Therapeutic Value of Low-Dose Acetylsalicylic Acid for the Prevention of Preeclampsia in High-Risk Bulgarian Women.

Introduction Preeclampsia (PE) is a syndrome that affects pregnant women after 20 weeks of gestation and involves numerous organ systems. Screening for PE is essential to prevent complications and guide management. Some existing guidelines for screening have limitations in terms of detection rates and false positives. The aim of this study is to assess the therapeutic value of low-dose acetylsalicylic acid (ASA) for the prevention of PE in high-risk Bulgarian women. Methodology A prospective cohort research was carried out, encompassing women who were recruited from several routine consultations, such as booking, scanning, and regular prenatal visits. We utilized the purposive sampling technique to carefully choose potential participants. The study was conducted by a maternal-fetal medicine center located in Plovdiv, Bulgaria. The data-gathering period spanned from January 2018 to November 2020. At the appointment, the following procedures were conducted: 1) recording history; 2) assessing height, weight, and blood pressure; 3) collecting blood specimens for biochemical markers; and 4) ultrasound examination. Results A total sample size of 1,383 individuals was categorized into two distinct groups: high-risk patients (n = 506) and low-risk patients (n = 877). The mean uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP) ratios were all greater in high-risk group women (p < 0.05). The data revealed that a significant number of high-risk women failed to adhere to the prescribed dosage or regular use of ASA as recommended by their doctor. There were only 384 (75.9%) high-risk women who took low-dose ASA regularly. Conclusion The findings emphasize the importance of personalized prenatal care and early risk assessment to improve maternal and fetal outcomes. Therefore, it is crucial to educate pregnant women, considering the benefits and risks of low-dose ASA when appropriately indicated.

Anti-Inflammatory Effects of Quercetin, Rutin, and Troxerutin Result From the Inhibition of NO Production and the Reduction of COX-2 Levels in RAW 264.7 Cells Treated with LPS.

Flavonols effectively scavenge the reactive nitrogen species (RNS) and reactive oxygen species (ROS) and act as immune-enhancing, anti-inflammatory, anti-diabetic, and anti-carcinogenic agents. Here, we explored the comparative antioxidant and anti-inflammatory properties of plant-originating flavonols, like quercetin, rutin, and troxerutin against acetylsalicylic acid. Quercetin and rutin showed a high ability to remove active ROS, but troxerutin and acetylsalicylic acid exhibited little such function. In RAW 264.7 cells, quercetin, rutin, and troxerutin did not exhibit cellular toxicity at low concentrations. In addition, quercetin, rutin, and troxerutin considerably (p < 0.05) lowered the protein expression of cyclooxygenase 2 (COX-2) as compared to acetylsalicylic acid in cells inflamed with lipopolysaccharides (LPS). Additionally, in inflamed cells, quercetin and rutin significantly down-regulated the nitrogen oxide (NO) level (p < 0.05) at higher concentrations, whereas Troxerutin did not reduce the NO level. In addition, Troxerutin down-regulated the pro-inflammatory protein markers, such as TNF-α, COX-2, NF-κB, and IL-1ß better than quercetin, rutin, and acetylsalicylic acid. We observed that troxerutin exhibited a significantly greater anti-inflammatory effect than acetylsalicylic acid did. Acetylsalicylic acid did not significantly down-regulated the expression of COX-2 and TNF-α (p < 0.05) compared to troxerutin. Hence, it can be concluded that the down-regulation of NO levels and the expression of COX-2 and TNF-α proteins could be mechanisms of action for the natural compounds quercetin, rutin, and troxerutin in preventing inflammation.

Targeting z-Crystallin by aspirin restores the sensitivity to cisplatin in resistant A2780 ovarian cancer cells.

