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Introduction: Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective in managing musculoskeletal pain, but often are associated with side effects. Therefore, topical anti-inflammatory drugs are considered a suitable alternative for certain patients. Objective: To determine the skin penetration capacity and anti-inflammatory efficacy of a methyl salicylate gel (MS) with turpentine essence, camphor and menthol (GelSMETAM). Methods: Human skin explants were used (three biological replicates with 3 technical replicates each were performed). To assess penetration capacity, methyl salicylate (MS) levels were quantified at different intervals using liquid chromatography with tandem mass spectrometry (LC-MS/MS). For the anti-inflammatory effect, the gene expression of major pro-inflammatory factors was quantified 30 minutes, 8 hours, and 12 hours after an impact; comparing GelSMETAM application with untreated controls. Results: The results showed that approximately 0.8% of the total applied methyl salicylate penetrated the skin with a time-dependent concentration increase. The anti-inflammatory effect demonstrated a significant reduction in the gene expression of TNFα, IL1α, IL6, IL8, and NFKβ at 30 minutes (between -39% and -53.6% compared to control), which was maintained at 8 hours except for TNFα (between -59% and -92.6%) and persisted even at 12 hours (-69.4%) for IL1α. Conclusion: The results support the hypothesis that GelSMETAM provides an effective and prolonged anti-inflammatory response, positioning it as a suitable option for the management of musculoskeletal pain. [ABSTRACT FROM AUTHOR]

ObjectivesTo investigate if hepatitis A virus cell receptor 1/kidney injury molecule 1 (HAVCR1/KIM1) in urine is detectable concurrently with increases in serum creatinine concentrations in horses receiving a recommended dose of phenylbutazone (PBZ) for 7 days.DesignPreliminary study.MethodsTen clinically healthy horses with normal physical examination and laboratory work were randomly assigned to PBZ or placebo groups (5 each). The PBZ group received PBZ at 4.4 mg/kg mixed with corn syrup orally every 12 hours. The placebo group received corn syrup orally every 12 hours. Both groups were treated for 7 days. Kidney ultrasonography was performed, and venous blood and urine samples were collected prior to commencement and at the end of treatment. Samples from 1 additional healthy horse, 3 horses with acute kidney failure, and 1 horse with chronic kidney failure were also evaluated.ResultsNone of the 10 horses had detectable HAVCR1/KIM1 in urine at baseline. Serum creatinine concentrations in placebo group did not increase, and HAVCR1/KIM1 was undetectable in urine. At the end of treatment, 3 of 5 horses receiving PBZ developed increases in serum creatinine of >26.5 μmol/L (>0.3 mg/dL), and HAVCR1/KIM1 was detectable in urine, despite normal findings on kidney ultrasonography in all horses.ConclusionsHAVCR1/KIM1 is detectable in urine and is associated with increases in serum creatinine concentrations of >26.5 μmol/L in horses following treatment with PBZ for 7 consecutive days. Thus, HAVCR1/KIM1 might aid in the early detection of acute kidney injury in horses.

Why you should read this article: • To enhance your knowledge of blunt mechanism chest wall injury • To understand the acute care priorities for patients with blunt mechanism chest wall injury following initial assessment • To contribute towards revalidation as part of your 35 hours of CPD (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers). Blunt mechanism chest wall injury (CWI) is commonly seen in the emergency department (ED), since it is present in around 15% of trauma patients. The thoracic cage protects the heart, lungs and trachea, thereby supporting respiration and circulation, so injury to the thorax can induce potentially life-threatening complications. Systematic care pathways have been shown to improve outcomes for patients presenting with blunt mechanism CWI, but care is not consistent across the UK. Emergency nurses have a crucial role in assessing and treating patients who present to the ED with blunt mechanism CWI. This article discusses the initial assessment and acute care priorities for this patient group. It also presents a prognostic model for predicting the probability of in-hospital complications following blunt mechanism CWI. [ABSTRACT FROM AUTHOR]

Corinne van den Berg, Maaike Dirckx, Frank JPM Huygen, Jitske Tiemensma Department of Anesthesiology, Center for Pain Medicine, Erasmus University Medical Center, Rotterdam, the NetherlandsCorrespondence: Corinne van den Berg, Department of Anesthesiology, Center for Pain Medicine, Erasmus University Medical Center, Postbus 2040, Rotterdam, 3000CA, the Netherlands, Tel +31 107040140, Fax +31 107035184, Email c.vandenberg.6@erasmusmc.nlPurpose: Complex regional pain syndrome (CRPS) is a multi-mechanism disease, with an exaggerated inflammatory response as an important underlying mechanism. Auto-inflammation can theoretically be combated by anti-inflammatories, such as TNF-α inhibitors. This study’s aim was to assess the effectiveness of intravenous infliximab, a TNF-α inhibitor, in patients with CRPS.Patients and Methods: CRPS patients treated with infliximab between January 2015 and January 2022 were approached to participate in this retrospective study. Medical records were screened for age, gender, medical history, CRPS duration, and CRPS severity score. Additionally, treatment effect, dose and duration, and side effects were extracted from medical records. Patients who still receive infliximab completed a short global perceived effect survey.Results: Eighteen patients received infliximab, and all but two gave consent. Trial treatment with three sessions of 5 mg/kg intravenous infliximab was completed in 15 patients (93.7%). Eleven patients (73.3%) were categorized as responders with a positive treatment effect. Treatment was continued in nine patients, and seven patients are currently treated. Infliximab dose is 5 mg/kg, and frequency is every four to six weeks. Seven patients completed a global perceived effect survey. All patients reported improvement (median 2, IQR 1– 2) and treatment satisfaction (median 1, IQR 1– 2). One patient described side effects such as itching and rash.Conclusion: Infliximab proved effective in 11 out of 15 CRPS patients. Seven patients are still being treated. Further research is needed on the role of infliximab in the treatment of CRPS and possible predictors of response to treatment.Keywords: complex regional pain syndrome, CRPS, TNF-α inhibitors, treatment, inflammation, anti-inflammatories

