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Turkish Journal of Medical Sciences 2023To investigate the effects of acetylsalicylic acid (ASA) and the use of ultrasound elastography on testicular torsion.
BACKGROUND/AIM
To investigate the effects of acetylsalicylic acid (ASA) and the use of ultrasound elastography on testicular torsion.
MATERIALS AND METHODS
Herein, 6 equal groups of rats were formed (n: 48): control group, sham group, torsion/detorsion (T/D)-1 h group, T/D-1 h + ASA group, T/D-8 h group, and T/D-8 h + ASA group. Testicular torsion was created by rotating the left testis 720° clockwise. At 30 min before torsion, 100 mg/kg of ASA was injected intraperitoneally. Elastography was performed at 8 and 24 h. After orchiectomy, specimens were collected for histopathological evaluation.
RESULTS
When comparing the left testicular volume (LV) parameters obtained from the elastography applied at 8 h, significant differences were observed between the following group pairs: the sham and T/D-8 h groups, T/D-1 h and T/D-8 h groups, and T/D-1 h + ASA and T/D-8 h groups (p = 0.004, p = 0.023, and p = 0.026, respectively). The mean LVS (velocity) (stiffness assessment) of the groups was similar at 8 h. When comparing the LV parameters at 24 h, significant differences were found between the T/D-1 h and T/D-8 h groups and between the T/D-8 h and T/D-8 h + ASA groups (p = 0.008 and p = 0.004, respectively). For the LVS mean values at 24 h, significant differences were found between the control and sham groups, sham and T/D-1 h groups, sham and T/D-8 h groups, and sham and T/D-8 h + ASA groups (p = 0.009, p = 0.021, p = 0.027, and p = 0.009, respectively).Histopathological evaluation showed a decrease in the morphological grades and an increase in the mean testicular injury scores in the T/D-1 h + ASA group compared to the T/D-1 h group. The T/D-8 h + ASA group had a higher morphological grade than the T/D-8 h group, whereas their mean testicular injury scores were similar.
CONCLUSION
ASA treatment for testicular torsion was shown to be ineffective. Elastography can be a complementary method to Doppler ultrasonography in the diagnosis of testicular torsion and can guide surgeons in their approach to surgery.
Topics: Male; Spermatic Cord Torsion; Animals; Aspirin; Elasticity Imaging Techniques; Rats; Testis; Disease Models, Animal; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38813515
DOI: 10.55730/1300-0144.5729 -
Research and Practice in Thrombosis and... Mar 2024Assessment of platelet function is key in diagnosing bleeding disorders and evaluating antiplatelet drug efficacy. However, there is a prevailing "one-size-fits-all"...
BACKGROUND
Assessment of platelet function is key in diagnosing bleeding disorders and evaluating antiplatelet drug efficacy. However, there is a prevailing "one-size-fits-all" approach in the interpretation of measures of platelet reactivity, with arbitrary cutoffs often derived from healthy volunteer responses.
OBJECTIVES
Our aim was to compare well-used platelet reactivity assays.
METHODS
Blood and platelet-rich plasma obtained from the Framingham Heart Study ( = 3429) were assayed using a range of agonists in 5 platelet assays: light transmission aggregometry, Optimul aggregometry, Multiplate impedance aggregometry (Roche Diagnostics), Total Thrombus-Formation Analysis System, and flow cytometry. Using linear mixed-effect models, we determined the contribution of preanalytical and technical factors that modulated platelet reactivity traits.
RESULTS
A strong intra-assay correlation of platelet traits was seen in all assays, particularly Multiplate velocity ( = 0.740; ristocetin vs arachidonic acid). In contrast, only moderate interassay correlations were observed ( = 0.375; adenosine diphosphate Optimul E vs light transmission aggregometry large area under the curve). As expected, antiplatelet drugs strongly reduced platelet responses, with aspirin use primarily targeting arachidonic acid-induced aggregation, and explained substantial variance (β = -1.735; = 4.59 × 10; variance proportion = 46.2%) and P2Y antagonists blocking adenosine diphosphate responses (β = -1.612; = 6.75 × 10; variance proportion = 2.1%). Notably, female sex and older age were associated with enhanced platelet reactivity. Fasting status and deviations from standard venipuncture practices did not alter platelet reactivity significantly. Finally, the agonist batch, phlebotomist, and assay technician (more so for assays that require additional sample manipulation) had a moderate to large effect on measured platelet reactivity.
CONCLUSION
Caution must be exercised when extrapolating findings between assays, and the use of standard ranges must be medication-specific and sex-specific at a minimum. Researchers should also consider preanalytical and technical variables when designing experiments and interpreting platelet reactivity measures.
PubMed: 38813256
DOI: 10.1016/j.rpth.2024.102406 -
Heliyon May 2024In the 21st century, cancer remains a serious threat to people's health and has become a prominent public health problem. NFKBIA is involved in the pathological process...
