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https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#1
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27734446/exertional-rhabdomyolysis-epidemiology-diagnosis-treatment-and-prevention
#2
Joseph J Knapik, Francis G O'Connor
Exertional rhabdomyolysis (ER) is a medical condition whereby damage to skeletal muscle is induced by excessive physical activity in otherwise healthy individuals. The individual performs so much activity that he/ she presumably depletes local muscle energy stores and muscle cells are unable to maintain cellular integrity, resulting in cell damage and the release of cellular contents, with resultant secondary complications. In the military services, the incidence of ER appeared to increase in the period 2004 to 2015...
2016: Journal of Special Operations Medicine: a Peer Reviewed Journal for SOF Medical Professionals
https://www.readbyqxmd.com/read/27703296/rhabdomyolysis-in-critically-ill-surgical-patients
#3
Biljana Kuzmanovska, Emilija Cvetkovska, Igor Kuzmanovski, Nikola Jankulovski, Mirjana Shosholcheva, Andrijan Kartalov, Tatjana Spirovska
INTRODUCTION: Rhabdomyolysis is a syndrome of injury of skeletal muscles associated with myoglobinuria, muscle weakness, electrolyte imbalance and often, acute kidney injury as severe complication. THE AIM: of this study is to detect the incidence of rhabdomyolysis in critically ill patients in the surgical intensive care unit (ICU), and to raise awareness of this medical condition and its treatment among the clinicians. MATERIAL AND METHODS: A retrospective review of all surgical and trauma patients admitted to surgical ICU of the University Surgical Clinic "Mother Teresa" in Skopje, Macedonia, from January 1(st) till December 31(st) 2015 was performed...
July 27, 2016: Medical Archives
https://www.readbyqxmd.com/read/27529136/evaluations-of-lipid-peroxidation-and-inflammation-in-short-term-glycerol-induced-acute-kidney-injury-in-rats
#4
Akina Nara, Daisuke Yajima, Sayaka Nagasawa, Hiroko Abe, Yumi Hoshioka, Hirotaro Iwase
Rhabdomyolysis is characterised by acute kidney injury (AKI) resulting from skeletal muscle injury. Lipid peroxidation-mediated oxidant injury and pro-inflammatory cytokine-mediated inflammatory response play critical roles in the pathogenesis of rhabdomyolysis-induced AKI. The present study aimed to investigate the short-term effects of both lipid peroxidation and inflammatory responses on rhabdomyolysis-induced AKI in a rat model of glycerol-induced rhabdomyolysis. Rhabdomyolysis was induced by the intramuscular injection of 50% glycerol in saline (10 mL/kg) into the hind limbs of rats...
August 16, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27483401/-not-available
#5
Jörg Carlsson, Thony Ragnarsson, Tom Danielsson, Therése Johansson, Hendrik Schreyer, Antonia Breyne, Patrick Bergman
Biochemical changes after strenuous exercise - data from the Kalmar Ironman Strenuous and prolonged exercise like marathon, ultra running and triathlon can lead to changes in biomarkers of cardiac, muscle and kidney functional damage. We present the data of 30 (15 men, 15 women) participants of the Kalmar Ironman 2015. Pre-race electrocardiograms and echocardiograms showed a high frequency of abnormalities. Post race elevations of troponin T, creatine kinase, myoglobin, N-terminal prohormone of brain natriuretic peptide, and creatinine returned to normal in almost all cases within 5-8 days...
2016: Läkartidningen
https://www.readbyqxmd.com/read/27377078/the-related-risk-factors-analysis-of-snake-bite-induced-acute-kidney-injury
#6
Wei Li, Fang Chen, Shukun Wu
BACKGROUND The pathogenic mechanism of snake-bite induced acute kidney injury (AKI) remains unclear. Analyzing the risk factors for snake-bite induced AKI may provide the guidance needed for AKI prevention and early treatment. MATERIAL AND METHODS This retrospective study included 119 snake-bite patients who were hospitalized at the emergency department of Sichuan Provincial People's Hospital from January 2011 to September 2013. The patients were divided into AKI and non-AKI groups according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline...
July 5, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27329933/the-role-of-myoglobin-degradation-in-nephrotoxicity-after-rhabdomyolysis
#7
Ljubava D Zorova, Irina B Pevzner, Anastasia A Chupyrkina, Savva D Zorov, Denis N Silachev, Egor Y Plotnikov, Dmitry B Zorov
The fate of myoglobin in renal cells was explored in an animal model of rhabdomyolysis known as the pathology highly related to oxidative stress resulting in impairment of renal functioning. The working hypothesis was that the proper degradation of myoglobin in rhabdomyolytic kidney can activate the reparative processes in the tissue. We found that incubation of myoglobin with kidney cells causes its accumulation in the cytoplasm. In rhabdomyolytic rats, the level of heme and free iron in cytoplasm and mitochondria of kidney cells is remarkably increased while inhibition of proteolysis results in further elevation of myoglobin content in the renal tissue...
