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Sample records for cell-type-specific adverse effects

  1. Cell Type-Specific Effects of Adenosine on Cortical Neurons

    Science.gov (United States)

    van Aerde, Karlijn I.; Qi, Guanxiao; Feldmeyer, Dirk

    2015-01-01

    The neuromodulator adenosine is widely considered to be a key regulator of sleep homeostasis and an indicator of sleep need. Although the effect of adenosine on subcortical areas has been previously described, the effects on cortical neurons have not been addressed systematically to date. To that purpose, we performed in vitro whole-cell patch-clamp recordings and biocytin staining of pyramidal neurons and interneurons throughout all layers of rat prefrontal and somatosensory cortex, followed by morphological analysis. We found that adenosine, via the A1 receptor, exerts differential effects depending on neuronal cell type and laminar location. Interneurons and pyramidal neurons in layer 2 and a subpopulation of layer 3 pyramidal neurons that displayed regular spiking were insensitive to adenosine application, whereas other pyramidal cells in layers 3–6 were hyperpolarized (range 1.2–10.8 mV). Broad tufted pyramidal neurons with little spike adaptation showed a small adenosine response, whereas slender tufted pyramidal neurons with substantial adaptation showed a bigger response. These studies of the action of adenosine at the postsynaptic level may contribute to the understanding of the changes in cortical circuit functioning that take place between sleep and awakening. PMID:24108800

  2. Cell Type-Specific Effects of Mutant DISC1: A Proteomics Study.

    Science.gov (United States)

    Xia, Meng; Broek, Jantine A C; Jouroukhin, Yan; Schoenfelder, Jeannine; Abazyan, Sofya; Jaaro-Peled, Hanna; Sawa, Akira; Bahn, Sabine; Pletnikov, Mikhail

    2016-05-01

    Despite the recent progress in psychiatric genetics, very few studies have focused on genetic risk factors in glial cells that, compared to neurons, can manifest different molecular pathologies underlying psychiatric disorders. In order to address this issue, we studied the effects of mutant disrupted in schizophrenia 1 (DISC1), a genetic risk factor for schizophrenia, in cultured primary neurons and astrocytes using an unbiased mass spectrometry-based proteomic approach. We found that selective expression of mutant DISC1 in neurons affects a wide variety of proteins predominantly involved in neuronal development (e.g., SOX1) and vesicular transport (Rab proteins), whereas selective expression of mutant DISC1 in astrocytes produces changes in the levels of mitochondrial (GDPM), nuclear (TMM43) and cell adhesion (ECM2) proteins. The present study demonstrates that DISC1 variants can perturb distinct molecular pathways in a cell type-specific fashion to contribute to psychiatric disorders through heterogenic effects in diverse brain cells.

  3. Cell type specific redox status is responsible for diverse electromagnetic field effects.

    Science.gov (United States)

    Simkó, Myrtill

    2007-01-01

    Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (ELF-EMF) has been performed for a long time. Epidemiologic studies regarding ELF-EMF-exposure have focused primarily on leukaemia development due to residential sources in children and adults, and from occupational exposure in adults, but also on other kinds of cancer. Genotoxic investigations of EMF have shown contradictory results, a biological mechanism is still lacking that can explain the link between cancer development and ELF-EMF-exposure. Recent laboratory research has attempted to show general biological effects, and such that could be related to cancer development and/or promotion. Metabolic processes which generate oxidants and antioxidants can be influenced by environmental factors, such as ELF-EMF. Increased ELF-EMF exposure can modify the activity of the organism by reactive oxygen species leading to oxidative stress. It is well established that free radicals can interact with DNA resulting in single strand breaks. DNA damage could become a site of mutation, a key step to carcinogenesis. Furthermore, different cell types react differently to the same stimulus, because of their cell type specific redox status. The modulation of cellular redox balance by the enhancement of oxidative intermediates, or the inhibition or reduction of antioxidants, is discussed in this review. An additional aspect of free radicals is their function to influence other illnesses such as Parkinson's and Alzheimer's diseases. On the other hand, modulation of antioxidants by ELF-EMF can lower the intracellular defence activity promoting the development of DNA damage. It has also been demonstrated that low levels of reactive oxygen species trigger intracellular signals that involve the transcription of genes and leading to responses including cell proliferation and apoptosis. In this review, a general overview is given about oxidative stress, as well as

  4. Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Skladchikova, Galina; Lepekhin, Eugene E

    2010-01-01

    ABSTRACT: BACKGROUND: The anti-epileptic drug valproic acid (VPA) has attracted attention as an anti-cancer agent. Methods: The present study investigated effects of VPA exposure on histone deacetylase (HDAC) inhibition, cell growth, cell speed, and the degree of Erk1/2 phosphorylation in 10 cell....../2 phosphorylation were inhibited, activated, or unaffected by VPA in a cell type-specific manner. Importantly, no relationship was found between the effects of VPA on HDAC inhibition and changes in the degree of Erk1/2 phosphorylation, cell growth, or motility. In contrast, VPA-induced modulation of the MAPK....../2 phosphorylation are also important for the anti-cancer properties of VPA....

  5. The sneaking ligand approach for cell type-specific modulation of intracellular signalling pathways.

    Science.gov (United States)

    Sehnert, Bettina; Burkhardt, Harald; Finzel, Stephanie; Dübel, Stefan; Voll, Reinhard E

    2017-09-01

    Small molecules interfering with intracellular signalling pathways are used in the treatment of multiple diseases including RA. However, small molecules usually affect signalling in most cell types, not only in those which need to be targeted. This general inhibition of signalling pathways causes often adverse effects, which could be avoided by cell type-specific inhibitors. For cell-type specific modulation of signal transduction, we developed the sneaking ligand fusion proteins (SLFPs). SLFPs contain three domains: (1) the binding domain mediating cell type-specific targeting and endocytosis; (2) the endosomal release sequence releasing the effector domain into the cytoplasm; (3) the effector domain modulating signalling. Using our SLFP NF-kappaB inhibitor termed SLC1 we demonstrated that cell-type-specific modulation of intracellular signalling pathways is feasible, that endothelial NF-kappaB activation is critical for arthritis and peritonitis and that SLFPs help to identify disease-relevant pathways in defined cell types. Hence, SLFPs may improve risk-benefit ratios of therapeutic interventions. Copyright © 2017. Published by Elsevier Inc.

  6. Adverse Effects of Bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    events in bisphosphonate-treated patients was based on published information from case reports, case series, claims databases, national databases, surveys, adverse event reporting databases, and single or pooled clinical trials. The most common acute adverse events with bisphosphonates for osteoporosis...... and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  7. Adverse effects of bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, Bo

    2010-01-01

    events in bisphosphonate-treated patients was based on published information from case reports, case series, claims databases, national databases, surveys, adverse event reporting databases, and single or pooled clinical trials. The most common acute adverse events with bisphosphonates for osteoporosis...... and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse...

  8. Neurophysiology of space travel: energetic solar particles cause cell type-specific plasticity of neurotransmission.

    Science.gov (United States)

    Lee, Sang-Hun; Dudok, Barna; Parihar, Vipan K; Jung, Kwang-Mook; Zöldi, Miklós; Kang, Young-Jin; Maroso, Mattia; Alexander, Allyson L; Nelson, Gregory A; Piomelli, Daniele; Katona, István; Limoli, Charles L; Soltesz, Ivan

    2017-07-01

    In the not too distant future, humankind will embark on one of its greatest adventures, the travel to distant planets. However, deep space travel is associated with an inevitable exposure to radiation fields. Space-relevant doses of protons elicit persistent disruptions in cognition and neuronal structure. However, whether space-relevant irradiation alters neurotransmission is unknown. Within the hippocampus, a brain region crucial for cognition, perisomatic inhibitory control of pyramidal cells (PCs) is supplied by two distinct cell types, the cannabinoid type 1 receptor (CB 1 )-expressing basket cells (CB 1 BCs) and parvalbumin (PV)-expressing interneurons (PVINs). Mice subjected to low-dose proton irradiation were analyzed using electrophysiological, biochemical and imaging techniques months after exposure. In irradiated mice, GABA release from CB 1 BCs onto PCs was dramatically increased. This effect was abolished by CB 1 blockade, indicating that irradiation decreased CB 1 -dependent tonic inhibition of GABA release. These alterations in GABA release were accompanied by decreased levels of the major CB 1 ligand 2-arachidonoylglycerol. In contrast, GABA release from PVINs was unchanged, and the excitatory connectivity from PCs to the interneurons also underwent cell type-specific alterations. These results demonstrate that energetic charged particles at space-relevant low doses elicit surprisingly selective long-term plasticity of synaptic microcircuits in the hippocampus. The magnitude and persistent nature of these alterations in synaptic function are consistent with the observed perturbations in cognitive performance after irradiation, while the high specificity of these changes indicates that it may be possible to develop targeted therapeutic interventions to decrease the risk of adverse events during interplanetary travel.

  9. Cell-type specific four-component hydrogel.

    Directory of Open Access Journals (Sweden)

    Timo Aberle

    Full Text Available In the field of regenerative medicine we aim to develop implant matrices for specific tissue needs. By combining two per se, cell-permissive gel systems with enzymatic crosslinkers (gelatin/transglutaminase and fibrinogen/thrombin to generate a blend (technical term: quattroGel, an unexpected cell-selectivity evolved. QuattroGels were porous and formed cavities in the cell diameter range, possessed gelation kinetics in the minute range, viscoelastic properties and a mechanical strength appropriate for general cell adhesion, and restricted diffusion. Cell proliferation of endothelial cells, chondrocytes and fibroblasts was essentially unaffected. In contrast, on quattroGels neither endothelial cells formed vascular tubes nor did primary neurons extend neurites in significant amounts. Only chondrocytes differentiated properly as judged by collagen isoform expression. The biophysical quattroGel characteristics appeared to leave distinct cell processes such as mitosis unaffected and favored differentiation of sessile cells, but hampered differentiation of migratory cells. This cell-type selectivity is of interest e.g. during articular cartilage or invertebral disc repair, where pathological innervation and angiogenesis represent adverse events in tissue engineering.

  10. Differential Regulation of Cell Type-specific Apoptosis by Stromelysin-3

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    Mathew, Smita; Fu, Liezhen; Fiorentino, Maria; Matsuda, Hiroki; Das, Biswajit; Shi, Yun-Bo

    2009-01-01

    Matrix metalloproteinases (MMPs) have been extensively studied because of their functional attributes in development and diseases. However, relatively few in vivo functional studies have been reported on the roles of MMPs in postembryonic organ development. Amphibian metamorphosis is a unique model for studying MMP function during vertebrate development because of its dependence on thyroid hormone (T3) and the ability to easily manipulate this process with exogenous T3. The MMP stromelysin-3 (ST3) is induced by T3, and its expression correlates with cell death during metamorphosis. We have previously shown that ST3 is both necessary and sufficient for larval epithelial cell death in the remodeling intestine. To investigate the roles of ST3 in other organs and especially on different cell types, we have analyzed the effect of transgenic overexpression of ST3 in the tail of premetamorphic tadpoles. We report for the first time that ST3 expression, in the absence of T3, caused significant muscle cell death in the tail of premetamorphic transgenic tadpoles. On the other hand, only relatively low levels of epidermal cell death were induced by precocious ST3 expression in the tail, contrasting what takes place during natural and T3-induced metamorphosis when ST3 expression is high. This cell type-specific apoptotic response to ST3 in the tail suggests distinct mechanisms regulating cell death in different tissues. Furthermore, our analyses of laminin receptor, an in vivo substrate of ST3 in the intestine, suggest that laminin receptor cleavage may be an underlying mechanism for the cell type-specific effects of ST3. PMID:19429683

  11. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    2010-10-01

    Full Text Available A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions.Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells.These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  12. PINK1 is required for timely cell-type specific mitochondrial clearance during Drosophila midgut metamorphosis.

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    Liu, Yan; Lin, Jingjing; Zhang, Minjie; Chen, Kai; Yang, Shengxi; Wang, Qun; Yang, Hongqin; Xie, Shusen; Zhou, Yongjian; Zhang, Xi; Chen, Fei; Yang, Yufeng

    2016-11-15

    Mitophagy is the selective degradation of mitochondria by autophagy, which is an important mitochondrial quality and quantity control process. During Drosophila metamorphosis, the degradation of midgut involves a large change in length and organization, which is mediated by autophagy. Here we noticed a cell-type specific mitochondrial clearance process that occurs in enterocytes (ECs), while most mitochondria remain in intestinal stem cells (ISCs) during metamorphosis. Although PINK1/PARKIN represent the canonical pathway for the elimination of impaired mitochondria in varied pathological conditions, their roles in developmental processes or normal physiological conditions have been less studied. To examine the potential contribution of PINK1 in developmental processes, we monitored the dynamic expression pattern of PINK1 in the midgut development by taking advantage of a newly CRISPR/Cas9 generated knock-in fly strain expressing PINK1-mCherry fusion protein that presumably recapitulates the endogenous expression pattern of PINK1. We disclosed a spatiotemporal correlation between the expression pattern of PINK1 and the mitochondrial clearance or persistence in ECs or ISCs respectively. By mosaic genetic analysis, we then demonstrated that PINK1 and PARKIN function epistatically to mediate the specific timely removal of mitochondria, and are involved in global autophagy in ECs during Drosophila midgut metamorphosis, with kinase-dead PINK1 exerting dominant negative effects. Taken together, our studies concluded that the PINK1/PARKIN is crucial for timely cell-type specific mitophagy under physiological conditions and demonstrated again that Drosophila midgut metamorphosis might serve as an elegant in vivo model to study autophagy. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Adverse effects of cannabis.

    Science.gov (United States)

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  14. Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells.

    Science.gov (United States)

    Zhao, Ming-Tao; Shao, Ning-Yi; Hu, Shijun; Ma, Ning; Srinivasan, Rajini; Jahanbani, Fereshteh; Lee, Jaecheol; Zhang, Sophia L; Snyder, Michael P; Wu, Joseph C

    2017-11-10

    Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression. We profiled genome-wide transcriptional activity and a variety of epigenetic marks in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in human endothelial cells (CD31+CD144+), cardiac progenitor cells (Sca-1+), fibroblasts (DDR2+), and their respective induced pluripotent stem cells. We uncovered 2 classes of regulatory DNA elements: class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. Both class I and class II regulatory elements exhibited stimulatory roles in nearby gene expression in a given cell type. However, class I promoters displayed more dominant regulatory effects on transcriptional abundance regardless of distal enhancers. Transcription factor network analysis indicated that human induced pluripotent stem cells and somatic cells from the heart selected their preferential regulatory elements to maintain cell type-specific gene expression. In addition, we validated the function of these enhancer elements in transgenic mouse embryos and human cells and identified a few enhancers that could possibly regulate the cardiac-specific gene expression. Given that a large number of genetic variants associated with human diseases are located in regulatory DNA elements, our study provides valuable resources for deciphering the

  15. In vivo FRET-FLIM reveals cell-type-specific protein interactions in Arabidopsis roots.

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    Long, Yuchen; Stahl, Yvonne; Weidtkamp-Peters, Stefanie; Postma, Marten; Zhou, Wenkun; Goedhart, Joachim; Sánchez-Pérez, María-Isabel; Gadella, Theodorus W J; Simon, Rüdiger; Scheres, Ben; Blilou, Ikram

    2017-08-03

    During multicellular development, specification of distinct cell fates is often regulated by the same transcription factors operating differently in distinct cis-regulatory modules, either through different protein complexes, conformational modification of protein complexes, or combinations of both. Direct visualization of different transcription factor complex states guiding specific gene expression programs has been challenging. Here we use in vivo FRET-FLIM (Förster resonance energy transfer measured by fluorescence lifetime microscopy) to reveal spatial partitioning of protein interactions in relation to specification of cell fate. We show that, in Arabidopsis roots, three fully functional fluorescently tagged cell fate regulators establish cell-type-specific interactions at endogenous expression levels and can form higher order complexes. We reveal that cell-type-specific in vivo FRET-FLIM distributions reflect conformational changes of these complexes to differentially regulate target genes and specify distinct cell fates.

  16. Characterization of Cell-Type-Specific Drug Transport and Resistance of Breast Cancers Using Tumor-Microenvironment-on-Chip.

    Science.gov (United States)

    Shin, Kyeonggon; Klosterhoff, Brett S; Han, Bumsoo

    2016-07-05

    Heterogeneous response and resistance of cancer cells to chemotherapeutic drugs pose a significant challenge for successful cancer treatments. In this study, an integrated experimental and theoretical analysis of cellular drug transport was developed. The experimental platform, called tumor-microenvironment-on-chip (T-MOC), is a microfluidic platform where cancer cells were cultured within a three-dimensional extracellular matrix perfused with interstitial fluid. Three types of human breast cancer cell lines (MCF-7, MDA-MB-231, and SUM-159PT) were cultured on this T-MOC platform, and their drug response and resistance to doxorubicin were characterized by time-lapse quantitative fluorescence microscopy. To study the effects of nanoparticle-mediated drug delivery, the transport and action of doxorubicin encapsulated nanoparticles were also examined. Based on the experimental data obtained, a theoretical model was developed to quantify and ultimately predict the cellular transport processes of drugs cell-type specifically. The results demonstrate that the cellular drug transport can be cell-type-specifically quantified by rate constants representing the uptake and efflux of doxorubicin across the cellular membrane.

  17. Molecular characterization of arabidopsis GAL4/UAS enhancer trap lines identifies novel cell-type-specific promoters

    NARCIS (Netherlands)

    Radoeva, Tatyana; Hove, ten C.A.; Saiga, Shunsuke; Weijers, Dolf

    2016-01-01

    Cell-type-specific gene expression is essential to distinguish between the numerous cell types of multicellular organism. Therefore, cell-type-specific gene expression is tightly regulated and for most genes RNA transcription is the central point of control. Thus, transcriptional reporters are

  18. Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

    Science.gov (United States)

    Zhou, Jiehua; Rossi, John J.

    2014-01-01

    One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges. PMID:24936916

  19. Gene-regulatory interactions in embryonic stem cells represent cell-type specific gene regulatory programs.

    Science.gov (United States)

    Ha, Misook; Hong, Soondo

    2017-10-13

    Pluripotency, the ability of embryonic stem cells to differentiate into specialized cell types, is determined by ESC-specific gene regulators such as transcription factors and chromatin modification factors. It is not well understood how ESCs are poised for differentiation, however, and methods are needed for prognosis of the molecular changes in the differentiation of ESCs into specific organs. We describe a new approach to infer cell-type specific gene regulatory programs based on gene regulatory interactions in ESCs. Our method infers the molecular logic of gene regulatory mechanisms by mapping the position-specific combinatory patterns of numerous regulators in ESCs into cell-type specific gene regulations. We validate the proposed approach by recapitulating the RNA-seq and microarray data of neuronal progenitor cells, adult liver cells, and ESCs from the integrated patterns of diverse gene regulators in ESCs. We find that the collective functions of diverse gene regulators in ESCs represent distinct gene regulatory programs in specialized cell types. Our new approach expands our understanding of the differential gene regulatory information in developments encoded in regulatory networks of ESCs. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. MultiSite Gateway-Compatible Cell Type-Specific Gene-Inducible System for Plants.

    Science.gov (United States)

    Siligato, Riccardo; Wang, Xin; Yadav, Shri Ram; Lehesranta, Satu; Ma, Guojie; Ursache, Robertas; Sevilem, Iris; Zhang, Jing; Gorte, Maartje; Prasad, Kalika; Wrzaczek, Michael; Heidstra, Renze; Murphy, Angus; Scheres, Ben; Mähönen, Ari Pekka

    2016-02-01

    A powerful method to study gene function is expression or overexpression in an inducible, cell type-specific system followed by observation of consequent phenotypic changes and visualization of linked reporters in the target tissue. Multiple inducible gene overexpression systems have been developed for plants, but very few of these combine plant selection markers, control of expression domains, access to multiple promoters and protein fusion reporters, chemical induction, and high-throughput cloning capabilities. Here, we introduce a MultiSite Gateway-compatible inducible system for Arabidopsis (Arabidopsis thaliana) plants that provides the capability to generate such constructs in a single cloning step. The system is based on the tightly controlled, estrogen-inducible XVE system. We demonstrate that the transformants generated with this system exhibit the expected cell type-specific expression, similar to what is observed with constitutively expressed native promoters. With this new system, cloning of inducible constructs is no longer limited to a few special cases but can be used as a standard approach when gene function is studied. In addition, we present a set of entry clones consisting of histochemical and fluorescent reporter variants designed for gene and promoter expression studies. © 2016 American Society of Plant Biologists. All Rights Reserved.

  1. Cell type-specific responses to salinity - the epidermal bladder cell transcriptome of Mesembryanthemum crystallinum.

    Science.gov (United States)

    Oh, Dong-Ha; Barkla, Bronwyn J; Vera-Estrella, Rosario; Pantoja, Omar; Lee, Sang-Yeol; Bohnert, Hans J; Dassanayake, Maheshi

    2015-08-01

    Mesembryanthemum crystallinum (ice plant) exhibits extreme tolerance to salt. Epidermal bladder cells (EBCs), developing on the surface of aerial tissues and specialized in sodium sequestration and other protective functions, are critical for the plant's stress adaptation. We present the first transcriptome analysis of EBCs isolated from intact plants, to investigate cell type-specific responses during plant salt adaptation. We developed a de novo assembled, nonredundant EBC reference transcriptome. Using RNAseq, we compared the expression patterns of the EBC-specific transcriptome between control and salt-treated plants. The EBC reference transcriptome consists of 37 341 transcript-contigs, of which 7% showed significantly different expression between salt-treated and control samples. We identified significant changes in ion transport, metabolism related to energy generation and osmolyte accumulation, stress signalling, and organelle functions, as well as a number of lineage-specific genes of unknown function, in response to salt treatment. The salinity-induced EBC transcriptome includes active transcript clusters, refuting the view of EBCs as passive storage compartments in the whole-plant stress response. EBC transcriptomes, differing from those of whole plants or leaf tissue, exemplify the importance of cell type-specific resolution in understanding stress adaptive mechanisms. No claim to original US government works. New Phytologist © 2015 New Phytologist Trust.

  2. Mechanisms of epigenetic and cell-type specific regulation of Hey target genes in ES cells and cardiomyocytes.

    Science.gov (United States)

    Weber, David; Heisig, Julia; Kneitz, Susanne; Wolf, Elmar; Eilers, Martin; Gessler, Manfred

    2015-02-01

    Hey bHLH transcription factors are critical effectors of Notch signaling. During mammalian heart development they are expressed in atrial and ventricular cardiomyocytes and in the developing endocardium. Hey knockout mice suffer from lethal cardiac defects, such as ventricular septum defects, valve defects and cardiomyopathy. Despite this functional relevance, little is known about the regulation of downstream targets in relevant cell types. The objective of this study was to elucidate the regulatory mechanisms by which Hey proteins affect gene expression in a cell type specific manner. We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey proteins generally correlates with the extent of Hey-binding to target promoters, Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These also lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4. Ectopic Nkx2-5 overexpression in ESC blocks Hey-mediated repression of these genes. Thus, Hey proteins mechanistically repress target genes via Hdac recruitment and histone deacetylation. In CM Hey-repression is counteracted by cardiac activators, which recruit histone acetylases and prevent Hey mediated deacetylation and subsequent repression for a subset of genes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.

    Directory of Open Access Journals (Sweden)

    Christopher D Brown

    Full Text Available Genetic variants in cis-regulatory elements or trans-acting regulators frequently influence the quantity and spatiotemporal distribution of gene transcription. Recent interest in expression quantitative trait locus (eQTL mapping has paralleled the adoption of genome-wide association studies (GWAS for the analysis of complex traits and disease in humans. Under the hypothesis that many GWAS associations tag non-coding SNPs with small effects, and that these SNPs exert phenotypic control by modifying gene expression, it has become common to interpret GWAS associations using eQTL data. To fully exploit the mechanistic interpretability of eQTL-GWAS comparisons, an improved understanding of the genetic architecture and causal mechanisms of cell type specificity of eQTLs is required. We address this need by performing an eQTL analysis in three parts: first we identified eQTLs from eleven studies on seven cell types; then we integrated eQTL data with cis-regulatory element (CRE data from the ENCODE project; finally we built a set of classifiers to predict the cell type specificity of eQTLs. The cell type specificity of eQTLs is associated with eQTL SNP overlap with hundreds of cell type specific CRE classes, including enhancer, promoter, and repressive chromatin marks, regions of open chromatin, and many classes of DNA binding proteins. These associations provide insight into the molecular mechanisms generating the cell type specificity of eQTLs and the mode of regulation of corresponding eQTLs. Using a random forest classifier with cell specific CRE-SNP overlap as features, we demonstrate the feasibility of predicting the cell type specificity of eQTLs. We then demonstrate that CREs from a trait-associated cell type can be used to annotate GWAS associations in the absence of eQTL data for that cell type. We anticipate that such integrative, predictive modeling of cell specificity will improve our ability to understand the mechanistic basis of human

  4. Cell-type-specific inhibition of the dendritic plateau potential in striatal spiny projection neurons.

    Science.gov (United States)

    Du, Kai; Wu, Yu-Wei; Lindroos, Robert; Liu, Yu; Rózsa, Balázs; Katona, Gergely; Ding, Jun B; Kotaleski, Jeanette Hellgren

    2017-09-05

    Striatal spiny projection neurons (SPNs) receive convergent excitatory synaptic inputs from the cortex and thalamus. Activation of spatially clustered and temporally synchronized excitatory inputs at the distal dendrites could trigger plateau potentials in SPNs. Such supralinear synaptic integration is crucial for dendritic computation. However, how plateau potentials interact with subsequent excitatory and inhibitory synaptic inputs remains unknown. By combining computational simulation, two-photon imaging, optogenetics, and dual-color uncaging of glutamate and GABA, we demonstrate that plateau potentials can broaden the spatiotemporal window for integrating excitatory inputs and promote spiking. The temporal window of spiking can be delicately controlled by GABAergic inhibition in a cell-type-specific manner. This subtle inhibitory control of plateau potential depends on the location and kinetics of the GABAergic inputs and is achieved by the balance between relief and reestablishment of NMDA receptor Mg2+ block. These findings represent a mechanism for controlling spatiotemporal synaptic integration in SPNs.

  5. [Adverse ocular effects of vaccinations].

    Science.gov (United States)

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

  6. The female gametophyte: an emerging model for cell type-specific systems biology in plant development

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    Marc William Schmid

    2015-11-01

    Full Text Available Systems biology, a holistic approach describing a system emerging from the interactions of its molecular components, critically depends on accurate qualitative determination and quantitative measurements of these components. Development and improvement of large-scale profiling methods (omics now facilitates comprehensive measurements of many relevant molecules. For multicellular organisms, such as animals, fungi, algae, and plants, the complexity of the system is augmented by the presence of specialized cell types and organs, and a complex interplay within and between them. Cell type-specific analyses are therefore crucial for the understanding of developmental processes and environmental responses. This review first gives an overview of current methods used for large-scale profiling of specific cell types exemplified by recent advances in plant biology. The focus then lies on suitable model systems to study plant development and cell type specification. We introduce the female gametophyte of flowering plants as an ideal model to study fundamental developmental processes. Moreover, the female reproductive lineage is of importance for the emergence of evolutionary novelties such as an unequal parental contribution to the tissue nurturing the embryo or the clonal production of seeds by asexual reproduction (apomixis. Understanding these processes is not only interesting from a developmental or evolutionary perspective, but bears great potential for further crop improvement and the simplification of breeding efforts. We finally highlight novel methods, which are already available or which will likely soon facilitate large-scale profiling of the specific cell types of the female gametophyte in both model and non-model species. We conclude that it may take only few years until an evolutionary systems biology approach toward female gametogenesis may decipher some of its biologically most interesting and economically most valuable processes.

  7. Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress.

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    Hamilton, Peter J; Burek, Dominika J; Lombroso, Sonia I; Neve, Rachael L; Robison, Alfred J; Nestler, Eric J; Heller, Elizabeth A

    2018-01-01

    Chronic social defeat stress regulates the expression of Fosb in the nucleus accumbens (NAc) to promote the cell-type-specific accumulation of ΔFosB in the two medium spiny neuron (MSN) subtypes in this region. ΔFosB is selectively induced in D1-MSNs in the NAc of resilient mice, and in D2-MSNs of susceptible mice. However, little is known about the consequences of such selective induction, particularly in D2-MSNs. This study examined how cell-type-specific control of the endogenous Fosb gene in NAc regulates susceptibility to social defeat stress. Histone post-translational modifications (HPTMs) were targeted specifically to Fosb using engineered zinc-finger proteins (ZFPs). Fosb-ZFPs were fused to either the transcriptional repressor, G9a, which promotes histone methylation or the transcriptional activator, p65, which promotes histone acetylation. These ZFPs were expressed in D1- vs D2-MSNs using Cre-dependent viral expression in the NAc of mice transgenic for Cre recombinase in these MSN subtypes. We found that stress susceptibility is oppositely regulated by the specific cell type and HPTM targeted. We report that Fosb-targeted histone acetylation in D2-MSNs or histone methylation in D1-MSNs promotes a stress-susceptible, depressive-like phenotype, while histone methylation in D2-MSNs or histone acetylation in D1-MSNs increases resilience to social stress as quantified by social interaction behavior and sucrose preference. This work presents the first demonstration of cell- and gene-specific targeting of histone modifications, which model naturally occurring transcriptional phenomena that control social defeat stress behavior. This epigenetic-editing approach, which recapitulates physiological changes in gene expression, reveals clear differences in the social defeat phenotype induced by Fosb gene manipulation in MSN subtypes.

  8. [Finasteride adverse effects: An update].

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    Carreño-Orellana, Néstor; Moll-Manzur, Catherina; Carrasco-Zuber, Juan Eduardo; Álvarez-Véliz, Sergio; Berroeta-Mauriziano, Daniela; Porras-Kusmanic, Ninoska

    2016-12-01

    Finasteride is a 5-α reductase inhibitor that is widely used in the management of benign prostate hyperplasia and male pattern hair loss. It is well known that these agents improve the quality of life in men suffering from these conditions. However, they are associated with some transient and even permanent adverse effects. The aim of this article is to clarify the controversies about the safety of finasteride by analyzing the evidence available in the literature.

  9. Integrated metabolic modelling reveals cell-type specific epigenetic control points of the macrophage metabolic network.

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    Pacheco, Maria Pires; John, Elisabeth; Kaoma, Tony; Heinäniemi, Merja; Nicot, Nathalie; Vallar, Laurent; Bueb, Jean-Luc; Sinkkonen, Lasse; Sauter, Thomas

    2015-10-19

    The reconstruction of context-specific metabolic models from easily and reliably measurable features such as transcriptomics data will be increasingly important in research and medicine. Current reconstruction methods suffer from high computational effort and arbitrary threshold setting. Moreover, understanding the underlying epigenetic regulation might allow the identification of putative intervention points within metabolic networks. Genes under high regulatory load from multiple enhancers or super-enhancers are known key genes for disease and cell identity. However, their role in regulation of metabolism and their placement within the metabolic networks has not been studied. Here we present FASTCORMICS, a fast and robust workflow for the creation of high-quality metabolic models from transcriptomics data. FASTCORMICS is devoid of arbitrary parameter settings and due to its low computational demand allows cross-validation assays. Applying FASTCORMICS, we have generated models for 63 primary human cell types from microarray data, revealing significant differences in their metabolic networks. To understand the cell type-specific regulation of the alternative metabolic pathways we built multiple models during differentiation of primary human monocytes to macrophages and performed ChIP-Seq experiments for histone H3 K27 acetylation (H3K27ac) to map the active enhancers in macrophages. Focusing on the metabolic genes under high regulatory load from multiple enhancers or super-enhancers, we found these genes to show the most cell type-restricted and abundant expression profiles within their respective pathways. Importantly, the high regulatory load genes are associated to reactions enriched for transport reactions and other pathway entry points, suggesting that they are critical regulatory control points for cell type-specific metabolism. By integrating metabolic modelling and epigenomic analysis we have identified high regulatory load as a common feature of metabolic

  10. Adverse effects of marijuana use.

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    Feeney, Kathleen E; Kampman, Kyle M

    2016-05-01

    Marijuana has consistently been reported as the most commonly used illicit substance in the United States each year. Currently, the legalization of marijuana is up for debate across the nation. While marijuana use is prevalent among the adolescent population, research has shown that there can be devastating effects on health and well-being. A review of the literature shows that marijuana use can have a negative impact on physical health, psychological well-being, and multiple psychosocial outcomes. Adolescents who used marijuana more frequently and began using marijuana at an earlier age experienced worse outcomes and long-lasting effects. This article reviews recent literature regarding adverse effects of marijuana use. Negative effects of marijuana use relating to physical health, psychological well-being, and outcomes such as academic performance are discussed, especially in relation to the adolescent population.

  11. Adverse effects of antiretroviral treatment

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    Sharma Ajay

    2008-01-01

    Full Text Available Background: The introduction of highly active antiretroviral therapy (HAART has led to significant reduction in acquired immune deficiency syndrome (AIDS-related morbidity and mortality. Adverse drug reactions (ADRs to antiretroviral treatment (ART are however, major obstacles in its success. Aims: We sought to study the adverse effects of ART in a resource-restricted setting in India. Methods: Hundred patients on ART were studied prospectively over a period of two years. All patients were asked to visit the clinic if they developed any symptoms or on a monthly basis. They were screened clinically and investigated suitably for any ADRs. Result: Out of the 100 patients, ten patients did not come for follow-up; only 90 cases were available for evaluation. ADRs were observed in 64 cases (71.1% - the maximal frequency of ADRs was seen with zidovudine (AZT (50% followed by stavudine (d4T (47.9%, efavirenz (EFV (45.4% and finally, Nevirapine (NVP (18.4%. Most common ADRs were cutaneous (44.4% followed by hematological (32.2%, neurological (31.1%, metabolic (22.2% and gastrointestinal (20%. Most common cutaneous ADRs observed were nail hyperpigmentation (14.4% and rash (13.3%. Immune reconstitution inflammatory syndrome (IRIS was observed as a paradoxical reaction to ART in 20 (22.2% cases. Conclusion: To optimize adherence and thus, efficacy of ART, clinicians must focus on preventing adverse effects whenever possible, and distinguish those that are self-limited from those that are potentially serious.

  12. Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

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    Jue Lin

    2016-01-01

    Full Text Available Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL in CD4+, CD8+CD28+, and CD8+CD28− T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28− cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

  13. Cell-type-specific resonances shape the responses of striatal neurons to synaptic input.

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    Beatty, Joseph A; Song, Soomin C; Wilson, Charles J

    2015-02-01

    Neurons respond to synaptic inputs in cell-type-specific ways. Each neuron type may thus respond uniquely to shared patterns of synaptic input. We applied statistically identical barrages of artificial synaptic inputs to four striatal cell types to assess differences in their responses to a realistic input pattern. Each interneuron type fired in phase with a specific input-frequency component. The fast-spiking interneuron fired in relation to the gamma-band (and higher) frequencies, the low-threshold spike interneuron to the beta-band frequencies, and the cholinergic neurons to the delta-band frequencies. Low-threshold spiking and cholinergic interneurons showed input impedance resonances at frequencies matching their spiking resonances. Fast-spiking interneurons showed resonance of input impedance but at lower than gamma frequencies. The spiny projection neuron's frequency preference did not have a fixed frequency but instead tracked its own firing rate. Spiny cells showed no input impedance resonance. Striatal interneurons are each tuned to a specific frequency band corresponding to the major frequency components of local field potentials. Their influence in the circuit may fluctuate along with the contribution of that frequency band to the input. In contrast, spiny neurons may tune to any of the frequency bands by a change in firing rate. Copyright © 2015 the American Physiological Society.

  14. Cell type-specific expression analysis to identify putative cellular mechanisms for neurogenetic disorders.

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    Xu, Xiaoxiao; Wells, Alan B; O'Brien, David R; Nehorai, Arye; Dougherty, Joseph D

    2014-01-22

    Recent advances have substantially increased the number of genes that are statistically associated with complex genetic disorders of the CNS such as autism and schizophrenia. It is now clear that there will likely be hundreds of distinct loci contributing to these disorders, underscoring a remarkable genetic heterogeneity. It is unclear whether this genetic heterogeneity indicates an equal heterogeneity of cellular mechanisms for these diseases. The commonality of symptoms across patients suggests there could be a functional convergence downstream of these loci upon a limited number of cell types or circuits that mediate the affected behaviors. One possible mechanism for this convergence would be the selective expression of at least a subset of these genes in the cell types that comprise these circuits. Using profiling data from mice and humans, we have developed and validated an approach, cell type-specific expression analysis, for identifying candidate cell populations likely to be disrupted across sets of patients with distinct genetic lesions. Using human genetics data and postmortem gene expression data, our approach can correctly identify the cell types for disorders of known cellular etiology, including narcolepsy and retinopathies. Applying this approach to autism, a disease where the cellular mechanism is unclear, indicates there may be multiple cellular routes to this disorder. Our approach may be useful for identifying common cellular mechanisms arising from distinct genetic lesions.

  15. Cell-type-specific gene expression patterns in the knee cartilage in an osteoarthritis rat model.

    Science.gov (United States)

    Korostynski, Michal; Malek, Natalia; Piechota, Marcin; Starowicz, Katarzyna

    2018-01-01

    Osteoarthritis (OA) is a chronic degenerative disease that leads to joint failure, pain, and disability. Gene regulation is implicated as a driver of the imbalance between the expression of catabolic and anabolic factors that eventually leads to the degeneration of osteoarthritic cartilage. In our model, knee-joint OA was induced in male Wistar rats by intra-articular sodium monoiodoacetate (MIA) injections. Whole-genome microarrays were used to analyse the alterations in gene expression during the time-course of OA development (at 2, 14, and 28 days post-injection) in rat knee joints. The identified co-expressed groups of genes were analysed for enriched regulatory mechanisms, functional classes, and cell-type-specific expression. This analysis revealed 272 regulated transcripts (ANOVA FDR  2). Functionally, the five major gene expression patterns (A-E) were connected to PPAR signalling and adipogenesis (in cluster A), WNT signalling (in cluster B), endochondral ossification (in cluster C), matrix metalloproteinases and the ACE/RAGE pathway (in cluster D), and the Toll-like receptor, and IL-1 signalling pathways (in cluster E). Moreover, the dynamic profiles of these transcriptional changes were assigned to cellular compartments of the knee joint. Classifying the molecular processes associated with the development of cartilage degeneration provides novel insight into the OA disease process. Our study identified groups of co-regulated genes that share functional relationships and that may play an important role in the early and intermediate stages of OA.

  16. Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.

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    Martin H Schaefer

    2014-06-01

    Full Text Available Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors and the output (transcription factors layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types.

  17. Cell type-specific translational repression of Cyclin B during meiosis in males.

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    Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T

    2015-10-01

    The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I. © 2015. Published by The Company of Biologists Ltd.

  18. Layer- and cell-type-specific suprathreshold stimulus representation in rat primary somatosensory cortex

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    de Kock, C P J; Bruno, R M; Spors, H; Sakmann, B

    2007-01-01

    Sensory stimuli are encoded differently across cortical layers and it is unknown how response characteristics relate to the morphological identity of responding cells. We therefore juxtasomally recorded action potential (AP) patterns from excitatory cells in layer (L) 2/3, L4, L5 and L6 of rat barrel cortex in response to a standard stimulus (e.g. repeated deflection of single whiskers in the caudal direction). Subsequent single-cell filling with biocytin allowed for post hoc identification of recorded cells. We report three major conclusions. First, sensory-evoked responses were layer- and cell-type-specific but always < 1 AP per stimulus, indicating low AP rates for the entire cortical column. Second, response latencies from L4, L5B and L6 were comparable and thus a whisker deflection is initially represented simultaneously in these layers. Finally, L5 thick-tufted cells dominated the cortical AP output following sensory stimulation, suggesting that these cells could direct sensory guided behaviours. PMID:17317752

  19. Cell-Type-Specific Cytokinin Distribution within the Arabidopsis Primary Root Apex[OPEN

    Science.gov (United States)

    Antoniadi, Ioanna; Plačková, Lenka; Simonovik, Biljana; Doležal, Karel; Turnbull, Colin; Ljung, Karin; Novák, Ondřej

    2015-01-01

    Cytokinins (CKs) play a crucial role in many physiological and developmental processes at the levels of individual plant components (cells, tissues, and organs) and by coordinating activities across these parts. High-resolution measurements of intracellular CKs in different plant tissues can therefore provide insights into their metabolism and mode of action. Here, we applied fluorescence-activated cell sorting of green fluorescent protein (GFP)-marked cell types, combined with solid-phase microextraction and an ultra-high-sensitivity mass spectrometry (MS) method for analysis of CK biosynthesis and homeostasis at cellular resolution. This method was validated by series of control experiments, establishing that protoplast isolation and cell sorting procedures did not greatly alter endogenous CK levels. The MS-based method facilitated the quantification of all the well known CK isoprenoid metabolites in four different transgenic Arabidopsis thaliana lines expressing GFP in specific cell populations within the primary root apex. Our results revealed the presence of a CK gradient within the Arabidopsis root tip, with a concentration maximum in the lateral root cap, columella, columella initials, and quiescent center cells. This distribution, when compared with previously published auxin gradients, implies that the well known antagonistic interactions between the two hormone groups are cell type specific. PMID:26152699

  20. Adverse effects of antihypertensive drugs.

    Science.gov (United States)

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  1. Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.

    Science.gov (United States)

    Wang, Xin; Lin, Peijie; Ho, Joshua W K

    2018-01-19

    It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model. We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar. Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.

  2. Campylobacter jejuni mediated disruption of polarized epithelial monolayers is cell-type specific, time dependent, and correlates with bacterial invasion.

    Science.gov (United States)

    Wine, Eytan; Chan, Voon L; Sherman, Philip M

    2008-12-01

    The precise mechanism by which the most common cause of bacterial enterocolitis in humans, Campylobacter jejuni, perturbs the intestinal mucosa remains elusive. To define effects of C. jejuni infection on mucosal permeability, Madin-Darby canine kidney (MDCK)-I and T84 cell monolayers were infected with C. jejuni for up to 48 h. All three tested C. jejuni strains caused a 73-78% reduction in transepithelial electrical resistance (TER) in intestinal (T84) cell monolayers, whereas only one strain slightly reduced TER of MDCK-I cells by 25% after 48 h infection. Infection with C. jejuni strains also caused a 2.3-4.5-fold increase in dextran permeability, but only in T84 cells. C. jejuni infection of monolayers also caused morphologic changes in desmosomes, observed by transmission electron microscopy. The cell-type specificity, demonstrated by increased T84 monolayer permeability, correlated with higher bacterial invasion into these cells, relative to MDCK-I cells. In T84 cells, invasion and bacterial translocation preceded barrier disruption and inhibition of C. jejuni invasion using a pharmacological inhibitor of phosphoinositide 3-kinase, reduced the drop in TER. These findings suggest that C. jejuni disruption of monolayers is mediated by invasion, provide new insights into C. jejuni-host epithelial barrier interactions, and offer potential mechanisms of intestinal injury and chronic immune stimulation.

  3. Epigenetic regulation of normal human mammary cell type-specific miRNAs

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    Vrba, Lukas [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Inst. of Plant Molecular Biology, Ceske Budejovice (Czech Republic). Biology Centre ASCR; Garbe, James C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Stampfer, Martha R. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Futscher, Bernard W. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center and Dept. of Pharmacology & Toxicology

    2011-08-26

    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  4. A machine learning approach for identifying novel cell type-specific transcriptional regulators of myogenesis.

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    Brian W Busser

    TFs that coordinate cell type-specific developmental gene expression patterns.

  5. A machine learning approach for identifying novel cell type-specific transcriptional regulators of myogenesis.

    Science.gov (United States)

    Busser, Brian W; Taher, Leila; Kim, Yongsok; Tansey, Terese; Bloom, Molly J; Ovcharenko, Ivan; Michelson, Alan M

    2012-01-01

    coordinate cell type-specific developmental gene expression patterns.

  6. Cell-type specificity of ChIP-predicted transcription factor binding sites

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    Håndstad Tony

    2012-08-01

    Full Text Available Abstract Background Context-dependent transcription factor (TF binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding? Results We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity. Conclusions Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.

  7. Cell type-specific glycoconjugates of collecting duct cells during maturation of the rat kidney.

    Science.gov (United States)

    Holthöfer, H

    1988-08-01

    The ontogeny of lectin-positive epithelial cell types and the maturation of polarized expression of the glycocalyx of the collecting ducts (CD) of the rat kidney were studied from samples of 18th-day fetal and neonatal kidneys of various ages. Lectins from Dolichos biflorus (DBA) and Vicia villosa (VVA), with preferential affinity to principal cells, stained virtually all CD cells of the fetal kidneys. However, within two days postnatally, the number of cells positive for DBA and VVA decreased to amounts found in the adult kidneys. Moreover, a characteristic change occurred rapidly after birth in the intracellular polarization of the reactive glycoconjugates, from a uniform plasmalemmal to a preferentially apical staining. In contrast, lectins from Arachis hypogaea (PNA), Maclura pomifera (MPA) and Lotus tetragonolobus (LTA), reacting indiscriminatively with principal and intercalated cells of adult kidneys, stained most CD cells in the fetal kidneys, and failed to show any postnatal change in the amount of positive cells or in the intracellular polarization. The immunocytochemical tests for (Na + K)-ATPase and carbonic anhydrase (CA II) revealed the characteristic postnatal decrease in the amount of principal cells and simultaneous increase in the amount of CA II rich intercalated cells. DBA and VVA reactive cells also decreased postnatally, paralleling the changes observed in the (Na + K)-ATPase positive principal cells. The present results suggest that the expression of the cell type-specific glycocalyx of principal and intercalated cells is developmentally regulated, undergoes profound changes during maturation, and is most likely associated with electrolyte transport phenomena.

  8. Lim homeobox genes in the Ctenophore Mnemiopsis leidyi: the evolution of neural cell type specification

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    Simmons David K

    2012-01-01

    Full Text Available Abstract Background Nervous systems are thought to be important to the evolutionary success and diversification of metazoans, yet little is known about the origin of simple nervous systems at the base of the animal tree. Recent data suggest that ctenophores, a group of macroscopic pelagic marine invertebrates, are the most ancient group of animals that possess a definitive nervous system consisting of a distributed nerve net and an apical statocyst. This study reports on details of the evolution of the neural cell type specifying transcription factor family of LIM homeobox containing genes (Lhx, which have highly conserved functions in neural specification in bilaterian animals. Results Using next generation sequencing, the first draft of the genome of the ctenophore Mnemiopsis leidyi has been generated. The Lhx genes in all animals are represented by seven subfamilies (Lhx1/5, Lhx3/4, Lmx, Islet, Lhx2/9, Lhx6/8, and LMO of which four were found to be represented in the ctenophore lineage (Lhx1/5, Lhx3/4, Lmx, and Islet. Interestingly, the ctenophore Lhx gene complement is more similar to the sponge complement (sponges do not possess neurons than to either the cnidarian-bilaterian or placozoan Lhx complements. Using whole mount in situ hybridization, the Lhx gene expression patterns were examined and found to be expressed around the blastopore and in cells that give rise to the apical organ and putative neural sensory cells. Conclusion This research gives us a first look at neural cell type specification in the ctenophore M. leidyi. Within M. leidyi, Lhx genes are expressed in overlapping domains within proposed neural cellular and sensory cell territories. These data suggest that Lhx genes likely played a conserved role in the patterning of sensory cells in the ancestor of sponges and ctenophores, and may provide a link to the expression of Lhx orthologs in sponge larval photoreceptive cells. Lhx genes were later co-opted into patterning more

  9. Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors.

    Science.gov (United States)

    Qi, Yong; Yang, Yunlei

    2015-09-23

    It remains largely unknown whether and how hunger states control activity-dependent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). We here report that both LTP and LTD of excitatory synaptic strength within the appetite control circuits residing in hypothalamic arcuate nucleus (ARC) behave in a manner of hunger states dependence and cell type specificity. For instance, we find that tetanic stimulation induces LTP at orexigenic agouti-related protein (AgRP) neurons in ad libitum fed mice, whereas it induces LTD in food-deprived mice. In an opposite direction, the same induction protocol induces LTD at anorexigenic pro-opiomelanocortin (POMC) neurons in fed mice but weak LTP in deprived mice. Mechanistically, we also find that food deprivation increases the expressions of NR2C/NR2D/NR3-containing NMDA receptors (NMDARs) at AgRP neurons that contribute to the inductions of LTD, whereas it decreases their expressions at POMC neurons. Collectively, our data reveal that hunger states control the directions of activity-dependent synaptic plasticity by switching NMDA receptor subpopulations in a cell type-specific manner, providing insights into NMDAR-mediated interactions between energy states and associative memory. Significance statement: Based on the experiments performed in this study, we demonstrate that activity-dependent synaptic plasticity is also under the control of energy states by regulating NMDAR subpopulations in a cell type-specific manner. We thus propose a reversible memory configuration constructed from energy states-dependent cell type-specific bidirectional conversions of LTP and LTD. Together with the distinct functional roles played by NMDAR signaling in the control of food intake and energy states, these findings reveal a new reciprocal interaction between energy states and associative memory, one that might serve as a target for therapeutic treatments of the energy-related memory disorders or vice versa

  10. Comprehensive Identification and Annotation of Cell Type-Specific and Ubiquitous CTCF-Binding Sites in the Human Genome

    Science.gov (United States)

    Shu, Wenjie; Bo, Xiaochen; Wang, Shengqi

    2012-01-01

    Chromatin insulators are DNA elements that regulate the level of gene expression either by preventing gene silencing through the maintenance of heterochromatin boundaries or by preventing gene activation by blocking interactions between enhancers and promoters. CCCTC-binding factor (CTCF), a ubiquitously expressed 11-zinc-finger DNA-binding protein, is the only protein implicated in the establishment of insulators in vertebrates. While CTCF has been implicated in diverse regulatory functions, CTCF has only been studied in a limited number of cell types across human genome. Thus, it is not clear whether the identified cell type-specific differences in CTCF-binding sites are functionally significant. Here, we identify and characterize cell type-specific and ubiquitous CTCF-binding sites in the human genome across 38 cell types designated by the Encyclopedia of DNA Elements (ENCODE) consortium. These cell type-specific and ubiquitous CTCF-binding sites show uniquely versatile transcriptional functions and characteristic chromatin features. In addition, we confirm the insulator barrier function of CTCF-binding and explore the novel function of CTCF in DNA replication. These results represent a critical step toward the comprehensive and systematic understanding of CTCF-dependent insulators and their versatile roles in the human genome. PMID:22829947

  11. Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei.

    Science.gov (United States)

    Brunert, Daniela; Tsuno, Yusuke; Rothermel, Markus; Shipley, Michael T; Wachowiak, Matt

    2016-06-22

    Serotonergic neurons in the brainstem raphe nuclei densely innervate the olfactory bulb (OB), where they can modulate the initial representation and processing of olfactory information. Serotonergic modulation of sensory responses among defined OB cell types is poorly characterized in vivo Here, we used cell-type-specific expression of optical reporters to visualize how raphe stimulation alters sensory responses in two classes of GABAergic neurons of the mouse OB glomerular layer, periglomerular (PG) and short axon (SA) cells, as well as mitral/tufted (MT) cells carrying OB output to piriform cortex. In PG and SA cells, brief (1-4 s) raphe stimulation elicited a large increase in the magnitude of responses linked to inhalation of ambient air, as well as modest increases in the magnitude of odorant-evoked responses. Near-identical effects were observed when the optical reporter of glutamatergic transmission iGluSnFR was expressed in PG and SA cells, suggesting enhanced excitatory input to these neurons. In contrast, in MT cells imaged from the dorsal OB, raphe stimulation elicited a strong increase in resting GCaMP fluorescence with only a slight enhancement of inhalation-linked responses to odorant. Finally, optogenetically stimulating raphe serotonergic afferents in the OB had heterogeneous effects on presumptive MT cells recorded extracellularly, with an overall modest increase in resting and odorant-evoked responses during serotonergic afferent stimulation. These results suggest that serotonergic afferents from raphe dynamically modulate olfactory processing through distinct effects on multiple OB targets, and may alter the degree to which OB output is shaped by inhibition during behavior. Modulation of the circuits that process sensory information can profoundly impact how information about the external world is represented and perceived. This study investigates how the serotonergic system modulates the initial processing of olfactory information by the

  12. Drug and cell type-specific regulation of genes with different classes of estrogen receptor beta-selective agonists.

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    Sreenivasan Paruthiyil

    2009-07-01

    Full Text Available Estrogens produce biological effects by interacting with two estrogen receptors, ERalpha and ERbeta. Drugs that selectively target ERalpha or ERbeta might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERbeta-selective compounds have been identified. One class of ERbeta-selective agonists is represented by ERB-041 (WAY-202041 which binds to ERbeta much greater than ERalpha. A second class of ERbeta-selective agonists derived from plants include MF101, nyasol and liquiritigenin that bind similarly to both ERs, but only activate transcription with ERbeta. Diarylpropionitrile represents a third class of ERbeta-selective compounds because its selectivity is due to a combination of greater binding to ERbeta and transcriptional activity. However, it is unclear if these three classes of ERbeta-selective compounds produce similar biological activities. The goals of these studies were to determine the relative ERbeta selectivity and pattern of gene expression of these three classes of ERbeta-selective compounds compared to estradiol (E(2, which is a non-selective ER agonist. U2OS cells stably transfected with ERalpha or ERbeta were treated with E(2 or the ERbeta-selective compounds for 6 h. Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERbeta-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile. FRET analysis showed that all compounds induced a similar conformation of ERbeta, which is consistent with the finding that most genes regulated by the ERbeta-selective compounds were similar to each other and E(2. However, there were some classes of genes differentially regulated by the ERbeta agonists and E(2. Two ERbeta-selective compounds, MF101 and liquiritigenin had cell type-specific effects as they regulated different genes in HeLa, Caco-2 and Ishikawa cell lines expressing ERbeta. Our gene profiling studies

  13. Drug and cell type-specific regulation of genes with different classes of estrogen receptor beta-selective agonists.

    Science.gov (United States)

    Paruthiyil, Sreenivasan; Cvoro, Aleksandra; Zhao, Xiaoyue; Wu, Zhijin; Sui, Yunxia; Staub, Richard E; Baggett, Scott; Herber, Candice B; Griffin, Chandi; Tagliaferri, Mary; Harris, Heather A; Cohen, Isaac; Bjeldanes, Leonard F; Speed, Terence P; Schaufele, Fred; Leitman, Dale C

    2009-07-17

    Estrogens produce biological effects by interacting with two estrogen receptors, ERalpha and ERbeta. Drugs that selectively target ERalpha or ERbeta might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERbeta-selective compounds have been identified. One class of ERbeta-selective agonists is represented by ERB-041 (WAY-202041) which binds to ERbeta much greater than ERalpha. A second class of ERbeta-selective agonists derived from plants include MF101, nyasol and liquiritigenin that bind similarly to both ERs, but only activate transcription with ERbeta. Diarylpropionitrile represents a third class of ERbeta-selective compounds because its selectivity is due to a combination of greater binding to ERbeta and transcriptional activity. However, it is unclear if these three classes of ERbeta-selective compounds produce similar biological activities. The goals of these studies were to determine the relative ERbeta selectivity and pattern of gene expression of these three classes of ERbeta-selective compounds compared to estradiol (E(2)), which is a non-selective ER agonist. U2OS cells stably transfected with ERalpha or ERbeta were treated with E(2) or the ERbeta-selective compounds for 6 h. Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERbeta-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile. FRET analysis showed that all compounds induced a similar conformation of ERbeta, which is consistent with the finding that most genes regulated by the ERbeta-selective compounds were similar to each other and E(2). However, there were some classes of genes differentially regulated by the ERbeta agonists and E(2). Two ERbeta-selective compounds, MF101 and liquiritigenin had cell type-specific effects as they regulated different genes in HeLa, Caco-2 and Ishikawa cell lines expressing ERbeta. Our gene profiling studies demonstrate that

  14. Coordinated cell type-specific epigenetic remodeling in prefrontal cortex begins before birth and continues into early adulthood.

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    Hennady P Shulha

    2013-04-01

    Full Text Available Development of prefrontal and other higher-order association cortices is associated with widespread changes in the cortical transcriptome, particularly during the transitions from prenatal to postnatal development, and from early infancy to later stages of childhood and early adulthood. However, the timing and longitudinal trajectories of neuronal gene expression programs during these periods remain unclear in part because of confounding effects of concomitantly occurring shifts in neuron-to-glia ratios. Here, we used cell type-specific chromatin sorting techniques for genome-wide profiling of a histone mark associated with transcriptional regulation--H3 with trimethylated lysine 4 (H3K4me3--in neuronal chromatin from 31 subjects from the late gestational period to 80 years of age. H3K4me3 landscapes of prefrontal neurons were developmentally regulated at 1,157 loci, including 768 loci that were proximal to transcription start sites. Multiple algorithms consistently revealed that the overwhelming majority and perhaps all of developmentally regulated H3K4me3 peaks were on a unidirectional trajectory defined by either rapid gain or loss of histone methylation during the late prenatal period and the first year after birth, followed by similar changes but with progressively slower kinetics during early and later childhood and only minimal changes later in life. Developmentally downregulated H3K4me3 peaks in prefrontal neurons were enriched for Paired box (Pax and multiple Signal Transducer and Activator of Transcription (STAT motifs, which are known to promote glial differentiation. In contrast, H3K4me3 peaks subject to a progressive increase in maturing prefrontal neurons were enriched for activating protein-1 (AP-1 recognition elements that are commonly associated with activity-dependent regulation of neuronal gene expression. We uncovered a developmental program governing the remodeling of neuronal histone methylation landscapes in the prefrontal

  15. Cell-type-specific responses of RT4 neural cell lines to dibutyryl-cAMP: branch determination versus maturation.

    OpenAIRE

    Droms, K; Sueoka, N

    1987-01-01

    This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of...

