Toxicity

Source: vetmedicine.about.com --- 22 days ago
Chocolate is a popular treat all year round. Care must be taken when animals are around, though. Chocolate can be toxic, and sometimes even fatal, for animals. Dogs are most commonly affected, due to their ability to find it and the common 'sweet tooth' they seem to have. It is important to remember that cats and other species are susceptible to the toxic effects of chocolate, too. ...

Source: biotech.about.com --- 31 days ago
Nanotechnology has found its way into our everyday lives and, alarmingly enough, with nearly no attention paid to determining the potential for Toxicity or lasting effects on the health of... ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles Measures of drug Toxicity in older adults. Arch Intern Med. 2008 Sep 22;168(17):1930-1; author reply 1931-2 Authors: Hilmer SN, Abernethy DR PMID: 18809825 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 11 hours ago
Two faces of nitric oxide: implications for cellular mechanisms of oxygen Toxicity. J Appl Physiol. 2008 Oct 9; Authors: Allen BW, Demchenko IT, Piantadosi CA Recent investigations have elucidated some of the diverse roles played by reactive oxygen and nitrogen species (ROS and RNS) in events that lead to oxygen Toxicity and defend against it. The focus of this review is on toxic and protective mechanisms in hyperoxia that have been investigated in our laboratories, with an emphasis on interactions of nitric oxide (NO) with other endogenous chemical species and with different physiological systems. It is now emerging from these studies that the anatomical localization of NO release, which depends in part on whether the oxygen exposure is normobaric or hyperbaric, strongly influences whether Toxicity emerges and what form it takes-for example acute lung injury, CNS excitation, or both. Spatial effects also contribute to differences in the susceptibility of different cells in organs at risk from hyperoxia, especially in the brain and lungs. As additional nodes are identified in this interactive network of toxic and protective responses, future advances may open up the possibility of novel pharmacologic interventions to extend both the time and partial pressures of oxygen exposures that can be safely tolerated. The implications of a better understanding of the mechanisms by which NO contributes to CNS oxygen Toxicity may include new ins ...

Source: www.ncbi.nlm.nih.gov --- 1 day ago
Related Articles Intestinal permeability and Toxicity of second-line therapeutic agents in ovarian cancer. Tumori. 2008 Jul-Aug;94(4):624-6 Authors: Melichar B, Hyspler R, Dragounová E, Kalábová H, Dvorák J PMID: 18825807 [PubMed - indexed for MEDLINE] ...

Source: www.ncbi.nlm.nih.gov --- 2 days ago
Related Articles An in vitro study of liposomal curcumin: Stability, Toxicity and biological activity in human lymphocytes and Epstein-Barr virus-transformed human B-cells. Int J Pharm. 2008 Sep 17; Authors: Chen C, Johnston TD, Jeon H, Gedaly R, McHugh PP, Burke TG, Ranjan D Curcumin is a multi-functional and pharmacologically safe natural agent. Used as a food additive for centuries, it also has anti-inflammatory, anti-virus and anti-tumor properties. We previously found that it is a potent inhibitor of cyclosporin A (CsA)-resistant T-cell co-stimulation pathway. It inhibits mitogen-stimulated lymphocyte proliferation, NFkappaB activation and IL-2 signaling. In spite of its safety and efficacy, the in vivo bioavailability of curcumin is poor, and this may be a major obstacle to its utility as a therapeutic agent. Liposomes are known to be excellent carriers for drug delivery. In this in vitro study, we report the effects of different liposome formulations on curcumin stability in phosphate buffered saline (PBS), human blood, plasma and culture medium RPMI-1640+10% FBS (pH 7.4, 37 degrees C). Liposomal curcumin had higher stability than free curcumin in PBS. Liposomal and free curcumin had similar stability in human blood, plasma and RPMI-1640+10% FBS. We looked at the Toxicity of non-drug-containing liposomes on (3)H-thymidine incorporation by concanavalin A (Con A)-stimulated human lymphocytes, splenocytes and Epstein-Barr virus (E ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles Evaluation and interpretation of maternal Toxicity in Segment II studies: issues, some answers, and data needs. Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):367-74 Authors: Rogers JM, Chernoff N, Keen CL, Daston GP Biologically rational regulatory policies with regards to developmental Toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal Toxicity, and the developmental effects of this Toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts dealing with the relationship of maternal and developmental Toxicity. Maternally mediated developmental Toxicity occurs with a number of agents, and toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal Toxicity. Relevant studies are reviewed here, and s ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles New models and molecular markers in evaluation of developmental Toxicity. Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):495-500 Authors: Huuskonen H Mammalian and non-mammalian embryos and embryonic stem cells may be used as models in mechanistic studies and in testing embryotoxicity of compounds. In addition to conventional culture methods, genetic modifications and use of molecular markers offer significant advantages in mechanistic studies as well as in developing new test methods for embryotoxicity. Zebrafish model has been used for a long time and at present several applications are available. It is an easy vertebral non-mammalian model, whose genome is largely known and several genetic modifications are easily constructed to study gene expression or knocked down genes. Fluorescent marker proteins can be used also in zebrafish to indicate gene activation in transgenic models. Chemical genetics approach has been developed using zebrafish model. This is a new approach to screen small molecules that regulate signaling pathways. Embryonic stem cells have been used in mechanistic studies and mouse embryonic stem cell test has been validated to study embryotoxicity in vitro. This method has been improved using quantitative measurements of molecular endpoints by real-time RT-PCR or fluorescent activated cell sorting methods (FACS). Methods facilitating differentiation to several different cell types are available. We h ...

