Common Non-steroidal Anti-inflammatory Drugs Research Articles

Aspirin may be more suitable for patients with major depression: Evidence from two-sample Mendelian randomization analysis.

Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint. We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on p-value, OR (Odds Ratio), and 95% confidence interval (95% CI). From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609-3.327; p = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780-3.653; p = 0.002), respectively. No significant causal relationship was found between aspirin and MD (p > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030-1.054, p = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007-1.023, p = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009-1.030, p = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings. This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen.

Effectiveness of Pulse Intravenous Infusion of Methylprednisolone on Pain in Patients with Lumbar Disc Herniation: A Randomized Controlled Trial

Background: Lumbar disc herniation (LDH) can cause pain in the lower back and leg, as well as numbness or weakness in the affected area. Various steroids, including methylprednisolone, are currently used for treatment. Objectives: This study aimed to compare the effectiveness of pulse intravenous infusion of 500 mg methylprednisolone with common non-steroidal anti-inflammatory drugs (NSAIDs) in relieving pain and improving the clinical condition of patients with lumbar disc herniation. Methods: This clinical trial, registered under code IRCT20211116053077N1, included an experimental group (37 patients) and a control group (35 patients). Pain assessments were conducted before treatment, and at one, two, and three weeks, as well as one and six months after treatment. The control group received common painkillers (diclofenac sodium tablets 100 mg), while the experimental group received a single dose of 500 mg methylprednisolone sodium succinate (intravenous injection in 500 cc normal saline). Pain scores were analyzed using SPSS 16 and statistical tests such as ANOVA, independent t-tests, and repeated measures ANOVA. Results: Prior to intervention, the mean (SD) pain score was 8.7 (3.57) in the experimental group and 8.17 (0.66) in the control group (P > 0.76). Six months after methylprednisolone injection, the mean (SD) pain score in the experimental group was 1.56 (0.83), compared to 6.48 (0.91) in the control group (P = 0.000). Analysis of variance indicated that methylprednisolone significantly reduced pain in patients with LDH (P = 0.000, F = 660.668). Conclusions: Given the effectiveness of intravenous pulse infusion of 500 mg methylprednisolone compared to common NSAIDs in relieving pain and improving clinical outcomes for patients with lumbar disc herniation, the use of this drug is recommended for pain reduction in these patients.

Environmental risk of diclofenac in European groundwaters and implications for environmental quality standards

Groundwater harbours unique species adapted to perpetual darkness. Groundwater fauna plays a crucial role in global ecosystem services, but contamination poses a threat to this keystone ecosystem. Diclofenac is a common non-steroidal anti-inflammatory drug of particular concern, due to its presence in both surface and groundwater. We assess the environmental risk of diclofenac in European groundwaters using different scenarios, analyzing Measured Environmental Concentrations (MECs) of diclofenac and estimating the Predicted No Effect Concentration (PNECs) through two approaches: considering the sensitivity of the groundwater crustacean Proasellus lusitanicus (Isopoda: Asellidae), and using surface water species as proxies. Our results show that scenarios based on surrogate species predict that groundwater ecosystems are at risk due to diclofenac contamination. On the other hand, the MECs of diclofenac were consistently lower than the PNEC of P. lusitanicus, suggesting that the current MECs do not pose a significant threat to this groundwater-adapted species. However, risk scenarios differ considering the sensitivity of other groundwater species, emphasizing the importance of considering multiple species’ sensitivities in risk assessment. Therefore, we recommend establishing an environmental quality standard for diclofenac in groundwater at 5 ng/L, a value that accounts the need for precautionary measures to safeguard groundwater ecosystems, essential for preserving their unique biota and services.

The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: A promising therapeutic compound against the cytokine storm.

The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 μM, 95% CI = 7.4 to 10.4 μM) was comparable to that of paracetamol (IC50 = 7.73 μM, 95% CI = 6.14 to 9.73 μM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.

