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https://www.readbyqxmd.com/read/28346009/reactions-with-antisera-and-pathological-effects-of-staphylococcus-aureus-gamma-toxin-in-the-cornea
#1
Michael A Bierdeman, Angela M Torres, Armando R Caballero, Aihua Tang, Richard J O'Callaghan
PURPOSE: This study analyzed the toxicity of purified gamma-toxin from Staphylococcus aureus and the protectiveness of antisera to gamma-toxin in the rabbit cornea. MATERIALS AND METHODS: Gamma-toxin was purified from cultures of alpha-toxin deficient S. aureus strain Newman Δhla. Antisera to native gamma-toxin (Hlg) were produced in rabbits. These antisera and a commercial polyclonal antibody to recombinant HlgB (rHlgB) were analyzed for specificity and toxin neutralization...
March 27, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28344595/alpha-type-phospholipase-a2-inhibitors-from-snake-blood
#2
REVIEW
Norival A Santos-Filho, Claudia T Santos
It is of popular and scientific knowledge that toxins from snake venom (among them the PLA2 and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA2 inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28335389/characteristics%C3%A2-and%C3%A2-lethality%C3%A2-of%C3%A2-a%C3%A2-novel%C3%A2-recombinant%C3%A2-dermonecrotic%C3%A2-venom%C3%A2-phospholipase%C3%A2-d%C3%A2-from%C3%A2-hemiscorpius%C3%A2-lepturus
#3
Elham Torabi, Mahdi Behdani, Mohammad Hosseininejad Chafi, Reza Moazzami, Jean-Marc Sabatier, Vahid Khalaj, Delavar Shahbazzadeh, Kamran Pooshang Bagheri
Hemoscorpius lepturus is the most medically important scorpion in Iran. The clinical signs of H. lepturus envenomation are remarkably similar to those reported for brown spiders, including dermonecrosis, hematuria, renal failure and even death. The lethality and toxicity of brown spiders' venom have been attributed to its phospholipase D activity. This study aims to identify a phospholipase D with possible lethality and dermonecrotic activity in H. lepturus venom. In this study, a cDNA library of the venom glands was generated by Illumina RNA sequencing...
March 13, 2017: Toxins
https://www.readbyqxmd.com/read/28330073/cladosporium-cladosporioides-from-the-perspectives-of-medical-and-biotechnological-approaches
#4
REVIEW
Manaf AlMatar, Essam A Makky
Fungi are important natural product sources that have enormous potential for the production of novel compounds for use in pharmacology, agricultural applications and industry. Compared with other natural sources such as plants, fungi are highly diverse but understudied. However, research on Cladosporium cladosporioides revealed the existence of bioactive products such as p-methylbenzoic acid, ergosterol peroxide (EP) and calphostin C as well as enzymes including pectin methylesterase (PME), polygalacturonase (PG) and chlorpyrifos hydrolase...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28327300/rbaltmip-a-recombinant-alpha-type-myotoxin-inhibitor-from-bothrops-alternatus-rhinocerophis-alternatus-snake-as-a-potential-candidate-to-complement-the-antivenom-therapy
#5
Norival A Santos-Filho, Tiago S Sousa, Johara Boldrini-França, Ludier K Santos-Silva, Danilo L Menaldo, Flávio Henrique-Silva, Adélia C O Cintra, Helen J Laure, Carla C N Mamede, Fábio Oliveira, Thalita B Riul, Marcelo Dias-Baruffi, José C Rosa, Suely V Sampaio
Phospholipase A2 inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A2 inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.8 and molecular masses of ∼21 kDa by SDS-PAGE and 19.57 kDa by MALDI/TOF MS. After tryptic peptides sequencing, the results were compared with other PLIs available in databases, showing 100% identity between rBaltMIP and its native inhibitor BaltMIP and from 92% to 96% identity with other inhibitors...
December 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28327134/the-effect-of-intra-articular-botulinum-toxin-a-on-substance-p-prostaglandin-e2-and-tumor-necrosis-factor-alpha-in-the-canine-osteoarthritic-joint
#6
Helka M Heikkilä, Anna K Hielm-Björkman, John F Innes, Outi M Laitinen-Vapaavuori
BACKGROUND: Recently, intra-articular botulinum toxin A (IA BoNT A) has been shown to reduce joint pain in osteoarthritic dogs. Similar results have been reported in human patients with arthritis. However, the mechanism of the antinociceptive action of IA BoNT A is currently not known. The aim of this study was to explore this mechanism of action by investigating the effect of IA BoNT A on synovial fluid (SF) and serum substance P (SP), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α) in osteoarthritic dogs...
