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Pharmaceuticals (Basel, Switzerland) May 2024Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective...
Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective COX-1-inhibitory activities of four newly synthesized compounds, -, along with their abilities to inhibit platelet aggregation against ADP and collagen. The target compounds - were synthesized using the conventional method, sonication, and microwave-assisted methods. Microanalytical and spectral data were utilized to elucidate the structures of the new compounds -. Additionally, a spectral NMR experiment [NOESY] was conducted to emphasize the configuration around the double bond of the imine group C=N. The obtained results revealed no observed correlation between any of the neighboring protons, suggesting that the configuration at the C=N double bond is . Biological results revealed that all the screened compounds - might serve as selective COX-1 inhibitors. They showed IC values ranging from 0.71 μM to 4.82 μM against COX-1 and IC values ranging from 9.26 μM to 15.24 μM against COX-2. Their COX-1 selectivity indices ranged between 2.87 and 18.69. These compounds show promise as promising anti-platelet aggregation agents. They effectively prevented platelet aggregation induced by ADP with IC values ranging from 0.11 μM to 0.37 μM, surpassing the standard aspirin with an IC value of 0.49 μM. Additionally, they inhibited the platelet aggregation induced by collagen with IC values ranging from 0.12 μM to 1.03 μM, demonstrating superior efficacy compared to aspirin, which has an IC value of 0.51 μM. In silico molecular modeling was performed for all the target compounds within the active sites of COX-1 and COX-2 to rationalize their selective inhibitory activities towards COX-1. It was found that the binding interactions of the designed compounds within the COX-1 active site had remained unaffected by the presence of celecoxib. Molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were performed to study the stability of -forms with respect to -forms for the investigated compounds. A strong correlation was observed between the experimental observations and the quantum chemical descriptors.
PubMed: 38931377
DOI: 10.3390/ph17060710 -
Journal of Personalized Medicine May 2024When clinicians opt for antithrombotic therapy to manage or prevent thrombotic complications during pregnancy, it is imperative to consider the unique physiological... (Review)
Review
When clinicians opt for antithrombotic therapy to manage or prevent thrombotic complications during pregnancy, it is imperative to consider the unique physiological state of the pregnant woman's body, which can influence the pharmacokinetics of the drug, its ability to traverse the placental barrier, and its potential teratogenic effects on the fetus. While the efficacy and safety of aspirin during pregnancy have been relatively well-established through numerous clinical studies, understanding the effects of newer, more potent antiplatelet agents has primarily stemmed from individual clinical case reports necessitating immediate administration of potent antiplatelet therapy during pregnancy. This review consolidates the collective experiences of clinicians confronting novel thrombotic complications during pregnancy, often requiring the use of dual antiplatelet therapy. The utilization of potent antiplatelet therapy carries inherent risks of bleeding, posing threats to both the pregnant woman and the fetus, as well as the potential for teratogenic effects on the fetus. In the absence of official guidelines regarding the use of potent antiplatelet drugs in pregnancy, a plethora of cases have demonstrated the feasibility of preventing recurrent thrombotic complications, mitigating bleeding risks, and successfully managing pregnancies, frequently culminating in cesarean deliveries, through meticulous selection and dosing of antiplatelet medications.
PubMed: 38929781
DOI: 10.3390/jpm14060560 -
Diagnostics (Basel, Switzerland) Jun 2024The risk of developing cardiovascular disease is significantly higher for individuals with diabetes compared to those without. Aspirin has been widely used for primary...
Evaluating the Efficacy and Safety of Aspirin for Primary Cardiovascular Prevention in Asian Patients with Type 2 Diabetes: A Population-Based and Propensity Score-Matched Study.
