Identification of Genes Relevant to Pesticides and Biology from Global Transcriptome Data of Monochamus alternatus Hope (Coleoptera: Cerambycidae Larvae.

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Songqing Wu

Full Text Available Monochamus alternatus Hope is the main vector in China of the Pine Wilt Disease caused by the pine wood nematode Bursaphelenchus xylophilus. Although chemical control is traditionally used to prevent pine wilt disease, new strategies based in biological control are promising ways for the management of the disease. However, there is no deep sequence analysis of Monochamus alternatus Hope that describes the transcriptome and no information is available about gene function of this insect vector. We used next generation sequencing technology to sequence the whole fourth instar larva transcriptome of Monochamus alternatus Hope and successfully built a Monochamus alternatus Hope transcriptome database. In total, 105,612 unigenes were assigned for Gene Ontology (GO terms, information for 16,730 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs database, and 13,024 unigenes matched with 224 predicted pathways in the Kyoto Encyclopedia of Genes and Genome (KEGG. In addition, genes related to putative insecticide resistance-related genes, RNAi, the Bt receptor, intestinal digestive enzymes, possible future insect control targets and immune-related molecules are described. This study provides valuable basic information that can be used as a gateway to develop new molecular tools for Monochamus alternatus Hope control strategies.

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone.

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Gabriella Neves Leal Santos Barreto

2017-03-01

Full Text Available Bothrops atrox snakes are the leading cause of snake bites in Northern Brazil. The venom of this snake is not included in the antigen pool used to obtain the Bothrops antivenom. There are discrepancies in reports on the effectiveness of this antivenom to treat victims bitten by B. atrox snakes. However, these studies were performed using a pre-incubation of the venom with the antivenom and, thus, did not simulate a true case of envenomation treatment. In addition, the local lesions induced by Bothrops venoms are not well resolved by antivenom therapy. Here, we investigated the efficacy of the Bothrops antivenom in treating the signs and symptoms caused by B. atrox venom in mice and evaluated whether the combination of dexamethasone and antivenom therapy enhanced the healing of local lesions induced by this envenomation. In animals that were administered the antivenom 10 minutes after the envenomation, we observed an important reduction of edema, dermonecrosis, and myonecrosis. When the antivenom was given 45 minutes after the envenomation, the edema and myonecrosis were reduced, and the fibrinogen levels and platelet counts were restored. The groups treated with the combination of antivenom and dexamethasone had an enhanced decrease in edema and a faster recovery of the damaged skeletal muscle. Our results show that Bothrops antivenom effectively treats the envenomation caused by Bothrops atrox and that the use of dexamethasone as an adjunct to the antivenom therapy could be useful to improve the treatment of local symptoms observed in envenomation caused by Bothrops snakes.

Reactividad inmunoquímica de sueros anti- Caiman yacare y Caiman latirostris frente a sueros de diferentes especies

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de Roodt, Adolfo Rafael

2010-06-01

Full Text Available Se estudió la reactividad inmunoquímica entre los sueros de distintas especies de reptiles frente a sueros hiperinmunes experimentales anti-suero de Caiman yacare y anti-suero de Caiman latirostris. Los sueros que se probaron fueron los homólogos de Caiman yacare, Caiman latirostris y los heterólogos de Alligator missisipiensis, Tupinambis merinae, Tupinambis rufescens, Chelonoidis chilensis, Clelia rustica, Waglerophis merremii, Lystrophys dorbignyi, Phyton molurus, Boa constrictor occidentalis, Eunectes notaeus, Crotalus durissus terrificus, Bothrops alternatus, Bothrops diporus, Bothrops jararaca, Bothrops jararacussu, Bothrops moojeni, Pitangus sulphuratus y Gallus gallus. La reactividad inmunoquímica se determinó mediante las técnicas de doble inmunodifusión y ELISA, mostrándose importante entre los sueros de los crocodrílidos y baja entre estos y los de las otras especies de reptiles estudiadas. Se observó mayor reactividad entre los antisueros anti-Caiman respecto a los sueros de Caiman latirostris y Caiman yacare que frente al suero de Alligator missisipiensis. Además, se encontró una fuerte reactividad entre ambos sueros anti-Caiman y el de Gallus gallus poniendo en evidencia la fuerte reactividad entre los sueros de arcosaurios. In order to study the immunochemical reactivity among sera from different species of reptiles regarding sera from Caiman, the immunoreactivity of sera from reptiles against antisera to Caiman yacare or anti-Caiman latirostris sera was studied. These hiperimmune sera were tested against sera from Alligator missisipiensis, Tupinambis merinae, Tupinambis rufescens, Chelonoidis chilensis, Clelia rustica, Waglerophis merremii, Lystrophys dorbignyi, Phyton molurus, Boa constrictor occidentalis, Eunectes notaeus, Crotalus durissus terrificus, Bothrops alternatus, Bothrops neuwiedii, Bothrops jararaca, Bothrops jararacussu, Bothrops moojeni, Pitangus sulphuratus and Gallus gallus. The immunochemical

Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation.

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Pedro Henrique França Gois

2017-11-01

Full Text Available Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo in an experimental model of Bothrops jararaca venom (BJ-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg was intravenously injected during 40'. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg 40' after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine. Allo ameliorated GFR, renal blood flow (RBF, renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.

Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation

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Martines, Monique Silva; Ferreira, Daniela; Volpini, Rildo; Canale, Daniele; Malaque, Ceila; Crajoinas, Renato; Girardi, Adriana Castello Costa; Massola Shimizu, Maria Heloisa; Seguro, Antonio Carlos

2017-01-01

Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40’. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40’ after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug. PMID:29155815

Dispersal of the Japanese pine sawyer, Monochamus alternatus (Coleoptera: Cerambycidae, in mainland China as inferred from molecular data and associations to indices of human activity.

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Shao-ji Hu

Full Text Available The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae, is an important forest pest as well as the principal vector of the pinewood nematode (PWN, Bursaphelenchus xylophilus (Steiner et Buhrer, in mainland China. Despite the economic importance of this insect-disease complex, only a few studies are available on the population genetic structure of M. alternatus and the relationship between its historic dispersal pattern and various human activities. The aim of the present study was to further explore aspects of human activity on the population genetic structure of M. alternatus in mainland China. The molecular data based on the combined mitochondrial cox1 and cox2 gene fragments from 140 individuals representing 14 Chinese populations yielded 54 haplotypes. Overall, a historical (natural expansion that originated from China's eastern coast to the western interior was revealed by the haplotype network, as well as several recent, long-distant population exchanges. Correlation analysis suggested that regional economic status and proximity to marine ports significantly influenced the population genetic structure of M. alternatus as indicated by both the ratio of shared haplotypes and the haplotype diversity, however, the PWN distribution in China was significantly correlated with only the ratio of shared haplotypes. Our results suggested that the modern logistical network (i.e., the transportation system in China is a key medium by which humans have brought about population exchange of M. alternatus in mainland China, likely through inadvertent movement of infested wood packaging material associated with trade, and that this genetic exchange was primarily from the economically well-developed east coast of China, westward, to the less-developed interior. In addition, this study demonstrated the existence of non-local M. alternatus in new PWN-infested localities in China, but not all sites with non-local M. alternatus were

Hemostatic properties of Venezuelan Bothrops snake venoms with special reference to Bothrops isabelae venom.

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Rodríguez-Acosta, Alexis; Sánchez, Elda E; Márquez, Adriana; Carvajal, Zoila; Salazar, Ana M; Girón, María E; Estrella, Amalid; Gil, Amparo; Guerrero, Belsy

