Steroidal Anti-inflammatory Drugs Research Articles

Preemptive oral analgesia with steroidal and nonsteroidal anti-inflammatory drugs in periodontal surgery: a systematic review

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling post-operative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries.Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out.Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8 mg, etoricoxib 90 mg or 120 mg and ketorolac 20 mg seems to be more effective for controlling post-operative pain than placebo.Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted.

EXPERIMENTAL RESEARCH OF THE PHARMACOLOGICAL EFFECT OF CARBON DIOXIDE IN THE CORRECTION OF INFLAMMATION

Osteoarthritis is considered one of the leading causes of chronic disability and is a significant problem on human health and the economy. Chronic pain is the dominant symptom that prompts patients to seek medical attention. Pain mechanisms in osteoarthritis remained unknown for a long time. However, it is known that chronic inflammation of the joint can be a key factor in the occurrence and exacerbation of pain or changes in the perception of pain. Pharmacological therapy is often based on the use of steroidal and non-steroidal anti-inflammatory drugs, but their long-term use or large doses can cause side effects. That is why the development of new methods of treatment of inflammatory processes is the object of active research, as they can affect various mechanisms. In this context, carboxytherapy is an interesting alternative or addition to existing treatment regimens aimed at reducing pain in patients with osteoarthritis. This method involves the administration of medical carbon dioxide (CO2) to improve blood supply to tissues, which can contribute to humoral, biochemical and tissue mechanisms. Studying the effects of carboxytherapy in animal models of inflammation is important for understanding its potential benefits and mechanisms of action. Objective. Study of anti-inflammatory properties of carboxytherapy both in monotherapy and in its combined use. Methods. Carboxytherapy is the injection of carbon dioxide in monotherapy and when used in combination on the formalin model of inflammation in animals. Results. The obtained research results prove the anti-inflammatory properties of carbon dioxide on the model of formalin inflammationin animals. Conclusions. The combined use of carboxytherapy enhanced the effect of conventional drugs on the formalin model of inflammation in animals. The establishment of an anti-inflammatory effect of carboxytherapy indicates the therapeutic value of CO2, while emphasizing the need for further in-depth studies to explore its mechanisms and confirm the efficacy for clinical use.

Value of Urinary NGAL for Predicting Acute Kidney Injury Secondary to Decompensated Cirrhosis

Abstract Background Physicians caring for patients with cirrhosis should recognize the acute or chronic character of renal disease; the causes of renal injury; the clinical conditions leading concomitantly to acute kidney injury (AKI) and liver dysfunction, and the prognostic factors associated with the progression of AKI. Hypovolemia (due to diuretics, hemorrhage, diarrhea), acute tubular necrosis, sepsis, nephrotoxic agents (such as non steroidal anti-inflammatory drugs, aminoglycosides radiological contrasts) and hepatorenal syndrome-type 1 are the most common causes of AKI in cirrhotic patients. Aim of the Work The aim of this study was to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis. Patients and Methods This was a cross sectional study done in patients with liver cirrhosis hospitalized at the Gastroenterology Department of the Ain shams university hospital. Results We found that in the comparison between HRS and AKI regarding HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, there was highly statistically significant difference found between two groups regarding Urinary Na and Fe Na%, Platelets, AST, Bilirubin and Na, and there was no statistically significant difference found between two groups regarding HB, WBCs, ALT, Albumin, INR, Urea, Creatinine and Urinary Cr. While in the Correlation between NGAL With Age, HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, we found that there was Non statically significant correlation Between NGAL, Age, HB, WBCs, Platelets, ALT, Albumin, INR, Bilirubin, Urea, Creatinine, Na and Urinary Cr, and there was statically significant Negative correlation Between NGAL, Urinary Na and FeNa%, and there was statically significant positive correlation Between NGAL and AST. Conclusion It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. NGAL is a newly identified member of the lipocalin family that is signifcantly expressed in injured epithelial cells. It can lead to rapid increases in NGAL secretion from glomeruli, thus increasing NGAL concentrations in the urine. In addition, its concentration often increases within 2 h of kidney injury. Urinary NGAL has the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI. These findings, if confirmed in larger cohorts, could lead to the development of biomarker algorithms to rapidly identify patients with HRS and ATN and accurately predict prognosis.

