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Aims The Standard care vs. Celecoxib Outcome Trial (SCOT) found similar risk of cardiovascular events with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase-2-selective drug celecoxib. While pre-clinical work has suggested roles for vascular and renal dysfunction in NSAID cardiovascular toxicity, our understanding of these mechanisms remains incomplete. A post hoc analysis of the SCOT cohort was performed to identify clinical risk factors and circulating biomarkers of cardiovascular events in NSAID users. Methods and results Within SCOT (7295 NSAID users with osteoarthritis or rheumatoid arthritis), clinical risk factors associated with cardiovascular events were identified using least absolute shrinkage and selection operator regression. A nested case–control study of serum biomarkers including targeted proteomics was performed in individuals who experienced a cardiovascular event within 1 year (n = 49), matched 2:1 with controls who did not (n = 97). Risk factors significantly associated with cardiovascular events included increasing age, male sex, smoking, total cholesterol:HDL ratio ≥5, and aspirin use. Statin use was cardioprotective [odds ratio (OR) 0.68; 95% confidence interval (CI) 0.46–0.98]. There was significantly higher immunoglobulin (Ig)G anti-malondialdehyde-modified LDL (MDA-LDL), asymmetric dimethylarginine (ADMA), and lower arginine/ADMA. Targeted proteomic analysis identified serum growth differentiation factor 15 (GDF-15) as a candidate biomarker [area under the curve of 0.715 (95% CI 0.63–0.81)]. Conclusion Growth differentiation factor 15 has been identified as a candidate biomarker and should be explored for its mechanistic contribution to NSAID cardiovascular toxicity, particularly given the remarkable providence that GDF-15 was originally described as NSAID-activated gene-1. [ABSTRACT FROM AUTHOR]

A circular shunt is a poor prognostic factor associated with Ebstein's anomaly. Targeting the constriction of the ductus arteriosus (DA) in order to limit or resolve the circular shunt, has been shown to improve fetal outcomes. Prenatal non-steroidal anti-inflammatory drugs (NSAIDs) have been known to constrict the DA. Recently, prenatal NSAIDs have been used for that purpose in the treatment of circular shunt. Limited research shows that it may be an effective treatment leading to improved fetal outcomes. In this article, we did an extensive review of literature to describe this therapy's effectiveness and outcomes. 82% of fetuses were able to achieve ductal constriction with prenatal NSAID therapy. For fetuses who achieved ductal constriction, fetal demise was less likely (6%) when compared to those who were unable to achieve the same (50%). Of all the fetuses with hydrops, 50% had resoluation of hydrops with prenatal NSAID treatment. [ABSTRACT FROM AUTHOR]

Although the efficacy of ketorolac in pain management and the short duration of use align well with current clinical practice guidelines, few studies have specifically evaluated the impact of ketorolac on bony union after fracture or surgery. The purpose of this study was to review the current basic science and clinical literature on the use of ketorolac for pain management after fracture and surgery and the subsequent risk of delayed union or nonunion. Animal studies demonstrate a dose-dependent risk of delayed union in rodents treated with high doses of ketorolac for 4 weeks or greater; however, with treatment for 7 days or low doses, there is no evidence of risk of delayed union or nonunion. Current clinical evidence has also shown a dose-dependent increased risk of pseudoarthrosis and nonunion after post-operative ketorolac administration in orthopedic spine surgery. However, other orthopedic subspecialities have not demonstrated increased risk of delayed union or nonunion with the use of peri-operative ketorolac administration. While evidence exists that long-term ketorolac use may represent risks with regard to fracture healing, insufficient evidence currently exists to recommend against short-term ketorolac use that is limited to the peri-operative period. Level of evidence V: Narrative Review [ABSTRACT FROM AUTHOR]

Type two Diabetes Mellitus (T2DM) is a rising epidemic. Available therapeutic strategies have provided glycaemic control via HbA1c reduction but fail to provide clinically meaningful reduction in microvascular and macrovascular (cardiac, renal, ophthalmological, and neurological) complications. Inflammation is strongly linked to the pathogenesis of T2DM. Underlying inflammatory mechanisms include oxidative stress, endoplasmic reticulum stress amyloid deposition in the pancreas, lipotoxicity, and glucotoxicity. Molecular signalling mechanisms in chronic inflammation linked to obesity and diabetes include JANK, NF-kB, and AMPK pathways. These activated pathways lead to a production of various inflammatory cytokines, such as Interleukin (IL-6), tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP), which create a chronic low-grade inflammation and ultimately dysregulation of glucose homeostasis in the liver, skeletal muscle, and smooth muscle. Anti-inflammatory agents are being tested as anti-diabetic agents such as the IL-1b antagonist, Anakinra, the IL-1b inhibitor, Canakinuma, the IL-6 antagonists such as Tocilizumab, Rapamycin (Everolimus), and the IKK-beta kinase inhibitor, Salsalate. Salsalate is a century old safe anti-inflammatory drug used in the treatment of arthritis. Long-term safety and efficacy of Salsalate in the treatment of T2DM have been evaluated, which showed improved fasting plasma glucose and reduced HbA1C levels as well as reduced pro-inflammatory markers in T2DM patients. Current publication summarizes the literature review of pathophysiology of role of inflammation in T2DM and clinical efficacy and safety of Salsalate in the treatment of T2DM. [ABSTRACT FROM AUTHOR]

