Search Results (989)

Chronic pain is a debilitating condition that affects millions of patients worldwide, contributing to a high disease burden and millions of dollars in lost wages, missed workdays, and healthcare costs. Opioids, NSAIDs, acetaminophen, gabapentinoids, muscle relaxants, anticonvulsants, and antidepressants are the most used medications for chronic pain and carry significant side effects, including gastric bleeding, hepatotoxicity, stroke, kidney damage, constipation, dizziness, and arrhythmias. Opioids in particular carry the risk of long-term dependence, drug tolerance, and overdose. In 2022, 81,806 people died from opioid overdose in the United States alone. Alternative treatments for chronic pain are critically needed, and nanotechnology has emerged as a promising means of achieving effective long-term analgesia while avoiding the adverse side effects associated with conventional pharmacological agents. Nanotechnology-based treatments include liposomes, Poly Lactic-co-Glycolic Acid (PLGA) and other polymeric nanoparticles, and carbon-based polymers, which can help mitigate those adverse side effects. These nanomaterials can serve as drug delivery systems that facilitate controlled release and drug stability via the encapsulation of free molecules and protein-based drugs, leading to longer-lasting analgesia and minimizing side effects. In this review, we examine the role of nanotechnology in addressing concerns associated with conventional chronic pain treatments and discuss the ongoing efforts to develop novel, nanotechnology-based treatments for chronic pain such as nanocapacitor patches, gene therapy, the use of both viral and non-viral vectors, CRISPR, and scavengers. Full article

Background: During the COVID-19 pandemic, paracetamol was widely recommended in different clinical settings, and sometimes advised over non-steroidal anti-inflammatory drugs (NSAIDs). These recommendations sparked a strong debate, with reports suggesting either potential benefits or harms for the individuals infected with SARS-CoV-2. As no systematic review is available, we performed a meta-analysis to estimate the impact of paracetamol on COVID-19 clinical outcomes compared to a placebo, no use, or NSAIDs. Methods: We searched PubMed, Scopus, Web of Science, and ClinicalTrials.gov for randomized trials or observational studies evaluating any COVID-19 clinical outcome. Data were combined using a generic inverse-variance approach. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to determine the certainty of evidence for each outcome. Results: One randomized trial and five observational studies, enrolling over 34,000 patients, were included. Overall, as compared to the patients using NSAIDs or receiving no treatment, the individuals who received paracetamol showed no significant differences in the risk of death (summary relative risks 0.93 and 0.91, respectively: both p > 0.05), need to transfer to the intensive care unit, need for respiratory support, or cardiovascular or renal complications. All studies showed a high risk of bias, with a low overall quality of evidence. Conclusions: This meta-analysis found no evidence of harmful or beneficial effects of paracetamol on main COVID-19-related outcomes. Also, the current literature does not provide sufficient data to support a preferential choice between paracetamol and NSAIDs for COVID-19 symptoms management. Further research is needed to confirm the present findings and provide critical insights on the policies to adopt in the case of future pandemics. Full article

Background/Objectives: Endometriosis is a chronic condition that affects 6–10% of women of reproductive age, with pain and infertility being its primary symptoms. The most common aspects of pain are overall pelvic pain, dysmenorrhea, and dyspareunia. Our aim was to compare the available medical treatments for endometriosis-related pain. Methods: A systematic search was conducted in three medical databases to assess available drug options for pain management. Randomized controlled trials (RCTs) investigating various medical treatments for endometriosis-related pain on different pain scales were included. Results were presented as p-scores and, in cases of placebo controls, as mean differences (MD) with 95% confidence intervals (CI). From the available data, a network meta-analysis was carried out. Results: The search yielded 1314 records, of which 45 were eligible for data extraction. Eight networks were created, and a total of 16 treatments were analyzed. The highest p-score, meaning greatest pain relief (p-score: 0.618), for the treatment of dysmenorrhea was achieved using gonadotropin-releasing hormone (GnRH) agonists for 3 months on a scale of 0–100. Additionally, a p-score of 0.649 was attained following a 6-month treatment with GnRH agonists combined with hormonal contraceptives (CHCs). In the case of dyspareunia on a scale of 0–100 following 3 months of treatment, CHCs (p-score: 0.805) were the most effective, and CHCs combined with aromatase inhibitors (p-score: 0.677) were the best treatment option following 6 months of treatment. In the case of overall pelvic pain, CHCs (p-score: 0.751) yielded the highest p-score on a scale of 0–100 following 3 months of treatment, and progestins combined with aromatase inhibitors (p-score: 0.873) following 6 months of treatment. Progestins (p-score: 0.901) were most effective in cases of overall pelvic pain on a scale of 0–3 following 3 months of treatment. Conclusions: Our network meta-analysis showed that in cases of dysmenorrhea, GnRH agonists supplemented with CHCs reduced pain the most following 3 months of treatment. Regarding dyspareunia CHCs were most effective, and in the case of overall pelvic pain, CHCs or progestins combined with aromatase inhibitors yielded the most desirable results. Full article

