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Marcos H Toyama - One of the best experts on this subject based on the ideXlab platform.
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bioaffinity fishing procedure using secretory phospholipase a2 for screening for bioactive components modulation of pharmacological effect induced by spla2 from Crotalus durissus terrificus by hispidulin from moquiniastrum floribundum
Molecules, 2020Co-Authors: Adeilso Bispo Dos Santos, Cinthia I Tamayose, Marcelo J P Ferreira, Mariana Novo Belchor, Caroline R C Costa, Marcos Antonio De Oliveira, Marcos H ToyamaAbstract:Bioaffinity capturing of molecules allows the discovery of bioactive compounds and decreases the need for various stages in the natural compound isolation process. Despite the high selectivity of this technique, the screening and identification methodology depends on the presence of a protein to capture potential ligands. However, some proteins, such as snake secretory phospholipase A2 (sPLA2), have never been investigated using this approach. The purpose of this study was to evaluate the use of a new method for screening natural compounds using a bioaffinity-guided ultrafiltration method on Crotalus durissus terrificus sPLA2 followed by HPLC-MS to identify the compounds, and this method could be used to discover new anti-inflammatory compounds from the various organisms originating from biodiversity. Different extracts were selected to evaluate their ability to inhibit sPLA2 activity. The extracts were incubated with sPLA2 and the resulting mixture was ultrafiltrated to elute unbound components. The resulting compounds were identified by HPLC-MS. We identified hispidulin as one of the components present in the Moquiniastrum floribundum leaf and evaluated the ability of this isolated compound to neutralize the inflammatory activity of sPLA2 from Crotalus durissus terrificus.
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renal and vascular effects of the natriuretic peptide isolated from Crotalus durissus cascavella venom
Toxicon, 2008Co-Authors: Janaina Serra Azul Monteiro Evangelista, Marcos H Toyama, Alice Maria Costa Martins, Nilberto R F Nascimento, Clauber Mota Sousa, Renata De Sousa Alves, Daniela De Oliveira Toyama, Joao Jose F Evangelista, Dalgimar Beserra De Menezes, M C FontelesAbstract:Crotalus durissus cascavella is a snake that is usually found in the scrublands of northeast Brazil. The components of its venom may have effects on the vascular and renal systems. Recently, a new bradykinin inhibitory peptide has been identified in the venom of the Crotalinae family. The aim of the present study was to investigate the renal and vascular effects of the natriuretic peptide isolated from the venom of Crotalus durissus cascavella (NP2_Casca). The chromatographic profile showed the fractionation of substances identified as convulxin, gyroxin, crotoxin and crotamine, as well as fractions V and VI. The electrophoretic profile of fraction V consisted of several bands ranging from approximately 6kDa to 13kDa, while fraction VI showed only two main electrophoretic bands with molecular weights of approximately 6 and 14kDa. Reverse-phase chromatography showed that NP2_Casca corresponds to about 18% of fraction VI and that this fraction is the main natriuretic peptide. NP2_Casca was compared to other natriuretic peptides from other sources of snake venom. All amino acid sequences that were compared showed a consensus region of XGCFGX, XLDRIX and XSGLGCX. The group treated with NP2_Casca showed an increase in perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. The percent of total and proximal tubular transport of sodium was reduced significantly after administration of the peptide. The mean arterial pressure showed a dose-dependent decrease after infusion of NP2_Casca, and an increase in nitrite production. In the aortic ring assay, NP2_Casca caused a relaxant effect in endothelium-intact thoracic aortic rings precontracted with phenylephrine in the presence and absence of isatin. NP2_Casca failed to relax the aortic rings precontracted with an isosmotic potassium Krebs-Henseleit solution. In conclusion, the natriuretic peptide isolated from Crotalus durissus cascavella venom produced renal and vascular effects. NP2_Casca reduced total and proximal sodium tubular transport, leading to an increase in sodium excretion, thereby demonstrating a diuretic action. A hypotensive effect was displayed in an arterial pressure assay, with an increase in nitrite production, suggesting a possible vasoactive action.
