Anti-inflammatory Research Articles

Intake of dietary flavonoids in relation to overactive bladder among U.S. adults: a nutritional strategy for improving urinary health.

The increasing influence of overactive bladder (OAB) on physical as well as mental health of individuals is becoming more pronounced annually, as evidenced by the urge urinary incontinence and nocturia. Symptoms in OAB patients may be influenced by inflammation and oxidative stress. Flavonoids are recognized as significant anti-inflammatory and antioxidant agents, which are commonly available in fruits, tea, vegetables, etc. Previous research has demonstrated the therapeutic potential of flavonoids and their subclasses in treating inflammation, and oxidative stress. Despite this, there remains a paucity of research exploring the potential correlation between flavonoid consumption, specifically within distinct subclasses, and OAB. Thus, our study aims to investigate the relationship between flavonoid intake and OAB to identify possible dietary interventions for OAB management. We utilized the survey data from the National Health and Nutrition Examination Survey (NHANES) and the USDA Food and Nutrient Database for Dietary Studies (FNDDS) to investigate the relationship between dietary intake of total and subclass flavonoids and the risk of OAB based on 13,063 qualified American adults. The dietary flavonoid intake was estimated from two 24-h dietary recalls. Weighted multivariate logistic regression model, quantile-based g-computation, restricted cubic spline model, and stratified analysis were used to explore the association between flavonoid intake and OAB, respectively. The participants diagnosed with OAB exhibited a higher percentage of being female, older, Non-Hispanic Black, unmarried, former drinkers, having a lower annual household income, lower poverty to income ratio, lower educational attainment, and a higher likelihood of being obese and smokers. Upon adjusting for confounding factors, the weighted logistic regression models revealed that the third quartile of consumption of anthocyanidin and the second quartile of consumption of flavone were significantly associated with the reduced odds of OAB, while total flavonoid consumption did not show a significant correlation with the risk of OAB. The quantile-based g-computation model indicated that flavone, anthocyanidin and flavonol were the primary contributors to the observed negative correlation. Furthermore, the restricted cubic spline models demonstrated a J-shaped non-linear exposure-response association between anthocyanidin intake and the risk of OAB (P nonlinear = 0.00164). The stratified and interaction analyses revealed that the relationship between anthocyanidin intake and the risk of OAB was significantly influenced by age (P interaction = 0.01) and education level (P interaction = 0.01), while the relationship between flavone intake and the risk of OAB was found to vary by race (P interaction = 0.02) and duration of physical activity (P interaction = 0.05). Our research suggests that consuming a diet rich in flavonoid subclass anthocyanidin and flavone is associated with a reduced risk of OAB, potentially offering clinical significance in the prevention of OAB development. This underscores the importance of dietary adjustments in the management of OAB symptoms.

Deprescribing NSAIDs: The Potential Role of Community Pharmacists

Non-steroidal anti-inflammatory drugs (NSAIDs) are largely used for controlling various pain conditions and are widely available in community pharmacies, with and without prescription. Despite their effectiveness, NSAIDs can pose significant risks due to potential side effects and drug interactions, particularly in polypharmacy and comorbidity contexts and for vulnerable users. This study investigated whether and how NSAID deprescribing can be conducted at the community pharmacy level by assessing pharmacists’ confidence, attitudes, and potential barriers and facilitators. Additionally, we aimed to identify any deprescribing guidelines that pharmacists could use. A literature search and a cross-sectional digital questionnaire targeting community pharmacists in Norway were conducted. Results showed that study participants (N = 73) feel confident in identifying needs for deprescribing NSAIDs but barriers such as time constraints, lack of financial compensation, and communication challenges were noted. Participants reported positive attitudes toward deprescribing but highlighted a need for better guidelines and training. This study highlights a gap in specific guidelines for deprescribing NSAIDs and a potential for enhancing pharmacists’ roles in the deprescribing process, for example, through training and improved financial incentives. Further research is encouraged to develop concrete strategies for an effective implementation where community pharmacists can be involved in the deprescribing of NSAIDs.

