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https://www.readbyqxmd.com/read/28448685/adult-neurobehavioral-alterations-in-male-and-female-mice-following-developmental-exposure-to-paracetamol-acetaminophen-characterization-of-a-critical-period
#1
Gaëtan Philippot, Torsten Gordh, Anders Fredriksson, Henrik Viberg
Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected...
April 27, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28447858/risk-prediction-of-hepatotoxicity-in-paracetamol-poisoning
#2
Anselm Wong, Andis Graudins
CONTEXT: Paracetamol (acetaminophen) poisoning is the most common cause of acute liver failure in the developed world. A paracetamol treatment nomogram has been used for over four decades to help determine whether patients will develop hepatotoxicity without acetylcysteine treatment, and thus indicates those needing treatment. Despite this, a small proportion of patients still develop hepatotoxicity. More accurate risk predictors would be useful to increase the early detection of patients with the potential to develop hepatotoxicity despite acetylcysteine treatment...
April 27, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28435077/improving-blend-content-uniformity-via-dry-particle-coating-of-micronized-drug-powders
#3
Zhonghui Huang, Wannan Xiong, Kuriakose Kunnath, Sayani Bhaumik, Rajesh N Davé
Content uniformity of low dose blends with fine active pharmaceutical ingredients (API) is adversely impacted due to API agglomeration caused by high powder cohesion. Dry coating using high-intensity vibratory mixing is employed to reduce API cohesion and granular Bond number as well as agglomeration as predicted by contact models, hence improve blend content uniformity (CU). Micronized acetaminophen (mAPAP) (~10μm), a model API, was dry coated with nano-silica R972P (20nm), and mixed with Avicel 102. The amount of silica was varied from 0 to 2...
April 20, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28432019/feasibility-of-mini-tablets-as-a-flexible-drug-delivery-tool
#4
Biplob Mitra, Jessica Chang, Sy-Juen Wu, Chad N Wolfe, Robert L Ternik, Thomas Z Gunter, Michael C Victor
Mini-tablets have potential applications as a flexible drug delivery tool in addition to their generally perceived use as multi-particulates. That is, mini-tablets could provide flexibility in dose finding studies and/or allow for combination therapies in the clinic. Moreover, mini-tablets with well controlled quality attributes could be a prudent choice for administering solid dosage forms as a single unit or composite of multiple mini-tablets in patient populations with swallowing difficulties (e.g., pediatric and geriatric populations)...
April 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28429935/saponins-ginsenosides-from-the-leaves-of-panax-quinquefolius-ameliorated-acetaminophen-induced-hepatotoxicity-in-mice
#5
Xing-Yue Xu, Jun-Nan Hu, Zhi Liu, Rui Zhang, Yu-Fang He, Wei Hou, Zhi-Qing Wang, Ge Yang, Wei Li
Acetaminophen (APAP) overdose is one of the most common inducements of drug-induced liver injury (DILI) in the world. The main purpose of this paper was to investigate the liver protection activity of saponins (ginsenosides) from the leaves of Panax quinquefolius (PQS) against APAP-induced hepatotoxicity, and the involved mechanisms were demonstrated for the first time. Mice were pretreated with PQS (150 and 300 mg/kg) by oral gavage for 7 days before being treated with 250 mg/kg APAP. Severe liver injury was exerted at 24 h post-APAP, and hepatotoxicity was assessed...
April 25, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28419483/pharmacokinetic-study-of-intravenous-acetaminophen-administered-to-critically-ill-multiple-trauma-patients-at-the-usual-dosage-and-a-new-proposal-for-administration
#6
Oscar Fuster-Lluch, Pedro Zapater-Hernández, Manuel Gerónimo-Pardo
The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen...
April 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28412881/glutathione-s-transferase-a1-gsta1-as-a-marker-of-acetaminophen-induced-hepatocyte-injury-in-vitro
#7
Rui Li, Fangping Liu, Yicong Chang, Xin Ma, Minmin Li, Changwen Li, Chenxi Shi, Jingshan He, Ying Li, Zhi Li, Yuexia Lin, Qing Han, Yulin Zhao, Dening Wang
Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1 (GSTA1) plays a significant role in the metabolism of APAP. Primary mouse hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and determine whether GSTA1 could be a prognostic marker in vitro. A significant increase (p<0.05) in GSTA1 in cell culture supernatant was detected at 6 h after APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) showed marked differences (p<0...
