Nonsteroidal Research Articles

Duodenal Peptic Ulcer Perforation in the Puerperium Case Report Series

Peptic ulcers, and complications such as perforation, are rare during pregnancy and the puerperium. Accordingly, many clinicians may place these diagnoses low on their differential diagnosis. We present two case reports of primigravida, advanced maternal age females with history of irritable bowel syndrome and nonsteroidal anti-inflammatory drug (NSAID) use found to have perforated duodenal ulcers after Cesarean section. Postpartum surgical abdomens may not present with classic guarding and rigidity. A low threshold for imaging and identification of risk factors are critical to timely diagnosis and management.

Pharmacodynamic interaction profile of apigenin with diclofenac in an experimental model of inflammation in rats

Objectives: Chronic use of non-steroidal anti-inflammatory drugs(NSAID’s) is often limited by their side effect, necessitating the development of safer therapeutic alternatives. Apigenin, A plant flavonoid, has shown potential in enhancing the efficacy of NSAIDs while potentially reducing their adverse effects. This study aimed to evaluate the synergistic effects of apigenin combined with a subtherapeutic dose of diclofenac on inflammation in a rat model, to determine whether such a combination can improve anti-inflammatory effectiveness and reduce the drug dose required. Materials and Methods: A total of 42 Wistar albino rats were randomised into seven groups to receive various treatments including control (normal saline), standard diclofenac (100 mg/kg), three doses of apigenin (10, 20 and 40 mg/kg), a subtherapeutic dose of diclofenac (50 mg/kg) and a combination of apigenin (20 mg/kg) with diclofenac (50 mg/kg). Inflammation was induced using carrageenan, and paw volume was measured at multiple time points to assess oedema. The percentage change from baseline paw volume and percentage protection against paw oedema was calculated for each group. Results: The study found that the combination of 20 mg/kg apigenin with 50 mg/kg diclofenac significantly enhanced the anti-inflammatory response, achieving a peak reduction in paw volume of up to 49.66% at 3 h post-administration. This was superior to the responses seen with apigenin or diclofenac alone, where the maximal dose of apigenin (40 mg/kg) only managed a peak reduction of 28.18%, and the standard dose of diclofenac (100 mg/kg) reached a peak inhibition of 66.66% at 6 h. The subtherapeutic dose of diclofenac (50 mg/kg), used alone, showed a lower peak effect of 21.47% at 3 h. These results underscore the enhanced efficacy of the combination therapy, potentially allowing for lower doses of diclofenac while maintaining effective anti-inflammatory action. Conclusion: The findings suggest that combining apigenin with diclofenac enhances anti-inflammatory responses, supporting the potential of flavonoid-NSAID combinations as more effective and safer anti-inflammatory therapies. Future studies should explore the long-term effects and mechanisms of action to fully understand the benefits and limitations of such combinations in managing chronic inflammation.

Intravenously Administered Nonsteroidal Anti-Inflammatory Drugs in Clinical Practice: A Narrative Review

Intravenously administered nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a crucial component of multimodal analgesia strategies in surgical settings. This narrative review aims to provide an up-to-date evaluation of the efficacy, safety, and clinical use of intravenous (IV) NSAIDs for perioperative pain management in adults and children. The NSAIDs and selective COX-2 inhibitors (coxibs) approved in Europe for the short-term symptomatic treatment of acute, moderate perioperative pain via IV infusion in adults and/or children have been influenced by US and global guidelines and practice: the drugs primarily reviewed here are ibuprofen, ketorolac, ketoprofen, naproxen, paracetamol, and acetylsalicylic acid. Furthermore, intravenous ibuprofen is authorized for the short-term symptomatic treatment of fever. In contrast to intravenous ketoprofen, intravenous ibuprofen is authorized for administration to children over 6 years of age or weighing more than 20 kg. Overall, IV ibuprofen had a more favorable profile with regard to peri- and postoperative opioid sparing and pain relief. Oral ibuprofen and IV ibuprofen have similar levels of efficacy, although IV ibuprofen has a shorter onset of action and is required in patients who are unable to take oral medications. The frequency of significant adverse events appears to be similar for ibuprofen and paracetamol. Systematic reviews and meta-analyses report that intravenous NSAIDs reduce postoperative opioid consumption by approximately 20–60%, improving pain management with fewer opioid-related side effects. In indications in infants, the choice of medication is limited, and the oral route is not always feasible; IV formulations of ibuprofen are preferred in this setting. Topics for further research should include head-to-head trials of IV NSAIDs.

