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Tetrodotoxin

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https://www.readbyqxmd.com/read/28714912/urinary-excretion-of-tetrodotoxin-modeled-in-a-porcine-renal-proximal-tubule-epithelial-cell-line-llc-pk%C3%A2
#1
Takuya Matsumoto, Yui Ishizaki, Keika Mochizuki, Mitsuru Aoyagi, Yoshiharu Mitoma, Shoichiro Ishizaki, Yuji Nagashima
This study examined the urinary excretion of tetrodotoxin (TTX) modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK₁. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA), l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH), and unaffected by 1-methyl-4-phenylpyridinium (MPP+), oxaliplatin, and cefalexin...
July 17, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28710688/death-by-food
#2
Roger W Byard
Although death from food is not an uncommon finding in forensic facilities worldwide, the range of underlying lethal mechanisms and associated conditions that should be sought at the time of autopsy is quite disparate. Deaths may occur from i) infectious agents including bacteria, viruses, protozoa, cestodes, nematodes and prions; ii) natural toxins including amanita toxins, tetrodotoxin, ciguatera and scombroid; iii) anaphylaxis; iv) poisoning; v) mechanical issues around airway and gut obstruction and/or perforation; and vi) miscellaneous causes...
July 15, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28695626/mucosal-glucagon-like-peptide-1-glp-1-responses-are-mediated-by-calcitonin-gene-related-peptide-cgrp-in-the-mouse-colon-and-both-peptide-responses-are-area-specific
#3
I R Tough, R Moodaley, H M Cox
BACKGROUND: Glucagon-like peptide (GLP)-1 is an incretin hormone and its mimetics are proven antidiabetic and antiobesity drugs. GLP-1 exerts antimotility and mucosal proliferative activities but its epithelial ion transport effects are uncharacterized and these may contribute to the gastrointestinal (GI) disturbance, i.e., diarrhea experienced with some GLP-1 mimetics. Our aim was to establish GLP-1 agonist mechanisms and identify potential mucosal mediator(s) in the colonic tissue from C57BL/6J mice...
July 11, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28679669/a-small-molecule-trkb-ligand-restores-hippocampal-synaptic-plasticity-and-object-location-memory-in-rett-syndrome-mice
#4
Wei Li, Alba Bellot-Saez, Mary L Phillips, Tao Yang, Frank M Longo, Lucas Pozzo-Miller
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (MECP2), a transcriptional regulator of many genes, including brain-derived neurotrophic factor (BDNF). BDNF levels are reduced in RTT autopsy brains and in multiple brain areas of Mecp2-deficient mice. Furthermore, experimental interventions that increase BDNF levels improve RTT-like phenotypes in Mecp2 mutant mice. Here, we characterized the actions of a small-molecule ligand of the BDNF receptor TrkB in hippocampal function in Mecp2 mutant mice...
July 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28671709/transient-receptor-potential-a1-trpa1-agonists-inhibit-contractions-of-the-isolated-human-ureter
#5
Philipp Weinhold, Martin Hennenberg, Frank Strittmatter, Christian G Stief, Christian Gratzke, Petter Hedlund
AIMS: Mechanoafferent and peristaltic mechanisms of the human ureter involve transient receptor potential V1 (TRPV1)- and purinoceptor-mediated functions. Hydrogen sulphide, an endogenous TRPA1 ligand, is linked to inhibitory neurotransmission of the pig ureter. No information is available on TRPA1 activity in the human ureter. We therefore examined the distribution and function of TRPA1 in the human ureter. METHODS: Expression of TRPA1 in human ureter tissue was studied by Western blot and immunofluorescence...