  16. Cell-type-specific responses of RT4 neural cell lines to dibutyryl-cAMP: branch determination versus maturation.

    Science.gov (United States)

    Droms, K; Sueoka, N

    1987-01-01

    This report describes the induction of cell-type-specific maturation, by dibutyryl-cAMP and testololactone, of neuronal and glial properties in a family of cell lines derived from a rat peripheral neurotumor, RT4. This maturation allows further understanding of the process of determination because of the close lineage relationship between the cell types of the RT4 family. The RT4 family is characterized by the spontaneous conversion of one of the cell types, RT4-AC (stem-cell type), to any of three derivative cell types, RT4-B, RT4-D, or RT4-E, with a frequency of about 10(-5). The RT4-AC cells express some properties characteristic of both neuronal and glial cells. Of these neural properties expressed by RT4-AC cells, only the neuronal properties are expressed by the RT4-B and RT4-E cells, and only the glial properties are expressed by the RT4-D cells. This in vitro cell-type conversion of RT4-AC to three derivative cell types is a branch point for the coordinate regulation of several properties and seems to resemble determination in vivo. In our standard culture conditions, several other neuronal and glial properties are not expressed by these cell types. However, addition of dibutyryl-cAMP induces expression of additional properties, in a cell-type-specific manner: formation of long cellular processes in the RT4-B8 and RT4-E5 cell lines and expression of high-affinity uptake of gamma-aminobutyric acid, by a glial-cell-specific mechanism, in the RT4-D6-2 cell line. These new properties are maximally expressed 2-3 days after addition of dibutyryl-cAMP. This indicates that conversion of RT4-AC to the derivative cell types is also a branch point for the regulation of cell-type-specific properties whose expression is responsive to cAMP. Thus, the potential for maturation in response to increased cAMP is a property that segregates in a cell-type-specific manner and is activated at the determinational level in this system. Images PMID:3029777

  17. Perspective on Lithotripsy Adverse Effects

    Science.gov (United States)

    Knoll, Thomas; Wendt-Nordahl, Gunnar

    2008-09-01

    Shock wave lithotripsy (SWL) is an effective and without any doubt the least invasive procedure to treat upper urinary tract calculi. Acute complications are rarely reported and do not require specific treatment in most cases. However, one should be aware that energy levels sufficient for stone breakage are capable of damaging tissue as well, and significant hematoma—not only in the kidney but as well in surrounding organs—has been observed. Furthermore, only little is known about the long-term effects of SWL. Some authors have reported an increased incidence of hypertension and possibly also diabetes mellitus. Such chronic diseases—if indeed related to prior SWL—may be a late result of acute SWL-related trauma but the discussion on the underlying pathogenesis is controversial. Many factors have to be considered, such as the natural history of recurrent stone formers, technical principles of SWL, and differences in treatment protocols. Promising studies are currently underway to optimize stone breakage while limiting potential collateral damage. With this progress, SWL remains a safe treatment option for most urinary calculi.

  18. CAST-ChIP Maps Cell-Type-Specific Chromatin States in the Drosophila Central Nervous System

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    Tamás Schauer

    2013-10-01

    Full Text Available Chromatin organization and gene activity are responsive to developmental and environmental cues. Although many genes are transcribed throughout development and across cell types, much of gene regulation is highly cell-type specific. To readily track chromatin features at the resolution of cell types within complex tissues, we developed and validated chromatin affinity purification from specific cell types by chromatin immunoprecipitation (CAST-ChIP, a broadly applicable biochemical procedure. RNA polymerase II (Pol II CAST-ChIP identifies ∼1,500 neuronal and glia-specific genes in differentiated cells within the adult Drosophila brain. In contrast, the histone H2A.Z is distributed similarly across cell types and throughout development, marking cell-type-invariant Pol II-bound regions. Our study identifies H2A.Z as an active chromatin signature that is refractory to changes across cell fates. Thus, CAST-ChIP powerfully identifies cell-type-specific as well as cell-type-invariant chromatin states, enabling the systematic dissection of chromatin structure and gene regulation within complex tissues such as the brain.

  19. Cell-type specific oxytocin gene expression from AAV delivered promoter deletion constructs into the rat supraoptic nucleus in vivo.

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    Raymond L Fields

    Full Text Available The magnocellular neurons (MCNs in the hypothalamus selectively express either oxytocin (OXT or vasopressin (AVP neuropeptide genes, a property that defines their phenotypes. Here we examine the molecular basis of this selectivity in the OXT MCNs by stereotaxic microinjections of adeno-associated virus (AAV vectors that contain various OXT gene promoter deletion constructs using EGFP as the reporter into the rat supraoptic nucleus (SON. Two weeks following injection of the AAVs, immunohistochemical assays of EGFP expression from these constructs were done to determine whether the EGFP reporter co-localizes with either the OXT- or AVP-immunoreactivity in the MCNs. The results show that the key elements in the OT gene promoter that regulate the cell-type specific expression the SON are located -216 to -100 bp upstream of the transcription start site. We hypothesize that within this 116 bp domain a repressor exists that inhibits expression specifically in AVP MCNs, thereby leading to the cell-type specific expression of the OXT gene only in the OXT MCNs.

  20. MultiSite Gateway-Compatible Cell Type-Specific Gene-Inducible System for Plants1[OPEN

    Science.gov (United States)

    Siligato, Riccardo; Wang, Xin; Yadav, Shri Ram; Lehesranta, Satu; Ma, Guojie; Ursache, Robertas; Sevilem, Iris; Zhang, Jing; Gorte, Maartje; Prasad, Kalika; Heidstra, Renze

    2016-01-01

    A powerful method to study gene function is expression or overexpression in an inducible, cell type-specific system followed by observation of consequent phenotypic changes and visualization of linked reporters in the target tissue. Multiple inducible gene overexpression systems have been developed for plants, but very few of these combine plant selection markers, control of expression domains, access to multiple promoters and protein fusion reporters, chemical induction, and high-throughput cloning capabilities. Here, we introduce a MultiSite Gateway-compatible inducible system for Arabidopsis (Arabidopsis thaliana) plants that provides the capability to generate such constructs in a single cloning step. The system is based on the tightly controlled, estrogen-inducible XVE system. We demonstrate that the transformants generated with this system exhibit the expected cell type-specific expression, similar to what is observed with constitutively expressed native promoters. With this new system, cloning of inducible constructs is no longer limited to a few special cases but can be used as a standard approach when gene function is studied. In addition, we present a set of entry clones consisting of histochemical and fluorescent reporter variants designed for gene and promoter expression studies. PMID:26644504

  1. Cell type specificity and structural determinants of IRES activity from the 5' leaders of different HIV-1 transcripts.

    Science.gov (United States)

    Plank, Terra-Dawn M; Whitehurst, James T; Kieft, Jeffrey S

    2013-07-01

    Internal ribosome entry site (IRES) RNAs are important regulators of gene expression, but their diverse molecular mechanisms remain partially understood. The HIV-1 gag transcript leader contains an IRES that may be a good model for understanding the function of many other IRESs. We investigated the possibility that this IRES' function is linked to both the structure of the RNA and its cellular environment. We find that in the context of a bicistronic reporter construct, HIV-1 gag IRES' activity is cell type-specific, with higher activity in T-cell culture systems that model the natural target cells for HIV-1 infection. This finding underscores how an IRES may be fine tuned to function in certain cells, perhaps owing to cell type-specific protein factors. Using RNA probing and mutagenesis, we demonstrate that the HIV-1 gag IRES does not use pre-folded RNA structure to drive function, a finding that gives insight into how conformationally dynamic IRESs operate. Furthermore, we find that a common exon drives IRES activity in a diverse set of alternatively spliced transcripts. We propose a mechanism in which a structurally plastic RNA element confers the ability to initiate translation internally, and activity from this common element is modulated by 3' nucleotides added by alternative splicing.

  2. Cell type-specific manipulation with GFP-dependent Cre recombinase.

    Science.gov (United States)

    Tang, Jonathan C Y; Rudolph, Stephanie; Dhande, Onkar S; Abraira, Victoria E; Choi, Seungwon; Lapan, Sylvain W; Drew, Iain R; Drokhlyansky, Eugene; Huberman, Andrew D; Regehr, Wade G; Cepko, Constance L

    2015-09-01

    There are many transgenic GFP reporter lines that allow the visualization of specific populations of cells. Using such lines for functional studies requires a method that transforms GFP into a molecule that enables genetic manipulation. We developed a method that exploits GFP for gene manipulation, Cre recombinase dependent on GFP (CRE-DOG), a split component system that uses GFP and its derivatives to directly induce Cre/loxP recombination. Using plasmid electroporation and AAV viral vectors, we delivered CRE-DOG to multiple GFP mouse lines, which led to effective recombination selectively in GFP-labeled cells. Furthermore, CRE-DOG enabled optogenetic control of these neurons. Beyond providing a new set of tools for manipulation of gene expression selectively in GFP(+) cells, we found that GFP can be used to reconstitute the activity of a protein not known to have a modular structure, suggesting that this strategy might be applicable to a wide range of proteins.

  3. Genetic interactions between Brn3 transcription factors in retinal ganglion cell type specification.

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    Melody Shi

    Full Text Available Visual information is conveyed from the retina to the brain via 15-20 Retinal Ganglion Cell (RGC types. The developmental mechanisms by which RGC types acquire their distinct molecular, morphological, physiological and circuit properties are essentially unknown, but may involve combinatorial transcriptional regulation. Brn3 transcription factors are expressed in RGCs from early developmental stages, and are restricted in adults to distinct, partially overlapping populations of RGC types. Previously, we described cell autonomous effects of Brn3b (Pou4f2 and Brn3a (Pou4f1 on RGC axon and dendrites development.We now have investigated genetic interactions between Brn3 transcription factors with respect to RGC development, by crossing conventional knock-out alleles of each Brn3 gene with conditional knock-in reporter alleles of a second Brn3 gene, and analyzing the effects of single or double Brn3 knockouts on RGC survival and morphology. We find that Brn3b loss results in axon defects and dendritic arbor area and lamination defects in Brn3a positive RGCs, and selectively affects survival and morphology of specific Brn3c (Pou4f3 positive RGC types. Brn3a and Brn3b interact synergistically to control RGC numbers. Melanopsin positive ipRGCs are resistant to combined Brn3 loss but are under the transcriptional control of Isl1, expanding the combinatorial code of RGC specification.Taken together these results complete our knowledge on the mechanisms of transcriptional control of RGC type specification. They demonstrate that Brn3b is required for the correct development of more RGC cell types than suggested by its expression pattern in the adult, but that several cell types, including some Brn3a, Brn3c or Melanopsin positive RGCs are Brn3b independent.

  4. Cell type-specific regulation of brain-derived neurotrophic factor in states of allergic inflammation.

    Science.gov (United States)

    Groneberg, D A; Fischer, T C; Peckenschneider, N; Noga, O; Dinh, Q T; Welte, T; Welker, P

    2007-09-01

    Brain-derived neurotrophic factor (BDNF) is a molecule influencing neuronal proliferation and differentiation. In states of allergy, it may orchestrate inflammatory changes by linking the immune system with the nervous system. Because the precise regulation of gene transcription in mast cells MCs is not clear, the present studies assessed the gene regulation of BDNF in this inflammatory cell type. Transcriptional expression of BDNF in human skin was studied in isolated cells using RT-PCR. In situ lesional MC BDNF protein expression was analysed by immunohistochemistry and related to the differential staining of MCs and functional effects of BDNF on HaCaT keratinocytes. BDNF mRNA expression was found in isolated human skin MCs, keratinocytes, and fibroblasts. Also, low levels were found in endothelial cells and melanocytes. BDNF protein expression was found in situ in lesional and non-lesional MCs. A significantly decreased expression of BDNF protein was found in atopic dermatitis lesional MCs when compared with control MC expression. Functional in vitro experiments demonstrated that a decrease in BDNF stimulation led to increased secretion rates for stem cell factor and IL-8 in HaCaT keratinocytes. The demonstration of a decreased level of BDNF gene transcription in lesional MCs points to a differential regulation of MC-released neutrotrophins in cutaneous allergic inflammation. Topically administered neurotrophin receptor-modulating compounds should be receptor target specific and not universally acting in diseases such as atopic dermatitis or allergic asthma.

  5. eFORGE: A Tool for Identifying Cell Type-Specific Signal in Epigenomic Data.

    Science.gov (United States)

    Breeze, Charles E; Paul, Dirk S; van Dongen, Jenny; Butcher, Lee M; Ambrose, John C; Barrett, James E; Lowe, Robert; Rakyan, Vardhman K; Iotchkova, Valentina; Frontini, Mattia; Downes, Kate; Ouwehand, Willem H; Laperle, Jonathan; Jacques, Pierre-Étienne; Bourque, Guillaume; Bergmann, Anke K; Siebert, Reiner; Vellenga, Edo; Saeed, Sadia; Matarese, Filomena; Martens, Joost H A; Stunnenberg, Hendrik G; Teschendorff, Andrew E; Herrero, Javier; Birney, Ewan; Dunham, Ian; Beck, Stephan

    2016-11-15

    Epigenome-wide association studies (EWAS) provide an alternative approach for studying human disease through consideration of non-genetic variants such as altered DNA methylation. To advance the complex interpretation of EWAS, we developed eFORGE (http://eforge.cs.ucl.ac.uk/), a new standalone and web-based tool for the analysis and interpretation of EWAS data. eFORGE determines the cell type-specific regulatory component of a set of EWAS-identified differentially methylated positions. This is achieved by detecting enrichment of overlap with DNase I hypersensitive sites across 454 samples (tissues, primary cell types, and cell lines) from the ENCODE, Roadmap Epigenomics, and BLUEPRINT projects. Application of eFORGE to 20 publicly available EWAS datasets identified disease-relevant cell types for several common diseases, a stem cell-like signature in cancer, and demonstrated the ability to detect cell-composition effects for EWAS performed on heterogeneous tissues. Our approach bridges the gap between large-scale epigenomics data and EWAS-derived target selection to yield insight into disease etiology. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. One-pot synthesis of aptamer-functionalized silver nanoclusters for cell-type-specific imaging.

    Science.gov (United States)

    Li, Jingjing; Zhong, Xiaoqin; Cheng, Fangfang; Zhang, Jian-Rong; Jiang, Li-Ping; Zhu, Jun-Jie

    2012-05-01

    As an emerging category of fluorescent metal nanoclusters, oligonucleotide-templated silver nanoclusters (Ag NCs) have attracted a lot of interest and have shown wide application in biorelated disciplines. However, the weak fluorescence emission and poor permeability to cell membranes tethered further intracellular applications of Ag NCs. AS1411 is an antiproliferative G-rich phosphodiester oligonucleotide and currently an anticancer agent under phase II clinical trials. Herein, we present a strategy to synthesize AS1411-functionalized Ag NCs with excellent fluorescence through a facile one-pot process. Confocal laser scanning microscopy and Z-axis scanning confirmed that the AS1411-functionalized Ag NCs could be internalized into MCF-7 human breast cancer cells and were able to specifically stain nuclei with red color. To our surprise, 3-[4,5-dimethylthiazol-z-yl]-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated the Ag NCs were cytocompatible and showed better inhibition effects than pure AS1411 on MCF-7 human breast cancer cells. In addition, a universal design of the oligonucleotide scaffold for synthesis of Ag NCs was extended to other aptamers, such as Sgc8c and mucin 1 aptamer. Due to the facile synthesis procedure and capability of specific target recognition, this fluorescent platform will potentially broaden the applications of Ag NCs in biosensing and biological imaging.

  7. Cell-type-specific modulation of innate immune signalling by vitamin D in human mononuclear phagocytes.

    Science.gov (United States)

    Kundu, Rhiannon; Theodoraki, Aikaterini; Haas, Carolin T; Zhang, Yanjing; Chain, Benjamin; Kriston-Vizi, Janos; Noursadeghi, Mahdad; Khoo, Bernard

    2017-01-01

    Vitamin D is widely reported to inhibit innate immune signalling and dendritic cell (DC) maturation as a potential immunoregulatory mechanism. It is not known whether vitamin D has global or gene-specific effects on transcriptional responses downstream of innate immune stimulation, or whether vitamin D inhibition of innate immune signalling is common to different cells. We confirmed vitamin D inhibition of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signalling in monocyte-derived DC (MDDC) stimulated with lipopolysaccharide (LPS). This was associated with global but modest attenuation of LPS-induced transcriptional changes at genome-wide level. Surprisingly, vitamin D did not inhibit innate immune NF-κB activation in monocyte-derived macrophages. Consistent with our findings in MDDC, ex vivo vitamin D treatment of primary peripheral blood myeloid DC also led to significant inhibition of LPS-inducible NF-κB activation. Unexpectedly, in the same samples, vitamin D enhanced activation of both NF-κB and MAPK signalling in primary peripheral blood monocytes. In a cross-sectional clinical cohort, we found no relationship between peripheral blood vitamin D levels and LPS-inducible activation of NF-κB and MAPK pathways in monocytes of myeloid DC. Remarkably, however, in vivo supplementation of people with vitamin D deficiency in this clinical cohort also enhanced LPS-inducible MAPK signalling in peripheral blood monocytes. Therefore, we report that vitamin D differentially modulates the molecular response to innate immune stimulation in monocytes, macrophages and dendritic cells. These results are of importance in the design of studies on vitamin D supplementation in infectious and immunological diseases. © 2016 The Authors. Immunology Published by John Wiley & Sons Ltd.

  8. Tuning local calcium availability: cell-type-specific immobile calcium buffer capacity in hippocampal neurons.

    Science.gov (United States)

    Matthews, Elizabeth A; Schoch, Susanne; Dietrich, Dirk

    2013-09-04

    It has remained difficult to ascribe a specific functional role to immobile or fixed intracellular calcium buffers in central neurons because the amount of these buffers is unknown. Here, we explicitly isolated the fixed buffer fraction by prolonged whole-cell patch-clamp dialysis and quantified its buffering capacity in murine hippocampal slices using confocal calcium imaging and the "added-buffer" approach. In dentate granule cells, the calcium binding ratio (κ) after complete washout of calbindin D28k (Cb), κfixed, displayed a substantial value of ∼100. In contrast, in CA1 oriens lacunosum moleculare (OLM) interneurons, which do not contain any known calcium-binding protein(s), κfixed amounted to only ∼30. Based on these values, a theoretical analysis of dendritic spread of calcium after local entry showed that fixed buffers, in the absence of mobile species, decrease intracellular calcium mobility 100- and 30-fold in granule cells and OLM cells, respectively, and thereby strongly slow calcium signals. Although the large κfixed alone strongly delays the spread of calcium in granule cells, this value optimizes the benefits of additionally expressing the mobile calcium binding protein Cb. With such high κfixed, Cb effectively increases the propagation velocity to levels seen in OLM cells and, contrary to expectation, does not affect the peak calcium concentration close to the source but sharpens the spatial and temporal calcium gradients. The data suggest that the amount of fixed buffers determines the temporal availability of calcium for calcium-binding partners and plays a pivotal role in setting the repertoire of cellular calcium signaling regimens.

  9. Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein in GABAergic Interneurons in the Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Kyle D. Ketchesin

    2017-10-01

    Full Text Available Corticotropin-releasing hormone-binding protein (CRH-BP is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC. Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized. In the current study, we sought to determine the cell type-specific expression of CRH-BP in the PFC to begin to define the neural circuits in which this key regulator is acting. To characterize the expression of CRH-BP in excitatory and/or inhibitory neurons, we utilized dual in situ hybridization to examine the cellular colocalization of CRH-BP mRNA with vesicular glutamate transporter (VGLUT or glutamic acid decarboxylase (GAD mRNA in different subregions of the PFC. We show that CRH-BP is expressed predominantly in GABAergic interneurons of the PFC, as revealed by the high degree of colocalization (>85% between CRH-BP and GAD. To further characterize the expression of CRH-BP in this heterogenous group of inhibitory neurons, we examined the colocalization of CRH-BP with various molecular markers of GABAergic interneurons, including parvalbumin (PV, somatostatin (SST, vasoactive intestinal peptide (VIP and cholecystokinin (CCK. We demonstrate that CRH-BP is colocalized predominantly with SST in the PFC, with lower levels of colocalization in PV- and CCK-expressing neurons. Our results provide a more comprehensive characterization of the cell type-specific expression of CRH-BP and begin to define its potential role within circuits of the PFC. These results will serve as the basis for future in vivo studies to manipulate CRH-BP in a cell type-specific manner to better

  10. Psychiatric Adverse Effects of Dermatological Drugs

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    Mine Özmen

    2010-07-01

    Full Text Available Dermatological drugs, mostly corticosteroids and isotretinoin, cause different psychiatric adverse effects. During steroid therapy, a wide range of psychiatric conditions, from minor clinical symptoms like insomnia and anxiety to serious psychiatric syndromes like psychosis and delirium might be seen. In medical literature, a causal connection is usually suggested between “isotretinoin”, which is used for treatment of acne vulgaris and depression and suicide attempts. However, there are no statistically significant double-blind randomized studies that support this connection. Clinicians must know patient’s psychiatric history before using any dermatological treatment known as causing psychiatric adverse effects, and psychiatric consultation should be established whenever necessary.

  11. Investigation of Neuronal Cell Type-Specific Gene Expression of Ca2+/Calmodulin-dependent Protein Kinase II.

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    Mima Kazuko

    2002-01-01

    Full Text Available The promoter activity of the rat Ca2+/calmodulin-dependent protein kinase II gene was analyzed using the luciferase reporter gene in neuronal and non-neuronal cell lines. Neuronal cell type-specific promoter activity was found in the 5'-flanking region of &agr; and &bgr; isoform genes of the kinase. Silencer elements were also found further upstream of promoter regions. A brain-specific protein bound to the DNA sequence of the 5'-flanking region of the gene was found by gel mobility shift analysis in the nuclear extract of the rat brain, including the cerebellum, forebrain, and brainstem, but not in that of non-neuronal tissues, including liver, kidney and spleen. The luciferase expression system and gel shift analysis can be used as an additional and better index by which to monitor gene expression in most cell types.

  12. Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2.

    Science.gov (United States)

    Zaglia, Tania; Pianca, Nicola; Borile, Giulia; Da Broi, Francesca; Richter, Claudia; Campione, Marina; Lehnart, Stephan E; Luther, Stefan; Corrado, Domenico; Miquerol, Lucile; Mongillo, Marco

    2015-08-11

    Extrasystoles lead to several consequences, ranging from uneventful palpitations to lethal ventricular arrhythmias, in the presence of pathologies, such as myocardial ischemia. The role of working versus conducting cardiomyocytes, as well as the tissue requirements (minimal cell number) for the generation of extrasystoles, and the properties leading ectopies to become arrhythmia triggers (topology), in the normal and diseased heart, have not been determined directly in vivo. Here, we used optogenetics in transgenic mice expressing ChannelRhodopsin-2 selectively in either cardiomyocytes or the conduction system to achieve cell type-specific, noninvasive control of heart activity with high spatial and temporal resolution. By combining measurement of optogenetic tissue activation in vivo and epicardial voltage mapping in Langendorff-perfused hearts, we demonstrated that focal ectopies require, in the normal mouse heart, the simultaneous depolarization of at least 1,300-1,800 working cardiomyocytes or 90-160 Purkinje fibers. The optogenetic assay identified specific areas in the heart that were highly susceptible to forming extrasystolic foci, and such properties were correlated to the local organization of the Purkinje fiber network, which was imaged in three dimensions using optical projection tomography. Interestingly, during the acute phase of myocardial ischemia, focal ectopies arising from this location, and including both Purkinje fibers and the surrounding working cardiomyocytes, have the highest propensity to trigger sustained arrhythmias. In conclusion, we used cell-specific optogenetics to determine with high spatial resolution and cell type specificity the requirements for the generation of extrasystoles and the factors causing ectopies to be arrhythmia triggers during myocardial ischemia.

  13. Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

    Science.gov (United States)

    Wolfart, Jakob; Laker, Debora

    2015-01-01

    Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723

  14. The adverse effects of inferior innovations

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    Chang Joseph W.

    2017-09-01

    Full Text Available This research advances brand innovation research by examining the adverse effects of inferior innovative extensions on the brand innovability of own parent brands. Brand innovability conceptually consists of brand quality and innovativeness. The results reveal that radical and incremental inferior innovations exert asymmetric adverse effects on brand quality and innovability. For brand quality, inferior radical innovations exert more negative impacts on the quality of pioneer brands than on the quality of follower brands. However, inferior incremental innovations exert identical negative impacts on the quality of both pioneer and follower brands. For brand innovability, both inferior radical and incremental innovations exert more negative impacts on the innovability of pioneer brands than on the innovability of follower brands. In comparison, brand innovability is less susceptible than brand quality to inferior innovation information. The findings suggest that it is more justified to evaluate innovative brands with brand innovability, instead of brand quality, for two reasons. Firstly, brand innovability is more realistic than brand quality because brand innovability is more relevant than brand quality to profits. Secondly, brand innovability is inclusive of brand innovativeness, which ameliorates adverse effects when innovative extensions are inferior. The threat of inferior innovative extensions is less horrible than expectation if the adverse effects on the innovative brands are assessed with brand innovability, instead of brand quality. However, being innovative is like a double-edged sword. On the one hand, it helps generating more profits. On the other hand, it endangers innovative brands to be more susceptible to inferior innovative extensions. Therefore, for marketing implications, pioneer brands are more obliged than follower brands to ensure the success of radical innovations in order to avoid the possible adverse effects of inferior

  15. Psychiatric adverse effects of pediatric corticosteroid use.

    Science.gov (United States)

    Drozdowicz, Linda B; Bostwick, J Michael

    2014-06-01

    Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions

  16. Dual-specificity anti-sigma factor reinforces control of cell-type specific gene expression in Bacillus subtilis.

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    Mónica Serrano

    2015-04-01

    Full Text Available Gene expression during spore development in Bacillus subtilis is controlled by cell type-specific RNA polymerase sigma factors. σFand σE control early stages of development in the forespore and the mother cell, respectively. When, at an intermediate stage in development, the mother cell engulfs the forespore, σF is replaced by σG and σE is replaced by σK. The anti-sigma factor CsfB is produced under the control of σF and binds to and inhibits the auto-regulatory σG, but not σF. A position in region 2.1, occupied by an asparagine in σG and by a glutamate in οF, is sufficient for CsfB discrimination of the two sigmas, and allows it to delay the early to late switch in forespore gene expression. We now show that following engulfment completion, csfB is switched on in the mother cell under the control of σK and that CsfB binds to and inhibits σE but not σK, possibly to facilitate the switch from early to late gene expression. We show that a position in region 2.3 occupied by a conserved asparagine in σE and by a conserved glutamate in σK suffices for discrimination by CsfB. We also show that CsfB prevents activation of σG in the mother cell and the premature σG-dependent activation of σK. Thus, CsfB establishes negative feedback loops that curtail the activity of σE and prevent the ectopic activation of σG in the mother cell. The capacity of CsfB to directly block σE activity may also explain how CsfB plays a role as one of the several mechanisms that prevent σE activation in the forespore. Thus the capacity of CsfB to differentiate between the highly similar σF/σG and σE/σK pairs allows it to rinforce the cell-type specificity of these sigma factors and the transition from early to late development in B. subtilis, and possibly in all sporeformers that encode a CsfB orthologue.

  17. [Complications and adverse effects of respiratory physiotherapy].

    Science.gov (United States)

    Remondière, R; Roeseler, J; Delguste, P

    1990-01-01

    Physiotherapy of the chest is used to mobilize manually respiratory secretions and to increase the amount of tracheobronchial mucus cleared from the respiratory tract. Today, the term chest physiotherapy has expanded to include a wide variety of manual techniques. Complications of chest physiotherapy have seldom been reported, but when they occurred they were mild or moderately severe. Adverse effects associated with this type of treatment were present in a small proportion of the patients studied and generally of modest clinical significance. Recognizing the nature of the potential for complications and adverse effects of chest physiotherapy enables therapeutists to modify the treatment so that it can be administered safely to critically and chronically ill patients.

  18. Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression

    Science.gov (United States)

    Ruijtenberg, Suzan; van den Heuvel, Sander

    2016-01-01

    ABSTRACT Cell proliferation and differentiation show a remarkable inverse relationship. Precursor cells continue division before acquiring a fully differentiated state, while terminal differentiation usually coincides with proliferation arrest and permanent exit from the division cycle. Mechanistic insight in the temporal coordination between cell cycle exit and differentiation has come from studies of cells in culture and genetic animal models. As initially described for skeletal muscle differentiation, temporal coordination involves mutual antagonism between cyclin-dependent kinases that promote cell cycle entry and transcription factors that induce tissue-specific gene expression. Recent insights highlight the contribution of chromatin-regulating complexes that act in conjunction with the transcription factors and determine their activity. In particular SWI/SNF chromatin remodelers contribute to dual regulation of cell cycle and tissue-specific gene expression during terminal differentiation. We review the concerted regulation of the cell cycle and cell type-specific transcription, and discuss common mutations in human cancer that emphasize the clinical importance of proliferation versus differentiation control. PMID:26825227

  19. Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics.

    Science.gov (United States)

    Gilroy, Kathryn L; Terry, Anne; Naseer, Asif; de Ridder, Jeroen; Allahyar, Amin; Wang, Weiwei; Carpenter, Eric; Mason, Andrew; Wong, Gane K-S; Cameron, Ewan R; Kilbey, Anna; Neil, James C

    2016-01-01

    Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types.

  20. Modelling epigenetic regulation of gene expression in 12 human cell types reveals combinatorial patterns of cell-type-specific genes.

    Science.gov (United States)

    Lu, Yiming; Qu, Wubin; Min, Bo; Liu, Zheyan; Chen, Changsheng; Zhang, Chenggang

    2014-06-01

    The maintenance of the diverse cell types in a multicellular organism is one of the fundamental mysteries of biology. Modelling the dynamic regulatory relationships between the histone modifications and the gene expression across the diverse cell types is essential for the authors to understand the mechanisms of the epigenetic regulation. Here, the authors thoroughly assessed the histone modification enrichment profiles at the promoters and constructed quantitative models between the histone modification abundances and the gene expression in 12 human cell types. The author's results showed that the histone modifications at the promoters exhibited remarkably cell-type-dependent variability in the cell-type-specific (CTS) genes. They demonstrated that the variable profiles of the modifications are highly predictive for the dynamic changes of the gene expression across all the cell types. Their findings revealed the close relationship between the combinatorial patterns of the histone modifications and the CTS gene expression. They anticipate that the findings and the methods they used in this study could provide useful information for the future studies of the regulatory roles of the histone modifications in the CTS genes.

  1. Adverse Effects of Nutraceuticals and Dietary Supplements.

    Science.gov (United States)

    Ronis, Martin J J; Pedersen, Kim B; Watt, James

    2018-01-06

    Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.

  2. Dose-dependent and cell type-specific cell death and proliferation following in vitro exposure to radial extracorporeal shock waves

    Science.gov (United States)

    Hochstrasser, Tanja; Frank, Hans-Georg; Schmitz, Christoph

    2016-01-01

    Radial extracorporeal shock wave (rESW) therapy is widely used in musculoskeletal disorders and wound repair. However, the mechanisms of action are still largely unknown. The current study compared the effects of rESWs on two cell types. Human fetal foreskin fibroblasts (HFFF2) and human placental choriocarcinoma cell line JEG-3 were exposed to 0, 100, 200, 500 or 5000 rESWs generated with a Swiss DolorClast device (2.5 bar, 1 Hz). FACS analysis immediately after rESW exposure showed that initially, rESWs rather induced mechanical cell destruction than regulated or programmed cell death. Cell damage was nearly negated by reducing cavitation. Furthermore, cell viability decreased progressively with higher numbers of rESWs. Exposure to rESWs had no impact on growth potential of JEG-3 cells, but dose-dependently increased growth potential of HFFF2 cells. Cultivation of cells that were initially exposed to sham-rESWs in conditioned media increased the growth potential of HFFF2 cells, nevertheless, an even stronger effect was achieved by direct exposure to rESWs. Additionally, cell cycle distribution analysis demonstrated a shift in proportion from G0/G1 to G2/M phase in HFFF2 cells, but not in JEG-3 cells. These data demonstrate that rESWs leads to initial and subsequent dose-dependent and cell type-specific effects in vitro. PMID:27477873

  3. In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency

    Science.gov (United States)

    Tourlakis, Marina E.; Zhang, Siyi; Ball, Heather L.; Gandhi, Rikesh; Liu, Hongrui; Zhong, Jian; Yuan, Julie S.; Guidos, Cynthia J.; Durie, Peter R.; Rommens, Johanna M.

    2015-01-01

    Genetic models of ribosome dysfunction show selective organ failure, highlighting a gap in our understanding of cell-type specific responses to translation insufficiency. Translation defects underlie a growing list of inherited and acquired cancer-predisposition syndromes referred to as ribosomopathies. We sought to identify molecular mechanisms underlying organ failure in a recessive ribosomopathy, with particular emphasis on the pancreas, an organ with a high and reiterative requirement for protein synthesis. Biallelic loss of function mutations in SBDS are associated with the ribosomopathy Shwachman-Diamond syndrome, which is typified by pancreatic dysfunction, bone marrow failure, skeletal abnormalities and neurological phenotypes. Targeted disruption of Sbds in the murine pancreas resulted in p53 stabilization early in the postnatal period, specifically in acinar cells. Decreased Myc expression was observed and atrophy of the adult SDS pancreas could be explained by the senescence of acinar cells, characterized by induction of Tgfβ, p15Ink4b and components of the senescence-associated secretory program. This is the first report of senescence, a tumour suppression mechanism, in association with SDS or in response to a ribosomopathy. Genetic ablation of p53 largely resolved digestive enzyme synthesis and acinar compartment hypoplasia, but resulted in decreased cell size, a hallmark of decreased translation capacity. Moreover, p53 ablation resulted in expression of acinar dedifferentiation markers and extensive apoptosis. Our findings indicate a protective role for p53 and senescence in response to Sbds ablation in the pancreas. In contrast to the pancreas, the Tgfβ molecular signature was not detected in fetal bone marrow, liver or brain of mouse models with constitutive Sbds ablation. Nevertheless, as observed with the adult pancreas phenotype, disease phenotypes of embryonic tissues, including marked neuronal cell death due to apoptosis, were determined to

  4. Adolescent maturation of inhibitory inputs onto cingulate cortex neurons is cell-type specific and TrkB dependent

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    Angela eVandenberg

    2015-02-01

    Full Text Available The maturation of inhibitory circuits during adolescence may be tied to the onset of mental health disorders such as schizophrenia. Neurotrophin signaling likely plays a critical role in supporting inhibitory circuit development and is also implicated in psychiatric disease. Within the neocortex, subcircuits may mature at different times and show differential sensitivity to neurotrophin signaling. We measured miniature inhibitory and excitatory postsynaptic currents (mIPSC and mEPSCs in Layer 5 cell-types in the mouse anterior cingulate across the periadolescent period. We differentiated cell-types mainly by Thy1 YFP transgene expression and also retrobead injection labeling in the contralateral cingulate and ipsilateral pons. We found that YFP- neurons and commissural projecting neurons had lower frequency of mIPSCs than neighboring YFP+ neurons or pons projecting neurons in juvenile mice (P21-25. YFP- neurons and to a lesser extent commissural projecting neurons also showed a significant increase in mIPSC amplitude during the periadolescent period (P21-25 vs. P40-50, which was not seen in YFP+ neurons or pons projecting neurons. Systemic disruption of tyrosine kinase receptor B (TrkB signaling during P23-50 in TrkBF616A mice blocked developmental changes in mIPSC amplitude, without affecting miniature excitatory post synaptic currents (mEPSCs. Our data suggest that the maturation of inhibitory inputs onto layer 5 pyramidal neurons is cell-type specific. These data may inform our understanding of adolescent brain development across species and aid in identifying candidate subcircuits that may show greater vulnerability in mental illness.

  5. Improved salinity tolerance of rice through cell type-specific expression of AtHKT1;1.

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    Darren Plett

    Full Text Available Previously, cell type-specific expression of AtHKT1;1, a sodium transporter, improved sodium (Na(+ exclusion and salinity tolerance in Arabidopsis. In the current work, AtHKT1;1, was expressed specifically in the root cortical and epidermal cells of an Arabidopsis GAL4-GFP enhancer trap line. These transgenic plants were found to have significantly improved Na(+ exclusion under conditions of salinity stress. The feasibility of a similar biotechnological approach in crop plants was explored using a GAL4-GFP enhancer trap rice line to drive expression of AtHKT1;1 specifically in the root cortex. Compared with the background GAL4-GFP line, the rice plants expressing AtHKT1;1 had a higher fresh weight under salinity stress, which was related to a lower concentration of Na(+ in the shoots. The root-to-shoot transport of (22Na(+ was also decreased and was correlated with an upregulation of OsHKT1;5, the native transporter responsible for Na(+ retrieval from the transpiration stream. Interestingly, in the transgenic Arabidopsis plants overexpressing AtHKT1;1 in the cortex and epidermis, the native AtHKT1;1 gene responsible for Na(+ retrieval from the transpiration stream, was also upregulated. Extra Na(+ retrieved from the xylem was stored in the outer root cells and was correlated with a significant increase in expression of the vacuolar pyrophosphatases (in Arabidopsis and rice the activity of which would be necessary to move the additional stored Na(+ into the vacuoles of these cells. This work presents an important step in the development of abiotic stress tolerance in crop plants via targeted changes in mineral transport.

  6. Improved salinity tolerance of rice through cell type-specific expression of AtHKT1;1.

    Science.gov (United States)

    Plett, Darren; Safwat, Gehan; Gilliham, Matthew; Skrumsager Møller, Inge; Roy, Stuart; Shirley, Neil; Jacobs, Andrew; Johnson, Alexander; Tester, Mark

    2010-09-03

    Previously, cell type-specific expression of AtHKT1;1, a sodium transporter, improved sodium (Na(+)) exclusion and salinity tolerance in Arabidopsis. In the current work, AtHKT1;1, was expressed specifically in the root cortical and epidermal cells of an Arabidopsis GAL4-GFP enhancer trap line. These transgenic plants were found to have significantly improved Na(+) exclusion under conditions of salinity stress. The feasibility of a similar biotechnological approach in crop plants was explored using a GAL4-GFP enhancer trap rice line to drive expression of AtHKT1;1 specifically in the root cortex. Compared with the background GAL4-GFP line, the rice plants expressing AtHKT1;1 had a higher fresh weight under salinity stress, which was related to a lower concentration of Na(+) in the shoots. The root-to-shoot transport of (22)Na(+) was also decreased and was correlated with an upregulation of OsHKT1;5, the native transporter responsible for Na(+) retrieval from the transpiration stream. Interestingly, in the transgenic Arabidopsis plants overexpressing AtHKT1;1 in the cortex and epidermis, the native AtHKT1;1 gene responsible for Na(+) retrieval from the transpiration stream, was also upregulated. Extra Na(+) retrieved from the xylem was stored in the outer root cells and was correlated with a significant increase in expression of the vacuolar pyrophosphatases (in Arabidopsis and rice) the activity of which would be necessary to move the additional stored Na(+) into the vacuoles of these cells. This work presents an important step in the development of abiotic stress tolerance in crop plants via targeted changes in mineral transport.

  7. In Vivo Senescence in the Sbds-Deficient Murine Pancreas: Cell-Type Specific Consequences of Translation Insufficiency.

    Directory of Open Access Journals (Sweden)

    Marina E Tourlakis

    2015-06-01

    Full Text Available Genetic models of ribosome dysfunction show selective organ failure, highlighting a gap in our understanding of cell-type specific responses to translation insufficiency. Translation defects underlie a growing list of inherited and acquired cancer-predisposition syndromes referred to as ribosomopathies. We sought to identify molecular mechanisms underlying organ failure in a recessive ribosomopathy, with particular emphasis on the pancreas, an organ with a high and reiterative requirement for protein synthesis. Biallelic loss of function mutations in SBDS are associated with the ribosomopathy Shwachman-Diamond syndrome, which is typified by pancreatic dysfunction, bone marrow failure, skeletal abnormalities and neurological phenotypes. Targeted disruption of Sbds in the murine pancreas resulted in p53 stabilization early in the postnatal period, specifically in acinar cells. Decreased Myc expression was observed and atrophy of the adult SDS pancreas could be explained by the senescence of acinar cells, characterized by induction of Tgfβ, p15(Ink4b and components of the senescence-associated secretory program. This is the first report of senescence, a tumour suppression mechanism, in association with SDS or in response to a ribosomopathy. Genetic ablation of p53 largely resolved digestive enzyme synthesis and acinar compartment hypoplasia, but resulted in decreased cell size, a hallmark of decreased translation capacity. Moreover, p53 ablation resulted in expression of acinar dedifferentiation markers and extensive apoptosis. Our findings indicate a protective role for p53 and senescence in response to Sbds ablation in the pancreas. In contrast to the pancreas, the Tgfβ molecular signature was not detected in fetal bone marrow, liver or brain of mouse models with constitutive Sbds ablation. Nevertheless, as observed with the adult pancreas phenotype, disease phenotypes of embryonic tissues, including marked neuronal cell death due to apoptosis

  8. Cell-type specific segregation of transcriptional expression of glial genes in the rat peripheral neurotumor RT4 cell lines.

    Science.gov (United States)

    Hagiwara, N; Imada, S; Sueoka, N

    1993-12-15

    Four types of cells, RT4-AC (stem cell type), RT4-B and RT4-E (neuronal cell types), and RT4-D (glial cell type) were previously isolated from an ethylnitrosourea (ENU) induced rat peripheral neurotumor RT4. In a phenomenon termed cell-type conversion, RT4-AC spontaneously and permanently gives rise to the three other cell types in culture. In the RT4 system the expression of glial fibrillary acidic protein (GFAP) and S100 beta protein genes segregates in a cell-type specific manner. To further characterize the RT4 family, the expression of four myelin-forming glial genes--P0 glycoprotein, suppressed cAMP inducible POU (SCIP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), and myelin basic protein (MBP)--has been studied in the RT4 cell lines. In addition to these genes, the expression of the low-affinity nerve growth factor (LNGF) receptor (expressed in immature Schwann cells) has been examined. We have found the following results. 1) The stem cell type RT4-AC and the glial cell type RT4-D express mRNA transcripts of P0, SCIP, and CNP (the larger form, 2.8 kb), and the amount of mRNA of these genes was increased by forskolin. 2) RT4-AC and RT4-D also express a low level of MBP mRNA upon forskolin treatment. 3) The neuronal cell types RT4-B and RT4-E do not express any of these myelin-forming glial genes with or without forskolin treatment. 4) The LNGF receptor mRNA is expressed in RT4-AC and RT4-D and at a lower level in RT4-B; its expression is stimulated by forskolin.

  9. Theophylline: Adverse Effects, Poisoning and Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Muhammed Charehsaz

    2011-09-01

    Full Text Available Abstract: Theophylline, which is a methylxanthine derivative, has been commonly used in all over the world for many years due to its cheapness and effectiveness in treatment of asthma and chronic obstructive pulmonary disease (COPD. There is a close relationship between its bronchodilator effect and blood levels of theophylline. Maintenance of its blood level between 10-20 μg/ml is important to obtain a maximum bronchodilator effect. Besides having a narrow therapeutic range, its alteration of pharmacokinetic characteristics due to individually factors, drugs, diet, and habits such as smoking and alcohol has led to requirement of more carefully use of theophylline for patients at every age. In the present review article, in addition to pharmacokinetic/ dynamic properties of theophylline, its adverse effects, poisoning with over dose of theophylline and approaches of its treatment have been given.

  10. The NAS Perchlorate Review: Adverse Effects?

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  11. Do SSRIs increase the risk of gastrointestinal adverse effects?

    NARCIS (Netherlands)

    Pouwels, Koen; Kalkman, Arno; Schagen, Daan; Visser, Sipke; Hak, Eelko

    2013-01-01

    Background: Selective serotonin reuptake inhibitors (SSRIs) have been associated with gastrointestinal (GI) adverse effects. However, conflicting results were obtained by studies that evaluated the association between SSRIs, whether or not in combination with NSAIDs, and GI adverse effects.

  12. Adverse effects profile of multidrug-resistant tuberculosis treatment ...

    African Journals Online (AJOL)

    Background: Highly active antiretroviral therapy (HAART) and drugs that are used to treat multidrug-resistant tuberculosis have potentially overlapping adverse effects. Few South African studies have documented adverse effects in the multidrugresistant tuberculosis population. This study examined the adverse effects ...

  13. Perioperative opioid usage: avoiding adverse effects.

    Science.gov (United States)

    Funk, Robert D; Hilliard, Paul; Ramachandran, Satya Krishna

    2014-10-01

    Opioids remain the most common analgesic tool for the surgeon, owing to their cost-effectiveness in both the inpatient and outpatient setting. Aside from these attributes, opioids have significant side effects that are associated with morbidity and mortality. Specifically, obese patients, patients with sleep apnea, and the elderly may be at an increased risk of experiencing sedation and respiratory depression in response to opioids. Opioid reduction strategies prove useful for decreasing total opioid dose and, in turn, their associated adverse effects. Such strategies may include adjuvant nonopioid analgesics such as α-2 agonists, gabapentinoids, and N-methyl-D-aspartate receptor agonists as well as local, regional, or neuraxial anesthesia and modification of surgical technique where possible for operative patients. Patients may also present to surgeons while taking chronic opioids, including high-dose opioids and opioid agonist/antagonists. These clinical scenarios are associated with extreme challenges in postoperative analgesic management. With all opioid prescribing, other sedative medications should be limited or avoided as the risk for additive sedation is significant. This review aims to describe systematic methods to reduce opioid side effects and identify specific risk-reduction strategies within each risk group.

  14. Beneficial and adverse effects of chemopreventive agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Mu; Park, Kwang-Kyun

    2003-03-01

    The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents.

  15. Adverse effects of IgG therapy.

    Science.gov (United States)

    Berger, Melvin

    2013-01-01

    IgG is widely used for patients with immune deficiencies and in a broad range of autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG may be associated with adverse effects (AEs), which are mostly uncomfortable or unpleasant but often are not serious. The most common infusion-related AE is headache. More serious reactions, including true anaphylaxis and anaphylactoid reactions, occur less frequently. Most reactions are related to the rate of infusion and can be prevented or treated just by slowing the infusion rate. Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or corticosteroids also may be helpful in preventing or treating these common AEs. IgA deficiency with the potential of IgG or IgE antibodies against IgA increases the risk of some AEs but should not be viewed as a contraindication if IgG therapy is needed. Potentially serious AEs include renal dysfunction and/or failure, thromboembolic events, and acute hemolysis. These events usually are multifactorial, related to combinations of constituents in the IgG product as well as risk factors for the recipient. Awareness of these factors should allow minimization of the risks and consequences of these AEs. Subcutaneous IgG is absorbed more slowly into the circulation and has a lower incidence of AEs, but awareness and diligence are necessary whenever IgG is administered. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  16. Adverse Effects of COX-2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Jagdish N. Sharma

    2005-01-01

    Full Text Available Cyclooxygenase-2 selective inhibitors (COXIBs were developed with the prime object of minimizing gastrointestinal adverse effects, which are seen with the use of traditional nonsteroidal anti-inflammatory drugs (NSAIDs. Their long-term use is limited by the development of hypertension, edema, and congestive heart failure in a significant proportion of patients. NSAIDs block the activity of both COX isozymes, COX-1 and COX-2, which mediate the enzymatic conversion of arachidonate to prostaglandin H2 (PGH2 and other prostaglandin (PG metabolites. It is well established that the cardiovascular profile of COX-2 inhibitors can be accounted for by inhibition of COX-dependent PG synthesis. Following the COX-mediated synthesis of PGH2 from arachidonate, PGH2 is metabolized to one of at least five bioactive PGs, including PGE2, PGI2, PGF2, PGD2, or thromboxane A2 (TXA2. These prostanoids have pleiotropic cardiovascular effects, altering platelet function and renal function, and they are acting either as vasodilators or vasoconstrictors. Although COX-1 and COX-2 exhibit similar biochemical activity in converting arachidonate to PGH2in vitro, the ultimate prostanoids they produce in vivo may be different due to differential regulation of COX-1 and COX-2, tissue distribution, and availability of the prostanoid synthases. PGs have been established as being critically involved in mitigating hypertension, helping to maintain medullary blood flow (MBF, promoting urinary salt excretion, and preserving the normal homeostasis of thrombosis, and the researchers found that the use of COX-2 inhibitors caused many serious complications in altering the normal body homeostasis. The purpose of the present research is to explain briefly the side effects of COX-2 inhibitors on the renal and cardiovascular system.

  17. Cell Type-Specific Immunomodulation Induced by Helminthes: Effect on Metainflammation, Insulin Resistance and Type-2 Diabetes.

    Science.gov (United States)

    Aravindhan, Vivekanandhan; Anand, Gowrishankar

    2017-12-01

    Recent epidemiological studies have documented an inverse relationship between the decreasing prevalence of helminth infections and the increasing prevalence of metabolic diseases ("metabolic hygiene hypothesis"). Chronic inflammation leading to insulin resistance (IR) has now been identified as a major etiological factor for a variety of metabolic diseases other than obesity and Type-2 diabetes (metainflammation). One way by which helminth infections such as filariasis can modulate IR is by inducing a chronic, nonspecific, low-grade, immune suppression mediated by modified T-helper 2 (Th2) response (induction of both Th2 and regulatory T cells) which can in turn suppress the proinflammatory responses and promote insulin sensitivity (IS). This article provides evidence on how the cross talk between the innate and adaptive arms of the immune responses can modulate IR/sensitivity. The cross talk between innate (macrophages, dendritic cells, natural killer cells, natural killer T cells, myeloid derived suppressor cells, innate lymphoid cells, basophils, eosinophils, and neutrophils) and adaptive (helper T [CD4 + ] cells, cytotoxic T [CD8 + ] cells and B cells) immune cells forms two opposing circuits, one associated with IR and the other associated with IS under the conditions of metabolic syndrome and helminth-mediated immunomodulation, respectively.

  18. Psychiatric adverse effects of chloroquine

    Directory of Open Access Journals (Sweden)

    Anna Bogaczewicz

    2017-06-01

    Full Text Available Chloroquine is a prototype antimalarial drug, widely used in several branches of medicine. Antimalarial drugs are used in the treatment of various dermatological, immunological, rheumatological and infectious diseases. Examples of off-labelled indications for chloroquine analogues use include dermatomyositis, sarcoidosis, polymorphous light eruption, disseminated granuloma annulare and porfiria cutanea tarda. There is a relatively small number of adverse effects related to chloroquine analogues used in standard doses, such as gastrointestinal disturbances, headaches, skin reactions, hypotension, convulsions, extrapyramidal symptoms and visual disturbances. Psychiatric side effects of chloroquine seem to be rare, but may manifest in a wide range of symptoms, such as confusion, disorientation, ideas of persecution, agitation, outbursts of violence, loss of interest, feeling sad, suicidal ideas and impaired insight. There is also a report of a manic episode with psychotic features in the course of bipolar disorder, and another case report of persecutory delusions, anxiety, derealisation and visual illusions triggered by chloroquine. The duration of psychiatric symptoms usually ranges from one to two weeks, and symptoms usually disappear within several days following cessation of chloroquine usage and starting psychiatric treatment where indicated. This article reviews the case studies of patients diagnosed with mental disorders resulting from the use of chloroquine, and discusses the management in such cases.

  19. The oral adverse effects of isotretinoin treatment in acne vulgaris ...

    African Journals Online (AJOL)

    Background: Isotretinoin is the most effective therapy to treat severe acne vulgaris and its systemic adverse effects have been well documented, but little is known on dental side effects over the course of treatment. Objectives: This prospective case-control study aimed to evaluate the oral adverse effects of isotretinoin in ...

  20. Effectiveness of adverse effects search filters: drugs versus medical devices

    Directory of Open Access Journals (Sweden)

    Kelly Farrah, MLIS, AHIP

    2016-09-01

    Full Text Available Objective: The study tested the performance of adverse effects search filters when searching for safety information on medical devices, procedures, and diagnostic tests in MEDLINE and Embase. Methods: The sensitivity of 3 filters was determined using a sample of 631 references from 131 rapid reviews related to the safety of health technologies. The references were divided into 2 sets by type of intervention: drugs and nondrug health technologies. Keyword and indexing analysis were performed on references from the nondrug testing set that 1 or more of the filters did not retrieve. Results: For all 3 filters, sensitivity was lower for nondrug health technologies (ranging from 53%– 87% than for drugs (88%–93% in both databases. When tested on the nondrug health technologies set, sensitivity was lower in Embase (ranging from 53%–81% than in MEDLINE (67%–87% for all filters. Of the nondrug records that 1 or more of the filters missed, 39% of the missed MEDLINE records and 18% of the missed Embase records did not contain any indexing terms related to adverse events. Analyzing the titles and abstracts of nondrug records that were missed by any 1 filter, the most commonly used keywords related to adverse effects were: risk, complications, mortality, contamination, hemorrhage, and failure. Conclusions: In this study, adverse effects filters were less effective at finding information about the safety of medical devices, procedures, and tests compared to information about the safety of drugs.

  1. THE ADVERSE-EFFECT POLICY FOR AGRICULTURAL LABOR.

    Science.gov (United States)

    DELLON, HOWARD N.

    THE BASIC PHILOSOPHY UNDERLYING THE REGULATION OF FOREIGN WORKER IMPORTATIONS INTO THE UNITED STATES FOR AGRICULTURAL EMPLOYMENT IS THAT EMPLOYMENT OF SUCH WORKERS WILL NOT BE PERMITTED IF IT WILL HAVE AN ADVERSE EFFECT ON DOMESTIC WORKERS. THE "ADVERSE-EFFECT" POLICY HAS BEEN FOLLOWED SINCE THE ENACTMENT OF PUBLIC LAW 78 IN 1951 WHICH GOVERNED…

  2. Management of Adverse Effects of Antituberculosis Drugs | Anakwue ...

    African Journals Online (AJOL)

    Tuberculosis (TB) is an infectious disease with increasing morbidity and mortality particularly because of HIV infection. Drug therapy which is central in the management of TB may be associated with adverse effects. These may be classified as minor or major. The adverse effects may not affect drug therapy and reassurance ...

  3. Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.

    Science.gov (United States)

    Marshall, Owen J; Southall, Tony D; Cheetham, Seth W; Brand, Andrea H

    2016-09-01

    This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007); doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile transcription and chromatin binding in a cell-type-specific manner is a powerful aid to understanding cell-fate specification and cellular function in multicellular organisms. We recently developed targeted DamID (TaDa) to enable genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins in vivo without cell isolation. As a protocol extension, this article describes substantial modifications to an existing protocol, and it offers additional applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA-binding profiles of proteins, by coupling it with the GAL4 system in Drosophila to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion proteins are expressed at very low levels, thus avoiding toxicity and potential artifacts from overexpression. The modifications to the core DamID technique presented here also increase the speed of sample processing and throughput, and adapt the method to next-generation sequencing technology. TaDa is robust, reproducible and highly sensitive. Compared with other methods for cell-type-specific profiling, the technique requires no cell-sorting, cross-linking or antisera, and binding profiles can be generated from as few as 10,000 total induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol II), TaDa can also identify transcribed genes in a cell-type-specific manner. Here we describe a detailed protocol for carrying out TaDa experiments and preparing the material for next-generation sequencing. Although we developed TaDa in Drosophila, it should be easily adapted to other organisms with an inducible expression system. Once transgenic animals are obtained, the entire experimental procedure-from collecting tissue samples to generating sequencing libraries-can be accomplished within 5 d.

  4. Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

    OpenAIRE

    Chan Zhou; Benoit Molinie; Kaveh Daneshvar; Pondick, Joshua V.; Jinkai Wang; Nicholas Van Wittenberghe; Yi Xing; Giallourakis, Cosmas C.; Mullen, Alan C.

    2017-01-01

    N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs a...

  5. Transcription of mouse Sp2 yields alternatively spliced and sub-genomic mRNAs in a tissue- and cell type-specific fashion

    Science.gov (United States)

    Yin, Haifeng; Nichols, Teresa D.; Horowitz, Jonathan M.

