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https://www.readbyqxmd.com/read/28225807/increased-liver-specific-proteins-in-circulating-extracellular-vesicles-as-potential-biomarkers-for-drug-and-alcohol-induced-liver-injury
#1
Young-Eun Cho, Eun-Ju Im, Pyong-Gon Moon, Esteban Mezey, Byoung-Joon Song, Moon-Chang Baek
Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury...
2017: PloS One
https://www.readbyqxmd.com/read/28216953/therapeutic-potential-of-alpha-ketoglutarate-against-acetaminophen-induced-hepatotoxicity-in-rats
#2
Lalita Mehra, Yasha Hasija, Gaurav Mittal
OBJECTIVE: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28215574/the-impact-of-pharmacy-services-on-opioid-prescribing-in-dental%C3%A2-practice
#3
Autumn Stewart, Kelsey J Zborovancik, Kara L Stiely
OBJECTIVES: To compare rates of dental opioid prescribing between periods of full and partial integration of pharmacy services and periods of no integration. METHODS: This observational study used a retrospective chart review of opioid prescriptions written by dental providers practicing in a free dental clinic for the medically underserved over a period of 74 months. Pharmacy services were fully integrated into the practice model for 48 of the 74 months under study...
February 15, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28213943/a-phase-2-safety-study-of-accelerated-elotuzumab-infusion-over-less-than-1-hour-in-combination-with-lenalidomide-and-dexamethasone-in-patients-with-multiple-myeloma
#4
James Berenson, Robert Manges, Suprith Badarinath, Alan Cartmell, Kristi McIntyre, Roger Lyons, Wael Harb, Hesham Mohamed, Ali Nourbakhsh, Robert Rifkin
Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, ∼3-hour infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM...
February 18, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28210203/wnt-%C3%AE-catenin-signaling-drives-thioacetamide-mediated-heteroprotection-against-acetaminophen-induced-lethal-liver-injury
#5
Vivekkumar P Dadhania, Bharat Bhushan, Udayan Apte, Harihara M Mehendale
Preplacement of compensatory tissue repair (CTR) by exposure to a nonlethal dose of a toxicant protects animals against a lethal dose of another toxicant. Although CTR is known to heteroprotect, the underlying molecular mechanisms are not completely known. Here, we investigated the mechanisms of heteroprotection using thioacetamide (TA): acetaminophen (APAP) heteroprotection model. Male Swiss Webster mice received a low dose of TA or distilled water (DW) vehicle 24 hours prior to a lethal dose of APAP. Liver injury, tissue repair, and promitogenic signaling were studied over a time course of 24 hours after APAP overdose to the TA- and DW-primed mice (TA + APAP and DW + APAP, respectively)...
January 2017: Dose-response: a Publication of International Hormesis Society
https://www.readbyqxmd.com/read/28209544/sestrin2-protects-against-acetaminophen-induced-liver-injury
#6
Seung Jung Kim, Kyu Min Kim, Ji Hye Yang, Sam Seok Cho, Sang Kyu Lee, Sae Kwang Ku, Il Je Cho, Sung Hwan Ki
Acetaminophen (APAP) overdose accounts for half of the cases of acute liver failure worldwide. We previously reported that that Sestrin2 (Sesn2) protects against d-galactosamine/lipopolysaccharide-induced acute fulminant liver failure. In this study, we demonstrated that Sesn2 protects APAP-induced liver injury in mice, using a recombinant adenovirus encoding Sesn2 (Ad-Sesn2). First, we found that treatment of mice with toxic levels of APAP significantly reduced Sesn2 expression. Tail-vein injection with Ad-Sesn2 inhibited APAP-induced serum alanine aminotransferase and aspartate aminotransferase levels and markedly reduced hepatocyte degeneration and inflammatory cell infiltration...
February 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28205121/effect-of-n-acetylcysteine-on-mortality-and-liver-transplantation-rate-in-non-acetaminophen-induced-acute-liver-failure-a-multicenter-study
#7
Samar K Darweesh, Mona F Ibrahim, Mahmoud A El-Tahawy
INTRODUCTION AND AIM: Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF. PATIENTS AND METHODS: In a prospective, multicenter, observational study, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were enrolled...
February 15, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28181214/aspirin-single-dose-for-perineal-pain-in-the-early-postpartum-period
#8
REVIEW
Sujana Molakatalla, Emily Shepherd, Rosalie M Grivell
BACKGROUND: Perineal trauma (due to spontaneous tears, surgical incision (episiotomy) or in association with operative vaginal birth) is common after vaginal birth, and is often associated with postpartum perineal pain. Birth over an intact perineum may also lead to perineal pain. There are adverse health consequences associated with perineal pain for the women and their babies in the short- and long-term, and the pain may interfere with newborn care and the establishment of breastfeeding...