Dynamic Behavior of the Glassy and Supercooled Liquid States of Aceclofenac Assessed by Dielectric and Calorimetric Techniques

Aceclofenac (ACF), a non-steroidal anti-inflammatory drug, was obtained in its amorphous state by cooling from melt. The glass transition was investigated using dielectric and calorimetric techniques, namely, dielectric relaxation spectroscopy (DRS), thermally stimulated depolarization currents (TSDC), and conventional and temperature-modulated differential scanning calorimetry (DSC and TM-DSC). The dynamic behavior in both the glassy and supercooled liquid states revealed multiple relaxation processes. Well below the glass transition, DRS was able to resolve two secondary relaxations, γ and β, the latter of which was also detectable by TSDC. The kinetic parameters indicated that both processes are associated with localized motions within the molecule. The main (α) relaxation was clearly observed by DRS and TSDC, and results from both techniques confirmed a non-Arrhenian temperature dependence of the relaxation times. However, the glass transition temperature (Tg) extrapolated from DRS data significantly differed from that obtained via TSDC, which in turn showed reasonable agreement with the calorimetric Tg (Tg-DSC = 9.2 °C). The values of the fragility index calculated by the three experimental techniques converged in attributing the character of a moderately fragile glass former to ACF. Above the α relaxation, TSDC showed a well-defined peak. In DRS, after “removing” the high-conductivity contribution using ε’ derivative analysis, a peak with shape parameters αHN = βHN = 1 was also detected. The origin of these peaks, found in the full supercooled liquid state, has been discussed in the context of structural and dynamic heterogeneity. This is supported by significant differences observed between the FTIR spectra of the amorphous and crystalline samples, which are likely related to aggregation differences resulting from variations in the hydrogen bonds between the two phases. Additionally, the pronounced decoupling between translational and relaxational motions, as deduced from the low value of the fractional exponent x = 0.72, derived from the fractional Debye–Stokes–Einstein (FDSE) relationship, further supports this interpretation.

Study on Lyophilised Orodispersible Tablets from Plant-Based Drinks as Bulking Agents

Background/Objectives: Oral administration of active pharmaceutical ingredients (APIs) is the most commonly used route of administration. As dysphagia is a prevalent problem, the size of the swallowed dosage form could negatively influence patient adherence. Orally disintegrating tablets (ODTs) are beneficial dosage forms because they disintegrate within a few seconds in the oral cavity without water. Lactose is one of the most commonly used excipients in the pharmaceutical industry; it served as the central concept of a recent publication on the formulation of milk-based ODTs despite lactose malabsorption being widespread worldwide. Consequently, the plant-based alternative market has grown exponentially and has become a prevailing food trend, with various alternatives to choose from. For this reason, the development of a nonsteroidal anti-inflammatory drug (NSAID)-containing ODT with plant-based drinks (PBDs) was assessed for its innovative potential. Methods: Different PBDs were investigated and compared to traditional and lactose-free milk. The liquids’ viscosity, pH, and particle size were determined, and an electronic tongue was used for the sensory evaluation. The various ODTs were prepared with the freeze-drying method, and then the qualitative characteristics of the dosage form were investigated. Results: Our different measurements show that different plant beverages differ from each other and that these differences have an impact on the technological processing. According to the HPLC-DAD measurements, all values were in the required range. Conclusions: These measurements suggest that the soya drink is the most similar to traditional cow milk and would be the most appropriate choice among the investigated plant-based drinks to be used as a carrier system for an ibuprofen-containing ODT.

Pharmacologic Management of Acute Pain in Children: A Systematic Review and Network Meta-Analysis.

