scholarly journals Radionuclide Imaging of the Molecular Mechanisms Linking Heart and Brain in Ischemic Syndromes

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Frank M. Bengel ◽  
Nele Hermanns ◽  
James T. Thackeray
Keyword(s):  
Molecular Mechanisms ◽  
Temporal Dynamics ◽  
Systemic Disease ◽  
Nuclear Imaging ◽  
Whole Body ◽  
Ischemic Event ◽  
Clinical Observations ◽  
Increased Risk ◽  
Imaging Markers ◽  
The Brain

For the heart and the brain, clinical observations suggest that an acute ischemic event experienced by one organ is associated with an increased risk for future acute events and chronic dysfunction of the reciprocal organ. Beyond atherosclerosis as a common systemic disease, various molecular mechanisms are thought to be involved in this interaction. Molecular-targeted nuclear imaging may identify the contribution of factors, such as the neurohumoral, circulatory, or especially the immune system, by combining specific radiotracers with whole-body acquisition and global as well as regional multiorgan analysis. This may be integrated with complementary functional imaging markers and systemic biomarkers for comprehensive network interrogation. Such systems-based strategies go beyond the traditional organ-centered approach and provide novel mechanistic insights, information about temporal dynamics, and a foundation for future interventions aiming at optimal preservation of function of both organs.

scholarly journals Future of environmental research in the age of epigenomics and exposomics

2017 ◽  
Vol 32 (1-2) ◽  
pp. 45-54 ◽  
Author(s):  
Nina Holland
Keyword(s):  
Public Health ◽  
Molecular Mechanisms ◽  
Environmental Research ◽  
Whole Body ◽  
Epigenetic Mechanisms ◽  
Multifactorial Diseases ◽  
Adverse Health Outcomes ◽  
Increased Risk ◽  
Susceptible Populations ◽  
Risk Of Cancer

Abstract Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma. Rapidly evolving methodologies of exposure assessment and the conceptual framework of the Exposome, first introduced in 2005, are new frontiers of environmental research. Metabolomics and adductomics provide remarkable opportunities for a better understanding of exposure and prediction of potential adverse health outcomes. Metabolomics, the study of metabolism at whole-body level, involves assessment of the total repertoire of small molecules present in a biological sample, shedding light on interactions between gene expression, protein expression, and the environment. Advances in genomics, transcriptomics, and epigenomics are generating multidimensional structures of biomarkers of effect and susceptibility, increasingly important for the understanding of molecular mechanisms and the emergence of personalized medicine. Epigenetic mechanisms, particularly DNA methylation and miRNA expression, attract increasing attention as potential links between the genetic and environmental determinants of health and disease. Unlike genetics, epigenetic mechanisms could be reversible and an understanding of their role may lead to better protection of susceptible populations and improved public health.

scholarly journals Exercise prevents whole-body type 2 diabetes risk factors better than estradiol replacement in rats

2021 ◽  
Author(s):  
Luke J. Fritsch ◽  
Skylar J. McCaulley ◽  
Colton R. Johnson ◽  
Nicholaus J. Lawson ◽  
Brittany K. Gorres-Martens
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Body Weight Gain ◽  
Serum Insulin ◽  
Whole Body ◽  
Body Type ◽  
Increased Risk

Introduction: The absence of estrogens in postmenopausal women is linked to an increased risk of type 2 diabetes (T2D), and estradiol replacement can decrease this risk. Notably, exercise can also treat and prevent T2D. This study seeks to understand the molecular mechanisms by which estradiol and exercise induce their beneficial effects via assessing whole-body and cellular changes. Methods: Female Wistar rats were ovariectomized and fed a high-fat diet for 10 weeks and divided into the following 4 experimental groups: 1) no treatment (control), 2) exercise (Ex), 3) estradiol replacement, and 4) Ex+estradiol. Results: Both Ex and estradiol decreased the total body weight gain. However, only exercise effectively reduced the white adipose tissue (WAT) weight gain, food intake, blood glucose levels and serum insulin levels. At the molecular level, exercise increased the non-insulin stimulated pAkt levels in the WAT. In the liver, estradiol increased the protein expression of ACC and FAS, and estradiol decreased the hepatic protein expression of LPL. In the WAT, estradiol and exercise increased the protein expression of ATGL. Conclusion: Exercise provides better protection against T2D when considering whole body measurements, which may be due to increased non-insulin stimulated pAkt in the WAT. However, at the cellular level, several molecular changes in fat metabolism and fat storage occurred in the liver and WAT with estradiol treatment.