February 9, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28177174/a-case-controlled-comparison-of-postoperative-analgesic-dosing-between-girls-with-rett-syndrome-and-girls-with-and-without-developmental-disability-undergoing-spinal-fusion-surgery
#9
Chantel C Barney, Alyssa M Merbler, Kelsey Quest, Breanne J Byiers, George L Wilcox, Scott Schwantes, Samuel A Roiko, Timothy Feyma, Arthur Beisang, Frank J Symons
BACKGROUND: Rett syndrome is associated with severe motor and communicative impairment making optimal postoperative pain management a challenge. There are case reports documenting reduced postoperative analgesic requirement in Rett syndrome. AIM: The goal of this preliminary investigation was to compare postoperative analgesic management among a sample of girls with Rett syndrome compared to girls with and without developmental disability undergoing spinal fusion surgery...
March 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28153389/gold-nanoparticles-ameliorate-acetaminophen-induced-hepato-renal-injury-in-rats
#10
Mohd Salim Reshi, Sadhana Shrivastava, Amita Jaswal, Neelu Sinha, Chhavi Uthra, Sangeeta Shukla
Valuable effects of gold particles have been reported and used in complementary medicine for decades. The aim of this study was to evaluate the therapeutic efficacy of gold nanoparticles (AuNPs) against acetaminophen (APAP) induced toxicity. Albino rats were administered APAP at a dose of 2g/kg p.o. once only. After 24h of APAP intoxication, animals were treated with three different doses of AuNPs (50μg/kg, 100μg/kg, 150μg/kg) orally or silymarin at a dose of 50mg/kg p.o., once only. Animals of all the groups were sacrificed after 24h of last treatment...
January 30, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28152447/astaxanthin-pretreatment-attenuates-acetaminophen-induced-liver-injury-in-mice
#11
Jingyao Zhang, Simin Zhang, Jianbin Bi, Jingxian Gu, Yan Deng, Chang Liu
BACKGROUND: Acetaminophen (APAP) is a conventional drug widely used in the clinic because of its antipyretic-analgesic effects. However, accidental or intentional APAP overdoses induce liver injury and even acute liver failure (ALF). Astaxanthin (ASX) is the strongest antioxidant in nature that shows preventive and therapeutic properties, such as ocular protection, anti-tumor, anti-diabetes, anti-inflammatory, and immunomodulatory effects. The aim of present study was to determine whether ASX pretreatment provides protection against APAP-induced liver failure...
January 31, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28150939/antinociceptive-effects-of-a-novel-%C3%AE-2-%C3%AE-3-subtype-selective-gabaa-receptor-positive-allosteric-modulator
#12
Lakeisha A Lewter, Janet L Fisher, Justin N Siemian, Kashi Reddy Methuku, Michael M Poe, James M Cook, Jun-Xu Li
Pain remains a challenging clinical condition and spinal GABAA receptors are crucial modulators of pain processing. α2/α3-subtype GABAA receptors mediate the analgesic actions of benzodiazepines. Positive allosteric modulators (PAMs) at α2/α3-subtype GABAA receptors may have analgesic potential. Here we report a new selective α2/α3-subtype GABAA receptor PAM in in vitro and in vivo pain assays. KRM-II-81 demonstrated similar efficacy at α1/α2/α3 GABAA receptors and negligible efficacy at α4/α5/α6 GABAA receptors, with α2 and α3-subtypes being 17- and 28-fold more potent than α1 subtypes in HEK-293T cells expressing GABAA receptors with different α subunits...
February 2, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28143430/a-multicenter-randomized-open-label-active-comparator-trial-to-determine-the-efficacy-safety-and-pharmacokinetics-of-intravenous-ibuprofen-for-treatment-of-fever-in-hospitalized-pediatric-patients
#13
Samia N Khalil, Barry J Hahn, Corrie E Chumpitazi, Amy D Rock, Byron A Kaelin, Charles G Macias
BACKGROUND: Oral antipyretics are commonly used to treat pediatric patients who develop fevers. However, patients presenting to the emergency department or undergoing surgery are frequently unable to tolerate oral antipyretics. Rectal formulations are available; however, this route of administration is unpredictable. The main objectives of this randomized controlled study was to evaluate the efficacy and safety of single or multiple doses of intravenous ibuprofen to acetaminophen (oral or suppository) in pediatric patients with fever and to assess plasma ibuprofen concentrations...