Source: www.ncbi.nlm.nih.gov --- 10 days ago
Related Articles Prospective evaluation of mitotane Toxicity in adrenocortical cancer patients treated adjuvantly. Endocr Relat Cancer. 2008 Sep 29; Authors: Daffara F, De Francia S, Reimondo G, Zaggia B, Aroasio E, Porpiglia F, Volante M, Termine A, Di Carlo F, Dogliotti L, Angeli A, Berruti A, Terzolo M Toxicity of adjuvant mitotane treatment is poorly known; thus, our aim was to assess prospectively the unwanted effects of adjuvant mitotane treatment and correlate the findings with mitotane concentrations. Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane Toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All patients reached mitotane concentrations >14 mg/l and none of them discontinued definitively mitotane for Toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cort ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles Male-mediated developmental Toxicity. Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):506-13 Authors: Anderson D In recent years, the public has become more aware that exposure of males to certain agents can adversely affect their offspring and cause infertility and cancer. The hazards associated with exposure to ionising radiation have been recognised for nearly a century, but interest was aroused when a cluster of leukaemia cases was identified in young children living in Seascale, close to the nuclear processing plant at Sellafield in West Cumbria. There was a civil court case on behalf of two of the alleged victims of paternal irradiation at Seascale against British Nuclear Fuels. The case foundered on "the balance of probabilities". Nevertheless, there was support for paternal exposure from Japanese experimental X-ray studies in mice. The tumours were clearly heritable as shown by F2 transmission. Also, effects of a relatively non-toxic dose of radiation (1Gy) on cell proliferation transmitted to the embryo were manifested in the germ line of adult male mice even after two generations. In addition in humans, smoking fathers appear to give rise to tumours in the F(1) generation. Using rodent models, developmental abnormalities/congenital malformations and tumours can be studied after exposure of males in an extended dominant lethal assay and congenital malformations can be determined which have similar manifestatio ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles Resveratrol protects auditory hair cells from gentamicin Toxicity. Ear Nose Throat J. 2008 Oct;87(10):570-3 Authors: Bonabi S, Caelers A, Monge A, Huber A, Bodmer D Resveratrol is a naturally occurring polyphenol that is synthesized by a variety of plant species. It is abundant in grapes and grape products (e.g., red wine). Resveratrol has demonstrated reactive oxygen species (ROS) scavenger activity, and it has been linked to nuclear factor-kappa B (NF-kappaB) activity. We recently demonstrated that NF-kappaB is important to the survival of immature mammalian hair cells. Therefore, we undertook an in vitro experiment to determine if resveratrol is able to exert some protective influence against gentamicin-induced damage to and death of auditory hair cells. To accomplish this, we dissected the organ of Corti (OC) from newborn Sprague-Dawley rats and cultured the OCs in medium overnight for recovery. We treated two groups of OC explants with different concentrations of resveratrol plus gentamicin for 24 hours; for comparison and control purposes, we also treated a group of explants with gentamicin only and we left a group untreated. We found that resveratrol in both concentrations had a moderate but statistically significant protective effect against gentamicin-induced Toxicity in vitro. PMID: 18833534 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 5 days ago
Related Articles Enhancement of glucose Toxicity by hyperbaric oxygen exposure in diabetic rats. Tohoku J Exp Med. 2008 Oct;216(2):127-32 Authors: Matsunami T, Sato Y, Morishima T, Mano Y, Yukawa M The side effects of hyperbaric oxygen (HBO) treatment, such as oxidative stress and oxygen Toxicity, have long been of interest. However, there are no comprehensive studies evaluating such toxic effects in diabetes mellitus (DM). The purpose of this study was to determine the effects of HBO on glucose homeostasis and histological changes in pancreatic beta-cells of experimentally induced diabetic rats. A total of 24 male Wistar rats were randomly divided into 4 groups: 1) Control group, no diabetic induction without HBO treatment; 2) HBO group, exposed to 100% oxygen at 2.8 ATA (atmosphere absolute) for 2 h once daily, for 7 days; 3) DM group, diabetes induced by streptozotocin (STZ) injection; and 4) DM + HBO group, received both STZ injection and HBO exposure. HBO treatment, with clinically recommended pressures and duration of therapy, was started on day 5 after STZ injection, when the blood glucose levels were significantly increased. After the last HBO treatment, the pancreatic tissues were immunostained to measure the areas of insulin immunoreactive beta-cells in the islets of Langerhans. The blood glucose increased significantly following exposure to HBO, with the highest levels achieved in rats, which had been treated with both HBO ...

