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1.
Sci Total Environ ; 736: 139515, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32485372

RESUMO

Toxic cyanobacteria are a concern worldwide because they can adversely affect humans, animals, and ecosystems. However, neurotoxins produced by freshwater cyanobacteria are understudied relative to microcystin. Thus, the objective of this critical review was to provide a comprehensive examination of the modes of action, production, fate, and occurrence of the freshwater neurotoxins anatoxin-a and saxitoxin as they relate to human, animal, and ecosystem health. Literature on freshwater anatoxin-a and saxitoxin was obtained and reviewed for both laboratory and field studies. Current (2020) research identifies as many as 41 anatoxin-a producing species and 15 saxitoxin-producing species of freshwater cyanobacteria. Field studies indicate that anatoxin-a and saxitoxin have widespread distribution, and examples are given from every continent except Antarctica. Human and animal health concerns can range from acute to chronic. However, few researchers studied chronic or sublethal effects of freshwater exposures to anatoxin-a or saxitoxin. Ecosystem health also is a concern, as the effects of toxicity may be far reaching and include consequences throughout the food web. Several gaps in knowledge were identified for anatoxin-a and saxitoxin, including triggers of production and release, environmental fate and degradation, primary and secondary exposure routes, diel variation, food web effects, effects of cyanotoxin mixtures, and sublethal health effects on individual organisms and populations. Despite the gaps, this critical review facilitates our current understanding of freshwater neurotoxins and thus can serve to `` guide future research on anatoxin-a, saxitoxin, and other cyanotoxins.


Assuntos
Toxinas Bacterianas , Saxitoxina , Animais , Regiões Antárticas , Ecossistema , Água Doce , Humanos , Microcistinas , Neurotoxinas , Tropanos
2.
Artigo em Inglês | MEDLINE | ID: mdl-32361630

RESUMO

Ibotenic acid (IBA) is an amino acid and muscimol (MUS) is the decarboxyl derivative of IBA. They are mushroom neurotoxins with high polarity and low molecular weight. Only one transition (159->113 for IBA and 115->98 for MUS) can be found when directly measured by high performance liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS). Therefore, the identification and quantification of trace amount of the toxins in biomaterial are difficult. A highly sensitive and accurate analytical method for IBA and MUS in plasma was developed by LC-MS/MS with the application of bimolecular dansylation and internal standard calibration. Acetonitrile was used for protein precipitation and for toxin extraction from plasma. The toxins and internal standards (L-tyrosine-13C9,15N for IBA and tyramine-d4 for MUS) were derivatized with dansyl chloride (DNSCl). The reaction conditions of the bimolecular dansylation were optimized and the fragmentation pathways of the derivatives in MS/MS were studied. Method validation was carried out according to the Bioanalytical Method Validation Guidance for Industry (FDA, USA, 2018). The limits of detection for IBA and MUS in plasma were 0.3 ng mL-1 and 0.1 ng mL-1, respectively. The linear ranges in plasma were 1-500 ng mL-1 and 1-200 ng mL-1 with the correlation coefficients of 0.998 and 0.999 for IBA and MUS, respectively. The recoveries at three spiked levels were 90.7-111.4% with relative standard deviations (RSDs) of 6.4-10.3% for IBA and the results were 85.1-94.2% with RSDs of 5.0-8.9% for MUS. The toxin levels in patients' plasma samples under different poisoning degree were presented.


Assuntos
Agaricales/química , Ácido Ibotênico/sangue , Muscimol/sangue , Neurotoxinas/sangue , Espectrometria de Massas em Tandem/métodos , Acetonitrilos/química , Cromatografia Líquida de Alta Pressão , Compostos de Dansil/química , Humanos , Limite de Detecção , Padrões de Referência , Reprodutibilidade dos Testes
3.
Aquat Toxicol ; 222: 105422, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32112996

RESUMO

The proliferations of cyanobacteria are increasingly prevalent in many rivers and water bodies due especially to eutrophication. This work aims to study in female medaka fish the toxicity, the transfer and the depuration of the anatoxin-a, a neurotoxin produced by benthic cyanobacterial biofilms. This work will provide answers regarding acute toxicity induced by single gavage by anatoxin-a and to the risks of exposure by ingestion of contaminated fish flesh, considering that data on these aspects remain particularly limited. The oral LD50 and NOAEL of a single dose of (±)-anatoxin-a were determined at 11.50 and 6.67 µg.g-1, respectively. Subsequently, the toxico-kinetics of the (±)-anatoxin-a was observed in the guts, the livers and the muscles of female medaka fish for 10 days. Anatoxin-a was quantified by high-resolution qTOF mass spectrometry coupled upstream to a UHPLC chromatographic chain. The toxin could not be detected in the liver after 12 h, and in the gut and muscle after 3 days. Overall, the medaka fish do not appear to accumulate (±)-anatoxin-a and to largely recover after 24 h following a single sub-acute oral liquid exposure at the NOAEL.


Assuntos
Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Oryzias/metabolismo , Tropanos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cianobactérias/metabolismo , Eutrofização , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Dose Letal Mediana , Fígado/efeitos dos fármacos , Fígado/metabolismo , Toxinas Marinhas/metabolismo , Modelos Teóricos , Músculos/efeitos dos fármacos , Músculos/metabolismo , Neurotoxinas/metabolismo , Nível de Efeito Adverso não Observado , Rios/química , Toxicocinética , Tropanos/metabolismo , Poluentes Químicos da Água/metabolismo
4.
PLoS Negl Trop Dis ; 14(3): e0008060, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163415

RESUMO

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.


Assuntos
Morte Celular/efeitos dos fármacos , Microcefalia/patologia , Envenenamento/complicações , Envenenamento/patologia , Saxitoxina/toxicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/patologia , Animais , Toxinas Bacterianas/análise , Toxinas Bacterianas/toxicidade , Encéfalo/patologia , Brasil/epidemiologia , Células Cultivadas , Modelos Animais de Doenças , Surtos de Doenças , Feminino , Humanos , Incidência , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Camundongos Endogâmicos C57BL , Microcistinas/análise , Microcistinas/toxicidade , Modelos Teóricos , Neurotoxinas/análise , Neurotoxinas/toxicidade , Saxitoxina/análise , Água/química
5.
Toxicol Lett ; 326: 31-51, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32145396

RESUMO

Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person's quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the association between pesticide exposure, cognition and dementia. Additionally, we present potential mechanisms through which pesticides may act neurotoxically and lead to neurodegeneration. Study designs rarely presented homogeneity and the estimation of the exposure to pesticides has been most frequently performed without measuring the synergic effects and the possible interactions between the toxicants within mixtures, and also overlooking low exposures to environmental toxicants. It is possible that a Real-Life Risk Simulation approach would represent a robust alternative for future studies, so that the safe exposure limits and the net risk that pesticides confer to impaired cognitive function can be examined. Previous studies that evaluated the effect of low dose chronic exposure to mixtures of pesticides and other chemicals intending to simulate real life exposure scenarios showed that hormetic neurobehavioral effects can appear after mixture exposure at doses considered safe for individual compounds and these effects can be exacerbated by a coexistence with specific conditions such as vitamin deficiency. However, there is an overall indication, derived from both epidemiologic and laboratory evidence, supporting an association between exposure to neurotoxic pesticides and cognitive dysfunction, dementia and Alzheimer's disease.


Assuntos
Doença de Alzheimer/induzido quimicamente , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Exposição Ambiental/efeitos adversos , Neurotoxinas/toxicidade , Praguicidas/toxicidade , Animais , Feminino , Humanos , Masculino , Modelos Animais , Medição de Risco/métodos
6.
Aquat Toxicol ; 221: 105425, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32058875

RESUMO

Neurotoxin ß-N-methylamino-L-alanine (BMAA) has been widely detected in diverse aquatic organisms and hypothesized as an environmental risk to neurodegenerative diseases in humans. However, the knowledge of its toxicity to marine organisms requires attention. In the present study, embryos and sperm of the sea urchin, Lytechinus pictus, were used to assess the toxicity of BMAA. Effects of BMAA on fertilization and development of sea urchin embryos were measured, and its impacts on efflux transport of sea urchin blastula were also assayed. Results demonstrated that the fertilization and development of embryos were significantly inhibited by high concentrations of BMAA above 300 µg L-1. The EC50 values indicated by active swimming larvae and total larvae numbers at 96 HPF (hours post fertilization) were 165 µg L-1 (1.4 µmol L-1) and 329 µg L-1 (2.8 µmol L-1), respectively. Additionally, sperm exposed to BMAA for 10 min significantly reduced the fertilization ratio of sea urchin eggs. However, the ABC transport activity on the cytomembrane of sea urchin blastula was not inhibited by the presence of BMAA at 50 µg L-1, even up to 500 µg L-1. Abnormal division and developmental malformations occurred at different developmental stages for sea urchin embryos exposed to BMAA at 500 µg L-1. The inhibitory effects of BMAA on sea urchin embryos were reported at the first time in this study, for which the toxicological mechanisms will be explored in future studies.


Assuntos
Diamino Aminoácidos/toxicidade , Organismos Aquáticos/efeitos dos fármacos , Fertilização/efeitos dos fármacos , Lytechinus/efeitos dos fármacos , Neurotoxinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Organismos Aquáticos/crescimento & desenvolvimento , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Humanos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Lytechinus/crescimento & desenvolvimento , Masculino , Espermatozoides/efeitos dos fármacos
7.
Mol Immunol ; 119: 144-153, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32023500

RESUMO

Crotoxin (Ctx) is the main lethal component of Crotalus durissus terrificus venom. It is a neurotoxin, composed of two subunits associated by noncovalent interactions, the non-toxic acid subunit (CA), named Crotapotin, and the basic subunit (CB), with phospholipase A2 (PLA2) activity. Employing the SPOT synthesis technique, we determined two epitopes located in the C-terminal of each Ctx subunit. In addition, 3 other epitopes were mapped in different regions of Ctx using subcutaneous spot implants surgically inserted in mice. All epitopes mapped here were expressed together as recombinant multi-epitopic protein (rMEPCtx), which was used to immunize New Zealand rabbits. Anti-rMEPCtx rabbit serum cross-reacted with Ctx and crude venoms from C. d. terrificus, Crotalus durissus ruruima, Peruvian C. durissus and Bothrops jararaca (with lower intensity). Furthermore, anti-rMEPCtx serum was able to neutralize Ctx lethal activity. As the recombinant multiepitopic protein is not toxic, it can be administered in larger doses without causing adverse effects on the immunized animals health. Therefore, our work evidences the identification of neutralizing epitopes of Ctx and support the use of recombinant multiepitopic proteins as an innovation to immunotherapeutics production.


Assuntos
Anticorpos Neutralizantes/imunologia , Crotoxina/imunologia , Neurotoxinas/imunologia , Animais , Anticorpos Neutralizantes/biossíntese , Antivenenos/genética , Antivenenos/imunologia , Crotoxina/química , Crotoxina/genética , Mapeamento de Epitopos , Epitopos/genética , Epitopos/imunologia , Feminino , Camundongos , Modelos Moleculares , Neurotoxinas/química , Neurotoxinas/genética , Engenharia de Proteínas , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia
8.
Mar Drugs ; 18(2)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32033403

