By W. Killian. Thomas Aquinas College, Santa Paula CA. 2018.

One of a number of environmental factors that have been proposed as a reason for the escalation in asthma prevalence is a decreasing intake of dietary antioxidants [60] cheap 1 mg prograf fast delivery. Selenium has been implicated in inflammation by reducing the severity of the inflammatory response through modulation of the pro-inflammatory leu kotrienes discount prograf 1mg with amex, important mediators of acute asthmatic reactions as well as sustaining the inflam matory process causing a late allergic reaction metabolism [62] buy 1mg prograf. Evidence from randomized controlled trials [63] and basic mechanistic work investigating the effect of selenium on markers of inflammation and oxidative stress [62]. Evidences have supported a protective role for selenium in asthma, although other studies have not [64-66]. However, there was a modest association between lower plasma selenium and whole blood glutathione peroxidase activity and higher incidence of persistent wheeze [67]. Selenium in preventing oxidative stress The reactivity of organoselenium compounds [22,68] characterized by high nucleophilicity and antioxidant potential, and provides the basis for their pharmacological activities in mammalian models. Organochalcogens have been widely studied given their antioxidant activity, which confers neuroprotection, antiulcer, and antidiabetic properties. Given the complexity of mammalian models, understanding the cellular and molecular effects of orga nochalcogens has been hampered. In reference [69] the nematode worm Caenorhabditis ele gans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging, and in vivo live analysis of toxicity. Manganese (Mn)-exposed worms exhibit oxidative-stress-induced neurodegeneration and life-span reduction. These physiological conditions could be food deprivation [70], and iodine and/or selenium (Se) deficiency [71,72] and antithyroid drugs [73] affects bone maturation. Selenium is an important protective ele ment that may be used as a dietary supplement protecting against oxidative stress, cellular damage and bone impairments [74]. Since the beginning of the pandemic in 1981, over 25 million people are estimated to have died from the disease [75]. It is currently a leading cause of death in many parts of the world, and a disease that disproportionately affects the marginalized and socially disadvantaged. There is a historical record showing that organoselenium compounds can be used as antivi ral and antibacterial agents. Selenium in the brain In addition to the well-documented functions of Se as an antioxidant and in the regulation of the thyroid and immune function [80]. Recent advances have indicated a role of Se in the maintenance of brain function [81]. Selenium is widely distributed throughout the body, but is particularly well maintained in the brain, even upon prolonged dietary Se deficiency [82]. In the brain, the highest concentration of Se is found in the gray matter, an area responsible for chemical synaptic communication [83]. It has been shown that rats on a Se-deficient diet for thirteen weeks retained Se in their brain, while their plasma Se concentrations were de pleted [84]. After intraperitoneal injection of SeO3 into Se-deficient rats, the brain rapidly75 2- sequesters a large portion of the available Se [85]. Interestingly, Se retention in the brain depends on Selenoprotein P expression [86]. Because the body preferentially allocates available Se to the brain during Se deficiency, Se may play an essential role in the brain. Se concen tration in Alzheimers brains was found to be 60% of the age-matched control individuals [88]. Accumulated lines of evidence indicate important roles of selenoproteins in the mainte nance of optimal brain functions via redox regulation. Decreased expression of several sele noproteins is associated with the pathologies of a few age-associated neurodisorders, including Parkinsons disease, Alzheimers disease and epilepsy [81]. The functions of selenium as an antioxidant trace element are believed to be carried out by selenoproteins that possess antioxidant activities and the ability to promote neuronal cell survival [89]. It is known the role of selenium in a detoxifying enzyme, glutathione peroxidase, this element has been demonstrated to have a positive biological function in various aspects of human health [90]. Oxidative stress and generation of reactive oxygen species are strongly implicated in a num ber of neurologic disorders including seizure disorders. Oxidative phosphorylation occur ring in the mitochondria produces oxygen radicals routinely in all tissues as well as the nervous system. Selenium- requiring processes are involved in normal maintenance of cell function. However, when the system is overused or chronically activated beyond its normal state, such as recurrent or intractable seizures, abnormal increases in by-products can produce neuronal cell damage. The pro posed mechanisms are mainly through the functions of seleno-dependent enzymes and sele noproteins [82,91]. It seems that selenium plays an important role in stopping the vicious cycle of oxidative stress and neuronal damage in patients with intractable seizures by restor ing the defense mechanism. Selenium and the thyroid Some selenoproteins of the human selenoproteome display multiple genes performing simi lar functions.