Treatment Strategies for Filamentous Fungi Keratitis.

This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids. This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records. Improvement of BVCA was noted in 68% of eyes. Mean BCVA of the study population increased from 0.75 logMAR [median 0.40, standard deviation (SD) 0.82, range 0-2.3] to 0.48 logMAR (median 0.10, SD 0.88, range - 0.1 to 3). The most commonly used antifungal topical treatment was a combination of natamycin 5% and voriconazole 2% (44% of eyes), followed by voriconazole 2% in 36% of cases. An antiinflammatory topical steroid was applied in 52%. In 16% of the eyes, penetrating keratoplasty (pKP) was performed. Diagnosis of filamentous fungi keratitis is often difficult or delayed. Outcomes can be poor even with intensive treatment because of high resistance to common antifungals. Access to natamycin 5% seems to lead to favourable outcomes in filamentous fungi keratitis.

Isothiocyanate-Corticosteroid Conjugates against asthma: Unity makes strength

Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need for chronic pharmacological treatments. The standard gold therapy of inflammation in asthmatic patients involves the use of glucocorticoids even if their chronic use is often related to serious adverse effects. Growing evidence suggests the biological relevance of hydrogen sulfide (H2S) in the pathogenesis of airway diseases. Hence, aiming to associate the beneficial effects of steroidal anti-inflammatory drugs (SAIDs) to H2S biological activity, we designed and synthesized novel multi-target molecules by chemically combining a group of glucocorticoids, usually employed in asthma treatment, with an isothiocyanate moiety, well-known for its H2S releasing properties. Firstly, the synthesized compounds have been screened for their H2S-releasing profile using an amperometric approach and for their in vitro effects on the degranulation process, using RBL-2H3 cell line. The physicochemical profile, in terms of solubility, chemical and enzymatic stability of the newly hybrid molecules, has been assessed at different physiological pH values and in esterase-rich medium (bovine serum albumin, BSA). The selected compound 5c, through both its corticosteroid and H2S releasing component, has been evaluated in vivo in experimental model of asthma. The compound 5c inhibited in vivo all asthma features with a significative effect on the restoration of pulmonary structure and reduction of lung inflammation.

Potential of natural products in inflammation: biological activities, structure-activity relationships, and mechanistic targets.

A balance between the development and suppression of inflammation can always be found in the body. When this balance is disturbed, a strong inflammatory response can damage the body. It sometimes is necessary to use drugs with a significant anti-inflammatory effect, such as nonsteroidal anti-inflammatory drugs and steroid hormones, to control inflammation in the body. However, the existing anti-inflammatory drugs have many adverse effects, which can be deadly in severe cases, making research into new safer and more effective anti-inflammatory drugs necessary. Currently, numerous types of natural products with anti-inflammatory activity and distinct structural features are available, and these natural products have great potential for the development of novel anti-inflammatory drugs. This review summarizes 260 natural products and their derivatives with anti-inflammatory activities in the last two decades, classified by their active ingredients, and focuses on their structure-activity relationships in anti-inflammation to lay the foundation for subsequent new drug development. We also elucidate the mechanisms and pathways of natural products that exert anti-inflammatory effects via network pharmacology predictions, providing direction for identifying subsequent targets of anti-inflammatory natural products.

Subacute Thyroiditis Following COVID-19 and COVID-19 Vaccination

ObjectiveCOVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. MethodsA population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. ResultsA total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). ConclusionBased on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.

Assessing Pharmacogenomic loci Associated with the Pharmacokinetics of Vamorolone in Boys with Duchenne Muscular Dystrophy.