Atherosclerosis is a lipid-driven immune-inflammatory disease that affects the arteries, leading to multifocal plaque development. The inflammatory process involves the activation of immune cells and various inflammatory pathways. Anti-inflammatory drugs have been shown to be effective in reducing cardiovascular events in individuals with coronary disease. However, their use is still limited due to concerns about long-term follow-up, cost-effectiveness, adverse effects, and the identification of the ideal patient profile to obtain maximum benefits. This review aims to improve the understanding of inflammation in coronary atherosclerosis and explore potential therapeutic interventions, encompassing both traditional and non-traditional anti-inflammatory approaches. By addressing these concepts, we seek to contribute to the advancement of knowledge about this type of treatment for coronary artery disease. [ABSTRACT FROM AUTHOR]

Anthocyanins (ACNs) are phytochemicals with numerous bioactivities, e.g., antioxidant and anti-inflammatory. Health benefits from consuming ACN-rich foods, extracts, and supplements have been studied in clinical trials (CT). However, the individual effect of single ACNs and their correlation with doses and specific bioactivities or molecular targets have not been thoroughly analyzed. This review shows a recompilation of single anthocyanins composition and concentrations used in CT, conducted to investigate the effect of these anti-inflammatory derivatives in obese condition. Single anthocyanin doses with changes in the levels of frequently monitored markers were correlated. In addition, the analysis was complemented with reports of studies made in vitro with single ACNs. Anthocyanins' efficacy in diseases with high baseline obesity-related inflammation markers was evidenced. A poor correlation was found between most single anthocyanin doses and level changes of commonly monitored markers. Correlations between cyanidin, delphinidin, and pelargonidin derivatives and specific molecular targets were proposed. Our analysis showed that knowledge of specific compositions and anthocyanin concentrations determined in future studies would provide more information about mechanisms of action.

Polyphenols are compounds found in various plants and foods, known for their antioxidant and anti-inflammatory properties. Recently, researchers have been exploring the therapeutic potential of marine polyphenols and other minor nutrients that are found in algae, fish and crustaceans. These compounds have unique chemical structures and exhibit diverse biological properties, including anti-inflammatory, antioxidant, antimicrobial and antitumor action. Due to these properties, marine polyphenols are being investigated as possible therapeutic agents for the treatment of a wide variety of conditions, such as cardiovascular disease, diabetes, neurodegenerative diseases and cancer. This review focuses on the therapeutic potential of marine polyphenols and their applications in human health, and also, in marine phenolic classes, the extraction methods, purification techniques and future applications of marine phenolic compounds. [ABSTRACT FROM AUTHOR]

The inflammatory response plays an important role in neuroprotection and regeneration after ischemic insult. The use of non-steroidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects. In this context, the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stroke, but its ability to inhibit both cyclooxygenase isoforms (1 and 2) could be a promising strategy to modulate post-ischemic inflammation. This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats, measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area. We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia. Moreover, meloxicam treatment modulated glial scar reactivity, which matched with an increase in axonal sprouting. However, this treatment decreased the formation of neuronal progenitor cells. This study discusses the dual role of anti-inflammatory treatments after stroke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.

Why you should read this article: • To enhance your understanding of the risks of opioid use for managing non-malignant chronic pain • To read about a US-based pilot project that aimed to support patients to manage their pain and reduce their use of opioids • To appreciate the benefits of multidisciplinary education programmes to support patients to reduce their opioid use when managing non-malignant chronic pain As the US is experiencing an opioid epidemic, patients with non-malignant chronic pain must understand the risks of opioids and identify safe and effective treatment alternatives. Multidisciplinary pain management programmes have been shown to be effective in reducing non-malignant chronic pain. A pilot project was conducted in a primary care clinic in the US with the aim of educating patients on the neurophysiology of pain, biopsychosocial responses to pain, risks and benefits of opioids and non-opioid alternatives, and pain management techniques. The programme was shown to be associated with use of reduced amounts of opioids, reduced catastrophising and reduced pain among the 13 participants. After the programme, participants reported having a better understanding of pain and pain management and being willing to work with primary care clinicians to decrease their use of opioids. Programmes that teach patients how to manage chronic pain and reduce opioid use are crucial to addressing the opioid epidemic in the US. [ABSTRACT FROM AUTHOR]

