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In 2015, the United States Food and Drug Administration (FDA) approved uridine triacetate to treat overdose and severe toxicity of the fluoropyrimidine chemotherapy agents 5‐fluorouracil (5‐FU) and its oral prodrug capecitabine. Uridine triacetate is as an oral prodrug of uridine that competes with cytotoxic fluoropyrimidine metabolites for incorporation into nucleotides. Two million people worldwide start fluoropyrimidine chemotherapy each year, with 20‐30% developing severe or life‐threatening adverse effects, often attributable to a genetic predisposition such as dihydropyrimidine dehydrogenase deficiency. Whilst genetic prescreening is recommended prior to starting fluoropyrimidine agents, this only prevents 20‐30% of early‐onset life‐threatening toxicity and so does not obviate the need for an antidote. Initial in‐human studies established that uridine triacetate more than doubles the maximum tolerated weekly 5‐FU bolus dose. A lack of clinical equipoise meant a placebo‐controlled phase III trial was not ethical and so the phase III trials used historical controls. These found that uridine triacetate improved survival in those with fluoropyrimidine overdose and severe toxicity from 16% to 94%, with 34% able to resume chemotherapy within 30 days. Five case reports of delayed fluoropyrimidine toxicity demonstrate improvement following uridine triacetate treatment 120‐504 h after last fluoropyrimidine administration, suggesting efficacy beyond the FDA licencing indications. Mechanistically uridine triacetate would be expected to be effective for overdose and severe toxicity of tegafur (a 5‐FU prodrug), but there are no published case reports describing this. Uridine triacetate is available internationally through an expanded access scheme and has been available in the UK since 2019 on a named patient basis. [ABSTRACT FROM AUTHOR]

Pralidoxime salts are important medical countermeasures towards different organophosphorus compounds, either nerve agents or pesticides, as they act as acetylcholinesterase reactivators, avoiding health issues and even death that can result from intoxication with such chemicals. In this work, we present an expeditious study focuses on the optimization of a two‐step continuous‐flow synthesis of 2‐PAM. Initial attempts to replace the solvent composition in the oxime formation reaction with acetonitrile resulted in lower yields, highlighting the significance of a polar protic solvent. Subsequent optimization under continuous‐flow conditions revealed the successful execution of oxime formation at room temperature with a residence time of 20 minutes, achieving an impressive 96 % conversion, surpassing literature‐reported conditions. The methylation step required a high residence time of 60 minutes at 120 °C for a substantial conversion of 78 %. The two‐step continuous‐flow process demonstrated robustness, yielding 75 %, with space‐time yields of 0.32 g/h and 0.18 g/h. Further concentration adjustments increased space‐time yields to 3.2 g/h and 2.2 g/h. Despite solvent incompatibility, a strategic alteration of the reaction sequence allowed for a successful cascade process, integrating the methylation step in acetonitrile and the oxime formation in water. The continuous‐flow system, incorporating a heat exchanger, exhibited stability, maintaining full conversion and a space‐time yield of 0.3 g/h over extended periods. This systematic optimization not only enhances the efficiency of 2‐PAM synthesis but also provides insights into a scalable and practical continuous‐flow cascade process. [ABSTRACT FROM AUTHOR]

All living organisms require mineral iron, but excess iron can lead to the production of free radicals and organ damage, such as liver damage in humans. This study investigated the diatom Chaetoceros sp. as an iron adsorbent in iron overload. First, the morphology and chemical composition of the diatom was characterized by spectroscopic and microscopic techniques. It was defined that diatoms have spherical particles with an average size of less than 2.0 μm. The affinity of diatoms for ionic Fe (II) uptake was evaluated. Fe (II) adsorption capacity was determined in vitro in two simulated intestinal and gastric aqueous media with pH values of 7.2 and 1.2. In both media, the diatom acted as a super‐adsorbent of Fe (II), while the highest adsorption occurred in a medium with a pH of 1.2. The correlation of the adsorption isotherm data was well studied with three well‐known equations, Langmuir, Fruindlich, and Redlich‐Peterson. The Langmuir model fitted the adsorption data best. The pseudo‐first‐order reaction model also provided a good fit for the adsorption kinetic data. In the in vivo study, the diatom was administered to iron‐overloaded rats. Biochemical parameters of organ damage and plasma Fe levels were determined at 2 h and 24 h intervals after diatom administration. The results show that diatoms can prevent acute iron poisoning by reducing plasma levels. Diatoms proved to be potent antidote agents in iron overdose conditions. [ABSTRACT FROM AUTHOR]

As an effective and non‐invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber‐optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post‐PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black‐hole quencher BHQ‐3 conjugated with a bicyclo[6.1.0]non‐4‐yne (BCN) moiety and a tetrazine‐substituted boron dipyrromethene‐based photosensitizer. By using tumor‐bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ‐3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT. [ABSTRACT FROM AUTHOR]

Growing clinical and basic science data support the use of fomepizole as an adjunct to N‐acetylcysteine in paracetamol poisoning. This safe antidote may be helpful in severely poisoned patients. [ABSTRACT FROM AUTHOR]

Licorice is the dried roots and rhizomes of various species of the genus Glycyrrhiza (Fabaceae) that have been used in folk medicine from ancient times. Many important research projects have established several beneficial effects for this medicinal herb, including antiinflammatory, antimicrobial, antiviral, antiprotozoal, antioxidant, antihyperglycemic, antihyperlipidemic, hepatoprotective, and neuroprotective. Licorice contains important bioactive components, such as glycyrrhizin (glycyrrhizic, glycyrrhizinic acid), liquiritigenin, liquiritin, and glycyrrhetinic acid. The protective effects of licorice and its main chemical components against toxins and toxicants in several organs including the brain, heart, liver, kidney, and lung have been shown. In this comprehensive review article, the protective effects of these constituents against natural, industrial, environmental, and chemical toxicities with attention on the cellular and molecular mechanism are introduced. Also, it has been revealed that this plant and its main compounds can inhibit the toxicity of different toxins by the antioxidant, antiinflammatory, and anti‐apoptotic properties as well as the modulation of Inhibitor of kappaB kinase (IKK), Extracellular signal‑regulated protein kinase1/2 (ERK1/2), p38, inducible nitric oxide synthase, and nuclear factor‐κB (NF‐κB) signaling pathways. More high‐quality investigations in both experimental and clinical studies need to firmly establish the efficacy of licorice and its main constituents against toxic agents. [ABSTRACT FROM AUTHOR]

