Nonsteroidal Research Articles

Reusable Ni-immobilized MOF Catalyst for Dehydrogenation of N-heterocycles Under Milder Conditions.

Herein, we have demonstrated the design and synthesis of a novel Ni-immobilized MOF as heterogeneous catalyst for the dehydrogenation of N-heterocycles. A series of five and six-member N-heteroarenes bearing one or more heteroatoms were synthesized in up to 98% yield (> 33 examples). Late stage functionalization to the synthesis of b-glucuronides inhibitor, antimalarial drug quinine, and the nonsteroidal anti-inflammatory drug (NSAID) indomethacin were obtained under milder reactions conditions. A series of mechanistic studies revealed the detection of H2 and H2O2 during the progress of the reactions and suggested the involvement of enamine-imine intermediate species for sequential dehydrogenation. Detailed characterization of the fresh catalyst and reused catalyst were performed using SEM, TEM, BET, PXRD, and EDX elemental mappings. The catalyst could be recycled up to four-times without much loss in catalytic activities. In-situ formed defects, pore size enlargement and additional Lewis acid sites within catalyst nanocrystals assisted in attaining high activity and selectivity to N-heteroarenes.

Canis lupus familiaris and diclofenac: understanding the potential risks of this association

In many homes worldwide, dogs are considered part of the family. Every possible care is given to animals, including drug treatments. However, many animal guardians, in an attempt to minimize pain or improve the quality of life of their dogs, provide drugs without a veterinarian’s prescription. Diclofenac, a non-steroidal anti-inflammatory drug that acts on cyclooxygenase-1 and cyclooxygenase-2 enzymes, is associated with several adverse events, especially related to the gastrointestinal tract, both in humans and pet animals. Therefore, the availability of information about the effects of this drug in different species is always essential. This narrative review aims to present adverse reactions the domestic dog (Canis lupus familiaris) can suffer when exposed to diclofenac. Scientific publications, books, and case reports were consulted, and inquiries were also carried out with regulatory agencies. Many reports of suspected adverse reactions, especially related to the gastrointestinal tract, were found. Other clinical manifestations and lesions were also identified in the cardiovascular system, liver, kidneys, and hematological examinations. Therefore, diclofenac may constitute a hazard to dogs, mainly due to possible damage to the gastrointestinal tract. This fact reinforces the need to seek veterinary advice before providing any drug to animals, in addition to recommendations on ensuring the correct storage of medications to avoid accidental exposure.

Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV osteochondral lesions of the talus.

To explore the efficacy and feasibility of arthroscopy combined with bone tunnel technique in treating Berndt and Harty stage III or IV osteochondral lesions of the talus (OLT). A retrospective analysis was conducted on the clinical data of 21 patients with Berndt and Harty stage III or IV OLT who underwent surgical treatment at our institution from September 2017 to September 2022. Under arthroscopy, the displaced talar osteochondral lesion was restored. A 2.0mm Kirschner wire (K-wire) was used to create a bone tunnel from the medial (or lateral) malleolus to the realigned osteochondral lesion. A 1.5mmK-wire was then used to drill through this tunnel into the osteochondral fragment, and a 1.5mm absorbable bone rod was inserted for fixation. Preoperative and final follow-up visual analogue scale (VAS) for pain and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale were recorded and compared. All 21 patients were followed up for an average of 23.95 ± 6.01months. All wounds healed by primary intention, with no nerve, blood vessel, or tendon injuries. All osteochondral lesions healed, with an average healing time of 3.71 ± 0.62months. The VAS score decreased from a preoperative average of 5.38 ± 0.59 to 0.48 ± 0.51 at the final follow-up. The AOFAS ankle-hindfoot scale increased from a preoperative average of 56.29 ± 5.98 to 88.43 ± 2.68 at the final follow-up (P < 0.05), showing statistically significant differences. Two cases experienced medial pain after 12months, which was tolerable with non-steroidal anti-inflammatory drugs. Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV OLT has the advantages of minimal injury, visualization of fracture reduction, and fewer complications.

