Alginate-coated activated charcoal enhances fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice, with fewer side effects than uncoated one.

Activated charcoal (AC) is a potential candidate antidote against dioxins. However, it is difficult to take AC as a supplement on a daily basis, because its long-term ingestion causes side effects such as constipation and deficiency of fat-soluble essential nutrients and hypocholesterolemia. Alginate-coated AC, termed Health Carbon (HC), was developed to decrease the side effects of AC, but its pharmacological effects, including side effects, remains unclear. Here, we show that HC enhanced fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and decreased some side effects of unmodified AC, such as hypocholesterolemia, in male mice. Basal diet mixed with HC or unmodified AC at various concentrations was fed to mice for 16 days following a single intraperitoneal administration of [3H]TCDD. Both HC and unmodified AC at 3% or more significantly increased fecal excretion of [3H]TCDD in comparison with the control basal diet. Consistent with this, [3H]TCDD radioactivity in the liver-a major TCDD storage organ-was markedly decreased by HC at concentrations of 3% and 10%. In an examination of potential side effects, unmodified AC at 10% or more caused significant body weight reduction and at 20% caused significant hypocholesterolemia. In contrast, HC caused weight gain reduction only at a concentration of 20%, and there was no evidence of hypocholesterolemia at any dietary HC concentration. HC not only retains the ability of AC to enhance fecal excretion of TCDD but also reduces some of the side effects of AC.

Efficacy and expenses of succimer vs. d-penicillamine plus garlic in the treatment of lead poisoning: a retrospective cross-sectional study.

PURPOSE: Lead Poisoning is a major health problem in Iran. We aimed to compare efficacy of a standard regimen (Succimer) with that of a low-priced combination of D-penicillamine and Garlic in outpatients with lead poisoning. METHODS: In this retrospective cross-sectional study, year-long clinical files of outpatients with lead poisoning in two referral toxicology clinics in Mashhad, Iran were reviewed. A total of 79 patients (all men), received either Succimer or a combination of D-penicillamen plus garlic (DPN + Gar), for 19 and 30 days, respectively. Clinical and laboratory data, including blood lead level (BLL), were analyzed and treatment expanses were compared between the two regimens. RESULTS: Of 79 male patients, 42 were treated by DPN + Gar and 37 received Succimer. Mean BLL of DPN + Gar group before treatment (965.73 ± 62.54 µg/L) was higher than that of the Succimer group (827.59 ± 24.41) (p < 0.001). After treatment, BLL in both groups significantly reduced to 365.52 ± 27.61 µg/L and 337.44 ± 26.34 µg/L, respectively (p < 0.001). The price of a 19-day treatment with Succimer was approximately 28.6 times higher than a one-month course of treatment with garlic plus DPN. None of the treatments caused serious side effects in the patients. CONCLUSION: Combination therapy with DPN + Gar is as effective as Succimer in Pb poisoning, while treatment with Succimer is significantly more expensive.

Intramuscular cobinamide as an antidote to methyl mercaptan poisoning.

BACKGROUND: Methyl mercaptan occurs naturally in the environment and is found in a variety of occupational settings, including the oil, paper, plastics, and pesticides industries. It is a toxic gas and deaths from methyl mercaptan exposure have occurred. The Department of Homeland Security considers it a high threat chemical agent that could be used by terrorists. Unfortunately, no specific treatment exists for methyl mercaptan poisoning. METHODS: We conducted a randomized trial in 12 swine comparing no treatment to intramuscular injection of the vitamin B12 analog cobinamide (2.0 mL, 12.5 mg/kg) following acute inhalation of methyl mercaptan gas. Physiological and laboratory parameters were similar in the control and cobinamide-treated groups at baseline and at the time of treatment. RESULTS: All six cobinamide-treated animals survived, whereas only one of six control animals lived (17% survival) (p = 0.0043). The cobinamide-treated animals returned to a normal breathing pattern by 3.8 ± 1.1 min after treatment (mean ± SD), while all but one animal in the control group had intermittent gasping, never regaining a normal breathing pattern. Blood pressure and arterial oxygen saturation returned to baseline values within 15 minutes of cobinamide-treatment. Plasma lactate concentration increased progressively until death (10.93 ± 6.02 mmol [mean ± SD]) in control animals, and decreased toward baseline (3.79 ± 2.93 mmol [mean ± SD]) by the end of the experiment in cobinamide-treated animals. CONCLUSION: We conclude that intramuscular administration of cobinamide improves survival and clinical outcomes in a large animal model of acute, high dose methyl mercaptan poisoning.