Several pharmacologic options exist for the management of acute pediatric pain; however, their comparative effectiveness remains uncertain. To assess the relative benefits and harms of pharmacotherapy for acute pediatric pain through a network meta-analysis of randomized clinical trials. Cochrane Database of Systematic Reviews, Medline, Embase, CINAHL, Web of Science, and Scopus to October 2023. Trials that enrolled children (aged <18 years) with acute pain and randomized them to receive a pharmacologic analgesic vs an alternate analgesic or placebo were included. Pairs of reviewers independently reviewed abstracts, extracted data, and assessed risk of bias of eligible trials. A frequentist random-effects model was used for all meta-analyses, and the certainty of evidence was assessed for treatment effects using the Grading of Recommendations Assessment, Development, and Evaluation approach. The primary outcomes were pain severity (range, 0-10 cm using a visual analog scale; minimally important difference [MID], 1 cm), need for rescue medication, symptom relief, and adverse drug events. A total of 41 trials involving 4935 children were included. High- to moderate-certainty evidence found that compared with placebo, nonsteroidal anti-inflammatory drugs (NSAIDs) (weighted mean difference [WMD], -1.29; 95% CI, -1.89 to -0.70; modeled risk difference [RD] for achieving the MID, 16%), ketamine (WMD, -1.12; 95% CI, -2.09 to -0.14; modeled RD for achieving the MID, 14%), and mid-high potency opioids (WMD, -1.19; 95% CI, -1.83 to -0.55; modeled RD for achieving the MID, 15%) reduced pain. Only NSAIDs reduced the need for rescue medication (relative risk [RR], 0.31; 95% CI, 0.14 to 0.68; modeled RD, 16% fewer patients). Neither NSAIDs (RR, 0.69; 95% CI, 0.31 to 1.55) nor acetaminophen (RR, 0.63; 95% CI, 0.21 to 1.87) increased the risk of short-term gastrointestinal adverse events. All other comparisons showed moderate-certainty evidence of little to no difference from placebo or were supported by low/very low-certainty evidence. Compared with placebo, NSAIDs, ketamine, and mid- to high-potency opioids are effective in reducing acute pediatric pain. NSAIDs provide the greatest benefits and least harm, suggesting that they should be the first-line therapy for acute painful conditions in children.

The Impact of Ramadan Fasting on Dyspeptic Complaints.

Dyspepsia, a common gastrointestinal issue characterized by upper abdominal discomfort, can be influenced by diet, medication, and lifestyle changes. Ramadan fasting involves refraining from food and drink from dawn to sunset, affecting various physiological processes, including digestion. The fasting period can range from 12 to 18 hours depending on the year, potentially impacting the prevalence of dyspeptic symptoms. This study aimed to assess the effect of fasting on dyspeptic symptoms, taking into account demographic and clinical factors. A cohort study examined 1258 clinic patients, with 150 meeting specific inclusion criteria. Dyspepsia was diagnosed using Rome IV criteria, with fasting hours taken into consideration. The relationship between dyspepsia, fasting, Non-Steroidal Anti-Inflammatory Drug use, and demographics was analyzed. Dyspepsia was more prevalent in females (32%) compared with males (23%), with a higher proportion of non-fasting women among dyspeptic patients. Older patients (>65y) had a higher prevalence of dyspepsia (P = 0.026). Fasting individuals had a 2.1 times greater likelihood of experiencing dyspeptic symptoms. Although Non-Steroidal Anti-Inflammatory Drug use was lower in fasting patients, no significant association with dyspepsia was observed (P = 0.139). Ramadan fasting increases the risk of dyspeptic symptoms, particularly in women and older adults. Factors such as medication timing and dietary changes during fasting may contribute to this risk. Highlighting the importance of the pre-dawn meal (Suhoor) in managing dyspeptic symptoms is essential. Tailored guidance should be provided to individuals at higher risk during Ramadan.

Combined Endocannabinoid and Cyclooxygenase Inhibition Additively Attenuates Post-Surgical Pain.

