EXS最新文献

{"title":"Toxins from bacteria.","authors":"James S Henkel,&nbsp;Michael R Baldwin,&nbsp;Joseph T Barbieri","doi":"10.1007/978-3-7643-8338-1_1","DOIUrl":"https://doi.org/10.1007/978-3-7643-8338-1_1","url":null,"abstract":"<p><p>Bacterial toxins damage the host at the site of bacterial infection or distant from the site. Bacterial toxins can be single proteins or oligomeric protein complexes that are organized with distinct AB structure-function properties. The A domain encodes a catalytic activity. ADP ribosylation of host proteins is the earliest post-translational modification determined to be performed by bacterial toxins; other modifications include glucosylation and proteolysis. Bacterial toxins also catalyze the non-covalent modification of host protein function or can modify host cell properties through direct protein-protein interactions. The B domain includes two functional domains: a receptor-binding domain, which defines the tropism of a toxin for a cell and a translocation domain that delivers the A domain across a lipid bilayer, either on the plasma membrane or the endosome. Bacterial toxins are often characterized based upon the secretion mechanism that delivers the toxin out of the bacterium, termed types I-VII. This review summarizes the major families of bacterial toxins and also describes the specific structure-function properties of the botulinum neurotoxins.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"100 ","pages":"1-29"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8338-1_1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28894704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-molecular weight protein toxins of marine invertebrates and their elaborate modes of action.","authors":"Daniel Butzke,&nbsp;Andreas Luch","doi":"10.1007/978-3-7643-8338-1_6","DOIUrl":"https://doi.org/10.1007/978-3-7643-8338-1_6","url":null,"abstract":"<p><p>High-molecular weight protein toxins significantly contribute to envenomations by certain marine invertebrates, e.g., jellyfish and fire corals. Toxic proteins frequently evolved from enzymes meant to be employed primarily for digestive purposes. The cellular intermediates produced by such enzymatic activity, e.g., reactive oxygen species or lysophospholipids, rapidly and effectively mediate cell death by disrupting cellular integrity. Membrane integrity may also be disrupted by pore-forming toxins that do not exert inherent enzymatic activity. When targeted to specific pharmacologically relevant sites in tissues or cells of the natural enemy or prey, toxic enzymes or pore-forming toxins even may provoke fast and severe systemic reactions. Since toxin-encoding genes constitute \"hot spots\" of molecular evolution, continuous variation and acquirement of new pharmacological properties are guaranteed. This also makes individual properties and specificities of complex proteinaceous venoms highly diverse and inconstant. In the present chapter we portray high-molecular weight constituents of venoms present in box jellyfish, sea anemones, sea hares, fire corals and the crown-of-thorns starfish. The focus lies on the latest achievements in the attempt to elucidate their molecular modes of action.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"100 ","pages":"213-32"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8338-1_6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28894706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drugs and pharmaceuticals: management of intoxication and antidotes.","authors":"Silas W Smith","doi":"10.1007/978-3-7643-8338-1_12","DOIUrl":"10.1007/978-3-7643-8338-1_12","url":null,"abstract":"<p><p>The treatment of patients poisoned with drugs and pharmaceuticals can be quite challenging. Diverse exposure circumstances, varied clinical presentations, unique patient-specific factors, and inconsistent diagnostic and therapeutic infrastructure support, coupled with relatively few definitive antidotes, may complicate evaluation and management. The historical approach to poisoned patients (patient arousal, toxin elimination, and toxin identification) has given way to rigorous attention to the fundamental aspects of basic life support--airway management, oxygenation and ventilation, circulatory competence, thermoregulation, and substrate availability. Selected patients may benefit from methods to alter toxin pharmacokinetics to minimize systemic, target organ, or tissue compartment exposure (either by decreasing absorption or increasing elimination). These may include syrup of ipecac, orogastric lavage, activated single- or multi-dose charcoal, whole bowel irrigation, endoscopy and surgery, urinary alkalinization, saline diuresis, or extracorporeal methods (hemodialysis, charcoal hemoperfusion, continuous venovenous hemofiltration, and exchange transfusion). Pharmaceutical adjuncts and antidotes may be useful in toxicant-induced hyperthermias. In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N-acetylcysteine, physostigmine, L-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. In summary, patients generally benefit from aggressive support of vital functions, careful history and physical examination, specific laboratory analyses, a thoughtful consideration of the risks and benefits of decontamination and enhanced elimination, and the use of specific antidotes where warranted. Data supporting antidotes effectiveness vary considerably. Clinicians are encouraged to utilize consultation with regional poison centers or those with toxicology training to assist with diagnosis, management, and administration of antidotes, particularly in unfamiliar cases.