The Initial Common Pathway of Inflammation, Disease, and Sudden Death

In reviewing the literature pertaining to interfacial water, colloidal stability, and cell membrane function, we are led to propose that a cascade of events that begins with acute exogenous surfactant-induced interfacial water stress can explain the etiology of sudden death syndrome (SDS), as well as many other diseases associated with modern times. A systemic lowering of serum zeta potential mediated by exogenous cationic surfactant administration is the common underlying pathophysiology. The cascade leads to subsequent inflammation, serum sickness, thrombohemorrhagic phenomena, colloidal instability, and ultimately even death. We propose that a sufficient precondition for sudden death is lowered bioavailability of certain endogenous sterol sulfates, sulfated glycolipids, and sulfated glycosaminoglycans, which are essential in maintaining biological equipose, energy metabolism, membrane function, and thermodynamic stability in living organisms. Our literature review provides the basis for the presentation of a novel hypothesis as to the origin of endogenous bio-sulfates which involves energy transduction from sunlight. Our hypothesis is amply supported by a growing body of data showing that parenteral administration of substances that lower serum zeta potential results in kosmotropic cationic and/or chaotropic anionic interfacial water stress, and the resulting cascade

The role of statin drugs in combating cardiovascular diseases –A review

Statins clearly confer substantial benefit in people with established cardiovascular (CV) disease. Increased cholesterol levels have been associated with cardiovascular diseases (CVD), and statins are therefore used in the prevention of these diseases. Studies have found that the ability of a particular statin to lower or reduce LDL is proportional to the amount it can increase HDL levels. This review article will focus on the effective role of statin in cardiovascular disease and comparison was made between various classes of statin drugs

Peripartum cardiomyopathy: an update

Purpose of Review Peripartum cardiomyopathy (PPCM) is an idiopathic disorder defined as heart failure occurring in women during the last month of pregnancy and up to 5 months postpartum. In this review, we outline recent reports about the disease pathogenesis and management and highlight the use of diagnosis and prognosis biomarkers. Recent Findings Novel data strengthen the implication of endothelial function in PPCM pathogenesis. The first international registry showed that patient presentations were similar globally, with heterogeneity in patient management and outcome. Summary Despite large improvement in patient management and treatment, there is still a sub-group of women who die from PPCM or who will not recover their cardiac function. Remarkable advances in the comprehension of disease incidence, pathogenesis, and prognosis could be determined with multi-center and international registries

Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor

derived cells (CDCs) are a cardiac progenitor cell population, which have been shown to possess cardiac regenerative properties and can improve heart function in a variety of cardiac diseases. Studies in large animal models have predominantly focussed on using autologous cells for safety, however allogeneic cell banks would allow for a practical, cost-effective and efficient use in a clinical setting. The aim of this work was to determine the immunomodulatory status of these cells using CDCs and lymphocytes from 5 dogs. CDCs expressed MHC I but not MHC II molecules and in mixed lymphocyte reactions demonstrated a lack of lymphocyte proliferation in response to MHC-mismatched CDCs. Furthermore, MHC-mismatched CDCs suppressed lymphocyte proliferation and activation in response to Concanavalin A. Transwell experiments demonstrated that this was predominantly due to direct cell-cell contact in addition to soluble mediators whereby CDCs produced high levels of PGE2 under inflammatory conditions. This led to down-regulation of CD25 expression on lymphocytes via the EP4 receptor. Blocking prostaglandin synthesis restored both, proliferation and activation (measured via CD25 expression) of stimulated lymphocytes. We demonstrated for the first time in a large animal model that CDCs inhibit proliferation in allo-reactive lymphocytes and have potent immunosuppressive activity mediated via PGE2

Biomarkers of Inflammation and Fibrosis in Kawasaki Disease Patients Years After Initial Presentation With Low Ejection Fraction.