Many thanks to ever yone in the Biology Department at Boston College 1mg prograf overnight delivery, and especially all the current and past fri ends who have made my time here at Boston College a great experience and a fun working environment generic prograf 1 mg with mastercard. Assay for the Sectrophotometric Measurement of - 221 Hydroxybutyrate (D-3-hydroxybutyrate) D cheap prograf 1 mg. Influence of Diet Therapies on Neurodegenerative and 162 Neurological Animal Models 11. Influence of Diet on Wire Suspension Latency in Mecp2 and 110 308/y Mecp2 Mice 16. Influence of Diet on Incline Latency (Negative Geotaxis) in 112 +/y 308/y Mecp2 and Mecp2 Mice +/y 17. Influence of Diet on Dark to Light Emergence in Mecp2 and 114 308/y Mecp2 Mice +/y 18. Influence of Diet on Total Time in the Light in Mecp2 and 116 308/y Mecp2 Mice 19. Influence of Isocalorically Restricted Ketogenic and Standard 155 Diets on Body Weight of Adult Mice 24. Relationship of Circulating Plasma Metabolites in the 159 Management of Neurodegenerative and Neurological Diseases 26. Hippocrates later suggested that epilepsy could be a hereditary disease and not connected to witchcraft. Epilepsy is a disabling chronic and socially isolating neurological disorder involving recurrent abnormal discharges of neurons that produce epileptic seizures (Engel and Pedley, 1997; Johnston and Smith, 2008). Genetic heterogeneity, variable age of onset, and multifactorial inheritance has hindered progress in identifying the genetic and biochemical components responsible for the most common forms of human idiopathic generalized epilepsies (Tan et al. While some idiopathic epilepsies are inherited as simple Mendelian traits, most are multifactorial where more than one gene together with environmental factors contribute to the disease phenotype (Berkovic, 1998; Todorova et al. In contrast to idiopathic epilepsy, symptomatic or acquired epilepsy often accompanies brain trauma, injury, or neurostructural defects. Generalized seizures tend to involve both cerebral hemispheres, whereas partial (also called local or focal) seizures are localized in one cerebral hemisphere (Hauser, 1982; Hauser, 1992). Natural occurring models of epilepsy are especially important, since many of the non-natural models (e. Epidemiological data indicate that 20-40% of the patients with newly diagnosed epilepsy will become refractory to treatment, due to both environmental (e. Diet therapies for the control of epilepsy are as old as the disease itself, with references of their usage dating back to the time of the ancient Greeks and Romans (Temkin, 1971; Eadie and Bladin, 2001). Although, these early diet therapies were designed to rid the brain of toxic agents that were believed to underlie the development of epileptic seizures, the type or composition of antiepileptic diets (e. Fasting and the Ketogenic Diet Fasting has long been recognized as an effective antiepileptic therapy for a broad range of seizure disorders (Lennox and Cobb, 1928; Lennox, 1960; Freeman et al. Interestingly, 6 reference to fasting as a cure for epileptic seizures can be found as back as the biblical times (Mark 9:14-29) (Seyfried et al. This latter finding is of great importance in regard to brain energy metabolism and trying to decode the antiepileptic mechanism of action of fasting. Under normal physiological conditions brain cells derive most of their energy from glucose or glucose-derived metabolites (e. This metabolic transition was also observed in Lennoxs patients, where blood glucose levels were reduced and blood ketone levels were increased (ketosis) upon fasting (Lennox, 1960). Amazingly, after fasting was terminated through food intake some of Lennoxs patients remained seizure free for extended periods, indicating individual variability for the anticonvulsant (a phenomenon where only seizures are reduced) and antiepileptic (a phenomenon where all or some aspects of epilepsy are affected) effects of fasting (Lennox, 1960; Seyfried et al. Although clinically effective in managing seizure disorders, fasting is impractical for the long-term seizure management due largely to issues of compliance (Seyfried et al. It was originally thought that ketone bodies (-hydroxybutyrate and acetoacetate) might play an important role in the antiepileptic effects of fasting (Wilder, 1921; Lennox, 1960). An explanation for this may stem from the fact that brain ketone utilization depends on the plasma levels of ketones, glucose, and other metabolites (Nehlig and Pereira de Vasconcelos, 1993). Thus associations between plasma ketone levels and seizure protection may be masked (Seyfried et al. Based on all aforementioned findings, a great interest is developing in the natural therapeutic potential of the ketogenic diet in the treatment of neurological disorders other than epilepsy, including Alzheimers and Parkinsons disease (Gasior et al. Studies in these neurodegenerative disorders have led to the hypothesis that the ketogenic diet may not only provide symptomatic benefit, but could have beneficial disease-modifying activity applicable to a broad range of brain disorders characterized by the death of neurons (Gasior et al. Very few studies have investigated the relationship among ketones, glucose, and seizure susceptibility under long-term antiepileptic diet therapies. Finally, my thesis provides the first guidelines for standardizing the implementation of diet therapies in the management of an array of neurodegenerative, neurological, or other types of diseases.