Robenacoxib (RX) is a veterinary cyclooxygenase‐2 selective inhibitor drug. It has never been tested on birds and is only labelled for use in cats and dogs. The purpose of this study was to assess its pharmacokinetics in geese after single intravenous (IV) and oral (PO) administrations. Four‐month healthy female geese (n = 8) were used. Geese were subjected to a two‐phase, single‐dose (2 mg/kg IV, 4 mg/kg PO), open, longitudinal study design with a four‐month washout period between the IV and the PO phases. Blood was collected from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma RX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analysed using ThothPro™ 4.3 software in a non‐compartmental approach. Following IV administration, terminal elimination half‐life, volume of distribution, and total clearance were 0.35 h, 0.34 L/kg, and 0.68 L/h/kg, respectively. For the PO route, the mean peak plasma concentration was 6.78 μg/mL at 0.50 h. The t1/2λz was very short and significantly different between the IV and PO administrations (0.35 h IV vs. 0.99 h PO), suggesting the occurrence of a flip‐flop phenomenon. The Cl values corrected for the F% were significantly different between IV and PO administrations. It might have been a consequence of the longitudinal study design and the altered physiological and environmental conditions after a 4‐month washout period. The absolute oral F% computed with the AUC method surpassed 150%, but after normalizing it to t1/2λz, it was 46%. In conclusion, the administration of RX might not be suitable for geese, due to its short t1/2λz. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of dydrogesterone combined with non-steroidal anti-inflammatory drugs(NSAIDs) in the treatment of patients with mild endometriosis. Methods: This was a clinical comparative study. Eighty patients with mild endometriosis were recruited at Affiliated Hospital of Hebei University, randomly divided experimental group (n=40) and control group (n=40) from March 2022 to March 2023. Both groups started treatment with dydrogesterone on the 5th day of menstruation. Patients in the control group were treated with dydrogesterone monotherapy, while those in the experimental group were treated with mefenamic acid the basis of the therapy of the control group. The clinical efficacy, differences in the levels of humoral immune indexes, the levels of inflammatory factor and the incidence of adverse drug reactions of the two groups was compared and analyzed. Results: The efficacy of the experimental group was significantly higher than the control group, with a statistically significant difference(P=0.02). The levels of C3 and C4 in the experimental group after treatment were significantly lower than those in the control group, with a statistically significant difference(P=0.00). After treatment, TNF-a, CRP, IL-6 and other indexes in the experimental group were significantly lower than those in the control group, with statistically significant differences(P=0.00). The incidence of adverse reactions after treatment had no statistically significant difference(P=0.45). Conclusion: Dydrogesterone combined with non-steroidal anti-inflammatory drugs is a safe and effective treatment for patients with endometriosis. It can improve various obvious curative effects, such as marked relief of pain symptoms, reduction of complement and inflammatory factor levels without a significant increase in adverse reactions. [ABSTRACT FROM AUTHOR]

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The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence for the outcomes of different nonantibiotic options including cranberry, D-mannose and non-steroidal anti-inflammatory drugs (NSAIDs). PubMed, Embase and Scopus were searched for manuscripts relating to nonantibiotic treatment of UTI including cranberry, mannose and NSAIDs. After title and abstract screening, data were extracted from 21 papers that were published in English and related to the treatment or prevention of uncomplicated UTI in adult women. We identified twelve papers examining the effects of cranberry, two papers examining D-mannose, two papers examining combination treatments (cranberry and D-mannose) and five manuscripts investigating the effects of NSAIDs. There is low-level evidence, from a small number of studies, supporting the use of D-mannose or combination treatments for potentially preventing UTIs in adult women without producing burdening side effects. However, larger and more randomised double-blinded trials are needed to confirm this. In comparison, the multiple studies of cranberry and NSAIDs produced conflicting evidence regarding their effectiveness. [ABSTRACT FROM AUTHOR]

Tolfenamic acid (TOL) is a frequently detected non-steroidal anti-inflammatory painkiller in wastewater treatment plant effluents and the environment. Consequently, the fate of TOL in water treatment processes should be studied as some of the water treatment processes are known to produce toxic by-products. Chlorination is a widely used disinfection method, and UV/chlorination is an advanced oxidation process that has been frequently studied. This study investigated the kinetics and mechanism of TOL degradation by chlorination and UV/chlorination. The treatment of TOL by UV/chlorination has not been reported elsewhere. TOL reacted with the free available chlorine (FAC) during chlorination with the second-order rate constant of 1–41 M−1 min−1. The rate constants were decreased with increasing pH from 5 to 8 due to the reducing HOCl molar fraction. The TOL removal was largely improved by UV/chlorination. The reactive hydroxyl radical generated from the photolysis of FAC was the main species that improved the TOL removal. The removal of TOL by UV/chlorination can be enhanced by increasing the concentration of FAC. The efficiency of UV/chlorination in removing TOL was higher under acidic conditions due to the higher molar fraction of HOCl. For ecotoxicity study, TOL treatment with chlorination for 24 h produced non-toxic effluent. However, the toxicity of the TOL solution increased with prolonged exposure to UV/chlorination. Chlorinated TOL and 2-amino-5-chlorobenzoic acid were identified as the transformation by-products of TOL. The computational study predicted that chlorinated TOL is more toxic than TOL, and 2-amino-5-chlorobenzoic acid was less harmful than TOL. [ABSTRACT FROM AUTHOR]

Meloxicam is a commonly prescribed non-steroidal anti-inflammatory drug for backyard poultry that has demonstrated pharmacodynamic efficacy at a single high dose of 5 mg/ kg. This study characterized the adverse effects of meloxicam administered in chickens at an approximate dose of 5 mg/kg orally twice daily for 5 days. Twenty-one adult Rhode Island Red hens (Gallus gallus domesticus), judged to be healthy based on an external physical examination, complete blood count (CBC), and plasma biochemistry panel, were recruited for this study. The subject birds were randomly assigned to a treatment (n = 11) or control group (n = 10) and received a 15-mg tablet of meloxicam or a nonmedicated feed pellet, respectively, orally twice daily. Physical examinations and body weight measurements were performed daily, and observation for clinical signs occurred twice daily. Following completion of the 5-day treatment course, an external physical examination, blood collection for a CBC and plasma biochemistry panel, euthanasia, necropsy, and measurement of meloxicam tissue residues were performed. During the treatment course, 1 hen from the treatment group died with peracute clinical signs, 2 hens from the treatment group died suddenly with no clinical signs, and 1 hen from the treatment group became acutely lethargic and was euthanized. Within the meloxicam group, 7 out of 11 hens had gross and histologic evidence of varying levels of renal acute tubular injury and gout. Plasma uric acid concentrations were above the species reference intervals in all affected hens in the treatment group that were still available for testing. The control group had no evidence of renal injury or gout based on postmortem examinations. Based on the results of this study, repeated oral dosing of meloxicam in chickens at 5 mg/kg twice daily is not recommended. [ABSTRACT FROM AUTHOR]

Abstract Gout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3–5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl)

The use of antibiotics in the treatment of UTIs is contributing to resistance. Hence, the outcome of human clinical trials of nonantibiotic remedies for preventing or treating UTI is of significant interest. This systematic review aimed to identify, summarise and evaluate the evidence for the outcomes of different nonantibiotic options including cranberry, D-mannose and non-steroidal anti-inflammatory drugs (NSAIDs). PubMed, Embase and Scopus were searched for manuscripts relating to nonantibiotic treatment of UTI including cranberry, mannose and NSAIDs. After title and abstract screening, data were extracted from 21 papers that were published in English and related to the treatment or prevention of uncomplicated UTI in adult women. We identified twelve papers examining the effects of cranberry, two papers examining D-mannose, two papers examining combination treatments (cranberry and D-mannose) and five manuscripts investigating the effects of NSAIDs. There is low-level evidence, from a small number of studies, supporting the use of D-mannose or combination treatments for potentially preventing UTIs in adult women without producing burdening side effects. However, larger and more randomised double-blinded trials are needed to confirm this. In comparison, the multiple studies of cranberry and NSAIDs produced conflicting evidence regarding their effectiveness.

