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Determinants of condom use by men in extramarital relationships in Nigeria
Ankomah A, Adebayo SB, Anyanti J, Ladipo O, Ekweremadu B (Source: Therapeutics and Clinical Risk Management)
Source: Therapeutics and Clinical Risk Management - May 24, 2013 Category: Drugs & Pharmacology Source Type: research
Effects of tramadol on viscero‐visceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis
This article is protected by copyright. All rights reserved. (Source: Fundamental and Clinical Pharmacology)
Source: Fundamental and Clinical Pharmacology - May 24, 2013 Category: Drugs & Pharmacology Authors: Mariangela Lopopolo, Giannapia Affaitati, Alessandra Fabrizio, Francesca Massimini, Domenico Lapenna, Maria Adele Giamberardino, Raffaele Costantini Tags: Original Article Source Type: research
Pharmacokinetics and pharmacodynamics of levofloxacin injection in healthy Chinese volunteers and dosing regimen optimization
Summary What is known and objectiveThe pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin were investigated following administration of levofloxacin injection in healthy Chinese volunteers for optimizing dosing regimen. MethodsThe PK study included single‐dose (750 mg/150 mL) and multiple‐dose (750 mg/150 mL once daily for 7 days) phases. The concentration of levofloxacin in blood and urine was determined using HPLC method. Both non‐compartmental and compartmental analyses were performed to estimate PK parameters. Taking fCmax/MIC ≥5 and fAUC24 h/MIC ≥30 as a target, the cumulative fraction of ...
Source: Journal of Clinical Pharmacy and Therapeutics - May 24, 2013 Category: Drugs & Pharmacology Authors: G. Cao, J. Zhang, X. Wu, J. Yu, Y. Chen, X. Ye, D. Zhu, Y. Zhang, B. Guo, Y. Shi Tags: Original Article Source Type: research
A UK retrospective observational study of clinical outcomes and healthcare resource utilisation of infliximab treatment in Crohn's disease
ConclusionsThe observed reductions in numbers of hospitalisations, surgical procedures and consultations with healthcare professionals are key indicators of the clinical effectiveness of infliximab for the treatment of CD. These benefits result in overall decreases in healthcare resource utilisation, which translate into cost savings for the NHS. (Source: Alimentary Pharmacology and Therapeutics)
Source: Alimentary Pharmacology and Therapeutics - May 24, 2013 Category: Drugs & Pharmacology Authors: J. O. Lindsay, R. Chipperfield, A. Giles, C. Wheeler, T. Orchard, Tags: Original Article Source Type: research
Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings).
Abstract For more than 50 years, ketamine has proven to be a safe anesthetic drug with potent analgesic properties. The active enantiomer is S(+)-ketamine. Ketamine is mostly metabolized in norketamine, an active metabolite. During "dissociative anesthesia", sensory inputs may reach cortical receiving areas, but fail to be perceived in some association areas. Ketamine also enhances the descending inhibiting serotoninergic pathway and exerts antidepressive effects. Analgesic effects persist for plasma concentrations ten times lower than hypnotic concentrations. Activation of the (N-Methyl-D-Aspartate [NMDA]) recept...
Source: CNS Neuroscience and Therapeutics - May 23, 2013 Category: Neuroscience Authors: Mion G, Villevieille T Tags: CNS Neurosci Ther Source Type: research
Ex Vivo Characterization of Particle
Transport in Mucus Secretions Coating Freshly Excised Mucosal Tissues
Molecular PharmaceuticsDOI: 10.1021/mp400087y (Source: Molecular Pharmaceutics)
Source: Molecular Pharmaceutics - May 23, 2013 Category: Drugs & Pharmacology Authors: Laura M. Ensign, Andreas Henning, Craig S. Schneider, Katharina Maisel, Ying-Ying Wang, Marc D. Porosoff, Richard Cone and Justin Hanes Source Type: research
PPARα is involved in the multitargeted effects of a pretreatment with atorvastatin in experimental stroke
Abstract There is now substantial data in the literature showing that statins can protect against cerebral ischemia. This neuroprotective potency is related to their pleiotropic effects that modulate various pathways implicated in the pathophysiology of stroke. It has been demonstrated that statins exert anti‐inflammatory and vasculoprotective effects, thus contributing to a reduction in infarct size. The underlying mechanisms are still incompletely known. As a cross‐talk between statins and the nuclear receptor PPARα has been described, we hypothesized that this cross‐talk is necessary to neuroprotection in stroke....