RESUMO

Saxitoxin is an alkaloid neurotoxin originally isolated from the clam Saxidomus giganteus in 1957. This group of neurotoxins is produced by several species of freshwater cyanobacteria and marine dinoflagellates. The saxitoxin biosynthesis pathway was described for the first time in the 1980s and, since then, it was studied in more than seven cyanobacterial genera, comprising 26 genes that form a cluster ranging from 25.7 kb to 35 kb in sequence length. Due to the complexity of the genomic landscape, saxitoxin biosynthesis in dinoflagellates remains unknown. In order to reveal and understand the dynamics of the activity in such impressive unicellular organisms with a complex genome, a strategy that can carefully engage them in a systems view is necessary. Advances in omics technology (the collective tools of biological sciences) facilitated high-throughput studies of the genome, transcriptome, proteome, and metabolome of dinoflagellates. The omics approach was utilized to address saxitoxin-producing dinoflagellates in response to environmental stresses to improve understanding of dinoflagellates gene-environment interactions. Therefore, in this review, the progress in understanding dinoflagellate saxitoxin biosynthesis using an omics approach is emphasized. Further potential applications of metabolomics and genomics to unravel novel insights into saxitoxin biosynthesis in dinoflagellates are also reviewed.


Assuntos
Dinoflagelados/genética , Dinoflagelados/metabolismo , Saxitoxina/biossíntese , Saxitoxina/química , Vias Biossintéticas , Cianobactérias/metabolismo , Genômica , Metabolômica , Neurotoxinas/metabolismo , Biossíntese de Proteínas , Proteômica , Saxitoxina/metabolismo , Transcriptoma
9.
Toxicon ; 178: 20-32, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32094099

RESUMO

Botulinum neurotoxins (BoNTs) are highly potent toxins responsible for a severe disease, called botulism. They are also efficient therapeutic tools with an increasing number of indications ranging from neuromuscular dysfunction to hypersecretion syndrome, pain release, depression as well as cosmetic application. BoNTs are known to mainly target the motor-neurons terminals and to induce flaccid paralysis. BoNTs recognize a specific double receptor on neuronal cells consisting of gangliosides and synaptic vesicle protein, SV2 or synaptotagmin. Using cultured neuronal cells, BoNTs have been established blocking the release of a wide variety of neurotransmitters. However, BoNTs are more potent in motor-neurons than in the other neuronal cell types. In in vivo models, BoNT/A impairs the cholinergic neuronal transmission at the motor-neurons but also at neurons controlling secretions and smooth muscle neurons, and blocks several neuronal pathways including excitatory, inhibitory, and sensitive neurons. However, only a few reports investigated the neuronal selectivity of BoNTs in vivo. In the intestinal wall, BoNT/A and BoNT/B target mainly the cholinergic neurons and to a lower extent the other non-cholinergic neurons including serotonergic, glutamatergic, GABAergic, and VIP-neurons. The in vivo effects induced by BoNTs on the non-cholinergic neurons remain to be precisely investigated. We report here a literature review of the neuronal selectivity of BoNTs.


Assuntos
Toxinas Botulínicas , Neurotoxinas , Animais , Toxinas Botulínicas Tipo A , Botulismo , Células Cultivadas , Endocitose , Gangliosídeos , Humanos , Neurônios Motores , Neurotransmissores , Transmissão Sináptica , Vesículas Sinápticas/metabolismo
10.
Plast Reconstr Surg ; 145(3): 629e-636e, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32097334

RESUMO

Pain is an unpleasant experience resulting from either tissue damage or insults to the somatosensory system. Approaches to pain management evolve as we better understand both pain pathways and the tools available to interrupt these. The interest surrounding botulinum neurotoxin as a chemodenervating agent has expanded to include its potential applications in painful pathologies, both within and beyond the confines of plastic surgery. In this article, the authors discuss botulinum neurotoxin's mechanism of action as it pertains to both muscular paralysis and its interplay in the modulation of proinflammatory pain mediators. In addition, the authors review evidence supporting the use of botulinum neurotoxin in common painful conditions, in order to prepare the readership to aptly provide their patients with evidence-based recommendations. After reading this article, the participant should be able to discuss both mechanism of action and common applications of botulinum neurotoxin in painful conditions.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Neurotoxinas/farmacologia , Nociceptividade/efeitos dos fármacos , Manejo da Dor/métodos , Dor/fisiopatologia , Toxinas Botulínicas Tipo A/uso terapêutico , Medicina Baseada em Evidências/métodos , Humanos , Neurotoxinas/uso terapêutico , Nociceptividade/fisiologia
11.
World Neurosurg ; 136: 7-11, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31917316

RESUMO

BACKGROUND: Cavernous angiomas (CAs) are vascular malformations that may result in stroke. CASE DESCRIPTION: Herein, we evaluate a CA patient with chronic migraine who experienced 2 documented symptomatic hemorrhages after receiving respective high doses of botulinum toxin (Btx). CONCLUSIONS: Recently, bacterial lipopolysaccharide has been reported to contribute to CA development through Toll-like receptor signaling, causing hemorrhagic angiogenic proliferation. Lipopolysaccharide and Btx share a common intracellular signaling pathway driving CA development and hemorrhage. Significance of these observations is demonstrated by previous works on plasma molecules showing prognostic associations with symptomatic hemorrhages in human CA, related to the same canonical pathways. Authors suggest careful tracking of the association of Btx and hemorrhage in CA patients.


Assuntos
Toxinas Botulínicas Tipo A/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Hemangioma Cavernoso/tratamento farmacológico , Hemorragias Intracranianas/etiologia , Neurotoxinas/efeitos adversos , Adulto , Toxinas Botulínicas Tipo A/administração & dosagem , Dor Crônica , Feminino , Humanos , MAP Quinase Quinase Quinase 3/metabolismo , Angiografia por Ressonância Magnética , Transtornos de Enxaqueca/etiologia , Neurotoxinas/administração & dosagem , Receptores Toll-Like/metabolismo
12.
Food Chem Toxicol ; 136: 110942, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705926

RESUMO

An imbalance in mitochondrial dynamics is strongly associated with Parkinson's disease. The fusion protein optic atrophy 1 (OPA1) is up-regulated through the activation of parkin-mediated IκB kinase γ (IKKγ)/p65 signaling. This study investigated whether the neuroprotection of carnosic acid (CA) from rosemary is involved in mitochondrial dynamics and OPA1 protein induction by parkin/IKKγ/p65 signaling. The neurotoxin 6-hydroxydopamine (6-OHDA) treated with SH-SY5Y cells decreased OPA1 and mitofusin 2 fusion proteins, but increased fission 1 and dynamin related protein 1 (DRP1) fission proteins. By immunofluorescence, 6-OHDA induced the fluorescence of green spots outside the mitochondria, indicating that cytochrome c was released to the cytoplasm. Except for the effects on DRP1 protein, CA pretreatment reversed these effects of 6-OHDA. Additionally, CA treatment increased the ubiquitination of IKKγ, nuclear p65 protein, OPA1-p65 DNA binding activity, and OPA1 protein. However, transfection of parkin small interfering RNA (siRNA) attenuated these effects of CA. Furthermore, transfection of OPA1 siRNA abolished the action of CA to reverse 6-OHDA-increased cytosolic cytochrome c protein, apoptotic-related protein cleavage, and cell death. In conclusion, the mechanism by which CA counteracts the toxicity of 6-OHDA is through modulation of mitochondrial dynamics and upregulation of OPA1 via activation of the parkin/IKKγ/p65 pathway.


Assuntos
Abietanos/farmacologia , GTP Fosfo-Hidrolases/metabolismo , Quinase I-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Ubiquitina-Proteína Ligases/metabolismo , Apoptose/efeitos dos fármacos , Sequência de Bases , Linhagem Celular Tumoral , Humanos , Quinase I-kappa B/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Neurotoxinas/toxicidade , Oxidopamina/toxicidade , Fator de Transcrição RelA/metabolismo , Ubiquitinação/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
13.
Chem Biol Interact ; 315: 108884, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31678113

RESUMO

Quinolinic acid (QA) known as a neuro-active metabolite associated with the kynurenine pathway. At high concentrations, QA is often involved in the initiation and development of several human neurologic diseases, like Alzheimer's disease. Because of the QA action as the NMDA receptor, it is considered as a potent excitotoxin in vivo. Since it is probable that different mechanisms are employed by QA, activation of NMDA receptors cannot fully explain the revealed toxicity and it is even believed that there are multiple unknown mechanisms/targets leading to QA cytotoxicity. Herein we report accelerated amyloid oligomerization of 1N4R Tau under the effect of QA, in vitro, then the molecular structure, morphology and toxicity of the protein aggregate were documented by using various theoretical/experimental approaches. The possible mechanism of action of QA-induced Tau oligomerization has also been explored.