Novel strategies for the treatment of acetaminophen hepatotoxicity.

INTRODUCTION: Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Despite extensive investigations into the mechanisms of cell death, only a single antidote, N-acetylcysteine, is in clinical use. However, there have recently been more efforts made to translate mechanistic insight into identification of therapeutic targets and potential new drugs for this indication. AREAS COVERED: After a short review of the key events in the pathophysiology of APAP-induced liver injury and recovery, the pros and cons of targeting individual steps in the pathophysiology as therapeutic targets are discussed. While the re-purposed drug fomepizole (4-methylpyrazole) and the new entity calmangafodipir are most advanced based on the understanding of their mechanism of action, several herbal medicine extracts and their individual components are also considered. EXPERT OPINION: Fomepizole (4-methylpyrazole) is safe and has shown efficacy in preclinical models, human hepatocytes and in volunteers against APAP overdose. The safety of calmangafodipir in APAP overdose patients was shown but it lacks solid preclinical efficacy studies. Both drugs require a controlled phase III trial to achieve regulatory approval. All studies of herbal medicine extracts and components suffer from poor experimental design, which questions their clinical utility at this point.

An Appraisal of Antidotes' Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements.

Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or snake envenomation. Since the advent of Albert Calmette's cobra venom antidote, efforts have been geared towards antidotes development for various poisons to date. While there are resources and facilities to tackle poisoning in urban areas, rural areas and developing countries are challenged with poisoning management due to either the absence of or inadequate facilities and this has paved the way for phyto-antidotes, some of which have been scientifically validated. This review presents the scope of antidotes' effectiveness in different experimental models and biotechnological advancements in antidote research for future applications. While pockets of evidence of the effectiveness of antidotes exist in vitro and in vivo with ample biotechnological developments, the utilization of analytic assays on existing and newly developed antidotes that have surpassed the proof of concept stage, as well as the inclusion of antidote's short and long-term risk assessment report, will help in providing the required scientific evidence(s) prior to regulatory authorities' approval.

Management of epistaxis in patients on novel oral anticoagulation therapy.

BACKGROUND: Individuals on anticoagulation therapy are at increased risk of bleeding, including epistaxis. There is a lack of available reversal agents for novel oral anticoagulation therapy. OBJECTIVE: This paper reviews the current literature on epistaxis in the context of novel oral anticoagulation use, in order to recommend guidelines on management. METHOD: A comprehensive search of published literature was conducted to identify all relevant articles published up to April 2019. RESULTS: Patients on oral anticoagulation therapy are over-represented in individuals with epistaxis. Those on novel oral anticoagulation therapy were more likely to relapse compared to patients on classic oral anticoagulants or non-anticoagulated patients. Idarucizumab is an effective antidote for bleeding associated with dabigatran use. Recommendations for epistaxis management in patients on novel oral anticoagulation therapy are outlined. CONCLUSION: Clinicians need to be aware of the potential severity of epistaxis and the increased likelihood of recurrence. High-quality studies are required to determine the efficacy and safety of andexanet alfa and ciraparantag, as well as non-specific reversal agents.

Rebound metabolic acidosis following intentional amygdalin supplement overdose.

Introduction: Amygdalin, marketed misleadingly as supplement "Vitamin B17," is a cyanogenic glycoside. When swallowed, it is hydrolyzed into cyanide in the small intestine, which causes histotoxic hypoxia via inhibition of cytochrome c oxidase. It remains available for purchase online despite a ban from the US Food and Drug Administration. We report a case of massive intentional amygdalin overdose resulting in recurrent cyanide toxicity after initial successful antidotal therapy.Case summary: A 33-year-old woman intentionally ingested 20 g of "apricot POWER B17 Amygdalin" supplements. She presented five hours post-ingestion with vital signs: P 127 bpm, BP 112/65 mmHg, RR 25/min, temperature 98.1 °F, and SpO2 98% RA. She was in agitated delirium, diaphoretic, and mydriatic. Her VBG was notable for a pH of 7.27 (rr 7.32-7.42) and lactate 14.1 mmol/L (rr 0.5-2.2), with ECG demonstrating QTc 538 ms (normal <440 ms). She was empirically treated with hydroxocobalamin and supportive care, but worsened clinically, requiring intubation and additional hydroxocobalamin and sodium thiosulfate, which resolved her toxicity. Twelve hours later, she developed recurrent hypotension, acidemia, and QTc prolongation that resolved with repeat hydroxocobalamin and sodium thiosulfate dosing.Discussion: Our case demonstrates rebound metabolic acidosis after massive amygdalin overdose. Toxicity was associated with prolonged QTc, which warrants further investigation into clinical significance. Redosing of combination antidotal therapy suggested efficacy without adverse effects.