March 21, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28324240/neurocognitive-profiles-in-msud-school-age-patients
#7
Juliette Bouchereau, Julie Leduc-Leballeur, Samia Pichard, Apolline Imbard, Jean-François Benoist, Marie-Thérèse Abi Warde, Jean-Baptiste Arnoux, Valérie Barbier, Anaïs Brassier, Pierre Broué, Aline Cano, Brigitte Chabrol, Gilles Damon, Claire Gay, Isabelle Guillain, Florence Habarou, Delphine Lamireau, Chris Ottolenghi, Laetitia Paermentier, Frédérique Sabourdy, Guy Touati, Hélène Ogier de Baulny, Pascale de Lonlay, Manuel Schiff
Maple syrup urine disease (MSUD), an inborn error of amino acids catabolism is characterized by accumulation of branched chain amino acids (BCAAs) leucine, isoleucine, valine and their corresponding alpha-ketoacids. Impact on the cognitive development has been reported historically, with developmental delays of varying degree. Currently, earlier diagnosis and improved management allow a better neurodevelopment, without requirement of special education. However, specific impairments can be observed, and so far, results of detailed neurocognitive assessments are not available...
March 21, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28323513/transmembrane-tnf-dependent-uptake-of-anti-tnf-antibodies
#8
Arun Deora, Subramanya Hegde, Jacqueline Lee, Chee-Ho Choi, Qing Chang, Cheryl Lee, Lucia Eaton, Hua Tang, Dongdong Wang, David Lee, Mark Michalak, Medha Tomlinson, Qingfeng Tao, Nidhi Gaur, Bohdan Harvey, Shaun McLoughlin, Boris Labkovsky, Tariq Ghayur
TNF-alpha (TNF), a pro-inflammatory cytokine is synthesized as a 26 kDa protein, anchors in the plasma membrane as transmembrane TNF (TmTNF), and is subjected to proteolysis by the TNF-alpha converting enzyme (TACE) to release the 15 kDa form of soluble TNF (sTNF). TmTNF and sTNF interact with two distinct receptors, TNF-R1 (p55) and TNF-R2 (p75), to mediate the multiple biological effects of TNF described to date. Several anti-TNF biologics that bind to both forms of TNF and block their interactions with the TNF receptors are now approved for the treatment of a variety of immune-mediated diseases...
March 21, 2017: MAbs
https://www.readbyqxmd.com/read/28260040/antiproliferation-effect-of-the-uremic-toxin-para%C3%A2-cresol-on-endothelial-progenitor-cells-is-related-to-its-antioxidant-activity
#9
Limin Pan, Xiaoting Ye, Jiguang Ding, Yu Zhou
Endothelial dysfunction and impaired endothelial regenerative capacity are key contributors to the high incidence of cardiovascular disease in patients with chronic kidney disease (CKD). Uremic toxins are associated with this pathogenesis. Previous studies have revealed that a uremic toxin, para‑cresol (p‑cresol), exerts an antiproliferation effect on human endothelial progenitor cells (EPCs), but the mechanism remains unclear. In the present study, reactive oxygen species (ROS) were confirmed to function as signaling molecules that regulate growth factor‑dependent EPC proliferation...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259756/preparation-and-characterization-of-a-human-scfv-against-the-clostridium-perfringens-type-a-alpha-toxin
#10
Dongdong Wang, Yuhuan Yue, Guangmou Wu, Yuan Tian, Yuling Liu, Jia Yu, Yuangang Ji, Jinpeng Wang, Jian Li, Rongrong Pan, Hongyuan Ma, Guoli Zhang
Alpha-toxin produced by Clostridium perfringens is an important virulence factor, causing food poisoning and gas gangrene in humans. As such, it is considered a potential bioterrorism threat. To date, there is still no human effective therapeutic drug against alpha-toxin. In this study, a human single chain antibody against alpha-toxin was produced from synthetic (Tomlinson I + J) naive phage display libraries, and its preventive and therapeutic efficacy in mice was examined. To prove the neutralizing potential of the scFv, alpha-toxin was preincubated with scFv and subsequently tested for its lecithinase and hemolytic activity, as well as its lethal effect in mice following intravenous administration...