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The effect of phospholipase A2 from Crotalus durissus collilineatus on Leishmania (Leishmania) amazonensis infection
Parasitology Research, 2008Co-Authors: Luiz Felipe Domingues Passero, Thaise Yumie Tomokane, Marcia Dalastra Laurenti, Carlos Eduardo P. Corbett, Marcos H ToyamaAbstract:In this study, the effect of phospholipase A2 (PLA2) derived from Crotalus durissus collilineatus was evaluated in vitro and in vivo on experimental cutaneous leishmaniasis. The promastigote and amastigote forms treated with PLA2 presented increased growth rate. In vivo studies showed that PLA2-treated Leishmania ( Leishmania ) amazonensis promastigotes increased the size of lesions in BALB/c mice, and histopathological analysis showed numerous necrotic regions presenting a higher density of polymorphonuclear, mononuclear, and amastigote cells. Additionally, infected macrophages treated with PLA2 were able to generate prostaglandin E2 (PGE2). Cytokine quantification showed that the supernatant from infected macrophages presented moderate and high amounts of IL-2 and IL-10, respectively. However, in PLA2-treated infected macrophages, suppression of IL-2 levels occurred, but not of IL-10 levels. Observation also revealed that both the supernatant and lysate of L. ( L. ) amazonensis promastigotes exhibited PLA2 activity, which, in the presence of dexamethasone, showed no reduction in their activities; while glucocorticoid maintained the ability of promastigote forms to infect macrophages, which presented values similar to controls. In conclusion, the results indicate that PLA2 may be a progression factor for cutaneous leishmaniasis, since the PLA2 effect suppressed IL-2 levels and generated PGE2, an inflammatory lipid mediator.
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comparative studies of the anti leishmanial activity of three Crotalus durissus ssp venoms
Parasitology Research, 2007Co-Authors: Luiz Felipe Domingues Passero, Thaise Yumie Tomokane, Carlos Eduardo Pereira Corbett, Marcia Dalastra Laurenti, Marcos H ToyamaAbstract:In this study, we compared the anti-leishmanial activity of three crotalic venoms (Crotalus durissus terrificus-Cdt, Crotalus durissus cascavella-Cdca, and Crotalus durissus collilineatus-Cdcol). Different concentrations of each venom incubated with Leishmania (Leishmania) amazonensis promastigotes were used. Cdt venom exhibited a higher anti-leishmanial activity (Inhibitory concentration-IC50-value of 4.70+/-1.72 microg/ml) in comparison with that of Cdca venom (IC50 value of 9.41+/-1.21 microg/ml), while Cdcol venom increased parasite numbers in 50% at a concentration of 44.30+/-2.18 microg/ml. In addition, this venom showed a low anti-leishmanial activity in higher concentrations (IC50 value of 281.00+/-9.50 microg/ml). The main fractions of Cdca venom were isolated and assayed under similar conditions used for assessing crude venom. The most active fractions were gyroxin and crotamine that had IC50 values of 3.80+/-0.52 microg/ml and 19.95+/-4.21 microg/ml, respectively. Convulxin also inhibited parasite growth rate, although this effect was not dose-dependent. Crotoxin was the least effective fraction with an IC50 value of 99.80+/-2.21 microg/ml. None of the protein fractions presented cytotoxic effects against J774 cells in culture. In vivo assays using BALB/c mice revealed that crotoxin and crotamine were the main toxic fractions. In conclusion, C. durissus cascavella venom has three main fractions with anti-leishmanial activity. These results open new possibilities to find proteins that might be used as possible agents against cutaneous leishmaniasis.
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isolation of a new l amino acid oxidase from Crotalus durissus cascavella venom
Toxicon, 2006Co-Authors: Marcos H Toyama, Edson Antunes, Luiz Felipe Domingues Passero, Thaise Yumie Tomokane, Carlos Eduardo Pereira Corbett, Marcia Dalastra Laurenti, Fabiana Vieira Fonseca, Daniela De Oliveira Toyama, Paulo Pinto Joazeiro, L O S BeriamAbstract:Abstract A novel l -amino acid oxidase (LAO) (Casca LAO) from Crotalus durissus cascavella venom was purified to a high degree of molecular homogeneity using a combination of molecular exclusion and ion-exchange chromatography system. The purified monomer of LAO presented a molecular mass of 68 kDa and pI estimated in 5.43, which were determined by two-dimensional electrophoresis. The 71st N-terminal amino acid sequence of the LAO from Crotalus durissus cascavella presented a high amino acid sequence similarities with other LAOs from Colloselasma rhosostoma , Crotalus adamanteus , Agkistrodon h. blomhoffi , Agkistrodon h. halys and Trimeresurus stejnegeri . LAO displayed a Michaelis-Menten behavior with a kilometer of 46.7 μM and an optimum pH for enzymatic activity of 6.5. Casca LAO induced a dose-dependent platelet aggregation, which was abolished by catalase and inhibited by indomethacin and aspirin. These results suggest that the production of H 2 O 2 is involved in subsequent activation of inflammatory enzymes, such as thromboxane. Casca LAO also inhibited the bacterial growth of Gram-negative ( Xanthomonas axonopodis pv passiflorae ) and Gram-positive ( S. mutans ) strains. Electron microscopy assessments of both bacterial strains suggest that the hydrogen peroxide produced by LAO induce bacterial membrane rupture and consequently loss of cytoplasmatic content. This LAO exhibited a high antileishmanic activity against the promastigote of Leishmania amazonensis in vitro, its activity was dependent on the production of hydrogen peroxide, and the 50% inhibitory concentration was estimated in 2.39 μg/ml.
