Search Results (275)

Wastewater-based epidemiology (WBE) is an approach that uses information obtained from the analysis of various metabolites or residues in wastewater with the aim of assessing the consumption of or exposure to chemicals or pathogens in a population connected to a sewage system. The aim of this work was to develop methods for the isolation and analysis of seven beta-blockers (acebutolol, atenolol, betaxolol, metoprolol, nadolol, pindolol and propranolol) in wastewater samples collected from the influent of the wastewater treatment plant in Cluj-Napoca, Romania, in order to estimate their consumption among the population in two time periods (February and October 2024) using WBE. The selected beta-blockers were extracted by solid phase extraction using a Strata C18-U cartridge and analyzed by liquid chromatography coupled with tandem mass spectrometry. The consumption was estimated using the daily mass load of pharmaceutical products reported per 1000 inhabitants (mg/day/1000inh) and varied in the following ranges: atenolol 0.03–3.74, nadolol 0.03–0.1, propranolol 0.04–0.72, betaxolol 0.07–0.38, and metoprolol 54.85–276.45. From the obtained results, it can be observed that metoprolol is the most used beta-blocker in the investigated population, followed by atenolol, propranolol and betaxolol. Other beta-blockers are consumed in small quantities or occasionally. Full article

This study evaluated the efficiency and ecotoxicological impact of the Fenton oxidation process with different metal-based catalysts (FeSO₄, CuSO₄, MnSO₄) in removing pharmaceuticals and organic contaminants from real hospital wastewater. All catalytic systems achieved high oxidation, with COD reduction reaching 81–89% after 4 h. Two complementary approaches were applied: targeted LC-MS/MS quantification of a model mixture of antibiotics and pharmaceuticals, and untargeted GC-MS/MS screening method for assessing the overall organic contaminant profile. Toxicity was assessed using Microtox^®. Targeted analysis showed complete or near-complete degradation of β-lactams, tetracyclines and most sulfonamides, with slightly lower removal for sulfamethoxazole in FeSO₄ system (96%). Fluoroquinolones and selected pharmaceuticals, such as caffeine and propranolol were more resistant, particularly with CuSO₄ and MnSO₄ catalysts. The untargeted GC-MS/MS screening revealed the highest overall reduction in chromatographic peak areas for FeSO₄ (70%), followed by MnSO₄ (39%) and CuSO₄ (36%). GC-MS/MS profiling confirmed that the Fe-catalyzed process was the most effective in reducing the total chromatographic peak area (70%). However, ecotoxicological assays revealed a significant increase in toxicity post-treatment, with growth inhibition of Allivibrio fischeri reaching 98%. This suggests that high oxidation does not directly correlate with biological safety, likely due to the presence of unconsumed reagents or the formation of transformation products with higher acute toxicity. These findings emphasize the necessity of integrating bioassays into treatment evaluation protocols to assess the true environmental risk of treated effluents. Full article