scholarly journals Estrogen and neuroprotection: from clinical observations to molecular mechanisms

2002 ◽  
Vol 4 (2) ◽  
pp. 149-161 ◽  
Keyword(s):  
Molecular Mechanisms ◽  
Science Studies ◽  
Adult Brain ◽  
Health Concern ◽  
Past Century ◽  
Clinical Observations ◽  
Protective Actions ◽  
Increased Risk ◽  
The Impact

We now appreciate that estrogen is a pleiotropic gonadal steroid that exerts profound effects on the plasticity and cell survival of the adult brain. Over the past century, the life span of women has increased, but the age of the menopause remains constant. This means that women may now live over one third of their lives in a hypoestrogenic, postmenopausal state. The impact of prolonged hypoestrogenicity on the brain is now a critical health concern as we realize that these women may suffer an increased risk of cognitive dysfunction and neurodegeneration due to a variety of diseases. Accumulating evidence from both clinical and basic science studies indicates that estrogen exerts critical protective actions against neurodegenerative conditions such as Alzheimer's disease and stroke. Here, we review the discoveries that comprise our current understanding of estrogen action against neurodegeneration. These findings carry far-reaching possibilities for improving the quality of life in our aging population.

Diversity and Regulation of Astrocyte Neurotoxicity in Alzheimer's Disease

2021 ◽  
Vol 18 ◽  
Author(s):  
Sadayuki Hashioka ◽  
James G. McLarnon ◽  
Andis Klegeris
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Nuclear Imaging ◽  
Resonance Spectroscopy ◽  
Tnf Α ◽  
Factor Α ◽  
The Brain ◽  
Harmful Effects ◽  
Necrosis Factor

: Astrocytes contribute to brain development and homeostasis and support diverse functions of neurons. These cells also respond to the pathological processes in Alzheimer’s disease (AD). There is still considerable debate concerning the overall contribution of astrocytes to AD pathogenesis since both the protective and harmful effects of these cells on neuronal survival have been documented. This review focuses exclusively on the neurotoxic potential of astrocytes while acknowledging that these cells can contribute to neurodegeneration through other mechanisms, for example, by lowered neurotrophic support. We identify reactive oxygen and nitrogen species, tumor necrosis factor α (TNF-α), glutamate, and matrix metalloproteinase (MMP)-9 as molecules that can be directly toxic to neurons and are released by reactive astrocytes. There is also considerable evidence suggesting their involvement in AD pathogenesis. We further discuss the signaling molecules that trigger the neurotoxic response of astrocytes with a focus on human cells. We also highlight microglia, the immune cells of the brain, as critical regulators of astrocyte neurotoxicity. Nuclear imaging and magnetic resonance spectroscopy (MRS) could be used to confirm the contribution of astrocyte neurotoxicity to AD progression. The molecular mechanisms discussed in this review could be targeted in the development of novel therapies for AD.

scholarly journals Putative Role of MicroRNA-Regulated Pathways in Comorbid Neurological and Cardiovascular Disorders

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Sébastien S. Hébert
Keyword(s):  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Heart Cell ◽  
Cardiovascular Disorders ◽  
Increased Risk ◽  
Mirna Expression Profiles ◽  
And Function ◽  
The Brain