Human genetic variation (polymorphisms) in genes coding proteins involved in the absorption, distribution, metabolism, and elimination (ADME) of drugs can have a strong effect on drug exposure and downstream efficacy and safety outcomes. Vamorolone, a dissociative steroidal anti-inflammatory drug for treating Duchenne muscular dystrophy (DMD), primarily undergoes oxidation by CYP3A4 and CYP3A5 and glucuronidation by UDP-glucuronosyltransferases. This work assesses the pharmacokinetics (PKs) of vamorolone and sources of interindividual variability (IIV) in 81 steroid-naïve boys with DMD aged 4 to <7 years old considering the genetic polymorphisms of CYPS3A4 (CYP3A4*22, CYP3A4*1B), CYP3A5 (CYP3A5*3), and UGT1A1 (UGT1A1*60) utilizing population PK modeling. A one-compartment model with zero-order absorption (Tk0, duration of absorption), linear clearance (CL/F), and volume (V/F) describes the plasma PK data for boys with DMD receiving a wide range of vamorolone doses (0.25-6 mg/kg/day). The typical CL/F and V/F values of vamorolone were 35.8 L/h and 119 L, with modest IIV. The population Tk0 was 3.14 h yielding an average zero-order absorption rate (k0) of 1.16 mg/kg/h with similar absorption kinetics across subjects at the same vamorolone dose (i.e., no IIV on Tk0). The covariate analysis showed that none of the genetic covariates had any significant impact on the PKs of vamorolone in boys with DMD. Thus, the PKs of vamorolone is very consistent in these young boys with DMD.

RECENT ADVANCES IN NANOTECHNOLOGY - BASED DRUG DELIVERY SYSTEMS FOR DELIVERY OF PHYTOCONSTITUENTS WITH SPECIAL EMPHASIS ON PSORIASIS MANAGEMENT

Psoriasis is an inflammatory, autoimmune disorder characterized by thick and silvery lesions of the skin. Beyond its physical dimension, this disease has a significant adverse effect on quality of life and represents a huge social health burden. Based on symptoms, psoriasis may be characterized from mild to severe. A range of therapeutic agents are available to treat the disease, but none is able to provide permanent cure of the disease. The most commonly used medicines for treatment of psoriasis include anti-inflammatory drugs, steroids, biological and immunosuppressants. Though these drugs cure the disease to an extent, they are associated with many contra-indicative manifestations. Hence, an alternative system of medicine could be an excellent approach in the management of this disease, and numerous studies proved that bio-actives derived from natural sources have potential anti-psoriatic activity. Further, the therapeutic actions of these natural products can be enhanced by incorporating them in nano-formulations. The present era of medicine is focusing on implementation of natural product based nanotechnology to overcome the drawbacks of conventional treatment. This review primarily aims to focus on the recent advances in the field of natural product based nanomedicines for the effective management of psoriasis.

Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives-A Review.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.

Aspirin Does Not Inhibit Platelet-Rich Plasma Releasate Efficacy in a Murine Model of Rotator Cuff Tendinopathy

Background: Platelet-rich plasma (PRP) has been shown to be a promising treatment for subacromial impingement, and although its interaction with aspirin (ASA) is controversial, many providers ask patients to stop non–steroidal anti-inflammatory drug use before PRP administration. Purpose: This studied aimed to identify the effect of PRP in a murine model of subacromial impingement and to explore the effect of ASA on PRP treatment. Methods: A murine model of subacromial impingement was used, incorporating 48 wild-type C57BL/6 mice. After impingement surgery, mice received either human PRP activated via calcium chloride or saline injected into the subacromial space. The mice received either drinking water with ASA or standard drinking water, creating 4 groups: saline injection, saline injection + ASA, PRP injection, and PRP injection + ASA. All injections occurred at 3 weeks after impingement surgery, and mice were evaluated at 6 weeks. Each mouse underwent gait analysis, biomechanical analysis (N = 10 shoulders), histological analysis (N = 6), and gene expression analysis (N = 8). Results: Biomechanical testing showed increased load to failure in the PRP group compared to the ASA group, and increased stiffness in PRP vs saline, PRP vs ASA, and PRP vs ASA + PRP. Gene expression analysis identified 17 downregulated genes between the ASA + PRP and saline groups. Eight of these differentially expressed genes contribute to collagen biosynthesis and modification, 4 to extracellular matrix (ECM) synthesis, and 4 to ECM degradation. Conclusions: In this preliminary analysis, PRP injections in a murine model of subacromial impingement demonstrated mixed effects on tendon quality and pain, and ASA did not have a consistent effect on the response to PRP.

