Search Results (971)

Medicines are pharmaceutical substances used to treat, prevent, or relieve symptoms of different diseases in animals and humans. However, their large-scale production and use worldwide cause their release to the environment. Pharmaceutical molecules are currently considered emerging pollutants that enter water bodies due to inadequate management, affecting water quality and generating adverse effects on aquatic organisms. Hence, different alternatives for pharmaceuticals removal from water have been sought; among them, the use of agro-industrial wastes has been proposed, mainly because of its high availability and low cost. This review highlights the adverse ecotoxicological effects related to the presence of different pharmaceuticals on aquatic environments and analyzes 94 investigations, from 2012 to 2024, on the removal of 17 antibiotics, highlighting sulfamethoxazole as the most reported, as well as 6 non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac and ibuprofen, and 27 pharmaceutical drugs with different pharmacological activities. The removal of these drugs was evaluated using agro-industrial wastes such as wheat straw, mung bean husk, bagasse, bamboo, olive stones, rice straw, pinewood, rice husk, among others. On average, 60% of the agro-industrial wastes were transformed into biochar to be used as a biosorbents for pharmaceuticals removal. The diversity in experimental conditions among the removal studies makes it difficult to stablish which agro-industrial waste has the greatest removal capacity; therefore, in this review, the drug mass removal rate (DMRR) was calculated, a parameter used with comparative purposes. Almond shell-activated biochar showed the highest removal rate for antibiotics (1940 mg/g·h), while cork powder (CP) (10,420 mg/g·h) showed the highest for NSAIDs. Therefore, scientific evidence demonstrates that agro-industrial waste is a promising alternative for the removal of emerging pollutants such as pharmaceuticals substances. Full article

The objective of our research was to determine the effects of xanthohumol (XN), a flavonoid isolated from hops (Humulus lupulus), and the anti-inflammatory drug niflumic acid (NA), separately and in combination with each other, on the proliferation of human cancer cells. Additionally, so as to understand the mechanism underlying the anticancer properties of the tested compounds, their effects on the biophysical parameters of a model membrane were assessed. The cells were incubated with XN and NA at various concentrations, either individually or in combination with each other. Cell proliferation was quantified using the sulforodamine B (SRB) assay. In addition, the IC₅₀ values for niflumic acid and xanthohumol applied separately were determined by cell proliferation tests for the following human cancer cell lines: 5637 (urinary bladder carcinoma), A-431 (epidermoid carcinoma), UM-SCC-17A (head and neck squamous carcinoma), SK-MEL-3 (melanoma), MCC13 (Merkel cell cancer), and A172 (glioblastoma), in comparison with the mouse normal fibroblasts (BALB/3T3 clone A31). The results show that the two-compound combinations of XN and NA significantly decreased the proliferation of cancer cells in a dose-dependent manner, and the effects were stronger than the additive responses to XN and NA individually. The membrane studies revealed a synergistic effect on the membrane rigidity when using the mixture of XN and NA, which may explain the observed increase in anticancer activity for the combined XN and NA. Our results suggest that NSAIDs, such as niflumic acid, may be a promising strategy for co-application with xanthohumol as anticancer drugs. Full article

Pericardial disease is increasingly recognized in cancer patients, including acute pericarditis, pericardial effusion, and constrictive pericarditis, often indicating a poor prognosis. Acute pericarditis arises from direct tumor involvement, cancer therapies, and radiotherapy. Immune checkpoint inhibitor (ICI)-related pericarditis, though rare, entails significant mortality risk. Treatment includes NSAIDs, colchicine, and corticosteroids or anti-IL1 drugs in refractory cases. Pericardial effusion is the most frequent manifestation, primarily caused by lung cancer, followed by breast cancer, lymphoma, leukemia, gastrointestinal tumors, and melanoma. Chemotherapy, immunotherapy, and radiotherapy may also cause fluid accumulation in the pericardial space. Symptomatic relief for pericardial effusion may require pericardiocentesis, prolonged catheter drainage, or a pericardial window. Instillation of intrapericardial cytostatic agents may reduce recurrence. Constrictive pericarditis, though less common, often develops from radiotherapy and requires multimodality imaging for diagnosis, with pericardiectomy as the definitive treatment. Primary pericardial tumors are rare, with metastases being more frequent. Patients with cancer and pericardial disease generally have poor survival, emphasizing the need for early detection. A multidisciplinary approach involving hematologists, oncologists, and cardiologists is crucial to tailoring pericardial disease treatment to a patient’s clinical status, thereby improving the quality of life and prognosis. Full article

