Steroidal Anti-inflammatory Drugs Research Articles

A Comprehensive Update on the Medical Treatment of Endometriosis-Correlated Pain Clinically with Emphasis over Pharmacokinetics, Pharmacodynamics, Biochemistry, Safety and Effectiveness of Accessible Options in a Condition not having Permanent Cure Till Date: A Narrative Review

Having comprehensively reviewed the etiopathogenesis, medical, surgical therapies in addition to revival of surgery in endometriosis, in particular circumstances earlier here our main idea is to present the update of the available medical treatments, specifically in case of pain amelioration with emphasis over Pharmacokinetics, Pharmacodynamics, Biochemistry, Safety and effectiveness of currently accessible medical treatment for Endometriosis-correlated pain. Here we conducted a narrative review utilizing search engine PubMed, Google scholar, Web of science, Embase, Cochrane review library utilizing the Mesh terms like; endometriosis; medical treatments; Non Steroidal Anti Inflammatory Drugs (NSAIDS); Combined Oral contraceptives (COC); progestins; selective estrogen receptors modulators (SERM); selective Progesterone receptors modulators (SPRMs); Aromatase Inhibitors (AI); GnRH agonists; GnRH antagonists; Levonorgestrel releasing intra uterine system (LNG-IUS) from 1993 till April 2024.We found a total of 1500 articles out of which we selected 115 articles for this review. No meta-analysis was done. Thereby we have reviewed in detail pros &cons of various NSAIDS, COC’s, SERM’s, SERM’s tamoxifen Raloxifene, Bazedoxifene (BZA) fulvestrant of which are none clinically of use SPRMs, Progestins inclusive of medroxy progesterone acetate (MPA), Norethindrone acetate (NETA) and dienogest, of GnRH agonists-Leuprolide Acetate, of oral GnRH antagonist, relugolix linzagolix, elagolix, of AI’s letrozole, anastrazole, of the SPRMs mifepristone, Asoprisnil, ulipristal acetate (UPA) Vilaprisan & Lonaprisan of which till now only mifepristonel is of little use & UPA for select few where no history of liver disease of all these NSAIDS, COC’s, progestins need to be first line with them having better tolerability, efficacy and economical overall in contrast to 2nd line GnRH agonists, GnRH antagonists or AI’s. Dependent over this, key preferences are isolation of new noncontraceptive in addition to non-hormonal’ approaches for diminishing propagation of endometriosisis, thus chances of pregnancy getting feasible.

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.].

Medikamentozna terapija postoperativnog bola

Postoperative pain is a widespread and underestimated problem both in Serbia and globally. Numerous studies conducted in countries with advanced healthcare systems have shown that even in the 21st century, postoperative pain is not adequately managed. More than 80% of patients undergoing surgical procedures experience acute postoperative pain, with 75% describing it as moderate, severe, or extreme. Postoperative recovery depends on patient characteristics and factors that facilitate postoperative recovery, including the presence or absence of postoperative complications. The pharmacology of postoperative pain targets pathophysiological mechanisms such as nociception, peripheral sensitization, ectopic activity, and central sensitization. Modern pharmacological management of postoperative pain involves balanced multimodal analgesia. The principle of multimodal analgesia is based on the multifactorial nature and complexity of pain transmission pathways and is defined as the use of various medications or techniques with different mechanisms of action on the peripheral or central nervous system, which can have additive or synergistic effects. Several drug groups are involved in the multimodal approach, each with a specific pathophysiological mechanism of action. The effectiveness of opioid analgesics in treating moderate to severe postoperative pain is achieved due to the lack of a ceiling effect. However, increasing dosage leads to increased side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors (COX-2), and systemic steroids reduce the inflammatory component of surgical pain. Systemic and local anesthetics reduce the release of inflammatory mediators, interleukin-(IL-6, IL-1b, and IL-1 receptor antagonist (-1RA)). Gabapentinoids bind to the a-2-d-1 subunit of voltage-gated Ca2+ channels in the central nervous system (CNS), reducing the release of key excitatory neurotransmitters involved in nociception. a-2-agonists, such as clonidine and dexmedetomidine, modulate pain impulse transmission by activating the spinal cord's presynaptic and postsynaptic a2 receptors. Local anesthetics (e.g. lidocaine) block neural transmission by inhibiting voltage-gated Na+ channels, thus preventing the transmission of pain stimuli from the periphery to the central nervous system. N-methyl-D-aspartate receptor (NMDA receptor) antagonists, ketamine and magnesium, reduce central sensitization mechanisms.

