2,351 research outputs found
Purity and impurity in nondualistic Ćaiva Tantrism
Indian civilisation has been strongly characterised by the work of containment erected by the Brahmanical elite over the almost two thousand years of its grandiose attempt at culturally and so- cially dominating the Indian world as a whole. Lacking any direct power, the Brahmans have re- placed it by successfully imposing, as an alternative, an opposition between purity and impurity that has marked every aspect of Indian culture: purity of spirit, purity of philosophy, purity of rites, purity of language, purity of social and religious conduct, etc. Nondualistic SÌaiva Tantrismâs re- sponse starts by questioning the legitimacy and very basis of the division between pure and impure, destined to crumble progressively beneath the thrust of deliberate ânon-dualâ behaviour (advaitaÌcaÌra). Purity or impurity are not properties of things. They are quali cations pertaining to the knower depending on whether he perceives the object as united with consciousness or not. âImpure is what has fallen away from consciousness: therefore everything is pure if it has achieved identity with consciousness.â Moreover, if SÌiva âisâ the universe, there may be no impu- rity. In the Tantric texts special emphasis is laid on the necessity to overcome sÌanÌkaÌ (âhesitation, inhibitionâ), viewed as the ultimate purpose of the Brahmanical rules concerning purity/impurity, acting as a subtle and effective instrumentum regni
Novel perspectives in redox biology and pathophysiology of failing myocytes: modulation of the intramyocardial redox milieu for therapeutic interventions - A review article from the Working Group of Cardiac Cell Biology, Italian Society of Cardiology
The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, and economic costs, in spite of
huge efforts in understanding pathogeneticmechanisms and in developing effective therapies that have transformed this syndrome
into a chronic disease. Myocardial redox imbalance is a hallmark of this syndrome, since excessive reactive oxygen and nitrogen
species can behave as signaling molecules in the pathogenesis of hypertrophy and heart failure, leading to dysregulation of cellular
calcium handling, of the contractile machinery, of myocardial energetics and metabolism, and of extracellular matrix deposition.
Recently, following new interesting advances in understanding myocardial ROS and RNS signaling pathways, new promising
therapeutical approaches with antioxidant properties are being developed, keeping in mind that scavenging ROS and RNS tout
court is detrimental as well, since these molecules also play a role in physiological myocardial homeostasis
Adult cardiac stem cell aging: A reversible stochastic phenomenon?
Aging is by far the dominant risk factor for the development of cardiovascular diseases, whose prevalence dramatically increases with increasing age reaching epidemic proportions. In the elderly, pathologic cellular and molecular changes in cardiac tissue homeostasis and response to injury result in progressive deteriorations in the structure and function of the heart. Although the phenotypes of cardiac aging have been the subject of intense study, the recent discovery that cardiac homeostasis during mammalian lifespan is maintained and regulated by regenerative events associated with endogenous cardiac stem cell (CSC) activation has produced a crucial reconsideration of the biology of the adult and aged mammalian myocardium. The classical notion of the adult heart as a static organ, in terms of cell turnover and renewal, has now been replaced by a dynamic model in which cardiac cells continuously die and are then replaced by CSC progeny differentiation. However, CSCs are not immortal. They undergo cellular senescence characterized by increased ROS production and oxidative stress and loss of telomere/telomerase integrity in response to a variety of physiological and pathological demands with aging. Nevertheless, the old myocardium preserves an endogenous functionally competent CSC cohort which appears to be resistant to the senescent phenotype occurring with aging. The latter envisions the phenomenon of CSC ageing as a result of a stochastic and therefore reversible cell autonomous process. However, CSC aging could be a programmed cell cycle-dependent process, which affects all or most of the endogenous CSC population. The latter would infer that the loss of CSC regenerative capacity with aging is an inevitable phenomenon that cannot be rescued by stimulating their growth, which would only speed their progressive exhaustion. The resolution of these two biological views will be crucial to design and develop effective CSC-based interventions to counteract cardiac aging not only improving health span of the elderly but also extending lifespan by delaying cardiovascular disease-related deaths
Optimal Drug Synergy in Antimicrobial Treatments