Natural and chemical toxic agents cause severe adverse effects on people's health in a variety of exposing ways. Herbal medications have taken into consideration as alternative safe treatments for toxicities. Rosmarinus officinalis also known as rosemary belongs to the Lamiaceae family. Rosemary and its constituents including carnosic acid, rosmarinic acid, and carnosol have a lot of benefits such as anti‐inflammatory, antioxidant, anti‐mutagenic, anti‐bacterial, antiviral, antinociceptive, and neuroprotective activities. In this literate review, we focused on the protective effects of rosemary and its main compounds against natural and chemical toxicities in both in vitro and in vivo studies. The protective effects of rosemary and its components are mostly mediated through different mechanisms such as the inhibition of oxidative stress, reduction of inflammatory mediators including tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), interleukin‐17 (IL‐17), cyclooxygenase‐2 (COX‐2) and nuclear factor ĸB (NF‐ĸB) as well as the modulation of apoptosis and mitogen‐activated protein kinase (MAPK) signaling pathways. [ABSTRACT FROM AUTHOR]

Pd/C catalyst is a widely applied hydrogenation catalyst in organic synthesis for the reduction of many organic compounds. It has been reported that it suffers from sulfur poisoning. Herein we report that catalytic amounts of triphenylphosphine (TPP), which is also an usual poison to Pd/C, could greatly improve the catalytic performance of Pd/C in sulfur‐containing systems. The sulfur‐poisoned Pd/C catalyst can be activated when adding TPP. The characterizations show that TPP partly reduced the deactivated layer of palladium sulfide formed during the reaction at higher temperature, and expose the high active sites of metallic Pd to keep the hydrogenation process. TPP may promote the hydrogenation of nitro compounds and olefins in the presence of sulfur compounds, proving to be an efficient antidote for Pd/C hydrogenation catalyst poisoning. [ABSTRACT FROM AUTHOR]

Accidental intoxications from environmental pollutants, as well as intentional self‐ and chemical warfare‐related poisonings affect millions of people worldwide each year. While many toxic agents can readily enter the central nervous system (CNS), the blood‐brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. Consequently, poisoning antidotes usually cannot reach their site of action in the CNS in therapeutically relevant concentrations, and thus only provide effective protection to the peripheral nervous system. This limitation can be overcome by encapsulating the antidotes in nanoparticles (NP), which can enhance their CNS accumulation without damaging the integrity of the BBB. Among nanocarriers, polymer‐based drug delivery systems exhibit remarkable benefits, such as bioavailability, cell uptake and tissue retention. Furthermore, due to their capacity to mask unfavorable physicochemical properties of cargo drugs, polymeric NPs were able to improve BBB transport of various pharmaceuticals. However, while polymer NP‐mediated treatment of various pathological brain conditions, such as glioma and Alzheimer's disease were exhaustively studied, the application of polymeric nanocarriers for brain‐targeted delivery of antidote molecules has not been adequately examined. To display its therapeutic potential, we review the state of the art of polymer NP‐assisted CNS delivery of antidotes for various poisonings, including heavy metal and organophosphorus intoxications. While many toxins can enter the central nervous system (CNS), the blood‐brain barrier (BBB) prevents brain uptake of most antidotes. A possible solution to this problem is the encapsulation of antidote molecules in polymeric nanoparticles, which can enhance their CNS accumulation without damaging the BBB. Therefore, we review the potential of polymeric nanocarriers in the CNS delivery of antidotes for various poisonings, such as heavy metal and organophosphorus intoxications. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine whether methylene blue (MB) could directly oppose the neurological toxicity of a lethal cyanide (CN) intoxication. KCN, infused at the rate of 0.375 mg/kg/min intravenously, produced 100% lethality within 15 min in unanaesthetized rats (n = 12). MB at 10 (n = 5) or 20 mg/kg (n = 5), administered 3 min into CN infusion, allowed all animals to survive with no sequelae. No apnea and gasping were observed at 20 mg/kg MB (P < 0.001). The onset of coma was also significantly delayed and recovery from coma was shortened in a dose‐dependent manner (median of 359 and 737 seconds, respectively, at 20 and 10 mg/kg). At 4 mg/kg MB (n = 5), all animals presented faster onset of coma and apnea and a longer period of recovery than at the highest doses (median 1344 seconds, P < 0.001). MB reversed NaCN‐induced resting membrane potential depolarization and action potential depression in primary cultures of human fetal neurons intoxicated with CN. MB restored calcium homeostasis in the CN‐intoxicated human SH‐SY5Y neuroblastoma cell line. We conclude that MB mitigates the neuronal toxicity of CN in a dose‐dependent manner, preventing the lethal depression of respiratory medullary neurons and fatal outcome. [ABSTRACT FROM AUTHOR]

Garlic (Allium sativum, Liliaceae) is used widely as a spice and medicinal herb not only in its native region (Central Asia and northeastern Iran) but also all around the world. Garlic has abundance chemical compounds such as allicin, alliin, S-allyl cysteines, thiacremonone, diallyl-disulfide, diallylsulfide, and others. This medicinal plant and its constituents offer a lot of benefits including free-radical scavenging, anti-inflammatory, anticholesterolemic, anti-gastric ulcer, antimicrobial, anticancer, and antioxidant properties. Garlic also modulates the activity of several metabolizing enzymes. This review summarizes various in vitro and animal studies on the protective effects of garlic against natural and chemical toxicities. It has been shown that garlic and its major components can ameliorate the toxicity of different agents in brain, kidney, blood, liver, embryo, spleen, pancreas, heart, reproductive system in part through radical scavenging, antioxidant effect, reducing lipid peroxidation, anti-inflammatory, chelating agent, cytoprotective activities, increase protein synthesis in damaged tissues, suppressing apoptosis, modulation of p53, phosphoinositide 3-kinase, Akt, nuclear factor (erythroid-derived 2)-like 2, antioxidant responsive element, p38 MAPK, inducible nitric oxide synthase, cyclooxygenase-2, cytosolic phospholipases A2, cleaved-caspase-9, cleaved-caspase-3 Bcl-2, Bcl-2-associated X, peroxisome proliferator-activated receptor gamma, NF-jB, nuclear factor-kappaB signaling pathways and cytochrome P450 enzymes. With controlled clinical trials, garlic may be introduced as a universal antidote or protective plant against many toxic agents. [ABSTRACT FROM AUTHOR]