Changes in intracellular folate metabolism during high-dose methotrexate and Leucovorin rescue therapy in children with acute lymphoblastic leukemia.

BACKGROUND: Methotrexate (MTX) is an important anti-folate agent in pediatric acute lymphoblastic leukemia (ALL) treatment. Folinic acid rescue therapy (Leucovorin) is administered after MTX to reduce toxicity. Previous studies hypothesized that Leucovorin could 'rescue' both normal healthy cells and leukemic blasts from cell death. We assessed whether Leucovorin is able to restore red blood cell folate levels after MTX. METHODS: We prospectively determined erythrocyte folate levels (5-methyltetrahydrofolate (THF) and non-methyl THF) and serum folate levels in 67 children with ALL before start (T0) and after stop (T1) of HD-MTX and Leucovorin courses. RESULTS: Erythrocyte folate levels increased between T0 and T1 (mean ± SD: 416.7 ± 145.5 nmol/L and 641.2 ± 196.3 nmol/L respectively, p<0.001). This was due to an increase in 5-methyl THF levels (mean increase: 217.7 ± 209.5 nmol/L, p<0.001), whereas non-methyl THF levels did not change (median increase: 0.6 nmol/L [-9.9-11.1], p = 0.676). Serum folate levels increased between T0 and T1 (median increase: 29.2 nmol/L [32.9-74.0], p<0.001). Results were not significantly affected by age, sex, ALL immunophenotype and MTHFR c.677C>T genotype. CONCLUSION: Intracellular folate levels accumulate after HD-MTX and Leucovorin therapy in children with ALL, suggesting that Leucovorin restores the intracellular folate pool. Future studies are necessary to assess concomitant lower uptake of MTX.

Natural antidotes and management of metal toxicity.

The global burden of heavy metal especially mercury, arsenic, lead, and cadmium toxicities remains a significant public health challenge. Developing nations are particularly at high risk and carry the highest burden of this hazard. Chelation therapy has been the mainstay for treatment of heavy metal poisoning where the chelating agent binds metal ions to form complex ring-like structures called "chelates" to enhance their elimination from the body. Metal chelators have some drawbacks such as redistribution of some heavy metals from other tissues to the brain thereby increasing its neurotoxicity, causing loss of essential metals such as copper and zinc as well as some serious adverse effects, e.g., hepatotoxicity. The use of natural antidotes, which are easily available, affordable, and with little or no side effects compared to the classic metal chelators, is the focus of this review and suggested as cheaper options for developing nations in the treatment of heavy metal poisoning.

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats.

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3 ) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti-apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status and electrocardiographic parameters in rats after AlP poisoning. To do this, AlP was given to rats by gavage to induce toxicity. Selegiline was injected intraperitoneally in the treatment groups 1 hour after AlP poisoning. Selegiline treatment after AlP intoxication was not associated with a significant difference in the mortality rate of animals. However, selegiline reduced oxidative stress (decreased the reactive oxygen species and malondialdehyde) and increased glutathione in the cardiac tissue of rats exposed to AlP. Further, the mitochondrial membrane potential (ΔΨm) collapse reversed after treatment with selegiline. Selegiline also improved the electrocardiographic (ECG) parameters and enhanced heart rate. The histopathological evaluation revealed that selegiline eliminated the inflammation and injuries induced by AlP in the stomach and duodenum, as well as cardiac tissue. In conclusion, selegiline treatment can ameliorate the AlP-induced cardiac and gastrointestinal injuries in rats via boosting redox status and mitochondrial function with no significant effect on survival. We suggest that using selegiline, apart from other clinical treatments, may improve the quality of treatment process for AlP toxicity.

Effects of Modified Palygorskite Supplementation on Egg Quality and Mineral Element Content, and Intestinal Integrity and Barrier Function of Laying Hens.