The rapid proliferation of antibiotic-resistant pathogens has spurred the use of drug combinations to maintain clinical efficacy and combat the evolution of resistance. Drug pairs can interact synergistically or antagonistically, yielding inhibitory effects larger or smaller than expected from the drugs' individual potencies. Clinical strategies often favor synergistic interactions because they maximize the rate at which the infection is cleared from an individual, but it is unclear how such interactions affect the evolution of multi-drug resistance. We used a mathematical model of in vivo infection dynamics to determine the optimal treatment strategy for preventing the evolution of multi-drug resistance. We found that synergy has two conflicting effects: it clears the infection faster and thereby decreases the time during which resistant mutants can arise, but increases the selective advantage of these mutants over wild-type cells. When competition for resources is weak, the former effect is dominant and greater synergy more effectively prevents multi-drug resistance. However, under conditions of strong resource competition, a tradeoff emerges in which greater synergy increases the rate of infection clearance, but also increases the risk of multi-drug resistance. This tradeoff breaks down at a critical level of drug interaction, above which greater synergy has no effect on infection clearance, but still increases the risk of multi-drug resistance. These results suggest that the optimal strategy for suppressing multi-drug resistance is not always to maximize synergy, and that in some cases drug antagonism, despite its weaker efficacy, may better suppress the evolution of multi-drug resistance.Molecular and Cellular Biolog
Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy
It is generally believed that increase in adult contractile cardiac mass can be accomplished only by hypertrophy of existing myocytes. Documentation of myocardial regeneration in acute stress has challenged this dogma and led to the proposition that myocyte renewal is fundamental to cardiac homeostasis. Here we report that in human aortic stenosis, increased cardiac mass results from a combination of myocyte hypertrophy and hyperplasia. Intense new myocyte formation results from the differentiation of stem-like cells committed to the myocyte lineage. These cells express stem cell markers and telomerase. Their number increased >13-fold in aortic stenosis. The finding of cell clusters with stem cells making the transition to cardiogenic and myocyte precursors, as well as very primitive myocytes that turn into terminally differentiated myocytes, provides a link between cardiac stem cells and myocyte differentiation. Growth and differentiation of these primitive cells was markedly enhanced in hypertrophy, consistent with activation of a restricted number of stem cells that, through symmetrical cell division, generate asynchronously differentiating progeny. These clusters strongly support the existence of cardiac stem cells that amplify and commit to the myocyte lineage in response to increased workload. Their presence is consistent with the notion that myocyte hyperplasia significantly contributes to cardiac hypertrophy and accounts for the subpopulation of cycling myocytes
Observations on surveillance imaging after endovascular sealing of abdominal aortic aneurysms with the Nellix system
Purpose: To describe and interpret the findings of computed tomography images acquired before and after endovascular aneurysm sealing (EVAS) with the Nellix endoprosthesis and consider the potential implications of these findings on EVAS planning and performance. Methods: A retrospective review was performed of perioperative imaging from 30 consecutive patients (median age 79 years; 19 men) undergoing elective EVAS at our center between December 2013 and November 2014. The images were systematically reviewed specifically looking for endobag collapse, aortic thrombus compression, and aortic wall disruption according to definitions set a priori. Results: There was no perioperative mortality or endoleak after the EVAS procedure. Endobag collapse, which could potentially result in type II endoleak if occurring near a patent side branch, was seen in the endobags of 12 patients. Aortic thrombus compression, which affects the accuracy of preoperative volume measurements in predicting the amount of polymer needed to perform EVAS, was seen in 15 patients. There was one aortic wall disruption, which could potentially result in intraoperative hemorrhage, though this did not occur in this case. Conclusion: These observations and their potential implications should help clinicians in planning and performing EVAS, as well as in interpreting postoperative imaging
Relating GPCRs pharmacological space based on ligands chemical similarities
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Mediterranean jellyfish sting-induced Tako-Tsubo cardiomyopathy.
We report a case of a 53-year-old woman swimming in the southern Mediterranean Sea on the Calabrian coast that was suddenly stung on her right forearm by a mauve-pink jellyfish. She got extremely scared and while swimming back to the shore, she accused fatigue and an intense itch sensation. She lost consciousness on the beach as a consequence of a condition of pulseless electrical activity
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