The risk of developing cardiovascular disease is significantly higher for individuals with diabetes compared to those without. Aspirin has been widely used for primary prevention in diabetic patients. However, evidence is limited in the Asian population. We aimed to compare the effectiveness and safety of aspirin versus placebo for primary cardiovascular prevention in the Asian population with type 2 diabetes. In this study, we performed propensity score matching with non-aspirin users from January 2006 to December 2015 ( = 37,095 in each group after matching, PSM). We analyzed the incidence risk of all-cause mortality, composite cardiovascular events, and hospitalized major bleeding. The propensity score-matched (PSM) cohort of patients who received aspirin within one year of diabetes diagnosis was compared with the non-aspirin diabetic (DM) cohort. Baseline characteristics were balanced between the two groups. The median follow-up duration was 78 months. Aspirin users exhibited a slightly but significantly lower rate of all-cause mortality (HR: 0.92; 95% CI: 0.87 to 0.96). However, they also had a significantly higher composite cardiovascular risk (HR: 1.34; 95% CI: 1.28-1.40), including non-fatal acute myocardial infarction (HR: 1.33; 95% CI: 1.18 to 1.50), non-fatal ischemic stroke (HR: 1.38; 95% CI: 1.30 to 1.45), heart failure (HR: 1.18; 95% CI: 1.09 to 1.27), and coronary revascularization (HR: 1.94; 95% CI: 1.73 to 2.17). Aspirin users also faced a significantly higher risk of hospitalized major bleeding (HR: 1.08; 95% CI: 1.03 to 1.14). The presence of one or more additional risk factors did not influence the effectiveness and safety outcomes of aspirin, according to stratified analysis. In conclusion, in this real-world Asian diabetic population, aspirin was associated with a significantly lower mortality risk but also with higher risks of cardiovascular events and hospitalized bleeding. Aspirin may not play a role in the primary prevention of cardiovascular disease in such patients, regardless of additional risk factors.
PubMed: 38928627
DOI: 10.3390/diagnostics14121211 -
BMC Pediatrics Jun 2024Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age....
BACKGROUND
Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age. Muscular weakness is a rare manifestation of KD, and only 11 pediatric patients with KD combined with muscular weakness have been reported, of which evidence of myositis was found in 2/3 of the patients, and 1/3 could not be explained by myositis, the mechanism of which is still unclear. Cases of KD combined with bladder retention are even more rare, and there has been only 1 case report of KD combined with bladder retention in a child with no previous underlying disease.
CASE PRESENTATION
We report a 22-month-old Asian child with incomplete Kawasaki disease (IKD) who initially presented with fever and progressive muscular weakness in the lower extremities, followed by the bladder and bowel retention abnormalities and rapid onset of heart failure, respiratory failure and shock. The child developed coronary artery ectasia (CAA) without the main clinical features of KD such as rash, conjunctival congestion, desquamation of the extremity endings, orofacial changes and enlarged lymph nodes in the neck. Creatine kinase and electromyography were normal. Temperature gradually normalized and muscle strength recovered slightly after intravenous immunoglobulin. The child could be helped to walk after 1 week of aspirin combined with steroid therapy.
CONCLUSIONS
We present the case of a 22-month-old child with IKD. The child began with progressive muscular weakness in the extremities, followed by the bladder and bowel retention abnormalities, and rapidly developed heart failure, respiratory failure, and shock. Despite early failure to detect the disease, the child recovered rapidly and had a favorable prognosis. KD comorbidities with muscular weakness as the main manifestation are uncommon. This is the first case report of IKD combined with both muscular weakness and bladder and bowel retention, which may provide clinicians with diagnostic and therapeutic ideas, as well as a basis for future exploration of the mechanisms of KD combined with muscular weakness or bladder and bowel retention abnormalities.
Topics: Humans; Infant; Immunoglobulins, Intravenous; Mucocutaneous Lymph Node Syndrome; Muscle Weakness; Urinary Retention
PubMed: 38926640
DOI: 10.1186/s12887-024-04874-0 -
Discovery Medicine Jun 2024Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of...
BACKGROUND
Atypical acinar cell foci (AACF) seen in pancreatic cancer are fatal and have been studied with some causative agents. However, for the first time, the effect of acetylsalicylic acid with nitric oxide (NO-ASA) on AACF was examined in this study. Although NO-ASA has very successful inhibitory effects against some types of cancer, it has not been investigated whether they can exert their inhibition effects on AACFs.
METHODS
For experimental purposes, 21 14-day-old male Wistar albino rats were used. Azaserine (30 mg/kg) was dissolved in 0.9% NaCl solution and injected intraperitoneally (i.p.) into 14 rats, except for the Control group (Cont) rats, for three weeks. Rats that were injected with azaserine once a week for three weeks and those that did not receive treatment were divided into experimental groups. 15 days after the end of the azaserine injection protocol, NO-ASA was applied to azaserine with NO-ASA (Az+NO-ASA) group rats three consecutive times with an interval of 15 days by gavage. At the end of the 5-month period, pancreatic tissue was dissected and weighed. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One-way analysis of variance (ANOVA) non-parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and Control groups.