Background. The conserved noncoding microRNAs (miRNAs) that function to regulate gene expression are essential for the development and function of the brain and heart. Changes in miRNA expression profiles are associated with an increased risk for developing neurodegenerative disorders as well as heart failure. Here, the hypothesis of how miRNA-regulated pathways could contribute to comorbid neurological and cardiovascular disorders will be discussed. Presentation. Changes in miRNA expression occurring in the brain and heart could have an impact on coexisting neurological and cardiovascular characteristics by (1) modulating organ function, (2) accentuating cellular stress, and (3) impinging on neuronal and/or heart cell survival. Testing. Evaluation of miRNA expression profiles in the brain and heart tissues from individuals with comorbid neurodegenerative and cardiovascular disorders will be of great importance and relevance. Implications. Careful experimental design will shed light to the deeper understanding of the molecular mechanisms tying up those different but yet somehow connected diseases.

scholarly journals Measles Encephalitis: Towards New Therapeutics

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1017 ◽  
Author(s):  
Ferren ◽  
Horvat ◽  
Mathieu
Keyword(s):  
Measles Virus ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Systemic Disease ◽  
Small Animal ◽  
Cns Infection ◽  
Vaccine Preventable Diseases ◽  
The Brain

Measles remains a major cause of morbidity and mortality worldwide among vaccine preventable diseases. Recent decline in vaccination coverage resulted in re-emergence of measles outbreaks. Measles virus (MeV) infection causes an acute systemic disease, associated in certain cases with central nervous system (CNS) infection leading to lethal neurological disease. Early following MeV infection some patients develop acute post-infectious measles encephalitis (APME), which is not associated with direct infection of the brain. MeV can also infect the CNS and cause sub-acute sclerosing panencephalitis (SSPE) in immunocompetent people or measles inclusion-body encephalitis (MIBE) in immunocompromised patients. To date, cellular and molecular mechanisms governing CNS invasion are still poorly understood. Moreover, the known MeV entry receptors are not expressed in the CNS and how MeV enters and spreads in the brain is not fully understood. Different antiviral treatments have been tested and validated in vitro, ex vivo and in vivo, mainly in small animal models. Most treatments have high efficacy at preventing infection but their effectiveness after CNS manifestations remains to be evaluated. This review describes MeV neural infection and current most advanced therapeutic approaches potentially applicable to treat MeV CNS infection.

Treatment of a B-Cell, Primary Central Nervous System Lymphoma Patient with Radioimmunotherapy Using Zevalin®: A Proof-of-Principal Case.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4639-4639
Author(s):  
Ruby Meredith ◽  
Louis Nabors ◽  
Sui Shen ◽  
John Fiveash ◽  
Sthepen Besh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Frontal Lobe ◽  
Systemic Disease ◽  
Pet Scan ◽  
Whole Body ◽  
High Dose ◽  
The Right ◽  
The Brain

