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Hepatotoxic Medication

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2161. Total phenolic, flavonoid contents, in-vitro antioxidant activities and hepatoprotective effect of aqueous leaf extract of Atalantia ceylanica. Full Text available with Trip Pro

Total phenolic, flavonoid contents, in-vitro antioxidant activities and hepatoprotective effect of aqueous leaf extract of Atalantia ceylanica. Decoction prepared from leaves of Atalantia ceylanica is used in traditional medicine in Sri Lanka for the treatment of various liver ailments since ancient times. Lyophilized powder of the water extract of A. ceylanica leaves was investigated for its phytochemical constituents, antioxidant and hepatoprotective activity in-vitro.The total phenolic (...) and flavonoid contents were determined using Folin Ciocalteu method and aluminium chloride colorimetric assay respectively. The antioxidant activities of the decoction were investigated using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical, nitric oxide scavenging assays and ferric ion reducing power assay. Hepatotoxicity was induced on porcine liver slices with ethanol to study hepatoprotective activity. Porcine liver slices were incubated at 37°C with different concentrations of the water extract

2014 BMC Complementary and Alternative Medicine

2162. Trovafloxacin Potentiation of Lipopolysaccharide-Induced Tumor Necrosis Factor Release from RAW 264.7 Cells Requires Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase Full Text available with Trip Pro

Trovafloxacin Potentiation of Lipopolysaccharide-Induced Tumor Necrosis Factor Release from RAW 264.7 Cells Requires Extracellular Signal-Regulated Kinase and c-Jun N-Terminal Kinase Trovafloxacin (TVX) is a fluoroquinolone antibiotic known to cause idiosyncratic, drug-induced liver injury (IDILI) in humans. The mechanism underlying this toxicity remains unknown. Previously, an animal model of IDILI in mice revealed that TVX synergizes with inflammatory stress from bacterial lipopolysaccharide (...) (LPS) to produce a hepatotoxic interaction. The liver injury required prolongation of the appearance of tumor necrosis factor-α (TNF) in the plasma. The results presented here describe a model of TVX/LPS coexposure in RAW 264.7 cells acting as a surrogate for TNF-releasing cells in vivo. Pretreating cells with TVX for 2 hours before LPS addition led to increased TNF protein release into culture medium in a concentration- and time-dependent manner relative to cells treated with LPS or TVX alone

2014 The Journal of pharmacology and experimental therapeutics

2163. Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease. (Abstract)

Acetaminophen-induced liver injury in obesity and nonalcoholic fatty liver disease. Although acetaminophen (APAP) is usually considered as a safe drug, this painkiller can lead to acute liver failure after overdoses. Moreover, there is evidence that the maximum recommended dosage can induce hepatic cytolysis in some individuals. Several predisposing factors appear to enhance the risk and severity of APAP-induced liver injury including chronic alcoholic liver disease and nonalcoholic fatty liver (...) disease (NAFLD), which refers to a large spectrum of hepatic lesions linked to obesity. In contrast, obesity by itself does not seem to be associated with a higher risk of APAP-induced liver injury. Since 1987, seven studies dealt with APAP-induced hepatotoxicity in rodent models of NAFLD and five of them found that this liver disease was associated with higher APAP toxicity. Unfortunately, these studies did not unequivocally established the mechanism(s) whereby NAFLD could favour APAP hepatotoxicity

2014 Liver International

2164. Panaxatriol saponin ameliorated liver injury by acetaminophen via restoring thioredoxin-1 and pro-caspase-12. (Abstract)

(TRX-1) is an important redox regulator, which plays roles in resisting oxidative stress, regulating inflammation and inhibiting apoptosis. Panaxatriol saponin (PTS) is one of the biologically active fractions of Panax notoginseng which is a traditional Chinese medicine. The aim of this study was to investigate the mechanism on PTS protecting liver from APAP hepatotoxicity.Mice were divided into three groups, control group, APAP group and APAP combined with PTS group. Alanine aminotransferase (ALT (...) ) and tumour necrosis factor-alpha (TNF-α) were detected by ELISA. TRX-1 and pro-caspase-12 were examined by Western blotting.Our results showed PTS inhibited the levels of ALT and TNF-α by APAP. Pretreatment with PTS ameliorated liver injury induced by APAP. The decrease in TRX-1 expression was restored by PTS, as well as decreased pro-caspase-12 expression was inhibited by PTS. These data suggest that PTS has roles in suppressing the hepatotoxicity by APAP.Panaxatriol saponin ameliorated liver injury