2010-11-01

In Venezuela, Bothrops snakes are responsible for more than 80% of all recorded snakebites. This study focuses on the biological and hemostatic characteristics of Bothrops isabelae venom along with its comparative characteristics with two other closely related Bothrops venoms, Bothrops atrox and Bothrops colombiensis. Electrophoretic profiles of crude B. isabelae venom showed protein bands between 14 and 100 kDa with the majority in the range of 14-31 kDa. The molecular exclusion chromatographic profile of this venom contains five fractions (F1-F5). Amidolytic activity evaluation evidenced strong thrombin-like followed by kallikrein-like activities in crude venom and in fractions F1 and F2. The fibrinogenolytic activity of B. isabelae venom at a ratio of 100:1 (fibrinogen/venom) induced a degradation of A alpha and B beta chains at 15 min and 2 h, respectively. At a ratio of 100:10, a total degradation of A alpha and B beta chains at 5 min and of gamma chains at 24 h was apparent. This current study evidences one of rarely reported for Bothrops venoms, which resembles the physiologic effect of plasmin. B. isabelae venom as well as F2 and F3 fractions, contain fibrinolytic activity on fibrin plate of 36, 23.5 and 9.45 mm(2)/microg, respectively using 25 microg of protein. Crude venom and F1 fraction showed gelatinolytic activity. Comparative analysis amongst Venezuelan bothropoid venoms, evidenced that the LD(50) of B. isabelae (5.9 mg/kg) was similar to B. atrox-Puerto Ayacucho 1 (6.1 mg/kg) and B. colombiensis-Caucagua (5.8 mg/kg). B. isabelae venom showed minor hemorrhagic activity, whereas B. atrox-Parguasa (Bolivar state) was the most hemorrhagic. In this study, a relative high thrombin-like activity was observed in B. colombiensis venoms (502-568 mUA/min/mg), and a relative high factor Xa-like activity was found in B. atrox venoms (126-294 mUA/min/mg). Fibrinolytic activity evaluated with 10 microg protein, showed that B. isabelae venom contained higher

21 CFR 864.8100 - Bothrops atrox reagent.

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2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bothrops atrox reagent. 864.8100 Section 864.8100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8100 Bothrops atrox reagent. (a...

Multiple cerebral infarctions following a snakebite by Bothrops caribbaeus.

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Numeric, Patrick; Moravie, Victor; Didier, Martin; Chatot-Henry, Didier; Cirille, Sylvia; Bucher, Bernard; Thomas, Laurent

2002-09-01

Bothrops caribbaeus, a species of the Bothrops complex, is found only in the island of Saint Lucia, West Indies. Snakebite from this pitviper is very rare. We report the case of a healthy 32-year-old Saint Lucian man who developed multiple cerebral infarctions following envenoming by this snake. This patient developed signs and symptoms very similar to those observed in patients envenomed by Bothrops lanceolatus, a snake found only in Martinique, the neighbor island of Saint Lucia. This clinical presentation differs dramatically from coagulopathies and systemic bleeding observed with the Central and South American bothropic envenomings. The exact mechanism of this thrombogenic phenomenon, leading to a unique envenoming syndrome, remains unknown.

Biochemical and immunological alterations of {sup 60} Co irradiated Bothrops jararacussu venom; Alteracoes bioquimicas e imunologicas do veneno de Bothrops jararacussu irradiado com {sup 60} Co

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Spencer, Patrick J.

1995-12-31

Proteins irradiation leads to structural alterations resulting in activity and function loss. This process has been useful to detoxify animal venoms and toxins, resulting in low toxicity products which increased immunogenicity. The Bothrops jararacussu venom behaves as a weak immunogen and its lethal activity in not neutralized by either autologous, heterologous or bothropic polyvalent antisera. This venom is markedly myotoxic and and the commercial bothropic antiserum does not neutralize this activity, because of this low immunogenicity of the myotoxins. This present work was done in order to evaluate the possibility of irradiating Bothrops jararacussu, intending to increase the immunogenicity of the myotoxic components, leading to productions of myotoxins neutralizing antibodies. Bothrops jararacussu venom samples were irradiated with 500, 1000 and 2000 Gy of {sup 60} Co gamma rays. A 2.3 folds decrease of toxicity was observed for the 1000 Gy irradiated samples while the 2000 Gy irradiated sample was at least 3.7 folds attenuated. On the other hand, the 500 Gy did not promote any detoxification. Electrophoresis and HPLC data indicate that the irradiation lead to the formation of high molecular weight products (aggregates). The proteolytic and phospholipasic activities decreased in a dose dependent manner, the phospholipases being more resistant than the proteases. Both the animals (rabbit) immunized with either native or 2000 Gy irradiated venom produced native venom binding antibodies, a slightly higher titer being obtained in the serum of the rabbit immunized with the irradiated samples. Western blot data indicate that the anti-irradiated venom Ig Gs recognised a greater amount of either autologous or heterologous venom bands, both sera behaving as genus specific. The anti-native serum did not neutralize the myotoxic activity of native venom, while the anti-irradiated one was able to neutralize this activity. (author). 56 refs., 7 figs.

