Excessive Action Research Articles

Criterion Technical Efficiency of Line Distance Relay Protection

The estimation technical efficiency of functioning of relay protection as differences potentially possible effect in the form of an index of faults on protected object and losses (refusals of work, false and excessive actions) are carried to potential effect is an actual problem for designing and operation relay protection of electric equipment and electric networks. Distance relay protections have some special features compared with the current relay protections and the criterion technical efficiency is an objective indicator quality of functioning distance relay protection. Therefore base on its extremum is possible to define the optimum values of interest of practical problems, in particular the optimal settings of distance relay protection.

The influence of angiotensin-(1–7) Mas receptor agonist (AVE 0991) on mitochondrial proteome in kidneys of apoE knockout mice

Excessive action of angiotensin II on mitochondria has been shown to play an important role in mitochondrial dysfunction, a common feature of atherogenesis and kidney injury. Angiotensin-(1–7)/Mas receptor axis constitutes a countermeasure to the detrimental effects of angiotensin II on AT1 receptors. The aim of the study was to assess the effects of angiotensin-(1–7) peptidomimetic AVE0991 on the kidney mitochondrial proteome in widely used animal model of atherosclerosis (apoE−/− mice). Proteins changed in apoE−/− mice belonged to the groups of antioxidant enzymes, apoptosis regulators, inflammatory factors and metabolic enzymes. Importantly, AVE0991 partially reversed atherosclerosis-related changes in apoE−/− mice.

Focal Adhesion Kinase: A Key Mediator of Transforming Growth Factor Beta Signaling in Fibroblasts

There is no effective drug therapy for scarring and fibrotic disease. The cytokine transforming growth factor beta (TGF-β) promotes tissue repair, but its excessive action can lead to over exuberant scarring and fibrotic disease. However, owing to the multifunctional nature of TGF-β, broad targeting of the canonical Smad-TGF-β signaling pathway in vivo is likely to have unintended, deleterious consequences. (1) The myofibroblast is the essential cell type that mediates tissue repair and fibrosis. (2) TGF-β is an essential contributor to myofibroblast differentiation and activity. (3) TGF-β selectively promotes tissue repair and fibrosis via the noncanonical focal adhesion kinase (FAK) pathway; FAK mediates myofibroblast differentiation, and hence may represent a novel intervention point for drugs treating fibrotic disease. Excessive scarring (e.g., in hypertrophic scars, keloids, and scleroderma) is characterized by enhanced TGF-β signaling and is a major clinical problem. Drugs that selectively and effectively control the profibrotic action of TGF-β is therefore of clinical relevance. FAK inhibition may represent a novel therapy for scarring disorders.

Hirsutism in a Female Adolescent Induced by Long-Acting Injectable Risperidone

Hirsutism in a Female Adolescent Induced by Long-Acting Injectable Risperidone

Occupy Theology: Hyperbolic Christianity and American Culture

Two competing and often contradictory hyperboles appear to exist in harmony. On the one hand is the extravagant call of Christianity to love the “other” in excess, to forgive without limit, and to offer as well as to accept exorbitant grace. On the other hand are societal and economic systems that advocate loving the “self” in excess, consuming without reserve, and taking what is given freely with no thought of reciprocity. The problem, then, is that the message of Christianity often directly opposes this more economic, materialistic way of viewing the world. This essay primarily approaches these issues of religion and economy from a rhetorical perspective to reveal instances when Christianity and a consumeristic culture driven by economic interests and materialistic desires interact in often-unnoticed ways. Specifically, it will re-define hyperbole and will argue that competing hyperboles in public discourse can be equally oppressive and transformative. Overall, a hyper-consumerist American culture constantly uses exaggerated claims and promises in order to sell various products, which may seem harmless enough, but what is troubling is that traditional religious practices and expressions such as “spirituality” are also being turned into products for mass consumption in the marketplace. They are being “occupied,” re-branded, re-packaged, and stripped of their ethical religious underpinnings. However, Christianity itself is equally extravagant and excessive in its own claims about love, grace, redemption, and forgiveness. Through these excessive claims and actions one can resist, disrupt, and transform the “occupation,” or re-branding and selling, of Christian practices and expressions as products. By engaging in a perpetual critique of society as well as a critique of its own doctrines and expressions, one can participate in a more radical form of Christianity.