The present study examines whether the systemic application of naringenin (NRG) reduces inflammation-induced hyperexcitability in the spinal trigeminal nucleus caudalis (SpVc) related to hyperalgesia, and compares its impact with that of diclofenac (DIC). To provoke inflammation, the whisker pads of rats were injected with complete Freund’s adjuvant, and subsequently, mechanical stimuli were administered to the orofacial region to determine the escape threshold. Compared to naïve rats, the inflamed rats showed a significantly lower mechanical threshold, and this reduced threshold returned to normal levels two days post-administration of NRG, DIC, and half-dose DIC plus half-dose NRG (1/2 DIC + 1/2 NRG). Using extracellular single-unit recordings, the activity of SpVc wide-dynamic range neurons was measured in response to mechanical stimulation of the orofacial area under anesthesia. The average firing rate of SpVc neurons when exposed to both non-painful and painful mechanical stimuli was significantly reduced in inflamed rats following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The heightened average spontaneous activity of SpVc neurons in rats with inflammation was significantly reduced following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The increased average receptive field size observed in inflamed rats reverted to normal levels after either NRG, DIC, or 1/2 DIC + 1/2 NRG treatment. These findings indicate that NRG administration can reduce inflammatory hyperalgesia linked to the heightened excitability of SpVc wide-dynamic range neurons. Full article

Fluorinated organic compounds have demonstrated remarkable utility in medicinal chemistry due to their enhanced metabolic stability and potent therapeutic efficacy. Several examples exist of fluorinated non-steroidal anti-inflammatory drugs (NSAIDs), including diflunisal, flurbiprofen, and trifluoromethylated pyrazoles celecoxib and mavacoxib. These trifluoromethylated pyrazoles, which are most commonly constructed through the cyclocondensation of a trifluorinated 1,3-dicarbonyl and an aryl hydrazine, are also found in numerous other drug candidates. Here, we interrogate the effects of solvents and the presence of Brønsted or Lewis acid catalysts on catalyzing this process. We highlight the utility of benchtop ¹⁹F NMR spectroscopy in enabling the real-time quantification of reaction progress and the identification of fluorinated species present in crude reaction mixtures without the need for cost-prohibitive deuterated solvents. Ultimately, we find that the reaction solvent has the greatest impact on the rate and product yield, and also found that the relationship between the keto-enol equilibrium of the dicarbonyl starting material pyrazole formation rate is highly solvent-dependent. More broadly, we describe the optimization of the yield and kinetics of trifluoromethylpyrazole formation in the synthesis of celecoxib and mavacoxib, which is made possible through high-throughput reaction screening on benchtop NMR. Full article

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in therapy due to their anti-inflammatory and analgesic properties. However, their clinical use is often associated with gastrointestinal complications. Thus, this study aimed to investigate the protective effect of a sulfated iota-carrageenan isolated from the marine alga Solieria filiformis (IC-Sf) against naproxen-induced gastrointestinal injury. Methods: Parameters of gastrointestinal injury, secretory and motor functions, and toxicity were evaluated. Results: The results demonstrated that IC-Sf significantly reduced naproxen-induced gastrointestinal macroscopic injury, with a maximum effect observed at 30 mg/kg. IC-Sf also preserved gastrointestinal antioxidant defense and prevented lipid peroxidation, with a reduction in the non-protein sulfhydryl group (NP-SH) and malondialdehyde (MDA) concentrations induced by naproxen. Additionally, IC-Sf mitigated naproxen-induced gastrointestinal inflammation, as evidenced by reduced myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). IC-Sf did not alter gastric secretion or gastrointestinal motility. In addition, the animals treated with IC-Sf did not present toxic effects. Conclusions: In conclusion, IC-Sf protected the gastrointestinal tract against the harmful effects of naproxen by inhibiting the inflammatory response and lipid peroxidation, suggesting its potential as a new therapeutic agent or food additive. Full article