Sergio Marangoni - One of the best experts on this subject based on the ideXlab platform.
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Neuromuscular effects of venoms and crotoxin-like proteins from Crotalus durissus ruruima and Crotalus durissus cumanensis.
Toxicon : official journal of the International Society on Toxinology, 2015Co-Authors: Walter L.g. Cavalcante, Sergio Marangoni, Luis Alberto Ponce-soto, Márcia GallacciAbstract:A myographic study was performed to compare the neuromuscular effects of venoms and crotoxin-like proteins from Crotalus durissus ruruima and Crotalus durissus cumanensis in mice phrenic-diaphragm preparation. It was concluded that both venoms present neurotoxic activity as a consequence of their crotoxin content. Furthermore, crotoxin from C.d. cumanensis is more potent than that from C.d. ruruima venom. At the concentration range in which both venoms express neurotoxic activity, only C.d. cumanensis venom also manifest a direct myotoxic effect that probably involves the synergic participation of other components than crotoxin.
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structural and pharmacological characterization of the crotamine isoforms iii 4 myx4_crocu and iii 7 myx7_crocu isolated from the Crotalus durissus cumanensis venom
Toxicon, 2010Co-Authors: Luis Alberto Poncesoto, Daniel Martinsdesouza, Sergio MarangoniAbstract:Two major crotamine isoforms (III-4 and III-7) were obtained combining two chromatographic steps on molecular exclusion chromatography (Sephadex G-75) and ion-exchange column (Protein Pack SP 5PW) of the rattlesnake Crotalus durissus cumanensis venom. The "in vivo" myotoxic effect of the venom, its "in vitro" cytotoxicity in myoblasts and myotubes (C2C12) and the neurotoxic and edema-forming activity were characterized. The molecular masses of the crotamine isoforms were 4907.94 Da (III-4) and 4985.02 Da (III-7) and, as determined by mass spectrometry, both contained six Cys residues. Enzymatic hydrolysis followed by de novo sequencing through tandem mass spectrometry was used to determine the primary structure of both isoforms. III-4 and III-7 isoforms presented a 42-amino acid residues sequence and showed high molecular amino acid sequence identity with other crotamine-like proteins from Crotalus durissus terrificus. In vivo, both crotamine isoforms induced myotoxicty and a systemic interleukin-6 response upon intramuscular injection. These new crotamine isoforms induced low cytotoxicity in skeletal muscle myoblasts and myotubes (C2C12) and both induced a facilitatory effect on neuromuscular transmission in young chick biventer cervicis preparation. Edema-forming activity was also analyzed by injection of the crotamine isoforms into the right paw, since both crotamine isoforms exert a strong pro-inflammatory effect.
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Biochemical and biological characterization of a PLA2 from crotoxin complex of Crotalus durissus cumanensis.