2014 Liver International

2165. Non-invasive hepatic biomarkers (ELF and CK18) in people with type 2 diabetes: the Edinburgh type 2 diabetes study. Full Text available with Trip Pro

). Statistically significant associations were found between both biomarkers and a number of metabolic risk factors. Neither CK18 nor ELF was consistently or strongly associated with established hepatic risk factors (alcohol excess, hepatotoxic medication use and positive immunology titres).We identified the distribution of CK18 and ELF in a large cohort of older people with type 2 diabetes and showed that these markers are associated with an adverse metabolic risk factor profile, although much

2014 Liver International

2166. Efficacy and safety of etravirine-containing regimens in a large cohort of HIV/HCV coinfected patients according to liver fibrosis. Full Text available with Trip Pro

Efficacy and safety of etravirine-containing regimens in a large cohort of HIV/HCV coinfected patients according to liver fibrosis. Etravirine has become an alternative in HIV/HCV coinfected patients because of safety and lack of interactions with anti-HCV drugs. The aim of this study was to establish the risk of liver toxicity in HIV/HCV coinfected patients receiving etravirine in the clinical setting, according to the degree of liver fibrosis and different accompanying drugs.Cohort study (...) of 211 patients initiating etravirine as part of their antiretroviral regimen. HCV coinfection was defined as a positive RNA-HCV, whereas baseline liver fibrosis was assessed by transient elastography at baseline. Hepatotoxicity was defined as an increased AST/ALT, 5-fold higher over upper, normal limits for patients with normal baseline values, or 3.5-fold if altered at baseline.HCV coinfection was observed in 145 patients (69%) with a longer time of HIV infection and time on HAART than mono

2014 Journal of the International AIDS Society

2167. Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/HCV-coinfected patients. Preliminary results of the hEPAtic Study. Full Text available with Trip Pro

Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/HCV-coinfected patients. Preliminary results of the hEPAtic Study. Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic events, such as transaminase elevations (TE), are still a matter of concern. RPV/FTC/TDF (EPA) is a new single tablet regimen which is widely used in real life practice. Clinical trials showed an adequate profile of liver safety in the sub-population of HIV/HCV (...) -coinfected patients receiving rilpivirine. However, the number of individuals included in these analyses is low (1). The aim of this ongoing study is to evaluate the incidence of TE and total bilirubin elevations (TBE) during the first 48 weeks of EPA-based therapy in a large population of HIV/HCV-coinfected subjects outside of clinical trials.This is a retrospective analysis of HIV/HCV-coinfected subjects who started EPA at the infectious diseases units of 14 centres throughout Spain, included as cases

2014 Journal of the International AIDS Society

2168. Quinone Methide Bioactivation Pathway: Contribution to Toxicity and/or Cytoprotection? Full Text available with Trip Pro

Quinone Methide Bioactivation Pathway: Contribution to Toxicity and/or Cytoprotection? The formation of quinone methides (QMs) from either direct 2-electron oxidation of 2- or 4-alkylphenols, isomerization of o-quinones, or elimination of a good leaving group could explain the cytotoxic/cytoprotective effects of several drugs, natural products, as well as endogenous compounds. For example, the antiretroviral drug nevirapine and the antidiabetic agent troglitazone both induce idiosyncratic (...) hepatotoxicity through mechanisms involving quinone methide formation. The anesthetic phencyclidine induces psychological side effects potentially through quinone methide mediated covalent modification of crucial macromolecules in the brain. Selective estrogen receptor modulators (SERMs) such as tamoxifen, toremifene, and raloxifene are metabolized to quinone methides which could potentially contribute to endometrial carcinogenic properties and/or induce detoxification enzymes and enhance the chemopreventive

2014 Current Organic Chemistry

2169. Potent Inhibition of Alcohol Self-Administration in Alcohol-Preferring Rats by a κ-Opioid Receptor Antagonist Full Text available with Trip Pro

