Nonsteroidal Research Articles

An eco-friendly strategy for emerging contaminants removal in water: Study of the adsorption properties and kinetics of self-polymerized PHEMA in green solvents

Water contaminants severely affect human health and aquatic ecosystems, and adsorption poses an economic, available, and feasible technology for remediation that needs to be accompanied by eco-friendly and sustainable materials. This study proposes an eco-friendly strategy for removing emerging contaminants using polyhydroxyethyl methacrylate polymers synthesized by self-polymerization with hydrophilic first-generation deep eutectic solvents. The polymers were characterized using structural and physical characterization techniques and their adsorption capacity against four emerging contaminants: a non-steroidal anti-inflammatory drug, an antibiotic, a pesticide, and a non-ionic surfactant. The experimental results showed high adsorption capacity for the urea: choline chloride-derived polymer with 6.21, 7.19, 6.01, and 6.99 mg⋅g-1 for paracetamol, ciprofloxacin, glyphosate, and triton X-100, respectively; these values are comparable to those obtained for similar systems. Kinetic, isothermal, and thermodynamics were also studied using various mathematical models to understand the adsorption mechanism, further complemented by DFT analysis. Chemisorption was found to be the primary mechanism by exothermic and ordered processes, which is thermodynamically favored. The study demonstrated for the first-time the effectiveness of self-polymerized PHEMA without chemical modification as a reusable adsorbent material and its ability to remove different types of emerging contaminants, thereby offering a promising solution for water treatment in environmental science.

Response of crop seed germination and primary root elongation to a binary mixture of diclofenac and naproxen.

Non-steroidal anti-inflammatory drugs, diclofenac (DCF) and naproxen (NPX), represent a group of environmental contaminants often detected in various water and soil samples. This work aimed to assess possible phytotoxic effects of DCF and NPX in concentrations 0.1, 1 and 10 mg/L, both individually and in binary mixtures, on the seed germination and primary root elongation of crops, monocots Allium porrum and Zea mays, and dicots Lactuca sativa and Pisum sativum. Results proved that the seed germination was affected by neither individual drugs nor their mixture. The response of primary root length in monocot and dicot species to the same treatment was different. The Inhibition index (%) comparing the root length of drug-treated plants to controls proved to be approximately 10% inhibition in the case of dicots lettuce and pea, and nearly 20% inhibition in monocot leek, but almost 20% stimulation in monocot maize. Assessment of the binary mixture effect confirmed neither synergistic nor antagonistic interaction of DCF and NPX on early plant development in the applied concentration range.

Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management.

Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.

Facile synthesis and fabrication of Mg2SnO4/carbon black as a sustainable electrode for determination of non-steroidal anti-inflammatory drug-flutamide

The accumulation of hazardous pharmaceutical wastes in aquatic organisms, particularly nonsteroidal anti-inflammatory drug molecules, has severe toxicological consequences for both aquatic life and humans. To protect the environment, it is essential to develop a highly efficient device with dual-purpose capabilities for drug detection while minimizing catalyst expenditure. In this work, we explored a simple and effective design for fabricating a magnesium stannate combined with carbon black (Mg2SnO4/CB) nanocomposite as a cost-effective, sustainable electrode material for the electrochemical detection of flutamide (Flu). The Mg2SnO4/CB nanocomposite was synthesized through a simple hydrothermal process followed by sonication. Various analytical methods were used to determine its physico-chemical characteristics. The electrochemical efficiency of Mg2SnO4/CB/GCE was evaluated by detecting Flu, showing a remarkable linear range from 0.6 to 198.4 µM with a sensitivity of 3.91 μA μM−1 cm−2. In addition, the constructed sensor demonstrated excellent selectivity, high repeatability, outstanding reproducibility, and long-lasting stability. The anti-interference experiments yielded a definite current response without any change in peak shifts. Consequently, Mg2SnO4/CB/GCE demonstrated superior performance in determining Flu in human urine and river water samples.

Parecoxib inhibits tumorigenesis and angiogenesis in hepatocellular carcinoma through ERK-VEGF/MMPs signaling pathway.