Sodium Cromolyn Modulates Carrageenan-Induced Acute Inflammation Through the Interleukin-6 Levels

Background: Previous studies have indicated that sodium cromolyn does not negatively affect steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs). Objective: This study aimed to investigate the anti-inflammatory effects of sodium cromolyn on carrageenan-induced paw edema in rats and assess its impact on IL-6, an anti-inflammatory cytokine. Methods: The carrageenan-induced paw edema model is widely used for studying inflammatory mechanisms and evaluating anti-inflammatory drugs. The test groups received intraperitoneal injections of sodium cromolyn at doses of 25, 50, and 100 mg/kg alongside a positive control group (indomethacin at 5 mg/kg) and a negative control group (which received the solvent, saline). Thirty minutes after drug administration, carrageenan (1% w/v) was injected into the right hind paws of the rats. Changes in paw volume were measured using a plethysmometer at 0.5, 1, 2, and 3 hours post-carrageenan injection. Blood and paw tissue samples were collected three hours after carrageenan administration, and IL-6 levels were determined using the standard rat Interleukin-6 ELISA kit. Results: The plasma and tissue IL-6 levels in the group treated with cromolyn (25 mg/kg) were significantly higher than those in the positive control group (indomethacin 5 mg/kg). Sodium cromolyn at a dose of 25 mg/kg had a negligible effect on reducing paw edema and IL-6 levels in serum and paw tissues compared to indomethacin (5 mg/kg). The IL-6 levels in plasma and tissues for the group receiving 50 mg/kg of cromolyn were not significantly different from those in the indomethacin group (5 mg/kg). However, IL-6 levels in the group treated with 100 mg/kg of cromolyn were significantly lower than those in the indomethacin group. Among the groups treated with sodium cromolyn, the highest and lowest IL-6 levels were observed in the groups receiving 25 mg/kg and 100 mg/kg of sodium cromolyn, respectively. The anti-inflammatory effects of sodium cromolyn at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg were analyzed, revealing that 25 mg/kg of cromolyn sodium was not significantly effective at any time point (P &lt; 0.05). Additionally, no significant differences (P &lt; 0.05) were observed between the 50 mg/kg and 100 mg/kg doses at any study hour. Sodium cromolyn at a 50 mg/kg dose was as effective as indomethacin (5 mg/kg) in significantly reducing paw edema. Conclusions: Sodium cromolyn, at doses of 50 and 100 mg/kg, effectively reduced paw edema and the concentration of serum and paw tissue IL-6 (P &lt; 0.05), demonstrating significant anti-inflammatory activity. Sodium cromolyn at a 50 mg/kg dose is recommended as the anti-inflammatory dose of this drug.