Background: Essential tremor (ET) is a common movement disorder that predominantly affects older adults, with rising global prevalence due to population aging. Pharmacological treatments, including propranolol and primidone, are often limited by inadequate efficacy or poor tolerability, and surgical options carry inherent risks. Acupuncture has shown promise as an alternative or adjunctive therapy for ET, but evidence comparing the effectiveness of different acupuncture modalities remains limited. Objective: To systematically evaluate the comparative efficacy and safety of various acupuncture-related interventions for essential tremor (ET) through a network meta-analysis, and to provide evidence-based recommendations for clinical practice. Methods: We systematically searched eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and CBM) from inception to 20 October 2025. Randomized controlled trials (RCTs) evaluating any form of acupuncture therapy for ET were included. Conventional pairwise meta-analysis and network meta-analysis were performed to compare the efficacy (response rate, Tremor Six Score) and safety (adverse events) of different interventions. Surface under the cumulative ranking curve (SUCRA) values were used to rank treatment modalities. Results: Twenty randomized controlled trials involving 1067 participants were included. Traditional meta-analysis indicated that acupuncture-related interventions significantly outperformed controls in improving response rate [RR 4.36, 95% CI (3.14, 6.03), p < 0.00001], reducing Tremor Six Score [MD −1.99, 95% CI (−2.25, −1.73), p < 0.00001], and lowering the incidence of adverse events [RR 0.13, 95% CI (0.07, 0.25), p < 0.00001]. Network meta-analysis based on SUCRA values revealed that: for symptom relief, scalp acupuncture (S) demonstrated the highest effectiveness (SUCRA = 81.5%); for reducing Tremor Six Score, manual acupuncture (A) showed the most significant effect (SUCRA = 76.6%); and for safety outcomes, Acupuncture + Scalp Acupuncture + Propranolol (A+S+P) achieved the highest SUCRA score (SUCRA = 73.1%). Conclusions: This network meta-analysis demonstrates that acupuncture-related interventions are effective and safe for treating essential tremor. However, caution is warranted in interpreting these findings due to methodological limitations in the included randomized controlled trials (small sample sizes, lack of blinding, inadequate allocation concealment), sparse data for some interventions, and the concentration of studies within China, which limits their generalizability. Despite these limitations, acupuncture offers a valuable non-pharmacological treatment option for patients with poor medication tolerance. Future large-scale, multicenter trials with rigorous designs are needed to validate these findings. Full article

Background: The issue of beta blocker poisoning has received little attention, despite the widespread use of these compounds in cardiac and neuropsychiatric care. Safety profiles differ, and some beta blockers appear in poisonings far beyond what their usage rates imply. This study characterizes beta blocker intoxication patterns in Belgium, focusing on propranolol, by integrating national prescription data, poisoning reports, and adverse drug reaction records. Methods: Belgian prescription data, poison centre reports, and European ADR databases were analysed to identify intoxication patterns and demographic or clinical characteristics associated with these events. Results: Poisoning data revealed propranolol as markedly overrepresented compared to prescription rates and was the primary beta blocker implicated in self-harm-related overdoses. These cases occurred mainly in women, younger individuals, and patients with psychiatric or cardiovascular comorbidities. Co-exposures with benzodiazepines, antidepressants, and other psychoactive agents were frequent, and propranolol was linked to more complex intoxication patterns than other beta blockers. Conclusions: Propranolol shows a distinct toxicological profile and is disproportionately involved in intoxications, especially in vulnerable groups and in combination with psychoactive drugs. These findings highlight the need for greater awareness, targeted prevention, and careful monitoring. Full article

Background: The role of nonselective beta blockers (NSBB) in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) has been a subject of debate. Conflicting studies exist regarding their impact on mortality in this population. This study aims to evaluate the effect of NSBB on mortality in patients with cirrhotic ascites and a history of SBP. Methods: Data were obtained from the TRNETX database, identifying patients aged 18 to 80 years with cirrhosis, ascites, and SBP using ICD-9 and ICD-10 codes. The study period spanned from September 2001 to January 2024. Patients were divided into two groups: those with SBP receiving NSBB (SBP + NSBB), such as carvedilol, nadolol, and propranolol, and those with SBP not receiving NSBB (SBP − NSBB). The primary outcome was all-cause mortality, and the secondary outcome was the development of acute kidney injury (AKI). Outcomes were assessed over a two-year follow-up period. Additionally, we evaluated the association of NSBB use and mortality in cirrhotic ascites by creating two separate cohorts: patients with cirrhotic ascites on NSBB (Ascites + NSBB) and those not on NSBB (Ascites − NSBB). A 1:1 propensity score matching was conducted based on baseline demographics, comorbidities, and laboratory parameters, including creatinine, INR, sodium, albumin, and bilirubin. Results: Before propensity matching, 18,160 patients were identified in the SBP-NSBB cohort, and 14,198 patients were in the SBP + NSBB cohort. After matching, each group comprised 11,801 patients. Patients with SBP who did not receive NSBB therapy exhibited higher mortality than those on NSBB therapy [OR 1.12, 95% CI 1.05–1.21]. Conversely, the incidence of AKI was higher in the SBP + NSBB group [OR 0.91, 95% CI 0.87–0.95]. In the cirrhotic ascites cohort, patients not receiving NSBB (Ascites − NSBB) demonstrated higher mortality compared to those on NSBB (Ascites + NSBB) [OR 1.17, 95% CI 1.13–1.20]. Conclusions: In a propensity-matched analysis of large patient cohorts, NSBB therapy was associated with reduced mortality in both patients with cirrhotic ascites and those with SBP. Despite a higher incidence of AKI in the SBP + NSBB group, NSBB treatment appears beneficial in reducing overall mortality in these populations. Full article

