Search Results (56)

Excessive alcohol consumption causes millions of deaths annually, yet current pharmacological treatments for alcohol use disorders show limited efficacy and poor adherence, creating an urgent need for new therapeutic alternatives. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde, a key mediator of the rewarding effects of alcohol in the brain, making ALDH2 activation a promising therapeutic target. This study investigated whether flurbiprofen, an FDA-approved nonsteroidal anti-inflammatory drug that activates ALDH2, reduces alcohol intake compared to the experimental ALDH2 activator Alda-1 and the structurally similar NSAID ibuprofen. Male alcohol-preferring UChB rats received oral flurbiprofen (2.5–10 mg/kg), Alda-1 (5 mg/kg), or ibuprofen (5 mg/kg) during acquisition and chronic phases of voluntary alcohol consumption under a two-bottle free-choice paradigm. Both flurbiprofen and Alda-1 reduced alcohol intake by approximately 60% and similarly increased ALDH2 activity 3–4-fold in brain and liver tissues. Ibuprofen showed modest effects (25% alcohol intake reduction). In vitro assays confirmed that flurbiprofen and Alda-1, but not ibuprofen, activated ALDH2 in PC-12 cells. Enzymatic assays and molecular docking revealed that Alda-1 lacks cyclooxygenase-inhibitory activity, unlike flurbiprofen, suggesting that ALDH2 activation is the primary mechanism underlying reduced alcohol consumption. These findings identify flurbiprofen as a clinically available ALDH2 activator with significant translational potential for treating alcohol use disorders. Full article

Background/Objectives: Improper medication use, premature treatment discontinuation, and inadequate disposal contribute to irrational drug consumption and environmental contamination. Although pharmaceutical take-back programs have expanded globally, real-world evidence on household medication accumulation in academic and community settings remains limited. This study aimed to describe longitudinal patterns of medication collection during an eleven-year university-based take-back campaign, with detailed pharmacological characterization available for selected post-pandemic years. Methods: Real-world data were analyzed from a sustainable medication take-back campaign conducted annually at the University of Colima between 2015 and 2025. Expired or unused medications were voluntarily returned by students and community members. Total collected weight was recorded for all years, while detailed classification by dosage form, Anatomical Therapeutic Chemical (ATC) group, and Mexican regulatory fraction (Fractions II, IV, V, and VI) was performed for years with complete records (2023–2025). All materials were disposed of through an authorized hazardous-waste company in compliance with NOM-052-SEMARNAT-2005. Descriptive analyses were performed using SPSS version 29.0. Results: Approximately 3.9 tons of pharmaceutical products were collected over eleven years, reflecting persistent household accumulation of unused or expired medicines. In the years with detailed analysis, oral solid dosage forms predominated. In 2025, ATC groups M, A, and C were most frequently returned, consistent with medications used for chronic conditions. Therapeutic composition varied annually, with NSAIDs/analgesics predominating in 2023–2024 and antibiotics in 2025. Across analyzed years, 5–7% of collected items corresponded to non-medication products. Conclusions: This long-term campaign provides valuable real-world evidence on medication non-use and disposal, highlighting ongoing challenges in rational medicine use, treatment continuity, and environmentally responsible pharmaceutical waste management. Full article

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics. However, their inappropriate or excessive use may lead to serious adverse effects. The aim of the study was to analyze behavioral patterns and attitudes toward the use of over-the-counter (OTC) NSAIDs, as well as the perception of risks associated with their use. Methods: A cross-sectional survey was conducted among 567 respondents. An anonymous questionnaire consisting of 26 items was used, addressing sociodemographic characteristics, frequency of reading drug information leaflets, frequency of NSAID use, and awareness of potential adverse effects associated with these medications. Results: The demographic factors significantly influenced NSAID-related behaviors. Women were significantly more likely than men to read drug information leaflets and reported more frequent use of OTC NSAIDs. Older respondents exhibited greater adherence to the principles of responsible NSAID use. Higher educational attainment was associated with more frequent and attentive reading of drug information leaflets. Urban residents reported higher median frequencies of NSAID use, whereas students demonstrated greater awareness of potential NSAID adverse effects compared with non-students. Conclusions: The results reveal complex patterns of NSAID consumption and underscore the need for implementing targeted public health interventions. Full article