March 1, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28215985/detection-of-clostridium-perfringens-toxin-genes-in-the-gut-microbiota-of-autistic-children
#11
Sydney M Finegold, Paula H Summanen, Julia Downes, Karen Corbett, Tomoe Komoriya
We studied stool specimens from 33 autistic children aged 2-9 years with gastrointestinal (GI) abnormalities and 13 control children without autism and without GI symptoms. We performed quantitative comparison of all Clostridium species and Clostridium perfringens strains from the fecal microbiota by conventional, selective anaerobic culture methods. We isolated C. perfringens strains and performed PCR analysis for the main C. perfringens toxin genes, alpha, beta, beta2, epsilon, iota and C. perfringens enterotoxin gene...
February 17, 2017: Anaerobe
https://www.readbyqxmd.com/read/28210460/cloning-and-expression-of-clostridium-perfringens-type-d-vaccine-strain-epsilon-toxin-gene-in-e-coli-as-a-recombinant-vaccine-candidate
#12
Parastoo Aziminia, Reza Pilehchian-Langroudi, Kasra Esmaeilnia
BACKGROUND AND OBJECTIVES: Clostridium perfringens, a Gram-positive obligate anaerobic bacterium, is able to form resistant spores which are widely distributed in the environment. C. perfringens is subdivided into five types A to E based on its four major alpha, beta, epsilon and iota toxins. The aim of the present study was cloning and expression of C. perfringens type D vaccine strain epsilon toxin gene. MATERIALS AND METHODS: Genomic DNA was extracted and the epsilon toxin gene was amplified using Pfu DNA polymerase...
August 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/28209480/thermal-stabilization-of-anti-%C3%AE-cobratoxin-single-domain-antibodies
#13
George P Anderson, Jessica H Liu, Dan Zabetakis, Jinny L Liu, Ellen R Goldman
There is an unmet need for snake antivenoms that can be stored ready to use near the point of care. To address that need we have taken two anti-α-cobratoxin single domain antibodies and increased their thermal stability to improve their ambient temperature shelf-life. The anti-α-cobratoxin single domain antibodies C2 and C20 were first isolated, and demonstrated to be toxin neutralizing by Richard et al., 2013 (Richard, G., Meyers, A.J., McLean, M.D., Arbabi-Ghahroudi, M., MacKenzie, R., Hall, J.C., 2013...
February 14, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28209477/characterizing-the-biological-and-biochemical-profile-of-six-different-scorpion-venoms-from-the-buthidae-and-scorpionidae-family
#14
Sebastian Estrada-Gómez, Lyz Gomez-Rave, Leidy Johana Vargas-Muñoz, Arie van der Meijden
The objective of this study was to characterize six different scorpion venoms using biological and biochemical methods, including a preliminary MS/MS and a post-translational modifications analysis. Despite the diversity of scorpion species of medical importance in Africa and Colombia, the venoms of these arachnids have been poorly studied in these two regions. We report the biochemical, electrophoretic, chromatographic profile, internal peptide sequences with a post-translational modification report, and a preliminary antitumor activity of five different scorpions of the Buthidae family, Androctonus amoreuxi, Babycurus jacksoni, Grosphus grandidieri, Hottentotta gentili and Tityus fuhrmanni, and one of the Scorpionidae family Pandinus imperator...
February 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28209206/rethinking-the-role-of-alpha-toxin-in-clostridium-perfringens-associated-enteric-diseases-a-review-on-bovine-necro-haemorrhagic-enteritis
#15
REVIEW
Evy Goossens, Bonnie R Valgaeren, Bart Pardon, Freddy Haesebrouck, Richard Ducatelle, Piet R Deprez, Filip Van Immerseel
Bovine necro-haemorrhagic enteritis is an economically important disease caused by Clostridium perfringens type A strains. The disease mainly affects calves under intensive rearing conditions and is characterized by sudden death associated with small intestinal haemorrhage, necrosis and mucosal neutrophil infiltration. The common assumption that, when causing intestinal disease, C. perfringens relies upon specific, plasmid-encoded toxins, was recently challenged by the finding that alpha toxin, which is produced by all C...