Functional and proteomic comparison of Bothrops jararaca venom from captive specimens and the Brazilian Bothropic Reference Venom.

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Farias, Iasmim Baptista de; Morais-Zani, Karen de; Serino-Silva, Caroline; Sant'Anna, Sávio S; Rocha, Marisa M T da; Grego, Kathleen F; Andrade-Silva, Débora; Serrano, Solange M T; Tanaka-Azevedo, Anita M

2018-03-01

Snake venom is a variable phenotypic trait, whose plasticity and evolution are critical for effective antivenom production. A significant reduction of the number of snake donations to Butantan Institute (São Paulo, Brazil) occurred in recent years, and this fact may impair the production of the Brazilian Bothropic Reference Venom (BBRV). Nevertheless, in the last decades a high number of Bothrops jararaca specimens have been raised in captivity in the Laboratory of Herpetology of Butantan Institute. Considering these facts, we compared the biochemical and biological profiles of B. jararaca venom from captive specimens and BBRV in order to understand the potential effects of snake captivity upon the venom composition. Electrophoretic analysis and proteomic profiling revealed few differences in venom protein bands and some differentially abundant toxins. Comparison of enzymatic activities showed minor differences between the two venoms. Similar cross-reactivity recognition pattern of both venoms by the antibothropic antivenom produced by Butantan Institute was observed. Lethality and neutralization of lethality for B. jararaca venom from captive specimens and BBRV showed similar values. Considering these results we suggest that the inclusion of B. jararaca venom from captive specimens in the composition of BBRV would not interfere with the quality of this reference venom. Snakebite envenomation is a neglected tropical pathology whose treatment is based on the use of specific antivenoms. Bothrops jararaca is responsible for the majority of snakebites in South and Southeastern Brazil. Its venom shows individual, sexual, and ontogenetic variability, however, the effect of animal captivity upon venom composition is unknown. Considering the reduced number of wild-caught snakes donated to Butantan Institute in the last decades, and the increased life expectancy of the snakes raised in captivity in the Laboratory of Herpetology, this work focused on the comparative

Biochemical and immunological alterations of 60 Co irradiated Bothrops jararacussu venom

International Nuclear Information System (INIS)

Spencer, Patrick J.

1995-01-01

Proteins irradiation leads to structural alterations resulting in activity and function loss. This process has been useful to detoxify animal venoms and toxins, resulting in low toxicity products which increased immunogenicity. The Bothrops jararacussu venom behaves as a weak immunogen and its lethal activity in not neutralized by either autologous, heterologous or bothropic polyvalent antisera. This venom is markedly myotoxic and and the commercial bothropic antiserum does not neutralize this activity, because of this low immunogenicity of the myotoxins. This present work was done in order to evaluate the possibility of irradiating Bothrops jararacussu, intending to increase the immunogenicity of the myotoxic components, leading to productions of myotoxins neutralizing antibodies. Bothrops jararacussu venom samples were irradiated with 500, 1000 and 2000 Gy of 60 Co gamma rays. A 2.3 folds decrease of toxicity was observed for the 1000 Gy irradiated samples while the 2000 Gy irradiated sample was at least 3.7 folds attenuated. On the other hand, the 500 Gy did not promote any detoxification. Electrophoresis and HPLC data indicate that the irradiation lead to the formation of high molecular weight products (aggregates). The proteolytic and phospholipasic activities decreased in a dose dependent manner, the phospholipases being more resistant than the proteases. Both the animals (rabbit) immunized with either native or 2000 Gy irradiated venom produced native venom binding antibodies, a slightly higher titer being obtained in the serum of the rabbit immunized with the irradiated samples. Western blot data indicate that the anti-irradiated venom Ig Gs recognised a greater amount of either autologous or heterologous venom bands, both sera behaving as genus specific. The anti-native serum did not neutralize the myotoxic activity of native venom, while the anti-irradiated one was able to neutralize this activity. (author)

Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

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Picolo G.