In this work, a liquid-liquid microextraction methodology using solidified floating organic drop (SFODME) was combined with liquid chromatography and UV/Vis detection to determine non-steroidal anti-inflammatory drugs (NSAIDs) naproxen (NPX), diclofenac (DCF), and mefenamic acid (MFN) in tap water, surface water, and seawater samples. Parameters that can influence the efficiency of the process were evaluated, such as the type and volume of the extractor and dispersive solvents, effect of pH, agitation type, and ionic strength. The optimized method showed low detection limits (0.09 to 0.25 μg L−1), satisfactory recovery rates (90 to 116%), and enrichment factors in the range between 149 and 199. SFODME showed simplicity, low cost, speed, and high concentration capacity of the analytes under study. Its use in real samples did not demonstrate a matrix effect that would compromise the effectiveness of the method, being possible to apply it successfully in water samples with different characteristics. [ABSTRACT FROM AUTHOR]

Castration and tail-docking of pre-wean piglets are common procedures that are known to induce pain and would benefit from pain mitigation. Flunixin meglumine (FM) is a non-steroidal anti-inflammatory drug currently approved in the United States for pyrexia in swine and lameness pain in cattle. The objective of this study was to establish the pharmacokinetic (PK) parameters resulting from intravenous (IV), intramuscular (IM), oral (PO) and transdermal (TD) administration of FM in pre-wean piglets. FM was administered to thirty-nine pre-wean piglets at a target dose of 2.2 mg/kg for IV and IM and 3.3 mg/kg for PO and TD route. Plasma was collected at twenty-seven time points from 0 to 9 days after FM administration and concentrations were determined using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Pharmacokinetic data were analyzed using noncompartmental analysis (NCA) methods and nonlinear mixed-effects (NLME). Initial plasma concentration for IV (C0) 11,653 μg/L and mean peak plasma concentrations (Cmax) 6,543 μg/L (IM), 4,883 μg/L (PO), and 31.5 μg/L (TD) were measured. The time points of peak FM concentrations (tmax) were estimated 30 min, 1 h, and 24 h for IM, PO, and TD, respectively. The bioavailability (F) of PO and IM FM was estimated at >99%, while the bioavailability of TD FM was estimated to be 7.8%. The reported Cmax of FM after IM and PO administration is consistent with therapeutic concentration ranges that mitigate pain in other species and adult pigs. However, the low estimated concentration of FM after TD dosing is not expected to mitigate pain in pre-wean piglets. The low F of TD FM suggests that expanding the surface area of application is unlikely to be sufficient to establish an effective TD dose for pain, while the high bioavailability for PO FM should allow for an effective dose regimen to be established.

Abstract Background Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design of the trials is not usually homogeneous. Efficacy of the trial is determined depending on the selected primary endpoint and usually other different outcomes are measured. We aim to critically appraise which were the employed outcomes through a systematic review. Methods We conducted a systematic review of literature focusing on studies on primary headache evaluating acute relief of pain, following the PRISMA guideline. The study population included patients participating in a controlled study about symptomatic treatment. The comparator could be placebo or the standard of care. The collected information was the primary outcome of the study and all secondary outcomes. We evaluated the studied drug, the year of publication and the type of journal. We performed a search and we screened all the potential papers and reviewed them considering inclusion/exclusion criteria. Results The search showed 4288 clinical trials that were screened and 794 full articles were assessed for eligibility for a final inclusion of 495 papers. The studies were published in headache specific journals (58%), general journals (21.6%) and neuroscience journals (20.4%). Migraine was the most studied headache, in 87.8% studies, followed by tension type headache in 4.7%. Regarding the most evaluated drug, triptans represented 68.6% of all studies, followed by non-steroidal anti-inflammatories (25.1%). Only 4.6% of the papers evaluated ergots and 1.6% analyzed opioids. The most frequent primary endpoint was the relief of the headache at a determinate moment, in 54.1%. Primary endpoint was evaluated at 2-h in 69.9% of the studies. Concerning other endpoints, tolerance was the most frequently addressed (83%), followed by headache relief (71.1%), improvement of other symptoms (62.5%) and presence of relapse (54%). The number of secondary endpoints increased from 4.2 (SD = 2.0) before 1991 to 6.39 after 2013 (p = 0.001). Conclusion Headache relief has been the most employed primary endpoint but headache disappearance starts to be firmly considered. The number of secondary endpoints increases over time and other outcomes such as disability, quality of life and patients’ preference are receiving attention.

This document presents the conclusions of a detailed discussion on the role of topical NSAIDs during a round table Global Pain Faculty meeting held in Amsterdam in 2019 and subsequent discussions online. The aim of this evidence-based document is to describe the impact of musculoskeletal pain both in terms of the large numbers of sufferers and its economic impact. The document considers the place of topical therapies alongside other pharmacological and non-pharmacological treatments and presents the evidence for the benefits and harms of topical NSAIDS including indicators of efficacy for three main topical NSAIDs– diclofenac, ibuprofen and ketoprofen – based on almost 15,000 participants in randomized controlled trials for acute and chronic musculoskeletal pain. These topical NSAIDs have the largest body of evidence. For acute pain, numbers needed to treat to achieve at least 50% reduction in pain are as follows with 95% confidence intervals in brackets: Diclofenac emulgel 1.8(1.5–2.1) (5170 participants), Ibuprofen gel 2.7 (1.7–4.2) (436 participants), Ketoprofen gel 2.2 (1.7–2.8) (683 participants). For chronic pain, the NNTs are Diclofenac any formulation 9.5(7–14) (5995 participants). Ketoprofen 6.9(5.5–9.3) (2573 participants). Randomized controlled trial evidence suggests that adverse events for active topical NSAIDs are similar to placebo. Finally the gaps in knowledge are considered with suggestions on how further research might help. The global pain faculty was brought together by GSK under an unrestricted educational grant. [ABSTRACT FROM AUTHOR]