Background: Fibromyalgia syndrome (FMS) and post-traumatic stress disorder (PTSD) may co-occur and are associated with increased symptom burden, functional impairment, and reduced quality of life. Accumulating evidence suggests shared neurobiological mechanisms. Trauma-focused interventions targeting maladaptive memory processes may therefore represent a relevant therapeutic approach in this population. Objective: To evaluate the feasibility, tolerability, and preliminary clinical associations of a brief reconsolidation-based therapy in women with comorbid FMS and PTSD. Methods: This multicenter pilot study included adult women diagnosed with FMS and PTSD who underwent six sessions of reconsolidation therapy combining traumatic memory reactivation with propranolol administration. Clinical outcomes were assessed at baseline and at 3-month follow-up using the Fibromyalgia Impact Questionnaire (FIQ), the Impact of Event Scale–Revised (IES-R), the Montgomery–Åsberg Depression Rating Scale (MADRS), the Beck Depression Inventory (BDI), the Rosenberg Self-Esteem Scale (RSES), and the SF-36. Changes over time were analyzed using paired statistical tests and linear mixed-effects models. Results: Fourteen participants completed the intervention and follow-up assessments. The intervention was feasible and well tolerated. Changes over time were observed in fibromyalgia-related quality of life (FIQ scores), PTSD symptom severity (IES-R), and depressive symptoms (MADRS, BDI), as well as in selected SF-36 domains, including vitality, social functioning, and mental health. A progressive decrease in IES-R scores was observed across treatment sessions. Conclusions: This pilot study suggests that reconsolidation-based therapy is feasible in women with comorbid FMS and PTSD and was associated with changes in PTSD symptoms and fibromyalgia-related functional impact. Given the exploratory design and absence of a control group, these findings should be interpreted cautiously and warrant confirmation in larger, controlled trials. Full article

Background/Objectives: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by recurrent epistaxis, anemia, and visceral arteriovenous malformations. Epistaxis is the most frequent and disabling manifestation, with limited effective pharmacological options. Propranolol, a non-selective beta-blocker with vasoconstrictive and antiangiogenic properties, has shown benefit in other vascular anomalies but remains scarcely studied in HHT. This study aimed to evaluate the effect of oral propranolol on nasal bleeding in patients with HHT. Methods: A retrospective observational study including 151 adults with HHT (44 treated with propranolol, 107 untreated) was conducted using data from an Institutional HHT Registry from a referral center. Baseline demographic and clinical variables were recorded. Outcomes at 6 months included changes in hemoglobin, adherence to nasal hygiene, use of bleeding-related therapies, and improvement in epistaxis frequency and intensity according to the Sadick–Bergler scale. Logistic regression models were adjusted for confounders and indication bias using inverse probability of treatment weighting (IPTW). Results: After IPTW adjustment, propranolol was significantly associated with reduced frequency of epistaxis (adjusted OR: 3.8; 95% CI: 1.3–11.2; p = 0.016), while no effect was observed on intensity. Hemoglobin levels increased modestly in both groups without a significant difference. Patients without propranolol showed greater antifibrinolytic use, whereas adherence to nasal care remained stable among treated patients. Conclusions: Oral propranolol reduced nasal bleeding frequency in HHT, even among patients with greater baseline severity. Given its accessibility, safety, and potential to lessen treatment burden, it may represent a valuable adjunct therapy. This study represents the largest cohort of HHT patients treated with propranolol reported to date. Randomized trials including standardized bleeding scores and patient-reported outcomes are warranted to confirm clinical and quality-of-life benefits. Full article