Abstract 142: HDAC3 is required for pathognomonic features of Langerhans cell histiocytes

Abstract Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm that develops due to dysregulated dendritic cell (DC) development and most commonly affects the children with an incidence of 2.6 to 8.9 cases per million individuals per year. BRAFV600E, the most common disease-driving mutation, activates the mitogen-activated protein kinase (MAPK) pathway causing pathognomonic features that lead to the accumulation of LCH cells and formation of granulomatous lesions. These features include enhanced myelopoiesis, reduced tissue-egress and acquisition of an oncogene induced senescence-associated secretory phenotype (SASP) (marked by increased expression of anti-apoptotic proteins and inflammatory cytokines). Accumulation of LCH cells can occur in any organ causing a wide range of clinical sequelae, which is directly related to the originating cell bearing the oncogenic mutation. Frontline therapy for LCH involves combination chemotherapy and steroidal anti-inflammatories, or MAPK inhibitors, which have significant toxicity and fail to eliminate disease causing precursors. We have found that HDAC3 is required for epidermal LC homeostasis and hypothesized that LCH cells rely on similar epigenetic factors to LCs. CD11cCre LSL-BRAFV600E (BRAFV600ECD11c) mice develop severe multifocal LCH with pronounced lesion development in their livers and lungs, hepatosplenomegaly, and a reduced lifespan due to the accumulation of LCH cells. To test our hypothesis, we generated BRAFV600ECD11c HDAC3fl/fl (BRAFV600EHD3KO) mice, which produce LCH cells that harbor a conditional deletion in the deacetylase domain of HDAC3. Compared to BRAFV600ECD11c mice, BRAFV600EHD3KO mice exhibited significantly less hepatosplenomegaly, reduced lesional burden, and improved survival indicating reduced LCH disease burden. Compared to BRAFV600ECD11c, flow cytometry showed BRAFV600EHD3KO had reduced numbers of LCH cells in lungs and livers, which were more apoptotic. We also found decreased frequencies of circulating LCH cells and LCH precursors, indicating that a lack of HDAC3 activity prevents the development of LCH cells. Bone-marrow derived LCH-like cells provide a valuable drug screening tool. We treated Bone-marrow derived LCH-like cells with RGFP966, an HDAC3-specific inhibitor, increased apoptosis indicated by annexin-V and DAPI staining, reduced expression of Bcl-2, increased CCR7 expression, and decreased S6 phosphorylation (an indication of a loss of the SASP), thus inhibition of HDAC3 may prove therapeutically efficacious by abrogating pathognomonic features of LCH cells. Together, our findings identify HDAC3 as a critical epigenetic regulator LCH cell pathophysiology and HDAC3 blockade would address a great need in treatment of patients with LCH. Furthermore, our results indicate that LCH cells rely on similar epigenetic regulators as epidermal LCs despite coming from a different myeloid lineage. Citation Format: Peter Dimitrion, Jugmohit Toor, James Ge, Qiyan Wang, Carl Allen, Li Zhou, Qing-Sheng Mi. HDAC3 is required for pathognomonic features of Langerhans cell histiocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 142.

Resveratrol and Neuroinflammation: Total-Scale Analysis of the Scientific Literature

Neuroinflammation plays a crucial role in the development of various neurological diseases, including neurodegenerative disorders, leading to significant neuronal dysfunction. Current treatments involve the use of non-steroidal anti-inflammatory drugs and steroids; however, they are associated with serious adverse effects, limiting their efficacy. Exploring natural products with anti-inflammatory properties appears promising, with resveratrol, a polyphenol found in various plants, standing out for its potential benefits. Studies on resveratrol and its anti-inflammatory properties have been increasing in recent years, and analyzing the profile of this knowledge area can bring benefits to the scientific community. Therefore, this study conducted bibliometric analyses, using “resveratrol AND neuroinflammation” as search terms in the Web of Science Core Collection database. The analysis, performed with VOSviewer software version 1.6.18, encompasses 323 publications. Key terms in the studies include “resveratrol”, “neuroinflammation”, and “oxidative stress”, with China leading in the number of publications. The Federal University of Rio Grande do Sul in Brazil emerges as the institution with the highest contribution, and a phase 2 clinical study on resveratrol was the most cited. These results provide an overview of the global research landscape related to resveratrol and neuroinflammation, aiding decision making for future publications and advancing scientific understanding in this field.