Age is a Risk Factor for Poor Knowledge About Venous Thromboembolism Treatment.

To limit complications and optimize anticoagulant therapy, some units treating venous thrombo embolism offer a formalized educational program to patients. In our clinic we developed a patient questionnaire to target aspects of patient knowledge about their venous thromboembolism (VTE) disease and their treatment that require reinforcement. The VTE questionnaire, composed of 7 questions, has been proposed to adult patients with a diagnosis of deep venous thrombosis or pulmonary embolism requiring anticoagulant therapy for at least 3 months. Patients who completed the VTE questionnaire between March 2022 and February 2023 were included in the present retrospective study. A poor score was defined as < 5 correct answers. We investigated the factors associated with a poor score on the questionnaire, using univariable and multivariable analysis, in order to better target patients education in our unit. A total of 132 patients were included. The majority were men (56.8%) and the mean (±SD) age was 55.4 (±18.3) years. The total score was < 5 in 43.2% of patients. Those with a poor score most frequently lacked knowledge regarding the treatment; only 22.8% of patients knew of the risk of bleeding, 5.3% the contraindication of non steroidal anti inflammatory drugs NSAIDs, and 19.3% knew of the precautions related to physical activity. In multivariate analysis the only factor associated with poor VTE questionnaire score was age ≥ 55 years (OR 2.61, 95%CI 1.14-5.94). Poor knowledge of venous thrombo embolism concerned older patients and particularly treatment-related aspects.

Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA

IntroductionExposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have...

Recurrent Kikuchi Fujimoto Disease with Aseptic Meningitis and Familial Occurrence: A Rare Presentation

Recurrent Kikuchi Fujimoto Disease (KFD) with neurological manifestations is a rare entity. It usually presents with fever and cervical lymphadenopathy. Diagnosis is based on clinical grounds and typical histological findings of lymph node biopsy. Mostly KFD is self-limiting. Treatment with non-steroidal anti-inflammatory drugs or steroids may be needed in severe recurrent disease.We report a case of recurrent KFD in a 28-year-old male presenting with aseptic meningitis who has a family history of KFD.

Gastric perforation in neonates: Our experience

Background: Neonatal gastric perforation (NGP) is a life-threatening condition with a high mortality rate. It accounts for 7% of all gastrointestinal tract (GIT) perforations. The number of NGP cases has been increasing due to the rise in premature and low birth weight neonates. In this study, we present our experience with gastric perforation in neonates. Methods: This retrospective study analyzed all cases of gastric perforation in neonates that were treated at Loma Linda University Medical Center's Neonatal Intensive Care Unit (NICU) between the years 2000 and 2023. The study looked at several variables including patient demographics, birth weight, age at admission and surgery, comorbidities, use of non-steroidal anti-inflammatory drugs (NSAIDs) and steroids, and mortality rate. Results: We treated 15 patients with neonatal gastric perforation (NGP) during the study tenure. The median age at admission was 2 days, with 67% admitted within that timeframe. Surgery occurred at a median age of 5.5 days, and the median birth weight was 2.075 kg, with 26.67% below 1 kg. Males comprised 67%, and 60% had patent ductus arteriosus. Steroids were given to 46.66%, and 30-day mortality was 26.67%, with higher rates among males. Idiopathic cases were common, with notable etiologies including ischemia, necrosis, and congenital anomalies. Primary surgical repair was the main modality, and perforations occurred at various locations. Two cases had necrotizing enterocolitis. Six patients had favorable outcomes, while others experienced mild to moderate complications. Conclusion: Our research supports the idea that males have a worse outcome in terms of both prevalence and survival rates in neonatal gastric perforation (NGP) patients. However, our findings did not confirm the notion that NGP mortality risk is higher in neonates with low birth weight. We also discovered that the median time between admission and surgery in our study group was 1.5 days, emphasizing the importance of early detection of NGP in neonates. Early diagnosis can lead to better decision-making regarding treatment options and surgical intervention.

