scholarly journals A Role of Glucose Overload in Diabetic Cardiomyopathy in Nonhuman Primates

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xiu Wang ◽  
Shi Jin ◽  
Weina Hu

Type 2 diabetes (T2D) plays a major role in the development of heart failure. Patients with T2D have an increased risk to develop HF than healthy subjects, and they always have very poor outcomes and survival rates. However, the underlying mechanisms for this are still unclear. To help develop new therapeutic interventions, well-characterized animal models for preclinical and translational investigations in T2D and HF are urgently needed. Although studies in rodents are more often used, the research findings in rodents have often failed to be translated into humans due to the significant metabolic differences between rodents and humans. Nonhuman primates (NHPs) serve as valuable translational models between basic studies in rodent models and clinical studies in humans. NHPs can recapitulate the natural progress of these diseases in humans and study the underlying mechanism due to their genetic similarity and comparable spontaneous T2D rates to humans. In this review, we discuss the importance of using NHPs models in understanding diabetic cardiomyopathy (DCM) in humans with aspects of correlations between hyperglycemia and cardiac dysfunction progression, glucose overload, and altered glucose metabolism promoting cardiac oxidative stress and mitochondria dysfunction, glucose, and its effect on cardiac resynchronization therapy with defibrillator (CRT-d), the currently available diabetic NHPs models and the limitations involved in the use of NHP models.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 242-242
Author(s):  
Somer Case-Eads ◽  
Lois B. Travis ◽  
Chunkit Fung ◽  
Howard D. Sesso ◽  
Darren R. Feldman ◽  
...  

242 Background: Testicular cancer (TC) is the most common cancer in men aged 15-40, with survival rates after diagnosis > 95%. Testicular cancer survivors (TCS) are known to be at increased risk for certain acute and chronic medical conditions, but few studies have examined barometers of their psychological health. The objective is to characterize the prevalence of PSM use and associations with demographics, health behaviors, and treatment-associated toxicities among TCS. Methods: TCS aged < 50 years at first-line CHEM completed a questionnaire regarding co-morbidities and prescription drug use, including PSMs. For co-morbidities, peripheral neuropathy (PN) responses of ‘a little’, “quite a bit”, or “very much” were scored ‘yes.’ Fisher’s exact test was used to examine the significance of various associations. Results: Among the first 680 consecutively enrolled TCS, median age at TC diagnosis was 31y (range, 15-49y) and median time since CHEM completion was 52mo (range 12-360mo). 85 TCS (12.5%) reported PSM use, including antidepressants (N = 65 [76.5%]), anxiolytics (N = 23 [27%]), and stimulants (N = 21 [25%]) with 20 TCS on ≥ 2 PSMs (23%). Compared to non-users, more PSM users were unemployed (11.8% vs. 4.4%%; P < .01), self-rated their health as fair/poor (12.2% vs 4%; P < .01), and had gained > 20lb since CHEM (39.8% vs 23.4%;P < .01). PSM users were more likely to have tinnitus (49.4% vs. 36.4%; P < 0.04), both tinnitus and PN (43.5% vs. 27.2%; P < 0.01), cardiovascular disease (26.2% vs. 15.6%; P < .02), and greater use of prescription medications for pain control (20% vs. 4.7%; P < 0.01), hypertension (16.5% vs. 7.1%; P < 0.01), diabetes (8.3% vs. 2.9%; P < 0.02), and testosterone replacement (10.6% vs. 5.0%; P = 0.048). Conclusions: Future studies should aim for identification of high-risk patients in need of intensified preventive and therapeutic interventions.


Author(s):  
Márta Sárközy ◽  
Zoltán Varga ◽  
Renáta Gáspár ◽  
Gergő Szűcs ◽  
Mónika G. Kovács ◽  
...  

AbstractCancer management has undergone significant improvements, which led to increased long-term survival rates among cancer patients. Radiotherapy (RT) has an important role in the treatment of thoracic tumors, including breast, lung, and esophageal cancer, or Hodgkin's lymphoma. RT aims to kill tumor cells; however, it may have deleterious side effects on the surrounding normal tissues. The syndrome of unwanted cardiovascular adverse effects of thoracic RT is termed radiation-induced heart disease (RIHD), and the risk of developing RIHD is a critical concern in current oncology practice. Premature ischemic heart disease, cardiomyopathy, heart failure, valve abnormalities, and electrical conduct defects are common forms of RIHD. The underlying mechanisms of RIHD are still not entirely clear, and specific therapeutic interventions are missing. In this review, we focus on the molecular pathomechanisms of acute and chronic RIHD and propose preventive measures and possible pharmacological strategies to minimize the burden of RIHD.


2021 ◽  
Vol 22 (11) ◽  
pp. 5973
Author(s):  
Petra Grubić Rotkvić ◽  
Zrinka Planinić ◽  
Ana-Marija Liberati Pršo ◽  
Jozica Šikić ◽  
Edvard Galić ◽  
...  

