score was linked with monthly practice-level data on prescribing indicators relating to antibiotics, hypnotics and non-steroidal anti-inflammatory drugs. The sample covers practices receiving their first inspection between September 2014 and December 2018. Regression analysis and the differential timing of inspections is used to identify the impact on prescribing. RESULTS: Better-rated practices had better prescribing in the period before inspections began. In the six months following inspections, no overall change in prescribing was observed. However, the differences between the best and worse rated practices were reduced but not fully. The same is also true when taking a longer-term view. There is little evidence that practices responded in anticipation of inspection or reacted differently once the ratings were made public. CONCLUSION: While some of the observed historic variation in prescribing behaviour has been lessened by the process of inspection and ratings, we find this change is small and appears to come from both improvements among lower-rated practices and deteriorations among higher-rated practices. While inspection and rating no doubt had other impacts, these prescribing indicators were largely unchanged.

Imrecoxib: Advances in Pharmacology and Therapeutics.

Imrecoxib, a cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug (NSAID), was discovered via the balanced inhibition strategy of COX-1/COX-2. It is indicated for the relief of painful symptoms of osteoarthritis. There have been some pharmacological and therapeutic advances since the approval of imrecoxib in 2011. However, an update review in this aspect is not yet available. Relevant literature until January 2024 was identified by search of PubMed, Web of science, Embase and CNKI. From the perspective of efficacy, imrecoxib provides relief of osteoarthritis symptoms, and potential off-label use for treatment of idiopathic pulmonary fibrosis, perioperative pain, hand-foot syndrome, axial spondyloarthritis, COVID-19, cartilage injury, and malignancies such as lung and colon cancer. From a safety point of view, imrecoxib showed adverse effects common to NSAIDs; however, it has lower incidence of new-onset hypertension than other types of selective COX-2 inhibitors, less gastrointestinal toxicities than non-selective NSAIDs, weaker risk of drug interaction than celecoxib, and more suitable for elderly patients due to balanced inhibition of COX-1/COX-2. From a pharmacoeconomic perspective, imrecoxib is more cost-effective than celecoxib and diclofenac for osteoarthritis patients. With the deepening of the disease pathophysiology study of osteoarthritis, new therapeutic schemes and pharmacological mechanisms are constantly discovered. In the field of osteoarthritis treatment, mechanisms other than the analgesic and anti-inflammatory effects of COX-2 inhibitors are also being explored. Taken together, imrecoxib is a moderate selective COX-2 inhibitor with some advantages, and there would be more clinical applications and research opportunities in the future.

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action. Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30 ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24 min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42 cm/h for rat skin, 13.64 cm/h for mice skin, and 18.97 cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Gastrointestinal Conditions: Peptic Ulcer Disease.

Peptic ulcer disease (PUD) involves ulceration of the mucosa in the stomach and/or proximal duodenum. The main causes are Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) use. PUD occurs in 5% to 10% of people worldwide, but rates have decreased by more than half during the past 20 years. This reduction is thought to be because of H pylori management, more conservative use of NSAIDs, and/or widespread use of proton pump inhibitors (PPIs). Common symptoms include postprandial abdominal pain, nausea, vomiting, and weight loss. These symptoms have broad overlap with those of other conditions, making clinical diagnosis difficult. Endoscopy is the gold standard for diagnosis, especially in older patients and those with alarm symptoms, but a test-and-treat strategy (noninvasive test for H pylori and treat if positive) can be used for younger patients with no alarm symptoms. Numerous treatment regimens are available, all of which include PPIs plus antibiotics. As an alternative to PPIs, a new triple therapy with vonoprazan (which blocks acid production) plus antibiotics has been approved and appears to be superior to conventional therapy with PPIs plus antibiotics. At least 4 weeks after treatment, repeat testing for H pylori should be obtained to confirm cure. When possible, NSAIDs should be discontinued; when not possible, antisecretory cotherapy should be considered.

Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males.

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.

NSAID-induced corneal melt as the first presentation of Sjögren's syndrome.

A non-diabetic woman in her 80s presented 1 week following uncomplicated left eye cataract surgery complaining of decreased vision, gritty sensation and photophobia in the same eye. Postoperative treatment included G. Acular (Ketorolac Tromethamine 0.5%, NSAID: non-steroidal anti-inflammatory drug) and G. Tobradex (Tobramycin 0.3% and Dexamethasone 0.1%, antibiotic and steroid, respectively) each prescribed four times a day for 2 weeks. On examination, the patient had a corneal epithelial defect which progressed to a full-thickness perforation despite ceasing the NSAID drops. Cyanoacrylate glue application with a plastic drape patch failed to seal the perforation, and a full-thickness tectonic corneal transplant was performed. On investigation, the patient had positive anti-RO and anti-LA antibodies, suggesting a diagnosis of Sjögren's syndrome. We advocate for careful preoperative assessment prior to cataract surgery, patient education, close follow-up and cautious medication use postoperatively including avoiding NSAID drops in patients with risk factors for postoperative dry eye disease.

Effectiveness of the pharmacological therapy to prevent post ERCP acute pancreatitis: a network meta-analysis.

OBJECTIVE: To determine the effectiveness of the different pharmacological agents in preventing post-ERCP acute pancreatitis. METHODS: We included clinical trials of pharmacological interventions for prophylaxis of acute post-ERCP pancreatitis. The event evaluated was acute pancreatitis. We conducted a search strategy in MEDLINE (OVID), EMBASE, and Cochrane Central Register of Controlled Trials from inception to nowadays. We reported the information in terms of relative risks (RR) with a 95% confidence interval. We assessed the heterogeneity using the I2 test. RESULTS: We included 84 studies for analysis (30,463 patients). The mean age was 59.3 years (SD ± 7.01). Heterogeneity between studies was low (I2 = 34.4%) with no inconsistencies (p = 0.2567). Post ERCP pancreatitis was less in prophylaxis with NSAIDs (RR 0.65 95% CI [0.52 to 0.80]), aggressive hydration with Lactate Ringer (RR 0.32 95% CI [0.12-0.86]), NSAIDs + isosorbide dinitrate (RR 0.28 95% CI [0.11-0.71]) and somatostatin and analogues (RR 0.54 [0.43 to 0.68]) compared with placebo. CONCLUSIONS: NSAIDs, the Combination of NSAIDs + isosorbide dinitrate, somatostatin and analogues, and aggressive hydration with lactate ringer are pharmacological strategies that can prevent post-ERCP pancreatitis when compared to placebo. More clinical trials are required to determine the effectiveness of these drugs.

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%.

Simultaneous Treatment of 5-Aminosalicylic Acid and Treadmill Exercise More Effectively Improves Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 µL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC.