Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations.

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 ∼ 50-100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 ∼ 40-60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation.

Increase in ENHANCER OF SHOOT REGENERATION2 expression by treatment with strigolactone-related inhibitors and kinetin during adventitious shoot formation in ipecac.

KEY MESSAGE: Increase of ENHANCER OF SHOOT REGENERATION 2 expression was consistent to treatment with kinetin, TIS108, and KK094 in adventitious shoot formation of ipecac. Unlike many plant species, ipecac (Carapichea ipecacuanha (Brot.) L. Andersson) can form adventitious shoots in tissue culture without cytokinin (CK) treatment. Strigolactone (SL) biosynthesis and signaling inhibitors stimulate adventitious shoot formation in ipecac, suggesting their potential use as novel growth regulators in plant tissue culture, but the molecular mechanism of their action is unclear. In this study, we compared the effects of SL-related inhibitors (TIS108 and KK094) and CKs (2iP, tZ, and kinetin) on adventitious shoot formation in ipecac. Exogenously applied SL-related inhibitors and CKs stimulated adventitious shoot formation. Combinations of SL-related inhibitors and kinetin also promoted adventitious shoot formation, but without additive effects. We also analyzed the expression of CK biosynthesis genes in ipecac. TIS108 increased the expression of the ipecac homolog of ISOPENTENYL TRANSFERASE 3 (CiIPT3) but decreased that of LONELY GUY 7 homolog (CiLOG7), presumably resulting in no change in 2iP-type CK levels. KK094 and kinetin increased CiLOG7 expression, elevating 2iP-type CK levels. Among pluripotency- and meristem-related genes, TIS108, KK094, and kinetin consistently increased the expression of ENHANCER OF SHOOT REGENERATION 2 homolog (CiESR2), which has a key role in shoot regeneration, in the internodal segment region that formed adventitious shoots. We propose that CiESR2 might be a key stimulator of adventitious shoot formation in ipecac.

Gene expression profiling before and after internode culture for adventitious shoot formation in ipecac.

BACKGROUND: In ipecac (Carapichea ipecacuanha (Brot.) L. Andersson), adventitious shoots can be induced simply by placing internodal segments on phytohormone-free culture medium. The shoots form locally on the epidermis of the apical region of the segments, but not the basal region. Levels of endogenous auxin and cytokinin transiently increase in the segments after 1 week of culture. RESULTS: Here, we conducted RNA-seq analysis to compare gene expression patterns in apical and basal regions of segments before culture and after 1 week of culture for adventitious shoot formation. The results revealed 8987 differentially expressed genes in a de novo assembly of 76,684 genes. Among them, 276 genes were upregulated in the apical region after 1 week of culture relative to before culture and the basal region after 1 week of culture. These genes include 18 phytohormone-response genes and shoot-formation-related genes. Validation of the gene expression by quantitative real-time PCR assay confirmed that the expression patterns were similar to those of the RNA-seq data. CONCLUSIONS: The transcriptome data show that expression of cytokinin biosynthesis genes is induced along with the acquisition of cellular pluripotency and the initiation of cell division by wounding in the apical region of internodal segments, that trigger adventitious shoot formation without callusing.

Ipecac root extracts and isolated circular peptides differentially suppress inflammatory immune response characterised by proliferation, activation and degranulation capacity of human lymphocytes in vitro.

Circular peptides are attractive lead compounds for drug development; this study investigates the immunomodulatory effects of defined root powder extracts and isolated peptides (called cyclotides) from Carapichea ipecacuanha (Brot.) L. Andersson ('ipecac'). Changes in the viability, proliferation and function of activated human primary T cells were analysed using flow cytometry-based assays. Three distinct peptide-enriched extracts of pulverised ipecac root material were prepared via C18 solid-phase extraction and analysed by reversed-phase HPLC and mass spectrometry. These extracts induced caspase 3/7 dependent apoptosis, thus leading to a suppressed proliferation of activated T cells and a reduction of the number of cells in the G2 phase. Furthermore, the stimulated T cells had a lower activation potential and a reduced degranulation capacity after treatment with ipecac extracts. Six different cyclotides were isolated from C. ipecacuanha and an T cell proliferation inhibiting effect was determined. Furthermore, the degranulation capacity of the T cells was diminished specifically by some cyclotides. In contrast to kalata B1 and its analog T20K, secretion of IL-2 and IFN- γ was not affected by any of the caripe cyclotides. The findings add to our increased understanding of the immunomodulating effects of cyclotides, and may provide a basis for the use of ipecac extracts for immunomodulation in conditions associated with an exessive immune responses.

Strigolactone signaling inhibition increases adventitious shoot formation on internodal segments of ipecac.

MAIN CONCLUSION: SL inhibited adventitious shoot formation of ipecac, whereas the SL-related inhibitors promoted adventitious shoot formation. SL-related inhibitors might be useful as new plant growth regulators for plant propagation. In most plant species, phytohormones are required to induce adventitious shoots for propagating economically important crops and regenerating transgenic plants. In ipecac (Carapichea ipecacuanha (Brot.) L. Andersson), however, adventitious shoots can be formed without phytohormone treatment. Here we evaluated the effects of GR24 (a synthetic strigolactone, SL), SL biosynthetic inhibitors, and an SL antagonist on adventitious shoot formation during tissue culture of ipecac. We found that exogenously applied GR24 suppressed indole-3-acetic acid transport in internodal segments and decreased the number of adventitious shoots formed; in addition, the distribution of adventitious shoots changed from the apical to middle region of the internodal segments. In contrast, the SL-related inhibitors promoted adventitious shoot formation on both apical and middle regions of the segments. In particular, SL antagonist treatment increased endogenous cytokinin levels and induced multiple shoot development. These results indicate that SL inhibits adventitious shoot formation in ipecac. In ipecac, one of the shoots in each internodal segment becomes dominant and auxin derived from that shoot suppresses the other shoot growth. Here, this dominance was overcome by application of SL-related inhibitors. Therefore, SL-related inhibitors might be useful as new plant growth regulators to improve the efficiency of plant propagation in vitro.

Endogenous auxin determines the pattern of adventitious shoot formation on internodal segments of ipecac.

MAIN CONCLUSION: Endogenous auxin determines the pattern of adventitious shoot formation. Auxin produced in the dominant shoot is transported to the internodal segment and suppresses growth of other shoots. Adventitious shoot formation is required for the propagation of economically important crops and for the regeneration of transgenic plants. In most plant species, phytohormones are added to culture medium to induce adventitious shoots. In ipecac (Carapichea ipecacuanha (Brot.) L. Andersson), however, adventitious shoots can be formed without phytohormone treatment. Thus, ipecac culture allows us to investigate the effects of endogenous phytohormones during adventitious shoot formation. In phytohormone-free culture, adventitious shoots were formed on the apical region of the internodal segments, and a high concentration of IAA was detected in the basal region. To explore the relationship between endogenous auxin and adventitious shoot formation, we evaluated the effects of auxin transport inhibitors, auxin antagonists, and auxin biosynthesis inhibitors on adventitious shoot formation in ipecac. Auxin antagonists and biosynthesis inhibitors strongly suppressed adventitious shoot formation, which was restored by exogenously applied auxin. Auxin biosynthesis and transport inhibitors significantly decreased the IAA level in the basal region and shifted the positions of adventitious shoot formation from the apical region to the middle region of the segments. These data indicate that auxin determines the positions of the shoots formed on internodal segments of ipecac. Only one of the shoots formed grew vigorously; this phenomenon is similar to apical dominance. When the largest shoot was cut off, other shoots started to grow. Naphthalene-1-acetic acid treatment of the cut surface suppressed shoot growth, indicating that auxin produced in the dominant shoot is transported to the internodal segment and suppresses growth of other shoots.

Attenuation of brain mitochondria oxidative damage by Albizia julibrissin Durazz: neuroprotective and antiemetic effects.

Medicinal plants, as new drugs, are considered for treatment of insomnia, anxiety, depression, confusion, nausea, and vomiting symptoms. The current study aimed to evaluate the neuroprotective and antiemetic effects of Albizia. julibrissin Durazz. flower extract in the chickens. Emesis was induced by copper sulfate and ipecac (60 and 600 mg/kg, orally, respectively) and the methanolic extract (50, 100, and 200 mg/kg) were injected intraperitoneally (i.p.). Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC) content, and catalase activity as biomarkers of oxidative damage were evaluated in the brain mitochondria. All doses of extract showed significant (p < 0.001) antiemetic activity against induced emesis by copper sulfate and ipecac. Brain mitochondria function (by 50, 100, and 200 mg/kg of extract) were increased 48%, 85%, and 90% against emesis induced by ipecac and 32%, 18%, and 24% against emesis induced by copper sulfate, respectively. LPO and PC contents were significantly decreased after the administration of extract in emesis induced by copper sulfate and ipecac. A significant decrease (p < 0.01) of CAT activity was observed in the extract (200 mg/kg) group in emesis induced by copper sulfate in chickens brain mitochondria. The present study suggests that the extract had antiemetic effects against emesis induced by copper sulfate and ipecac in young chickens via peripheral and central mechanisms. Neuroprotective effect of the extract could be due to the increase in bioactive compounds, plasma antioxidants, or direct free radical scavenging that could prevent lipid and protein alteration and impede the formation of oxidative damage.

First aid interventions by laypeople for acute oral poisoning.

BACKGROUND: Oral poisoning is a major cause of mortality and disability worldwide, with estimates of over 100,000 deaths due to unintentional poisoning each year and an overrepresentation of children below five years of age. Any effective intervention that laypeople can apply to limit or delay uptake or to evacuate, dilute or neutralize the poison before professional help arrives may limit toxicity and save lives. OBJECTIVES: To assess the effects of pre-hospital interventions (alone or in combination) for treating acute oral poisoning, available to and feasible for laypeople before the arrival of professional help. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, ISI Web of Science, International Pharmaceutical Abstracts, and three clinical trials registries to 11 May 2017, and we also carried out reference checking and citation searching. SELECTION CRITERIA: We included randomized controlled trials comparing interventions (alone or in combination) that are feasible in a pre-hospital setting for treating acute oral poisoning patients, including but potentially not limited to activated charcoal (AC), emetics, cathartics, diluents, neutralizing agents and body positioning. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed study selection, data collection and assessment. Primary outcomes of this review were incidence of mortality and adverse events, plus incidence and severity of symptoms of poisoning. Secondary outcomes were duration of symptoms of poisoning, drug absorption, and incidence of hospitalization and ICU admission. MAIN RESULTS: We included 24 trials involving 7099 participants. Using the Cochrane 'Risk of bias' tool, we assessed no study as being at low risk of bias for all domains. Many studies were poorly reported, so the risk of selection and detection biases were often unclear. Most studies reported important outcomes incompletely, and we judged them to be at high risk of reporting bias.All but one study enrolled oral poisoning patients in an emergency department; the remaining study was conducted in a pre-hospital setting. Fourteen studies included multiple toxic syndromes or did not specify, while the other studies specifically investigated paracetamol (2 studies), carbamazepine (2 studies), tricyclic antidepressant (2 studies), yellow oleander (2 studies), benzodiazepine (1 study), or toxic berry intoxication (1 study). Eighteen trials investigated the effects of activated charcoal (AC), administered as a single dose (SDAC) or in multiple doses (MDAC), alone or in combination with other first aid interventions (a cathartic) and/or hospital treatments. Six studies investigated syrup of ipecac plus other first aid interventions (SDAC + cathartic) versus ipecac alone. The collected evidence was mostly of low to very low certainty, often downgraded for indirectness, risk of bias or imprecision due to low numbers of events.First aid interventions that limit or delay the absorption of the poison in the bodyWe are uncertain about the effect of SDAC compared to no intervention on the incidence of adverse events in general (zero events in both treatment groups; 1 study, 451 participants) or vomiting specifically (Peto odds ratio (OR) 4.17, 95% confidence interval (CI) 0.30 to 57.26, 1 study, 25 participants), ICU admission (Peto OR 7.77, 95% CI 0.15 to 391.93, 1 study, 451 participants) and clinical deterioration (zero events in both treatment groups; 1 study, 451 participants) in participants with mixed types or paracetamol poisoning, as all evidence for these outcomes was of very low certainty. No studies assessed SDAC for mortality, duration of symptoms, drug absorption or hospitalization.Only one study compared SDAC to syrup of ipecac in participants with mixed types of poisoning, providing very low-certainty evidence. Therefore we are uncertain about the effects on Glasgow Coma Scale scores (mean difference (MD) -0.15, 95% CI -0.43 to 0.13, 1 study, 34 participants) or incidence of adverse events (risk ratio (RR) 1.24, 95% CI 0.26 to 5.83, 1 study, 34 participants). No information was available concerning mortality, duration of symptoms, drug absorption, hospitalization or ICU admission.This review also considered the added value of SDAC or MDAC to hospital interventions, which mostly included gastric lavage. No included studies investigated the use of body positioning in oral poisoning patients.First aid interventions that evacuate the poison from the gastrointestinal tractWe found one study comparing ipecac versus no intervention in toxic berry ingestion in a pre-hospital setting. Low-certainty evidence suggests there may be an increase in the incidence of adverse events, but the study did not report incidence of mortality, incidence or duration of symptoms of poisoning, drug absorption, hospitalization or ICU admission (103 participants).In addition, we also considered the added value of syrup of ipecac to SDAC plus a cathartic and the added value of a cathartic to SDAC.No studies used cathartics as an individual intervention.First aid interventions that neutralize or dilute the poison No included studies investigated the neutralization or dilution of the poison in oral poisoning patients.The review also considered combinations of different first aid interventions. AUTHORS' CONCLUSIONS: The studies included in this review provided mostly low- or very low-certainty evidence about the use of first aid interventions for acute oral poisoning. A key limitation was the fact that only one included study actually took place in a pre-hospital setting, which undermines our confidence in the applicability of these results to this setting. Thus, the amount of evidence collected was insufficient to draw any conclusions.

International Variability in Gastrointestinal Decontamination With Acute Poisonings.

BACKGROUND AND OBJECTIVES: Identifying international differences in the management of acute pediatric poisonings may help improve the quality of care. The objective of this study was to assess the international variation and appropriateness of gastrointestinal decontamination (GID) procedures performed in children and adolescents who present with acute poisonings to emergency departments. METHODS: This was an international, multicenter, cross-sectional prospective study including children <18 years with poisoning exposures presenting to 105 emergency departments in 20 countries from 8 global regions belonging to the Pediatric Emergency Research Networks. Data collection started between January and September 2013 and continued for 1 year. The appropriateness of GID procedures performed was analyzed using the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists' recommendations. Multivariate logistic regression was performed to identify independent risk factors for performing GID procedures. RESULTS: We included 1688 patients, 338 of whom (20.0%, 95% confidence interval 18.1%-22.0%) underwent the following GID procedures: activated charcoal (166, 49.1%), activated charcoal and gastric lavage (122, 36.1%), gastric lavage (47, 13.9%), and ipecac (3, 0.9%). In 155 (45.8%, 40.5%-51.2%), the GID procedure was considered appropriate, with significant differences between regions. Independent risk factors for GID procedures included age, toxin category, mechanism of poisoning, absence of symptoms, and the region where the intoxication occurred (P < .001). CONCLUSIONS: Globally, there are substantial differences in the use and appropriateness of GID procedures in the management of pediatric poisonings. International best practices need to be better implemented.

Caracterização e avaliação morfológica da parte aérea de acessos de Psychotria ipecacuanha (Brot. ) Stokes (IPECA) / Characterization and morphological evaluation of aerial parts of accessions of Psychotria ipecacuanha (Brot. ) Stokes (IPECA)

Introduction: The species Psychotria ipecacuana (Brotero) Stokes, Rubiaceae, commonly known as ipeca, ipecacuanha or poaia, is under threat of genetic erosion and in danger of extinction. Objectives: Identify and evaluate the morphological characters of accessions of Psychotria ipecacuana and identify their descriptors. Methods: A study was conducted of 17 accessions of Psychotria ipecacuana preserved in vivo at EMBRAPA Eastern Amazonia for 19 morphological characters of the aerial parts of the plant, thirteen qualitative and six quantitative. Of this total, twelve were subjected to multivariant analysis. Principal component analysis was used to select the descriptors. Results: Accessions of Psychotria ipecacuana fluctuated for most characters, and seven were qualitative and nonvariable. Two characters were considered redundant and ten were selected as descriptors. Genetic dissimilarity ranged from 0.19 to 0.77 with a mean value of 0.55, and could be separated into two groups with various subgroups and six different groups by the UPGMA and Tocher methods, respectively. The characters plant height and first branch height were the main contributors to the discrepancy between the accessions. Conclusions: Accessions of Psychotria ipecacuana display great morphological variation in the aerial part of the plant, with ten characters selected as descriptors for the species. These data about the species had never been published before, and they constitute the basis for management at the germplasm bank when selecting characters of interest for improvement programs as well as to provide key information facilitating the identification of specimens from natural or planted ecosystems(AU)

Introducción: la especie Psychotria ipecacuana (Brotero) Stokes, Rubiaceae, popularmente conocida como ipeca, ipecacuanha o poaia, se ve amenazada por la erosión genética y en peligro de extinción. Objetivos: identificar y evaluar accesos del Banco Activo de Germoplasma de Psychotria ipecacuana por caracteres morfológicos, e identificar los descriptores. Métodos: se estudiaron 17 accesiones de Psychotria ipecacuana, conservado in vivo en Embrapa Amazonia Oriental, para 19 caracteres morfológicos de la parte aérea de la planta, siendo trece cualitativo y seis cuantitativo. De este total doce fueron sometidos a análisis multivariante. La selección de descriptores se llevó a cabo mediante el análisis de componentes principales. Resultados: los accesos de Psychotria ipecacuana fluctuaron para la mayoría de los caracteres, sendo siete variables cualitativas y no variables. Dos caracteres se consideraron redundante y diez seleccionados como descriptores. La disimilitud genética varió desde 0,19 hasta 0,77 con una media de 0,55 y se dejó separar en dos grupos con diversos subgrupos y seis grupos diferentes por métodos UPGMA y Tocher, respectivamente. Los caracteres altura de las plantas y altura de la primera rama fueron los principales contribuyentes a la discrepancia entre los accesos. Conclusiones: los accesos de Psychotria ipecacuana tienen una amplia variación morfológica de la parte aérea de la planta con diez caracteres fueran considerados descriptores para esta especie. Estos datos son inéditos para la especie y forman la base para la gestión de banco de germoplasma, en la selección de caracteres de interés para los programas de mejoramiento y para proporcionar información clave que facilitará la identificación de especímenes en los ecosistemas naturales o plantados(AU)

Introdução: a espécie Psychotria ipecacuanha (Brotero) Stokes, Rubiaceae, conhecida popularmente como ipeca, ipecacuanha ou poaia, encontra-se ameaçada de erosão genética e em vias de extinção. Objetivos: caracterizar e avaliar acessos do Banco Ativo de Germoplasma de Psychotria ipecacuanha por caracteres morfológicos, e identificar descritores. Métodos: foram estudados 17 acessos de Psychotria ipecacuanha, conservados in vivo na Embrapa Amazônia Oriental para 19 caracteres morfológicos da parte aérea da planta, sendo treze qualitativos e seis quantitativos. Desse total doze foram submetidos às análises multivariadas. A seleção dos descritores foi realizada pela análise de componentes principais. Resultados: os acessos de Psychotria ipecacuanha apresentaram variações para boa parte dos caracteres, sendo sete qualitativos não variáveis. Dois caracteres foram considerados redundantes e dez selecionados como descritores. As dissimilaridades genéticas variaram de 0,19 a 0,77 com média de 0,55 e permitiram separar os acessos em dois com vários subgrupos e seis grupos divergentes pelos métodos UPGMA e de Tocher, respectivamente. Os caracteres Altura da planta e Altura da primeira ramificação foram os que mais contribuíram para a divergência entre os acessos. Conclusões: os acessos de Psychotria ipecacuanha possuem ampla variação morfológica para a parte aérea da planta com dez caracteres sendo considerados descritores para essa espécie. Estas informações são inéditas para a espécie e servirão de base para o manejo do banco de germoplasma, na seleção de indivíduos de interesse dos programas de melhoramento e para fornecer informações fundamentais que facilitarão a identificação de espécimes em ecossistemas nativos ou plantados(AU)

Caracterização e avaliação morfológica da parte aérea de acessos de Psychotria ipecacuanha (Brot. ) Stokes (IPECA) / Caracterización y evaluación morfológica de partes aéreas de accesiones de Psychotria ipecacuanha (Brot. ) Stokes (IPECA) / Characterization and morphological evaluation of aerial parts of accessions of Psychotria ipecacuanha (Brot. ) Stokes (IPECA)

