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https://www.readbyqxmd.com/read/29350304/defective-mitochondrial-atpase-due-to-rare-mtdna-m-8969g-a-mutation-causing-lactic-acidosis-intellectual-disability-and-poor-growth
#1
Pirjo Isohanni, Christopher J Carroll, Christopher B Jackson, Max Pohjanpelto, Tuula Lönnqvist, Anu Suomalainen
Mutations in mitochondrial ATP synthase 6 (MT-ATP6) are a frequent cause of NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) or Leigh syndromes, especially a point mutation at nucleotide position 8993. M.8969G>A is a rare MT-ATP6 mutation, previously reported only in three individuals, causing multisystem disorders with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia or IgA nephropathy. We present two siblings with the m.8969G>A mutation and a novel, substantially milder phenotype with lactic acidosis, poor growth, and intellectual disability...
January 19, 2018: Neurogenetics
https://www.readbyqxmd.com/read/29348686/defects-in-the-mitochondrial-trna-modification-enzymes-mto1-and-gtpbp3-promote-different-metabolic-reprogramming-through-a-hif-ppar%C3%AE-ucp2-ampk-axis
#2
Rachid Boutoual, Salvador Meseguer, Magda Villarroya, Elena Martín-Hernández, Mohammed Errami, Miguel A Martín, Marta Casado, M-Eugenia Armengod
Human proteins MTO1 and GTPBP3 are thought to jointly catalyze the modification of the wobble uridine in mitochondrial tRNAs. Defects in each protein cause infantile hypertrophic cardiomyopathy with lactic acidosis. However, the underlying mechanisms are mostly unknown. Using fibroblasts from an MTO1 patient and MTO1 silenced cells, we found that the MTO1 deficiency is associated with a metabolic reprogramming mediated by inactivation of AMPK, down regulation of the uncoupling protein 2 (UCP2) and transcription factor PPARγ, and activation of the hypoxia inducible factor 1 (HIF-1)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29340159/recurrent-lactic-acidosis-and-hypoglycemia-with-inadvertent-metformin-use-a-case-of-look-alike-pills
#3
Tess Jacob, Renee Garrick, Michael D Goldberg
Metformin is recommended as the first-line agent for the treatment of type 2 diabetes. Although this drug has a generally good safety profile, rare but potentially serious adverse effects may occur. Metformin-associated lactic acidosis, although very uncommon, carries a significant risk of mortality. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such as renal and hepatic disease. Plasma metformin levels do not reliably correlate with the severity of lactic acidosis...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29339119/targeting-of-stress-response-pathways-in-the-prevention-and-treatment-of-cancer
#4
REVIEW
Jaroslav Zelenka, Martina Koncošová, Tomáš Ruml
The hallmarks of tumor tissue are not only genetic aberrations but also the presence of metabolic and oxidative stress as a result of hypoxia and lactic acidosis. The stress activates several prosurvival pathways including metabolic remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis, whose upregulation in tumors is associated with a poor survival of patients, while their activation in healthy tissue with statins, metformin, physical activity, and natural compounds prevents carcinogenesis...
January 12, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29331171/the-genotypic-and-phenotypic-spectrum-of-mto1-deficiency
#5
James J O'Byrne, Maja Tarailo-Graovac, Aisha Ghani, Michael Champion, Charu Deshpande, Ali Dursun, Riza K Ozgul, Peter Freisinger, Ian Garber, Tobias B Haack, Rita Horvath, Ivo Barić, Ralf A Husain, Leo A J Kluijtmans, Urania Kotzaeridou, Andrew A Morris, Colin J Ross, Saikat Santra, Jan Smeitink, Mark Tarnopolsky, Saskia B Wortmann, Johannes A Mayr, Michaela Brunner-Krainz, Holger Prokisch, Wyeth W Wasserman, Ron A Wevers, Udo F Engelke, Richard J Rodenburg, Teck Wah Ting, Robert McFarland, Robert W Taylor, Ramona Salvarinova, Clara D M van Karnebeek
BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10)...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29327822/efficacy-and-safety-of-long-term-entecavir-therapy-in-a-european-population
#6
Alessandro Collo, Paola Belci, Sharmila Fagoonee, Lucia Loreti, Valeria Gariglio, Ramona Parise, Paola Magistroni, Marilena Durazzo
BACKGROUND: Therapy in chronic hepatitis B (CHB) patients aims at improving their survival by preventing disease progression to cirrhosis and its complications. Entecavir (ETV) is currently a first line therapeutic agent recommended for the treatment of CHB. Our aim was to evaluate the long term outcome of a cohort of CHB patients treated with ETV. METHODS: Thirty-four patients treated with ETV for at least 6 months were included in this study. The virologic response was determined by the dosage of serum HBV-DNA, HBsAg, HBeAg, anti-HBs and anti-HBe antibodies...