Background/Objectives: Situations previously paired with drug use can become conditioned stimuli (i.e., physical stress or psychosocial stress) that elicit intense craving and relapse, even after prolonged abstinence. Previous studies have shown that pharmacological disruption of reconsolidation after memory reactivation could be promising for reducing pathological fear and stress-related responses. For this reason, the aim of this research was to examine the role of β-AR in the retrieval of aversive memories through the potential of β-AR antagonism to mitigate the effects of exposure to stressful stimuli. Methods: This question was addressed using a model to assess the re-emergence of an aversive contextual memory induced by both physical stressors (restraint and tail-pinch) and psychosocial stress (social defeat) in morphine- or saline-treated mice previously subjected to a conditioned place aversion (CPA) paradigm, in which naloxone was administered to precipitate opioid withdrawal. To assess the effects of propranolol on aversive memories related to opioid addiction, the number of chamber crossings and the time spent in the naloxone-paired compartment were measured. Results: Our results showed that morphine-treated mice spent significantly less time in the naloxone-paired chamber than saline mice during the post-test and after exposure to stressful stimuli, than during the pre-test, showing an effect for aversive memories in addiction. In contrast, when propranolol was administered intraperitoneally 30 min before the exposure to both social and physical stress, the time spent enhanced significantly (p < 0.01), supporting a role for propranolol in addiction-related memories. Conclusions: These results suggest that propranolol could attenuate the aversive memories that may contribute to relapse to opioid addiction. Full article

The development of advanced macromolecular systems with tailored structural and functional properties is a key objective in modern materials science, particularly for biomedical applications such as targeted drug delivery. In this study, hydrogel (HG), a polymer-based formulation, was investigated as a functional carrier for the enhanced intradermal and transdermal delivery of propranolol hydrochloride (PRO-HCl), a highly water-soluble model compound, and its potential was compared to other vehicles easily obtained by pharmacists: ointment (OM), liposomal cream (LCR), and microemulsion (ME). The formulations were characterized by their physicochemical and rheological characteristics, and evaluated in vitro and ex vivo using vertical diffusion cells equipped with synthetic membranes, intact porcine skin, and skin pretreated with solid microneedles (MNs). The HG formulation exhibited superior release performance (2396.85 ± 48.18 μg/cm²) and the highest intradermal drug deposition (19.87 ± 4.12 μg/cm²), while its combination with MNs significantly enhanced transdermal permeation (p = 0.0017). In contrast, the synergistic effect of MNs and ME led to a pronounced increase in drug accumulation within the skin (up to 60.3-fold). These findings highlight the crucial role of matrix composition and properties in modulating molecular transport through biological barriers. The study demonstrates that polymeric HGs represent versatile, functional materials with tunable structural and mechanical features, suitable for controlled release and potential systemic delivery applications. Full article

