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Metabolic Syndrome: Is It Time to Add the Central Nervous System?
Rojas, M, Chávez-Castillo, M, Pirela, D, Parra, H, Nava, M, Chacín, M, Angarita, L, Añez, R, Salazar, J, Ortiz, R, et al
Nutrients. 2021;(7)
Abstract
Metabolic syndrome (MS) is a set of cardio-metabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias. The syndrome affects 25% of adults worldwide. The definition of MS has evolved over the last 80 years, with various classification systems and criteria, whose limitations and benefits are currently the subject of some controversy. Likewise, hypotheses regarding the etiology of MS add more confusion from clinical and epidemiological points of view. The leading suggestion for the pathophysiology of MS is insulin resistance (IR). IR can affect multiple tissues and organs, from the classic "triumvirate" (myocyte, adipocyte, and hepatocyte) to possible effects on organs considered more recently, such as the central nervous system (CNS). Mild cognitive impairment (MCI) and Alzheimer's disease (AD) may be clinical expressions of CNS involvement. However, the association between MCI and MS is not understood. The bidirectional relationship that seems to exist between these factors raises the questions of which phenomenon occurs first and whether MCI can be a precursor of MS. This review explores shared pathophysiological mechanisms between MCI and MS and establishes a hypothesis of a possible MCI role in the development of IR and the appearance of MS.
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2.
Creatine Defects and Central Nervous System.
Fons, C, Campistol, J
Seminars in pediatric neurology. 2016;(4):285-289
Abstract
Creatine deficiency syndromes are a group of disorders of creatine (Cr) synthesis and transport characterized by intellectual disability, language delay, epilepsy, autism spectrum disorder, and movement disorders secondary to decrease of Cr concentration in the brain. Synthesis defects are treatable, therefore an early diagnosis and treatment is essential. The aim of this article is to review the Cr metabolism and function in the central nervous system. We describe the optimal diagnostic protocol in Cr deficiency syndromes based on biochemical methods, neuroradiological (1H-MRS), and molecular analysis. Finally, a treatment approach of the different Cr deficiency syndromes is described.
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3.
Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities.
Adibhatla, RM, Hatcher, JF
Antioxidants & redox signaling. 2010;(1):125-69
Abstract
Reactive oxygen species (ROS) are produced at low levels in mammalian cells by various metabolic processes, such as oxidative phosphorylation by the mitochondrial respiratory chain, NAD(P)H oxidases, and arachidonic acid oxidative metabolism. To maintain physiological redox balance, cells have endogenous antioxidant defenses regulated at the transcriptional level by Nrf2/ARE. Oxidative stress results when ROS production exceeds the cell's ability to detoxify ROS. Overproduction of ROS damages cellular components, including lipids, leading to decline in physiological function and cell death. Reaction of ROS with lipids produces oxidized phospholipids, which give rise to 4-hydroxynonenal, 4-oxo-2-nonenal, and acrolein. The brain is susceptible to oxidative damage due to its high lipid content and oxygen consumption. Neurodegenerative diseases (AD, ALS, bipolar disorder, epilepsy, Friedreich's ataxia, HD, MS, NBIA, NPC, PD, peroxisomal disorders, schizophrenia, Wallerian degeneration, Zellweger syndrome) and CNS traumas (stroke, TBI, SCI) are problems of vast clinical importance. Free iron can react with H(2)O(2) via the Fenton reaction, a primary cause of lipid peroxidation, and may be of particular importance for these CNS injuries and disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Atherosclerosis, the major risk factor for ischemic stroke, involves accumulation of oxidized LDL in the arteries, leading to foam cell formation and plaque development. This review will discuss the role of lipid oxidation/peroxidation in various CNS injuries/disorders.
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4.
A case of reversible restless legs syndrome (RLS) and sleep-related eating disorder relapse triggered by acute right leg herpes zoster infection: literature review of spinal cord and peripheral nervous system contributions to RLS.
Mahowald, MW, Cramer Bornemann, MA, Schenck, CH
Sleep medicine. 2010;(6):583-5
Abstract
Restless legs syndrome (RLS) is thought to be due to abnormalities of iron metabolism in the central nervous system; however, occasional cases are associated with lesions of the spinal cord, spinal rootlets, and peripheral nervous system. This is a case report of RLS exacerbated by shingles with a review of the literature of extra-cerebral lesions or disorders causing or contributing to RLS.
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5.
[Neurosteroids and their function].