Parecoxib, a well-recognized nonsteroidal anti-inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Hoechst/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real-time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose- and time-dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial-mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK-VEGF/MMPs signaling pathway.

Development and evaluation of mucoadhesive buccal films for the sustained release of diclofenac sodium: An innovative approach for pain management

The research explores the development and evaluation of mucoadhesive buccal films for the sustained release of diclofenac sodium, a widely used non-steroidal anti-inflammatory drug (NSAID) for pain relief. Mucoadhesive buccal films are an innovative drug delivery system designed to adhere to the mucous membrane in the oral cavity, enabling the controlled release of drugs directly into the bloodstream, bypassing first-pass metabolism and improving therapeutic outcomes. These films provide sustained release, localized action, and improved compliance, making them more convenient for patients. Mucus membranes, which are moist surfaces lining body cavities, are the main components of mucus gels. The wetting theory applies to mucoadhesion, which involves the release of mucus from the mucosal surface into the bloodstream. The study aims to develop a more efficient and effective method for the controlled release of diclofenac sodium, a potent anti-inflammatory and analgesic drug.

Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review

: Cyclooxygenases (COX) play a pivotal role in inflammation and are responsible for the production of prostaglandins (PGs). Two types of COXs have been identified as key biological targets for drug design: Constitutive COX-1 and inducible COX-2. Nonsteroidal anti-inflammatory drugs (NSAIDs) target COX-1, while selective COX-2 inhibitors are designed for COX-2. These COX isoforms are involved in multiple physiological and pathological pathways throughout the body. Overproduction of tumor necrosis factor-alpha (TNF-α) plays a role in COX-2's inflammatory activity. Tumor necrosis factor-alpha can contribute to cardiac fibrosis, heart failure, and various cancers by upregulating the COX-2/PGE2 axis. Therefore, suppressing COX activity has emerged as a potentially effective treatment for chronic inflammatory disorders and cancer. This review explores the mechanisms of TNF-α-induced COX-2/PGE2 expression, a significant pathophysiological feature of cancer development. Furthermore, we summarize chemical compounds with dual COX-2/TNF-α inhibitory actions, providing an overview of their structure-activity relationship. These insights may contribute to the development of new generations of dual-acting COX-2/TNF-α inhibitors with enhanced efficacy.

P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.

The pro-inflammatory enzyme cyclooxygenase 2 (COX-2) has been known to impart metastatic property to cancer cells. However, blocking of COX-2 with nonsteroidal anti-inflammatory drugs or COX-2-specific inhibitors has failed in clinical trials due to adverse effects associated with their prolonged use. We have previously shown that extracellular ATP (eATP), a major component of the tumor microenvironment, enhances COX-2 expression several-fold, both in macrophages and in various cancer cells, by acting on purinergic (P2) receptors. In this study, we show that blocking of P2 receptors significantly reduced tumor growth in a mouse model of lymphoma. Tumors were induced in mice through subcutaneous injection of syngeneic EL4 lymphoma cells. Various P2 receptor antagonists were injected within the tumors after they were palpable. The broad-spectrum P2 receptor antagonist, suramin, P2X7 receptor-specific antagonist, oATP, P2Y6 receptor-specific antagonist, MRS 2578, and P2Y12 receptor-specific antagonist, AR-C 69931, all showed significant arrest in tumor growth. Both suramin and AR-C 69931-treated tumors showed strong reduction in COX-2 expression and modulation of various metastatic markers. Disaggregated cells from AR-C 69931-treated tumors, when injected intravenously in naïve mice, did not exhibit metastasis in various tissues which was observed in mice injected with cells from saline-treated tumors. Our results show that blocking of P2 receptors is a therapeutic alternative to inhibit COX-2 expression, and thereby, arrest tumor progression and metastasis.

Sequential Release of Ibuprofen and the Gasotransmitter Hydrogen sulfide using Oxanorbornane-Based Synthetic Lipids as Carriers.