Ibuprofen is one of the most commonly prescribed anti-inflammatory drugs in pediatric practice. This drug inhibits the cyclooxygenase enzyme, reducing the production of prostaglandin, an important mediator on male reproductive function. We examined if pre-pubertal treatment with ibuprofen in male rats can affect the reproductive parameters of these animals in adult life and on their descendants. Male rats (23 days old) received ibuprofen (0; 2.4; 7.2 or 14.3 mg/kg/day), per gavage, from postnatal day (PND) 23 to 53. At sexual maturity, treated males were placed with untreated females for obtaining the next generation (F1). The highest dose of ibuprofen interfered in sexual behavior and reduced the fertility potential of these animals in adulthood. Additionally, the ibuprofen treatment altered the sperm quantity and quality, as evidenced by a decrease in sperm motility and in the daily sperm production in the testis. Testosterone levels were also reduced by pre-pubertal treatment. The paternal treatment with this drug also influenced the reproductive outcomes of progeny. The male offspring from males treated exhibited acceleration in sperm transit time in the epididymis and the number and volume of Leydig cell nuclei were decreased, while the estrous cyclicity was displayed and the fertility potential reduced in the female offspring. The pre-pubertal ibuprofen-treatment caused negative reproductive impacts in adulthood, compromising sperm quality and quantity, as well as interfered in the reproductive outcomes of the next generation. [ABSTRACT FROM AUTHOR]

Celecoxib is a breakthrough for pain relievers under the trade name Celebrex®, which is a Non-Steroid Anti-Inflammatory drug with its activity as an analgesic, antipyretic and anti-inflammatory. The purpose of this study was to find out the effect of celecoxib on blood uric acid levels of female white mice was induced with fresh cow liver extract. Experimental animals were divided into five groups, namely the control group (-), the control group (+) and the three dose groups, respectively 0.26, 0.52 and 1.04 mg/20 g. Observations were made on 7, 14 and 21 days with the Enzymatic Photometric method. The results showed that administration of celecoxib suspension at a dose of 0.26, 0.52 and 1.04 mg/20 g did not affect blood uric acid levels when compared with controls (P> 0.05).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used and prescribed medications because of their important role in reducing inflammation and pain, in addition to their non-addictive properties and safety profiles. However, some studies have documented an association between NSAIDs and delayed union or nonunion of joint arthrodesis procedures due to a potential inhibition of the bone's inflammatory healing response. As a result, some orthopedic surgeons hesitate to prescribe NSAIDs after an arthrodesis procedure. The purpose of this meta-analysis is to review all relevant literature regarding the effect of NSAIDs on union rates after arthrodesis and determine if NSAID therapy increases the risk of non-union in the setting of arthrodesis procedures. The study hypothesis was that NSAIDs would not have a significant effect on the risk of nonunion after arthrodesis. A thorough systematic review of Medline, Embase, the Cochrane Database of Systematic Reviews, and the Web of Science identified 3,050 articles to be screened. The variables of interest encompassed demographic factors, procedural details, type and administration of NSAIDs, the number of patients exposed to NSAIDs with and without successful union (case group), as well as the number of patients who did not receive NSAIDs with and without successful union (control group). All the data were analyzed using a maximum likelihood random-effects model. The number of non-union events versus routine healing from each study was used to calculate the odds ratio (OR) of successful healing after arthrodesis procedures with versus without NSAID therapy. Thirteen articles met the inclusion criteria for the meta-analysis. NSAID exposure showed an increased risk of nonunion, delayed union, or both following arthrodesis procedures; however, this did not meet statistical significance (OR, 1.48; confidence interval [CI], 0.96 to 2.30). A sub-analysis of pediatric and adult studies showed a significant increase in non-union risk in adults (OR, 1.717; CI, 1.012 to 2.914) when removing the pediatric cohort (p = 0.045). This meta-analysis provides evidence that NSAIDs can increase the risk of nonunion, delayed union, or both following arthrodesis procedures in adults. However, the study did not identify a risk of nonunion, delayed union, or both following arthrodesis procedures in the pediatric population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rowe et al.)

The dairy industry needs evidence-based solutions to mitigate painful procedures and conditions in dairy cattle. The objective of this study was to compare the pharmacokinetic properties of orally versus subcutaneously administered meloxicam in early-lactation dairy cattle. The study was conducted at a commercial dairy herd in southwesternOntario, Canada. Twelve postpartumcowswere enrolled in the study, receiving either subcutaneousmeloxicam(MET) at 0.5mg/kg body weight (n = 6) or oral meloxicam (MOS) at a higher dose of 1.0 mg/kg body weight (n = 6) immediately following parturition. The predicted half-life (12.5 ± 2.0 vs. 28.5 ± 2.0 h), Cmax (1.59 ± 0.15 vs. 1.95 ± 0.16 μg/mL), Tmax (5.33 vs. 11.7 h), and AUC0!1 (39.6 ± 7.4 vs. 115.6 ± 19 h * μg/mL) differed significantly between MET and MOS cows, respectively. After controlling for the treatment group, first lactation cows had a significantly higher half-life (4.1 ± 2.1 h), Cmax (0.56 ± 0.2 μg/mL), and AUC0!1 (21.6 ± h * μg/mL) relative to second lactation or greater cows, respectively. Administration of meloxicam through the subcutaneous or oral route results in appreciable, dose-dependent systemic levels. [ABSTRACT FROM AUTHOR]

Nontyphoidal Salmonella commonly induces intestinal infections; however, spondylitis arising from this bacterium is exceedingly rare. A comprehensive review of the clinical attributes of nontyphoidal Salmonella-induced spondylitis in adult populations is lacking in the literature. We report a case of an 83-year-old female who presented with a fever lasting three days, accompanied by anorexia and pervasive malaise. A month prior, she had been prescribed celecoxib and had received a trigger point injection. The patient was initially diagnosed with acute pyelonephritis and treated with an antimicrobial regimen. However, a week later, although her fever persisted, there was no complaint of back pain. The discontinuation of celecoxib led to back pain. Subsequent urine and blood cultures, coupled with MRI findings, confirmed the diagnosis of pyogenic spondylitis attributable to the Salmonella O7 group. The patient's fever abated with the administration of antimicrobial agents, and her back pain subsided. The antimicrobial regimen was continued for 12 weeks, with no resurgence of fever or back pain following treatment. Local pain and fever are important indicators for the diagnosis of spondylitis caused by nontyphoidal Salmonella. It is critical to take an accurate history of non-steroidal anti-inflammatory drugs (NSAIDs) use, such as celecoxib, since NSAIDs can obscure the symptoms. Blood cultures are equally important, given their propensity to yield positive results in these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Hamada et al.)