2002-01-01

Full Text Available Neutralization of hyperalgesia induced by Bothrops jararaca and B. asper venoms was studied in rats using bothropic antivenom produced at Instituto Butantan (AVIB, 1 ml neutralizes 5 mg B. jararaca venom and polyvalent antivenom produced at Instituto Clodomiro Picado (AVCP, 1 ml neutralizes 2.5 mg B. aspar venom. The intraplantar injection of B. jararaca and B. asper venoms caused hyperalgesia, which peaked 1 and 2 h after injection, respectively. Both venoms also induced edema with a similar time course. When neutralization assays involving the independent injection of venom and antivenom were performed, the hyperalgesia induced by B. jararaca venom was neutralized only when bothropic antivenom was administered iv 15 min before venom injection, whereas edema was neutralized when antivenom was injected 15 min or immediately before venom injection. On the other hand, polyvalent antivenom did not interfere with hyperalgesia or edema induced by B. asper venom, even when administered prior to envenomation. The lack of neutralization of hyperalgesia and edema induced by B. asper venom is not attributable to the absence of neutralizing antibodies in the antivenom, since neutralization was achieved in assays involving preincubation of venom and antivenom. Cross-neutralization of AVCP or AVIB against B. jararaca and B. asper venoms, respectively, was also evaluated. Only bothropic antivenom partially neutralized hyperalgesia induced by B. asper venom in preincubation experiments. The present data suggest that hyperalgesia and edema induced by Bothrops venoms are poorly neutralized by commercial antivenoms even when antibodies are administered immediately after envenomation.

Occurrence of Microcerella halli (Engel (Diptera, Sarcophagidae in snake carrion in southeastern Brazil Ocorrência de Microcerella halli (Engel (Diptera, Sarcophagidae em uma Carcaça de Cobra no Sudeste Brasileiro

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Thiago de C. Moretti

2009-06-01

Full Text Available The occurrence of 27 second-instar larvae of the flesh fly Microcerella halli (Engel, 1931 (Diptera, Sarcophagidae in a carcass of a snake usually called as Urutu, Bothrops alternatus (Duméril, Bibron & Duméril, 1854 (Serpentes, Viperidae, Crotalinae is reported. The snake was kept in captivity in a snake farm in Morungaba, São Paulo state, Brazil. Descriptions of reptile carcass colonization by insects and general biological data of this flesh fly are scarce and this necrophagic behavior is described for the first time in literature.A ocorrência de 27 larvas de segundo estádio do sarcofagídeo Microcerella halli (Engel, 1931 (Diptera, Sarcophagidae em uma carcaça de urutu Bothrops alternatus (Duméril, Bibron & Duméril, 1854 (Serpentes, Viperidae, Crotalinae é relatada. A cobra era mantida em cativeiro em um serpentário no município de Morungaba, estado de São Paulo, Brasil. Descrições de colonização de carcaças de répteis por insetos e dados gerais da biologia deste sarcofagídeo são escassos, e este comportamento necrófago é descrito pela primeira vez na literatura.

Bothrops fonsecai snake venom activities and cross-reactivity with commercial bothropic venom.

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Collaço, Rita de Cássia O; Randazzo-Moura, Priscila; Tamascia, Mariana L; da Silva, Igor Rapp F; Rocha, Thalita; Cogo, José C; Hyslop, Stephen; Sanny, Charles G; Rodrigues-Simioni, Léa