Source: Fundamental and Clinical Pharmacology - May 23, 2013 Category: Drugs & Pharmacology Authors: Thavarak Ouk, Camille Potey, Maud Laprais, Sophie Gautier, Rémi Hanf, Raphaël Darteil, Bart Staels, Patrick Duriez, Régis Bordet Tags: Original Article Source Type: research
Protein kinase C pharmacology: refining the toolbox.
Abstract PKC (protein kinase C) has been in the limelight since the discovery three decades ago that it acts as a major receptor for the tumour-promoting phorbol esters. Phorbol esters, with their potent ability to activate two of the three classes of PKC isoenzymes, have remained the best pharmacological tool for directly modulating PKC activity. However, with the discovery of other phorbol ester-responsive proteins, the advent of various small-molecule and peptide modulators, and the need to distinguish isoenzyme-specific activity, the pharmacology of PKC has become increasingly complex. Not surprisingly, many of...
Source: The Biochemical Journal - May 22, 2013 Category: Biochemistry Authors: Wu-Zhang AX, Newton AC Tags: Biochem J Source Type: research
Pharmaco-epidemiological description of the population of the Marche Region (central Italy) treated with the antipsychotic drug olanzapine.
CONCLUSIONS: Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions. PMID: 23535129 [PubMed - in process] (Source: Ann Ist Super Sanita)
Source: Ann Ist Super Sanita - May 22, 2013 Category: Biomedical Science Authors: Mignini F, Sabbatini M, Pascucci C, Petrelli F, Grappasonni I, Vanacore N Tags: Ann Ist Super Sanita Source Type: research
Abstract This Teaching Resource provides three animated lessons that describe the storage and utilization of energy across plasma membranes. The "Na,K ATPase" animation explains how these pumps establish the electrochemical gradient that stores energy across plasma membranes. The "ATP synthesizing complexes" animation shows how these complexes transfer energy from the inner mitochondrial membrane to adenosine triphosphate (ATP). The "action potential" lesson explains how charged membranes are used to propagate signals along the axons of neurons. These animations serve as valuable resources for any collegiate-level ...
Source: Science Signaling - May 22, 2013 Category: Biomedical Science Authors: Thatcher JD Tags: Sci Signal Source Type: research
Coupled transport protein systems.
Abstract This set of animated lessons provides examples of how transport proteins interact in coupled systems to produce physiologic effects. The gastric pumps animation depicts the secretion of hydrochloric acid into the gastric lumen. The animation called glucose absorption depicts glucose absorption by intestinal epithelial cells. The CFTR animation explains how the cystic fibrosis conductance transmembrane regulator (CFTR) functions as a key component of a coupled system of transport proteins that clears the pulmonary system of mucus and inhaled particulates. These animations serve as valuable resources for any...
Source: Science Signaling - May 22, 2013 Category: Biomedical Science Authors: Thatcher JD Tags: Sci Signal Source Type: research
Design, Synthesis, and Characterization of New 5-Fluorocytosine
Molecular PharmaceuticsDOI: 10.1021/mp400070a (Source: Molecular Pharmaceutics)
Source: Molecular Pharmaceutics - May 22, 2013 Category: Drugs & Pharmacology Authors: Sathyanarayana R. Perumalla, Venkateswara R. Pedireddi and Changquan C. Sun Source Type: research
Metabolomic changes in follicular fluid induced by soy isoflavones administered to rats from weaning until sexual maturity.
Abstract Female Wistar rats at 21days of age were treated with one of three concentrations of soy isoflavones (SIF) (50, 100 or 200mg/kg body weight, orally, once per day) from weaning until sexual maturity (3months) in order to evaluate the influence of SIF on ovarian follicle development. After treatment, the serum sex hormone levels and enumeration of ovarian follicles of the ovary were measured. The metabolic profile of follicular fluid was determined using HPLC-MS. Principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) was used to identify differences in metabolites and rev...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Wang W, Zhang W, Liu J, Sun Y, Li Y, Li H, Xiao S, Shen X Tags: Toxicol Appl Pharmacol Source Type: research
Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity.
In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. PMID: 23438451 [PubMed - in process] (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Das S, Kumar A, Seth RK, Tokar EJ, Kadiiska MB, Waalkes MP, Mason RP, Chatterjee S Tags: Toxicol Appl Pharmacol Source Type: research
Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc.
Abstract Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the ...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Cooper KL, King BS, Sandoval MM, Liu KJ, Hudson LG Tags: Toxicol Appl Pharmacol Source Type: research
Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice.