Toxicon : official journal of the International Society on Toxinology, 2009Co-Authors: Jaime Andrés Pereañez, Sergio Marangoni, Vitelbina Núñez, Salomón Huancahuire-vega, Luis Alberto Ponce-sotoAbstract:A new PLA2 (Cdcum6) from crotoxin complex of Colombian Crotalus durissus cumanensis rattlesnake was purified using molecular exclusion chromatography and RP-HPLC. The molecular mass of Cdcum6 was determined by SDS-PAGE approximately 14 KDa and confirmed by MALDI-TOF (14321.98 Da). The enzyme showed Km 6.0 mM, Vmax 3.44 nmol/min, optimum pH was 8.0 and temperature was between 30 and 45 degrees C, and it had a strict requirement of Ca2+ for its activity. The N-terminal sequence of PLA2 was SLVQF EKMIK EVAGK NGVPWY. Comparison of amino acid sequence data with other PLA2 from South American Crotalus durissus rattlesnakes showed that Cdcum6 shares the highest sequence identity with Cdr13 an isoform PLA2 from Crotalus durissus ruruima, nevertheless, Cdcum6 showed high content of basic and hydrophobic amino acids. In mice, Cdcum6 presented higher LD50 than crotoxin complex from C d. cumanensis. Additionally, Cdcum6 induced a conspicuous local myotoxic effect and moderate footpad edema; in vitro, it was antigoagulant in doses as low as 0.5 microg/l ml, and it was not cytotoxic on myoblast but Cdcum6 was able to lyse myotubes.
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ability of rabbit antiserum against crotapotin to neutralize the neurotoxic myotoxic and phospholipase a2 activities of crotoxin from Crotalus durissus cascavella snake venom
Toxicology in Vitro, 2008Co-Authors: Daniela G Beghini, Daniela C S Damico, Maria Alice Da Cruzhofling, Lea Rodriguessimioni, Maria Carolina Delatorre, Stephen Hyslop, Sergio MarangoniAbstract:The toxicity of crotoxin, the major toxin of Crotalus durissus terrificus (South American rattlesnake) venom, is mediated by its basic phospholipase A2 (PLA2) subunit. This PLA2 is non-covalently associated with crotapotin, an acidic, enzymatically inactive subunit of the crotoxin complex. In this work, rabbit antiserum raised against crotapotin purified from Crotalus durissus cascavella venom was tested for its ability to neutralize the neurotoxicity of this venom and its crotoxin in vitro. The ability of this antiserum to inhibit the enzymatic activity of the crotoxin complex and PLA2 alone was also assessed, and its potency in preventing myotoxicity was compared with that of antisera raised against crotoxin and PLA2. Antiserum to crotapotin partially neutralized the neuromuscular blockade caused by venom and crotoxin in electrically stimulated mouse phrenic nerve-hemidiaphragm preparations and prevented the venom-induced myotoxicity, but did not inhibit the enzymatic activity of crotoxin and purified PLA2. In contrast, previous findings showed that antisera against crotoxin and PLA2 from C. d. cascavella effectively neutralized the neuromuscular blockade and PLA2 activity of this venom and its crotoxin. The partial neutralization of crotoxin-mediated neurotoxicity by antiserum to crotapotin probably reduced the binding of crotoxin to its receptor following interaction of the antiserum with the crotapotin moiety of the complex.
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structural and functional characterization of basic pla2 isolated from Crotalus durissus terrificus venom
Journal of Protein Chemistry, 2002Co-Authors: Daniela Oliveira, Jc Novello, Marcos H Toyama, L O S Beriam, Sergio MarangoniAbstract:The venom of Crotalus durissus terrificus was fractionated by reverse-phase HPLC to obtain crotapotins (F5 and F7) and PLA2 (F15, F16, and F17) of high purity. The phospholipases A2 (PLA2s) and crotapotins showed antimicrobial activity against Xanthomonas axonopodis pv. passiflorae, although the unseparated crotoxin did not. The F17 of the PLA2 also revealed significant anticoagulant activity, althrough for this to occur the presence of Glu 53 and Trp 61 is important. The F17 of the PLA2 showed allosteric behavior in the presence of a synthetic substrate. The amino acid sequence of this PLA2 isoform, determined by automatic sequencing, was HLLQFNKMLKFETRKNAVPFYAFGCYCGWGGQRRPKDATDRCCFVHDCCYEKVTKCNTKWDFYRYSLKSGYITCGKGTWCKEQICECDRVAAECLRRSLSTYKNEYMFYPDSRCREPSETC. Analysis showed that the sequence of this PLA2 isoform differed slightly from the amino acid sequence of the basic crotoxin subunit reported in the literature. The homology with other crotalid PLA2 cited in the literature varied from 60% to 90%. The pL was estimated to be 8.15, and the calculated molecular weight was 14664.14 as determined by Tricine SDS-PAGE, two-dimensional electrophoresis, and MALDI-TOFF. These results also suggested that the enzymatic activity plays an important role in the bactericidal effect of the F17 PLA2 as well as that of anticoagulation, although other regions of the molecule may also be involved in this biological activity.