Pharmaceuticals are increasingly recognized as contaminants of emerging concern, yet monitoring strategies often do not reflect actual consumption patterns or ecological risk. Greece presents a particularly relevant case due to high pharmaceutical use and fragmented monitoring data. In the present study, 359 pharmaceuticals, metabolites, and transformation products were reviewed, as reported in monitoring studies in Greek wastewater, surface waters, and drinking water. Consumption data (from the Organization for Economic Co-operation and Development, OECD), environmental occurrence (from 55 studies), and ecotoxicity thresholds (i.e., from the NORMAN Database) were integrated to calculate risk quotients (RQs) and assess monitoring gaps. RQ values were derived for 241 compounds: 38 (16%) high-risk, 60 (25%) medium-risk, and 143 (59%) low-risk. High-risk substances included several NSAIDs, macrolide and fluoroquinolone antibiotics, synthetic hormones, contrast agents, and triclosan. Major under-monitoring was observed for widely consumed classes A and B, while antibiotics, NSAIDs, antidepressants, and analgesics were disproportionately targeted. Several metabolites showed higher RQs than their parent compounds but were rarely analyzed. These findings reveal significant mismatches between pharmaceutical use, environmental occurrence, and ecological risk in Greece. Results support adopting risk-based prioritization for environmental monitoring and align with ongoing updates to EU water policy. Full article

Diabetic foot ulcers (DFUs) represent 6.3% of the various complications of type 2 diabetes mellitus, with a risk of development of up to 34%. Several factors contribute to the formation of ulcers, which are very difficult to treat as they hinder efficient wound healing. Patients experience persistent pain, which leads to the consumption of various medications (polypharmacy) due to the lesions not resolving. Conversely, this can increase the risk of various factors, including a chronic inflammatory state, which hinders the body’s own regenerative processes. Until now, treatment options have been limited to washing the wound and stimulating new tissue growth, but this is a painful and unsuccessful process. One of the treatment options is therefore cell therapy with mesenchymal stem cells, which have immunomodulatory characteristics and allow tissue regeneration, although the effect directly in pain is not totally clear. We have previously reported in our working group that patients with ulcers treated with mesenchymal stem cells (MSCs) have been able to integrate into their daily lives, although the pain related to the inflammatory state and polypharmacy has not been studied. Objective: This study investigates how the local administration of MSCs improves the condition of an ulcer by inducing tissue regeneration. It also shows how the concentration of systemic inflammatory biomarkers is modified in direct correlation with pain and the consumption of medications over time. Methods: Local administration of MSCs at 7 and 14 days, measuring pro- and anti-inflammatory cytokines relative to the healthy control group, evaluating wound healing, and monitoring the medications taken by the patient in conjunction with pain perception. Results: Cell administration showed that inflammatory molecules were reduced and anti-inflammatory molecules increased. This is reflected in the consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in relation to wound improvement, with a decrease in pain medication consumption of less than 50%. We provide evidence that locally administered mesenchymal stem cells influence systemic inflammatory processes necessary for tissue recovery, impacting patients’ polypharmacy consumption due to reduced perceived pain. Conclusions: This report establishes a direct link between mesenchymal stem cells and pain relief in type 2 diabetes ulcers, potentially paving the way for new pain therapies. Full article