In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. PMID: 23506792 [PubMed - in process] (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: van Swelm RP, Laarakkers CM, Pertijs JC, Verweij V, Masereeuw R, Russel FG Tags: Toxicol Appl Pharmacol Source Type: research
Modeling mixtures of thyroid gland function disruptors in a vertebrate alternative model, the zebrafish eleutheroembryo.
Abstract Maternal thyroxine (T4) plays an essential role in fetal brain development, and even mild and transitory deficits in free-T4 in pregnant women can produce irreversible neurological effects in their offspring. Women of childbearing age are daily exposed to mixtures of chemicals disrupting the thyroid gland function (TGFDs) through the diet, drinking water, air and pharmaceuticals, which has raised the highest concern for the potential additive or synergic effects on the development of mild hypothyroxinemia during early pregnancy. Recently we demonstrated that zebrafish eleutheroembryos provide a suitable al...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Thienpont B, Barata C, Raldúa D Tags: Toxicol Appl Pharmacol Source Type: research
ATP-dependent transport of statins by human and rat MRP2/Mrp2.
Abstract Multidrug resistance associated protein-2, MRP2 (human), Mrp2 (rat) are an efflux transporter, responsible for the transport of numerous endogenous and xenobiotic compounds including taurocholate, methotrexate and carboxydichlorofluorescein (CDF). The present study aims to characterise transport of statins by human and rat MRP2/Mrp2 using membrane and vesicle preparations. All statins tested (simvastatin, pravastatin, pitavastatin, fluvastatin, atorvastatin, lovastatin and rosuvastatin) stimulated vanadate-sensitive ATPase activity in membranes expressing human or rat MRP2/Mrp2, suggesting that all statins...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Ellis LC, Hawksworth GM, Weaver RJ Tags: Toxicol Appl Pharmacol Source Type: research
Pulmonary instillation of low doses of titanium dioxide nanoparticles in mice leads to particle retention and gene expression changes in the absence of inflammation.
Abstract We investigated gene expression, protein synthesis, and particle retention in mouse lungs following intratracheal instillation of varying doses of nano-sized titanium dioxide (nano-TiO2). Female C57BL/6 mice were exposed to rutile nano-TiO2 via single intratracheal instillations of 18, 54, and 162μg/mouse. Mice were sampled 1, 3, and 28days post-exposure. The deposition of nano-TiO2 in the lungs was assessed using nanoscale hyperspectral microscopy. Biological responses in the pulmonary system were analyzed using DNA microarrays, pathway-specific real-time RT-PCR (qPCR), gene-specific qPCR arrays, and tis...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Husain M, Saber AT, Guo C, Jacobsen NR, Jensen KA, Yauk CL, Williams A, Vogel U, Wallin H, Halappanavar S Tags: Toxicol Appl Pharmacol Source Type: research
Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage.
Abstract The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with l-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhib...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Kim KA, Shim SH, Ahn HR, Jung SH Tags: Toxicol Appl Pharmacol Source Type: research
Bisphenol A differentially activates protein kinase C isoforms in murine placental tissue.
Abstract Bisphenol A is utilized to make polycarbonate plastics and is an environmental pollutant. Recent research has indicated that it is an endocrine disruptor and may interfere with reproductive processes. Our lab has previously shown that bisphenol A could regulate corticotrophin releasing hormone and aromatase in cultured placental cells. In the present study, the effect of bisphenol A on these two genes in the placenta was investigated in mice. Pregnant ICR mice were gavaged with bisphenol A at 2, 20 and 200mg/kg body weight/day from E13 to E16 and were euthanized at E17. Compared to the control mice, increa...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Tan W, Huang H, Wang Y, Wong TY, Wang CC, Leung LK Tags: Toxicol Appl Pharmacol Source Type: research
Quercitrin protects skin from UVB-induced oxidative damage.
Abstract Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated t...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Yin Y, Li W, Son YO, Sun L, Lu J, Kim D, Wang X, Yao H, Wang L, Pratheeshkumar P, Hitron AJ, Luo J, Gao N, Shi X, Zhang Z Tags: Toxicol Appl Pharmacol Source Type: research
Phytoestrogens in menopausal supplements induce ER-dependent cell proliferation and overcome breast cancer treatment in an in vitro breast cancer model.