Pericarditis. Causes, Mechanisms of Development, Variants of Course and Therapeutic Approaches in Modern Conditions

Under physiological conditions, the pericardial cavity contains serous fluid (15-50 ml), which belongs to the plasma ultrafiltrate and is visualized during echocardiography only in systole. The thickness of the pericardium in an adult averages 2 mm (1-3 mm). Inflammatory lesions of the pericardium with or without effusion into its cavity can act as an independent disease, and as a secondary manifestation of another pathological condition. Pericarditis of infectious (14-16%) and non-infectious (15-20%) nature, primary and secondary, acute, chronic and recurrent are commonly distinguished. The prevalence of acute and idiopathic recurrent pericarditis is 27.7 per 100,000 population and 5.4-8.1 per 100,000 population, respectively. Currently, idiopathic recurrent pericarditis belongs to polygenic autoinflammatory diseases, where an important role in the initiation of the pathologic process belongs to the inflammatory cytokine — interleukin-1 (β and α). The most characteristic manifestations of acute pericarditis are chest pain, dyspnea and fever. The article summarizes the main aspects of etiology, clinical manifestations, diagnosis and therapy of pericarditis, including the peculiarities of its treatment taking into account specific conditions. A clinical case demonstrated a case of acute effusion pericarditis with recurrence, which was characterized by rapid progression of heart failure symptoms, as well as systemic manifestations (anemia, hypercytokinemia, marked muscle weakness). The results of echocardiography allowed to identify the presence of pericardial effusion. Steroid and non-steroidal anti-inflammatory, anticoagulant and antibacterial therapy led to the disappearance of pericardial effusion and normalization of the activity of inflammatory markers in serum. However, in the dynamics of observation the attempt to suspend glucocorticoid therapy again led to fluid accumulation in the pericardium, which required continuation of steroidal and non-steroidal anti-inflammatory drugs.

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection.

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets in vitro. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection in vitro. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the in vivo therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.IMPORTANCEAntivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.

Study of the anti-exudative activity of new 3-cyano-1,4- dihydropyridines, cyanotioacetamide derivatives, on the model of acute formalin edema

The inflammatory process accompanies most of the pathologies and requires pharmacological correction. In spite of significant achievements of scientists in the field of medicine and pharmacology, existing steroid and nonsteroidal antiinflammatory drugs have a number of undesirable reactions. To date, one of the most urgent directions is the search for new effective and safe drugs with anti-inflammatory activity. The aim of the study was to investigate the anti-exudative properties of new 3-cyano-1,4-dihydropyridines, cyanothioacetamide derivatives in the classical test of acute formalin edema. Material and methods. The study was conducted on 88 white rats weighing 210–250 g. The effectiveness of compounds was determined in a model of acute formalin edema, which was induced by subplantar injection of 0.1 ml of 2 % formalin solution into the right hind limb of the animals. The severity of exudation was evaluated oncometrically in comparison with reference drugs – ibuprofen, indomethacin, meloxicam and metamizole sodium. The studied substances were administered intragastrically at a dose of 5 mg/kg 1.5 hours before the induction of inflammation. Results. It was found that some compounds exhibit anti-exudative activity, more pronounced or similar to the activity of reference drugs. The laboratory sample with code mar-137 was the leading sample and outperformed the comparators; 24 hours after the modeling of edema, it exceeded ibuprofen (by 2.39 %), metamizole sodium (by 4.77 %) in anti-exudative efficacy and had an anti-inflammatory effect similar to the activity of indomethacin and meloxicam. Conclusions. Newly synthesized laboratory samples of 3-cyano-1,4-dihydropyridines, cyanothioacetamide derivatives, were found to exhibit pronounced anti-exudative activity and are of interest for further research as a new class of anti-inflammatory drugs.