Glucagon is an endogenous peptide that is produced in the pancreas. Via glucagon receptors, glucagon increases the beating rate in cultured rat neonatal cardiomyocytes and also in isolated right atrial preparations from adult rats. Moreover, in living adult mice, injections of glucagon can elevate the heart rate. It is unknown whether these effects of glucagon in living adult mice are mediated via central glucagon receptors or via a direct effect on cardiac glucagon receptors. Thus, we tested the hypothesis that glucagon can exert a direct positive chronotropic effect in the adult mouse heart. We measured the contractile effects of cumulatively increasing concentrations of glucagon (0.1–100 nM) in isolated paced (1 Hz) left atrial preparations, in isolated spontaneously beating right atrial preparations and in isolated spontaneously beating retrogradely perfused whole hearts. We detected in isolated right atrial preparations time- and concentration-dependent positive chronotropic effects of glucagon that were reversed by the glucagon receptor antagonists SC203972 and desglucagon. The positive chronotropic effects of glucagon were also attenuated by 1 µM of ivabradine, an inhibitor of the hyperpolarization-activated cation channels (HCN), but not by 100 nM rolipram, a phosphodiesterase 4 inhibitor, nor by 10 µM of propranolol, a β-adrenoceptor antagonist. Moreover, the positive chronotropic effects of glucagon were also attenuated by stimulation of the A₁-adenosine receptor or muscarinic receptors. Glucagon decreased the force of contraction in right atrial preparations. In left atrial preparations, glucagon failed to alter the force of contraction. In isolated adult mouse hearts perfused in the Langendorff mode, 10 nM of glucagon increased the beating rate and reduced left ventricular force of contraction. The gene expression of the glucagon receptors was lowest in the left atrium, higher in the ventricle and highest in the right atrium of adult mice. In summary, glucagon exerted a positive chronotropic effect in the mouse heart via glucagon receptors, mediated, at least in part, via HCN channels in the sinus node. Full article

Wastewater treatment plants (WWTPs) have been identified as the major sources of contaminants of emerging concern (CECs) in water bodies, as they are not designed to remove organic micropollutants efficiently. Consequently, many technologies have been explored for WWTP upgrading, including activated carbon adsorption. However, the high production cost and environmental challenges associated with activated carbon production limit its application in industrial settings. Therefore, a wide range of alternative materials has been investigated as potential replacements. In this study, biochar produced from waste raspberry biomass was evaluated as an adsorbent for the removal of pharmaceuticals and pesticides quantified in the secondary effluent of municipal WWTP. The results showed that the biochar efficiently removed almost all detected compounds, except for three compounds (clarithromycin, propranolol, and linuron). The wastewater pH (6–8) did not significantly affect removal efficiency significantly, and kinetic tests demonstrated rapid adsorption. The potential for biochar reuse was confirmed through three consecutive batch adsorption cycles. A comparative study between biochar and powdered activated carbon (PAC) revealed some differences in efficiency, primarily attributed to the larger surface area of PAC. π-π interactions, hydrogen bonding, and pore-filling were proposed as possible adsorption mechanisms based on the adsorption efficiency and biochar characterization. Full article

An 8-year-old castrated male Pomeranian with a non-resectable functional thyroid carcinoma and concurrent myxomatous mitral valve disease was referred for radioactive-iodine therapy. Due to clinical thyrotoxicosis at referral and concurrent cardiac disease, the radioiodine dose was selected conservatively at the lower end of the reported therapeutic range. Despite a conservative radioactive iodine dose, the dog developed acute thyrotoxic decompensation consistent with thyroid storm (manifesting as anxiety, diarrhea, hyperthermia, hypersalivation, and marked tachycardia) within hours of treatment. Propranolol and butorphanol administration led to rapid clinical stabilization. Before the second radioactive iodine therapy, methimazole and propranolol were used for subsequent management, effectively controlling thyrotoxicosis risk and enabling a higher radioiodine dose. Serum thyroxine normalized within 1 month after the second treatment, and the dog maintained complete clinical remission thereafter. Radioactive iodine therapy served as definitive therapy to prevent recurrent life-threatening thyrotoxicosis, resulting in a euthyroid state and long-term survival. This case describes the first documented case of a dog with thyroid carcinoma developing probable thyroid storm associated with radioiodine treatment and subsequently achieving a favorable prognosis. Full article

