scholarly journals Cardiotoxic effects of methamphetamine associated with electrophysiological and epigenetic aberrations in Zebrafish

2021 ◽  
Author(s):  
Jimmy Zhang ◽  
Anh H Nguyen ◽  
Lauren Heine ◽  
Tai N Le ◽  
Xing Xia ◽  
...  

Long-term methamphetamine abuse damages functional and molecular changes in the brain that causes chronic and relapsing disease. In this study, we sought to investigate a relationship between cardiotoxicity and arrhythmia with associated methamphetamine abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with methamphetamine as well as to assess the applicability of zebrafish as an appropriate model for cardiac-related drug screening studies. Over a two-week duration, zebrafish were first treated with various concentrations of methamphetamine, ranging from 0 to 50 μM. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement for electrophysiological analysis. Results show that a higher incidence of increased heart rate over the duration of the experiment, corroborating with results from previous human case studies involving methamphetamine users. However, abnormalities commonly cited in those same case studies, such as prolongation of QTc, were not significantly presented in obtained ECG recordings. We have also conducted genetic, epigenetic, and histochemical analysis in an attempt to understand the cardiotoxic effects of methamphetamine on zebrafish cardiac function. These results suggested myocardial damage and decrease in gene expression associated with normal physiological function. Finally, this manuscript provides an analysis into potential reasons for the apparent discrepancies in our data with prior research as well as a future outlook of zebrafish cardiotoxic drug screening studies.

2012 ◽  
Vol 93 (3) ◽  
pp. 442-446
Author(s):  
E D Teplyakova ◽  
A A Savis’ko ◽  
A V Shestopalov ◽  
K S Aslanyan

Aim. To determine the frequency and nature of myocardial damage in children on the background of long-term remission of acute lymphoblastic leukemia, to assess the significance of the concentration of the N-terminal precursor of the brain natriuretic peptide and of the protein that binds fatty acids in blood serum. Methods. The observation group included 22 children aged 7 to 17 years, who are in long-term remission of acute lymphoblastic leukemia. The average duration of the remission was 6.1±1.0 years. All children were treated according to the standard and intermediate risk group protocol ALL-MB-2002. The control group included 65 children. A clinical and instrumental examination, including 12-lead electrocardiography, as well as complex transthoracic Doppler echocardiography was conducted. Analysis of the diastolic function of the myocardium was performed during assessment of the ratio of peak transmitral flow velocities (E/A), of the index of myocardial stiffness and of the time indicator B(E-Ea). The content of the N-terminal precursor of the brain natriuretic peptide and of the protein that binds fatty acids in blood serum was determined by enzyme immunoassay. Results. In 70% of the children with acute lymphoblastic leukemia who are in the remission stage for over 5 years, noted was the development of early signs of diastolic myocardial dysfunction, in 50% of the patients of this group reported was a significant increase in the concentration of the marker of heart failure - brain natriuretic peptide. At the same time, in a third of the examined individuals an increase in concentration of the protein that binds fatty acids was revealed, which may be indicative of myocardial damage at the cellular level. Positive correlation links between the indicators of initial manifestations of the evolving left ventricular diastolic dysfunction in children, who are in long-term remission of acute lymphoblastic leukemia, and the content of the N-terminal precursor of the brain natriuretic peptide have been revealed. Conclusion. The increase in the levels of the mentioned indicators makes it possible to identify high-risk groups for cardiovascular disease development among the cohort of children who are in long-term remission of acute lymphoblastic leukemia in order to develop preventive and rehabilitative programs.


2021 ◽  
Author(s):  
Tai Le ◽  
Jimmy Zhang ◽  
Anh Hung Nguyen ◽  
Ramses S. Trigo Torres ◽  
Khuong Vo ◽  
...  

The zebrafish (Dario rerio) has proven to be an excellent animal model for biological research owing to its small size, low cost for maintenance, short generation time, amenable genetics, and optical transparency. Zebrafish have been extensively used in cardiovascular studies in which mutant lines with cardiovascular defects were introduced and analyzed. Despite the small size, technological advances have paved the way to effectively assess cardiac functions of zebrafish. Here, we present a novel art for long-term simultaneous monitoring and analysis of electrocardiogram (ECG) in multiple zebrafish with controlled environment. The system helps minimize the effect of anesthetic drug and temperature to cardiac rhythm side effects as well as save time and efforts by 40-50 fold compared with the conventional approach. We further employed the system to study the Na+ sensitivity in the development of sinus arrest in Tg(SCN5A-D1275N) fish, a study model of the sick sinus syndrome, as well as the relationship between this variant and drug administration. The novel ECG system developed in this study holds promise to greatly accelerate other cardiovascular studies and drug screening using zebrafish.