Assuntos
Amiloide/metabolismo , Neurotoxinas/efeitos adversos , Agregados Proteicos/efeitos dos fármacos , Piridinas/efeitos adversos , Ácido Quinolínico/efeitos adversos , Doença de Alzheimer/metabolismo , Humanos , Cinurenina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
14.
Water Res ; 170: 115335, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31812811

RESUMO

Diverse taxa of cyanobacteria, dinoflagellates and diatoms produce ß-N-methylamino-l-alanine (BMAA), a non-lipophilic, non-protein amino acid. BMAA is a neurotoxin in mammals. Its ingestion may be linked to human neurodegenerative diseases, namely the Amyotrophic lateral sclerosis/Parkinsonism dementia complex, based on epidemiological evidence from regions where cyanobacterial harmful algal blooms occur frequently. In controlled environments, cyanobacteria produce BMAA in response to ecophysiological cues such as nutrient availability, which may explain the elevated BMAA concentrations in freshwater environments that receive nutrient-rich agricultural runoff. This critical review paper summarizes what is known about how BMAA supports ecophysiological functions like nitrogen metabolism, photosyntheis and provides a competitive advantage to cyanobacteria in controlled and natural environments. We explain how BMAA production affected competitive interactions among the N2-fixing and non-N2-fixing populations in a freshwater cyanobacterial bloom that was stimulated by nutrient loading from the surrounding agricultural landscape. Better control of nutrients in agricultural fields is an excellent strategy to avoid the negative environmental consequences and public health concerns related to BMAA production.


Assuntos
Diamino Aminoácidos , Saúde Pública , Animais , Humanos , Neurotoxinas , Nutrientes
15.
Sci Total Environ ; 703: 135513, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31761374

RESUMO

ß-N-Methylamino-l-alanine (BMAA), a new cyanobacterial toxin, is found in different aquatic ecosystems worldwide and is to threaten the human nervous system. Therefore, it is important for water plants to develop feasible methods to counter the effects of BMAA. In this study, the removal of BMAA by chlorine, as well as its intermediate products, at different pH values and the mechanism of pH on the removal BMAA were investigated. The results showed that the chlorination of BMAA is in accordance with the second-order kinetics model. The reaction rate of chlorinated BMAA increased with the increase in the concentration of chlorine. The pH of the solution significantly affected the reaction rate. The apparent kinetic constant (kapp) decreased from 6.00 × 103 M-1·min-1 to 35.5 M-1·min-1 when the pH increased from 4.5 to 9 in the chlorine concentration of 32.23 µM. It is probable that the species distribution and proportion of BMAA and chlorine at different pH values were the main causes of this phenomenon. Additionally, the chlorination reaction consisted of four elementary reactions and hydrogen ions were beneficial to the reaction. The temperature also affected the reaction rate and the activation energy of the reaction was 16.6 ± 1.99 kJ·M-1. A variety of degradation products were detected and the path of degradation was speculated. Chlorination, dechlorination, and decarboxylation were the main processes of oxidative degradation. Furthermore, the composition of the degradation products was the same at different pH values.