Diverse roles of SARS-CoV-2 Spike and Nucleocapsid proteins in EndMT stimulation through the TGF-β-MRTF axis inhibited by aspirin

BackgroundThe SARS-CoV-2 virus causes severe COVID-19 in one-fifth of patients. In addition to high mortality, infection may induce respiratory failure and cardiovascular complications associated with inflammation. Acute or prolonged inflammation results in organ fibrosis, the cause of which might be endothelial disorders arising during the endothelial-mesenchymal transition (EndMT).MethodsHUVECs and HMEC-1 cells were stimulated with SARS-CoV-2 S (Spike) and N (Nucleocapsid) proteins, and EndMT induction was evaluated by studying specific protein markers via Western blotting. Wound healing and tube formation assays were employed to assess the potential of SARS-CoV-2 to stimulate changes in cell behaviour. MRTF nuclear translocation, ROS generation, TLR4 inhibitors, TGF-β-neutralizing antibodies, and inhibitors of the TGF-β-dependent pathway were used to investigate the role of the TGF-β-MRTF signalling axis in SARS-CoV-2-dependent EndMT stimulation.ResultsBoth viral proteins stimulate myofibroblast trans-differentiation. However, the N protein is more effective at EndMT induction. The TGF-β-MRTF pathway plays a critical role in this process. The N protein preferentially favours action through TGF-β2, whose secretion is induced through TLR4-ROS action. TGF-β2 stimulates MRTF-A and MRTF-B nuclear translocation and strongly regulates EndMT. In contrast, the Spike protein stimulates TGF-β1 secretion as a result of ACE2 downregulation. TGF-β1 induces only MRTF-B, which, in turn, weakly regulates EndMT. Furthermore, aspirin, a common nonsteroidal anti-inflammatory drug, might prevent and reverse SARS-CoV-2-dependent EndMT induction through TGF-β-MRTF pathway deregulation.ConclusionThe reported study revealed that SARS-CoV-2 infection induces EndMT. Moreover, it was demonstrated for the first time at the molecular level that the intensity of the EndMT triggered by SARS-CoV-2 infection may vary and depend on the viral protein involved. The N protein acts through TLR4-ROS-TGF-β2-MRTF-A/B, whereas the S protein acts through ACE2-TGF-β1-MRTF-B. Furthermore, we identified aspirin as a potential anti-fibrotic drug for treating patients with SARS-CoV-2 infection.

Utilization of diamondback puffer (Lagocephalus guentheri) biomass for the production of bioactive oligopeptides and their inflammation suppressing effects invitro

Development of new anti-inflammatory drugs has always been of prime interest due to various side effects exerted by common non-steroidal anti-inflammatory drugs (NSAIDs). Hence, due to the biochemical diversity and efficient anti-inflammatory activities of bioactive peptides from oceanic sources, their demand is increasing. In this study, the common diamondback puffer fish (Lagocephalus guentheri) muscle (PM) and visceral (PV) mass waste was used to produce enzymatic hydrolysates using trypsin, alcalase and papain digestion which were further used to obtain inflammation suppressing peptides. High pressure liquid chromatography (HPLC) analysis showed abundant essential amino acids like arginine, alanine, tyrosine, and glutamic acid in muscle as well as visceral part. The data obtained by the anti-inflammatory assays such as albumin denaturation inhibition and membrane stabilization assay of hydrolysates showed that alcalase 12th hr and 6th hr showed highest activity for PM and PV respectively. Further, out of the fractions obtained through ultrafiltration, 10-3 kDa showed higher anti-inflammatory activity which was subsequently purified with gel filtration chromatography. Moreover, the purified active peaks were analysed using LC-MS/MS to acquire a peptide sequence of MEPLGQG (731 Da) and LLHA (453 Da) for PMpep and PVpep respectively. In vitro studies revealed non-cytotoxic effects of peptide and pro-inflammatory cytokine suppression post LPS-stimulation in RAW264.7 cells. Thus, the puffer fish and other marine waste can be exploited for the isolation of potential nutraceutical and therapeutic compounds.

Oral Ketorolac for Renal Colic in Outpatient Settings

What Is the Issue?
 
 Renal colic is a common problem that is primarily caused by kidney stones. Renal colic, specifically kidney stones, can be a recurrent condition that can negatively impact a person’s quality of life and health system utilization.
 Ketorolac through IV or intramuscular routes is a common nonsteroidal anti-inflammatory drug (NSAID) used in hospital to treat renal colic. Oral ketorolac for the management of renal colic may reduce patients’ need for opioids after discharge but it is unclear if it is clinically effective when compared to alternative analgesics or whether it is recommended for use in the management of people with renal colic.
 