Background: Primary graft dysfunction (PGD) is a common occurrence following lung transplantation and contributes to short‐ and long‐term morbidity and mortality. Current management strategies are limited, and robust data to support their use is lacking. Preventative strategies attenuating the recipient's inflammatory state suggest statin therapy may decrease the incidence and severity of PGD. This study aims to evaluate the impact of pre‐transplant statin use on the incidence and severity of PGD following lung transplantation. Methods: A retrospective cohort study was performed evaluating all patients undergoing bilateral lung transplantation from September 2012 to December 2019. The primary outcome was the incidence of PGD by grade, defined as the highest grade of PGD experienced in the first 72 h. Secondary outcomes included length of intensive care unit and hospital stays and mortality. Results: Of the 357 patients included in the study, 107 received statin therapy prior to transplant (statin group) and 250 did not (no statin group). PGD occurred in 257 (72%) patients; in the entire cohort, 99 (28%) patients experienced PGD grade 1, 59 (17%) grade 2, and 99 (28%) grade 3. A significantly lower incidence of PGD was observed in the statin group (64.5% vs 75.2%, p = 0.039); however, the association did not remain significant on multinominal analysis for an overall incidence of any PGD (p = 0.275) or incidence of severe PGD (p = 0.240). Statin intensity was not associated with the development of PGD. Conclusions: Pre‐transplant statin therapy did not appear to impact the development of PGD following lung transplantation. Future prospective studies should further evaluate the impact of statin intensity and duration on the incidence and severity of PGD. [ABSTRACT FROM AUTHOR]

Equine herpesvirus type 1 (EHV-1) is a highly transmissible pathogen that leads to a variety of clinical disease outcomes in infected horses. A major sequela that can occur after an EHV-1 infection is a neurological disease termed equine herpesvirus myeloencephalopathy (EHM). Clinical manifestations of EHM include fever, ataxia, incontinence, and partial to full paralysis, which may ultimately lead to the euthanization of the infected horse. To develop an effective treatment strategy for EHM, it is critical that the specific virus–host interactions that lead to EHM be investigated so that safe and effective therapeutic interventions can be developed and delivered. In this study, we examined the ability of four non-steroidal anti-inflammatory drugs (NSAIDs), a steroidal anti-inflammatory drug (dexamethasone), a Rho-kinase (ROCK) inhibitor, and a JAK/STAT inhibitor (AG490) to reduce EHV-1 virus yields and cell-to-cell spread. We show that the NSAID, flunixin meglumine (FM), and the JAK/STAT inhibitor, AG490, significantly reduced virus yields in endothelial and epithelial cell lines, and this inhibition was similar for two neurologic and two non-neurologic EHV-1 strains. In addition to reducing virus yields, AG490 and FM also significantly reduced the ability of EHV-1 to spread laterally from cell to cell.

Atherosclerosis is a lipid-driven immune-inflammatory disease that affects the arteries, leading to multifocal plaque development. The inflammatory process involves the activation of immune cells and various inflammatory pathways. Anti-inflammatory drugs have been shown to be effective in reducing cardiovascular events in individuals with coronary disease. However, their use is still limited due to concerns about long-term follow-up, cost-effectiveness, adverse effects, and the identification of the ideal patient profile to obtain maximum benefits. This review aims to improve the understanding of inflammation in coronary atherosclerosis and explore potential therapeutic interventions, encompassing both traditional and non-traditional anti-inflammatory approaches. By addressing these concepts, we seek to contribute to the advancement of knowledge about this type of treatment for coronary artery disease.

Heterocyclic compounds make a very important branch of organic chemistry, and it has always been an interesting area of study in medical chemistry. They are present in a variety of drugs, vitamins and biologically active compounds. Over two decades, 1,3,4-oxadiazoles have been of interest to chemists owing to their diverse therapeutic potential; the studies focus mainly on the principles of combinatorial chemistry with a broad spectrum of biological activity. In the continuation of the review article, the general literature sources that consider chemical heteryl derivatives of 2,5-disubstituted 1,3,4-oxadiazoles as important synthetic substrates and precursors for biologically oriented synthesis, are systematized. Heterocyclic 1,3,4-oxadiazoles and their derivatives are widely used as antibacterial, fungicidal, anti-inflammatory, antidiabetic, anticancer, antitubercular, antioxidant, antimalarial, analgesic, anticonvulsant, antidepressant and anti-HIV drugs. It is important to note that the combination of 1,3,4-oxadiazole nuclei with different heterocyclic moieties in some cases had synergistic effect. The aim of the work is the search for new activities, systematization and generalization of literature sources on methods of biologically oriented drug synthesis (BIODS) based on heteryl derivatives of 2,5-disubstituted 1,3,4-oxadiazoles. Conclusions. The article analyzes, generalizes and systematizes the data obtained from the literature that describes the results of the study of the biological activity of 1,3,4-oxadiazoles, which allowed to confirm their diverse pharmacological and biological potential. It is established that oxadiazoscafold as the main structural component is found in various biologically active compounds which evidences the relevance of its further studies as a perspective structural matrix for construction of drug-like molecules. The analysis of the presented material demonstrates the significance and prospectivity of biologically oriented drugs of this segment of the chemistry of nitrogen-containing heterocycles.