Introduction: Post-surgical pain arises following a clinical operation, often persisting throughout recovery. While current treatments reduce pain, repeated use increases the probability of adverse events. monoacylglycerol lipase (MAGL) inhibition has previously been shown to produce analgesia, either through CB1 or CB2 mechanisms, dependent on the underlying pain phenotype. Thus, this study investigated the analgesic potential of inhibiting MAGL, alone and in combination with the analgesic non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium in a model of post-surgical pain. Methods: Male and female C57BL/6J mice were subjected to hindpaw incision (HPI) surgery. Mechanical allodynia, climbing, grip strength, and thermal preference were measured 24 h following HPI. The dose-dependent anti-allodynic effects of the MAGL inhibitors (irreversible MAGL inhibitor [JZL184] and selective MAGL inhibitor [MJN110]) and the NSAID diclofenac, as well as the additive potential of combined MAGL and cyclooxygenase (COX) inhibition, were assessed. Selective antagonists of CB1 and CB2 receptors were used to challenge the cannabinoid-receptor mechanism of JZL184. Similarly, the anti-allodynic effects of the CB2-selective agonist (LY2828360) were tested. JZL184 was administered repeatedly to determine tolerance. Finally, hindpaw cytokines were quantified via multiplex ELISA 24 h after HPI surgery. Results: Approximately 24 h post-surgery, the MAGL inhibitors JZL184 (≥4 mg/kg) or MJN110 (≥5 mg/kg), as well as the NSAID diclofenac sodium (≥16.67 mg/kg), attenuated HPI-induced mechanical allodynia, as assessed with von Frey filaments. The anti-allodynic effects of JZL184 (40 mg/kg) were blocked by pre-treatment of the CB2 antagonist SR144528 (3 mg/kg) but not the CB1-selective antagonist rimonabant (SR141716A; 3 mg/kg), suggesting a CB2-mediated mechanism of anti-allodynia via MAGL inhibition. Similarly, LY2828360 (3 mg/kg) reduced HPI-induced allodynia. Moreover, when administered repeatedly, the anti-allodynic effects of JZL184 (8 mg/kg) persisted and did not undergo tolerance. A separate cohort was administered a sub-analgesic dose of JZL184 (1 mg/kg), diclofenac sodium (1.85 mg/kg), or both compounds concurrently. This subthreshold JZL184 and diclofenac sodium combination attenuated HPI-induced allodynia, suggesting an additive drug interaction. Finally, HPI per se increased pro-inflammatory cytokine levels, which were unaltered by MAGL inhibition despite the anti-allodynia assessed behaviorally. Conclusion: These data support simultaneously targeting endocannabinoids and COX enzymes as a potential post-operative pain management approach.

Toxic epidermal necrolysis induced by moxifloxacin and exacerbated by clindamycin in an elderly patient: A case report

Toxic Epidermal Necrolysis (TEN) is a severe skin-mucosal reaction induced by medications, commonly characterized by blister formation and widespread epidermal detachment. Typical causative agents include allopurinol, antibiotics, anticonvulsants, and non-steroidal anti-inflammatory drugs (NSAIDs), with trimethoprim/sulfamethoxazole and penicillin being the most frequently implicated among antibiotics. However, lincosamide antibiotics as the cause of aggravation are rarely reported in clinical settings. This case report presents a patient with TEN induced by quinolone antibiotics, who experienced rapid progression of the condition after combining with lincomycin antibiotics. Clinical remission was achieved through a combination of corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. This report aims to enhance clinicians’ understanding of TEN by providing a detailed case presentation and discussion.

Development and Characterization of Magnetic Nanoemulsion-Based Senolytic Peptides for Osteoarthritis Treatment

The formulation and characterization of a novel nanoemulsion (NE) delivery system for senomodulator peptides aimed at enhancing the treatment of osteoarthritis (OA) are reported, in combination with magnetic nanoparticles (MNPs), for improving targeted delivery and traceability. Osteoarthritis, a prevalent degenerative joint disease associated with aging, is currently not effectively treated by disease-modifying therapies, posing a consistent health burden on individuals and healthcare systems worldwide. Existing treatments, such as nonsteroidal anti-inflammatory drugs and intra-articular injections, are limited by inadequate local drug concentrations and rapid clearance, often necessitating costly joint replacement. Lipid-based NE composed of biocompatible and biodegradable vitamin E and sphingomyelin, associated with the senolytic peptide NE:TUB1, is able to target senescent cells implicated in OA progression. Improved cellular retention and therapeutic effects of the associated TUB1 peptide, compared to its free form, have been demonstrated, suggesting a significant enhancement in therapeutic potential. The incorporation of MNPs to obtain NE:TUB1-MNP formulations offers the advantage of being traceable in vivo through clinically available imaging technologies, with the potential to enhance targeting capabilities through magnetic guidance. The characterization of NE:TUB1-MNPs involved the assessment of their physical and chemical properties, interaction with cells, cytotoxicity profile, and nanoparticle uptake in vitro using human primary adipose-derived stem cells. NE and NE:TUB1-MNP are shown to be stable, non-toxic, and capable of efficient intracellular uptake. The inclusion of MNPs not only supports cell viability and proliferation but also facilitates medium and long-term product traceability within joints, offering a promising approach for localized treatment. The enhanced anti-senescent role of NE:TUB1-MNP formulations are highlighted, suggesting their potential utility in mitigating OA progression and possibly other degenerative diseases. In conclusion, the study presents a novel therapeutic approach for OA, NE:TUB1-MNPs, leveraging the synergistic effects of peptide-functionalized nanoemulsions and magnetic nanoparticles to improve targeted delivery and therapeutic outcomes. This innovative formulation could pave the way for new treatments for OA and other joint-related conditions, offering significant advancements in regenerative medicine.