Background/Objectives: Gastric mucosal lesions represent a significant health burden, with Helicobacter pylori infection being the primary cause of chronic gastritis worldwide. However, the role of modifiable lifestyle factors in modulating the severity of gastric lesions remains incompletely characterized, particularly in Eastern European populations. This study aimed to analyze the relationship between dietary behaviors, smoking, alcohol consumption, and the severity of endoscopic gastric lesions in Romanian patients. Methods: We conducted a cross-sectional study including 361 patients who underwent upper gastrointestinal endoscopy at Târgu Mureș County Clinical Emergency Hospital between 2019 and 2025. Endoscopic lesion severity was classified on an ordinal scale (0 = normal; 1 = edema/erythema; 2 = erosions; 3 = ulcer/bleeding). Dietary intake was assessed using a validated food frequency questionnaire, with foods classified as pro-inflammatory or protective. Ordinal logistic regression models were used to examine associations between lifestyle factors and the severity of gastric lesions, adjusted for age, sex, and H. pylori status. Results: Among participants (median age 65 years, 46.5% male), 45.2% had clinically significant lesions (≥2). H. pylori infection was present in 31.6% of participants. Current smoking (15.2% of participants) showed a trend toward increased severity of gastric lesions (fully adjusted OR 1.59, 95% CI 0.93–2.71, p = 0.092), though not statistically significant. Among current smokers, 52.7% had clinically significant lesions versus 43.8% among non/former smokers. The smoking–alcohol interaction was not statistically significant (interaction OR = 1.19, 95% CI: 0.34–4.17, p = 0.780). Dietary balance score showed no association with the severity of gastric lesions (OR = 1.061 per 10-unit increase, p = 0.355). NSAID use emerged as the strongest predictor (OR = 1.68, 95% CI 1.01–2.78, p = 0.044). The number of cumulative risk factors correlated significantly with clinically significant lesions (Spearman r = 0.107, p = 0.042), with prevalence increasing from 34.5% in patients with 0–1 factors to 83.3% with 6+ factors. Conclusions: Current smoking showed a trend toward increased severity of gastric lesions in this Romanian cohort, though not reaching statistical significance. NSAID use was the only significant independent predictor. The dose–response relationship between cumulative risk factors and the severity of lesions emphasizes the importance of comprehensive risk assessment and multi-factorial interventions in gastric disease prevention. However, as a cross-sectional study, these associations cannot establish causality and should be confirmed in prospective cohorts. Full article

Background: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a critical medical–surgical emergency associated with significant morbidity, mortality, and healthcare burden worldwide. Despite advances in diagnostic and therapeutic modalities, NVUGIB continues to pose complex clinical challenges, particularly in resource-limited settings. Methods: This retrospective observational study analyzed 364 consecutive adult patients diagnosed with NVUGIB and hospitalized at the First Surgical Clinic of the County Emergency Clinical Hospital Craiova between January 2009 and December 2014. Inclusion criteria required a confirmed diagnosis based on clinical presentation, laboratory findings, and upper gastrointestinal endoscopy (UGIE). Demographic variables, etiology, comorbidities, drug-induced triggers, laboratory parameters, onset-to-admission and onset-to-surgery intervals, endoscopic findings, therapeutic interventions (medical, endoscopic, surgical), rebleeding rates, and mortality were recorded and analyzed. Results were descriptively compared with historical data from the national and international literature. Due to the retrospective and aggregate nature of the data, survival analysis (Kaplan–Meier) was not applicable. Results: Peptic ulcers, erosive gastritis, Mallory–Weiss syndrome, and gastric neoplasms were the predominant etiologies. NSAID use, oral anticoagulation, and alcohol consumption emerged as major risk factors. Endoscopic hemostasis was achieved in the majority of cases; surgical intervention was required in 11.5% of patients, mainly for refractory or recurrent bleeding. The overall mortality rate was 10.9%, consistent with historical benchmarks. Comparative analysis revealed trends in etiology and management reflecting evolving clinical practice standards. Conclusions: NVUGIB remains a significant clinical challenge with persistent mortality and rebleeding risks. This cohort highlights the need for timely diagnosis, risk stratification, and an evidence-based therapeutic strategy integrating modern endoscopic and surgical options. An updated diagnostic and management algorithm is proposed to guide practical decision-making and optimize outcomes in similar tertiary care settings. Full article