Objectives: To examine if the electronic N‐acetyl cysteine (NAC) order reduced prescribing errors. Methods: This was a retrospective chart review of all patients presenting over 2 years to Cairns Hospital ED with a discharge diagnosis of 'paracetamol overdose'. Data were collected for any patient who received i.v. NAC. Any error, and a description of the error such as dose, volume of fluid, time of infusion and incorrect patient weight was recorded. Results: There were 172 presentations with paracetamol poisoning with 86 receiving i.v. NAC. In the 75 (87%) where the electronic NAC order was used, there were no errors in dose of NAC, volume of i.v. fluid and length of time of infusion. In the 11 presentations where the manual NAC order was used, there were multiple errors identified. Conclusion: The use of this electronic NAC order removed errors in NAC prescription and should be considered for prescribing and administering i.v. NAC. [ABSTRACT FROM AUTHOR]

Nowadays in our developing and industrial world, humans' health or even their life is threatened by exposure to poisons. In this situation, detecting a protective compound could be helpful and interesting. In the present article, we collected and reviewed all studies, which have been conducted so far about the protective effects of Ginkgo biloba L. (GB), one of the most ancient medicinal tree species, against toxicities induced by chemical toxic agents, natural toxins, and also radiation. In overall, investigations showed that GB exerts the antioxidant, antiinflammatory, antiapoptotic, and antigenotoxicity effects in different toxicities. There are also some special mechanisms about its protective effects against some specific toxic agents, such as acetylcholine esterase inhibition in the aluminium neurotoxicity or membrane-bond phosphodiesterase activation in the triethyltin toxicity. Ginkgolide A was the most investigated active ingredient of G. biloba leaf extract as a protective compound against toxicities, which had the similar effects of total extract. A few clinical studies have been conducted in this field, which demonstrated the beneficial effects of GB against toxic agents. However, the promising effects of this valuable herbal extract will practically remain useless without carrying out more clinical studies and proving its effects on human beings. [ABSTRACT FROM AUTHOR]

The harmful use of methanol is a worldwide problem resulting in millions of deaths, including thousands of young lives lost. Although methanol itself may be harmless, it is oxidized to formaldehyde and, further, it breaks down to formic acid, which is lethal for humans with high concentration. The primary treatment of methanol poisoning is the administration of ethanol to slow down the formation of toxic metabolites by competitive substitution of the methanol due to its intrinsic binding affinity. Moreover, supportive role of administering sodium bicarbonate in the patient assists the neutralization of the metabolic acidosis in human for the accumulation of formic acid. In this research article, we formulate a mathematical model to study the effect of co‐administration of ethanol and sodium bicarbonate to treat methanol toxicity. This treatment procedure may help the health workers to provide at least a basic emergency care to minimize the death toll in the remote and distant places. The experimental data were used to acquire the model generated time and dosing prediction through which patient is to be benefited in obtaining the normalcy within minimum therapy time. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non‐valvular atrial fibrillation. Non‐vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta‐analysis to evaluate the risk of fatal NOAC‐related ICH compared with VKA‐related ICH. Methods: We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC‐related ICH in patients treated with and without NOAC‐specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30–90 days following symptom onset. Results: Our literature search identified six eligible studies (four randomized controlled trials and two open‐label trials of NOAC‐specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36–0.58] with no heterogeneity (I2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC‐related and VKA‐related (RR, 1.00; 95% CI, 0.84–1.19) ICH with no evidence of heterogeneity (I2 = 0%). In the indirect analysis, the case fatality rate of NOAC‐related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11–24%) vs. 41% (95% CI, 34–49%); P < 0.001]. Conclusions: Non‐vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non‐valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC‐specific reversal agents may be associated with a lower case fatality rate in NOAC‐related ICH. [ABSTRACT FROM AUTHOR]

Metal organic frameworks (MOFs) UiO‐66 (UiO stands for University of Oslo) and NH2‐UiO‐66 were prepared and characterized as sorbent (antidotal agents) for curcumin (CUR) adsorption. The structure of products were characterized by X‐ray powder diffraction (XRD), Field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), Attenuated Total Reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR), and N2 adsorption–desorption measurements. FESEM showed NH2‐UiO‐66 displayed symmetrical crystals with triangular base pyramid morphology, with the particle size around 100 nm and uniform size distribution. Adsorption capacities of CUR/MOFs with different mass ratios in the feed were investigated in the present study, and this investigation revealed that when the CUR/MOFs with mass ratio was around 0.4, the absorption capacity of NH2‐UiO‐66 had tended to maximum. Although, functionalization reduced the specific surface area and free volume, introducing polar amine groups could improve the affinity of NH2‐UiO‐66 respect to CUR. Kinetic studies showed that the kinetic data are well fitted with the pseudo‐ second‐order model. MTT assay revealed that MOFs at the concentration range of 0–560 μg/ml had no cytotoxic effect on the Human Foreskin Fibroblast normal cell line (HFF‐2). These results suggest that these MOFs could be safe as sorbent for adsorb CUR from the body. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aims: Take‐home naloxone can prevent death from heroin/opioid overdose, but pre‐provision is difficult because naloxone is usually given by injection. Non‐injectable alternatives, including naloxone nasal sprays, are currently being developed. To be effective, the intranasal (i.n.) spray dose must be adequate but not excessive, and early absorption must be comparable to intramuscular (i.m.) injection. We report on the pharmacokinetics (PK) of a specially produced concentrated novel nasal spray. The specific aims were to: (1) estimate PK profiles of i.n. naloxone, (2) compare early systemic exposure with i.n. versus i.m. naloxone and (3) estimate i.n. bioavailability. Design: Open‐label, randomized, five‐way cross‐over PK study. Setting: Clinical trials facility (Croydon, UK). Participants: Thirty‐eight healthy volunteers (age 20–54 years; 11 female). Intervention and comparator: Three doses of i.n. (1 mg/0.1 ml, 2 mg/0.1 ml, 4 mg/0.2 ml) versus 0.4 mg i.m. (reference) and 0.4 mg intravenous (i.v.) naloxone. Measurements: Regular blood samples were taken, with high‐frequency sampling during the first 15 minutes to capture early systemic exposure. PK parameters were determined from plasma naloxone concentrations. Exploratory analyses involved simulation of repeat administration. Findings: Mean peak concentration (Cmax) values for 1 mg (1.51 ng/ml), 2 mg (2.87 ng/ml) and 4 mg (6.02 ng/ml) i.n. exceeded 0.4 mg i.m. (1.27 ng/ml) naloxone. All three i.n. doses rapidly achieved plasma levels > 50% of peak concentrations (T50%) by 10 minutes, peaking at 15–30 minutes (Tmax). For comparison, the i.m. reference reached Tmax at 10 minutes. Mean bioavailability was 47–51% for i.n. relative to i.m. naloxone. Simulation of repeat dosing (2 × 2 mg i.n. versus 5 × 0.4 mg i.m. doses) at 3‐minute intervals showed that comparable plasma naloxone concentrations would be anticipated. Conclusions: Concentrated 2 mg intranasal naloxone is well‐absorbed and provides early exposure comparable to 0.4 mg intramuscular naloxone, following the 0.4 mg intramuscular curve closely in the first 10 minutes post‐dosing and maintaining blood levels above twice the intramuscular reference for the next 2 hours. [ABSTRACT FROM AUTHOR]

Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB). As an alternative to protamine, a recombinant inactive antithrombin (riAT) was designed as an antidote to heparin and was previously shown to be as potent as protamine in-vitro. In the present study, riAT was assessed for its ability to neutralize heparin after CPB in a rat model. After 60 min of CPB under heparin, rats received 5 mg/kg protamine, 37.5 mg/kg riAT or phosphate buffered saline (PBS) as placebo. Residual anticoagulant activity was assessed using the activated partial thromboplastin time assay before, and 10-30 min after reversion. Haemodynamic monitoring was performed and plasma histamine concentration was also measured. In this model, riAT appeared to be as efficient as protamine in neutralizing heparin. Ten minutes after injection, riAT and protamine both decreased heparin activity, to 1.8 ± 1.3 and 4.5 ± 1.4 u/ml, respectively (23.1 ± 5.1 u/ml in placebo group). Furthermore, evolution of mean carotid arterial pressure, heart rate and plasma histamine levels was comparable in rats treated with PBS or riAT, while protamine exhibited haemodynamic side effects and increased histamine plasma concentration. Thus, riAT could represent an advantage over protamine in CPB because it efficiently reverses heparin activity without negative effects on haemodynamic parameters and plasma histamine level. [ABSTRACT FROM AUTHOR]

Abstract: Inadequate antidote stocking is a global problem in hospitals. Insufficient supplies and delays in the administration of antidotes could lead to death and additional potentially negative clinical consequences. Our objective was to determine the availability of antidotes in hospitals listed on the Saudi Ministry of Health website in the Riyadh Province and to evaluate the leading poison in Saudi Arabia. A cross‐sectional study was conducted using questionnaires. The questionnaires were distributed to pharmacist directors and emergency room‐treating physicians in 17 public hospitals throughout the Riyadh Province. None (0/17) of the pharmacies contained the 24 recommended essential antidotes by the expert consensus guidelines for stocking of antidotes in hospitals. Polyvalent scorpion antivenom, atropine sulphate, calcium gluconate, flumazenil and naloxone hydrochloride were stocked in 94.12% (16/17) of hospitals. 66.67% of patients presented with osmolality, and 55.56% of referral patients with opiates, barbiturates, acetaminophen and salicylate. Our findings have important implications for healthcare institutions and pharmaceutical practices. National practice guidelines are needed to assist pharmacists in selecting appropriate antidotes based on the local pattern of poisoning incidents. Therefore, further study in the Kingdom of Saudi Arabia needs to be completed to fully evaluate the availability of antidotes throughout the country. [ABSTRACT FROM AUTHOR]

Abstract: Background & Aims: The analgesic flupirtine has been linked to cases of severe idiosyncratic drug‐induced liver injury (sFILI). We therefore examined whether N‐acetylcysteine (NAC) and glucocorticoid therapy is effective in the management of sFILI. Methods: In a retrospective cohort study efficacy of NAC‐infusion and oral prednisolone treatments on liver‐function‐tests (LFTs) and clinical outcome of 21 sFILI cases was evaluated by comparing it to an external cohort of 30 sFILI cases not receiving the antidote. LFTs were also assayed in human hepatocyte cultures treated with flupirtine for 96 hours. Additionally, modulation of glutathione stores in cultures of human hepatocytes treated with 80 drugs was investigated. Results: Upon admission, patients presented Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin elevations of up to 90‐, 35‐ and 30‐fold of upper limits of normal (ULN) respectively. The average INR was 2.2, and 50% of patients had a high Model for end‐stage liver disease (MELD) score of ≥25 and included 5 cases of 28‐32. The combined NAC/prednisolone treatment was well tolerated and led to significant ALT, AST and INR improvements within 2 weeks. However, the hyperbilirubinaemia resolved slowly. Two patients with late start of NAC/prednisolone treatment developed hepatic encephalopathy and required liver transplantation; the remaining patients recovered without long‐term sequela. Based on serum biochemistries sFILI cases resolved more rapidly (P < .01) when compared to untreated sFILI patients and included a case with fatal outcome. Additionally, in vitro studies revealed glutathione depletion as a common culprit for drugs with liver liabilities. Conclusions: Based on these initial findings a prospective randomized clinical trial (RCT) is needed to confirm safety and efficacy of NAC/prednisolone treatment in sFILI. [ABSTRACT FROM AUTHOR]

