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VEGF Inhibitors in Hematologic Cancers and Hypertension/Cardiac Effects.

The therapeutic landscape of hematologic malignancies has undergone a paradigm shift with the increasing incorporation of targeted therapies, including inhibitors of vascular endothelial growth factor (VEGF) signaling. While VEGF-directed agents have historically been developed and deployed in solid tumors, their application in hematologic cancers-particularly multiple myeloma, select leukemias, and rare lymphomas-has expanded in investigational and clinical settings. VEGF is fundamental to angiogenesis, maintenance of endothelial integrity, and regulation of vascular tone. As a result, therap

Successful allogeneic stem cell transplant in a patient with a left ventricular assist device: a novel case report.

Historically, severe heart failure has been considered a contraindication for hematopoietic stem cell transplant (HSCT). Despite the growing use of the left ventricular assist device (LVAD), clinicians have avoided HSCT in patients with hematologic malignancies and an LVAD due to a multitude of potential complicating factors, including the use of cardiotoxic conditioning regimens and severe post-transplant thrombocytopenia requiring anticoagulation interruption. Currently, there are no published reports of a successful allogeneic HSCT in a patient with an LVAD. The case herein documents a 36-y

Dimer Dissociation and Aggregation Hot-spot Exposure Synergistically Accelerate Light Chain Variable Domain Aggregation Associated With AL Amyloidosis.

Light chain (AL) amyloidosis is a life-threatening systemic disorder caused by the aggregation and deposition of antibody light chain (LC) fragments in multiple organs, including the heart and kidneys. In this study, we investigated the early events of aggregation of the highly unstable variable domain (VL) from AL55, a known amyloidogenic and cardiotoxic light chain. Our results show that dimer disruption and exposure of aggregation hot spots synergistically accelerate aggregation. At neutral pH, concentration-dependent dimerization reduces aggregation by limiting aggregation-competent monome

Cocaine and aortic dissection: the need for collaboration to overcome the underreporting bias.

The dissection of the aorta is a serious and potentially fatal consequence of cocaine use. Nonetheless, the underlying mechanisms and characteristics of this phenomenon remain to be deeply studied. The autopsy case of a 46-year-old white male found irresponsive and unconscious in his house and had a history of abusing cocaine is presented. Autopsy findings showed aortic arch and thoracic aorta of regular calibre, with evidence of a mid-adventitial dissecting aneurysm of the ascending intrapericardial portion of the aorta. Forensic toxicological analyses evidenced a positivity to cocaine and it

Diselenide Nanogels Modulate Mitochondrial Function and Mitigate Oxidative Stress in Cardiomyocytes for Enhanced Cardiac Repair.

Mitochondrial dysfunction and oxidative stress are pivotal factors contributing to the loss of cardiac function following heart injury, yet these aspects are frequently underappreciated in the medication design paradigm. Here we have developed diselenide-cross-linked zwitterionic nanogels to restore mitochondrial homeostasis and boost energy supply for damaged heart repair. These nanogels exhibit an enhanced circulation time within the bloodstream post systemic administration and have been observed to concentrate at the site of the damaged myocardium in both myocardial infarct (MI) rat model a

The protective effects of esculetin against Doxorubicin-Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways.

Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX-induced hepatotoxicity in rat livers. Forty-eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The admini

Fatal poisoning due to ingestion of boiled oleander leaf extract.

Nerium oleander is an ornamental evergreen shrub belonging to the family Apocynaceae. The Apocynaceae family includes the attractive evergreen shrub known as oleander. The cardiotoxic glycoside, oleandrin, is present in all portions of the common oleander plant. Oleander consumption can result in deadly situations accidentally or as a suicide attempt. After consuming kettle-boiled oleander leaf extract as part of a suicide attempt, an 80-year-old man was discovered comatose in his home and taken to our emergency room. The patient's heart rate was 30 beats per minute, and he had hypotension. Ar

The role of microRNAs in the pathophysiology, diagnosis, and treatment of diabetic cardiomyopathy.

INTRODUCTION: Diabetic cardiomyopathy (DCM) is an end-point macrovascular complication associated with increased morbidity and mortality in 12% of diabetic patients. MicroRNAs (miRNAs) are small noncoding RNAs that can act as cardioprotective or cardiotoxic agents in DCM. METHODS: We used PubMed as a search engine to collect and analyse data in published articles on the role of miRNAs on the pathophysiology, diagnosis and treatment of DCM. RESULTS: MiRNAs play an essential role in the pathophysiology, diagnosis and treatment of DCM due to their distinct gene expression patterns in diabetic p

How to Differentiate General Toxicity-Related Endocrine Effects from Endocrine Disruption: Systematic Review of Carbon Disulfide Data.

This review provides an overview of the assessment of the endocrine disrupting (ED) properties of carbon disulfide (CS2), following the methodology used at the European level to identify endocrine disruptors. Relevant in vitro, in vivo studies and human data are analyzed. The assessment presented here focuses on one endocrine activity, i.e., thyroid disruption, and two main adverse effects, neurotoxicity and cardiotoxicity. The data available on the different ED or non-ED modes of action (MoA), known to trigger these adverse effects, are described and the strength of evidence of the different …

Influencing factors of cardiorespiratory fitness in allogeneic stem cell transplant candidates prior to transplantation.

