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The effects of magnesium administration on cardiac ventricular function, heart rate variability, and myocardial morphological changes in a chronic diabetes disease model in rats
Introduction:
Diabetes mellitus (DM) is a leading cause of morbidity and mortality all over the world, and the main cause of the mortality is cardiovascular complications. Such diabetic cardiovascular complications include coronary heart disease, cardiac autonomic neuropathy and ventricular dysfunction. Furthermore, DM is associated with electrolyte disturbances such as those involving potassium, calcium and magnesium (Mg2+). Among these electrolyte disturbances hypomagnesemia is common in diabetes and is associated with increased cardiovascular risk. Recent evidence has shown that Mg2+ supplementation can prevent cardiac autonomic dysfunction and improve ventricular compliance in acute DM. However, the underlying mechanisms of Mg2+ action and Mg2+ effects in chronic DM are unknown. Therefore, the present study explored the effects of Mg2+ administration and its possible mechanisms of action in chronic streptozotocin (STZ) induced diabetic rats.
Methods:
Adult male Wistar rats were injected intraperitoneally (i.p) once with either STZ (50 mg/Kg body weight) or the STZ vehicle (citrate buffer). The rats were then injected i.p once daily with either magnesium sulphate (MgSO4; 270 mg/Kg body weight) or the MgSO4 vehicle (normal saline) for 28 consecutive days. Blood glucose and body weight were measured throughout the period of the study. On day 28 of the experiments, in-vivo heart rate variability (HRV) parameters were measured to assess cardiac autonomic function using tail pulse plethysmography. Orthostatic stress was induced by tilting the animals from flat position to 70° head-up position. Ex-vivo hemodynamic and electrocardiograph (ECG) measurements were performed on a Langendorff perfusion system. Histological studies of ventricular tissue were performed using haematoxylin-eosin and Masson’s trichrome staining. Western blot analyses of the cardiac autonomic presynaptic marker (synaptophysin) and of the mitochondrial marker of oxidative stress (ATP5A) were performed on right atrial tissue. Plasma Mg2+ concentration was measured using automated photometric assays.
Results:
STZ treatment significantly increased the blood glucose level and decreased the body weight, and these STZ effects were not prevented by Mg2+ treatment. Diabetes decreased the root mean square differences of successive normal-to-normal intervals (RMSSD) and increased the low frequency (LF) /high frequency (HF) power ratio, which are both indicative of abnormal HRV. These diabetes effects on HRV parameters were significantly prevented by Mg2+ treatments (P < 0.05, STZ+Mg vs. STZ). DM also reduced both the heart rate and orthostatic stress-induced tachycardia, and these effects were reversed by Mg2+ treatment (P < 0.05, STZ+Mg vs. STZ). DM also decreased the left ventricular (LV) developed pressure and the maximal rate of LV pressure increase (+dP/dt), and these diabetic effects were prevented by Mg2+ treatment (P < 0.05, STZ+Mg vs. STZ). DM also decreased the maximal rate of LV pressure decline (-dP/dt) and the rate pressure product, but these parameters were not improved by Mg2+ treatment. DM and Mg2+ treatment did not affect the ECG waveforms and the coronary flow rate in all groups. Histologically, there were no differences in ventricular cardiomyocyte width or in the extent of interstitial fibrosis in all groups. Western blot analysis qualitatively showed a decrease in the expression of synaptophysin in DM that was prevented by Mg2+ treatment. Neither DM nor Mg2+ treatment altered ATP5A expression. The plasma Mg2+ concentration was not altered by DM or Mg2+ treatment.
Conclusion:
This study showed that Mg2+ treatment prevented cardiac autonomic dysfunction and improved hemodynamic function impairment in chronic DM. Based on the expression of synaptophysin, the mechanism through which Mg2+ improved cardiac autonomic function could involve the prevention of synaptic degradation in diabetes. The effects of Mg2+ on hemodynamic impairment in diabetes seemed to be unrelated to the Mg2+ effects on the cardiac histological structure or on the changes in coronary perfusion. Moreover, the overall effects of Mg2+ in diabetes were independent of its effects on the blood glucose level or the alteration of plasma Mg2+ level. Thus, Mg2+ treatment may have long-lasting therapeutic effects on ventricular dysfunction and cardiac autonomic impairment in chronic diabetes, but further studies are needed to explore the precise underlying mechanisms
Investigation of the mechanisms underlying the effects of hyperglycaemia on cardiac structural and electrical remodelling
Background: Diabetes mellitus with uncontrolled hyperglycaemia is a major cause of cardiovascular complications and mortality. The developing foetal heart in-utero is particularly susceptible to hyperglycaemia through pathological remodelling, which results in life-long structural abnormalities such as cardiomyopathy and electrical defects like arrhythmias. However, the underlying mechanisms and potential therapeutic drug targets remain unclear. In this study, a cardiac developmental cellular model was used to study hyperglycaemia-induced remodelling. Methods: Mouse embryonic stem cells (mESCs) were differentiated into pulsatile, cardiac-like cells via embryoid body (EB) formation and cultured under baseline- or high glucose conditions. A Ca2+ -sensitive fluorescent dye Fluo-4 was used to measure calcium transients and a voltage-sensitive dye di-4-ANEPPS was used to record action potentials. Cellular biomarkers were detected using immunocytochemistry, confocal microscopy, and Western blotting as well as terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) and 5-ethynyl-2-deoxyuridine (EdU) assay. Results: Undifferentiated mESCs were positive for pluripotent transcription factors Nanog and Oct3/4, whereas the cardiac differentiated mESCs were positive for cardiac proteins troponin T, α-actinin 2, connexin 43, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA 2) and α- and β-myosin heavy chain. Hyperglycaemia decreased the number of beating EBs, their beating rate, and their amplitude of contraction. It also decreased the calcium transient amplitude and the contractile response to ryanodine receptor stimulation by caffeine but did not alter the SERCA 2 expression. The amplitude and duration of action potentials in beating EBs were not altered by hyperglycaemia. However, structural changes included a decrease in EB size and expression of myofilament proteins, α-actinin and α- and β-myosin heavy chain and a disruption of the striated organization of the myofilaments. Hyperglycaemia increased the proportion of TUNEL-positive cells and the expression of the pro-apoptotic marker cytochrome c and decreased the anti-apoptotic protein Bcell lymphoma 2 but did not alter the mitochondrial staining with Mitotracker. It also increased the oxidative stress marker nitrotyrosine but did not alter the extent of EdU nuclear staining nor the expression of the receptor of advanced glycation end-product. The antioxidant n-acetyl cysteine decreased the fraction of hyperglycaemia-induced TUNEL-positive cells and improved the α-actinin striated pattern. Conclusion: Hyperglycaemia suppressed the cardiac differentiation and contractile activity of mESCs as well as disrupted the cardiac myofilament organisation and expression. These effects of hyperglycaemia were likely mediated by mitochondrial-dependent apoptosis triggered by oxidative stress as well as by the abnormalities in calcium signalling. These results have potential clinical implications in foetal diabetic cardiac disease and add novel insights into the mechanistic factors that represent new therapeutic drug targets in the developing foetal heart
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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