Toxicological reviews最新文献

{"title":"The role of insulin and glucose (hyperinsulinaemia/euglycaemia) therapy in acute calcium channel antagonist and beta-blocker poisoning.","authors":"Bruno Mégarbane,&nbsp;Souheil Karyo,&nbsp;Frédéric J Baud","doi":"10.2165/00139709-200423040-00002","DOIUrl":"https://doi.org/10.2165/00139709-200423040-00002","url":null,"abstract":"<p><p>The inotropic effect of insulin has been long established. High-dose (0.5-1 IU/kg/hour) insulin, in combination with a glucose infusion to maintain euglycaemia (hyperinsulinaemia/euglycaemia therapy), has been proposed as a treatment for calcium channel antagonist (CCA) and beta-adrenoceptor antagonist (beta-blocker) poisonings. However, the basis for its beneficial effect is poorly understood.CCAs inhibit insulin secretion, resulting in hyperglycaemia and alteration of myocardial fatty acid oxidation. Similarly, blockade of beta(2)-adrenoceptors in beta-blocker poisoning results in impaired lipolysis, glycogenolysis and insulin release. Insulin administration switches cell metabolism from fatty acids to carbohydrates and restores calcium fluxes, resulting in improvement in cardiac contractility. Experimental studies in verapamil poisoning have shown that high-dose insulin significantly improved survival compared with calcium salts, epinephrine or glucagon. In several life-threatening poisonings in humans, the administration of high-dose insulin produced cardiovascular stabilisation, decreased the catecholamine vasopressor infusion rate and improved the survival rate. In a canine model of propranolol intoxication, high-dose insulin provided a sustained increase in systemic blood pressure, cardiac performance and survival rate compared with glucagon or epinephrine. In contrast, insulin had no effect on heart rate and electrical conduction in the myocardium. In another study, high-dose insulin reversed the negative inotropic effect of propranolol to 80% of control function and normalised heart rate. High-dose insulin produced a significant decrease in the left ventricular end-diastolic pressure and a significant increase in the stroke volume and cardiac output. The vasodilator effect was explained by an enhanced cardiac output leading to withdrawal of compensatory vasoconstriction. No clinical studies have yet been performed. Although not effective in all cases, we recommend hyperinsulinaemia/euglycaemia therapy in patients with severe CCA poisoning who present with hypotension and respond poorly to fluid, calcium salts, glucagon and catecholamine infusion. However, careful monitoring of blood glucose and serum potassium concentrations is required to avoid serious adverse effects. More clinical data are needed before this therapy can be recommended in beta-blocker poisoning. There is a need for large prospective clinical trials to confirm safety and efficacy of hyperinsulinaemia/euglycaemia therapy in both CCA and beta-blocker poisoning.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 4","pages":"215-22"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423040-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25287118","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":"Does occupational exposure to organic solvents affect colour discrimination?","authors":"Richard B Lomax,&nbsp;Peter Ridgway,&nbsp;Maureen Meldrum","doi":"10.2165/00139709-200423020-00004","DOIUrl":"https://doi.org/10.2165/00139709-200423020-00004","url":null,"abstract":"<p><p>This review assesses the evidence regarding the effects of occupational exposure to organic solvents on colour discrimination and investigates exposure-response relationships and reversibility. This review also considers the current state of knowledge of the possible mechanisms underlying changes in colour vision, and the human health significance of any reported changes. Among the commonly used organic solvents, styrene has been investigated the most thoroughly. Studies of styrene-exposed workers in Germany, Italy and Japan provide a sufficiently consistent body of evidence to support a robust conclusion that styrene does cause an impairment of colour discrimination relative to age-matched controls. Generally, the impairment of colour discrimination observed in styrene-exposed workers tends to be of the tritan (blue-yellow) type, although some cases of red-green impairment have also been found. The limited information available on exposure-response relationships indicates that the effects on colour discrimination would not be expected at 8-hour time weighted average (8 h TWA) exposures <20 ppm, although a precise threshold cannot be determined. The data on reversibility are limited and inconclusive. The results from the most rigorous study in which this aspect was investigated point to a reversibility of effects after a 4-week exposure-free period, whereas results from a study with limitations suggest a persistence of effect. The effects of toluene, tetrachloroethylene or mixed solvent exposure have also been investigated, although the information available is generally less reliable than for styrene. For toluene, it can be confidently concluded that this solvent does not have an acute effect on colour discrimination, even when exposures are relatively high (50-150 ppm 8 h TWA, and 290-360 ppm 30 minutes