Source: www.ncbi.nlm.nih.gov --- 3 days ago
Related Articles Cardiac Toxicity of Sunitinib and Sorafenib in Patients With Metastatic Renal Cell Carcinoma. J Clin Oncol. 2008 Oct 6; Authors: Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, Ruhsam M, Hejna M, Schmidinger H PURPOSE: Sunitinib and sorafenib are tyrosine kinase inhibitors (TKIs) that have considerable efficacy in metastatic renal cell carcinoma. TKI-associated cardiotoxicity was reported in approximately 10% of the patients. Detailed cardiovascular monitoring during TKI treatment may reveal early signs of myocardial damage. PATIENTS AND METHODS: In this observational, single-center study, all patients intended for TKI treatment were analyzed for coronary artery disease (CAD) risk factors, history or evidence of CAD, hypertension, rhythm disturbances, and heart failure. Monitoring included assessment of symptoms, ECGs, and biochemical markers (ie, creatine kinase-MB, troponin T). Echocardiography was performed at baseline in selected patients and in all patients who experienced a cardiac event. A cardiac event was defined as the occurrence of increased enzymes if normal at baseline, symptomatic arrhythmia that required treatment, new left ventricular dysfunction, or acute coronary syndrome. RESULTS: A total of 86 patients were treated with either sunitinib or sorafenib. Among 74 eligible patients, 33.8% experienced a cardiac event, 40.5% had ECG changes, and 18% were symptomatic. Seven patients (9.4% ...

Source: www.ncbi.nlm.nih.gov --- 26 days ago
Related Articles Toxicity from modafinil ingestion. Clin Toxicol (Phila). 2008 Sep 11;:1-4 Authors: Spiller HA, Borys D, Griffith JR, Klein-Schwartz W, Aleguas A, Sollee D, Anderson DA, Sawyer TS Introduction. Modafanil, a non-amphetamine stimulant, is used for narcolepsy, sleep apnea, and shift work sleep disorder. There is little available information on the Toxicity of modafinil overdose. Method. We performed a retrospective multi-poison center chart review of patients from 11 states who had a single substance ingestion of modafanil with follow up to a known outcome for the years 2000-2007. Data collected included age, gender, dose ingested, clinical effects, length of hospital stay, and medical outcome. Results. There were 137 patients, of whom 85 (63%) were female. Ages ranged from 1 to 82 years with a mean and median of 22 years (+18) and 20 years, respectively, with 43 patients (31%) aged <6 years. Most frequently reported clinical effects were tachycardia (n = 38), insomnia (n = 33), agitation (n = 27), dizziness (n = 25), and anxiety (n = 24). Forty-five patients were managed at home and 92 in a health-care setting, with only 23 (17%) requiring a medical admission. Therapies included benzodiazepines (n = 14), diphenhydramine (n = 5), beta-blockers (n = 3), haloperidol (n = 2), IV fluid hydration (n = 2), and one each of nitroglycerin, epinephrine, benztropine, and promethazine. Conclusions. In this case series, clinical effect ...

