Steroidal Anti-inflammatory Drugs Research Articles

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.

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.

Modulatory role of N-acetyl-cysteine on gastric mucosal lesions and some biochemical changes in Wistar rats subjected to cold restraint stress

Background: Gastric ulcer affects many people worldwide and it is caused by many factors such as stress, medications, particularly non- steroidal anti-inflammatory drugs, infections caused by Helicobacter pylori and Cytomegalovirus. Exposure to Cold restraint stress (CRS)  has been established to cause oxidative stress leading to cellular death. Nacetyl-cysteine (NAC) is an antioxidant that protects the lipid  bio-membrane against oxidative stress. This study investigated the effect NAC on gastric mucosal lesion and some biochemical changes  in Wistar rats subjected to CRS.&#x0D; Methodology: Sixteen (16) adult male rats were divided into four (4) groups; Group I (Control): Distilled  water/Kg Group II: Distilled water + CRS 3½ hrs (Ulcer group), Group III: NAC 500 mg/kg orally + CRS 3½ hrs Group IV: Ranitidine 50 mg/ kg + CRS 3½ hrs. All treatment lasted for 7 days while exposure to CRS was for 3½ hours on 7th day. Three hours after exposure of rats to  CRS, rats of all groups were euthanized under diazepam and ketamine anesthesia. The stomach and blood samples were collected for  physical and biochemical analysis. Data were analysed using ANOVA and p &lt; 0.05 was considered significant.&#x0D; Results: The P index of NAC  in CRS induced ulcer was found to be 66.7 %. A significant increase (P = 0.001) in body weight was observed in CRS + Ranitidine group,  when compared to the control. A significant (P = 0.001) increase was observed in the INOS concentration in NAC + CRS, Ranitidine + CRS,  when compared to the control.&#x0D; Conclusion: We surmise that acute administration of NAC significantly increased body weight of rats  subjected to CRS. The high preventive index of N-acetyl cysteine on CRS induced ulcer was as the result of the antioxidant properties of  NAC which might have contributed to its’ gastro protection against gastric mucosal lesions. 

ХАРАКТЕРИСТИКА КАРДИОВАСКУЛЯРНОГО РИСКА У БОЛЬНЫХ С ПСОРИАТИЧЕСКИМ АРТРИТОМ

Abstract. Introduction. Patients with psoriatic arthritis are exposed to a higher risk of developing cardiovascular complications. Development and progression of these disorders are based on a complex of closely interrelated factors, such as traditional cardiovascular risk factors, cardiovascular toxicity of some antirheumatic drugs, primarily non- steroidal anti-inflammatory drugs and glucocorticoids, and chronic autoimmune inflammation, which, according to many researchers, is the leading pathogenetic mechanism of atherosclerotic vascular lesions. The aim of the study was to assess the prevalence of traditional risk factors, the state of the blood lipid spectrum, and atherosclerotic remodeling of peripheral arteries in patients with psoriatic arthritis. Materials and Methods. We examined 84 patients (41 women and 43 men) aged 20 to 65 years. Arthritis was diagnosed based on the CASPAR criteria. Patients were assessed regarding traditional risk factors, such as hypertension, obesity, smoking, aggravated family history of CVD, diabetes, physical inactivity, and dyslipidemia; ten-year total coronary risk was calculated using the SCORE scale. To diagnose subclinical atherosclerosis, the patients underwent Doppler ultrasound of the carotid arteries with an assessment of the intima-media complex thickness. Results and Discussion. Assessment of disease development risk factors showed that all patients with psoriatic arthritis had from one to five risk factors. More common risk factors were smoking in 50 (59.5 %) patients, AO in 44 (52.4 %), dyslipidemia in 48 (57.1 %), and arterial hypertension. Patients with a long history of the disease have a higher prevalence of risk factors. According to the results of calculating the ten-year total coronary risk (SCORE scale), most patients were in the group of low (46.4 %) and moderate (38 %) risk. An association was found between the level of total coronary risk and arthritis activity in groups of patients with low and moderate risk. The average intima-media complex thickness of the common carotid artery in the group of patients with psoriatic arthritis was statistically significantly higher than in those in the control group (p=0.0361).Conclusions. An increased risk of cardiovascular complications was found in patients with psoriatic arthritis, while most patients have several risk factors in various proportions. According to the risk assessment on the SCORE scale, it was found to be statistically significant in the group of patients with psoriatic arthritis, which correlates with disease activity. The presence of subclinical atherosclerosis was detected in form of a statistically significant increase in the intima-media complex thickness of the carotid arteries. All the above indicates the current problem of psoriasis comorbidity, which dictates a personalized comprehensive approach to therapy for the selection of safe and adequate therapy for all diseases diagnosed in an individual patient.

The intrafollicular concentrations of biologically active cortisol in women rise abruptly shortly before ovulation and follicular rupture.