 What Did We Do?
 
 To inform decisions about oral ketorolac for the management of outpatients with renal colic, we sought to identify and summarize literature comparing the clinical effectiveness of oral ketorolac and alternative analgesics. We also searched for evidence-based guidelines that provide recommendations about the use of oral ketorolac for the management of people with renal colic.
 A research information specialist conducted literature searches of peer-reviewed and grey literature sources published between January 1, 2013, and December 4, 2023. The search was limited to English-language documents. One reviewer screened articles for inclusion based on predefined criteria.
 
 What Did We Find?
 
 The tailored search for this rapid review did not find any studies evaluating the clinical effectiveness of oral ketorolac versus alternative analgesics for the management of people with renal colic in outpatient settings that met our criteria for this review. There is therefore no specific evidence available on the efficacy oral ketorolac in the management of renal colic in the community setting in this review.
 We did not find any eligible evidence-based guidelines concerning the use of oral ketorolac for the management of people with renal colic in outpatient settings. NSAIDs have been generally mentioned as an option for renal colic in the available guidance.
 Research regarding ketorolac for renal colic published since 2013 has focused on IV or intramuscular administration. Research regarding oral ketorolac focused on indications other than renal colic (e.g., postoperative pain) may be of interest; these are listed in the appendix. These studies suggest the effectiveness of ketorolac for pain management for other indications, such as pain management following endoscopy.
 
 What Does It Mean?
 
 Without comparative evidence, decision-makers may want to consider how oral ketorolac is used for related indications (e.g., procedures for removing kidney stones, ureteroscopies) to examine how it performed compared with alternative analgesics.
 Research focused on the management of renal colic is needed to evaluate the clinical effectiveness of oral ketorolac and inform guidance concerning oral ketorolac in outpatient settings.

Inhibition of Streptococcus mutans growth and biofilm formation through protein acetylation.

Numerous cellular processes are regulated in response to the metabolic state of the cell, and one such regulatory mechanism involves lysine acetylation. Lysine acetylation has been proven to play an important role in the virulence of Streptococcus mutans, a major cariogenic bacterial species. S. mutans' glucosyltransferases (Gtfs) are responsible for synthesizing extracellular polysaccharides (EPS) and contributing to biofilm formation. One of the most common nonsteroidal anti-inflammatory drugs is acetylsalicylic acid (ASA), which can acetylate proteins through a nonenzymatic transacetylation reaction. Herein, we investigated the inhibitory effects of ASA on S. mutans. ASA treatment was observed to impede the growth of S. mutans, leading to a reduction in the production of water-insoluble EPS and the formation of biofilm. Moreover, ASA decreased the enzyme activity of Gtfs while increasing the protein acetylation level. The in vivo anticaries efficacy of ASA has further been proved using the rat caries model. In conclusion, ASA as an acetylation agent attenuated the cariogenic virulence of S. mutans, suggesting the potential value of protein acetylation on antimicrobial and anti-biofilm applications to S. mutans.

Bentonite Modified with Surfactants—Efficient Adsorbents for the Removal of Non-Steroidal Anti-Inflammatory Drugs

Organobentonites have been applied for the removal of two common non-steroidal anti-inflammatory drugs, ibuprofen (IBU) and diclofenac sodium (DS), from aqueous solutions. Two surfactants, one with and the other without benzyl group (octadecyldimethylbenzylammonium chloride, ODMBA, and hexadecyltrimethylammonium bromide, HDTMA), in amounts equivalent to 50, 75, and 100% of the cation exchange capacity of bentonite were used for the preparation of organobentonites. Successful modification of bentonite was confirmed by several methods: X-ray powder diffraction (XRPD), point of the zero charge (pHPZC), determination of exchanged inorganic cations in bentonite, determination of textural properties, and scanning electron microscopy (SEM). Kinetic and thermodynamic data on the adsorption of IBU and DS showed that drug adsorption was controlled by the type and the amount of surfactant incorporated into the bentonite and by their arrangement in the interlayer space and at the surface of organobentonites. The adsorption of both drugs increased with an increase in the amount of both surfactants in organobentonites. The presence of the benzyl group in organobentonites enhanced the adsorption of IBU and DS and was more pronounced for IBU. Drug adsorption fits the pseudo-second-order kinetic model the best. The thermodynamic data revealed that the adsorption process was endothermic in nature and with increase of the amount of both surfactants drug adsorption processes were more spontaneous. The results obtained from this study revealed that adsorbents based on surfactants modified bentonite are promising candidates for IBU and DS removal from contaminated water.