Fibroblast Growth Factor 23 and Klotho Are Present in the Growth Plate

Introduction: Regulation of phosphate homeostasis is essential for mineralization and enchondral ossification. Fibroblast growth factor 23 (FGF23) and its obligatory co-receptor Klotho (KL) play a key role in this process by influencing both renal phosphate reabsorption and vitamin D metabolism. In disease, excessive action of FGF23 leads to hypophosphatemic rickets, while its deficiency causes tumoral calcinosis. Although osteocytes and osteoblasts are widely seen as the primary source of FGF23 under physiological conditions, the origin of systemic FGF23 remains controversial. In this study, we investigated the expression of FGF23 and KL in porcine growth plate cartilage, adjacent tissues, and parenchymal tissues.Materials and Methods: Tissue samples were obtained from 4- to 6-week-old piglets. mRNA expression was quantified by real-time PCR and normalized to 18S rRNA. Immunohistochemical staining was performed for FGF23, KL, collagen type X, and FGF receptor 1. Growth plate chondrocyte subpopulations were acquired by collagenase digestion of growth plate explants and subsequent density gradient centrifugation.Results: We could detect both FGF23 and KL mRNA and protein in growth plate chondrocytes. FGF23 expression was mainly found in hypertrophic and resting chondrocytes. Furthermore, significant expression of both genes was observed in bone, liver, and spleen.Conclusion: These data challenge previous expression analyses, in particular theories of bone as the exclusive source of FGF23. Moreover, significant expression of FGF23 and KL within the growth plate and adjacent tissues imply a potential local role of FGF23 in chondrocyte differentiation and tissue mineralization.

Atomic Force Microscopy reveals Diversity of Serpin Polymers

Polymerization of a mutated form of antitrypsin is postulated to cause serpinopathy, a rare and incurable genetic disease. Antitrypsin is the canonical member of the serpin superfamily of structurally homologous proteins with metastable native structures. Most of serpins, including antitrypsin, are regulators of serine and cysteine protease cascades, and protect tissues from excessive actions of extracellular proteolytic enzymes. Polymerization of the mutant Z variant of antitrypsin results in the “loss of function” proteolytic damage of lungs, or in the “gain of function” degeneration of liver cells, loaded with toxic polymers. The understanding of polymerization mechanism holds the key to disease prevention, diagnostics and cures. However, metastability of serpins and complexity of their polymers makes structural studies a difficult task. There are several models of polymerization, based on in vitro studies and molecular modeling, however their relevance to in vivo polymerization and disease etiology has not been established. Here we employed atomic force microscopy (AFM) to compare topography of in vitro and in vivo formed antitrypsin polymers and oligomers. We found that commonly used in vitro methods to induce polymerization result in formation of topographically a very diverse population of oligomers. Most, if not all classes of the in vitro formed oligomers corresponded to similar classes of oligomers isolated from liver. The in vitro polymerization, however did not produce long strands of polymerized antitrypsin. The presence of such strands is the most striking feature in liver cells of human serpinopathy patients and in a mouse model. Here, we report results of our scanning probe microscopy structural analysis of long serpin polymers and propose the mechanism of their formation.