February 16, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28196960/repair-of-a-bacterial-small-%C3%AE-barrel-toxin-pore-depends-on-channel-width
#16
Gisela von Hoven, Amable J Rivas, Claudia Neukirch, Martina Meyenburg, Qianqian Qin, Sapun Parekh, Nadja Hellmann, Matthias Husmann
Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca(2+)-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca(2+) influx, lysosomal exocytosis, and membrane repair...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28186774/quantitative-map-of-%C3%AE-lactone-induced-virulence-regulation
#17
Joanna Krysiak, Matthias Stahl, Jan Vomacka, Christian Fetzer, Markus Lakemeyer, Anja Fux, Stephan A Sieber
β-Lactones have recently been introduced as the first selective ClpP inhibitors that attenuate virulence of both sensitive Staphylococcus aureus and multiresistant strains (MRSA). Although previous knockout studies showed that ClpP is essential for S. aureus alpha-toxin production, a link between β-lactone inhibition and molecular virulence mechanisms has been lacking so far. We here perform a chemical-proteomic approach to elucidate antivirulence pathways. First, we demonstrate by gel-free activity-based protein profiling that ClpP is the predominant target of β-lactones...
February 10, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28137816/effects-of-tedizolid-phosphate-on-survival-outcomes-and-suppression-of-production-of-staphylococcal-toxins-in-a-rabbit-model-of-mrsa-necrotizing-pneumonia
#18
Vien T M Le, Hoan N Le, Marcos Gabriel Pinheiro, Kenneth J Hahn, Mary L Dinh, Kajal B Larson, Shawn D Flanagan, Cedric Badiou, Gerard Lina, Christine Tkaczyk, Bret R Sellman, Binh An Diep
The protective efficacy of tedizolid phosphate, a second-generation oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, or saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. A rabbit dosing regimen of 6 mg/kg tedizolid phosphate IV twice daily, which yielded AUC0-24h values approximating those in humans, was used. Overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P=0...
January 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28115346/targeting-alpha-toxin-to-mitigate-its-lethal-toxicity-in-ferret-and-rabbit-models-of-staphylococcus-aureus-necrotizing-pneumonia
#19
Binh An Diep, Jamese J Hillard, Vien T M Le, Christine Tkaczyk, Hoan N Le, Vuvi G Tran, Renee L Rao, Etyene Castro Dip, Eliane P Pereira-Franchi, Paulyn Cha, Scott Jacobson, Rosemary Broome, Lily I Cheng, William Weiss, Laszlo Prokai, Vien Nguyen, C Ken Stover, Bret R Sellman
The role broad spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on the healthy microbiome have led to advances in pathogen specific approaches for the prevention or treatment of serious bacterial infections. One approach in clinical testing is passive immunization with a monoclonal antibody (mAb) targeting alpha toxin for the prevention or treatment of Staphylococcus aureus pneumonia. Passive immunization with the human anti-alpha toxin mAb, MEDI4893* has been shown to improve disease outcome in murine S...
January 23, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28104376/lipidomic-profile-of-gm95-cell-death-induced-by-clostridium-perfringens-alpha-toxin
#20
Marco M Manni, Juan G Valero, Miriam Pérez-Cormenzana, Ainara Cano, Cristina Alonso, Félix M Goñi
Clostridium perfringens alpha-toxin (ATX) is considered as a prototype of cytotoxic bacterial phospholipases C, and is the major virulence factor in C. perfringens-induced gas gangrene. It is known that, depending on the dose, ATX causes membrane disruption and cytolysis or only limited hydrolysis of its substrates. In the latter case, toxin activity leads to the unregulated generation of bioactive lipids that can ultimately induce cell death. We have characterized apoptosis and necrosis in highly ATX-sensitive, ganglioside-deficient cells exposed to different concentrations of ATX and we have studied the lipidomic profile of cells treated with ATX as compared to native cells to detect the main changes in the lipidomic profile and the possible involvement of lipid signals in cell death...
January 16, 2017: Chemistry and Physics of Lipids
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