Estimating the economic effect of harm associated with high risk prescribing of oral non-steroidal anti-inflammatory drugs in England: population based cohort and economic modelling study

ObjectivesTo quantify prevalence, harms, and NHS costs in England of problematic oral non-steroidal anti-inflammatory drug (NSAID) prescribing in high risk groups.DesignPopulation based cohort and economic modelling study.SettingEconomic models estimating patient...

Exhausted Lag-3+ CD4+ T cells are increased in pediatric Inflammatory Bowel Disease.

T cells are one of the main drivers of inflammatory bowel diseases (IBD). Infliximab (IFX) is used in the treatment of IBD as an anti-inflammatory drug to induce remission by neutralizing TNFα. We determined the individual chemokine/homing receptor and cytokine profile in pediatric IBD patients before and during IFX therapy to identify predictive biomarkers for therapy success. Peripheral blood CD4+ cells from pediatric patients with IBD were immunomagnetically isolated and either directly analyzed by FACS for cell distribution and chemokine/homing receptor expression or evaluated for cytokine production after in-vitro-stimulation. 21 responders (RS) and 21 non-responders (NRS) were recruited. Before IFX therapy, flow cytometry revealed decreased percentages of naïve conventional T cells in pediatric IBD patients. The proportions of CD62-L+ T cells were decreased in both CD and UC therapy responders. The cytokine profile of T cells was highly altered in IBD patients compared to healthy controls (HC). During IFX therapy, the frequencies of conventional memory and regulatory memory T cells expanded in both cohorts. IFX response was marked by a decrease of α4β7+ and IFNγ+ memory T cells in both CD and UC. In contrast, frequencies of Lag-3+ T cells proved to be significantly increased in NRS. These observations were irrespective of the underlying disease. T cells of pediatric IBD patients display an activated and rather Th1/Th17 shifted phenotype The increased expression of the checkpoint molecule Lag-3 on T cells of NRS resembles a more exhausted phenotype than in RS and HC which appeared to be a relevant predictive marker for therapy failure.

A single, maximal dose of celecoxib, ibuprofen, or flurbiprofen does not reduce the muscle signalling response to plyometric exercise in young healthy adults.

Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise. This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200mg), IBU (800mg), FLU (100mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05. We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05). A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.

Axial spondyloarthritis—current aspects

Axial spondyloarthritis (axSpA) is a frequent inflammatory rheumatic disease mainly affecting the axial skeleton causing inflammatory back pain. If chronic inflammation persists new bone formation may occur possibly leading to irreversible spinal stiffness. The disease has a strong genetic background with HLA-B27 as the major factor. For diagnostic purposes, imaging is of critical importance—especially conventional radiography and magnetic resonance imaging (MRI). While the former has advantages in the detection of bony changes such as the syndesmophytes, MRI is used to detect axial inflammation but also erosions in the sacroiliac joint. Treatment follows the treat-to-target strategy starting with non-steroidal anti-inflammatory drugs (NSAIDs) in the first line, and later, if high disease activity persists, therapy with biologic disease modifying anti-rheumatic drugs (bDMARDs) is according to international recommendations indicated. For the treatment of axSpA, important targets such as tumor necrosis factor alpha (TNFα) and interleukin (IL)-17 have been identified, and several of their inhibitors (i) including some biosimilars for the former have been approved. Recently, also inhibition of Janus kinases was shown to be efficacious. There is evidence that long term inhibition of inflammation with TNFi can reduce bone formation.