Background and Aims Lack of non-injectable naloxone formulations has impeded widespread take-home provision for the prevention of heroin/opioid overdose deaths. For non-injectable formulations that are finally being investigated, rapid onset of action and sufficient bioavailability will be vital. We present analysis of data from a study of concentrated naloxone nasal spray formulations. Our aims are: to assess (1) pharmacokinetic properties and (2) suitability for overdose reversal in terms of naloxone absorption within 30 minutes post-dosing. Design and interventions/comparator Open-label, randomized, four-way cross-over Latin-square pharmacokinetic study of naloxone administration by three routes: intranasal at two doses (8 mg/0.4 ml, 16 mg/0.4 ml) versus sublingual (16 mg/ml) versus intravenous reference (1 mg/ml). Setting Clinical Pharmacology Unit at The Ohio State University (Columbus, OH, USA). Participants Twelve healthy volunteers (age 20-41; seven female). Measurements From blood plasma naloxone concentrations, (1) standard pharmacokinetic parameters, including maximum plasma concentration (Cmax) and mean absolute bioavailability ( F%, relative to intravenous injection), were determined; as well as (2) partial area under the curve (AUC) values, tmax (time to maximum plasma concentration) and t50% (time to 50% of maximum plasma concentration) as measures of early absorption. Findings (1) Bioavailability was F% = 25-28% for intranasal naloxone. Sublingual had low bioavailability ( F% = 2%) and was not considered further. Mean Cmax values for 8 mg (12.83 ng/ml) and 16 mg (18.25 ng/ml) intranasal exceeded 1 mg intravenous (9.64 ng/ml) naloxone. (2) Following intranasal administration, t50% was reached within 8 minutes and tmax within 20 minutes. Mean naloxone absorption from dosing to 30 minutes (AUC30) was greater following 8 mg (4.17 h × ng/ml) and 16 mg (5.91 h × ng/ml) intranasal than following 1 mg intravenous (1.70 h × ng/ml) administration. Conclusions Concentrated naloxone nasal spray has a promising pharmacokinetic profile, with substantial bioavailability. Its early absorption time-course suggests that concentrated nasal naloxone is suitable for emergency administration in the community, where rapid restoration of respiratory function is essential for opioid overdose reversal. [ABSTRACT FROM AUTHOR]

Objective To describe a case in which digoxin-specific immune Fab was used successfully in a dog with severe oleander toxicosis secondary to ingesting plant material. Case Summary A 6-year-old intact female Rhodesian Ridgeback mixed breed dog was presented for severe oleander toxicosis and was refractory to all antiarrhythmic therapies and supportive care. Digoxin-specific immune Fab was successful in treating this dog. The dog recovered but suffered ischemic injuries, the long-term effects of which are unknown. New or Unique Information Provided This report describes the successful use of digoxin-specific immune Fab in the treatment of oleander toxicosis in a dog, which has not previously been published in veterinary literature. Oleander poisoning can be associated with permanent cardiac arrhythmias due to the ischemic damage. [ABSTRACT FROM AUTHOR]

Objective To describe the successful treatment of loperamide toxicosis in a dog using intravenous lipid emulsion (ILE). Case Summary An 8-month-old male neutered Rough Collie weighing 20.0 kg was given a total dose of 0.75 mg/kg loperamide over 3 days as treatment for diarrhea. The dog was subsequently evaluated for signs of dull mentation, anxiety, ptyalism and ataxia, thought to be a result of loperamide intoxication. The dog was treated with a 1.5 mL/kg IV bolus of 20% ILE solution followed by 0.25 mL/kg/min of the same solution for 2 hours. The dog's mentation improved rapidly following ILE infusion, and he was neurologically normal 3 hours after initiation of ILE treatment. The dog was subsequently found to be homozygous for the ATP-binding cassette (ABC) transporter gene (ABCB1-1∆) mutation. There were no adverse effects noted during or following ILE infusion. New or Unique Information Provided ILE was successful in the treatment of loperamide toxicosis in a Collie with the ABCB1-1∆ mutation. ILE may be of benefit for treatment of other intoxications in dogs with ABCB1-1Δ mutations. [ABSTRACT FROM AUTHOR]

Key Clinical Message Bleeding is a rare complication of direct oral anticoagulant potentially associated with high mortality rates. Biological monitoring is necessary for more than 24 h after idarucizumab antidote therapy in case of bleeding with dabigatran therapy. [ABSTRACT FROM AUTHOR]

The article focuses on the fact that science is an antidote to horse trading in the Australian Alps and urgent action is needed to substantially reduce feral horse numbers in Australia's alpine national parks. It states that scientific basis of this imperative is unequivocal and the scientific heritage of the Australian Alps is extraordinarily rich and Australian Alps were used for grazing domestic livestock for over a century and it impacts of such grazing on alpine ecosystems.

An understanding of mechanisms, potential benefits and risks of antidotes is essential for clinicians who manage poisoned patients. Of the dozens of antidotes currently available, only a few are regularly used. These include activated charcoal, acetylcysteine, naloxone, sodium bicarbonate, atropine, flumazenil, therapeutic antibodies and various vitamins. Even then, most are used in a minority of poisonings. There is little randomized trial evidence to support the use of most antidotes. Consequently, decisions about when to use them are often based on a mechanistic understanding of the poisoning and the expected influence of the antidote on the patient's clinical course. For some antidotes, such as atropine and insulin, the doses employed can be orders of magnitude higher than standard dosing. Importantly, most poisoned patients who reach hospital can recover with supportive care alone. In low risk patients, the routine use of even low risk antidotes such as activated charcoal is unwarranted. In more serious poisonings, decisions regarding antidote use are generally guided by a risk/benefit assessment based on low quality evidence. [ABSTRACT FROM AUTHOR]

Management of cardiovascular instability resulting from calcium channel antagonist (CCB) or beta-adrenergic receptor antagonist (BB) poisoning follows similar principles. Significant myocardial depression, bradycardia and hypotension result in both cases. CCBs can also produce vasodilatory shock. Additionally, CCBs, such as verapamil and diltiazem, are commonly ingested in sustained-release formulations. This can also be the case for some BBs. Peak toxicity can be delayed by several hours. Provision of early gastrointestinal decontamination with activated charcoal and whole-bowel irrigation might mitigate this. Treatment of shock requires a multimodal approach to inotropic therapy that can be guided by echocardiographic or invasive haemodynamic assessment of myocardial function. High-dose insulin euglycaemia is commonly recommended as a first-line treatment in these poisonings, to improve myocardial contractility, and should be instituted early when myocardial dysfunction is suspected. Catecholamine infusions are complementary to this therapy for both inotropic and chronotropic support. Catecholamine vasopressors and vasopressin are used in the treatment of vasodilatory shock. Optimizing serum calcium concentration can confer some benefit to improving myocardial function and vascular tone after CCB poisoning. High-dose glucagon infusions have provided moderate chronotropic and inotropic benefits in BB poisoning. Phosphodiesterase inhibitors and levosimendan have positive inotropic effects but also produce peripheral vasodilation, which can limit blood pressure improvement. In cases of severe cardiogenic shock and/or cardiac arrest post-poisoning, extracorporeal cardiac assist devices have resulted in successful recovery. Other treatments used in refractory hypotension include intravenous lipid emulsion for lipophilic CCB and BB poisoning and methylene blue for refractory vasodilatory shock. [ABSTRACT FROM AUTHOR]

Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for paracetamol poisoning and has effectively reduced rates of hepatotoxicity and death. The current three-bag intravenous regimen with an initial high loading dose was empirically derived four decades ago and has not changed since. This regimen is associated with a high rate of adverse effects due mainly to the high initial peak acetylcysteine concentration. Furthermore, there are concerns that the acetylcysteine concentration is not adequate for 'massive' overdoses and that the dose and duration may need to be altered. Various novel regimens have been proposed, looking to address these issues. Many of these modified regimens aim to decrease the rate of adverse reactions by slowing the loading dose and thereby decrease the peak concentration. We used a published population pharmacokinetic model of acetylcysteine to simulate these modified regimens. We determined mean peak and 20 h acetylcysteine concentrations and area under the under the plasma concentration-time curve to compare these regimens. Those regimens that resulted in a lower peak acetylcysteine concentration have been shown in studies to have a lower rate of adverse events. However, these studies were too small to show whether they are as effective as the traditional regimen. Further research is still needed to determine the optimum dose and duration of acetylcysteine that results in the fewest side-effects and treatment failures. Indeed, a more patient-tailored approach might be required, whereby the dose and duration are altered depending on the paracetamol dose ingested or paracetamol concentrations. [ABSTRACT FROM AUTHOR]

In the present work, aptamers against aflatoxin M1 and aflatoxin B1 were generated and tested for creating proof of principle of recognition of aflatoxin M1 by generated aptamers. The aptamers were selected through the process referred as systematic evolution of ligands by exponential enrichment. A total of 41 different aptamer (36 aptamers for aflatoxin M1 and 5 for aflatoxin B1) sequences were obtained. The determination of dissociation constant (Kd) values revealed that aptamers generated against aflatoxin M1 exhibited Kd values in the range of 35-1515 nM. Selected aptamers were grouped on the basis of the presence of common motifs or G-quadruplex. We find it interesting that one aptamer with no conserved motif or G-quadruplex had lowest Kd value (Kd = 35 nM). This structural motif is very distinct from motifs present in other aptamers. The Kd values of selected aptamers for aflatoxin B1 were in the range of 96-221 nM. One aptamer from each group was further tested for its ability to be used in aptasensor. The aptamer recognized aflatoxin M1 as indicated by color change (red to purple or blue) of aptamer-coated gold nanoparticles in the presence of 250-500 nM aflatoxin M1. The aptamers can be used in developing methods for detection/estimation/separation of aflatoxin or antidote for aflatoxin toxicity. [ABSTRACT FROM AUTHOR]

The SNAP 12-h regimen allows for both shortened treatment for low risk patients and an increased dose of acetylcysteine for massive paracetamol ingestions. The SNAP 12-h regimen may offer a good solution (and be the one size fits all approach), with high risk patients continuing acetylcysteine if the paracetamol concentration is >20 mg/L or there is evidence of liver toxicity at 12 h. Keywords: acetylcysteine; antidote; clinical toxicology; overdose and poisoning; paracetamol EN acetylcysteine antidote clinical toxicology overdose and poisoning paracetamol 715 716 2 03/05/21 20210301 NES 210301 Paracetamol toxicity is a major problem in Western countries, and acute overdose remains the commonest cause of acute liver failure in Europe, North America and Australia.1,2 In 2018, the American Association of Poison Control Centres provided approximately 2.1 million tele-consults for the United States and associated territories, of these over 100 000 calls related to paracetamol exposure.3 There are increasing cases of poisoning and liver injury, with increasing availability of paracetamol, including modified release formulations.4 The current challenges in managing paracetamol toxicity include the changing profile of paracetamol toxicity with "massive" and modified release ingestions and providing a more tailored approached to acetylcysteine therapy. [Extracted from the article]

Heparin has been the most commonly used anticoagulant drug for nearly a century. The drug heparin is generally categorized into three forms according to its molecular weight: unfractionated ( UF, average molecular weight 13 000), low molecular weight (average molecular weight 5000) and ultra-low-molecular-weight heparin ( ULMWH, average molecular weight 2000). An overdose of heparin may lead to very dangerous bleeding in patients. Protamine sulfate may be administered as an antidote to reverse heparin's anticoagulant effect. However, there is no effective antidote for ULMWH. In the current study, we examine the use of human N-acetylglucosamine 6-sulfatase ( NG6S), expressed in Chinese hamster ovary cells, as a reversal agent for ULMWH. NG6S removes a single 6- O-sulfo group at the non-reducing end of the ULMWH Arixtra® (fondaparinux), effectively removing its ability to bind to antithrombin and preventing its inhibition of coagulation factor Xa. These results pave the way to developing human NG6S as an antidote for neutralizing the anticoagulant activity of ULMWHs. [ABSTRACT FROM AUTHOR]