    2010-01-01

    The Sp-family of transcription factors is comprised by nine members, Sp1-9, that share a highly-conserved DNA-binding domain. Sp2 is a poorly characterized member of this transcription factor family that is widely expressed in murine and human cell lines yet exhibits little DNA-binding or trans-activation activity in these settings. As a prelude to the generation of a “knock-out” mouse strain, we isolated a mouse Sp2 cDNA and performed a detailed analysis of Sp2 transcription in embryonic and adult mouse tissues. We report that (1) the 5′ untranslated region of Sp2 is subject to alternative splicing, (2) Sp2 transcription is regulated by at least two promoters that differ in their cell-type specificity, (3) one Sp2 promoter is highly active in nine mammalian cell lines and strains and is regulated by at least five discrete stimulatory and inhibitory elements, (4) a variety of sub-genomic messages are synthesized from the Sp2 locus in a tissue- and cell type-specific fashion and these transcripts have the capacity to encode a novel partial-Sp2 protein, and (5) RNA in situ hybridization assays indicate that Sp2 is widely expressed during mouse embryogenesis, particularly in the embryonic brain, and robust Sp2 expression occurs in neurogenic regions of the post-natal and adult brain. PMID:20353838

  6. Identifying Cell Type-Specific Transcription Factors by Integrating ChIP-seq and eQTL Data-Application to Monocyte Gene Regulation.

    Science.gov (United States)

    Choudhury, Mudra; Ramsey, Stephen A

    2016-01-01

    We describe a novel computational approach to identify transcription factors (TFs) that are candidate regulators in a human cell type of interest. Our approach involves integrating cell type-specific expression quantitative trait locus (eQTL) data and TF data from chromatin immunoprecipitation-to-tag-sequencing (ChIP-seq) experiments in cell lines. To test the method, we used eQTL data from human monocytes in order to screen for TFs. Using a list of known monocyte-regulating TFs, we tested the hypothesis that the binding sites of cell type-specific TF regulators would be concentrated in the vicinity of monocyte eQTLs. For each of 397 ChIP-seq data sets, we obtained an enrichment ratio for the number of ChIP-seq peaks that are located within monocyte eQTLs. We ranked ChIP-seq data sets according to their statistical significances for eQTL overlap, and from this ranking, we observed that monocyte-regulating TFs are more highly ranked than would be expected by chance. We identified 27 TFs that had significant monocyte enrichment scores and mapped them into a protein interaction network. Our analysis uncovered two novel candidate monocyte-regulating TFs, BCLAF1 and SIN3A. Our approach is an efficient method to identify candidate TFs that can be used for any cell/tissue type for which eQTL data are available.

  7. The Oral Adverse Effects of Isotretinoin Treatment in Acne Vulgaris ...

    African Journals Online (AJOL)

    2016-01-31

    Jan 31, 2016 ... Assessment System, isotretinoin, salivary flow. The Oral Adverse Effects of Isotretinoin Treatment in Acne Vulgaris. Patients: A Prospective, Case–control Study. U Erdemir, G Okan1, S Gungor2, B Tekin3, SO Yildiz4, E Yildiz isotretinoin adversely affects salivary flow and buffer capacity.[6-8]. Dental caries is ...

  8. Community Awareness of Adverse Effects of Nonsteroidal Anti ...

    African Journals Online (AJOL)

    Secretary

    health personnel to educate patients on the potential adverse effects of the non- steroidal anti-inflammatory drugs. Key words: Non-steroidal anti-inflammatory drugs, adverse drug reactions, community knowledge, Ilala Municipality. INTRODUCTION. Nonsteroidal anti-inflammatory drugs. (NSAIDs) are drugs with analgesic,.

  9. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner.

    Science.gov (United States)

    Vasilopoulou, E; Loubière, L S; Lash, G E; Ohizua, O; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S Y

    2014-06-01

    cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro. Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo. Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental development through the regulation of the secretion of critical cytokines and angiogenic growth factors by human decidual cells. Our data suggest that there is an ontogenically determined regulatory 'switch' in T3 responsiveness between the first and second trimesters, and support the notion that the timely and early correction of maternal thyroid dysfunction is critical in influencing pregnancy outcomes. This study is funded by Wellbeing of Women (RG/1082/09 to S.Y.C., M.D.K., J.A.F., L.S.L., G.E.L.) and Action Medical Research - Henry Smith Charity (SP4335 to M.D.K., S.Y.C., L.S.L., J.A.F.). The authors have no conflicts of interest to disclose.

  10. Systematic reviews of adverse effects: framework for a structured approach

    Directory of Open Access Journals (Sweden)

    Herxheimer Andrew

    2007-07-01

    Full Text Available Abstract Background As every healthcare intervention carries some risk of harm, clinical decision making needs to be supported by a systematic assessment of the balance of benefit to harm. A systematic review that considers only the favourable outcomes of an intervention, without also assessing the adverse effects, can mislead by introducing a bias favouring the intervention. Much of the current guidance on systematic reviews is directed towards the evaluation of effectiveness; but this differs in important ways from the methods used in assessing the safety and tolerability of an intervention. A detailed discussion of why, how and when to include adverse effects in a systematic review, is required. Methods This discussion paper, which presupposes a basic knowledge of systematic review methodology, was developed by consensus among experienced reviewers, members of the Adverse Effects Subgroup of The Cochrane Collaboration, and supplemented by a consultation of content experts in reviews methodology, as well as those working in drug safety. Results A logical framework for making decisions in reviews that incorporate adverse effects is provided. We explore situations where a comprehensive investigation of adverse effects is warranted and suggest strategies to identify practicable and clinically useful outcomes. The advantages and disadvantages of including observational and experimental study designs are reviewed. The consequences of including separate studies for intended and unintended effects are explained. Detailed advice is given on designing electronic searches for studies with adverse effects data. Reviewers of adverse effects are given general guidance on the assessment of study bias, data collection, analysis, presentation and the interpretation of harms in a systematic review. Conclusion Readers need to be able to recognize how strategic choices made in the review process determine what harms are found, and how the findings may affect

  11. Systematic reviews of adverse effects: framework for a structured approach.

    Science.gov (United States)

    Loke, Yoon K; Price, Deirdre; Herxheimer, Andrew

    2007-07-05

    As every healthcare intervention carries some risk of harm, clinical decision making needs to be supported by a systematic assessment of the balance of benefit to harm. A systematic review that considers only the favourable outcomes of an intervention, without also assessing the adverse effects, can mislead by introducing a bias favouring the intervention. Much of the current guidance on systematic reviews is directed towards the evaluation of effectiveness; but this differs in important ways from the methods used in assessing the safety and tolerability of an intervention. A detailed discussion of why, how and when to include adverse effects in a systematic review, is required. This discussion paper, which presupposes a basic knowledge of systematic review methodology, was developed by consensus among experienced reviewers, members of the Adverse Effects Subgroup of The Cochrane Collaboration, and supplemented by a consultation of content experts in reviews methodology, as well as those working in drug safety. A logical framework for making decisions in reviews that incorporate adverse effects is provided. We explore situations where a comprehensive investigation of adverse effects is warranted and suggest strategies to identify practicable and clinically useful outcomes. The advantages and disadvantages of including observational and experimental study designs are reviewed. The consequences of including separate studies for intended and unintended effects are explained. Detailed advice is given on designing electronic searches for studies with adverse effects data. Reviewers of adverse effects are given general guidance on the assessment of study bias, data collection, analysis, presentation and the interpretation of harms in a systematic review. Readers need to be able to recognize how strategic choices made in the review process determine what harms are found, and how the findings may affect clinical decisions. Researchers undertaking a systematic review that

  12. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    Directory of Open Access Journals (Sweden)

    M J Pont

    Full Text Available Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage-restricted expression as potential targets for immunotherapy of hematological cancers.

  13. Generation of cell type-specific monoclonal antibodies for the planarian and optimization of sample processing for immunolabeling.

    Science.gov (United States)

    Forsthoefel, David J; Waters, Forrest A; Newmark, Phillip A

    2014-12-21

    Efforts to elucidate the cellular and molecular mechanisms of regeneration have required the application of methods to detect specific cell types and tissues in a growing cohort of experimental animal models. For example, in the planarian Schmidtea mediterranea, substantial improvements to nucleic acid hybridization and electron microscopy protocols have facilitated the visualization of regenerative events at the cellular level. By contrast, immunological resources have been slower to emerge. Specifically, the repertoire of antibodies recognizing planarian antigens remains limited, and a more systematic approach is needed to evaluate the effects of processing steps required during sample preparation for immunolabeling. To address these issues and to facilitate studies of planarian digestive system regeneration, we conducted a monoclonal antibody (mAb) screen using phagocytic intestinal cells purified from the digestive tracts of living planarians as immunogens. This approach yielded ten antibodies that recognized intestinal epitopes, as well as markers for the central nervous system, musculature, secretory cells, and epidermis. In order to improve signal intensity and reduce non-specific background for a subset of mAbs, we evaluated the effects of fixation and other steps during sample processing. We found that fixative choice, treatments to remove mucus and bleach pigment, as well as methods for tissue permeabilization and antigen retrieval profoundly influenced labeling by individual antibodies. These experiments led to the development of a step-by-step workflow for determining optimal specimen preparation for labeling whole planarians as well as unbleached histological sections. We generated a collection of monoclonal antibodies recognizing the planarian intestine and other tissues; these antibodies will facilitate studies of planarian tissue morphogenesis. We also developed a protocol for optimizing specimen processing that will accelerate future efforts to

  14. An atlas for Schistosoma mansoni organs and life-cycle stages using cell type-specific markers and confocal microscopy.

    Directory of Open Access Journals (Sweden)

    James J Collins

    2011-03-01

    Full Text Available Schistosomiasis (bilharzia is a tropical disease caused by trematode parasites (Schistosoma that affects hundreds of millions of people in the developing world. Currently only a single drug (praziquantel is available to treat this disease, highlighting the importance of developing new techniques to study Schistosoma. While molecular advances, including RNA interference and the availability of complete genome sequences for two Schistosoma species, will help to revolutionize studies of these animals, an array of tools for visualizing the consequences of experimental perturbations on tissue integrity and development needs to be made widely available. To this end, we screened a battery of commercially available stains, antibodies and fluorescently labeled lectins, many of which have not been described previously for analyzing schistosomes, for their ability to label various cell and tissue types in the cercarial stage of S. mansoni. This analysis uncovered more than 20 new markers that label most cercarial tissues, including the tegument, the musculature, the protonephridia, the secretory system and the nervous system. Using these markers we present a high-resolution visual depiction of cercarial anatomy. Examining the effectiveness of a subset of these markers in S. mansoni adults and miracidia, we demonstrate the value of these tools for labeling tissues in a variety of life-cycle stages. The methodologies described here will facilitate functional analyses aimed at understanding fundamental biological processes in these parasites.

  15. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics.

    Science.gov (United States)

    Charoenviriyakul, Chonlada; Takahashi, Yuki; Morishita, Masaki; Matsumoto, Akihiro; Nishikawa, Makiya; Takakura, Yoshinobu

    2017-01-01

    Exosomes are small membrane vesicles secreted from cells and are expected to be used as drug delivery systems. Important characteristics of exosomes, such as yield, physicochemical properties, and pharmacokinetics, may be different among different cell types. However, there is limited information about the effect of cell type on these characteristics. In the present study, we evaluated these characteristics of exosomes derived from five different types of mouse cell lines: B16BL6 murine melanoma cells, C2C12 murine myoblast cells, NIH3T3 murine fibroblasts cells, MAEC murine aortic endothelial cells, and RAW264.7 murine macrophage-like cells. Exosomes were collected using a differential ultracentrifugation method. The exosomes collected from all the cell types were negatively charged globular vesicles with a diameter of approximately 100nm. C2C12 and RAW264.7 cells produced more exosomes than the other types of cells. The exosomes were labeled with a fusion protein of Gaussia luciferase and lactadherin to evaluate their pharmacokinetics. After intravenous injection into mice, all the exosomes rapidly disappeared from the systemic circulation and mainly distributed to the liver. In conclusion, the exosome yield was significantly different among the cell types, and all the exosomes evaluated in this study showed comparable physicochemical and pharmacokinetic properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Adverse effects of methotrexate in three psoriatic arthritis patients.

    Science.gov (United States)

    Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

    2014-04-01

    Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

  17. Adverse Health Effects of Nighttime Lighting

    Science.gov (United States)

    Motta, M.

    2012-06-01

    The effects of poor lighting and glare on public safety are well-known, as are the harmful environmental effects on various species and the environment in general. What is less well-known is the potential harmful medical effects of excessive poor nighttime lighting. A significant body of research has been developed over the last few years regarding this problem. One of the most significant effects is the startling increased risk for breast cancer by excessive exposure to nighttime lighting. The mechanism is felt to be by disruption of the circadian rhythm and suppression of melatonin production from the pineal gland. Melatonin has an anticancer effect that is lost when its production is disrupted. I am in the process of developing a monograph that will summarize this important body of research, to be presented and endorsed by the American Medical Association, and its Council of Science and Public health. This paper is a brief overall summary of this little known potential harmful effect of poor and excessive nighttime lighting.

  18. Classification of Mouse Retinal Bipolar Cells: Type-Specific Connectivity with Special Reference to Rod-Driven AII Amacrine Pathways.

    Science.gov (United States)

    Tsukamoto, Yoshihiko; Omi, Naoko

    2017-01-01

    We confirmed the classification of 15 morphological types of mouse bipolar cells by serial section transmission electron microscopy and characterized each type by identifying chemical synapses and gap junctions at axon terminals. Although whether the previous type 5 cells consist of two or three types was uncertain, they are here clustered into three types based on the vertical distribution of axonal ribbons. Next, while two groups of rod bipolar (RB) cells, RB1, and RB2, were previously proposed, we clarify that a half of RB1 cells have the intermediate characteristics, suggesting that these two groups comprise a single RB type. After validation of bipolar cell types, we examined their relationship with amacrine cells then particularly with AII amacrine cells. We found a strong correlation between the number of amacrine cell synaptic contacts and the number of bipolar cell axonal ribbons. Formation of bipolar cell output at each ribbon synapse may be effectively regulated by a few nearby inhibitory inputs of amacrine cells which are chosen from among many amacrine cell types. We also found that almost all types of ON cone bipolar cells frequently have a minor group of midway ribbons along the axon passing through the OFF sublamina as well as a major group of terminal ribbons in the ON sublamina. AII amacrine cells are connected to five of six OFF bipolar cell types via conventional chemical synapses and seven of eight ON (cone) bipolar cell types via electrical synapses (gap junctions). However, the number of synapses is dependent on bipolar cell types. Type 2 cells have 69% of the total number of OFF bipolar chemical synaptic contacts with AII amacrine cells and type 6 cells have 46% of the total area of ON bipolar gap junctions with AII amacrine cells. Both type 2 and 6 cells gain the greatest access to AII amacrine cell signals also share those signals with other types of bipolar cells via networked gap junctions. These findings imply that the most sensitive

  19. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

    OpenAIRE

    Talih, Farid; Ajaltouni, Jean

    2015-01-01

    The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of ou...

  20. Differential microRNA expression signatures and cell type-specific association with Taxol resistance in ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Kim YW

    2014-02-01

    downregulation of the two miRNAs was associated with better survival, perhaps increasing the sensitivity of cancer cells to Taxol. In the chemo-sensitive patient group, only miR-647 could be a prognosis marker. These miRNAs inhibit several interacting genes of p53 networks, especially in TUOS-3 and TUOS-4, and showed cell line-specific inhibition effects. Taken together, the data indicate that the three miRNAs are closely associated with Taxol resistance and potentially better prognosis factors. Our results suggest that these miRNAs were successfully and reliably identified and would be used in the development of miRNA therapies in treating ovarian cancer. Keywords: microRNA, ovarian cancer, Taxol resistance, Kaplan–Meier survival analysis

  1. Adverse effects of stress on microbiota

    Science.gov (United States)

    The complex communities of microorganisms that colonize the gastrointestinal tract impact the health status of an animal. The health of an animal as well as production traits are also affected by exposure to stress. The aim of present study was to evaluate the effects of dehorning stress on the gut ...

  2. Rare and very rare adverse effects of clozapine

    Directory of Open Access Journals (Sweden)

    De Fazio P

    2015-08-01

    Full Text Available Pasquale De Fazio,1 Raffaele Gaetano,1 Mariarita Caroleo,1 Gregorio Cerminara,1 Francesca Maida,2 Antonio Bruno,3 Maria Rosaria Muscatello,3 Maria Jose Jaén Moreno,4 Emilio Russo,2 Cristina Segura-García1 1Department of Health Sciences, School of Specialization in Psychiatry, 2Department of Health Sciences, School of Specialization in Pharmacology, University “Magna Graecia”, Catanzaro, 3Department of Neurosciences, School of Specialization in Psychiatry, University of Messina, Messina, Italy; 4Department of Social Health Sciences, Radiology and Physical Medicine, University of Cordoba, Cordoba, Spain Abstract: Clozapine (CLZ is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate

  3. Adverse Effects of Electronic Cigarette Use: A Concept Mapping Approach.

    Science.gov (United States)

    Soule, Eric K; Nasim, Aashir; Rosas, Scott

    2016-05-01

    Electronic cigarette (ECIG) use has grown rapidly in popularity within a short period of time. As ECIG products continue to evolve and more individuals begin using ECIGs, it is important to understand the potential adverse effects that are associated with ECIG use. The purpose of this study was to examine and describe the acute adverse effects associated with ECIG use. This study used an integrated, mixed-method participatory approach called concept mapping (CM). Experienced ECIG users (n = 85) provided statements that answered the focus prompt "A specific negative or unpleasant effect (ie, physical or psychological) that I have experienced either during or immediately after using an electronic cigarette device is…" in an online program. Participants sorted these statements into piles of common themes and rated each statement. Using multidimensional scaling and hierarchical cluster analysis, a concept map of the adverse effects statements was created. Participants generated 79 statements that completed the focus prompt and were retained by researchers. Analysis generated a map containing five clusters that characterized perceived adverse effects of ECIG use: Stigma, Worry/Guilt, Addiction Signs, Physical Effects, and Device/Vapor Problems. ECIG use is associated with adverse effects that should be monitored as ECIGs continue to grow in popularity. If ECIGs are to be regulated, policies should be created that minimize the likelihood of user identified adverse effects. This article provides a list of adverse effects reported by experienced ECIG users. This article organizes these effects into a conceptual model that may be useful for better understanding the adverse outcomes associated with ECIG use. These identified adverse effects may be useful for health professionals and policy makers. Health professionals should be aware of potential negative health effects that may be associated with ECIG use and policy makers could design ECIG regulations that minimize the

  4. Cell-type-specific H+-ATPase activity in root tissues enables K+ retention and mediates acclimation of barley (Hordeum vulgare) to salinity stress

    DEFF Research Database (Denmark)

    Shabala, Lana; Zhang, Jingyi; Pottosin, Igor

    2016-01-01

    conferring higher sensitivity of apical root cells to salinity in barley (Hordeum vulgare). We show that salinity application to the root apex arrests root growth in a highly tissue- and treatment-specific manner. Although salinity-induced transient net Na(+) uptake was about 4-fold higher in the root apex......While the importance of cell type specificity in plant adaptive responses is widely accepted, only a limited number of studies have addressed this issue at the functional level. We have combined electrophysiological, imaging, and biochemical techniques to reveal the physiological mechanisms...... depolarization, and (3) a higher reactive oxygen species production under NaCl and a larger density of reactive oxygen species-activated cation currents in the apex. Salinity treatment increased (2- to 5-fold) the content of 10 (out of 25 detected) amino acids in the root apex but not in the mature zone...

  5. Protein Storage Vacuoles Are Transformed into Lytic Vacuoles in Root Meristematic Cells of Germinating Seedlings by Multiple, Cell Type-Specific Mechanisms1[W

    Science.gov (United States)

    Zheng, Huiqiong; Staehelin, L. Andrew

    2011-01-01

    We have investigated the structural events associated with vacuole biogenesis in root tip cells of tobacco (Nicotiana tabacum) seedlings preserved by high-pressure freezing and freeze-substitution techniques. Our micrographs demonstrate that the lytic vacuoles (LVs) of root tip cells are derived from protein storage vacuoles (PSVs) by cell type-specific sets of transformation events. Analysis of the vacuole transformation pathways has been aided by the phytin-dependent black osmium staining of PSV luminal contents. In epidermal and outer cortex cells, the central LVs are formed by a process involving PSV fusion, storage protein degradation, and the gradual replacement of the PSV marker protein α-tonoplast intrinsic protein (TIP) with the LV marker protein γ-TIP. In contrast, in the inner cortex and vascular cylinder cells, the transformation events are more complex. During mobilization of the stored molecules, the PSV membranes collapse osmotically upon themselves, thereby squeezing the vacuolar contents into the remaining bulging vacuolar regions. The collapsed PSV membranes then differentiate into two domains: (1) vacuole “reinflation” domains that produce pre-LVs, and (2) multilamellar autophagosomal domains that are later engulfed by the pre-LVs. The multilamellar autophagosomal domains appear to originate from concentric sheets of PSV membranes that create compartments within which the cytoplasm begins to break down. Engulfment of the multilamellar autophagic vacuoles by the pre-LVs gives rise to the mature LVs. During pre-LV formation, the PSV marker α-TIP disappears and is replaced by the LV marker γ-TIP. These findings demonstrate that the central LVs of root cells arise from PSVs via cell type-specific transformation pathways. PMID:21278307

  6. Neuro-, Cardio-, and Immunoplasticity: Effects of Early Adversity.

    Science.gov (United States)

    Pakulak, Eric; Stevens, Courtney; Neville, Helen

    2018-01-04

    The relationship between early adversity and outcomes across the lifespan is apparent in a striking range of measures. Evidence suggests that many of these outcomes can be traced to the impacts of early adversity on multiple and integrated biological systems mediated by the brain. In this review, we integrate empirical and theoretical advances in the understanding of relationships among the brain and the functions of the endocrine, autonomic, and immune systems. We emphasize the effects of environmental experiences related to caregiver relationships because it is these experiences, in particular, that shape regulatory and threat response systems in ways that increase vulnerability and may underlie the wide range of poor outcomes associated with early adversity. Thus, we metaphorically extend the concept of plasticity to highlight our goal of a broader consideration of these interconnected mechanisms. We conclude by discussing implications for neurobiologically informed interventions that can potentially ameliorate the broad and costly effects of early adversity.

  7. Systematic identification and annotation of human methylation marks based on bisulfite sequencing methylomes reveals distinct roles of cell type-specific hypomethylation in the regulation of cell identity genes.

    Science.gov (United States)

    Liu, Hongbo; Liu, Xiaojuan; Zhang, Shumei; Lv, Jie; Li, Song; Shang, Shipeng; Jia, Shanshan; Wei, Yanjun; Wang, Fang; Su, Jianzhong; Wu, Qiong; Zhang, Yan

    2016-01-08

    DNA methylation is a key epigenetic mark that is critical for gene regulation in multicellular eukaryotes. Although various human cell types may have the same genome, these cells have different methylomes. The systematic identification and characterization of methylation marks across cell types are crucial to understand the complex regulatory network for cell fate determination. In this study, we proposed an entropy-based framework termed SMART to integrate the whole genome bisulfite sequencing methylomes across 42 human tissues/cells and identified 757 887 genome segments. Nearly 75% of the segments showed uniform methylation across all cell types. From the remaining 25% of the segments, we identified cell type-specific hypo/hypermethylation marks that were specifically hypo/hypermethylated in a minority of cell types using a statistical approach and presented an atlas of the human methylation marks. Further analysis revealed that the cell type-specific hypomethylation marks were enriched through H3K27ac and transcription factor binding sites in cell type-specific manner. In particular, we observed that the cell type-specific hypomethylation marks are associated with the cell type-specific super-enhancers that drive the expression of cell identity genes. This framework provides a complementary, functional annotation of the human genome and helps to elucidate the critical features and functions of cell type-specific hypomethylation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Misuse of topical corticosteroids: A clinical study of adverse effects

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Dey

    2014-01-01

    Full Text Available Background: Misuse of topical corticosteroids is a widespread phenomenon among young people in India, especially women. The practice is associated with significant adverse effects and poor awareness of these effects among the general public. Aim: This study was conducted to examine the misuse and adverse effects of topical corticosteroids among the people in Bastar region in Chhattisgarh state of India. Materials and Methods: Data collected from patients presenting with at least one of the adverse effects of topical corticosteroids as the chief complaint, from November 2010 to October 2011. Results: Out of the 6723 new patients, 379 (5.63% had presented with misuse and adverse effects of topical corticosteroids, of whom 78.89% were females. More than 65% of the patients were in the age group 10-29 years. The main reason for using the topical corticosteroids was to lighten skin colour and treat melasma and suntan. Acne (37.99% and telangiectasia (18.99% were the most common adverse effects noted. Conclusions: Misuse of topical corticosteroids has a huge impact on dermatological practice, leading to a significant proportion of visits to the dermatologist. This hydra-headed problem needs multi-dimensional interventions, involving educational, legal and managerial approaches with cooperation from different sectors of society.

  9. Topical corticosteroids abuse: A clinical study of cutaneous adverse effects

    Directory of Open Access Journals (Sweden)

    Soniya Meena

    2017-01-01

    Full Text Available Background: Topical corticosteroids (TC are one of the most widely used agents in dermatology practice. Misuse of these agents may lead to a wide range of adverse effects. Aim: This study was conducted to assess the magnitude of abuse of topical corticosteroids (TC and clinical patterns of cutaneous adverse effects amongst patients attending dermatology department of a teaching hospital at South Rajasthan. Materials and Methods: All patients who reported with adverse effects of topical steroids during one year from September 2015 to August 2016 were evaluated. Patients fulfilling the study criteria were registered for further workup. Results: Out of the 85280 new patients, 370 (0.43% presented with adverse effects of TC. Males (232/370;62.70% outnumbered females (138/370;37.30. Age group 11-30 years was most commonly (74.05% affected. The main reason for using TC was fungal infection (52.43%. Tinea incognito (49.46% and acne (30.27% were the most common adverse effects recorded. Conclusions: Abuse of TC, particularly the superpotent and potent is rampant amongst general population. Topical corticosteroids are frequently used for indications where they should be avoided.

  10. Locally advanced prostate cancer: effective treatments, but many adverse effects.

    Science.gov (United States)

    2013-01-01

    Locally advanced prostate tumours, i.e. those that extend beyond the prostate gland but are not metastatic, often carry a poor prognosis: between 10% and 40% of patients die within 5 years after diagnosis. Various treatments are proposed to improve their prognosis. Which treatments have a proven survival benefit, and what are their adverse effects? To answer these questions, we reviewed the literature using the standard Prescrire methodology. Prostatectomy has not been evaluated in controlled trials versus either watchful waiting or radiation therapy alone. Prostatectomy is mainly proposed to patients who are in good general health. Five years after prostatectomy, mortality from prostate cancer is between 2% and 16%, depending on the study.Three-quarters of patients who have surgery at this stage experience erectile dysfunction, and at least 20% of patients develop urinary incontinence. External beam radiation therapy alone has not been compared with watchful waiting or prostatectomy. External beam radiation therapy has documented benefits in patients with locally advanced prostate cancer treated with gonadorelin agonists, preventing 8 to 10 deaths from all causes after 7 to 10 years of follow-up among 100 treated patients. However, about 60% of patients experience erectile dysfunction, about 15% symptomatic radiation proctitis, and about 5% urinary incontinence. When combined with prostatectomy, radiation therapy did not affect the 5-year survival rate but prolonged survival by about 2 years in a trial with more than 10 years of follow-up. When used without concomitant androgen suppression, antiandrogens have no proven impact on overall survival in patients with locally advanced prostate cancer. In the absence of radical prostatectomy or radiation therapy, androgen suppression, by means of orchiectomy or gonadorelin agonist, has a minimal impact on overall survival among patients with locally advanced cancer. In one randomised trial, androgen suppression in

  11. [Registration of suspected adverse effects by the Bureau Adverse Effects Drugs; research activities in 1993].

    Science.gov (United States)

    Stricker, B H; Ottervanger, J P; van der Klauw, M M

    1994-10-15

    In 1993, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 1585 reports of suspected adverse reactions. The most important reports concerned myocardial infarction due to sumatriptan, cholestatic hepatitis due to itraconazole, agranulocytosis due to trazodone and bleeding due to fluoxetine and fluvoxamine. Other published reports concerned cholestatic hepatitis due to amoxicillin/clavulanic acid, hair loss due to beta-blockers, muscle necrosis due to diclofenac, bronchospasm, apnoea and cardiac arrest due to dipyridamole perfusion scintigraphy, interaction of fluvoxamine/fluoxetine and coumarins, liver enzyme elevations due to heparin, skin reactions due to Imedeen, deafness due to neomycin, addiction to nicotine chewing gum, atrial fibrillation and skin reactions due to nicotine patches, interaction between oral contraceptives and terbinafine, neonatal problems caused by psychopharmacological agents, parapemphigus caused by sulfasalazine, taste loss due to terbinafine en intracranial bleeding after use of tranylcypromine and beer. Pharmacoepidemiological studies were performed concerning methods for record linkage, the communication process with respect to the acitretin alert and the adverse events due to sumatriptan.

  12. A comparative overview of the adverse effects of antiulcer drugs.

    Science.gov (United States)

    Piper, D W

    1995-02-01

    During the past 2 decades, great advances have been made in the treatment of ulcer disease. This has involved the development of new drugs that are not only well tolerated, but are relatively inexpensive. The lack of significant adverse effects has revealed a degree of tolerability that, to write a review of the adverse effects, poses a difficult task. Most of the adverse effects are related to an excessive reaction to the relevant pharmacological characteristic that mediates the therapeutic response. The drug dosage can be reduced, freeing the patient of the adverse reaction, but leaving behind a background activity adequate to produce a therapeutically beneficial effect. The adverse effects of H2-antagonists fall into 2 groups. Firstly, there are poorly defined symptoms that have a prevalence similar to that in the community; these include headache, giddiness, dizziness, fatigue, constipation and diarrhoea. Secondly, they may delay the metabolism of drugs metabolised by the the cytochrome P450 system, and rarely be androgenic. Many antacids and the site-protective agent sucralfate contain aluminium, which can be absorbed, producing elevation of serum aluminium levels. In view of the possible association of aluminium with Alzheimer's disease, anxiety has arisen as to whether aluminium from these sources may, in those on prolonged treatment, cause Alzheimer's disease. However, the evidence so far indicates that aluminium is not a risk factor for Alzheimer's disease. The association of gastric cancer with achlorhydria has led to the fear that long term use of potent acid inhibitors may cause cancer. This fear has been accentuated by the observation that some rats, given omeprazole over their lifetime, developed carcinoid tumours of the stomach. However, enthusiastic research, both clinical and epidemiological, indicates that drug-induced achlorhydria is unlikely to be a problem in humans. Site protective agents have a role in certain conditions such as pregnancy

  13. Adverse effects of voriconazole: Over a decade of use.

    Science.gov (United States)

    Levine, Miriam T; Chandrasekar, Pranatharthi H

    2016-11-01

    Voriconazole use has increased since the drug's introduction in 2002, and new and unique adverse effects are emerging as patients undergo prolonged therapy. Most concerning is the increased risk of cutaneous malignancies, primarily squamous cell carcinoma (SCC); this risk is duration dependent and the associated malignancies tend to be more aggressive and multifocal. Voriconazole is also associated with phototoxicity (which may be a precursor to malignancy), periostitis, hallucinations and encephalopathy, peripheral neuropathy, alopecia, nail changes, hyponatremia, and other adverse effects. Some toxicities (neuropsychiatric and gastrointestinal including hepatic) are seen in clear association with supratherapeutic serum voriconazole levels; thus, careful monitoring of voriconazole levels is a critical component of safe drug use. Guidelines for screening for adverse effects after long-term voriconazole use may be beneficial and need to be established. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Adverse urinary effects of allopurinol in dogs with leishmaniasis.

    Science.gov (United States)

    Torres, M; Pastor, J; Roura, X; Tabar, M D; Espada, Y; Font, A; Balasch, J; Planellas, M

    2016-06-01

    The objective of this study was to describe the adverse effects of allopurinol on the urinary system during treatment of canine leishmaniasis. Retrospective case series of 42 dogs that developed xanthinuria while receiving allopurinol treatment for leishmaniasis. Of 320 dogs diagnosed with leishmaniasis, 42 (13%) developed adverse urinary effects. Thirteen (of 42) dogs (31%) developed xanthinuria, renal mineralisation and urolithiasis; 11 (26·2%) showed xanthinuria with renal mineralisation; 9 (21·4%) had xanthinuria with urolithiasis and 9 (21·4%) developed xanthinuria alone. Urinary clinical signs developed in 19 dogs (45·2%). This study demonstrates that urolithiasis and renal mineralisation can occur in dogs receiving allopurinol therapy. Dogs receiving therapy should be monitored for the development of urinary adverse effects from the beginning of treatment. © 2016 British Small Animal Veterinary Association.

  15. Mechanisms of Hexachlorobenzene-induced Adverse Immune Effects

    NARCIS (Netherlands)

    Ezendam, Janine

    2004-01-01

    Hexachlorobenzene (HCB) is an environmental pollutant that can induce adverse immune effects in humans and rats. Brown Norway rats (BN) appeared to be very susceptible to HCB-induced immune effects. Oral exposure causes inflammatory skin and lung lesions, enlarged spleen and lymph nodes (LN) and

  16. The adverse effects of albendazole and praziquantel in mass drug ...

    African Journals Online (AJOL)

    The adverse effects of albendazole and praziquantel in mass drug administration by trained schoolteachers. ... In this study, one trained schoolteacher could administer treatment to three hundred children in one day, which makes the approach cost effective and should be adopted nationally. Keywords: albendazole ...

  17. Adverse Health Effects in Relation to Urban Residential Soundscapes

    Science.gov (United States)

    SKÅNBERG, A.; ÖHRSTRÖM, E.

    2002-02-01

    Noise pollution from road traffic in residential areas is a growing environmental problem. New approaches to turn the negative trend are needed. The programme “Soundscape Support to Health” will achieve new knowledge about the adverse health effects of noise pollution on humans and will investigate the link between well-being and health and perceived soundscapes for optimizing the acoustic soundscapes in urban residential areas. This paper will briefly present the programme and presents preliminary results from the first study of how various adverse health effects are related to individual noise exposures among individuals in residential areas with and without access to a quiet side of the dwelling.

  18. A novel BAT3 sequence generated by alternative RNA splicing of exon 11B displays cell type-specific expression and impacts on subcellular localization.

    Directory of Open Access Journals (Sweden)

    Nadine Kämper

    Full Text Available The human lymphocyte antigen (HLA encoded BAT3/BAG6 recently attracted interest as a regulator of protein targeting and degradation, a function that could be exerted in the cytosol and in the nucleus. The BAT3 gene was described to consist of 25 exons. Diversity of transcripts can be generated by alternative RNA splicing, which may control subcellular distribution of BAT3.By cDNA sequencing we identified a novel alternatively spliced sequence of the BAT3 gene located between exons 11 and 12, which was designated as exon 11B. Using PCR and colony hybridization we identified six cDNA variants, which were produced by RNA splicing of BAT3 exons 5, 11B and 24. In four examined cell types the content of BAT3 splice variants was examined. Most of the cDNA clones from monocyte-derived dendritic cells contain exon 11B, whereas this sequence was almost absent in the B lymphoma Raji. Exon 5 was detected in most and exon 24 in approximately half of the cDNA clones. The subcellular distribution of endogenous BAT3 largely correlates with a cell type specific splicing pattern. In cells transfected with BAT3 variants, full-length and Δ24 BAT3 displayed nearly exclusive nuclear staining, whereas variants deleted of exon 11B showed substantial cytosolic expression. We show here that BAT3 is mainly expressed in the cytosol of Raji cells, while other cell types displayed both cytosolic and nuclear staining. Export of BAT3 from the nucleus to the cytosol is inhibited by treatment with leptomycin B, indicating that the Crm1 pathway is involved. Nuclear expression of BAT3 containing exon 11B suggests that this sequence plays a role for nuclear retention of the protein.Cell type-specific subcellular expression of BAT3 suggests distinct functions in the cytosol and in the nucleus. Differential expression of BAT3 variants may reconcile the multiple roles described for BAT3.

  19. Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Hironori Waki

    2011-10-01

    Full Text Available Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type-specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq. FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA-mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our

  20. Enhanced detection with spectral imaging fluorescence microscopy reveals tissue- and cell-type-specific compartmentalization of surface-modified polystyrene nanoparticles.

    Science.gov (United States)

    Kenesei, Kata; Murali, Kumarasamy; Czéh, Árpád; Piella, Jordi; Puntes, Victor; Madarász, Emília

    2016-07-07

    Precisely targeted nanoparticle delivery is critically important for therapeutic applications. However, our knowledge on how the distinct physical and chemical properties of nanoparticles determine tissue penetration through physiological barriers, accumulation in specific cells and tissues, and clearance from selected organs has remained rather limited. In the recent study, spectral imaging fluorescence microscopy was exploited for precise and rapid monitoring of tissue- and cell-type-specific distribution of fluorescent polystyrene nanoparticles with chemically distinct surface compositions. Fluorescent polystyrene nanoparticles with 50-90 nm diameter and with carboxylated- or polyethylene glycol-modified (PEGylated) surfaces were delivered into adult male and pregnant female mice with a single intravenous injection. The precise anatomical distribution of the particles was investigated by confocal microscopy after a short-term (5 min) or long-term (4 days) distribution period. In order to distinguish particle-fluorescence from tissue autofluorescence and to enhance the detection-efficiency, fluorescence spectral detection was applied during image acquisition and a post hoc full spectrum analysis was performed on the final images. Spectral imaging fluorescence microscopy allowed distinguishing particle-fluorescence from tissue-fluorescence in all examined organs (brain, kidney, liver, spleen and placenta) in NP-treated slice preparations. In short-time distribution following in vivo NP-administration, all organs contained carboxylated-nanoparticles, while PEGylated-nanoparticles were not detected in the brain and the placenta. Importantly, nanoparticles were not found in any embryonic tissues or in the barrier-protected brain parenchyma. Four days after the administration, particles were completely cleared from both the brain and the placenta, while PEGylated-, but not carboxylated-nanoparticles, were stuck in the kidney glomerular interstitium. In the spleen

  1. An Essential Role for the Tetraspanin LHFPL4 in the Cell-Type-Specific Targeting and Clustering of Synaptic GABAA Receptors

    Directory of Open Access Journals (Sweden)

    Elizabeth C. Davenport

    2017-10-01

    Full Text Available Inhibitory synaptic transmission requires the targeting and stabilization of GABAA receptors (GABAARs at synapses. The mechanisms responsible remain poorly understood, and roles for transmembrane accessory proteins have not been established. Using molecular, imaging, and electrophysiological approaches, we identify the tetraspanin LHFPL4 as a critical regulator of postsynaptic GABAAR clustering in hippocampal pyramidal neurons. LHFPL4 interacts tightly with GABAAR subunits and is selectively enriched at inhibitory synapses. In LHFPL4 knockout mice, there is a dramatic cell-type-specific reduction in GABAAR and gephyrin clusters and an accumulation of large intracellular gephyrin aggregates in vivo. While GABAARs are still trafficked to the neuronal surface in pyramidal neurons, they are no longer localized at synapses, resulting in a profound loss of fast inhibitory postsynaptic currents. Hippocampal interneuron currents remain unaffected. Our results establish LHFPL4 as a synapse-specific tetraspanin essential for inhibitory synapse function and provide fresh insights into the molecular make-up of inhibitory synapses.

  2. Correlation of mRNA and protein levels: Cell type-specific gene expression of cluster designation antigens in the prostate

    Directory of Open Access Journals (Sweden)

    Deutsch Eric W

    2008-05-01

    Full Text Available Abstract Background: Expression levels of mRNA and protein by cell types exhibit a range of correlations for different genes. In this study, we compared levels of mRNA abundance for several cluster designation (CD genes determined by gene arrays using magnetic sorted and laser-capture microdissected human prostate cells with levels of expression of the respective CD proteins determined by immunohistochemical staining in the major cell types of the prostate – basal epithelial, luminal epithelial, stromal fibromuscular, and endothelial – and for prostate precursor/stem cells and prostate carcinoma cells. Immunohistochemical stains of prostate tissues from more than 50 patients were scored for informative CD antigen expression and compared with cell-type specific transcriptomes. Results: Concordance between gene and protein expression findings based on 'present' vs. 'absent' calls ranged from 46 to 68%. Correlation of expression levels was poor to moderate (Pearson correlations ranged from 0 to 0.63. Divergence between the two data types was most frequently seen for genes whose array signals exceeded background (> 50 but lacked immunoreactivity by immunostaining. This could be due to multiple factors, e.g. low levels of protein expression, technological sensitivities, sample processing, probe set definition or anatomical origin of tissue and actual biological differences between transcript and protein abundance. Conclusion: Agreement between these two very different methodologies has great implications for their respective use in both molecular studies and clinical trials employing molecular biomarkers.

  3. A cell-type-specific defect in border cell formation in the Acacia mangium root cap developing an extraordinary sheath of sloughed-off cells.

    Science.gov (United States)

    Endo, Izuki; Tange, Takeshi; Osawa, Hiroki

    2011-08-01

    Root caps release border cells, which play central roles in microbe interaction and root protection against soil stresses. However, the number and connectivity of border cells differ widely among plant species. Better understanding of key border-cell phenotype across species will help define the total function of border cells and associated genes. The spatio-temporal detachment of border cells in the leguminous tree Acacia mangium was investigated by using light and fluorescent microscopy with fluorescein diacetate, and their number and structural connectivity compared with that in soybean (Glycine max). Border-like cells with a sheet structure peeled bilaterally from the lateral root cap of A. mangium. Hydroponic root elongation partially facilitated acropetal peeling of border-like cells, which accumulate as a sheath that covers the 0- to 4-mm tip within 1 week. Although root elongation under friction caused basipetal peeling, lateral root caps were minimally trimmed as compared with hydroponic roots. In the meantime, A. mangium columella caps simultaneously released single border cells with a number similar to those in soybean. These results suggest that cell type-specific inhibitory factors induce a distinct defective phenotype in single border-cell formation in A. mangium lateral root caps.

  4. A novel cell type-specific role of p38alpha in the control of autophagy and cell death in colorectal cancer cells.

    Science.gov (United States)

    Comes, F; Matrone, A; Lastella, P; Nico, B; Susca, F C; Bagnulo, R; Ingravallo, G; Modica, S; Lo Sasso, G; Moschetta, A; Guanti, G; Simone, C

    2007-04-01

    Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of these pathways in tumor cells. In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38alpha/beta kinases. We report that p38alpha is required for colorectal cancer cell homeostasis as the inhibition of its kinase function by pharmacological blockade or genetic inactivation causes cell cycle arrest, autophagy and cell death in a cell type-specific manner. Deficiency of p38alpha activity induces a tissue-restricted upregulation of the GABARAP gene, an essential component of autophagic vacuoles and autophagosomes, whereas simultaneous inhibition of autophagy significantly increases cell death by triggering apoptosis. These data identify p38alpha as a central mediator of colorectal cancer cell homeostasis and establish a rationale for the evaluation of the pharmacological manipulation of the p38alpha pathway in the treatment of colorectal cancer.

  5. MMAD: microarray microdissection with analysis of differences is a computational tool for deconvoluting cell type-specific contributions from tissue samples.

    Science.gov (United States)

    Liebner, David A; Huang, Kun; Parvin, Jeffrey D

    2014-03-01

    One of the significant obstacles in the development of clinically relevant microarray-derived biomarkers and classifiers is tissue heterogeneity. Physical cell separation techniques, such as cell sorting and laser-capture microdissection, can enrich samples for cell types of interest, but are costly, labor intensive and can limit investigation of important interactions between different cell types. We developed a new computational approach, called microarray microdissection with analysis of differences (MMAD), which performs microdissection in silico. Notably, MMAD (i) allows for simultaneous estimation of cell fractions and gene expression profiles of contributing cell types, (ii) adjusts for microarray normalization bias, (iii) uses the corrected Akaike information criterion during model optimization to minimize overfitting and (iv) provides mechanisms for comparing gene expression and cell fractions between samples in different classes. Computational microdissection of simulated and experimental tissue mixture datasets showed tight correlations between predicted and measured gene expression of pure tissues as well as tight correlations between reported and estimated cell fraction for each of the individual cell types. In simulation studies, MMAD showed superior ability to detect differentially expressed genes in mixed tissue samples when compared with standard metrics, including both significance analysis of microarrays and cell type-specific significance analysis of microarrays. We have developed a new computational tool called MMAD, which is capable of performing robust tissue microdissection in silico, and which can improve the detection of differentially expressed genes. MMAD software as implemented in MATLAB is publically available for download at http://sourceforge.net/projects/mmad/.

  6. Divergent co-transcriptomes of different host cells infected with Toxoplasma gondii reveal cell type-specific host-parasite interactions.

    Science.gov (United States)

    Swierzy, Izabela J; Händel, Ulrike; Kaever, Alexander; Jarek, Michael; Scharfe, Maren; Schlüter, Dirk; Lüder, Carsten G K

    2017-08-03

    The apicomplexan parasite Toxoplasma gondii infects various cell types in avian and mammalian hosts including humans. Infection of immunocompetent hosts is mostly asymptomatic or benign, but leads to development of largely dormant bradyzoites that persist predominantly within neurons and muscle cells. Here we have analyzed the impact of the host cell type on the co-transcriptomes of host and parasite using high-throughput RNA sequencing. Murine cortical neurons and astrocytes, skeletal muscle cells (SkMCs) and fibroblasts differed by more than 16,200 differentially expressed genes (DEGs) before and after infection with T. gondii. However, only a few hundred of them were regulated by infection and these largely diverged in neurons, SkMCs, astrocytes and fibroblasts indicating host cell type-specific transcriptional responses after infection. The heterogeneous transcriptomes of host cells before and during infection coincided with ~5,400 DEGs in T. gondii residing in different cell types. Finally, we identified gene clusters in both T. gondii and its host, which correlated with the predominant parasite persistence in neurons or SkMCs as compared to astrocytes or fibroblasts. Thus, heterogeneous expression profiles of different host cell types and the parasites' ability to adapting to them may govern the parasite-host cell interaction during toxoplasmosis.

  7. Alternative pre-mRNA processing regulates cell-type specific expression of the IL4l1 and NUP62 genes

    Directory of Open Access Journals (Sweden)

    Poustka Annemarie

    2005-07-01

    Full Text Available Abstract Background Given the complexity of higher organisms, the number of genes encoded by their genomes is surprisingly small. Tissue specific regulation of expression and splicing are major factors enhancing the number of the encoded products. Commonly these mechanisms are intragenic and affect only one gene. Results Here we provide evidence that the IL4I1 gene is specifically transcribed from the apparent promoter of the upstream NUP62 gene, and that the first two exons of NUP62 are also contained in the novel IL4I1_2 variant. While expression of IL4I1 driven from its previously described promoter is found mostly in B cells, the expression driven by the NUP62 promoter is restricted to cells in testis (Sertoli cells and in the brain (e.g., Purkinje cells. Since NUP62 is itself ubiquitously expressed, the IL4I1_2 variant likely derives from cell type specific alternative pre-mRNA processing. Conclusion Comparative genomics suggest that the promoter upstream of the NUP62 gene originally belonged to the IL4I1 gene and was later acquired by NUP62 via insertion of a retroposon. Since both genes are apparently essential, the promoter had to serve two genes afterwards. Expression of the IL4I1 gene from the "NUP62" promoter and the tissue specific involvement of the pre-mRNA processing machinery to regulate expression of two unrelated proteins indicate a novel mechanism of gene regulation.

  8. Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

    Directory of Open Access Journals (Sweden)

    Chan Zhou

    2017-08-01

    Full Text Available N6-methyladenosine (m6A is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ RNAs. We developed a computational pipeline (AutoCirc that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification.

  9. Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs.

    Science.gov (United States)

    Zhou, Chan; Molinie, Benoit; Daneshvar, Kaveh; Pondick, Joshua V; Wang, Jinkai; Van Wittenberghe, Nicholas; Xing, Yi; Giallourakis, Cosmas C; Mullen, Alan C

    2017-08-29

    N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that, together with depletion of ribosomal RNA and m6A immunoprecipitation, defined thousands of m6A circRNAs with cell-type-specific expression. The presence of m6A circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A circRNAs are frequently derived from exons that are not methylated in mRNAs, whereas mRNAs that are methylated on the same exons that compose m6A circRNAs exhibit less stability in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Cell type-specific protein and transcription profiles implicate periarbuscular membrane synthesis as an important carbon sink in the mycorrhizal symbiosis.

    Science.gov (United States)

    Gaude, Nicole; Schulze, Waltraud X; Franken, Philipp; Krajinski, Franziska

    2012-04-01

    The development of an arbuscular mycorrhizal (AM) symbiosis is a non-synchronous process with typical mycorrhizal root containing different symbiotic stages at one time. Methods providing cell type-specific resolution are therefore required to separate these stages and analyze each particular structure independently from each other. We established an experimental system for analyzing specific proteomic changes in arbuscule-containing cells of Glomus intraradices colonized Medicago truncatula roots. The combination of laser capture microdissection (LCM) and liquid chromatography-tandem mass chromatography (LC-MS/MS) allowed the identification of proteins with specific or increased expression in arbuscule-containing cells. Consistent with previous transcriptome data, the proteome of arbuscule-containing cells showed an increased number of proteins involved in lipid metabolism, most likely related to the synthesis of the periarbuscular membrane. In addition, transcriptome data of non-colonized cells of mycorrhizal roots suggest mobilization of carbon resources and their symplastic transport toward arbuscule-containing cells for the synthesis of periarbuscular membranes. This highlights the periarbuscular membrane as important carbon sink in the mycorrhizal symbiosis.

  11. Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble?

    NARCIS (Netherlands)

    Wanten, G.J.A.

    2015-01-01

    Lipid emulsions (LEs) are indispensable sources of fuel calories and (essential) fatty acids (FAs) in modern parenteral nutrition formulations. The use of LE, however, also remains associated with the development of adverse effects. Intolerance for LE mostly becomes apparent upon the development of

  12. Community Awareness of Adverse Effects of Nonsteroidal Anti ...

    African Journals Online (AJOL)

    About 4% drank a lot of water when they had a headache, while 1% performed massage at the site of pain. One percent visited traditional healers to seek treatment for the pain. Only 8% of the study participants knew some adverse effects caused by non-steroidal anti-inflammatory drugs. Hence, there is a need for health ...

  13. Adverse Effects of Waste Generation in Calabar Urban, Nigeria ...

    African Journals Online (AJOL)

    There was no significant difference between the working groups in their perception of the adverse effects of wastes, except as it concerned death, birth defect or cancer, environmental degradation, blocking of drainage and emission of greenhouse gases. We found a number of health hazards, ranging from pollution to ...

  14. Adverse effects of plant food supplements and botanical preparations

    DEFF Research Database (Denmark)

    Di Lorenzo, Chiara; Ceschi, Alessandro; Kupferschmidt, Hugo

    2015-01-01

    .2%), Camellia sinensis/green tea ( 8.7%) and Ginkgo biloba/gingko (8.5%). Considering the length of time examined and the number of plants included in the review, it is remarkable that: (i) the adverse effects due to botanical ingredients were relatively infrequent, if assessed for causality; and (ii...

  15. Gum pigmentation: an unusual adverse effect of sublingual immunotherapy

    OpenAIRE

    Goh, Anne; Chiang, Wen Chin; Kang, Liew Woei; Rao, Rajeshwar; Lim, Hwee Hoon; Chng, Chai Kiat

    2014-01-01

    Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is...

  16. Adverse Effects of Silver Diamine Fluoride Treatment among Preschool Children.

    Science.gov (United States)

    Duangthip, D; Fung, M H T; Wong, M C M; Chu, C H; Lo, E C M

    2017-12-01

    This randomized clinical trial aimed to compare the adverse effects and parental satisfaction following the different regimes of silver diamine fluoride (SDF) treatment among preschool children. A total of 888 preschool children who had active dentin caries received different SDF application regimes: group 1, 12% SDF applied annually; group 2, 12% SDF applied semiannually; group 3, 38% SDF applied annually; and group 4, 38% SDF applied semiannually. Information on adverse effects-including tooth or gum pain, gum swelling, gum bleaching, and systemic toxicity-was collected through a parent-reported questionnaire within 1 wk after every SDF or placebo application. Information of parental satisfaction on children's dental appearance was collected at baseline and 30-mo examination. At the 30 mo, 799 children (90%) remained in the study. No acute systemic illness or major adverse effect was reported. No differences of all minor adverse effects among the 4 groups were found ( P > 0.05). Overall, prevalence of tooth and gum pain as perceived by patients and reported by parents was 6.6%, while gum swelling and gum bleaching were 2.8% and 4.7%, respectively. Blackening of carious lesions was common among all groups, with 36.7%, 49.5%, 65.6% and 76.3% in groups 1 to 4, respectively (χ2 test, P 0.05). Based on parental reporting, SDF does not cause acute systemic illness. Tooth or gum pain, gum swelling, and gum bleaching were uncommon and not significantly different among the study groups. Parental satisfaction with children's dental appearance was similar among all groups. The use of SDF following the study protocol for caries arrest is safe for preschool children. Collecting information on parental satisfaction and adverse effects is beneficial for dental professionals when deciding to adopt SDF treatment for preschool children (ClinicalTrials.gov NCT02385474).

  17. [Adverse effects of compression in treatment of limb lymphedema].

    Science.gov (United States)

    Vignes, S; Arrault, M

    2009-11-01

    Limb lymphedema, whether primary or secondary, is a chronic disease. Compression is the cornerstone of therapy and includes multilayer low-stretch bandages and elastic garments. Compression is usually well-tolerated. The aim of our study was to identify all the different types of adverse effects of compression. Since January 2005, we have recorded all adverse events occurring in outpatients and inpatients consulting in a single lymphology department, spontaneously reported by patient during consultations or physical examinations, and noted the type of compression material used. Adverse effects were secondary to poor choice of therapeutic material, excessive pressure or contact dermatitis. For the arms, an elastic garment stopping at the wrist can be responsible for lymphedema of the hand and fingers. Rubbing of sleeve seams may cause pain and even ulcers between the thumb and forefinger. Open-toed elastic stockings may exacerbate digital lymphedema, leading to the formation of oozing lymph vesicles. Hyperpressure may cause severe pain localized to the first and fifth toes, overlapping toes, interdigital corns and/or ingrown toenails. Silicone-banded soft-fit elastic garments may cause painful phlyctena, urticaria or eczematiform lesions. Elastic bandages may induce pain or purpuric lesions. Compression can be responsible for adverse effects, sometimes severe, requiring treatment change or withdrawal. Further studies are needed to precisely determine their frequency to improve prescriptions and currently available products.

  18. Thai traditional massage: Issues causing possible adverse effects.

    Science.gov (United States)

    Wiwanitkit, Viroj

    2015-01-01

    Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed.

  19. Thai traditional massage: Issues causing possible adverse effects

    OpenAIRE

    Wiwanitkit, Viroj

    2015-01-01

    Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed.

  20. Energy Drink Consumption: Beneficial and Adverse Health Effects.

    Science.gov (United States)

    Alsunni, Ahmed Abdulrahman

    2015-10-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents.

  1. Cell type-specific recognition of human metapneumoviruses (HMPVs) by retinoic acid-inducible gene I (RIG-I) and TLR7 and viral interference of RIG-I ligand recognition by HMPV-B1 phosphoprotein.

    Science.gov (United States)

    Goutagny, Nadege; Jiang, Zhaozhao; Tian, Jane; Parroche, Peggy; Schickli, Jeanne; Monks, Brian G; Ulbrandt, Nancy; Ji, Hong; Kiener, Peter A; Coyle, Anthony J; Fitzgerald, Katherine A

    2010-02-01

    Human metapneumoviruses (HMPVs) are recently identified Paramyxoviridae that contribute to respiratory tract infections in children. No effective treatments or vaccines are available. Successful defense against virus infection relies on early detection by germ line-encoded pattern recognition receptors and activation of cytokine and type I IFN genes. Recently, the RNA helicase retinoic acid-inducible gene I (RIG-I) has been shown to sense HMPV. In this study, we investigated the abilities of two prototype strains of HMPV (A1 [NL\\1\\00] and B1 [NL\\1\\99]) to activate RIG-I and induce type I IFNs. Despite the abilities of both HMPV-A1 and HMPV-B1 to infect and replicate in cell lines and primary cells, only the HMPV-A1 strain triggered RIG-I to induce IFNA/B gene transcription. The failure of the HMPV-B1 strain to elicit type I IFN production was dependent on the B1 phosphoprotein, which specifically prevented RIG-I-mediated sensing of HMPV viral 5' triphosphate RNA. In contrast to most cell types, plasmacytoid dendritic cells displayed a unique ability to sense both HMPV-A1 and HMPV-B1 and in this case sensing was via TLR7 rather than RIG-I. Collectively, these data reveal differential mechanisms of sensing for two closely related viruses, which operate in cell type-specific manners.

  2. In vitro model for DNA double-strand break repair analysis in breast cancer reveals cell type-specific associations with age and prognosis.