August 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27162559/cd163-macrophages-are-involved-in-rhabdomyolysis-induced-kidney-injury-and-may-be-detected-by-mri-with-targeted-gold-coated-iron-oxide-nanoparticles
#8
Alfonso Rubio-Navarro, Mónica Carril, Daniel Padro, Melanie Guerrero-Hue, Carlos Tarín, Rafael Samaniego, Pablo Cannata, Ainhoa Cano, Juan Manuel Amaro Villalobos, Ángel Manuel Sevillano, Claudia Yuste, Eduardo Gutiérrez, Manuel Praga, Jesús Egido, Juan Antonio Moreno
Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed...
2016: Theranostics
https://www.readbyqxmd.com/read/27034948/rhabdomyolysis-following-cardiac-surgery-a-prospective-descriptive-single-center-study
#9
Amr S Omar, Hesham Ewila, Sameh Aboulnaga, Alejandro Kohn Tuli, Rajvir Singh
PURPOSE: Rhabdomyolysis (RML) following cardiac surgery and its relationship with acute kidney injury (AKI) require investigation. PATIENTS AND METHODS: All patients undergoing cardiac surgery in our hospital were enrolled in this prospective study during a 1-year period. To investigate the occurrence of RML and its association with AKI, all patients in the study underwent serial assessment of serum creatine kinase (CK) and myoglobin levels. Serial renal function, prior statin treatment, and outcome variables were recorded...
2016: BioMed Research International
https://www.readbyqxmd.com/read/26995204/snakebite-envenoming-by-sochurek-s-saw-scaled-viper-echis-carinatus-sochureki
#10
Jiří Valenta, Zdeněk Stach, Pavel Michálek
A snake breeder, 47-years-old man, was bitten by the saw-scaled viper (Echis carinatus sochureki). After admission to Toxinology Centre, within 1.5 h, laboratory evaluation showed clotting times prolonged to non-measurable values, afibrinogenaemia, significantly elevated D-dimers, haemolysis and myoglobin elevation. Currently unavailable antivenom was urgently imported and administered within 10 hours. In 24 hours, oligoanuric acute kidney injury (AKI) and mild acute respiratory distress syndrome (ARDS) developed...
2016: Prague Medical Report
https://www.readbyqxmd.com/read/26987113/penehyclidine-hydrochloride-pretreatment-ameliorates-rhabdomyolysis-induced-aki-by-activating-the-nrf2-ho-1-pathway-and-alleviating-corrected-endoplasmic-reticulum-stress-in-rats-the
#11
Wei Zhao, XuDong Huang, LiXia Zhang, XinJun Yang, LiHui Wang, YunShuang Chen, JingHua Wang, GuangLi Wu
Acute kidney injury (AKI) is one of the most severe complications of rhabdomyolysis (RM). The underlying mechanisms and potential preventions need to be investigated. Penehyclidine hydrochloride (PHC) was reported to ameliorate renal ischemia-reperfusion injury, but the effect of PHC on RM-reduced AKI is unknown. In this study, we established a rat model of RM-induced AKI using an intramuscular glycerol injection in the hind limbs. Rats were pretreated with PHC before the glycerol injection, and the heme oxygenase-1 (HO-1) inhibitor ZnPP was introduced to evaluate the effect of HO-1 on RM-induced AKI...
2016: PloS One
https://www.readbyqxmd.com/read/26888609/fatal-rhabdomyolysis-after-torture-by-reverse-hanging
#12
Michael S Pollanen
PURPOSE: Reverse hanging (also known as Palestinian hanging) is a form of positional torture where the victim is suspended for a prolonged period of time by the wrists, after the wrists are bound at the back. We report the first autopsy case of reverse hanging. We have discovered that fatal myoglobinuric renal failure due to rhabdomyolysis can be a complication of Palestinian hanging. METHOD: An adult detainee, who underwent interrogation by authorities, was admitted to hospital from a prison and died in hospital after a few days...
June 2016: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/26734834/myalgias-and-myopathies-rhabdomyolysis
#13
REVIEW
Courtney Dawley
Rhabdomyolysis is the rapid breakdown of skeletal muscle with release of electrolytes, myoglobin, and other proteins into the circulation. The clinical presentation encompasses a spectrum of patients ranging from those with asymptomatic increases in creatine kinase (CK) levels to those with fulminant disease complicated by acute kidney injury (AKI), severe electrolyte abnormalities, compartment syndrome, and disseminated intravascular coagulation. A CK level at least 10 times the upper limit of normal typically is considered diagnostic, as is myoglobinuria...