July 3, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28659731/modulatory-effect-of-intestinal-polyamines-and-trace-amines-on-the-spontaneous-phasic-contractions-of-the-isolated-ileum-and-colon-rings-of-mice
#6
Manuel Sánchez, Lorena Suárez, María Teresa Andrés, Blanca Henar Flórez, Javier Bordallo, Sabino Riestra, Begoña Cantabrana
Background: Gastrointestinal motility modulatory factors include substances of the intestinal content, such as polyamines and trace amines (TAs), the focus of this study. Methods: The amines of food, intestinal content and from faecal bacteria of Swiss mice were determined by HPLC and functionally characterised in isolated distal ileum and medial colon rings. Results: Mouse food and intestinal content contain polyamines (spermidine>putrescine>spermine) and TAs (isoamylamine>cadaverine). Intestinal bacteria mainly produce putrescine and cadaverine...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28651990/a-novel-function-of-vitellogenin-subdomain-vwf-type-d-as-a-toxin-binding-protein-in-the-pufferfish-takifugu-pardalis-ovary
#7
Xianzhe Yin, Aya Kiriake, Akira Ohta, Yoichiro Kitani, Shoichiro Ishizaki, Yuji Nagashima
Marine pufferfish of the Tetraodontidae family contain high levels of tetrodotoxin (TTX) in the liver and ovary. TTX is suggested to transfer from the liver to the ovary in female pufferfish during maturation. TTX in pufferfish eggs may act as a repellent against predators and as a sexual pheromone to attract male pufferfish. The toxification mechanism of the pufferfish ovary is poorly understood. Here we evaluated the chemical form of TTX and its related substances in the ovary of the panther pufferfish Takifugu pardalis by LC-ESI/MS...
June 23, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28638222/corticotropin-releasing-factor-stimulates-colonic-motility-via-muscarinic-receptors-in-the-rat
#8
Kyung-Jo Kim, Ki Bae Kim, Soon Man Yoon, Joung-Ho Han, Hee Bok Chae, Seon Mee Park, Sei Jin Youn
AIM: To measure exogenous corticotropin-releasing factor (CRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on CRF-induced motility. METHODS: The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous CRF was administered in a stepwise manner and the concentration of CRF yielding maximal colonic motility was selected...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28635651/effects-of-tetrodotoxin-in-mouse-models-of-visceral-pain
#9
Rafael González-Cano, Miguel Ángel Tejada, Antonia Artacho-Cordón, Francisco Rafael Nieto, José Manuel Entrena, John N Wood, Cruz Miguel Cendán
Visceral pain is very common and represents a major unmet clinical need for which current pharmacological treatments are often insufficient. Tetrodotoxin (TTX) is a potent neurotoxin that exerts analgesic actions in both humans and rodents under different somatic pain conditions, but its effect has been unexplored in visceral pain. Therefore, we tested the effects of systemic TTX in viscero-specific mouse models of chemical stimulation of the colon (intracolonic instillation of capsaicin and mustard oil) and intraperitoneal cyclophosphamide-induced cystitis...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28634472/antifungal-activity-against-filamentous-fungi-of-ts1-a-multifunctional-toxin-from-tityus-serrulatus-scorpion-venom
#10
Welligton M Santussi, Karla C F Bordon, Ana P N Rodrigues Alves, Camila T Cologna, Suraia Said, Eliane C Arantes
Antimicrobial peptides (AMPs) are ubiquitous and multipotent components of the innate immune defense arsenal used by both prokaryotic and eukaryotic organisms. The search for new AMPs has increased in recent years, due to the growing development of microbial resistance to therapeutical drugs. In this work, we evaluate the effects of Tityus serrulatus venom (Tsv), its fractions and its major toxin Ts1, a beta-neurotoxin, on fungi growth. The fractions were obtained by ion-exchange chromatography of Tsv. The growth inhibition of 11 pathogenic and non-pathogenic filamentous fungi (Aspergillus fumigatus, A...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28623807/hiv-tat-excites-d1-receptor-like-expressing-neurons-from-rat-nucleus-accumbens
#11
G Cristina Brailoiu, Elena Deliu, Jeffrey L Barr, Linda M Console-Bram, Alexandra M Ciuciu, Mary E Abood, Ellen M Unterwald, Eugen Brailoiu
BACKGROUND: HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. METHODS: We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca(2+) homeostasis of NAcc neurons...
