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1.
Vet Q ; 44(1): 1-11, 2024 Dec.
Article En | MEDLINE | ID: mdl-38711265

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


Animal Welfare , Anti-Inflammatory Agents, Non-Steroidal , Heterocyclic Compounds , Macrolides , Animals , Cattle , Male , Cross-Sectional Studies , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Disaccharides/pharmacology , Disaccharides/therapeutic use , Cattle Diseases/drug therapy , Cattle Diseases/microbiology , Mycoplasma bovis/drug effects , Anti-Infective Agents/therapeutic use , Anti-Infective Agents/pharmacology , Mycoplasma Infections/veterinary , Mycoplasma Infections/drug therapy
2.
FP Essent ; 540: 16-23, 2024 May.
Article En | MEDLINE | ID: mdl-38767885

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


Anti-Bacterial Agents , Anti-Inflammatory Agents, Non-Steroidal , Helicobacter Infections , Helicobacter pylori , Peptic Ulcer , Proton Pump Inhibitors , Humans , Peptic Ulcer/diagnosis , Proton Pump Inhibitors/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Helicobacter Infections/complications , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination , Sulfonamides/therapeutic use , Pyrroles
4.
BMJ Case Rep ; 17(5)2024 May 22.
Article En | MEDLINE | ID: mdl-38782445

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


Anti-Inflammatory Agents, Non-Steroidal , Corneal Perforation , Sjogren's Syndrome , Humans , Female , Sjogren's Syndrome/complications , Sjogren's Syndrome/drug therapy , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Corneal Perforation/chemically induced , Aged, 80 and over , Cataract Extraction/adverse effects , Corneal Transplantation , Postoperative Complications/chemically induced
5.
Korean J Gastroenterol ; 83(5): 197-199, 2024 May 25.
Article En | MEDLINE | ID: mdl-38783621

5-Aminosalicylic acid (5-ASA) is recommended for managing ulcerative colitis. Common adverse effects associated with 5-ASA include gastrointestinal disorders, headaches, and skin rashes. Perimyocarditis induced by 5-ASA is a rare adverse effect, with only a limited number of cases reported. This paper presents a case of 5-ASA-induced perimyocarditis in a 29-year-old female who had been taking 5-ASA for three weeks. The patient was admitted to the emergency department with dyspnea, chest discomfort, and fever. She subsequently underwent laboratory investigations, including electrocardiography, transthoracic echocardiography, chest computed tomographic angiography, cardiac magnetic resonance imaging, and heart biopsy. Intravenous steroid was administered, and 5-ASA was discontinued. The patient's signs and symptoms improved significantly within a few days of discontinuing 5-ASA, leading to her subsequent discharge. This case highlights the importance of considering perimyocarditis in patients exhibiting cardiac symptoms during 5-ASA therapy, despite it being a rare adverse effect. Drug withdrawal in such cases may lead to rapid clinical improvement.


Anti-Inflammatory Agents, Non-Steroidal , Colitis, Ulcerative , Echocardiography , Electrocardiography , Mesalamine , Myocarditis , Humans , Female , Mesalamine/therapeutic use , Mesalamine/adverse effects , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/diagnosis , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Myocarditis/diagnosis , Myocarditis/chemically induced , Myocarditis/drug therapy , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Computed Tomography Angiography
6.
Curr Opin Rheumatol ; 36(4): 302-308, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38712691

PURPOSE OF REVIEW: This review evaluates recent advancements in disease-modifying therapies for axial spondyloarthritis (axSpA). RECENT FINDINGS: A recent study could not demonstrate an additional effect of NSAID therapy on golimumab [Tumor Necrosis Factor-α inhibitor (TNFi)] on structural progression; however, this might be due to the fact that the study was underpowered. While DMARDs have shown promise in suppressing inflammation, their impact on structural progression remains uncertain. A well powered trial showed no difference in spinal progression between secukinumab [Interleukin17A inhibitor (IL17Ai)] and adalimumab-biosimilar (TNFi). Preliminary data on Janus kinase inhibitors (JAKi) focus on MRI findings but lack evidence on radiographic spinal progression. While some studies suggest promising outcomes, others reveal limitations and inconclusive findings. SUMMARY: Recent studies explore the effectiveness of NSAIDs, biological disease-modifying antirheumatic drugs like TNFi and IL-17i, as well as JAK inhibitors in axSpA. Conflicting evidence surrounds these therapies' ability to impede structural progression, with challenges in study design and interpretation. Moreover, changes in demographics and treatment methods underscore the importance of examining trends over time when assessing disease outcomes. Ultimately, ongoing research could benefit from new imaging tools when evaluating therapeutic strategies for modifying disease progression in axSpA.