2010 ◽  
Vol 24 (4) ◽  
pp. 249-252 ◽  
Author(s):  
Márk Molnár ◽  
Roland Boha ◽  
Balázs Czigler ◽  
Zsófia Anna Gaál

This review surveys relevant and recent data of the pertinent literature regarding the acute effect of alcohol on various kinds of memory processes with special emphasis on working memory. The characteristics of different types of long-term memory (LTM) and short-term memory (STM) processes are summarized with an attempt to relate these to various structures in the brain. LTM is typically impaired by chronic alcohol intake but according to some data a single dose of ethanol may have long lasting effects if administered at a critically important age. The most commonly seen deleterious acute effect of alcohol to STM appears following large doses of ethanol in conditions of “binge drinking” causing the “blackout” phenomenon. However, with the application of various techniques and well-structured behavioral paradigms it is possible to detect, albeit occasionally, subtle changes of cognitive processes even as a result of a low dose of alcohol. These data may be important for the consideration of legal consequences of low-dose ethanol intake in conditions such as driving, etc.


Author(s):  
Peter R. Breggin

BACKGROUND: The vaccine/autism controversy has caused vast scientific and public confusion, and it has set back research and education into genuine vaccine-induced neurological disorders. The great strawman of autism has been so emphasized by the vaccine industry that it, and it alone, often appears in authoritative discussions of adverse effects of the MMR and other vaccines. By dismissing the chimerical vaccine/autism controversy, vaccine defenders often dismiss all genuinely neurological aftereffects of the MMR (measles, mumps, and rubella) and other vaccines, including well-documented events, such as relatively rare cases of encephalopathy and encephalitis. OBJECTIVE: This report explains that autism is not a physical or neurological disorder. It is not caused by injury or disease of the brain. It is a developmental disorder that has no physical origins and no physical symptoms. It is extremely unlikely that vaccines are causing autism; but it is extremely likely that they are causing more neurological damage than currently appreciated, some of it resulting in psychosocial disabilities that can be confused with autism and other psychosocial disorders. This confusion between a developmental, psychosocial disorder and a physical neurological disease has played into the hands of interest groups who want to deny that vaccines have any neurological and associated neuropsychiatric effects. METHODS: A review of the scientific literature, textbooks, and related media commentary is integrated with basic clinical knowledge. RESULTS: This report shows how scientific sources have used the vaccine/autism controversy to avoid dealing with genuine neurological risks associated with vaccines and summarizes evidence that vaccines, including the MMR, can cause serious neurological disorders. Manufacturers have been allowed by the US Food and Drug Administration (FDA) to gain vaccine approval without placebo-controlled clinical trials. CONCLUSIONS: The misleading vaccine autism controversy must be set aside in favor of examining actual neurological harms associated with vaccines, including building on existing research that has been ignored. Manufacturers of vaccines must be required to conduct placebo-controlled clinical studies for existing vaccines and for government approval of new vaccines. Many probable or confirmed neurological adverse events occur within a few days or weeks after immunization and could be detected if the trials were sufficiently large. Contrary to current opinion, large, long-term placebo-controlled trials of existing and new vaccines would be relatively easy and safe to conduct.


2011 ◽  
Vol 3 (1) ◽  
pp. 80
Author(s):  
Alexander Feldman ◽  
Jonathan M Kalman ◽  
◽  

Focal atrial tachycardia (AT) is a relatively uncommon cause of supraventricular tachycardia, but when present is frequently difficult to treat medically. Atrial tachycardias tend to originate from anatomically determined atrial sites. The P-wave morphology on surface electrocardiogram (ECG) together with more sophisticated contemporary mapping techniques facilitates precise localisation and ablation of these ectopic foci. Catheter ablation of focal AT is associated with high long-term success and may be viewed as a primary treatment strategy in symptomatic patients.