MR enterography in Crohns disease and beyond: a pictorial review : Beyond Crohn's: a pictorial guide to MR enterography in small bowel disease.

Magnetic resonance enterography (MRE) has become an essential imaging modality for evaluating small bowel disorders, particularly Crohn's disease (CD), due to its superior soft-tissue contrast, multiplanar capabilities, and lack of ionizing radiation. While radiologists are generally familiar with the MRE findings of CD, several other small bowel entities can present with similar imaging features, potentially leading to diagnostic challenges. This pictorial review comprehensively illustrates the MRE findings of CD and its various mimickers, including Ulcerative colitis (UC), intestinal tuberculosis (ITB), Non-steroidal anti-inflammatory drug (NSAID) induced enteropathy, cryptogenic multifocal ulcerating and stenosing enteropathy (CMUSE), celiac disease, gastrointestinal endometriosis, intestinal lipomatosis, lymphangiectasia, eosinophilic enteritis, encapsulating peritoneal sclerosis, adhesions, radiation enteropathy, and intestinal angioedema etc. We discuss the key imaging features that can help a radiologist differentiate these conditions, highlight specific MRE sequences useful for diagnosis, and provide clinically relevant context for each entity. This review serves as a practical guide for radiologists and clinicians in recognizing and distinguishing various small bowel pathologies that may simulate CD on MRE, ultimately aiding in appropriate patient management.

Stromal Vascular Fraction of Adipose Tissue: Prospects for Use in the Treatment of Osteoarthritis and Articular Cartilage Injuries (Literature Review)

Summary. Osteoarthritis (OA) is a chronic, progressive, degenerative-dystrophic joint disease primarily caused by damage to the articular cartilage. Conservative pharmacological treatment of OA consists of prescribing nonsteroidal anti-inflammatory drugs, chondroprotectors, hyaluronic acid injections, and therapeutic blockades with glucocorticosteroids. The use of orthobiological agents represents an alternative method in OA treatment. Among the variety of orthobiological approaches, adipose tissue serves as a new and attractive source of stem cells for the treatment of OA. The stromal vascular fraction creates an environment where stem cells can interact and stimulate regeneration.

Determination of hematologic reference intervals for free-living King vultures (Sarcoramphus papa).

As obligate scavengers, New World vultures (Cathartiformes: Cathartidae) play a key role in carcass removal and disease control. Associated with this ecosystem service, vultures are exposed to the consumption of harmful substances such as poisons, heavy metals, antibiotics, or non-steroidal anti-inflammatory drugs. Monitoring the health status of vulture populations is a priority and an important conservation strategy, and hematologic analysis is a practical and effective method that can be useful for this purpose. Report hematologic reference intervals in free-living King vultures (Sarcoramphus papa), one of the least studied New World vulture species. Red blood cell concentration, packed cell volume, hemoglobin (Hb) concentration, MCV, MCH, MCHC, WBC concentration, differential count and absolute WBC concentration, heterophil to lymphocyte ratio, and total protein concentration were determined. We used a non-parametric method to calculate the reference intervals. In addition, we compared our results with the hematologic measurands reported for the Black vulture (Coragyps atratus), the Andean condor (Vultur gryphus) and the California condor (Gymnogyps californianus). With the exception of Hb, monocyte, basophil, and eosinophil concentrations, the mean hematologic measurands observed in the King vulture were similar to those recorded for the other New World vulture species, and the heterophil to lymphocyte ratio was lower in the King vulture compared to the Black vulture. In this study, we have reported for the first time the hematologic reference intervals in a free-living population of King vultures in Costa Rica. Future research should consider comparison among free-living New World vulture species.