Background Currently, the commercial formulations of the herbicide paraquat are highly toxic to humans, and no effective antidote is available for paraquat poisoning. The aim of the present study was to develop a safe formulation, combining paraquat and the known antidote lysine acetylsalicylate. The toxicity of a mixture of Gramoxone® (20% paraquat) and lysine acetylsalicylate in adult Wistar male rats and the herbicidal efficacy against grass lawn (50% of Poa pratensis and 50% of Festuca arundinacea) were evaluated. This new formulation was administered to Wistar rats by gavage at 125 mg kg−1 of paraquat ion and lysine acetylsalicylate at 79, 158 or 316 mg kg−1 body weight, and the survival rate was observed for 30 days. Results The survival rate of the paraquat group was only 40%, while lysine acetylsalicylate provided effective protection, with full survival observed in the groups that received 125 mg kg−1 of paraquat ion and 316 mg kg−1 of lysine acetylsalicylate. Both formulations of paraquat, either in the absence or in the presence of lysine acetylsalicylate, provided the same herbicidal activity against the tested herbal species. Conclusions The present formulation of paraquat containing lysine acetylsalicylate, significantly decreases mammalian toxicity while maintaining effective herbicidal activity. © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Objective To describe the clinical signs, treatment, and outcomes of dogs and cats following envenomation by the eastern coral snake and to report our clinical experience with the use of Coralmyn. Design Retrospective study (1996-2011). Setting University teaching hospital. Animals Sixteen dogs and 4 cats with eastern coral snake envenomation. Measurements and Main Results Medical records meeting the study inclusion criteria were reviewed and evaluated for signalment, date and time of the snake encounter, elapsed time between encounter and hospital examination, initial physical examination findings, antivenom type, length of hospitalization, and outcome. Initial physical examination findings included: quiet mentation, tetraparesis, ptyalism, tachypnea, abdominal breathing, shallow breathing, decreased to absent gag reflex, ataxia, muscle fasciculations, and decreased spinal reflexes. Laboratory findings in dogs included proteinuria, bilirubinuria, hemeproteinuria, increased aspartate aminotransferase activity, increased alanine aminotransferase activity, and hemolysis. Four dogs and 2 cats received Coralmyn and 4 dogs received North American Coral Snake Antivenom. Adverse reaction to antivenom was suspected in 1 dog that received North American Coral Snake Antivenom. Eight of 11 envenomated dogs survived with a median length of hospitalization of 4.5 days. Two of 3 envenomated cats survived with a median length of hospitalization of 4 days. Two dogs were euthanized, 1 dog suffered acute respiratory arrest, and 1 cat developed tachycardia that progressed to pulseless electrical activity. Five dogs and 1 cat in the encounter group survived to discharge. Conclusions Diagnosis of eastern coral snake envenomation is likely in the dog that has concomitant lower motor neuron neuropathy, bulbar palsy, and hemolysis. Early diagnosis is crucial as antivenom administration can reduce morbidity. Prognosis is considered good with 71% of the envenomated patients in this study surviving to discharge. Supportive care that may include ventilator assistance and antivenom administration are the mainstays of therapy. [ABSTRACT FROM AUTHOR]

Cyanide poisoning is uncommon, but generates interest because of the presumed utility of an antidote immediately available in those areas with a high risk of cyanide exposure. As part of its regular review of guidelines, the Australian Resuscitation Council conducted a systematic review of the human evidence for the use of various proposed cyanide antidotes, and a narrative review of the relevant pharmacological and animal studies. There have been no relevant comparative or placebo-controlled human trials. Nine case series were identified. Treatment with hydroxocobalamin was reported in a total of 361 cases. No serious adverse effects of hydroxocobalamin were reported, and many patients with otherwise presumably fatal poisoning survived. Sodium thiosulphate use was reported in two case series, similarly with no adverse effects. Treatment with a combination of sodium nitrite, amyl nitrite and sodium thiosulphate was reported in 74 patients, with results indistinguishable from those of hydroxocobalamin and sodium thiosulphate. No case series using dicobalt edetate or 4-dimethylaminophenol were identified, but successful use in single cases has been reported. Hydroxocobalamin and sodium thiosulphate differ from alternatives in having negligible adverse effects, and on the basis of current evidence are the antidotes of choice. The indications for the use of an antidote, the requirements for supportive care and a recommended approach for workplaces where there is a risk of cyanide poisoning are presented. [ABSTRACT FROM AUTHOR]

The author explains the role of expanded access to intranasal naloxone in reducing harmful effects from opioid use. Data on average U.S. mortality rate related to opioid overdose in 2006 is presented. The chemical composition of naloxone hydrochloride and its mechanism of action is explained in detail. A discussion on reduction strategies for pain management and the role of the pharmacist is highlighted.

Objective– To determine the safety and efficacy of high-dose fomepizole compared with ethanol (EtOH) in cats with ethylene glycol (EG) toxicosis. Design– Prospective study. Setting– University veterinary research laboratory. Animals– Thirteen cats. Interventions– Two cats received injections of high-dose fomepizole (Study 1). Three cats received lethal doses of EG and fomepizole treatment was initiated 1, 2, or 3 hours later (Study 2). Eight cats received a lethal dose of EG and were treated with fomepizole or EtOH (Study 3). Cats treated with fomepizole received 125 mg/kg IV initially, then 31.25 mg/kg at 12, 24, and 36 hours. Cats treated with EtOH received 5 mL of 20% EtOH/kg IV initially, then every 6 hours for 5 treatments, then every 8 hours for 4 treatments. Cats also received fluids and supportive therapy as needed. Measurements and Main Results– Clinical signs were monitored and serial blood analyses performed. Cats receiving fomepizole experienced mild sedation but no biochemical evidence of toxicity. Cats receiving fomepizole for EG intoxication survived if therapy was initiated within 3 hours of EG ingestion. One of the 6 developed acute renal failure (ARF) but survived. Only 1 of the 3 cats treated with EtOH 3 hours following EG ingestion survived; 2 developed ARF and were euthanized. Cats treated 4 hours following EG ingestion developed ARF, whether treated with EtOH or fomepizole. Conclusions– Fomepizole is safe when administered to cats in high doses, prevents EG-induced fatal ARF when therapy is instituted within 3 hours of EG ingestion, and is more effective than treatment with EtOH. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to asses the efficacy of lipid emulsion as antidotal therapy outside the accepted setting of local anesthetic toxicity. Methods: Literature was accessed through PubMed, OVID (1966–February 2009), and EMBASE (1947–February 2009) using the search terms “intravenous” AND [“fat emulsion” OR “lipid emulsion” OR “Intralipid”] AND [“toxicity” OR “resuscitation” OR “rescue” OR “arrest” OR “antidote”]. Additional author and conference publication searches were undertaken. Publications describing the use of lipid emulsion as antidotal treatment in animals or humans were included. Results: Fourteen animal studies, one human study, and four case reports were identified. In animal models, intravenous lipid emulsion (ILE) has resulted in amelioration of toxicity associated with cyclic antidepressants, verapamil, propranolol, and thiopentone. Administration in human cases has resulted in successful resuscitation from combined bupropion/lamotrigine-induced cardiac arrest, reversal of sertraline/quetiapine-induced coma, and amelioration of verapamil- and beta blocker–induced shock. Conclusions: Management of overdose with highly lipophilic cardiotoxic medications should proceed in accord with established antidotal guidelines and early poisons center consultation. Data from animal experiments and human cases are limited, but suggestive that ILE may be helpful in potentially lethal cardiotoxicity or developed cardiac arrest attributable to such agents. Use of lipid emulsion as antidote remains a nascent field warranting further preclinical study and systematic reporting of human cases of use. [ABSTRACT FROM AUTHOR]