PurposeCardiorespiratory fitness (CRF) seems to be prognostic prior to allogeneic stem cell transplantation (allo-HSCT). Influencing factors of CRF in allo-HSCT candidates have not been studied so far. Aim was to identify potentially influencing factors on CRF.MethodsTo assess CRF, a maximal cardiopulmonary exercise test (CPET) was performed on average 2.6 ± 7.2 days prior to admission. A regression analysis was conducted, with the following predictors: gender, age, body mass index (BMI), time between last therapy and allo-HSCT (t_Therapies), number of cardiotoxic therapies (n_Cardiotox), numb

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… Otherwise, older cancer patients might be at increased risk of chemotherapy-related cardiotoxicity due to physiologic changes of several organ systems [ 36 ] or reduced tolerance of drug toxicity due to lower lean mass [ 37 ]. … Chemotherapy and cardiotoxicity in hematologic malignancies. Curr Cancer Drug Targets. 2017;17:311–324. doi: 10.2174/1568009617666161121141607. 26. Scott JM, Nilsen TS, Gupta D, Jones LW. Exercise therapy and cardiovascular toxicity in cancer. …

The Structural Determinants for α1-Adrenergic/Serotonin Receptors Activity among Phenylpiperazine-Hydantoin Derivatives.

Several studies confirmed the reciprocal interactions between adrenergic and serotoninergic systems and the influence of these phenomena on the pathogenesis of anxiety. Hence, searching for chemical agents with a multifunctional pharmacodynamic profile may bring highly effective therapy for CNS disorders. This study presents a deep structural insight into the hydantoin-arylpiperazine group and their serotonin/α-adrenergic activity. The newly synthesized compounds were tested in the radioligand binding assay and the intrinsic activity was evaluated for the selected derivatives. The computer-aid

Local Preirradiation of Infarcted Cardiac Tissue Substantially Enhances Cell Engraftment.

The success of cell therapy for the treatment of myocardial infarction depends on finding novel approaches that can substantially implement … scle to improve cell engraftment, but it has never been taken in cardiac tissue. To avoid long-term cardiotoxicity induced by full heart irradiation we developed a rat model of a catheter-based heart irradiation system to locally impact a delimited region of the infarcted cardiac tissue. As proof of concept, we transferred ZsGreen+ iPSCs in the infarcted heart, …

Pooled Multicenter Analysis of Cardiovascular Safety and Population Pharmacokinetic Properties of Piperaquine in African Patients with Uncomplicated Falciparum Malaria.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicenter trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90-ms mean QTc prolongation per 100-ng/ml increase in piperaquine concentration. The effect of piperaquine on absolute QTc interval

Lithium induced oxidative damage and inflammation in the rat's heart: Protective effect of grape seed and skin extract.

Lithium (Li) is a relevant mood stabilizer metal for the treatment of bipolar disorder (BD), as it protects from both depression and mania and reduces the risk of suicide. However, Lihas some clinical concerns as a narrow therapeutic index requiring routine monitoring of the serum level. The present study was designed to analyze the cardio-toxic side effect of Li and the ability of grape seed and skin extract (GSSE) to protect the heart against such toxicity. After 30days of exposure to Li (0, 2, 5 and 100mg/kg bw) and prevention with GSSE (4000mg/kg bw), rats were killed by decapitation and t

Computational Studies of Snake Venom Toxins.

Most snake venom toxins are proteins, and participate to envenomation through a diverse array of bioactivities, such as bleeding, inflammation, and pain, cytotoxic, cardiotoxic or neurotoxic effects. The venom of a single snake species contains hundreds of toxins, and the venoms of the 725 species of venomous snakes represent a large pool of potentially bioactive proteins. Despite considerable discovery efforts, most of the snake venom toxins are still uncharacterized. Modern bioinformatics tools have been recently developed to mine snake venoms, helping focus experimental research on the most

Successful recovery and allogeneic stem cell transplant following chemotherapy-induced severe cardiomyopathy: literature review of management and prognostic factors.

Chemotherapy-induced cardiomyopathy is one of the major possible hazards that can result from potential cardiotoxic agents while treating cancer. Prognostic risk factors include the rate of drug administration, history of hypertension, female gender, extremes of age, previous history of mediastinal irradiation, cumulative dose and pre-existing heart disease. Close monitoring of the patients, timely diagnosis, use of well-known biomarkers including cardiac troponins, NT-ProBNP and imaging studies like 2D Echo or cardiac MRI are essential. Emerging biomarkers include carbonyl reductases (CBR1 an

The emerging role of outdoor and indoor air pollution in cardiovascular disease.

Outdoor and indoor air pollution poses a significant cardiovascular risk, and has been associated with atherosclerosis, the main underlying … disease, with specific focus on the types of air pollutants and mechanisms of air pollution-induced cardiotoxicity. Published literature on pollution was systematically reviewed and cited in this article. It is hoped that this review will provide a better understanding of the harmful cardiovascular effects induced by air pollution exposure. This will help to bri …

[Tricyclic antidepressant overdose rescued by percutanenous cardiopulmonary support: report of two cases].

We report the case of two patients tricyclic antidepressant (TCA) overdoses complicated with severe circulatory failure, successfully resuscitated using percutaneous cardiopulmonary support (PCPS). In case 1, a woman transferred to our emergency department, presented with severe circulatory failure and developed cardiopulmonary arrest. She received prolonged cardiopulmonary resuscitation, and initiated with PCPS. In case 2, a woman presented our emergency department on foot. 3 hours after admission, she falled into severe circulatory failure with polymorphic ventricular tachycardia, and PCPS w

Cardiac assessment of patients for haematopoietic stem cell transplantation.

The expanding role of haematopoietic stem-cell transplantation (HSCT) renders the previous policy of avoiding transplantation in high-risk cardiac patients obsolete. Patients with amyloid, autoimmune conditions, sickle-cell disease, or thalassaemia, and patients over the age of 60 years are increasingly being offered HSCT. It is evident that the policy of avoiding transplantation in patients with impaired systolic function fails to identify all high-risk patients in such groups, and will deprive some patients of the benefits of HSCT unnecessarily. The development of an appropriate algorithm fo