TWA). However, studies are inconclusive on whether long-term or repeated exposure to toluene can cause a persistent impairment of colour discrimination. There are few studies that have specifically investigated the effects of tetrachloroethylene on colour discrimination. Among these studies, none has examined the potential for any acute effects of this solvent vapour. A large-scale study in Japanese workers showed no effects of long-term exposure to tetrachloroethylene concentrations in the region of 12-13 ppm. However, the test methodology used was relatively insensitive to changes in colour discrimination, hence the results do not provide reassurance for an absence of subtle effects. A study in Italian dry-cleaners suggested a slight impairment of colour discrimination relative to controls, associated with relatively low exposures to tetrachloroethylene (mean 8 h TWA exposure approximately 6 ppm). The studies concerning the effects of mixed solvent exposure on colour discrimination are based on workers exposed to solvents in paints and lacquers, workers from the printing and petrochemical industries, people working in or living near to m","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 2","pages":"91-121"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423020-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24844132","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 gamma-hydroxybutyrate withdrawal syndrome.","authors":"Asim F Tarabar,&nbsp;Lewis S Nelson","doi":"10.2165/00139709-200423010-00005","DOIUrl":"https://doi.org/10.2165/00139709-200423010-00005","url":null,"abstract":"<p><p>gamma-Hydroxybutyrate (GHB) is endogenous inhibitory transmitter that, when administered in pharmacological doses, has sedative-hypnotic properties. It is used in anaesthesia for the treatment of narcolepsy/catalepsy and in alcohol/opioid detoxification treatment regimens. Based on its purported anabolic effects, GHB use became established among bodybuilders. As the euphorigenic effects of GHB became publicised, attendees at dance clubs and rave parties began to use it alone or in combination with other psychoactive drugs. Following the ban of GHB in 1990, several precursor products (e.g. gamma-butyrolactone, butanediol) became widely used as replacement drugs until their ultimate proscription from lawful use in 2000. GHB and its precursors, like most sedative-hypnotic agents, can induce tolerance and produce dependence. Although many GHB users will experience a mild withdrawal syndrome upon drug discontinuation, those with chronic heavy GHB use can experience severe withdrawal. This syndrome clinically resembles the withdrawal syndrome noted from alcohol and other sedative-hypnotic drugs (e.g. benzodiazepines). Distinct clinical features of GHB withdrawal are its relatively mild and brief autonomic instability with prolonged psychotic symptoms. Patients with fulminant GHB withdrawal require aggressive treatment with cross-tolerant sedative hypnotics, such as benzodiazepines.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"23 1","pages":"45-9"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200423010-00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40895092","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":"Toxicological Reviews","authors":"A. Vale, J. Brent","doi":"10.2165/00139709-200322010-00001","DOIUrl":"https://doi.org/10.2165/00139709-200322010-00001","url":null,"abstract":"","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322010-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68155266","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":"Sulphur mustard injuries of the skin. Pathophysiology and management.","authors":"Paul Rice","doi":"10.2165/00139709-200322020-00006","DOIUrl":"https://doi.org/10.2165/00139709-200322020-00006","url":null,"abstract":"<p><p>Sulphur mustard is a vesicant (blistering agent), which produces chemical burns with widespread blistering. It was used extensively as a chemical warfare agent in the First World War, and has allegedly been employed in a number of conflicts since then, most recently by Iraq against Iran (1984-1987). The potential further use of mustard in military conflicts and by terrorists remains a significant threat that if realised in practice would result in a large number of casualties with severely incapacitating, partial thickness burns. Such injuries clearly present a huge potential wound care problem. The development and healing of mustard-induced cutaneous injuries has not only been observed in human casualties, but has been studied recently at the microscopic and ultrastructural levels in several animal models. Vesication generally begins on the second day after exposure, and may progress for up to 2 weeks. Wound healing is considerably slower than for a comparable thermal burn, and patients often require extended hospital treatment. The current management strategy is essentially symptomatic and supportive. Recently, two techniques for removing damaged tissue and improving wound healing have been investigated. Mechanical dermabrasion and laser debridement ('lasablation') both produced an increased rate of wound healing in animal models, and may be of benefit in a clinical context.