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body’s inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby blocking the synthesis of prostaglandins (PGs), which play a role in inflammation, cancer, and various cardiovascular conditions. However, long-term COX inhibition and reduced PGs synthesis can result in serious side effects. Recent studies have increasingly shown that some selective COX-2 inhibitors and NSAIDs, such as Meloxicam, may exert effects beyond COX inhibition. This emerging understanding prompts a re-evaluation of the mechanisms by which NSAIDs operate, suggesting that their benefits in cancer and CVD treatment may not solely depend on COX targeting. In this review, we will explore the potential COX-independent mechanisms of Meloxicam and other NSAIDs in addressing oncology and cardiovascular health. Full article

(1) Background: The purpose of this systematic review is to investigate the prevalent use of non-steroidal anti-inflammatory drugs (NSAIDs) in athletes and to comprehensively review the effectiveness and the results of these medications as it relates to injury management, training response, and overall sport performance. (2) Methods: An electronic literature search was performed in accordance with the recommendations and guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. A total of 7 randomized controlled studies met the review’s specific inclusion criteria from the 2250 studies initially identified within the PubMed database. (3) Results: In total, 346 adult female and male athletes from a variety of sporting activities and fitness levels were observed, of which 175 athletes were treated with either oral, topical, or local muscular infusion of an NSAID. Depending on study design, the outcomes focused on results obtained through physical exam findings, questionnaires, various performance metrics, and direct tissue sampling from microdialysis or biopsies. Across the 7 total studies, 2 articles focused on injured athletes and their varying pain responses with NSAIDs; 2 studies assessed the limited impact of NSAIDs on performance; and 3 articles revealed the use of NSAIDs correlating to no increases in either collagen synthesis or satellite cell activity after exercise. (4) Conclusions: The systematic review affirmed that NSAIDs can be effective for managing acute pain. However, their value appears to diminish when treating chronic injuries or if NSAIDs are expected to improve performance or have other ergogenic effects in athletes, as the aggregate data did not support such benefits. (5) Practical applications: NSAIDs can be beneficial for athletes in the right situation, but the fact that there are risks and possible disadvantageous results with their use highlights the importance of promoting appropriate expectations and the judicious use of these medications with the athletic community. Full article

Cutaneous metastases from clear cell renal carcinoma (ccRC) are uncommon and often indicate a poor prognosis. These metastases typically occur on the scalp, face, and trunk, and they can be difficult to diagnose due to their resemblance to benign dermatological tumors. We report the case of a 56-year-old patient with a history of ccRC (TNM stage 4) who was referred to our dermatology department with two rapidly enlarging, painful lesions on the left jawline and scalp, which had developed one month and one week earlier, respectively. On examination, the lesions appeared as well-defined, round to oval plaques with a central ulceration and a peripheral red rim, suggestive of an inflammatory appearance. Dermoscopic examination revealed a structureless pink to orange pattern, atypical central vessels, and irregular linear vessels in a corona-like arrangement. Despite the patient’s stable oncological treatment for six months, pain management had recently included paracetamol, tramadol, and NSAIDs. The primary presumptive diagnosis was of cutaneous metastasis, considering the patient’s history of metastatic ccRC. However, given the recent initiation of new pharmacological agents, the rapid progression of the cutaneous lesions, and their clinical presentation, alternative differential diagnoses were considered, including drug-induced reactions such as erythema multiforme or fixed drug eruption. A biopsy of the facial lesion revealed immunohistochemical positivity for CD10, CAIX, and PAX8, confirming the diagnosis of metastatic ccRC with sarcomatoid differentiation. Unfortunately, despite continued targeted therapies and palliative care, the patient’s condition deteriorated rapidly, leading to death two months later. This case highlights the potential for extremely rapidly evolving cutaneous metastases from ccRC and their capacity to occasionally mimic atypical drug eruptions. Additionally, it reaffirms the poor prognosis of such metastases, as evidenced by the patient’s death within two months. Full article