Antipyretic and Antinociceptive Effect of the Methanol Leaf Extract of Ficus asperifolia in Murine Models

Pyrexia occurs as a result of the resetting of the hypothalamic set-point. Non steroidal anti-inflammatory drugs used for the treatment of fever and related illnesses are associated with side effects including gastrointestinal irritation, bleeding, ulcers and perforation. In traditional medicine, many plants have been found to possess antipyretic activity. Ficus asperifolia (Miq), family Moraceae has been traditionally used to treat pain and fevers. The aim of the study was thus to evaluate the antipyretic and antinociceptive activity of the methanol leaf extract of Ficus asperifolia (FME) in murine models. Preliminary phytochemical screening and oral acute toxicity studies were conducted using standard protocols. Antipyretic activity was evaluated using the Brewer’s yeast induced pyrexia model. Antinociceptive effects were investigated using the acetic acid and thermal induced models. The mechanism of action of the plant was also evaluated against several antagonists. FME significantly (p&lt;0.05) and dose dependently reduced yeast induced pyrexia. FME at doses 125, 250 and 500 mg/kg significantly (p&lt;0.05) decreased acetic acid induced abdominal writhes and increased the mean reaction time of mice to thermal-induced pain stimulus. Pre-treatment of mice with naloxone (a non-selective opioid receptor antagonist), glibenclamide (a potassium channel blocker) and L-NNA (a nitric oxide synthase inhibitor) significantly reversed the analgesic action of the extract suggesting that the activity is likely mediated via the involvement of these pathways.

PREPARATION AND EVALUATION OF MELOXICAM CHEWABLE TABLETS FOR BETTER ORAL DELIVERY

In the current study, meloxicam (MXM) chewable tablets were formulated and evaluated with an aim of improving its solubility, bioavailability and masking its bitter taste in order to create an effective oral drug delivery system. Meloxicam (BCS class II drug), non steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties, acts by inhibition of prostaglandin synthetase leading to inhibition of prostaglandin synthesis. MXM chewable tablets were made by three different techniques: AG (aqueous granulation), NAG (non-aqueous granulation) and DC (direct compression). The chewable tablets of MXM so prepared were assessed for various parameters, namely, palatability test, hardness, weight variation, mechanical strength, disintegration, friability, percent assay and in vitro testing for dissolution profile. The variation found in dissolution profile for all prepared batches was in the order: DC&gt;NAG&gt;AG. The percent assay was found within the range (90-110%). Observations from palatability study showed good overall tolerance levels for DC and AG and moderate tolerance levels for NAG.

Nonsteroidal Anti-Inflammatory Drug Injections versus Steroid Injections in the Management of Upper and Lower Extremity Orthopedic Conditions: A Systematic Review with Meta-Analysis.

Although corticosteroid injections are an effective treatment for musculoskeletal pathologies, they may not be suitable for all patients. The purpose of this systematic review was to compare clinical outcomes between patients who received NSAID and corticosteroid injections for various orthopedic conditions. Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched, and meta-analyses were performed using a random-effects model for outcomes presented in three or more studies. Other studies were qualitatively analyzed. A total of 28 articles with 2113 patients were included. A meta-analysis of five studies in patients with shoulder impingement syndrome demonstrated that there was no significant difference in the pain visual analogue scale (VAS) between subacromial NSAID injections and corticosteroid injections at 1 month [weighted mean difference (WMD) -0.244; 95% CI, -1.232 to 0.745; I2, 94.5%]. For patients with knee osteoarthritis, a meta-analysis of three studies demonstrated that there was no significant difference between intraarticular NSAID injections and corticosteroid injections in pain VAS at 1 month (WMD 0.754; 95% CI, -0.413 to 1.921; I2, 90.2%) and 3 months (WMD-0.089; 95% CI, -0.345 to 0.166; I2, 0%). A review of the studies assessing pain outcomes for hip osteoarthritis, adhesive capsulitis, and plantar fasciitis showed no significant differences between the NSAID and corticosteroid groups. NSAID injections may be safe and effective alternatives to steroid injections, especially in shoulder impingement syndrome and knee osteoarthritis.