Marginal ulcer causing anastomotic perforation and delayed penetration following one anastomosis gastric bypass

We report the rare clinical case of perforation and delayed penetration of an ulcer at the gastro-jejunal anastomosis following 14 months after laparoscopic one anastomosis gastric bypass in a young female patient. No significant ulcer predictors at baseline: a chronic ulcer formed within the first six months after one anastomosis gastric bypass against the background of continued proton pump inhibitor therapy, regardless of smoking, helicobacter infection or use of non-steroidal anti-inflammatory drugs. Initially the patient underwent the laparotomy with perforation suturing and Roux-jejunojejunostomy formation to exclude the bile reflux into the gastric pouch. The result of the first surgery (non-healing ulcer with the development of delayed penetration six months later) is agree with the recent literature about the possible overstatement of the role of biliary reflux in ulcer formation after one anastomosis gastric bypass. The follow-up surgery was performed by the laparoscopic approach in condition of pronounced adhesion process in abdominal cavity and included adhesiolysis, resection of the gastric pouch with the anastomosis and reconstructive Roux-Y-gastric bypass. Clinical and endoscopic evaluation of the result of the reconstructive surgery 10 months after indicates the patient's recovery.

Self-Cascade API Nanozyme for Synergistic Anti-Inflammatory, Antioxidant, and Ferroptosis Modulation in the Treatment of Corneal Neovascularization.

Corneal neovascularization is a common pathological ocular change that can severely impairs vision, potentially leading to blindness. Although steroids and non-steroidal anti-inflammatory drugs are the primary treatments, their side effects, such as ocular hypertension, eye irritation, and corneal lysis, limit their widespread use. In the present study, an active pharmaceutical ingredient (API) nanozyme (PC-DS NE) is developed through the metal-organic coordination of ferrous sulfate with the anti-inflammatory agent diclofenac sodium and the natural antioxidant proanthocyanidin. PC-DS NE exhibited a spheroid morphology with a particle size of 39.7 ± 5.2 nm, and could achieve the short-term release of diclofenac sodium and sustained release of proanthocyanidin. Notably, the PC-DS NE possessed favorable biocompatibility, self-cascade redox regulation capacity, and significant anti-inflammatory activity. In corneal alkali burn experiments, PC-DS NE effectively inhibited corneal neovascularization by scavenging reactive oxygen species, inhibiting the expression of inflammatory cytokines and pro-angiogenic factors, and down-regulating ferroptosis. These synergistic effects highlighted the potential of PC-DS NE as a promising treatment for ocular inflammatory diseases.

Proton pump inhibitors - possible side effects of long-term therapy: a review

Introduction and purpose: Proton pump inhibitors (PPIs), which have been on the market for more than 30 years, are widely regarded as safe and effective medications. For this reason, they are very popular with both doctors and patients. PPIs find their use in the treatment of such ailments as gastroesophageal reflux, gastric ulcer disease or as a shielding therapy when taking non-steroidal anti-inflammatory drugs. Nevertheless, their long-term use may be associated with many side effects. The purpose of our review is to summarize the knowledge in the current medical literature on the possible complications of chronic use of PPIs. The review is based on 30 articles from the most recent publications on chronic PPI treatment. Publications were searched for the words PPI chronic therapy, gastric cancer, omeprazole in PubMed databases. Articles from 2018-2024 represent 70% of all publications from the references. A brief description of the state of knowledge: Although the use of PPIs in the short term is relatively safe, the number of people taking these drugs has increased significantly in recent years. They are prescribed not always as indicated, patients often take them for too long - this in turn leads to an increasing incidence of side effects. Some of them can permanently affect health and significantly reduce the comfort of life - such as kidney diseases, cardiovascular disorders or gastric cancer. Summary: Considering the widespread availability and popularity of PPIs, it is important to adequately educate both patients and healthcare professionals of the possible side effects. It is crucial to use medications as prescribed, with an appropriate assessment of the risk-benefit ratio. It might result in reducing health care expenditures to deal with the consequences of IPP therapy.