Ovarian cancer is the deadliest gynaecologic malignancies worldwide. Platinum based chemotherapy is the mainstay treatment for ovarian cancer; however, frequent recurrence and chemoresistance onset in patients with advanced diseases remain a therapeutic challenge. Although mechanisms underlying the development of chemoresistance are still ambiguous, the B-cell lymphoma-2 (Bcl-2) family is closely associated with chemoresistance in ovarian cancer. We previously disclosed that Zeta-Crystallin (CryZ) is a post-transcriptional regulator of Bcl-2 gene expression, by binding to Bcl-2 mRNA and increasing its half-life. Here, we investigated the role of CryZ as a novel therapeutic target in A2780 ovarian carcinoma cells by modulating the protein activity with acetylsalicylic acid (ASA) to restore chemosensitivity. Molecular docking and fragment-mapping based approach revealed potential interaction of ASA within CryZ protein. Inhibition of CryZ binding activity to Bcl-2 and Bcl-xl mRNA targets by ASA was demonstrated in A375 cells. Cytotoxicity assays were conducted in A2780S and A2780R ovarian cancer cells to evaluate if CryZ binding activity inhibition and CryZ silencing were able to reverse cisplatin resistance. ASA-treatment determined a downregulation of Bcl-2 and Bcl-xl mRNA levels in A2780S and A2780R cells. ASA-treatment or CryZ silencing were able to increase and restore the chemosensitivity in both sensitive and resistant A2780 ovarian cancer cells, respectively. In this research article we demonstrated that the pharmacological or genetic inhibition of CryZ restores the sensitivity to cisplatin in a model of sensitive or resistant ovarian cancer cells. These findings suggest a new gene-targeted chemotherapeutic approach to restore the cytotoxicity in drug-resistant ovarian cancers and increase the sensitivity in non-resistant cells.

Haemorrhagic Complications After Microsurgical Treatment for Intracranial Aneurysms Under Acetylsalicylic Acid: An Impact Analysis.

BACKGROUND: Patients with intracranial aneurysms often have comorbidities that require them to take acetylsalicylic acid (ASA). In recent years, many patients with aneurysms have been prescribed ASA to prevent aneurysm enlargement. ASA is also prescribed to patients with intracranial aneurysms in preparation for surgical revascularization. METHODS: From 2016 to 2021, 64 patients underwent microsurgical aneurysm clipping without revascularization, and an additional 20 patients underwent extracranial to intracranial (EC-IC) bypass. The following parameters were analysed: the frequency of hemorrhagic complications, the blood loss volume, the duration of surgery and inpatient treatment, the change in hemoglobin level (Hb), hematocrit (Ht), erythrocytes, and clinical outcomes according to the modified Rankin scale (mRS). RESULTS: At the time of surgery, laboratory-confirmed effect of the ASA was registered in 22 patients (main group). In 42 patients, the ASA was not functional on assay (control group). Hemorrhagic complications were noted in two patients in the ASA group. In both cases, the hemorrhagic component did not exceed 15 ml in volume and did not require additional surgical interventions. Statistical analysis showed no significant differences in hemorrhagic postoperative complications. CONCLUSION: Taking low doses of acetylsalicylic acid during planned microsurgical clipping of cerebral aneurysms does not affect intraoperative blood loss volume, risk of postoperative hemorrhagic complications, length of stay in the hospital, or functional outcomes.

Comparison of Utero-Placental Perfusion Development From First to Second Trimester Between Low-Risk and High-Risk Pre-eclampsia Groups With Aspirin Prophylaxis.

Introduction Pre-eclampsia (PE) is a common diagnosis in pregnancy and affects pregnancies worldwide. Early-onset PE often leads to severe maternal and fetal complications. Prophylactic use of aspirin (150 mg/day) before the 16th week of pregnancy can reduce the risk of PE. This study aimed to investigate the effects of maternal factors on the development of uteroplacental perfusion and fetal biometry from the first to the second trimester in a risk group receiving aspirin prophylaxis compared to a control group without Aspirin. Methods This case-control study included 448 women at high risk for PE (risk group, RG) receiving aspirin prophylaxis and 468 women at low PE risk without aspirin intake (control group, CG). Parameters recorded and considered in the first (T1) and second (T2) trimesters included uterine artery pulsatility multiple of the median (UtAPI MoM), notching at T1 and T2 and fetal biometry parameters at T2. Maternal factors were also captured, and their respective effects were examined. Results UtAPI MoM at T1 and T2 showed a significant positive correlation (r = 0.39, p < 0.001), with UtAPI MoM at T2 significantly higher for notching "yes" at T1. Pre-existing arterial hypertension and UtAPI development demonstrated a significant association (p = 0.006). Women without this risk factor showed a significantly (p < 0.001) greater decline in UtAPI development. The likelihood of notching "yes" at T2 (p < 0.001; OR: 5.80) was increased with higher UtAPI MoM at T1. The mean values (T1 and T2) of UtAPI MoM were significantly higher in the risk group than in the control group. Patients in the risk group exhibited notching at T2 (p < 0.001; OR: 5.64) more often compared to the control group. The 95% CI of the estimated fetal weight for notching "yes" at T1 was below the 50th percentile. Gestational age and head circumference/abdomen circumference (HC/AC) ratio showed a significant negative correlation (p < 0.001; b = -0.01). The control group showed significantly higher estimated fetal weights than the risk group. The HC/AC ratio in the risk group was above the HC/AC ratio in the control group but without proving significance. Conclusions Persistent notching and elevated UtAPI MoM levels in the second trimester may be risk factors for early-onset PE. Women with pre-existing arterial hypertension, notching and elevated UtAPI MoM values ​​in the first and second trimesters require special monitoring during the course of pregnancy.

Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin).

Patients with diabetes face a 2-4-fold greater cardiovascular risk compared to those without diabetes. Both metformin and acetylsalicylic acid (aspirin) treatment have demonstrated a significant reduction in this risk. This single-center, open-label, sequence randomized, 2 × 2 crossover, single-dose clinical trial evaluated the pharmacokinetics profile and comparative bioavailability of a novel oral fixed-dose combination (FDC) of metformin/acetylsalicylic acid (500/100 mg tablet) versus the reference mono-drugs administered concomitantly, metformin 500 mg tablet and acetylsalicylic acid 100 mg tablet, in 22 healthy Mexican adult volunteers under fasting conditions. Blood samples were collected predose and at specified intervals across a 24-hour period following administration and were analyzed for metformin and salicylic acid using high-performance liquid chromatography coupled with tandem mass spectrometry. Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0 -t), and (area under the plasma drug concentration-time cruve from 0 up to infinity (AUC0 ∞) data were within the range of 80%-125%. The results obtained from the present clinical study demonstrate the comparative bioavailability of the FDC when compared with the coadministration of reference mono-drugs. There were no adverse events or adverse reactions reported throughout the study.

Shar-Pei autoinflammatory disease with skin necrosis due to neutrophilic vasculitis: a case report.

A 4-month-old female Shar-pei dog was admitted with apathy, anorexia, and vomiting. The patient had an appropriate vaccination protocol, with the last vaccine administered 2.5 weeks prior to the onset of clinical signs. Physical examination revealed tachycardia, fever and swelling of the tibiotarsal joints. Several diagnostic tests including complete blood cell count, biochemistry profile, urinalysis, thoracic radiographs, hind limbs radiographs, abdominal ultrasound, and infectious diseases tests, were conducted to determine the underlying cause. Shar-Pei Auto-inflammatory Disease (SPAID) was diagnosed. Additionally, the patient developed skin necrosis in the inner aspect of the tibiotarsal joints as a complication. A skin biopsy revealed cutaneous vasculopathy causing degeneration, abrupt ulceration, and ischemic necrosis with intense neutrophilic inflammation of the dermis and subcutis. Moreover, a hospital-acquired infection was identified by skin culture. Debridement of the necrotic skin was performed, and due to its' severity and extent, the wound was closed by secondary intention. A diagnostic protocol and the therapeutic dose of acetylsalicylic acid, which led to clinical improvement, are recommended here. The patient has continued to present episodic manifestations of SPAID mainly fever and swelling of the tibiotarsal joints, but there has been no recurrence of necrosis or other cutaneous lesion in the last two years.

Antiplatelet and Antithrombotic Properties of Compound L-36, a 6H-1,3,4-Thiadiazine Derivative.

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC50) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen).

Acetylsalicylic acid inhibition of the lipoxygenase pathway: Implications for HIV prevention.

BACKGROUND: 1.5 million new HIV infections occurred in 2021, suggesting new prevention methods are needed. Inflammation increases the risk for HIV acquisition by attracting HIV target cells to the female genital tract (FGT). In a pilot study, acetylsalicylic acid (ASA/Aspirin) decreased the proportion of FGT HIV target cells by 35 %. However, the mechanism remains unknown. METHODS: Women from Nairobi, Kenya took low-dose ASA (81 mg) daily for 6-weeks. Free oxylipins in the plasma were quantified by high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Oxylipins from 9 fatty acid substrates were detected, with more than one analyte from 4 substrates reduced post-ASA. Summary analysis found ASA downregulated cyclooxygenase and lipoxygenase but not cytochrome P450 activity with a lower n-6/n-3 oxylipin profile, reflecting reduced inflammation post-ASA. CONCLUSIONS: Inflammation is associated with increased lipoxygenase activity and HIV risk. Our data suggests ASA reduces inflammation through downregulation of oxylipins. Understanding how ASA reduces inflammation may lead to novel HIV prevention approaches.