Anti-Inflammatory Agents, Non-Steroidal , Antirheumatic Agents , Axial Spondyloarthritis , Humans , Antirheumatic Agents/therapeutic use , Axial Spondyloarthritis/drug therapy , Axial Spondyloarthritis/diagnosis , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Disease Progression , Antibodies, Monoclonal/therapeutic use , Treatment Outcome
7.
Expert Rev Gastroenterol Hepatol ; 18(4-5): 203-215, 2024.
Article En | MEDLINE | ID: mdl-38725175

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


Anti-Inflammatory Agents, Non-Steroidal , Cholangiopancreatography, Endoscopic Retrograde , Pancreatitis , Aged , Humans , Middle Aged , Acute Disease , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Fluid Therapy/methods , Network Meta-Analysis , Pancreatitis/prevention & control , Pancreatitis/etiology , Ringer's Lactate/therapeutic use , Ringer's Lactate/administration & dosage , Risk Factors , Somatostatin/analogs & derivatives , Somatostatin/therapeutic use , Treatment Outcome
8.
Best Pract Res Clin Gastroenterol ; 69: 101906, 2024 Mar.
Article En | MEDLINE | ID: mdl-38749582

Endoscopic retrograde cholangiopancreatography (ERCP) is a common endoscopic procedure which plays a key role in the management of diseases of the bile ducts and the pancreas. Despite ERCP being performed routinely since more than 4 decades, it is still related to a considerable rate of complications with post-ERCP pancreatitis being the most frequent one. Lately, endoscopic techniques have evolved, and numerous modalities have been developed to prevent or manage ERCP-related complications, especially PEP, such as the use of intra-rectal non-steroidal anti-inflammatory drugs (NSAIDs), insertion of prophylactic stents in the pancreatic duct (PD) or intravenous hyperhydration. Knowledge of the various risk factors and applying validated preventive methods are keys in providing a safe procedure and optimizing overall patient care.


Cholangiopancreatography, Endoscopic Retrograde , Pancreatitis , Stents , Humans , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Risk Factors , Pancreatitis/prevention & control , Pancreatitis/etiology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
9.
Bioorg Chem ; 147: 107420, 2024 Jun.
Article En | MEDLINE | ID: mdl-38718461

Phytochemical analysis of Chloranthus henryi var. hupehensis roots led to the identification of a new eudesmane sesquiterpenoid dimer, 18 new sesquiterpenoids, and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer that is assembled by a unique oxygen bridge (C11-O-C8') of two highly rearranged eudesmane-type sesquiterpenes with the undescribed C16 carbon framework. (+)-2 and (-)-2 were a pair of new skeleton dinorsesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures were elucidated using spectroscopic data, single-crystal X-ray diffraction analysis, and quantum chemical computations. In the LPS-induced BV-2 microglial cell model, 17 suppressed IL-1ß and TNF-α expression with EC50 values of 6.81 and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production in a dose dependent manner and without cytotoxicity. In subsequent mechanism studies, compounds 3, 16, and 17 could reduce IL-1ß and TNF-α production by inhibiting IKBα/p65 pathway activation.


Dose-Response Relationship, Drug , Plant Roots , Sesquiterpenes , Signal Transduction , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Plant Roots/chemistry , Signal Transduction/drug effects , Molecular Structure , Mice , Animals , Structure-Activity Relationship , Transcription Factor RelA/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Drug Discovery , NF-KappaB Inhibitor alpha/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification
11.
J Med Case Rep ; 18(1): 242, 2024 May 10.
Article En | MEDLINE | ID: mdl-38724965

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


Anti-Bacterial Agents , Antimicrobial Stewardship , Humans , Female , Middle Aged , Anti-Bacterial Agents/therapeutic use , Viscosupplementation , Knee Joint , Treatment Outcome , C-Reactive Protein/analysis , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Osteoarthritis, Knee/drug therapy
12.
BMC Biotechnol ; 24(1): 26, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724967

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


Anti-Inflammatory Agents, Non-Steroidal , Arthritis, Rheumatoid , Hydrogels , Hydrogels/chemistry , Animals , Mice , Arthritis, Rheumatoid/drug therapy , RAW 264.7 Cells , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Extracellular Matrix/metabolism , Extracellular Matrix/drug effects , Diclofenac/pharmacology , Diclofenac/therapeutic use , Drug Liberation
13.
J Assoc Physicians India ; 72(1): 14-16, 2024 Jan.
Article En | MEDLINE | ID: mdl-38736068