Modified Zeolites for the Removal of Emerging Bio-Resistive Pollutants in Water Resources

The increasing presence of pollutants, including pharmaceuticals and pesticides, in water resources necessitates the development of effective remediation technologies. Zeolites are promising agents for pollutant removal due to their high surface area, ion-exchange capacity, natural abundance, and diverse tailorable porous structures. This review focuses on the efficient application of modified zeolites and mesoporous materials as photocatalysts and adsorbents for removing contaminants from water bodies. The adsorption and photodegradation of pesticides and selected non-steroidal anti-inflammatory drugs and antibiotics on various zeolites reveal optimal adsorption and degradation conditions for each pollutant. In most reported studies, higher SiO2/Al2O3 ratio zeolites exhibited improved adsorption, and thus photodegradation activities, due to increased hydrophobicity and lower negative charge. For example, SBA-15 demonstrated high efficiency in removing diclofenac, ibuprofen, and ketoprofen from water in acidic conditions. Metal doped into the zeolite framework was found to be a very active catalyst for the photodegradation of organic pollutants, including pesticides, pharmaceuticals, and industrial wastes. It is shown that the photocatalytic activity depends on the zeolite-type, metal dopant, metal content, zeolite pore structure, and the energy of the irradiation source. Faujasite-type Y zeolites combined with ozone achieved up to 95% micropollutant degradation. Bentonite modified with cellulosic biopolymers effectively removed pesticides such as atrazine and chlorpyrifos, while titanium and/or silver-doped zeolites showed strong catalytic activity in degrading carbamates, highlighting their environmental application potential.

Anti-inflammatory effect of Plantago asiatica crude extract in rat gout arthritis model

Plantago asiatica L., a perennial herb in the family Plantaginaceae, has been shown to impart several pharmacologic activities, including anti-oxidative, anti-inflammatory, and diuretic effects. In the study here, the anti-gout(y) arthritis (GA) effects of a crude extract from P. asiatica L. (PAE) were investigated in a rat GA model. For this, PAE was prepared by ethanol extraction and analyzed for phytochemicals by RP-HPLC and Q-TOF-MS. Thereafter, potential therapeutic effects of the PAE were investigated in rats; Wistar rats (male, 8 wk-of-age) were randomly allocated into four groups (n = 9/group) and intra-articularly injected with 3 mg monosodium urate (MSU) in saline solution to establish a GA model. For the study, rats received oral dosings of 0.3 mg colchicine/kg or 1 g PAE/kg (w/w) before and after gout was established. At fixed times after the treatments, assessment of joint swelling ratios and pathological changes in the joints, as well as of select cytokine expression in the blood, was done. RP-HPLC results showed the PAE contained at least 8 ‘active’ ingredients, with plantamajoside, verbascoside, and cymaroside being the most abundant. In comparison to in control rats, MSU induced joint space narrowing, ankle joint swelling, and increased levels of pro-inflammatory interleukin (IL)-1β, IL-17a, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, and reductions in anti-inflammatory IL-10 in the blood. PAE treatment significantly reversed patho- genic joint space narrowing and swelling, reversed the MSU-induced changes in inflammatory factors, and in general imparted effects very similar to those seen with colchicine (COL; known non-steroidal anti-inflammatory drug for clinical treatment of GA). Collectively, these findings provide experimental evidence supporting the potential applicability of PAE to treat gouty arthritis.