Effects of low-dose acetylsalicylic acid on the inflammatory response to experimental sleep restriction in healthy humans.

BACKGROUND: Sleep deficiencies, such as manifested in short sleep duration or insomnia symptoms, are known to increase the risk for multiple disease conditions involving immunopathology. Inflammation is hypothesized to be a mechanism through which deficient sleep acts as a risk factor for these conditions. Thus, one potential way to mitigate negative health consequences associated with deficient sleep is to target inflammation. Few interventional sleep studies investigated whether improving sleep affects inflammatory processes, but results suggest that complementary approaches may be necessary to target inflammation associated with sleep deficiencies. We investigated whether targeting inflammation through low-dose acetylsalicylic acid (ASA, i.e., aspirin) is able to blunt the inflammatory response to experimental sleep restriction. METHODS: 46 healthy participants (19F/27M, age range 19-63 years) were studied in a double-blind randomized placebo-controlled crossover trial with three protocols each consisting of a 14-day at-home monitoring phase followed by an 11-day (10-night) in-laboratory stay (sleep restriction/ASA, sleep restriction/placebo, control sleep/placebo). In the sleep restriction/ASA condition, participants took low-dose ASA (81 mg/day) daily in the evening (22:00) during the at-home phase and the subsequent in-laboratory stay. In the sleep restriction/placebo and control sleep/placebo conditions, participants took placebo daily. Each in-laboratory stay started with 2 nights with a sleep opportunity of 8 h/night (23:00-07:00) for adaptation and baseline measurements. Under the two sleep restriction conditions, participants were exposed to 5 nights of sleep restricted to a sleep opportunity of 4 h/night (03:00-07:00) followed by 3 nights of recovery sleep with a sleep opportunity of 8 h/night. Under the control sleep condition, participants had a sleep opportunity of 8 h/night throughout the in-laboratory stay. During each in-laboratory stay, participants had 3 days of intensive monitoring (at baseline, 5th day of sleep restriction/control sleep, and 2nd day of recovery sleep). Variables, including pro-inflammatory immune cell function, C-reactive protein (CRP), and actigraphy-estimated measures of sleep, were analyzed using generalized linear mixed models. RESULTS: Low-dose ASA administration reduced the interleukin (IL)-6 expression in LPS-stimulated monocytes (p<0.05 for condition*day) and reduced serum CRP levels (p<0.01 for condition) after 5 nights of sleep restriction compared to placebo administration in the sleep restriction condition. Low-dose ASA also reduced the amount of cyclooxygenase (COX)-1/COX-2 double positive cells among LPS-stimulated monocytes after 2 nights of recovery sleep following 5 nights of sleep restriction compared to placebo (p<0.05 for condition). Low-dose ASA further decreased wake after sleep onset (WASO) and increased sleep efficiency (SE) during the first 2 nights of recovery sleep (p<0.001 for condition and condition*day). Baseline comparisons revealed no differences between conditions for all of the investigated variables (p>0.05 for condition). CONCLUSION: This study shows that inflammatory responses to sleep restriction can be reduced by preemptive administration of low-dose ASA. This finding may open new therapeutic approaches to prevent or control inflammation and its consequences in those experiencing sleep deficiencies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03377543.

Early postoperative acetylsalicylic acid administration does not increase the risk of postoperative intracranial bleeding in patients with spontaneous intracerebral hemorrhage.

