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https://www.readbyqxmd.com/read/29775413/human-cerebral-collateral-arteriole-function-in-normal-cognition-mild-cognitive-impairment-and-dementia-subjects
#1
Raymond Q Migrino, Seth Truran, Nina Karamanova, Geidy Serrano, Calvin Madrigal, Hannah A Davies, Jillian Madine, Peter Reaven, Thomas G Beach
Clinical and preclinical studies suggest a link between cardiovascular disease and dementia disorders but the role of collateral brain circulation in cognitive dysfunction remains unknown. We aim to test the hypothesis that leptomeningeal arteriole (LMA) function and response to metabolic stressors differ among dementia, mild cognitive impairment (MCI) and normal cognition (CN) subjects. Following rapid autopsy, LMA were isolated from CN (N=10), MCI (N=12) or dementia subjects (N=42, Alzheimer's disease [AD], vascular dementia [VaD], or Other Dementia) and endothelial and smooth muscle-dependent function were measured at baseline and following exposure to β-amyloid (Aβ42 2 μM), palmitic acid (PA 150 μM) or medin (5μM) and compared...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29774539/clinical-and-molecular-characterization-of-indian-patients-with-fructose-1-6-bisphosphatase-deficiency-identification-of-a-frequent-variant-e281k
#2
Pratibha Bhai, Sunita Bijarnia-Mahay, Ratna D Puri, Renu Saxena, Deepti Gupta, Udhaya Kotecha, Anil Sachdev, Dhiren Gupta, Vyomesh Vyas, Divya Agarwal, Vivek Jain, Rajeev K Bansal, Tapisha G Kumar, Ishwar Chander Verma
Fructose-1, 6-bisphosphatase deficiency is an autosomal recessive disorder of gluconeogenesis caused by genetic defect in the FBP1 gene. It is characterized by episodic, often life-threatening metabolic acidosis, liver dysfunction, and hyperlactatemia. Without a high index of suspicion, it may remain undiagnosed with devastating consequences. Accurate diagnosis can be achieved either by enzyme assay or gene studies. Enzyme assay requires a liver biopsy and is tedious, invasive, expensive, and not easily available...
May 18, 2018: Annals of Human Genetics
https://www.readbyqxmd.com/read/29774469/higher-serum-levels-of-uric-acid-are-associated-with-a-reduced-insulin-clearance-in-non-diabetic-individuals
#3
Teresa Vanessa Fiorentino, Franz Sesti, Elena Succurro, Elisabetta Pedace, Francesco Andreozzi, Angela Sciacqua, Marta Letizia Hribal, Francesco Perticone, Giorgio Sesti
AIMS: Decreased insulin clearance has been reported to be associated with insulin resistance-related disorders and incident type 2 diabetes. The aim of this study was to evaluate whether higher levels of uric acid (UA), a known risk factor of type 2 diabetes, are associated with a reduced insulin clearance. METHODS: 440 non-diabetic individuals were stratified in tertiles according to serum UA levels. Insulin clearance and skeletal muscle insulin sensitivity were assessed by euglycemic hyperinsulinemic clamp...
May 17, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29774465/effect-of-inositol-stereoisomers-at-different-dosages-in-gestational-diabetes-an-open-label-parallel-randomized-controlled-trial
#4
Federica Fraticelli, Claudio Celentano, Isaia Al Zecca, Giacoma Di Vieste, Basilio Pintaudi, Marco Liberati, Marica Franzago, Marta Di Nicola, Ester Vitacolonna
AIMS: Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. The aim of the study is to compare the effect of different dosages of inositol stereoisomers supplementation on insulin resistance levels and several maternal-fetal outcomes in GDM women. METHODS: Participants were randomly allocated to receive daily: 400 mcg folic acid (control treatment), 4000 mg myo-inositol plus 400 mcg folic acid (MI treatment), 500 mg D-chiro-inositol plus 400 mcg folic acid (DCI treatment) or 1100/27...