Evaluation of the Treatment Efficacy of Bone Traction Combined with Small Splint External Fixation for Tibiofibular Fractures

Objective: To evaluate the clinical efficacy of bone traction combined with small splint external fixation in treating tibiofibular fractures. Methods: 378 patients with tibiofibular fractures who were treated in the Department of Orthopedics of our hospital from January 2019 to January 2023 were selected as study subjects. According to the specific conditions of the patients and the indications for surgery, they were divided into the observation group (bone traction combined with small splint external fixation) and the control group (conventional plaster fixation), with 189 cases in each group. Both groups of patients immobilized the affected limb as instructed by their doctors and were treated with oral anti-inflammatory and pain-relieving medications. The healing of the fractures was monitored using imaging techniques such as X-rays, computed tomography scans, and magnetic resonance imaging, while postoperative complications were also recorded. Results: The incidence rate of non-healing in the control group (7.41%) was significantly higher than that in the observation group (1.06%) (P &lt; 0.05); the complications in the observation group were mainly three cases of limb deformity, three cases of pressure sores, and four cases of skin necrosis, with a total of 10 cases and an incidence rate of 5.29%; while in the control group, there were three cases of fracture nonunion, nine cases of skin necrosis, seven cases of pressure sores, and three cases of limb deformity, with a total of 22 cases and an incidence rate of 5.29%, the difference between the two groups was statistically significant (χ2 = 4.916, P = 0.027). Conclusion: Bone traction combined with small splint external fixation has shown remarkable efficacy in the treatment of tibiofibular fractures, which can not only quickly stabilize the fracture end, reduce pain, and promote fracture healing, but also reduce the occurrence of complications and shorten the treatment period.

Targeting inflammation through inhibition of COX-2 by substituted 4-thiazolidinone analogues: in-vitro, in-vivo and in-silico studies

The prolonged or chronic use of anti-inflammatory agents that are being used clinically is highly unsafe. This flaw or disadvantage has motivated scientists to create new heterocyclic compounds with minimal toxicity and possible anti-inflammatory effects. The design and synthesis of ten 4-thiazolidinone containing pyridine derivatives are reported in the current study article. After conducting an in vitro study, it was discovered that they had anti-inflammatory potential. The compounds were analysed for the COX-2 inhibitory activity. VSA6 found to be most potent candidate, screened further. Also. VSA6 emerged as most potent inhibitor against COX-2 with IC50 of 17.32±1.06µM. Further the antioxidant potential of the candidates was analysed in-vitro data suggested that, synthesized compounds showed the anti-oxidant activity with VSA6, and VSA10 being remarkably potent compounds with IC50 values of 34.39 and 37.32 µM respectively. In RAW 264.7 cells, VSA6 demonstrated dose-dependent suppression of mitochondrial superoxide generation at concentrations of 10 and 20 µM. It decreased intracellular expression of the LPS induced reactive oxygen species; mitochondria induced superoxide, MAPK7 and NF-κβ. The molecule also diminished the expression of extracellular of TNF-α, IL-6, MAPK7, NF-κβ and COX-2 and enhanced the expression of anti-oxidant enzymes i.e. GSH and SOD2. To further validate the COX-2 inhibitory activity of VSA6, gene and protein level expression study was conducted; VSA6 decreased the LPS induced COX-2 expression analysed by flow cytometer, immunofluorescence assay and RT-qPCR. The most efficient compound showed encouraging anti-inflammatory action when tested for in vivo anti-inflammatory potential in carrageenan induced model. To find out how this developed compound interacted with COX-2, an anti-inflammatory target, molecular docking analysis was used. According to the findings, the majority of the compounds could make good candidates for the creation of brand-new anti-inflammatory drugs.

TNF-alpha blockade in Primary Chronic Non-Bacterial Osteomyelitis of the Mandible.