Source: www.ncbi.nlm.nih.gov --- 28 days ago
Related Articles Calpastatin overexpression attenuates beta amyloid peptide Toxicity in differentiated PC12 cells. Neuroscience. 2008 Aug 19; Authors: Vaisid T, Barnoy S, Kosower NS Amyloid beta peptide (Abeta) plays a major role in the pathogenesis of Alzheimer's disease (AD). Abeta is toxic to neurons, possibly through causing initial synaptic dysfunction and neuronal membrane dystrophy, promoted by increased cellular Ca(2+). Calpain (Ca(2+)-dependent protease) and caspase have been implicated in AD. Previously, we used calpain and caspase pharmacological inhibitors to study effects of Abeta25-35 (sAbeta) on neuronal-like differentiated PC12 cells. We reported that sAbeta-treated cells exhibited calpain activation and protein degradation (due to both calpain and caspase-8). We have now found that overexpression of the calpain specific inhibitor calpastatin in differentiated PC12 cells significantly inhibited the sAbeta-induced calpain activation and decreased the protease activity. Calpastatin overexpression inhibited the sAbeta-promoted degradation of fodrin, protein kinase Cepsilon, beta-catenin (membrane structural proteins and proteins involved in signal transduction pathways), and prevented the sAbeta-induced alteration of neurite structure (manifested by varicosities). Overexpression of calpastatin also inhibited Ca(2+)-promoted calpain activation and protein degradation; this is consistent with the notion that the Abeta-induc ...

Source: www.ncbi.nlm.nih.gov --- 29 days ago
Related Articles Decreasing systemic Toxicity via transdermal delivery of anticancer drugs. Curr Drug Metab. 2008 Sep;9(7):592-7 Authors: Fang JY, Liu PF, Huang CM When used at a high dose, many anticancer drugs produce undesirable side effects including hepatotoxicity. Transdermal delivery bypasses first-pass metabolism, allowing the use of a lower dose of drug while decreasing systemic Toxicity. In this review, we summarize various advanced technologies for improving anticancer drug delivery via the skin. This technology is discussed in the context of three anticancer drugs, 5-fluorouracil (5-FU), methotrexate (MTX) and 5-aminolevulinic acid (5-ALA). The use of a erbium:YAG (Er:YAG) laser for transdermal delivery of anticancer drugs is specifically highlighted in this review. PMID: 18781910 [PubMed - in process] ...

Source: www.ncbi.nlm.nih.gov --- 33 days ago
Related Articles Novel Suppressors of Alpha-Synuclein Toxicity Identified Using Yeast. Hum Mol Genet. 2008 Sep 4; Authors: Liang J, Clark-Dixon C, Wang S, Flower TR, Williams-Hart T, Zweig R, Robinson LC, Tatchell K, Witt SN The mechanism by which the Parkinson's disease-related protein alpha-synuclein (alpha-syn) causes neurodegeneration has not been elucidated. To determine the genes that protect cells from alpha-syn, we used a genetic screen to identify suppressors of the super sensitivity of the yeast Saccharomyces cerevisiae expressing alpha-syn to killing by hydrogen peroxide. Forty genes in ubiquitin-dependent protein catabolism, protein biosynthesis, vesicle trafficking, and the response to stress were identified. Five of the forty genes-ENT3, IDP3, JEM1, ARG2, and HSP82-ranked highest in their ability to block alpha-syn-induced reactive oxygen species (ROS) accumulation, and these five genes were characterized in more detail. The deletion of any of these five genes enhanced the Toxicity of alpha-syn as judged by growth defects compared to wild-type cells expressing alpha-syn, which indicates that these genes protect cells from alpha-syn. Strikingly, four of the five genes are specific for alpha-syn in that they fail to protect cells from the Toxicity of the two inherited mutants A30P or A53T. This finding suggests that alpha-syn causes Toxicity to cells via a different pathway than these two inherited mutants. Lastly, overexpr ...