) and binge-like P-rats. Previous studies showed that compounds closely related to compound 5 possessed favorable properties regarding penetration of the blood-brain barrier. Pharmacokinetic studies showed that compound 5 had acceptable bioavailability. In contrast to other κ-receptor antagonists, in particular norbinaltorphimine, compound 5 showed favorable drug-like properties. Based on these findings, further studies were done. Safety studies showed that compound 5 was not hepatotoxic at doses 200-fold (...) -rats trained to self-administer a 10% (w/v) ethanol solution, using operant techniques, showed very potent efficacy (i.e., estimated ED50 values of 4-5 μg/kg). In a binge-like P-rat animal model, inhibition of alcohol self-administration by compound 5 had an estimated ED50 value of 8 μg/kg. The results suggest that compound 5 is a potent drug-like κ-opioid receptor antagonist of utility in alcohol cessation medications development.Copyright © 2014 by The American Society for Pharmacology

2014 The Journal of pharmacology and experimental therapeutics

2170. Aspirin-Induced Acute Liver Injury Full Text available with Trip Pro

Aspirin-Induced Acute Liver Injury Aspirin is thought to be a relatively safe drug in adults. The association of aspirin and Reye syndrome in children is well documented. We report a 41-year-old female with pericarditis who was treated with high-dose aspirin and developed subsequent acute liver injury. After discontinuation of aspirin, liver enzyme elevation and right upper quadrant pain both resolved. We conclude that high-dose aspirin should be considered as a potentially hepatotoxic agent.

2014 ACG case reports journal

2171. The effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite: paracetamol glucuronide Full Text available with Trip Pro

The effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite: paracetamol glucuronide The study aimed to examine the effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both drugs share metabolic pathways in the liver, and the drug interactions between sunitinib and paracetamol administered in higher doses were reported. These interactions resulted in hepatotoxicity. The adult New Zealand (...) doses, neither of the drugs, whether administered alone or together, had hepatotoxic effects. The present study was not able to confirm that sunitinib, administered at low doses in conjunction with paracetamol, displays a hepatoprotective effect. Significant differences were observed in some pharmacokinetic parameters of paracetamol.

2014 European journal of drug metabolism and pharmacokinetics

2172. MITOsym®: A Mechanistic, Mathematical Model of Hepatocellular Respiration and Bioenergetics Full Text available with Trip Pro

MITOsym®: A Mechanistic, Mathematical Model of Hepatocellular Respiration and Bioenergetics MITOsym, a new mathematical model of hepatocellular respiration and bioenergetics, has been developed in partnership with the DILIsym® model with the purpose of translating in vitro compound screening data into predictions of drug induced liver injury (DILI) risk for patients. The combined efforts of these two models should increase the efficiency of evaluating compounds in drug development in addition (...) such as rotenone, FCCP, and oligomycin.MITOsym can be used to simulate hepatocellular respiration and bioenergetics and provide mechanistic hypotheses to facilitate the translation of in vitro data collection to predictions of in vivo human hepatotoxicity risk for novel compounds.

2014 Pharmaceutical research

2173. A Pilot Study of Allopurinol As A Modifier of 6-MP Metabolism in Pediatric ALL

: September 11, 2018 See Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Study Details Study Description Go to Brief Summary: This research is being done to determine if allopurinol can change the metabolism of the oral chemotherapeutic medication 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL). 6-MP is originally started at a standard dose in children (...) allopurinol with 6-MP can decrease side effects associated with high doses of 6-MP and also increase the efficacy of 6-MP. Allopurinol is approved by the Food and Drug Administration for the treatment of tumor lysis syndrome in ALL. Through this research study, the investigators hope to show that the combination of allopurinol and 6-MP will be safe, tolerable, and effective in children with ALL. Condition or disease Intervention/treatment Phase Acute Lymphoblastic Leukemia (ALL) Drug: Allopurinol Early

2014 Clinical Trials

2174. Fermented soshiho-tang with Lactobacillus plantarum enhances the antiproliferative activity in vascular smooth muscle cell. Full Text available with Trip Pro

Fermented soshiho-tang with Lactobacillus plantarum enhances the antiproliferative activity in vascular smooth muscle cell. Soshiho-tang (SST) is a traditional medicine widely used for the treatment of chronic hepatitis. SST has been shown to confer a variety of pharmacological activities, including prevention of hepatotoxicity, promotion of liver regeneration, and modulation of liver fibrosis. In this study, we investigated the antiproliferative activity of native and fermented (FSST