An Extensive Comparison of Analytical Data Using Various Stability Condition of Non-SteroidalAnti-InflammatoryDrug (NSAID) For Paracetamol Infusionof Various Manufacturers of Branded (Innovator) Drug Product and Generic Drug Product

An Extensive Comparison of Analytical Data Using Various Stability Condition of Non-SteroidalAnti-InflammatoryDrug (NSAID) For Paracetamol Infusionof Various Manufacturers of Branded (Innovator) Drug Product and Generic Drug Product

Chronic recurrent multifocal osteomyelitis in pediatric patients: A Chinese single center observational study and literature review.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disorder that commonly poses diagnostic challenges due to its atypical symptomatology. This observational study aimed to investigate the clinical features, laboratory test results, imaging features, and treatment strategies for pediatric patients with CRMO. We retrospectively analyzed 7 pediatric patients with CRMO treated at the Department of Pediatric Orthopedics, First Affiliated Hospital of Guangzhou University of Chinese Medicine between January 2018 and February 2022. This study aimed to enhance current understanding of CRMO by exploring in-depth clinical data. The study cohort comprised 5 males and 2 females, aged 3 to 13 years. All patients experienced symptoms for a median duration of 6 months prior to hospitalization, at which point they presented with recurrent pain and various accompanying signs including hypothermia (14.28%), swelling (42.85%), localized skin warmth (42.85%), and plantar pustules (14.28%). The femurs (71.42%) and tibia (71.42%) were frequently affected. Radiographic and computed tomography scans revealed osteosclerosis and osteolytic lesions, while magnetic resonance imaging revealed bone marrow edema. Histological examination of bone biopsies from 4 patients revealed fibrous tissue hyperplasia and lymphocytic and neutrophilic infiltration, despite negative bacterial cultures. Laboratory test results were either normal or slightly elevated. Symptomatic improvement was observed in 6 patients (85.72%) treated with nonsteroidal anti-inflammatory drugs, while 1 patient (14.28%) resistant to nonsteroidal anti-inflammatory drugs responded well to tumor necrosis factor inhibitors. The clinical presentation of CRMO lacks specificity, with unexplained bone pain being the most common symptom. Precise diagnosis and timely intervention depend on a thorough magnetic resonance imaging evaluation for lesion detection, which facilitates CRMO diagnosis. This study offers valuable insights into the clinical manifestations, laboratory findings, imaging features, and treatment strategies of CRMO in pediatric patients.

A model for monitoring the medication rechallenge system in Queen Savang Vadhana Memorial Hospital

A rechallenge process is crucial for patients who need to use drugs known to cause allergic reactions. Establishing a standardized rechallenge protocol is essential to protect patients and increase the likelihood of using effective medications. This study aimed to evaluate the outcomes of the rechallenge monitoring system implemented at Queen Savang Vadhana Memorial Hospital. In this retrospective study, rechallenges focused on two drugs categories: antimicrobial drugs and non-steroidal anti-inflammatory drugs. The confirmed rechallenge protocol was introduced in 2018, and data from October 2019 and November 2022 were extracted from the hospital’s electronic database. The primary outcome measured was the number of adverse events during rechallenges. Trends in severe allergic reactions were documented, and descriptive statistics were used. Out of 81 total rechallenge events, with a history of 77 mild reactions (95.1%) and 4 serious events (4.9%), only 3 mild reaction (3.7%) occurred. A positive trend in successful rechallenges was observed following the implementation of the monitoring model, along with a decrease in medication error levels B and C. Importantly, no harmful levels D and E were detected. The rechallenge monitoring system improved the chance of safe medication use and reduced the occurrence of seriously adverse drug events.

Rare and Fatal Complication: A Case of Ketorolac-Induced Anaphylaxis Leading to Cardiac Arrest and Hypoxic-Ischemic Brain Injury in a Young Adult

Background: Anaphylaxis is a severe, life-threatening allergic reaction that can lead to cardiac arrest and hypoxic-ischemic brain injury (HIBI). Ketorolac, a nonsteroidal anti-inflammatory drug (NSAID) commonly used for postoperative pain management, has been rarely associated with anaphylaxis. Case presentation: We present the case of a 32-year-old woman who developed anaphylaxis and subsequent cardiac arrest following intravenous administration of ketorolac after an appendectomy. Despite successful resuscitation, the patient suffered from HIBI and remained in a persistent vegetative state. Conclusion: This report highlights the potential for fatal complications associated with ketorolac administration and emphasizes the importance of prompt recognition and management of anaphylaxis in the perioperative setting. This case underscores the need for heightened vigilance regarding potential anaphylactic reactions to ketorolac, even in patients with no prior history of drug allergies. Early recognition and aggressive management of anaphylaxis are crucial to minimize the risk of severe complications like cardiac arrest and HIBI.