Administration of acetylsalicylic acid (ASA) at early stage after surgery for spontaneous intracerebral hemorrhage (SICH) may increase the risk of postoperative intracranial bleeding (PIB), because of potential inhibition of platelet function. This study aimed to investigate whether early ASA administration after surgery was related to increased risk of PIB. This retrospective study enrolled SICH patients receiving surgery from September 2019 to December 2022 in seven medical institution. Based on postoperative ASA administration, patients who continuously received ASA more than three days within seven days post-surgery were identified as ASA users, otherwise as non-ASA users. The primary outcome was symptomatic PIB events within seven days after surgery. Incidence of PIB was compared between ASA users and non-ASA users using survival analysis. This study included 744 appropriate patients from 794 SICH patients. PIB occurred in 42 patients. Survival analysis showed no statistical difference between ASA users and non-ASA users in incidence of PIB (P = 0.900). Multivariate Cox analysis demonstrated current smoker (hazard ratio [HR], 2.50, 95%CI, 1.33-4.71, P = 0.005), dyslipidemia (HR = 3.03; 95%CI, 1.31-6.99; P = 0.010) and pre-hemorrhagic antiplatelet therapy (HR = 3.05; 95% CI, 1.64-5.68; P < 0.001) were associated with PIB. Subgroup analysis manifested no significant difference in incidence of PIB between ASA users and non-ASA users after controlling the effect from factors of PIB (i.e., sex, age, current smoker, regular drinker, dyslipidemia, pre-hemorrhagic antiplatelet therapy and hematoma location). This study revealed that early ASA administration to SICH patients after surgery was not related to increased risk of PIB.

Salicylate Poisoning and Rebound Toxicity.

Salicylate exposure and toxicity are associated with a myriad of symptoms and signs, and a comprehensive knowledge of diagnosing and treating salicylate poisoning is needed. Here, we present a case of a 29-year-old female with a past medical history of schizoaffective disorder and bipolar disorder with multiple suicide attempts brought to our hospital, Nassau University Medical Center, East Meadow, by the Emergency Medical Service (EMS) due to an intentional overdose of 300 pills of acetylsalicylic acid. She had mixed acid-base disturbance with respiratory alkalosis and metabolic acidosis. She was started on bicarbonate infusion in the emergency department to maintain a blood pH of 7.5 and to maintain a urine pH of more than 7.5. As her salicylate levels were 98.2 at admission with altered mental status, she was started on slow, low-efficiency hemodialysis. A few hours later, she developed a rebound increase in salicylate levels to 129, associated with a change in mental status and the patient was more confused. She was started on regular hemodialysis with improvement in mental status and elimination of salicylate steadily. Given the extensive nature of toxic effects, a patient with severe salicylate toxicity can deteriorate rapidly and can be challenging to manage. As there is no specific antidote for aspirin, the goals of therapy depend primarily on limiting the absorption of salicylate, enhancing elimination, and providing supportive care. Monitoring the acid-base status and serum salicylate levels closely and monitoring for rebound increase in salicylate levels is of paramount importance. Aggressive hydration to maintain euvolemia, alkalinization, aggressive replenishment of potassium and magnesium, activated charcoal to decrease absorption, and hemodialysis remain the cornerstones of treatment.

Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). METHODS: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). RESULTS: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). CONCLUSIONS: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

Controversy in cardiology: clopidogrel or acetylsalicylic acid in the treatment of chronic coronary syndromes?

Secondary prevention of patients with chronic coronary syndrome is based on the long-term use of a single anti-aggregating drug which is traditionally represented by acetylsalicylic acid (ASA) in light of the results of studies and meta-analyses which have demonstrated a clear anti-ischaemic efficacy against of an acceptable increase in the risk of bleeding, especially intracranial and gastrointestinal bleeding. The availability of drugs such as clopidogrel, which inhibits platelet activity through the P2Y12 receptor pathway, has called into question this paradigm, also in consideration of the fact that the scientific evidence that supports the use of ASA in secondary prevention is based on dated studies with some limitations. Over the last few years, randomized trials have demonstrated how clopidogrel has an efficacy profile comparable to that of ASA and a safety profile that is sometimes even better. In light of the new evidence, it is therefore legitimate to ask whether in this clinical scenario, ASA should still be considered the drug of choice or whether clopidogrel could represent the preferable alternative.

Kawasaki Disease in a Young Adult: A Case Report and a Review of the Literature.

This case report describes a 21-year-old female who was diagnosed with Kawasaki disease (KD), a rare condition in adults. Careful clinical assessment, including the history of a recent upper respiratory tract infection and the physical findings of fever, sinus tachycardia, strawberry tongue, and skin peeling of the hands and feet, prompted further evaluation. Laboratory findings supported an inflammatory process, and multidisciplinary consultations led to the diagnosis of KD. Prompt treatment with acetylsalicylic acid and intravenous immunoglobulin resulted in rapid improvement and prevention of the severe complications associated with untreated KD, particularly in the cardiovascular system. This case emphasizes the importance of the high risk of suspicion and the need for a comprehensive evaluation in atypical presentations of KD in adults, where early recognition and management are crucial to prevent long-term sequelae such as coronary artery aneurysms and myocardial infarction.