Christian Betzel - One of the best experts on this subject based on the ideXlab platform.
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structure of the polypeptide crotamine from the brazilian rattlesnake Crotalus durissus terrificus
Acta Crystallographica Section D-biological Crystallography, 2013Co-Authors: Monika A Coronado, Dessislava Georgieva, Raghuvir K Arni, A G Gabdulkhakov, Banumathi Sankaran, Mario T Murakami, Christian BetzelAbstract:The crystal structure of the myotoxic, cell-penetrating, basic polypeptide crotamine isolated from the venom of Crotalus durissus terrificus has been determined by single-wavelength anomalous dispersion techniques and refined at 1.7 A resolution. The structure reveals distinct cationic and hydrophobic surface regions that are located on opposite sides of the molecule. This surface-charge distribution indicates its possible mode of interaction with negatively charged phospholipids and other molecular targets to account for its diverse pharmacological activities. Although the sequence identity between crotamine and human β-defensins is low, the three-dimensional structures of these functionally related peptides are similar. Since crotamine is a leading member of a large family of myotoxic peptides, its structure will provide a basis for the design of novel cell-penetrating molecules.
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purification crystallization and preliminary x ray diffraction analysis of crotamine a myotoxic polypeptide from the brazilian snake Crotalus durissus terrificus
Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2012Co-Authors: Monika A Coronado, Dessislava Georgieva, Raghuvir K Arni, Friedrich Buck, Azat H Gabdoulkhakov, Anwar Ullah, P J Spencer, Christian BetzelAbstract:Crotamine, a highly basic myotoxic polypeptide (molecular mass 4881 Da) isolated from the venom of the Brazilian rattlesnake Crotalus durissus terrificus, causes skeletal muscle contraction and spasms, affects the functioning of voltage-sensitive sodium channels by inducing sodium influx and possesses antitumour activity, suggesting potential pharmaceutical applications. Crotamine was purified from C. durissus terrificus venom; the crystals diffracted to 1.9 A resolution and belonged to the orthorhombic space group I212121 or I222, with unit-cell parameters a = 67.75, b = 74.4, c = 81.01 A. The self-rotation function indicated that the asymmetric unit contained three molecules. However, structure determination by molecular replacement using NMR-determined coordinates was unsuccessful and a search for potential derivatives has been initiated.
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snake venomic of Crotalus durissus terrificus correlation with pharmacological activities
Journal of Proteome Research, 2010Co-Authors: Dessislava Georgieva, Michaela Ohler, Jana Seifert, Martin Von Bergen, Raghuvir K Arni, Nicolay Genov, Christian BetzelAbstract:The snake venomic of Crotalus durissus terrificus was analyzed by 2-D and 1-D electrophoresis and subsequent MS/MS and enzymatic assays. The venomic of the South American rattlesnake comprises toxins from seven protein families: phospholipases A2, serine proteinases, ecto-5′-nucleotidases, metalloproteinases, nerve growth factors, phosphodiesterases, and glutaminyl cyclase. The venom toxin composition correlates with the clinical manifestation of the crotalinae snake bites and explains pathological effects of the venom such as neurotoxicity, systemic myonecrosis, hemostatic disorders, myoglobinuria, and acute renal failure. The vast majority of toxins are potentially involved in neurotoxicity, myotoxicity, and coagulopathy. The predominant venom components are neurotoxic phospholipases A2 and serine proteinases. The venom is a rich source of 5′-nucleotidases (7.8% of the identified toxins) inducing hemostatic disorders. Analysis of the venom protein composition provided a catalogue for secreted toxins. Th...
Tobias Wang - One of the best experts on this subject based on the ideXlab platform.
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Pharmacodynamics of propofol and alfaxalone in rattlesnakes (Crotalus durissus).