Elbow arthritis

Most patients with primary osteoarthritis of the elbow report a history of heavy lifting work with the affected upper limb. Conservative treatment, including activity modifications, nonsteroidal anti-inflammatory drug (NSAID) intake, and intra-articular injections can provide sufficient pain relief in the early stages when used in combination. If surgery is required, many patients experience significant pain relief from joint-preserving procedures despite existing cartilage damage. Although open debridement procedures are effective, arthroscopic osteocapsular arthroplasty has become established as the preferred surgical procedure. The ulnar nerve should be assessed during surgery and treated if necessary. Total elbow arthroplasty (TEP) is successful in terms of pain relief and function; however, it is recommended for older patients with advanced osteoarthritis or for whom joint-preserving procedures have failed.

Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface-modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and B-cell-activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), which has significant anti-inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

Bilateral Rectus Sheath Block with Continuous Bupivacaine Infusions After Elective Open Gastrectomy: A Randomized Controlled Trial

Background and Objectives: Multimodal analgesia has been shown to be effective in facilitating early postoperative gastrointestinal function and rehabilitation in patients undergoing open gastrectomy. We conducted a clinical trial to investigate the effectiveness of bilateral rectus sheath block (RSB) with continuous bupivacaine infusion in comparison with placebo following elective open gastrectomy. Materials and Methods: Patients indicated for elective open gastrectomy were screened, enrolled, and randomised between October 2021 and September 2023. The patients were randomised to either Group A (intervention—continuous bupivacaine) or Group B (control—NaCl saline). The primary outcome measures were the quantity of an opioid analgesic administered during the initial 72 h post-surgery and the level of postoperative pain as indicated by the visual analogue scale (VAS). Mann–Whitney U test was used for quantitative analysis while Pearson Chi-square was used for categorical variables. Results: A total of 60 patients completed the trial, with 30 patients in each of the two groups. Patients in Group A reported lower median VAS pain scores at all observed time points following surgery (p &lt; 0.001). No patient in Group A required rescue opioid analgesia, although non-steroidal anti-inflammatory drugs were necessary during the initial 12 h postoperatively. Clinically, Group A patients had a significantly shorter time to first gas (p = 0.001), a shorter time to first bowel movement (p &lt; 0.001), a shorter time to first out-of-bed activity (p &lt; 0.001), and a shorter overall hospitalisation duration (p &lt; 0.001) compared to Group B patients. Conclusions: Bilateral RSB with continuous bupivacaine infusion is effective in managing pain and can reduce the use of opioid analgesics in the postoperative period. Furthermore, it promotes early recovery, and a shorter hospital stay.

Prevalence, risk factors, and severity of erectile dysfunction following renal transplantation.

Sexual dysfunction is common among dialysis and transplant patients. Our study evaluated the prevalence, risk factors, and severity of erectile dysfunction (ED) post-transplant in a single center. We conducted a single-centre, observational, non-interventional study of adult male renal graft recipients. Sociodemographic and clinical data were collected, and erectile function was assessed with the International Index of Erectile Function (IIEF) questionnaire. 179 patients transplanted between 1995 and 2021 were enrolled (170 answered the questionnaire). Mild, moderate, and severe ED was noted in 33.5%, 20.6% and 10.6% of cases, respectively. ED prevalence increased with age (42.6% of patients < 40, 47.4% of patients aged 40-60, 78.9% of patients > 60). The total mean IIEF score was 16.32 ± 6.93 (erectile function 19.22 ± 7.9, orgasmic function 6.8 ± 2.9, sexual desire 6.43 ± 2.1, intercourse satisfaction 8.96 ± 3.7, overall satisfaction 6.78 ± 2.6). Age, alcohol consumption, type, time on dialysis pre-transplant, and donor type were significantly associated with erectile dysfunction (p < 0.05). Most patients (93.5%) were treated for comorbidities in addition to immunosuppression. Severe ED was significantly more common among patients taking alpha blockers and non-steroidal anti-inflammatory drugs. Self-reported erectile dysfunction post renal transplantation seems influenced by age, alcohol intake, dialysis history, donor type and certain drugs, but not by comorbidities (hypertension, diabetes, heart disease).