Potential Drug-Nutrient Interactions of 45 Vitamins, Minerals, Trace Elements, and Associated Dietary Compounds with Acetylsalicylic Acid and Warfarin-A Review of the Literature.

In cardiology, acetylsalicylic acid (ASA) and warfarin are among the most commonly used prophylactic therapies against thromboembolic events. Drug-drug interactions are generally well-known. Less known are the drug-nutrient interactions (DNIs), impeding drug absorption and altering micronutritional status. ASA and warfarin might influence the micronutritional status of patients through different mechanisms such as binding or modification of binding properties of ligands, absorption, transport, cellular use or concentration, or excretion. Our article reviews the drug-nutrient interactions that alter micronutritional status. Some of these mechanisms could be investigated with the aim to potentiate the drug effects. DNIs are seen occasionally in ASA and warfarin and could be managed through simple strategies such as risk stratification of DNIs on an individual patient basis; micronutritional status assessment as part of the medical history; extensive use of the drug-interaction probability scale to reference little-known interactions, and application of a personal, predictive, and preventive medical model using omics.

The 125th Anniversary of Aspirin-The Story Continues.

The year 2024 marks the 125th anniversary of aspirin, still one of the most frequently used drugs worldwide. Despite its veritable age, it is still relevant in pharmacotherapy and its use has spread to new areas over time. Due to aspirin's multiple pharmacological actions unified in one single molecule (i.e., analgesic, antipyretic, anti-inflammatory, antithrombotic, and antiviral effects), it continues to attract considerable attention in the scientific community and is subject to intense basic and clinical research. In fact, recent results confirmed aspirin's potential role as an antiviral drug and as an agent that can block harmful platelet functions in inflammatory/immunological processes. These features may open up new horizons for this ancient drug. The future of aspirin looks, therefore, bright and promising. Aspirin is not yet ready for retirement; on the contrary, its success story continues. This 125th anniversary paper will concisely review the various therapeutic uses of aspirin with a particular emphasis on the latest research results and their implications (e.g., use as an antiviral agent). In addition, the reader is provided with future perspectives for this remarkable drug.

Aspirin hypersensitivity: a practical guide for cardiologists.

Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.

Physiological healing of chronic gastric ulcer is not impaired by the hydrogen sulphide (H2S)-releasing derivative of acetylsalicylic acid (ATB-340): functional and proteomic approaches.

Gastric ulcers affect approx. 10% of population. Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA) predispose to or impair the physiologically complex healing of pre-existing ulcers. Since H2S is an endogenous cytoprotective molecule, we hypothesized that new H2S-releasing ASA-derivative (ATB-340) could overcome pathological impact of NSAIDs on GI regeneration.Clinically translational gastric ulcers were induced in Wistar rats using state-of-the-art microsurgical model employing serosal application of acetic acid. This was followed by 9 days long i.g. daily treatment with vehicle, ATB-340 (6-24 mg/kg) or equimolar ASA doses (4-14 mg/kg). Ulcer area was assessed macro- and microscopically. Prostaglandin (PG)E2  levels, indicating pharmacological activity of NSAIDs and 8-hydroxyguanozine content, reflecting nucleic acids oxidation in serum/gastric mucosa, were determined by ELISA. Qualitative and/or quantitative pathway-specific alterations at the ulcer margin were evaluated using real-time PCR and mass spectrometry-based proteomics.ASA, unlike ATB-340, dose-dependently delayed/impaired gastric tissue recovery, deregulating 310 proteins at the ulcer margin, including Ras signalling, wound healing or apoptosis regulators. ATB-340 maintained NSAIDs-specific cyclooxygenase-inhibiting capacity on systemic and GI level but in time-dependent manner. High dose of ATB-340 (24 mg/kg daily), but not ASA, decreased nucleic acids oxidation and upregulated anti-oxidative/anti-inflammatory heme oxygenase-1, 24-dehydrocholesterol reductase or suppressor of cytokine signalling (SOCS3) at the ulcer margin.Thus, ASA impairs the physiological healing of pre-existing gastric ulcers, inducing the extensive molecularly functional and proteomic alterations at the wound margin. H2S-releasing ATB-340 maintains the target activity of NSAIDs with limited impact on gastric PGE2 signalling and physiological GI regeneration, enhancing anti-inflammatory and anti-oxidative response, and providing the pharmacological advantage.