Objective: The present study investigates the incidence of postoperative acute kidney injury (AKI) and related risk factors in patients undergoing total joint arthroplasty. Methods: Included in the study were patients undergoing joint arthroplasty in 2015–2020. The patients with acute or chronic renal failure were excluded. The participants’ demographical data, American Society of Anesthesiologist (ASA) score, Charlson Comorbidity Index (CCI), type of operation, duration of surgery, presence of comorbidities, preoperative anemia, preoperative albumin levels, use of nephrotoxic agents, number of transfusions during perioperative period, presence of AKI according to Kidney Disease Improving Global Outcome (KDIGO) scores, and length of hospital and intensive care unit stay were evaluated. Results: The study was initiated with 1780 patients: 113 patients were excluded due to chronic kidney failure, 108 patients were excluded due to acute kidney failure, 648 patients were excluded because their data could not be reached, and finally, 911 patients were included in the study. AKI was detected in 134 patients (14.7%), and the number of patients in the KDIGO1 and KDIGO2 groups were 120 and 14, respectively. When evaluated according to the variable significance test result and clinical significance, the model consists of variables such as ASA, CCI, hypertension, nonsteroidal anti-inflammatory drugs (NSAIDs), vancomycin, beta lactam, contrast material and preoperative anemia, operation type, and anesthesia management. Machine learning analyses were performed using 11 variables (10 independent and 1 dependent variable). Logistic regression, naive Bayes, multilayer perceptron, bagging, and random forrest approaches were used for evaluation of the predictive performance. In an evaluation of the true classification ratio, the best result was obtained with the logistic regression method at 85.2%. Conclusions: The study revealed advanced age, high ASA and CCI, presence of diabetes and hypertension, NSAID, vancomycin and contrast material, and the presence of preoperative anemia to be independent risk factors for AKI. Full article

Background: Etoricoxib is a widely used anti-inflammatory drug, but its safety profile concerning cardiovascular and renal health remains inadequately explored. This study aimed to assess the nephro- and cardiotoxic effects of etoricoxib in a murine model, with a focus on its impact on arachidonic acid-metabolizing enzymes and beta-adrenergic receptors associated with drug-induced toxicity. Methods: Thirty-five BALB/C mice were randomly assigned to five groups: control, low-dose etoricoxib, high-dose etoricoxib, low-dose celecoxib, and high-dose celecoxib (a well-known nephro- and cardiotoxic NSAID). The treatments were administered for 28 days, after which hearts and kidneys were excised for physical and histopathological analysis, and the expression of arachidonic acid-metabolizing enzymes (cytochrome P450s, lipoxygenases, cyclooxygenases) and beta-1 adrenergic receptor (adrb1) and angiotensin-converting enzyme (ace2) genes were quantified using quantitative reverse transcription PCR (qRT-PCR). Results: Etoricoxib administration resulted in dose-dependent nephro- and cardiotoxic effects. Renal histology revealed glomerular atrophy or hypertrophy and significant damage to the proximal and distal convoluted tubules, including epithelial flattening, cytoplasmic vacuolation, and luminal widening. Cardiac analysis showed disorganized muscle fibers and hyaline degeneration. These changes were associated with altered gene expression: the downregulation of cox2, cyp1a1, and cyp2c29 in the kidneys and the upregulation of cyp4a12, cox2, and adrb1, along with the downregulation of cyp2c29 and ace2 in the heart. Conclusions: Etoricoxib induces nephro- and cardiotoxicity, marked by alterations in arachidonic acid metabolism and beta-adrenergic signaling pathways. The drug affects the expression of arachidonic acid-metabolizing enzymes and adrb1 in the heart while downregulating cox2 and other related enzymes in the kidneys. These findings underscore the need for caution when prescribing etoricoxib, particularly in patients with pre-existing renal or cardiac conditions. Full article

In this study, a new composite adsorbent consisting of aluminum-modified activated carbon (abbreviated hereafter AC@Al) was synthesized for the removal of the Ibuprofen compound (IBU), a non-steroidal anti-inflammatory drug (NSAID). Coconut shells were used as a source material for activated carbon, which was then modified with AlCl₃ to improve its properties. Adsorbent dosage, pH and initial IBU concentration, as well as contact time and temperature, are some of the factors affecting adsorption that were investigated in this work. Specifically, at pH 2.0 ± 0.1 with the application of 0.5 g/L of AC@Al in 100 mg/L of IBU, more than 90% was removed, reaching 100% with the addition of 1.0 g/L of the adsorbent. The IBU kinetic data followed the pseudo-second-order kinetic model. Non-linear Langmuir, Freundlich, Sips and Redlich–Peterson isotherm models were used to interpret the adsorption. According to the correlation coefficient (R²), the Langmuir model was found to best match the experimental data. The maximum adsorption capacity (Q_max) according to the Langmuir model was found to be as high as 2053 mg/g. The positive values of ΔH⁰ (42.92 kJ/mol) confirmed the endothermic nature of the adsorption. Due to the increasing values of ΔG⁰ with temperature, the adsorption of IBU onto AC@Al proved to be spontaneous. Also, the adsorbent was regenerated and reused for five cycles. This study shows that AC@Al could be used as a cost-effective adsorbent. Full article