In the 21st century, cancer remains a serious threat to people's health and has become a prominent public health problem. NFKBIA is involved in the pathological process of many diseases including cancer, but its specific role in pan-cancer has not yet been fully elucidated. This study aims to deepen the understanding of cancer pathology by analyzing the potential functions of NFKBIA in pan-cancer. We used TCGA data to analyze differences of expression of NFKBIA in pan-cancer. We explored the prognostic value, clinical relevance, immune relevance, potential biological function, and diagnosis and treatment value of NFKBIA in pan-cancer through bioinformatics analysis. This study found that in pan-cancer, NFKBIA exhibits differences in expression, which correlate with the prognosis, diagnosis, treatment value and clinical and immune parameters. We have identified that Aspirin, Astaxanthin and Bardoxolone methyl are expected to play a potential therapeutic role in pan-cancer. The results of this study will help to improve our understanding of the role and potential mechanism of NFKBIA in cancer pathology, which may provide guidance for cancer-related research and clinical diagnosis and treatment.
PubMed: 38813139
DOI: 10.1016/j.heliyon.2024.e31204 -
BMC Cardiovascular Disorders May 2024Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic... (Review)
Review
BACKGROUND
Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired).
CASE PRESENTATION
We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward.
CONCLUSIONS
Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.
Topics: Humans; Male; Middle Aged; Acute Coronary Syndrome; Treatment Outcome; Aortic Diseases; Recurrence; Thrombosis; Anticoagulants; Computed Tomography Angiography; Coronary Angiography; Platelet Aggregation Inhibitors; Non-ST Elevated Myocardial Infarction; Aortography
PubMed: 38811879
DOI: 10.1186/s12872-024-03956-2 -
BMC Gastroenterology May 2024Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such...
BACKGROUND
Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs.
METHODS
Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers.
RESULTS
Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy.
CONCLUSIONS
Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
Topics: Animals; Aspirin; Omeprazole; Rats, Sprague-Dawley; Proton Pump Inhibitors; Gastric Mucosa; Gastrins; Male; Rats; Drug Administration Schedule; Humans; Peptic Ulcer; Intestinal Mucosa; Stomach Ulcer
PubMed: 38811868
DOI: 10.1186/s12876-024-03265-0 -
JACC. Cardiovascular Interventions May 2024
Topics: Humans; Aspirin; Drug Administration Schedule; Hemorrhage; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38811106
DOI: 10.1016/j.jcin.2024.04.020 -
Science Advances May 2024Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on...
Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit ), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit ), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
Topics: Humans; Colorectal Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Aspirin; Receptors, Prostaglandin E, EP4 Subtype; Male; Genetic Predisposition to Disease; Female; Case-Control Studies; Middle Aged; Genetic Loci; Aged
PubMed: 38809988
DOI: 10.1126/sciadv.adk3121 -
World Journal of Psychiatry May 2024Cerebral infarction (CI) is characterized by a high prevalence, disability, and mortality. Timely or improper treatment greatly affects patient prognosis.
BACKGROUND
Cerebral infarction (CI) is characterized by a high prevalence, disability, and mortality. Timely or improper treatment greatly affects patient prognosis.
AIM
To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life (QOL), anxiety and depression in CI patients.
METHODS
We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group (OG) (combination therapy of aspirin and edaravone, 65 patients) or a control group (CG) (aspirin monotherapy, 59 patients). The therapeutic effects, pre- and posttreatment National Institutes of Health Stroke Scale (NIHSS) scores, activities of daily living, degree of cognitive impairment, protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and S-100B, occurrence of adverse reactions, and serum high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were evaluated, detected and compared between the two groups. Finally, posttreatment QOL, anxiety, and depression were assessed by the Medical Outcomes Study 36- Item Short Form Health Survey Scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), respectively.
RESULTS
Compared with the CG, the OG had markedly better therapeutic effects, greater improvements in activities of daily living, and better alleviation in cognitive dysfunction after treatment, as well as lower posttreatment NIHSS scores and serum NSE, GFAP, S-100B, hs-CRP, IL-6, and TNF-α levels; the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL; and the OG also had lower SDS and SAS scores than the CG after treatment.
CONCLUSION
Aspirin plus edaravone had a good curative effect on CI. It can reverse cranial nerve damage in patients, improve neurological function and prognosis, and alleviate inflammation, anxiety, and depression; thus, it is considered safe and worthy of clinical application.
PubMed: 38808092
DOI: 10.5498/wjp.v14.i5.644 -
Cell Communication and Signaling : CCS May 2024The SARS-CoV-2 virus causes severe COVID-19 in one-fifth of patients. In addition to high mortality, infection may induce respiratory failure and cardiovascular...
BACKGROUND
The SARS-CoV-2 virus causes severe COVID-19 in one-fifth of patients. In addition to high mortality, infection may induce respiratory failure and cardiovascular complications associated with inflammation. Acute or prolonged inflammation results in organ fibrosis, the cause of which might be endothelial disorders arising during the endothelial-mesenchymal transition (EndMT).