2017-01-01

In this work, we examined some biochemical and biological activities of Bothrops fonsecai venom, a pitviper endemic to southeastern Brazil, and assessed their neutralization by commercial bothropic antivenom (CAv). Cross-reactivity of venom with CAv was also assessed by immunoblotting and size-exclusion high performance chromatography (SE-HPLC). Bothrops fonsecai venom had PLA 2 , proteolytic and esterase activities that were neutralized to varying extents by venom:antivenom ratios of 5:1 and 5:2 (PLA 2 and esterase activities) or not significantly by either venom:antivenom ratio (proteolytic activity). The minimum hemorrhagic dose (69.2μg) was totally neutralized by both ratios. Clotting time in rat citrated plasma was 33±10.5s (mean±SD; n=5) and was completely neutralized by a 5:2 ratio. Edema formation was dose-dependent (1-30μg/site) and significantly inhibited by both ratios. Venom (10-300μg/mL) caused neuromuscular blockade in extensor digitorum longus preparations; this blockade was inhibited best by a 5:2 ratio. Venom caused myonecrosis and creatine kinase release in vivo (gastrocnemius muscle) and in vitro (extensor digitorum longus) that was effectively neutralized by both venom:antivenom ratios. Immunoblotting showed that venom components of ~25-100kDa interacted with CAv. SE-HPLC profiles for venom incubated with CAv or specific anti-B. fonsecai antivenom raised in rabbits (SAv) indicated that CAv had a higher binding capacity than SAv, whereas SAv had higher affinity than CAv. These findings indicate that B. fonsecai venom contains various activities that are neutralized to different extents by CAv and suggest that CAv could be used to treat envenoming by B. fonsecai. Copyright © 2016. Published by Elsevier Inc.

Comparison of Phylogeny, Venom Composition and Neutralization by Antivenom in Diverse Species of Bothrops Complex

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Peixoto, Pedro S.; Bernardoni, Juliana L.; Oliveira, Sâmella S.; Portes-Junior, José Antonio; Mourão, Rosa Helena V.; Lima-dos-Santos, Isa; Sano-Martins, Ida S.; Chalkidis, Hipócrates M.; Valente, Richard H.; Moura-da-Silva, Ana M.

2013-01-01

In Latin America, Bothrops snakes account for most snake bites in humans, and the recommended treatment is administration of multispecific Bothrops antivenom (SAB – soro antibotrópico). However, Bothrops snakes are very diverse with regard to their venom composition, which raises the issue of which venoms should be used as immunizing antigens for the production of pan-specific Bothrops antivenoms. In this study, we simultaneously compared the composition and reactivity with SAB of venoms collected from six species of snakes, distributed in pairs from three distinct phylogenetic clades: Bothrops, Bothropoides and Rhinocerophis. We also evaluated the neutralization of Bothrops atrox venom, which is the species responsible for most snake bites in the Amazon region, but not included in the immunization antigen mixture used to produce SAB. Using mass spectrometric and chromatographic approaches, we observed a lack of similarity in protein composition between the venoms from closely related snakes and a high similarity between the venoms of phylogenetically more distant snakes, suggesting little connection between taxonomic position and venom composition. P-III snake venom metalloproteinases (SVMPs) are the most antigenic toxins in the venoms of snakes from the Bothrops complex, whereas class P-I SVMPs, snake venom serine proteinases and phospholipases A2 reacted with antibodies in lower levels. Low molecular size toxins, such as disintegrins and bradykinin-potentiating peptides, were poorly antigenic. Toxins from the same protein family showed antigenic cross-reactivity among venoms from different species; SAB was efficient in neutralizing the B. atrox venom major toxins. Thus, we suggest that it is possible to obtain pan-specific effective antivenoms for Bothrops envenomations through immunization with venoms from only a few species of snakes, if these venoms contain protein classes that are representative of all species to which the antivenom is targeted. PMID

Neutralization of toxicological activities of medically-relevant Bothrops snake venoms and relevant toxins by two polyvalent bothropic antivenoms produced in Peru and Brazil.

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Estevao-Costa, Maria I; Gontijo, Silea S; Correia, Barbara L; Yarleque, Armando; Vivas-Ruiz, Dan; Rodrigues, Edith; Chávez-Olortegui, Carlos; Oliveira, Luciana S; Sanchez, Eladio F

