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Distribution of charge in the exclusion zone and water beyond the exclusion zone as shown by electrical potential measurements and pH- sensitive dye studies. Protons spread in bulk water, although some cling to the negatively charged EZ. b Disposition of charge anticipated in a tubular configuration. (Reproduced from Rohani and Pollack, 2013 72 , with permission from the American Chemical Society. Copyright © 2013)
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Despite a vast literature, atherosclerosis and the associated ischemia/reperfusion injuries remain today in many ways a mystery. Why do atheromatous plaques make and store a supply of cholesterol and sulfate within the major arteries supplying the heart? Why are treatment programs aimed to suppress certain myocardial infarction risk factors, such a...
Citations
... 25 Reduced cholesterol sulfation is further implicated in cholesterol accumulation and may be essential in atherosclerosis. 26 DHEAS is the second most abundant steroid sulfate in human plasma 23 and reduced sulfation increases androgenic activity, as evidenced by premature adrenarche and/or PCOS in PAPSS2 deficiency. 18,27 Although the patient had an age-appropriate onset of puberty and normal sulfated androgen levels, the long-term implications for his androgen profile might be more subtle. ...
Sulfate is the fourth most abundant anion in human plasma but is not measured in clinical practice and little is known about the consequences of sulfate deficiency. Nevertheless, sulfation plays an essential role in the modulation of numerous compounds, including proteoglycans and steroids. We report the first patient with a homozygous loss‐of‐function variant in the SLC13A1 gene, encoding a renal and intestinal sulfate transporter, which is essential for maintaining plasma sulfate levels. The homozygous (Arg12Ter) variant in SLC13A1 was found by exome sequencing performed in a patient with unexplained skeletal dysplasia. The main clinical features were enlargement of joints and spondylo‐epi‐metaphyseal radiological abnormalities in early childhood, which improved with age. In addition, autistic features were noted. We found profound hyposulfatemia due to complete loss of renal sulfate reabsorption. Cholesterol sulfate was reduced. Intravenous N‐acetylcysteine administration temporarily restored plasma sulfate levels. We conclude that loss of the SLC13A1 gene leads to profound hypersulfaturia and hyposulfatemia, which is mainly associated with abnormal skeletal development, possibly predisposing to degenerative bone and joint disease. The diagnosis might be easily missed and more frequent.
... EZs would also have effects on fluid movement, since, within tubular structures, such as blood capillaries, fluids can move independently of the pressure gradient. This occurs due to a potential difference between the nucleus of the tubule and the internal surface of EZs, creating a flow that the authors call "self-driven flow" [98,99]. ...
... The negative charge provided by sulfate ions attached to glycosaminoglycans in the capillary wall generates an electromagnetic field called electrokinetic vascular streaming potential (EVSP) [96,99]. This determines not only the ease of movement of the fluid due to a buffer effect, but also a reaction of the endothelium itself, promoting the release of nitric oxide [100]. ...
... The displacement of fluids would therefore not be linked only to anatomy, as considered up to now, but could be dependent on the structure of the EZ in vessels and capillaries [96,[98][99][100]. This mechanism could also intervene at the level of the interstitium and in larger areas of the body [131] with greater freedom of fluid movement. ...
Over the years, several authors have discussed the possibility of considering somatic dysfunction (SD) as a “nosological element” detectable on palpation. There are many aspects to consider regarding the etiology and diagnosis of SD, and the literature on osteopathic issues provides details on physiological signs that characterize it, including tissue texture changes. Recent knowledge suggests that how tissue and, in particular, connective tissue, responds to osteopathic treatment may depend on the modulation of the inflammation degree. Low-grade inflammation (LGI) may act on the extracellular matrix (ECM) and on cellular elements; and these mechanisms may be mediated by biological water. With its molecules organized in structures called exclusion zones (EZ), water could explain the functioning of both healthy and injured tissues, and how they can respond to osteopathic treatment with possible EZ normalization as a result. The relationship between inflammation and DS and the mechanisms involved are described by several authors; however, this review suggests a new model relating to the characteristics of DS and to its clinical implications by linking to LGI. Tissue alterations detectable by osteopathic palpation would be mediated by body fluids and in particular by biological water which has well-defined biophysical characteristics. Research in this area is certainly still to be explored, but our suggestion seems plausible to explain many dynamics related to osteopathic treatment. We believe that this could open up a fascinating scenario of therapeutic possibilities and knowledge in the future.