2014 BMC Complementary and Alternative Medicine

2175. Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial). Full Text available with Trip Pro

Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial). To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.HIV-infected adults with CD4+ T cell count ≤ 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg (...) of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between

2014 PloS one Controlled trial quality: uncertain

2176. Viral Infections of the Mouth (Follow-up)

the neoplastic cells. General medical care Establishing the diagnosis is important because the differential diagnoses include diseases that are conventionally treated with immunosuppressive agents. Immunosuppressive therapy may not be prudent for an active herpetic infection because it could promote dissemination. Herpesvirus infections may trigger erythema multiforme. If recurrences are common and debilitating, long-term suppressive antiviral therapy may reduce the recurrence of herpes and thus erythema (...) prophylactic antiviral medication may be indicated for patients who experience 6 or more recurrences a year or for patients who experience repeated bouts of erythema multiforme induced by herpes. [ ] Medical care for HHV-3 (varicella-zoster virus) Antiviral therapy is most effective in limiting the area of involvement and the duration of the symptoms if instituted within the first 48-72 hours. Acyclovir may control the size of the lesions, but it is less effective than valacyclovir or famciclovir

2014 eMedicine.com

2177. Toxicity, Cocaine (Diagnosis)

. Cocaine may cause generalized tonic and clonic convulsions as well as focal seizures. Intense stimulation of sigma and muscarinic receptors by cocaine and increased synaptic concentration of serotonin have been proposed as causal. Cocaine lowers the threshold for seizures and may produce a kindling effect on neurons that promotes convulsions. Seizure frequency ranges from 1-29%–perhaps reflecting variations in use and concurrent use of other drugs. Of 474 patients with medical complications of cocaine (...) , 2018 Author: Lynn Barkley Burnett, MD, EdD, LLB(c); Chief Editor: Sage W Wiener, MD Share Email Print Feedback Close Sections Sections Cocaine Toxicity Overview Practice Essentials Despite being overshadowed by opioids in recent years, cocaine remains one of the most common causes of drug-related emergency department (ED) visits in the United States. [ ] Although nearly every organ system can be affected by cocaine toxicity, most patients present with cardiovascular complaints. [ ] In addition

2014 eMedicine.com

2178. Toxicity, Mushroom (Diagnosis)

of Emergency Medicine, Washington University School of Medicine Michael E Mullins, MD is a member of the following medical societies: and Disclosure: Johnson & Johnson stock ownership None; Savient Pharmaceuticals stock ownership None Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System Daniel R Ouellette, MD, FCCP is a member of the following medical (...) societies: and Disclosure: Boehringer Ingleheim Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Astra Zeneca Honoraria Speaking and teaching Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut

2014 eMedicine.com

2179. Tuberculous Meningitis (Follow-up)

to , , , , , and for more complete information on these topics. Next: Antibiotic Therapy and Adjunctive Corticosteroid Therapy The best antimicrobial agents in the treatment of TBM include isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and streptomycin (SM), all of which enter cerebrospinal fluid (CSF) readily in the presence of meningeal inflammation. Ethambutol is less effective in meningeal disease unless used in high doses. The second-line drugs include ethionamide, cycloserine, ofloxacin, and para (...) -aminosalicylic acid (PAS). INH, RIF, and PZA are bactericidal. RIF and SM achieve optimal CSF levels only when the meninges are inflamed. Usually, intrathecal drugs are not necessary. Treatment is best started with INH, RIF, and PZA. The addition of a fourth drug is left to the choice of the local physicians and their experience, with little evidence to support the use of one over the other. Evidence concerning the duration of treatment is conflicting. The duration of conventional therapy is 6-9 months

2014 eMedicine.com

2180. Tuberculosis (Follow-up)

Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center Richard H Sinert, DO is a member of the following medical societies: and Disclosure: Nothing to disclose. Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure (...) the tubercle bacillus. Continue isolation until sputum smears are negative for 3 consecutive determinations (usually after approximately 2-4 wk of treatment). Unfortunately, these measures are neither possible nor practical in countries where TB is a public health problem. Drug therapy For initial empiric treatment of TB, start patients on a 4-drug regimen: isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Once the TB isolate is known to be fully susceptible, ethambutol

2014 eMedicine.com

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