2016-11-01

Snakebite envenoming is a neglected public pathology, affecting especially rural communities or isolated areas of tropical and subtropical Latin American countries. The parenteral administration of antivenom is the mainstay and the only validated treatment of snake bite envenoming. Here, we assess the efficacy of polyspecific anti-Bothrops serum (α-BS) produced in the Instituto Nacional de Salud (INS, Peru) and at the Fundação Ezequiel Dias (FUNED, Brazil), to neutralize the main toxic activities induced by five medically-relevant venoms of: Bothrops atrox, B. barnetti, and B. pictus from Peru, and the Brazilian B. jararaca and B. leucurus, all of them inhabiting different geographical locations. Protein electrophoretic patterns of these venoms showed significant differences in composition, number and intensity of bands. Another goal was to evaluate the efficacy and safety of lyophilized α-BS developed at INS to neutralize the detrimental effects of these venoms using in vivo and in vitro assays. The availability of lyophilized α-BS has relevant significance in its distribution to distant rural communities where the access to antivenom in health facilities is more difficult. Despite the fact that different antigen mixtures were used for immunization during antivenom production, our data showed high toxin-neutralizing activity of α-BS raised against Bothrops venoms. Moreover, the antivenom cross-reacted even against venoms not included in the immunization mixture. Furthermore, we have evaluated the efficacy of both α-BS to neutralize key toxic compounds belonging to the predominant protein families of Bothrops snakes. Most significantly, both α-BS cross-specifically neutralized the main toxicological activities e.g. lethality and hemorrhage induced by these venoms. Thus, our data indicate that both α-BS are equally effective to treat snake bite victims inflicted by Bothrops snakes particularly B. atrox, responsible for the largest numbers of human

Pine wilt disease in Yunnan, China: Evidence of non-local pine sawyer Monochamus alternatus (Coloptera: Cerambycidae) populations revealed by mitochondrial DNA

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Da-Ying Fu; Shao-Ji Hu; Hui Ye; Robert A. Haack; Ping-Yang. Zhou

2010-01-01

Monochamus alternatus (Hope) specimens were collected from nine geographical populations in China,where the pinewood nematode Bursaphelenchus xylophilus (Steiner et Buhrer) was present. There were seven populations in southwestern China in Yunnan Province (Ruili,Wanding, Lianghe, Pu'er, Huaning, Stone Forest and Yongsheng),...

An alternative method to isolate protease and phospholipase A2 toxins from snake venoms based on partitioning of aqueous two-phase systems

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GN Gómez

2012-01-01

Full Text Available Snake venoms are rich sources of active proteins that have been employed in the diagnosis and treatment of health disorders and antivenom therapy. Developing countries demand fast economical downstream processes for the purification of this biomolecule type without requiring sophisticated equipment. We developed an alternative, simple and easy to scale-up method, able to purify simultaneously protease and phospholipase A2 toxins from Bothrops alternatus venom. It comprises a multiple-step partition procedure with polyethylene-glycol/phosphate aqueous two-phase systems followed by a gel filtration chromatographic step. Two single bands in SDS-polyacrylamide gel electrophoresis and increased proteolytic and phospholipase A2 specific activities evidence the homogeneity of the isolated proteins.

Biological and immunological characteristics of the poison of Bothrops cotiara (Serpentes: Viperidae)

International Nuclear Information System (INIS)

Roodt, Adolfo Rafael de; Dolab, Jorge Adrian; Manzanelli, Marcelo Victor; Pineiro, Nicolas; Estevez, Judith; Paniagua, Jorge Francisco; Urs Vogt, Alejandro

2006-01-01

Bothrops cotiara is a venomous snake sporadically found in the province of Misiones in Argentina, South of Brazil and Paraguay. Data on the clinics of the poisoning produced by its bite and on its venom are scarce. There is no information on the neutralizing capacity of the antivenoms available. In this study, the lethal potency, hemorrhagic, necrotizing, coagulant and thrombin-like, defibrinogenasing, indirect hemolytic and fibrinolytic activities of the venom of B. cotiara specimens from the province of Misiones were determined. The toxic activities were within the range of those described for the other Bothrops species from Argentina, and the electrophoretic and chromatographic studies showed similarities with those described for the other bothropic venoms. The immunochemical reactivity of six South American anti Viper antivenoms (ELISA) have a strong reactivity with all the antivenoms studied. The neutralizing capacity of three of these therapeutic antivenoms against the lethal potency and hemorrhagic, necrotizing, coagulant, thrombin-like and hemolytic activities showed a very close neutralizing capacity. Our data strongly suggest that the antivenoms for therapeutic use available in this area of South America are useful to neutralize the toxic and enzymatic activities of the venom of this uncommon specie of Bothrops. (author) [es

Isolation and Functional Characterization of an Acidic Myotoxic Phospholipase A₂ from Colombian Bothrops asper Venom.