Comparative Study to Assess the Safety and Effectiveness of Allopurinol &amp; Febuxostat in Patients Diagnosed with Gout

Introduction: Gout is placed under the umbrella term ‘arthritis’ - a wide variety of joint illness and joint pain. Some types of arthritis cause inflammation in the joints, while others do not. It is the most prevalent form of inflammatory arthritis which arises due to the elevated levels of Serum Uric acid (SUA), leading to the deposition of Mono Sodium Urate (MSU) crystals in and around joints. burden of gout has risen in recent decades with a prevalence rate of &lt;1% to 6.8% and the patients with gout may have significant medical comorbidity load asociated with pain, disability and activity limitation which inturn affects the patients’ Health-related quality of life (HRQOL). Several drugs are used to treat acute attacks of gout which includes Colchicine, Non steroidal anti inflammatory drugs (NSAIDs), and Corticosteroids. Long term management of gout focuses on lowering SUA level to normal (&lt;0.36mmol/L). There are two major classes of drugs used to reduce SUA levels, Urate-lowering therapy (ULT), specifically Uricosuric drugs and Xanthine oxidase inhibitors (XOIs). Hence, it is necessary to compare the safety and effectiveness of Allopurinol and Febuxostat used in the management of gout and there is a growing need to research the impact of gout on patients’ HRQOL inorder to improve productivity and QOL of patients. Objectives: The goal of the study was to compare the safety and effectiveness of Allopurinol and Febuxostat in patients diagnosed with Gout. The study also aimed to assess the effect of these on renal profile and the study further assessed the Health-related quality of life of the patients. Methodology: This was an observational study conducted in the selected Orthopedic clinics in T. Dasarahalli, Bengaluru District for a period of 6 months by enrolling 50 subjects, based on various inclusion and exclusion criteria. The subject’s demographic details, laboratory data and responses were collected with the help of a self-designed questionnaire. ...........

The Delayed-Steroid-Strategy (DSS) for Idiopathic Granulomatous Mastitis during the COVID-19 Pandemic: A Case Series

Idiopathic granulomatous mastitis (IGM) is an inflammatory disease. It is often treated with steroids which could result in the recipient having an impaired immune defence and increases risk of getting infections. This could also hinder an adequate immune response post vaccination and render vaccines to be less effective. This was a study to assess the role and outcome of non steroidal anti-inflammatory drugs (NSAIDs) to delay corticosteroid treatment. This strategy aims to allow the patients to achieve complete vaccination with adequate post vaccination response for better COVID-19 protection prior to commencement of steroids. All three newly diagnosed patients with IGM completed their NSAIDs bridging therapy. None of them reported any worsening of disease during that time.

Evaluation of Anti-nociceptive and Anti-Inflammatory Effects of Markhamia tomentosa Cream Co-Formulated with Eucalyptus Oil

Background: Pain is a noxious, sensory, and emotional experience due to intense stimuli. Pain is intimately linked with nociception. The clinical therapies available at the moment for pain are tricyclic antidepressants, non -steroidal anti-inflammatory drugs, and opioids. There is a need to develop and investigate safer alternatives that minimise the chances of psychological or physical drug dependence and drug dose tolerance. The purpose of this research is to develop an anti-inflammatory and anti-nociceptive formulation (Markhamia tomentosa cream co-formulated with Eucalyptus oil as a permeation enhancer) and evaluate its efficacy. Methods: In this study, Markhamia tomentosa was extracted from its leaves using maceration technique. A qualitative screening of the Markhamia tomentosa ethanolic extract (EEMT) was carried out. Five emulsions (A1-A5) containing varying compositions of Markhamia tomentosa were developed, and a negative control (an emulsion that did not contain Markhamia tomentosa or Eucalyptus oil) was also developed using fusion method. The anti-inflammatory and anti-nociceptive properties of the topical creams were evaluated using mice paw-licking and xylene-induced ear oedema tests. Diclofenac and aspirin administered at 20 mg/kg and 50mg/kg orally, respectively, were used as standards. All experiments were carried out in triplicates. Results: The phytochemical investigation of the Markhamia tomentosa extract showed a marked presence of key phyto-constituents such as saponins, flavonoids, alkaloids, and terpenoids. A1 and A2 had significantly higher percentage of nociception inhibition at phase I—neurogenic and phase II—inflammatory stages compared to Diclofenac 20 mg/kg. A1 and A3 had anti-inflammatory properties more potent than Aspirin 50mg/kg. In both tests, the negative controls did not show any level of potency. All results in this investigation were expressed as mean ± S.D (n=3) and (p&lt;0.05) for all data sets. Formulation A1 had the highest concentration of EEMT. No rash, erythema, or oedema was observed in the Draize test implying that the formulations are safe for topical application. Conclusion: Markhamia tomentosa and eucalyptus oil cream showed potent anti-nociceptive and anti-inflammatory activity. Markhamia tomentosa cream co-formulated with Eucalyptus oil as a permeation enhancer can be used effectively as a non-opioid, anti-nociceptive, and anti-inflammatory cream topically for pain and its symptoms