April 16, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28410226/use-of-acetaminophen-and-risk-of-endometrial-cancer-evidence-from-observational-studies
#8
Yuan-Yuan Ding, Peng Yao, Surya Verma, Zhen-Kai Han, Tao Hong, Yong-Qiang Zhu, Hong-Xi Li
Previous meta-analyses suggested that aspirin was associated with reduced risk of endometrial cancer. However, there has been no study comprehensively summarize the evidence of acetaminophen use and risk of endometrial cancer from observational studies. We systematically searched electronic databases (PubMed , EMBASE, Web of Science, and Cochrane Library) for relevant cohort or case-control studies up to February 28, 2017. Two independent authors performed the eligibility evaluation and data extraction. All differences were resolved by discussion...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409533/control-of-oxygen-tension-recapitulates-zone-specific-functions-in-human-liver-microphysiology-systems
#9
Felipe T Lee-Montiel, Subin M George, Albert H Gough, Anup D Sharma, Juanfang Wu, Richard DeBiasio, Lawrence A Vernetti, D Lansing Taylor
This article describes our next generation human Liver Acinus MicroPhysiology System (LAMPS). The key demonstration of this study was that Zone 1 and Zone 3 microenvironments can be established by controlling the oxygen tension in individual devices over the range of ca. 3 to 13%. The oxygen tension was computationally modeled using input on the microfluidic device dimensions, numbers of cells, oxygen consumption rates of hepatocytes, the diffusion coefficients of oxygen in different materials and the flow rate of media in the MicroPhysiology System (MPS)...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28393561/hsp72-is-an-early-biomarker-to-detect-cisplatin-and-acetaminophen-nephrotoxicity
#10
Rosalba Pérez-Villalva, Jonatan Barrera-Chimal, Juan Carlos Aguilar-Carrasco, Ixchel Lima-Posada, Cristino Cruz, Victoria Ramirez, Yvett González-Bobadilla, Norma Uribe, Laura Trumper, Norma A Bobadilla
OBJECTIVE: To evaluate whether the urinary HSP72 levels (uHSP72) are a useful biomarker for early diagnosis of AKI induced by two widely used drugs: cisplatin and acetaminophen. MATERIALS AND METHODS: To analyze the time-course of nephrotoxic injury and uHSP72 levels, male Wistar rats were administered a single high dose of cisplatin (7-mg/kg) or acetaminophen (750- mg/kg) and were assessed at 6, 12, 24, 48, 72, 96 and 120-h. RESULTS: AKI induced by cisplatin was characterized by tubular injury that started at 6-h and was enhanced 48-h after...
April 10, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/28392133/patients-at-risk-large-opioid-prescriptions-after-total-knee-arthroplasty
#11
Nicholas M Hernandez, Joshua A Parry, Michael J Taunton
BACKGROUND: Opioids are an effective, and often necessary, treatment of postoperative pain after total knee arthroplasty (TKA). However, it is often difficult to know how much medication patients will need after discharge. The purpose of this study was to determine if patients discharged with greater quantities of opioids after TKA are more likely to request refills. METHODS: This is a retrospective review of 105 primary TKAs performed with at least 1 year of follow-up...
March 2, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28386382/protective-effects-of-an-ethanol-extract-of-angelica-keiskei-against-acetaminophen-induced-hepatotoxicity-in-hepg2-and-heparg-cells
#12
Yoon-Hee Choi, Hyun Sook Lee, Cha-Kwon Chung, Eun Ji Kim, Il-Jun Kang
BACKGROUND/OBJECTIVE: Although Angelica keiskei (AK) has widely been utilized for the purpose of general health improvement among Asian, its functionality and mechanism of action. The aim of this study was to determine the protective effect of ethanol extract of AK (AK-Ex) on acute hepatotoxicity induced by acetaminophen (AAP) in HepG2 human hepatocellular liver carcinoma cells and HepaRG human hepatic progenitor cells. MATERIALS/METHODS: AK-Ex was prepared HepG2 and HepaRG cells were cultured with various concentrations and 30 mM AAP...
April 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28382198/adverse-drug-reactions-in-therapeutic-hypothermia-after-cardiac-arrest
#13
Robert Witcher, Amy L Dzierba, Catherine Kim, Pamela L Smithburger, Sandra L Kane-Gill
BACKGROUND: Therapeutic hypothermia (TH) improves survival and neurologic function in comatose survivors of cardiac arrest. Many medications used to support TH have altered pharmacokinetics and pharmacodynamics during this treatment. It is unknown if or at what frequency the medications used during TH cause adverse drug reactions (ADRs). METHODS: A retrospective chart review was conducted for patients admitted to an intensive care unit (ICU) after cardiac arrest and treated with TH from January 2009 to June 2012 at two urban, university-affiliated, tertiary-care medical centres...