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"100 ","pages":"397-460"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28892998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venomous animals: clinical toxinology.","authors":"Julian White","doi":"10.1007/978-3-7643-8338-1_7","DOIUrl":"https://doi.org/10.1007/978-3-7643-8338-1_7","url":null,"abstract":"<p><p>Venomous animals occur in numerous phyla and present a great diversity of taxa, toxins, targets, clinical effects and outcomes. Venomous snakes are the most medically significant group globally and may injure >1.25 million humans annually, with up to 100 000 deaths and many more cases with long-term disability. Scorpion sting is the next most important cause of envenoming, but significant morbidity and even deaths occur following envenoming with a wide range of other venomous animals, including spiders, ticks, jellyfish, marine snails, octopuses and fish. Clinical effects vary with species and venom type, including local effects (pain, swelling, sweating, blistering, bleeding, necrosis), general effects (headache, vomiting, abdominal pain, hypertension, hypotension, cardiac arrhythmias and arrest, convulsions, collapse, shock) and specific systemic effects (paralytic neurotoxicity, neuroexcitatory neurotoxicity, myotoxicity, interference with coagulation, haemorrhagic activity, renal toxicity, cardiac toxicity). First aid varies with organism and envenoming type, but few effective first aid methods are recommended, while many inappropriate or frankly dangerous methods are in widespread use. For snakebite, immobilisation of the bitten limb, then the whole patient is the universal method, although pressure immobilisation bandaging is recommended for bites by non-necrotic or haemorrhagic species. Hot water immersion is the most universal method for painful marine stings. Medical treatment includes both general and specific measures, with antivenom being the principal tool in the latter category. However, antivenom is available only for a limited range of species, not for all dangerous species, is in short supply in some areas of highest need, and in many cases, is supported by historical precedent rather than modern controlled trials.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"100 ","pages":"233-91"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8338-1_7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28895774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical warfare agents.","authors":"K. Kuča, M. Pohanka","doi":"10.1007/978-3-7643-8338-1_16","DOIUrl":"https://doi.org/10.1007/978-3-7643-8338-1_16","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":"100 1","pages":"543-58"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8338-1_16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"51412087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of toxicoproteomics in assessing organ specific toxicity.","authors":"B Alex Merrick,&nbsp;Frank A Witzmann","doi":"10.1007/978-3-7643-8336-7_13","DOIUrl":"https://doi.org/10.1007/978-3-7643-8336-7_13","url":null,"abstract":"<p><p>Aims of this chapter on the role of toxicoproteomics in assessing organ-specific toxicity are to define the field of toxicoproteomics, describe its development among global technologies, and show potential uses in experimental toxicological research, preclinical testing and mechanistic biological research. Disciplines within proteomics deployed in preclinical research are described as Tier I analysis, involving global protein mapping and protein profiling for differential expression, and Tier II proteomic analysis, including global methods for description of function, structure, interactions and post-translational modification of proteins. Proteomic platforms used in toxicoproteomics research are briefly reviewed. Preclinical toxicoproteomic studies with model liver and kidney toxicants are critically assessed for their contributions toward understanding pathophysiology and in biomarker discovery. Toxicoproteomics research conducted in other organs and tissues are briefly discussed as well. The final section suggests several key developments involving new approaches and research focus areas for the field of toxicoproteomics as a new tool for toxicological pathology.