The effect of nonsteroidal and steroid anti-inflammatory drugs on platelet activation IN VITRO

The article presents the results of a study on the effect of steroid and nonsteroidal anti-inflammatory drugs on platelets.The object of the study was plasma obtained from rat blood (n=10). Blood sampling (2.0 ml from each animal) was carried out from the tail vein into test tubes with sodium citrate. Cell elements were counted directly in blood and in platelet plasma using a MEK-6550 hematological analyzer.The ability to influence platelet activation was determined in drugs such as dexamethasone, ketarol and miloxicam, which were injected into test tubes before plasma reactivation. It was found that the drugs of these groups affect the metabolism of these cells and inhibit their ability to cause clot contraction. It was found that the strength of the negative effect on clot contraction in the steroid drug dexamethasone, which through intermediaries suppresses the activity of phospholipase-A2 and the nonsteroidal drug ketarol, which is the predominant inhibitor of cyclooxygenase of the first type, are similar. It was also found out that the drug meloxicam, which is a predominant inhibitor of cyclooxygenase of the second type, causes only a slight decrease in platelet clot contraction. The results obtained in the experiment indicate a direct positive relationship between the degree of clot contraction and the amount of thromboxane-A2, which is synthesized and released by activated platelets. It is known that the ability of platelets to accelerate and enhance regenerative processes is also directly related to their activation. Based on this, it is suggested that patients who have been prescribed plateletenriched plasma therapy should not use glucocorticoids and preparations with a high degree of selectivity to cyclooxygenase of the first type as anti-inflammatory drugs.

Possible Participation of Adenine Nucleotide Translocase ANT1 in the Cytotoxic Action of Progestins, Glucocorticoids, and Diclofenac on Tumor Cells.

A comparative analysis of the cytostatic effects of progestins (gestobutanoyl, megestrol acetate, amol, dienogest, and medroxyprogesterone acetate), glucocorticoids (hydrocortisone, dexamethasone), and diclofenac on tumor cells was carried out in order to confirm their in silico predicted probabilities experimentally. The results showed the different sensitivity of HeLa, MCF-7, Hep-2, K-562, and Wi-38 cell lines to progestins, glucocorticoids, and diclofenac. The minimum IC50 was found for progestin gestobutanoyl (GB) as 18 µM for HeLa cells, and varied from 31 to 38 µM for MCF-7, Hep-2, and K-562. Glucocorticoids and diclofenac were much less cytotoxic in the HeLa, MCF-7, and Hep-2 cell lines than progestins, with IC50 values in the range of 150-3000 μM. Myelogenous leukemia K-562 cells were the least sensitive to the action of progestins and glucocorticoids but the most sensitive to diclofenac, which showed a pronounced cytotoxic effect with an IC50 of 31 μM. As we have shown earlier, progestins can uniquely modulate MPTP opening via the binding of adenine nucleotide translocase. On this basis, we evaluated the expression of adenylate nucleotide translocase ANT1 (SLC25 A4) as a possible participant in cytotoxic action in these cell lines after 48 h incubation with drugs. The results showed that progestins differently regulated ANT1 expression in different cell lines. Gestobutanoyl had the opposite effect on ANT1 expression in the HeLa, K562, and Wi-38 cells compared with the other progestins. It increased the ANT1 expression more than twofold in the HeLa and K562 cells but had no influence on the Wi-38 cells. Glucocorticoids and diclofenac increased ANT1 expression in the Wi-38 cells and decreased it in the K562, MCF-7, and Hep-2 cells. The modulation of ANT1 expression discovered in our study can be a new explanation of the cytotoxic and cytoprotective effects of hormones, which can vary depending on the cell type. ANT isoforms in normal and cancerous cells could be a new target for steroid hormone and anti-inflammatory drug action.