... Both NO and PGI 2 inhibit platelet aggregation and NO dilates the vessel, reduces smooth muscle cell proliferation and counteracts inflammation [44,45]. NO is considered vasoprotective under physiological conditions but may induce disruption of the endothelial surface layer when production is sustained [46,47]. ...
Granulomatosis with polyangiitis is an immunologically mediated small to medium vessel vasculitis associated with the formation of antineutrophil cytoplasmic antibodies. Advances in immunosuppressive therapy have expanded patients’ life expectancy in recent decades and have required an expansion of clinical attention to include management of chronic disease manifestations and long-term comorbidities. Though the heart and coronary arteries specifically are typically not primarily affected in GPA, studies have shown that patients are at an increased risk of cardiovascular and thromboembolic events. In many patients, metabolic risk factors promoting the formation of atherosclerotic plaques are not sufficiently controlled or screened for and potentially exacerbated by undesired treatment effects. This review aims to provide clinical physicians with an overview of the current literature on epidemiology, pathophysiology and prevention of coronary artery disease in the context of granulomatosis with polyangiitis and help to identify and lower the risk of cardiovascular events in this high-risk population.
... При отсутствии единых представлений о триггерных механизмах развития, тем не менее, все теории атерогенеза признают неоспоримые морфологические признаки -образование пенистых клеток и отложение кристаллов холестерина в интиме сосуда. Поэтому, согласно утверждениям одного из последних отчетов ВОЗ (2 июня 2018), холестерин «является ключевым компонентом в развитии атеросклероза» и в сочетании с показателями уровней липопротеинов низкой плотности (ЛПНП), используется в качестве основного маркера повышенного риска развития и прогноза течения ССЗ практически во всех странах [7,10,12,14,15,17]. ...
Understanding the pathogenetic mechanism of development and identifying trigger markers of the disease will significantly increase the efficiency of pre-nosological diagnosis and medical follow-up of patients. In this case, one should take into account the role of mutations in cytokine genes, which affect their biochemical activity and production level. The objective of the study was to investigate the role of mediators of acute and chronic inflammation (IL-17A, IL-1â, TNFá and IL-4), the ratio of natural killer cell subpopulations (CD56 hi CD16 ⁻ /CD56 lo CD16 ⁺ ) in pathogenesis of coronary atherosclerosis resulting into coronary heart disease.
To analyze the results, an integrated approach was used, including molecular genetic methods such as polymerase chain reaction, typing of single-nucleotide substitutions in cytokine genes, isolation and cultivation of peripheral blood mononuclear cells, assessment of spontaneous and in vitro -induced production of immune system mediators, enzyme-linked immunosorbent assay, cytotoxic test, flow cytometry with monoclonal antibodies (Beckman Coulter, USA) to CD16, CD56 NK markers.
The study included 130 residents of the North Caucasus, including the patients (n = 62) treated at the Cardiology Department of the Adyghe Republican Clinical Hospital (ARCB) with a verified diagnosis of ischemic heart disease (IHD), and a control group (n = 68), represented by unrelated healthy donors.