Excessive Self-Defence: Third-Party Problems

Excessive self-defense presupposes the existence of a 'self-defense situation': there must objectively have been a situation in which self-defense would have been available. If in such a situation the limits of the necessary defense are exceeded, for example, because the defense reaction was disproportionate, the defendant may nevertheless be excused as long as his actions comply with the requirement of double causation. The excessive action must be directly caused by a 'strong emotion' that was in turn caused by the attack. In this case, the Supreme Court (Netherlands) for the first time has given a ruling on the question whether a defense of excessive self-defense is possible in a situation in which violence was used on a third person, rather than on the person who had attacked the defendant. In more general terms, the Supreme Court set out that a defense of excessive self-defense could not be conceptually denied a priori in cases where the attack had not come directly from the victim, for example, in situations where the defendant did have 'a part' in the attack or in the imminent threat of an attack, or if there were 'other acts' by the victim, of which it could reasonably be said that they caused the person attacked to retaliate against the victim. The defendant's appeal, however, was dismissed, because the Supreme Court ruled that the Court of Appeal had not found that the victim had acted violently towards the defendant, and that an involvement of the victim in the attack had not been stated by the defendant. Furthermore, it had not been shown by the defendant that there had been other acts that might excuse her on the ground of excessive self-defense.

Significance of FGF23 measurement

Excess and deficient actions of FGF23 cause hypophosphatemic rickets/osteomalacia and hyperphosphatemic tumoral calcinosis, respectively. There are two kinds of assays for FGF23. Full-length assay detects only full-length FGF23 with biological activity. In contrast, C-terminal assay measures both full-length FGF23 and processed C-terminal fragment of FGF23. FGF23 measurement is useful for the diagnosis and follow-up of patients with FGF23-related hypophosphatemic diseases. In addition, full-length assay can be used for the differential diagnosis of hypophosphatemic diseases. Furthermore, many epidemiological studies indicated the association between FGF23 levels and several adverse events including higher mortality, cardiovascular diseases and progression of CKD especially in patients with CKD. Therefore, it is possible that FGF23 can be a new marker in the risk assessment of patients with CKD.

Consequences of Essential Fatty Acids

Essential fatty acids (EFA) are nutrients that form an amazingly large array of bioactive mediators that act on a large family of selective receptors. Nearly every cell and tissue in the human body expresses at least one of these receptors, allowing EFA-based signaling to influence nearly every aspect of human physiology. In this way, the health consequences of specific gene-environment interactions with these nutrients are more extensive than often recognized. The metabolic transformations have similar competitive dynamics for the n-3 and n-6 homologs when converting dietary EFA from the external environment of foods into the highly unsaturated fatty acid (HUFA) esters that accumulate in the internal environment of cells and tissues. In contrast, the formation and action of bioactive mediators during tissue responses to stimuli tend to selectively create more intense consequences for n-6 than n-3 homologs. Both n-3 and n-6 nutrients have beneficial actions, but many common health disorders are undesired consequences of excessive actions of tissue n-6 HUFA which are preventable. This review considers the possibility of preventing imbalances in dietary n-3 and n-6 nutrients with informed voluntary food choices. That action may prevent the unintended consequences that come from eating imbalanced diets which support excessive chronic actions of n-6 mediators that harm human health. The consequences from preventing n-3 and n-6 nutrient imbalances on a nationwide scale may be very large, and they need careful evaluation and implementation to avoid further harmful consequences for the national economy.

Hiperaldosteronismo primario y secundario

Primary aldosteronism is the most common cause of secondary hypertension with and stimated prevalence ranging from 5 to 10% of all hypertensive patients. This entity presents with hypertension, in a minority of cases hypokalemia, and an increased risk of cardiovascular damage due to aldosterone excess. The diagnosis is made following a three-step approach: case-detection accomplished by measuring an ambulatory random plasmatic aldosterone concentration- renin activity ratio on standard testing conditions, aldosterone confirmatory supression testing, and then, an initial subtype classification by means of an adrenal imaging test (CT) to exclude potential malignant lesions. Unilateral laparoscopic adrenalectomy and mineralocorticoid receptor antagonist drugs are the choice treatment for patients with unilateral and bilateral disease, respectively. Other entities presenting with mineralocorticoid excess action but low aldosterone plasmatic concentration are apparent mineralocorticoid excess syndrome, primary cortisol resistance, Liddle's syndrome, deoxycorticosterone-producing tumors, certain types of congenital adrenal hyperplasia and hypertension exacerbated by pregnancy.

What's new in FGF23 research?