Chronic Nonbacterial Osteomyelitis in Inflammatory Bowel Disease.

Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Comparative Study of Topical Steroids Vs Non steroidal Anti-Inflammatory Drugs to Control Post-Cataract Surgery Macular Edema

Purpose: To compare the efficacy of topical steroids with non-steroidal anti-inflammatory drugs in controlling post-cataract surgery macular edema. Study Design: Quasi experimental study. Place and Duration of Study: “Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan” from 1st July 2022 to 31st December 2022. Methods: Forty patients who had undergone cataract surgery were selected for this study by convenient sampling. After informed consent, patients were divided into two groups: Group S (n = 20) was given 1% prednisone eye drops for 14 days while group N (n = 20) was given 0.1% nepafenac acid eye drops for 14 days. 30 days after surgery, central macular thickness (CMT), using OCT, was assessed and documented in both groups. Data was analyzed by SPSS 21. Results: Mean age of patients was 44.02 ± 6.08 years. There were 60% (24) males and 40% females. Mean pre-operative CMT difference between two groups was statistically insignificant. Post-operative CMT was significantly lower in group N as compared to group S [243.00 ± 21.71 µm vs 223.90 ± 17.52 µm; p = 0.004]. Frequency of post-operative ME was lower in group N as compared to group S [35% (7) vs 15% (3); p = 0.144]. Conclusion: Topical eye drops containing NSAIDs and steroids are useful to control post-cataract surgery macular edema but NSAIDs drops have better efficacy in controlling post-cataract surgery macular edema.

Comparative evaluation of the analgesic activity and efficacy of the divergent non steroidal anti-inflammatory drugs in experimental model

Comparative evaluation of the analgesic activity and efficacy of the divergent non steroidal anti-inflammatory drugs in experimental model

Diagnosis, Treatment, and Outcomes of Crystalline Arthropathy in the Setting of Total Knee Arthroplasty: A Critical Analysis Review.

» Emerging evidence suggests the prevalence of crystalline arthropathy (CA) in the setting of total knee arthroplasty (TKA) is increasing, and diagnosis of CA is often intricate because of symptom overlap with other common postoperative complications such as periprosthetic joint infection (PJI). Consequently, an accurate and timely diagnosis becomes pivotal in guiding the choice of treatment.» CA includes gout and calcium pyrophosphate deposition (CPPD) disease, and accurate diagnosis in patients with prior TKA requires a multifaceted approach. The diagnosis algorithm plays a critical role in determining the appropriate treatment approach.» Management of CA typically involves a conservative strategy, encompassing the administration of nonsteroidal anti-inflammatory drugs, colchicine, and steroids, regardless of whether patients have undergone prior TKA.» There is conflicting evidence on the effect CA has on the surgical outcomes in postoperative TKA patients. While these patients may expect excellent functional outcomes and pain relief, they may be at a higher risk of complications such as infections, medical complications, and revision procedures.» Additional research is required to fully comprehend the impact of CA on postoperative TKA outcomes and to establish effective strategies for enhancing patient care and optimizing long-term joint function.