The elderly population is growing worldwide. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed, but their adverse events can pose significant risks. Different NSAID molecules can exhibit varying risk profiles. This study aims to evaluate the cardiovascular, gastrointestinal, and renal safety profiles of ibuprofen, naproxen, acemetacin, diclofenac, celecoxib, and etoricoxib in elderly patients. A comprehensive literature search was conducted in PubMed and Cochrane Library. For the selection of articles, we used Medical Subject Headings (MeSH) terms “aged” sequentially and together with “ibuprofen”, “diclofenac”, “naproxen”, “acemetacin”, “celecoxib”, and “etoricoxib”. To assess the quality and interest of the articles, four independent reviewers screened titles and abstracts to identify potentially eligible studies. Strength of Recommendation Taxonomy (SORT) was used to rate the quality of individual studies and to establish recommendation strengths (RS). From 2086 articles identified, 39 studies met the inclusion criteria. Twenty studies analyzed cardiovascular safety, fourteen gastrointestinal safety, and four renal safety. When CV risk is the main concern celecoxib or naproxen are a good first choice (RS B). In high GI risk addition of PPI to naproxen or celecoxib use should be recommended (RS A). When renal function is on focus, celecoxib remains as first line of therapy (RS A). Diclofenac in the geriatric population should be avoided (RS B). Celecoxib is a good choice for elderly patients for whom it is difficult to direct pain treatment based on a single known risk factor (RS B). Full article

Background: the role of the R202Q (c.605G>A, p.Arg202Gln) missense variant of the MEFV gene has been debated as either a benign polymorphism or a potentially pathogenic mutation. We report and discuss here the case of a young female with corticosteroid-dependent recurrent pericarditis carrying the homozygous R202Q variant, exhibiting distinctive clinical features possibly influenced by this genetic variant. Methods: a 30-year-old woman with a previous diagnosis of cancer and recent respiratory infection presented with severe pleuritic chest pain, hypotension, tachycardia, and fever. Initial diagnostic evaluation indicated cardiac tamponade, and emergent pericardiocentesis was performed. Despite initial treatment with NSAIDs, colchicine, and corticosteroids, the patient experienced multiple recurrences. Genetic testing identified homozygous R202Q variant in the MEFV gene. Given the corticosteroid dependency and recurrent nature of her condition, IL-1 inhibitor anakinra was introduced, leading to significant improvement, although tapering below 150 mg per week failed to prevent recurrences. Results: the introduction of anakinra resulted in rapid symptom relief and resolution of pericardial effusion. However, attempts to taper or discontinue anakinra led to pericarditis recurrences. Ultimately, a maintenance dose of 50 mg every three days was established, which maintained remission for 18 months without recurrence. Despite multiple tapering attempts, further reduction in anakinra dosage was unsuccessful without triggering relapses. Conclusions: the R202Q variant, although typically considered benign, may contribute to an autoinflammatory phenotype resembling familial Mediterranean fever. This case underscores the potential pathogenicity of the homozygous R202Q variant in recurrent pericarditis and its responsiveness to IL-1 inhibition. In patients with corticosteroid-dependent recurrent pericarditis, genetic testing for the R202Q variant should be considered when anti-IL-1 drugs cannot be withdrawn. Further studies are warranted to elucidate the variant’s role in pericardial inflammation and guide personalized treatment strategies. Full article

Background: Multimorbidity, polypharmacy, and inappropriate prescribing are significant challenges in the geriatric population. Tools such as the Beers List, FORTA, and STOPP/START criteria have been developed to identify potentially inappropriate prescribing (PIP). STOPP/START criteria detect both potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). The latest, third version of STOPP/START criteria expands the tool, based on the growing literature. The study aimed to evaluate the prevalence of PIP and the number of PIP per person identified by STOPP/START version 3 and to compare it to the previous version. Methods: This retrospective, cross-sectional study enrolled one hundred geriatric patients with polypharmacy from two day-care centers for partially dependent people in Poland. Collected data included demographic and medical data. STOPP/START version 3 was used to identify potentially inappropriate prescribing, whereas the previous version served as a reference. Results: STOPP version 3 detected at least one PIM in 73% of the study group, a significantly higher result than that for version 2 (56%). STOPP version 3 identified more PIMs per person than the previous version. Similarly, START version 3 had a significantly higher prevalence of PPOs (74% vs. 57%) and a higher number of PPOs per person than the previous version. The newly formed STOPP criteria with high prevalence were those regarding NSAIDs, including aspirin in cardiovascular indications. Frequent PPOs regarding newly formed START criteria were the lack of osmotic laxatives for chronic constipation, the lack of mineralocorticoid receptor antagonists, and SGLT-2 inhibitors in heart failure. Conclusions: This study showed the high effectiveness of the STOPP/START version 3 criteria in identifying potentially inappropriate prescribing, with a higher detection rate than version 2. Full article