After understanding the biological signaling roles of hydrogen sulfide and its involvement in various physiological processes, there has been enormous interest in exploring its therapeutic utility in areas such as cancer, inflammation, cardiovascular diseases, etc. There is also growing interest in using suitable H2S donors in combination with other drugs to improve the treatment outcome through the modulation of multiple pathways. The premature release of H2S from small molecule donors and the difficulty in controlling its spatio-temporal distribution are the major challenges during these efforts. Hence the development of appropriate carriers that can release this gasotransmitter along with the therapeutic entity of interest in a controlled manner has high significance. In this regard, this report presents a novel drug delivery system from oxanorbornane-based synthetic lipids that carries a H2S-releasing 1,2-dithiole-3-thione moiety as part of the head group. Nanoaggregates of the resulting conjugate are not only capable of efficiently entrapping a non-steroidal anti-inflammatory drug such as ibuprofen, but also release this drug and H2S in a controlled and sequential manner.

Peptic Ulcer Disease: A Review.

In the US, peptic ulcer disease affects 1% of the population and approximately 54 000 patients are admitted to the hospital annually for bleeding peptic ulcers. Approximately 10% of patients presenting with upper abdominal pain in a primary care setting have a peptic ulcer as the cause of their symptoms. The principal causes of peptic ulcer disease are Helicobacter pylori infection, which affects approximately 42% of patients with peptic ulcer disease, and aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, which are etiologic factors in approximately 36% of people with peptic ulcer disease. Complications of peptic ulcer include bleeding (73% of patients), perforation (9% of patients), and pyloric obstruction (3% of patients). Annually, 10 000 people die of peptic ulcer disease in the US. Endoscopy definitively diagnoses peptic ulcer disease. Acid blockers, such as omeprazole, can heal peptic ulcers in approximately 80% to 100% of patients within 4 weeks, but gastric ulcers larger than 2 cm may require 8 weeks of treatment. Eradication of H pylori decreases peptic ulcer recurrence rates from approximately 50% to 60% to 0% to 2%. Discontinuing NSAIDs heals 95% of ulcers identified on endoscopy and reduces recurrence from 40% to 9%. When discontinuing an NSAID is not desirable, changing the NSAID (eg, from ketorolac to ibuprofen), adding a proton pump inhibitor such as omeprazole or lansoprazole, and eradicating H pylori with treatment such as bismuth, metronidazole, and tetracycline combined with omeprazole can reduce recurrence rates. Peptic ulcer disease is associated with increased hospitalization rates and mortality. Acid blocking with proton pump inhibitors, such as omeprazole or lansoprazole, is the primary treatment. Recurrence of ulcers can be prevented by eradicating H pylori if present and discontinuing aspirin or NSAIDs if applicable.

Short-pulse of systemic steroids in acute pericarditis: an alternative in refractory cases

Abstract Introduction Acute pericarditis accounts for 5% of emergency room admissions for chest pain. First line treatment consists of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine. Systemic corticosteroids (SCS) are usually reserved as a second-line therapy due to a higher rate of recurrences and side effects. Whether a short pulse of low-dose SCS is safe and effective during the acute phase of the disease remains unknown. Purpose To investigate safety and efficacy of a 3 day pulse of 40 mg intravenous methylprednisolone in patients hospitalized for acute pericarditis with a lack of response to NSAIDs and colchicine. Methods A retrospective, observational and unicentric study was performed including patients hospitalized for acute pericarditis between 2019 and 2023. Patients with asymptomatic pericardial effusion or predominance of myocardial injury were excluded. Patients were considered to be refractory to conventional treatment when at least one of the following criteria was present despite five days of high-dose NSAIDs and colchicine: 1- Moderate/severe pericardial effusion persistence. 2- Chest pain persistence. 3- Increase of inflammatory biomarkers. These patients received methylprednisolone 40mg for three days on top of standard treatment. Baseline characteristics, treatment received during hospitalization and events during follow-up were analysed. Data were expressed as mean and standard deviation (quantitative variables) and percentages (categorical variables). Two-sided P value of less than 0.05 was considered statistically significant. Results 70 patients with acute pericarditis requiring hospitalization were included (54±19 years; 71% male) with a mean follow-up of 10±21 months. 26 of them (37%) received methylprednisolone 40mg for three days due to lack of response to standard treatment. Table 1 includes a comparison of patients who received systemic corticosteroids versus those who did not (control group). C-reactive protein (CRP) was significantly higher in the group receiving corticosteroids (188±86 mg/L vs 135±85 mg/L; p=0.014) and it significantly decreased during hospital stay compared to the control group (151±87 mg/L vs 97±74 mg/L; p=0.013). 14 patients (20%) experienced a recurrence of chest pain during follow-up with no significant difference according to the treatment received (27% vs 16%; p=0.266) Conclusion A 3-day pulse of low-dose SCS seems to be useful and safe for hospitalized patients with acute pericarditis who show lack of response to NSAIDs and colchicine, with no increase in recurrence rate. However, more evidence based on randomized control trials is needed to support this therapeutic approach.Table 1

