Treatment advances and higher participation rates in clinical trials have rapidly increased the number of survivors of childhood cancer. However, chemotherapy and radiation treatments are cardiotoxic ...and can cause cardiomyopathy, conduction defects, myocardial infarction, hypertension, stroke, pulmonary oedema, dyspnoea and exercise intolerance later in life. These cardiotoxic effects are often progressive and irreversible, emphasizing a need for effective prevention and treatment to reduce or avoid cardiotoxicity. Medical interventions, such as angiotensin-converting enzyme inhibitors, β-blockers, and growth hormone therapy, might be used to treat cardiotoxicity in childhood cancer survivors. Preventative strategies should include the use of dexrazoxane, which provides cardioprotection without reducing the oncological efficacy of doxorubicin chemotherapy; less-toxic anthracycline derivatives and the use of antioxidant nutritional supplements might also be beneficial. Continuous-infusion doxorubicin provides no benefit over bolus infusion in children. Identifying patient-related (for example, obesity and hypertension) and drug-related (for example, cumulative dose) risk factors for cardiotoxicity could help tailor treatments to individual patients. However, all survivors of childhood cancer are at increased risk of cardiotoxicity, suggesting that survivor screening recommendations for assessment of global risk of premature cardiovascular disease should apply to all survivors. Optimal, evidence-based monitoring strategies and multiagent preventative treatments still need to be identified.
Excessive inflammation and impaired healing of cardiac tissue following a myocardial infarction (MI) can drive the development of heart failure. Cardiac repair begins immediately after the onset of ...MI and continues for months. The repair process can be divided into the following 3 overlapping phases, each having distinct functions and sequelae: the inflammatory phase, the proliferative phase, and the maturation phase. Macrophages, neutrophils, and lymphocytes are present in the myocardium throughout the repair process and govern the duration and function of each of these phases. However, changes in the functions of these cell types across each phase are poorly characterized. Numerous immunomodulatory therapies that specifically target inflammation have been developed for promoting cardiac repair and preventing heart failure after MI. However, these treatments have been largely unsuccessful in large-scale clinical randomized controlled trials. A potential explanation for this failure is the lack of a thorough understanding of the time-dependent evolution of the functions of immune cells after a major cardiovascular event. Failure to account for this temporal plasticity in cell function may reduce the efficacy of immunomodulatory approaches that target cardiac repair. This review is concerned with how the functions of different immune cells change with time following an MI. Improved understanding of the temporal changes in immune cell function is important for the future development of effective and targeted treatments for preventing heart failure after MI.
Clinically, girls appear to be more sensitive than boys to the cardiotoxic effects of doxorubicin, whereas the opposite may be true for adults. To identify and characterize potential sex-related ...differences, adult male and female spontaneously hypertensive rats (SHR; some ovariectomized OVX) received 1 mg/kg of doxorubicin or saline iv weekly for 9, 10, or 12 weeks. Weight gain was slower in treated males. Serum concentrations of cholesterol and triglycerides increased and those of albumin decreased in both sexes, but changes were more pronounced in treated males. Treated males had significantly more severe cardiomyopathy scores and higher serum levels of cTnT than females. The increased cardiotoxicity was accompanied by higher numbers of cardiac mast cells (MCs) and percentage of cardiac MCs undergoing degranulation. Doxorubicin-treated OVX animals had significantly increased numbers of cardiac MCs, more severe myocardial lesions, and elevated serum concentrations of cTnT compared to doxorubicin-treated normal female SHR. The severity of cardiac lesions in the OVX female was similar to that observed in doxorubicin-treated males. This study demonstrated the presence of sex-related differences in the cardiotoxic effects elicited by doxorubicin and identified variations in the level of cardiac MC activity as a factor which could possibly contribute to the male-female dissimilarity.
Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. Treatment-related cardiac damage is progressive and often difficult to reverse. Strategies to minimize ...cardiotoxicity during treatment are crucial to prevent severe lasting effects on health and quality of life.
This comprehensive review covers the pathophysiology and various presentations, both clinical and subclinical, of treatment-induced cardiotoxicity and characteristics associated with increased risk of cardiac dysfunction in childhood ALL survivors. Additionally, contemporary prevention strategies such as limiting cumulative anthracycline dose, altering drug administration schedule, the use of anthracycline structural analogs, liposomal encapsulated anthracyclines, cardioprotective agents and nutritional supplements are critically analyzed. Finally, this review covers the management options of chemotherapy-induced damage and other treatment-related cardiotoxicity.
Higher lifetime cumulative doses of anthracyclines, younger age at diagnosis, longer follow-up, female sex, higher dose rates and cranial irradiation are associated with more severe cardiotoxic effects. Long-term adverse effects of both anthracycline and non-anthracycline chemotherapeutic agents are becoming an increasing focus during treatment of childhood malignancies. There must be a careful balance between achieving remission of childhood ALL while avoiding the development of another often-fatal illness, heart failure.