January 10, 2018: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/29327420/expanding-the-phenotype-of-slc25a42-associated-mitochondrial-encephalomyopathy
#7
M Almannai, A Alsamri, A Alqasmi, E Faqeih, F AlMutairi, M Alotaibi, M M Samman, W Eyaid, Y I Aljadhai, H E Shamseldin, W Craigen, F S Alkuraya
SLC25A42 gene encodes an inner mitochondrial membrane protein that imports Co-enzyme A (CoA) into the mitochondrial matrix. A mutation in this gene was recently reported in a subject born to consanguineous parents who presented with mitochondrial myopathy with muscle weakness and lactic acidosis. In this report, we present 12 additional individuals with the same founder mutation who presented with variable manifestations ranging from asymptomatic lactic acidosis to a severe phenotype characterized by developmental regression and epilepsy...
January 12, 2018: Clinical Genetics
https://www.readbyqxmd.com/read/29316923/comparative-assessment-of-probiotics-and-monensin-in-the-prophylaxis-of-acute-ruminal-lactic-acidosis-in-sheep
#8
Leonardo Frasson Reis, Rejane Santos Sousa, Francisco Leonardo Costa Oliveira, Frederico Augusto Mazzocca Lopes Rodrigues, Carolina Akiko Sato Cabral Araújo, Enoch Brandão Souza Meira-Júnior, Raimundo Alves Barrêto-Júnior, Clara Satsuki Mori, Antonio Humberto Hamad Minervino, Enrico Lippi Ortolani
BACKGROUND: Acute ruminal lactic acidosis (ARLA) is a major nutritional and metabolic disorder usually characterized by excessive or non-adapted intake of diets rich in nonstructural carbohydrates. Feed additives that regulate the ruminal environment have been used to prevent ARLA, such as ionophores and, more recently, yeast culture. Thus, we aimed to compare the efficacy of a yeast-based culture (Saccharomyces cerevisiae) with that of monensin sodium in the prevention of ARLA in sheep...
January 9, 2018: BMC Veterinary Research
https://www.readbyqxmd.com/read/29310939/lactic-acidosis-and-mitral-valve-surgery-defining-the-relationship
#9
EDITORIAL
Hakeem O Yusuff, Vasileios Zochios
No abstract text is available yet for this article.
October 2, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/29301418/hypoglycemia-and-lactic-acidosis-outperform-king-s-college-criteria-for-predicting-death-or-transplant-in-acetaminophen-toxic-patients
#10
Michael Levine, Samuel J Stellpflug, Anthony F Pizon, David A Peak, Janna Villano, Timothy Wiegand, Christian Dib, Stephen H Thomas
IMPORTANCE: Acetaminophen toxicity is common and is characterized by hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require hepatic transplant. While there are various criteria to predict patients who might benefit from transplant, the King's College criteria remain one of the most widely used. However, the King's College criteria have several limitations and do not incorporate glucose, an important marker of hepatic function...
January 5, 2018: Clinical Toxicology
https://www.readbyqxmd.com/read/29296771/red-blood-cells-in-hemorrhagic-shock-a-critical-role-for-glutaminolysis-in-fueling-alanine-transamination-in-rats
#11
Julie A Reisz, Anne L Slaughter, Rachel Culp-Hill, Ernest E Moore, Christopher C Silliman, Miguel Fragoso, Erik D Peltz, Kirk C Hansen, Anirban Banerjee, Angelo D'Alessandro
Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], <30 mm Hg) in comparison with sham rats (MAP, >80 mm Hg)...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29286581/bone-marrow-features-in-pearson-syndrome-with-neonatal-onset-a-case-report-and-review-of-the-literature
#12
Elisa Tadiotto, Evelina Maines, Daniela Degani, Rita Balter, Andrea Bordugo, Simone Cesaro
Pearson syndrome (PS) is a rare mitochondrial disorder that usually presents with transfusion-dependent macrocytic anemia, exocrine pancreatic dysfunction, and lactic acidosis. Typical bone marrow (BM) features are vacuolization in hematopoietic progenitors, hypocellularity, and ringed sideroblasts. At the neonatal age, PS may have a variable clinical onset. Moreover, there is little information about BM features at this age and the timing of their presentation. We report a neonatal case of PS that presented with refractory anemia and atypical BM features...
December 29, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29286387/establishment-of-an-extracellular-acidic-ph-culture-system
#13
Ayano Kondo, Tsuyoshi Osawa
Conditions of the tumor microenvironment, such as hypoxia or nutrient starvation, play critical roles in cancer progression and malignancy. However, the role of acidic extracellular pH in tumor aggressiveness and its underlying mechanism has not been extensively studied compared to hypoxic or nutrient starvation conditions. In addition, a well-defined culture method to mimic the acidic extracellular tumor microenvironment has not been fully reported. Here we present a simple in vitro culture method to maintain acidic extracellular pH using reduced bicarbonate and increased lactate or HCl concentrations in the culture medium...