HDAC3 Is Required for Pathognomonic Features of Langerhans Cell Histiocytes

Langerhans cell histiocytosis (LCH) is a pediatric inflammatory myeloid neoplasm that develops due to dysregulated myeloid cell development. BRAFV600E is the most common disease-causing mutation and constitutively activates the mitogen-activated protein kinase (MAPK) pathway in myeloid lineage precursors leading to the key pathognomonic features of LCH cells. Enhanced myelopoiesis and reduced CCR7 expression promote accumulation of LCH cells in tissues by simultaneously increasing the production of pathological DCs and preventing tissue egress. Furthermore, LCH cells acquire an oncogene induced senescence-associated secretory phenotype (SASP) that depends on mammalian target of rapamycin (mTOR), which is hallmarked by increased expression of anti-apoptotic proteins, inflammatory cytokines, and matrix metalloproteinases enhancing survival of LCH cells and promoting recruitment of inflammatory immune cells forming characteristic granulomatous lesions. These pathognomonic features result in the accumulation of LCH cells in any organ causing a wide range of clinical symptoms. 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. New therapeutic approaches are urgently needed. Here, using multiple genetic mouse models, we show that normal epidermal Langerhans cells (LCs) depend on HDAC3 for their development, differentiation, and survival. Integrative RNA and chromatin-immunoprecipitation-sequencing show loss of HDAC3 abrogates the expression of master regulators of myeloid development and function including Csf1r, Spi1, Id2 and Runx3. LCH cells are also known to rely on Csf1r and Pu.1 for their development and homeostasis, thus we hypothesized that LCH cells similarly rely on HDAC3 for their development and survival. CD11c Cre LSL-BRAFV600E ( BRAFV600E CD11c) mice develop severe multifocal LCH with pronounced lesion development in their livers and lungs, hepatosplenomegaly, and a reduced lifespan due to the accumulation of pathological dendritic cells (DCs). We generated BRAFV600E CD11c HDAC3 fl/fl ( BRAFV600E HD3KO) mice, which produce pathological DCs that simultaneously express BRAFV600E and harbor a conditional deletion in the deacetylase domain of HDAC3. Compared to BRAFV600E CD11c mice, BRAFV600E HD3KO mice exhibited significantly less hepatosplenomegaly, reduced lesional burden (Panel A), attenuated disease progression, and improved survival indicating reduced LCH disease burden. Compared to BRAFV600E CD11c flow cytometry showed BRAFV600E HD3KO had reduced numbers of LCH cells in lungs and livers linking improved disease outcomes to abrogation of pathological DCs. Flow cytometric analysis of circulating myeloid cells further found reduced frequency of circulating DCs and DC progenitors, indicating that a lack of HDAC3 activity prevents the development of pathological DCs (Panel B). LCH-like cells can be generated in vitro by culturing BRAFV600E CD11c bone marrow with granulocyte-monocyte colony-stimulating factor (GM-CSF), providing a valuable drug screening tool. Treating 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 decreased mTOR activity), showing that pharmacological inhibition of HDAC3 may prove therapeutically efficacious by abrogating pathognomonic features of LCH cells. Together, our findings identify HDAC3 as a critical epigenetic regulator for both healthy and pathological LCs. We further show, HDAC3 is required for multiple pathognomonic features of LCH cells and could be a promising drug target. Furthermore, if HDAC3 is required for the development of pathological DC and DC progenitors, HDAC3 blockade would address a great need in treatment of patients with LCH.

Ethological and pathophysiolocal justification of the calcium gluconate usage for the treatment of calves with bronchopneumonia

A prominent feature of the pathogenesis of bronchopneumonia in calves is the development of an inflammatory reaction that negatively affects the structure (consolidation) and function of lung tissue. Due to the spread of the inflammatory reaction, structural and functional changes can become irreversible. The purpose of the study was to compare the effectiveness of calcium gluconate and the nonsteroidal anti–inflammatory drug ketoprofen in the treatment of calves with bronchopneumonia. The research was conducted on the basis of a dairy farm with an average annual yield of 8,500 kg of milk per cow and a scientific laboratory of the Department of Normal and Pathological Physiology of Animals of Bilotserkivsky Bila Tserkva National University. Sick animals aged 3–4.5 months were divided into two groups, control (16 heads) and experimental (12 heads). All sick calves were prescribed antibiotic therapy using the preparation Clamoxan (BioTestLab). Calves of the control group were additionally prescribed the non–steroidal anti–inflammatory drug Kefen (Merial, France), and calcium gluconate (UkrZooVet–organisation ) was prescribed to the calves of the experimental group. The course of bronchopneumonia in calves is characterized by the development of characteristic clinical signs (depressed general condition, tachypnea, tachycardia, cough, secretion of mucus from the nasal passages), minor leukocytosis (13.38±0.46) and signs of dehydration, which is evidenced by relatively high indicators of hematocrit (45.47±2.18%) and total protein (61.14±2.22 g/l). The dynamics of clinical and laboratory indicators were similar in sick calves of both groups. The pathogenetic effect and anti–inflammatory activity are equally effective in both studied drugs: caffeine and calcium gluconate. In calves with bronchopneumonia, a 3–10–fold delay in the conditioned feeding reflex was established. The normalization of clinical and laboratory indicators was accompanied by the restoration of the duration of the implementation of the conditioned feeding reflex, which allows recommending the use of the studied ethological indicators for monitoring the course of bronchopneumonia in calves. We consider the study of the effectiveness of calcium gluconate preparations in other inflammatory pathologies in animals and the extension of indications to the use of ethological indicators to monitor the course of diseases in domestic animals to be a promising direction for further research. Key words: calves, bronchopneumonia, treatment, calcium gluconate, behavior.