Associations between the use of common nonsteroidal anti-inflammatory drugs, genetic susceptibility and dementia in participants with chronic pain: A prospective study based on 194,758 participants from the UK Biobank

ObjectiveTo investigate the potential relationship between common nonsteroidal anti-inflammatory drugs (NSAIDs), genetic susceptibility and all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD) among individuals experiencing chronic pain. MethodsThis study was based on 194,758 chronic pain participants form UK biobank with a median follow-up of 13.7 years. Participants were categorized into different NSAIDs painkiller regimen groups: No NSAIDs group, Aspirin group, Ibuprofen group, Paracetamol group, and 2–3 NSAIDs group. Cox proportional risk models were used to examine the correlation between regular NSAIDs usage and the risk of ACD, AD, and VD. In addition, we further performed subgroup analyses and sensitivity analyses. Results1) Compared to the No NSAIDs group, the aspirin group (HR = 1.12, 95% CI:1.01–1.24, P < 0.05), the paracetamol group (HR = 1.15, 95% CI:1.05–1.27, P < 0.01), and the 2–3 NSAIDs group (HR = 1.2, 95% CI:1.08–1.33, P < 0.05) showed a higher risk of ACD. Furthermore, the 2–3 NSAIDs group was also associated with a higher risk of VD (HR = 1.39, 95% CI: 1.08–1.33, P < 0.05). 2) At high dementia GRS participants with chronic pain, the paracetamol group (HR = 1.2, 95% CI: 1.03–1.43, P < 0.05) and the NSAIDs group (HR = 1.3, 95% CI: 1.07–1.59, P < 0.05) were associated with a higher risk of ACD compared to the no painkiller group. 3) There was no significant association between ibuprofen use and higher risk of dementia. ConclusionIn individuals with chronic pain, the use of aspirin and paracetamol was associated with a higher risk of ACD, whereas the use of ibuprofen was not significantly associated with a higher risk of ACD.

Synergistic Antimicrobial Effects of Ibuprofen Combined with Standard-of-Care Antibiotics against Cystic Fibrosis Pathogens.

Cystic fibrosis (CF) is a common life-shortening genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Lungs of CF patients are often colonized or infected with microorganisms requiring frequent courses of antibiotics. Antibiotic-resistant bacterial infections have been a growing concern in CF patients. Chronic bacterial infections and concomitant airway inflammation damage the lungs, ultimately leading to respiratory failure. Several clinical trials have demonstrated that high-dose ibuprofen reduces the rate of pulmonary function decline in CF patients. This beneficial effect has been attributed to the anti-inflammatory properties of ibuprofen. Previously, we have confirmed that high-dose ibuprofen demonstrates antimicrobial activity against P. aeruginosa both in vitro and in vivo. However, no study has examined the antimicrobial effect of combining ibuprofen with standard-of-care antimicrobials. Here, we evaluated the possible synergistic activity of combinations of common nonsteroidal anti-inflammatory drugs (NSAIDs), namely, ibuprofen, naproxen, and aspirin, with commonly used antibiotics for CF patients. The drug combinations were screened against different CF clinical isolates. Antibiotics that demonstrated increased efficacy in the presence of ibuprofen were further tested for potential synergistic effects between these NSAIDS and antimicrobials. Finally, a survival analysis of a P. aeruginosa murine infection model was used to demonstrate the efficacy of the most potent combination identified in in vitro screening. Our results suggest that combinations of ibuprofen with commonly used antibiotics demonstrate synergistic antimicrobial activity against drug-resistant, clinical bacterial strains in vitro. The efficacy of the combination of ceftazidime and ibuprofen against resistant P. aeruginosa was demonstrated in an in vivo pneumonia model.