Abstract Primary Central Nervous System NHL (PCNSL) has increased in incidence across all age groups over the past decades. 90% are B-cell NHL. Resection has not been shown to improve survival and standard chemotherapy is not effective. While radiation therapy (RT) was formerly the standard therapy, high-dose methotrexate (Mtx) is the single most active agent. High-dose Mtx alone or in combination with RT has resulted in response rates of 100% and median survival ranging between 30–60 months, although the risk of relapse is 50%. The prognosis at relapse is poor; clearly, new strategies are needed for these patients. There are no previous cases or clinical trials to evaluate the efficacy of Zevalin in PCNSL. We report a single patient with PCNSL treated with Zevalin. A 26YO male with a CD20+/CD19+ PCNSL was diagnosed in 05/01 when he presented with a left frontal mass. The patient underwent surgical resection (pathology: pleomorphic xanthoastrocytoma). By 09/01 local progression was documented and a second excision was done. Pathology showed a CD20+/CD19+, PCNSL (previous pathology was reviewed and the diagnosis was confirmed). No systemic disease was found and the patient was HIV negative. While the patient was waiting to start RT, the lesion progressed and a third resection was done, followed by RT. By 01/03 progression was documented by imaging studies but the lesion was found in the right frontal lobe, just across the previous lesion in the left side; diagnosis was confirmed with a stereotactic biopsy. Systemic disease was not documented. PET scan showed area of increased uptake in the right frontal lobe of the brain consistent with active lymphoma with no areas of abnormally increased F-18 uptake in the rest of the body. It was decided to treat the patient with Zevalin RIT. The study utilized the standard Zevalin kit and the preparation, administration and storage were followed in the drug labeling directions. On day 1 he received Rituxan 250 mg/m2 followed by 5.0 mCi of 111In-2B8 for biodistribution evaluation. Whole body scintogram planar images were obtained 24 and 48 hours after the infusion of the 111In-2B8 and they showed increased activity in the right frontal lobe consistent with the patients known lymphoma. Otherwise, there was normal blood pool and organ distribution of the radiolabeled antibody. On day 8 the patient received Rituxan 250 mg/m2 followed by 29.1 mCi of Zevalin (0.4 mCi/Kg). Tumor localization of radioactivity was evident at 24 hours. The estimated localization per gram of tumor at 24 hours was 0.21% of the injected dose (marrow 0.0042%, liver 0.0069%, kidney 0.0065%, spleen 0.015%). The anticipated hematologic toxicity nadired on week 5 and recovered by week 7. MRI was performed on weeks 6, 14, 20 indicating stable disease with an interval decrease in the right frontal abnormal T2 hyperintensity. PET scan performed on week 20 indicating interval decrease in the right frontal lobe uptake. On week 32, an MRI of the brain and a PET scan showed progression. This report is the first description in humans using Zevalin in PCNSL, and serves as a proof-of-principle. We have proposed a hypothesis-driven pilot study to confirm our observation that Zevalin binds to the PCNSL and it is able to deliver local radiation. If positive, a more definitive design would be pursued. Images (MRI, PET, Indium Scans) will be presented in the meeting.

scholarly journals Molecular Mechanisms of Cancer-Induced Sleep Disruption

2019 ◽  
Author(s):  
William H. Walker II ◽  
Jeremy C. Borniger
Keyword(s):  
Molecular Mechanisms ◽  
Systemic Disease ◽  
Sleep Disruption ◽  
Poor Sleep ◽  
Therapeutic Approaches ◽  
Treatment Regimens ◽  
Patients With Cancer ◽  
And Behavior ◽  
The Brain

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

Rheumatoid Arthritis: History, Stages, Epidemiology, Pathogenesis, Diagnosis and Treatment

2017 ◽  
Vol 9 (02) ◽  
Author(s):  
Abeer Fauzi Al-Rubaye ◽  
Mohanad Jawad Kadhim ◽  
Imad Hadi Hameed
Keyword(s):  
Rheumatoid Arthritis ◽  
Medicinal Plants ◽  
Systemic Disease ◽  
Modern Medicine ◽  
Whole Body ◽  
Internal Organs ◽  
Synthetic Drugs ◽  
Relieve Pain ◽  
Medicinal Treatment ◽  
Natural Drugs

The pharmacological mechanisms of the medicinal plants traditionally used for RA in Persian medicine are discussed in the current review. Further investigations are mandatory to focus on bioefficacy of these phytochemicals for finding novel natural drugs. Rheumatoid arthritis is chronic, progressive, disabling autoimmune disease characterized by systemic inflammation of joints, damaging cartilage and bone around the joints. It is a systemic disease which means that it can affect the whole body and internal organs such as lungs, heart and eyes. Although numbers of synthetic drugs are being used as standard treatment for rheumatoid arthritis but they have adverse effect that can compromise the therapeutic treatment. Unfortunately, there is still no effective known medicinal treatment that cures rheumatoid arthritis as the modern medicine can only treat the symptoms of this disease that means to relieve pain and inflammation of joints. It is possible to use the herbs and plants in various forms in order to relieve the pain and inflammation in the joints. There are so many medicinal plants that have shown anti rheumatoid arthritis properties. So the plants and plant product with significant advantages are used for the treatment of rheumatoid arthritis. The present review is focused on the medicinal plants having anti rheumatoid arthritis activity

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