Background/Aims: The main purpose of this study was to investigate the effects of celecoxib and ibuprofen, both non-steroidal anti-inflammatory drugs (NSAIDs), on the decreased gluconeogenesis observed in liver of Walker-256 tumor-bearing rats. Methods: Celecoxib and ibuprofen (both at 25 mg/Kg) were orally administered for 12 days, beginning on the same day when the rats were inoculated with Walker-256 tumor cells. Results: Celecoxib and ibuprofen treatment reversed the reduced production of glucose, pyruvate, lactate and urea from alanine as well as the reduced production of glucose from pyruvate and lactate in perfused liver from tumor-bearing rats. Besides, celecoxib and ibuprofen treatment restored the decreased ATP content, increased triacylglycerol levels and reduced mRNA expression of carnitine palmitoyl transferase 1 (CPT1), while ibuprofen treatment restored the reduced mRNA expression of peroxisome proliferator-activated receptor alpha (PPARα) in the liver of tumor-bearing rats. Both treatments tended to decrease TNFα, IL6 and IL10 in the liver of tumor-bearing rats. Finally, the treatment with celecoxib, but not with ibuprofen, reduced the growth of Walker-256 tumor. Conclusion: Celecoxib and ibuprofen restored the decreased gluconeogenesis in the liver of Walker-256 tumor-bearing rats. These effects did not involve changes in tumor growth and probably occurred by anti-inflammatory properties of these NSAIDs, which increased expression of genes associated with fatty acid oxidation (PPARα and CPT1) and consequently the ATP production, normalizing the energy status in the liver of tumor-bearing rats.

Highlights • Higher impairment is significantly associated with larger NSAID-treatment related positive changes in activity. • Impairment level should be controlled for in clinical trials involving dogs with osteoarthritis. • Using higher impaired dogs may result in greater treatment effects, increasing the power of the study Abstract In veterinary medicine, evaluation of osteoarthritis (OA) treatment efficacy remains challenging. Measurement of activity, utilizing accelerometers, provides a surrogate measure of pain through measuring effects on activity, and the objective data collected can be used to assess the efficacy of treatments. However, little is known about how dog characteristics impact the accelerometry-measured response to treatment. The objectives of this study were to evaluate the effect of signalment and initial impairment level on accelerometer-measured changes in activity in osteoarthritic dogs after receiving a non-steroidal anti-inflammatory (NSAID). Fifty-seven client-owned dogs with OA-associated pain and mobility impairment were administered meloxicam for 2 weeks, following a 2-week baseline, and spontaneous activity was measured using an Actical accelerometer unit. Signalment factors and disease variables were recorded (age, sex, weight, impairment level, forelimb or hindlimb pain). Initial degree of impairment had a significant effect on changes in weekly (P = 0.009), weekday (P = 0.044) activity following NSAID treatment. Greater initial impairment was associated with larger positive changes in activity. Degree of impairment should be taken into consideration during the development of a clinical trial. Appropriate selection of candidates based on initial degree of impairment may permit a greater treatment effect, therefore increasing the power of the study. [ABSTRACT FROM AUTHOR]

Highlights • M-NCPEG and M-NC did not alter toxicological parameters in vitro and in vivo models. • H 2 O 2 -inducing damage was partially reverted by M-NCPEG and M-NC. • M-NCPEG is safe to be used as an alternative treatment for inflammatory-related diseases. Abstract Meloxicam is an anti-inflammatory drug that has a potential protective effect in many common diseases. However, this molecule is quickly eliminated from the body due to it short half-life. One way to overcome this problem is to incorporate meloxicam into lipid-core nanocapsules which may increase it anti-inflammatory effects. In view of this, the objective of this work was to evaluate the potential toxicity and safety of these novel nanomaterials both in vitro and in vivo. Here, we evaluated the effects of uncoated meloxicam-loaded nanocapsules (M-NC), uncoated and not loaded with meloxicam or blank (B-NC), PEGylated meloxicam-loaded lipid-core nanocapsules (M-NCPEG), blank PEGylated lipid-core nanocapsules (B-NCPEG) and free meloxicam (M-F) in vitro through the analysis of cell viability, caspase activity assays and gene expression of perforin and granzyme B. Meanwhile, the in vivo safety was assessed using C57BL/6 mice that received nanocapsules for seven days. Thus, no change in cell viability was observed after treatments. Furthermore, M-NC, M-NCPEG and M-F groups reversed the damage caused by H 2 O 2 on caspase-1, 3 and 8 activities. Overall, in vivo results showed a safe profile of these nanocapsules including hematological, biochemical, histological and genotoxicity analysis. In conclusion, we observed that meloxicam nanocapsules present a safe profile to use in future studies with this experimental protocol and partially reverse in vitro damage caused by H 2 O 2. [ABSTRACT FROM AUTHOR]

Increased attention has been directed toward the role of exercise as an intervention for cancer patients and survivors. There is a paucity of information endorsing the effectiveness of physical activity in reducing in the incidence of specific cancers and prolonging survivorship. This chapter is a review of the expanding literature on exercise as a beneficial therapy throughout the spectrum of cancer care. A review of the literature identified 15 international guidelines from seven countries and regions. Overall, exercise-induced improvements in disease- and treatment-related effects were affirmed, with analogous exercise recommendations across all reports. However, current guidelines remain generic and insufficient to develop personalized exercise regiments, including modality, intensity, frequency, and duration, for this heterogeneous disease profile. Moreover, the perception of exercise as an unnecessary distress by both patients and physicians continues to act as a barrier to the dissemination of physical activity as a beneficial tool. This knowledge gap necessitates that additional studies be conducted to elucidate the dose-response relationship of physical activity and optimal exercise programs for the treatment and management of specific cancer-types. [ABSTRACT FROM AUTHOR]