June 8, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28621434/eea1-restores-homeostatic-synaptic-plasticity-in-hippocampal-neurons-from-rett-syndrome-mice
#12
Xin Xu, Lucas Pozzo-Miller
Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in MECP2, the gene encoding the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2). Deletion of Mecp2 in mice results in an imbalance of synaptic excitation and inhibition in hippocampal pyramidal neurons, which affects "Hebbian" long-term synaptic plasticity. Since the excitatory/inhibitory (E/I) balance is maintained by homeostatic mechanisms, we examined the role of MeCP2 in homeostatic synaptic plasticity (HSP) at excitatory synapses...
June 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28605704/4-5-dichloro-2-octyl-4-isothiazolin-3-one-dcoit-modifies-synaptic-transmission-in-hippocampal-ca3-neurons-of-rats
#13
Masahito Wakita, Kiyomitsu Shoudai, Yasuo Oyama, Norio Akaike
4,5-Dichloro-2-octyl-4-isothiazolin-3-one (DCOIT) is an alternative to organotin antifoulants, such as tributyltin and triphenyltin. Since DCOIT is found in harbors, bays, and coastal areas worldwide, this chemical compound may have some impacts on ecosystems. To determine whether DCOIT possesses neurotoxic activity by modifying synaptic transmission, we examined the effects of DCOIT on synaptic transmission in a 'synaptic bouton' preparation of rat brain. DCOIT at concentrations of 0.03-1 μM increased the amplitudes of evoked synaptic currents mediated by GABA and glutamate, while it reduced the amplitudes of these currents at 3-10 μM...
May 29, 2017: Chemosphere
https://www.readbyqxmd.com/read/28596834/acute-cocaine-exposure-elicits-rises-in-calcium-in-arousal-related-laterodorsal-tegmental-neurons
#14
Mads Ødum Lambert, Theis Højland Ipsen, Kristi Anne Kohlmeier
Cocaine has strong reinforcing properties, which underlie its high addiction potential. Reinforcement of use of addictive drugs is associated with rises in dopamine (DA) in mesoaccumbal circuitry. Excitatory afferent input to mesoaccumbal circuitry sources from the laterodorsal tegmental nucleus (LDT). Chronic, systemic cocaine exposure has been shown to have cellular effects on LDT cells, but acute actions of local application have never been demonstrated. Using calcium imaging, we show that acute application of cocaine to mouse brain slices induces calcium spiking in cells of the LDT...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28595006/selective-targeting-of-neurons-with-inorganic-nanoparticles-revealing-the-crucial-role-of-nanoparticle-surface-charge
#15
Silvia Dante, Alessia Petrelli, Enrica Maria Petrini, Roberto Marotta, Alessandro Maccione, Alessandro Alabastri, Alessandra Quarta, Francesco De Donato, Tiziana Ravasenga, Ayyappan Sathya, Roberto Cingolani, Remo Proietti Zaccaria, Luca Berdondini, Andrea Barberis, Teresa Pellegrino
Nanoparticles (NPs) are increasingly used in biomedical applications but the factors that influence their interactions with living cells need to be elucidated. Here, we reveal the role of NP surface charge in determining their neuronal interactions and electrical responses. We discovered that negatively charged NPs administered at low concentration (10nM) interact with the neuronal membrane and at the synaptic cleft, whereas positively- and neutrally-charged NPs never localize on neurons. This effect is shape and material independent...
June 8, 2017: ACS Nano
https://www.readbyqxmd.com/read/28591591/activation-of-sodium-channel-by-a-novel-%C3%AE-scorpion-toxin-bmk-nt2-stimulates-erk1-2-and-cerb-phosphorylation-through-a-ca-2-dependent-pathway-in-neocortical-neurons
#16
Xiaohan Zou, Ying Wu, Juan Chen, Fang Zhao, Fan Zhang, Boyang Yu, Zhengyu Cao
Neuronal excitability controls the expression of a variety of genes and proteins and therefore regulates neurite outgrowth and synapse formation, fundamental physiological processes controlling learning and memory. Scorpion venom contains many neurotoxins which alter ion channel activities that influence neuronal excitability. In this study, a novel scorpion peptide termed BmK NT2 was purified from venom of Chinese scorpion Buthus martensii Karsch by combining mass spectrum mapping and intracellular Ca(2+) concentration measurement in primary cultured neocortical neurons...