May 17, 2018: Acta Diabetologica
https://www.readbyqxmd.com/read/29774402/subtrochanteric-and-diaphyseal-femoral-fractures-in-hypophosphatasia-not-atypical-at-all
#5
F Genest, L Seefried
Risk for subtrochanteric and diaphyseal femoral fractures is considered increased in patients with hypophosphatasia (HPP). Evaluating a large cohort of HPP patients, we could for the first time quantify the prevalcence and identify both morphometric features as well as predisposing factors for this complication of severe HPP. INTRODUCTION: Subtrochanteric and diaphyseal femoral fractures have been associated with both, long-term antiresorptive treatment and metabolic bone disorders, specifically Hypophosphatasia (HPP)...
May 17, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29774380/-thyroid-and-pregnancy
#6
REVIEW
K A Iwen, H Lehnert
During pregnancy thyroid hormones have profound effects on embryonal/fetal development and maternal health. Therefore, thyroid gland disorders should be immediately diagnosed and adequately treated. Pregnancy-specific physiological alterations during pregnancy cause changes in the reference interval for thyroid-stimulating hormone levels and trimester-specific thresholds must be taken into account. This article summarizes the most important diagnostic and therapeutic aspects before, during and after pregnancy...
May 17, 2018: Der Internist
https://www.readbyqxmd.com/read/29774166/hemostatic-state-augmented-with-platelet-indices-among-sudanese-diabetic-septic-foot
#7
Bashir Abdrhman Bashir, Mohamed Salih Ali
Background: Diabetes mellitus is a very rampant metabolic disorder, particularly type II. It has many complications such as the septic foot. Diabetic septic foot (DSF) patients are at high risk for coagulation abnormalities as well as surgical hazards. Owing to the potential sequelae of coagulation and vascular abnormalities, this work aimed at studying the hemostatic state and platelet indices in diabetes type II patients with septic foot. Methods: A case-control study was conducted during the period from July to September 2017 at Dr...
2018: BMC Hematology
https://www.readbyqxmd.com/read/29774002/on-the-drive-specificity-of-freudian-drives-for-the-generation-of-seeking-activities-the-importance-of-the-underestimated-imperative-motor-factor
#8
Michael Kirsch, Wolfgang Mertens
Doubters of Freud's theory of drives frequently mentioned that his approach is outdated and therefore cannot be useful for solving current problems in patients with mental disorders. At present, many scientists believe that affects rather than drives are of utmost importance for the emotional life and the theoretical framework of affective neuroscience, developed by Panksepp, strongly underpinned this view. Panksepp evaluated seven so-called command systems and the SEEKING system is therein of central importance...
2018: Frontiers in Psychology
https://www.readbyqxmd.com/read/29773951/the-role-of-neuroinflammation-and-neurovascular-dysfunction-in-major-depressive-disorder
#9
REVIEW
Sang Won Jeon, Yong-Ku Kim
Although depression has generally been explained with monoamine theory, it is far more multifactorial, and therapies that address the disease's pathway have not been developed. In this context, an understanding of neuroinflammation and neurovascular dysfunction would enable a more comprehensive approach to depression. Inflammation is in a sense a type of allostatic load involving the immune, endocrine, and nervous systems. Neuroinflammation is involved in the pathophysiology of depression by increasing proinflammatory cytokines, activating the hypothalamus-pituitary-adrenal axis, increasing glucocorticoid resistance, and affecting serotonin synthesis and metabolism, neuronal apoptosis and neurogenesis, and neuroplasticity...
