Cardiovascular & hematological agents in medicinal chemistry最新文献

Introduction: Approximately 3% of patients treated with heparinoids develop heparin- induced thrombocytopenia (HIT). Although HIT is characterized by thrombocytopenia, type 2 HIT is associated with a high risk of thrombotic events in approximately 30-75% of cases. In some patients, thrombocytopenia represents the primary clinical manifestation of HIT. Early diagnosis of HIT is critical to prevent thrombotic complications by allowing timely replacement of heparin with an alternative anticoagulant. Clinical observations suggest a potential gap in the diagnosis and management of HIT among patients receiving heparinoid therapy in Iran.

Aims: Hence, this study aimed to compile and analyze published data on the frequency and prevalence of HIT across various provinces in Iran, a representative developing country. The aim of this systematic review was to identify and highlight potential gaps in the diagnosis of HIT within different regions of the country.

Methods: To investigate this hypothesis, a systematic review was conducted to assess the prevalence of HIT and the adequacy of its detection in the country. Literature searches were performed using PubMed, Google Scholar, Web of Science, and local databases, yielding 81 articles. Following a rigorous evaluation, five studies met the inclusion criteria for the systematic review. The pooled analysis revealed an estimated HIT prevalence of 6.93% among the studied population. The mean age of participants ranged between 58 and 69 years, falling within the late-adolescent to early-elderly spectrum. The overall male-to-female ratio was 175:121 (59.2% male vs. 40.8% female).

Results: This study highlights a significant gap in the diagnosis of HIT in the country, suggesting that similar challenges may exist in other developing countries.

Conclusion: In conclusion, addressing this issue requires increased clinical awareness and improved diagnostic strategies to mitigate associated risks.

Background: Myocardial infarction (MI) is a disease characterised by myocardial necrosis due to acute and prolonged ischaemic hypoxia in the coronary arteries. MOTS-c is a mitochondrial- derived peptide that has been reported to have protective effects on cardiac tissue. Although this peptide is thought to be decreased in various diseases and can serve as a potential biomarker, current studies remain limited.

Objectives: This study aimed to evaluate how the post-treatment process affects circulating MOTS- c peptide levels in myocardial infarction patients.

Methods: For this purpose, patients without obstructive coronary lesions on angiography were included in the control group, while those with significant obstructive coronary lesions on angiography were included in the infarction group. Routine biochemistry tests were performed using an autoanalyzer. Besides, serum MOTS-c levels were measured using ELISA.

Results: Our findings showed CRP, ESR, and troponin I levels to be higher in the MI group compared to the control group. Also, there was no significant change in MOTS-c levels between the control and the MI group, while time-dependent changes (day 0, day 3, and day 30) occurred within the MI group. However, a negative correlation was found between MOTS-c and platelet levels in the MI group at day 0 (r: -0.4417, p =0.0450). Similarly, MOTS-c was found to be negatively correlated with troponin I in the MI group at day 3 (r: -0.4571, p =0.0372).

Conclusion: The negative correlation of MOTS-c level with both platelet and troponin I has shown that this peptide may contribute to the diagnostic and therapeutic evaluation of the MI process along with other parameters.

Background: Warfarin is an effective anticoagulant but requires close International Normalized Ratio (INR) monitoring and may occasionally require correction of excessive anticoagulation. Current guidelines provide limited practical guidance on the administration of vitamin K for the management of supratherapeutic INR levels ≥ 5.0 in non-bleeding outpatients.

Objectives: Based on expert consensus and guidelines, the Atrius Health Anticoagulation Management Services (AMS) has developed internal guidance for oral vitamin K use in highly selected populations. This study will describe the internal guidance for oral vitamin K use and present associated results and clinical outcomes.

Methods: Episodes with INR > 5.0 were included, with vitamin K considered for episodes with INR ≥ 6. Moreover, compelling indications and exclusions to select ideal patients for vitamin K intervention were also defined.