The dairy industry needs evidence-based solutions to mitigate painful procedures and conditions in dairy cattle. The objective of this study was to compare the pharmacokinetic properties of orally versus subcutaneously administered meloxicam in early-lactation dairy cattle. The study was conducted at a commercial dairy herd in southwestern Ontario, Canada. Twelve postpartum cows were enrolled in the study, receiving either subcutaneous meloxicam (MET) at 0.5 mg/kg body weight (n = 6) or oral meloxicam (MOS) at a higher dose of 1.0 mg/kg body weight (n = 6) immediately following parturition. The predicted half-life (12.5 ± 2.0 vs. 28.5 ± 2.0 h), Cmax (1.59 ± 0.15 vs. 1.95 ± 0.16 μg/mL), Tmax (5.33 vs. 11.7 h), and AUC0→∞ (39.6 ± 7.4 vs. 115.6 ± 19 h * µg/mL) differed significantly between MET and MOS cows, respectively. After controlling for the treatment group, first lactation cows had a significantly higher half-life (4.1 ± 2.1 h), Cmax (0.56 ± 0.2 µg/mL), and AUC0→∞ (21.6 ± h * µg/mL) relative to second lactation or greater cows, respectively. Administration of meloxicam through the subcutaneous or oral route results in appreciable, dose-dependent systemic levels.

What is known and objective Non-steroidal anti-inflammatory drugs ( NSAIDs) have been commonly used to treat pain in sickle-cell disease ( SCD), but NSAID use is associated with renal, gastrointestinal and cardiovascular toxicities. Our objective was to evaluate the use of aspirin and non-aspirin NSAIDs in SCD. Comment Despite analgesic and anti-inflammatory benefits in SCD, non-aspirin NSAIDs are associated with renal, cardiovascular and gastrointestinal toxicities in this patient population. Aspirin may have less renal and cardiovascular toxicities. The different side effect profile of NSAIDs is related to the COX-1/ COX-2 selectivity at their therapeutic doses. Individual risk factors and genetic biomarkers should be considered when selecting appropriate NSAIDs and their dose. What is new and conclusion NSAIDs have the potential to be an important component of pain regimens in SCD, but the use of NSAIDs should be individualized based on potential side effects and patient risk factors and the lowest effective dose should be prescribed with proper monitoring in patients with SCD. [ABSTRACT FROM AUTHOR]

Background Context: Non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used treatment for low back pain (LBP). Literature on NSAID use in articular cartilage has shown detrimental effects; however, minimal data exist to detail the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a major cause of LBP, we explored the effects of indomethacin, a commonly used NSAID, on disc matrix homeostasis in an animal model of IDD.Purpose: This study aimed to determine the effects of oral indomethacin administration on IDD in an in vivo rabbit model. This study hypothesized that indomethacin use would accelerate the progression of IDD based upon serial imaging and tissue outcomes.Study Design/setting: This was a laboratory-based, controlled, in vivo evaluation of the effects of oral indomethacin administration on rabbit intervertebral discs.Methods: Six skeletally mature New Zealand white rabbits were divided into two groups: disc puncture alone to induce IDD (Puncture group) and disc puncture plus indomethacin (Punc+Ind group). The Punc+Ind group received daily administration of 6mg/kg oral indomethacin. Serial magnetic resonance imaging (MRI) was obtained at 0, 4, 8, and 12 weeks. The MRI index and the nucleus pulposus (NP) area were calculated. Discs were harvested at 12 weeks for determination of disc glycosaminoglycan (GAG) content, relative gene expression measured by real-time polymerase chain reaction, and histologic analyses.Results: The MRI index and the NP area of punctured discs in the Punc+Ind group demonstrated no worsening of degeneration compared with the Puncture group. Histologic analysis was consistent with less severe disc degeneration in the Punc+Ind group. Minimal differences in gene expression of matrix genes were observed between Puncture and Punc+Ind groups. The GAG content was higher in animals receiving indomethacin in both annulus fibrosus and NP at adjacent uninjured discs.Conclusions: Oral indomethacin administration did not result in acceleration of IDD in an in vivo rabbit model. Future research is needed to ascertain long-term effects of indomethacin and other NSAIDs on disc matrix homeostasis. [ABSTRACT FROM AUTHOR]

Inflammation has been found to be an important part of the carcinogenic process. As such, potential use of nonsteroidal anti-inflammatory drugs (NSAIDs) to lower inflammation and mitigate the risk of carcinogenesis has been investigated. Genetic variations and short nucleotide variants (SNVs) may contribute to differences in the efficacy of NSAIDs in cancer prevention. The purpose of this literature review is to present evidence regarding biomarkers significantly associated with the chemopreventative capacity of regular NSAID use. A literature search was conducted in Medline and Embase databases utilizing the keywords "cancer," "inflammation" and "biomarkers." Articles that reported on genetic or protein biomarkers associated with cancer prevention, cancer recurrence, and/or the clinical efficacy and toxicity of NSAIDs for cancer treatment were considered eligible. Eight articles were included in this review and 33 genetic predictors were found to be associated with the prophylactic efficacy and toxicity of NSAID use in cancer. The current literature related to colorectal, lung, and prostate cancers has failed to consistently support the ability of NSAIDs to reduce cancer risk; however, a negative association between breast cancer and the use of COX-2 (also known as PTGS2) inhibitors has been suggested. The inconsistent nature of the current state of research demands further study and exploration into the pharmacogenetics of NSAIDs. [ABSTRACT FROM AUTHOR]

Applying analgesics to feed is a potentially easy method of providing pain-relief to sheep and lambs that undergo painful husbandry procedures. To be effective, the medicated feed needs to be readily accepted by sheep and its consumption needs to result in therapeutic concentrations of the drug. In the present experiment, pelleted feed was supplemented with flunixin (4.0 mg/kg live weight) and offered to eight sheep. To test the palatability of flunixin, the individually penned sheep were offered normal feed and feed supplemented with flunixin in separate troughs for two consecutive days. A trend for a day by feed-type (control versus flunixin supplemented) interaction suggested that sheep may have had an initial mild aversion to pellets supplemented with flunixin on the first day of exposure, however, by on the second day there was no difference in consumption of normal feed and feed supplemented with flunixin. To test pharmacokinetics, sheep were offered 800 g of flunixin supplemented feed for a 12 h period. Blood samples were taken over 48 h and plasma drug concentrations were determined using ultra-high-pressure liquid chromatography, negative electrospray ionisation and tandem mass spectrometry. The mean ± S.D. time required to reach maximum concentration was 6.00 ± 4.14 h and ranged from 1 to 12 h. Average maximum plasma concentration was 1.78 ± 0.48 µg/mL and ranged from 1.61 to 2.80 µg/mL. The average half-life of flunixin was 7.95 ± 0.77 h and there was a mean residence time of 13.62 ± 1.17 h. Free access to flunixin supplemented feed enabled all sheep to obtain inferred therapeutic concentrations of flunixin in plasma within 6 h of starting to consume the feed. Provision of an analgesic in feed may be an alternative practical method for providing pain relief to sheep.