    Science.gov (United States)

    Deniz, Miriam; Kaufmann, Julia; Stahl, Andreea; Gundelach, Theresa; Janni, Wolfgang; Hoffmann, Isabell; Keimling, Marlen; Hampp, Stephanie; Ihle, Michaela; Wiesmüller, Lisa

    2016-11-01

    Dysfunction of homologous recombination is a common denominator of changes associated with breast cancer-predisposing mutations. In our previous work, we identified a functional signature in peripheral blood lymphocytes from women who were predisposed that indicated a shift from homologous recombination to alternative, error-prone DNA double-strand break (DSB) repair pathways. To capture both hereditary and nonhereditary factors, we newly established a protocol for isolation and ex vivo analysis of epithelial cells, epithelial-mesenchymal transition cells (EMTs), and fibroblasts from breast cancer specimens (147 patients). By applying a fluorescence-based test system, we analyzed the error-prone DSB repair pathway microhomology-mediated end joining in these tumor-derived cell types and peripheral blood lymphocytes. In parallel, we investigated DNA lesion processing by quantitative immunofluorescence microscopy of histone H2AX phosphorylated on Ser139 focus after radiomimetic treatment. Our study reveals elevated histone H2AX phosphorylated on Ser139 damage removal in epithelial cells, not EMTs, and poly(ADP-ribose)polymerase inhibitor sensitivities, which suggested a DSB repair pathway shift with increasing patient age. Of interest, we found elevated microhomology-mediated end joining in EMTs, not epithelial cells, from patients who received a treatment recommendation of adjuvant chemotherapy, that is, those with high-risk tumors. Our discoveries of altered DSB repair activities in cells may serve as a method to further classify breast cancer to predict responsiveness to adjuvant chemotherapy and/or therapeutics that target DSB repair-dysfunctional tumors.-Deniz, M., Kaufmann, J., Stahl, A., Gundelach, T., Janni, W., Hoffmann, I., Keimling, M., Hampp, S., Ihle, M., Wiesmüller, L. In vitro model for DNA double-strand break repair analysis in breast cancer reveals cell type-specific associations with age and prognosis. © FASEB.

  3. p53 shapes genome-wide and cell type-specific changes in microRNA expression during the human DNA damage response.

    Science.gov (United States)

    Hattori, Hiroyoshi; Janky, Rekin's; Nietfeld, Wilfried; Aerts, Stein; Madan Babu, M; Venkitaraman, Ashok R

    2014-01-01

    The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been implicated in the DDR, there is as yet no comprehensive description of genome-wide changes in the expression of miRNAs triggered by DNA breakage in human cells. We have used next-generation sequencing (NGS), combined with rigorous integrative computational analyses, to describe genome-wide changes in the expression of miRNAs during the human DDR. The changes affect 150 of 1523 miRNAs known in miRBase v18 from 4-24 h after the induction of DNA breakage, in cell-type dependent patterns. The regulatory regions of the most-highly regulated miRNA species are enriched in conserved binding sites for p53. Indeed, genome-wide changes in miRNA expression during the DDR are markedly altered in TP53-/- cells compared to otherwise isogenic controls. The expression levels of certain damage-induced, p53-regulated miRNAs in cancer samples correlate with patient survival. Our work reveals genome-wide and cell type-specific alterations in miRNA expression during the human DDR, which are regulated by the tumor suppressor protein p53. These findings provide a genomic resource to identify new molecules and mechanisms involved in the DDR, and to examine their role in tumor suppression and the clinical outcome of cancer patients.

  4. Adverse effects of antipsychotic agents. Do newer agents offer advantages?

    Science.gov (United States)

    Owens, D G

    1996-06-01

    Although antipsychotic drugs are effective in treating the so-called positive features of schizophrenia, between one-quarter and one-third of patients respond poorly. Furthermore, the incidence of adverse effects is high, especially those reflecting disruption of extrapyramidal function, and is a major source of non-compliance. There is a clear need for new compounds that are more efficacious and/or better tolerated. Until recently, the classical dopamine hypothesis, with its emphasis on D2 blockade as the key mechanism of antipsychotic action, dominated drug development, though the emphasis is now shifting. Three 'new' antipsychotics have reached the international market in the past 5 years-the newly rehabilitated clozapine and the genuinely new remoxipride and risperidone. Claims of enhanced tolerability have been made for each of these, but as none is free from adverse effects, their place in treatment can only be meaningfully established in relation to the efficacy of each in different clinical situations. Clozapine has an extensive profile of general, nonhaematological adverse effects which is slightly different in emphasis from, but comparable in incidence to, that of chlorpromazine. There is a 0.8% risk of agranulocytosis in the first year of exposure, which can be fatal, though the boundary separating it from other (especially phenothiazine) antipsychotics in this regard is becoming increasingly blurred. It has a clearly diminished liability to cause extrapyramidal adverse effects. Its proven efficacy in operationally defined treatment-resistant schizophrenia and in patients intolerant to the extrapyramidal adverse effects of standard drugs establishes its credentials for advantage in these groups. There is on present evidence, however, only a hint of enhanced efficacy in acute schizophrenia: this requires further investigation. Open maintenance studies provide impressive data on long term outcome, especially in terms of quality-of-life parameters, but this

  5. Ocular surface adverse effects of ambient levels of air pollution

    Directory of Open Access Journals (Sweden)

    André Augusto Miranda Torricelli

    2011-10-01

    Full Text Available It is widely recognized today that outdoor air pollution can affect human health. Various chemical components that are present in ambient pollution may have an irritant effect on the mucous membranes of the body, particularly those of the respiratory tract. Much less attention has been focused on the adverse effect on the ocular surface, despite the fact that this structure is even more exposed to air pollution than the respiratory mucosa since only a very thin tear film separates the corneal and conjunctival epithelia from the air pollutants. So far, clinical data are the more widespread tools used by ophthalmologists for assessing possible aggression to the ocular surface; however, clinical findings alone appears not to correlate properly with the complaints presented by the patients pointing out the need for further clinical and laboratory studies on the subject. The purpose of this study is to review signs and symptoms associated with chronic long-term exposure to environmental air pollutants on the ocular structures currently defined as the ocular surface and to review clinical and laboratory tests used to investigate the adverse effects of air pollutants on such structures. We also review previous studies that investigated the adverse effects of air pollution on the ocular surface and discuss the need for further investigation on the subject.

  6. Energy Drink Consumption: Beneficial and Adverse Health Effects

    OpenAIRE

    Alsunni, Ahmed Abdulrahman

    2015-01-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carri...

  7. Effect of early childhood adversity on child health.

    Science.gov (United States)

    Flaherty, Emalee G; Thompson, Richard; Litrownik, Alan J; Theodore, Adrea; English, Diana J; Black, Maureen M; Wike, Traci; Whimper, Lakecia; Runyan, Desmond K; Dubowitz, Howard

    2006-12-01

    To examine the effect of child abuse and other household dysfunction on child health outcomes. Data from the Longitudinal Studies of Child Abuse and Neglect collected through interviews and questionnaires administered when target children were 4 years old and 6 years old. Children in the South, East, Midwest, Northwest, and Southwest United States. One thousand forty-one children at high risk for child abuse and neglect (3 cohorts derived primarily from among children recruited through social service mechanisms, 1 cohort recruited at birth from among high-risk infants, and 1 cohort recruited from a medical setting). (1) Association of 7 adverse exposures (3 categories of child abuse [physical abuse, sexual abuse, and psychological maltreatment] and 4 categories of household dysfunction [caregiver problem drinking, caregiver depression, caregiver treated violently, and criminal behavior in the household]) derived from data collected when the child was 4 years old. (2) Indexes of child physical health at age 6 years (caregiver overall assessment of child health and reports of illness requiring medical attention). Two thirds of the sample had experienced at least 1 adverse exposure. One adverse exposure almost doubled the risk of overall poor health (odds ratio, 1.89; 95% confidence interval, 1.02-3.48), and 4 adverse exposures or more almost tripled the risk of illness requiring medical attention (odds ratio, 2.83; 95% confidence interval, 1.10-7.31). Adverse environmental exposures, including child abuse and other household dysfunction, are associated with poor child health even at an early age, although our data do not support a dose-response relationship.

  8. Pharmacology, Toxicology, and Adverse Effects of Synthetic Cannabinoid Drugs.

    Science.gov (United States)

    Gurney, S M R; Scott, K S; Kacinko, S L; Presley, B C; Logan, B K

    2014-01-01

    Synthetic cannabinoid drugs have become an established part of the recreational drug landscape in the United States and internationally. These drugs are manufactured in clandestine laboratories internationally and distributed in the United States in smoking mixtures, use of which produces effects very similar to use of marijuana. The adverse-effect profile of the drugs has not been studied in humans and infrequently in animal models, so much of the information about their toxicity comes from emergency department and treatment reports and forensic case studies. This review considers the discovery and characterization of the endocannabinoid system, approaches to receptor-binding studies of various synthetic cannabinoids from the first wave of naphthoylindoles (e.g., JWH-018) to the emerging adamantoylindole drugs (e.g., AKB-48), and their analogs, to evaluate the potential activity of drugs in this class. Currently employed approaches to assessing functional activity of the drugs using in vitro and in vivo models is also described, and comparisons made to the effects of THC. The physiological effects of activation of the endocannabinoid system in humans are reviewed, and the physiological effects of cannabinoid use are described. Case reports of adverse events including emergency department admissions, mental health admissions, and clinical and forensic case reports are presented in detail and discussed to summarize the current state of knowledge of adverse effects, both clinical and forensic in humans, including effects on driving ability, and tissue injury and death. The greatest weight is accorded to those reports that include toxicological confirmation of use. Finally, we discuss the current status of attempts to schedule and control the distribution of synthetic cannabinoids and the relevance of receptor binding and functional activity in this context. There is growing toxicological and pharmacological evidence of impairment, psychosis, tissue injury, and

  9. Ketamine for Pain Management-Side Effects & Potential Adverse Events.

    Science.gov (United States)

    Allen, Cheryl A; Ivester, Julius R

    2017-12-01

    An old anesthetic agent, ketamine is finding new use in lower doses for analgesic purposes. There are concerns stemming from its potential side effects-specifically psychomimetic effects. These side effects are directly related to dose amount. The doses used for analgesic purposes are much lower than those used for anesthesia purposes. A literature review was performed to ascertain potential side effects and/or adverse events when using ketamine for analgesia purposes. The search included CINAHL, PubMed, and Ovid using the search terms "ketamine," "ketamine infusion," "pain," "adverse events," "practice guideline," and "randomized controlled trial." Searches were limited to full-text, peer-reviewed articles and systematic reviews. Initially 1,068 articles were retrieved. The search was then narrowed by using the Boolean connector AND with various search term combinations. After adjusting for duplication, article titles and abstracts were reviewed, leaving 25 articles for an in-depth analysis. Specific exclusion criteria were then applied. The literature supports the use of ketamine for analgesic purposes, and ketamine offers a nonopioid option for the management of some pain conditions. Because ketamine is still classified as an anesthetic agent, health care institutions should develop their own set of policies and protocols for the administration of ketamine. By using forethought and understanding of the properties of ketamine, appropriate care may be planned to mitigate potential side effects and adverse events so that patients are appropriately cared for and their pain effectively managed. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  10. Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line.

    Science.gov (United States)

    Lizio, Marina; Ishizu, Yuri; Itoh, Masayoshi; Lassmann, Timo; Hasegawa, Akira; Kubosaki, Atsutaka; Severin, Jessica; Kawaji, Hideya; Nakamura, Yukio; Suzuki, Harukazu; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R

    2015-01-01

    Mammals are composed of hundreds of different cell types with specialized functions. Each of these cellular phenotypes are controlled by different combinations of transcription factors. Using a human non islet cell insulinoma cell line (TC-YIK) which expresses insulin and the majority of known pancreatic beta cell specific genes as an example, we describe a general approach to identify key cell-type-specific transcription factors (TFs) and their direct and indirect targets. By ranking all human TFs by their level of enriched expression in TC-YIK relative to a broad collection of samples (FANTOM5), we confirmed known key regulators of pancreatic function and development. Systematic siRNA mediated perturbation of these TFs followed by qRT-PCR revealed their interconnections with NEUROD1 at the top of the regulation hierarchy and its depletion drastically reducing insulin levels. For 15 of the TF knock-downs (KD), we then used Cap Analysis of Gene Expression (CAGE) to identify thousands of their targets genome-wide (KD-CAGE). The data confirm NEUROD1 as a key positive regulator in the transcriptional regulatory network (TRN), and ISL1, and PROX1 as antagonists. As a complimentary approach we used ChIP-seq on four of these factors to identify NEUROD1, LMX1A, PAX6, and RFX6 binding sites in the human genome. Examining the overlap between genes perturbed in the KD-CAGE experiments and genes with a ChIP-seq peak within 50 kb of their promoter, we identified direct transcriptional targets of these TFs. Integration of KD-CAGE and ChIP-seq data shows that both NEUROD1 and LMX1A work as the main transcriptional activators. In the core TRN (i.e., TF-TF only), NEUROD1 directly transcriptionally activates the pancreatic TFs HSF4, INSM1, MLXIPL, MYT1, NKX6-3, ONECUT2, PAX4, PROX1, RFX6, ST18, DACH1, and SHOX2, while LMX1A directly transcriptionally activates DACH1, SHOX2, PAX6, and PDX1. Analysis of these complementary datasets suggests the need for caution in interpreting Ch

  11. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B

    2011-01-01

    Glucocorticoids are commonly used in treatment of paediatric diseases, but evidence of associated adverse cerebral effects is accumulating. The various pharmacokinetic profiles of the exogenous glucocorticoids and the changes in pharmacodynamics during childhood, result in different exposure...... of nervous tissue to exogenous glucocorticoids. Glucocorticoids activate two types of intracellular receptors, the mineralocorticoid receptor and the glucocorticoid receptor. The two receptors differ in cerebral distribution, affinity and effects. Exogenous glucocorticoids favor activation...... of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids...

  12. The effects of early life adversity on the immune system.

    Science.gov (United States)

    Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

    2017-08-01

    Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Review article. Adverse hematological effects of hexavalent chromium: an overview

    Directory of Open Access Journals (Sweden)

    Ray Rina Rani

    2016-06-01

    Full Text Available Workers of tanneries, welding industries, factories manufacturing chromate containing paints are exposed to hexavalent chromium that increas¬es the risk of developing serious adverse health effects. This review elucidates the mode of action of hexavalent chromium on blood and its adverse effects. Both leukocyte and erythrocyte counts of blood sharply decreased in Swiss mice after two weeks of intraperitoneal treatment with Cr (VI, with the erythrocytes transforming into echinocytes. The hexavalent chromium in the blood is readily reduced to trivalent form and the reductive capacity of erythrocytes is much greater than that of plasma. Excess Cr (VI, not reduced in plasma, may enter erythrocytes and lymphocytes and in rodents it induces microcytic anemia. The toxic effects of chromium (VI include mitochondrial injury and DNA damage of blood cells that leads to carcinogenicity. Excess Cr (VI increases cytosolic Ca2+ activity and ATP depletion thereby inducing eryptosis. Se, vitamin C, and quercetin are assumed to have some protective effect against hexavalent chromium induced hematological disorders.

  14. Adverse health effects of anabolic-androgenic steroids.

    Science.gov (United States)

    van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred

    2010-06-01

    Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm. (c) 2010 Elsevier Inc. All rights reserved.

  15. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    Directory of Open Access Journals (Sweden)

    Kitzmiller JP

    2016-10-01

    Full Text Available Joseph P Kitzmiller,1 Eduard B Mikulik,1 Anees M Dauki,2 Chandrama Murkherjee,1 Jasmine A Luzum3 1Department of Biological Chemistry and Pharmacology, College of Medicine, 2College of Pharmacy, The Ohio State University, Columbus, OH, 3Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA Abstract: Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes, statin efficacy (eg, drug targets and pathways, and end-organ toxicity (eg, myopathy pathways highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. Keywords: cholesterol, myopathy, lipids, muscle toxicity, pharmacokinetics, pharmacogenetics

  16. Adverse Effects of Smoking on Outcomes of Orthopaedic Surgery

    Directory of Open Access Journals (Sweden)

    Sheung-tung Ho

    2017-12-01

    Full Text Available Smoking has many adverse effects on the musculoskeletal system, particularly on the outcomes after orthopaedic surgery. Smoking is associated with surgical site infection and postoperative wound complications after spine surgery, total joint arthroplasty, and fracture fixation; nonunion after spinal fusion, ankle fusion, osteotomy, and internal fixation and bone grafting for scaphoid nonunion; worse outcomes after lumbar disc prolapse, spinal stenosis, and cervical myelopathy surgery; periprosthetic joint infection and lower survival after total hip, knee, and shoulder arthroplasty; worse outcome after shoulder rotator cuff repair and anterior cruciate ligament reconstruction; and wound complications after microsurgery. Orthopaedic surgeons should inform smokers and motivate them to quit smoking before orthopaedic operations.

  17. Adverse cardiovascular effects of anabolic steroids: pathophysiology imaging.

    Science.gov (United States)

    Golestani, Reza; Slart, Riemer H J A; Dullaart, Robin P F; Glaudemans, Andor W J M; Zeebregts, Clark J; Boersma, Hendrikus H; Tio, René A; Dierckx, Rudi A J O

    2012-07-01

      Anabolic-androgenic steroids (AAS) are widely abused for enhancing muscle mass, strength, growth and improving athletic performance.   In recent years, many observational and interventional studies have shown important adverse cardiovascular effects of AAS abuse.   This review discusses established and future perspectives of novel molecular imaging techniques that may serve as potential tools for early detection of AAS-associated cardiovascular disorders. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

  18. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products

    Directory of Open Access Journals (Sweden)

    F. Saverio Bersani

    2015-01-01

    Full Text Available Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications.

  19. The adverse effects of hypothyroidism and hyperthyroidism during pregnancy

    Directory of Open Access Journals (Sweden)

    Mahnaz Boroumand Rezazadeh

    2015-06-01

    Full Text Available Due to the important role of thyroid disorders on reproductive health of the women of childbearing age, pregnancy outcome, fetal health, and neurodevelopment of the infant, providing comprehensive assessment of the treatments used for preventing hyperthyroidism and hypothyroidism seems to be essential. Therefore, evaluating the efficacy of different treatments of the thyroid disorders would be beneficial in better managing and controlling the disease during pregnancy. Hypothyroidism (a deficiency of thyroid hormone is a common thyroid disorder, which might increase the incidence rate of miscarriage, pre-eclampsia, placental abruption, and preterm delivery. Hyperthyroidism, which is not a common disorder during the pregnancy not only leads to similar adverse effects as hypothyroidism but also can result in stillbirth and intrauterine growth restriction. Levothyroxine is the preferred treatment of hypothyroidism and the only drug therapy recommended for treating hyperthyroidism during pregnancy. In this study, we aimed to briefly review the adverse effects of hyperthyroidism and hypothyroidism during pregnancy and review the effects of recent suggested treatments for controlling thyroid disorders on pregnancy outcomes.

  20. Adverse effects of outdoor pollution in the elderly.

    Science.gov (United States)

    Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

    2015-01-01

    With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

  1. Symptomatic sinus bradycardia: A rare adverse effect of intravenous ondansetron

    Directory of Open Access Journals (Sweden)

    Md Shahnawaz Moazzam

    2011-01-01

    Full Text Available Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind.

  2. Gum pigmentation: an unusual adverse effect of sublingual immunotherapy.

    Science.gov (United States)

    Goh, Anne; Chiang, Wen Chin; Kang, Liew Woei; Rao, Rajeshwar; Lim, Hwee Hoon; Chng, Chai Kiat

    2014-07-01

    Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is pigmentation of the gums which can occur anytime during the course of the immunotherapy. It resolves on stopping the immunotherapy and is likely due to a local inflammatory process occurring in the gums of these children. There is no associated pain or itching with the pigmentation. It can persist as long as the child is on the immunotherapy.

  3. Pharmacovigilance, risks and adverse effects of self-medication.

    Science.gov (United States)

    Montastruc, Jean-Louis; Bondon-Guitton, Emmanuelle; Abadie, Delphine; Lacroix, Isabelle; Berreni, Aurélia; Pugnet, Grégory; Durrieu, Geneviève; Sailler, Laurent; Giroud, Jean-Paul; Damase-Michel, Christine; Montastruc, François

    2016-04-01

    Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  4. Mechanisms and assessment of statin-related muscular adverse effects

    Science.gov (United States)

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  5. Adverse testicular effects of Botox® in mature rats

    Energy Technology Data Exchange (ETDEWEB)

    Breikaa, Randa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Mosli, Hisham A. [Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Nagy, Ayman A. [Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Forensic Medicine and Toxicology, Faculty of Medicine, Tanta University, Tanta (Egypt); Abdel-Naim, Ashraf B., E-mail: abnaim.pharma@gmail.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah (Saudi Arabia)

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause. - Highlights: • Botox® injections are the trend nowadays, for both medical and non-medical uses. • They were recently suggested for cryptorchidism and

  6. Neurological Adverse Effects after Radiation Therapy for Stage II Seminoma

    DEFF Research Database (Denmark)

    Ebbeskov Lauritsen, Liv; Meidahl Petersen, Peter; Daugaard, Gedske

    2012-01-01

    against the tumour bed) with a conventional fractionation of 2 Gy/day, 5 days per week. RT was applied as hockey-stick portals, also called L-fields. In 2 cases, the symptoms fully resolved. Therapeutic irradiation can cause significant injury to the peripheral nerves of the lumbosacral plexus and....../or to the spinal cord. RT is believed to produce plexus injury by both direct toxic effects and secondary microinfarction of the nerves, but the exact pathophysiology of RT-induced injury is unclear. Since reported studies of radiation-induced neurological adverse effects are limited, it is difficult to estimate...... their frequency and outcome. The treatment of neurological symptoms due to RT is symptomatic....

  7. Aloe vera: A review of toxicity and adverse clinical effects.

    Science.gov (United States)

    Guo, Xiaoqing; Mei, Nan

    2016-04-02

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex.

  8. Does cannabidiol protect against adverse psychological effects of THC?

    Directory of Open Access Journals (Sweden)

    Raymond J.M. eNiesink

    2013-10-01

    Full Text Available The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD. A literature search was performed in the bibliographic databases PubMed, PsycINFO and Web of Science using the keyword ‘cannabidiol.’ After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users.

  9. Adverse health effects associated with Islamic fasting -A literature review

    Directory of Open Access Journals (Sweden)

    Nania Mohamed Pakkir Maideen

    2017-09-01

    Full Text Available Introduction: Millions of Muslims across the world observe Islamic fasting during the holy month of Ramadan, as well as the other specific dates in the lunar calendar year. While fasting during this month, Muslims refrain from eating or drinking from dawn to dusk. Islamic fasting is similar to alternate day fasting (ADF since it incorporates an average of 12 hours of fasting and 12 hours of feasting periods. This present review study is aimed to find out the common adverse health effects associated with Islamic fasting and the preventive measures to be followed to avoid them. Methods: The literature was reviewed through searching in databases such as PubMed, Google Scholar, and reference lists to identify the related articles. Results: Many health benefits have been attributed to Islamic fasting, including the reduced risk of cardiovascular diseases, diabetes, cancer, hypertension, and asthma. On the other hand, some studies have mentioned a few health problems associated with Islamic fasting, such as headaches, heartburn, constipation, dehydration, decreased sleep quality, and anemia, which may occur in some fasting individuals during Ramadan. Conclusion: Islamic fasting could be beneficial for health if it is performed correctly. During Ramadan, fasting individuals are advised to adhere to a balanced diet that contains sufficient portions of fruits and vegetables, whole grains, pulses, meat, fish, milk, and dairy products. Moreover, fasting individuals must drink adequate fluids, such as water, fresh fruit juices, and soups, in order to prevent the possible adverse health effects associated with Islamic fasting.

  10. The Adverse Effects of Air Pollution on the Nervous System

    Science.gov (United States)

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  11. Adverse effects of aromatherapy: a systematic review of case reports and case series.

    Science.gov (United States)

    Posadzki, Paul; Alotaibi, Amani; Ernst, Edzard

    2012-01-01

    This systematic review was aimed at critically evaluating the evidence regarding the adverse effects associated with aromatherapy. Five electronic databases were searched to identify all relevant case reports and case series. Forty two primary reports met our inclusion criteria. In total, 71 patients experienced adverse effects of aromatherapy. Adverse effects ranged from mild to severe and included one fatality. The most common adverse effect was dermatitis. Lavender, peppermint, tea tree oil and ylang-ylang were the most common essential oils responsible for adverse effects. Aromatherapy has the potential to cause adverse effects some of which are serious. Their frequency remains unknown. Lack of sufficiently convincing evidence regarding the effectiveness of aromatherapy combined with its potential to cause adverse effects questions the usefulness of this modality in any condition.

  12. Melatonin ameliorates the adverse effects of leptin on sperm

    Directory of Open Access Journals (Sweden)

    Fayez A Almabhouh

    2017-01-01

    Full Text Available This study examined the effects of melatonin on leptin-induced changes in sperm parameters in adult rats. Five groups of Sprague-Dawley rats were treated with either leptin or leptin and melatonin or melatonin for 6 weeks. Leptin was given daily via the intraperitoneal route (60 μg kg−1 body weight and melatonin was given in drinking water (10 mg kg−1 or 20 mg kg−1 body weight per day. Upon completion, sperm count, sperm morphology, 8-hydroxy-2-deoxyguanosine, Comet assay, TUNEL assay, gene expression profiles of antioxidant enzymes, respiratory chain reaction enzymes, DNA damage, and apoptosis genes were estimated. Data were analyzed using ANOVA. Sperm count was significantly lower whereas the fraction of sperm with abnormal morphology, the level of 8-hydroxy-2-deoxyguanosine, and sperm DNA fragmentation were significantly higher in rats treated with leptin only. Microarray analysis revealed significant upregulation of apoptosis-inducing factor, histone acetyl transferase, respiratory chain reaction enzyme, cell necrosis and DNA repair genes, and downregulation of antioxidant enzyme genes in leptin-treated rats. Real-time polymerase chain reaction showed significant decreases in glutathione peroxidase 1 expression with increases in the expression of apoptosis-inducing factor and histone acetyl transferase in leptin-treated rats. There was no change in the gene expression of caspase-3 (CASP-3. In conclusion, the adverse effects of leptin on sperm can be prevented by concurrent melatonin administration.

  13. Saxagliptin overview: special focus on safety and adverse effects.

    Science.gov (United States)

    Ali, Shamsa; Fonseca, Vivian

    2013-01-01

    Saxagliptin (see drug summary box) is a glucose-lowering agent that belongs to the class of Dipeptidylpeptidase-4 (DDP-4) inhibitors used in the treatment of T2DM. Clinical efficacy of saxagliptin as single agent as well as in combination with other medications used for the treatment of T2DM has been well established in several randomized trials. Treatment with saxagliptin is effective, generally safe and well tolerated, apart from a small increase in the incidence of infections such as nasopharyngitis. Its use is not associated with increase risk of hypoglycemia and it is weight neutral. Saxagliptin can be used safely in renal failure (with dose adjustment) and in hepatic impairment. When saxagliptin is used in combination with a strong inhibitor of CYP3A4/A5, reduction in the daily dosage is recommended. This paper briefly discusses efficacy and pharmacokinetics of saxagliptin. The paper highlights in detail saxagliptin-associated adverse effects, drug interactions, its use in patients with renal and hepatic disease and long-term safety concerns. Saxagliptin has comparable efficacy with other DPP-4 inhibitors. It is generally safe and well tolerated; however, it requires dose adjustment in renal disease as well as when used with drugs that are strong inhibitor or inducer of CYP3A4/A5 isoforms. Future safety questions regarding immune system and development of cancer still remain to be completely answered.

  14. Neurological AdverseEffects after Radiation Therapyfor Stage II Seminoma

    Directory of Open Access Journals (Sweden)

    Liv Ebbeskov Lauritsen

    2012-08-01

    Full Text Available We report 3 cases of patients with testicular cancer and stage II seminoma who developed neurological symptoms with bilateral leg weakness about 4 to 9 months after radiation therapy (RT. They all received RT to the para-aortic lymph nodes with a total dose of 40 Gy (36 Gy + 4 Gy as a boost against the tumour bed with a conventional fractionation of2 Gy/day, 5 days per week. RT was applied as hockey-stick portals, also called L-fields. In 2 cases, the symptoms fully resolved. Therapeutic irradiation can cause significant injury to the peripheral nerves of the lumbosacral plexus and/or to the spinal cord. RT is believed to produce plexus injury by both direct toxic effects and secondary microinfarction of the nerves, but the exact pathophysiology of RT-induced injury is unclear. Since reported studies of radiation-induced neurological adverse effects are limited, it is difficult to estimate their frequency and outcome. The treatment of neurological symptoms due to RT is symptomatic.

  15. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects.

    Science.gov (United States)

    Judd, Lewis L; Schettler, Pamela J; Brown, E Sherwood; Wolkowitz, Owen M; Sternberg, Esther M; Bender, Bruce G; Bulloch, Karen; Cidlowski, John A; de Kloet, E Ronald; Fardet, Laurence; Joëls, Marian; Leung, Donald Y M; McEwen, Bruce S; Roozendaal, Benno; Van Rossum, Elisabeth F C; Ahn, Junyoung; Brown, David W; Plitt, Aaron; Singh, Gagandeep

    2014-10-01

    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as ways to prevent and treat these disturbances. An illustrative case vignette is presented describing a patient's experience of cycles of manic-like behavior and depression while on high-dosage prednisone, with long-term cognitive disorganization, vulnerability to stress, and personality changes. Severe neuropsychiatric consequences (including suicide, suicide attempt, psychosis, mania, depression, panic disorder, and delirium, confusion, or disorientation) have been reported to occur in 15.7 per 100 person-years at risk for all glucocorticoid courses, and 22.2 per 100 person-years at risk for first courses. The majority of patients experience less severe but distressing and possibly persistent changes in mood, cognition, memory, or behavior during glucocorticoid treatment or withdrawal. Although prediction of such effects is difficult, risks vary with age, gender, dosage, prior psychiatric history, and several biological markers. Key mechanisms thought to underlie these risk factors are briefly described. Recommendations are given for identifying individual risk factors and for monitoring and managing adverse neuropsychiatric effects of glucocorticoids.

  16. Minimizing AED adverse effects: improving quality of life in the interictal state in epilepsy care.

    Science.gov (United States)

    St Louis, Erik K; Louis, Erik K

    2009-06-01

    The goals of epilepsy therapy are to achieve seizure freedom while minimizing adverse effects of treatment. However, producing seizure-freedom is often overemphasized, at the expense of inducing adverse effects of treatment. All antiepileptic drugs (AEDs) have the potential to cause dose-related, "neurotoxic" adverse effects (i.e., drowsiness, fatigue, dizziness, blurry vision, and incoordination). Such adverse effects are common, especially when initiating AED therapy and with polytherapy. Dose-related adverse effects may be obviated in most patients by dose reduction of monotherapy, reduction or elimination of polytherapy, or substituting for a better tolerated AED. Additionally, all older and several newer AEDs have idiosyncratic adverse effects which usually require withdrawal in an affected patient, including serious rash (i.e., Stevens-Johnson Syndrome, toxic epidermal necrolysis), hematologic dyscrasias, hepatotoxicity, teratogenesis in women of child bearing potential, bone density loss, neuropathy, and severe gingival hyperplasia. Unfortunately, occurrence of idiosyncratic AED adverse effects cannot be predicted or, in most cases, prevented in susceptible patients. This article reviews a practical approach for the definition and identification of adverse effects of epilepsy therapies, and reviews the literature demonstrating that adverse effects result in detrimental quality of life in epilepsy patients. Strategies for minimizing AED adverse effects by reduction or elimination of AED polytherapy, appropriately employing drug-sparing therapies, and optimally administering AEDs are outlined, including tenets of AED selection, titration, therapeutic AED laboratory monitoring, and avoidance of chronic idiosyncratic adverse effects.

  17. Shocking Results on the Adverse Effects of CO2 Exposures

    Science.gov (United States)

    James, John T.

    2012-01-01

    Carbon dioxide (CO2) is released in large quantities from humans while they live and work in spacecraft or work outside the spacecraft during extravehicular activity (EVA). Removal of this anthropogenic pollutant requires major resources, and these resources increase dramatically as the levels of CO2 set to protect human health and performance are reduced. The current Spacecraft Maximum Allowable Concentration of CO2 aboard the ISS is 0.7% or 5.3 mmHg; however, according to Chits (mission action requests), NASA and its international partners have agreed to control CO2 levels to less than 4 mmHg. In the meantime, retrospective investigations attempting to associate crew symptoms with elevated CO2 levels over the life if the International Space Station (ISS) are underway to determine if this level is sufficient to protect against health and performance decrements. Anecdotal reports suggest that crewmembers are not able to perform complex tasks as readily in spaceflight as they were able during ground-based training. While physiological effects of CO2 have been studied for many decades, it is only recently that the effects of CO2 on higher reasoning capabilities have been studied. The initial results are shocking. For example, one study published in the respected journal Environmental Health Perspectives showed obvious adverse effects of CO2 exposures on higher reasoning at 1.9 mmHg. The implications and limitations of this study are paramount in determining future CO2 SMACs for human spaceflight, both aboard the ISS and in exploration-class missions. Key Words: carbon dioxide, spacecraft, air quality, toxic effects

  18. Adverse testicular effects of Botox® in mature rats.

    Science.gov (United States)

    Breikaa, Randa M; Mosli, Hisham A; Nagy, Ayman A; Abdel-Naim, Ashraf B

    2014-03-01

    Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Fidget spinners: Purported benefits, adverse effects and accepted alternatives.

    Science.gov (United States)

    Schecter, Rachel A; Shah, Jay; Fruitman, Kate; Milanaik, Ruth Lynn

    2017-10-01

    In the span of a few months, fidget spinners have caught the eyes of millions of children, parents, educators and paediatricians. Fidget spinners, hand-held toys designed to spin freely in your grasp, have become a source of entertainment for consumers of all ages. Despite a lack of scientific evidence, toy marketers have advertised the benefits of fidget spinners for children with attention-deficit/hyperactivity disorder and other disorders (e.g. autism, anxiety, sensory issues). Parents are incentivized by these purported benefits to purchase fidget spinners to improve their child's concentration and decrease stress. While fidget spinners are a new phenomenon, existing therapy toys (e.g. sensory putty) have been used by occupational therapists for similar reasons, with comparably little research supporting these claims. The purpose of this review is to explore literature regarding sensory toys and examine educator/professional-reported concerns and medical adverse effects of using fidget spinners. Due to a recent surge in popularity, fidget spinners and other self-regulatory occupational therapy toys have yet to be subjected to rigorous scientific research. Thus, their alleged benefits remain scientifically unfounded. Paediatricians should be aware of potential choking hazards with this new fad, and inform parents that peer-reviewed studies do not support the beneficial claims.

  20. Steam inhalation therapy: severe scalds as an adverse side effect

    Science.gov (United States)

    Baartmans, Martin; Kerkhof, Evelien; Vloemans, Jos; Dokter, Jan; Nijman, Susanne; Tibboel, Dick; Nieuwenhuis, Marianne

    2012-01-01

    Background Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. Aim To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. Design and setting A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. Method Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. Results Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were €115 500 (£93 000), emotional costs are not reflected. Conclusion As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID:22781995

  1. Hidden Suffering and the Effects of Adverse Childhood Experiences

    Directory of Open Access Journals (Sweden)

    William Fulford

    2017-02-01

    Full Text Available To understand suffering is to understand what it means to be human. Suffering focuses our attention on our vulnerability, which we would rather ignore or deny. As health care professionals (HCP we need to be able to listen, to attune and be empathic to the suffering patient. If we act as an “enlightened witness” we provide a safe place for a suffering patient to grieve their loss and be vulnerable. This is skilled and demanding work, it is also important to tend to our own needs through a practice of self-care and reflection to prevent burn-out and compassion fatigue. The topic of adverse childhood experiences (ACE, which are common in the general population, are addressed in the second part of this paper. Their effects are profound, and increase with the degree of maltreatment. The maltreatment and suffering of these children usually remains hidden into adulthood beneath years of shame and denial. One aspect of our job in health care is to help patients acknowledge, experience, and bear the reality of life with all its pleasures and heartache. In order to do this well, we need to keep in touch with our own humanity, but also continue to take care of ourselves.

  2. Evaluation of adverse effects in tamoxifen exposed healthy female dogs

    Directory of Open Access Journals (Sweden)

    Cavalcanti Guilherme AO

    2010-12-01

    Full Text Available Abstract Background Mammary tumors are among the most frequent neoplasms in female dogs, but the strategies employed in animal treatment are limited. In human medicine, hormone manipulation is used in cancer therapy. Tamoxifen citrate is a selective inhibitor of oestrogen receptors and exerts a potent anti-oestrogen effect on the mammary gland. The aim of this study was to evaluate the adverse effects when exposing healthy female dogs to tamoxifen. Methods Tamoxifen was administered for 120 days at a dose of 0.5 or 0.8 mg/kg/day to either intact or spayed female dogs. The effects were assessed through clinical examination, haematology, serum biochemistry, ophthalmology and bone marrow aspirate examination. Ovariohysterectomy was performed and the uterus examined by histopathology. Results Vulva oedema and purulent vaginal discharge developed with 10 days of tamoxifen exposure in all groups. Pyometra was diagnosed after around 90 days of exposure in intact females with frequencies increasing during the following 30 days of exposure. Up to 50% of dogs within the groups developed retinitis but none of the dogs had signs of reduced visual acuity. The prevalence of retinitis in each group was similar after 120 days of exposure. Haematological, biochemical and bone marrow changes were not observed. Due to the high risk of developing pyometra after prolonged exposure to tamoxifen, only spayed animals should be given this medication. Conclusions A dose of 0.8 mg tamoxifen/kg body weight/day is recommended when treating tamoxifen-responsive canine mammary tumors. Due to the high risk of developing pyometra, ovariohysterectomy is recommended.

  3. PERTINENT DRY NEEDLING CONSIDERATIONS FOR MINIMIZING ADVERSE EFFECTS - PART ONE.

    Science.gov (United States)

    Halle, John S; Halle, Rob J

    2016-08-01

    Dry needling is an evidence-based treatment technique that is accepted and used by physical therapists in the United States. This treatment approach focuses on releasing or inactivating muscular trigger points to decrease pain, reduce muscle tension, and assist patients with an accelerated return to active rehabilitation. While commonly used, the technique has some patient risk and value of the treatment should be based on benefit compared to the potential risk. Adverse effects (AEs) with dry needling can be mild or severe, with overall incidence rates varying from zero to rates of approximately 10 percent. While mild AEs are the rule, any procedure that involves a needle insertion has the potential for an AE, with select regions and the underlying anatomy increasing the risk. Known significant AEs from small diameter needle insertion include pneumothorax, cardiac tamponade, hematoma, infection, central nervous system injury, and other complications. Underlying anatomy across individuals has variability, requiring an in-depth knowledge of anatomy prior to any needle placement. This commentary is an overview of pertinent anatomy in the region of the thorax, with a 'part two' that addresses the abdomen, pelvis, back, vasovagal response, informed consent and other pertinent issues. The purpose of the commentary is to minimize the risk of a dry needling AE. Dry needling is an effective adjunct treatment procedure that is within the recognized scope of physical therapy practice. Physical therapy education and training provides practitioners with the anatomy, basic sciences, and clinical foundation to use this intervention safely and effectively. A safe and evidenced-based implementation of the procedure is based on a thorough understanding of the underlying anatomy and the potential risks, with risks coordinated with patients via informed consent. Level 5.

  4. Eliciting adverse effects data from participants in clinical trials.

    Science.gov (United States)

    Allen, Elizabeth N; Chandler, Clare Ir; Mandimika, Nyaradzo; Leisegang, Cordelia; Barnes, Karen

    2018-01-16

    Analysis of drug safety in clinical trials involves assessing adverse events (AEs) individually or by aggregate statistical synthesis to provide evidence of likely adverse drug reactions (ADR). While some AEs may be ascertained from physical examinations or tests, there is great reliance on reports from participants to detect subjective symptoms, where he/she is often the only source of information. There is no consensus on how these reports should be elicited, although it is known that questioning methods influence the extent and nature of data detected. This leaves room for measurement error and undermines comparisons between studies and pooled analyses. This review investigated comparisons of methods used in trials to elicit participant-reported AEs. This should contribute to knowledge about the methodological challenges and possible solutions for achieving better, or more consistent, AE ascertainment in trials. To systematically review the research that has compared methods used within clinical drug trials (or methods that would be specific for such trials) to elicit information about AEs defined in the protocol or in the planning for the trial. Databases (searched to March 2015 unless indicated otherwise) included: Embase; MEDLINE; MEDLINE in Process and Other Non-Indexed Citations; Cochrane Methodology Register (July 2012); Cochrane Central Register of Controlled Trials (February 2015); Cochrane Database of Systematic Reviews; Database of Abstracts of Reviews of Effects (January 2015); Health Technology Assessment database (January 2015); CINAHL; CAB Abstracts; BIOSIS (July 2013); Science Citation Index; Social Science Citation Index; Conference Proceedings Citation Index - Science. The search used thesaurus headings and synonyms for the following concepts: (A): Adverse events AND measurement; (B): Participants AND elicitation (also other synonyms for extraction of information about adverse effects from people); (C): Participants AND checklists (also other

  5. A signal detection method for temporal variation of adverse effect with vaccine adverse event reporting system data.

    Science.gov (United States)

    Cai, Yi; Du, Jingcheng; Huang, Jing; Ellenberg, Susan S; Hennessy, Sean; Tao, Cui; Chen, Yong

    2017-07-05

    To identify safety signals by manual review of individual report in large surveillance databases is time consuming; such an approach is very unlikely to reveal complex relationships between medications and adverse events. Since the late 1990s, efforts have been made to develop data mining tools to systematically and automatically search for safety signals in surveillance databases. Influenza vaccines present special challenges to safety surveillance because the vaccine changes every year in response to the influenza strains predicted to be prevalent that year. Therefore, it may be expected that reporting rates of adverse events following flu vaccines (number of reports for a specific vaccine-event combination/number of reports for all vaccine-event combinations) may vary substantially across reporting years. Current surveillance methods seldom consider these variations in signal detection, and reports from different years are typically collapsed together to conduct safety analyses. However, merging reports from different years ignores the potential heterogeneity of reporting rates across years and may miss important safety signals. Reports of adverse events between years 1990 to 2013 were extracted from the Vaccine Adverse Event Reporting System (VAERS) database and formatted into a three-dimensional data array with types of vaccine, groups of adverse events and reporting time as the three dimensions. We propose a random effects model to test the heterogeneity of reporting rates for a given vaccine-event combination across reporting years. The proposed method provides a rigorous statistical procedure to detect differences of reporting rates among years. We also introduce a new visualization tool to summarize the result of the proposed method when applied to multiple vaccine-adverse event combinations. We applied the proposed method to detect safety signals of FLU3, an influenza vaccine containing three flu strains, in the VAERS database. We showed that it had high

  6. Ziconotide: new drug. Limited analgesic efficacy, too many adverse effects.

    Science.gov (United States)

    2008-10-01

    (1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type

  7. Bacillary Prostatitis after Intravesical Immunotherapy:A Rare Adverse Effect

    Directory of Open Access Journals (Sweden)

    Ana Joaquim

    2012-02-01

    Full Text Available Nowadays, the most efficient form of intravesical immunotherapy for superficial transitional cell carcinoma of the urinary bladder is the instillation of bacillus Calmette-Guérin (BCG, proceeding from an attenuated strain of Mycobacterium bovis. In up to 40% of cases, its instillation is associated with significantly elevated prostate-specific antigen (PSA levels. In these cases, prostate biopsy should be withheld for 3 months and PSA should be monitored. Bacillary prostatitis is a rare occurrence in patients treated with intravesical BCG immunotherapy. Although symptomatic bacillary prostatitis is even rarer, it is the worst type of this condition. The aims of this study are to report a case of bacillary prostatitis as a rare adverse effect of intravesical BCG immunotherapy and to make a theoretical review about how to manage this complication. A 58-year-old man, former smoker, underwent a transurethral resection of the bladder in February 2004 because of a papillary transitional cell carcinoma of the bladder (pT1G2N0M0. After surgery, BCG instillation therapy was given in a total of 15 instillations, the last one in March 2007. In the last 3 months of therapy, until May 2007, a progressive increase in his PSA level was registered, and he underwent a prostate biopsy revealing granulomatous prostatitis of bacillary etiology. The semen culture was positive for M. bovis. After 3 months of a two-drug (isoniazid and rifampin antituberculous regimen, the semen culture became negative and the PSA level decreased. The early identification of intravesical BCG immunotherapy complications allows their effective treatment. However, when a histological diagnosis of asymptomatic granulomatous prostatitis is made, the execution and type of treatment are controversial.

  8. PERTINENT DRY NEEDLING CONSIDERATIONS FOR MINIMIZING ADVERSE EFFECTS - PART TWO.

    Science.gov (United States)

    Halle, John S; Halle, Rob J

    2016-10-01

    Dry needling (DN) is an evidence based treatment technique that is accepted and used by physical therapists in the United States. This clinical commentary is the second in a two-part series outlining some of the pertinent anatomy and other issues that are needed for optimal utilization of this treatment modality. Part one was an overview of the thorax with a summary of reported adverse effects (AEs) and the underlying anatomy that could be used to minimize patient risk. As is the case with any intervention, the technique of dry needling has some inherent patient risk. The incidence of AEs with this procedure is typically low, ranging from zero to approximately 10 percent. Knowledge of the underlying anatomy can be a key factor associated with decreasing the likelihood of an AE. The second part of this clinical commentary goes beyond the thorax, to explore the anatomy associated with dry needling the abdomen, pelvis, and back. In the abdomen, pelvis and back, dry needling can penetrate the peritoneal cavity or adjacent organs, resulting in AEs. A physiological reaction that is an AE secondary to a needle insertion, pain or fear, is an autonomic vasovagal response. Additionally, suggestions for dealing with the fearful patient, the obese patient, universal precautions, and other clinical considerations, are discussed. The purpose of parts one and part two of this clinical commentary is to minimize the risk of a dry needling AE. Dry needling is an effective adjunctive treatment procedure that is within the recognized scope of practice of the physical therapist. An evidence-based implementation of the procedure must be based on a thorough understanding of the underlying anatomy and the potential risks, with risks communicated to patients via informed consent. Level 5.

  9. Pycnogenol may alleviate adverse effects in oncologic treatment.

    Science.gov (United States)

    Belcaro, G; Cesarone, M R; Genovesi, D; Ledda, A; Vinciguerra, G; Ricci, A; Pellegrini, L; Gizzi, G; Ippolito, E; Dugall, M; Cacchio, M; Di Renzo, A; Stuard, S

    2008-09-01

    A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology. Specific medications exist to target individual side effects. The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient's quality of life. Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition, both physically and psychologically, were recruited for this study and divided into two groups. These patients received their first cycle of radiotherapy or chemotherapy, which lasted from 10 days up to 1 month. Then one group of patients received 150 mg Pycnogenol, the control group comparable placebo in a single-blinded fashion. The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy, respectively. Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo, though in many categories the difference was limited. The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes. A decreased incidence of nausea /vomiting, diarrhoea, edema and weakness was noticed, which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group. Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group (2.9% vs 10%). Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30

  10. Sources of patients' knowledge of the adverse effects of psychotropic medication and the perceived influence of adverse effects on compliance among service users attending community mental health services.

    LENUS (Irish Health Repository)

    Agyapong, Vincent I O

    2009-12-01

    Noncompliance with medication has been a complex issue with patients with severe mental illness during the last few decades, and adverse effects of medication have been identified as a major contributor to noncompliance.

  11. Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects

    DEFF Research Database (Denmark)

    Köhler, Ole; Benros, Michael E; Nordentoft, Merete

    2014-01-01

    IMPORTANCE: Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents. OBJECTIVE: To systematically review the antidepressant and possible......) and odds ratios (ORs) were calculated. MAIN OUTCOMES AND MEASURES: Depression scores after treatment and adverse effects. RESULTS: Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4...... properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased...

  12. Antiestrogenic activity of flavnoid phytochemicals mediated via c-Jun N-terminal protein kinase pathway. Cell-type specific regulation of estrogen receptor alpha

    Science.gov (United States)

    Flavonoid phytochemicals act as both agonists and antagonists of the human estrogen receptors (ERs). While a number of these compounds act by directly binding to the ER, certain phytochemicals, such as the flavonoid compounds chalcone and flavone, elicit antagonistic effects on estrogen signaling in...

  13. SB202190-induced cell type-specific vacuole formation and defective autophagy do not depend on p38 MAP kinase inhibition.

    Directory of Open Access Journals (Sweden)

    Manoj B Menon

    Full Text Available SB202190, a widely used inhibitor of p38 MAPKα and β, was recently described to induce autophagic vacuoles and cell death in colon and ovarian cancer cells lines and, therefore, this effect was supposed to be specific for transformed cells and to open therapeutic options. Here, we demonstrate that SB202190 and the structurally related inhibitor SB203580 induce pro-autophagic gene expression and vacuole formation in various cancer and non-cancer cell lines of human, rat, mouse and hamster origin. This effect seems to induce defective autophagy leading to the accumulation of acidic vacuoles, p62 protein and lipid conjugated LC3. Using further p38 inhibitors we show that p38 MAPK inhibition is not sufficient for the autophagic response. In line with these results, expression of a SB202190-resistant mutant of p38α, which significantly increases activity of the p38 pathway under inhibitory conditions, does not block SB202190-dependent vacuole formation, indicating that lack of p38α activity is not necessary for this effect. Obviously, the induction of autophagic vacuole formation by SB203580 and SB202190 is due to off-target effects of these inhibitors on post-translational protein modifications, such as phosphorylation of the MAPKs ERK1/2 and JNK1/2, ribosomal protein S6, and PKB/Akt. Interestingly, the PI3K-inhibitor wortmannin induces transient vacuole formation indicating that the PI3K-PKB/Akt-mTOR pathway is essential for preventing autophagy and that cross-inhibition of this pathway by SB202190 could be the reason for the early part of the effect observed.

  14. Are adverse effects incorporated in economic models? An initial review of current practice.

    Science.gov (United States)

    Craig, D; McDaid, C; Fonseca, T; Stock, C; Duffy, S; Woolacott, N

    2009-12-01

    To identify methodological research on the incorporation of adverse effects in economic models and to review current practice. Major electronic databases (Cochrane Methodology Register, Health Economic Evaluations Database, NHS Economic Evaluation Database, EconLit, EMBASE, Health Management Information Consortium, IDEAS, MEDLINE and Science Citation Index) were searched from inception to September 2007. Health technology assessment (HTA) reports commissioned by the National Institute for Health Research (NIHR) HTA programme and published between 2004 and 2007 were also reviewed. The reviews of methodological research on the inclusion of adverse effects in decision models and of current practice were carried out according to standard methods. Data were summarised in a narrative synthesis. Of the 719 potentially relevant references in the methodological research review, five met the inclusion criteria; however, they contained little information of direct relevance to the incorporation of adverse effects in models. Of the 194 HTA monographs published from 2004 to 2007, 80 were reviewed, covering a range of research and therapeutic areas. In total, 85% of the reports included adverse effects in the clinical effectiveness review and 54% of the decision models included adverse effects in the model; 49% included adverse effects in the clinical review and model. The link between adverse effects in the clinical review and model was generally weak; only 3/80 (models including adverse effects, 67% used a clinical adverse effects parameter, 79% used a cost of adverse effects parameter, 86% used one of these and 60% used both. Most models (83%) used utilities, but only two (2.5%) used solely utilities to incorporate adverse effects and were explicit that the utility captured relevant adverse effects; 53% of those models that included utilities derived them from patients on treatment and could therefore be interpreted as capturing adverse effects. In total, 30% of the models

  15. A multi-omics approach identifies key hubs associated with cell type-specific responses of airway epithelial cells to staphylococcal alpha-toxin.

    Directory of Open Access Journals (Sweden)

    Erik Richter

    Full Text Available Responsiveness of cells to alpha-toxin (Hla from Staphylococcus aureus appears to occur in a cell-type dependent manner. Here, we compare two human bronchial epithelial cell lines, i.e. Hla-susceptible 16HBE14o- and Hla-resistant S9 cells, by a quantitative multi-omics strategy for a better understanding of Hla-induced cellular programs. Phosphoproteomics revealed a substantial impact on phosphorylation-dependent signaling in both cell models and highlights alterations in signaling pathways associated with cell-cell and cell-matrix contacts as well as the actin cytoskeleton as key features of early rHla-induced effects. Along comparable changes in down-stream activity of major protein kinases significant differences between both models were found upon rHla-treatment including activation of the epidermal growth factor receptor EGFR and mitogen-activated protein kinases MAPK1/3 signaling in S9 and repression in 16HBE14o- cells. System-wide transcript and protein expression profiling indicate induction of an immediate early response in either model. In addition, EGFR and MAPK1/3-mediated changes in gene expression suggest cellular recovery and survival in S9 cells but cell death in 16HBE14o- cells. Strikingly, inhibition of the EGFR sensitized S9 cells to Hla indicating that the cellular capacity of activation of the EGFR is a major protective determinant against Hla-mediated cytotoxic effects.

  16. Pharmacodynamic modeling of adverse effects of anti-cancer drug treatment

    NARCIS (Netherlands)

    de Vries Schultink, A H M; Suleiman, A A; Schellens, J H M; Beijnen, J H; Huitema, A D R

    PURPOSE: Adverse effects related to anti-cancer drug treatment influence patient's quality of life, have an impact on the realized dosing regimen, and can hamper response to treatment. Quantitative models that relate drug exposure to the dynamics of adverse effects have been developed and proven to

  17. The Course of Adverse Effects of Nortriptyline and Venlafaxine in Elderly Patients with Major Depression

    NARCIS (Netherlands)

    Kok, Rob M.; Aartsen, Marja; Nolen, Willem A.; Heeren, Thea J.

    2009-01-01

    OBJECTIVES To evaluate tolerability and course of adverse effects of antidepressants in elderly patients and to study the association between number and severity of adverse effects and age, physical comorbidity, antidepressant dose. and depression severity. DESIGN Double-blind, randomized controlled

  18. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Toxic or adverse effect incident reports. 159.184 Section 159.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Information § 159.184 Toxic or adverse effect incident reports. (a) General. Information about incidents...

  19. Genome-wide progesterone receptor binding: cell type-specific and shared mechanisms in T47D breast cancer cells and primary leiomyoma cells.

    Directory of Open Access Journals (Sweden)

    Ping Yin

    Full Text Available BACKGROUND: Progesterone, via its nuclear receptor (PR, exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells. PRINCIPAL FINDINGS: ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs, whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2, a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types. CONCLUSIONS: Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in

  20. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

    Directory of Open Access Journals (Sweden)

    Yu-Yo Sun

    Full Text Available The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α through inhibition of prolyl hydrolase 2 (PHD2 and activation of the phosphatidylinositide-3 kinase (PI3K/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo and vascular endothelial growth factor (VEGF, two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.

  1. Transient Adverse Side Effects During Neurofeedback Training: A Randomized, Sham-Controlled, Double Blind Study.

    Science.gov (United States)

    Rogel, Ainat; Guez, Jonathan; Getter, Nir; Keha, Eldad; Cohen, Tzlil; Amor, Tali; Todder, Doron

    2015-09-01

    The benefits of clinical neurofeedback training are well known, however, its adverse side-effects are less studied. This research focuses on the transient adverse side effects of neurofeedback training via a double-blind, sham/controlled methodology. Thirty healthy undergraduate students volunteers were randomly divided into three treatment groups: increasing a modified Sensory Motor Rhythm, increasing Upper Alpha, and Sham/control group who receive a random reward. The training sessions were administered for a total of ten sessions. Questionnaires of transient adverse side effects were completed by all volunteers before each session. The results suggest that similar to most medical treatments, neurofeedback can cause transient adverse side effects. Moreover, most participants reported experiencing some side effects. The side effects can be divided into non-specific side effect, associated with the neurofeedback training in general and specific ones associated with the particular protocol. Sensory Motor Rhythm protocol seems to be the most sensitive to side effects.

  2. Genetic inhibition of CETP, ischemic vascular disease and mortality, and possible adverse effects

    DEFF Research Database (Denmark)

    Johannsen, Trine Holm; Frikke-Schmidt, Ruth; Schou, Jesper

    2012-01-01

    This study tested whether genetic variation in the CETP gene is consistent with a protective effect of cholesteryl ester transfer protein (CETP) inhibition on risk of ischemic events and on total mortality, without the adverse effects reported for torcetrapib....

  3. Genetic Predictors of Adverse Radiotherapy Effects: the Gene-PARE project

    DEFF Research Database (Denmark)

    Ho, Alice Y.; Atencio, David P.; Peters, Sheila

    2006-01-01

    PURPOSE: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of speci...