Background and Objectives: Psoriasis is a chronic inflammatory skin disease, and biologic therapies have revolutionized treatment by targeting key cytokine pathways. While these therapies effectively control psoriatic lesions, their impact on other cutaneous structures, such as cherry angiomas and solar lentigines, remains unclear. Angiomas are benign vascular proliferations influenced by systemic inflammation and hormonal factors, whereas solar lentigines are UV-induced pigmentary lesions associated with aging and sun exposure. This study aimed to assess the impact of biologic therapies on the development of these lesions in psoriasis patients. Materials and Methods: This retrospective observational study was conducted over a five-year period (2019–2024) at a tertiary dermatological center in Southeastern Europe. Clinical and demographic data, including treatment history, were extracted from medical records, while digital dermoscopy was used to assess lesion progression. Statistical analyses evaluated associations among biologic therapy classes, systemic inflammation, and cutaneous lesion development. Results: Angioma prevalence was significantly higher among postmenopausal women and those with osteoporosis, suggesting a hormonal influence on vascular proliferation. Patients with psoriatic arthritis had a greater angioma burden, reinforcing the role of chronic inflammation in angiogenesis. IL-23 inhibitors were linked to increased angioma formation compared to TNF-α inhibitors, while methotrexate and UVB therapy appeared to have a protective effect. Solar lentigines were more frequent in postmenopausal women and in patients with systemic inflammatory conditions. In contrast, smoking and moderate alcohol consumption were associated with lower lesion counts. Conclusions: Our findings suggest that biologic therapies, particularly IL-23 inhibitors, may contribute to angiogenesis and pigmentary changes in psoriasis patients, highlighting the influence of systemic inflammation on vascular and melanocytic activity. Additionally, TNF-α inhibitors and NSAIDs were associated with an increased prevalence of solar lentigines, while methotrexate and UVB therapy appeared to have a protective effect. Given these associations, further research is needed to elucidate the underlying mechanisms and refine treatment strategies to optimize dermatologic care for psoriasis patients. Full article

Background: This study evaluated the postoperative effects of hyaluronic acid (HA) on pain, swelling, and trismus following mandibular third molar surgery. Material and Methods: Thirty healthy patients with bilateral impacted mandibular third molars underwent two surgeries at 21-day intervals. In a split-mouth design, one extraction socket was treated with 0.2 mL of high-molecular-weight hyaluronic acid gel (Monovisc^® [molecular weight ≈ 1.5–2.2 million Da]), while the contralateral socket received no additional treatment. Perioperative medications, including NSAIDs, were standardized for all patients. Data collection included postoperative pain, swelling (using Gabka and Matsumura’s method), analgesic consumption, and trismus (mouth opening) on designated days. Data were analyzed using the Mann–Whitney U and Wilcoxon signed-rank tests with Bonferroni correction (adjusted significance level: p > 0.0083). Results: The mean VAS pain scores on day 1 were 63.5 ± 22.3 in the HA group and 61.9 ± 12.5 in the control group, decreasing to 3.9 ± 7.6 and 3.3 ± 7.2, respectively, by day 7 (p > 0.0083). The maximum interincisal distance on day 7 was 45.9 ± 7.4 mm in the HA group and 43.5 ± 7.3 mm in the control group, showing a slight improvement (p = 0.002). Swelling, measured using the tragus–pogonion distance, was 164.6 ± 20.7 mm in the HA group and 166.3 ± 18.9 mm in the control group on day 7 (p > 0.0083). Analgesic consumption remained comparable across all postoperative days (p > 0.0083). No statistically significant differences were observed between the HA and the control groups at any evaluated time point. Conclusions: Hyaluronic acid application after mandibular third molar surgery demonstrated a slight improvement in trismus on day 7, but no significant long-term advantages in pain or swelling. While early postoperative improvements in trismus were observed, these findings require further validation. Additional studies are needed to explore HA’s potential clinical applications in oral surgery. Full article