RESULTS
AACF burden in both groups injected with azaserine was found to be statistically significant in all categories compared to that of the Control group ( < 0.05). The average Calculated Estimated average AACF volume (mm) values, the Calculated estimated average AACF diameter (μm), the Estimated average number of AACF per unit volume, AACF rate as a % of Calculated Organ Volume were higher in the AzCont group rats than in the Az+NO-ASA group, when compared, and there was an important level statistical difference between the groups ( < 0.05). It was determined that for all parameters AACFs load in Az+NO-ASA group rats were significantly reduced compared to that of AzCont group rats ( < 0.05).
CONCLUSIONS
We observed that, as a result of the NO-ASA application, the experimental AACF focus ratio created by azaserine injection was significantly inhibited. The inhibitory effect of AACFs in Az+NO-ASA group rats may have resulted from the significant and independent chemopreventive and/or chemotherapeutic activity of NO-ASA against exocrine pancreatic AACF foci.
Topics: Animals; Male; Aspirin; Rats, Wistar; Nitric Oxide; Rats; Pancreatic Neoplasms; Acinar Cells; Pancreas, Exocrine
PubMed: 38926102
DOI: 10.24976/Discov.Med.202436185.106 -
Circulation Jun 2024This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia.
BACKGROUND
This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia.
METHODS
Between 1 August 2019 and 28 February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks.
RESULTS
Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events.
CONCLUSIONS
The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.
PubMed: 38923439
DOI: 10.1161/CIRCULATIONAHA.124.069907 -
The Archives of Bone and Joint Surgery 2024Deep Vein Thrombosis (DVT) is a significant medical concern characterized by the formation of blood clots within the venous system. Surgical procedures are known to...
OBJECTIVES
Deep Vein Thrombosis (DVT) is a significant medical concern characterized by the formation of blood clots within the venous system. Surgical procedures are known to increase the risk of DVT. While enoxaparin has proven to be highly effective in treating DVT, concerns about bleeding and accurate dosage regulation may restrict its application. Recent research has focused on aspirin's potential in preventing DVT after various surgeries. This study aimed to determine whether aspirin was as effective as enoxaparin in preventing DVT after spine surgery.
METHODS
This randomized controlled trial enrolled study patients who underwent spine surgery at Shahid Kamyab Emergency Hospital in Mashhad, and had a Caprini score > 5, indicating a higher risk of DVT. In the control group, patients received subcutaneous injections of enoxaparin at a dosage of 40 mg, while the intervention group received oral aspirin tablets with a daily dosage of 81 mg. An experienced radiologist performed a Doppler ultrasound of the lower limbs' veins seven days after surgery to diagnose DVT. The outcomes of the two groups were then compared.
RESULTS
A total of 100 patients participated in the clinical trial and were equally assigned to the aspirin and enoxaparin groups. Both groups were homogeneous regarding the basic and clinical characteristics. The incidence of postoperative DVT was 4.0% in the aspirin group and 10.0% in the enoxaparin group (p=0.092). The incidence of hemorrhage was 2.0% in the aspirin group and 4.0% in the enoxaparin group (p=0.610).
CONCLUSION
These findings indicate that aspirin may be a promising alternative to enoxaparin for DVT prevention after surgery, but additional research is essential to validate these results and further assess the benefits and risks associated with aspirin usage in this context.
PubMed: 38919740
DOI: 10.22038/ABJS.2024.74693.3458 -
Frontiers in Endocrinology 2024Preeclampsia is a disease with an unknown pathogenesis and is one of the leading causes of maternal and perinatal morbidity. At present, early identification of...
INTRODUCTION
Preeclampsia is a disease with an unknown pathogenesis and is one of the leading causes of maternal and perinatal morbidity. At present, early identification of high-risk groups for preeclampsia and timely intervention with aspirin is an effective preventive method against preeclampsia. This study aims to develop a robust and effective preeclampsia prediction model with good performance by machine learning algorithms based on maternal characteristics, biophysical and biochemical markers at 11-13 + weeks' gestation, providing an effective tool for early screening and prediction of preeclampsia.
METHODS
This study included 5116 singleton pregnant women who underwent PE screening and fetal aneuploidy from a prospective cohort longitudinal study in China. Maternal characteristics (such as maternal age, height, pre-pregnancy weight), past medical history, mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A, and placental growth factor were collected as the covariates for the preeclampsia prediction model. Five classification algorithms including Logistic Regression, Extra Trees Classifier, Voting Classifier, Gaussian Process Classifier and Stacking Classifier were applied for the prediction model development. Five-fold cross-validation with an 8:2 train-test split was applied for model validation.