This study was conducted to investigate effects of modified palygorskite (MPal) supplementation on the laying performance, egg quality and mineral element content, immunity, oxidative status, and intestinal integrity and barrier function of laying hens. A total of 360 52-week-old Hyline Brown hens were randomly assigned into four dietary treatments for a 7-week feeding trial. The birds were fed a basal diet supplemented with 0 (control group), 0.25, 0.5, and 1 g/kg MPal, respectively. The supplementation of MPal did not alter laying performance and egg quality among groups. Compared with the control group, MPal inclusion decreased lead (Pb) content in yolks at 49 days, and either 0.5- or 1-g/kg MPal supplementation decreased Pb accumulation in yolks at 25 days and manganese (Mn) accumulation in yolks at 25 and 49 days. The contents of jejunal secretory immunoglobulin A (SIgA), ileal SIgA, and immunoglobulin G were decreased by the dietary 0.5-g/kg MPal supplementation. The supplementation of MPal also decreased malondialdehyde content in jejunum and ileum, and decreased serum diamine oxidase activity of the laying hens at 25 and 49 days. The inclusion of 0.5 and 1 g/kg MPal enhanced villus height in jejunum and ileum, and also increased the ratio of villus height to crypt depth in ileum. In conclusion, MPal supplementation decreased Pb and Mn contents in yolks, and exhibited beneficial effects on the intestinal immunity, oxidative status, and intestinal integrity and barrier function of laying hens and its optimal dosage was 0.5 g/kg.

Acute Liver Failure due to Amanita phalloides Poisoning: Therapeutic Approach and Outcome.

INTRODUCTION: Amanita phalloides poisoning is a potentially fatal cause of acute liver failure. The aim of this study was to analyze the impact of initial patients' characteristics and different treatment modalities on the outcome of patients with liver failure caused by Amanita poisoning. MATERIAL AND METHODS: We retrospectively evaluated 23 patients admitted to our center between July 2007 and August 2016. RESULTS: Mean time interval between Amanita phalloides ingestion and the onset of gastrointestinal symptoms was 12.48 ± 9.88 hours and the interval between ingestion and hospital admission 26.26 ± 15.14 hours. The treatment was intiated by oral decontamination using activated charcoal followed by intravenous rehydration and high doses of intravenous N-acetylcysteine and silibinin. Fourteen patients (61%) underwent extracorporeal elimination method. Ten patients had plasmapheresis, 1 patient had hemoperfusion, and 5 patients had fractionated plasma separation and adsorption. Seven patients who met King's College Criteria were listed for urgent liver transplantation; one of them died before transplantation. Six patients underwent liver transplantation; the mean waiting time was 6.5 ± 12.0 days (range, 1-31 days). One patient died 2 months afterward. All 16 patients who did not meet King's College Criteria and received conservative treatment survived. CONCLUSION: Our results documented a good prognostic value of standard King's College Criteria for indication of urgent liver transplantation in acute liver failure caused by Amanita phalloides poisoning. Fractionated plasma separation and adsorption may contribute to low mortality on the waiting list. Intensive care and extracorporeal elimination methods seem to be crucial points of the conservative treatment.

Treatment of severe fluoroacetamide poisoning in patient with combined multiple organ dysfunction syndrome by evidence-based integrated Chinese and Western medicines: A case report.

RATIONALE: Fluoroacetamide poisoning is the acute and severe disease of human, which leads to nervous, digestive, and cardiovascular system damage or even death in a short period of time. PATIENT CONCERNS: We report a case of a 65-year-old woman with loss of consciousness, nausea, and vomiting who was sent to the hospital by passers-by. DIAGNOSIS: She was diagnosed with severe fluoroacetamide poisoning with combined multiple organ dysfunction syndrome. INTERVENTIONS: When the diagnosis was unclear, we gave gastric lavage, support and symptomatic treatment, and closely with the vital sign. When the diagnosis was clear, based on the evidence of retrieved, muscle injection of acetamide, calcium gluconate, and vitamin C. Traditional Chinese medicine aspect, oral administration of mung bean soup of glycyrrhizae and Da-Cheng-Qi decoction enema. OUTCOMES: By setting reasonable treatment for patients, she had no special discomfort and complications after treatment. Besides, through 1-month follow-up, it was confirmed that the treatments were effective. LESSONS: Evidence-based integrated Chinese and Western medicines can effectively improve the therapeutic effects in severe fluoroacetamide-poisoned patients with combined MODS.

Low risk of seizures with slow flumazenil infusion and routine anticonvulsant prophylaxis for high-dose benzodiazepine dependence.