Prevalence of potentially inappropriate medication use in the older population living in Germany

Abstract Background Potentially inappropriate medications (PIM) are medicines for which the risks for adverse events (AEs) usually outweigh the clinical benefits in older adults. PIM is associated with an increased risk of AEs, hospitalizations, mortality and higher health care costs. This analysis presents the prevalence of PIM use and associated factors in people aged 66+ years living in Germany. Methods Data from the nationally representative Study on Health of Older People in Germany (Gesundheit 65+) conducted between 2021-2023 by the Robert Koch Institute, was analyzed. All medicines used, prescribed and over-the-counter (OTC), in the 7 days before the interview were classified into anatomical therapeutic chemical codes. PIM use was identified based on the PRISCUS 2.0 list. Weighted prevalences and associated factors for PIM use are presented. Results 96% of the sample (N = 1,474) took at least 1 medication in the 7 days before the interview. The prevalence of PIM use was 29% (95% CI: 26%-32%), 23% took 1 PIM and 6% 2+. There were no sex differences but a significant increase with age: 23% in the age group 66-74, 33% in the age group 75-84, and 39% in the age group 85 + (29% 1 PIM and 10% 2+). People with a low educational level had a PIM prevalence of 32% compared to 21% in those with a high educational level. Among those reporting having chronic diseases, the PIM prevalence was 34% compared to 19% among those not reporting them. The prevalence of PIM increased with the number of medicines used: 13% in 1-4 medicines, 31% in 5-9 medicines, and 53% in 10+ medicines. The most frequently used PIM in this sample was ginkgo biloba leaf extract (plant-based antidementia drug) followed by diclofenac (non-steroidal anti-inflammatory drug), and then by tricyclic antidepressant drugs (opipramol and amitriptyline). Conclusions PIM use was higher than suggested by prescription data analysis. It was associated with higher age, chronic diseases, polypharmacy and a low educational level. Key messages • PIM use was common, affecting more people with chronic diseases, older age groups and people with a low educational level. • Strategies to promote and monitor appropriate medication use are needed.

Clinical picture, outcomes and predictors of relapse in eosinophilia-associated coronary vasospasm: data from a European multicentric study