Diclofenac is one of the most common, commercially available, non-steroidal anti-inflammatory drugs (NSAIDs) in the world, with thousands of tons produced and consumed per year, which creates issues related to its presence in water bodies and the need for its removal from them. Diclofenac forms complexes with cations of each metal, which has inspired a study to check if the formation/precipitation of such complexes can be used for effective diclofenac removal from water solutions. It was found that iron salts, e.g., FeCl₃, can be used to remove diclofenac from a water solution in the form a of precipitated complex, provided that a high excess of iron salt was used. It has been observed that the diclofenac initial concentration of 5 × 10⁻⁴ M, as a result of FeCl₃ addition, after 48 h, decreased by two orders of magnitude. Salts of other metals were found less effective in reducing diclofenac concentration. The iron cation–diclofenac interaction was found to be specific, since the precipitation of other drugs by iron cations has not been observed. In order to quantitively analyze the diclofenac removal (precipitation) by iron and other metal cations, the HPLC/ESI-MS analyses were performed. Full article

Evaluation of pharmacokinetic properties is a significant step at the early stages of drug development. In this study, an in vitro evaluation of the pharmacokinetic properties of five newly synthesized compounds was performed. These compounds belong to N-hydroxyurea and hydroxamic acid derivatives and analogs of NSAIDs indomethacin, flurbiprofen, diclofenac, ibuprofen, and naproxen (compounds 1, 2, 3, 11, and 12, respectively) with dual COX-2 and 5-LOX inhibitory activity. Two in vitro methods (biopartitioning micellar chromatography (BMC) and PAMPA) were used to evaluate passive gastrointestinal absorption, while high-performance affinity chromatography (HPAC) and differential pulse voltammetry (DPV) were used to evaluate binding to human serum albumin (HSA). The introduction of N-hydroxyurea and hydroxamic acid groups into the structure of NSAIDs decreases both expected passive gastrointestinal absorption (BMC k values were from 3.02 to 9.50, while for NSAIDs were from 5.29 to 13.36; PAMPA –logPe values were between 3.81 and 4.76, while for NSAIDs were ≤3.46) and HSA binding (HPAC logk values were from 2.03 to 9.54, while for NSAIDs were ≥11.03; DPV peak potential shifts were between 7 and 34, while for NSAIDs were ≥54). Structural modifications of all tested compounds that increase lipophilicity could be considered to enhance their passive gastrointestinal absorption. Considering lower expected HSA binding and higher lipophilicity of tested compounds compared to corresponding NSAIDs, it can be expected that the volume of distribution of compounds 1, 2, 3, 11, and 12 will be higher. Reduced HSA binding may also decrease interactions with other drugs in comparison to corresponding NSAIDs. All tested compounds showed significant microsomal instability (25.07–58.44% decrease in concentration) in comparison to indomethacin (14.47%) and diclofenac (20.99%). Full article

Migraine has a high prevalence worldwide and is one of the main disabling neurological diseases in individuals under the age of 50. In general, treatment includes the use of oral analgesics or non-steroidal anti-inflammatory drugs (NSAIDs) for mild attacks, and, for moderate or severe attacks, triptans or 5-HT_1B/1D receptor agonists. However, the administration of antimigraine drugs in conventional oral pharmaceutical dosage forms is a challenge, since many molecules have difficulty crossing the blood-brain barrier (BBB) to reach the brain, which leads to bioavailability problems. Efforts have been made to find alternative delivery systems and/or routes for antimigraine drugs. In vivo studies have shown that it is possible to administer drugs directly into the brain via the intranasal (IN) or the nose-to-brain route, thus avoiding the need for the molecules to cross the BBB. In this field, the use of lipid nanoparticles, in particular solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has shown promising results, since they have several advantages for drugs administered via the IN route, including increased absorption and reduced enzymatic degradation, improving bioavailability. Furthermore, SLN and NLC are capable of co-encapsulating drugs, promoting their simultaneous delivery to the site of therapeutic action, which can be a promising approach for the acute migraine treatment. This review highlights the potential of using SLN and NLC to improve the treatment of acute migraine via the nose-to-brain route. First sections describe the pathophysiology and the currently available pharmacological treatment for acute migraine, followed by an outline of the mechanisms underlying the nose-to-brain route. Afterwards, the main features of SLN and NLC and the most recent in vivo studies investigating the use of these nanoparticles for the treatment of acute migraine are presented. Full article