What is the temporal activity and the concentration in follicular fluid (FF) of the anti-inflammatory steroid cortisol during the ovulatory process in humans? Intrafollicular concentrations of cortisol become massively upregulated close to ovulation concomitant with an exceptionally high biological activity securing a timely and efficient termination of inflammatory processes. Ovulation has been described as a local, controlled inflammatory process resulting in the degeneration of the follicle wall which facilitate oocyte extrusion. Ovulation also affects the glucocorticoid metabolism of granulosa cells (GCs) and although de novo synthesis of cortisol only occurs in the adrenal cortex, the mid-cycle surge has been shown to induce a change from high expression of HSD11B2, inactivating cortisol to cortisone, to high expression of HSD11B1 which reversibly catalyses cortisol production from cortisone. Furthermore, high concentrations of progesterone and 17OH-progesterone within follicles may cause dislodging of cortisol from cortisol binding protein (CBP) thereby activating the biological activity of cortisol. This prospective cohort study included 50 women undergoing fertility treatment according to a standard antagonist protocol at a university hospital-affiliated fertility clinic in Denmark. Women donated FF and GCs from one follicle for research purpose aspirated at one of four time points during the process of final maturation of follicles: T = 0 h, T = 12 h, T = 17 h, T = 32 h. A second sample was collected at oocyte pick up at T = 36 h. The concentration of cortisol and cortisone together with a range of sex steroids was measured by LC-MS/MS in FF collected at the five time points mentioned above. Whole genome microarray data, validated by q-PCR analysis, was used to evaluate gene expression of CYP11B1, CYP21A2, HSD11B1, HSD11B2, and NR3C1 in GCs at the same time points. The concentration of cortisol was significantly increased from a few nM at 0 h to around 100-140 nM (P ≤ 0.0001) at 32-36 h, whilst cortisone was almost constant from 0 to 17 h at a concentration of between 90 and 100 nM being significantly reduced to 25-40 nM (P ≤ 0.0001) at 32-36 h. This was paralleled by a 690-fold upregulation of HSD11B1 from 0 to 12 h increasing to a more than 20.000-fold change at 36 h. HSD11B2 was quickly downregulated 15- to 20-fold after ovulation induction. Concentrations of progesterone and 17OH-progesterone increased during the ovulatory process to high levels which in essence displaces cortisol from its binding protein CBP due to similar binding affinities. Furthermore, a significant decrease in 11-deoxycortisol expression was seen, but CYP11B1 expression was below detection limit in GCs. The study included women undergoing ovarian stimulation and results may differ from the natural cycle. More observations at each specific time point may have strengthened the conclusions. Furthermore, we have not been able to measure the actual active biological concentration of cortisol. For the first time, this study collectively evaluated the temporal pattern of cortisol and cortisone concentrations during human ovulation, rendering a physiological framework for understanding potential dysregulations in the inflammatory reaction of ovulation. This research was supported by the University Hospital of Copenhagen, Rigshospitalet, and Novo Nordisk Foundation grant number NNF21OC00700556. Interreg V ÔKS through ReproUnion (www.reprounion.eu); Region Zealand Research Foundation. The funders had no role in study design, collection of data, analyses, writing of the article, or the decision to submit it for publication. The authors have no conflicts of interest to declare. N/A.

Reviving Intervertebral Discs: Treating Degeneration Using Advanced Delivery Systems.

Intervertebral disc degeneration (IVDD) is commonly associated with many spinal problems, such as low back pain, and significantly impacts a patient's quality of life. However, current treatments for IVDD, which include conservative and surgical methods, are limited in their ability to fully address degeneration. To combat IVDD, delivery-system-based therapy has received extensive attention from researchers. These delivery systems can effectively deliver therapeutic agents for IVDD, overcoming the limitations of these agents, reducing leakage and increasing local concentration to inhibit IVDD or promote intervertebral disc (IVD) regeneration. This review first briefly introduces the structure and function of the IVD, and the related pathophysiology of IVDD. Subsequently, the roles of drug-based and bioactive-substance-based delivery systems in IVDD are highlighted. The former includes natural source drugs, nonsteroidal anti-inflammatory drugs, steroid medications, and other small molecular drugs. The latter includes chemokines, growth factors, interleukin, and platelet-rich plasma. Additionally, gene-based and cell-based delivery systems are briefly involved. Finally, the limitations and future development of the combination of therapeutic agents and delivery systems in the treatment of IVDD are discussed, providing insights for future research.

Analgesic Efficacy of Selective COX -2 Inhibitors in Post Endodontic Pain: A Systematic Review

Background: Endodontic treatment is considered a harrowing experience for patients in dental practice. COX-2 is a prime agent in inflammation and cell growth due to its relation with pro- inflammatory cytokines. Non -steroidal anti-inflammatory drugs are the most suited for treatment of post endodontic pain owing to their anti-inflammatory properties with the avoidance of cumbersome side effects such as nausea, vomiting, and respiratory problems associated with opioids. Aim: To assess the clinical efficacy of selective COX -2 inhibitors in comparison with other analgesics for managing postendodontic pain. Methods: This is an updated systematic review of studies between 2000 and 2023. Google Scholar, Web of science, Cochrane and PubMed databases were used to explore studies regarding our subject. The keywords included “selective COX-2 inhibitors; selective non- steroidal anti-inflammatory drug; endodontic pain; meloxicam; etoricoxib; metabolic complications” and were used in various combinations. In addition, original research reporting the clinical efficacy of selective COX -2 inhibitors in managing endodontic pain was evaluated. Full-text publications served as the inclusion criterion. Results: Among 100 articles were obtained, only nine met the inclusion criteria. All the studies were double-blinded randomized clinical trials. The study population was comprised of 1645 patients with endodontic pain. Conclusion: Selective COX -2 Inhibitors was an effective choice in managing endodontic pain. Celebrex was more effective than Celecoxib in relieving post-endodontic pain. When comparing Ibuprofen and Celecoxib, both were equally effective in relieving post-endodontic pain. Celecoxib was more effective than Naproxen in treating post-endodontic pain with minor gastrointestinal effects. Furthermore, etoricoxib considerably reduces post-endodontic pain with a single dosage.

Surgically Induced Scleritis Associated With Suture Hypersensitivity Following Strabismus Surgery.

A 67-year-old woman with history of mild suture hyper-sensitivity presented with localized scleritis after strabismus surgery. After infection was ruled out, the patient was prescribed topical and systemic non-steroidal anti-inflammatory drugs and systemic steroids, which led to full clinical resolution. [J Pediatr Ophthalmol Strabismus. 2024;61(1):e4-e6.].