Source: www.ncbi.nlm.nih.gov --- 38 days ago
Related Articles Toxicity and intraocular properties of a novel long-acting anti-proliferative and anti-angiogenic compound IMS2186. Curr Eye Res. 2008 Jul;33(7):599-609 Authors: Falkenstein IA, Cheng L, Wong-Staal F, Tammewar AM, Barron EC, Silva GA, Li QX, Yu D, Hysell M, Liu G, Ke N, Macdonald JE, Freeman WR PURPOSE: To investigate the intraocular properties and Toxicity of IMS2186, a small molecule developed as an anti-choroidal neovascularization (anti-CNV) drug. MATERIALS AND METHODS: Cellular Toxicity and mechanism of action was tested on cell lines in vitro. Intraocular studies used rabbits for drug dissolution as well as Toxicity and rats for the treatment study as well as the Toxicity confirmation study. Rabbits' eyes were injected with 2.5 mg of IMS2186 and observed for 36 weeks. Laser-induced CNV in rats was treated with IMS2186, Kenalog, or phosphate-buffered saline (pBS). Fluorescein angiography (FA) and immunohistochemical processing of the globes was performed. RESULTS: The anti-proliferative IC(50) of IMS2186 for human fibroblast cells was 1.0-3.0 microM and 0.3-3.0 microM for human cancer cells; the IC(50) of IMS2186 to inhibit endothelial tube formation was 0.1-0.3 microM. The IC(50) of IMS2186 for inhibiting the production of pro-inflammatory cytokines was 0.3-1 microM. The IC(50) of IMS2186 for inhibiting macrophage migration was 1 micrM. These biological properties were not species specific. IMS2186 can be formula ...

Source: www.ncbi.nlm.nih.gov --- 23 days ago
Related Articles The amino terminus of tau inhibits kinesin-dependent axonal transport: Implications for filament Toxicity. J Neurosci Res. 2008 Sep 16; Authors: Lapointe NE, Morfini G, Pigino G, Gaisina IN, Kozikowski AP, Binder LI, Brady ST The neuropathology of Alzheimer's disease (AD) and other tauopathies is characterized by filamentous deposits of the microtubule-associated protein tau, but the relationship between tau polymerization and neurotoxicity is unknown. Here, we examined effects of filamentous tau on fast axonal transport (FAT) using isolated squid axoplasm. Monomeric and filamentous forms of recombinant human tau were perfused in axoplasm, and their effects on kinesin- and dynein-dependent FAT rates were evaluated by video microscopy. Although perfusion of monomeric tau at physiological concentrations showed no effect, tau filaments at the same concentrations selectively inhibited anterograde (kinesin-dependent) FAT, triggering the release of conventional kinesin from axoplasmic vesicles. Pharmacological experiments indicated that the effect of tau filaments on FAT is mediated by protein phosphatase 1 (PP1) and glycogen synthase kinase-3 (GSK-3) activities. Moreover, deletion analysis suggested that these effects depend on a conserved 18-amino-acid sequence at the amino terminus of tau. Interestingly, monomeric tau isoforms lacking the C-terminal half of the molecule (including the microtubule binding region) recapitu ...

Source: www.ncbi.nlm.nih.gov --- 30 days ago
Related Articles Cyclosporin and organ specific Toxicity: clinical aspects, pharmacogenetics and perspectives. Curr Clin Pharmacol. 2008 Sep;3(3):166-73 Authors: Magnasco A, Rossi A, Catarsi P, Gusmano R, Ginevri F, Perfumo F, Ghiggeri GM Cyclosporine (CsA) has considerably modified the graft survival in solid organ and bone marrow transplantations. It is also the treatment of choice in chronic diseases such as steroid resistance and/or dependence nephrotic syndrome and autoimmune-diseases, especially in those cases that require long term treatments. Renal Toxicity is the major adverse effect of chronic CsA administration. Deterioration of renal function and renal histopathology are the basic elements of the diagnosis. Overall, available studies suggest a good degree of safety related to appropriate drug dosages even if they require an adequate degree of surveillance in case of rapid changes of renal functions and long term evaluation of renal pathology. CsA neurotoxicity is the second major problem that seems underestimated especially in case of subtle manifestations in children. The full blown picture of the acute form is characterized by convulsion and sudden alteration of mental function that are reversible upon drug withdrawal. The diagnosis is based on typical CT and MRI aspects of extensive bilateral white-matter abnormalities in the occipital region of the brain that mimics the posterior encephalopathy syndrome. Prospective ev ...