Primary chronic Non-Bacterial Osteomyelitis of the jaw is a rare auto-inflammatory disease of unknown aetiology that bears pathophysiological resemblance to both the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome in adults and chronic recurrent multifocal osteomyelitis (CRMO) in children. Both SAPHO and CRMO respond to TNF-alpha blockade. Previously reported treatment regimens in CNOM including non-steroidal anti-inflammatory drugs, corticosteroids, antibiotics, anti-resorptive therapy, and surgery all bear disappointing results. TNF- α blockade is suggested as a treatment option by some experts but this is not backed by any clinical data.We sought to retrospectively and exhaustively report our experience of anti-TNF alpha therapy in refractory CNOM. Fifteen patients with refractory CNOM and high disease burden were referred to our centre. TNF- α blockade was attempted in 10 cases, given its efficacy in neighbouring diseases, its good tolerance profile and failure of previous treatment strategiesWe herein retrospectively report detailed outcomes for all patients having received anti-TNF alpha therapy for this indication in our centre. TNF-α-targeting therapy resulted in a rapid and sustained remission in a majority of patients with CNOM, without serious adverse events. Treatment was tapered and stopped without relapse in some patients despite a refractory course of several years. Male sex seems to be associated with a poorer outcome. Our results suggest that blocking TNF-α is efficient and safe in CNOM.

Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative disease that afflicts more than 250 million people worldwide, impairing their mobility and quality of life. However, conventional drug therapy is palliative. Exosomes (Exo), although with the potential to fundamentally repair cartilage, face challenges in their efficient enrichment and delivery. In this study, we developed magnetic polysaccharide hydrogel particles as microcarriers for synergistic therapy of OA. The microcarriers were composed of modified natural polysaccharides, hyaluronic acid (HAMA), and chondroitin sulfate (CSMA), and were generated from microfluidic electrospray in combination with a cryogelation process. Magnetic nanoparticles with spiny structures capable of capturing stem cell Exo were encapsulated within the microcarriers together with an anti-inflammatory drug diclofenac sodium (DS). The released DS and Exo from the microcarriers had a synergistic effect in alleviating the OA symptoms and promoting cartilage repair. The in vitro and in vivo results demonstrated the excellent performance of the microcarrier for OA treatment. We believe this work has potential for Exo therapy of OA and other related diseases.

Breakthrough Opportunities of Nanotheranostics in Psoriasis: From Pathogenesis to Management Strategy.

In this paper, we have discussed recent advances in our understanding of the aetiology of psoriasis, particularly as they relate to aryl hydrocarbon receptors in DCs, Langerhans cells, macrophages, signal transducer and activator of transcription 3 pathways, and dermal vascular endothelial cells. Here, we have shown that the ability to target specific cellular and molecular components of psoriasis pathogenesis with nanoscale precision using phos-phodiesterase 4 inhibitors represents a transformative opportunity to address the complex nature of this dermatological condition. In this review, we have examined the molecular mechanisms behind the pathogenic features of psoriasis and new treatments being tested in clinical settings. There is research being done on new treatments created in the last ten years. This field highlights the advantages of nan-otechnological technologies as cutting-edge candidates for drug delivery systems in psoriasis and other inflammatory chronic skin disorders. Future Developments: Nanotechnology-based treatments currently under study show good effi-cacy and low side effect profiles. However, long-term prospective trials are required to demon-strate long-term safety and effectiveness. Phosphodiesterase inhibitors, Janus kinase inhibitors, nonsteroidal anti-inflammatory drugs, combinations of vitamin D3 derivatives and corticoster-oids, and coal tar formulations are some of the newer topical treatments for psoriasis. The psoriasis treatment continues to involve conventional medications (i.e., medi-cines that are generally acknowledged as either normal therapy or outdated remedies), whether used topically or orally. Nonetheless, we are starting to see initiatives to create pharmaceuticals and biosimilars with better therapeutic results, fewer side effects, and greater efficacy.