  4. Esophageal candidiasis--an adverse effect of inhaled corticosteroids therapy.

    Science.gov (United States)

    Aun, Marcelo Vivolo; Ribeiro, Marisa Rosimeire; Costa Garcia, Cláudia Leite; Agondi, Rosana Câmara; Kalil, Jorge; Giavina-Bianchi, Pedro

    2009-05-01

    Over the last few decades, inhaled corticosteroids (ICs) became the cornerstone in the treatment of persistent asthma. Their use improved asthma control, decreased mortality and also minimized adverse reactions associated with systemic steroid. Esophageal candidiasis is a rare complication resulting from the use of ICs. Although, in recent years, as their prescriptions has increased, more cases have been reported, especially in Japan. Listed are 4 case reports regarding esophageal candidiasis in asthmatic patients associated with inhaled budesonide administration. In the cases reported herein, the use of a different device of dry powder budesonide might have favored esophageal drug deposition and Candida infection. Patients denied using systemic corticosteroids in the previous 6 months. Furthermore, none of the patients presented Diabetes mellitus, malignant disease, HIV infection, or other immunosuppressive conditions. We conclude that patients treated with high doses of ICs are at higher risk of developing esophageal candidiasis. These patients should undergo upper gastrointestinal endoscopy whenever they present symptoms. Nevertheless, we must keep in mind that infection might also be asymptomatic and esophageal candidiasis prevalence may be higher than that reported thus far.

  5. Adverse effects of extra-articular corticosteroid injections: a systematic review

    Directory of Open Access Journals (Sweden)

    Brinks Aaltien

    2010-09-01

    Full Text Available Abstract Background To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue corticosteroid injection. Methods A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing and minor ones (transient, not requiring intervention. Results The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting. Conclusion In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported.

  6. Undiagnosed metabolic syndrome and other adverse effects among ...

    African Journals Online (AJOL)

    effects, including prolongation of the QT-interval, agranulocytosis and metabolic syndrome. However, few data exist on the prevalence of clozapine side-effects in patients of Xhosa descent. Objective. To gather data from Xhosa patients with ...

  7. Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

    Science.gov (United States)

    Hall, Wayne

    2017-04-01

    The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. The adverse effects of albendazole and praziquantel in mass drug ...

    African Journals Online (AJOL)

    nausea, headache and dizziness ... and headache. This shows that more pupils from Mwea, (albendazole and praziquantel) than from Ndia (albendazole alone) experienced minor side effects. ..... in pediatric infectious disease. 2000; 11: ...

  9. Sleep board review questions: medications and their adverse effects

    Directory of Open Access Journals (Sweden)

    Budhiraja

    2012-12-01

    Full Text Available No abstract available. Article truncated after first page. Question: Which of the following medications is not matched with a characteristic side effect? 1. Pramipexole -Pathological gambling 2. Eszopiclone - Unpleasant taste 3. Modafinil - Headache 4. Mirtazapine - Weight Loss

  10. Respiratory adverse effects of Sofosbuvir-based regimens for treatment of chronic hepatitis C virus

    Directory of Open Access Journals (Sweden)

    Dina Abouelkheir Abdalla

    2017-04-01

    Conclusion: Sofosbuvir-based regimens used for treatment of chronic HCV infection are considered safe with minor respiratory adverse effects. However, larger multicenter studies are required for further assessment.

  11. Management of chemotherapy-induced adverse effects in the treatment of colorectal cancer

    NARCIS (Netherlands)

    Jansman, FGA; Sleijfer, DT; de Graaf, JC; Coenen, JLLM; Brouwers, JRBJ

    2001-01-01

    The anticancer agents fluorouracil, raltitrexed, irinotecan and oxaliplatin show limited efficacy in the treatment of colorectal cancer and may be associated with substantial toxicity. Therefore, the prevention and reduction of chemotherapy-induced adverse effects is of major significance, in

  12. A man who wanted to commit suicide by hanging himself: an adverse effect of ciprofloxacin.

    NARCIS (Netherlands)

    Ahmed, A.I.A.; Heijden, F.M.M.A. van der; Berkmortel, H. van den; Kramers, K.

    2011-01-01

    In this case report, we describe a man who developed recurrent depression and suicidal ideation with a serious plan to commit suicide as definite adverse effect of ciprofloxacin, which had been prescribed for recurrent prostatitis.

  13. Monitoring of NSAIDs adverse effects based on spontaneous reports from Wrocław regional adverse drug reactions monitoring center.

    Science.gov (United States)

    Jaźwińska-Tarnawska, Ewa; Wiela-Hojeńska, Anna; Wolańczyk-Medrala, Anna; Patkowski, Janusz; Nittner-Marszalska, Marita; Głowacka, Krystyna

    2012-01-01

    The mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) in majority of cases is responsible for adverse reactions of these therapeutic agents. Obtaining post-registration information on adverse drug reactions (ADRs) by means of the Yellow Card System is a significant element in the process of enhancing the safety of pharmacotherapy. The aim of the study was to analyze ADRs of NSAIDs (anti-inflammatory and analgesic drugs) reported to the Regional Centre for the Monitoring of Adverse Drug Reactions (RCMADR) in Wrocław in the years 2007-2009. The study material included 232 spontaneous reports, which were sent by physicians and pharmacists to the RCMADR in Wrocław, out of which 80 concerned mentioned drugs. Analysis of the obtained data revealed a relationship between the incidence and kind of ADRs and the age, gender of the patients, centre from which the data were supplied, geographical region of administered medication. A significant role of post-registration monitoring of adverse drug reactions during therapy with antiinflammatory and analgesic drugs was confirmed in view of geographically conditioned differences affecting the profile of instituted therapy and the source of information. With an increasing global use of these medications, only thorough monitoring of every adverse reaction, encouraging spontaneous reports, as well as analysis at a global level may increase the knowledge on adverse drug reactions and enable correction of the safety profile of every drug from this group.

  14. Self-reported adverse effects as barriers to adherence to ...

    African Journals Online (AJOL)

    ... use of non-prescribed drugs, and the presence of side effects such as insomnia, headaches and abdominal pain; while eating well was a facilitator. These findings emphasise the need for better communication between patients and clinicians, and the need for integrating pharmacovigilance concepts in clinical practice.

  15. Effect of Progressive Muscle Relaxation on the Adverse ...

    African Journals Online (AJOL)

    Background: The altered stress reactivity in polycystic ovarian syndrome (PCOS) may constitute a link between depression, overweight, and cardiovascular risk factors. Aims: To study the effects of progressive muscle relaxation (PMR) on the stress levels of PCOS patients and their influence on the cardiovascular risk factors ...

  16. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B

    2011-01-01

    reduces neurogenesis and cerebral volume, impairs memory and increases the incidence of cerebral palsy. Cerebral effects of glucocorticoids in later childhood have been less thoroughly studied, but apparent brain atrophy, reduced size of limbic structures and neuropsychiatric symptoms have been reported...

  17. Indoor allergens: assessing and controlling adverse health effects

    National Research Council Canada - National Science Library

    Pope, Andrew MacPherson; Patterson, Roy; Burge, Harriet

    1993-01-01

    ... on the Health Effects of Indoor Allergens Division of Health Promotion and Disease Prevention INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. 1993 i Copyrightthe cannot be not from book, paper however, version for formatting, original authoritative the typesetting-specific the as from created publication files XML from other this and...

  18. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    Mulder, Renée L.; van Dalen, Elvira C.; van den Hof, Malon; Bresters, Dorine; Koot, Bart G. P.; Castellino, Sharon M.; Loke, Yoon; Leclercq, Edith; Post, Piet N.; Caron, Huib N.; Postma, Aleida; Kremer, Leontien C. M.

    2011-01-01

    Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer.

  19. The uses and adverse effects of beryllium on health

    DEFF Research Database (Denmark)

    Cooper, Ross G.; Harrison, Adrian Paul

    2009-01-01

    published in sources unobtainable through requests at the British Library, and some had no impact factor and were excluded. Conclusion: Beryllium has some useful but undoubtedly harmful effects on health and well-being. Measures needed to be taken to prevent hazardous exposure to this element, making its...

  20. Hepatic late adverse effects after antineoplastic treatment for childhood cancer

    NARCIS (Netherlands)

    Mulder, Renee L.; van Dalen, Elvira C.; Van den Hof, Malon; Bresters, Dorine; Koot, Bart G. P.; Castellino, Sharon M.; Loke, Yoon; Leclercq, Edith; Post, Piet N.; Caron, Huib N.; Postma, Aleida; Kremer, Leontien C. M.

    2011-01-01

    Background Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood

  1. The performance of adverse effects search filters in MEDLINE and EMBASE.

    Science.gov (United States)

    Golder, Su; Loke, Yoon K

    2012-06-01

     Search filters can potentially improve the efficiency of searches involving electronic databases such as medline and embase. Although search filters have been developed for identifying records that contain adverse effects data, little is known about the sensitivity of such filters.  This study measured the sensitivity of using available adverse effects filters to retrieve papers with adverse effects data.   A total of 233 included studies from 26 systematic reviews of adverse effects were used for analysis. Search filters from medline and embase were tested for their sensitivity in retrieving the records included in these reviews. In addition, the sensitivity of each individual search term used in at least one search filter was measured.  Subheadings proved the most useful search terms in both medline and embase. No indexing terms in medline achieved over 12% sensitivity. The sensitivity of published search filters varied in medline from 3% to 93% and in embase from 57% to 97%. Whether this level of sensitivity is acceptable will be dependent on the purpose of the search.  Although no adverse effects search filter captured all the relevant records, high sensitivity could be achieved. Search filters may therefore be useful in retrieving adverse effects data. © 2012 The authors. Health Information and Libraries Journal © 2012 Health Libraries Group Health Information and Libraries Journal.

  2. Late adverse effects of radiation therapy for rectal cancer - a systematic overview

    Energy Technology Data Exchange (ETDEWEB)

    Birgisson, Helgi; Paahlman, Lars; Gunnarsson, Ulf [Dept. of Surgery, Univ. Hospital, Univ. of Uppsala, Uppsala (Sweden); Glimelius, Bengt [Dept. of Oncology, Radiology and Clinical Immunology, Univ. Hospital, Univ. of Uppsala, Uppsala (Sweden); Dept. of Oncology and Pathology, Karolinska Inst., Stockholm (Sweden)

    2007-05-15

    Purpose. The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. Methods. Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5x5 Gy radiation therapy with surgery alone. Results. The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. Conclusions. These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued.

  3. Energy drink usage among university students in a Caribbean country: Patterns of use and adverse effects.

    Science.gov (United States)

    Reid, Sandra D; Ramsarran, Jonathan; Brathwaite, Rachel; Lyman, Sarika; Baker, Ariane; Cornish, D'Andra C; Ganga, Stefan; Mohammed, Zahrid; Sookdeo, Avinash T; Thapelo, Cathrine K

    2015-06-01

    There has been little inquiry addressing whether or not concerns about adverse effects of energy drink usage are relevant in the Caribbean. This survey investigated energy drink usage and adverse consequences among tertiary level students in Trinidad and Tobago. A cross-sectional survey of 1994 students from eight institutions was conducted using a de novo questionnaire based on findings from a focus group of students. Chi-squared analyses and logistic regression were used to assess relationships between energy drink usage, adverse effects and other factors affecting energy drink use, and to verify predictors of energy drink use. Prevalence of use was 86%; 38% were current users. Males were more likely to use, used more frequently and at an earlier age. Energy drinks were used most commonly to increase energy (50%), combat sleepiness (45%) and enhance academic performance (40%), and occurred during sports (23%) and mixed with alcohol (22.2%). The majority (79.6%) consumed one energy drink per sitting; 62.2% experienced adverse effects, most commonly restlessness (22%), jolt and crash (17.1%) and tachycardia (16.6%). Awareness of adverse effects was associated with no use (p=0.004), but adverse effects were not a deterrent to continued use. Energy drink usage is prevalent among students. The use is not excessive, but associated with high rates of adverse effects and occurs in potentially dangerous situations like during exercise and with alcohol. There is a need to educate students about the potential adverse effects of energy drinks. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  4. Pulmonary Adverse Effects of Welding Fume in Automobile Assembly Welders

    Directory of Open Access Journals (Sweden)

    Seyed Akbar Sharifian

    2011-02-01

    Full Text Available Welding is one of the key components of numerous manufacturing industries, which has potential physical and chemical health hazards. Many components of welding fumes can potentially affect the lung function. This study investigates the effects of welding fumes on lung function and respiratory symptoms among welders of an automobile manufacturing plant in Iran. This historical cohort study assesses 43 male welders and 129 office workers by a questionnaire to record demographic data, smoking habits, work history and respiratory symptoms as well as lung function status by spirometry. The average pulmonary function values of welders were lower relative to controls with dose-effect relationship between work duration and pulmonary function impairment. The prevalence of chronic bronchitis was higher in welders than controls. Our findings suggest that welders are at risk for pulmonary disease.

  5. Adverse effects of fluoride towards thyroid hormone metabolism

    Directory of Open Access Journals (Sweden)

    Enggar Abdullah Idris MZ

    2008-03-01

    Full Text Available An easily ionized fluoride compound like Sodium Fluoride (NaF has been used thus far as a dental caries prevention substance. However, fluoride ions also have a negative effect because it is very toxic. Several types of research on the effect of fluoride on guinea pigs and human beings indicate the presence synthesis obstruction of T3 and T4 that causes declined production, known as hypothyroidism. Hypothyroidism condition may obstruct tissue growth process and metabolism so as to impact various body organ systems. Preventive efforts against hypothyroidism caused by fluoride include avoiding diffusible fluoride compound intake, like NaF, in a long run systemic use, whereas efforts to overcome fluoride intoxication include consuming food that is rich in calcium, vitamin D, and antioxidant.

  6. Abuse potential and adverse cognitive effects of mitragynine (kratom).

    Science.gov (United States)

    Yusoff, Nurul H M; Suhaimi, Farah W; Vadivelu, Raja K; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C; Mansor, Sharif M; Navaratnam, Visweswaran; Müller, Christian P

    2016-01-01

    Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug. © 2014 Society for the Study of Addiction.

  7. [Adverse effects of intravenous arsenic trioxide and their prevention].

    Science.gov (United States)

    Wu, Nan; Hu, Long-hu; Zhou, Jin; Fan, Sheng-jin; Wang, Yan; Han, Xue-ying

    2006-04-01

    To study the main side effects of As(2)O(3) and the way of prevention. The changes of body weight and various systems of body were observed after treatment with As(2)O(3) injection. The arsenic content in blood, urine and hair was detected with atom absorbed-spectrum analysis. Mild reactions were observed in 57.43% (147/256) of the patients and they could subside after cessation of arsenic treatment or allotherapy. Chronic mild poisoning manifestations including arsenic furuncle, liver dysfunction and peripheral nerve injury were found in 2.73% (7/256) of the patients and they subsided gradually after treatment. Chronic severe poisoning was found in 1.17% of the patients and all of them died of liver failure. As(2)O(3) might cause decrease of peripheral blood WBC in catabatic patients. There was no infection after allopathy without ceasing arsenic medication. The results showed that As(2)O(3) could distribute over and discharge from the plasma without accumulation in blood. The results also demonstrated the main route of excretion for As(2)O(3) is through urine and there is definite accumulation in the hair 50 days after treatment. Most of the side effects of As(2)O(3) are mild and recoverable. Allotherapy could be effective to relieve the complications without stopping arsenic medication. A few patients with complicating hepatitis may suffer from chronic poisoning. As(2)O(3) may cause increase of peripheral blood WBC in induced catabatic APL patients. The side effects must be prevented early.

  8. Acute mucocutaneous and systemic adverse effects of Etretinate

    Directory of Open Access Journals (Sweden)

    "Mortazavi H

    2003-06-01

    Full Text Available This cross sectional study was carried out between 1993 to 1998 at Razi Skin Hospital, the affiliated Dermatology Department of Tehran University of Medical Sciences. Eight hundred patients receiving etretinate for various skin diseases took part in this study. Among them, 457 patients with first admission to dermatologic clinic who had at least four regular sequential visits and responding to our questionnaire were selected to enter the study for evaluating acute toxicity of etretinate. Cheilitis with a frequency of 88 percent was the most frequent side effect. Hair loss (22.97%, dry mouth with thirst (15.09%, dryness of mucous membranes (13.12%, xerosis with pruritus (11.15%, nose bleeding (8.31%, paronychia (5.47%, facial dermatitis (3.06%, conjunctivitis (2.84% and in addition to mucocutaneous ones, chills (2.63%, headache (2.19%, mental depression (2.19%, urinary frequency (1.53% and papilledema (0.44% were among the other observed toxicities, The relationship between mucocutaneous side effect with dosage of etretinate, sex and, age of the patients was evaluated. The association between mucoctaneous toxicities and sex was significant, sex and, age of the patients was evaluated. The association between mucocutaneous toxicities and sex was significant (P<0.05. We observed four rare side effect in the patients including hair color lightening appering as whitening or blondness, hair waving, dyspareunia and gynecomastia. In conclusion, females were more to acute mucocutaneous toxicities of etretinate.

  9. Methylmercury exposure and adverse cardiovascular effects in Faroese whalingmen

    DEFF Research Database (Denmark)

    Choi, Anna L; Weihe, Pál; Budtz-Jørgensen, Esben

    2009-01-01

    consumption of pilot whale meat. METHODS: We assessed exposure levels from mercury analysis of toenails and whole blood (obtained at the time of clinical examination), and a hair sample collected 7 years previously. Outcome measures included heart rate variability (HRV), blood pressure (BP), common carotid...... intima-media thickness (IMT), and brainstem auditory evoked potentials (BAEP). We carried out multiple regression and structural equation model (SEM) analyses to determine the confounder-adjusted effect of mercury exposure. Taking into account correlations among related measures, we categorized exposure...

  10. Endocrine disrupting chemicals – probability of adverse environmental effect

    Directory of Open Access Journals (Sweden)

    Henryka Langauer-Lewowicka

    2015-03-01

    Full Text Available The paper presents some information about current state of knowledge of the risk due to exposure to endocrine disrupting chemicals (EDCs. Endocrine disruptors are defined as chemicals substances with either agonist or antagonist endocrine effects in human and wildlife. Exposure to EDCs in animals models correlate positively with an increased incidence of malformations of genital tract, on neoplasmas, obesity, alternations on male and female reproduction and changes in neuroendocrinology and behavior. Results from animal models, human clinical observations and epidemiological studies converge to implicate EDCs as a significant risk to public health.

  11. [Serious adverse side effects after pupillary dilation in preterm infants].

    Science.gov (United States)

    Lux, A-L; Mouriaux, F; Guillois, B; Fedrizzi, S; Peyro-Saint-Paul, L; Denion, E

    2015-03-01

    This study aimed at investigating serious side effects of the pupillary dilation protocol used in Caen University Hospital for the screening of retinopathy of prematurity. This protocol includes one drop of phenylephrine 5% and two drops of tropicamide 0.5% instilled at a 5-minute interval. This retrospective study included all premature infants with a birth weight less than or equal to 1500 g and/or a gestational age less than or equal to 30 gestational weeks, hospitalized in the neonatal intensive care unit of Caen University Medical Center, having ocular fundus examinations for retinopathy of prematurity screening between 2009 and 2014. The medical records of patients who died or developed necrotizing enterocolitis were reviewed to analyze the imputability of the two eye drops used for pupil dilation. Five-hundred and twelve infants were included, corresponding to 1033 ocular fundus examinations. No case of death could be ascribed to the use of eye drops. Two cases of necrotizing enterocolitis could be ascribed to the use of tropicamide with a doubtful and plausible intrinsic imputability according to French imputability criteria. The pupillary dilation protocol used in Caen University Hospital for screening of retinopathy of prematurity might be implicated in two cases of necrotizing enterocolitis with an uncertain imputability of tropicamide 0.5% eye drops. No serious side effect could be ascribed to the use of phenylephrine 5% eye drops in this study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Are the adverse effects of stressors on amphibians mediated by their effects on stress hormones?

    Science.gov (United States)

    Gabor, Caitlin R; Knutie, Sarah A; Roznik, Elizabeth A; Rohr, Jason R

    2017-12-08

    Adverse effects of anthropogenic changes on biodiversity might be mediated by their impacts on the stress response of organisms. To test this hypothesis, we crossed exposure to metyrapone, a synthesis inhibitor of the stress hormone corticosterone, with exposure to the herbicide atrazine and the fungal pathogen Batrachochytrium dendrobatidis (Bd) to assess whether the effects of these stressors on tadpoles and post-metamorphic frogs were mediated by corticosterone. Metyrapone countered atrazine- and Bd-induced corticosterone elevations. However, atrazine- and Bd-induced reductions in body size were not mediated by corticosterone because they persisted despite metyrapone exposure. Atrazine lowered Bd abundance without metyrapone but increased Bd abundance with metyrapone for tadpoles and frogs. In contrast, atrazine reduced tolerance of Bd infections because frogs exposed to atrazine as tadpoles had reduced growth with Bd compared to solvent controls; this effect was not countered by metyrapone. Our results suggest that the adverse effects of atrazine and Bd on amphibian growth, development, and tolerance of infection are not mediated primarily by corticosterone. A possible mechanism for these effects is energy lost from atrazine detoxification, defense against Bd, or repair from damage caused by atrazine and Bd. Additional studies are needed to evaluate how often the effects of anthropogenic stressors are mediated by stress hormones.

  13. Assessment of Aerobic Exercise Adverse Effects during COPD Exacerbation Hospitalization

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    Caroline Knaut

    2017-01-01

    Full Text Available Introduction. Aerobic exercise performed after hospital discharge for exacerbated COPD patients is already recommended to improve respiratory and skeletal muscle strength, increase tolerance to activity, and reduce the sensation of dyspnea. Previous studies have shown that anaerobic activity can clinically benefit patients hospitalized with exacerbated COPD. However, there is little information on the feasibility and safety of aerobic physical activity performed by patients with exacerbated COPD during hospitalization. Objective. To evaluate the effects of aerobic exercise on vital signs in hospitalized patients with exacerbated COPD. Patients and Methods. Eleven COPD patients (63% female, FEV1: 34.2 ± 13.9% and age: 65 ± 11 years agreed to participate. Aerobic exercise was initiated 72 hours after admission on a treadmill; speed was obtained from the distance covered in a 6-minute walk test (6MWT. Vital signs were assessed before and after exercise. Results. During the activity systolic blood pressure increased from 125.2 ± 13.6 to 135.8 ± 15.0 mmHg (p=0.004 and respiratory rate from 20.9 ± 4.4 to 24.2 ± 4.5 rpm (p=0.008 and pulse oximetry (SpO2 decreased from 93.8 ± 2.3 to 88.5 ± 5.7% (p<0.001. Aerobic activity was considered intense, heart rate ranged from 99.2 ± 11.5 to 119.1 ± 11.1 bpm at the end of exercise (p=0.092, and patients reached on average 76% of maximum heart rate. Conclusion. Aerobic exercise conducted after 72 hours of hospitalization in patients with exacerbated COPD appears to be safe.

  14. The adverse effect of overweight in assisted reproduction treatment outcomes.

    Science.gov (United States)

    Sampo, Antonella Valeria; Palena, Celina; Ganzer, Luciano; Maccari, Virginia; Estofán, Gustavo; Hernández, Mariana

    2017-09-01

    To assess Body Mass Index (BMI) effects on the results obtained from ICSI cycles. We studied 266 ICSI cycles performed between January 2014 and December 2016. The patients were grouped according to their BMI in: Normal (18.5-24.9), Overweight (25.0-29.9) and Obese (>30). We compared the following variables between the groups: number of antral follicles, ovarian stimulation length, gonadotropin dose used, maximum estradiol level, follicles developed/antral follicles, retrieved oocytes/developed follicles and mature/retrieved oocytes, normal fertilization rate, embryo achieved/normal fertilized oocytes, clinical pregnancy and implantation rates. We used the Kruskal-Wallis and the Chi square tests. p<0.05 was considered significant. Normal, Overweight and Obese patients presented comparable values for number of antral follicles (11.6±5.4, 12.5±5.5, 12.2±5.7), ovarian stimulation length (7.5±1.4, 7.6±1.1, 7.8±1.3) and gonadotropin dose used (2043±489, 1940±536, 2109±605). Obese patients had lower values of estradiol (1560±610, 1511±635, 1190±466; p=0.018), developed follicles (81%, 76%, 70%; p<0.0001), and retrieved oocytes (91%, 90%, 84%; p=0.0017); and not significantly lower values of mature oocytes (82%, 82%, 77%; p=0.26). The groups had comparable fertilization rates (72%, 73%, 69%) and embryo achieved rates (67%, 63%, 72%). The normal group had higher, but not significantly higher pregnancy and implantation rates (43%, 40%, 38%, p=0.53; and 33%, 26%, 23%; p=0.11), and significantly higher ongoing pregnancy rates (37%, 33%, 33%, p=0.042). Increased BMI patients had impaired ovarian response and lower pregnancy rates in ICSI cycles.

  15. Adverse Effects of Antidepressants for Chronic Pain: A Systematic Review and Meta-analysis

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    Carina Riediger

    2017-07-01

    Full Text Available BackgroundAntidepressants are widely used in the treatment of chronic pain. Applied doses are lower than those needed to unfold an antidepressive effect. While efficacy of antidepressants for chronic pain has been reported in large randomized-controlled trials (RCT, there is inconsistent data on adverse effects and tolerability. We aimed at synthesizing data from RCT to explore adverse effect profiles and tolerability of antidepressants for treatment of chronic pain.MethodsSystematic literature research and meta-analyses were performed regarding side effects and safety of different antidepressants in the treatment of chronic pain according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The National Center for Biotechnology Information library and MEDLINE were searched. Randomized placebo-controlled trials were included in quantitative data synthesis.ResultsOut of 1,975 screened articles, 33 papers published between 1995 and 2015 were included in our review and 23 studies were included in the meta-analyses. A higher risk for adverse effects compared to placebo was observed in all antidepressants included in our analyses, except nortriptyline. The most prevalent adverse effects were dry mouth, dizziness, nausea, headache, and constipation. Amitriptyline, mirtazapine, desipramine, venlafaxine, fluoxetine, and nortriptyline showed the highest placebo effect-adjusted risk of adverse effects. Risk for withdrawal due to adverse effects was highest in desipramine (risk ratio: 4.09, 95%-confidence interval [1.31; 12.82] followed by milnacipran, venlafaxine, and duloxetine. The most common adverse effects under treatment with antidepressants were dry mouth, dizziness, nausea, headache, and constipation followed by palpitations, sweating, and drowsiness. However, overall tolerability was high. Each antidepressant showed distinct risk profiles of adverse effects.ConclusionOur synthesized data analysis confirmed overall

  16. Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation

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    Suzy Maria Montenegro Pontes

    Full Text Available ABSTRACT Objective: To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV. Methods: We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP or continuous positive airway pressure (CPAP. Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. Results: The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%. Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%. The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. Conclusions: The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin.

  17. Alcohol Consumption and Its Adverse Effects in Poland in Years 1950–2005

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    Agnieszka Bielinska-Kwapisz

    2011-01-01

    Full Text Available This study examines changes in alcohol consumption and its adverse effects in Poland from 1950 to 2005. First, we estimate the total alcohol demand function and test Becker and Murphy's (1988 rational addiction model. Next, we explore substitution effects between beer, wine, and spirits and report income and own- and cross-price elasticities of demand for beer, wine, and spirits. Finally, we examine some adverse effects of alcohol consumption: traffic accidents, suicide rates, and vandalism rates. In particular, the effect of lowering the blood alcohol level limit (BAC on traffic accidents is estimated.

  18. Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

    Energy Technology Data Exchange (ETDEWEB)

    Hayhurst, Caroline; Monsalves, Eric [Gamma Knife Unit, Division of Neurosurgery, University Health Network, Toronto (Canada); Prooijen, Monique van [Physics Department, Princess Margaret Hospital, Toronto (Canada); Cusimano, Michael [Division of Neurosurgery, St Michael' s Hospital, Toronto (Canada); Tsao, May [Radiation Oncology Program, Sunnybrook Hospital, University of Toronto (Canada); Menard, Cynthia [Radiation Oncology Program, Princess Margaret Hospital, University of Toronto (Canada); Kulkarni, Abhaya V. [Division of Neurosurgery, Hospital for Sick Children, University of Toronto (Canada); Schwartz, Michael [Division of Neurosurgery, Sunnybrook Hospital, University of Toronto (Canada); Zadeh, Gelareh, E-mail: gelareh.zadeh@uhn.on.ca [Gamma Knife Unit, Division of Neurosurgery, University Health Network, Toronto (Canada)

    2012-02-01

    Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the

  19. Pretreatment predictors of adverse radiation effects after radiosurgery for arteriovenous malformation.

    Science.gov (United States)

    Hayhurst, Caroline; Monsalves, Eric; van Prooijen, Monique; Cusimano, Michael; Tsao, May; Menard, Cynthia; Kulkarni, Abhaya V; Schwartz, Michael; Zadeh, Gelareh

    2012-02-01

    To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzed to identify predictors of adverse radiation effects. There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm(3), above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series suggest the optic radiation is a critical radiosensitive structure. Crown Copyright © 2012. Published

  20. Care-seeking behavior of Japanese gynecological cancer survivors suffering from adverse effects

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    Oshima Sumiko

    2013-01-01

    Full Text Available Abstract Background Post-treatment follow-up visits for gynecological cancer survivors should provide opportunities for management of adverse physical/psychological effects of therapy and early recurrence detection. However, the adequacy of such visits in Japan is poorly documented. We qualitatively explored care-seeking experiences of Japanese gynecological cancer survivors and deduced factors influencing care-seeking behaviors and treatment access. Methods We conducted 4 semi-structured focus groups comprising altogether 28 Japanese gynecological cancer survivors to collect a variety of participants’ post-treatment care-seeking behaviors through active interaction with participants. Factors influencing access to treatment for adverse effects were analyzed qualitatively. Results Survivors sought care through specialty clinic visits when regular post-treatment gynecological follow-ups were inadequate or when symptoms seemed to be non-treatment related. Information provided by hospital staff during initial treatment influenced patients’ understanding and response to adverse effects. Lack of knowledge and inaccurate symptom interpretation delayed help-seeking, exacerbating symptoms. Gynecologists’ attitudes during follow-ups frequently led survivors to cope with symptoms on their own. Information from mass media, Internet, and support groups helped patients understand symptoms and facilitated care seeking. Conclusions Post-treatment adverse effects are often untreated during follow-up visits. Awareness of possible post-treatment adverse effects is important for gynecological cancer survivors in order to obtain appropriate care if the need arises. Consultation during the follow-up visit is essential for continuity in care.

  1. Adverse effects associated with intravenous pentamidine isethionate as treatment of Pneumocystis carinii pneumonia in AIDS patients

    DEFF Research Database (Denmark)

    Balslev, U; Nielsen, T L

    1992-01-01

    % of the total number of patients with PCP in the department during that period. Four patients died during treatment and were not evaluated for side effects. Thirteen patients (13/17 = 76%) suffered from one or more minor side effects. The most common of these were gastrointestinal discomfort, pancreatitis......, nephro- and hepatotoxicity. Five patients (5/17 = 29%) experienced a major adverse effect. These were cardiac arrest (one patient), severe hypoglycaemia (one patient) and severe pancreatitis (three patients). In two patients, discontinuation of treatment was necessary due to adverse reactions. As long......To evaluate the adverse effects of intravenous pentamidine isethionate, a retrospective study was carried out over a four-year period. Twenty-one acquired immunodeficiency syndrome (AIDS) patients received intravenous pentamidine as treatment of Pneumocystis carinii pneumonia (PCP). This was 13...

  2. Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy.

    Science.gov (United States)

    Kerns, Sarah L; Ostrer, Harry; Rosenstein, Barry S

    2014-02-01

    Normal-tissue adverse effects following radiotherapy are common and significantly affect quality of life. These effects cannot be accounted for by dosimetric, treatment, or demographic factors alone, and evidence suggests that common genetic variants are associated with radiotherapy adverse effects. The field of radiogenomics has evolved to identify such genetic risk factors. Radiogenomics has two goals: (i) to develop an assay to predict which patients with cancer are most likely to develop radiation injuries resulting from radiotherapy, and (ii) to obtain information about the molecular pathways responsible for radiation-induced normal-tissue toxicities. This review summarizes the history of the field and current research. A single-nucleotide polymorphism–based predictive assay could be used, along with clinical and treatment factors, to estimate the risk that a patient with cancer will develop adverse effects from radiotherapy. Such an assay could be used to personalize therapy and improve quality of life for patients with cancer. 2014 AACR

  3. "First do no harm." A systematic review of the prevalence and management of antipsychotic adverse effects.

    Science.gov (United States)

    Young, Su Ling; Taylor, Mark; Lawrie, Stephen M

    2015-04-01

    We aim to identify the prevalence and management strategies of nine clinically important categories of antipsychotic adverse effects, namely: extrapyramidal symptoms; sedation; weight gain; type II diabetes; hyperprolactinaemia; metabolic syndrome, dyslipidaemia; sexual dysfunction; and cardiovascular effects. Antipsychotic drugs are widely prescribed for schizophrenia and other mental disorders. The adverse effects of antipsychotics are common, with a potential negative impact on adherence and engagement. Despite this, the scientific study of the prevalence or management of adverse antipsychotic effects is a neglected area. A systematic review was undertaken using pre-defined search criteria and three databases, with hand searching of citations and references. Inclusion was agreed on by two independent researchers after review of abstracts or full text. Quality analysis of included studies was conducted using pre-agreed criteria. In total, 53 studies met inclusion criteria, revealing the following: (1) antipsychotic polypharmacy was associated with increased frequency of adverse effects, and (2) a longer duration of treatment is associated with greater severity (e.g. higher BMI); (3) clozapine was more strongly associated with metabolic disturbance than other antipsychotics in three studies and olanzapine was associated with the most weight gain in three studies; (4) hyperprolactinaemia was more common in women than men, but 50% men noted sexual dysfunction versus 25-50% in women; (5) despite clinical guideline recommendations there is a low rate of baseline testing for lipids and glucose; and (6) seven studies described adverse effect management strategies, but only two examined their efficacy - one found a significant reduction in weight with non-pharmacological group therapy and the other found a significant reduction in dyslipidaemia with statins. Antipsychotic adverse effects are diverse and frequently experienced, but are not often systematically assessed

  4. Finasteride adverse effects and post-finasteride syndrome; implications for dentists

    Directory of Open Access Journals (Sweden)

    Stana Paunica

    2016-04-01

    Full Text Available Finasteride is a 5α-reductase inhibitor widely used in present in the therapeutic approach of androgenic alopecia. Adverse effects consist in variable sign and symptoms, the most common being represented by mental troubles (reduced feeling of life pleasure or emotions, depression, physical impairments (loss of muscle tone and/or mass and sexual complains (loss of libido and sexual potency. An increasing number of studies identify and describe even a post-finasteride syndrome (persistent adverse affects three months or more after finasteride cessation or new adverse effects including but not limited at the skin level or oral cavity (marginal periodontium. We intend to present in this study several oral adverse effects encountered during finasteride administration, represented by mild and moderate signs which generally responded to topical procedures without to require the stop of the drug administration. New studies on large samples will further document the existing relation between the described oral adverse effects and the implied pathophysiological mechanisms. For this moment, we are taking into account as possible mechanisms- a direct action of finasteride administration, possible indirect consequences due to hormonal interferences, or coexisting factors with finasteride administration that were not detected.

  5. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

    Directory of Open Access Journals (Sweden)

    Nusrat Bano

    2013-01-01

    Full Text Available The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (, whereas frequency and onset of peripheral neuropathy were highly significant ( in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles even at low doses (85 mg/m2, whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2 after few treatment cycles.

  6. Characterization of scientific studies usually cited as evidence of adverse effects of GM food/feed.

    Science.gov (United States)

    Sánchez, Miguel A; Parrott, Wayne A

    2017-10-01

    GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  7. Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

    Directory of Open Access Journals (Sweden)

    Mashhood Ahmed Sheikh

    2017-08-01

    Full Text Available The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support. The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530, a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV, and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V. Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (% of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71 in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18, and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001. Smoking in adulthood did not significantly

  8. The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

    Science.gov (United States)

    Nicholi, Armand M., Jr.

    1983-01-01

    This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

  9. Energy drinks and their adverse health effects: A systematic review of the current evidence.

    Science.gov (United States)

    Ali, Fahad; Rehman, Hiba; Babayan, Zaruhi; Stapleton, Dwight; Joshi, Divya-Devi

    2015-04-01

    With the rising consumption of so-called energy drinks over the last few years, there has been a growing body of literature describing significant adverse health events after the ingestion of these beverages. To gain further insight about the clinical spectrum of these adverse events, we conducted a literature review. Using PubMed and Google-Scholar, we searched the literature from January 1980 through May 2014 for articles on the adverse health effects of energy drinks. A total of 2097 publications were found. We then excluded molecular and industry-related studies, popular media reports, and case reports of isolated caffeine toxicity, yielding 43 reports. Energy drink consumption is a health issue primarily of the adolescent and young adult male population. It is linked to increased substance abuse and risk-taking behaviors. The most common adverse events affect the cardiovascular and neurological systems. The most common ingredient in energy drinks is caffeine, and it is believed that the adverse events are related to its effects, as well as potentiating effects of other stimulants in these drinks. Education, regulation, and further studies are required.

  10. Effect of dacryocystorhinostomy on systemic adverse effects of topical timolol maleate

    Directory of Open Access Journals (Sweden)

    Kakoli Roy

    2012-01-01

    Full Text Available Purpose: To evaluate whether transformation of the naso-lacrimal passage as happens after dacryocystorhinostomy (DCR operation has any effect on the systemic adverse effects of topically administered timolol maleate. Materials and Methods: Fifty otherwise healthy adult patients without any prior history of cardiac or pulmonary problems scheduled for elective DCR surgery received a drop of timolol maleate 0.5% on the healthy eye. This eye served as a control. Six weeks after successful DCR surgery, the operated eye received the same medication. Parameters compared included intraocular pressure (IOP, pulse rate, blood pressure and forced expiratory volume in the first second (FEV1 findings. Observations: Post DCR patients showed an increased incidence of reduced pulse rate and FEV1. Conclusion: Timolol maleate ophthalmic preparation should be used with caution in post-DCR patients.

  11. Adverse effects of biologics: a network meta-analysis and Cochrane overview

    DEFF Research Database (Denmark)

    Singh, J. A.; Wells, G. A.; Christensen, Robin Daniel Kjersgaard

    2011-01-01

    Background Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious...... infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates. Objectives To compare the adverse effects of tumor necrosis factor blocker...... controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane...

  12. Adverse effects of pharmacological therapy of benign prostatic hyperplasia on sexual function in men

    OpenAIRE

    Stojanović Nebojša A.; Ignjatović Ivan; Đenić Nebojša; Bogdanović Dragan

    2015-01-01

    Introduction. The development of effective medications makes pharmacological therapy of BPH the dominant mode of treatment today. It improves urinary symptoms and prevents disease progression while producing side effects on male sexual function. Objective. The aim of the study is to present the effects of BPH pharmacological treatment on the occurrence of sexually adverse effects in men: changes in sexual desire, erectile, ejaculatory and the orgasmic funct...

  13. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain.

    Science.gov (United States)

    Labianca, Roberto; Sarzi-Puttini, Piercarlo; Zuccaro, Stefano Maria; Cherubino, Paolo; Vellucci, Renato; Fornasari, Diego

    2012-02-01

    Chronic pain is a debilitating condition that is associated with many common diseases; this places a major burden on the healthcare system. There are currently numerous analgesic agents available for the treatment of chronic pain. In general, the oral non-opioid analgesic, paracetamol, is recommended for the initial treatment of mild to moderate pain. Therapeutic doses of paracetamol do not appear to result in hepatotoxicity, although overdose may lead to acute liver failure. Current data suggest that paracetamol has acceptable gastrointestinal tolerability. Another class of non-opioid analgesic with confirmed efficacy for the treatment of chronic mild to moderate pain are non-steroidal anti-inflammatory drugs (NSAIDs), although this efficacy is offset by the potential of adverse gastrointestinal events. In particular, non-selective NSAIDs, also known as cyclooxygenase (COX) inhibitors, carry an increased risk of serious upper gastrointestinal complications, including ulcers, perforation and bleeding. The introduction of COX-2 inhibitors provided a NSAID-based option with improved gastrointestinal safety, but increased risk of cardiovascular effects. Opioids are powerful analgesic agents used to treat moderate to severe chronic pain. However, treatment with opioids is associated with a number of common adverse effects, including constipation, nausea or vomiting, pruritus, somnolence or cognitive impairment, dry mouth, tolerance or dependence and urinary retention. Although there are multiple strategies in place to manage adverse events that arise from both non-opioid and opioid analgesic therapy, a better understanding of the mechanisms involved in the development of specific drug-related adverse effects is required along with proper prescribing practices and adequate physician/patient education. Balanced against the adverse effects of pain management medications, there is a need to be mindful of the widespread, often serious, adverse consequences of poorly managed

  14. Post-Finasteride Adverse Effects in Male Androgenic Alopecia: A Case Report of Vitiligo.

    Science.gov (United States)

    Motofei, Ion G; Rowland, David L; Georgescu, Simona R; Tampa, Mircea; Paunica, Stana; Constantin, Vlad D; Balalau, Cristian; Manea, Mirela; Baleanu, Bogdan C; Sinescu, Ioanel

    2017-01-01

    Finasteride has proved to be relatively safe and effective in the therapeutic management of male androgenic alopecia. However, literature data report several endocrine imbalances inducing various adverse effects, which often persist after treatment cessation in the form of post-finasteride syndrome. Here we present the case of a 52-year-old man receiving finasteride (1 mg/day) who developed an uncommon adverse effect represented by generalized vitiligo 2 months after finasteride discontinuation. Associated adverse effects encountered were represented by mild sexual dysfunction (as determined by the International Index of Erectile Function, IIEF) and moderate depressive symptoms (according to DSM-V criteria), all of these manifestations aggregating within/as a possible post-finasteride syndrome. Further studies should develop and compare several therapeutic approaches, taking into account not only compounds that decrease the circulating dihydrotestosterone level but also those that could block the dihydrotestosterone receptors (if possible, compounds with selective tropism towards the skin). In addition, the possibility of predicting adverse effects of finasteride (according to hand preference and sexual orientation) should be taken into account. © 2017 S. Karger AG, Basel.

  15. A replication of the study ‘Adverse effects of spinal manipulation: a systematic review’

    Directory of Open Access Journals (Sweden)

    Tuchin Peter

    2012-09-01

    the application of SMT and related adverse effects.

  16. The Adverse Events and Hemodynamic Effects of Adenosine-Based Cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Voigtlander, Thomas; Magedanz, Annett; Schmermund, Axel [Cardiovascular Center Bethanien (CCB), Frankfurt (Germany); Bramlage, Peter [Technical University of Dresden, Dresden (Germany); Elsaesser, Amelie [University of Mainz, Mainz (Germany); Kauczor, Hans-Ulrich; Mohrs, Oliver K. [University of Heidelberg, Heidelberg (Germany)

    2011-08-15

    We wanted to prospectively assess the adverse events and hemodynamic effects associated with an intravenous adenosine infusion in patients with suspected or known coronary artery disease and who were undergoing cardiac MRI. One hundred and sixty-eight patients (64 {+-} 9 years) received adenosine (140 {mu}g/kg/min) during cardiac MRI. Before and during the administration, the heart rate, systemic blood pressure, and oxygen saturation were monitored using a MRI-compatible system. We documented any signs and symptoms of potential adverse events. In total, 47 out of 168 patients (28%) experienced adverse effects, which were mostly mild or moderate. In 13 patients (8%), the adenosine infusion was discontinued due to intolerable dyspnea or chest pain. No high grade atrioventricular block, bronchospasm or other life-threatening adverse events occurred. The hemodynamic measurements showed a significant increase in the heart rate during adenosine infusion (69.3 {+-} 11.7 versus 82.4 {+-} 13.0 beats/min, respectively; p < 0.001). A significant but clinically irrelevant increase in oxygen saturation occurred during adenosine infusion (96 {+-} 1.9% versus 97 {+-} 1.3%, respectively; p < 0.001). The blood pressure did not significantly change during adenosine infusion (systolic: 142.8 {+-} 24.0 versus 140.9 {+-} 25.7 mmHg; diastolic: 80.2 {+-} 12.5 mmHg versus 78.9 {+-} 15.6, respectively). This study confirms the safety of adenosine infusion during cardiac MRI. A considerable proportion of all patients will experience minor adverse effects and some patients will not tolerate adenosine infusion. However, all adverse events can be successfully managed by a radiologist. The increased heart rate during adenosine infusion highlights the need to individually adjust the settings according to the patient, e.g., the number of slices of myocardial perfusion imaging.

  17. Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis.

    Science.gov (United States)

    Gong, Qianwen; Janowski, Miroslaw; Luo, Mi; Wei, Hong; Chen, Bingjie; Yang, Guoyuan; Liu, Longqian

    2017-06-01

    Some uncertainty about the clinical value and dosing of atropine for the treatment of myopia in children remains. To evaluate the efficacy vs the adverse effects of various doses of atropine in the therapy for myopia in children. Data were obtained from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from inception to April 30, 2016. The reference lists of published reviews and clinicaltrials.gov were searched for additional relevant studies. Key search terms included myopia, refractive errors, and atropine. Only studies published in English were included. Randomized clinical trials and cohort studies that enrolled patients younger than 18 years with myopia who received atropine in at least 1 treatment arm and that reported the annual rate of myopia progression and/or any adverse effects of atropine therapy were included in the analysis. Two reviewers independently abstracted the data. Heterogeneity was statistically quantified by Q, H, and I2 statistics, and a meta-analysis was performed using the random-effects model. The Cochrane Collaboration 6 aspects of bias and the Newcastle-Ottawa Scale were used to assess the risk for bias. The primary outcome was a difference in efficacy and the presence of adverse effects at different doses of atropine vs control conditions. The secondary outcomes included the differences in adverse effects between Asian and white patients. Nineteen unique studies involving 3137 unique children were included in the analysis. The weighted mean differences between the atropine and control groups in myopia progression were 0.50 diopters (D) per year (95% CI, 0.24-0.76 D per year) for low-dose atropine, 0.57 D per year (95% CI, 0.43-0.71 D per year) for moderate-dose atropine, and 0.62 D per year (95% CI, 0.45-0.79 D per year) for high-dose atropine (P myopia progression (P = .15). High-dose atropine were associated with more adverse effects, such as the 43.1% incidence of photophobia compared with 6.3% for low

  18. Adverse radiation effect after stereotactic radiosurgery for brain metastases : incidence, time course, and risk factors

    NARCIS (Netherlands)

    Sneed, Penny K.; Mendez, Joe; Vemer-van den Hoek, Johanna; Seymour, Zachary A.; Ma, Lijun; Molinaro, Annette M.; Fogh, Shannon E.; Nakamura, Jean L.; McDermott, Michael W.

    OBJECT The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases. METHODS All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at

  19. Alkaloids in the human food chain - Natural occurrence and possible adverse effects

    NARCIS (Netherlands)

    Koleva, I.; Beek, van T.A.; Soffers, A.E.M.F.; Dusemund, B.; Rietjens, I.

    2012-01-01

    Alkaloid-containing plants are an intrinsic part of the regular Western diet. The present paper summarizes the occurrence of alkaloids in the food chain, their mode of action and possible adverse effects including a safety assessment. Pyrrolizidine alkaloids are a reason for concern because of their

  20. Impact of censoring on estimates of adverse drug effects: A simulation study

    NARCIS (Netherlands)

    Groenwold, Rolf H.; Van Staa, Tjeerd P.; De Boer, Anthonius; Klungel, Olaf H.

    2013-01-01

    Background: The results from studies on adverse drug effects in electronic health care databases may vary due to multiple reasons, one of them being differences in (left and right) censoring mechanisms between databases. Such censoring mechanisms can be features of the database and are therefore

  1. Late adverse effects of whole cranial irradiation in childhood hematological disorders

    Energy Technology Data Exchange (ETDEWEB)

    Someya, Masanori; Nakata, Kensei; Nagakura, Hisayasu; Oouchi, Atsushi; Sakata, Kohichi; Hareyama, Masato [Sapporo Medical Coll. (Japan)

    2003-03-01

    The purpose of this study was to examine the late adverse effects of childhood hematological disorders treated with chemotherapy and radiotherapy including whole cranial irradiation at Sapporo Medical University Hospital. Twenty-eight patients were treated with chemotherapy and 18-24 Gy of prophylactic cranial irradiation (PCI) for acute lymphoblastic leukemia (ALL), and 14 patients were treated with 3-12.8 Gy of total body irradiation (TBI) and bone marrow transplantation (BMT) for ALL, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), myelodysplastic syndrome (MDS), malignant lymphoma, and aplastic anemia (AA). Age at diagnosis ranged from 2 to 15 years old, and 28 were males and 14 were females. All patients were disease-free more than 2 years after diagnosis. Of 42 patients, 4 patients had decreased height (less than -2 S.D.), 3 patients required hormone replacement therapy, 2 patients had mental retardation, 3 patients had leukoencephalopathy, and 1 patient had a second malignancy. Except for the cases of decreased height, 3 of 7 late adverse effects were occurred in patients who had relapse of disease, and the risk of the adverse effects seemed to be higher for those patients whose doses of PCI were 22 Gy or more, or who received an additional craniospinal irradiation due to relapse of disease, and 18 Gy of PCI did not increase the risk of adverse effects. (author)

  2. A Serious Adverse Effect of Pseudoephedrine Used For Common Cold Treatment : Ventricular Arrhythmia

    Directory of Open Access Journals (Sweden)

    Cenk Aypak

    2013-06-01

    Full Text Available Common cold is one of the frequently seen disease in childhood. Pseudoephedrine hydrochloride (PEH is a sympathomimetic drug which is widely used for treatment of common cold as a decongestant on children. The aim of this case report is, to draw attention to serious adverse effects of PEH treatment. [Cukurova Med J 2013; 38(3.000: 506-510

  3. Adverse effects of radical vaginal surgery and radiotherapy on ureteral function, their prevention and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pockrandt, H.; Jorde, A.

    1973-03-01

    The adverse effects of carcinoma therapy on ureteral function are described and placed in relationship to each other. The most essential precautions in prophylaxis and therapy before, during, and after surgery are described in detail. A delayed prophylaxis of a urological study in conjunction with recidivism study must be made. (JSR)

  4. Risk of serious adverse effects of biological and targeted drugs in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Eric Furst, Daniel; Boers, Maarten

    2017-01-01

    Objectives.: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA. Methods.: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized...... differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs. Systematic review registration number.: PROSPERO CRD42014014842....

  5. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

    NARCIS (Netherlands)

    Suter, Thomas M.; Procter, Marion; van Veldhuisen, Dirk J.; Muscholl, Michael; Bergh, Jonas; Carlomagno, Chiara; Perren, Timothy; Passalacqua, Rodolfo; Bighin, Claudia; Klijn, Jan G. M.; Ageev, Fail T.; Hitre, Erika; Groetz, Juergen; Iwata, Hiroji; Knap, Malgorzata; Gnant, Michael; Muehlbauer, Susanne; Spence, Alison; Gelber, Richard D.; Piccart-Gebhart, Martine J.

    2007-01-01

    Purpose The purpose of this analysis was to investigate trastuzumab- associated cardiac adverse effects in breast cancer patients after completion of ( neo) adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant ( HERA) trial is a three- group, multicenter,

  6. Adverse Effect of Child Abuse Victimization among Substance-Using Women in Treatment.

    Science.gov (United States)

    Kang, Sung-Yeon; Magura, Stephen; Laudet, Alexandre; Whitney, Shirley

    1999-01-01

    Study examined adverse effects of childhood sexual/physical abuse among substance-abusing women with children. Several significant differences between abused and nonabused women were found in service outcomes. Abused women had more problems relating to drug use and psychiatric/psychological adjustment at follow-up. Findings support a need for…

  7. Adverse effects of extra-articular corticosteroid injections: A systematic review

    NARCIS (Netherlands)

    A. Brinks (Tineke); B.W. Koes (Bart); A.C. Volkers (Aloysius); J.A.N. Verhaar (Jan); S.M. Bierma-Zeinstra (Sita)

    2010-01-01

    textabstractBackground. To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection. Methods. A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case

  8. The economic cost of adverse health effects from wildfire-smoke exposure: A review

    Science.gov (United States)

    Ikuho Kochi; Geoffrey H. Donovan; Patricia A. Champ; John B. Loomis

    2010-01-01

    The economic costs of adverse health effects associated with exposure to wildfire smoke should be given serious consideration in determining the optimal wildfire management policy. Unfortunately, the literature in this research area is thin. In an effort to better understand the nature of these economic costs, we review and synthesise the relevant literature in three...

  9. A man who wanted to commit suicide by hanging himself: an adverse effect of ciprofloxacin.

    Science.gov (United States)

    Ahmed, Amir I A; van der Heijden, Frank M M A; van den Berkmortel, Hanneke; Kramers, Kees

    2011-01-01

    In this case report, we describe a man who developed recurrent depression and suicidal ideation with a serious plan to commit suicide as definite adverse effect of ciprofloxacin, which had been prescribed for recurrent prostatitis. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. The Impact of Perceived Adverse Effects on Medication Changes in Heart Failure Patients

    NARCIS (Netherlands)

    De Smedt, Ruth H. E.; Jaarsma, Tiny; Haaijer-Ruskamp, Flora M.; Denig, Petra

    Background: Given the importance of patient safety and well-being, we quantified the likelihood and type of medication changes observed after 5 possible adverse effects (AE) perceived by heart failure (HF) patients. Methods and Results: We conducted a retrospective cohort study using 18 months

  11. Perceived medication adverse effects and coping strategies reported by chronic heart failure patients

    NARCIS (Netherlands)

    De Smedt, R.H.E.; Denig, P.; Haaijer-Ruskamp, F.M.; Jaarsma, T.

    Data on medication adverse effects (AEs) in chronic heart failure (CHF) are primarily based on results from clinical trials. Little is known about AEs perceived by CHF patients in daily practice and how patients deal with these subjective AEs. To describe the scope and nature of perceived AEs of CHF

  12. Adverse reactions, psychological factors, and their effect on donor retention in men and women

    NARCIS (Netherlands)

    Veldhuizen, I.; Atsma, F.; Dongen, A. van; Kort, W. de

    2012-01-01

    BACKGROUND: This study investigates the effect of a vasovagal reaction (VVR) or needle reaction (NR) on the risk of stopping as a blood donor, taking into account variables from the Theory of Planned Behavior (TPB). Is stopping risk solely related to the adverse reaction itself, or do the TPB

  13. The Influence of Adverse Effects on Quality of Life of Survivors of Gynecologic Cancer.

    Science.gov (United States)

    Omichi, Chiaki; Nakamura, Keiichiro; Haraga, Junko; Ida, Naoyuki; Saijo, Masayuki; Nishida, Takeshi; Kusumoto, Tomoyuki; Masuyama, Hisashi

    2017-11-01

    The objective of this observational study was to investigate correlations between adverse effects (lower-extremity lymphedema [LEL], dysuria, and severe gastrointestinal symptoms) and quality of life (QOL) (physical well-being [PWB], social well-being, emotional well-being [EWB], and functional well-being) before treatment, at least 6 weeks after treatment (posttreatment1), and 3 or 6 months after treatment (posttreatment2) of patients with gynecologic cancer (GC). From August 2012 to October 2016, questionnaire responses and clinical data of 75 patients with GC were collected and assessed by treatment received. The χ test was used to determine the significance of correlations. Participants with LEL had significantly poorer QOL than did those without it in the domains of PWB at posttreatment1 (P = 0.026) and EWB at posttreatment2 (P = 0.020). Moreover, patients with 2 adverse effects (LEL plus dysuria or severe gastrointestinal symptoms) had significantly poorer QOL than did those with no or single adverse effect in the domains of PWB at posttreatment1 and posttreatment2 (posttreatment1: P = 0.049, P = 0.001; posttreatment2: P = 0.002, P = 0.028) and poorer QOL compared with those with no adverse effect in the domain of EWB at posttreatment1 (P = 0.017). Poorer QOL in emotional and physical domains is associated with adverse effects of treatment in patients with GC. It is important to consider the effects of radical therapy not only on survival but also on the QOL of survivors.

  14. Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis

    DEFF Research Database (Denmark)

    Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens Einar

    2015-01-01

    BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk......-clinical control persons matched by gender, age and parents' socio-economic status. Assessment included the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Eighty-nine percent of the FEP group reported one or more adversities compared to 37......% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p

  15. The Role of Mindfulness in Reducing the Adverse Effects of Childhood Stress and Trauma

    Science.gov (United States)

    Ortiz, Robin; Sibinga, Erica M.