Overexpression of cytokines in IHD patients was associated with distinct single nucleotide substitutions in certain genes. Studying a group of residents from the Republic of Adygeya, the authors experimentally established that harboring the 511C allele of the IL-1 â gene (p < 0.0004; OR = 4.67), A197A of the IL-17A gene genotype (p < 0.04; OR = 3.88), G308 SNP of TNF á gene (p < 0.01; OR = 3.41), and 589T variant of IL-4 gene (p < 0.04; OR = 2.45) are associated with hyperproduction of the first-wave inflammatory mediators that increase the risk of developing ischemic heart disease. In atherosclerosis and associated cardiovascular diseases, we have noted a significant decrease in spontaneous and induced activity of natural killer cells involved in the utilization of “foamy cells”. The NK activity of peripheral blood mononuclear cell in patients with coronary heart disease is significantly reduced. In the IHD patients, an imbalance of phenotypically and functionally different CD56 hi CD16 ⁻ /CD56 lo CD16 ⁺ NK subpopulations with a predominance of CD56 hi CD16 ⁻ phenotype were revealed. Conclusions: Immuno-inflammatory mechanisms of evolving coronary atherosclerosis are associated with single-nucleotide substitutions, i.e., polymorphisms in the promoter regions of the IL-17A (G197A), IL-1 â (T511C), and TNF á (G308A) , the known mediators of acute and chronic inflammation.
Genetically determined overexpression of IL-17A, IL-1â, and TNFá, confirmed in experiments on evaluation of spontaneous and stimulated cytokine production in patients with CHD, together with reduced NK activity of РВМС, due to predominance of CD56 hi CD16 ⁻ , a subpopulation with high cytokine production, manifested by an increased pro-inflammatory component that triggers and provides long-term support to pathophysiological processes of atherosclerosis.
... On the exposure of stressful conditions like high temperature or toxic substances cells start synthesis of heat shock protein or stress proteins which is esteemed as weapon in cell's armamentarium against recovery from physical and chemical insult by environment (Mahmood et al. 2014;Kumar et al. 2017). eNOS is a dual-purpose enzyme, known to produce sulfate and nitric oxide when bound to membrane or in cytoplasm respectively hypothesize to have dual damaging role when overused in high-SPF sunscreens that the overuse of sunscreen (Seneff et al., 2015). There are various environmental toxicants like mercury, arsenic, cadmium, glyphosate and lead that supposed to disrupt the activity of CYP enzymes. ...
Rapid industrialization and successful green revolution have introduced a wide array of chemicals into our environment; some of these chemicals entered in ecosystem; gets accumulated and exert serious health and ecological problems. These toxic substances can enter the food chain and emphasize pathological changes which damage either cell, organ or system (circulatory, immune, respiratory, digestive, nervous, reproductive and musculo-skeletal etc.) by altering structure and/or function of biological components; DNA, RNA, proteins, lipids and carbohydrates. This review article provides certain molecular diagnostic techniques used for their robust and accurate detection at molecular level. Investigations conducted during 2020-2021 where various review and research articles were surveyed and then extracted to enlist congestive datum for rapid detection of toxicological changes in animals. In our investigations we concluded that toxic substances present in our environment affects health of animals by altering structure and functioning of biomolecules and their concerned system. These cytological and systemic changes can be detected with the help of molecular diagnostic techniques including dideoxysequencing, pyrosequencing, allele specific RT-PCR, CRISPER/Cas, genotyping and microarrays etc. present collection of data will provide congestive information for rapid toxicological detection at molecular level.
... Hypotheses regarding the development of the disease to unstable lesion types and triggers for rupture have been formed and reformed over time, describing atherosclerosis as a multi-factorial inflammatory disease [7][8][9][10][11][12][13]. Atherosclerotic plaques are classified into different stages based on plaque composition and size with histology as a golden standard for assessment [14]. ...
Atherosclerosis is a lipid-driven and an inflammatory disease of the artery walls. The composition of atherosclerotic plaque stratifies the risk of a specific plaque to cause a cardiovascular event. In an optical resolution photoacoustic microscopy setup, of 45 µm resolution, we extracted plaque lipid photoacoustic (PA) spectral signatures of human endarterectomy samples in the range of 1150 to 1240 nm, using matrix assisted laser desorption ionization mass spectrometry imaging as a reference. We found plaque PA signals to correlate best with sphingomyelins and cholesteryl esters. PA signal spectral variations within the plaque area were compared to reference molecular patterns and absorption spectra of lipid laboratory standards. Variability in the lipid spectroscopic features extracted by principal component analysis of all samples revealed three distinct components with peaks at: 1164, 1188, 1196 and 1210 nm. This result will guide the development of PA-based atherosclerosis disease staging capitalizing on lipidomics of atherosclerotic tissue.