Intravenously administered nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a crucial component of multimodal analgesia strategies in surgical settings. This narrative review aims to provide an up-to-date evaluation of the efficacy, safety, and clinical use of intravenous (IV) NSAIDs for perioperative pain management in adults and children. The NSAIDs and selective COX-2 inhibitors (coxibs) approved in Europe for the short-term symptomatic treatment of acute, moderate perioperative pain via IV infusion in adults and/or children have been influenced by US and global guidelines and practice: the drugs primarily reviewed here are ibuprofen, ketorolac, ketoprofen, naproxen, paracetamol, and acetylsalicylic acid. Furthermore, intravenous ibuprofen is authorized for the short-term symptomatic treatment of fever. In contrast to intravenous ketoprofen, intravenous ibuprofen is authorized for administration to children over 6 years of age or weighing more than 20 kg. Overall, IV ibuprofen had a more favorable profile with regard to peri- and postoperative opioid sparing and pain relief. Oral ibuprofen and IV ibuprofen have similar levels of efficacy, although IV ibuprofen has a shorter onset of action and is required in patients who are unable to take oral medications. The frequency of significant adverse events appears to be similar for ibuprofen and paracetamol. Systematic reviews and meta-analyses report that intravenous NSAIDs reduce postoperative opioid consumption by approximately 20–60%, improving pain management with fewer opioid-related side effects. In indications in infants, the choice of medication is limited, and the oral route is not always feasible; IV formulations of ibuprofen are preferred in this setting. Topics for further research should include head-to-head trials of IV NSAIDs. Full article

Background: Hypnosis sedation has recently been used for anesthesia in breast oncologic surgery. Methods: Between January 2017 and October 2019, 284 patients from our Breast Clinic (Cliniques Universitaires Saint-Luc, Université Catholique de Louvain) and from the Jolimont Hospital were prospectively included in an interventional non-randomized study approved by our two local ethics committees and registered on clinicaltrials.gov (NCT03330117). Ninety-three consecutive patients underwent surgery while on general anesthesia (GA group). Ninety-two consecutive patients underwent surgery while on general anesthesia preceded by a hypnorelaxation session (GAVRH group). Ninety-five consecutive patients underwent surgery while exclusively on hypnosis sedation (HYPS group). Clinical parameters (pain score, anxiety and distress score) were measured on days 0, 1 and 8 for all patients. All evaluable patients underwent NLR (neutrophil-to-lymphocyte ratio) and CRP (C-reactive protein) dosage on days 0, 1 and 8. Results: Pain scores and anxiety scores were statistically lower in the HYPS group on days 1 and 8, as was the duration of NSAID consumption. NLR and CRP values were significantly inferior on day 1 for all patients who benefited from hypnosis sedation. Conclusions: Some benefits of hypnosis sedation (reduction in postoperative pain, decrease in NSAID consumption) are correlated with a significant reduction in inflammatory parameters in the perioperative process. Full article

Glioblastoma multiforme (GBM) is a malignant primary brain tumor categorized as a Grade 4 astrocytic glioma by the World Health Organization (WHO). Some of the established risk factors of GBM include inherited genetic syndromes, body mass index, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and therapeutic ionizing radiation. Vascular anomalies, including local and peripheral thrombosis, are common features of GBM. Podoplanin (PDPN), a ligand of the C-type lectin receptor (CLEC-2), promotes platelet activation, aggregation, venous thromboembolism (VTE), lymphatic vessel formation, and tumor metastasis in GBM patients. It is regulated by Prox1 and is expressed in developing and adult mammalian brains. It was initially identified on lymphatic endothelial cells (LECs) as the E11 antigen and on fibroblastic reticular cells (FRCs) of lymphoid organs and thymic epithelial cells as gp38. In recent research studies, its expression has been linked with prognosis in GBM. PDPN-expressing cancer cells are highly pernicious, with a mutant aptitude to form stem cells. Such cells, on colocalization to the surrounding tissues, transition from epithelial to mesenchymal cells, contributing to the malignant carcinogenesis of GBM. PDPN can be used as an independent prognostic factor in GBM, and this review provides strong preclinical and clinical evidence supporting these claims. 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: 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