June 4, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28587910/evaluation-of-tetrodotoxins-in-puffer-fish-caught-along-the-mediterranean-coast-of-spain-toxin-profile-of-lagocephalus-sceleratus
#17
Maria Rambla-Alegre, Laia Reverté, Vanessa Del Río, Pablo de la Iglesia, Oscar Palacios, Cintia Flores, Josep Caixach, Katrina Campbell, Christopher T Elliott, Andrés Izquierdo-Muñoz, Mònica Campàs, Jorge Diogène
Although consumption of Tetraodontidae species is prohibited in the EU, intoxications are still reported. The evaluation of tetrodotoxins (TTXs) by mass spectrometry (LC-MS/MS and LC-HRMS) and a screening immunoassay (mELISA) in tetraodontid fishes caught along the Western Mediterranean Sea revealed high concentrations of TTXs in Lagocephalus sceleratus while no TTXs were identified in L. lagocephalus and Sphoeroides pachygaster individuals. The high TTXs content found in the L. sceleratus analysed herein demonstrate the occurrence of highly toxic puffer fish in the Western Mediterranean Sea...
June 3, 2017: Environmental Research
https://www.readbyqxmd.com/read/28580281/glucagon-like-peptide-2-promotes-gallbladder-refilling-via-a-tgr5-independent-glp-2r-dependent-pathway
#18
Bernardo Yusta, Dianne Matthews, Grace B Flock, John R Ussher, Brigitte Lavoie, Gary M Mawe, Daniel J Drucker
OBJECTIVE: Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome. Unexpectedly, reports of gallbladder disease have been associated with the use of both GLP-1R and GLP-2R agonists and after bariatric surgery, although the mechanisms remain unknown...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28579948/modulation-of-low-voltage-activated-inward-current-permeable-to-sodium-and-calcium-by-darpp-32-drives-spontaneous-firing-of-insect-octopaminergic-neurosecretory-cells
#19
Bruno Lapied, Antoine Defaix, Maria Stankiewicz, Eléonore Moreau, Valérie Raymond
Identification of the different intracellular pathways that control phosphorylation/dephosphorylation process of ionic channels represents an exciting alternative approach for studying the ionic mechanisms underlying neuronal pacemaker activity. In the central nervous system of the cockroach Periplaneta americana, octopaminergic neurons, called dorsal unpaired median (DUM; DUM neurons), generate spontaneous repetitive action potentials. Short-term cultured adult DUM neurons isolated from the terminal abdominal ganglion (TAG) of the nerve cord were used to study the regulation of a tetrodotoxin-sensitive low-voltage-activated (LVA) channel permeable to sodium and calcium (Na/Ca), under whole cell voltage- and current-clamp conditions...
2017: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28574462/a-study-of-11-%C3%A2-h-tetrodotoxin-absorption-distribution-metabolism-and-excretion-adme-in-adult-sprague-dawley-rats
#20
Bihong Hong, Hui Chen, Jiacai Han, Quanling Xie, Jianlin He, Kaikai Bai, Yanming Dong, Ruizao Yi
Tetrodotoxin (TTX) is a powerful sodium channel blocker that in low doses can safely relieve severe pain. Studying the absorption, distribution, metabolism and excretion (ADME) of TTX is challenging given the extremely low lethal dose. We conducted radiolabeled ADME studies in Sprague-Dawley rats. After a single dose of 6 μg/(16 μCi/kg) 11-[³H]TTX, pharmacokinetics of plasma total radioactivity were similar in male and female rats. Maximum radioactivity (5.56 ng Eq./mL) was reached in 10 min. [³H]TTX was below detection in plasma after 24 h...
June 2, 2017: Marine Drugs
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