    2017-01-01

    Research suggests that many children are exposed to adverse experiences in childhood. Such adverse childhood exposures may result in stress and trauma, which are associated with increased morbidity and mortality into adulthood. In general populations and trauma-exposed adults, mindfulness interventions have demonstrated reduced depression and anxiety, reduced trauma-related symptoms, enhanced coping and mood, and improved quality of life. Studies in children and youth also demonstrate that mindfulness interventions improve mental, behavioral, and physical outcomes. Taken together, this research suggests that high-quality, structured mindfulness instruction may mitigate the negative effects of stress and trauma related to adverse childhood exposures, improving short- and long-term outcomes, and potentially reducing poor health outcomes in adulthood. Future work is needed to optimize implementation of youth-based mindfulness programs and to study long-term outcomes into adulthood. PMID:28264496

  16. The Role of Mindfulness in Reducing the Adverse Effects of Childhood Stress and Trauma

    Directory of Open Access Journals (Sweden)

    Robin Ortiz

    2017-02-01

    Full Text Available Research suggests that many children are exposed to adverse experiences in childhood. Such adverse childhood exposures may result in stress and trauma, which are associated with increased morbidity and mortality into adulthood. In general populations and trauma-exposed adults, mindfulness interventions have demonstrated reduced depression and anxiety, reduced trauma-related symptoms, enhanced coping and mood, and improved quality of life. Studies in children and youth also demonstrate that mindfulness interventions improve mental, behavioral, and physical outcomes. Taken together, this research suggests that high-quality, structured mindfulness instruction may mitigate the negative effects of stress and trauma related to adverse childhood exposures, improving short- and long-term outcomes, and potentially reducing poor health outcomes in adulthood. Future work is needed to optimize implementation of youth-based mindfulness programs and to study long-term outcomes into adulthood.

  17. Adverse effects and Drug Interactions Associated with Inhaled Recreational and Medical Marijuana

    Directory of Open Access Journals (Sweden)

    Maisha Kelly Freeman

    2016-06-01

    Full Text Available Objectives: To provide an overview of the addiction potential; adverse effects (e.g., cardiovascular, immune dysfunction, respiratory system, mental health disorders; drug interactions; effects of accidental exposure; crime statistics; and pharmacist’s considerations for the use of inhaled medical marijuana. Methods: A PubMed search was conducted from 1966 to March 2016 to identify articles in which the safety of inhaled medical marijuana was assessed. Key MeSH search terms included medical marijuana with a subheading for adverse effect. Only articles in adult patients were considered. In addition, medical marijuana or cannabis plus one of the following search terms were searched: drug interactions, herb-drug interactions, drug-related side effects and adverse drug reactions, substance-related disorders, addiction, and abuse. A free-text search was also conducted to identify articles not included in the MeSH term search. A bibliographic search was also conducted. Articles were included if they addressed adverse effects of medical marijuana for the treatment of a condition. Meta-analyses, randomized controlled clinical trials, and case reports were included in the review if the primary focus of the article related to the adverse effect profile of inhaled medical marijuana. Medical marijuana efficacy studies were not assessed. In the absence of this information, case reports or reports of inhaled recreational marijuana use was used. Studies were excluded if published in languages other than English. In addition, studies highlighting mechanisms of action, studies of pharmacodynamics or pharmacokinetic effects were excluded, unless these effects were due to drug-drug interactions. Prescription products containing marijuana or derivatives were excluded from evaluation. An Internet search was conducted to locate the most up-to-date information on the laws concerning medical marijuana. Key findings: A PubMed search revealed 58 articles and 28 of

  18. The adverse effect of real effective exchange rate change on trade balance in European transition countries

    Directory of Open Access Journals (Sweden)

    Selena Begović

    2017-12-01

    Full Text Available Most European transition countries have fixed or highly managed flexible exchange rate regimes. This exchange rate rigidity is sometimes argued to worsen the trade balance by keeping the currency overvalued. However, there is no unambiguous evidence that currency depreciation/devaluation positively affects trade balance and leads towards the adjustment, even in the short-run. Therefore, we examine the effect of real effective exchange rate (hereafter REER on trade balance in European transition economies over the period 2000-2015. By using fixed effect model for static and generalised method of moments for dynamic estimation, we find that there is an adverse effect of the REER on trade balance in European transition countries over the period 2000-2015. Namely, depreciation of REER deteriorates trade balance in European transition countries, which could be explained by high import dependence and low export capacity. This implies that policymakers in European transition countries should not use exchange rate policy to improve trade balance. This is important in the light of their accession towards European economic and monetary integration, implying that these countries should focus more on using fiscal, rather than monetary (and exchange rate, policy to adjust trade balance, which is one of the required real convergence towards the EU standards.

  19. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    Directory of Open Access Journals (Sweden)

    Herxheimer Andrew

    2002-03-01

    Full Text Available Abstract Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

  20. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

    OpenAIRE

    Bain, Emily S; Middleton, Philippa F; Crowther, Caroline A

    2013-01-01

    Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studi...

  1. Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China.

    Science.gov (United States)

    Wu, Junyi; Hu, Yanmei; Zhu, Yin; Yin, Ping; Litscher, Gerhard; Xu, Shifen

    2015-01-01

    As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world.

  2. Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

    Science.gov (United States)

    Wu, Junyi; Hu, Yanmei; Zhu, Yin; Yin, Ping; Xu, Shifen

    2015-01-01

    As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world. PMID:26339265

  3. Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

    Directory of Open Access Journals (Sweden)

    Junyi Wu

    2015-01-01

    Full Text Available As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world.

  4. Adverse effects of industrial multiwalled carbon nanotubes on human pulmonary cells

    Science.gov (United States)

    Tabet, Lyes; Bussy, Cyrill; Amara, Nadia; Setyan, Ari; Grodet, Alain; Rossi, Michel J.; Pairon, Jean-Claude; Boczkowski, Jorge; Lanone, Sophie

    2009-01-01

    The aim of this study was to evaluate adverse effects of multi-walled carbon nanotubes (MWCNT) produced for industrial purposes, on the human epithelial cell line A549. MWCNT were dispersed in dipalmitoyl lecithin (DPL), a component of pulmonary surfactant, and the effects of dispersion in DPL were compared to those in 2 other media: ethanol (EtOH) and phosphate buffer saline (PBS). Effects of MWCNT were also compared to those of 2 asbestos fibers (chrysotile and crocidolite) and carbon black (CB) nanoparticles, not only in A549 cells, but also on mesothelial cells (MeT5A human cell line), used as an asbestos-sensitive cell type. MWCNT formed agglomerates on top of both cell lines (surface area 15–35 μm2), that were significantly larger and more numerous in PBS than in EtOH and DPL. Whatever the dispersion media, incubation with 100 μg/ml MWCNT induced a similar decrease in metabolic activity without changing cell membrane permeability or apoptosis. Neither MWCNT cellular internalization nor oxidative stress were observed. In contrast, asbestos fibers penetrated into the cells, decreased metabolic activity but not cell membrane permeability and increased apoptosis, without decreasing cell number. CB was internalized without any adverse effects. In conclusion, this study demonstrates that MWCNT produced for industrial purposes exert adverse effects without being internalized by human epithelial and mesothelial pulmonary cell lines. PMID:19034795

  5. Mining multi-item drug adverse effect associations in spontaneous reporting systems

    Directory of Open Access Journals (Sweden)

    Chase Herbert S

    2010-10-01

    Full Text Available Abstract Background Multi-item adverse drug event (ADE associations are associations relating multiple drugs to possibly multiple adverse events. The current standard in pharmacovigilance is bivariate association analysis, where each single drug-adverse effect combination is studied separately. The importance and difficulty in the detection of multi-item ADE associations was noted in several prominent pharmacovigilance studies. In this paper we examine the application of a well established data mining method known as association rule mining, which we tailored to the above problem, and demonstrate its value. The method was applied to the FDAs spontaneous adverse event reporting system (AERS with minimal restrictions and expectations on its output, an experiment that has not been previously done on the scale and generality proposed in this work. Results Based on a set of 162,744 reports of suspected ADEs reported to AERS and published in the year 2008, our method identified 1167 multi-item ADE associations. A taxonomy that characterizes the associations was developed based on a representative sample. A significant number (67% of the total of potential multi-item ADE associations identified were characterized and clinically validated by a domain expert as previously recognized ADE associations. Several potentially novel ADEs were also identified. A smaller proportion (4% of associations were characterized and validated as known drug-drug interactions. Conclusions Our findings demonstrate that multi-item ADEs are present and can be extracted from the FDA’s adverse effect reporting system using our methodology, suggesting that our method is a valid approach for the initial identification of multi-item ADEs. The study also revealed several limitations and challenges that can be attributed to both the method and quality of data.

  6. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume

    Directory of Open Access Journals (Sweden)

    Nicholas D. Walsh

    2014-01-01

    Full Text Available Exposure to childhood adversities (CA is associated with subsequent alterations in regional brain grey matter volume (GMV. Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age = 18.4 with (n = 27 or without (n = 31 CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE recorded at 14 and 17 years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life.

  7. Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

    Science.gov (United States)

    El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

    2011-09-01

    Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

  8. Sacroiliitis after use of oral isotretinoin - association with acne fulminans or adverse effect?*

    Science.gov (United States)

    Geller, Ariane Silva Bastos; Alagia, Roberta Ferreira Nazareth

    2013-01-01

    Acne fulminans is a rare and severe form of acne that may evolve from acne vulgaris, especially in male adolescents, or occur as an adverse effect of oral isotretinoin. Arthritis is a serious clinical manifestation when the musculoskeletal system is compromised by AF and has been reported as a rare adverse effect of isotretinoin. Involvement of the sacroiliac joints occurs in 21% of acne fulminans cases. We present the case of a 18-year-old male patient in whom acne fulminans evolved from acne vulgaris grade IV and after inflammation resolution started treatment with oral isotretinoin. Within a 30-day period of retinoid treatment he presented with back pain followed by rapid, progressive inability to deambulate. PMID:24346917

  9. Statistical Mining of Potential Drug Interaction Adverse Effects in FDA’s Spontaneous Reporting System

    Science.gov (United States)

    Harpaz, Rave; Haerian, Krystl; Chase, Herbert S.; Friedman, Carol

    2010-01-01

    Many adverse drug effects (ADEs) can be attributed to drug interactions. Spontaneous reporting systems (SRS) provide a rich opportunity to detect novel post-marketed drug interaction adverse effects (DIAEs), as they include populations not well represented in clinical trials. However, their identification in SRS is nontrivial. Most existing research have addressed the statistical issues used to test or verify DIAEs, but not their identification as part of a systematic large scale database-wide mining process as discussed in this work. This paper examines the application of a highly optimized and tailored implementation of the Apriori algorithm, as well as methods addressing data quality issues, to the identification of DIAEs in FDAs SRS. PMID:21346985

  10. A Cohort Study on Long-Term Adverse Effects of Parental Drinking: Background and Study Design

    Directory of Open Access Journals (Sweden)

    Ingunn Olea Lund

    2015-01-01

    Full Text Available Although many studies have addressed adverse outcomes in children of parents with alcohol abuse/dependence, less is known about the possible long-term effects of more normative patterns of parental alcohol consumption, including drinking at lower risk levels and heavy episodic or binge drinking. The extent of harm from parental drinking may therefore be underestimated. With this research proposal, we describe a project that aims to assess possible long-term adverse effects of parental drinking by combining survey and nationwide registry data. Advantages of a longitudinal general population cohort design include that it allows for detailed information on parental drinking through survey data and identification of possible negative long-term health and social outcomes from exposure to parental drinking 1–19 years after exposure through continuously updated nationwide registers. The rich information available from combining survey and registry data allows us to take into account important confounders, mediators, and moderators.

  11. [Management of adverse effects related to human immunoglobulin therapy: Recommendations for clinical practice].

    Science.gov (United States)

    Marie, I; Chérin, P; Michallet, M; Pelus, E; Dantal, J; Crave, J-C; Delain, J-C; Viallard, J-F

    2017-05-01

    Both intravenous and subcutaneous immunoglobulins are therapeutic modalities approved in various conditions, including primary and secondary immune deficiencies and autoimmune disorders. To date, immunoglobulins have more often been considered as a safe medication, with minor adverse effects such as hypertension, fever and chills, nausea, myalgia or headache. However, with the wider use of immunoglobulins in the treatment of autoimmune diseases, severe side effects have also been reported to occur in immunoglobulin-treated patients, especially anaphylaxis, aseptic meningitis, acute renal impairment, thrombotic events as well as haematological manifestations. This paper reviews all the potential adverse events related to immunoglobulin therapy and establishes a comprehensive guideline for the management of these events. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  12. Finasteride adverse effects and post-finasteride syndrome; implications for dentists

    OpenAIRE

    Stana Paunica; Marina Giurgiu; Andrei Vasilache; Ioana Paunica; Ion Motofei; Adriana Vasilache; Horia Traian Dumitriu; Anca Silvia Dumitriu

    2016-01-01

    Finasteride is a 5α-reductase inhibitor widely used in present in the therapeutic approach of androgenic alopecia. Adverse effects consist in variable sign and symptoms, the most common being represented by mental troubles (reduced feeling of life pleasure or emotions, depression), physical impairments (loss of muscle tone and/or mass) and sexual complains (loss of libido and sexual potency). An increasing number of studies identify and describe even a post-finasteride syndrome (persistent ad...

  13. Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark; Gentili, Fred [Gamma Knife Unit, Division of Neurosurgery, University Health Network, Toronto (Canada); Heydarian, Mostafa; Tsao, May [Radiation Medicine Program, Princess Margaret Hospital, Toronto (Canada); Schwartz, Michael [Radiation Oncology Program and Division of Neurosurgery, Sunnybrook Hospital, Toronto (Canada); Prooijen, Monique van [Radiation Medicine Program, Princess Margaret Hospital, Toronto (Canada); Millar, Barbara-Ann; Menard, Cynthia [Radiation Oncology Program, Princess Margaret Hospital, Toronto (Canada); Kulkarni, Abhaya V. [Division of Neurosurgery, Hospital for Sick Children, University of Toronto (Canada); Laperriere, Norm [Radiation Oncology Program, Princess Margaret Hospital, Toronto (Canada); Zadeh, Gelareh, E-mail: Gelareh.Zadeh@uhn.on.ca [Gamma Knife Unit, Division of Neurosurgery, University Health Network, Toronto (Canada)

    2012-04-01

    Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; and trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.

  14. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

    Science.gov (United States)

    Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

    2012-04-15

    Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine.

  15. Rodenticide incidents of exposure and adverse effects on non-raptor birds

    Science.gov (United States)

    Vyas, Nimish B.

    2017-01-01

    Interest in the adverse effects of rodenticides on birds has focused primarily on raptors. However, non-raptor birds are also poisoned (rodenticide exposure resulting in adverse effects including mortality) by rodenticides through consumption of the rodenticide bait and contaminated prey. A literature search for rodenticide incidents (evidence of exposure to a rodenticide, adverse effects, or exposure to placebo baits) involving non-raptor birds returned 641 records spanning the years 1931 to 2016. The incidents included 17 orders, 58 families, and 190 non-raptor bird species. Nineteen anticoagulant and non-anticoagulant rodenticide active ingredients were associated with the incidents. The number of incidents and species detected were compared by surveillance method. An incident was considered to have been reported through passive surveillance if it was voluntarily reported to the authorities whereas the report of an incident found through field work that was conducted with the objective of documenting adverse effects on birds was determined to be from active surveillance. More incidents were reported from passive surveillance than with active surveillance but a significantly greater number of species were detected in proportion to the number of incidents found through active surveillance than with passive surveillance (z = 7.61, p < 0.01). Results suggest that reliance on only one surveillance method can underestimate the number of incidents that have occurred and the number of species that are affected. Although rodenticides are used worldwide, incident records were found from only 15 countries. Therefore, awareness of the breadth of species diversity of non-raptor bird poisonings from rodenticides may increase incident reportings and can strengthen the predictions of harm characterized by risk assessments.

  16. Knowledge synthesis of benefits and adverse effects of measles vaccination: the Lasbela balance sheet

    OpenAIRE

    Andersson Neil; Fleming John; Ledogar Robert J

    2009-01-01

    Abstract Background In preparation for a cluster-randomized controlled trial of a community intervention to increase the demand for measles vaccination in Lasbela district of Pakistan, a balance sheet summarized published evidence on benefits and possible adverse effects of measles vaccination. Methods The balance sheet listed: 1) major health conditions associated with measles; 2) the risk among the unvaccinated who contract measles; 3) the risk among the vaccinated; 4) the risk difference b...

  17. Adverse effects to transfusion with red donor blood cells are frequent

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Nørgaard, Astrid; Burcharth, Jakob

    2014-01-01

    Adverse effects to transfusion with red donor blood cells are potentially life-threatening. Due to screening, transmission of infectious diseases has decreased; however, the risk is still present. Various immune reactions are common including simple allergic reactions as well as devastating...... conditions such as transfusion-related acute lung injury and circulatory overload in patients with heart disease. Knowledge of the clinical signs of transfusion-related complications is important for clinicians in order to provide the best possible treatment....

  18. [Adverse effects to transfusion with red donor blood cells are frequent].

    Science.gov (United States)

    Pommergaard, Hans-Christian; Nørgaard, Astrid; Burcharth, Jakob; Larsen, Rune; Rosenberg, Jacob

    2014-03-31

    Adverse effects to transfusion with red donor blood cells are potentially life-threatening. Due to screening, transmission of infectious diseases has decreased; however, the risk is still present. Various immune reactions are common including simple allergic reactions as well as devastating conditions such as transfusion-related acute lung injury and circulatory overload in patients with heart disease. Knowledge of the clinical signs of transfusion-related complications is important for clinicians in order to provide the best possible treatment.

  19. Cumulative Effects of Neighborhood Social Adversity and Personal Crime Victimization on Adolescent Psychotic Experiences.

    Science.gov (United States)

    Newbury, Joanne; Arseneault, Louise; Caspi, Avshalom; Moffitt, Terrie E; Odgers, Candice L; Fisher, Helen L

    2018-02-15

    Little is known about the impact of urbanicity, adverse neighborhood conditions and violent crime victimization on the emergence of adolescent psychotic experiences. Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins who were interviewed about adolescent psychotic experiences at age 18. Urbanicity, neighborhood characteristics, and personal victimization by violent crime were measured during childhood and adolescence via geocoded census data, surveys of over 5000 immediate neighbors of the E-Risk participants, and interviews with participants themselves. Adolescents raised in urban vs rural neighborhoods were significantly more likely to have psychotic experiences (OR = 1.67, 95% CI = 1.21-2.30, P = .002). This association remained significant after considering potential confounders including family socioeconomic status, family psychiatric history, and adolescent substance problems (OR = 1.43, 95% CI = 1.01-2.03, P = .042), but became nonsignificant after considering adverse social conditions in urban neighborhoods such as low social cohesion and high neighborhood disorder (OR = 1.35, 95% CI = 0.94-1.92, P = .102). The combined association of adverse neighborhood social conditions and personal crime victimization with adolescent psychotic experiences (adjusted OR = 4.86, 95% CI = 3.28-7.20, P crime victimization (interaction contrast ratio = 1.81, 95% CI = -0.03 to 3.65) that was significant at the P = .054 level. Cumulative effects of adverse neighborhood social conditions and personal victimization by violent crime during upbringing partly explain why adolescents in urban settings are more likely to report psychotic experiences. Early intervention efforts for psychosis could be targeted towards victimized youth living in urban and socially adverse neighborhoods.

  20. Cell-type specific DNA-protein interactions at the tissue-type plasminogen activator promoter in human endothelial and HeLa cells in vivo and in vitro.

    Science.gov (United States)

    Arts, J; Herr, I; Lansink, M; Angel, P; Kooistra, T

    1997-01-15

    B and Fra-2. In the light of previous studies involving mutational analysis of the human and murine t-PA promoter our results underline an important role of the five identified promoter regions in basal and PMA-stimulated t-PA gene expression in intact human endothelial cells and HeLa cells. The small differences in DMS protection pattern and differences in the individual AP-1 components bound in endothelial cells and HeLa cells point to subtle cell-type specific differences in t-PA gene regulation.

  1. The Potential Return on Public Investment in Detecting Adverse Drug Effects.

    Science.gov (United States)

    Huybrechts, Krista F; Desai, Rishi J; Park, Moa; Gagne, Joshua J; Najafzadeh, Mehdi; Avorn, Jerry

    2017-06-01

    Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present. These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.

  2. Air pollution in India and related adverse respiratory health effects: past, present, and future directions.

    Science.gov (United States)

    Khilnani, Gopi C; Tiwari, Pawan

    2018-03-01

    The review describes current status of air pollution in India, summarizes recent research on adverse health effects of ambient and household air pollution, and outlines the ongoing efforts and future actions required to improve air quality and reduce morbidity and mortality because of air pollution in India. Global burden of disease data analysis reveals more than one million premature deaths attributable to ambient air pollution in 2015 in India. More than one million additional deaths can be attributed to household air pollution. Particulate matter with diameter 2.5 μm or less has been causatively linked with most premature deaths. Acute respiratory tract infections, asthma, chronic obstructive pulmonary disease, exacerbations of preexisting obstructive airway disease and lung cancer are proven adverse respiratory effects of air pollution. Targeting air quality standards laid by WHO can significantly reduce morbidity and mortality because of air pollution in India. India is currently exposed to high levels of ambient and household air pollutants. Respiratory adverse effects of air pollution are significant contributors to morbidity and premature mortality in India. Substantial efforts are being made at legislative, administrative, and community levels to improve air quality. However, much more needs to be done to change the 'status quo' and attain the target air quality standards. VIDEO ABSTRACT: http://links.lww.com/COPM/A24.

  3. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

    Science.gov (United States)

    Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

    2014-01-01

    Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Multi-omic landscape of Rheumatoid Arthritis: re-evaluation of drug adverse effects

    Directory of Open Access Journals (Sweden)

    Paolo eTieri

    2014-11-01

    Full Text Available Objective: To provide a frame to estimate the systemic impact (side/adverse events of (novel therapeutic targets by taking into consideration drugs potential on the numerous districts involved in rheumatoid arthritis (RA from the inflammatory and immune response to the gut-intestinal (GI microbiome.Methods: We curated the collection of molecules from high-throughput screens of diverse (multi-omic biochemical origin, experimentally associated to RA. Starting from such collection we generated RA-related protein-protein interaction (PPI networks (interactomes based on experimental PPI data. Pharmacological treatment simulation, topological and functional analyses were further run to gain insight into the proteins most affected by therapy and by multi-omic modelling.Results: Simulation on the administration of MTX results in the activation of expected (apoptosis and adverse (nitrogenous metabolism alteration effects. Growth factor receptor-bound protein 2 (GRB2 and Interleukin-1 Receptor Associated Kinase-4 (IRAK4, already an RA target emerge as relevant nodes. The former controls the activation of inflammatory, proliferative and degenerative pathways in host and pathogens. The latter controls immune alterations and blocks innate response to pathogens.Conclusions: This multi-omic map properly recollects in a single analytical picture known, yet complex, information like the adverse/side effects of MTX, and provides a reliable platform for in silico hypothesis testing or recommendation on novel therapies. These results can support the development of RA translational research in the design of validation experiments and clinical trials, as such we identify GRB2 as a robust potential new target for RA for its ability to control both synovial degeneracy and dysbiosis, and, conversely, warn on the usage of IRAK4-inhibitors recently promoted, as this involves potential adverse effects in the form of impaired innate response to pathogens.

  5. Adverse effects of parenteral dexamethasone in the treatment of pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Mohammad Jamal Uddin

    2016-08-01

    Full Text Available Background: Pemphigus vulgaris is associated with high morbidity as well as significant mortality rate. Today the risk of death in pemphigus from the side effect of oral prednisolone is greater than risk of death from the disease itself. Objec­tive: To observe the adverse effects of parenteral dexamethasone compared with oral prednisolone in the treatment of pemphigus vulgaris. Methods: An interventional study was carried out in the department of Dermatology and Venereol­ogy, Bangabandu Sheikh Mujib Medical University, Dhaka, Bangladesh. Total number of patients was thirty and among them fifteen patients were treated with parenteral dexamethasone (Group-A and other fifteen were treated with oral prednisolone (Group-B. Results: The study showed statistically significant differences of skin lesion as well as mucosal lesion of pemphigus after 6 weeks of therapy between of two groups (P<0.05. The most common adverse effects were increased body weight(40%, increased appetite(40%, and puffy face(40% in dexamethasone group. In prednisolone group, these side effects were 60% of the subjects. Other side effects in dexamethasone group were hyperglycemia (33.33%, hypertension (26.66%, and sleep disturbance (13.33%. In prednisolone group, other side effects were hyperglycemia(33.33%, hypertension(40%, gastritis (33.33%, nausea, vomiting (13.33% in each , reactivation of tuberculosis, herpes zoster infection, sleep disturbance, and mood change were 6.66% in each group. Conclusion: In the light of the findings of the study, we conclude that each of the treatment of dexamethasone group and prednisolone group is individually effective and safe in the treatment of pemphigus vulgaris but adverse effects are less in parenteral dexamethasone group than oral prednisolone group. So parenteral dexamethasone can be used as an alternative drug in the treatment of pemphigus vulgaris.

  6. The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver

    Directory of Open Access Journals (Sweden)

    Markus Heine

    2014-09-01

    Full Text Available Semiconductor quantum dots (QD and superparamagnetic iron oxide nanocrystals (SPIO have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene (PMAOD. The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr-/- as well as Apoe-/- mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα or chemokine (C-X-C motif ligand 10 (Cxcl10 indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications.

  7. Cannabis: an overview of its adverse acute and chronic effects and their implications.

    Science.gov (United States)

    Ford, Talitha C; Hayley, Amie C; Downey, Luke A; Parrott, Andrew C

    2017-07-12

    In many communities, cannabis is perceived as a low-risk drug, leading to political lobbying to decriminalise its use. However, acute and chronic cannabis use has been shown to be harmful to several aspects of psychological and physical health, such as mood states, psychiatric outcomes, neurocognition, driving and general health. Furthermore, cannabis is highly addictive, and the adverse effects of withdrawal can lead to regular use. These in turn have adverse implications for public safety and health expenditure. Although the cannabinoid cannabidiol (CBD) has been shown to have positive health outcomes with its antioxidant, anticonvulsant, anti-inflammatory and neuroprotective properties, high-potency cannabis is particularly damaging due to its high tetrahydrocannabinol (THC), low CDB concentration. It is this high-potency substance that is readily available recreationally. While pharmaceutical initiatives continue to investigate the medical benefits of CDB, "medicinal cannabis" still contains damaging levels of THC. Altogether, we argue there is insufficient evidence to support the safety of cannabis and its subsequent legalisation for recreational use. Furthermore, its use for medicinal purposes should be done with care. We argue that the public conversation for the legalisation of cannabis must include scientific evidence for its adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Best–worst scaling survey of preferences regarding the adverse effects of tobacco use in China

    Directory of Open Access Journals (Sweden)

    Takeshi Mori

    2017-12-01

    Full Text Available We use best–worst scaling to assess two types of concern levels of the adverse consequences of smoking in China. While the smoking cessation policy has worked well in Taiwan, more than 1 million people in mainland China are estimated to die every year from tobacco use. This study compares the preferences of Chinese individuals in the two jurisdictions (mainland versus Taiwan and explores the possibility of information-based interventions. The relative importance of 13 adverse effects was assessed by conducting a web-based survey on a sample of 480 Chinese participants. The 13 items consist of various adverse effects of tobacco use: from long-term health risk, such as lung cancer and cardiovascular diseases, to reduction of physical capacity and sexual dysfunction, and disturbance to non-smokers. The resulting data suggest possible strategies to curb smoking. Subgroup analysis, focusing on gender, smoking status, and nicotine dependence, was also conducted. Lung cancer, cardiovascular diseases, and chronic obstructive pulmonary disease, in this order, rank highest for both types of respondents. On the other hand, high expenditures (13th and weight gain after cessation (12th are the lowest ranked for both. Measuring individual best–worst scores reveals substantial heterogeneity among respondents and that information-based intervention can help curb smoking.

  9. Infant titi monkey behavior in the open field test and the effect of early adversity.

    Science.gov (United States)

    Larke, Rebecca H; Toubiana, Alice; Lindsay, Katrina A; Mendoza, Sally P; Bales, Karen L

    2017-09-01

    The open field test is commonly used to measure anxiety-related behavior and exploration in rodents. Here, we used it as a standardized novel environment in which to evaluate the behavioral response of infant titi monkeys (Callicebus cupreus), to determine the effect of presence of individual family members, and to assess how adverse early experience alters infant behavior. Infants were tested in the open field for 5 days at ages 4 and 6 months in four successive 5 min trials on each day. A transport cage, which was situated on one side of the open field, was either empty (non-social control) or contained the father, mother, or sibling. Infant locomotor, vocalization, and exploratory behavior were quantified. Results indicated that age, sex, social condition, and early experience all had significant effects on infant behavior. Specifically, infants were generally more exploratory at 6 months and male infants were more exploratory than females. Infants distinguished between social and non-social conditions but made few behavioral distinctions between the attachment figure and other individuals. Infants which had adverse early life experience demonstrated greater emotional and physical independence, suggesting that early adversity led to resiliency in the novel environment. © 2017 Wiley Periodicals, Inc.

  10. Nonlinear and Dynamic Aerodynamic Models for Commercial Transport Aircraft with Adverse Weather Effects

    Directory of Open Access Journals (Sweden)

    Ray C. Chang

    2010-01-01

    Full Text Available The flight dynamic equations in mathematics for aircraft response to the adverse weathers, such as wind shear, atmospheric turbulence, and in-flight icing, are nonlinear and unsteady. To effectively analyze the performance degradation and variations in stability of commercial aircraft that encountered these weather hazards, the nonlinear and dynamic (i.e., time dependent aerodynamic models based on flight data would be needed. In the present paper, a numerical modeling method based on a fuzzy-logic algorithm will be presented to estimate the aerodynamic models for a twin-jet transport by using the flight data from the flight data recorder (FDR. The aerodynamic models having the capability to generate continuous stability derivatives, especially for sensitivity study of unknown factors in adverse weather conditions, will be demonstrated in this paper.

  11. Drag-Reduction Effectiveness of Riblet Films in Adverse Pressure Gradients

    Science.gov (United States)

    Boomsma, Aaron; Sotiropoulos, Fotis

    2013-11-01

    Riblet films are micro-grooved structures that are widely known to passively reduce skin friction. Past studies have almost solely focused on riblet performance in channel-flows. However, possible applications of riblets include wind turbine blades, gas turbine blades, and other complex bodies that are exposed to non-zero pressure gradient flows--specifically adverse pressure gradients. We use high-resolution large eddy simulations of turbulent flow over three-dimensional riblets under an adverse pressure gradient. We analyze the computed results to quantify drag reduction effectiveness for different riblet shapes and to examine pertinent turbulent structures to gain a fundamental understanding of riblet performance. Supported by the DOE Wind Energy Consortium

  12. Adverse Renal Effects of Novel Molecular Oncologic Targeted Therapies: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Kenar D. Jhaveri

    2017-01-01

    Full Text Available Novel targeted anti-cancer therapies have resulted in improvement in patient survival compared to standard chemotherapy. Renal toxicities of targeted agents are increasingly being recognized. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here we review the adverse renal effects associated with a selection of currently approved targeted cancer therapies, directed to EGFR, HER2, BRAF, MEK, ALK, PD1/PDL1, CTLA-4, and novel agents targeted to VEGF/R and TKIs. In summary, electrolyte disorders, renal impairment and hypertension are the most commonly reported events. Of the novel targeted agents, ipilumumab and cetuximab have the most nephrotoxic events reported. The early diagnosis and prompt recognition of these renal adverse events are essential for the general nephrologist taking care of these patients.

  13. Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

    Science.gov (United States)

    Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

    2017-05-01

    Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

  14. Adverse reactions, psychological factors, and their effect on donor retention in men and women.

    Science.gov (United States)

    Veldhuizen, Ingrid; Atsma, Femke; van Dongen, Anne; de Kort, Wim

    2012-09-01

    This study investigates the effect of a vasovagal reaction (VVR) or needle reaction (NR) on the risk of stopping as a blood donor, taking into account variables from the Theory of Planned Behavior (TPB). Is stopping risk solely related to the adverse reaction itself, or do the TPB variables play a role as well? Emphasis is placed on possible sex differences. TPB variables were assessed within 12,051 whole blood donors. Also, donors reported the occurrence of adverse reactions during or after their last donation. Blood bank records were used to determine whether donors stopped donating within the next 2 years. Logistic regression analyses were performed to estimate the effect of self-reported adverse reactions on stopping risk, adjusting for the TPB variables. Analyses were performed separately for both sexes. Men have a lower odds of reporting a NR or a VVR than women (odds ratio [OR] 0.34, 95% confidence interval [CI], 0.28-0.43; and OR 0.26, 95% CI 0.19-0.36, for NR and VVR, respectively). For both sexes, only a VVR was associated with stopping risk, which is higher in men (men, OR 3.95, 95% CI 2.19-7.11; women, OR 1.78, 95% CI 1.35-2.35). After adjusting for the TPB variables both ORs declined (men, OR 3.38, 95% CI 1.86-6.15; women, OR 1.58, 95% CI 1.17-2.14). Also, self-efficacy and affective attitude are negatively associated with adverse reactions. Female donors report more VVRs than male donors, but male donors have a higher stopping risk after a VVR than female donors. Coping differences and possible reporting tendencies might play a role. For donor retention purposes, prevention and coping techniques should take sex differences into account. © 2012 American Association of Blood Banks.

  15. Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

    Science.gov (United States)

    DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H; Caudill, Jonathan W; Trulson, Chad R; Baglivio, Michael T

    2017-03-22

    Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered.

  16. Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

    Science.gov (United States)

    Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

    2016-06-01

    Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. Published by Elsevier Inc.

  17. The effect of adverse information and positive promotion on women's preferences for prescribed contraceptive products.

    Science.gov (United States)

    Knox, Stephanie A; Viney, Rosalie C; Gu, Yuanyuan; Hole, Arne R; Fiebig, Denzil G; Street, Deborah J; Haas, Marion R; Weisberg, Edith; Bateson, Deborah

    2013-04-01

    Recent rapid growth in the range of contraceptive products has given women more choice, but also adds complexity to the resultant decision of which product to choose. This paper uses a discrete choice experiment (DCE) to investigate the effect of adverse information and positive promotion on women's stated preferences for prescribed contraceptive products. In November 2007, 527 Australian women aged 18-49 years were recruited from an online panel. Each was randomly allocated to one of three information conditions. The control group only received basic information on contraceptive products. One treatment group also received adverse information on the risks of the combined oral pill. The other group received basic information and promotional material on the vaginal ring, newly introduced into Australia and on the transdermal patch, which is unavailable in Australia. Respondents completed 32 choice sets with 3 product options where each option was described by a product label: either combined pill, minipill, injection, implant, hormonal IUD, hormonal vaginal ring, hormonal transdermal patch or copper IUD; and by the attributes: effect on acne, effect on weight, frequency of administration, contraceptive effectiveness, doctor's recommendation, effect on periods and cost. Women's choices were analysed using a generalized multinomial logit model (G-MNL) and model estimates were used to predict product shares for each information condition. The predictions indicated that adverse information did not affect women's preferences for products relative to only receiving basic information. The promotional material increased women's preferences for the transdermal patch. Women in all groups had a low preference for the vaginal ring which was not improved by promotion. The findings highlight the need for researchers to pay attention to setting the context when conducting DCEs as this can significantly affect results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. In-hospital gastric protection with proton pump inhibitors: adverse effects beyond (overutilization?

    Directory of Open Access Journals (Sweden)

    Paolo Montanari

    2013-04-01

    Full Text Available Background: Proton pump inhibitors (PPIs have provided important benefits in the management of gastroesophageal reflux disease (GERD, peptic ulcer disease and in the prevention of non steroidal antiinflammatory drugs and aspirin-related ulcer complications. PPIs are also the most commonly used medications for stress ulcer prophylaxis, despite little evidence to support their use in non-intensive care unit. Discussion: Considering the widespread use of PPIs, these agents’ overall safety profile is unquestionable. However, there is growing evidence that PPIs use may be associated with an increased risk of enteric infections, pneumonia, hip fractures, vitamin B12 deficiency. Overall, until now, none of these adverse effects have discouraged the PPIs treatment. Recently attention has been placed on a more important potential adverse effect of PPIs, their interaction with clopidogrel to which they are associated for the prophylaxis of gastrointestinal bleeding. Preliminary results of laboratory tests suggest that omeprazole reduces clopidogrel’s antiplatelet effect. The interaction seems to involve the competitive inhibition of the CYP2C19 isoenzyme. The effect appears to be clinically important, as some retrospective studies have shown an increase in adverse cardiovascular outcomes when PPIs and clopidogrel are used concomitantly. Some studies indicate that pantoprazole and esomeprazole are not associated with impaired response to clopidogrel. However, the available data for PPIs other than omeprazole do not allow definitive conclusions to be drawn about whether is a class effect. Conclusions: Specifically designed and randomized clinical studies are needed to define the interaction between PPIs and clopidogrel. Moreover, alternative treatment strategies with histamine- 2 receptor antagonists that are not dependent on cytochrome p450 2C19 should be tested in future studies.

  19. Are the adverse effects of glitazones linked to induced testosterone deficiency?

    Directory of Open Access Journals (Sweden)

    Jankowska E

    2008-10-01

    Full Text Available Abstract Background Adverse side-effects of the glitazones have been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ and pioglitazone (PGZ, including congestive heart failure, osteoporosis, weight gain, oedema and anaemia. These led to consideration of an evidence-based hypothesis which would explain these diverse effects, and further suggested novel approaches by which this hypothesis could be tested. Presentation of hypothesis The literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of testosterone in diabetes, metabolic syndrome, and cardiovascular disease is reviewed, and the following unifying hypothesis advanced: "Glitazones induce androgen deficiency in patients with Type 2 Diabetes Mellitus resulting in pathophysiological changes in multiple tissues and organs which may explain their observed clinical adverse effects." This also provides further evidence for the lipocentric concept of diabetes and its clinical implications. Testing of the hypothesis Clinical studies to investigate the endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women with T2DM before and after RGZ and PGZ treatment in placebo controlled groups, are necessary to provide data to substantiate this hypothesis. Also, studies on T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen therapy. Basic sciences investigations on the inhibition of androgen biosynthesis by glitazones are also warranted. Implications of the hypothesis Glitazones reduce androgen biosynthesis, increase their binding to SHBG, and attenuate androgen receptor activation, thus reducing the physiological actions of testosterone, causing relative and absolute androgen deficiency. This hypothesis explains the adverse effects of glitazones on the heart and

  20. Adverse effects during specific oral tolerance induction: in-hospital "rush" phase.

    Science.gov (United States)

    Barbi, E; Longo, G; Berti, I; Neri, E; Saccari, A; Rubert, L; Matarazzo, L; Montico, M; Ventura, A

    2012-02-01

    Specific oral tolerance induction (SOTI) is a promising approach in the treatment of severe food allergies. Different protocols have demonstrated its efficacy. Nevertheless, SOTI is still considered an experimental method and should be limited to highly controlled settings. To define the incidence and severity of adverse reactions, possible risk factors, and the safety and effectiveness of nebulized epinephrine as a first-line treatment of respiratory reactions during in-hospital SOTI for cow's milk allergy. A retrospective study was conducted by reviewing the medical records of patients admitted for SOTI beginning in 2001. Reactions were classified as mild, moderate and severe on a partially modified Clark scale. Adverse reactions were treated following the International Guidelines with the introduction of nebulized epinephrine for level four reactions. Of 209 patients, 17 were excluded due to the absence of objective reactions. The remaining 192 were classified as follows: Mild Reactions (Clark Scale 1 to 3): 100 patients received either no treatment, oral antihistamines or nebulized steroids; Moderate Reactions (Clark Scale 4): 87 patients treated with nebulized epinephrine and, depending on their symptoms, oral antihistamines, corticosteroids (nebulized, oral or IV) or nebulized beta 2 agonists; Severe Reactions (Clark Scale 5): 5 children, 4 of whom initially underwent one nebulization of epinephrine and eventually required an IM dose. The fifth patient was immediately treated with IM epinephrine due to hypotension. adverse reactions during this in-hospital SOTI protocol were frequent but easily manageable. Nebulized epinephrine can play a relevant role in the treatment of respiratory reactions.

  1. Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity.

    Science.gov (United States)

    Melnik, Bodo C

    2017-02-08

    Isotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment.

  2. Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects.

    Science.gov (United States)

    Vyas, Purvi; Thakar, A B; Baghel, M S; Sisodia, Arvind; Deole, Yogesh

    2010-10-01

    Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy.

  3. Radiation exposure exerts its adverse effects on sperm maturation through estrogen-induced hypothalamohypophyseal axis inhibition in rats

    CSIR Research Space (South Africa)

    Makinta, MJ

    2005-10-01

    Full Text Available Irradiation has adverse effects on reproductive aspects such as spermatogenic cell population and cell malformation, leading to reduced sperm count and non-viable spermatozoa. This has overshadowed possible effects of radiation exposure...

  4. Identifying Adverse Effects of HIV Drug Treatment and Associated Sentiments Using Twitter.

    Science.gov (United States)

    Adrover, Cosme; Bodnar, Todd; Huang, Zhuojie; Telenti, Amalio; Salathé, Marcel

    2015-01-01

    Social media platforms are increasingly seen as a source of data on a wide range of health issues. Twitter is of particular interest for public health surveillance because of its public nature. However, the very public nature of social media platforms such as Twitter may act as a barrier to public health surveillance, as people may be reluctant to publicly disclose information about their health. This is of particular concern in the context of diseases that are associated with a certain degree of stigma, such as HIV/AIDS. The objective of the study is to assess whether adverse effects of HIV drug treatment and associated sentiments can be determined using publicly available data from social media. We describe a combined approach of machine learning and crowdsourced human assessment to identify adverse effects of HIV drug treatment solely on individual reports posted publicly on Twitter. Starting from a large dataset of 40 million tweets collected over three years, we identify a very small subset (1642; 0.004%) of individual reports describing personal experiences with HIV drug treatment. Despite the small size of the extracted final dataset, the summary representation of adverse effects attributed to specific drugs, or drug combinations, accurately captures well-recognized toxicities. In addition, the data allowed us to discriminate across specific drug compounds, to identify preferred drugs over time, and to capture novel events such as the availability of preexposure prophylaxis. The effect of limited data sharing due to the public nature of the data can be partially offset by the large number of people sharing data in the first place, an observation that may play a key role in digital epidemiology in general.

  5. Industrial PM2.5cause pulmonary adverse effect through RhoA/ROCK pathway.

    Science.gov (United States)

    Yan, Junyan; Lai, Chia-Hsiang; Lung, Shih-Chun Candice; Chen, Chongjun; Wang, Wen-Cheng; Huang, Pin-I; Lin, Chia-Hua

    2017-12-01

    According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM 2.5 ) is associated with adverse health effects, the major action mechanisms of different compositions of PM 2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM 2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM 2.5 , including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM 2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM 2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM 2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM 2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM 2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM 2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM 2.5 . Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Study on Corticosteroids use Pattern in Dermatological Practice and Investigating Adverse Effect of Corticosteroids Including its Associated Factors.

    Science.gov (United States)

    Shakya Shrestha, S; Bhandari, M; Shrestha, R; Thapa, S R; Karki, A; Prajapati, M; Shrestha, S; Kc, S; Karna, D

    2015-01-01

    Background Corticosteroids are highly effective drugs with anti-inflammatory and immunosuppressive properties. Due to this, they have become a mainstay of pharmacotherapy in dermatology. However, improper and long term uses are associated with a number of serious adverse effects. Objective To investigate the corticosteroids use pattern, adverse effects and various factors associated with adverse effects in dermatological practice. Method A cross-sectional study was conducted in a dermatology department of tertiary care hospital. All patients using at least one corticosteroids, either topically or systemically or the combination were included in this study. Informed consent was taken from the patients and interviewed using structured questionnaire. Statistical analysis was performed by using SPSS 20. p-value corticosteroids with low potency (25%). Most of them had used corticosteroids for urticaria. Adverse effects were reported by 33.30% of the patients. The most common adverse effect reported was the shedding of skin. Adverse effects was significantly associated with gender; use of systemic corticosteroids; regular use of corticosteroids; discontinuation of dose abruptly; and missed dose. However, there was no significant association between adverse effects and the duration of use of corticosteroids. Conclusion In conclusion, the present study suggested that the proper counselling and clear instruction regarding the use of corticosteroid should be provided to the patients for avoiding the abrupt discontinuation of the prescribed medication leading to treatment failure.

  7. Safety Profile of Finasteride: Distribution of Adverse Effects According to Structural and Informational Dichotomies of the Mind/Brain.

    Science.gov (United States)

    Motofei, Ion G; Rowland, David L; Manea, Mirela; Georgescu, Simona R; Păunică, Ioana; Sinescu, Ioanel

    2017-06-01

    Finasteride is currently used extensively for male androgenic alopecia and benign prostatic hyperplasia; however, some adverse effects are severe and even persistent after treatment cessation, the so-called 'post-finasteride syndrome'. The following most severe adverse effects-sexual dysfunction and depression-often occur together and may potentiate one other, a fact that could explain (at least in part) the magnitude and persistence of finasteride adverse effects. This paper presents the pharmacological action of finasteride and the corresponding adverse effects, the biological base explaining the occurrence, persistence and distribution of these adverse effects, and a possible therapeutic solution for post-finasteride syndrome. The distribution of finasteride adverse effects is presented within a comprehensive and modern neuro-endocrine perspective related to structural and informational dichotomies of the brain. Understanding the variation of finasteride side effects among different populations would be necessary not only to delineate the safety profile of finasteride for different subgroups of men (a subject may or may not be affected by a certain anti-hormonal compound dependent on the individual neuro-endocrine profile), but also as a possible premise for a therapeutic approach of finasteride adverse effects. Such therapeutic approach should include administration of exogenous hormones, which are deficient in men with post-finasteride syndrome, namely dihydrotestosterone (in right-handed men) or progesterone/dihydroprogesterone (in left-handed subjects).

  8. Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial.

    Science.gov (United States)

    Slow, Sandy; Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

    2014-12-15

    To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Opportunistic addition to an established randomised double blind placebo controlled trial. Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly

  9. Polytraumatization and Trauma Symptoms in Adolescent Boys and Girls: Interpersonal and Noninterpersonal Events and Moderating Effects of Adverse Family Circumstances

    Science.gov (United States)

    Nilsson, Doris Kristina; Gustafsson, Per E.; Svedin, Carl Goran

    2012-01-01

    The objective of this study was to investigate the cumulative effect of interpersonal and noninterpersonal traumatic life events (IPEs and nIPEs, respectively) on the mental health of adolescents and to determine if the adverse impacts of trauma were moderated by adverse family circumstances (AFC). Adolescents (mean age 16.7 years) from the…

  10. Adverse effects of low level heavy metal exposure on male reproductive function.

    Science.gov (United States)

    Wirth, Julia J; Mijal, Renée S

    2010-04-01

    Lead, cadmium, mercury, and arsenic, often referred to as "heavy metals", are toxic for wildlife, experimental animals, and humans. While experimental animal and human occupational studies with high exposure levels generally support an adverse role for these metals in human reproductive outcomes, information on the effects of low, environmentally-realistic exposure levels of these metals on male reproductive outcomes is limited. We review the literature on effects of exposure to low levels of these metals on measures of male fertility (semen quality and reproductive hormone levels) and provide supporting evidence from experimental and occupational studies. Potentially modifying effects of genetic polymorphisms on these associations are discussed. A brief review of the literature on the effects of three trace metals, copper, manganese, and molybdenum, that are required for human health, yet may also cause adverse reproductive effects, follows. Overall, there were few studies examining the effects of exposure to low levels of these metals on male reproductive health. For all metals, there were several well-designed studies with sufficient populations appropriately adjusted for potential confounders and many of these reported harmful effects. However, many studies lacked sufficient numbers of participants to be able to detect differences in outcomes between exposed and non-exposed individuals, did not clearly identify the source and characteristics of the participants, and did not control for other exposures that could alter or contribute to the outcomes. The evidence for the effects of low exposure was strongest for cadmium, lead, and mercury and less certain for arsenic. The potential modifying effects of genetic polymorphisms has not been fully explored. Additional studies on the reproductive effects of these toxic ubiquitous metals on male reproduction are required to expand the knowledge base and to resolve inconsistencies.

  11. ALERT. Adverse late effects of cancer treatment. Vol. 1. General concepts and specific precepts

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Considers in detail the general concepts and principles relevant to the adverse late effects of cancer treatment. Explains the molecular, cytologic and histopathologic events that lead to altered physiologic and metabolic functions and their clinical manifestations. Includes chapters on legal issues, economic aspects, nursing, psychological issues and quality of life. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 1 of this two-volume work focuses on the general concepts and principles relevant to late effects and on the dynamic interplay of molecular, cytologic and histopathologic events that lead to altered physiologic and metabolic functions and their clinical manifestations. Chapters are also included on legal issues, economic aspects, nursing, psychological issues and quality of life.

  12. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects.

    Directory of Open Access Journals (Sweden)

    Sebastian J Padayatty

    2010-07-01

    Full Text Available Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM practitioners. The scale of such use in the U.S. and associated side effects are unknown.We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550, 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25 g/50 ml vials were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study.High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.

  13. Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects

    Science.gov (United States)

    Chen, Qi; Espey, Michael Graham; Drisko, Jeanne; Levine, Mark

    2010-01-01

    Background Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown. Methods and Findings We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25g/50ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study. Conclusions High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit. PMID:20628650

  14. [Antivaccine misinformation about rate of adverse effects and toxicity of vaccines].

    Science.gov (United States)

    Mats, A N; Gol'dshteĭn, A V

    2010-01-01

    Two widely known antivaccine inventions are discussed: "vaccination is accompanied by adverse effects, which exceeded complications of respective infections on frequency and severity" and "vaccines represent appalling conglomerate of toxic substances, which is unnaturally to administer to children". Informational and psychological nature of dissemination of these inventions is analyzed. On the basis of recent literature data conclusion was made about the absence of real toxicity (including neurotoxicity), carcinogenicity, allergenicity and autopathogenicity of phenol, folmaldehyde, aluminium hydroxide, Twin 80, squalen (MF59) and ethylmercury in concentrations found in vaccines of national immunization schedule.

  15. Possible adverse effects of the quadrivalent human papillomavirus vaccine in the Region of Southern Denmark

    DEFF Research Database (Denmark)

    Cramon, Cecilie; Lindegaard Poulsen, Christina; Hartling, Ulla Birgitte

    2017-01-01

    and laboratory tests. RESULTS: The study comprised 200 patients. The median age at referral was 22 (interquartile range (IQR): 19.5-26) years, and age at first vaccination was 14 (IQR: 12-21) years. The most common symptoms were headache (93%), fatigue/tiredness (93%) and dizziness when standing up (90......INTRODUCTION: Since the introduction of the quadrivalent human papillomavirus vaccine, young girls and women have reported a broad range of symptoms. These have been described as possible adverse effects of the vaccine. In this study, we describe demographic characteristics, symptomatology...... associated with the vaccine. FUNDING: none. TRIAL REGISTRATION: not relevant....

  16. The use of exercise interventions to overcome adverse effects of androgen deprivation therapy

    DEFF Research Database (Denmark)

    Østergren, Peter Busch; Kistorp, Caroline; Bennedbæk, Finn Noe

    2016-01-01

    Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass...... existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue...

  17. Adverse health effects of Asian dust particles and heavy metals in Japan.

    Science.gov (United States)

    Onishi, Kazunari; Otani, Shinji; Yoshida, Atsushi; Mu, Haosheng; Kurozawa, Youichi

    2015-03-01

    Asian dust events are now considered an environmental problem rather than a natural seasonal phenomenon. In this study, we evaluated the associations between daily adverse health effects and Asian dust events in Yonago, Japan. Participants included 54 healthy volunteers, who were distributed survey sheets on nasal, ocular, respiratory, and skin effects in February 2009. Moreover, we collected meteorological and air pollutant (nitric oxide, sulfur dioxide, suspended particulate matter) data and determined pollen and metallic element concentrations in total suspended particulates. Both soil-derived metals (Fe, Ca, Al) and contaminating metals (Pb, Cr, Mn, Ni, Zn) were significantly increased on Asian dust days. Multiple regression analyses showed that the score of the skin effect was significantly associated with the levels of suspended particulate matter and Ni. The results show that increased air pollutants on Asian dust days may have skin effects. © 2011 APJPH.

  18. Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome

    Directory of Open Access Journals (Sweden)

    Treharne GJ

    2002-09-01

    Full Text Available Abstract Background To investigate the effects of intravenous lignocaine infusions (IV lignocaine in fibromyalgia. Methods Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia. Results Prospective study: Two major (pulmonary oedema and supraventricular tachycardia and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases. Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ± 6.5 weeks. Conclusions Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials.

  19. Seeking optimal management for radioactive iodine therapy-induced adverse effects

    Directory of Open Access Journals (Sweden)

    Andreas Charalambous

    2017-01-01

    Full Text Available Radioactive iodine therapy (RAIT is one of the important treatment modalities in the management of differentiated thyroid cancer (DTC. RAIT with iodine-131 has long been used in the management of DTC for the ablation of residual thyroid or treatment of its metastases. Despite being reasonably safe, radioiodine therapy is not always without side effects. Even relatively low administered activities of RAIT used for remnant ablation have been associated with the more clinically significant side effects of sialadenitis, xerostomia, salivary gland pain and swelling, dry eyes, excessive tearing, or alterations in taste in as many as 25% of patients. Given that there is a lack of comprehensive management of these RAIT-induced adverse effects, this paper explores the use of other nonpharmacological measures and their effectiveness as interventions to minimize salivary gland damage.

  20. Adverse effects of pharmacological therapy of benign prostatic hyperplasia on sexual function in men

    Directory of Open Access Journals (Sweden)

    Stojanović Nebojša A.

    2015-01-01

    Full Text Available Introduction. The development of effective medications makes pharmacological therapy of BPH the dominant mode of treatment today. It improves urinary symptoms and prevents disease progression while producing side effects on male sexual function. Objective. The aim of the study is to present the effects of BPH pharmacological treatment on the occurrence of sexually adverse effects in men: changes in sexual desire, erectile, ejaculatory and the orgasmic function. Methods. A prospective study involving 156 BPH patients. The average age was 61.16±2.97. Four groups of 39 patients each were formed. The 4 groups were administered tamsulosin (alpha-blocker, finasteride (5-alpha reductase inhibitor, combination therapy (tamsulosin and finasteride respectively, while the control group received no treatment. IPSS-QoL, IIEF and MSHQ-EjD questionnaires were used to evaluate the symptoms of voiding and sexual function. Follow-up examinations were performed 3 and 6 months into treatment. Results. Voiding symptoms improved in all groups receiving therapy. The side effects on the sexual function in all these groups include significant disorders of ejaculation and the orgasmic function. Ejaculation disorders: tamsulosin (-4.38±2.55; p<0.001, combined therapy (-3.89±2.84 and finasteride (-1.49±2.52. Orgasmic function disorders: tamsulosin (-1.03±1.94, combined therapy (-0.76±2.07 and finasteride (-0.54±1.68. Complete absence of ejaculation was experienced by 23% of patients on combined therapy, 15% on tamsulosin and 5% on finasteride. Conclusion. Pharmacological therapy of BPH improved voiding symptoms producing different effects on male sexual function. The main adverse effect on sexual function in men is the deterioration in ejaculation or the absence thereof. Clinical consideration of BPH should include the elements of male sexual function, patients’ age, the characteristics and effects of each group of drugs.

  1. Drugs with potential cardiac adverse effects: Retrospective study in a large cohort of parkinsonian patients.

    Science.gov (United States)

    Heranval, A; Lefaucheur, R; Fetter, D; Rouillé, A; Le Goff, F; Maltête, D

    2016-01-01

    Drugs with potential cardiac adverse effects are commonly prescribed in Parkinson's disease (PD). To describe demographic and clinical characteristics in a group of PD patients with cardiac events and to evaluate risk factors. We sampled 506 consecutive PD patients (211 women/295 men), median age 68.3±10.6 years (range 36-95) and median disease duration 11.2±6.5 years (range 1-49). Medications with potential cardiac effects, i.e. QT prolongation (citalopram, escitalopram, venlafaxine, sertraline, domperidone, amantadine, solifenacin), ventricular arrhythmia (rivastigmine, clozapine, midodrine, sildenafil, tadalafil) and ischemic heart disease (rasagiline, entacapone, tadalafil) were recorded. Demographic and clinical data were collected prospectively; cardiac events were obtained retrospectively. Twenty-four patients (4.7%) (9 women/15 men) presented a cardiac event. Fifteen (62.5%) patients had dysautonomia, 4 (16.6%) a history of heart disease and 8 (33.3%) were taking one or more drugs with a definite potential cardiac adverse effect. Age (75.9±6.6 yr vs. 67.8±11 yr), disease duration (14.7±3.6 yr vs. 11±6.5 yr), dysautonomia (62.5% vs. 24.5%) and dementia associated with PD (37.5% vs. 14.6%) were significantly higher in the group with cardiac events (PParkinson's disease is associated with a higher risk of cardiovascular complications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Therapeutic and adverse effects of flunixin-meglumine in adult and young cats.

