Search Results (267)

Background/Objectives: This study aims to develop a sustainable and environmentally friendly drug delivery system by synthesizing a novel drug–drug eutectic mixture (DDEM) of acetylsalicylic acid (ASA) and pyrazinamide (PZA) using a green and efficient mechanochemical approach. Methods: The DDEM was characterized using various techniques, including differential scanning calorimetry (DSC), thermogravimetry and differential thermal analysis (TG-DTA), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and Raman spectroscopy. Binary phase diagrams and Tammann’s triangle analysis determined the eutectic point. Density functional theory (DFT) calculations were performed on the starting compounds. The new system was evaluated for aqueous solubility, dissolution, and hygroscopicity. Results: A V-shaped binary phase diagram indicated the formation of a DDEM with a 2:1 molar ratio of ASA to PZA. A positive mixing enthalpy suggested a quasi-eutectic structure. The solubility of ASA and PZA increased by 61.5% and 85.8%, respectively, in the DDEM compared to the pure drugs. Conclusions: These findings highlight the potential of DDEMs to enhance drug properties and delivery. The synergistic interaction between ASA and PZA in the eutectic mixture may further improve therapeutic efficacy, warranting further investigation. 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

Ethenzamide (2-ethoxybenzamide), besides acetylsalicylic acid, is one of the mostly used salicylic acid derivatives in pharmaceuticals. It has analgesic and anti-inflammatory effects that originate from the inhibition of cyclooxygenase (COX-1) activity, thus blocking prostaglandin synthesis. In this work, efficient and eco-friendly methods were developed for the synthesis of ethenzamide via the O-alkylation reaction of salicylamide. The reactions were carried out under conventional conditions in a solvent-free system using variant solvents and different phase transfer catalysts (PTC) in the presence of microwave radiation or ultrasonic conditions. It was shown that in solvent-free conditions using TBAB as a catalyst, ethenzamide can be obtained within 15 min at 80 °C with 79% yield. Meanwhile, using microwave radiation under the same conditions, the reaction time can be shortened to 90 s with 92% yield. Notably, high yields can be achieved under PTC in water (or organic solvent-free) conditions using microwave radiation (2 min, 94%) or ultrasound (10 min, 95% efficiency). The studies prove that the PTC synthesis process of ethenzamide can be conducted under mild conditions, with a shorter reaction time and remarkably lower energy consumption in comparison to conventional processes, thus actualizing “green chemistry” for practical ethenzamide preparation. Full article

Aspirin (ASA) is one of the most used medications worldwide and has shown various effects on cellular processes, including stem cell differentiation. However, the effect of ASA on adipogenesis of adipose tissue-derived stem cells (ASCs) remains largely unknown. Considering the potential application of ASCs in regenerative medicine and cell-based therapies, this study investigates the effects of ASA on adipogenic differentiation in human ASCs. ASCs were exposed to varying concentrations of ASA (0 µM, 400 µM, and 1000 µM) and evaluated for changes in morphology, migration, and adipogenic differentiation. While ASA exposure did not affect self-renewal potential, migration ability, or cell morphology, it significantly reduced lipid vacuole formation at 1000 µM after 21 days of adipogenic differentiation (p = 0.0025). This visible inhibition correlated with decreased expression of adipogenic markers (PPARG, ADIPOQ, and FABP4) and the proliferation marker MKi67 under ASA exposure in comparison to the control (ns). Overall, the findings demonstrate that ASA inhibits adipogenic differentiation of human ASCs in a dose-dependent manner in vitro, contrasting its known role in promoting osteogenic differentiation. This research highlights ASA’s complex effects on ASCs and emphasizes the need for further investigation into its mechanisms and potential therapeutic applications in obesity and metabolic diseases. The inhibitory effects of ASA on adipogenesis should be considered in cell-based therapies using ASCs. Full article

Background: several experimental findings and epidemiological observations indicated that aspirin/acetylsalicylic acid (ASA) may be endowed with anticancer effects against a variety of human malignancies, including thyroid carcinomas. Among these, undifferentiated/anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal human cancers, refractory to all currently available therapies. Methods: we here evaluated in a preclinical setting the effects of ASA on a panel of three ATC-derived cell lines: the CAL-62, the 8305C, and the 8505C. Results: the data obtained demonstrated the ability of ASA to inhibit, in a dose- and time-dependent manner, the proliferation of all ATC cell lines investigated, with IC₅₀ values comprised between 2.0 and 4.3 mM. Cell growth was restrained with the same efficacy when the ASA treatment was applied to three-dimensional soft-agar cultures. In addition, ASA significantly reduced migration and invasion in two of the three ATC cell lines. We finally investigated the effects of ASA on the MAPK and PI3K/Akt signaling pathways, which are often altered in ATC. The results showed that the phosphorylation status of the Akt1/2/3 kinases was significantly reduced following ASA treatment, while ERK1/2 phosphorylation was either unaffected or slightly upregulated. Conclusions: our findings support epidemiological evidence on the anticancer potential of ASA. On this basis, further investigations should be carried out to assess the usefulness of ASA as adjuvant therapy in patients affected by ATC. Full article