METHODS
HUVECs and HMEC-1 cells were stimulated with SARS-CoV-2 S (Spike) and N (Nucleocapsid) proteins, and EndMT induction was evaluated by studying specific protein markers via Western blotting. Wound healing and tube formation assays were employed to assess the potential of SARS-CoV-2 to stimulate changes in cell behaviour. MRTF nuclear translocation, ROS generation, TLR4 inhibitors, TGF-β-neutralizing antibodies, and inhibitors of the TGF-β-dependent pathway were used to investigate the role of the TGF-β-MRTF signalling axis in SARS-CoV-2-dependent EndMT stimulation.
RESULTS
Both viral proteins stimulate myofibroblast trans-differentiation. However, the N protein is more effective at EndMT induction. The TGF-β-MRTF pathway plays a critical role in this process. The N protein preferentially favours action through TGF-β2, whose secretion is induced through TLR4-ROS action. TGF-β2 stimulates MRTF-A and MRTF-B nuclear translocation and strongly regulates EndMT. In contrast, the Spike protein stimulates TGF-β1 secretion as a result of ACE2 downregulation. TGF-β1 induces only MRTF-B, which, in turn, weakly regulates EndMT. Furthermore, aspirin, a common nonsteroidal anti-inflammatory drug, might prevent and reverse SARS-CoV-2-dependent EndMT induction through TGF-β-MRTF pathway deregulation.
CONCLUSION
The reported study revealed that SARS-CoV-2 infection induces EndMT. Moreover, it was demonstrated for the first time at the molecular level that the intensity of the EndMT triggered by SARS-CoV-2 infection may vary and depend on the viral protein involved. The N protein acts through TLR4-ROS-TGF-β2-MRTF-A/B, whereas the S protein acts through ACE2-TGF-β1-MRTF-B. Furthermore, we identified aspirin as a potential anti-fibrotic drug for treating patients with SARS-CoV-2 infection.
Topics: Humans; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Transforming Growth Factor beta; COVID-19; Coronavirus Nucleocapsid Proteins; Aspirin; Signal Transduction; Epithelial-Mesenchymal Transition; Human Umbilical Vein Endothelial Cells; Transcription Factors; Toll-Like Receptor 4; Cell Line; Endothelial-Mesenchymal Transition; Phosphoproteins
PubMed: 38807115
DOI: 10.1186/s12964-024-01665-z -
Journal of the American Heart... Jun 2024ADP and ATP are importantly involved in vascular and thrombotic homeostasis, via multiple receptor pathways. Blockade of ADP P2Y receptors inhibits platelet aggregation... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo-Controlled Study.
BACKGROUND
ADP and ATP are importantly involved in vascular and thrombotic homeostasis, via multiple receptor pathways. Blockade of ADP P2Y receptors inhibits platelet aggregation and represents an effective cardiovascular disease prevention strategy. AZD3366 (APT102), a long-acting recombinant form of an optimized CD39L3 human apyrase, has effectively reduced ATP, ADP, and platelet aggregation and provided tissue protection in preclinical models, features that could be very beneficial in treating patients with cardiovascular disease.
METHODS AND RESULTS
We conducted this phase 1, first-in-human study of single ascending doses of intravenous AZD3366 or placebo, including doses added to dual antiplatelet therapy with ticagrelor and acetylsalicylic acid. The primary objective was safety and tolerability; secondary and exploratory objectives included pharmacokinetics, pharmacodynamics (measured as inhibition of platelet aggregation), adenosine diphosphatase (ADPase) activity, and ATP/ADP metabolism. In total, 104 participants were randomized. AZD3366 was generally well tolerated, with no major safety concerns observed. ADPase activity increased in a dose-dependent manner with a strong correlation to AZD3366 exposure. Inhibition of ADP-stimulated platelet aggregation was immediate, substantial, and durable. In addition, there was a prompt decrease in systemic ATP concentration and an increase in adenosine monophosphate concentrations, whereas ADP concentration appeared generally unaltered. At higher doses, there was a prolongation of capillary bleeding time without detectable changes in the ex vivo thromboelastometric parameters.
CONCLUSIONS
AZD3366 was well tolerated in healthy participants and demonstrated substantial and durable inhibition of platelet aggregation after single dosing. Higher doses prolonged capillary bleeding time without detectable changes in ex vivo thromboelastometric parameters.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04588727.
Topics: Humans; Male; Ticagrelor; Female; Apyrase; Platelet Aggregation; Aspirin; Platelet Aggregation Inhibitors; Middle Aged; Adult; Double-Blind Method; Dual Anti-Platelet Therapy; Drug Therapy, Combination; Young Adult; Adenosine Diphosphate; Blood Platelets; Dose-Response Relationship, Drug; Treatment Outcome; Recombinant Proteins; Purinergic P2Y Receptor Antagonists
PubMed: 38804212
DOI: 10.1161/JAHA.123.033985