... Except for sphingosine and its derivatives, the amount of cholesteryl sulfate decreased significantly in the high calcium group, compared to normal calcium group. The latest study in 2015 showed that sulfate ions in the blood vessels are important for maintaining endothelial cell health and microvascular permeability (24). After the decrease of sulfate ion, the cholesterol sulfate ester was reduced, making free cholesterol unable to form the atherosclerotic plaque. ...
... After the decrease of sulfate ion, the cholesterol sulfate ester was reduced, making free cholesterol unable to form the atherosclerotic plaque. Intake of foods with high sulfate may prevent progression of atherosclerosis (24). In this study, high calcium intake significantly decreased in vivo synthesis of cholesterol sulfate, which is coincided with the latest research results. ...
Calcium supplements were necessary for those people with low calcium intake and high risk of osteoporosis. Recent cohort studies have shown that long-term calcium supplements may raise the risk of cardiovascular disease, but its mechanism is still unclear. In this study, metabonomics were employed to evaluate the changes of metabolism in rats with long-term calcium supplementation and further seek the potential markers of cardiovascular risk. SD rats were divided into two groups including normal control group (calcium intake, 0.50 g/kg bw) and high calcium supplement group (calcium intake, 2.50 g/kg bw). After 6 mo, the cardiovascular system and bone mineral density were observed. UPLC-MS was used to analyze serum metabonomics in rats. The results showed that the contents of total cholesterol and low-density lipoprotein cholesterol in the high calcium group were significantly higher than those in normal control group (p<0.05). The interventricular septum thickness (IVS), left ventricular mass (LVM), left ventricular posterior wall thickness (LVPW) in the high calcium group were higher than those in normal control group (p<0.05). Serum metabonomics analysis showed that there were persistent changes in many metabolites such as sphingosine and its derivatives (p<0.01) in the comparison between the high calcium group and the normal group. These results indicated that long term calcium supplementation can lead to dyslipidemia in rats, such as the rise of cholesterol and low-density lipoprotein, which might induce myocardial hypertrophy. Long-term calcium supplementation can cause the changes of the amount of sphingosine and its derivatives in the body, which many have potential risk to cardiovascular diseases such as myocardial hypertrophy and atherosclerosis.
... The sulfate molecules are complexed with long aminosugar chains to form various biologically interesting molecules such as heparan sulfate, chondroitin sulfate, keratan sulfate and dermatan sulfate. These chains, collectively, are called glycosaminoglycans (GAGs), and are either attached to membrane-bound proteins or attached to freefloating proteins bound to hyaluronan, a very large polysaccharide that sprawls across the extracellular matrix space and also helps to maintain the gel (Seneff et al., 2015). These sulfated amino-sugar chains are also attached to lipid molecules, such as ceramide, to form the sulfonated lipid, sulfatide (Takahashi and Suzuki, 2012). ...
... This is very dangerous because the superoxide reacts with NO to form peroxynitrite (ONOO−) a highly damaging oxidizing agent. It has been proposed that eNOS is a moonlighting enzyme (Seneff et al., 2015, Seneff et al., 2012, that synthesizes not only NO but also sulfur dioxide (SO2), and that it switches between these two under exquisite external control, mediated by the viscosity of the flowing blood (Melkumyants et al., 1989) and communicated through electromagnetic signaling. This is in fact the reason for its complex control mechanisms. ...
... In this model, eNOS synthesis of SO 2 is catalyzed by sunlight. Infrared light expands the EZ water (Chai et al., 2009), UV light mobilizes electrons within the EZ water, and flavins bound to eNOS respond to blue light by emitting electrons needed to oxidize the sulfur atom (Seneff et al., 2015, Seneff et al, 2012. Light, including infrared, provides the energy source for the formation of EZ water (Hwang et al. 2018). ...