March 2017: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/28379590/hepatotoxicity-of-paracetamol-and-related-fatalities
#14
R Tittarelli, M Pellegrini, M G Scarpellini, E Marinelli, V Bruti, N M di Luca, F P Busardò, S Zaami
Paracetamol, also known as acetaminophen, is the most commonly used antipyretic and pain reliever and since 1955 it is available over-the-counter as a single formulation or in combination with other substances and, as indicated by the World Health Organization, it can be used in all the three steps of pain intensity. Paracetamol toxicity is one of the most common causes of poisoning worldwide. While paracetamol is described as relatively nontoxic when administered in therapeutic doses, it is known to cause toxicity when taken in a single or repeated high dose, or after chronic ingestion...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28378356/effect-of-an-orally-formulated-processed-black-cumin-from-iranian-traditional-medicine-pharmacopoeia-in-relieving-symptoms-of-knee-osteoarthritis-a-prospective-randomized-double-blind-and-placebo-controlled-clinical-trial
#15
Ahmad Salimzadeh, Anahita Ghourchian, Rasool Choopani, Homa Hajimehdipoor, Mohammad Kamalinejad, Maryam Abolhasani
AIM: Osteoarthritis is a global health problem, especially for the elderly. A good replacement for non-surgical treatments is the use of traditional medicines. We selected a revere plant (Nigella sativa L.), a widely utilized medicinal herb for the treatment of inflammatory conditions, from the Iranian traditional medicine (ITM) pharmacopoeia with proven anti-inflammatory and analgesic actions. METHODS: We performed a prospective, randomized, double-blind, and placebo-controlled clinical trial, in order to investigate whether the herb is useful in alleviating the symptoms of knee osteoarthritis...
April 5, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28376392/multi-targeted-protection-of-acetaminophen-induced-hepatotoxicity-in-mice-by-tannic-acid
#16
Jianping Zhang, Qiongtao Song, Xue Han, Yuanyuan Zhang, Ying Zhang, Xuan Zhang, Xi Chu, Fenghua Zhang, Li Chu
Tannic acid (TA) is the polyphenol that has beneficial health effects against oxidative stress. However, the hepatoprotective effects of TA are still relatively unknown. In the present study, we evaluated the effects of TA on an acetaminophen (APAP)-induced hepatotoxicity model, which was established by administration of 400mg/kg of APAP. The levels of alanine transferase (ALT), aspartate transferase (AST), dendothelin-1 (ET-1), nitric oxide (NO) and malondialdehyde (MDA) in the APAP-induced hepatotoxicity mice were significantly increased (up to ~200%), while their levels were reduced by pretreatment with TA (25 and 50mg/kg) (P<0...
April 1, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28374970/human-bj-fibroblasts-is-an-alternative-to-mouse-balb-c-3t3-cells-in-in-vitro-neutral-red-uptake-assay
#17
Marika Mannerström, Tarja Toimela, Jertta-Riina Sarkanen, Tuula Heinonen
The OECD GD 129 BALB/c 3T3 Neutral Red Uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in our GLP laboratory. Subsequently, in order to obtain more human relevant cytotoxicity data, we performed an intra-laboratory validation using human BJ fibroblasts in the NRU assay instead of mouse BALB/c 3T3 fibroblasts...
April 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28359199/protective-effect-of-cymbopogon-citratus-essential-oil-in-experimental-model-of-acetaminophen-induced-liver-injury
#18
Nancy Sayuri Uchida, Saulo Euclides Silva-Filho, Rafael Pazinatto Aguiar, Luiz Alexandre Marques Wiirzler, Gabriel Fernando Esteves Cardia, Heitor Augusto Otaviano Cavalcante, Francielli Maria de Souza Silva-Comar, Tânia Cristina Alexandrino Becker, Expedito Leite Silva, Ciomar Aparecida Bersani-Amado, Roberto Kenji Nakamura Cuman
To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO...
March 30, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28345743/opioids-and-nonopioids-for-postoperative-pain-control-in-patients-with-chronic-kidney-disease
#19
Michele Binhas, Julia Egbeola-Martial, Michael D Kluger, Francoise Roudot-Thoraval, Philippe Grimbert
OBJECTIVES: To evaluate postoperative pain management (POPM) practices by anesthesiologists caring for patients with chronic kidney disease (CKD). DESIGN: Prospective one-time survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR). SETTING: A self-administered online questionnaire was distributed to members of SFAR nationally. PARTICIPANTS: Three hundred seven SFAR members participated in the study...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28344490/comparison-of-physicochemical-properties-of-suppositories-containing-starch-hydrolysates
#20
Piotr Belniak, Katarzyna Świąder, Michał Szumiło, Aleksandra Hyla, Ewa Poleszak
The purpose of this work was to determine the effect of starch hydrolysates (SH) on the physicochemical properties of suppositories. The study was conducted with suppositories with acetaminophen (AAP) a typical antipyretic analgesic, as model drug on lipophilic (cocoa butter) and hydrophilic base (polyethylene glycol 1500 + 400). The suppositories with and without the addition of SH were examined for physicochemical tests according to European Pharmacopoeia 8th edition (Ph. Eur.): the uniformity of mass of single-dose preparation test, the softening time determination of lipophilic suppositories test, the disintegration of suppositories test, and dissolution test with flow-through apparatus...
March 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
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