Pain Management of Refractory Hidradenitis Suppurativa: Case Report

Background: Hidradenitis suppurativa (HS) is a chronic, relapsing, and painful inflammatory condition of the skin. Pain in HS is one of the most common symptoms and has a devastating effect on quality of life. Here, we present a unique case of a patient with HS and pain management guidelines used to treat her condition. Case Report: This is a 42-year-old woman with a history of HS, hypertension, depression who presented with one month of pain in her groin crease, vulva, and rectum. She was recently discharged from the hospital for HS superinfection. She was treated with intravenous and oral antibiotics. She previously tried treatment with acetaminophen, lidocaine 2% jelly, gabapentin 400 mg TID, oxycodone, dilaudid, adalimumab, infliximab, topical clindamycin, intralesional steroid injections, and doxycycline. The pain management specialist recommended continuing treatment with gabapentin 400 mg TID and titrate to 600 mg TID as tolerated, and to follow up with the dermatology team to restart infliximab. Discussion: This case demonstrates a complicated, refractory HS condition that necessitates first, second, and third line treatment modalities. Pain control in HS starts by having best control of the underlying disease. The United States and Canadian Hidradenitis Suppurativa Foundations clinical guidelines suggest acute pain management should include topical analgesics (ie, lidocaine), oral acetaminophen, and oral nonsteroidal anti-inflammatory drugs. Chronic pain management should focus on a multidisciplinary approach. Clinical guidelines recommend escalating oral analgesics for pain that doesn’t respond to first-line agents. Opiate use should follow the World Health Organization pain ladder of tramadol, codeine, hydrocodone, and morphine. Neuropathic pain can be treated with pregabalin or gabapentin, titrated as tolerated by patients. Chronic HS lesions can be treated with wide local scalpel, CO2, or electrosurgical excision, and recurrent nodules can be deroofed or excised. Superior hypogastric plexus block and/or ganglion impar block can be considered for refractory cases. Conclusion: HS is an extremely painful condition severely affecting quality of life. Adequate pain management is vital, and a stepwise approach is recommended.

Nonsteroidal anti-inflammatory drugs for analgesia in intensive care units: a survey of Canadian critical care physicians.

Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs). Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing. We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care. In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.

Discovery of 3-bromoflavone derivative D5 as a novel TLR4-MD2 antagonist for treatment of acute lung injury and sepsis

The aberrant activation of immune responses mediated by Toll-like receptor 4 (TLR4) generates severe inflammatory syndromes such as acute lung injury (ALI) and sepsis, thus targeting TLR4 is attractive as a potential pharmacological therapy for these diseases. The aim of this study is to develop a novel structural TLR4 inhibitor for the treatment of ALI and sepsis. Herein, we designed and synthesized a new series of 3-bromoflavone derivatives by screening and incorporating molecular docking. Their anti-inflammatory effects were evaluated by ELISA in macrophages and compound D5 was identified as the most potential anti-inflammatory candidate. Compound D5 inhibited lipopolysaccharide (LPS)-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in RAW264.7 cells with IC50 values of 0.215 and 4.211 µM, respectively. Immunoprecipitation, SPR, and immunoblotting demonstrated that D5 targeted TLR4-MD2 complex and competitively inhibited the binding of LPS to TLR4-MD2, resulting in inhibition of NF-κB and MAPK signaling pathways. In vivo administration of D5 significantly ameliorated various pathological indexes in LPS-induced ALI model and promoted the survival rate in LPS-induced septic model. Overall, our studies have identified a 3-bromoflavone derivative, D5, as a potent TLR4-MD2 antagonist and represented a very promising starting point for the development of anti-inflammatory agents for the treatment of ALI and sepsis.

Systemic aging fuels heart failure: Molecular mechanisms and therapeutic avenues.