Introduction: The species Psychotria ipecacuana (Brotero) Stokes, Rubiaceae, commonly known as ipeca, ipecacuanha or poaia, is under threat of genetic erosion and in danger of extinction. Objectives: Identify and evaluate the morphological characters of accessions of Psychotria ipecacuana and identify their descriptors. Methods: A study was conducted of 17 accessions of Psychotria ipecacuana preserved in vivo at EMBRAPA Eastern Amazonia for 19 morphological characters of the aerial parts of the plant, thirteen qualitative and six quantitative. Of this total, twelve were subjected to multivariant analysis. Principal component analysis was used to select the descriptors. Results: Accessions of Psychotria ipecacuana fluctuated for most characters, and seven were qualitative and nonvariable. Two characters were considered redundant and ten were selected as descriptors. Genetic dissimilarity ranged from 0.19 to 0.77 with a mean value of 0.55, and could be separated into two groups with various subgroups and six different groups by the UPGMA and Tocher methods, respectively. The characters plant height and first branch height were the main contributors to the discrepancy between the accessions. Conclusions: Accessions of Psychotria ipecacuana display great morphological variation in the aerial part of the plant, with ten characters selected as descriptors for the species. These data about the species had never been published before, and they constitute the basis for management at the germplasm bank when selecting characters of interest for improvement programs as well as to provide key information facilitating the identification of specimens from natural or planted ecosystems(AU)

Introducción: la especie Psychotria ipecacuana (Brotero) Stokes, Rubiaceae, popularmente conocida como ipeca, ipecacuanha o poaia, se ve amenazada por la erosión genética y en peligro de extinción. Objetivos: identificar y evaluar accesos del Banco Activo de Germoplasma de Psychotria ipecacuana por caracteres morfológicos, e identificar los descriptores. Métodos: se estudiaron 17 accesiones de Psychotria ipecacuana, conservado in vivo en Embrapa Amazonia Oriental, para 19 caracteres morfológicos de la parte aérea de la planta, siendo trece cualitativo y seis cuantitativo. De este total doce fueron sometidos a análisis multivariante. La selección de descriptores se llevó a cabo mediante el análisis de componentes principales. Resultados: los accesos de Psychotria ipecacuana fluctuaron para la mayoría de los caracteres, sendo siete variables cualitativas y no variables. Dos caracteres se consideraron redundante y diez seleccionados como descriptores. La disimilitud genética varió desde 0,19 hasta 0,77 con una media de 0,55 y se dejó separar en dos grupos con diversos subgrupos y seis grupos diferentes por métodos UPGMA y Tocher, respectivamente. Los caracteres altura de las plantas y altura de la primera rama fueron los principales contribuyentes a la discrepancia entre los accesos. Conclusiones: los accesos de Psychotria ipecacuana tienen una amplia variación morfológica de la parte aérea de la planta con diez caracteres fueran considerados descriptores para esta especie. Estos datos son inéditos para la especie y forman la base para la gestión de banco de germoplasma, en la selección de caracteres de interés para los programas de mejoramiento y para proporcionar información clave que facilitará la identificación de especímenes en los ecosistemas naturales o plantados(AU)

Introdução: a espécie Psychotria ipecacuanha (Brotero) Stokes, Rubiaceae, conhecida popularmente como ipeca, ipecacuanha ou poaia, encontra-se ameaçada de erosão genética e em vias de extinção. Objetivos: caracterizar e avaliar acessos do Banco Ativo de Germoplasma de Psychotria ipecacuanha por caracteres morfológicos, e identificar descritores. Métodos: foram estudados 17 acessos de Psychotria ipecacuanha, conservados in vivo na Embrapa Amazônia Oriental para 19 caracteres morfológicos da parte aérea da planta, sendo treze qualitativos e seis quantitativos. Desse total doze foram submetidos às análises multivariadas. A seleção dos descritores foi realizada pela análise de componentes principais. Resultados: os acessos de Psychotria ipecacuanha apresentaram variações para boa parte dos caracteres, sendo sete qualitativos não variáveis. Dois caracteres foram considerados redundantes e dez selecionados como descritores. As dissimilaridades genéticas variaram de 0,19 a 0,77 com média de 0,55 e permitiram separar os acessos em dois com vários subgrupos e seis grupos divergentes pelos métodos UPGMA e de Tocher, respectivamente. Os caracteres Altura da planta e Altura da primeira ramificação foram os que mais contribuíram para a divergência entre os acessos. Conclusões: os acessos de Psychotria ipecacuanha possuem ampla variação morfológica para a parte aérea da planta com dez caracteres sendo considerados descritores para essa espécie. Estas informações são inéditas para a espécie e servirão de base para o manejo do banco de germoplasma, na seleção de indivíduos de interesse dos programas de melhoramento e para fornecer informações fundamentais que facilitarão a identificação de espécimes em ecossistemas nativos ou plantados(AU)

hERG Channel Blocking Ipecac Alkaloids Identified by Combined In Silico - In Vitro Screening.