Bicíková, M, Hampl, R
Casopis lekaru ceskych. 2007;(3):223-6
Abstract
Neurosteroids are steroid structure hormones with neuroactive function. Neurosteroids have rapid, non-genomic actions in CNS. Non-conjugated metabolites of progesterone such as allopregnanolone, are potent positive modulators of GABAA receptors. They open ion channels for Cl- with analgetic, hypnotic, anxiolytic and anticonvulsant effects. By sulphatation the modulation on GABAA receptors is changed to negative with opposite effect. 19-C-steroids as dehydroepiandrosterone and its sulphate are negative modulators of GABAA receptors acting as an excitant and proconvulsant. They are able to modulate positively N-methyl-D-aspartate (NMDA) receptors and open ion canals for Ca2+. Changed (lowered) neurosteroid levels can be involved in many pathological processes as premenstrual syndrome, stress, depression, some forms of epilepsy, Alzheimer disease etc. Future study targeted on regulation of their production and metabolism and understanding of the mechanism of their actions will help to use them therapeutically.
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6.
[Pathophysiology of restless leg syndrome and periodic leg movement disorder in view of the latest research findings].
Köves, P, Szakács, Z
Ideggyogyaszati szemle. 2005;(5-6):148-63
Abstract
Both restless leg syndrome and periodic leg movement disorder have been classified as primary sleep disorders by the International Classification of Sleep Disorders. Considering the characteristic clinical symptoms, it is supposed that their pathomechanism involves the peripheral and central stimulus-processing mechanisms of the nervous system as well as several elements of the motor system. During the last couple of years many new elements of the pathomechanism have been discovered, in particular the dysfunction of the postsynaptic dopamine receptors related to the iron metabolism of the central nervous system, the role of opiate receptors, and the involvement of subclinical small fiber neuropathy. Many of these findings have been incorporated into the diagnostic and treatment protocols used in the management of patients with restless leg syndrome or periodic leg movement disorder. Considering the rapidly increasing number of publications on their pathomechanism and the various fields it involves, the authors found it necessary to evaluate these data and to interpret their relationships within the frame of sleep-wake regulation.
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7.
Comparative tolerability of the HMG-CoA reductase inhibitors.
Farmer, JA, Torre-Amione, G
Drug safety. 2000;(3):197-213
Abstract
The availability of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has revolutionised the treatment of lipid abnormalities in patients at risk for the development of coronary atherosclerosis. The relatively widespread experience with HMG-CoA therapy has allowed a clear picture to emerge concerning the relative tolerability of these agents. While HMG-CoA reductase inhibitors have been shown to decrease complications from atherosclerosis and to improve total mortality, concern has been raised as to the long term safety of these agents. They came under close scrutiny in early trials because ocular complications had been seen with older inhibitors of cholesterol synthesis. However, extensive evaluation demonstrated no significant adverse alteration of ophthalmological function by the HMG-CoA reductase inhibitors. Extensive experience with the potential adverse effect of the HMG-CoA reductase inhibitors on hepatic function has accumulated. The effect on hepatic function for the various HMG-CoA reductase inhibitors is roughly dose-related and 1 to 3% of patients experience an increase in hepatic enzyme levels. The majority of liver abnormalities occur within the first 3 months of therapy and require monitoring. Rhabdomyolysis is an uncommon syndrome and occurs in approximately 0.1% of patients who receive HMG-CoA reductase inhibitor monotherapy. However, the incidence is increased when HMG-CoA reductase inhibitors are used in combination with agents that share a common metabolic path. The role of the cytochrome P450 (CYP) enzyme system in drug-drug interactions involving HMG-CoA reductase inhibitors has been extensively studied. Atorvastatin, cerivastatin, lovastatin and simvastatin are predominantly metabolised by the CYP3A4 isozyme. Fluvastatin has several metabolic pathways which involve the CYP enzyme system. Pravastatin is not significantly metabolised by this enzyme and thus has theoretical advantage in combination therapy. The major interactions with HMG-CoA reductase inhibitors in combination therapy involving rhabdomyolysis include fibric acid derivatives, erythromycin, cyclosporin and fluconazole. Additional concern has been raised relative to overzealous lowering of cholesterol which could occur due to the potency of therapy with these agents. Currently, there is no evidence from clinical trials of an increase in cardiovascular or total mortality associated with potent low density lipoprotein reduction. However, a threshold effect had been inferred by retrospective analysis of the Cholesterol and Recurrent Events study utilising pravastatin and the role of aggressive lipid therapy is currently being addressed in several large scale trials.