Nicotine promotes non-small cell lung cancer (NSCLC) survival in part by elevating vascular endothelial growth factor (VEGF), yet the upstream regulatory mechanisms remain unclear. Here we identify a PKA–HA–p53 regulatory axis that governs nicotine-driven VEGF levels and survival in A549 (p53⁺/⁺) and H1299 (p53-null) cells. Nicotine increased VEGF levels in the media, an effect augmented by protein kinase A (PKA) activation and reduced by PKA inhibition. Blocking hyaluronan (HA) synthesis with 4-methylumbelliferone (4-MU) lowered VEGF levels and diminished the nicotine response, suggesting that HA–CD44 contributes to PKA-linked survival pathways. In A549, p53 inhibition or knockdown enhanced PKA activity and VEGF levels, indicating that p53 constrains this axis; by contrast, H1299 displayed sustained nicotine responsiveness consistent with p53 loss. Pharmacologic nAChR/β-adrenergic blockade blunted nicotine-induced PKA signaling. Functionally, VEGF immunodepletion or co-treatment with a PKA inhibitor, 4-MU, or anti-VEGF antibodies reduced nicotine-supported viability and increased apoptosis, while the addition of purified VEGF rescued survival, establishing the role of VEGF in this pathway. Collectively, these findings delineate a mechanistic network in which PKA, HA–CD44 signaling, and p53 integrate nicotinic cues to control VEGF media levels and cell survival, identifying potential targets (PKA, HA synthesis, VEGF) for mitigating nicotine-mediated NSCLC progression. Full article

Melanoma, in advanced stages, is the most invasive type of skin cancer, with currently available treatments showing limited efficiency. The number of melanoma cancer cases is expected to increase in the coming years, emphasizing the need for more efficient therapeutic strategies. The present study aimed to evaluate the potential of β-blockers, commonly used to treat cardiac conditions, to be repurposed for the treatment of melanoma. The effects of non-selective β-blockers (carvedilol and propranolol), β1 selective blockers (atenolol and metoprolol) and antineoplastics drugs (cisplatin and 5-fluorouracil) on the A375 melanoma cell line were studied, individually and in combined exposures, by assessing cell viability over a 72 h period. The 72 h half-maximal inhibitory concentrations (IC₅₀s) determined for A375 cells allow the ranking of toxicity as: cisplatin (2.46 (1.87–3.38) μM) > 5-fluorouracil (4.77 (4.48–5.07) μM) > carvedilol (16.91 (15.47–18.99) μM) > propranolol (58.03 (57.08–59.11) μM) > atenolol and metoprolol (β1 selective blockers that exhibited no significant effect on the cell’s viability). The effects of combined exposures were also studied. Metoprolol and carvedilol exhibited synergistic interactions with cisplatin at specific concentrations. Overall, the data highlight the concentration-dependent nature of mixture effects and support the potential application of β-blockers melanoma treatment. Full article

β-blockers are among the most widely prescribed cardiovascular drugs and are increasingly recognised as emerging pollutants due to their persistence, continuous release into aquatic environments, and potential toxicological effects on aquatic organisms. Their removal in conventional wastewater treatment plants is often inefficient, highlighting the need for biological remediation strategies. This study aimed to identify bacterial strains with the highest potential for the biotransformation of β-blockers. Therefore, we isolated and characterised bacterial strains capable of transforming two commonly used β-blockers—propranolol and metoprolol. The strains BB2 and BB3, which were able to transform propranolol and metoprolol, respectively, were identified as Raoultella terrigena and Stenotrophomonas terrae, respectively. BB2 showed broad metabolic versatility, utilising a wide range of carbon sources, whereas BB3 exhibited limited substrate utilisation. Antibiotic resistance profiling further distinguished the strains, with BB2 resistant across multiple antibiotic classes and BB3 largely sensitive. Co-metabolic assays demonstrated that supplementation with specific carbon and nitrogen sources markedly enhanced β-blocker removal, increasing propranolol biotransformation from 5% to 50% and metoprolol from 4% to 36%. These findings demonstrate the bioremediation potential of newly isolated strains and emphasise the importance of aligning microbial metabolic traits with nutrient conditions to improve pharmaceutical removal in wastewater treatment systems. Full article