EOLP-01. TREATMENT OF HEADACHES IN GLIOMA: A SYSTEMATIC REVIEW OF CURRENT PRACTICES AND FUTURE DIRECTIONS

Abstract INTRODUCTION Headaches are one of the most common morbidities in glioma reported in 36 to 62% of patients along the course of their disease. Gliomas represent 27% of primary CNS neoplasms and accounted for an average annual age-adjusted incidence rate of 6.0 per 100 000 population according to data collected between 2010 and 2014. OBJECTIVES: The goal of this review was to evaluate current treatment options for glioma patients presenting with headaches and identify current headache treatment methods that could play a role in those patients. METHODS A systematic review of studies involving headaches in patients with gliomas was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search was conducted on PubMed, Ovid Medline, and Embase databases through January 3rd, 2023, with the following search terms: (analgesic OR anti-inflammatory OR prophylaxis OR steroids) AND (headache) AND (glioma or glioblastoma) AND (treatment). For each patient, we extracted: the therapy used, its outcome, and any side effects. RESULTS There were 11 out of 195 articles included in the review. For the articles that were fully reviewed (n =93), the majority of the exclusions 49% (n=40) were due to lack treatment method for patients’ headache. The most reported treatment options were Analgesics (n=211), steroids (dexamethasone, n=116), Surgical resection (n=2), and CGRP inhibitor (Fremanezumab, n=1). Most of the included studies 55% (n=6) only discussed headache treatment in 1 patient with 67% (n=4) of them being case report highlighting the lack of evidence covering this topic. CONCLUSION Headache treatment in patients with gliomas is an area of neuro-oncology with much to be learned. There is a need to further study the etiology of headaches in order to provide effective treatment plans that could improve the quality of life in this patient population.

Considering the Promise of Vamorolone for Treating Duchenne Muscular Dystrophy.

This commentary provides an independent consideration of data related to the drug vamorolone (VBP15) as an alternative steroid proposed for treatment of Duchenne muscular dystrophy (DMD). Glucocorticoids such as prednisone and deflazacort have powerful anti-inflammatory benefits and are the standard of care for DMD, but their long-term use can result in severe adverse side effects; thus, vamorolone was designed as a unique dissociative steroidal anti-inflammatory drug, to retain efficacy and minimise these adverse effects. Extensive clinical trials (ongoing) have investigated the use of vamorolone for DMD, with two trials also for limb-girdle muscular dystrophies including dysferlinopathy (current), plus a variety of pre-clinical trials published. Vamorolone looks very promising, with similar efficacy and some reduced adverse effects (e.g., related to height) compared with other glucocorticoids, specifically prednisone/prednisolone, although it has not yet been directly compared with deflazacort. Of particular interest to clarify is the optimal clinical dose and other aspects of vamorolone that are proposed to provide additional benefits for membranes of dystrophic muscle: to stabilise and protect the sarcolemma from damage and enhance repair. The use of vamorolone (and other glucocorticoids) needs to be evaluated in terms of overall long-term efficacy and cost, and also in comparison with many candidate non-steroidal drugs with anti-inflammatory and other benefits for DMD.