Mechanistic understanding of the enhanced adsorption of diclofenac on a heat-treated and acid-leached halloysite

ABSTRACT Diclofenac (DCF), a common nonsteroidal anti-inflammatory drug, is frequently detected in aquatic environments, causing serious threat to aquatic organisms and humans through bioaccumulation, persistence, and toxicity. Using eco-friendly clay-based adsorbents, samples of halloysite (H) processed at 600°C (H600-0N) and then HCl-leached with 3 N concentration (H600-3N) were prepared, characterised by Inductively Coupled Plasma (ICP), N2 adsorption – desorption, and infrared spectroscopy with Fourier transform (FTIR), and used in DCF adsorption. H600-3N exhibited a substantial surface area increase from 63 m2 g−1 for H to 434 m2 g−1 due to an elevated SiO₂/Al₂O₃ ratio of 23.83 against 1.72 for H. In this context, H600-3N and H adsorbed 165 mg g−1 and 37.9 mg g−1 of DCF, respectively. The isotherms of H600-xN(x = 0 or 3) were adequately adjusted to the Langmuir-Freundlich model, while the kinetic data were suitably described by the pseudo-second order equation. Through cross-checking the results of characterisation, DCF adsorption and the FTIR investigation between DCF and H600-3N, a mechanism has been suggested that includes two main components: hydrogen bonding between the silanol’s hydrogen atom and the negatively charged carboxylate anion and hydrophobic interactions between the – Si – O – Si – entities and the DCF aromatic rings. The elucidation of intermolecular interactions between organic contaminants and 1:1 clay minerals is essential to develop the application of these abundant and low-cost materials in wastewater treatment.

Quantum Sensing for Real-Time Monitoring of Drug Efficacy in Synovial Fluid from Arthritis Patients.

Diamond-based T1 relaxometry is a new technique that allows nanoscale magnetic resonance measurements. Here we present its first application in patient samples. More specifically, we demonstrate that relaxometry can determine the free radical load in samples from arthritis patients. We found that we can clearly differentiate between osteoarthritis and rheumatoid arthritis patients in both the synovial fluid itself and cells derived from it. Furthermore, we tested how synovial fluid and its cells respond to piroxicam, a common nonsteroidal anti-inflammatory drug (NSAID). It is known that this drug leads to a reduction in reactive oxygen species production in fibroblast-like synoviocytes (FLS). Here, we investigated the formation of free radicals specifically. While FLS from osteoarthritis patients showed a drastic decrease in the free radical load, cells from rheumatoid arthritis retained a similar radical load after treatment. This offers a possible explanation for why piroxicam is more beneficial for patients with osteoarthritis than those with rheumatoid arthritis.

Medicinal and toxicological investigation of some common NSAIDs; A computer-aided drug design approach

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment of pain, fever, and inflammation. Their consumption rises some crucial side effects like gastrointestinal, cardiovascular, and renal injury because of the non-selective reduction of prostaglandin synthesis, with differences in the extent of inhibition of the cyclooxygenase. Attempts have been taken for a comparative biochemical, medicinal, and toxicological investigation to raise awareness of the consumption of NSAIDs. In-silico methods were incorporated to investigate their physicochemical, spectral, medicinal, pharmacological, and toxicological properties. Molecular docking and non-bonding calculations were performed against the human prostaglandin synthase protein to reveal their binding affinity and interactions with the amino acid residues of the receptor protein. Further, molecular dynamics simulation was conducted to validate the binding mode and drug-protein stability at the inhibiting binding pocket. The physical and chemical analysis supports their geometries and spectral results confirming the presence of essential functional groups at the core structure. From ADMET and PASS prediction, all the drugs are non-carcinogenic (except IBP), and nonselective NSAIDs showed relatively higher adverse effects compared to selective agents. Based on the above studies, this report can be helpful to understand more deeply the medicinal, and toxicological effects of the reported NSAIDs.