FGF23 is a hormone that regulates phosphate and vitamin D metabolism by binding to Klotho-fibroblast growth factor (FGF) receptor complex. Excess actions of FGF23 cause several kinds of hypophosphatemic diseases. The mechanism of overproduction of FGF23 in some of these diseases is becoming clear, whereas it is not yet completely understood. Several specific methods to inhibit FGF23 actions have been reported as candidates for new therapies for these FGF23-related hypophosphatemic diseases. On the other hand, many epidemiological studies indicated the association between high FGF23 levels and several adverse events in cardiovascular system, kidney, bone and mortality. FGF23 was recently shown to induce ventricular hypertrophy in a Klotho-independent manner. However, it is not yet shown whether this Klotho-independent action of FGF23 can explain all the results of epidemiological studies.

Metformin: Midlife maturity, maiden charm

Metformin is one of the most commonly prescribed drugs for management of Type 2 diabetes mellitus. It has been in use for almost five decades. Now, pharmacological properties of this agent are being exapted for use in a number of other indications. New facets of its personality are coming up, generating more interest of the scientific community in this “middle-aged” molecule. This article explores the role of metformin in cardioprotection and its hepatoprotective properties. Nephroprotective, protection against excess body fat and gonadoprotective actions, properties have also been discussed. Additionally, this manuscript briefly reviews the thyroid stimulating hormone (TSH)-lowering properties in diabetic and non-diabetic patients, besides reviewing its actions on different types of cancers. Some of these actions may become approved indications for use of metformin following generation of new evidence. Metformin still has many unexplored dimensions that deserve further exploration.

The Diversity of Mechanisms of Blockade of Ion Channels as a Pathway to the Design of New Pharmacological Agents

Impairments to glutamatergic synaptic transmission are seen in many pathological CNS states. Excess glutamate actions, inducing persistent depolarization of neurons and massive calcium influx, can lead to cell death. Despite the obvious importance of developing antiglutamate agents as neuroprotectors, the only one of the ionotropic glutamate receptor antagonists which has been introduced into practice is memantine. One of the causes of the multiple side effects occurring when glutamate receptor antagonists are used is that these pharmacological agents inhibit the whole of the receptor pool, both those receptors involved in pathological processes and those performing normal physiological functions. One possible approach to overcoming this problem consists of developing pharmacological agents whose actions are enhanced in potential pathological states, such as high-frequency stimulation of receptors, high glutamate concentrations, decreases in neuron membrane potential, etc. The efficacies of many types of antagonists, such as channel blockers, depends on the membrane potential and the nature of receptor activation. The present article provides a discussion of some of the characteristics of the mechanisms of blockade of glutamate receptor ion channels from the point of view of the potential to create neuroprotective agents. In particular, blockers with different interactions with channel gate structures and different types of blockade voltage dependence are compared, with analysis of the characteristics of the actions of blockers able to penetrate channels to enter cells. We suggest that only detailed study of the mechanisms of action of antagonists on glutamate receptors can bring us towards the ability to predict the results of using blockers in vivo on the basis of data obtained in vitro.

Fibroblast growth factor 23 as a phosphotropic hormone and beyond

Fibroblast growth factor 23 (FGF23) is produced by bone and reduces serum phosphate by inhibiting proximal tubular phosphate reabsorption and intestinal phosphate absorption. Excess actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia while deficient actions of FGF23 result in hyperphosphatemic tumoral calcinosis. In addition, FGF23 has been shown to prevent the development of hyperphosphatemia during the progression of chronic kidney disease-mineral and bone disorder. Epidemiological studies have indicated that high FGF23 levels are associated with unfavorable events including higher mortality, cardiovascular events, progression of CKD and fracture; however, these associations are not observed unequivocally and it is not evident why they are present. While FGF23 has been shown to be a hormone that regulates phosphate metabolism, it remains to be established whether FGF23 has roles other than regulating mineral homeostasis.