Background Coronary artery aneurysms and myocarditis are well-recognized complications of Kawasaki disease (KD) but no systematic evaluation of the consequences of myocarditis has been performed in the subset presenting with low ejection fraction (EF). We postulated that more severe myocardial inflammation as evidenced by low EF during the acute phase could lead to late myocardial fibrosis. Methods and Results We measured the carboxyterminal propeptide of procollagen type I (PIPC), soluble suppressor of tumorigenicity 2, galectin-3 (Gal-3), growth-differentiation factor-15, and calprotectin by ELISA in late convalescent blood samples from 16 KD patients who had an EF ≤55% on their initial echocardiogram. Results were compared with samples from sex- and age-matched KD patients with initial EF >60%. In the univariate analysis, the median Gal-3 and PIPC levels in the low EF group were significantly higher than those in the normal EF group (Gal-3: low EF 6.216 versus normal EF 4.976 mg/dL P=0.038, PIPC: low EF 427.4 versus normal EF 265.2 mg/dL, P=0.01). In a multivariable analysis, there were significant differences for Gal-3 and PIPC levels between the low and normal EF groups, adjusting for age, sex, and worst z score. Conclusions Convalescent KD patients with a history of low EF during the acute illness had significantly elevated levels of Gal-3 and PIPC when compared with matched-control KD patients with normal EF. These findings raise concern for myocardial fibrosis as a potential late sequela of the more severe myocarditis experienced by a subset of KD patients during the acute phase

Protein Aggregates and Polyglutamine Tracts In Neurodegenerative Disease

The incidence of neurodegenerative diseases such as Alzheimer\u27s Disease, Parkinson\u27s Disease, Huntington\u27s Disease and other Polyglutamine Diseases is projected to dramatically increase throughout the developed world, and yet the pathology of these diseases remains poorly understood. One pathway that these neurodegenerative diseases share is the accumulation of pathologic proteins which are not only harmful in their soluble form but may go on to form toxic aggregates. In many cases, a consensus has yet to be reached concerning the mechanism for protein aggregation. Therefore, the exploration of the roles of these proteins and their possible mechanisms, along with potential techniques for treatment, are more important than ever

Viral pathogens and acute lung injury: investigations inspired by the SARS epidemic and the 2009 H1N1 influenza pandemic.

Acute viral pneumonia is an important cause of acute lung injury (ALI), although not enough is known about the exact incidence of viral infection in ALI. Polymerase chain reaction-based assays, direct fluorescent antigen (DFA) assays, and viral cultures can detect viruses in samples from the human respiratory tract, but the presence of the virus does not prove it to be a pathogen, nor does it give information regarding the interaction of viruses with the host immune response and bacterial flora of the respiratory tract. The severe acute respiratory syndrome (SARS) epidemic and the 2009 H1N1 influenza pandemic provided a better understanding of how viral pathogens mediate lung injury. Although the viruses initially infect the respiratory epithelium, the relative role of epithelial damage and endothelial dysfunction has not been well defined. The inflammatory host immune response to H1N1 infection is a major contributor to lung injury. The SARS coronavirus causes lung injury and inflammation in part through actions on the nonclassical renin angiotensin pathway. The lessons learned from the pandemic outbreaks of SARS coronavirus and H1N1 capture key principles of virally mediated ALI. There are pathogen-specific pathways underlying virally mediated ALI that converge onto a common end pathway resulting in diffuse alveolar damage. In terms of therapy, lung protective ventilation is the cornerstone of supportive care. There is little evidence that corticosteroids are beneficial, and they might be harmful. Future therapeutic strategies may be targeted to specific pathogens, the pathogenetic pathways in the host immune response, or enhancing repair and regeneration of tissue damage

The role of genetics in cardiovascular disease: arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is a heritable cardiomyopathy characterized by frequent ventricular arrhythmias and progressive ventricular dysfunction. Risk of sudden cardiac death is elevated in ACM patients and can be the presenting symptom particularly in younger individuals and athletes. This review describes current understanding of the genetic architecture of ACM and molecular mechanisms of ACM pathogenesis. We consider an emerging threshold model for ACM inheritance in which multiple factors including pathogenic variants in known ACM genes, genetic modifiers, and environmental exposures, particularly exercise, are required to reach a threshold for disease expression. We also review best practices for integrating genetics—including recent discoveries—in caring for ACM families and emphasize the utility of genotype for both management of affected individuals and predictive testing in family members

Dietary effects on nontraditional risk factors for heart disease

Diet has long been known to play a key role in modifying the major risk factors for heartdisease, namely, dyslipidemia and hypertension. Numerous recent advances have suggested thatdietary components, particularly those in a traditional Mediterranean diet, may also improve nontraditional risk factors. Fish and fish n-3 fatty acids reduce the risk of cardiac arrhythmias. The monounsaturated fatty acids in olive oil may inhibit and reverse the clotting process. The phytochemicals in fruits and vegetables may reduce both inflammation and clotting. Alcohol,usually in the form of red wine, may lower inflammation and improves endothelial function. The traditional Mediterranean diet is low in processed foods containing trans fatty acids and highglycemic index ingredients which increase inflammation and raise lipoprotein (a). The combined effects of these foods has been shown to reduce significantly the risk of heart disease