RESULTS
We ultimately included 49 cases of preterm preeclampsia and 161 cases of term preeclampsia from the 4644 pregnant women data in the final analysis. Compared with other prediction algorithms, the AUC and detection rate at 10% FPR of the Voting Classifier algorithm showed better performance in the prediction of preterm preeclampsia (AUC=0.884, DR at 10%FPR=0.625) under all covariates included. However, its performance was similar to that of other model algorithms in all PE and term PE prediction. In the prediction of all preeclampsia, the contribution of PLGF was higher than PAPP-A (11.9% VS 8.7%), while the situation was opposite in the prediction of preterm preeclampsia (7.2% VS 16.5%). The performance for preeclampsia or preterm preeclampsia using machine learning algorithms was similar to that achieved by the fetal medicine foundation competing risk model under the same predictive factors (AUCs of 0.797 and 0.856 for PE and preterm PE, respectively).
CONCLUSIONS
Our models provide an accessible tool for large-scale population screening and prediction of preeclampsia, which helps reduce the disease burden and improve maternal and fetal outcomes.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Machine Learning; Adult; China; Prospective Studies; Cohort Studies; Longitudinal Studies; Biomarkers; Algorithms; Risk Factors; Prognosis; Placenta Growth Factor
PubMed: 38919479
DOI: 10.3389/fendo.2024.1345573 -
Scientific Reports Jun 2024The objective of this study was to investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age...
The objective of this study was to investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1-PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO (β = - 1.07, p = 6 × 10) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p = 0.0001), 44% (p < 2 × 10), and 55% (p < 2 × 10), compared to no use. An additive effect of aspirin (β = 7.62, p = 9 × 10) and PGS (β = - 1.58, p = 0.0149) was found for AAO without an interaction (p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1-PD (p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.
Topics: Humans; Parkinson Disease; Female; Male; Middle Aged; Aged; Life Style; Age of Onset; Multifactorial Inheritance; Genetic Predisposition to Disease; Proportional Hazards Models; Glucosylceramidase; Case-Control Studies; Risk Factors; Aspirin
PubMed: 38918550
DOI: 10.1038/s41598-024-65640-x -
Journal of Basic and Clinical... Jun 2024Benign prostatic hyperplasia (BPH) is a common urological condition affecting aging men worldwide. Among the treatment options available for BPH, transurethral resection...
Long-term functional outcomes and predictors of efficacy in thulium laser enucleation of the prostate (ThuLEP) for benign prostatic hyperplasia (BPH): a retrospective observational study.
OBJECTIVES
Benign prostatic hyperplasia (BPH) is a common urological condition affecting aging men worldwide. Among the treatment options available for BPH, transurethral resection of the prostate (TURP) is the gold-standard invasive intervention. To reduce the TURP-related non-negligible morbidity, loss-of-ejaculation rate, hospitalization, blood loss and catheterization time several laser techniques have been developed, such as the Thulium Laser Enucleation of the Prostate (ThuLEP). To investigate the efficacy outcomes of the ThuLEP as a treatment option for benign prostatic hyperplasia (BPH) we performed a retrospective observational study at Moriggia Pelascini Hospital (Como, Italy) between January 2015 and September 2018.
METHODS
We included 265 patients who underwent ThuLEP at a specific hospital between defined dates. Data on various parameters, including post-void residue volume, peak urinary flow rate (Qmax), International Prostate Symptom Score (IPSS) for urinary symptoms, IPSS Quality of Life (QoL) score, and International Index of Erectile Function (IIEF) score for erectile dysfunction, were collected at baseline and follow-up.
RESULTS
The analysis revealed significant improvements in voiding efficiency, urinary flow, urinary symptoms, quality of life, and erectile function following ThuLEP. Furthermore, certain baseline characteristics, such as post-void residue, peak urinary flow rate, age, prostate volume, and aspirin usage, were found to influence treatment outcomes.
CONCLUSIONS
Despite the study's limitations, these findings contribute to understanding ThuLEP's effectiveness in managing BPH and can aid in making informed clinical decisions for patient care. Prospective studies with longer follow-up periods are recommended to validate and extend these results.
PubMed: 38915209
DOI: 10.1515/jbcpp-2024-0036