Abstract Background and aims Eosinophilia-associated coronary vasospasm is an under-recognized and scarcely reported life-threatening condition for whose management is undefined. Preliminary data suggest that eosinophil-targeted therapies could be beneficial. Our aim is to provide an in-depth report of the clinical picture, outcomes and predictors of relapse in patients with eosinophilia-associated coronary vasospasm. Methods European multicentric retrospective study, gathering twenty centers across France, Italy and Spain. Patients of 15 years or more with definite or suspected coronary vasospasm according to the 2017 International standardization of diagnostic criteria for vasospastic and concomitant (± 48 hours) eosinophilia (threshold: 0.5 x 109/L) were included in this study. Outcomes included vasospasm relapse and other major cardiovascular events (MACE) during follow-up. Predictors of relapse were assessed using bidirectional stepwise regression analysis. Results Thirty-seven patients (median age: 52 [42-64] years, 43% women) were included, among which 16 (43%) had aspirin-exacerbated respiratory disease, 16 (43%) and 13 (35%) fulfilled classification criteria for Eosinophilic Granulomatosis with Polyangiitis (all with negative antineutrophil cytoplasmic antibodies) and Hypereosinophilic syndrome, respectively. There was no predominant coronary territory involved. A iatrogenic trigger was evidenced in 7 (19%) patients, consisting in all cases but one of non-steroidal anti-inflammatory drugs. After a median follow-up of 32 [12-63] months, 20 (54%) patients relapsed (median time to first relapse: 10 [5−29] months), despite vasodilators regimen in 95% of cases. Besides coronary vasospasm(s), 13 (35%) patients experienced an additional MACE. In multivariate analysis, persistent eosinophilia (i.e. absolute eosinophil count > 0.5 x 109/L at the time of coronary vasospasm relapse or at last follow-up for relapsing and non-relapsing patients respectively) was the sole indepedendent predictor of relapse (Odds Ratio 8.87 [3.28-24.82]; p<0.001). All six patients treated with interleukin-5 biologics remained relapse-free under treatment. Conclusions Eosinophilia-associated coronary vasospasm can occur in patients with type 2 inflammation. Long-term normalization of absolute eosinophil counts appears crucial in preventing the recurrence of eosinophilia-associated coronary vasospasm, while conventional use of vasodilators seems ineficient.

Pharmacological Pain Treatment in Older Persons.

Pharmacological pain treatment in older persons is presented by a multi-disciplinary group of European pain experts. Drugs recommended for acute or chronic nociceptive pain, also for neuropathic pain and the routes of administration of choice are the same as those prescribed for younger persons but comorbidities and polypharmacy in older persons increase the risk of adverse effects and drug interactions. Not all drugs are available or authorised in all European countries. For mild-to-moderate pain, non-opioids including paracetamol and non-steroidal anti-inflammatory drugs are first-line treatments, followed by nefopam and metamizole. Codeine, dihydrocodeine and tramadol are prescribed for moderate to severe pain and 'strong' opioids, including morphine, hydromorphone, oxycodone, fentanyl, buprenorphine, methadone and tapentadol, for severe pain. Chronic neuropathic pain treatment relies on coanalgesics, including anti-epileptics (gabapentinoids) and anti-depressants with additional option of topical lidocaine and capsaicine. The choice of analgesic(s) and the route of administration should be guided by the pain characteristics, as well as by the patient's comorbidities, organ function and medications. Several directions have been highlighted to optimise pharmacological pain management in older individuals: (1) before starting pain treatment adequately detect and assess pain and always perform a full geriatric assessment, (2) consider kidney function systematically to adjust the doses of analgesics and avoid the risks of overdose, (3) start with the lowest dose of an analgesic and increase it gradually under the control of the effect, (4) involve the older persons and family in their treatment, (5) reevaluate pain regularly during treatment and (6) combine pharmacological treatment with non-pharmacological approaches.

Management of Rotator Cuff Injuries: Surgical Repair vs. Conservative Treatment

Rotator cuff injuries are a common cause of shoulder pain and dysfunction, resulting from acute trauma or degenerative changes. These injuries, including partial and full-thickness tears, can significantly impair daily activities and reduce quality of life. Treatment options range from conservative measures, such as physical therapy and NSAIDs, to surgical interventions like arthroscopic repair. The choice of treatment depends on factors such as tear size, patient age, and activity level. This review compares the effectiveness of conservative treatment and surgical repair for rotator cuff injuries, focusing on pain relief, functional recovery, and complication rates. Conservative treatment is typically the first-line approach for partial-thickness tears or patients with lower physical demands. Physical therapy and nonsteroidal anti-inflammatory drugs are common modalities that can improve symptoms, particularly for smaller tears. Corticosteroid injections are also used to provide short-term relief, although their long-term benefits are less clear. For larger or full-thickness tears, surgery is often necessary due to the risk of progressive degeneration and persistent symptoms. Arthroscopic repair is particularly beneficial for younger or more active patients, offering superior long-term outcomes in terms of strength and function. Studies indicate that while conservative treatment and surgery may offer similar short-term outcomes for smaller tears, surgery provides better long-term recovery for more extensive injuries. Ultimately, the decision between conservative and surgical treatment should be individualized, considering tear size, patient age, activity level, and overall health. Surgery is recommended for full-thickness tears or when conservative treatment fails to yield sufficient improvement, while conservative management remains effective for many smaller tears.