A feeding trial using 220 weaner pigs which comprised two experimental series was conducted to investigate the effects of diets contaminated with the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) and to test the hypothesis that apple pomace acts as an antidote to these mycotoxins. Two diets without contaminated wheat, containing either no pomace or 8% pomace, and two diets with naturally contaminated wheat (3.2 mg DON and 0.06 mg ZON, and 2.1 mg DON and 0.25 mg ZON per kg diet in series 1 and 2 respectively), containing either no pomace or 8% pomace were fed ad libitum for 5 weeks. Mycotoxin exposure lowered feed intake (p < 0.01) and growth (p = 0.05), and tended to decrease the energy conversion ratio (p = 0.06). Although the intake of apple pomace did not increase feed intake, it increased the growth rate (p = 0.04), mainly by restoring growth in the presence of mycotoxins (p = 0.08 for the interaction mycotoxin × pomace). In the first experimental series, the animals were immunized with a parvovirus vaccine. The percentage of seroconverting animals did not differ between the treatments (p = 0.56), which indicates that DON did not affect the humoral immune response. In the second experimental series, female piglets fed the contaminated diets had heavier uteri than piglets fed the uncontaminated diets (p < 0.01), regardless of pomace supplementation. The results show that pomace may alleviate the negative effect of DON on growth but does not counteract the hormonal effects of ZON. [ABSTRACT FROM AUTHOR]

A 25-year-old, 54-kg Hispanic man who had recently started multidrug therapy for pulmonary tuberculosis presented in status epilepticus after ingesting 9 g of isoniazid in a suicide attempt. Successful management of this patient required collaboration between several institutions to provide the large amount of necessary intravenous pyridoxine. Ultimately, this single overdose depleted the supply of intravenous pyridoxine for a significant region of the state of Nebraska. Isoniazid is commonly used to treat tuberculosis, but it is encountered relatively infrequently as the cause of an acute overdose. Severe isoniazid overdoses may present as seizure activity that is refractory to conventional antiepileptic therapy. Although intravenous pyridoxine is an effective antidote for isoniazid overdoses in patients presenting with status epilepticus, this agent has few indications and is typically stocked in limited quantities. In regions with large populations of patients who receive antituberculosis therapy, collaborative networks must be created to ensure that adequate supplies of intravenous pyridoxine (≥ 20 g) are available for effective treatment of isoniazid poisonings. [ABSTRACT FROM AUTHOR]

Background: The Monthly Index of Medical Specialties (MIMS) contains Therapeutic Goods Administration-approved product information supplied by manufacturers. It is widely used by health-care professionals but is not specifically designed as a toxicology reference. Objectives: To determine how widespread the use of MIMS is as a toxicology reference. To evaluate the quality of poisoning management advice it contains. Methods: First, a survey of 500 consecutive calls to the NSW Poison Information Centre (PIC) was undertaken asking health-care workers which toxicology references were consulted prior to calling and which references they would use if the PIC were not available. Second, a consensus opinion for poisoning management was obtained, for 25 medications which are either commonly involved in poisoning or potentially life-threatening in overdose, by review of 5 current toxicology references for contraindicated treatments, ineffective treatments and specific recommended treatments and antidotes. MIMS poisoning management advice was then compared with this toxicology consensus opinion. Results: In total, 276 doctors and 222 nurses were surveyed. Prior to calling the PIC 22.8% of doctors and 6.8% of nurses consulted MIMS. In total, 25.7% of doctors and 39.6% nurses stated they would use the MIMS for poisoning management advice if the PIC were not available. For the 25 drugs assessed, 14 contained inaccurate poisoning management: 1 recommended ineffective treatments and 14 omitted specific treatments or antidotes. Conclusion: The MIMS is often used as a toxicology reference by physicians prior to calling the PIC. It contains a number of significant inaccuracies pertaining to management of poisonings and should not be used as a primary reference for poisoning advice. [ABSTRACT FROM AUTHOR]

Cyanide is both widely available and easily accessible throughout the world, Although the compound is 1101 Frequently encountered, it has been used as a poison and contaminant in the past and is a potential terrorist agent. Cyanide has the ability to cause significant social disruption and demands special attention to public health preparedness. It can be obtained from a variety 01 sources. including industrial. medical, and even common household products. Another frequently encountered source of cyanide exposure is residential fires. Exposure to high concentrations of the chemical can result in death within seconds to minutes. Long-term effects from cyanide exposure can cause significant morbidity. The only treatment for cyanide toxicity approved for use in the United States is a kit consisting of amyl nitrite, sodium nitrite, and sodium thiosulfate. Future research aims to find a faster-acting, more effective, and better tolerated treatment for cyanide toxicity. [ABSTRACT FROM AUTHOR]

A specific RNA aptamer (T705) against bovine thrombin had been obtained after seven rounds of SELEX (systematic evolution of ligands by exponential enrichment) selection from a random RNA library previously. In order to further investigate the relationship between the structure and function of this aptamer, three truncated RNA aptamers, T705a, T705b and T705c, were designed according to the secondary structure of T705 RNA. Our results showed that T705c keeping the precise stem–loop structure but lacking most of the stem region sequence of T705 could inhibit clot formation in vitro in the same way as its parental form. We also report here that single-stranded DNA (ssDNA) antisense oligonucleotides, c′ and c′-22, which were complementary to different portions of T705c could act as efficient antidotes reversing the inhibitory activity of T705. It is demonstrated for the first time that ssDNA antisense oligonucleotides are potential antidotes of RNA aptamers and this may be an effective, rapid strategy to find antidotes of RNA aptamers which would be of important usefulness in basic research and drug screening. [Copyright &y& Elsevier]

Paracetamol overdose is one of the commonest pharmaceutical poisonings in the world. For nearly four decades, intravenous acetylcysteine regimens have been used to treat most patients successfully and prevent or mitigate hepatotoxicity. However, the rate of occurrence of adverse reactions to acetylcysteine is quite high, and there is a potential for these to be reduced. Recent studies show that distributing the loading-dose of acetylcysteine over the first few hours of treatment may decrease the incidence of adverse reactions. In addition, varying the duration of acetylcysteine administration may potentially benefit certain cohorts of poisoned patients, depending on their risk of developing hepatotoxicity. [ABSTRACT FROM AUTHOR]