Results: Overall, episodes were managed conservatively; of the 246 collected episodes of excessive anticoagulation, in 18 episodes (7%), patients received vitamin K, and in 228 (93%) episodes, patients did not receive vitamin K. The mean index INR was 6.0 (range 5.0 - 10.5, SD 1.07), with nearly 57% of episodes achieving INR correction and 15% of episodes developing INR overcorrection. High thrombotic risk patients, regardless of hemorrhagic risk, were less likely to receive vitamin K. Three episodes (1.2%) resulted in bleeding complications. No thrombotic complications occurred during the 30-day follow-up of the index INR value ≥ 5.0.

Conclusion: Our internal guidance is a novel, standardized approach that serves as a decision support tool for the management of warfarin-associated coagulopathy and vitamin K intervention using patient-specific characteristics and index INR values. This guidance may assist other anticoagulation management services with practical applications and require validation in a prospective clinical trial.

Type 2 diabetes is characterized by elevated blood glucose levels, leading to an increased risk of cardiovascular diseases. Sodium butyrate, the sodium salt of the short-chain fatty acid butyric acid produced by gut microbiota fermentation, has shown promising effects on metabolic diseases, including type 2 diabetes and cardiovascular diseases. Sodium butyrate demonstrates anti-inflammatory, anti-oxidative, and lipid-lowering properties and can improve insulin sensitivity and reduce hepatic steatosis. In this review, we investigate how sodium butyrate influences cardiovascular complications of type 2 diabetes, including atherosclerosis (AS), heart failure (HF), hypertension, and angiogenesis. Moreover, we explore the pathophysiology of cardiovascular disease in type 2 diabetes, focusing on hyperglycemia, oxidative stress, inflammation, and genetic factors playing crucial roles. The review suggests that sodium butyrate can be a potential preventive and therapeutic agent for cardiovascular complications in individuals with type 2 diabetes.

Red blood cells with sickle cell anemia (SCA) have an irregular shape, and it is a genetic blood condition that can cause several problems and shorten life expectancy. Traditional treatments have focused on symptom management, but recent advancements in drug delivery systems offer promising pathways for targeted therapies. This abstract explores novel approaches to combat SCA through innovative drug delivery systems, gene therapy, and new pharmaceutical interventions. One novel pathway for targeting SCA involves utilizing advanced drug delivery systems to enhance the effectiveness of therapeutic agents. Nanotechnology-based delivery systems, such as nanoparticles and liposomes, offer precise drug targeting, controlled release, and improved bioavailability. These systems can encapsulate anti-sickling agents, like hydroxyurea, and enable their specific delivery to affected cells, reducing side effects and enhancing therapeutic outcomes. Additionally, therapy has become a ground-breaking method of treating SCA. CRISPR/Cas9 technology presents a groundbreaking opportunity to correct the genetic mutation responsible for sickle hemoglobin production. By precisely editing the HBB gene, which encodes the abnormal hemoglobin, researchers aim to restore normal hemoglobin expression, potentially offering a curative treatment for SCA. Furthermore, recent advancements in drug development have led to the discovery of promising candidates targeting specific pathways involved in SCA pathophysiology. Experimental drugs, such as voxelotor and crizanlizumab focus on modifying hemoglobin properties or inhibiting cell adhesion, respectively, thereby preventing sickle cell-related complications and reducing vaso-occlusive crisis frequency.

The recognition of oxidative stress as a factor influencing the development and progression of cardiovascular diseases (CVDs) is growing. By producing such reactive oxygen species (ROS) in diverse areas within cells, including mitochondria and Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NADPH)-oxidases, they end up causing damage through the oxidation of lipids, proteins, and DNA. ROS indicates the beginning of inflammatory responses and endothelial dysfunction, which are necessary to produce obstructions in blood vessels and decreased blood vessel function. The fact that oxidative stress plays a significant role in CVD development draws more attention to the need for novel therapies that aim to correct redox imbalances. Therefore, natural polyphenols and antioxidants like vitamin C or E have shown their efficacy in lowering levels of ROS and protecting against the damage caused by oxidative stress. Anyone attempting to cure CVDs should focus on improving the safety and efficacy of antioxidant treatments and identifying which patients will benefit from them the most. This paper discusses not only advanced treatments but also the role played by oxidative stress in such CVD as high blood pressure, hypercholesterolemia, and ischemic heart disease.