AUTH Why you should read this article: • To recognise the importance of providing rapid and effective pain relief for patients presenting to emergency departments (EDs) with traumatic injuries • To learn about the potential benefits of using methoxyflurane for patients with traumatic injuries in the ED • To understand how methoxyflurane is administered and the need for emergency nurses and ED clinicians to undergo training in its use Evidence suggests that pain is highly prevalent among patients with traumatic injuries who attend emergency departments (EDs), yet accurate assessment and management of patients with acute pain can be challenging in this setting. Effective and rapid pain management is beneficial for patients and can support timely discharge from the ED, which is particularly important in the context of the coronavirus disease 2019 (COVID-19) pandemic. This article describes a service development project that introduced the use of a patient-administered analgesic, methoxyflurane, for patients with traumatic injuries with moderate to severe pain in one ED. The author outlines the benefits and rationale for using methoxyflurane as a first-line analgesic in this patient group and describes the main elements of training sessions for emergency nurses and other ED clinicians in the administration and supervision of patient-administered methoxyflurane. [ABSTRACT FROM AUTHOR]

Introduction: Myocardial infarction (MI) is associated with a significant post-event inflammatory response which further contributes to post-MI prognosis. Colchicine, an anti-inflammatory agent, exhibits potential benefits in various cardiovascular conditions such as coronary artery disease, pericarditis and atrial fibrillation. This meta-analysis predominantly aimed to provide an up-to-date evaluation of the efficacy and safety of colchicine in reducing adverse cardiovascular events in patients following acute MI., Methods: A Comprehensive search was conducted on PubMed, Cochrane Library, Scopus, Google Scholar and clinicaltrials.gov for randomized controlled trials (RCTs) investigating the effect of colchicine on patients with MI from inception till May 2024. Our primary outcome was a composite of adverse cardiovascular events, while secondary outcomes included all-cause mortality, incidence of stroke, incidence of cardiac arrest, hospitalization urgency, incidence of recurrent MI, adverse gastrointestinal events and levels of high-sensitivity C - reactive protein (Hs-CRP). Risk ratios (RR) and mean differences (MD) were pooled under the random-effects model., Results: Eleven trials with 7161 patients were included in our analysis out of which 3546 (49.51 %) were allocated to colchicine and 3591 (50.14 %) received placebo. Colchicine demonstrated statistically significant reduction in the composite of adverse cardiovascular events (RR = 0.75, 95 % CI: 0.60-0.94, P = 0.01, I 2 = 47 %), and hospitalization urgency (RR = 0.46, 95 % CI: 0.31-0.68, P = 0.0001, I 2 = 0 %) but statistically significant increment in adverse gastrointestinal events (RR = 1.86, 95 % CI: 1.14-3.02, P = 0.01, I 2 = 79 %). However, all-cause mortality (RR = 1.00, 95 % CI: 0.72-1.39, P = 0.98, I 2 = 0 %), incidence of cardiac arrest (RR = 0.81, 95 % CI: 0.33-1.95, P = 0.63, I 2 = 0), incidence of stroke (RR = 0.45, 95 % CI: 0.17-1.19, P = 0.11, I 2 = 36 %), incidence of recurrent MI (RR = 0.78, 95 % CI: 0.57-1.06, P = 0.11, I 2 = 11 %) and the levels of hs-CRP (MD= -0.87, 95 %CI: -1.80-0.06, P=0.07, I 2 =67 % remained comparable across the two groups., Conclusion: The use of colchicine post-MI reduces the composite of adverse cardiovascular events, and hospitalization urgency but increases adverse gastrointestinal events. However, colchicine does not impact all-cause mortality, cardiac arrest, stroke incidence, incidence of recurrent MI and the levels of hs-CRP. Large scale multicenter RCTs especially with longer follow-up duration are warranted to validate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The presence of pharmaceutical compounds (PCs) in waters has concerned the scientific community because of their occurrence, persistence, and potentially deleterious effects on human health and aquatic ecosystems. Consequently, studies on the removal of PCs have intensified in the last decade. Because of the lack of deep analysis of this subject, the present study aimed to review the main methods for nonsteroidal anti-inflammatory drug (NSAID) removal from aqueous matrices using biosorbents. The study focused on the adsorption process using adsorbents derived from agro-industrial residues: raw materials, activated materials, biochar, and activated carbon. For this purpose, an overview of publications between 2011 and 2021 was performed on the scientific databases. The consulted literature focused on NSAIDs of highest incidence in water matrices (acetaminophen, ketoprofen, diclofenac, ibuprofen, naproxen, and paracetamol). The evaluated articles report several procedures for preparing and modifying adsorbent materials, in addition to studies concerning the equilibrium, kinetics, and thermodynamics of the adsorption process. Agro-industrial residues converted into activated carbon were the most reported and had improved performance compared to less-processed biosorbents. The use of adsorbents derived from agro-industrial residues is a promising strategy for NSAID removal from water and wastewater. However, further investigations are necessary to provide reliable parameters aimed at upscaling water treatment on a large scale.

In this study the adsorption of a mixture of seven pharmaceutical compounds on virgin and aged polylactic acid (PLA) microplastics (MPs) was investigated. PLA MPs were aged under UV radiation and simulated solar light (SSL) creating three types of MPs: i) virgin, ii) UV-aged and iii) SSL-aged PLA-MPs. The different PLA-MPs were characterized with various characterization techniques (FTIR, SEM, TGA) which revealed modifications on the surface of the aged MPs like cracks and pits, creating more adsorption sites. Pseudo-first, pseudo-second and the intraparticle diffusion model were applied to explore the mechanism and the rate limiting step of the adsorption mechanism. Isothermal study was also conducted and revealed better fitting with the Freundlich model indicating a multi-layer coverage on the MPs surface. Aging appears to enhance the adsorption capacity of the target compounds on the PLA-MPs for both types of aged MPs however the UV-aged showed higher uptake. Finally, the effect of other parameters, like the pH or the type of the water matrix were also investigated offering a deeper insight on the adsorption mechanism of the target compounds. [Display omitted] [ABSTRACT FROM AUTHOR]