In this study, interaction of phytoestrogens with the estrogen receptor alpha and TAM action was determined in an ER-reporter gene assay (BG1Luc4E2 cells) and human breast epithelial tumor cells (MCF-7). Potential interactions with aromatase activity and LET were determined in human adrenocorticocarcinoma H295R cells. We also used the previously described H295R/MCF-7 co-culture model to study interactions with steroidogenesis and tumor cell proliferation. In this model, genistein (GEN), 8-prenylnaringenin (8PN) and four commercially available menopausal supplements all induced ER-dependent tumor cell proliferation, which c...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: van Duursen MB, Smeets EE, Rijk JC, Nijmeijer SM, van den Berg M Tags: Toxicol Appl Pharmacol Source Type: research
In silico modeling to predict drug-induced phospholipidosis.
In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80-81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ≥80% leading to desired high negative and positive predictivity. These models are intended to be utilize...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Choi SS, Kim JS, Valerio LG, Sadrieh N Tags: Toxicol Appl Pharmacol Source Type: research
Human metabolites of synthetic cannabinoids JWH-018 and JWH-073 bind with high affinity and act as potent agonists at cannabinoid type-2 receptors.
Abstract K2 or Spice is an emerging drug of abuse that contains synthetic cannabinoids, including JWH-018 and JWH-073. Recent reports indicate that monohydroxylated metabolites of JWH-018 and JWH-073 retain high affinity and activity at cannabinoid type-1 receptors (CB1Rs), potentially contributing to the enhanced toxicity of K2 compared to marijuana. Since the parent compounds also bind to cannabinoid type-2 receptors (CB2Rs), this study investigated the affinity and intrinsic activity of JWH-018, JWH-073 and several monohydroxylated metabolites at human CB2Rs (hCB2Rs). The affinity of cannabinoids for hCB2Rs was ...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Rajasekaran M, Brents LK, Franks LN, Moran JH, Prather PL Tags: Toxicol Appl Pharmacol Source Type: research
Breast cancer drugs dampen vascular functions by interfering with nitric oxide signaling in endothelium.
In conclusion, results indicate that TC, CP and EP cause endothelial dysfunctions via the NO-sGC-cGMP pathway and these effects could be recovered using pharmaceutical agonists of NO signaling pathway. Further, the study proposes a combination therapy of chemotherapeutic drugs and cGMP analogs, which would confer protection against chemotherapy mediated vascular dysfunctions in cancer patients. PMID: 23531514 [PubMed - in process] (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Gajalakshmi P, Priya MK, Pradeep T, Behera J, Muthumani K, Madhuwanti S, Saran U, Chatterjee S Tags: Toxicol Appl Pharmacol Source Type: research
Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells.
Abstract Endocrine disrupting chemicals are the natural/synthetic compounds which mimic or inhibit the actions of endogenous hormones. Organotin compounds, such as tributyltin (TBT) are typical environmental contaminants and suspected endocrine-disrupting chemical. The present study evaluates the estrogenic potential of this compound in vitro in ER (+) breast adenocarcinoma, MCF-7 cell line. Our data showed that tributyltin chloride (TBTCl) had agonistic activities for estrogen receptor-α (ER-α). Its estrogenic potential was checked using cell proliferation assay, aromatase assay, transactivation assay, and prote...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Sharan S, Nikhil K, Roy P Tags: Toxicol Appl Pharmacol Source Type: research
Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling.
Abstract The current study aims to investigate the antiangiogenic responses and apoptotic death of human umbilical vein endothelial cells (HUVECs) by a newly synthesized compound named 2-(3'-methoxyphenyl)-6-pyrrolidinyl-4-quinazolinone (HMJ-38). This work attempted to not only explore the effects of angiogenesis on in vivo and ex vivo studies but also hypothesize the implications for HUVECs (an ideal cell model for angiogenesis in vitro) and further undermined apoptotic experiments to verify the underlying molecular signaling by HMJ-38. Our results demonstrated that HMJ-38 significantly inhibited blood vessel grow...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Chiang JH, Yang JS, Lu CC, Hour MJ, Chang SJ, Lee TH, Chung JG Tags: Toxicol Appl Pharmacol Source Type: research
Mitochondrial dysfunction and organophosphorus compounds.
Abstract Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. S...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Karami-Mohajeri S, Abdollahi M Tags: Toxicol Appl Pharmacol Source Type: research
Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4+ T cells.
Abstract Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designe...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Shu G, Yang T, Wang C, Su H, Xiang M Tags: Toxicol Appl Pharmacol Source Type: research
Plasma and liver acetaminophen-protein adduct levels in mice after acetaminophen treatment: Dose-response, mechanisms, and clinical implications.