January 2016: FP Essentials
https://www.readbyqxmd.com/read/26664265/clinical-and-laboratory-responses-of-cross-country-skiing-for-a-24-h-world-record-case-report
#14
Markus Niemelä, Jukka Juvonen, Päivikki Kangastupa, Onni Niemelä, Tatu Juvonen
The physiological consequences of ultra-endurance cross-country skiing in cold conditions are poorly known. We report here clinical, echocardiographic and laboratory findings from a 41-y old male elite skier in a world record trial for 24-h skiing. The athlete completed a total of 406.8 km outdoors with the temperature ranging between -24°C and -5°C during the 24-h period. Post exercise, notable increases from baseline values were observed in myoglobin (50-fold), creatinine kinase (30-fold) and proBNP (6-fold), whereas troponin T or troponin I levels remained unchanged...
December 2015: Journal of Sports Science & Medicine
https://www.readbyqxmd.com/read/26512883/molecular-mechanisms-and-novel-therapeutic-approaches-to-rhabdomyolysis-induced-acute-kidney-injury
#15
REVIEW
Nayara Panizo, Alfonso Rubio-Navarro, Juan Manuel Amaro-Villalobos, Jesús Egido, Juan Antonio Moreno
Rhabdomyolysis is a syndrome caused by injury to skeletal muscle that usually leads to acute kidney injury (AKI). Rhabdomyolysis has been linked to different conditions, including severe trauma and intense physical exercise. Myoglobin-induced renal toxicity plays a key role in rhabdomyolysis-associated kidney damage by increasing oxidative stress, inflammation, endothelial dysfunction, vasoconstriction, and apoptosis. New drugs that target the harmful effects of myoglobin have been recently developed, and some have been proven to be successful in animal models of acute renal failure secondary to rhabdomyolysis...
2015: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/26354573/acute-kidney-injury-a-rare-cause
#16
Satish Mendonca, Satish Barki, Mayank Mishra, R S V Kumar, Devika Gupta, Pooja Gupta
We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts...
September 2015: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/26183475/adaptation-of-iron-requirement-to-hypoxic-conditions-at-high-altitude
#17
REVIEW
Max Gassmann, Martina U Muckenthaler
Adequate acclimatization time to enable adjustment to hypoxic conditions is one of the most important aspects for mountaineers ascending to high altitude. Accordingly, most reviews emphasize mechanisms that cope with reduced oxygen supply. However, during sojourns to high altitude adjustment to elevated iron demand is equally critical. Thus in this review we focus on the interaction between oxygen and iron homeostasis. We review the role of iron 1) in the oxygen sensing process and erythropoietin (Epo) synthesis, 2) in gene expression control mediated by the hypoxia-inducible factor-2 (HIF-2), and 3) as an oxygen carrier in hemoglobin, myoglobin, and cytochromes...
December 15, 2015: Journal of Applied Physiology
https://www.readbyqxmd.com/read/26174727/rhabdomyolysis-and-acute-kidney-injury-in-dengue-fever
#18
Arvind Mishra, Varun Kumar Singh, Satyan Nanda
Rhabdomyolysis is a rare but potentially lethal complication of severe dengue fever. We present a case of 21-year-old man with fever, bodyache and black coloured and decreasing amount of urine. He was positive for NS1 (non-structural protein-1) antigen and IgM antibody for dengue. Platelet count was below 20 × 10(9)/L and kidney function test was deranged. Urine was positive for myoglobin. The patient was managed emergently on conservative lines and improved in 10 days. Rhabdomyolysis should always be kept in mind in a patient with severe dengue, as its early detection and prompt management can prevent further progression to acute renal failure...
2015: BMJ Case Reports
https://www.readbyqxmd.com/read/26155510/acute-kidney-injury-and-quadriparesis-due-to-rosuvastatin-induced-rhabdomyolysis-a-case-report
#19
Kamlesh S Suthar, Aruna V Vanikar, Hargovind L Trivedi
Statins as lipid lowering drugs, are safe and effective in reducing cardiovascular disease risk, but rarely produce myopathy like myalgia, myositis or rhabdomyolysis. We report the case of Rosuvastatin induced rhabdomyolytic acute renal failure and quadriparesis in a 67-year old male, a known case of type-2 diabetes mellitus and with a history of coronary angioplasty four months back. He was on antihypertensive, oral hypoglycemic and antiplatelet medications with Rosuvastatin 40mg/day. He was admitted with altered sensorium, breathlessness, vomiting, muscle weakness and decreased urine output and had raised serum creatinine, creatinine phosphokinase and myoglobin...
May 2015: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/26117289/marked-protection-against-acute-renal-and-hepatic-injury-after-nitrited-myoglobin-tin-protoporphyrin-administration
#20
Richard A Zager
The phenomenon known as renal "ischemic preconditioning," whereby an initial ischemic insult induces resistance against subsequent kidney damage, has been well established in the experimental literature. However, a clinically applicable way to safely recapitulate this state has not been defined. We hypothesized that a unique combination of agents (nitrited myoglobin [N-Mgb] + tin protoporphyrin [SnPP]) can achieve these ends safely and synergistically, increasing cytoprotective proteins (eg, heme oxygenase 1 [HO-1], interleukin 10 [IL-10], and haptoglobin) in kidney cells...
November 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
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