Telomeres are a repeated sequence -of bases found at the ends of chromosomes. In humans, this sequence is TTAGGG, which is repeated over 2000 times. Telomeres protect the ends chromosomes from fusion with nearby chromosomes, and allow effective replication of DNA. Each time a cell divides, 25-200 base pairs are lost from the terminal sequence of chromosomes. By becoming truncated during cell division, telomeres protect essential genes from being shortened and thus inactivated. In addition, telomeres are sensitive to inflammation and oxidative stress, which can further promote telomere shortening. Reduction in the length of telomeres leads to the cessation of cell division and thus cellular senescence and apoptosis. This review discusses evidence for the role of oxidative stress and inflammation in regulating the length of telomeres in mammalian cells during senescence. Evidence is presented suggesting that antioxidants and anti-inflammatories can reduce the pace of shortening of telomere length during aging. The distinctive properties of transformed cells suggest that treatment with such materials will have a deleterious rather than a protective effect on such abnormal cells.

Polyphenols are compounds found in various plants and foods, known for their antioxidant and anti-inflammatory properties. Recently, researchers have been exploring the therapeutic potential of marine polyphenols and other minor nutrients that are found in algae, fish and crustaceans. These compounds have unique chemical structures and exhibit diverse biological properties, including anti-inflammatory, antioxidant, antimicrobial and antitumor action. Due to these properties, marine polyphenols are being investigated as possible therapeutic agents for the treatment of a wide variety of conditions, such as cardiovascular disease, diabetes, neurodegenerative diseases and cancer. This review focuses on the therapeutic potential of marine polyphenols and their applications in human health, and also, in marine phenolic classes, the extraction methods, purification techniques and future applications of marine phenolic compounds.

Why you should read this article: • To enhance your knowledge of the structure and main functions of the skin • To understand the aetiology, manifestations and management of skin conditions commonly seen in children • To count towards revalidation as part of your 35 hours of CPD, or you may wish to write a reflective account (UK readers) • To contribute towards your professional development and local registration renewal requirements (non-UK readers) This article, the 13th in a series on the biological basis of child health, focuses on the skin. The skin is the largest organ in the body and covers its whole outer surface, protecting it from external threats, assisting in retaining body fluids, eliminating waste products and regulating temperature. The skin also has a crucial role in wound healing and vitamin D synthesis. Skin conditions in children are often distressing for children and parents, and may significantly affect their everyday lives. This article explains how the skin develops in utero, describes the structure and functions of the skin, and explores the aetiology, manifestations and management of skin conditions commonly seen in children. [ABSTRACT FROM AUTHOR]

The pathogenesis of arrhythmias is complex and multifactorial. The role of inflammation in the pathogenesis of both atrial and ventricular arrhythmias (VA) has been explored. However, developing successful pharmacotherapy regimens based on those pathways has proven more of a challenge. This narrative review provides an overview of five common arrhythmias impacted by inflammation, including atrial fibrillation (AF), myocardial infarction, arrhythmogenic cardiomyopathy, cardiac sarcoidosis, and QT prolongation, and the potential role for anti‐inflammatory therapy in their management. We identified arrhythmias and arrhythmogenic disease states with the most evidence linking pathogenesis to inflammation and conducted comprehensive searches of United States National Library of Medicine MEDLINE® and PubMed databases. Although a variety of agents have been studied for the management of AF, primarily in an effort to reduce postoperative AF following cardiac surgery, no standard anti‐inflammatory agents are used in clinical practice at this time. Although inflammation following myocardial infarction may contribute to the development of VA, there is no clear benefit with the use of anti‐inflammatory agents at this time. Similarly, although inflammation is clearly linked to the development of arrhythmias in arrhythmogenic cardiomyopathy, data demonstrating a benefit with anti‐inflammatory agents are limited. Cardiac sarcoidosis, an infiltrative disease eliciting an immune response, is primarily treated by immunosuppressive therapy and steroids, despite a lack of primary literature to support such regimens. In this case, anti‐inflammatory agents are frequently used in clinical practice. The pathophysiology of arrhythmias is complex, and inflammation likely plays a role in both onset and duration, however, for most arrhythmias the role of pharmacotherapy targeting inflammation remains unclear. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) complications and their clinical implications are poorly characterized in dogs treated surgically for acute thoracolumbar intervertebral disc extrusion (TL-IVDE). The objective of this retrospective study was to characterize GI signs (including vomiting, diarrhea, melena, and hematochezia) in dogs undergoing hemilaminectomy for acute TL-IVDE. One-hundred and sixteen dogs were included. Frequency, type and severity of GI signs during hospitalization, duration of hospitalization and outcome were obtained from the medical record. Potential risk factors for the development of GI signs were explored using univariable and multivariable analyses. Gastrointestinal signs occurred in 55/116 dogs (47%); 22/55 dogs (40%) had one episode and 21/55 (38%) had ≥5 episodes. Diarrhea was the most common (40/55, 73%) while melena was rare (1/55, 2%). GI signs developed in 8/11 dogs (73%) treated perioperatively with both non-steroidal anti-inflammatories and corticosteroids with or without a washout period and in 25/52 dogs (48%) treated prophylactically with proton pump inhibitors. Median hospitalization was 7 days (4–15 days) vs. 5 days (4–11 days) in dogs with or without GI signs, respectively. Duration of hospitalization was associated with development of any GI signs, diarrhea and more severe GI signs (p = 0.001, 0.005, 0.021, respectively). Pre-operative paraplegia with absent pain perception was identified on univariable analysis (p = 0.005) and longer anesthetic duration on multivariable analysis to be associated with development of more severe GI signs (p = 0.047). In dogs undergoing surgery for acute TL-IVDE, GI signs were common and associated with duration of hospitalization and anesthesia. The influence of specific medications and neurologic severity on development of GI signs requires further investigation.