Author(s):  
Sally M. Essawy ◽  
Basil Kamel ◽  
Mohamed S. Elsawy

Some buildings hold certain qualities of space design similar to those originated from nature in harmony with its surroundings. These buildings, mostly associated with religious beliefs and practices, allow for human comfort and a unique state of mind. This paper aims to verify such effect on the human brain. It concentrates on measuring brain waves when the user is located in several spots (coordinates) in some of these buildings. Several experiments are conducted on selected case studies to identify whether certain buildings affect the brain wave frequencies of their users or not. These are measured in terms of Brain Wave Frequency Charts through EEG Device. The changes identified on the brain were then translated into a brain diagram that reflects the spiritual experience all through the trip inside the selected buildings. This could then be used in architecture to enhance such unique quality.


2004 ◽  
pp. 406-412
Author(s):  
Paul Okunieff ◽  
Michael C. Schell ◽  
Russell Ruo ◽  
E. Ronald Hale ◽  
Walter G. O'Dell ◽  
...  

✓ The role of radiosurgery in the treatment of patients with advanced-stage metastatic disease is currently under debate. Previous randomized studies have not consistently supported the use of radiosurgery to treat patients with numbers of brain metastases. In negative-results studies, however, intracranial tumor control was high but extracranial disease progressed; thus, patient survival was not greatly affected, although neurocognitive function was generally maintained until death. Because the future promises improved systemic (extracranial) therapy, the successful control of brain disease is that much more crucial. Thus, for selected patients with multiple metastases to the brain who remain in good neurological condition, aggressive lesion-targeting radiosurgery should be very useful. Although a major limitation to success of this therapy is the lack of control of extracranial disease in most patients, it is clear that well-designed, aggressive treatment substantially decreases the progression of brain metastases and also improves neurocognitive survival. The authors present the management and a methodology for rational treatment of a patient with breast cancer who has harbored 24 brain metastases during a 3-year period.


Author(s):  
Amteshwar Singh Jaggi

Aim: The aim of the present study is to explore the neuroprotective effects of remote ischemic preconditioning in long term cognitive impairment after global cerebral ischemia induced-vascular dementia in mice. Material and methods: The mice were subjected to global cerebral ischemia by occluding the bilateral common carotid arteries for 12 minutes followed by the 24 hours of the reperfusion. The remote ischemic preconditioning stimulus was delivered in the form of 4 cycles of ischemia/reperfusion for 5 minutes each. The cerebral ischemic injury induced-long term cognitive impairment-related learning and memory alterations was assessed using morris water maze, the motor performances of the animals were evaluated using rota-rod test and neurological severity score. The cerebral infract size of the brain were quantified using triphenyltetrazolium chloride staining. Results: Global cerebral ischemia causes long term memory impairment, decreases motor performances and increases the brain infract size in animals. The delivery of remote ischemic preconditioning stimulus significantly abolished the long-term cognitive impairment and ameliorates the motor performances as well as cerebral infract size in brain. Conclusion: The remote ischemic preconditioning mediates neuro protection against global cerebral ischemic injury induced long-term cognitive impairment.


2017 ◽  
Vol 14 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Sofia Wenzler ◽  
Christian Knochel ◽  
Ceylan Balaban ◽  
Dominik Kraft ◽  
Juliane Kopf ◽  
...  

Depression is a common neuropsychiatric manifestation among Alzheimer’s disease (AD) patients. It may compromise everyday activities and lead to a faster cognitive decline as well as worse quality of life. The identification of promising biomarkers may therefore help to timely initiate and improve the treatment of preclinical and clinical states of AD, and to improve the long-term functional outcome. In this narrative review, we report studies that investigated biomarkers for AD-related depression. Genetic findings state AD-related depression as a rather complex, multifactorial trait with relevant environmental and inherited contributors. However, one specific set of genes, the brain derived neurotrophic factor (BDNF), specifically the Val66Met polymorphism, may play a crucial role in AD-related depression. Regarding neuroimaging markers, the most promising findings reveal structural impairments in the cortico-subcortical networks that are related to affect regulation and reward / aversion control. Functional imaging studies reveal abnormalities in predominantly frontal and temporal regions. Furthermore, CSF based biomarkers are seen as potentially promising for the diagnostic process showing abnormalities in metabolic pathways that contribute to AD-related depression. However, there is a need for standardization of methodological issues and for replication of current evidence with larger cohorts and prospective studies.


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