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 2","pages":"111-8"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322020-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24459005","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":"Idiopathic environmental intolerance: Part 2: A causation analysis applying Bradford Hill's criteria to the psychogenic theory.","authors":"Herman Staudenmayer,&nbsp;Karen E Binkley,&nbsp;Arthur Leznoff,&nbsp;Scott Phillips","doi":"10.2165/00139709-200322040-00006","DOIUrl":"https://doi.org/10.2165/00139709-200322040-00006","url":null,"abstract":"<p><p>Toxicogenic and psychogenic theories have been proposed to explain idiopathic environmental intolerance (IEI). Part 2 of this article is an evidence-based causality analysis of the psychogenic theory using an extended version of Bradford Hill's criteria. The psychogenic theory meets all of the criteria directly or indirectly and is characterised by a progressive research programme including double-blind, placebo-controlled provocation challenge studies. We conclude that IEI is a belief characterised by an overvalued idea of toxic attribution of symptoms and disability, fulfilling criteria for a somatoform disorder and a functional somatic syndrome. A neurobiological diathesis similar to anxiety, specifically panic disorder, is a neurobiologically plausible mechanism to explain triggered reactions to ambient doses of environmental agents, real or perceived. In addition, there is a cognitively mediated fear response mechanism characterised by vigilance for perceived exposures and bodily sensations that are subsequently amplified in the process of learned sensitivity. Implications for the assessment and treatment of patients are presented.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 4","pages":"247-61"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322040-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24558403","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":"Thallium toxicity and the role of Prussian blue in therapy.","authors":"Robert S Hoffman","doi":"10.2165/00139709-200322010-00004","DOIUrl":"https://doi.org/10.2165/00139709-200322010-00004","url":null,"abstract":"<p><p>Thallium salts have been used as medicinal agents, as key ingredients in a variety of manufacturing processes, and as a potent rodenticide. Additionally, environmental concerns are growing, as thallium is a waste product of coal combustion and the manufacturing of cement. Thallium salts are rapidly and nearly completely absorbed by virtually all routes, with gastrointestinal exposure being the most common route to produce toxicity. Thallium enters cells by a unique process governed by its similarity in charge and ionic radius to potassium. Although the exact mechanism of toxicity has not been established, thallium interferes with energy production at essential steps in glycolysis, the Krebs cycle, and oxidative phosphorylation. Additional effects include inhibition of sodium-potassium-adenosine triphosphatase and binding to sulfhydryl groups. The major manifestations of toxicity consist of a rapidly progressive, ascending, extremely painful sensory neuropathy and alopecia. Unlike exposure to most metal salts, gastrointestinal symptoms of thallium toxicity are relatively minor, and constipation is more characteristic than diarrhoea. Many other findings such as an autonomic neuropathy, cranial nerve abnormalities, altered mental status, motor weakness, cardiac, hepatic, and renal effects are described, but are less specific. Thallium also crosses the placenta freely and produces abnormalities in animals as well as fetal demise, overt toxicity and congenital abnormalities in humans. There are no controlled trials of treatments in thallium-poisoned patients. Thus, the literature is predominated by very small animal studies and case reports with very limited data. Strong evidence speaks against the use of traditional metal chelators such as dimercaprol (British Anti-Lewisite) and penicillamine, and the latter may cause redistribution of thallium into the central nervous system. Likewise, forced potassium diuresis appears harmful. The use of single- or multiple-dose activated charcoal is supported by in vitro binding experiments and some animal data, and charcoal haemoperfusion may be a useful adjunct. Multiple animal studies give evidence for enhanced elimination and improved survival with Prussian blue. Unfortunately, despite the fact that many humans have been treated with Prussian blue, the data presented are insufficient to comment definitively on its efficacy. However, Prussian blue's safety profile is superior to that of other proposed therapies and it should be considered the drug of choice in acute thallium poisoning. Public health efforts should focus on greater restrictions on access to, and use of, thallium salts.