High-yield dairy cows need high energy feed during periods of increased milk production. The transitional feeding to high energy feed increases the risk of developing a variety of metabolic disorders. Here, five Holstein cows were fed a four-stage feeding protocol (3 weeks for each stage) ranging from 54.9 to 73.7% total digestive nutrients (TDN). The purpose of the study was to investigate the effect of lactic acid bacteria on high-energy-fed cows associated with transitional feeding, and to evaluate the effects of probiotics on intestinal bacterial changes and inflammatory responses. Three feed transition periods were established for five cows, and Lactobacillus plantarum RGU-LP1 (LP1) was fed as a probiotic during the high-energy feeding period. The number of lymphocyte subsets such as CD3-, CD4-, and CD8 positive cells decreased in response to the high energy feed. Lipopolysaccharide (LPS)-induced cytokine (IL-1β and IL-2) gene expression in peripheral blood mononuclear cells (PBMCs) was shown to increase in those animals receiving the high energy feed. However, supplementation with LP1 resulted in an increase in the number of lymphocyte subsets and the expression of IL-1β and IL-2 were returned to the level at low energy diet. These results suggest that high energy diets induce inflammatory cytokine responses following LPS stimulation, and that the addition of LP1 mitigates these results by regulating the LPS-induced inflammatory reaction. Therefore, the functional lactic acid bacteria LP1 is expected to regulate inflammation resulting from high energy feeding, and this probiotic could be applied to support inflammatory regulation in high-yield dairy cows.

Introduction and objective. COVID-19 is a human infectious disease manifested by acute respiratory syndrome. On 30 January, 2020, the Word Heath Organization (WHO) declared a COVID-19 pandemic. The purpose of this article is to review publications on the search for substances that show inhibitory activity against SARS-CoV-2 infectivity, paying particular attention to the effect on different stages of the life cycle of the virus. Review methods. The review was based on an analysis of the latest available scientific literature and international databases. The data collected relate to the years 2020-2021. Brief description of the state of knowledge. Extremely intensive research is underway to find compounds that inhibit infection with the SARS-CoV-2 virus. Promising areas of research among the many current endeavours are antiviral compounds that stimulate the immune system, counter proliferation or affect individual viral replication cycles. These include, among others, interferons, monoclonal antibodies, natural compounds, peptides, aptamers, metal salts, and anti-inflammatory agents, inhibitors of viral enzymem, such as the RNA-dependent RNA polymerase. Preparations that help the body to combat the effects of infection have also assumed much importance. Conclusions. The ongoing research is focused on the development of new antiviral agents, as well as the use of the existing drugs on the market. The results of clinical trials are promising and give hope for the development of effective therapies against SARS-CoV-2 and emerging variants of this virus. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective: to investigate the biological activities of interest to the health of Jatropha multifida plant species in published scientific literature. Methods: this is an integrative review, with searches between May and June 2019, using the descriptors, combined through the Boolean operator AND, Jatropha multifida, anti-infective agents, wound healing, cytotoxicity and antioxidants, in LILACS, BDENF, MEDLINE, SciFinder, Web of Science and Scopus databases and in the virtual libraries SciELO and ScienceDirect. Results: twelve publications were retrieved that showed nine biological activities. The antioxidant activity was reported in 04 (33.33%) studies; antimicrobial and anticancer, addressed by 03 (25%) and 02 (16.66%); anti-inflammatory, anti-melanin deposition, healing, antiophidic, purgative and anti-influenza, seen in 01 (8.33%) each. Final considerations: although scarce, the published scientific production highlights the biological potential of J. multifida and supports the need for further studies.

Abstract Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega‐3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non‐steroidal anti‐inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti‐hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data.

Aim: To evaluate the antioxidant and anti-inflammatory activity in hydroalcoholic extracts of the aerial parts of Kalanchoe daigremontiana Raym. -Hamet & H. Perrier. Materials and methods: Extracts were obtained using ethanol (EtOH) and methanol (MeOH) as solvents at different concentrations. Total phenols and flavonoids were quantified using the Folin-Ciocalteu method and the aluminum complexation reaction, respectively. Methodology: The antioxidant activity of the extracts was determined using the DPPH• (2,2-diphenyl-1-picrylhydracil) free radical discoloration technique, while lipoxygenase (LOX) inhibition assays were used to measure the anti-inflammatory activity. Results: The 70% ethanolic extract showed a greater antioxidant capacity against DPPH• and a greater inhibition of the lipoxygenase enzyme, which should be related to the overall phenols and flavonoids content, suggesting that K. daigremontiana exhibits antioxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega‐3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non‐steroidal anti‐inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti‐hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data. [ABSTRACT FROM AUTHOR]