Comparative biochemistry and physiology. Part A Molecular & integrative physiology, 2021Co-Authors: Mads F. Bertelsen, Heidi M. Jensen, Cleo A. C. Leite, Rasmus Buchanan, Augusto S. Abe, Tobias WangAbstract:Abstract To characterise the effect of two common induction agents, propofol and alfaxalone, on mean arterial blood pressure (MAP) and heart rate (HR), we equipped 19 adult South American rattlesnakes (Crotalus durissus) with an indwelling arterial catheter approximately 24 h prior to recording of baseline resting values. Then, seven snakes received alfaxalone (15 mg kg−1) intravascularly (IV) through the catheter, while groups two and three (both n = 6) received propofol (15 mg kg−1 IV). The first two groups were not handled, while the propofol group was manually restrained for 2 min for a mock injection of 0.2 ml saline into the ventral tail vein. Baseline HR was similar in all groups and handling caused a significant tachycardia (p = 0.031) in group three. When given IV to undisturbed animals, both propofol and alfaxalone induced a significant increase in HR (p = 0.0022 and p = 0.0045, respectively) lasting approximately 30 min, but with values only significantly exceeding baseline for the first 5 min for propofol and the first 10 min with alfaxalone. Handling caused a significant increase in MAP (p = 0.0313). Propofol did not affect MAP (p = 0.1064), while alfaxalone caused a marked hypertension (although only significant at 2 min; p = 0.031). Manual restraint significantly increases both HR and MAP, which may lead to a masking of true cardiovascular effects of anaesthetic agents.
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The heart of the South American rattlesnake, Crotalus durissus.
Journal of morphology, 2010Co-Authors: Bjarke Jensen, Augusto Shinya Abe, Denis V. Andrade, Jens R. Nyengaard, Tobias WangAbstract:Most anatomical and physiological studies of the sauropsid heart have focused on species with extraordinary physiologies, and detailed anatomical descriptions of hearts from sauropsids with more com- mon physiologies are therefore warranted. Here, we present a comprehensive study of the cardiac anatomy of the South American rattlesnake (Crotalus durissus). The cardiovascular physiology of this species has been investigated in a number of studies, whereas only a few cursory studies exist on the cardiac anatomy of viperid snakes. The heart of C. durissus is typically squamate in many regards. Both atria are thin-walled sacs, and the right atrium is the most voluminous. The single ven- tricle contains three major septa; the vertical septum, the muscular ridge (MR), and the bulbuslamelle. These partially divide the ventricle into three chambers; the systemic and left-sided cavum arteriosum (CA), the pul- monary and right-sided cavum pulmonale, and the medial cavum venosum (CV). The MR is the most devel- oped septum, and several additional and minor septa are found within the CA and CV. An extraordinary thin cortical layer encloses the ventricle, and it is irrigated by a remarkably rich arborization of coronary arteries. Previous studies show high degrees of blood flow separa- tion in the Crotalus heart, and this can only be explained by the coordinated actions of the septa and the prominent atrioventricular valves. J. Morphol. 271:1066-1077, 2010. 2010 Wiley-Liss, Inc.
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the adrenergic regulation of the cardiovascular system in the south american rattlesnake Crotalus durissus
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2007Co-Authors: Gina L J Galli, Tobias Wang, Augusto Shinya Abe, Nini Skovgaard, E W TaylorAbstract:The present study investigates adrenergic regulation of the systemic and pulmonary circulations of the anaesthetised South American rattlesnake, Crotalus durissus. Haemodynamic measurements were made following bolus injections of adrenaline and adrenergic antagonists administered through a systemic arterial catheter. Adrenaline caused a marked systemic vasoconstriction that was abolished by phentolamine, indicating this response was mediated through alpha-adrenergic receptors. Injection of phentolamine gave rise to a pronounced vasodilatation (systemic conductance (G(sys)) more than doubled), while injection of propranolol caused a systemic vasoconstriction, pointing to a potent alpha-adrenergic, and a weaker beta-adrenergic tone in the systemic vasculature of Crotalus. Overall, the pulmonary vasculature was far less responsive to adrenergic stimulation than the systemic circulation. Adrenaline caused a small but non-significant pulmonary vasodilatation and there was tendency of reducing this dilatation after either phentolamine or propranolol. Injection of phentolamine increased pulmonary conductance (G(pul)), while injection of propranolol produced a small pulmonary constriction, indicating that alpha-adrenergic and beta-adrenergic receptors contribute to a basal regulation of the pulmonary vasculature. Our results suggest adrenergic regulation of the systemic vasculature, rather than the pulmonary, may be an important factor in the development of intracardiac shunts.
Stephen Hyslop - One of the best experts on this subject based on the ideXlab platform.