SMA-TB: study protocol for the phase 2b randomized double-blind, placebo-controlled trial to estimate the potential efficacy and safety of two repurposed drugs, acetylsalicylic acid and ibuprofen, for use as adjunct therapy added to, and compared with, the standard WHO recommended TB regimen

BackgroundThe duration and regimen of tuberculosis (TB) treatment is currently based predominantly on whether the M. tuberculosis (Mtb) strain is drug-sensitive (DS) or multidrug-resistant (MDR) with doses adjusted by patients’ weight only. The systematic stratification of patients for personalized treatment does not exist for TB. As each TB case is different, individualized treatment regimens should be applied to obtain better outcomes. In this scenario, novel therapeutic approaches are urgently needed to (1) improve outcomes and (2) shorten treatment duration, and host-directed therapies (HDT) might be the best solution. Within HDT, repurposed drugs represent a shortcut in drug development and can be implemented at the short term. As hyperinflammation is associated with worse outcomes, HDT with an anti-inflammatory effect might improve outcomes by reducing tissue damage and thus the risk of permanent sequelae.MethodsSMA-TB is a multicentre randomized, phase IIB, placebo-controlled, three-arm, double-blinded clinical trial (CT) that has been designed in the context of the EC-funded SMA-TB Project (www.smatb.eu) in which we propose to use 2 common non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA) and ibuprofen (Ibu), as an HDT for use as adjunct therapy added to, and compared with, the standard of care (SoC) World Health Organization (WHO)-recommended TB regimen in TB patients. A total of 354 South African and Georgian adults diagnosed with confirmed pulmonary TB will be randomized into SoC TB treatment + placebo, SoC + acetylsalicylic acid or SoC + ibuprofen.DiscussionSMA-TB will provide proof of concept of the HDT as a co-adjuvant treatment and identify the suitability of the intervention for different population groups (different epidemiological settings and drug susceptibility) in the reduction of tissue damage and risk of bad outcomes for TB patients. This regimen potentially will be more effective and targeted: organ saving, reducing tissue damage and thereby decreasing the length of treatment and sequelae, increasing cure rates and pathogen clearance and decreasing transmission rates. It will result in better clinical practice, care management and increased well-being of TB patients.Trial registrationClinicaltrials.gov NCT04575519. Registered on October 5, 2020.

An Abbreviated History of Aldosterone Metabolism, Current and Future Challenges.

The initial isolation of adrenal steroids from large quantities of animal adrenals resulted in an amorphous fraction resistant to crystallization and identification and had potent effects on electrolyte transport. Aldosterone was eventually isolated and identified in the fraction and was soon shown to cause hypertension when in excess. The autonomous and excessive production of aldosterone, primary aldosteronism, is the most common cause of secondary hypertension. Aldosterone is metabolized in the liver and kidney, and its metabolites are conjugated with glucuronic acid for excretion. The most common liver metabolite is 3α,5β-tetrahydroaldosterone-3-glucuronide, while that of the kidney is aldosterone-18-oxo-glucuronide. In terms of their value, especially the aldosterone-18-oxo-glucuronide, is commonly used for the diagnosis of primary aldosteronism because they provide an integrated value of the total daily production of aldosterone. Conversion of aldosterone to 18-oxo-glucuronide is impeded by drugs, like some common non-steroidal anti-inflammatory drugs that compete for UDP-glucuronosyltransferase-2B7, the most important glucuronosyltransferase for aldosterone metabolism. Tetrahydroaldosterone is the most abundant metabolite and the most reliable for the diagnosis of primary aldosteronism, but it is not commonly measured.

Hypersensitivity to Non-Steroidal Anti-Inflammatory Drugs on a pediatric Portuguese cohort.

Background. Non-steroidal anti-inflammatory drugs (NSAID)/analgesics (paracetamol) are among the most common causes of drug hypersensitivity reactions in children, with a reported prevalence of around 0.3% in the pediatric population. Paracetamol and ibuprofen are the most commonly reported culprits in the pediatric population. Our objective was to describe the allergy workup to NSAID/paracetamol of a pediatric population monitored in an allergy outpatient clinic. Methods. Retrospective observational study by consulting the medical records of patients evaluated in a pediatric outpatient clinic with history of NSAID/paracetamol, between January 2016 to August 2022. Results. A total of 43 patients have been evaluated for NSAID/paracetamol suspected allergy: 53.5% females, mean age of 9.8 ± 5.1 years, 47.7% atopic. The drugs reported as culprits were: ibuprofen (75.6%), paracetamol (17.8%), metamizole (4.4%) and naproxen (2.2%) and clinical manifestations were mainly urticaria/angioedema and maculopapular exanthema. Skin tests were performed in 7 patients: paracetamol (n = 5) and metamizole (n = 2), which were all negative. Fourty-six drug provocation tests were performed: 28 with the culprit drug and 18 with an alternative one; only 2 were positive (ibuprofen - culprit NSAID group): one immediate periorbital angioedema and one delayed lip edema with oropharyngeal tightness. Conclusions. The investigation of allergy to NSAID/paracetamol in children remains a challenge. In our population, ibuprofen was the most common NSAID reported. There were only 2 (4.3%) mild reactions on DPT. We could allow the use of the culprit NSAID/analgesic in 11 patients and an alternative one in 9 patients. This study highlights the importance of DPT in children for a correct diagnosis of NSAID hypersensitivity and selection of an alternative drug.