Abstract At therapeutic doses, acetaminophen (APAP) is a safe and effective analgesic. However, overdose of APAP is the principal cause of acute liver failure in the West. Binding of the reactive metabolite of APAP (NAPQI) to proteins is thought to be the initiating event in the mechanism of hepatotoxicity. Early work suggested that APAP-protein binding could not occur without glutathione (GSH) depletion, and likely only at toxic doses. Moreover, it was found that protein-derived APAP-cysteine could only be detected in serum after the onset of liver injury. On this basis, it was recently proposed that serum APAP-cy...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: McGill MR, Lebofsky M, Norris HR, Slawson MH, Bajt ML, Xie Y, Williams CD, Wilkins DG, Rollins DE, Jaeschke H Tags: Toxicol Appl Pharmacol Source Type: research
p53 activation by Ni(II) is a HIF-1α independent response causing caspases 9/3-mediated apoptosis in human lung cells.
We examined whether Ni(II) elicits a toxicologically significant activation of the tumor suppressor p53, which is typically associated with genotoxic responses. We found that treatments of H460 human lung epithelial cells with NiCl2 caused activating phosphorylation at p53-Ser15, accumulation of p53 protein and depletion of its inhibitor MDM4 (HDMX). Confirming the activation of p53, its knockdown suppressed the ability of Ni(II) to upregulate MDM2 and p21 (CDKN1A). Unlike DNA damage, induction of GADD45A by Ni(II) was p53-independent. Ni(II) also increased p53-Ser15 phosphorylation and p21 expression in normal human lung ...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Wong VC, Morse JL, Zhitkovich A Tags: Toxicol Appl Pharmacol Source Type: research
EGFR tyrosine kinase inhibitory peptide attenuates Helicobacter pylori-mediated hyper-proliferation in AGS enteric epithelial cells.
Abstract Helicobacter pylori infection is one of the most critical causes of stomach cancer. The current study was conducted to explore the protective effects of an isolated active peptide H-P-6 (Pro-Gln-Pro-Lys-Val-Leu-Asp-Ser) from microbial hydrolysates of Chlamydomonas sp. against H. pylori-induced carcinogenesis. The peptide H-P-6 has effectively suppressed H. pylori-induced hyper-proliferation and migration of gastric epithelial cells (AGS). However, the peptide did not inhibit the viability of the bacteria or invasion into AGS cells. Therefore, the effect of the peptide on regulating H. pylori-induced molecu...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Himaya SW, Dewapriya P, Kim SK Tags: Toxicol Appl Pharmacol Source Type: research
Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: Maternal diets rich in indole-3-carbinol versus sulforaphane.
In this study, transplacental and lactational exposure to a maternal dose of 15mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Shorey LE, Madeen EP, Atwell LL, Ho E, Löhr CV, Pereira CB, Dashwood RH, Williams DE Tags: Toxicol Appl Pharmacol Source Type: research
Protein tyrosine adduct in humans self-poisoned by chlorpyrifos.
In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. PMID: 23566956 [PubMed - in process] (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Li B, Eyer P, Eddleston M, Jiang W, Schopfer LM, Lockridge O Tags: Toxicol Appl Pharmacol Source Type: research
Arsenite suppression of BMP signaling in human keratinocytes.
Abstract Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP inductio...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Phillips MA, Qin Q, Hu Q, Zhao B, Rice RH Tags: Toxicol Appl Pharmacol Source Type: research
Prediction and evaluation of route dependent dosimetry of BPA in rats at different life stages using a physiologically based pharmacokinetic model.
Abstract Bisphenol A (BPA) has received considerable attention throughout the last decade due to its widespread use in consumer products. For the first time a physiologically based pharmacokinetic (PBPK) model was developed in neonatal and adult rats to quantitatively evaluate age-dependent pharmacokinetics of BPA and its phase II metabolites. The PBPK model was calibrated in adult rats using studies on BPA metabolism and excretion in the liver and gastrointestinal tract, and pharmacokinetic data with BPA in adult rats. For immature rats the hepatic and gastrointestinal metabolism of BPA was inferred from studies o...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Yang X, Doerge DR, Fisher JW Tags: Toxicol Appl Pharmacol Source Type: research
Sensitivity to methylmercury toxicity is enhanced in oxoguanine glycosylase 1 knockout murine embryonic fibroblasts and is dependent on cellular proliferation capacity.