Background: venous thromboembolism (VTE) prophylaxis is crucial for reducing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). This network meta-analysis was carried out to determine the most effective intervention among selective Xa inhibitors and low molecular weight heparins (LMWHs) for perioperative surgical thromboprophylaxis in major abdominal, pelvic, lumbar spine, and lower limb surgeries.

Methods: A systematic literature search was conducted for randomized controlled trials (RCTs) comparing selective factor Xa inhibitors, LMWHs, and placebo as thromboprophylaxis agents in major abdominal, pelvic, lumbar spine, and lower limb surgeries. A Bayesian network metaanalysis was performed to compare all interventions for the risk of developing DVT, VTE, major VTE, total bleeding, and major bleeding. The surface under the cumulative ranking curves was used to rank all interventions.

Results: Of 1788 retrieved references, 42 RCTs comparing 11 anticoagulants were included. As compared to enoxaparin, the risk of DVT was significantly reduced in patients treated with fondaparinux [RR: 0.53 (95% CrI: 0.31, 0.93)] and rivaroxaban [RR: 0.42 (95% CrI: 0.27, 0.64)]; VTE in patients treated with bemiparin [RR: 0.09 (95% CrI: 0, 0.7)], edoxaban [RR: 0.43 (95% CrI: 0.18, 0.96)], fondaparinux [RR: 0.55 (95% CrI: 0.34, 0.91)] and rivaroxaban [RR: 0.56 (95% CrI: 0.34, 0.85)]; major VTE in patients treated with rivaroxaban [RR: 0.26 (95% CrI: 0.11, 0.6)]. According to the surface under the cumulative ranking curves (SUCRA) value, fondaparinux and bemiparin increase the risk of serious bleeding more than other factor Xa inhibitors and LMWHs.

Conclusion: Rivaroxaban, fondaparinux, edoxaban, and bemiparin are superior perioperative thromboprophylaxis agents than enoxaparin in major surgeries. Fondaparinux and bemiparin have shown the highest risk of major bleeding compared to other factor Xa inhibitors and LMWHs.

Direct Oral Anticoagulants (DOACs) have transformed the management of thrombotic disorders, offering a more convenient and effective alternative to traditional vitamin K antagonists (VKAs). However, assessing thrombotic risk in patients treated with DOACS remains crucial due to the potential for recurrent events. Current clinical risk scores have limitations in predicting and monitoring venous thromboembolism (VTE) risk in specific DOAC populations. Several emerging biomarkers show promise in assessing thrombotic risk in patients treated with DOACS. Genetic factors like VKORC1 and CYP2C9 variants are well-established determinants of warfarin response, but the genetic landscape for DOAC outcomes appears more complex. Rare variants and polygenic approaches may play a role in personalizing anticoagulation therapy. Elevated factor VIII levels are associated with increased VTE recurrence risk after anticoagulation withdrawal in cancer-associated thrombosis (CAT) patients. In contrast, the circulating tissue factor is not useful for predicting VTE in this setting. Soluble P-selectin has emerged as a good marker of VTE recurrence, and its inclusion in the Vienna CATS risk model improves VTE prediction in cancer patients. While these biomarkers hold promise, larger studies are needed to validate their utility and establish standardized assays. Caution is warranted in patients at high bleeding risk. Integrating clinical factors, genetics, and circulating biomarkers will likely optimize thrombotic risk assessment in patients treated with DOACS. Continued research is crucial to develop personalized anticoagulation strategies to balance thrombosis and bleeding risks.

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