Diabetic patients are predisposed to diabetic cardiomyopathy, a specific form of cardiomyopathy which is characterized by the development of myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis that develops independently of concomitant macrovascular and microvascular diabetic complications. Its pathophysiology is multifactorial and poorly understood and no specific therapeutic guideline has yet been established. Diabetic cardiomyopathy is a challenging diagnosis, made after excluding other potential entities, treated with different pharmacotherapeutic agents targeting various pathophysiological pathways that need yet to be unraveled. It has great clinical importance as diabetes is a disease with pandemic proportions. This review focuses on the potential mechanisms contributing to this entity, diagnostic options, as well as on potential therapeutic interventions taking in consideration their clinical feasibility and limitations in everyday practice. Besides conventional therapies, we discuss novel therapeutic possibilities that have not yet been translated into clinical practice.


TAPPI Journal ◽  
2018 ◽  
Vol 17 (01) ◽  
pp. 31-37
Author(s):  
Bryan McCulloch ◽  
John Roper ◽  
Kaitlin Rosen

Barrier coatings are used in applications including food packaging, dry goods, and consumer products to prevent transport of different compounds either through or into paper and paperboard substrates. These coatings are useful in packaging to contain active ingredients, such as fragrances, or to protect contents from detrimental substances, such as oxygen, water, grease, or other chemicals of concern. They also are used to prevent visual changes or mechanical degradation that might occur if the paper becomes saturated. The performance and underlying mechanism depends on the barrier coating type and, in particular, on whether the barrier coating is designed to prevent diffusive or capillary transport. Estimates on the basis of fundamental transport phenomena and data from a broad screening of different barrier materials can be used to understand the limits of various approaches to construct barrier coatings. These estimates also can be used to create basic design rules for general classes of barrier coatings.


The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.


2020 ◽  
Vol 19 (1) ◽  
pp. 41-54 ◽  
Author(s):  
Stefanos Roumeliotis ◽  
Athanasios Roumeliotis ◽  
Xenia Gorny ◽  
Peter R. Mertens

In end-stage renal disease patients, the leading causes of mortality are of cardiovascular (CV) origin. The underlying mechanisms are complex, given that sudden heart failure is more common than acute myocardial infarction. A contributing role of oxidative stress is postulated, which is increased even at early stages of chronic kidney disease, is gradually augmented in parallel to progression to endstage renal disease and is further accelerated by renal replacement therapy. Oxidative stress ensues when there is an imbalance between reactive pro-oxidants and physiologically occurring electron donating antioxidant defence systems. During the last decade, a close association of oxidative stress with accelerated atherosclerosis and increased risk for CV and all-cause mortality has been established. Lipid peroxidation has been identified as a trigger for endothelial dysfunction, the first step towards atherogenesis. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from studies that test antioxidants for CV protection, such as vitamins E and C, statins, omega-3 fatty acids and N-acetylcysteine.


2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.


Author(s):  
Shamil D. Cooray ◽  
Jacqueline A. Boyle ◽  
Georgia Soldatos ◽  
Shakila Thangaratinam ◽  
Helena J. Teede

AbstractGestational diabetes mellitus (GDM) is common and is associated with an increased risk of adverse pregnancy outcomes. However, the prevailing one-size-fits-all approach that treats all women with GDM as having equivalent risk needs revision, given the clinical heterogeneity of GDM, the limitations of a population-based approach to risk, and the need to move beyond a glucocentric focus to address other intersecting risk factors. To address these challenges, we propose using a clinical prediction model for adverse pregnancy outcomes to guide risk-stratified approaches to treatment tailored to the individual needs of women with GDM. This will allow preventative and therapeutic interventions to be delivered to those who will maximally benefit, sparing expense, and harm for those at a lower risk.


Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 785
Author(s):  
Sanchai Naree ◽  
Rujira Ponkit ◽  
Evada Chotiaroonrat ◽  
Christopher L. Mayack ◽  
Guntima Suwannapong

Nosema ceranae is a large contributing factor to the most recent decline in honey bee health worldwide. Developing new alternative treatments against N. ceranae is particularly pressing because there are few treatment options available and therefore the risk of increased antibiotic resistance is quite high. Recently, natural products have demonstrated to be a promising avenue for finding new effective treatments against N. ceranae. We evaluated the effects of propolis extract of stingless bee, Tetrigona apicalis and chito-oligosaccharide (COS) on giant honey bees, Apis dorsata, experimentally infected with N. ceranae to determine if these treatments could improve the health of the infected individuals. Newly emerged Nosema-free bees were individually inoculated with 106N. ceranae spores per bee. We fed infected and control bees the following treatments consisting of 0%, 50%, propolis extracts, 0 ppm and 0.5 ppm COS in honey solution (w/v). Propolis extracts and COS caused a significant increase in trehalose levels in hemolymph, protein contents, survival rates and acini diameters of the hypopharyngeal glands in infected bees. Our results suggest that propolis and COS could improve the health of infected bees. Further research is needed to determine the underlying mechanisms responsible for the improved health of the infected bees.


Author(s):  
Khalaf Kridin ◽  
Jennifer E. Hundt ◽  
Ralf J. Ludwig ◽  
Kyle T. Amber ◽  
Dana Tzur Bitan ◽  
...  

AbstractThe association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.


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