Assuntos
Diamino Aminoácidos/química , Cloro/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Diamino Aminoácidos/análise , Halogenação , Neurotoxinas/química , Poluentes Químicos da Água/análise
16.
Toxicon ; 173: 39-47, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31734252

RESUMO

Neurotoxin ß-N-methylamino-L-alanine (BMAA) has been widely detected in diverse aquatic organisms within different ecosystem trophic levels in recent years. It was the goal of this study to investigate the accumulation and tissue distribution of BMAA in marine opossum shrimp (Neomysis awatschensis) and freshwater zebrafish (Danio rerio) in exposure experiments. A T-maze test was tentatively adopted to assess the effects of BMAA on the learning and memory ability of zebrafish. Interestingly, N. awatschensis was testified to be capable of accumulating free soluble BMAA from bathing seawater through a biological filtration pathway (max. 110.6 µg g-1 wet weight). BMAA was transferred quickly from viscus to muscle and head tissues of zebrafish after intraperitoneal administration of 16.3 µg BMAA per individual twice in two weeks. BMAA accumulated mainly as the total soluble form in both experimental organisms. Results do not support the hypothesis that free BMAA molecules can be largely incorporated into protein in aquatic animals. Behavior of zebrafish in the T-maze test demonstrated that the short-term learning and memory ability was negatively impacted to some degree after three-days exposure to BMAA. Moreover, on Day 3, certain individual zebrafish exhibited freezing and loitering behavior. However, further investigation will be required to discern the long-term effects of BMAA on animals in order to evaluate the risk of BMAA exposure to human health.


Assuntos
Diamino Aminoácidos/toxicidade , Comportamento Animal/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/toxicidade , Peixe-Zebra/fisiologia , Animais , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Neurotoxinas/toxicidade , Poluentes Químicos da Água/toxicidade
17.
Chemosphere ; 243: 125355, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31759214

RESUMO

Cyanobacteria produce a series of secondary metabolites, one of which is beta-N-methylamino-l-alanine (BMAA). BMAA is considered to be the cause of human neurodegeneration. Compared with other cyanotoxins, the role of BMAA in cyanobacteria remains unclear. To investigate this question, six strains of cyanobacteria were cultured and tested in this experiment with an optimized and validated BMAA determination method. The results show that four strains can produce BMAA. The effects of nutrient levels on the production of BMAA by Anabaena sp. FACHB-418 were studied by changing the initial concentrations of nitrate (NaNO3) and phosphate (K2HPO4) in mediums. Bound BMAA was detected in all samples and the concentrations were within 50-100 ng/g. Free BMAA was presence when the concentration of nitrogen was lower than 1.7 mg/L (121.43 µM). Free BMAA was released from the dead and ruptured cells during the cell decline period, so dissolved BMAA cannot be detectable in the adaptation and logarithmic periods, but could be abundant in the decline periods. Statistical analyses show that free BMAA concentrations were negatively correlated with nitrogen strongly (p = 2.334 × 10-10 and r = -0.842), but positively correlated with phosphorus weakly (p = 0.016 and r = 0.405). Moreover, the results of culture experiments indicated that exogenous BMAA could inhibit the growth of cyanobacteria that cannot produce BMAA, and the effect was enhanced as the concentration of exogenous BMAA increased. This phenomenon implies that the production of BMAA may be the stress response by some cyanobacteria to low nitrogen conditions to kill other cyanobacteria, i.e., their competitors.


Assuntos
Diamino Aminoácidos/metabolismo , Cianobactérias/metabolismo , Neurotoxinas/metabolismo , Anabaena/efeitos dos fármacos , Nitratos/metabolismo , Nitrogênio/metabolismo
18.
J Urol ; 203(4): 767-772, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31738115