November 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29280423/anemia-was-an-uncommon-complication-of-severe-malaria-in-a-high-transmission-rural-area-of-western-uganda
#14
Ross Boyce, Raquel Reyes, Corinna Keeler, Michael Matte, Moses Ntaro, Edgar Mulogo, Mark J Siedner
The clinical epidemiology of severe malaria among patients presenting to peripheral health centers has not been well described. We conducted a prospective, observational cohort study to describe the epidemiology and clinical manifestations of severe malaria in a highland area of declining transmission intensity in Western Uganda. Individuals presenting with a history of fever were screened with a malaria rapid diagnostic test (RDT). We prepared blood smears and conducted clinical and laboratory testing for those with a positive RDT...
December 26, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29260009/adult-onset-of-mitochondrial-myopathy-encephalopathy-lactic-acidosis-and-stroke-like-episodes-melas-syndrome-with-hypothyroidism-and-psychiatric-disorders
#15
Yu-Xing Ge, Bo Shang, Wen-Zhen Chen, You Lu, Jue Wang
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a clinical syndrome associated with mitochondrial disorders (MIDs). This report illustrates a case of MELAS syndrome with hypothyroidism and psychiatric disorders, which is different from the common clinical manifestations of MELAS syndrome, such as exercise intolerance, migraine-like headaches, hearing loss and seizures etc. There are considerable interests in the possibility that mitochondrial dysfunction may play a role in the pathogenesis of endocrine dysfunctions and psychiatric disorders in MELAS syndrome...
March 2017: ENeurologicalSci
https://www.readbyqxmd.com/read/29259930/intravascular-large-b-cell-lymphoma-with-multi-organ-failure-presenting-as-a-pancreatic-mass-a-case-with-atypical-presentation-and-definite-diagnosis-postmortem
#16
Faisal Mahmudul Huq Ronny, Margaret Ann Black, Arnaldo A Arbini
Intravascular large B-cell lymphoma (IVLBCL) is a very rare extra nodal lymphoma that tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules while sparing the organ parenchyma. The cause of its affinity for the vascular bed remains unknown. Because of its rarity and unremarkable clinical presentation, a timely diagnosis of IVLBCL is very challenging. Here, we describe a case of IVLBCL presenting as pancreatic mass that was ultimately diagnosed at autopsy. A 71-year-old Caucasian female presented with a 3-month history of fatigue, abdominal pain, and weight loss...
October 2017: Autopsy & Case Reports
https://www.readbyqxmd.com/read/29245964/phenformin-has-anti-tumorigenic-effects-in-human-ovarian-cancer-cells-and-in-an-orthotopic-mouse-model-of-serous-ovarian-cancer
#17
Amanda L Jackson, Wenchuan Sun, Joshua Kilgore, Hui Guo, Ziwei Fang, Yajie Yin, Hannah M Jones, Timothy P Gilliam, Chunxiao Zhou, Victoria L Bae-Jump
Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29237403/isolated-and-repeated-stroke-like-episodes-in-a-middle-aged-man-with-a-mitochondrial-nd3-t10158c-mutation-a-case-report
#18
Satomi Mezuki, Kenji Fukuda, Tomonaga Matsushita, Yoshihisa Fukushima, Ryu Matsuo, Yu-Ichi Goto, Takehiro Yasukawa, Takeshi Uchiumi, Dongchon Kang, Takanari Kitazono, Tetsuro Ago
BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, is the most common phenotype of mitochondrial disease. It often develops in childhood or adolescence, usually before the age of 40, in a maternally-inherited manner. Mutations in mitochondrial DNA (mtDNA) are frequently responsible for MELAS. CASE PRESENTATION: A 55-year-old man, who had no family or past history of mitochondrial disorders, suddenly developed bilateral visual field constriction and repeated stroke-like episodes...
December 13, 2017: BMC Neurology
https://www.readbyqxmd.com/read/29234163/clarifying-the-relationship-between-metformin-acute-kidney-injury-and-lactic-acidosis
#19
Samira Bell, Enrique Soto-Pedre, Paul Connelly, Shona Livingstone, Ewan Pearson
No abstract text is available yet for this article.
December 13, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29234161/further-clarifying-the-relationship-between-metformin-acute-kidney-injury-and-lactic-acidosis
#20
Connie M Rhee, Kamyar Kalantar-Zadeh
No abstract text is available yet for this article.
December 13, 2017: Nature Reviews. Nephrology
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