High-dose benzodiazepine (BZD) dependence represents an emerging and under-reported addiction phenomenon and is associated with reduced quality of life. To date there are no guidelines for the treatment of high-dose BZD withdrawal. Low-dose slow flumazenil infusion was reported to be effective for high-dose BZD detoxification, but there is concern about the risk of convulsions during this treatment. We evaluated the occurrence of seizures in 450 consecutive high-dose BZD dependence patients admitted to our unit from April 2012 to April 2016 for detoxification with low-dose slow subcutaneous infusion of flumazenil associated with routine anticonvulsant prophylaxis. In our sample, 22 patients (4.9%) reported history of convulsions when previously attempting BZD withdrawal. Only four patients (0.9%) had seizures during ( n = 2) or immediately after ( n = 2) flumazenil infusion. The two patients with seizures during flumazenil infusion were poly-drug misusers. The most common antiepileptic drugs (AEDs) used for anticonvulsant prophylaxis were either valproate 1000 mg or levetiracetam 1000 mg. Our data indicate that, when routinely associated with AEDs prophylaxis, low-dose slow subcutaneous flumazenil infusion represents a safe procedure, with low risk of seizure occurrence.

Neurotoxicity after high-dose methotrexate (MTX) is adequately explained by insufficient folinic acid rescue.

PURPOSE: To challenge the view that the dose of folinic acid rescue after high-dose methotrexate (MTX) has no significance in the prevention of neurotoxicity and to present the minority view that neurotoxicity can be prevented by an adequate dose of folinic acid, without compromising treatment results. Several fallacies that led to the misunderstanding of post MTX neurotoxicity are presented. METHODS: Data mining using search engines was used to find relevant publications, and an e-mail survey of more than 60 authors of articles in this field was performed. All relevant articles identified were read in their entirety. RESULTS: Examples of clinical studies with neurotoxicity following inadequate rescue are given. Some studies demonstrated no neurotoxicity when adequate doses of folinic acid rescue were started 24-36 h after the start of HDMTX rescue even after mega doses of MTX. Rescue started after 42 h was associated with neurotoxicity except in patients with low serum MTX levels after 24 and 36 h. ALL protocols with neurotoxicity, especially BFM-like protocols, are presented. Protocol is reported in which single protocol changes prevented neurotoxicity. CONCLUSIONS: From the published data, when folinic acid rescue is given in a sufficiently high enough dose and is started 24-36 h after the beginning of the methotrexate exposure, and virtually all forms of post MTX neurotoxicity can be prevented without compromising therapeutic results.

The efficacy of raw and concentrated bentonite clay in reducing the toxic effects of aflatoxin in broiler chicks.

The objective of this study was to evaluate the efficacy of two adsorbents, a raw bentonite clay (RC) and a concentrated bentonite clay (CC), in ameliorating the toxic effects of aflatoxin B1 (AFB1). Results of the in vitro study (pH 3.0) indicated the CC adsorbed more AFB1 than RC (93.39 mg/g vs. 79.30 mg/g) suggesting that CC may be more effective than RC in reducing the toxic effects of AFB1. One hundred and eighty day-old straight run broiler chicks were assigned to 6 replicate pens of 5 chicks each and assigned to 6 dietary treatments from hatch to day 21. Dietary treatments included: 1) basal diet (BD) containing no AFB1 or adsorbents; 2) BD plus 0.50% RC; 3) BD plus 0.50% CC; 4) BD plus 2.0 mg AFB1/kg; 5) BD plus 2.0 mg AFB1/kg plus 0.50% RC; and 6) BD plus 2.0 mg AFB1/kg plus 0.50% CC. Dietary AFB1 concentrations were confirmed by analysis and diets were screened for other mycotoxins prior to the start of the experiment. The addition of AFB1 to the feed reduced (P < 0.05) growth performance and increased (P < 0.05) relative liver weight (RLW) and kidney weight (RKW) of chicks fed AFB1 compared to control chicks on day 21. These changes were ameliorated (P < 0.05) by the addition of RC and CC to the AFB1 diet. Mild to moderate lesions of aflatoxicosis (2.25) were observed in chicks fed AFB1 alone on day 21. The addition of both RC and CC to the AFB1 diet decreased (P < 0.05) but did not prevent liver lesions (0.92 and 1.42, respectively). Results indicate that both RC and CC were effective in reducing the toxic effects of AFB1, however the cost of processing of CC would make the RC a more economical product for reducing the effects of AFB1 in young broiler chicks.