Human ether-a-go-go-related gene channel blocking is associated with QT interval prolongation and increased risk of potentially fatal arrhythmias. As natural products keep increasing in popularity, there is an urgent need for studies assessing human ether-a-go-go-related gene channel-related cardiotoxic risks. We selected 49 plant species based on the results of a pharmacophore-based virtual screening campaign, in parallel with a literature data survey concerning highly consumed herbal medicines with reported cardiac liabilities. Lead-like enhanced extracts were prepared, an initial in vitro screening was performed at 100 µg/mL by voltage clamp on Xenopus oocytes, and five human ether-a-go-go-related gene channel blocking extracts were identified. In accordance to the six virtually predicted alkaloids, the root extract of Carapichea ipecacuanha inhibited human ether-a-go-go-related gene channel currents by 32.5 %. A phytochemical workflow resulted in the isolation and identification of five out of the six virtually predicted alkaloids. All isolates blocked human ether-a-go-go-related gene channel currents to different extents. The major ipecac constituents emetine (1) and cephaeline (2) showed IC50 values of 21.4 and 5.3 µM, respectively, measured by whole-cell patch clamp in HEK293 cells. This is the first report on human ether-a-go-go-related gene channel blockers from C. ipecacuanha. Its roots and rhizomes are used to produce different pharmacopeial ipecac preparations that are mainly used as emetics for poisoning treatment. Our findings raise further questions regarding the safety and over-the-counter appropriateness of these herbal products.

Impact of a working group on gastrointestinal decontamination in Spanish emergency departments.

INTRODUCTION AND OBJECTIVES: The aim of this study is to analyze the impact of the actions carried out by the Intoxications Working Group (IWG) of Spanish Society of Pediatric Emergencies in the management of acute pediatric intoxications in Spain, specifically the publishing of a Handbook in 2004 or the creation of the Toxicologic Surveillance System in 2009. PATIENTS AND METHODS: Gastrointestinal decontamination procedures were analyzed in three periods of time in Pediatric Emergency Departments (PEDs) included in the IWG: group A (2001-2002, 17 PED, 2157 episodes), group B (2008-2009, 22 PED, 612 episodes), and group C (2009-2011, 42 PED, 400 episodes). These periods were chosen because the main actions of the IWG were developed in the time in-between them. RESULTS: Of the 3169 episodes included, a gastrointestinal decontamination procedure was performed in 1031. The use of ipecac syrup decreased from 22.8% in group A to 0 in group C and the performance of a gastric lavage decreased from 29.1% in group A to 26% in group C (NS), although on splitting yearly patients of group C, it decreased to 14.7% in 2011. CONCLUSION: Recommendations developed and spread by a Working Group have approached the management of acute pediatric intoxications in Spain to international guidelines on the basis of scientific evidence.

Position paper update: ipecac syrup for gastrointestinal decontamination.

CONTEXT: An update of the first position paper on ipecac syrup from 1997 was published by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists in 2004. The aims of this paper are to briefly summarize the content of the 2004 Position Paper and to present any new data. METHODS: A systematic review of the literature from the year 2003 forward. RESULTS: The literature search yielded a limited number of meaningful articles, and there remains no convincing evidence from clinical studies that ipecac improves the outcome of poisoned patients. Furthermore, the availability of ipecac is rapidly diminishing. CONCLUSIONS: The routine administration of ipecac at the site of ingestion or in the emergency department should definitely be avoided. Ipecac may delay the administration or reduce the effectiveness of activated charcoal, oral antidotes, and whole bowel irrigation. There is not sufficient evidence to warrant any change in the previous ipecac position papers. There are, however, insufficient data to support or exclude ipecac administration soon after ingestion of some specific poisons in rare situations.