There is growing evidence on the significant role of prolonged inflammation in triggering and progressing of numerous diseases with substantial health and socioeconomic impacts, such as musculoskeletal, cardiovascular and autoimmune disorders, and cancer. Therefore, there is an urgent need to develop therapies that can overcome the main challenges of currently used approaches, such as non-target action, partial modulation of the complex inflammatory pathways, and short-term effects, to effectively manage and resolve chronic inflammatory states. This work investigates the therapeutic synergy of clinically relevant anti-inflammatory agents approaching naïve and classically activated macrophages owing to their central role in inflammation. Aiming at human therapies, a dual-loading nanoplatform reunites molecules with different physico-chemical properties in a single system, seeking to more effectively and comprehensively regulate macrophage functions for precision cell guidance and greater versatility in disease managing. To build this platform, palmitic acid grafted chitosan, superparamagnetic iron oxide nanoparticles, the clinically approved NSAID celecoxib (also known as Celebrex^®), and RNA technologies were combined into superparamagnetic polymeric micelles (SPMs). Our findings demonstrated that traditional anti-inflammatory drugs such as celecoxib and microRNA molecules were efficiently delivered by the SPMs, altering the inflammatory profile of naïve (M0φ) and M1-primed macrophages (M1φ) assessed by gene and protein expression. The impact of the dual-loaded SPMs in naïve Mφ is an interesting finding towards the modulation of the initial immune response, reducing the potential for chronic inflammation and promoting tissue healing. Collectively, these encouraging results demonstrate the promise of multi-nanomedicine strategies to enhance the efficacy of therapeutic interventions by offering a fresh approach to more precisely and carefully regulated nanotherapeutics delivery. Full article

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition often mistaken for inflammatory breast cancer and, therefore, requires a biopsy for accurate diagnosis. Although not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. Differentiating IGM from other breast inflammations caused by infections is essential. IGM mostly affects premenopausal women and is potentially associated with recent pregnancies and breastfeeding. The risk factors, including smoking and contraceptive use, have inconsistent associations. Steroid responses suggest an autoimmune component, though specific markers are lacking. Methods: We performed a narrative review on potential risk factors, diagnostics, and therapy of IGM. Results: Diagnostics and clinical management of IGM are challenging. The treatment options include NSAIDs, steroids, surgery, antibiotics, immunosuppressants, prolactin suppressants, and observation, each with varying effectiveness and side effects. Conclusions: Current IGM treatment evidence is limited, based on case reports and small series. There is no consensus on the optimal management strategy for this disease. The GRAMAREG study by the EUBREAST Study Group aims to collect comprehensive data on IGM to improve diagnostic and treatment guidelines. By enrolling patients with confirmed IGM, the study seeks to develop evidence-based recommendations, enhancing patient care and understanding of this condition. Full article

Self-medication without a medical or dental prescription is an action that leads to a significant problems associated with the overuse of medication in Brazil. The inappropriate use of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) leads to problems related to microbial agent resistance and gastrointestinal complications. The purpose of this study was to elucidate the patterns of antibiotic and NSAIDs consumption among the adult population of Brazil. The questionnaire was answered by 400 people residing in Brazil who had access to the link in the year 2023. The findings showed that approximately 89.5% of the volunteers had used NSAIDs, and 32.2% had used antibiotics whether or not these medications had been prescribed by doctors or dentists. It was noted that a large proportion of the adverse effects reported by the volunteers involved symptoms related to gastrointestinal complaints. There was a high prevalence of NSAIDs consumption in the studied population, which is consistent with the high frequency of risk of adverse reactions caused by these drugs, particularly in the gastrointestinal tract. In relation to antibiotics, it was observed that the non-prescription consumption of these medications by the population was considered high, reaching one-third of the total number of volunteers who consumed such medications. Full article