    Science.gov (United States)

    Takata, Kenji; Hikasa, Yoshiaki; Satoh, Hiroshi

    2011-12-01

    In this study, we elucidated the difference in nonsteroidal anti-inflammatory drug sensitivities between young and adult cats on therapeutic and adverse effects. In the prevention of lipopolysaccharide (LPS)-induced hyperthermia using flunixin-meglumine, young (12 months old) cats of both sexes were given LPS (0.3 µg/kg, i.v.), and body temperature was measured 24 hr later. Flunixin (1 mg/kg, s.c.) was administered 30 min before the LPS injection. LPS-induced hyperthermia was almost completely inhibited by pre-treatment with flunixin in both adult and young cats. In addition, flunixin showed almost the same antipyretic effects in both young and adult cats. The animals were administered flunixin (1 mg/kg, s.c.) once a day for 3 days, and sacrificed 24 hr later to examine the gastrointestinal mucosal lesions. In adult cats, flunixin caused many severe lesions in the small intestine. In contrast, very few gastrointestinal lesions were produced by flunixin in young cats. In the pharmacokinetics of flunixin, plasma concentrations of flunixin were analysed using a high performance liquid chromatography. There were no significant differences in plasma concentration of flunixin between young and adult cats from 0.5 to 4 hr after the injection. These results demonstrated that NSAIDs could be used more safely in young than in adult cats from the points of gastrointestinal adverse effects. Furthermore, this difference in gastrointestinal lesions between adult and young cats was not related with the plasma concentration of flunixin.

  3. Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Ryti, Niilo R I; Guo, Yuming; Jaakkola, Jouni J K

    2016-01-01

    There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. "Cold spell" was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0-64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Ryti NR, Guo Y, Jaakkola JJ. 2016. Global association of cold spells and adverse health effects: a systematic review and meta

  4. Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review

    Science.gov (United States)

    Berman, Steven M.; Kuczenski, Ronald; McCracken, James T.; London, Edythe D.

    2009-01-01

    Rationale Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority 1. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Findings Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several-fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central

  5. Gratitude buffers the adverse effect of viewing the thin ideal on body dissatisfaction.

    Science.gov (United States)

    Homan, Kristin J; Sedlak, Brittany L; Boyd, Elizabeth A

    2014-06-01

    Gratitude has robust associations with multiple aspects of well-being. However, little research has explored whether the psychological benefits of gratitude extend to body image. We used a repeated measures experimental design to test whether a brief period of grateful reflection would buffer the adverse effect of exposure to thin-ideal media. Female undergraduates (N=67) completed three sessions one week apart. The conditions were specifically designed to isolate (a) the effects of viewing thin models on body dissatisfaction and (b) the moderating effect of grateful contemplation. Results showed that body dissatisfaction scores were lower for women who engaged in a brief period of grateful contemplation before viewing photographs of thin models than for women who reflected upon life hassles before viewing the same photographs. The magnitude of this decrease depended on BMI. Gratitude offers an innovative direction for future research directed toward helping women to accept their bodies. Copyright © 2014. Published by Elsevier Ltd.

  6. Review: Pharmacogenetic aspects of the effect of cytochrome P450 polymorphisms on serotonergic drug metabolism, response, interactions, and adverse effects.

    Science.gov (United States)

    Pilgrim, J L; Gerostamoulos, D; Drummer, Olaf H

    2011-06-01

    The field of pharmacogenetics contains a wealth of potential for the enhancement of clinical practice by providing a more effective match between patient and drug, consequently reducing the probability of an adverse drug reaction. Although a relatively novel concept in the forensic context, pharmacogenetics has the capability to assist in the interpretation of drug related deaths, particularly in unintentional drug poisonings where the cause of death remains unclear. However, the complex pharmacology of the drugs when subjected to genetic variations in metabolism makes interpretation of the expected response and adverse events difficult. Many possess multiple metabolic pathways, narrow therapeutic indices and active metabolites or enantiomers which may be eliminated via different pathways to the parent drug. A number of these drugs, which are metabolised primarily by the CYP450 system, are also associated with serotonin syndrome, or serotonin toxicity, especially when used concomitantly with other serotonin active drugs which rely on the same metabolic pathways for drug elimination. A comprehensive understanding of polymorphic drug metabolism and its expected outcomes is therefore essential when interpreting the involvement of drugs in adverse reactions. This review examines the genetically variable CYP450-mediated metabolism of a number of serotonin-active drugs that are often implicated in cases of serotonin toxicity, to assess the impact of pharmacogenetics on drug metabolism, response, interactions and adverse effects.

  7. Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review.

    Science.gov (United States)

    Bain, Emily S; Middleton, Philippa F; Crowther, Caroline A

    2013-10-21

    Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women's experiences with this treatment. Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects' overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised trials. Case reports supported an

  8. Wood combustion particles induce adverse effects to normal and diseased airway epithelia.

    Science.gov (United States)

    Krapf, Manuel; Künzi, Lisa; Allenbach, Sandrine; Bruns, Emily A; Gavarini, Ilaria; El-Haddad, Imad; Slowik, Jay G; Prévôt, André S H; Drinovec, Luka; Močnik, Griša; Dümbgen, Lutz; Salathe, Matthias; Baumlin, Nathalie; Sioutas, Constantinos; Baltensperger, Urs; Dommen, Josef; Geiser, Marianne

    2017-04-19

    Residential wood burning is a major source of poorly characterized, deleterious particulate matter, whose composition and toxicity may vary with wood type, burning condition and photochemical age. The causative link between ambient wood particle constituents and observed adverse health effects is currently lacking. Here we investigate the relationship between chemical properties of primary and atmospherically aged wood combustion particles and acute toxicity in human airway epithelial cells. Emissions from a log wood burner were diluted and injected into a smog chamber for photochemical aging. After concentration-enrichment and removal of oxidizing gases, directly emitted and atmospherically aged particles were deposited on cell cultures at the air-liquid interface for 2 hours in an aerosol deposition chamber mimicking physiological conditions in lungs. Cell models were fully differentiated normal and diseased (cystic fibrosis and asthma) human bronchial epithelia (HBE) and the bronchial epithelial cell line BEAS-2B. Cell responses were assessed at 24 hours after aerosol exposure. Atmospherically relevant doses of wood combustion particles significantly increased cell death in all but the asthma cell model. Expression of oxidative stress markers increased in HBE from all donors. Increased cell death and inflammatory responses could not be assigned to a single chemical fraction of the particles. Exposure to primary and aged wood combustion particles caused adverse effects to airway epithelia, apparently induced by several interacting components.

  9. Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers

    Directory of Open Access Journals (Sweden)

    Ping-Ho Chen

    2017-01-01

    Full Text Available Global reports estimate 600 million betel quid (BQ chewers. BQ chewing has been demonstrated not only to be a risk factor for cancers of the oral cavity and pharynx and oral potentially malignant disorders (OPMD but also to cause other cancers and adverse health effects. Herein, we summarized the international comparison data to aid in the understanding of the close relationship between the prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and adverse health effects. Potential biomarkers of BQ carcinogens, such as areca nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN, are closely associated with human health toxicology. Molecular mechanisms or pathways involving autophagy, hypoxia, COX-2, NF-κB activity, and stemness are known to be induced by BQ ingredients and are very closely related to the carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase (MAO gene was associated with the occurrence and progress of oral and pharyngeal cancers. In summary, our review article provides important insights into the potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine products MNPN and genetic factors (MAO and offers a basis for studies aiming to reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the future.

  10. HPV vaccines: their pathology-based discovery, benefits, and adverse effects.

    Science.gov (United States)

    Nicol, Alcina F; de Andrade, Cecilia V; Russomano, Fabio B; Rodrigues, Luana S L; Oliveira, Nathalia S; Provance, David William; Nuovo, Gerard J

    2015-12-01

    The discovery of the human papillomavirus (HPV) vaccine illustrates the power of in situ-based pathologic analysis in better understanding and curing diseases. The 2 available HPV vaccines have markedly reduced the incidence of cervical intraepithelial neoplasias, genital warts, and cervical cancer throughout the world. Concerns about HPV vaccine safety have led some physicians, health care officials, and parents to refuse providing the recommended vaccination to the target population. The aims of the study were to discuss the discovery of HPV vaccine and review scientific data related to measurable outcomes from the use of HPV vaccines. The strong type-specific immunity against HPV in humans has been known for more than 25 years. Multiple studies confirm the positive risk benefit of HPV vaccination with minimal documented adverse effects. The most common adverse effect, injection site pain, occurred in about 10% of girls and was less than the rate reported for other vaccines. Use of HPV vaccine should be expanded into more diverse populations, mainly in low-resource settings. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. [Long-term adverse effects on bladder filling phase in males submitted to the pelvic radiotherapy].

    Science.gov (United States)

    Méndez-Rubio, Santiago; Salinas-Casado, Jesús; Vírseda-Chamorro, Miguel; Esteban-Fuertes, Manuel; Menéndez-Sánchez, Pablo; Moreno-Sierra, Jesús

    2015-09-01

    To describe and quantify the long-term adverse effects on filling phase of lower urinary tract function in males submitted to radiotherapy. We performed a retrospective comparative study on a cohort of 99 men undergoing EBRT a mean of 4.7 years before for clinically localized prostate, rectum or colon neoplasia, and another cohort formed by 97 men over 50 years who did not undergo radiotherapy. Cystometric bladder capacity and bladder capacity at first voiding desire were significantly lower in the radiotherapy group. Univariate analysis showed that the radiotherapy group evinced a risk to present a diminished compliance of 3.5 times more and 9.3 times more to find stress urinary incontinence, but we did not found increased risk for detrusor overactivity. In multivariate analysis the history of radical surgery acted as a confounding factor in the risk of stress urinary incontinence, but not to suffer diminished bladder compliance. The main long-term adverse effect of pelvic radiotherapy on male bladder function during filling is the increased risk of low bladder compliance.

  12. Adverse effects of herbicide MCPA on dogs in a 90 day toxicological study.

    Science.gov (United States)

    Sadlonová, Irina; Hózová, Ruzena; Flaskárová, Eva

    2006-12-01

    This study was performed to investigate the toxicity of the herbicide MCPA after repeated treatment according to OECD No 409. The herbicide MCPA was administrated to dogs of both sexes in daily doses: 0, 1, 5 and 15 mg/kg per os during 90 days. Clinical observations were recorded, opthalmoscopic, haematological, clinical chemistry parameters were investigated. The morphological changes were examined using pathological and histological techniques. An increase in the activity of the enzyme ALT and of urea concentration was observed in the middle- and high-dose groups. ALP and creatinine were decreased in dogs of all dose groups. After 60 days of MCPA administration, the concentration of glucose decreased in the high-dose group. The relative weight of both testes was decreased in the males from the high-dose group in comparison to controls. The decrease in testes weight was associated with focal testicular atrophy and loss of spermatogenic cells in the lobuli of testes. Focal hepatocellular necrosis, inflammatory changes and mononuclear nodules were observed in the liver, predominantly in males of the high-dose group. Administration of MCPA did not cause mortality and had no adverse effects on hematological parameters of animals. The results of the study showed that MCPA treatment caused inflammatory lesions in the liver, moderate damage of the kidney, and had focal adverse effect on the development of spermiogenesis. The changes were reversible.

  13. Noise monitoring and adverse health effects in residents in different functional areas of Luzhou, China.

    Science.gov (United States)

    Han, Zhi-Xia; Lei, Zhang-Heng; Zhang, Chun-Lian; Xiong, Wei; Gan, Zhong-Lin; Hu, Ping; Zhang, Qing-Bi

    2015-03-01

    The purpose of the study was to investigate the noise pollution situation and the resulting adverse effect on residents' health in Luzhou, China, to provide data for noise pollution prevention policies and interventions. Four different functional areas (commercial, construction, residential, and transportation hub areas) were chosen to monitor noise level for 3 months. The survey was performed by questionnaire on the spot on randomly selected individuals; it collected data on the impact of noise on residents' health (quality of sleep, high blood pressure, subjective feeling of nervous system damage, and attention) as well as the knowledge of noise-induced health damage, the degree of adaptation to noise, and their solutions. The noise levels of residential, commercial, transportation, and construction areas exceeded the national standards (P health hazards associated with noise; 64.57% of residents have adapted to the current noise environment. Most of them have to close the doors and windows to reduce noise. The noise pollution situation in Luzhou, China, is serious, especially the traffic noise pollution. Residents pay less attention to it and adopt single measures to reduce the noise. We should work toward the prevention and control of traffic noise and improve the residents' awareness to reduce the adverse health effects of noise. © 2014 APJPH.

  14. Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults.

    Science.gov (United States)

    Delimaris, Ioannis

    2013-01-01

    Background. While high-protein consumption-above the current recommended dietary allowance for adults (RDA: 0.8 g protein/kg body weight/day)-is increasing in popularity, there is a lack of data on its potential adverse effects. Objective. To determine the potential disease risks due to high protein/high meat intake obtained from diet and/or nutritional supplements in humans. Design. Review. Subjects. Healthy adult male and female subjects. Method. In order to identify relevant studies, the electronic databases, Medline and Google Scholar, were searched using the terms:"high protein diet," "protein overconsumption," "protein overuse," and "high meat diet." Papers not in English were excluded. Further studies were identified by citations in retrieved papers. Results. 32 studies (21 experimental human studies and 11 reviews) were identified. The adverse effects associated with long-term high protein/high meat intake in humans were (a) disorders of bone and calcium homeostasis, (b) disorders of renal function, (c) increased cancer risk, (d) disorders of liver function, and (e) precipitated progression of coronary artery disease. Conclusions. The findings of the present study suggest that there is currently no reasonable scientific basis in the literature to recommend protein consumption above the current RDA (high protein diet) for healthy adults due to its potential disease risks. Further research needs to be carried out in this area, including large randomized controlled trials.

  15. Tiapride is more effective and causes fewer adverse effects than risperidone in the treatment of senile dementia.

    Science.gov (United States)

    Yuan, Y; Li, L H; Huang, Y J; Lei, L F

    2016-07-01

    We wanted to compare the effects of tiapride and risperidone in treating behavioral and psychological symptoms of senile dementia. 108 patients with senile dementia received respective treatments (54 patients per treatment, either with 100 mg/day risperidone or 2.0 mg tiapride/day) for 2 months. Outcomes included the positive and negative syndrome scale (PANSS) scores, the curative rate of senile dementia, and prevalence of adverse effects (somnolence, headache, loss of weight, extrapyramidal system response, irritation and insomnia). PANSS scores before treatment were comparable between treatment groups. On days 7, 15, 30, and 60 of the treatment, the differences between two treatment groups became evident. Thus, curative rates in patients treated with risperidone were 74.1% and in those treated with tiapride 88.9% (p senile dementia and causes fewer adverse effects.

  16. PTH prevents the adverse effects of focal radiation on bone architecture in young rats

    Science.gov (United States)

    Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A.; Altman, Allison R.; Cengel, Keith A.; Liu, X. Sherry; Qin, Ling

    2013-01-01

    Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. PMID:23466454

  17. Adverse Cardiovascular Effects of Nitrous Oxide: It is not all about Hyperhomocysteinaemia

    Directory of Open Access Journals (Sweden)

    Ata Mahmoodpoor

    2015-04-01

    Full Text Available Once admired for its supposed safety, nitrous oxide is presently blamed to increase adverse cardiovascular effects through augmenting plasma homocysteine concentrations (1, 2. Hemodynamic alterations following the administration of nitrous oxide are extremely complicated and sometimes contradictory. Enhanced venous return, arterial pressure, pulmonary and systemic vascular resistance, cardiac output, pupillary dilation and diaphoresis occur under nitrous oxide administration consistent with sympathomimetic properties of nitrous oxide (3. Conversely, reductions in arterial pressure are also probable, especially in patients with coronary artery disease. Nitrous oxide can also depress myocardial contractility due to decreased availability of Ca2+ for contractile activation; yet, myocardial relaxation kinetics remains intact (4. In the presence of a volatile anesthetic, nitrous oxide decreases MVO2 (Myocardial oxygen consumption and myocardial O2 extraction which may exacerbate myocardial ischemia during concomitant reductions in arterial pressure in patients with coronary artery disease. Consequently, it could be conjectured that probable adverse cardiovascular effects following nitrous oxide administration are variable and consequent of a multi-variable phenomenon rather than a single variable such as increased levels of homocysteine. Studied purely focusing on the effects of nitrous oxide are difficult to conduct due to the numerous confounding factors. In a study by Myles et al., hyperhomocysteinemia has been introduced as the source of the adverse cardiovascular effects of nitrous oxide. However, in this study, increased inspired oxygen concentrations were used to overcome arterial desaturation (1. Given the fact that a constant volume and flow rates are used throughout the anesthesia in a particular patient, increasing the concentrations of oxygen would be associated with decreased delivered nitrous oxide and volatile anesthetic concentrations

  18. Adverse Effects of Oral Hypoglycemic Agents and Adherence to them among Patients with Type 2 Diabetes Mellitus in Nepal

    Directory of Open Access Journals (Sweden)

    Jyoti Tara Manandhar Shrestha

    2017-06-01

    Full Text Available Introduction: Oral hypoglycemic agents (OHAs are the most common drugs used in Type 2 Diabetes Mellitus. There are various established adverse effects related to their use including hypoglycemia, weight gain, gastrointestinal disturbance, lactic acidosis, and fluid retention. However, the pattern of adverse effects related to OHAs in Nepalese patients still needs to be explored. Our study aims to determine the pattern of adverse effects resulting from the use of OHAs among Type 2 Diabetes mellitus patients and their adherence to the medication. Methods: All diabetic patients who met the inclusion criteria were enrolled in the study. After informed consent, patients were interviewed and evaluated as per the designed proforma. They were mainly studied for common drug used, adverse effects of the drugs, occurrence of hypoglycemia, and adherence to treatment. Results: The study comprised of 183 patients with mean age of 58.73 years (SD = 12.95. Fifty-six (30.6% patients said that they developed adverse effects of drugs but only 21 (11.5% of them reported to their treating physician. Most common adverse effect were related to central nervous system such as tingling sensation of hands and feet, dizziness, drowsiness, etc.  Though 91 (49.7% patients had developed symptoms suggestive of hypoglycemia, only 31 (16.9% knew that it was due to hypoglycemia. Majority of the patients (n = 143, 78.1% administered the drugs as prescribed by the physician. Among the defaulters, the most important reasons for failure to properly administer the drugs was forgetfulness in 82.5% (n = 33, N = 40 of cases. Among the study variables family history of chronic illness (p = 0.046 and information about adverse effects from physician (p = 0.001 had a significant relationship with incidence of adverse effects. Whereas none of them had a significant relationship with adherence to hypoglycemic medication. Conclusion: The incidence of adverse effects was high with hypoglycemia

  19. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

  20. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone.

    Science.gov (United States)

    Paudel, Robin; Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

  1. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

    Directory of Open Access Journals (Sweden)

    Robin Paudel

    2016-01-01

    Full Text Available Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

  2. Te Inclusions in CZT Detectors: New Method for Correcting Their Adverse Effects

    Energy Technology Data Exchange (ETDEWEB)

    Bolotnikov, A.E.; Babalola, S.; Camarda, G.S.; Cui, Y.; Egarievwe, S.U.; Hawrami, R.; Hossain, A.; Yang, G.; James, R.B.

    2009-10-25

    Both Te inclusions and point defects can trap the charge carriers generated by ionizing particles in CdZnTe (CZT) detectors. The amount of charge trapped by point defects is proportional to the carriers’ drift time and can be corrected electronically. In the case of Te inclusions, the charge loss depends upon their random locations with respect to the electron cloud. Consequently, inclusions introduce fluctuations in the charge signals, which cannot be easily corrected. In this paper, we describe direct measurements of the cumulative effect of Te inclusions and its influence on the response of CZT detectors of different thicknesses and different sizes and concentrations of Te inclusions. We also discuss a means of partially correcting their adverse effects.

  3. Adverse Effects of Osteocytic Constitutive Activation of ß-Catenin on Bone Strength and Bone Growth.

    Science.gov (United States)

    Chen, Sixu; Feng, Jianquan; Bao, Quanwei; Li, Ang; Zhang, Bo; Shen, Yue; Zhao, Yufeng; Guo, Qingshan; Jing, Junjun; Lin, Shuxian; Zong, Zhaowen

    2015-07-01

    The activation of the canonical Wnt/β-catenin signaling pathway in both mesenchymal stem cells and osteoblasts has been demonstrated to increase bone mass, showing promise for the treatment of low bone volume conditions such as osteoporosis. However, the possible side effects of manipulating this pathway have not been fully addressed. Previously, we reported that the constitutive activation of ß-catenin in osteoblasts impaired vertebral linear growth. In the present study, β-catenin was constitutively activated in osteocytes by crossing Catnb+/lox(exon 3) mice with dentin matrix protein 1(DMP1)-Cre transgenic mice, and the effects of this activation on bone mass, bone growth and bone strength were then observed. DMP1-Cre was found to be predominantly expressed in osteocytes, with weak expression in a small portion of osteoblasts and growth plate chondrocytes. After the activation, the cancellous bone mass was dramatically increased, almost filling the entire bone marrow cavity in long bones. However, bone strength decreased significantly. Thinner and more porous cortical bone along with impaired mineralization were responsible for the decrease in bone strength. Furthermore, the mice showed shorter stature with impaired linear growth of the long bones. Moreover, the concentration of serum phosphate decreased significantly after the activation of ß-catenin, and a high inorganic phosphate (Pi) diet could partially rescue the phenotype of decreased mineralization level and impaired linear growth. Taken together, the constitutive activation of β-catenin in osteocytes may increase cancellous bone mass; however, the activation also had adverse effects on bone strength and bone growth. These adverse effects should be addressed before the adoption of any therapeutic clinical application involving adjustment of the Wnt/β-catenin signaling pathway. © 2015 American Society for Bone and Mineral Research.

  4. Epidemiologic studies of adverse effects of anti-retroviral drugs: how well is statistical power reported.

    Science.gov (United States)

    Halpern, Scott D; Barton, Todd D; Gross, Robert; Hennessy, Sean; Berlin, Jesse A; Strom, Brian L

    2005-03-01

    To determine whether there is a difference in average statistical power between pharmacoepidemiologic studies of anti-retroviral adverse drug effects (ADEs) sponsored by for-profit versus non-profit organizations. We studied all published pharmacoepidemiologic studies of ADEs associated with the 15 anti-retroviral drugs approved through the end of 1999. A priori, the primary outcome was the power of each study to detect a clinically important difference in the risk for an adverse effect among patients exposed to the study drug(s). We could not evaluate this outcome because of the infrequent reporting of power calculations. We instead report the distribution of studies across a 5-tiered measure of adequacy of reporting of statistical power, as well as the sponsorship of these studies. Of 48 studies meeting our inclusion criteria, only 1 (2%) reported either a completed, a priori power calculation or sufficient details for readers to calculate the power to detect a pre-defined, clinically important effect. Thirty-five studies (73%) reported the minimum information required for sophisticated readers to determine the power to detect an event rate of interest to them; 6 additional studies (13%) reported confidence intervals around at least one summary effect measure and 6 (13%) provided no indication of power or uncertainty. Of the 41 studies for which sponsorship was determined, only 3 (7%) were sponsored by for-profit organizations. The poor reporting of statistical power in this sample suggests a need for guidelines to improve the reporting of pharmacoepidemiologic studies of ADEs. Future research is needed to determine whether the observed paucity of industry-sponsored observational studies of anti-retroviral ADEs extends to other clinical areas, and if so, to identify the causes of this phenomenon. Copyright 2004 John Wiley & Sons, Ltd.

  5. Rebound effect of modern drugs: serious adverse event unknown by health professionals.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2013-01-01

    Supported in the Hippocratic aphorism primum non nocere, the bioethical principle of non-maleficence pray that the medical act cause the least damage or injury to the health of the patient, leaving it to the doctor to assess the risks of a particular therapy through knowledge of possible adverse events of drugs. Among these, the rebound effect represents a common side effect to numerous classes of modern drugs, may cause serious and fatal disorders in patients. This review aims to clarify the health professionals on clinical and epidemiological aspects of rebound phenomenon. A qualitative, exploratory and bibliographic review was held in the PubMed database using the keywords 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor' and 'bisphosphonate'. The rebound effect occurs after discontinuation of numerous classes of drugs that act contrary to the disease disorders, exacerbating them at levels above those prior to treatment. Regardless of the disease, the drug and duration of treatment, the phenomenon manifests itself in a small proportion of susceptible individuals. However, it may cause serious and fatal adverse events should be considered a public health problem in view of the enormous consumption of drugs by population. Bringing together a growing and unquestionable body of evidence, the physician needs to have knowledge of the consequences of the rebound effect and how to minimize it, increasing safety in the management of modern drugs. On the other hand, this rebound can be used in a curative way, broadening the spectrum of the modern therapeutics. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

  6. Mediators and Adverse Effects of Child Poverty in the United States.

    Science.gov (United States)

    Pascoe, John M; Wood, David L; Duffee, James H; Kuo, Alice

    2016-04-01

    The link between poverty and children's health is well recognized. Even temporary poverty may have an adverse effect on children's health, and data consistently support the observation that poverty in childhood continues to have a negative effect on health into adulthood. In addition to childhood morbidity being related to child poverty, epidemiologic studies have documented a mortality gradient for children aged 1 to 15 years (and adults), with poor children experiencing a higher mortality rate than children from higher-income families. The global great recession is only now very slowly abating for millions of America's children and their families. At this difficult time in the history of our nation's families and immediately after the 50th anniversary year of President Lyndon Johnson's War on Poverty, it is particularly germane for the American Academy of Pediatrics, which is "dedicated to the health of all children," to publish a research-supported technical report that examines the mediators associated with the long-recognized adverse effects of child poverty on children and their families. This technical report draws on research from a number of disciplines, including physiology, sociology, psychology, economics, and epidemiology, to describe the present state of knowledge regarding poverty's negative impact on children's health and development. Children inherit not only their parents' genes but also the family ecology and its social milieu. Thus, parenting skills, housing, neighborhood, schools, and other factors (eg, medical care) all have complex relations to each other and influence how each child's genetic canvas is expressed. Accompanying this technical report is a policy statement that describes specific actions that pediatricians and other child advocates can take to attenuate the negative effects of the mediators identified in this technical report and improve the well-being of our nation's children and their families. Copyright © 2016 by the

  7. Duration of Internet use and adverse psychosocial effects among European adolescents.

    Science.gov (United States)

    Secades-Villa, Roberto; Calafat, Amador; Fernández-Hermida, José Ramón; Juan, Montse; Duch, Mariangels; Skärstrand, Eva; Becoña, Elisardo; Talic, Sanela

    2014-01-01

    Despite the significant contributions from previous studies about the prevalence of problematic Internet use (PIU) among adolescents in Europe, important questions remain regarding adverse consequences of PIU. This study aims to assess the relation between duration of Internet use and adverse psychosocial effects among adolescents from six European countries. The final sample included 7,351 adolescents (50.8% male and 49.2% female; mean age: 14.6±1.90) recruited from randomly selected schools within the six study sites. Results showed that 12.9% of adolescents used Internet more than 20 hours per week. There was a significant relationship between duration of Internet use and frequency of alcohol, tobacco, cannabis and other illegal drug use. Duration of Internet use is also significantly associated with school problems, with use of slot machines and with other psychosocial problems. These findings highlight the need to strengthen preventive efforts for reducing PIU and related consequences among adolescents. Key Words: Internet, adolescents, psychosocial problems.

  8. Adverse effect of pioglitazone in military personnel and their families: a preliminary report.

    Science.gov (United States)

    Vudhironarit, Thishnapha; Benjasuratwong, Yupin; Patarakitvanit, Supen; Temboonkiat, Supatta; Satyapan, Nisamanee

    2009-02-01

    Thiazolidinediones (rosiglitazone and pioglitazone) whether administered alone or in combination with metformin, sulfonylurea, or insulin, are often accompanied by an increase in weight and/or plasma volume. Several studies have shown the adverse effect of weight gain and edema with rosiglitazone. But there was less data with pioglitazone, especially in military personnel and their families. The authors prospectively recorded the adverse events in 40 patients with type 2 diabetes mellitus who underwent administration with pioglitazone 15 mg once daily between June 2005 to May 2007. Weight gain was reported in 30/40 of patients (75%). The mean weight gain was 2.25 +/- 2.23 kg and the median was 2 kg. The slightly lower proportion of patients, 21/40 (52.5%) developed edema and some of them were associated with weight gain. Pioglitazone was associated with a significant increase in body weight and edema. This finding may lead to increase the risk of myocardial infarction in military personnel and their families, especially those who had underlying disease of congestive heart failure, which was not included in the present study.

  9. A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors.

    Science.gov (United States)

    Yu, Li-Yuan; Sun, Lu-Ning; Zhang, Xue-Hui; Li, Yue-Qi; Yu, Lei; Yuan, Zi-Qing-Yun; Meng, Ling; Zhang, Hong-Wen; Wang, Yong-Qing

    2017-05-01

    Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.

  10. Observational Studies on Evaluating the Safety and Adverse Effects of Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Jung-Nein Lai

    2013-01-01

    Full Text Available Background. This study aims to share our experiences when carrying out observational studies of traditional Chinese medicine (TCM. Methods. We have proactively monitored the safety profiles of Duhuo Jisheng Tang (DJT, Suan Zao Ren Tang (SZRT, and TMN-1. A list of adverse events (AEs, complete blood counts, and liver and kidney function tests were obtained from the participants during their scheduled hospital visits. Retrospective observational studies were conducted based on the reimbursement database of the National Health Insurance system, Taiwan, to explore the relationship between the use of TCM that have been adulterated by aristolochic acid and the risk from both nephrotoxins and carcinogens. Results. A total of 221, 287, and 203 AEs were detected after SZRT, DJT, and TMN-1 had been taken, respectively. Dizziness, headache, stomach ache, and diarrhea were judged to be probably related to SZRT treatment. Retrospective observational studies found an association between the consumption of aristolochic acid-containing Chinese formulae such as Mu Tong and an increased risk of CKD, ESRD, and urinary tract cancer. Conclusion. Prospective and retrospective observational studies seem to have specific advantages when investigating the safety and adverse effects of TCM therapies, as well as possibly other alternative/complementary therapies.

  11. Review for carrageenan-based pharmaceutical biomaterials: favourable physical features versus adverse biological effects.

    Science.gov (United States)

    Liu, Jingjing; Zhan, Xiudan; Wan, Jianbo; Wang, Yitao; Wang, Chunming

    2015-05-05

    Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Effects of consanguineous marriage on reproductive behaviour, adverse pregnancy outcomes and offspring mortality in Oman.

    Science.gov (United States)

    Islam, M Mazharul

    2013-05-01

    The long tradition of high prevalence of consanguineous marriages in Omani society may have ramifications for reproductive behaviour and health of offspring. To examine the relevance of consanguinity to reproductive behaviour, adverse pregnancy outcome and offspring mortality in Oman. The data analysed came from the 2000 Oman National Health Survey. Selected indicators that are related to reproductive behaviour, adverse pregnancy outcome and offspring mortality were considered as explanatory variables. Various statistical methods and tests were used for data analysis. Consanguineous marriage was found to be associated with lower age at first birth, higher preference for larger family size, lower level of husband-wife communication about use of family planning methods and lower rate of contraceptive use. Although bivariate analysis showed elevated fertility and childhood mortality among the women with consanguineous marriage, after controlling for relevant socio-demographic factors in multivariate analysis, fertility, childhood mortality and foetal loss showed no significant association with consanguinity in Oman. Consanguinity plays an important role in determining some of the aspects of reproduction and health of newborns, but did not show any detrimental effects on fertility and offspring mortality. The high level of consanguinity and its relevance to reproduction in Oman need to be considered in its public health strategy in a culturally acceptable manner.

  13. Linking Adverse Childhood Effects and Attachment: A Theory of Etiology for Sexual Offending.

    Science.gov (United States)

    Grady, Melissa D; Levenson, Jill S; Bolder, Tess

    2016-01-25

    Sexual violence continues to be a significant public health problem affecting significant portions of the population. Unfortunately, an agreed upon theory of etiology remains elusive leading to challenges in developing effective prevention and treatment interventions. Recently, there is a growing body of literature examining the role of adverse childhood experiences (ACEs) in the development of sexually violent behavior. This research has begun to explore the rates of various types of child maltreatments and family dysfunction in individuals who have been convicted of a sexual crime. These empirical inquiries have been primarily descriptive in nature and have not yet provided a cohesive theoretical model as to why the presence of ACEs might contribute to sexually abusive behavior. This article suggests that attachment theory offers an explanatory link between early adversity and sexually abusive behavior in adulthood. We first summarize important attachment theory concepts, then integrate them with research in the area of developmental psychopathology and ACEs, and finally propose a model by which attachment can be used as an explanatory theory for subsequent sexualized coping and sexually abusive behaviors. Finally, this article explores the implications for practice, policy, and research using this explanatory theory as a framework for understanding sexual violence. © The Author(s) 2016.

  14. High salt intake causes adverse fetal programming--vascular effects beyond blood pressure.

    Science.gov (United States)

    Piecha, Grzegorz; Koleganova, Nadezda; Ritz, Eberhard; Müller, Annett; Fedorova, Olga V; Bagrov, Alexei Y; Lutz, Diana; Schirmacher, Peter; Gross-Weissmann, Marie-Luise

    2012-09-01

    High salt intake causes hypertension, adverse cardiovascular outcomes and potentially also blood pressure (BP)-independent target organ damage. Excess salt intake in pregnancy is known to affect BP in the offspring. The present study was designed to assess whether high salt intake in pregnancy affects BP and vascular morphology in the offspring. Sprague-Dawley rats were fed a standard rodent diet with low-normal (0.15%) or high (8.0%) salt content during pregnancy and lactation. After weaning at 4 weeks of age, offspring were maintained on the same diet or switched to a high- or low-salt diet, respectively. Vascular geometry was assessed in male offspring at 7 and 12 weeks postnatally. Up to 12 weeks of age, there was no significant difference in telemetrically measured BP between the groups of offspring. At 12 weeks of age, wall thickness of central (aorta, carotid), muscular (mesenteric) and intrapulmonary arteries was significantly higher in offspring of mothers on a high-salt diet irrespective of the post-weaning diet. This correlated with increased fibrosis of the aortic wall, more intense nitrotyrosine staining as well as elevated levels of marinobufagenin (MBG) and asymmetric dimethyl arginine (ADMA). High salt intake in pregnant rats has long-lasting effects on the modeling of central and muscular arteries in the offspring independent of postnatal salt intake and BP. Circulating MBG and ADMA and local oxidative stress correlate with the adverse vascular modeling.

  15. Observational Studies on Evaluating the Safety and Adverse Effects of Traditional Chinese Medicine

    Science.gov (United States)

    Tang, Jin-Ling; Wang, Jung-Der

    2013-01-01

    Background. This study aims to share our experiences when carrying out observational studies of traditional Chinese medicine (TCM). Methods. We have proactively monitored the safety profiles of Duhuo Jisheng Tang (DJT), Suan Zao Ren Tang (SZRT), and TMN-1. A list of adverse events (AEs), complete blood counts, and liver and kidney function tests were obtained from the participants during their scheduled hospital visits. Retrospective observational studies were conducted based on the reimbursement database of the National Health Insurance system, Taiwan, to explore the relationship between the use of TCM that have been adulterated by aristolochic acid and the risk from both nephrotoxins and carcinogens. Results. A total of 221, 287, and 203 AEs were detected after SZRT, DJT, and TMN-1 had been taken, respectively. Dizziness, headache, stomach ache, and diarrhea were judged to be probably related to SZRT treatment. Retrospective observational studies found an association between the consumption of aristolochic acid-containing Chinese formulae such as Mu Tong and an increased risk of CKD, ESRD, and urinary tract cancer. Conclusion. Prospective and retrospective observational studies seem to have specific advantages when investigating the safety and adverse effects of TCM therapies, as well as possibly other alternative/complementary therapies. PMID:24159351

  16. The effect of pre-donation hypotension on whole blood donor adverse reactions: a systematic review.

    Science.gov (United States)

    Pauwels, Nele S; Cusack, Leila; De Buck, Emmy; Compernolle, Veerle; Vandekerckhove, Philippe

    2014-06-01

    Blood services are reliant upon healthy blood donors to provide a safe and adequate supply of blood products. Inappropriate variables contained within blood donor exclusion criteria can defer potentially appropriate donors. The aim of this systematic review was to examine the effect of low pre-donation blood pressure, as compared with normal blood pressure, on adverse events in allogeneic whole blood donors. A systematic review was performed using highly sensitive search strategies within five databases (Cochrane Central Register of Controlled Trials, CINAHL, Embase, MEDLINE, and Web of Science) from inception date until April 12, 2013. Out of 8305 records, 10 observational studies were identified that addressed the question. Five of these studies (with a combined total of 1,482,020 donations and 2903 donors) included either a statistical analysis or an appropriate study design that controlled for possible confounding factors. Based on the currently available evidence, hypotension has not been shown to be an independent predictive factor for donor complications. However, the overall quality of evidence was rather limited and rated 'low,' using the GRADE approach. In conclusion there is currently no evidence that hypotensive blood donors have a greater risk for donor adverse events compared with their normotensive counterparts. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  17. Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation.

    Science.gov (United States)

    Pontes, Suzy Maria Montenegro; Melo, Luiz Henrique de Paula; Maia, Nathalia Parente de Sousa; Nogueira, Andrea da Nóbrega Cirino; Vasconcelos, Thiago Brasileiro; Pereira, Eanes Delgado Barros; Bastos, Vasco Pinheiro Diógenes; Holanda, Marcelo Alcantara

    2017-01-01

    To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin. Comparar a incidência e a intensidade de efeitos adversos agudos e a variação da temperatura da pele da face através da termografia após a aplicação de ventilação não invasiva (VNI). Foram incluídos 20 voluntários sadios, de ambos os gêneros, submetidos à VNI com máscara oronasal por 1 h e divididos aleatoriamente em

  18. Effect of concomitant use of montelukast and efavirenz on neuropsychiatric adverse events.

    Science.gov (United States)

    Ibarra-Barrueta, Olatz; Palacios-Zabalza, Itziar; Mora-Atorrasagasti, Oihana; Mayo-Suarez, Jose

    2014-01-01

    To report the case of an HIV patient who developed neuropsychiatric disturbances when montelukast was added to her therapy containing efavirenz. A 41-year-old woman with HIV infection had been on treatment with efavirenz, emtricitabine, and tenofovir disoproxil fumarate since 2007 with good tolerance. In November 2011, montelukast was started for asthma and shortly thereafter neuropsychiatric symptoms appeared, consisting of disturbed sleep, vivid dreams, irritability, confusion, and concentration difficulties. In January 2012, 2 months after the introduction of montelukast, she continued to report unbearable symptoms without any improvement; so, montelukast was withdrawn and the psychiatric symptoms completely disappeared. The combination of efavirenz and montelukast has not previously been associated with any pharmacokinetic interactions or worsening of neuropsychiatric symptoms. This case report indicates the possibility of adverse effects developing when the 2 drugs are used together. These symptoms might either be related to a drug-drug interaction or increased by the similar side effect profiles of the 2 drugs. The higher score on the Karch-Lasagna scale suggests that an adverse effect is the more likely explanation. We cannot, however, rule out a drug interaction, given that efavirenz inhibits the CYP 2C9, 2C19, and 3A4 isoenzymes and CYP 3A4, 2C9, and 2C8 are involved in the metabolism of montelukast. Considering that efavirenz is frequently used in antiretroviral therapy and that neuropsychiatric symptoms can limit its use, clinicians should consider the possibility of worsening of these symptoms, such as mood disorders and abnormal dreams, when montelukast is introduced.

  19. Responses and adverse effects of carboplatin-based chemotherapy for pediatric intracranial germ cell tumors

    Directory of Open Access Journals (Sweden)

    Suntae Ji

    2011-03-01

    Full Text Available Purpose : Cisplatin-based chemotherapy has been commonly used for the treatment of intracranial germ cell tumors (IC-GCTs. However, this treatment exhibits some adverse effects such as renal problems and hearing difficulty. Carboplatin-based chemotherapy was administered to pediatric patients with IC-GCTs from August 2004 at the Samsung Medical Center. In this study, we assessed the responses and adverse effects of carboplatin-based chemotherapy in pediatric IC-GCTs patients according to the risk group, and compared the results with those of the previous cisplatin-based chemotherapy. Methods : We examined 35 patients (27 men and 8 women diagnosed with IC-GCTs between August 2004 and April 2008 and received riskadapted carboplatin-based chemotherapy at the Samsung Medical Center. Patients were divided into either low-risk (LR or high-risk (HR groups and a retrospective analysis was performed using information from the medical records. Results : Although hematological complications were common, hearing difficulties or grade 3 or 4 creatinine level elevation were not observed in patients who underwent carboplatin-based chemotherapy. The frequency of febrile neutropenia did not differ between the risk groups. The overall survival was 100% and event-free survival (EFS was 95.7 %. The EFS rate was 100% in the LR group and 90% in the HR group, respectively. Conclusion : Despite their common occurrence in high-risk patients, no lethal hematological complications were associated with carboplatinbased treatment. The current carboplatin-based chemotherapy protocol is safe and effective for the treatment of pediatric patients with IC-GCTs.

  20. Surgical correction of scoliosis in children with spastic quadriplegia: benefits, adverse effects, and patient selection.

    Science.gov (United States)

    Legg, Julian; Davies, Evan; Raich, Annie L; Dettori, Joseph R; Sherry, Ned

    2014-04-01

    Cerebral palsy (CP) is a group of nonprogressive syndromes of posture and motor impairment associated with lesions of the immature brain. Spastic quadriplegia is the most severe form with a high incidence of scoliosis, back pain, respiratory compromise, pelvic obliquity, and poor sitting balance. Surgical stabilization of the spine is an effective technique for correcting deformity and restoring sitting posture. The decision to operate in this group of patients is challenging. The aim of this study is to determine the benefits of surgical correction of scoliosis in children with spastic quadriplegia, the adverse effects of this treatment, and what preoperative factors affect patient outcome after surgical correction. A systematic review was undertaken to identify studies describing benefits and adverse effects of surgery in spastic quadriplegia. Factors affecting patient outcome following surgical correction of scoliosis were assessed. Studies involving adults and nonspastic quadriplegia were excluded. A total of 10 case series and 1 prospective and 3 retrospective cohort studies met inclusion criteria. There was significant variation in the overall risk of complications (range, 10.9-70.9%), mortality (range, 2.8-19%), respiratory/pulmonary complications (range, 26.9-57.1%), and infection (range, 2.5-56.8%). Factors associated with a worse outcome were a significant degree of thoracic kyphosis, days in the intensive care unit, and poor nutritional status. Caregivers report a high degree of satisfaction with scoliosis surgery for children with spastic quadriplegia. There is limited evidence of preoperative factors that can predict patient outcome after scoliosis. There is a need for well-designed prospective studies of scoliosis surgery in spastic quadriplegia.

  1. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal.

    Science.gov (United States)

    Cooper, Ziva D

    2016-05-01

    Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies

  2. Mouth breathing: adverse effects on facial growth, health, academics, and behavior.

    Science.gov (United States)

    Jefferson, Yosh

    2010-01-01

    The vast majority of health care professionals are unaware of the negative impact of upper airway obstruction (mouth breathing) on normal facial growth and physiologic health. Children whose mouth breathing is untreated may develop long, narrow faces, narrow mouths, high palatal vaults, dental malocclusion, gummy smiles, and many other unattractive facial features, such as skeletal Class II or Class III facial profiles. These children do not sleep well at night due to obstructed airways; this lack of sleep can adversely affect their growth and academic performance. Many of these children are misdiagnosed with attention deficit disorder (ADD) and hyperactivity. It is important for the entire health care community (including general and pediatric dentists) to screen and diagnose for mouth breathing in adults and in children as young as 5 years of age. If mouth breathing is treated early, its negative effect on facial and dental development and the medical and social problems associated with it can be reduced or averted.

  3. Identifying and managing adverse environmental health effects: 1. Taking an exposure history.

    Science.gov (United States)

    Marshall, Lynn; Weir, Erica; Abelsohn, Alan; Sanborn, Margaret D

    2002-04-16

    Public concern and awareness are growing about adverse health effects of exposure to environmental contaminants. Frequently patients present to their physicians with questions or concerns about exposures to such substances as lead, air pollutants and pesticides. Most primary care physicians lack training in and knowledge of the clinical recognition, management and avoidance of such exposures. We have found that it can be helpful to use the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation, Personal habits, Diet and Drugs) as a tool to identify a patient's history of exposures to potentially toxic environmental contaminants. In this article we discuss why it is important to take a patient's environmental exposure history, when and how to take the history, and how to interpret the findings. Possible routes of exposure and common sources of potentially toxic biological, physical and chemical substances are identified. A case of sick-building syndrome is used to illustrate the use of the mnemonic.

  4. Study on the adverse effects of hydropower development on international shipping

    Science.gov (United States)

    Wang, Changhong

    2017-04-01

    The Lancang - Mekong river is an important international waterway to Southeast Asia and South Asia, which has important strategic significance for promoting regional economic cooperation and safeguarding national economic and security interests. On the Mekong River, the main aim is to develop hydropower resources utilization and shipping. River Hydropower Stations are in Laos and designed by foreign enterprises according to the construction of BOT. In this study, on the basis of a lot of research work and extensive collection of relevant information, and, through in-depth analysis of research, it reveals that the upper Mekong River hydropower development have many adverse effects on international shipping, put forward related suggestions for the healthy and sustainable development of international shipping.

  5. Burden of informal caregiving for stroke patients. Identification of caregivers at risk of adverse health effects.

    Science.gov (United States)

    van Exel, N J A; Koopmanschap, M A; van den Berg, B; Brouwer, W B F; van den Bos, G A M

    2005-01-01

    We assessed the objective and subjective burden of caregiving for stroke patients and investigated which characteristics of the patient, the informal caregiver and the objective burden contribute most to subjective burden and to the condition of feeling substantially burdened. We studied a sample of 151 stroke survivors and their primary informal caregivers. We collected data through patient and caregiver interviews 6 months after stroke. Both the level of subjective burden and the condition of feeling substantially burdened were associated with both caregiver's and patient's health-related quality of life, patient's age, and the number of caregiving tasks performed. These conditions can be used in clinical practice to identify potentially vulnerable caregivers in need of support and at risk of adverse health effects. Monitoring stroke survivors as well as their family caregivers at discharge may help to prevent or alleviate caregiver burden.

  6. Automatic Extraction of Drug Adverse Effects from Product Characteristics (SPCs): A Text Versus Table Comparison.

    Science.gov (United States)

    Lamy, Jean-Baptiste; Ugon, Adrien; Berthelot, Hélène

    2016-01-01

    Potential adverse effects (AEs) of drugs are described in their summary of product characteristics (SPCs), a textual document. Automatic extraction of AEs from SPCs is useful for detecting AEs and for building drug databases. However, this task is difficult because each AE is associated with a frequency that must be extracted and the presentation of AEs in SPCs is heterogeneous, consisting of plain text and tables in many different formats. We propose a taxonomy for the presentation of AEs in SPCs. We set up natural language processing (NLP) and table parsing methods for extracting AEs from texts and tables of any format, and evaluate them on 10 SPCs. Automatic extraction performed better on tables than on texts. Tables should be recommended for the presentation of the AEs section of the SPCs.

  7. Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

    Directory of Open Access Journals (Sweden)

    Janina Kueper

    2015-01-01

    Full Text Available Malnutrition and starvation’s possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

  8. Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

    DEFF Research Database (Denmark)

    Mathiesen, O; Wetterslev, Jørn; Kontinen, V K

    2014-01-01

    with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects...... of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality......, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single-dose GCCs were not significantly related to increased infection rates or delayed wound healing...

  9. Mitigating Adverse Effects of a Human Mission on Possible Martian Indigenous Ecosystems

    Science.gov (United States)

    Lupisella, M. L.

    2000-07-01

    Although human beings are, by most standards, the most capable agents to search for and detect extraterrestrial life, we are also potentially the most harmful. While there has been substantial work regarding forward contamination with respect to robotic missions, the issue of potential adverse effects on possible indigenous Martian ecosystems, such as biological contamination, due to a human mission has remained relatively unexplored and may require our attention now as this presentation will try to demonstrate by exploring some of the relevant scientific questions, mission planning challenges, and policy issues. An informal, high-level mission planning decision tree will be discussed and is included as the next page of this abstract. Some of the questions to be considered are: (1) To what extent could contamination due to a human presence compromise possible indigenous life forms? (2) To what extent can we control contamination? For example, will it be local or global? (3) What are the criteria for assessing the biological status of Mars, both regionally and globally? For example, can we adequately extrapolate from a few strategic missions such as sample return missions? (4) What should our policies be regarding our mission planning and possible interaction with what are likely to be microbial forms of extraterrestrial life? (5) Central to the science and mission planning issues is the role and applicability of terrestrial analogs, such as Lake Vostok for assessing drilling issues, and modeling techniques. Central to many of the policy aspects are scientific value, international law, public concern, and ethics. Exploring this overall issue responsibly requires an examination of all these aspects and how they interrelate. A chart is included, titled 'Mission Planning Decision Tree for Mitigating Adverse Effects to Possible Indigenous Martian Ecosystems due to a Human Mission'. It outlines what questions scientists should ask and answer before sending humans to Mars.

  10. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

    Science.gov (United States)

    Krentz, A J; Fujioka, K; Hompesch, M

    2016-06-01

    Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. © 2016 John Wiley & Sons Ltd.

  11. Registered Nurses' Knowledge about Adverse Effects of Analgesics when Treating Postoperative Pain in Patients with Dementia.

    Science.gov (United States)

    Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi

    2015-08-01

    Registered nurses (RNs) play a pivotal role in treating pain and preventing and recognizing the adverse effects (AEs) of analgesics in patients with dementia. The purpose of this study was to determine RNs' knowledge of potentially clinically relevant AEs of analgesics. A descriptive, cross-sectional study design was used. In all, 267 RNs treating orthopedic patients, including patients with dementia, in 7 university hospitals and 10 central hospitals in Finland, completed a questionnaire. Analgesics were defined according to the Anatomic Therapeutic Classification as strong opioids, weak opioids, nonsteroidal anti-inflammatory analgesics (NSAIDs), and paracetamol. Definitions of AEs were based on the literature. Logistic regression analysis was applied to analyze which variables predicted nurses' knowledge. The RNs had a clear understanding of the AEs of paracetamol and strong opioids. However, the AEs of NSAIDs, especially renal and cardiovascular AEs, were less well known. The median percentage of correct answers was 87% when asked about strong opioids, 73% for weak opioids, and 60% for NSAIDs. Younger RNs had better knowledge of opioid-related AEs (odds ratio [OR] per 1-year increase, 0.97; 95% confidence interval [CI], 0.94-1.00) and weak opioids (OR, 0.96; 95% CI, 0.93-0.99). This study provides evidence of a deficiency in RNs' knowledge, especially regarding the adverse renal and cardiovascular effects of NSAIDs. Such lack of knowledge indicates that hospitals may need to update the knowledge of older RNs, especially those who treat vulnerable patients with dementia. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  12. ADVERPred-Web Service for Prediction of Adverse Effects of Drugs.

    Science.gov (United States)

    Ivanov, Sergey M; Lagunin, Alexey A; Rudik, Anastasia V; Filimonov, Dmitry A; Poroikov, Vladimir V

    2018-01-22

    Application of structure-activity relationships (SARs) for the prediction of adverse effects of drugs (ADEs) has been reported in many published studies. Training sets for the creation of SAR models are usually based on drug label information which allows for the generation of data sets for many hundreds of drugs. Since many ADEs may not be related to drug consumption, one of the main problems in such studies is the quality of data on drug-ADE pairs obtained from labels. The information on ADEs may be included in three sections of the drug labels: "Boxed warning," "Warnings and Precautions," and "Adverse reactions." The first two sections, especially Boxed warning, usually contain the most frequent and severe ADEs that have either known or probable relationships to drug consumption. Using this information, we have created manually curated data sets for the five most frequent and severe ADEs: myocardial infarction, arrhythmia, cardiac failure, severe hepatotoxicity, and nephrotoxicity, with more than 850 drugs on average for each effect. The corresponding SARs were built with PASS (Prediction of Activity Spectra for Substances) software and had balanced accuracy values of 0.74, 0.7, 0.77, 0.67, and 0.75, respectively. They were implemented in a freely available ADVERPred web service ( http://www.way2drug.com/adverpred/ ), which enables a user to predict five ADEs based on the structural formula of compound. This web service can be applied for estimation of the corresponding ADEs for hits and lead compounds at the early stages of drug discovery.

  13. The adverse health effects of oil spills: a review of the literature and a framework for medically evaluating exposed individuals.

    Science.gov (United States)

    Levy, Barry S; Nassetta, William J

    2011-01-01

    In April 2010, an explosion on an oil rig in the Gulf of Mexico killed 11 workers, injured 17 workers, and spilled an estimated 185 million gallons of crude oil into the Gulf. Adverse effects on the health of cleanup workers, fishermen, and others as well as on the ecosystem are being studied. This paper reviews published studies of the adverse health effects due to previous oil spills. Acute effects have included: respiratory, eye, and skin symptoms; headache; nausea; dizziness; and tiredness or fatigue. Chronic effects have included: psychological disorders, respiratory disorders, genotoxic effects, and endocrine abnormalities. We also present a systematic approach to evaluating individuals exposed to oil spills.

  14. Effect of adverse weather on neonatal caribou survival — a review

    OpenAIRE

    Frank L. Miller; Anne Gunn

    1986-01-01

    This paper reviews the relationship between adverse weather and neonatal caribou (Rangifer tarandus spp.) survival in North America by examining the available literature and our own findings. The viewpoint that adverse weather on the calving ground can result in major losses of newborn barren-ground caribou (R. t. groenlandicus) calves is largely unsupported. Published reports of calf mortality caused by adverse weather are questionable because causes of death were rarely determined by postmo...

  15. Sensitivity and precision of adverse effects search filters in MEDLINE and EMBASE: a case study of fractures with thiazolidinediones.

    Science.gov (United States)

    Golder, Su; Loke, Yoon K

    2012-03-01

    Search filters have been developed in MEDLINE and EMBASE to help overcome the challenges of searching electronic databases for information on adverse effects. However, little evaluation of their effectiveness has been carried out. To measure the sensitivity and precision of available adverse effects search filters in MEDLINE and EMBASE. A case study systematic review of fracture related adverse effects associated with the use of thiazolidinediones was used. Twelve MEDLINE search strategies and three EMBASE search strategies were tested. Nineteen relevant references from MEDLINE and 24 from EMBASE were included in the review. Four search filters in MEDLINE achieved high sensitivity (95 or 100%) with an improved level of precision from searches without any adverse effects filter. High precision in MEDLINE could also be achieved (up to 53%) using search filters that rely on Medical Subject Headings. No search filter in EMBASE achieved high precision (all were under 5%) and the highest sensitivity in EMBASE was 83%. Adverse effects search filters appear to be effective in MEDLINE for achieving either high sensitivity or high precision. Search filters in EMBASE, however, do not appear as effective, particularly in improving precision. © 2011 The authors. Health Information and Libraries Journal © 2011 Health Libraries Group.

  16. More effective assessment of adverse effects and comorbidities in epilepsy: results of a Phase II communication study.

    Science.gov (United States)

    Stern, John M; Labiner, David M; Gilliam, Frank G; Penovich, Patricia E; Onofrey, Meaghan; Eagan, Corey A; Holmes, Gregory L

    2011-11-01

    Research was conducted to evaluate conversations about epilepsy between community-based neurologists and patients. Adverse effects of antiepileptic drugs and mood/behavioral issues were infrequently discussed, and neurologists and patients disagreed about these issues postvisit. Follow-up research was conducted to assess the impact of a previsit assessment tool on discussions of epilepsy. Twenty neurologists reviewed a tool incorporating questions from validated instruments (Adverse Events Profile [AEP] and Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]). Naturally occurring interactions between neurologists and 60 patients were recorded. Neurologists and patients were interviewed separately. All components were transcribed and analyzed using sociolinguistics. Using the previsit assessment tool increased the number of discussions about adverse effects and mood/behavioral issues and increased neurologist-patient agreement about issues postvisit. Visit length did not increase significantly when the tool was used. Ten months after follow-up research, 50% of neurologists reported continuing to use the tool in everyday practice with patients with epilepsy. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The incidence and predictors of overall adverse effects caused by low dose amiodarone in real-world clinical practice

    OpenAIRE

    Kim, Hack-Lyoung; Seo, Jae-Bin; Chung, Woo-Young; Kim, Sang-Hyun; Kim, Myung-A; Zo, Joo-Hee

    2014-01-01

    Background/Aims Most current knowledge regarding amiodarone toxicity derives from clinical trials. This study was performed to investigate the incidence and risk factors of overall adverse effects of amiodarone in real-world practice using a large sample size. Methods Between January 1, 2000 and March 10, 2012, a total of 930 consecutive patients who had been treated with amiodarone for arrhythmia were reviewed retrospectively. An amiodarone-associated adverse event was considered in cases of...

  18. The Effect of Adverse Childhood Experience on Clinical Diagnosis of a Substance Use Disorder: Results of a Nationally Representative Study.