Systemic aging influences various physiological processes and contributes to structural and functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a decline in left ventricular diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, elevating susceptibility to chronic heart failure (HF) in the elderly. Age-related cardiac dysfunction stems from prolonged exposure to genomic, epigenetic, oxidative, autophagic, inflammatory and regenerative stresses, along with the accumulation of senescent cells. Concurrently, age-related structural and functional changes in the vascular system, attributed to endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress and inflammation, impose additional strain on the heart. Dysregulated mechanosignalling and impaired nitric oxide signalling play critical roles in the age-related vascular dysfunction associated with HF. Metabolic aging drives intricate shifts in glucose and lipid metabolism, leading to insulin resistance, mitochondrial dysfunction and lipid accumulation within cardiomyocytes. These alterations contribute to cardiac hypertrophy, fibrosis and impaired contractility, ultimately propelling HF. Systemic low-grade chronic inflammation, in conjunction with the senescence-associated secretory phenotype, aggravates cardiac dysfunction with age by promoting immune cell infiltration into the myocardium, fostering HF. This is further exacerbated by age-related comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes and chronic kidney disease (CKD). CAD and atherosclerosis induce myocardial ischaemia and adverse remodelling, while hypertension contributes to cardiac hypertrophy and fibrosis. Obesity-associated insulin resistance, inflammation and dyslipidaemia create a profibrotic cardiac environment, whereas diabetes-related metabolic disturbances further impair cardiac function. CKD-related fluid overload, electrolyte imbalances and uraemic toxins exacerbate HF through systemic inflammation and neurohormonal renin-angiotensin-aldosterone system (RAAS) activation. Recognizing aging as a modifiable process has opened avenues to target systemic aging in HF through both lifestyle interventions and therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological cardiac remodelling in the elderly by countering processes linked to age-related chronic HF, such as mitochondrial dysfunction, inflammation, senescence and declining cardiomyocyte regeneration. Dietary interventions such as plant-based and ketogenic diets, caloric restriction and macronutrient supplementation are instrumental in maintaining energy balance, reducing adiposity and addressing micronutrient and macronutrient imbalances associated with age-related HF. Therapeutic advancements targeting systemic aging in HF are underway. Key approaches include senomorphics and senolytics to limit senescence, antioxidants targeting mitochondrial stress, anti-inflammatory drugs like interleukin (IL)-1β inhibitors, metabolic rejuvenators such as nicotinamide riboside, resveratrol and sirtuin (SIRT) activators and autophagy enhancers like metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors, all of which offer potential for preserving cardiac function and alleviating the age-related HF burden.

Acute and Preventive Treatment of COVID-19-Related Headache: A Series of 100 Patients.

To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.

Modern view on the effectiveness and safety of non-steroidal anti-inflammatory drugs

Issues of the effectiveness and safety of drugs remain relevant and controversial. The benefits and risks of drug therapy are two facets of one whole, called pharmacotherapy, which can have undesirable side and even negatively outweigh the benefits. The effectiveness and safety of drugs must be studied comprehensively because new effects of drugs may be discovered and new mechanisms for unregistered indications may be revealed. Moreover, a deep understanding of adverse drug reactions will allow for the accurate prescription of drugs and proper medical supervision of therapy. Nonsteroidal anti-inflammatory drugs are over-the-counter drugs perceived by patients as safe and do not require a doctor’s prescription, which can cause dangerous drug reactions, particularly when used uncontrollably. The review presents literature data from studies on the effectiveness of nonsteroidal anti-inflammatory drugs and current data on new therapeutic effects of individual drugs, risks of adverse reactions, their mechanisms, and treatment methods.

Ribbing disease of the femur: a rare entity.

Ribbing disease is a rare benign bone dysplasia characterized by progressive cortical thickening of the diaphyses of long bones in adult patients. The literature provides limited insight into its natural radiological progression and anatomical distribution. Single-bone involvement is particularly uncommon, with prior cases exclusively affecting the tibia. This case report outlines the unique presentation of Ribbing disease in a 20-year-old male, localized to the left femur. The patient's history revealed intermittent left thigh pain persisting for more than 2 years, with no identifiable triggers or relief factors. Early radiographic imaging revealed no significant abnormalities, but subsequent imaging, conducted 1 year after the initial presentation, revealed focal fusiform widening and cortical thickening of the mid-diaphysis of the left femur. MRI further revealed circumferential cortical thickening with bone marrow edema, corroborated by CT, which revealed cortical thickening with near-complete obliteration of the intramedullary cavity. The patient was managed with nonsteroidal anti-inflammatory drugs and activity modifications. Misinterpretation of the radiographic findings of the osteoid osteoma led the patient to undergo radiofrequency ablation. This case highlights the challenges in diagnosing Ribbing disease and emphasizes the importance of considering it in the differential diagnosis of chronic limb pain. Continued reporting of cases contributes to enhancing our understanding and management of this rare skeletal dysplasia.