Background/Objective: Perioperative acute pain management in pediatric patients is essential to reduce complications. Adenoidectomy-Tonsillectomy are surgical procedures requiring pain control, and risk minimization for postoperative bleeding, nausea, and vomiting. Despite their known secondary effects, the use of opioid analgesics is still preponderant in pediatric perioperative management. We performed a comprehensive review on adeno-tonsillectomy perioperative pain management in children. We developed and implemented a multimodal analgesia protocol aimed to improve patients’ pain management while consistently reducing opioids use. Methods/Results: relevant Information was summarized, then compared to our clinical needs. Learnings were used to create and implement a multimodal analgesia protocol that we use in patients 3–9 years-old undergoing adenoidectomy/tonsillectomy. The full protocol is presented. Analgesic strategies have emerged to reduce or avoid the use of opioids. Among these strategies, combining different non-opioid analgesics (Ibuprofen, Paracetamol, Metamizole) has been shown to be an effective and safe pharmacological strategy when implemented as part of perioperative multimodal analgesia protocols. Considerable evidence associating the use of NSAIDs with a bigger risk of postoperative bleeding does not exist. Conclusions: Perioperative management of adenotonsillectomy pain should include preventive and multimodal analgesia, which have shown to provide significantly more effective analgesia than some opioid regimens. Ibuprofen offers highly effective analgesia for postoperative pain, particularly when combined with acetaminophen. Full article

Background: Obesity, Western diet (WD) consumption, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) are co-occurring and modifiable factors associated with microbiome dysbiosis and anastomotic leakage. We studied the combined effect of a Western-type diet (WD) and diclofenac, a standard NSAID used in surgical patients, on anastomotic healing and gut microbiota composition following distal colon resection. Methods: Forty-two rats were fed a WD for 6 weeks, after which they were randomized to either parenteral diclofenac 3 mg/kg/day or saline started on the day of surgery and continued for three days. The surgical procedure involved distal colon resection with anastomosis. Animals were sacrificed on postoperative day (POD)-3 or POD-5. Anastomotic healing was assessed and correlated with diclofenac treatment and gut microbiota composition, analyzed by 16S rRNA marker gene amplicon sequencing. Mucosal integrity of the anastomosis was evaluated by histological analysis. Results: Anastomotic leakage rate was 100 percent (8/8) in diclofenac-treated rats and 10 percent (1/10) in saline-treated controls on POD-5. Diclofenac administration in WD-fed animals induced a shift in microbiota composition, characterized by an increase in microbiota diversity on POD-5 and a significant 15-fold, 4-fold, and 16-fold increase of Proteobacteria, Bacteroidetes, and Verrucomicrobia, respectively. Diclofenac use in WD-fed animals caused mucosal erosion on POD-5, a phenomenon not observed in control animals. Conclusions: Consumption of a Western diet combined with diclofenac administration shifts the microbiota composition, associated with clinically relevant AL in the distal colon of rats. Full article

The aim of this paper is to raise awareness of MC as a clinically significant condition and to highlight its under-recognition, risk factors, diagnosis, management, and complications. This paper underlines the diagnostic and therapeutic challenges associated with the often nonspecific symptoms of MC. In order to create this article, we reviewed available articles found in the PubMed database and searched for articles using the Google Scholar platform. Microscopic colitis (MC) is a chronic inflammatory bowel disease, classified into three types: lymphocytic, collagenous, and unspecified. The average age of onset of MC is around 62–65 years and the disease is more common in women than men (nine times more common). The main symptom of MC is watery diarrhoea without blood, other symptoms include defecatory urgency, faecal incontinence, abdominal pain, nocturnal bowel movements, and weight loss. Once considered a rare disease, MC is now being diagnosed with increasing frequency, but diagnosis remains difficult. To date, a number of causative factors for MC have been identified, including smoking, alcohol consumption, medications (including NSAIDs, PPIs, SSRIs, and ICPIs), genetic factors, autoimmune diseases, bile acid malabsorption, obesity, appendicitis, and intestinal dysbiosis. It may be difficult to recognize and should be differentiated from inflammatory bowel diseases (Crohn’s disease and ulcerative colitis), irritable bowel syndrome (IBS), coeliac disease, infectious bowel disease, and others. Diagnosis involves biopsy at colonoscopy and histopathological evaluation of the samples. Treatment consists of budesonide oral (the gold standard) or enema. Alternatives include bile acid sequestrants (cholestyramine, colesevelam, and colestipol), biologics (infliximab, adalimumab, and vedolizumab), thiopurines, methotrexate, and rarely, surgery. Full article