Background/Objectives: Abdominoplasties are prevalent surgical procedures for improving lower abdominal contours, necessitating effective pain management. Insufficient management can increase opioid usage, dependency risks, and adverse effects. This review investigates various strategies in abdominoplasty pain management, aiming to reduce opioid dependence and improve patient care. Methods: A comprehensive systematic literature search (MEDLINE, Cochrane, PubMed, Web of Science, EMBASE) was conducted, spanning from their inception to January 2024, using keywords such as ‘abdominoplasty’ and ‘postoperative pain management’. Included studies focused on nonopioid interventions in adults, encompassing various study designs. Non-English publications and those not meeting outcome criteria were excluded. Bias in studies was assessed using specific tools for randomized and non-randomized trials. Results: Thirty-five studies, published between 2005 and 2024, were included, involving 3636 patients with an average age of 41.8. Key findings highlighted the effectiveness of transversus abdominis plane blocks in reducing opioid use and pain. Pain pump catheters also showed promise in improving pain management and reducing opioid dependency. Local anesthetics demonstrated varying degrees of efficacy, while other alternatives like ketamine and NSAIDs successfully reduced postoperative pain and opioid requirements. The bias assessment of the RCTs revealed “low” and “some concerns” ratings, indicating a need for more detailed methodology reporting and management of missing data. The cohort studies generally attained “moderate” risks of bias, primarily due to confounding variables and outcome data reporting. Conclusions: Nonopioid analgesics show potential in postoperative pain management for abdominoplasties, but further research is needed to confirm their effectiveness and optimize patient care. Full article

In degenerative joint disease like osteoarthritis (OA), bioactive compounds like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin by executing epigenetic-modifying activities. Epigenetic modulation can target genes of disease pathophysiology via histone modification, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved in OA but have been less explored. OA patients often seek options that can improve the quality of their life in addition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bioactive and natural compounds exhibit therapeutic potential against OA, several disadvantages loom, like insolubility and poor bioavailability. Nanoformulated bioactive compounds promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive compounds as epigenetic and gut modulators in ameliorating OA. Moreover, it is not known whether the effects of polyphenolic bioactive compounds on gut microbial response are mediated by epigenetic modulatory activities in OA. This narrative review highlights the nanotherapeutic strategies utilizing bioactive compounds, reporting their effects on chondrocyte growth, metabolism, and epigenetic modifications in osteoarthritis amelioration. Full article

Camurati–Engelmann Disease (CED), or Progressive Diaphyseal Dysplasia, is a rare autosomal dominant disorder caused by heterozygous mutations in the TGFB1 Gene, essential for bone regeneration. This study examines the genotype–phenotype relationship in a family diagnosed with CED, specifically focusing on a missense variant (c.653G>A, p.Arg218Cys). The family comprised a mother and her two children, all of whom were found to carry the same disease-causing variant. The second child exhibited severe symptoms by age six, including progressive weakness and joint pain, leading to wheelchair dependency. The mother displayed milder symptoms with preserved independence. The firstborn son, initially asymptomatic, developed gait abnormalities and pain during adolescence. Clinical evaluations revealed characteristic hyperostosis of long bones, with significant variability in symptom onset and severity among family members, potentially indicative of genetic anticipation. This case underscores the importance of genetic testing and interdisciplinary management in CED, as traditional treatments, including corticosteroids and NSAIDs, often yield limited efficacy and notable side effects. Our findings contribute to the understanding of CED’s pathophysiology and highlight the necessity for tailored therapeutic approaches. The identification of the common TGFB1 variant in this family reinforces the critical role of TGFB1 in bone metabolism and suggests avenues for further research into targeted therapies. Such reports enhance awareness and provide valuable insights for healthcare professionals managing rare genetic disorders. Full article