RESUMO

PURPOSE: The use of onabotulinum toxin A to chemically denervate the testis has been studied as a minimally invasive therapy to treat chronic scrotal pain. To our knowledge no randomized, controlled trials of onabotulinum toxin A for chronic scrotal pain management have been reported to date. MATERIALS AND METHODS: In this double-blind, randomized, controlled trial men with chronic scrotal pain who achieved at least temporary pain relief following a cord block with local anesthesia were randomly assigned to a block using local anesthesia alone vs local anesthesia plus 200 IU onabotulinum toxin A. Standardized assessments of pain levels using a visual analogue score, disease impact, quality of life and mood were performed 1, 2, 3, 4, 12 and 18 weeks after injection. The study primary outcome was the change in the visual analogue score at 1 month. After study completion the men in the control group were given the option to receive onabotulinum toxin A as part of an open label trial. RESULTS: Of 64 men with a mean ± SD age of 45.9 ± 11 years and a mean 5.7 ± 5.7-year history of pain 32 received local anesthesia plus onabotulinum toxin A and 32 received local anesthesia alone. There was no statistically significant difference in any measured outcome when comparing those who received onabotulinum toxin A to controls. Nine of the 13 men (69.2%) in the open label trial achieved an improvement in the visual analogue score (mean group score 6.1 ± 1.66 to 4.5 ± 2.36, Student t-test p=0.022) with a reduction in persistent pain at 3 months in 6 of the 9 (66.7%). CONCLUSIONS: This randomized, double-blind, controlled trial showed no superiority of onabotulinum toxin A plus local anesthesia over local anesthesia alone for pain control in men with chronic scrotal pain. Interestingly, significant pain improvement was noted in our open label onabotulinum toxin A trial, suggesting a potential placebo effect.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Dor Crônica/terapia , Bloqueio Nervoso/métodos , Neurotoxinas/administração & dosagem , Manejo da Dor/métodos , Doenças Testiculares/terapia , Adulto , Dor Crônica/diagnóstico , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Doenças Testiculares/diagnóstico , Testículo/inervação , Resultado do Tratamento
19.
Am J Phys Med Rehabil ; 99(1): e7-e10, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31850946

RESUMO

Although accurate targeting of the causative muscles is of paramount importance in the treatment of focal dystonia, this is often challenging because of distortion of the affected anatomical structures and difficulty in proper positioning of injections. We report a case of idiopathic cervical dystonia that was treated by computed tomography-guided injection of botulinum toxin into multiple deep muscles. Based on clinical presentation of combined torticollis and retrocollis, and needle electromyography results, botulinum toxin was injected under electromyography guidance. This treatment resulted in no improvement. Subsequently, target muscles were identified using F-fludeoxyglucose fusion positron emission tomography/computed tomography. botulinum toxin was injected into the hypermetabolic muscles guided by computed tomography. This injection successfully relieved the symptoms, and nine months of follow-up using positron emission tomography/computed tomography confirmed that hypermetabolic muscles had been normalized. This case indicated that computed tomography guidance may facilitate accurate targeting of botulinum toxin injection. To the authors' knowledge, this is the first case reporting a positive effect of botulinum toxin on cervical dystonia symptoms that lasted 9 mos, confirmed by follow-up positron emission tomography/computed tomography.


Assuntos
Toxinas Botulínicas/administração & dosagem , Neurotoxinas/administração & dosagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Torcicolo/diagnóstico por imagem , Torcicolo/tratamento farmacológico , Adulto , Eletromiografia/métodos , Fluordesoxiglucose F18 , Seguimentos , Humanos , Injeções Intramusculares/métodos , Masculino , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Phys Med Rehabil Clin N Am ; 31(1): 57-68, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31760994

RESUMO

Identifying the subtypes of hypertonia is becoming increasingly important. Treatment strategies, including tone-modulating surgical interventions, medication type and dosing, and chemodenervation, may differ depending on the type of hypertonia present. It is important to delineate how hypertonia interferes with function and quality of life so that the appropriate intervention can be selected at the right time. Outcomes of treatment depend heavily on clear communication of goals. Botulinum toxin should not be used in isolation but as an adjunct to rehabilitation modalities.


Assuntos
Paralisia Cerebral/tratamento farmacológico , Distonia/tratamento farmacológico , Hipertonia Muscular/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Toxinas Botulínicas/administração & dosagem , Humanos , Injeções Intramusculares , Maconha Medicinal/uso terapêutico , Neurotoxinas/administração & dosagem , Qualidade de Vida
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