Abstract Methylmercury (MeHg) is a persistent environmental contaminant with potent neurotoxic action for which the underlying molecular mechanisms remain to be conclusively delineated. Our objectives herein were twofold: first, to corroborate our previous findings of an increased sensitivity of spontaneously-immortalized oxoguanine glycosylase 1-null (Ogg1(-/-)) murine embryonic fibroblasts (MEFs) to MeHg through generation of Simian virus 40 (SV40) large T antigen-immortalized wild-type and Ogg1(-/-) MEFs; and second, to determine whether MeHg toxicity is proliferation-dependent. As with the spontaneously-immorta...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Ondovcik SL, Tamblyn L, McPherson JP, Wells PG Tags: Toxicol Appl Pharmacol Source Type: research
Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro.
In this study, we studied the effects of SFN on CYP1A1 activity and genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The results showed that SFN inhibited TCDD-induced CYP1A1 activity in H4IIE cells by directly inhibiting CYP1A1 activity, probably through binding to aryl hydrocarbon receptor and/or CYP1A1 revealed by molecular docking. However, SFN promoted TCDD-induced DNA damage in yeast cells and reduced the viability of initiated yeast cells. Besides, it is surprising that SFN also failed to reduce genotoxicity induced by other genotoxic reagents which possess different mechanisms to lead to DNA dama...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Yang F, Zhuang S, Zhang C, Dai H, Liu W Tags: Toxicol Appl Pharmacol Source Type: research
Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally.
Abstract Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL+/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28mg/kg/day) postnatally from ...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Blossom SJ, Cooney CA, Melnyk SB, Rau JL, Swearingen CJ, Wessinger WD Tags: Toxicol Appl Pharmacol Source Type: research
The cyanobacterial neurotoxin beta-N-methylamino-l-alanine (BMAA) induces neuronal and behavioral changes in honeybees.
Abstract The cyanobacterially produced neurotoxin beta-N-methylamino-l-alanine (BMAA) is thought to induce amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC)-like symptoms. However, its mechanism of action and its pathway of intoxication are yet unknown. In vivo animal models suitable for investigating the neurotoxic effect of BMAA with applicability to the human are scarce. Hence, we used the honeybee (Apis mellifera) since its nervous system is relatively simple, yet having cognitive capabilities. Bees fed with BMAA-spiked sugar water had an increased mortality rate and a reduced ability to lea...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Okle O, Rath L, Galizia CG, Dietrich DR Tags: Toxicol Appl Pharmacol Source Type: research
Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells.
In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA....
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Fa S, Pogrmic-Majkic K, Samardzija D, Glisic B, Kaisarevic S, Kovacevic R, Andric N Tags: Toxicol Appl Pharmacol Source Type: research
Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome.
Abstract The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of in...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Ahmad I, Muneer KM, Tamimi IA, Chang ME, Ata MO, Yusuf N Tags: Toxicol Appl Pharmacol Source Type: research
Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism.
Abstract There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50nM and 5μM, on non- and activated cells. B[a]P interferes directly with the stimulati...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Murugaiyan J, Rockstroh M, Wagner J, Baumann S, Schorsch K, Trump S, Lehmann I, Bergen Mv, Tomm JM Tags: Toxicol Appl Pharmacol Source Type: research
Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes.
Abstract Reactive O2 species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O2 species involved in lung O2 metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0mg/kg body weight), and lung samples were analysed 1h after instillation. Tissue O2 consumption and NADPH oxidase (Nox) activity were...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Magnani ND, Marchini T, Vanasco V, Tasat DR, Alvarez S, Evelson P Tags: Toxicol Appl Pharmacol Source Type: research
Inverse antagonist activities of parabens on human oestrogen-related receptor γ (ERRγ): In vitro and in silico studies.
In this study, an in vitro nuclear receptor coactivator recruiting assay was developed and used to evaluate the binding activities of parabens, salicylates and benzoates via antagonist competitive binding on the human oestrogen-related receptor γ (ERRγ), which is known as both a diagnostic biomarker and a treatment target of breast cancer. The results showed that all of the test parabens (methyl-, ethyl-, propyl-, butyl- and benzylparaben) possessed clear inverse antagonist activities on ERRγ, with a lowest observed effect level (LOEL) of 10(-7)M and the 50% relative effective concentrations (REC50) varying from 3.09×1...
Source: Toxicology and Applied Pharmacology - May 22, 2013 Category: Toxicology Authors: Zhang Z, Sun L, Hu Y, Jiao J, Hu J Tags: Toxicol Appl Pharmacol Source Type: research