Introduction: Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective in managing musculoskeletal pain, but often are associated with side effects. Therefore, topical anti-inflammatory drugs are considered a suitable alternative for certain patients., Objective: To determine the skin penetration capacity and anti-inflammatory efficacy of a methyl salicylate gel (MS) with turpentine essence, camphor and menthol (GelSMETAM)., Methods: Human skin explants were used (three biological replicates with 3 technical replicates each were performed). To assess penetration capacity, methyl salicylate (MS) levels were quantified at different intervals using liquid chromatography with tandem mass spectrometry (LC-MS/MS). For the anti-inflammatory effect, the gene expression of major pro-inflammatory factors was quantified 30 minutes, 8 hours, and 12 hours after an impact; comparing GelSMETAM application with untreated controls., Results: The results showed that approximately 0.8% of the total applied methyl salicylate penetrated the skin with a time-dependent concentration increase. The anti-inflammatory effect demonstrated a significant reduction in the gene expression of TNFα, IL1α, IL6, IL8, and NFKβ at 30 minutes (between -39% and -53.6% compared to control), which was maintained at 8 hours except for TNFα (between -59% and -92.6%) and persisted even at 12 hours (-69.4%) for IL1α., Conclusion: The results support the hypothesis that GelSMETAM provides an effective and prolonged anti-inflammatory response, positioning it as a suitable option for the management of musculoskeletal pain., (Copyright SEFAC. Sociedad Española de Farmacia Clínica, Familiar y Comunitaria. This article is available from url https://www.farmaceuticoscomunitarios.org/.)

Introduction: Dysmenorrhea is the most common cause of gynecological pain among women that has considerable impact on quality of life and psychosocial wellbeing. Non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal therapies are most commonly used to treat dysmenorrhea. However, given these drugs are often associated with bothersome side effects and are less effective when there is an underlying cause contributing to dysmenorrhea (e.g. endometriosis), a patient-centered approach to managing dysmenorrhea is important. Various new drugs are currently being investigated for the treatment of primary and secondary dysmenorrhea., Areas Covered: This review provides an updated overview on new therapeutic targets and investigational drugs for the treatment of primary and secondary dysmenorrhea. The authors describe the clinical development and implications of these drugs., Expert Opinion: Among the investigative drugs discussed in this review, anti-inflammatories show the most promising results for the treatment of dysmenorrhea. However, given some trials have considerable methodological limitations, many drugs cannot be currently recommended. Research focused on understanding the mechanisms involved in menstruation and its associated symptoms will be important to identify new therapeutic targets for dysmenorrhea. Further robust clinical trials are required to better understand the efficacy and safety of investigational drugs for treating primary and secondary dysmenorrhea.

One of the most appreciated consequences of immunosenescence is an impaired response to vaccines with advanced age. While most studies report impaired antibody responses in older adults as a correlate of vaccine efficacy, it is now widely appreciated that this may fail to identify important changes occurring in the immune system with age that may affect vaccine efficacy. The impact of immunosenescence on vaccination goes beyond the defects on antibody responses as T cell-mediated responses are reshaped during aging and certainly affect vaccination. Likewise, age-related changes in the innate immune system may have important consequences on antigen presentation and priming of adaptive immune responses. Importantly, a low-level chronic inflammatory status known as inflammaging has been shown to inhibit immune responses to vaccination and pharmacological strategies aiming at blocking baseline inflammation can be potentially used to boost vaccine responses. Yet current strategies aiming at improving immunogenicity in the elderly have mainly focused on the use of adjuvants to promote local inflammation. More research is needed to understand the role of inflammation in vaccine responses and to reconcile these seemingly paradoxical observations. Alternative approaches to improve vaccine responses in the elderly include the use of higher vaccine doses or alternative routes of vaccination showing only limited benefits. This review will explore novel targets and potential new strategies for enhancing vaccine responses in older adults, including the use of anti-inflammatory drugs and immunomodulators.

The inflammatory response in the CF airway begins early in the disease process and becomes persistent through life in most patients. Inflammation, which is predominantly neutrophilic, worsens airway obstruction and plays a critical role in the development of structural lung damage. While cystic fibrosis transmembrane regulator modulators will likely have a dramatic impact on the trajectory of CF lung disease over the coming years, addressing other important aspects of lung disease such as inflammation will nevertheless remain a priority. Considering the central role of neutrophils and their products in the inflammatory response, potential therapies should ultimately affect neutrophils and their products. The ideal anti-inflammatory therapy would exert a dual effect on the pro-inflammatory and pro-resolution arms of the inflammatory cascade, both of which contribute to dysregulated inflammation in CF. This review outlines the key factors to be considered in the design of clinical trials evaluating anti-inflammatory therapies in CF. Important lessons have been learned from previous clinical trials in this area and choosing the right efficacy endpoints is key to the success of any anti-inflammatory drug development program. Identifying and validating non-invasive biomarkers, novel imaging techniques and sensitive lung function tests capable of monitoring disease activity and therapeutic response are important areas of research and will be useful for the design of future anti-inflammatory drug trials.