The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

Periodontitis is a chronic disease characterized by bone loss and inflammatory changes. We studied the effect of a homeopathic agent (Mercúrios Corrosivos 6 CH) and a non-steroidal anti-inflammatory drug (nimesulide) on the alveolar bone loss progression in experimentally induced periodontitis in rats. Sixty (60) Wistar rats were separated into group 1 (homeopathy), group 2 (nimesulide) and group 3 (saline solution). Silk ligatures were placed at the gingival margin level of the lower right first molar of all rats. Alveolar bone loss was evaluated by light microscopic analysis and analyzed using software Image J. The results were submitted to the analysis of variance (ANOVA) and Tukey’s posttest (p

Avaliou-se o efeito do ibuprofeno administrado uma hora antes da inovulação de embriões bovinos, com o objetivo de melhorar a taxa de prenhez. Após a avaliação da resposta ao protocolo de sincronização do estro, 76 fêmeas selecionadas como receptoras de embriões foram distribuídas em três grupos (G) experimentais: G1 (n=25) receptoras usadas como controle, G2 (n=30) receptoras que receberam ibuprofeno 5mg/kg, I.M, uma hora antes da inovulação dos embriões, e G3 (n=21) receptoras que receberam uma matriz polimérica de liberação controlada de ibuprofeno administrado por via subcutânea. As taxas de prenhez foram de 16% (4/25), 43,3% (13/30) e 14,2% (3/21), para G1, G2 e G3, respectivamente. Observou-se diferença (PThe effect of the administered ibuprofen was evaluated one hour before the embryo transfer of bovine embryos in order to improve pregnancy rates. After evaluating the response to protocol synchronization of estrus, 76 Females selected as the recipients of embryos were distributed into three experimental groups: G1 (n = 25) surrogate cows used as control, G2 (n = 30) surrogate cows that received 5mg/kg ibuprofen, IM, one hour before the embryo transfer, and G3 (n = 20) surrogate cows that received an array polymeric release of controlled ibuprofen subcutaneously administered. The pregnancy rates were 16% (4/25), 43.3% (13/30), and 14.2% (3/21) for G1, G2, and G3, respectively. There was statistical difference (P

Rationale: Renal tubular acidosis (RTA) is a cause of non-anion gap metabolic acidosis (NAGMA) that is infrequently diagnosed and is due to various underlying etiologies that impair the kidney's ability to retain bicarbonate or excrete acid. Ibuprofen is an over-the-counter non-steroidal anti-inflammatory medication that is used by patients widely for a variety of reasons. Although it is well known that ibuprofen and other non-steroidal anti-inflammatory drugs may have nephrotoxic effects, the role of ibuprofen as a cause of RTA and hypokalemia is not well recognized., Presenting Concerns: A 66-year-old man with chemotherapy-treated lymphoma in remission and ongoing heavy ibuprofen use for chronic pain presented to hospital with a 1-week history of increasing lethargy and otherwise unremarkable review of systems. Investigations showed acute kidney injury, hypokalemia, hyperchloremia, and NAGMA with elevated urinary pH and positive urine anion gap., Diagnoses: The final diagnosis of distal RTA secondary to ibuprofen was made after ruling out gastrointestinal bicarbonate loss and additional secondary causes of RTA, including other medications, autoimmune conditions, and obstructive uropathy., Interventions: The patient was admitted and treated with intravenous sodium bicarbonate for 24 hours with correction of hypokalemia via oral supplementation. His ibuprofen-containing medication was discontinued., Outcomes: His acute kidney injury and electrolyte abnormalities resolved within 48 hours of initiating treatment with concurrent resolution of his lethargy. He was discharged home and advised to stop taking ibuprofen., Lessons Learned: We report a case of patient with hypokalemia and NAGMA secondary to ibuprofen and highlight the importance of monitoring for this side effect in patients taking ibuprofen., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

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Background:Analgesic nephropathy (AN) is chronic renal impairment as a direct consequence of chronic heavy analgesia ingestion. An association between non-steroidal anti-inflammatory agents and chronic kidney disease (CKD) has long been suspected. Despite ample observational data obtained in recent decades the relationship remains uncertain. This systematic review intends to summarize the available literature and to define the role of non-steroidal anti-inflammatories in the natural history of AN. Methods:We conducted a systematic literature search for articles describing the association between non-steroidal anti-inflammatory abuse and renal insufficiency. No restriction was placed on publication date, but papers were limited to English language, observational design, and human studies. Results:Nine articles met our inclusion criteria and were discussed in this review. This includes 5 cohort studies and 4 case–control trials, with a combined population of 12,418 study subjects and 23,877 controls. Eight of the nine reports failed to identify any increased risk of chronic renal impairment with heavy non-steroidal anti-inflammatory consumption. Study methods were heterogeneous and the overall quality of data was relatively poor. Conclusion:A relationship between non-steroidal anti-inflammatory medicines and the development of CKD has never been proven. Based on the available scientific evidence non-steroidal anti-inflammatory agents do not appear to be implicated in the pathogenesis of AN. [ABSTRACT FROM AUTHOR]