The present study aimed to investigate and compare oxidative stress biomarkers and antioxidant enzyme activity in the serum of women at risk of developing preeclampsia (PE) to prevent adverse pregnancy outcomes through early intervention. Changes in soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels were measured between 11 and 13 gestational weeks (gw.) before the onset of preeclampsia and its associated complications. This study evaluated the feasibility of the sFlt-1/PlGF biomarker ratio in predicting preeclampsia and adverse pregnancy outcomes, with the goal of preventive therapy with acetylsalicylic acid (150 mg daily), with acetylsalicylic acid (75 mg daily) and Clampsilin. For this purpose, the following were evaluated: (1) the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as parameters of oxidative stress; (2) lipid oxidation; (3) antioxidant enzyme activity; and (4) cytokine production. Analysis of the results showed that pregnant women at risk of preeclampsia had significantly higher levels of ROS, lipid oxidation, and superoxide anion radical (•O₂⁻) levels compared to normal pregnancies. In PE, depleted levels of nitric oxide (NO), impaired NO synthase system (NOS), and reduced antioxidant enzyme activity (p < 0.03) suggest that PE patients cannot compensate for oxidative stress (OS). In conclusion, oxidative stress in PE plays a key role, which arises from placental problems and affects both mother and baby. The groups with acetylsalicylic acid therapy (150 mg and 75 mg) were better affected compared to those on Clampsillin. Full article

Since ancient times, essential oils obtained from various aromatic plants have been utilized as bioactive ingredients in medicines, foods and cosmetics. The present study aimed to investigate the chemical composition and biological activities of St John’s Wort (Hypericum perforatum L.) essential oil (SJW EO) from Bulgaria, which is known to possess various biological properties. Gas chromatography and mass spectrometry (GC–MS) analysis, determination of antioxidant activity (by the ABTS method), an antimicrobial activity test and an in vitro anti-inflammatory activity test were performed. The main classes of compounds identified by GC–MS analysis were monoterpenes (43.55%), followed by sesquiterpenes (36.81%) and alkanes (16.92%). The predominant chemical components of SJW EO were α-pinene (27.52%), followed by β-pinene (10.08%), β-caryophyllene (6.77%), germacrene D (6.37%) and caryophyllene oxide (4.48%). The highest antibacterial activity was observed against the Gram-negative bacteria Klebsiella pneumoniae ATCC 13883 (inhibition zone of 12.0 mm) and Pseudomonas aeruginosa ATCC 9027 (inhibition zone of 11.0 mm). SJW EO exhibited significant in vitro anti-inflammatory activity, as the results demonstrated that its anti-inflammatory effect was stronger than those of the conventional anti-inflammatory drugs Prednisolon Cortico and acetylsalicylic acid (Aspirin), which were used as controls (all in concentration of 1 mg/mL). The obtained results demonstrated that Bulgarian SJW EO can be used as an active ingredient in the composition of new products for the pharmaceutical and cosmetic industries. Full article

Pain is a frequent and disturbing symptom among hemodialysis patients. Protein-bound uremic toxins (PBUTs) are related to cardiovascular and overall mortality, and they are difficult to remove with current hemodialysis treatments. The PBUT displacers, such as furosemide, tryptophan, or ibuprofen, may be promising new strategies for improving their clearance. This study aims to compare ibuprofen versus other analgesic drugs in PBUT removal. A prospective study was carried out in 23 patients. Patients underwent four dialysis sessions with routine dialysis parameters, except for analgesic drugs administered (lysine acetylsalicylic acid, acetaminophen, dexketoprofen, and ibuprofen). The reduction ratios (RRs) of a wide range of molecular weight molecules were assessed, including total p-cresyl sulfate and total indoxyl-sulfate. There were no complications related to the administered drug, and pain was controlled independently of the drug. There were no differences in the RR of small-size and medium-sized molecules between all four study treatments. However, indoxyl sulfate and p-cresyl sulfate RRs when ibuprofen was administered were significantly higher than lysine acetylsalicylic acid, acetaminophen, and dexketoprofen treatments. In conclusion, patients with pain may benefit from treatment with ibuprofen instead of lysine acetylsalicylic acid, paracetamol, or dexketoprofen, since in addition to improving pain, it increases the removal of PBUTs. Full article