2018: Journal of Inflammation Research
https://www.readbyqxmd.com/read/29773809/super-resolution-imaging-reveals-the-sub-diffraction-phenotype-of-zellweger-syndrome-ghosts-and-wild-type-peroxisomes
#10
Kareem Soliman, Fabian Göttfert, Hendrik Rosewich, Sven Thoms, Jutta Gärtner
Peroxisomes are ubiquitous cell organelles involved in many metabolic and signaling functions. Their assembly requires peroxins, encoded by PEX genes. Mutations in PEX genes are the cause of Zellweger Syndrome spectrum (ZSS), a heterogeneous group of peroxisomal biogenesis disorders (PBD). The size and morphological features of peroxisomes are below the diffraction limit of light, which makes them attractive for super-resolution imaging. We applied Stimulated Emission Depletion (STED) microscopy to study the morphology of human peroxisomes and peroxisomal protein localization in human controls and ZSS patients...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773783/cholesteryl-ester-storage-disease-fatal-outcome-without-causal-therapy-in-a-female-patient-with-the-preventable-sequelae-of-progressive-liver-disease-after-many-years-of-mild-symptoms
#11
Ali Canbay, Meike N Müller, Stathis Philippou, Guido Gerken, Andreas Tromm
BACKGROUND Cholesteryl ester storage disease (CESD), also known as lysosomal acid lipase deficiency (LAL-D), is a rare autosomal-recessive inheritable lysosomal storage disease. Since 2015, a causal treatment with sebelipase alfa, which replaces the missing LAL enzyme, has been approved. We report a fatal course of LAL-D in a female patient. CASE REPORT In 1979, CESD was first diagnosed in a 13-year-old female with marked hepatomegaly. At that time, no specific treatment for CESD was available and the spontaneous course of the disease had to be awaited...
May 18, 2018: American Journal of Case Reports
https://www.readbyqxmd.com/read/29773163/epicardial-adipose-tissue-may-mediate-deleterious-effects-of-obesity-and-inflammation-on-the-myocardium
#12
REVIEW
Milton Packer
Epicardial adipose tissue has unique properties that distinguish it from other depots of visceral fat. Rather than having distinct boundaries, the epicardium shares an unobstructed microcirculation with the underlying myocardium, and in healthy conditions, produces cytokines that nourish the heart. However, in chronic inflammatory disorders (especially those leading to heart failure with preserved ejection fraction), the epicardium becomes a site of deranged adipogenesis, leading to the secretion of proinflammatory adipokines that can cause atrial and ventricular fibrosis...
May 22, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29773067/in-silico-molecular-docking-and-adme-studies-of-1-3-4-thiadiazole-derivatives-in-relation-to-in-vitro-pon1-activity
#13
Belgin Sever, Kaan Kucukoglu, Hayrunnisa Nadaroglu, Mehlika Dilek Altintop
BACKGROUND: Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins and cell membranes against oxidative modification. OBJECTIVE: Based on antioxidative properties of PON1 and widely usage of 1,3,4-thiadiazole derivatives in pharmaceutical, agricultural, and materials chemistry, herein we aimed to evaluate PON1 activator potentials of 1,3,4-thiadiazole based compounds. METHOD: 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio] acetophenone derivatives (1-18), previously synthesized by our research group, were in vitro evaluated for their activator effects on PON1 which was purified using ammonium sulfate precipitation (60-80%) and DEAE-Sephadex anion exchange chromatography...
May 17, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29773057/nucleophagy-plays-a-major-role-in-human-diseases
#14
Nian Fu, XueFeng Yang, Linxi Chen
Nucleophagy is a selective autophagy, which selectively remove damaged or non-essential nuclear material from a cell by the autophagy pathway. Additionally, nucleophagy is crucial for promoting cell longevity and ensure body proper function. Increasing evidences have shown that nucleophagy may play a major role in such human diseases as degenerative disorders, tumorigenesis, malnutrition and metabolic disorders, parakeratosis and psoriasis. Studies indicated that nucleophagy can improve degenerative disorders by delaying premature cell senescence, prevent malnutrition and metabolic disorder via maintaining nuclear structure and releasing nutrients for energy production, and alleviate parakeratosis and psoriasis...
May 17, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29772784/capsaicin-in-metabolic-syndrome
#15
REVIEW
Sunil K Panchal, Edward Bliss, Lindsay Brown
Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders...