BACKGROUND: In recent years, there has been an alarming increase in cases of gastric outlet obstruction (GOO) at our center due to drug abuse. So, we conducted this study to know the incidence of nonsteroidal anti-inflammatory drugs (NSAIDs) and synthetic opioid abuse in cases of GOO. METHODS: This was an observational study involving consecutive cases of GOO diagnosed from September 2017 to February 2019. A detailed history, including drug addiction history and clinical examination, was done. Investigations included routine biochemical and hematological tests, upper gastrointestinal endoscopy (UGIE), ultrasonography, rapid urease test (RUT), and histopathology of the diseased area. RESULTS: Among the 102 cases diagnosed with GOO, 62 (60.78%) cases had a history of drug addiction. The drug addiction history was as follows: NSAIDs and opioids in 56, opioids alone in four, and NSAIDs alone in two cases. The most common site of stricture was the second part of the duodenum. The features on histopathology were ulcerations of the mucosa infiltrated by eosinophils, plasma cells, and lymphocytes. CONCLUSION: There is an alarming increase in the incidence of GOO due to NSAIDs and opioid abuse at our center. Efforts should be made to control the indiscriminate use of these over-the-counter drugs to prevent dreaded complications.


Analgesics, Opioid , Anti-Inflammatory Agents, Non-Steroidal , Gastric Outlet Obstruction , Humans , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , India/epidemiology , Incidence , Male , Female , Adult , Analgesics, Opioid/adverse effects , Middle Aged , Gastric Outlet Obstruction/chemically induced , Gastric Outlet Obstruction/epidemiology , Gastric Outlet Obstruction/etiology , Opioid-Related Disorders/epidemiology , Young Adult , Aged
14.
Front Endocrinol (Lausanne) ; 15: 1384365, 2024.
Article En | MEDLINE | ID: mdl-38715797

Importance: Subacute thyroiditis (SAT) is a self-limiting and inflammatory thyroid disease. Although SAT usually improves on its own within weeks, it needs treatment when patients have pain, fever, and symptoms of thyrotoxicosis. Therapeutic drugs mainly include non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Currently, there is no systematic review or meta-analysis of the comparison of outcomes between NSAIDs and glucocorticoids for the treatment of SAT. Objectives: To conduct a systematic review and meta-analysis on the outcomes in subacute thyroiditis patients treated with glucocorticoids or NSAIDs. Data sources: Using the four electronic databases, including PubMed, Embase, Cochrane Library, Wanfang database and Web of Science. All publications until 21 June 2023 were searched. The reference lists of all selected articles were independently screened to identify additional studies left out in the initial search. Study selection: The literature comparing outcomes between glucocorticoids and non-steroidal anti-inflammatory drugs for patients with subacute thyroiditis will be included. Data extraction and synthesis: Two independent investigators (Anqi Yuan and Jialu Wu) extracted the data following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PRISMA) and then evaluated the quality of the eligible studies with the Newcastle-Ottawa Scale. Fixed-effects models for the meta-analyses were applied. Heterogeneity was assessed with the chi-squared (x²) test (Cochran's Q) and inconsistency index (I²). The robustness of the results was tested with the sensitivity analyses. The bias of publication was assessed with the Harbord test. Main outcomes and measures: The incidence of permanent hypothyroidism in SAT patients treated with corticosteroids or NSAIDs. Results: Our study included a total of ten comparative cohort studies with 1337 participants. We found that the incidence of developing permanent hypothyroidism in the SAT patients who received glucocorticoids treatment was significantly lower than those who received NSAIDs treatment. (OR, 0.56; 95% CI, 0.36-0.88; P = 0.01). The risk of permanent hypothyroidism in patients who received prednisone at an average initial dose < 40 mg/d was significantly lower than that in patients who received NSAIDs (OR, 0.37; 95% CI, 0.14-0.94; P = 0.04). There was no significant difference in the occurrence of permanent hypothyroidism between SAT patients who received an average initial dose ≥ 40 mg/d of prednisone and those who received only NSAIDs (OR, 0.7; 95% CI, 0.14-3.53; P = 0.67). In addition, the recurrence rate was observably higher in those receiving glucocorticoids than in those receiving NSAIDs (OR, 1.98; 95% CI, 1.12-3.5; p = 0.02). The recurrence rate was significantly higher in patients with an average initial prednisone dose of < 40 mg/d than in the NSAIDs group. There was no significant difference in the recurrence rate between patients in the mean initial prednisone dose ≥ 40 mg/d group and those in the NSAIDs group. Conclusions and relevance: In this meta-analysis, we compared the treatment outcomes of SAT patients between glucocorticoids and NSAIDs. Our results indicated that glucocorticoid treatment was associated with a lower incidence of permanent hypothyroidism than NSAID treatment. Patients treated with NSAIDs might have a lower recurrence rate. This finding might help to understand the outcome of the disease when choosing different drugs and help physicians to make appropriate decisions. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023427332.