Making Sense of Topical Pain Relief Options: Comparing Topical Analgesics in Efficacy and Safety.

In patients with musculoskeletal (MSK) conditions, pain is the leading contributor to disability and significantly limits mobility and dexterity. This narrative review describes the efficacy and safety of topical analgesics in common use today. Secondary literature gained via a literature search using PubMed.gov and the Cochrane library were used. Recent literature (2000-2023) on several major classes of topical analgesics and topical delivery systems were reviewed to provide strength of recommendation taxonomy (SORT) levels. A total of 86 articles were reviewed. Level 2. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) and cabbage leaf wraps (CLW) appear to be best suited for multiple types of acute MSK pain, and topical nitroglycerin is helpful when used specifically for rotator cuff pain in patients seeking relief while performing activities of daily living and willing to treat for long periods of time. For compounded topical formulations, it may be better to offer single agent creams based on patient preferences. Little data support the use of cryotherapy. Traumeel could be a promising natural analgesic that compares with diclofenac. Topical lidocaine appears best suited for postherpetic neuropathic pain. O24 is a reasonable alternative with a low risk profile to treat pain in patients with fibromyalgia syndrome. Choice of topical agents should be guided by current evidence accounting for type of pain, medication side effects, patient comorbidities, as well as patient preference, convenience, and cost. Of the topical analgesics and modalities reviewed, SORT level A evidence was found for topical NSAID use in decreasing MSK pain, topical lidocaine for postherpetic neuralgia, and nitroglycerin patches for treating rotator cuff pain if used for prolonged periods of time. Alternative treatments such as CLW and Traumeel show promising results (SORT level B).

Kikuchi lymphadenitis, a rare case: an overview of its clinical presentation, diagnostic challenges, and therapeutic approaches

Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, self-limiting condition typically presenting with lymphadenopathy and fever. The etiology remains unclear, but it is thought to be associated with viral infections and autoimmune processes. We report a case of a female who presented with cervical lymphadenopathy. An excisional biopsy of the lymph node was performed, showing characteristic histopathological features of KFD. Based on the clinical presentation and histopathological findings, a diagnosis of Kikuchi-Fujimoto disease was made. The patient was managed with supportive care, including antipyretics and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). No antibiotics or corticosteroids were administered. The patient's symptoms gradually resolved over a period. Follow-up at three months revealed the resolution of symptoms with no recurrence. The patient remained asymptomatic at subsequent visits. KFD should be considered in young patients presenting with fever and lymphadenopathy. Diagnosis is confirmed through lymph node biopsy demonstrating characteristic histopathological features. The disease typically follows a benign course with spontaneous resolution, and management is primarily supportive.

