Abraham A. Embi

Glycogen and the propensity for atrial fibrillation: intrinsic anatomic differences in glycogen in the left and right atria in the goat heart

Background: Previous experimental studies have demonstrated electrophysiological and structural remodeling in pacing induced atrial fibrillation. The latter has been characterized by glycogen accumulation but no connection to atrial fibrillation induction and maintenance has as yet been proposed. Aims: We determined the presence of glycogen in the right and left atrial appendages in the goat heart, in order to find any intrinsic disparity in distribution and concentration between these sites. Materials and Methods: Atrial appendages from 5 goats were stained by the Periodic acid Schiffmethod to determine the presence of glycogen and the concentration of glycogen by morphometric analysis. Results: We are reporting for the first time that the right atrial appendage showed scattered glycogen granules throughout the atrial myocytes which delineated the intercalated discs; whereas glycogen in the left atrial appendage was more dense within cells and coalesced against the intercalated discs and side to side junctions between myocytes. Also, morphometric analysis determined that the stained regions of the right atrial appendages averaged, 0.8 ± 1.3 μm2 compared to the left atrial appendage sections, 2.6 ± 3 μm2, P = 0.02. We show that glycogen is heterogeneously distributed in both atria in the normal goat heart; however, the density of glycogen deposits concentrating against the intercalated discs and side to side connections in the left atrial appendage is a critically distinct difference. Impediment of cell to cell conduction could result in a non-uniform wavefront of activation, with areas of slowed conduction, predisposing the left atrium to reentrant based atrial fibrillation. Conclusion: These findings provide a basis for the well-known greater propensity for atrial fibrillation in the left versus the right atrium.

An endocrine hypothesis for the genesis of atrial fibrillation: The hypothalamic-pituitary-adrenal axis response to stress and glycogen accumulation in atrial tissues

Background: The underlying role of intracellular glycogen in atrial fibrillation is unknown. Experimental models developed in the goat have shown an increase of intracellular glycogen concentration in atrial myocytes resulting from prolonged pacing induced atrial fibrillation (AF). These observed glycogen molecules are as a result of structural remodeling and are known to replace the intracellular myofibrils causing myolysis in studies done in different animal models. The accumulation of glycogen is progressively and directly related to the duration of pacing-induced AF. Similar responses have been seen in clinically derived atrial tissues. Aims: We intend to present an endocrine hypothesis supported by published evidence that stress acting through the hypothalamic-pituitary-adrenal axis (HPA) is a contributing metabolic factor responsible for the increase of glucose levels via the hormone cortisol. This excess glucose is then metabolized by the myocytes during each heart beat and stored as glycogen. A literature search was done, and published evidence supporting stress was shown to be the main factor for the formation of glucose leading to glycogen deposition to in the cardiac myocytes. Results: Stress on the HPA axis stimulates the adrenal glands to release the hormone cortisol in the blood stream; this in turn increases the cardiac tissue glycogen concentration. It is also known that during each beat, excess glucose is removed by the myocytes and stored as glycogen. As aforementioned, in the cardiac myocytes, dense glycogen content with/without loss of myofibrils has been detected in both human and animal models of AF. Conclusions: We hypothesize that the increase of the intrinsic glycogen concentration and distribution is a result of a metabolic disruption caused by stress through the HPA Axis. For example, in atrial myocytes, the glycogen molecules impede the normal intercellular communications leading to areas of slow conduction favoring reentrant-based AF.

Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells

BackgroundIn malignant melanoma, it has been published that up to 40% of cancer patients will suffer from brain metastasis. The prognosis for these patients is poor, with a life expectancy of 4 to 6 months. Calcium exchange is involved in numerous cell functions. Recently, three types of cellular calcium sequestration have been reported in the medical literature. The first describes a transgenic mouse model in which an increase of aberrant calcium channels triggers hypertrophy and apoptosis. The second provides a protective mechanism whereby astrocytes in the brain inhibit apoptosis of tumor cells by moving ionic calcium out of the tumor cells thru gap junctions. The third is via calcium chelation, which causes cell apoptosis by converting ionic calcium into a calcium salt. This process has been shown to operate in atrial myocardial cells, thus not allowing the intracellular calcium stores to flow through the myocytes intercalated discs. Ideally chemotherapeutic agents would be those that initiate apoptosis in tumor cells.Presentation of the HypothesisWe hypothesize that the recent reported intracellular calcium sequestration by oxalate chelation, due to its chemical process of converting ionic calcium into a calcium salt, may inhibit the protective effect of astrocytes on brain tumor metastasized melanoma cells by not allowing free calcium to leave the metastatic cells, simultaneously apoptosis of tumor and some healthy adjacent cells could occur. This hypothesis could be extended to include other cancerous tumors such as skin cancers amongst others.Testing the hypothesisUsing the experimental model showing the protective mechanism of co-cultured reactive astrocytes and tumor cells treated with oxalates could be used to test this hypothesis in vitro. The calcium specific von Kossa technique could be used to confirm the presence of chelated intracellular calcium architecture of the metastatic cells (which is a sign of apoptosis), and extracellular calcium chelation stores of the Astrocytes (which has been shown to slow neural conduction).Implications of the HypothesisThe life expectancy in patients with metastasized malignant melanoma brain tumors could be significantly prolonged if the chemotherapeutic issue of brain metastasis is overcome. Other cancerous tumors can also be treated by this Targeted Chelation Approach. Ionic calcium sequestration using naturally occurring calcium chelators, viz., oxalates, could accomplish this desired outcome.

In vivo technique for cellular calcium waves documentation: A light microscopy method

Background: We are introducing a novel in vivo technique to document cellular calcium deposits, which reflect a snapshot of the effect of calcium wave propagation. This technique however is not advocated enough to replace the accuracy and resolution of the confocal laser technique. Light microscopy equipment, calcium chelators and a histological calcium staining kit are essential. Aims: The purpose of this study is to introduce the use of standard light microscopy to display in vivo ionic cellular calcium deposits. Materials and Methods: Oxalic Acid (OA) (100 millimol) was the calcium chelator used in the study. This substance was injected into the dog right atrial tissue in vivo in an area of 1 cm2. Samples were fixed and stained by the calcium specific von Kossa protocol. Results and Conclusions: Histological slides demarcated the intracellular calcium as black dots. Heterogeneity of calcium deposits mimicked images of both, the calcium sparks and calcium waves theories. This light microscopy technique could expand the number of experimental studies in the function of cellular calcium physiology.

Endogenous electromagnetic forces emissions during cell respiration as additional factor in cancer origin.

BackgroundSeven decades ago, a seminal paper by Dr. Denham Harman in (J Gerontol 11(3):298–300, 1956), introduced a theory stating that there are good reasons for assuming that endogenous irradiation in the living cells could lead to cancer via an obscure mechanism. The main purpose of this manuscript is to shed some light in said mechanism by proposing a five-step eukaryotic cell cancer triggering cycle. In other words, a new factor is introduced, namely the recently found emissions of electromagnetic forces (EMFs) as a possible causing agent in diseases, including cancer.MethodsIntroduced is an eukaryotic cell cancer inducing cycle. It includes five sequential steps of endogenous biological process that are backed by published scientific reports.Results and DiscussionIt is a known fact that in order to achieve homeostasis, toxic reactive oxygen species (ROS) i.e. H2O2 molecules are broken down by the protein enzyme catalase. During this reaction EMFs are generated (Embi in AIS Physics 2(3):226–230, 2016). The EMFs recording breakthrough was possible due to the introduction of a novel table top microscopy technique to detect EMFs by using Prussian Blue Stain and nano-sized iron particles. There are different roots in molecular and clinical biology through which DNA damage could be programmed, EMFs emitted (during cell respiration) are herein proposed as an additional cause.