At the beginning of the twenty-first century, there are 30,000 golf courses and 55 million people who play golf worldwide. In the USA alone, the value of golf club memberships sold in the 1990s was ...US$3.2 billion. Underpinning this significant human activity is a wide variety of people researching and applying science to sustain and develop the game. The 11 golf science disciplines recognized by the World Scientific Congress of Golf have reported 311 papers at four world congresses since 1990. Additionally, scientific papers have been published in discipline-specific peer-reviewed journals, research has been sponsored by the two governing bodies of golf, the Royal and Ancient Golf Club of St. Andrews and the United States Golf Association, and confidential research is undertaken by commercial companies, especially equipment manufacturers. This paper reviews much of this human endeavour and points the way forward for future research into golf.
Currently threatening the world of medicine is a growing number of antibiotic-resistant diseases. More specifically, bacteria and nematodes have gained resistance to many of the world’s leading ...antibiotics and nematicides, respectively, making infections more difficult to treat. Subsequently, these parasitic organisms are able to continue damaging crops and other living organisms like humans without strong interference. To help people and the environment, the development of new and novel antibiotics is vital. Previous research suggests that phytochemicals are a potential solution that will not only help inhibit bacterial growth but also reduce nematode survival. We hypothesized that Myrica cerifera, a plant often used by the Lumbee tribe to treat illness, possesses antibacterial and nematicidal properties. To answer our hypothesis, we began by collecting plant specimens to extract material for biological assays and to subsequently isolate and elucidate the structures of active components. The extract was evaluated for antibacterial properties with an agar diffusion assay and then nematicidal properties using Caenorhabditis elegans. M. cerifera extract was added onto an agar lawn at various doses, and the nematodes’ lifespans were scored. The findings of this study show that extracts of this plant, more commonly referred to as ‘wax myrtle’, do significantly decrease the lifespan of C. elegans and increase the zone of inhibition for Staphylococcus epidermidis and Staphylococcus aureus. In addition, two compounds were isolated and characterized through chemical extraction, chromatographic separation, and spectroscopic analysis. These compounds could potentially be used to treat bacterial and nematode infections.
KEYWORDS: Antibacterial; Antimicrobial; Caenorhabditis elegans; Plant extract; Myrica cerifera; Nematicidal; NMR; Phytochemical
High cholesterol levels in pancreatic β-cells cause oxidative stress and decrease insulin secretion. β-cells can internalize apo (apolipoprotein) A-I, which increases insulin secretion. This study ...asks whether internalization of apoA-I improves β-cell insulin secretion by reducing oxidative stress.
Ins-1E cells were cholesterol-loaded by incubation with cholesterol-methyl-β-cyclodextrin. Insulin secretion in the presence of 2.8 or 25 mmol/L glucose was quantified by radioimmunoassay. Internalization of fluorescently labeled apoA-I by β-cells was monitored by flow cytometry. The effects of apoA-I internalization on β-cell gene expression were evaluated by RNA sequencing. ApoA-I-binding partners on the β-cell surface were identified by mass spectrometry. Mitochondrial oxidative stress was quantified in β-cells and isolated islets with MitoSOX and confocal microscopy.
An F
-ATPase β-subunit on the β-cell surface was identified as the main apoA-I-binding partner. β-cell internalization of apoA-I was time-, concentration-, temperature-, cholesterol-, and F
-ATPase β-subunit-dependent. β-cells with internalized apoA-I (apoA-I
cells) had higher cholesterol and cell surface F
-ATPase β-subunit levels than β-cells without internalized apoA-I (apoA-I
cells). The internalized apoA-I colocalized with mitochondria and was associated with reduced oxidative stress and increased insulin secretion. The IF
(ATPase inhibitory factor 1) attenuated apoA-I internalization and increased oxidative stress in Ins-1E β-cells and isolated mouse islets. Differentially expressed genes in apoA-I
and apoA-I
Ins-1E cells were related to protein synthesis, the unfolded protein response, insulin secretion, and mitochondrial function.
These results establish that β-cells are functionally heterogeneous, and apoA-I restores insulin secretion in β-cells with elevated cholesterol levels by improving mitochondrial redox balance.
Pediatric cardiomyopathies, which are rare but serious disorders of the muscles of the heart, affect at least one in every 100,000 children in the USA. Approximately 40% of children with symptomatic ...cardiomyopathy undergo heart transplantation or die from cardiac complications within 2 years. However, a significant number of children suffering from cardiomyopathy are surviving into adulthood, making it an important chronic illness for both pediatric and adult clinicians to understand. The natural history, risk factors, prevalence and incidence of this pediatric condition were not fully understood before the 1990s. Questions regarding optimal diagnostic, prognostic and treatment methods remain. Children require long-term follow-up into adulthood in order to identify the factors associated with best clinical practice including diagnostic approaches, as well as optimal treatment approaches. In this article, we comprehensively review current research on various presentations of this disease, along with current knowledge about their causes, treatments and clinical outcomes.
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