Anti-Inflammatory Agents, Non-Steroidal , Glucocorticoids , Thyroiditis, Subacute , Humans , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Thyroiditis, Subacute/drug therapy , Glucocorticoids/therapeutic use , Glucocorticoids/adverse effects , Glucocorticoids/administration & dosage , Treatment Outcome
15.
Bioorg Chem ; 147: 107403, 2024 Jun.
Article En | MEDLINE | ID: mdl-38691909

A novel series of pyrazole derivatives with urea/thiourea scaffolds 16a-l as hybrid sorafenib/erlotinib/celecoxib analogs was designed, synthesized and tested for its VEGFR-2, EGFRWT, EGFRT790M tyrosine kinases and COX-2, pro-inflammatory cytokines TNF-α and IL-6 inhibitory activities. All the tested compounds showed excellent COX-2 selectivity index in range of 18.04-47.87 compared to celecoxib (S.I. = 26.17) and TNF-α and IL-6 inhibitory activities (IC50 = 5.0-7.50, 6.23-8.93 respectively, compared to celecoxib IC50 = 8.40 and 8.50, respectively). Screening was carried out against 60 human cancer cell lines by National Cancer Institute (NCI), compounds 16a, 16c, 16d and 16 g were the most potent inhibitors with GI% ranges of 100 %, 99.63-87.02 %, 98.98-43.10 % and 98.68-23.62 % respectively, and with GI50 values of 1.76-15.50 µM, 1.60-5.38 µM, 1.68-7.39 µM and 1.81-11.0 µM respectively, in addition, of showing good safety profile against normal cell line (F180). Moreover, compounds 16a, 16c, 16d and 16 g had cell cycle arrest at G2/M phase with induced necrotic percentage compared to sorafenib of 2.06 %, 2.47 %, 1.57 %, 0.88 % and 1.83 % respectively. Amusingly, compounds 16a, 16c, 16d and 16 g inhibited VEGFR-2 with IC50 of 25 nM, 52 nM, 324 nM and 110 nM respectively, compared to sorafenib (IC50 = 85 nM), and had excellent EGFRWT and EGFRT790M kinase inhibitory activities (IC50 = 94 nM, 128 nM, 160 nM, 297 nM), (10 nM, 25 nM, 36 nM and 48 nM) respectively, compared to both erlotinib and osimertinib (IC50 = 114 nM, 56 nM) and (70 nM, 37 nM) respectively and showed (EGFRwt/EGFRT790M S.I.) of (range: 4.44-9.40) compared to erlotinib (2.03) and osmertinib (1.89).


Antineoplastic Agents , Cell Proliferation , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors , Protein Kinase Inhibitors , Pyrazoles , Thiourea , Urea , Vascular Endothelial Growth Factor Receptor-2 , Humans , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Pyrazoles/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemical synthesis , Structure-Activity Relationship , Cell Proliferation/drug effects , Thiourea/pharmacology , Thiourea/chemistry , Thiourea/chemical synthesis , Molecular Structure , Urea/pharmacology , Urea/chemistry , Urea/analogs & derivatives , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2 Inhibitors/chemistry , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cell Line, Tumor , Cyclooxygenase 2/metabolism , Drug Discovery , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis
16.
Clin Transl Sci ; 17(5): e13798, 2024 May.
Article En | MEDLINE | ID: mdl-38700290

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


Anti-Inflammatory Agents, Non-Steroidal , Cross-Over Studies , Drug Interactions , Humans , Male , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Adult , Young Adult , Healthy Volunteers , Area Under Curve , Meloxicam/pharmacokinetics , Meloxicam/administration & dosage , Naproxen/pharmacokinetics , Naproxen/administration & dosage , Celecoxib/pharmacokinetics , Celecoxib/administration & dosage , Middle Aged
18.
BMC Health Serv Res ; 24(1): 640, 2024 May 18.
Article En | MEDLINE | ID: mdl-38760660