Background: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis usually affects small blood vessels and is characterized by the presence of circulating autoantibodies (c-ANCA or p-ANCA). The risk of cardiovascular events is threefold higher compared to general population, and cardiac manifestations include myocarditis, pericarditis, valvulitis, aortitis, or coronary arteritis. Coronary involvement is very rare, but it is a potentially life-threatening manifestation. Methods: We present an atypical cardiac scenario of p-ANCA vasculitis. Results: A 68-year-old woman with known p-ANCA vasculitis and stage 5 chronic kidney disease (CKD) on hemodialysis presented with dizziness accompanied by low blood pressure and chest pain. Electrocardiogram on arrival showed slightly ST-T changes, with negative cardiac biomarkers and no abnormalities in cardiac regional wall motion. Five hours after presentation, the patient repeated chest pain, accompanied by a drop in blood pressure and junctional escape rhythm. The highly sensitive cardiac troponin I (hs-cTnI) was raised at 560 ng/L. Coronary angiography showed coronary arteries without significant stenosis. The provocative test with intracoronary ergonovine demonstrated coronary vasospasm of the anterior descending artery accompanied by chest pain, with resolution after intracoronary nitroglycerin. Under amlodipine, nitrate, acetylsalicylic acid, statin and corticosteroids the patient did not experience the recurrence of angina. Conclusions: This case illustrates coronary involvement, manifested as coronary spasm with favorable outcomes, in systemic vasculitis. The underlying mechanism is immune-mediated inflammation in vascular walls. Full article

Background/Objectives: Postoperative hemorrhages (POHs) after pituitary adenoma surgery can have devastating consequences for patients. Many patients take acetylsalicylic acid (ASA) for the primary or secondary prevention of cardiovascular or stroke events. However, the impact of continued low-dose ASA use on the risk of postoperative hemorrhage and the frequency of thromboembolic events after discontinuing ASA in these patients remain poorly understood. This study aims to investigate the potential interaction and correlation between low-dose ASA intake and two of the most common complications after neurosurgical surgery—acute postoperative hemorrhage and thromboembolism. Methods: A retrospective study involving 1862 patients who underwent brain tumor surgery over a decade at our neurosurgical institute examined the risk of postoperative hemorrhage and thromboembolic events. The study compared bleeding rates in patients with pituitary adenomas who received low-dose ASA medication to those who did not. Additionally, the study investigated the occurrence of venous thromboembolism (VTE) or arterial pulmonary embolisms (PEs) following surgery, as well as the impact of laboratory parameters, demographic characteristics and intraoperative factors. Results: A total of 108 patients underwent surgery for primary pituitary tumors between January 2008 and January 2018. Only six patients (5.6%) experienced POH. Among those with POH, just two (1.9%) required revision surgery due to neurological decline. Interestingly, none of the 13 patients (12%) taking ASA preoperatively suffered POH. No correlation was found between laboratory results, demographics and postoperative complications. The study also did not find an increase in VTE or PE events. Conclusions: In this analysis, the perioperative intake of low-dose ASA could not be associated with an increased rate of hemorrhagic complications following pituitary adenoma surgery. Low-dose ASA can be safely continued during brain tumor surgery in patients with a high cardiovascular and cerebrovascular risk. Full article

Background/Objectives: Patients with gliomas show an increased risk of spontaneous hemorrhages throughout the disease. Simultaneously, the number of patients taking acetylsalicylic acid (ASA) for primary and secondary prophylaxis is rising in daily clinical practice, and interrupting ASA intake before elective or emergency intracranial surgery is not always feasible. This study aims to evaluate the risks associated with continuing ASA use perioperatively while focusing on hemorrhage and potential thromboembolic events that may arise from discontinuing ASA, particularly in multimorbid patients undergoing glioma surgery. Methods: The clinical parameters and imaging data of 7149 patients who underwent intracranial surgery in our department over a 10-year period were retrospectively analyzed. Patients were categorized into two groups based on their ASA status: Group 1 (no ASA impact) included those with no ASA use or who discontinued ASA use more than seven days prior to surgery (low stroke or cardiovascular risk), and Group 2 (ASA impact) included those who continued ASA use within seven days prior to operation (high stroke or cardiovascular risk). Results: In this retrospective study, data from 650 patients with various types of glial tumors who underwent surgery between 2008 and 2018 were examined. Of these patients, 50 experienced a postoperative hemorrhage (POH), and 10 required reoperations due to clinical neurological deterioration and increased intracranial pressure caused by the space-occupying effect of the hemorrhage. In the ASA impact group, 2.7% developed POH, compared to 1.3% in the no ASA impact group (p = 0.098). Our analysis did not show a significantly increased risk of POH after surgery, although patients in the ASA impact group had a one- to two-fold higher risk of developing POH overall. Additionally, other factors contributing to postoperative hemorrhage following glioma surgery were investigated and evaluated. Conclusions: In this cohort, the perioperative use of ASA was not associated with an increased rate of hemorrhagic complications after intracranial glioma surgery, although a trend was observed. In patients with high stroke and cardiovascular risk, ASA can be continued during elective brain tumor surgery. Full article