White Analytical Chemistry‐Driven Approach to the Sample Preparation and LC–MS/MS Determination of Nonsteroidal Anti‐Inflammatory Drugs and Their Metabolites in Real Contaminated Matrices

ABSTRACTTraces of medicinal formulations and their metabolites often remain in animal products. The presence of nonsteroidal anti‐inflammatory drugs (NSAIDs) in food is a factor in chronic human health effects. Therefore, improved methods for their determination are needed for food safety. Usually, a complex sample preparation based on enzymatic, alkaline, or acidic hydrolysis is applied to recover residual NSAIDs from their hydroxyl‐, carboxyl‐, glucuronide‐, and other derivatives to the original forms. This work reports on a systematic study and comparison of the sample preparation of real samples for the determination of NSAIDs and their metabolites. The objects of analysis were meat and by‐products obtained from chickens that were treated with preparations containing metamizole, diclofenac, ketoprofen, ibuprofen, meloxicam, phenylbutazone, and mefenamic acid with their feed. The effects of acidity of the extraction solution, glucuronidase enzyme, and different sorbents for purification by solid‐phase extraction were studied. The hydroxyl‐ and carboxyl‐metabolites were detected by HPLC–MS/MS. It was shown that the long hydrolysis step during the sample preparation can be replaced with extraction into acetonitrile, making the full analytical procedure “whiter.”

Correction: Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration

Correction: Dogs receiving cyclooxygenase-2-sparing nonsteroidal anti-inflammatory drugs and/or nonphysiologic steroids are at risk of severe gastrointestinal ulceration

Structural and theoretical studies of amantadinium fenamates.

Two new crystals of amantadinium salts were obtained from fenamic and tolfenamic acid. The salt of fenamic acid is a model compound for interaction analysis, while amantadinium tolfenamate is a composition of a drug used in the treatment of symptoms of Parkinsonism and as a nonsteroidal anti-inflammatory drug. The crystal structures were studied and a theoretical analysis of the hydrogen bonds and weak interactions was carried out using quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) methods.

Current research status, applications and challenges of ketorolac-based sustained-release and controlled-release formulations.

Ketorolac, a nonsteroidal anti-inflammatory drug, exhibits moderate antipyretic and anti-inflammatory properties, as well as potent analgesic effects. It is widely used in clinical practice for pain relief in cases of mild and severe pain such as postoperative pain, fractures, sprains, toothaches and cancer pain. Due to its relatively short half-life, patients experiencing pain often need frequent injections or oral medications, leading to poor patient compliance. Thus, it is crucial to create long-acting sustained-release formulations of ketorolac. This paper provides an overview of the research, applications, and challenges associated with ketorolac sustained-release formulations over the past decade, based on a comprehensive review of the literature. The aim is to provide fresh insights for the research and development of long-acting, sustained-release, and controlled-release formulations of ketorolac.

The Anticonvulsant Effect of Nonsteroidal Anti-Inflammatory Drug, Fenoprofen, in Pentylenetetrazole-Induced Epileptic Rats: Behavioral, Histological, and Biochemical Evidence.

This study aimed to evaluate the anticonvulsant properties of fenoprofen on the experimental model of pentylenetetrazole (PTZ)-induced epilepsy. Male Wistar rats were randomly grouped into five, and the kindling model was induced by intraperitoneal injection of PTZ 35 (mg/kg) every other day for 1 month. Aside from the control and PTZ groups, three groups received intraperitoneal injections of fenoprofen at doses of 10, 20, and 40 (mg/kg) before each PTZ injection. Rats were challenged with PTZ 70 (mg/kg) 1 week after kindling development. Then rats were subjected to deep anesthesia, and serum and brain samples were prepared. Oxidative stress (OS) markers (malondialdehyde, superoxide dismutase, and glutathione peroxidase) were measured in serum samples. Hippocampal tissue was used to investigate the relative expression of OS-related genes (nuclear factor [erythroid-derived 2]-like 2 (Nrf2)/heme oxygenase 1 (Hmox1)) and histological studies. Seizure behavior was assessed based on Lüttjohann's score. In treated groups, the number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration decreased significantly, while myoclonic jerks and GTCS latency increased compared with the PTZ group. The biochemical evaluation revealed the antioxidative effects of fenoprofen. The decreased expression of Nrf2/HO-1 genes in the PTZ group was reversed after fenoprofen administration. The results of the histological study obtained from Nissl staining in the hippocampal tissue also confirmed the protective effect of fenoprofen. The anticonvulsant effects of fenoprofen seem to be through inhibition of OS-related markers, induction of protective effect in hippocampal tissue, and activation of the Nrf2/HO-1 signaling pathway.