The inflammatory response in the CF airway begins early in the disease process and becomes persistent through life in most patients. Inflammation, which is predominantly neutrophilic, worsens airway obstruction and plays a critical role in the development of structural lung damage. While cystic fibrosis transmembrane regulator modulators will likely have a dramatic impact on the trajectory of CF lung disease over the coming years, addressing other important aspects of lung disease such as inflammation will nevertheless remain a priority. Considering the central role of neutrophils and their products in the inflammatory response, potential therapies should ultimately affect neutrophils and their products. The ideal anti-inflammatory therapy would exert a dual effect on the pro-inflammatory and pro-resolution arms of the inflammatory cascade, both of which contribute to dysregulated inflammation in CF. This review outlines the key factors to be considered in the design of clinical trials evaluating anti-inflammatory therapies in CF. Important lessons have been learned from previous clinical trials in this area and choosing the right efficacy endpoints is key to the success of any anti-inflammatory drug development program. Identifying and validating non-invasive biomarkers, novel imaging techniques and sensitive lung function tests capable of monitoring disease activity and therapeutic response are important areas of research and will be useful for the design of future anti-inflammatory drug trials. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a novel coronavirus that causes the disease COVID-19. It is a highly contagious virus that has led to a pandemic. There are several known risk factors for COVID-19, including age, gender, chronic obstructive pulmonary disease, coronary heart disease, hypertension, diabetes and smoking. Asthma has only been a risk factor in a small number of cases. Despite the lack of information about asthma and the risk of contracting COVID-19, especially in children, it is a condition we need to take seriously. An important aspect of the role of the nurse in supporting patients with asthma in primary care is dispelling myths concerning COVID-19 and their condition by using telehealth and other forms of remote working. There is confusing data about patients with COVID-19 using steroids; there are even suggestions that patients with asthma should stop using their prescribed steroids. Recent national and worldwide recommendations state that patients with asthma should keep using their prescribed medications. It is therefore important that nurses supporting patients are aware of local and national guidelines and any new recommendations. [ABSTRACT FROM AUTHOR]

In this study, 19 endophytic fungi were isolated from Lafoensia pacari, Guazuma ulmifolia, Campomanesia xanthocarpa and Siparuna guianensis. Seventeen strains were molecularly identified as belonging to the genera Colletotrichum, Diaporthe, Bjerkandera, Talaromyces, Cochliobolus, Phaeophlebiopsis, Curvularia, and Xylaraceae. Assays for detecting antioxidant activity were performed by free radical scavenging activity using the DDPH and ABTS + methods. Based on the results with DPPH, two strains were selected to evaluate the presence of flavonoids and anti-inflammatory activity. A strong positive correlation was found between these activities and the presence of flavonoids. The anti-inflammatory activity of endophytic fungi is under explored; however, the Talaromyces obtained the best result of 87.33% protection of erythrocytes and Colletotrichium of 60.71%. This study demonstrated that endophytic fungi associated with selected plants are potential sources of novel antioxidant products. [ABSTRACT FROM AUTHOR]

Pain is a well-documented symptom of cancer, and pharmacological treatment options aside from opioids, which can have burdensome side effects, remain limited. Cannabinoids are compounds derived from the active components of the cannabis plant, and have been investigated for their potential medicinal use in treating cancer-related pain. Aim To analyse the evidence regarding the use of cannabinoids to treat cancer-related pain. Method A systematic search of databases was conducted to identify controlled trials that have tested cannabinoids to relieve cancer-related pain. Findings Ten trials were included in this review: five randomised controlled trials, four crossover trials and one observational study. At least half of the trials had a low risk of bias. In six studies, the cannabinoids used in the intervention arms produced a statistically significant reduction in pain. However, only one study found that cannabinoids had a clinically significant effect. Side effects were consistent across studies, with the most common side effects being nausea, dizziness and somnolence. Pain relief and side effects were shown to be dose-dependent. Conclusion The data does not provide sufficiently strong evidence to support the use of cannabinoids for treating cancer-related pain. The lack of evidence means that further research into the use of cannabinoids for treating cancer-related pain is required. [ABSTRACT FROM AUTHOR]

The occurrence of anti-inflammatory and analgesic pharmaceuticals (AIAPs) in the effluents of 16 hospitals, influent and effluent of wastewater treatment plant (WWTP), the contribution and mass load of each hospital to WWTP influent, and the removal efficiencies in WWTP were investigated. Environmental risk was also evaluated by toxicity tests using organisms from three different trophic levels. Acetaminophen had the highest concentration in summer and winter samples, followed by ketoprofen, ibuprofen, and naproxen. The total daily load of AIAPs detected in influent of WWTP was 1677 mg/day/1000 inhabitants in summer and 5074 mg/day/1000 inhabitants in winter. The contribution of 16 hospitals to the total AIAP load in influent of WWTP was 11.30% in summer and 7.09% in winter. The highest mass loads were calculated as 203 mg/bed.day in general hospital in summer and 300 mg/bed.day in pediatric hospital in winter. The removal efficiencies of AIAPs in WWTP ranged between 13% and 100% in summer and 0.88% and 99% in winter. WWTP is not sufficient to remove all the AIAPs. Diclofenac (in summer), mefenamic acid, indomethacin, and phenylbutazone exhibited poor removal below 50%. The effluents of the WWTP exhibited a low risk for fish and Daphnia magna and an insignificant risk for algae. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the efficacy of topical nonsteroidal anti-inflammatory drugs (NSAID) to relieve temporomandibular joint (TMJ) degenerative joint disease (DJD) pain. Methods: A search of the literature was made using electronic databases complemented with a manual search. Clinical trials comparing topical NSAID with either placebo or an alternative active treatment to treat TMJ DJD pain were identified. Outcomes evaluated were pain reduction/pain control and/or incidence of side effects. Results: A single study (double-blind randomized placebo-controlled trial) with 20 patients was identified that evaluated the efficacy of a topically prepared NSAID over a 12-week duration, measuring functional pain intensity, voluntary and assisted mouth opening, pain disability index, and a brief pain inventory analysis. This study revealed a pain intensity decrease within treatment groups but no significant difference between treatment groups. Conclusion: Presently, there is insufficient evidence to support the use of topically applied NSAID medications to palliate TMJ DJD pain. [ABSTRACT FROM AUTHOR]