N,N-Disubstituted 4-sulfamoylbenzoic Cid Derivatives as Inhibitors of Cytosolic Phospholipase A2α: Synthesis, Aqueous Solubility, and Activity in a Vesicle and a Whole Blood Assay.

Cytosolic phospholipase A2α (cPLA2α) is the key enzyme that initiates the arachidonic acid cascade through which proinflammatory lipid mediators can be formed. Therefore, cPLA2α is considered an interesting target for the development of anti-inflammatory drugs. Although several effective inhibitors of the enzyme have been developed, none of them has yet reached clinical application. Recently, we have prepared new 4-sulfamoylbenzoic acid derivatives based on a cPLA2α inhibitor found in a ligand-based virtual screening. The most effective of these compounds were now subjected to further variations in which the substitution pattern on the sulfamoyl nitrogen atom was changed. The new compounds were tested in vitro in a vesicle assay for cPLA2α inhibition as well as for their water solubility, metabolic stability, and selectivity towards related enzymes. In addition, they were evaluated ex vivo in a whole blood assay in which metabolites of the arachidonic acid cascade formed after activation of cPLA2α were quantified using a combined online dilution/online solid phase extraction HPLC-MS method. Inhibitors with submicromolar inhibitory in vitro potency were found with favourable water solubility and selectivity. However, their efficacy did not match that of the highly effective, known, structurally related cPLA2a inhibitor giripladib, which was also tested as a reference. One advantage of some of the new compounds compared to giripladib was their significantly improved water solubility. When analyzing the substances in the ex vivo whole blood assay, it was found that the obtained inhibition data correlated better with the in vivo results when the phorbol ester 12-Otetradecanoylphorbol-13-acetate was used for activation of the enzyme in the blood cells instead of the calcium ionophore A23187. New compounds with good activity towards cPLA2α and reasonable physicochemical properties were identified. Overall, the results obtained could be helpful in the development of clinically applicable inhibitors of this enzyme.

Effect of tannic acid on adiponectin and gonads in male Brandt’s voles (Lasiopodomys brandtii)

Adiponectin regulates steroid production and influences gonadal development. This study examined the effects of tannic acid (TA) on the adiponectin levels and gonads of male Brandt’s voles. Male Brandt’s voles aged 90 d were randomly separated into three groups: a control group (provided distilled water), a group given 600 mg∙kg-1 TA, and a group that received 1200 mg∙kg-1 TA (continuous gavage for 18 d). In this study, we examined the effects of TA on the adiponectin, antioxidant, and inflammatory levels in the testes. Furthermore, we examined the expression of important regulatory elements that influence adiponectin expression and glucose utilisation. In addition, the body weight, reproductive organ weight, and testicular shape were assessed. Our study observed that TA treatment increased serum adiponectin levels, DsbA-L and Ero1-Lα transcription levels, and AdipoR1, AMPK, GLUT1, and MCT4 expression levels in testicular tissue. TA enhanced pyruvate and lactic acid levels in the testicular tissue, boosted catalase activity, and reduced MDA concentrations. TA reduced the release of inflammatory factors in the testicular tissues of male Brandt’s voles. TA increased the inner diameter of the seminiferous tubules. In conclusion, TA appears to stimulate adiponectin secretion and gonadal growth in male Brandt’s voles while acting as an antioxidant and anti-inflammatory agent.