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"367-400"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2853963/pdf/nihms190613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27934500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular, clinical and environmental toxicology. Preface.","authors":"Andreas Luch","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"XI-XIV"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27935670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of biotransformation and bioactivation in toxicity.","authors":"Wolfgang Dekant","doi":"10.1007/978-3-7643-8336-7_3","DOIUrl":"https://doi.org/10.1007/978-3-7643-8336-7_3","url":null,"abstract":"<p><p>Biotransformation is essential to convert lipophilic chemicals to water-soluble and readily excretable metabolites. Formally, biotransformation reactions are classified into phase I and phase II reactions. Phase I reactions represent the introduction of functional groups, whereas phase II reactions are conjugations of such functional groups with endogenous, polar products. Biotransformation also plays an essential role in the toxicity of many chemicals due to the metabolic formation of toxic metabolites. These may be classified as stable but toxic products, reactive electrophiles, radicals, and reactive oxygen metabolites. The interaction of toxic products formed by biotransformation reactions with cellular macromolecules initiates the sequences resulting in cellular damage, cell death and toxicity.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"57-86"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8336-7_3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27936177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptors mediating toxicity and their involvement in endocrine disruption.","authors":"Joëlle Rüegg,&nbsp;Pauliina Penttinen-Damdimopoulou,&nbsp;Sari Mäkelä,&nbsp;Ingemar Pongratz,&nbsp;Jan-Ake Gustafsson","doi":"10.1007/978-3-7643-8336-7_11","DOIUrl":"https://doi.org/10.1007/978-3-7643-8336-7_11","url":null,"abstract":"<p><p>Many toxic compounds exert their harmful effects by activating of certain receptors, which in turn leads to dysregulation of transcription. Some of these receptors are so called xenosensors. They are activated by external chemicals and evoke a cascade of events that lead to the elimination of the chemical from the system. Other receptors that are modulated by toxic substances are hormone receptors, particularly the ones of the nuclear receptor family. Some environmental chemicals resemble endogenous hormones and can falsely activate these receptors, leading to undesired activity in the cell. Furthermore, excessive activation of the xenosensors can lead to disturbances of the integrity of the system as well. In this chapter, the concepts of receptor-mediated toxicity and hormone disruption are introduced. We start by describing environmental chemicals that can bind to xenosensors and nuclear hormone receptors. We then describe the receptors most commonly targeted by environmental chemicals. Finally, the mechanisms by which receptor-mediated events can disrupt the system are depicted.</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"289-323"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8336-7_11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27936185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Historical milestones and discoveries that shaped the toxicology sciences.","authors":"Antoinette N Hayes,&nbsp;Steven G Gilbert","doi":"10.1007/978-3-7643-8336-7_1","DOIUrl":"https://doi.org/10.1007/978-3-7643-8336-7_1","url":null,"abstract":"<p><p>Knowledge of the toxic and healing properties of plants, animals, and minerals has shaped civilization for millennia. The foundations of modern toxicology are built upon the significant milestones and discoveries of serendipity and crude experimentation. Throughout the ages, toxicological science has provided information that has shaped and guided society. This chapter examines the development of the discipline of toxicology and its influence on civilization by highlighting significant milestones and discoveries related to toxicology. The examples shed light on the beginnings of toxicology, as well as examine lessons learned and re-learned. This chapter also examines how toxicology and the toxicologist have interacted with other scientific and cultural disciplines, including religion, politics, and the government. Toxicology has evolved to a true scientific discipline with its own dedicated scientists, educational institutes, sub-disciplines, professional societies, and journals. It now stands as its own entity while traversing such fields as chemistry, physiology, pharmacology, and molecular biology. We invite you to join us on a path of discovery and to offer our suggestions as to what are the most significant milestones and discoveries in toxicology. Additional information is available on the history section of Toxipedia (www.toxipedia.org).</p>","PeriodicalId":77125,"journal":{"name":"EXS","volume":"99 ","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-7643-8336-7_1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27935671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}