In the present article, we have studied the photochemical behavior of a common non-steroidal anti-inflammatory drug (NSAIDs) namely flufenamic acid (FLUA) in aqueous solution. The absorption spectrum of such compound shows a significant absorption beyond 290 nm and the photochemical irradiation within the range 300–450 nm leads to its complete transformation in roughly 6 h. The quantum yield of FLUA transformation measured at 290 and 310 nm was evaluated to about 1.1 × 10 −4 without any significant effect of the excitation wavelength. The degradation process was inhibited in acidic solutions owing to the sharp increment in the absorption of FLUA in the wavelength region between 300 and 350 nm. The quantum yield was estimated to 1.2 × 10 −4 at pH 7. The effect of oxygen on the photochemical behavior of FLUA has also been investigated. The obtained results clearly indicate that oxygen is not significantly involved in the photochemical degradation process. The phototransformation of the flufenamic acid appears to occur through one pathway that involves the photohydrolysis of trifluoromethyl group, and thus leads to the formation of one specific photoproduct, namely 2,3′-imino-dibenzoic acid. This result was confirmed by the formation of the fluoride ions after irradiation during the irradiation of flufenamic acid. A mechanistic scheme for such transformation of flufenamic acid was proposed. [ABSTRACT FROM AUTHOR]

Introduction Postoperative pain, nausea and vomiting are frequent symptoms after tonsillectomy. There have been controversies concerning the advantages and drawbacks of different analgesics in this setting, especially non-steroidal anti-inflammatory drugs, because of potential side effects. We have evaluated the effectiveness and safety of a shift from prednisolone to ibuprofen for postoperative analgesia after tonsillectomy. Patients and methods Data from 1231 children scheduled for tonsillectomy over a period of 30 months were analysed. During the first period, children received a combination of paracetamol–prednisolone with codeine as a rescue therapy; in the second period, they received paracetamol and ibuprofen, with tramadol as a rescue therapy. All children received IV dexamethasone at 0.1 mg/kg for antiemetic prophylaxis. The primary end-point was the incidence of severe pain defined as an Objective Pain Scale (OPS) score ≥ 6 at the seventh postoperative day (POD7). Other end-points were postoperative nausea or emesis (PONV), sleep disturbance, oral intake and postoperative haemorrhage and reoperation. Results Six hundred and seventy-two and 559 children were included in the prednisolone and ibuprofen groups respectively. OPS scores ≥ 6 were observed in 3.1% of cases (95% confidence interval, 2.3–4.2%) on POD7 for the entire study population. Ibuprofen reduced the incidence of OPS scores ≥ 6 on POD7 (relative risk 0.37, 95% CI: 0.18–0.78; P = 0.009), OPS scores in the ambulatory unit ( P < 0.001) and POD1 ( P < 0.001), nalbuphine requirements (RR 0.42, 95% CI, 0.34–0.5, P < 0.0001), and PONV ( P = 0.01) compared with prednisolone. Ibuprofen enhanced sleep quality on POD0 ( P < 0.0001) and POD7 ( P = 0.02), and oral intake on POD1 ( P < 0.0001). The incidence of bleeding requiring reoperation was comparable between the two groups (RR 0.8 [95% CI, 0.13–4.78], p = 0.8). Predictive factors for an OPS score ≥ 6 at POD7 were OPS score > 4 on the morning and the evening of POD1 (OR 1.24, 95% CI 1.02–1.49, P = 0.03 and OR 1.30, 95% CI 1.12–1.55, P = 0.008, respectively) and prednisolone use (OR 2.37, 95% CI 1.06–5.31, P = 0.04). Conclusion The administration of ibuprofen compared to prednisolone improves postoperative comfort in children undergoing ambulatory tonsillectomy without increasing the incidence of side effects. [ABSTRACT FROM AUTHOR]

Background/Aims: The main purpose of this study was to investigate the effects of celecoxib and ibuprofen, both non-steroidal anti-inflammatory drugs (NSAIDs), on the decreased gluconeogenesis observed in liver of Walker-256 tumor-bearing rats. Methods: Celecoxib and ibuprofen (both at 25 mg/Kg) were orally administered for 12 days, beginning on the same day when the rats were inoculated with Walker-256 tumor cells. Results: Celecoxib and ibuprofen treatment reversed the reduced production of glucose, pyruvate, lactate and urea from alanine as well as the reduced production of glucose from pyruvate and lactate in perfused liver from tumor-bearing rats. Besides, celecoxib and ibuprofen treatment restored the decreased ATP content, increased triacylglycerol levels and reduced mRNA expression of carnitine palmitoyl transferase 1 (CPT1), while ibuprofen treatment restored the reduced mRNA expression of peroxisome proliferator-activated receptor alpha (PPARα) in the liver of tumor-bearing rats. Both treatments tended to decrease TNFα, IL6 and IL10 in the liver of tumor-bearing rats. Finally, the treatment with celecoxib, but not with ibuprofen, reduced the growth of Walker-256 tumor. Conclusion: Celecoxib and ibuprofen restored the decreased gluconeogenesis in the liver of Walker-256 tumor-bearing rats. These effects did not involve changes in tumor growth and probably occurred by anti-inflammatory properties of these NSAIDs, which increased expression of genes associated with fatty acid oxidation (PPARa and CPT1) and consequently the ATP production, normalizing the energy status in the liver of tumor-bearing rats. [ABSTRACT FROM AUTHOR]

Background: The benefit of pre and post-operative administration of non-steroidal anti-inflammatory drugs for the relief of post-operative pain and control of inflammation in horses following orthopaedic surgery has not been previously investigated in controlled clinical field trials, and the utility of such treatment is a matter of ongoing dispute. Recently the utility of post-operative pain management was emphasized. It was therefore our aim to determine the efficacy of meloxicam in horses following partial resection of fractured splint bones. This condition was selected since the limited extent of the insult and the defined surgical intervention allowed the conduct of a randomized, double blinded, placebo-controlled, parallel group, multi-centre clinical field study in a homogenous patient population. Results: Sixty-six client owned horses requiring unilateral partial splint bone resection were recruited in 15 centres in Germany and were allocated in a 1:1 ratio to receive meloxicam, 0.6 mg/kg for 5 days. Lameness at trot grades prior to surgery were similar in the meloxicam and placebo treatment groups but were significantly lower in the meloxicam group on day 6 post surgery. Clinical scores for soft tissue swelling and assessment of analgesic and anti-inflammatory efficacy by the investigators at the end of the study were significantly better for the meloxicam compared to the placebo group. No treatment-related adverse reactions were observed. Conclusion: The administration of meloxicam i.v. once prior to surgery followed by once daily oral administration for four consecutive days is efficacious for the control of post-operative pain and inflammation in horses undergoing orthopaedic surgery. [ABSTRACT FROM AUTHOR]