Inhibición de los efectos coagulante, fosfolipasa A2 y proteolítico del veneno de Bothrops asper por plantas usadas tradicionalmente en Centroamérica / Inhibition of the coagulant, phospholipase A2 and proteolytic effects of Bothrops asper venom by plants traditionally used in Central America

Existen pocos estudios científicos que demuestren el valor terapéutico de las plantas usadas en la medicina tradicional centroamericana para tratar el envenenamiento ofídico. En este estudio se evaluó la capacidad de los extractos etanólicos de nueve plantas de uso etnomédico en Centroamérica (Acacia hindsii, Aristolochia maxima, Bursera simaruba, Cissampelos pareira, Eryngium foetidum, Hamelia patens, Pimenta dioica, Piper peltatum y Sansevieria hyacinthoides) para inhibir el efecto coagulante del veneno de Bothrops asper. Tres de ellas (B. simaruba, E. foetidum y P. dioica) también fueron evaluadas en cuanto a su capacidad inhibitoria de los efectos fosfolipasa A2 (PLA2) y proteolítico del veneno. Las plantas fueron colectadas en Guatemala, secadas, extraídas con etanol y los efectos inhibitorios evaluados in vitro después de preincubar concentraciones variables de extracto con concentraciones fijas de veneno. Los resultados demostraron que ninguno de los extractos logró inhibir los efectos coagulante y PLA2, pero los extractos clorofilados de P. dioica y E. foetidum inhibieron efectivamente la actividad proteolítica del veneno. El tamizaje fitoquímico, mediante ensayos macro y semimicrométricos de cromatografía en capa fina, demostró la presencia de metabolitos secundarios reportados con actividad antiproteolítica (flavonoides, antocianinas, catequinas y taninos) en la composición química de los extractos de E. foetidum y P. dioica. Su efecto sobre el veneno se evaluó mediante electroforesis SDS-PAGE, demostrándose que no está mediado por degradación proteolítica de los componentes del veneno. El aislamiento y caracterización específica de sus metabolitos secundarios en futuros estudios, permitirá determinar el mecanismo de acción inhibitoria ejercido por estos extractos.

Medicinal plants have been traditionally used in Central America to treat snakebite envenomations, however, very few scientific studies aimed to demonstrate their efficacy and safety have been performed. In this study, ethanolic extracts of nine plants used in the region by traditional healers in snakebite cases (Acacia hindsii, Aristolochia maxima, Bursera simaruba, Cissampelos pareira, Eryngium foetidum, Hamelia patens, Pimenta dioica, Piper peltatum and Sansevieria hyacinthoides) were evaluated for their ability to inhibit the coagulant effect induced by the venom of the snake Bothrops asper. Three of these extracts (B. simaruba, E. foetidum and P. dioica) were also evaluated for their inhibitory effect on the phospholipase A2 (PLA2) and proteolytic activities of the venom. Plants were collected in Guatemala, dried, extracted with ethanol, and their inhibitory effects were evaluated in vitro after pre-incubation of several amounts of each extract with a challenge concentration of venom. Results showed that none of the extracts inhibited the coagulant and PLA2 effects; however, chlorophyllated extracts of E. foetidum and P. dioica effectively inhibited the proteolytic activity of the venom. Phytochemical analysis of these extracts, conducted by macrometric assays and semimicroanalysis by thin layer chromatography, identified secondary metabolites (flavones, anthocyanins, catequines and tannins) whose anti-proteolytic activities have been widely reported. SDS-PAGE analysis demonstrated that the mechanism of inhibition is not related to proteolytic degradation of the venom proteins by the plant extracts. Further studies are needed to isolate and identify the active venom inhibitory compounds of these plants, aimed to understand their mechanism of action.

Conventional and Unconventional Lifesaving Therapies in an Adolescent With Amlodipine Ingestion.

Amlodipine, a dihydropyridine calcium channel blocker, is commonly prescribed for the treatment of hypertension. Ingestion of an overdose leads to severe hypotension; if the hypotension is not treated, death may be imminent. Conventional and unconventional interventions were used to treat an adolescent who ingested a life-threatening dose of amlodipine. Severe hypotension resistant to conventional treatment with intralipids and hyperinsulinemia-euglycemia therapy led to the use of plasmapheresis and a pneumatic antishock garment as lifesaving measures. Plasmapheresis has been described in only one other case of severe amlodipine overdose, and the use of a pneumatic antishock garment has never been described in the management of a calcium channel blocker overdose. Because short-term use of a pneumatic antishock garment has associated risks, the critical care nurse's anticipation of side effects and promotion of safe use of the garment were instrumental in the patient's care and outcome. (Critical Care Nurse 2016; 36[4]:64-69).