BACKGROUND: Despite efforts to enhance the quality of medication prescribing in outpatient settings, potentially inappropriate prescribing remains common, particularly in unscheduled settings where patients can present with infectious and pain-related complaints. Two of the most commonly prescribed medication classes in outpatient settings with frequent rates of potentially inappropriate prescribing include antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). In the setting of persistent inappropriate prescribing, we sought to understand a diverse set of perspectives on the determinants of inappropriate prescribing of antibiotics and NSAIDs in the Veterans Health Administration. METHODS: We conducted a qualitative study guided by the Consolidated Framework for Implementation Research and Theory of Planned Behavior. Semi-structured interviews were conducted with clinicians, stakeholders, and Veterans from March 1, 2021 through December 31, 2021 within the Veteran Affairs Health System in unscheduled outpatient settings at the Tennessee Valley Healthcare System. Stakeholders included clinical operations leadership and methodological experts. Audio-recorded interviews were transcribed and de-identified. Data coding and analysis were conducted by experienced qualitative methodologists adhering to the Consolidated Criteria for Reporting Qualitative Studies guidelines. Analysis was conducted using an iterative inductive/deductive process. RESULTS: We conducted semi-structured interviews with 66 participants: clinicians (N = 25), stakeholders (N = 24), and Veterans (N = 17). We identified six themes contributing to potentially inappropriate prescribing of antibiotics and NSAIDs: 1) Perceived versus actual Veterans expectations about prescribing; 2) the influence of a time-pressured clinical environment on prescribing stewardship; 3) Limited clinician knowledge, awareness, and willingness to use evidence-based care; 4) Prescriber uncertainties about the Veteran condition at the time of the clinical encounter; 5) Limited communication; and 6) Technology barriers of the electronic health record and patient portal. CONCLUSIONS: The diverse perspectives on prescribing underscore the need for interventions that recognize the detrimental impact of high workload on prescribing stewardship and the need to design interventions with the end-user in mind. This study revealed actionable themes that could be addressed to improve guideline concordant prescribing to enhance the quality of prescribing and to reduce patient harm.


Anti-Bacterial Agents , Anti-Inflammatory Agents, Non-Steroidal , Inappropriate Prescribing , Practice Patterns, Physicians' , Qualitative Research , United States Department of Veterans Affairs , Humans , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , United States , Anti-Bacterial Agents/therapeutic use , Inappropriate Prescribing/statistics & numerical data , Inappropriate Prescribing/prevention & control , Practice Patterns, Physicians'/statistics & numerical data , Male , Female , Interviews as Topic , Middle Aged , Outpatients , Tennessee
19.
BMC Musculoskelet Disord ; 25(1): 344, 2024 May 01.
Article En | MEDLINE | ID: mdl-38693474

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


Anti-Inflammatory Agents, Non-Steroidal , Low Back Pain , Practice Guidelines as Topic , Low Back Pain/therapy , Low Back Pain/diagnosis , Humans , Practice Guidelines as Topic/standards , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Exercise Therapy/standards , Manipulation, Spinal/standards , Manipulation, Spinal/methods , Chronic Pain/therapy , Chronic Pain/diagnosis , Pain Management/standards , Pain Management/methods
20.
Molecules ; 29(10)2024 May 08.
Article En | MEDLINE | ID: mdl-38792071

Every year, new compounds contained in consumer products, such as detergents, paints, products for personal hygiene, and drugs for human and veterinary use, are identified in wastewater and are added to the list of molecules that need monitoring. These compounds are indicated with the term emerging contaminants (or Contaminants of Emerging Concern, CECs) since they are potentially dangerous for the environment and human health. To date, among the most widely used methodologies for the removal of CECs from the aquatic environment, adsorption processes play a role of primary importance, as they have proven to be characterized by high removal efficiency, low operating and management costs, and an absence of undesirable by-products. In this paper, the adsorption of ibuprofen (IBU), a nonsteroidal anti-inflammatory drug widely used for treating inflammation or pain, was performed for the first time using two different types of geopolymer-based materials, i.e., a metakaolin-based (GMK) and an organic-inorganic hybrid (GMK-S) geopolymer. The proposed adsorbing matrices are characterized by a low environmental footprint and have been easily obtained as powders or as highly porous filters by direct foaming operated directly into the adsorption column. Preliminary results demonstrated that these materials can be effectively used for the removal of ibuprofen from contaminated water (showing a concentration decrease of IBU up to about 29% in batch, while an IBU removal percentage of about 90% has been reached in continuous), thus suggesting their potential practical application.


Ibuprofen , Water Pollutants, Chemical , Water Purification , Ibuprofen/chemistry , Ibuprofen/isolation & purification , Water Pollutants, Chemical/isolation & purification , Water Pollutants, Chemical/chemistry , Adsorption , Water Purification/methods , Polymers/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Wastewater/chemistry , Kaolin/chemistry
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