Reactive arthritis

Reactive arthritis (ReA) is adisease caused by an extra-articular infection that manifests as asterile joint inflammation. In contrast to bacterial septic arthritis no pathogens can be cultured from the joint in ReA but pathogen components, such as antigens or DNA are more frequently detectable in the joint, suggesting an intra-articular culture-negative persistent infection or at least an intra-articular interaction between the host and pathogen components. The primary extra-articular infection in classical ReA is of bacterial origin and usually affects either the urogenital, gastrointestinal or, less frequently, the respiratory tract. Chlamydia (C.trachomatis and less frequently C.pneumoniae) and enterobacteria are among the most common pathogens causing ReA. The prevalence of ReA is estimated at 40/100,000 and the incidence at 5/100,000. Typical clinical manifestations are mostly self-limiting peripheral arthritis (monoarticular or oligoarticular), dactylitis and, more rarely, axial involvement and in half of the cases, there is an association with HLA-B27. Due to these similarities, classical ReA is categorized as aform of spondyloarthritis (SpA). The diagnosis is made on the basis of atypical clinical picture, evidence of aprevious or persistent infection and the exclusion of other causes of arthritis. Treatment includes physical measures, the use of anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs (NSAID) or glucocorticoids, in the case of persistent arthritis, immunomodulating substances such as sulphasalazine, methotrexate and in individual cases biologics and Janus kinase inhibitors (JAKi) are used. In general, antibiotic treatment of ReA does not shorten the duration of the disease.

Investigating pain-related medication use and contribution to polypharmacy in adults with intellectual disabilities: a systematic review

BackgroundAdults with intellectual disability experience more pain than adults without and, despite a higher number of medications being prescribed, may be less likely to receive medication for pain. We conducted a systematic review of existing literature on medication for pain and painful conditions in adults with intellectual disability to explore if there is any association with polypharmacy, multimorbidity or demographic characteristics.MethodsThis systematic review followed PRISMA guidelines. Medline, Embase, PubMed, PsycINFO, Web of Science, CINAHL, Cochrane Library and Scopus were searched from January 2000 to 21st October 2024. We included original, peer-reviewed observational, qualitative or mixed-method studies published in English with data on medication for pain or painful conditions in adults with intellectual disability. Two independent reviewers performed study selection, data extraction, and quality assessment; disagreements were resolved by a third reviewer. Adapted Newcastle–Ottawa Scale or the Critical Appraisal Skills Programme for qualitative studies was used for quality assessment of included studies and findings were reported via narrative synthesis. PROSPERO registration: CRD42023415051.ResultsTwenty-seven of 26,170 articles met the eligibility criteria. Adults with intellectual disability were more likely to have simple analgesic medication than non-steroidal anti-inflammatory drugs, opioids or adjuvant pain medications than the general population. Psychotropic medications were more commonly prescribed in adults with intellectual disability than medication for pain or painful conditions. Adults with intellectual disability and caregivers reported under-recognition and most likely under-treatment of pain.ConclusionsAdults with intellectual disability may receive less pharmacological management of pain with analgesics and medication for painful conditions despite the high prevalence of polypharmacy, suggesting pain is under-treated. Better assessment and pharmacological treatment of pain and painful conditions is a key future research priority to address this health inequality and improve quality of life for this vulnerable group of people.

Methods of Managing Postoperative Pain in Orthopedics

Postoperative pain management is a critical concern for patients undergoing orthopedic procedures, impacting both recovery and overall patient satisfaction. Effective pain control is essential for minimizing complications such as limited mobility and delayed healing. This paper reviews contemporary strategies for managing postoperative pain in orthopedics, focusing on both pharmacological and non-pharmacological approaches. Pharmacotherapy, including nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, is commonly utilized but must be carefully managed to prevent adverse effects such as dependence and gastrointestinal issues. Complementing these methods, non-pharmacological interventions such as physical therapy, cryotherapy, transcutaneous nerve stimulation, and music therapy offer holistic benefits without the associated risks of medication. The study emphasizes the importance of a multifaceted approach that includes early rehabilitation and patient education to enhance recovery outcomes. The combined use of diverse pain management techniques can optimize analgesic efficacy while promoting patient comfort and reducing hospital stays, ultimately leading to improved rehabilitation results.