Therapeutic potential of d-limonene in rheumatoid arthritis: Modulation of inflammatory, anti-inflammatory cytokines, and prostaglandin E2.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder predominantly affecting the joint structures, eliciting inflammatory responses, and ultimately leading to degenerative changes without proper medical intervention. Ultimately, this can severely impair joint function and impact the patient's quality of life. Current treatment approaches include disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drug, corticosteroids, and biologic therapies for RA management. The current study contributes to the ongoing advancements in RA treatment. d-Limonene is a monocyclic monoterpene. It is present in essential oils of various aromatic plants, such as Lippia alba and Artemisia dracunculus, and in citrus fruits such as lemon and orange. It has reported anti-inflammatory and anti-nociceptive properties and was selected for the current study as a potential anti-arthritic candidate. It was administered at three dosages (25, 50, 100 mg/kg, b.w., p.o) in Complete Freund's adjuvant-induced arthritic rats over 28 days. The efficacy of the compound was compared to piroxicam, a widely used standard drug for treating RA. The anti-arthritic activity of the compound was assessed by measuring arthritic scoring and plethysmometry at both baseline and post-intervention stages. Additional confirmation of the investigation was sought by performing biochemical and hematological activities. Moreover, quantitative polymerase chain reaction was employed to determine the levels of messenger RNA expression for transcription factors such as tumor necrosis factor-α, interleukin (IL)-1β, nuclear factor-κB, matrix metalloproteinase-3, IL-6, and IL-4 in the blood. The levels of PGE2 were evaluated by enzyme-linked immunosorbent assay. The histopathological and radiographic studies were also carried out for further confirmation. The results of these findings supported our assertion regarding the anti-arthritic potential of the compound.

Epidemiological Aspects, Clinicopathology, Hemato-biochemistry and Therapeutic Management of Viperine Snake Envenomation in Buffaloes (Bubalus bubalis)

Background: Poisonous snakebite is a neglected tropical disease, frequently reported in animals including buffaloes. Snakebites are responsible for considerable morbidity and mortality in animals causing economic losses to dairy farmers. Methods: To establish the baseline data of epidemiology, clinical syndrome, hemato-biochemistry and diagnosis of viper snakebites and to standardize the treatment of viper snakebite in buffaloes. Result: The highest incidence of viper envenomation was observed during the monsoon and post-monsoon season in female buffaloes above 4 years of age. The clinical signs such as tachycardia, increased respiration rate, ascending swelling of affected limbs, asymmetrical swelling with dyspnea in case of bite over face and bleeding at the site of bite were observed in envenomed buffaloes. Hemato-biochemical analysis revealed neutrophilic leukocytosis, thrombocytopenia, prolonged capillary blood clotting time, elevated values of blood urea nitrogen (BUN) and creatinine. Post-mortem examination showed hemorrhages and blood-stained serous fluid in subcutaneous tissue and skeletal muscles of the affected limbs. The histopathological changes such as extensive myonecrosis and hemorrhages with marked edema in skeletal muscles, widespread interstitial and intra-alveolar hemorrhages and fibrinous microthrombi in pulmonary vasculature, multifocal to coalescing areas of massive hemorrhages and coagulative necrosis within hepatic parenchyma and marked degeneration of renal tubular epithelium were evident. Therapeutic regimen consisting of polyvalent anti-snake venom, with antibiotics, diuretics, vitamin B complex, styptics, fluids and corticosteroids in non-pregnant while non-steroidal anti-inflammatory drugs in pregnant buffaloes was used. The present treatment strategy showed subsidence of clinical signs, restoration of platelet count, blood clotting time, urea nitrogen and creatinine values depicting clinical recovery with 88.15% survival rate in treated buffaloes.

Efficacy and Safety of Fixed-Dose Combinations for Pain in Older Adults.

Pain is common in older adults and managing pain in this population can be challenging owing to altered pharmacokinetics, multimorbidity, polypharmacy, cognitive impairment, and physical frailty. A fixed-dose combination (FDC) analgesic contains two or more pharmaceutical ingredients in a single pill and may offer more benefits when compared with loose-dose formulations. The benefits include reduced pill burden and better adherence, a broader analgesic spectrum well-suited to multimechanistic pain conditions and more predictable pharmacokinetic and pharmacodynamic properties. These advantages may outweigh disadvantages such as reduced flexibility in dose adjustment. Most of the commonly used FDC analgesics are made up of a combination of paracetamol, muscle relaxant, nonsteroidal anti-inflammatory drug or opioid. They have been shown to have better efficacy and similar safety profiles compared with individual drugs. Adverse effects from the use of FDC analgesics in older patients were comparable with that observed in younger populations. With proper patient selection and continuous surveillance, FDC analgesics will likely benefit older adults by simplifying dosing regimen and improving compliance.