May 17, 2018: Nutrients
https://www.readbyqxmd.com/read/29772672/mtor-signaling-and-neural-stem-cells-the-tuberous-sclerosis-complex-model
#16
REVIEW
Alice Polchi, Alessandro Magini, Danila Di Meo, Brunella Tancini, Carla Emiliani
The mechanistic target of rapamycin (mTOR), a serine-threonine kinase, plays a pivotal role in regulating cell growth and proliferation. Notably, a great deal of evidence indicates that mTOR signaling is also crucial in controlling proliferation and differentiation of several stem cell compartments. Consequently, dysregulation of the mTOR pathway is often associated with a variety of disease, such as cancer and metabolic and genetic disorders. For instance, hyperactivation of mTORC1 in neural stem cells (NSCs) is associated with the insurgence of neurological manifestation characterizing tuberous sclerosis complex (TSC)...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772309/attention-deficit-hyperactivity-disorder-and-obesity-a-review-and-model-of-current-hypotheses-explaining-their-comorbidity
#17
REVIEW
Tomasz Hanć, Samuele Cortese
Available meta-analyses point to a significant association between attention-deficit/hyperactivity disorder (ADHD) and obesity. The possible mechanisms underlying this relationship are unclear. Here, we overview the studies aimed at identifying the factors contributing to the comorbidity between ADHD and obesity, including genetic factors, fetal programming, executive dysfunctions, psychosocial stress, factors directly related to energy balance, and sleep patterns alterations. The bulk of current research has focused on reduced physical activity and abnormal eating patterns as possible causes of weight gain in individuals with ADHD...
May 14, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29772029/prolyl-carboxypeptidase-activity-in-the-circulation-and-its-correlation-with-body-weight-and-adipose-tissue-in-lean-and-obese-subjects
#18
Kaat Kehoe, Heidi Noels, Wendy Theelen, Emilie De Hert, Shenguan Xu, An Verrijken, Thierry Arnould, Erik Fransen, Nina Hermans, Anne-Marie Lambeir, Per Venge, Luc Van Gaal, Ingrid De Meester
BACKGROUND: Prolyl carboxypeptidase (PRCP) is involved in the regulation of body weight, likely by hydrolysing alpha-melanocyte-stimulating hormone and apelin in the hypothalamus and in the periphery. A link between PRCP protein concentrations in plasma and metabolic disorders has been reported. In this study, we investigated the distribution of circulating PRCP activity and assessed its relation with body weight and adipose tissue in obese patients and patients who significantly lost weight...
2018: PloS One
https://www.readbyqxmd.com/read/29770459/identification-of-correlative-shifts-in-indices-of-brain-cholesterol-metabolism-in-the-c57bl6-mecp2-tm1-1bird-mouse-a-model-for-rett-syndrome
#19
Dieter Lütjohann, Adam M Lopez, Jen-Chieh Chuang, Anja Kerksiek, Stephen D Turley
Rett syndrome (RS) is a pervasive neurodevelopmental disorder resulting from loss-of-function mutations in the X-linked gene methyl-Cpg-binding protein 2 (MECP2). Using a well-defined model for RS, the C57BL6/Mecp2 tm1.1Bird mouse, we have previously found a moderate but persistently lower rate of cholesterol synthesis, measured in vivo, in the brains of Mecp2 -/y mice, starting from about the third week after birth. There was no genotypic difference in the total cholesterol concentration throughout the brain at any age...
May 17, 2018: Lipids
https://www.readbyqxmd.com/read/29770436/all-i-s-on-the-radar-role-of-adar-in-gene-regulation
#20
REVIEW
Galina Shevchenko, Kevin V Morris
Adenosine to inosine (A-to-I) editing is the most abundant form of RNA modification in mammalian cells, which is catalyzed by adenosine deaminase acting on the double-stranded RNA (ADAR) protein family. A-to-I editing is currently known to be involved in the regulation of the immune system, RNA splicing, protein recoding, microRNA biogenesis, and formation of heterochromatin. Editing occurs within regions of double-stranded RNA, particularly within inverted Alu repeats, and is associated with many diseases including cancer, neurological disorders, and metabolic syndromes...
May 16, 2018: FEBS Letters
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