Anticancer drugs cause anemia in patients through eryptosis and hemolysis. We thus studied the in vitro toxicity of galangin (GAL) in red blood cells (RBCs). RBCs were exposed to 50–500 μM of GAL and analyzed for markers of eryptosis and hemolysis. Ca²⁺ nucleation, phosphatidylserine (PS) externalization, oxidative stress, and cell size were detected via fluorescence-activated cell sorting using Fluo4/AM, annexin-V-FITC, 2′,7′-dichlorodihydrofluorescein diacetate, and forward scatter (FSC), respectively. Acetylcholinesterase (AChE) activity was measured via Ellman’s assay and ultrastructural morphology was examined via scanning electron microscopy. Membrane rupture and extracellular hemoglobin, aspartate transaminase (AST), and lactate dehydrogenase (LDH) were assessed via colorimetric methods. Distinct experiments were carried out to identify protective agents and signaling pathways using small-molecule inhibitors. GAL triggered sucrose-sensitive hemolysis with AST and LDH leakage, increased annexin-V-FITC and Fluo4 fluorescence, and decreased FSC and AChE activity which was associated with the formation of granulated echinocytes. Ca²⁺ omission and energy replenishment with glucose, adenine, and guanosine blunted PS externalization and preserved cellular volume. Moreover, caffeine, Trolox, heparin, and uric acid had similar ameliorative effects. Hemolysis was abrogated via caffeine, Trolox, heparin, mannitol, lactate, melatonin, and PEG 8000. Notably, co-treatment of cells with GAL and staurosporin, D4476, or acetylsalicylic acid prevented PS externalization whereas only the presence of SB203580 and NSC23766 rescued the cells from GAL-induced hemolysis. Ca²⁺ nucleation and metabolic collapse mediated by PKC/CK1α/COX/p38/Rac1 drive GAL-induced eryptosis and hemolysis. These novel findings carry ramifications for the clinical prospects of GAL in anticancer therapy. Full article

Acetylsalicylic acid (ASA) represents a cornerstone of antiplatelet therapy for the treatment of atherosclerotic coronary artery disease (CAD). ASA is in fact indicated in case of an acute coronary syndrome or after a percutaneous coronary intervention with stent implantation. Aspirin hypersensitivity is frequently reported by patients, and this challenging situation requires a careful evaluation of the true nature of the presumed sensitivity and of its mechanisms, as well as to differentiate it from a more frequent (and more easily manageable) aspirin intolerance. Two main strategies are available to allow ASA administration for patients with CAD and suspected ASA hypersensitivity: a low-dose ASA challenge, aimed at assessing the tolerability of ASA at the antiplatelet dose of 100 mg, and desensitization, a therapeutic procedure which aims to induce tolerance to ASA. For those patients who cannot undergo ASA challenge and desensitization due to previous serious adverse reactions, or for those in whom desensitization was unsuccessful, a number of further alternative strategies are available, even if these have not been validated and approved by guidelines. The aim of this state-of-the-art review is therefore to summarize the established evidence regarding pathophysiology, clinical presentation, diagnosis, and management of aspirin hypersensitivity and to provide a practical guide for cardiologists (and clinicians) who have to face the not uncommon situation of a patient with concomitant coronary artery disease and aspirin hypersensitivity. Full article

A series of new isatin-3-hydrazones bearing different ammonium fragments was synthesized by a simple and easy work-up reaction of Girard’s reagents analogs with 1-(3,5-di-tert-butyl-4-hydroxybenzyl)isatin. All derivatives have been shown to have antioxidant properties. In terms of bactericidal activity against gram-positive bacteria, including methicillin-resistant strains of Staphylococcus aureus, the best compounds are 3a, 3e, and 3m, bearing octyl, acetal, and brucine ammonium centers, respectively. In addition, brucine and quinine derivatives 3l, and 3j exhibit platelet antiaggregation activity at the level of acetylsalicylic acid, and this series of isatin derivatives does not adversely affect the hemostasis system as a whole. Thus, all the obtained results can lay the groundwork for future pharmaceutical developments for the creation of effective antibacterial drugs with reduced systemic toxicity due to the presence of antioxidant properties. Full article

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size, and the content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor, respectively. The control group consisted of patients with risk factors for CHD, but with no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by the exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, and ADP 20, 5, 2.5 µM, and in the CHD/ACS groups, by TRAP 10 µM, and ADP 20 5 µM (±epinephrine 20 µM). Platelet size was assessed by the mean volume, % large forms, and forward scattering. RP were stained by thiazole orange. In the control group, activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease in platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in the CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and the reduced efficacy of antiplatelet therapy. Full article