Adsorption of Ibuprofen from Water Using Banana Peel Biochar: Experimental Investigation and Machine Learning Algorithms

Ibuprofen is a significant nonsteroidal anti-inflammatory drug that poses environmental and health risks when present in wastewater because of its persistence and probable toxicity. This study investigates the use of banana peel biochar (BPB) made at 600 °C to 900 °C to eliminate ibuprofen from aqueous solutions. The uniqueness of this work lies in the high-temperature pyrolysis process, which has not been previously explored for the ibuprofen removal efficiency using BPB. The batch experiment was conducted considering initial concentrations, pH, and contact time. The data were compared with different algorithms, with Linear Regression (LR), Support Vector Machines (SVM), Decision Trees (DT), Random Forest (RF), and k-Nearest Neighbor (k-NN) to forecast the performance. The results revealed that banana peel biochar at 900 °C exhibited the highest ibuprofen removal efficiency (69.28 ± 0.83%) at 125 mg/L concentration with the sequence of BPB900 &gt; BPB800 &gt; BPB700 &gt; BPB600. A maximum removal efficiency of 72.67 ± 0.75% was observed at pH 9. Adsorption behavior was analyzed using isotherm and kinetic models, with the Freundlich isotherm model (R2 value 0.9620) indicating heterogeneous adsorption and the pseudo-second-order (PSO) kinetic model (R2 value 0.9969) suggesting that physicochemical interactions govern the process. FTIR analysis ensured the existence of functional groups (hydroxyl, carboxylic, carbonyl, and aromatic rings) responsible for adsorption. Machine learning algorithms, especially RF, demonstrated outstanding performance with 90.07% accuracy in predicting the experimental data. In comparison to other adsorbents, BPB demonstrated superior removal efficiency, underscoring its effectiveness. The study suggests that BPB, particularly at 900 °C, is effective in removing ibuprofen, and due to its sustainable production, it offers a potential solution for wastewater treatment.

Construction of biocatalysts based on P450BM3 for the degradation of non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are widespread pollutants in aquatic environments, posing significant risks to both ecosystems and human health due to their persistence and bioaccumulation. Effective and sustainable degradation methods are urgently required to address this environmental challenge. This study aims to design and optimize a cytochrome P450BM3-based biocatalyst for the rapid and efficient degradation of NSAIDs by direct chemical intervention and protein engineering. The novel biocatalyst achieved efficient biodegradation of four common NSAIDs. Notably, the F87I/T268D mutant achieved 99.22% degradation of diclofenac (DCF) within 10min, and degraded meloxicam (MEL) and phenylbutazone (PBZ) at rates of 98.86% and 90.51% within 5min, respectively. Furthermore, the F87G mutant accomplished 99.08% degradation of acetaminophen (APAP) within just 2min. The catalytic properties of P450BM3 and its mutants were evaluated through kinetic studies, and potential degradation pathways of the four NSAIDs were proposed in conjunction with UPLC-MS. This study provides a novel biocatalytic approach for the rapid degradation of NSAIDs in aquatic systems, offering considerable environmental benefits for pollution mitigation.

Low Frequency of Upper Gastrointestinal Bleeding Despite Non-Steroidal Anti-Inflammatory Drugs and Corticosteroids in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. It has been identified that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids can be essential risk factors for developing complications such as upper gastrointestinal bleeding (UGIB). This study aimed to describe the safety profile of drugs used to treat RA focused in UGIB. A cross-sectional study of patients with RA between 2015 and 2021, a description of the population, and an evaluation of the relationship with UGIB through bivariate analysis and logistic regression. Of 405 individuals, 16 presented UGIB (93.8% women, mean age was 65±13.6 years). No statistically significant differences were found regarding UGIB and medication use, except for the mean dose of corticosteroids. In the multivariate analysis, it was found that the presence of anemia in the last three months had an adjusted OR (AOR) of 16.1 (95% CI 2.74- 24.23) and higher HAQ values during the previous three months had an AOR of 6.17 (95% CI 1.79- 21.24). This study found a low frequency of UGIB in patients with RA. More significant disability and anemia in the previous months were independently associated with UGIB. The low frequency of NSAID use in this population is noteworthy. In general, reasonable medication use related to this complication is recommended.