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compartment syndrome after south american rattlesnake Crotalus durissus terrificus envenomation
Clinical Toxicology, 2014Co-Authors: Fabio Bucaretchi, Stephen Hyslop, E M De Capitani, Sueli Moreira Mello, Carla Borrasca Fernandes, F Bergo, F B P NascimentoAbstract:AbstractContext. In order to report the outcome of a patient who developed compartment syndrome after South American rattlesnake (Crotalus durissus terrificus) envenomation, confirmed by subfascial pressure measurement and magnetic resonance imaging (MRI). Case details. A 63-year-old male was admitted 1 h after being bitten on the right elbow by a “large” snake, which was not brought for identification. Physical and laboratory features upon admission revealed two fang marks, local tense swelling, paresthesia, intense local pain, hypertension, coagulopathy, and CK = 1530 U/L (RV < 170 U/L). The case was initially treated with bothropic antivenom (80 mL, intravenously), with no improvement. Evolution within 13–14 h post-bite revealed generalized myalgia, muscle weakness, palpebral ptosis, and severe rhabdomyolysis (CK = 126,160 U/L) compatible with envenoming by C. d. terrificus. The patient was then treated with crotalic antivenom (200 mL, intravenously), fluid replacement, and urine alkalinization. Twenty...
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coagulopathy as the main systemic manifestation after envenoming by a juvenile south american rattlesnake Crotalus durissus terrificus case report
Clinical Toxicology, 2013Co-Authors: Fabio Bucaretchi, E M De Capitani, Maira Migliari Branco, Luciane C R Fernandes, Stephen HyslopAbstract:AbstractContext. Rattlesnake bites in Brazil are generally caused by adult individuals, with most of the envenomed patients showing systemic manifestations that include varying degrees of neurotoxicity (acute myasthenia), rhabdomyolysis and coagulopathy, with only mild or no local manifestations. We report a case of envenoming by a juvenile South American rattlesnake (Crotalus durissus terrificus) that involved coagulopathy as the main systemic manifestation. Case details. A 19-year-old male was admitted to our Emergency Department with coagulopathy (incoagulable PT, APTT and INR), no remarkable local manifestations and no signs/symptoms of myasthenia or rhabdomyolysis (serum CK, LDH, ALT and AST within reference levels) 5 days after being bitten by a small snake that was described as a rattlesnake but was not brought for identification at admission. The patient had already been treated in another Emergency Department with i.v. bothropic antivenom (AV) 1 h and 4 days post-bite. Based on the possibility of...
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ability of rabbit antiserum against crotapotin to neutralize the neurotoxic myotoxic and phospholipase a2 activities of crotoxin from Crotalus durissus cascavella snake venom
Toxicology in Vitro, 2008Co-Authors: Daniela G Beghini, Daniela C S Damico, Maria Alice Da Cruzhofling, Lea Rodriguessimioni, Maria Carolina Delatorre, Stephen Hyslop, Sergio MarangoniAbstract:The toxicity of crotoxin, the major toxin of Crotalus durissus terrificus (South American rattlesnake) venom, is mediated by its basic phospholipase A2 (PLA2) subunit. This PLA2 is non-covalently associated with crotapotin, an acidic, enzymatically inactive subunit of the crotoxin complex. In this work, rabbit antiserum raised against crotapotin purified from Crotalus durissus cascavella venom was tested for its ability to neutralize the neurotoxicity of this venom and its crotoxin in vitro. The ability of this antiserum to inhibit the enzymatic activity of the crotoxin complex and PLA2 alone was also assessed, and its potency in preventing myotoxicity was compared with that of antisera raised against crotoxin and PLA2. Antiserum to crotapotin partially neutralized the neuromuscular blockade caused by venom and crotoxin in electrically stimulated mouse phrenic nerve-hemidiaphragm preparations and prevented the venom-induced myotoxicity, but did not inhibit the enzymatic activity of crotoxin and purified PLA2. In contrast, previous findings showed that antisera against crotoxin and PLA2 from C. d. cascavella effectively neutralized the neuromuscular blockade and PLA2 activity of this venom and its crotoxin. The partial neutralization of crotoxin-mediated neurotoxicity by antiserum to crotapotin probably reduced the binding of crotoxin to its receptor following interaction of the antiserum with the crotapotin moiety of the complex.