February 1, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28134251/low-dose-acetaminophen-induces-early-disruption-of-cell-cell-tight-junctions-in-human-hepatic-cells-and-mouse-liver
#14
Wesam Gamal, Philipp Treskes, Kay Samuel, Gareth J Sullivan, Richard Siller, Vlastimil Srsen, Katie Morgan, Anna Bryans, Ada Kozlowska, Andreas Koulovasilopoulos, Ian Underwood, Stewart Smith, Jorge Del-Pozo, Sharon Moss, Alexandra Inés Thompson, Neil C Henderson, Peter C Hayes, John N Plevris, Pierre-Olivier Bagnaninchi, Leonard J Nelson
Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28128086/vesicular-contact-reaction-may-progress-into-erythema-multiforme
#15
Magdalena Czarnecka-Operacz, Dorota Jenerowicz, Joanna Szulczyńska-Gabor, Ewa Teresiak-Mikołajczak, Joanna Szyfter-Harris, Monika Bowszyc-Dmochowska
Dear Editor, Erythema multiforme is considered an acute skin condition, characterized by a self-limiting and sometimes recurrent course. It is regarded as a type IV hypersensitivity reaction associated with certain infections, medications, and other various triggers. Allergic contact dermatitis is in turn a delayed type of induced allergy as a result of cutaneous contact with a specific allergen to which the patient develops specific sensitivity. This type of cutaneous reaction is associated with inflammation manifesting with erythema, edema, and vesicles...
December 2016: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28125554/o-006-rapid-infliximab-infusion-in-children-with-inflammatory-bowel-disease-a-multi-center-north-american-experience
#16
Wael El-Matary, Charles Samson, Alisa Crim, Sabina Ali, Andrew Grossman
BACKGROUND: Infusions of infliximab (IFX), a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α) used to treat inflammatory bowel disease (IBD), can lead to development of anti-IFX antibodies (ATI), increasing risk of subsequent infusion reactions (IRs). IRs have been reported in as many as 5% of infusions and up to 10% to 20% of patients. The safety of rapid IFX infusion has been under-evaluated in children. In a multi-center study, the incidence of IRs associated with rapid infusion of IFX was examined...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28123123/-acute-phase-reaction-following-bisphosphonates
#17
Hiroshi Tsurukami
Bisphosphonates are effective in decreasing bone resorption, the incidence of fragility fracure, and pain from bone metastases. Although relatively well tolerated, the initial dose(s)of intravenous or oral monthly aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia within 3 days of dosing and lasting 7 days or less. Nitrogen-BPs(N-BPs)inhibit osteoclast function by acting as potent inhibitors of the enzyme farnesyl diphosphate(FPP)synthase in the mevalonate biosynthetic pathway...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28123000/dual-role-of-epidermal-growth-factor-receptor-in-liver-injury-and-regeneration-after-acetaminophen-overdose-in-mice
#18
Bharat Bhushan, Hemantkumar Chavan, Prachi Borude, Yuchao Xie, Kuo Du, Mitchell R McGill, Margitta Lebofsky, Hartmut Jaeschke, Partha Krishnamurthy, Udayan Apte
Epidermal growth factor receptor (EGFR) plays a crucial role in hepatocyte proliferation. Its role in acetaminophen (APAP)-mediated hepatotoxicity and subsequent liver regeneration is completely unknown. Role of EGFR after APAP-overdose in mice was studied using pharmacological inhibition strategy. Rapid, sustained and dose-dependent activation of EGFR was noted after APAP-treatment in mice, which was triggered by glutathione depletion. EGFR-activation was also observed in primary human hepatocytes after APAP-treatment, preceding elevation of toxicity markers...
February 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28118241/management-of-preschool-recurrent-wheezing-and-asthma-a-phenotype-based-approach
#19
Avraham Beigelman, Leonard B Bacharier
PURPOSE OF REVIEW: The purpose of this review is to summarize the recent evidence on the management of preschool children with wheezing and asthma, and to propose a phenotype-based approach to the management of these children. RECENT FINDINGS: Recent studies have begun to identify populations of preschool children that are likely to benefit from inhaled corticosteroids (ICS) therapy and defined ICS regimens: daily ICS in preschool children with persistent asthma, and pre-emptive high-dose intermittent ICS among preschool children with intermittent disease reduce the risk of exacerbation...
January 21, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28115551/early-detection-of-acute-drug-induced-liver-injury-in-mice-by-non-invasive-nir-fluorescence-imaging
#20
Kristine O Vasquez, Jeffrey D Peterson
Hepatocellular and cholestatic forms of drug induced liver injury (DILI) are major reasons for late stage termination of small molecule drug discovery research projects. Biochemical serum markers are limited in their ability to sensitively and specifically detect both of these common DILI forms in preclinical models, and tissue-specific approaches to assessing this are labor intensive, requiring extensive animal dosing, tissue preparation, and pathology assessment. In vivo fluorescent imaging offers non-invasive detection of biological changes detected directly in the livers of living animals...
January 23, 2017: Journal of Pharmacology and Experimental Therapeutics
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