Biological water exists in at least two distinct forms: bulk and interfacial. While the former possesses widely understood properties , little has been written about the formation , maintenance, and functional role of interfacial water in living systems. In this paper we equate interfacial water with Exclusion Zone (EZ) water described by Pol-lack and propose that it is the sulfate molecule that plays a fundamental role in providing the interfacial negative charge that builds and maintains the EZ in biological systems. We further propose novel roles for endothelial nitric oxide synthase (eNOS), erythrocytes, and cobalamin in sulfate production and ongoing regulation. Two exog-enous agents, the diabetes drug metformin and the herbicide glyphosate, and one lifestyle factor, vegetarianism/veganism, can contribute to reduced sulfate production and subsequent loss of EZ water. A set of compensatory changes in the body, often normally considered to be discrete patholo-gies, serve to reestablish adequate sulfate supply in the face of these and other detrimental impacts on sulfate production. Finally, we review additional pathologies associated with cobalamin deficiency and suggest that they, too, can be linked to the restoration of sulfate metabolism.
... Additionally, it has been demonstrated that CS is an inhibitor of gluconeogenesis in hepatocytes and play a role in sterologenesis in human Keratinocytes and Fibroblasts (Shi et al., 2014;Williams et al., 1985). CS deficiency has been proposed to be involved in the development of atherosclerosis (Seneff et al., 2015). In the brain, CS has been reported to be significantly high in the cerebellum compared to other regions, although the specific cerebellum associated role remains undefined (Ivanisevic et al., 2014). ...
Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and it is present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as an endogenous regulator of cholesterol synthesis. However, the role of CS in brain metabolism and neurological disorder is unclear. In the current study we investigated the neuroprotective action of CS as well as its role in brain energy metabolism. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte prepared from the cortex of postnatal day 0-2 C57BL/6 pups and a hippocampal HT-22 cell line using Calcein AM and MTT cell viability assay, flow cytometry, Seahorse extracellular flux analysis, and metabolism assay kits. We found that CS attenuates glutamate and rotenone induced cell death in HT-22 cells, decrease glutamate induced mitochondria membrane potential collapse, and reactive oxygen species production. Additionally, CS activates the Akt/Bcl2 pathway. We observed that CS impacts astrocyte metabolism by increasing mitochondrial phosphorylation, ATP, and glycogen contents. Our study demonstrated that CS modulates brain energy metabolism and its neuroprotective effects might be due to the activation of Akt signaling or its ability to decrease reactive oxygen species production.
... About 25% of the body's cholesterol is used in the brain and throughout the neurons of the body. 27 Cholesterol is so important to health that if you don't eat enough foods with cholesterol, the liver has evolved the ability to synthesize it. Smith-Lemli-Opitz syndrome is a genetic deficiency in cholesterol where the body cannot synthesize enough to maintain the body's needs. ...
After decades of improvement in the outlook for cardiovascular disease (CVD), we are now seeing a plateau. Statins, once believed to be the most important advance in the fight against heart disease, have not mitigated the incidence or prevalence of CVD.
Aim:
New research into lipid-lowering drugs is not only questioning their usefulness in primary care, but identifying them as harmful, resulting in the development of other diseases. When the original research is critically analyzed, the data do not reveal drugs that significantly reduce the incidence or prevalence for primary prevention of CVD in the United States.
Methods:
The current article sheds light on our current beliefs into lipid-lowering to treat potential CVD. Through a discussion of the difference between relative risk reduction and absolute risk reduction, the author suggests lifestyle modifications have been and always will be the best way to fight against this deadly chronic disease.
Results:
There is over 60 years-worth of scientific research that has been desperately trying to identify sugar as the culprit and driver of CVD disease; however, the medical system continues to fight against fat and cholesterol. This article makes the reader question what the US government, in association with the Medical Establishment (American Heart Association, American Diabetes Association and the American College of Cardiology) have been eschewing for the last 60-70 years as it has NOT been working.
Conclusion:
The time for a culture-wide paradigm change has come. The author suggests this will only happen if Big Pharma and Big Food industries will change their marketing habits from 'purely taste' to 'best for your health'.