    Science.gov (United States)

    LeTendre, McKenzie Lynn; Reed, Mark B

    2017-05-12

    Substance abuse is one of the most common health outcomes associated with adverse childhood experience, and poses a significant public health threat. The purpose of this study is to demonstrate a relationship between adverse childhood experience and a substance use disorder using nationally representative data as well as to test whether religion moderates this relationship. We conducted a secondary analysis using data from the National Longitudinal Study of Adolescent to Adult Health (n = 11,279). Three types of adverse childhood experiences were considered; physical, emotional, and sexual abuse. Logistic regression was used to determine whether risk for developing an alcohol use, cannabis use, or other drug use disorder in adulthood increased as exposure to multiple types of adverse childhood experiences increased while controlling for prior substance use and other demographic variables that have shown associations with substance use. In addition, religiosity was investigated as a possible moderator of the relationship between adverse childhood experience and substance abuse. The likelihood of developing a substance use disorder later in life increased as the score on the adverse childhood experience index increased. While religiosity did significantly reduce the likelihood of developing a substance use disorder, no moderating effects were observed. Conclusions/importance: This study underscores the long-term consequences of exposure to childhood adversity.

  19. Clinical review: kinase inhibitors: adverse effects related to the endocrine system.

    Science.gov (United States)

    Lodish, Maya B

    2013-04-01

    The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.

  20. Adverse Effect of Post-Discharge Care Fragmentation on Outcomes after Readmissions after Liver Transplantation.

    Science.gov (United States)

    Kothari, Anai N; Loy, Veronica M; Brownlee, Sarah A; Ezure, Yoshiki; Schaidle-Blackburn, Colleen; Cotler, Scott J; di Sabato, Diego; Kuo, Paul C; Lu, Amy D

    2017-07-01

    Post-discharge surgical care fragmentation is defined as readmission to any hospital other than the hospital at which surgery was performed. The objective of this study was to assess the impact of fragmented readmissions within the first year after orthotopic liver transplantation (OLT). The Healthcare Cost and Utilization Project State Inpatient Databases for Florida and California from 2006 to 2011 were used to identify OLT patients. Post-discharge fragmentation was defined as any readmission to a non-index hospital, including readmitted patients transferred to the index hospital after 24 hours. Outcomes included adverse events, defined as 30-day mortality and 30-day readmission after a fragmented readmission. All statistical analyses considered a hierarchical data structure and were performed with multilevel, mixed-effects models. We analyzed 2,996 patients with 7,485 readmission encounters at 299 hospitals; 1,236 (16.5%) readmissions were fragmented. After adjustment for age, sex, readmission reason, index liver transplantation cost, readmission length of stay, number of previous readmissions, and time from transplantation, post-discharge fragmentation increased the odds of both 30-day mortality (odds ratio [OR] = 1.75; 95% CI 1.16 to 2.65) and 30-day readmission (OR = 2.14; 95% CI 1.83 to 2.49). Predictors of adverse events after a fragmented readmission included increased number of previous readmissions (OR = 1.07; 95% CI 1.01 to 1.14) and readmission within 90 days of OLT (OR = 2.19; 95% CI 1.61 to 2.98). Post-discharge fragmentation significantly increases the risk of both 30-day mortality and subsequent readmission after a readmission in the first year after OLT. More inpatient visits before a readmission and less time elapsed from index surgery increase the odds of an adverse event after discharge from a fragmented readmission. These parameters could guide transfer decisions for patients with post-discharge fragmentation. Copyright © 2017 American

  1. DRD4-exonIII-VNTR moderates the effect of childhood adversities on emotional resilience in young-adults.

    Directory of Open Access Journals (Sweden)

    Debjani Das

    Full Text Available Most individuals successfully maintain psychological well-being even when exposed to trauma or adversity. Emotional resilience or the ability to thrive in the face of adversity is determined by complex interactions between genetic makeup, previous exposure to stress, personality, coping style, availability of social support, etc. Recent studies have demonstrated that childhood trauma diminishes resilience in adults and affects mental health. The Dopamine receptor D4 (DRD4 exon III variable number tandem repeat (VNTR polymorphism was reported to moderate the impact of adverse childhood environment on behaviour, mood and other health-related outcomes. In this study we investigated whether DRD4-exIII-VNTR genotype moderates the effect of childhood adversities (CA on resilience. In a representative population sample (n = 1148 aged 30-34 years, we observed an interactive effect of DRD4 genotype and CA (β = 0.132; p = 0.003 on resilience despite no main effect of the genotype when effects of age, gender and education were controlled for. The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. Resilience was also significantly associated with approach-/avoidance-related personality measures (behavioural inhibition/activation system; BIS/BAS measures and an interactive effect of DRD4-exIII-VNTR genotype and CA on BAS was observed. Hence it is possible that approach-related personality traits could be mediating the effect of the DRD4 gene and childhood environment interaction on resilience such that when stressors are present, the 7-repeat allele influences the development of personality in a way that provides protection against adverse outcomes.

  2. DRD4-exonIII-VNTR moderates the effect of childhood adversities on emotional resilience in young-adults.

    Science.gov (United States)

    Das, Debjani; Cherbuin, Nicolas; Tan, Xiaoyun; Anstey, Kaarin J; Easteal, Simon

    2011-01-01

    Most individuals successfully maintain psychological well-being even when exposed to trauma or adversity. Emotional resilience or the ability to thrive in the face of adversity is determined by complex interactions between genetic makeup, previous exposure to stress, personality, coping style, availability of social support, etc. Recent studies have demonstrated that childhood trauma diminishes resilience in adults and affects mental health. The Dopamine receptor D4 (DRD4) exon III variable number tandem repeat (VNTR) polymorphism was reported to moderate the impact of adverse childhood environment on behaviour, mood and other health-related outcomes. In this study we investigated whether DRD4-exIII-VNTR genotype moderates the effect of childhood adversities (CA) on resilience. In a representative population sample (n = 1148) aged 30-34 years, we observed an interactive effect of DRD4 genotype and CA (β = 0.132; p = 0.003) on resilience despite no main effect of the genotype when effects of age, gender and education were controlled for. The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. Resilience was also significantly associated with approach-/avoidance-related personality measures (behavioural inhibition/activation system; BIS/BAS) measures and an interactive effect of DRD4-exIII-VNTR genotype and CA on BAS was observed. Hence it is possible that approach-related personality traits could be mediating the effect of the DRD4 gene and childhood environment interaction on resilience such that when stressors are present, the 7-repeat allele influences the development of personality in a way that provides protection against adverse outcomes.

  3. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    Science.gov (United States)

    Kennedy, Ann

    The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

  4. Adverse effects of caffeinated energy drinks among youth and young adults in Canada: a Web-based survey.

    Science.gov (United States)

    Hammond, David; Reid, Jessica L; Zukowski, Sara

    2018-01-09

    Energy drink consumption has increased dramatically among young Canadians, with anecdotal evidence of adverse health effects. There is a lack of population-based studies to examine the prevalence of adverse events from energy drinks, particularly among young people. The current study sought to assess adverse events from energy drinks among a population-based sample of youth and young adults in Canada. An online survey was conducted in 2015 with a national sample of youth (aged 12-17 yr) and young adults (aged 18-24 yr) recruited from a consumer panel. Respondents reported prior consumption of energy drinks as well as adverse outcomes, concurrent activities associated with the outcomes and whether medical attention was sought or considered. Adverse events from coffee were also assessed for comparison. Weighted analyses are reported. Of the 2055 respondents, 1516 (73.8%) reported having ever consumed an energy drink, and 1741 (84.7%) reported having ever consumed coffee (unweighted). Overall, 55.4% of respondents who had ever consumed an energy drink reported that they had experienced at least 1 adverse event, including fast heartbeat (24.7%), difficulty sleeping (24.1%), headache (18.3%), nausea/vomiting/diarrhea (5.1%), chest pain (3.6%) and seizures (0.2%); 3.1% had sought or had considered seeking medical help for an adverse event. The prevalence of reported adverse events was significantly greater among energy drink consumers than among coffee consumers (36.0%) (odds ratio [OR] 2.67 [95% confidence interval (CI) 2.01-2.56]), as was the proportion who reported seeking or considering seeking medical help for adverse events (3.1% v. 1.4%) (OR 2.18 [95% CI 1.39-3.41]). More than half of youth and young adults who had consumed energy drinks reported adverse outcomes, some serious enough to warrant seeking medical help. The adverse outcomes were consistent with the physiologic effects of caffeine but were significantly more prevalent than with other sources of

  5. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial.

    Science.gov (United States)

    Suter, Thomas M; Procter, Marion; van Veldhuisen, Dirk J; Muscholl, Michael; Bergh, Jonas; Carlomagno, Chiara; Perren, Timothy; Passalacqua, Rodolfo; Bighin, Claudia; Klijn, Jan G M; Ageev, Fail T; Hitre, Erika; Groetz, Juergen; Iwata, Hiroji; Knap, Malgorzata; Gnant, Michael; Muehlbauer, Susanne; Spence, Alison; Gelber, Richard D; Piccart-Gebhart, Martine J

    2007-09-01

    The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > or = 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m(2) v 257 mg/m(2)) or epirubicin (480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index. Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

  6. Mycorrhiza reduces adverse effects of dark septate endophytes (DSE) on growth of conifers.

    Science.gov (United States)

    Reininger, Vanessa; Sieber, Thomas N

    2012-01-01

    Mycorrhizal roots are frequently colonized by fungi of the Phialocephala fortinii s.l.-Acephala applanata species complex (PAC). These ascomycetes are common and widespread colonizers of tree roots. Some PAC strains reduce growth increments of their hosts but are beneficial in protecting roots against pathogens. Nothing is known about the effects of PAC on mycorrhizal fungi and the PAC-mycorrhiza association on plant growth, even though these two fungal groups occur closely together in natural habitats. We expect reduced colonization rates and reduced negative effects of PAC on host plants if roots are co-colonized by an ectomycorrhizal fungus (ECM). Depending on the temperature regime interactions among the partners in this tripartite ECM-PAC-plant system might also change. To test our hypotheses, effects of four PAC genotypes (two pathogenic and two non-pathogenic on the Norway spruce), mycorrhization by Laccaria bicolor (strain S238N) and two temperature regimes (19°C and 25°C) on the biomass of the Douglas-fir (Pseudotsuga menziesii) and Norway spruce (Picea abies) seedlings were studied. Mycorrhization compensated the adverse effects of PAC on the growth of the Norway spruce at both temperatures. The growth of the Douglas-fir was not influenced either by PAC or mycorrhization at 19°C, but at 25°C mycorrhization had a similar protective effect as in the Norway spruce. The compensatory effects probably rely on the reduction of the PAC-colonization density by mycorrhizae. Temperature and the PAC strain only had a differential effect on the biomass of the Norway spruce but not on the Douglas-fir. Higher temperature reduced mycorrhization of both hosts. We conclude that ectomycorrhizae form physical and/or physiological barriers against PAC leading to reduced PAC-colonization of the roots. Additionally, our results indicate that global warming could cause a general decrease of mycorrhization making primary roots more accessible to other symbionts and pathogens.

  7. Mycorrhiza reduces adverse effects of dark septate endophytes (DSE on growth of conifers.

    Directory of Open Access Journals (Sweden)

    Vanessa Reininger

    Full Text Available Mycorrhizal roots are frequently colonized by fungi of the Phialocephala fortinii s.l.-Acephala applanata species complex (PAC. These ascomycetes are common and widespread colonizers of tree roots. Some PAC strains reduce growth increments of their hosts but are beneficial in protecting roots against pathogens. Nothing is known about the effects of PAC on mycorrhizal fungi and the PAC-mycorrhiza association on plant growth, even though these two fungal groups occur closely together in natural habitats. We expect reduced colonization rates and reduced negative effects of PAC on host plants if roots are co-colonized by an ectomycorrhizal fungus (ECM. Depending on the temperature regime interactions among the partners in this tripartite ECM-PAC-plant system might also change. To test our hypotheses, effects of four PAC genotypes (two pathogenic and two non-pathogenic on the Norway spruce, mycorrhization by Laccaria bicolor (strain S238N and two temperature regimes (19°C and 25°C on the biomass of the Douglas-fir (Pseudotsuga menziesii and Norway spruce (Picea abies seedlings were studied. Mycorrhization compensated the adverse effects of PAC on the growth of the Norway spruce at both temperatures. The growth of the Douglas-fir was not influenced either by PAC or mycorrhization at 19°C, but at 25°C mycorrhization had a similar protective effect as in the Norway spruce. The compensatory effects probably rely on the reduction of the PAC-colonization density by mycorrhizae. Temperature and the PAC strain only had a differential effect on the biomass of the Norway spruce but not on the Douglas-fir. Higher temperature reduced mycorrhization of both hosts. We conclude that ectomycorrhizae form physical and/or physiological barriers against PAC leading to reduced PAC-colonization of the roots. Additionally, our results indicate that global warming could cause a general decrease of mycorrhization making primary roots more accessible to other symbionts

  8. Mycorrhiza Reduces Adverse Effects of Dark Septate Endophytes (DSE) on Growth of Conifers

    Science.gov (United States)

    Reininger, Vanessa; Sieber, Thomas N.

    2012-01-01

    Mycorrhizal roots are frequently colonized by fungi of the Phialocephala fortinii s.l. – Acephala applanata species complex (PAC). These ascomycetes are common and widespread colonizers of tree roots. Some PAC strains reduce growth increments of their hosts but are beneficial in protecting roots against pathogens. Nothing is known about the effects of PAC on mycorrhizal fungi and the PAC-mycorrhiza association on plant growth, even though these two fungal groups occur closely together in natural habitats. We expect reduced colonization rates and reduced negative effects of PAC on host plants if roots are co-colonized by an ectomycorrhizal fungus (ECM). Depending on the temperature regime interactions among the partners in this tripartite ECM-PAC-plant system might also change. To test our hypotheses, effects of four PAC genotypes (two pathogenic and two non-pathogenic on the Norway spruce), mycorrhization by Laccaria bicolor (strain S238N) and two temperature regimes (19°C and 25°C) on the biomass of the Douglas-fir (Pseudotsuga menziesii) and Norway spruce (Picea abies) seedlings were studied. Mycorrhization compensated the adverse effects of PAC on the growth of the Norway spruce at both temperatures. The growth of the Douglas-fir was not influenced either by PAC or mycorrhization at 19°C, but at 25°C mycorrhization had a similar protective effect as in the Norway spruce. The compensatory effects probably rely on the reduction of the PAC-colonization density by mycorrhizae. Temperature and the PAC strain only had a differential effect on the biomass of the Norway spruce but not on the Douglas-fir. Higher temperature reduced mycorrhization of both hosts. We conclude that ectomycorrhizae form physical and/or physiological barriers against PAC leading to reduced PAC-colonization of the roots. Additionally, our results indicate that global warming could cause a general decrease of mycorrhization making primary roots more accessible to other symbionts and

  9. Agricultural sources of contaminants of emerging concern and adverse health effects on freshwater fish

    Science.gov (United States)

    Tillitt, Donald E.; Buxton, Herbert T.

    2011-01-01

    Agricultural contaminants of emerging concern (CECs) are generally thought of as certain classes of chemicals associated with animal feeding and production facilities. Veterinary pharmaceuticals used in animal food production systems represent one of the largest groups of CECs. In our review, we discuss the extensive increase in use of antibiotics in animal feeding operations (AFOs) around the world. AFOs are a major consumer of antibiotics and other veterinary pharmaceuticals and over the past decade there has been growing information on the occurrence, release, and fate of CECs from animal food production operations, including the application of pharmaceutical-containing manure to agricultural fields and releases from waste lagoons. Concentrations of CECs in surface and ground water in proximity to AFOs correspond to their presence in the AFO wastes. In many cases, the environmental concentrations of agriculturally-derived CECs are below toxicity thresholds. Hormones and hormone replacement compounds are a notable exception, where chemical concentrations near AFOs can exceed concentrations known to cause adverse effects on endocrine-related functions in fish. In addition, some agricultural pesticides, once thought to be safe to non-target organisms, have demonstrated endocrine-related effects that may pose threats to fish populations in agricultural regions. That is, we have pesticides with emerging concerns, thus, the concern is emerging and not necessarily the chemical. In this light, one must consider certain agricultural pesticides to be included in the list of CECs. Even though agricultural pesticides are routinely evaluated in regulatory testing schemes which have been used for decades, the potential hazards of some pesticides have only recently been emerging. Emerging concerns of pesticides in fish include interference with hormone signaling pathways; additive (or more than additive) effects from pesticide mixtures; and adverse population-level effects at

  10. The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes.

    Science.gov (United States)

    Perez-Navarro, Lucia Monserrat; Restrepo, Blanca I; Fuentes-Dominguez, Francisco Javier; Duggirala, Ravindranath; Morales-Romero, Jaime; López-Alvarenga, Juan Carlos; Comas, Iñaki; Zenteno-Cuevas, Roberto

    2017-03-01

    To evaluate the effect size of type 2 diabetes mellitus (T2DM) on tuberculosis (TB) treatment outcomes and multi drug resistance (MDR). A cohort with 507 individuals with diagnosed TB included 183 with coexistence of T2DM and TB (TB-T2DM). Participants were identified at the time of TB diagnosis and followed during the course of TB treatment. Then we computed relative risks and adjustments by Cox proportional hazards for outcome variables (drug resistance, death, relapse, treatment failure), and the size of their effect as Cohen's-d. Patients with TB-T2DM were more likely to remain positive for acid-fast bacilli after two months of anti-TB treatment RR = [2.01 (95% CI: 1.3, 3.1)], to have drug resistant (DR) [OR 3.5 (95% CI: 1.8, 6.7)] and multi-drug resistant (MDR) TB [OR 3.5 (95% CI: 1.8, 7.1)]. The Cohen's-d for DR or MDR in T2DM was 0.69 when compared with non-DM subjects. The T2DM patients had higher odds of resistance to isoniazid (OR 3.9, 95% CI: 2.01, 7.9), rifampicin (OR 3.4, 95% CI: 1.6, 7.2) and pyrazinamide (OR 9.4, 95% CI: 2.8, 25.6), and their effect sizes were ≥0.67. Patients with TB-T2DM (versus no DM) were more likely to present with MDR TB (HR 3.1; 95% CI: 1.7, 5.8; p < 0.001), treatment failure (HR 2.04; 95% CI: 1.07, 3.8; p = 0.02) and relapse (HR 1.86; 95% CI: 1.09, 3.1; p = 0.02), with effect size ≥0.34. T2DM showed a substantial contribution to the presence of DR or MDR-TB and to adverse clinical outcomes during and after TB treatment. Our findings support the importance for routine screening of T2DM among newly-diagnosed TB patients in order to stratify them for immediate DR assessment, and highlight the need for clinical trials to evaluate variations to the standard TB treatment in TB-T2DM to prevent adverse treatment outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Honeybees Produce Millimolar Concentrations of Non-Neuronal Acetylcholine for Breeding: Possible Adverse Effects of Neonicotinoids

    Science.gov (United States)

    Wessler, Ignaz; Gärtner, Hedwig-Annabel; Michel-Schmidt, Rosmarie; Brochhausen, Christoph; Schmitz, Luise; Anspach, Laura; Grünewald, Bernd; Kirkpatrick, Charles James

    2016-01-01

    The worldwide use of neonicotinoid pesticides has caused concern on account of their involvement in the decline of bee populations, which are key pollinators in most ecosystems. Here we describe a role of non-neuronal acetylcholine (ACh) for breeding of Apis mellifera carnica and a so far unknown effect of neonicotinoids on non-target insects. Royal jelly or larval food are produced by the hypopharyngeal gland of nursing bees and contain unusually high ACh concentrations (4–8 mM). ACh is extremely well conserved in royal jelly or brood food because of the acidic pH of 4.0. This condition protects ACh from degradation thus ensuring delivery of intact ACh to larvae. Raising the pH to ≥5.5 and applying cholinesterase reduced the content of ACh substantially (by 75–90%) in larval food. When this manipulated brood was tested in artificial larval breeding experiments, the survival rate was higher with food supplemented by 100% with ACh (6 mM) than with food not supplemented with ACh. ACh release from the hypopharyngeal gland and its content in brood food declined by 80%, when honeybee colonies were exposed for 4 weeks to high concentrations of the neonicotinoids clothianidin (100 parts per billion [ppb]) or thiacloprid (8,800 ppb). Under these conditions the secretory cells of the gland were markedly damaged and brood development was severely compromised. Even field-relevant low concentrations of thiacloprid (200 ppb) or clothianidin (1 and 10 ppb) reduced ACh level in the brood food and showed initial adverse effects on brood development. Our findings indicate a hitherto unknown target of neonicotinoids to induce adverse effects on non-neuronal ACh which should be considered when re-assessing the environmental risks of these compounds. To our knowledge this is a new biological mechanism, and we suggest that, in addition to their well documented neurotoxic effects, neonicotinoids may contribute to honeybee colony losses consecutive to a reduction of the ACh content

  12. Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

    Science.gov (United States)

    Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

    2016-11-01

    Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar

  13. A Review of Epidemiological Research on Adverse Neurological Effects of Exposure to Ambient Air Pollution

    Science.gov (United States)

    Xu, Xiaohui; Ha, Sandie Uyen; Basnet, Rakshya

    2016-01-01

    There is a growing body of epidemiological research reporting the neurological effects of ambient air pollution. We examined current evidence, identified the strengths and weaknesses of published epidemiological studies, and suggest future directions for research in this area. Studies were identified through a systematic search of online scientific databases, in addition to a manual search of the reference lists from the identified papers. Despite being a relatively new area of investigation, overall, there is mounting evidence implicating adverse effects of air pollution on neurobehavioral function in both adults and children. Further research is needed to expand our understanding of these relationships, including improvement in the accuracy of exposure assessments; focusing on specific toxicants and their relationships to specific health endpoints, such as neurodevelopmental disorders and neurodegenerative diseases; investigating the combined neurological effects of multiple air pollutants; and further exploration of genetic susceptibility for neurotoxicity of air pollution. In order to achieve these goals collaborative efforts are needed from multidisciplinary teams, including experts in toxicology, biostatistics, geographical science, epidemiology, and neurology. PMID:27547751

  14. [PHARMACOLOGICAL TREATMENT IN PALLIATIVE CARE. DRUG ADMINISTRATION ROUTE, CONTINUOUS SUBCUTANEOUS INFUSION, ADVERSE SIDE EFFECTS, SYMPTOM MANAGEMENT].

    Science.gov (United States)

    Dominguez Álvarez, Rocío; Calderón Carrasco, Justo; García Colchero, Francisco; Postigo Mota, Salvador; Alburquerque Medina, Eulalia

    2015-01-01

    To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice. Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected. The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication. Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm

  15. Adverse psychosocial working conditions and risk of severe depressive symptoms. Do effects differ by occupational grade?

    NARCIS (Netherlands)

    Rugulies, Reiner; Aust, Birgit; Madsen, Ida E. H.; Burr, Hermann; Siegrist, Johannes; Bultmann, Ute

    Background: Depression is a major concern for public health. Both adverse working conditions and low socio-economic position are suspected to increase risk of depression. In a representative sample of the Danish workforce we investigated (i) whether adverse psychosocial working conditions, defined

  16. Effects of Timing of Adversity on Adolescent and Young Adult Adjustment

    Science.gov (United States)

    Kiff, Cara J.; Cortes, Rebecca C.; Lengua, Liliana J.; Kosterman, Rick; Hawkins, J. David; Mason, W. Alex

    2012-01-01

    Exposure to adversity during childhood and adolescence predicts adjustment across development. Furthermore, adolescent adjustment problems persist into young adulthood. This study examined relations of contextual adversity with concurrent adolescent adjustment and prospective mental health and health outcomes in young adulthood. A longitudinal…

  17. Effects of Hurricane Katrina and Other Adverse Life Events on Adolescent Female Offenders: A Test of General Strain Theory.

    Science.gov (United States)

    Robertson, Angela R; Stein, Judith A; Schaefer-Rohleder, Lacey

    2010-11-01

    This study tested Agnew's General Strain Theory (GST) by examining the roles of anger, anxiety, and maladaptive coping in mediating the relationship between strain and three outcomes (serious delinquency, minor delinquency, and continued involvement in the juvenile justice system) among adolescent female offenders (N = 261). Strains consisted of adverse life events and exposure to Hurricane Katrina. Greater exposure to Hurricane Katrina was directly related to serious delinquency and maladaptive coping. Hurricane Katrina also had an indirect effect on minor delinquency and Post-Katrina juvenile justice involvement mediated through maladaptive coping. Adverse life events were associated with increased anger, anxiety, and maladaptive coping. Anger mediated the relationship between adverse life events and serious delinquency. Anxiety mediated the relationship between adverse life events and minor delinquency. Maladaptive coping strategies were associated with minor delinquency and juvenile justice involvement. Findings lend support to GST.

  18. Charge is an important determinant of hemodynamic and adverse cardiovascular effects of cationic drugs.

    Science.gov (United States)

    Pugsley, Michael K; Authier, Simon; Curtis, Michael J

    2015-12-01

    Cationic compounds are diverse and atypical therapeutic substances. In the present study we examined whether a prototypical class effect of cationic drugs in the cardiovascular system exists and whether this might be predictable on the basis of chemistry. The dose-dependent effects of cationic compounds of varying molecular weights and charge were examined on the blood pressure (BP), heart rate (HR) and the ECG in anesthetized rats. The compounds examined were protamine, hexadimethrine, tetraethylammonium (TEA), low molecular weight poly-L-lysine (LMW-PLL) and high molecular weight PLL (HMW-PLL). All of the compounds examined except TEA produced a dose-dependent reduction in BP. No changes occurred in HR even when high doses were administered. The ECG effects of these cationic compounds included a dose-dependent prolongation of the QT interval, especially at higher doses. All compounds transiently decreased the size of the P-wave after i.v. bolus administration whereas only protamine and hexadimethrine prolonged the PR and QRS intervals and only at the highest dose (32 mg/kg) administered. All cationic compounds, except TEA and saline, evoked ventricular premature beats (VPB), and protamine and HMW-PLL also evoked brief episodes of ventricular tachycardia (VT). The incidence and frequency of arrhythmias was not dose-dependent and no animals experienced protracted episodes of arrhythmia incidence. These dose dependent effects of the polycationic compounds tested suggest a collective mechanism of action that relates the effect of charge of the compound to the onset and persistence of observed cardiovascular toxicity, and adverse cardiovascular effect risk appears to be predictable on this basis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Update on raloxifene: mechanism of action, clinical efficacy, adverse effects, and contraindications.

    Science.gov (United States)

    Gizzo, Salvatore; Saccardi, Carlo; Patrelli, Tito Silvio; Berretta, Roberto; Capobianco, Giampiero; Di Gangi, Stefania; Vacilotto, Antonio; Bertocco, Anna; Noventa, Marco; Ancona, Emanuele; D'Antona, Donato; Nardelli, Giovanni Battista

    2013-06-01

    Raloxifene is the only selective estrogen receptor modulator approved for long-term treatment in the prevention of osteoporotic fractures and for the reduction of invasive breast cancer risk in post-menopausal women. The demonstrated beneficial effects on bone and mammalian tissue led clinical and molecular research to focus mainly on these organs, giving less attention to all other systemic effects. The aim of this review was to evaluate all described systemic effects of raloxifene, investigating its molecular and tissutal mechanism of action. A literature research was carried out in electronic databases MEDLINE, EMBASE, ScienceDirect, and the Cochrane Library in interval time between 2000 and 2012. Outcomes were considered in relation to positive/adverse effects concerning bone metabolism, lipid metabolism, coagulation pattern, menopausal symptoms, breast cancer onset, and endometrial cancer onset. Raloxifene acts as an estrogen agonist or antagonist depending on the tissue. This feature is related to specific actions on at least 2 distinct estrogen receptors, whose proportions vary according to tissue type. Raloxifene is a drug for the treatment of osteoporosis and for the prevention of estrogen receptor-positive breast cancer because it guarantees a safety profile on the endometrium. Raloxifene is furthermore an effective therapy in women with increased levels of plasma cholesterol. Raloxifene treatment shifts the coagulation pattern toward prothrombosis, and the patients should be exhaustively informed about the risks associated with therapy. Raloxifene does not show to affect memory and cognition. Finally, it is noteworthy that quality-of-life studies demonstrated some favorable effects of raloxifene.

  20. The Drosophilaforaginggene human orthologuePRKG1predicts individual differences in the effects of early adversity on maternal sensitivity.

    Science.gov (United States)

    Sokolowski, H Moriah; Vasquez, Oscar E; Unternaehrer, Eva; Sokolowski, Dustin J; Biergans, Stephanie D; Atkinson, Leslie; Gonzalez, Andrea; Silveira, Patricia P; Levitan, Robert; O'Donnell, Kieran J; Steiner, Meir; Kennedy, James; Meaney, Michael J; Fleming, Alison S; Sokolowski, Marla B

    2017-04-01

    There is variation in the extent to which childhood adverse experience affects adult individual differences in maternal behavior. Genetic variation in the animal foraging gene, which encodes a cGMP-dependent protein kinase, contributes to variation in the responses of adult fruit flies, Drosophila melanogaster , to early life adversity and is also known to play a role in maternal behavior in social insects. Here we investigate genetic variation in the human foraging gene ( PRKG1 ) as a predictor of individual differences in the effects of early adversity on maternal behavior in two cohorts. We show that the PRKG1 genetic polymorphism rs2043556 associates with maternal sensitivity towards their infants. We also show that rs2043556 moderates the association between self-reported childhood adversity of the mother and her later maternal sensitivity. Mothers with the TT allele of rs2043556 appeared buffered from the effects of early adversity, whereas mothers with the presence of a C allele were not. Our study used the Toronto Longitudinal Cohort (N=288 mother-16 month old infant pairs) and the Maternal Adversity and Vulnerability and Neurodevelopment Cohort (N=281 mother-18 month old infant pairs). Our findings expand the literature on the contributions of both genetics and gene-environment interactions to maternal sensitivity, a salient feature of the early environment relevant for child neurodevelopment.

  1. Potential adverse effects of applying phosphate amendments to immobilize soil contaminants.

    Science.gov (United States)

    Majs, Frantisek

    2011-01-01

    Seven-day batch equilibrium experiments were conducted to measure the efficacy of four phosphate amendments (trisodium trimetaphosphate [TP3], dodecasodium phytate [Na-IP6], precipitated calcium phytate [Ca-IP6], and hydroxyapatite [HA]) for immobilizing Ni and U in organic-rich sediment. Using the eight-step modified Miller's sequential extraction procedure and the USEPA's Toxicity Characteristic Leaching Procedure, the effect of these amendments on the distribution of Ni and U was assessed. Relative to unamended controls, equilibrium aqueous-phase U concentrations were lower following HA and Ca-IP6 additions but higher following TP3 and Na-IP6 amendments, whereas aqueous Ni concentrations were not decreased only in the Na-IP6 amended treatment relative to the control. The poor rates of contaminant immobilization following TP3 and Na-IP6 amendments correlate with the dispersion of organic matter and organo-mineral colloids, which probably contain sorbed U and Ni. While all amendments shifted the U distribution toward more recalcitrant soil fractions, Ni was redistributed to more labile soil fractions. This study cautions that the addition of orthophosphates and organophosphates as contaminant immobilizing amendments may in fact have adverse effects, especially in high-organic soils. Particular attention is warranted at sites with mixed contaminants with varying geochemical behaviors. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  2. The importance of age and smoking in evaluating adverse cytogenetic effects of exposure to environmental agents

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J.D. [Lawrence Livermore National Lab., CA (United States); Moore, D.H. II [California Pacific Medical Center, San Francisco, CA (United States). Cancer Research Institute

    1995-08-01

    Fluorescence in situ hybridization with chromosome-specific composite DNA probes (``chromosome painting``) is a reliable and efficient method for detecting structural chromosome aberrations. Painting is now being used to quantify chromosome damage in many human populations. In one such study we evaluated 91 unexposed people ranging in age from birth (cord bloods) to 79. We established a baseline frequency of stable aberrations that showed a highly significant curvi-linear increase with age (p < 0.00001) that accounted for 70% of the variance between donors. The magnitude of this effect illustrates the importance of understanding the cytogenetic changes that occur with age, which is particularly important for quantifying the effects of prior adverse environmental, occupational, or accidental exposure. In this paper we use the data obtained in our previous study to characterize the distribution of stable aberrations by age and pack-years of cigarette smoking. We also provide estimates of the number of cell equivalents that need to be scored to detect a given increase in aberrations above the background level surveyed in this population.

  3. Gold Bead Implantation in Acupoints for Coxofemoral Arthrosis in Dogs: Method Description and Adverse Effects.

    Science.gov (United States)

    Jæger, Gry T; Stigen, Øyvind; Devor, Morten; Moe, Lars

    2012-09-04

    Gold bead implantation has been used for years as an alternative method to improve function in chronic joint disease both in humans and dogs. The aims of the present study were to describe the technique of implanting 24-karat gold beads around the hip joints of dogs with chronic hip dysplasia, and to record any side effects or complications of such treatment. A prospective placebo-controlled double-blinded clinical trial was performed. Eighty dogs were randomly allocated to treatment or placebo, with 38 in the gold implantation group and 42 in the placebo group, and followed intensely for six months. The implantation technique was simple to perform, using fluoroscopy and with the dogs under inhalation anesthesia for about 30 minutes. Adverse effects, measured as pain or discomfort, were seen for a period of up to four weeks in 15 of the dogs in the gold implantation group, compared to six dogs in the placebo group. During implantation, a technical difficulty occurred as 82% of the dogs showed leakage of blood and/or synovia from the needles. The dogs in the gold implantation group were radiographed 18 months later. Of the 30 dogs that were radiographed at both inclusion and 24 months, 80% (24 dogs) showed a deterioration of the coxofemoral arthrosis, the other six had stable disease evaluated by radiography. Migration of gold beads was only observed in one dog.

  4. Effects of Adverse Childhood Experiences, Stress, and Social Support on the Health of College Students.

    Science.gov (United States)

    Karatekin, Canan; Ahluwalia, Rohini

    2016-12-01

    The goal of the study was to describe the nature of adverse childhood experiences (ACEs) reported by undergraduates and to examine the effect of ACEs, perceived stress, and perceived social support on their health. Although respondents ( N = 321) had parents with relatively high levels of education and indicated generally high levels of social support, results nevertheless showed a relatively high level of mental health problems and rates of ACEs that were similar to those in the general population in the state. Those with higher levels of ACEs had greater levels of stress and lower levels of social support. ACEs, social support, and stress explained more than half the variance in mental health scores, with stress making the greatest contribution. Despite the fact that we used different measures and an independent sample, findings generally replicated a previous study. Results point to a need to increase awareness of the association between ACEs and health on college campuses, to examine the effects of ACEs in more detail, and to design ACE-informed programs for this population.

  5. Gold Bead Implantation in Acupoints for Coxofemoral Arthrosis in Dogs: Method Description and Adverse Effects

    Directory of Open Access Journals (Sweden)

    Lars Moe

    2012-09-01

    Full Text Available Gold bead implantation has been used for years as an alternative method to improve function in chronic joint disease both in humans and dogs. The aims of the present study were to describe the technique of implanting 24-karat gold beads around the hip joints of dogs with chronic hip dysplasia, and to record any side effects or complications of such treatment. A prospective placebo-controlled double-blinded clinical trial was performed. Eighty dogs were randomly allocated to treatment or placebo, with 38 in the gold implantation group and 42 in the placebo group, and followed intensely for six months. The implantation technique was simple to perform, using fluoroscopy and with the dogs under inhalation anesthesia for about 30 minutes. Adverse effects, measured as pain or discomfort, were seen for a period of up to four weeks in 15 of the dogs in the gold implantation group, compared to six dogs in the placebo group. During implantation, a technical difficulty occurred as 82% of the dogs showed leakage of blood and/or synovia from the needles. The dogs in the gold implantation group were radiographed 18 months later. Of the 30 dogs that were radiographed at both inclusion and 24 months, 80% (24 dogs showed a deterioration of the coxofemoral arthrosis, the other six had stable disease evaluated by radiography. Migration of gold beads was only observed in one dog.

  6. In vitro assessment of the adverse effects of antiretroviral drugs on the human male gamete.

    Science.gov (United States)

    Ahmad, G; Moinard, N; Jouanolou, V; Daudin, M; Gandia, P; Bujan, L

    2011-03-01

    This study was designed to investigate the in vitro effects of didanosine, zidovudine, saquinavir and indinavir, commonly used in highly active antiretroviral therapy, on human sperm fertility parameters. Thirty semen samples from healthy men were collected and prepared by gradient density method. Aliquots of 90% fractions with >80% motile spermatozoa were incubated for 1, 3, and 6h with different concentrations of the antiretroviral drugs (20, 40, and 80 μg/ml). Sperm motility was evaluated by computer assisted sperm analysis system. Sperm mitochondrial potential was evaluated using 3,3'-dihexyloxacarbocyanine iodide (DIOC(6)) and the acrosome reaction was examined using pisum sativum agglutinin method. A dose-dependent decrease in sperm motility was observed with saquinavir. Saquinavir also induced a significant time and dose-dependent decrease in mitochondrial potential and an increase in spontaneous acrosome reaction. These findings indicate that, in vitro, higher doses of saquinavir have adverse effects on sperm motility, mitochondrial potential and acrosome reaction. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Beneficial and adverse effects of testosterone on the cardiovascular system in men.

    Science.gov (United States)

    Ruige, Johannes B; Ouwens, D Margriet; Kaufman, Jean-Marc

    2013-11-01

    The widespread use of T therapy, particularly in aging males, necessitates knowledge of the relationship between T and the cardiovascular system. The review is based on a 1970 to 2013 PubMed search with terms related to androgens in combination with cardiovascular disease, including T, dihydrotestosterone, trial, mortality, cardiovascular disease, myocardial infarction, blood pressure, endothelial function, dyslipidemia, thrombosis, ventricular function, and arrhythmia. Original articles, systematic reviews and meta-analyses, and relevant citations were screened. Low T has been linked to increased blood pressure, dyslipidemia, atherosclerosis, arrhythmia, thrombosis, endothelial dysfunction, as well as to impaired left ventricular function. On the one hand, a modest association is suggested between low endogenous T and incident cardiovascular disease or cardiovascular mortality, implying unrecognized beneficial T effects, residual confounding, or a relationship with health status. On the other hand, treatments with T to restore "normal concentrations" have so far not been proven to be beneficial with respect to cardiovascular disease; neither have they definitely shown specific adverse cardiovascular effects. The cardiovascular risk-benefit profile of T therapy remains largely evasive in view of a lack of well-designed and adequately powered randomized clinical trials. The important knowledge gap as to the exact relationship between T and cardiovascular disease would support a cautious, restrained approach to T therapy in aging men, pending clarification of benefits and risks by adequately powered clinical trials of sufficient duration.

  8. The Adverse Effect of Spasticity on 3-Month Poststroke Outcome Using a Population-Based Model

    Directory of Open Access Journals (Sweden)

    S. R. Belagaje

    2014-01-01

    Full Text Available Several devices and medications have been used to address poststroke spasticity. Yet, spasticity’s impact on outcomes remains controversial. Using data from a cohort of 460 ischemic stroke patients, we previously published a validated multivariable regression model for predicting 3-month modified Rankin Score (mRS as an indicator of functional outcome. Here, we tested whether including spasticity improved model fit and estimated the effect spasticity had on the outcome. Spasticity was defined by a positive response to the question “Did you have spasticity following your stroke?” on direct interview at 3 months from stroke onset. Patients who had expired by 90 days (n=30 or did not have spasticity data available (n=102 were excluded. Spasticity affected the 3-month functional status (β=0.420, 95 CI=0.194 to 0.645 after accounting for age, diabetes, leukoaraiosis, and retrospective NIHSS. Using spasticity as a covariable, the model’s R2 changed from 0.599 to 0.622. In our model, the presence of spasticity in the cohort was associated with a worsened 3-month mRS by an average of 0.4 after adjusting for known covariables. This significant adverse effect on functional outcomes adds predictive value beyond previously established factors.

  9. Electronic cigarettes: assessing the efficacy and the adverse effects through a systematic review of published studies.

    Science.gov (United States)

    Gualano, Maria Rosaria; Passi, Stefano; Bert, Fabrizio; La Torre, Giuseppe; Scaioli, Giacomo; Siliquini, Roberta

    2015-09-01

    To investigate the efficacy and the adverse effects (AEs) of the electronic cigarette, we performed a systematic review of published studies. We selected experimental and observational studies examining the efficacy (as reduction of desire to smoke and/or number of cigarettes smoked and/or quitting or as reduction of nicotine withdrawal symptoms) and the safety of EC (AEs self-reported or clinical/laboratory). The following search engines were used: PubMed, ISI Web of Knowledge and Cochrane Controlled Trials Register. Finally, six experimental studies and six cohort studies were included. In the prospective 12-month, randomized controlled trial, smoking reduction was documented in 22.3 and 10.3% at Weeks 12 and 52, respectively (P < 0.001 versus baseline). Moreover, two cohort studies reported a reduction in the number of cigarette/day (from 50 to 80%) after the introduction of the EC. 'Mouth and throat irritation', 'nausea', 'headache' and 'dry cough' were the most frequently AEs reported. The use of the EC can reduce the number of cigarettes smoked and withdrawal symptoms, but the AEs reported are mainly related to a short period of use. Long-term studies are needed to evaluate the effects of the EC usage after a chronic exposure. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. The role of Notch in the cardiovascular system: potential adverse effects of investigational Notch inhibitors

    Directory of Open Access Journals (Sweden)

    Paola eRizzo

    2015-01-01

    Full Text Available Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta- like ligand 4 (Dll4- activated Notch signalling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long term cardiotoxicity associated to Notch inhibition in cancer patients. In this review we will focus on mechanisms through which inhibition of Notch signalling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor

  11. Premedication with midazolam prior to caesarean section has no neonatal adverse effects.

    Science.gov (United States)

    Senel, Ahmet Can; Mergan, Fatih

    2014-01-01

    Like all surgical patients, obstetric patients also feel operative stress and anxiety. This can be prevented by giving patients detailed information about their operation and with preoperative pharmacological medications. Because of depressive effects of sedatives on newborns, pharmacological medications are omitted, especially in obstetric patients. The literature contains few studies concerning preoperative midazolam use in Caesarian section (C/S) patients. Our aim in this study was to help patients undergoing C/S surgery. One group scheduled for elective C/S received midazolam 0.025 mg kg(-1) intravenously, the other received saline. Maternal anxiety was evaluated using Amsterdam Preoperative Anxiety and Information Scale (APAIS) scores, and newborns were evaluated using Apgar and the Neonatal Neurologic and Adaptive Capacity Score (NACS). In conclusion, patients receiving midazolam 0.025 mg kg(-1) as premedication had significantly low anxiety scores, without any adverse effects on the newborns. Midazolam can therefore safely be used as a premedicative agent in C/S surgery. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  12. [Adverse side-effect on sexual function caused by psychotropic drugs and psychotropic substances].

    Science.gov (United States)

    Cohen, S; Kühn, K U; Sträter, B; Scherbaum, N; Weig, W

    2010-09-01

    Unhindered sexuality plays an important role in the quality of life and this also holds true for patients with psychiatric illnesses. Knowledge concerning the complex neuronal and endocrine control mechanisms of sexual function reveals areas of possible dysfunction caused by the interactions between the control system, psychiatric drugs and addictive psychoactive substances. The differentiation of the cause of the dysfunction between being caused by the underlying illness and caused by other factors is difficult in practice. Both classical tri-cyclic antidepressants and selective serotonin uptake inhibitors can frequently cause adverse effects in multiple dimensions of sexual function. This same is true for neuroleptics, whereby the differentiation between symptoms of schizophrenia and side-effects from the medication can make an evaluation difficult. The medication-based strategy used to treat opiate dependency by administration of methadone causes sexual dysfunction in many cases. The consideration of medication-induced sexual dysfunction has a great importance with regard to compliance. Possible solutions can be modification of the medication regime, additional medication, e.g. partial antagonists and PD5 inhibitors, as well as dysfunction-specific psychotherapy and psychoeducation.

  13. Adverse Structural and Functional Effects of Marijuana on the Brain: Evidence Reviewed.

    Science.gov (United States)

    Mandelbaum, David E; de la Monte, Suzanne M

    2017-01-01

    The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer disease, Parkinson disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, anecdotal data and the high level of interest in this treatment must not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure. This critical review focuses on evidence-based research designed to assess both therapeutic benefits and harmful effects of cannabis exposure and is combined with an illustration of the neuropathologic findings in a fatal case of cannabis-induced psychosis. The literature and reported case provide strong evidence that chronic cannabis abuse causes cognitive impairment and damages the brain, particularly white matter, where cannabinoid 1 receptors abound. Contrary to popular perception, there are few objective data supporting preferential use of cannabis over conventional therapy for restoration of central nervous system structure and function in disease states such as multiple sclerosis, epilepsy, or schizophrenia. Additional research is needed to determine if subsets of individuals with various neurological and psychiatric diseases derive therapeutic benefits from cannabis. Copyright © 2016. Published by Elsevier Inc.

  14. Adverse effects of the renal accumulation of haem proteins. Novel therapeutic approaches.

    Science.gov (United States)

    Guerrero-Hue, Melania; Rubio-Navarro, Alfonso; Sevillano, Ángel; Yuste, Claudia; Gutiérrez, Eduardo; Palomino-Antolín, Alejandra; Román, Elena; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2017-06-28

    Haemoglobin and myoglobin are haem proteins that play a key role as they help transport oxygen around the body. However, because of their chemical structure, these molecules can exert harmful effects when they are released massively into the bloodstream, as reported in certain pathological conditions associated with rhabdomyolysis or intravascular haemolysis. Once in the plasma, these haem proteins can be filtered and can accumulate in the kidney, where they become cytotoxic, particularly for the tubular epithelium, inducing acute kidney failure and chronic kidney disease. In this review, we will analyse the different pathological contexts that lead to the renal accumulation of these haem proteins, their relation to both acute and chronic loss of renal function, the pathophysiological mechanisms that cause adverse effects and the defence systems that counteract such actions. Finally, we will describe the different treatments currently used and present new therapeutic options based on the identification of new cellular and molecular targets, with particular emphasis on the numerous clinical trials that are currently ongoing. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  15. Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.

    Science.gov (United States)

    Meyers, Jacquelyn L; Shmulewitz, Dvora; Wall, Melanie M; Keyes, Katherine M; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J; Gelernter, Joel; Grant, Bridget F; Hasin, Deborah

    2015-01-01

    Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. © 2013 Society for the Study of Addiction.

  16. Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

    Directory of Open Access Journals (Sweden)

    Abdel-Tawab H. Mossa

    2015-01-01

    Full Text Available The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1 body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1 body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT, alkaline phosphatase (ALP, and gamma-glutamyl transferase (GGT, and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity.

  17. [Changes of menstruation patterns and adverse effects during the treatment of LNG-IUS for symptomatic adenomyosis].

    Science.gov (United States)

    Li, L; Leng, J H; Zhang, J J; Jia, S Z; Li, X Y; Shi, J H; Dai, Y; Zhang, J R; Li, T; Xu, X X; Liu, Z Z; You, S S; Chang, X Y; Lang, J H

    2016-09-25

    Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively( P 12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P > 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened-menstruation being the most common manifestations, while adverse effects decrease significantly. Changes of

  18. Effects of an educational patient safety campaign on patients' safety behaviours and adverse events.

    Science.gov (United States)

    Schwappach, David L B; Frank, Olga; Buschmann, Ute; Babst, Reto

    2013-04-01

    Rationale, aims and objectives  The study aims to investigate the effects of a patient safety advisory on patients' risk perceptions, perceived behavioural control, performance of safety behaviours and experience of adverse incidents. Method  Quasi-experimental intervention study with non-equivalent group comparison was used. Patients admitted to the surgical department of a Swiss large non-university hospital were included. Patients in the intervention group received a safety advisory at their first clinical encounter. Outcomes were assessed using a questionnaire at discharge. Odds ratios for control versus intervention group were calculated. Regression analysis was used to model the effects of the intervention and safety behaviours on the experience of safety incidents. Results  Two hundred eighteen patients in the control and 202 in the intervention group completed the survey (75 and 77% response rates, respectively). Patients in the intervention group were less likely to feel poorly informed about medical errors (OR = 0.55, P = 0.043). There were 73.1% in the intervention and 84.3% in the control group who underestimated the risk for infection (OR = 0.51, CI 0.31-0.84, P = 0.009). Perceived behavioural control was lower in the control group (meanCon  = 3.2, meanInt  = 3.5, P = 0.010). Performance of safety-related behaviours was unaffected by the intervention. Patients in the intervention group were less likely to experience any safety-related incident or unsafe situation (OR for intervention group = 0.57, CI 0.38-0.87, P = 0.009). There were no differences in concerns for errors during hospitalization. There were 96% of patients (intervention) who would recommend other patients to read the advisory. Conclusions  The results suggest that the safety advisory decreases experiences of adverse events and unsafe situations. It renders awareness and perceived behavioural control without increasing concerns for safety and

  19. Mesotherapy-induced panniculitis treated with dapsone: case report and review of reported adverse effects of mesotherapy.

    Science.gov (United States)

    Tan, Jennifer; Rao, Babar

    2006-01-01

    Mesotherapy is a procedure involving the injection of substances into the dermis and subcutaneous tissue. Used in Europe for decades in the treatment of various medical conditions and cosmetic fat dissolution, the technique only recently became widely available in the United States. Mesotherapy has been surrounded by controversy pertaining to efficacy and has been associated with localized complications, including allergic reactions, necrosis, and infections. Panniculitis is a rare adverse reaction to mesotherapy that may result from injection pressure, local trauma, or the type of injected substances. Treatment options for complications are limited. We report a case of mesotherapy-induced panniculitis successfully treated with dapsone. This case illustrates one of the potential adverse effects of mesotherapy and suggests that dapsone may be effective in the treatment of panniculitis resulting from such injections. Reported adverse effects associated with mesotherapy are also reviewed.

  20. Effects of Video Games on the Adverse Corollaries of Chemotherapy in Pediatric Oncology Patients: A Single-Case Analysis.

    Science.gov (United States)

    Kolko, David J.; Rickard-Figueroa, Jorge L.

    1985-01-01

    Assessed effects of video games on adverse corollaries of chemotherapy in three pediatric oncology patients. Results indicated that access to video games resulted in reduction in the number of anticipatory symptoms experienced and observed, as well as a diminution in the aversiveness of chemotherapy side effects. (Author/NRB)

  1. A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? : An analytical framework

    NARCIS (Netherlands)

    Thurston, George D; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W; Grigg, Jonathan; Heederik, Dick|info:eu-repo/dai/nl/072910542; Kelly, Frank J; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T; Rich, David; Ritz, Beate; Samet, Jonathan M; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert|info:eu-repo/dai/nl/067548180

    The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have

  2. A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework

    Science.gov (United States)

    Thurston, George D.; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D.; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W.; Grigg, Jonathan; Heederik, Dick; Kelly, Frank J.; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T.; Rich, David; Ritz, Beate; Samet, Jonathan M.; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert

    2017-01-01

    The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies. This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution. PMID:28077473

  3. A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework.

    Science.gov (United States)

    Thurston, George D; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W; Grigg, Jonathan; Heederik, Dick; Kelly, Frank J; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T; Rich, David; Ritz, Beate; Samet, Jonathan M; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert

    2017-01-01

    The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution. Copyright ©ERS 2017.

  4. Maternal adverse effects with different loading infusion rates of antenatal magnesium sulphate for preterm fetal neuroprotection: the IRIS randomised trial.

    Science.gov (United States)

    Bain, E S; Middleton, P F; Yelland, L N; Ashwood, P J; Crowther, C A

    2014-04-01

    To evaluate a slower (compared with a standard) infusion rate of the loading dose of magnesium sulphate for preterm fetal neuroprotection as a strategy to reduce maternal adverse effects. Randomised controlled trial. South Australian maternity hospital. Fifty-one women at magnesium sulphate over either 60 or 20 minutes (followed by maintenance of 1 g/hour until birth, or for up to 24 hours). Any maternal adverse effects associated with the infusion. Overall, 71% of women experienced adverse effects during the first hour of their infusion; the difference between groups was not significant [15/25 (60%) 60-minute loading; 21/26 (81%) 20-minute loading; risk ratio (RR) 0.74; 95% confidence interval (95% CI) 0.51-1.08]. Although no serious maternal complications occurred, adverse effects led to three women ceasing the loading treatment (1/25 in the 60-minute loading group; 2/26 in the 20-minute loading group; RR 0.52; 95% CI 0.05-5.38). Women in the 60-minute loading group experienced significantly less warmth and flushing at 20 minutes into the infusion (7/25 in the 60-minute loading group; 15/26 in the 20-minute loading group; RR 0.49; 95% CI 0.24-0.99). No other differences between groups for maternally reported and clinical adverse effects were shown. A slower rate of administering the loading dose of magnesium sulphate did not reduce the occurrence of maternal adverse effects overall. Flushing and warmth at 20 minutes into the infusion was reduced with a slower infusion. © 2014 Royal College of Obstetricians and Gynaecologists.

  5. Quantitative Adverse Outcome Pathway for Neurodevelopmental Effects of Thyroid Peroxidase-Induced Thyroid Hormone Synthesis Inhibition

    Data.gov (United States)

    U.S. Environmental Protection Agency — Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models....

  6. Vaccination-Related Side Effects, Humoral Immunity, and Adverse Events during the Civilian Smallpox Vaccination Campaign, Arkansas, 2003.

    Science.gov (United States)

    Haselow, Dirk

    2016-01-01

    Smallpox vaccination has been associated with notable side effects and adverse events. This study assessed the frequency of each among public health workers immunized during the 2003 Arkansas civilian smallpox vaccination campaign to allow individuals and policymakers to make informed decisions whether repeat vaccination, as recommended in 10-year intervals, should be considered. This descriptive study summarizes postvaccination surveillance data for all civilians receiving smallpox vaccine (Dryvax) in Arkansas in 2003. Rates of side effects and adverse events were determined. Vaccinia-specific antibody titers among a subset of public health response team members were also assessed. Of the 1,124 vaccine recipients, 87% had a major take response. Substantial symptomatology, a 2% adverse event rate, a 0.5% hospitalization rate, and zero inadvertent transmission following vaccination were observed. Vaccinia-specific antibody titers increased on average 9-fold from 2.21*10(2) to 2.16*10(3) one month after vaccination. We found no association of age, sex, or racial subgroups with adverse events, hospitalizations, a lower take response rate, or lower postvaccination antibody titers. Prominent side effect profiles and adverse events among study participants seem to support individual and institutional reluctance to vaccinate civilians in the absence of smallpox reemergence. © 2015 Wiley Periodicals, Inc.

  7. Can {alpha}-tocopherol and {beta}-carotene supplementation reduce adverse radiation effects on salivary glands?

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    Funegaard, U.; Johansson, I.; Ericson, T. [Umeaa Univ. (Sweden). Dept. of Cariology; Malmer, B.; Henriksson, R. [Umeaa Univ. (Sweden). Dept. of Oncology

    1995-12-31

    In this study, we evaluated whether supplementation with antioxidant vitamins can reduce the adverse effects of irradiation on the salivary glands in the rat. Four groups of adult Sprague-Dawley rats were given a basic diet providing 0.6 mg {alpha}-tocopherol and no {beta}-carotene per day. In two groups the basic diet was supplemented with 3.4 mg {alpha}-tocopherol and 6 mg {beta}-carotene per day from 14 days before irradiation until 12 days after complete irradiation. One group of rats given basic diet and one group given supplemented diet were irradiated with 7 Gy daily for five consecutive days. Isoproterenol and pilocarpine-stimulated whole saliva was collected from all rats 2, 4 and 26 weeks after irradiation. Vitamin-supplemented irradiated rats had higher secretion rates on all three occasions compared with those of irradiated rats given basic diet. The changes in saliva composition seen in irradiated rats were less accentuated in vitamin-supplemented, irradiated rats. The proportions of acinar cells were significantly decreased both in parotid and submandibular glands 26 weeks after irradiation. Supplementation with {alpha}-tocopherol and {beta}-carotene did not alter the morphology of the glands. (author).

  8. Reading from a Head-Fixed Display during Walking: Adverse Effects of Gaze Stabilization Mechanisms.

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    Olivier Borg

    Full Text Available Reading performance during standing and walking was assessed for information presented on earth-fixed and head-fixed displays by determining the minimal duration during which a numerical time stimulus needed to be presented for 50% correct naming answers. Reading from the earth-fixed display was comparable during standing and walking, with optimal performance being attained for visual character sizes in the range of 0.2° to 1°. Reading from the head-fixed display was impaired for small (0.2-0.3° and large (5° visual character sizes, especially during walking. Analysis of head and eye movements demonstrated that retinal slip was larger during walking than during standing, but remained within the functional acuity range when reading from the earth-fixed display. The detrimental effects on performance of reading from the head-fixed display during walking could be attributed to loss of acuity resulting from large retinal slip. Because walking activated the angular vestibulo-ocular reflex, the resulting compensatory eye movements acted to stabilize gaze on the information presented on the earth-fixed display but destabilized gaze from the information presented on the head-fixed display. We conclude that the gaze stabilization mechanisms that normally allow visual performance to be maintained during physical activity adversely affect reading performance when the information is presented on a display attached to the head.

  9. Adverse Effects of Daylight Saving Time on Adolescents' Sleep and Vigilance.