Adverse drug reactions of oral non-steroidal anti-inflammatory drugs and its fixed drug combinations: A 5-year retrospective observational study

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are very commonly prescribed worldwide. Due to this, the incidence of adverse drug reactions (ADRs) to NSAIDs is increased. Aims and Objectives: This study aims to analyze the ADRs reported to NSAIDs. Patient demographics, organ system affected severity of ADRs, and their causal association with the drug will be studied. Materials and Methods: It was a retrospective analysis of ADRs reported to oral NSAIDs and its combinations over a period of 5 years from January 2015 to December 2020. Prior ethics committee approval was obtained. These ADRs were collected as part of pharmacovigilance activities. Results: A total of 100 ADRs were reported due to NSAIDs. Most ADRs due to NSAIDs were reported in 30–39 years age group. Female gender was most affected by ADRs. Diclofenac was the most common NSAID causing ADRs. Skin and subcutaneous organ system was most affected. Six ADRs were reported as serious. Sixty-seven ADRs were categorized as probable using the World Health Organization causality assessment scale. Conclusion: NSAIDs are commonly prescribed drugs. Analyzing the ADRs reported to NSAIDs will help in finding the risk factors. Based on this knowledge, rational prescription of NSAIDs can be done which will improve the patient safety.

Prescribing pattern of NSAIDs in migraine patients of Neurology OPD at a tertiary care hospital in Bhubaneswar

NSAIDs (nonsteroidal anti-inflammatory drugs) are the most commonly used drugs in treatment of migraine. The present study is conducted to evaluate prescription patterns of NSAIDs in migraine patients in neurology OPD of a tertiary care hospital in Bhubaneswar. NSAIDs were prescribed to 30% of patients with complaint of headache and migration visiting Neurology OPD. 47.61% of migraine patients have received NSAID. 80.7% patients receiving NSAIDs were female. The median age of patients was 34 years. The average number of NSAIDs per prescription was 1.01. The present study showed the use of NSAIDs like Naproxen, Aspirin, Ibuprofen, Paracetamol, Diclofenac and Etoricoxib. Naproxen was the most common NSAIDs prescribed. About 7% of patients were prescribed with NSAIDs from the National List of Essential medicines, 2015. All NSAIDs were administered by oral route. The average cost of NSAIDs per patient was 128.53 INR. Only 10.3% of NSAIDs were co-prescribed with proton pump inhibitors.

Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment.

IntroductionIbuprofen is one of the most common non-steroidal anti-inflammatory drugs used to close patent ductus arteriosus (PDA) in preterm infants. PDA is associated with bronchopulmonary dysplasia (BPD), while PDA closure by ibuprofen did not reduce the incidence of BPD or death. Previous studies have indicated an anti-angiogenesis effect of ibuprofen. This study investigated the change of angiogenic factors after ibuprofen treatment in preterm infants.MethodsPreterm infants with hemodynamically significant PDA (hsPDA) were included. After confirmed hsPDA by color doppler ultrasonography within 1 week after birth, infants received oral ibuprofen for three continuous days. Paired plasma before and after the ibuprofen treatment was collected and measured by ELISA to determine the concentrations of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A), and hypoxia-inducible factor-2α (HIF-2α).Results17 paired plasma from infants with hsPDA were collected. The concentration of PDGF-BB and VEGF-A significantly decreased after ibuprofen treatment (1,908 vs. 442 pg/mL for PDGF-BB, 379 vs. 174 pg/mL for VEGF-A). HIF-2α level showed a tendency to decrease after ibuprofen treatment, although the reduction was not statistically significant (p = 0.077).ConclusionThis study demonstrated decreased vascular growth factors after ibuprofen exposure in hsPDA infants.