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 1","pages":"29-40"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322010-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045502","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":"Ricin. Mechanisms of cytotoxicity.","authors":"Michael J Lord,&nbsp;Nicholas A Jolliffe,&nbsp;Catherine J Marsden,&nbsp;Cassandra S Pateman,&nbsp;Daniel C Smith,&nbsp;Robert A Spooner,&nbsp;Peter D Watson,&nbsp;Lynne M Roberts","doi":"10.2165/00139709-200322010-00006","DOIUrl":"https://doi.org/10.2165/00139709-200322010-00006","url":null,"abstract":"<p><p>Ricin is a heterodimeric protein produced in the seeds of the castor oil plant (Ricinus communis). It is exquisitely potent to mammalian cells, being able to fatally disrupt protein synthesis by attacking the Achilles heel of the ribosome. For this enzyme to reach its substrate, it must not only negotiate the endomembrane system but it must also cross an internal membrane and avoid complete degradation without compromising its activity in any way. Cell entry by ricin involves a series of steps: (i) binding, via the ricin B chain (RTB), to a range of cell surface glycolipids or glycoproteins having beta-1,4-linked galactose residues; (ii) uptake into the cell by endocytosis; (iii) entry of the toxin into early endosomes; (iv) transfer, by vesicular transport, of ricin from early endosomes to the trans-Golgi network; (v) retrograde vesicular transport through the Golgi complex to reach the endoplasmic reticulum; (vi) reduction of the disulphide bond connecting the ricin A chain (RTA) and the RTB; (vii) partial unfolding of the RTA to render it translocationally-competent to cross the endoplasmic reticulum (ER) membrane via the Sec61p translocon in a manner similar to that followed by misfolded ER proteins that, once recognised, are targeted to the ER-associated protein degradation (ERAD) machinery; (viii) avoiding, at least in part, ubiquitination that would lead to rapid degradation by cytosolic proteasomes immediately after membrane translocation when it is still partially unfolded; (ix) refolding into its protease-resistant, biologically active conformation; and (x) interaction with the ribosome to catalyse the depurination reaction. It is clear that ricin can take advantage of many target cell molecules, pathways and processes. It has been reported that a single molecule of ricin reaching the cytosol can kill that cell as a consequence of protein synthesis inhibition. The ready availability of ricin, coupled to its extreme potency when administered intravenously or if inhaled, has identified this protein toxin as a potential biological warfare agent. Therapeutically, its cytotoxicity has encouraged the use of ricin in 'magic bullets' to specifically target and destroy cancer cells, and the unusual intracellular trafficking properties of ricin potentially permit its development as a vaccine vector. Combining our understanding of the ricin structure with ways to cripple its unwanted properties (its enzymatic activity and promotion of vascular leak whilst retaining protein stability and important immunodominant epitopes), will also be crucial in the development of a long awaited protective vaccine against this toxin.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 1","pages":"53-64"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322010-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24045504","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 human toxicology of polychlorinated biphenyls: 209 isomers in search of a disease.","authors":"Jeffrey Brent,&nbsp;Allister Vale","doi":"10.2165/00139709-200322040-00002","DOIUrl":"https://doi.org/10.2165/00139709-200322040-00002","url":null,"abstract":"","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 4","pages":"201-2"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322040-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24559052","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":"Does urine alkalinization increase salicylate elimination? If so, why?","authors":"Alex T Proudfoot,&nbsp;Edward P Krenzelok,&nbsp;Jeffrey Brent,&nbsp;J Allister Vale","doi":"10.2165/00139709-200322030-00001","DOIUrl":"https://doi.org/10.2165/00139709-200322030-00001","url":null,"abstract":"<p><p>Urine alkalinization is a treatment regimen that increases poison elimination by the administration of intravenous sodium bicarbonate to produce urine with a pH > or = 7.5. Experimental and clinical studies confirm that urinary alkalinization increases salicylate elimination, although the mechanisms by which this occurs have not been elucidated. The conventional view is that ionisation of a weak acid, such as salicylic acid, is increased in an alkaline environment. Since the ionisation constant (pKa) is a logarithmic function then, theoretically, a small change in urine pH will have a disproportionately larger effect on salicylate clearance. Hence, elimination of salicylic acid by the kidneys is increased substantially in alkaline urine. However, as salicylic acid is almost completely ionised within physiological pH limits, alkalinization of the urine could not, therefore, significantly increase the extent of ionisation further and the conventional view of the mechanism by which alkalinization is effective is patently impossible. Further experimental studies are required to clarify the mechanisms by which urine alkalinization enhances salicylate elimination.</p>","PeriodicalId":87031,"journal":{"name":"Toxicological reviews","volume":"22 3","pages":"129-36"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2165/00139709-200322030-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24552481","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}