Transformations of dialkyl(4-hydroxy-2-butynyl)-(3-phenylallyl)ammonium bromides in an KOH aqueous solution or in the presence of powdered KOH

Under the action of a twofold excess of KOH and heating in aqueous solution, and also under the conditions of the Stevens rearrangement (with KOH powder and a small amount of methanol) dialkyl-(4-hydroxy-2-butynyl)(3-phenylallyl)ammonium bromides form dialkyl[4-(1-phenylallyl)-2,5-dihydro-2-furyl]amines. Rearrangement–cleavage reaction also occurs under the same conditions.

Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms representing <5% of all pancreatic malignancies with an estimated incidence of 1–1.5 cases/100,000. PNETs are broadly classified as either functional or nonfunctional. Functional PNETs include insulinomas, gastrinomas, vasoactive intestinal peptideomas, glucagonomas, and somatostatinomas. The clinical manifestations associated with these tumors are the result of excessive hormonal secretion and action. The functional nature of these tumors makes pancreatic hormone testing critical not only for initial diagnosis but also for follow-up, because they are important tumor markers. Nonfunctional PNETs typically remain clinically silent until a substantial mass effect occurs. Although the majority of PNETs occur sporadically, it is important to recognize that these tumors may be associated with a variety of familial syndromes and in many cases genetic testing of PNET patients is warranted. This article familiarizes the reader with the clinical presentation and the biochemical, radiologic, and genetic testing indicated for diagnosis and follow-up of patients with PNET.

NEW ANTIPLATELET DRUGS (PART 1)

Antiplatelet agents are a necessary component of modern atherosclerosis therapy. The difficulties of antiplatelet treatment lie in the balance between the necessary therapeutic effect of the drug and the risk of excessive action leading to the bleeding. Possibility to control pharmacodynamics effects of antiplatelet agents is still very limited. Pharmacology of antiplatelet drugs is growing rapidly. Some of new antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor, elinogrel, inhibitors of thromboxane and thrombin receptors. Clinical pharmacology of these drugs is different. This requires a doctor's good knowledge of their identity to avoid the development of iatrogenic complications.

NEW ANTIPLATELET DRUGS. PART 2

Antiplatelet agents are a necessary component of modern therapy of atherosclerosis. The difficulties of the antiplatelet treatment lie in balance between the necessary therapeutic effect and the risk of excessive action, leads to the bleeding. The ability to monitor antiplatelet pharmacodynamics is still very limited. Pharmacology of antiplatelet drug has been developing rapidly. New antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor , elinogrel, thromboxane receptor inhibitors, thrombin receptors inhibitors. Clinical pharmacology of these drugs is different. Practitioner should know their specifics to avoid the development of iatrogenic complications.

Experimental hyperthyroidism treated with acupuncture ‐ metabolomic evaluation of Wistar rats' livers

Hyperthyroidism can be defined as the consequence of production and excessive action of the thyroid hormones. Acupuncture as been proven effective in the treatment of some pathologies, with minimum side effects.Twenty‐one male Wistar rats were divided into 3 groups: group I – control with no manipulation (Ctrl); group II – received levothyroxine (HT); group III ‐ received levothyroxine and acupuncture (HT+AC). Liver samples were snap frozen in liquid nitrogen and later analyzed by high rotation magic angle NMR spectroscopy (HRMAS) in a in a 14.1 Tesla Varian spectrometer. HRMAS spectral analysis followed by principal component statistical analysis demonstrated that lipids were significantly reduced in the HT group and increased in the HT+AC, the same happening with the aminoacids aspartate and glutamate. Glucose, as well as glycogen were significantly increased in both HT and HT+AC groups.The results suggest that HT reduces hepatic lipid contents, either by increased mobilization or reduced de novo lipogenesis, and that such reduction is reversed by AC treatment. The increase in glucose content is compatible with either an increase in glycogen breakdown or an increase in gluconeogenesis. Our results show an increase in glycogen content in both HT and HT+AC groups thus supporting the later. Accurate evaluation of lipogenesis and glucose turnover is currently underway using the 2H2O method.