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Posada Arias, Silvia; Rey-Suárez, Paola; Pereáñez J, Andrés; Acosta, Cristian; Rojas, Mauricio; Delazari Dos Santos, Lucilene; Ferreira, Rui Seabra; Núñez, Vitelbina

2017-10-26

Myotoxic phospholipases A₂ (PLA₂) are responsible for many clinical manifestations in envenomation by Bothrops snakes. A new myotoxic acidic Asp49 PLA₂ (BaCol PLA₂) was isolated from Colombian Bothrops asper venom using reverse-phase high performance liquid chromatography (RP-HPLC). BaCol PLA₂ had a molecular mass of 14,180.69 Da (by mass spectrometry) and an isoelectric point of 4.4. The complete amino acid sequence was obtained by cDNA cloning (GenBank accession No. MF319968) and revealed a mature product of 124 amino acids with Asp at position 49. BaCol PLA₂ showed structural homology with other acidic PLA₂ isolated from Bothrops venoms, including a non-myotoxic PLA₂ from Costa Rican B. asper . In vitro studies showed cell membrane damage without exposure of phosphatidylserine, an early apoptosis hallmark. BaCol PLA₂ had high indirect hemolytic activity and moderate anticoagulant action. In mice, BaCol PLA₂ caused marked edema and myotoxicity, the latter seen as an increase in plasma creatine kinase and histological damage to gastrocnemius muscle fibers that included vacuolization and hyalinization necrosis of the sarcoplasm.

First report of hepatic hematoma after presumed Bothrops envenomation

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Fernanda Cristina Cunha

2015-10-01

Full Text Available ABSTRACTIn Latin America, Bothrops envenomation is responsible for the majority of accidents caused by venomous snakes. Patients usually present local edema, bleeding and coagulopathy. Visceral hemorrhage is extremely rare and considered a challenge for diagnosis and management. We report the first case of hepatic hematoma owing to the bothropic envenomation in a 66-year-old man who was bitten in the left leg. He presented local edema, coagulopathy, and acute kidney injury. Radiological findings suggested hepatic hematoma, with a volume of almost 3 liters. The hepatic hematoma was gradually absorbed without the need for surgical intervention with complete resolution in 8 months.

Inhibition of local effects induced by Bothrops erythromelas snake venom: Assessment of the effectiveness of Brazilian polyvalent bothropic antivenom and aqueous leaf extract of Jatropha gossypiifolia.

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Félix-Silva, Juliana; Gomes, Jacyra A S; Xavier-Santos, Jacinthia B; Passos, Júlia G R; Silva-Junior, Arnóbio A; Tambourgi, Denise V; Fernandes-Pedrosa, Matheus F

2017-01-01

Bothrops erythromelas is a snake of medical importance responsible for most of the venomous incidents in Northeastern Brazil. However, this species is not included in the pool of venoms that are used in the Brazilian polyvalent bothropic antivenom (BAv) production. Furthermore, it is well known that antivenom therapy has limited efficacy against venom-induced local effects, making the search for complementary alternatives to treat snakebites an important task. Jatropha gossypiifolia is a medicinal plant widely indicated in folk medicine as an antidote for snakebites, whose effectiveness against Bothrops jararaca venom (BjV) has been previously demonstrated in mice. In this context, this study assessed the effectiveness of the aqueous extract (AE) of this plant and of the BAv against local effects induced by B. erythromelas venom (BeV). Inhibition of BeV-induced edematogenic and hemorrhagic local effects was assayed in mice in pre-treatment (treatment prior to BeV injection) and post-treatment (treatment post-envenomation) protocols. Inhibition of proteolytic, phospholipase A 2 (PLA 2 ) and hyaluronidase enzymatic activities of BeV were evaluated in vitro. BAv cross-reactivity and estimation of antibody titers against BeV and BjV were assessed by Ouchterlony double diffusion test. The results show that in pre-treatment protocol AE and BAv presented very similar effects (about 70% of inhibition for edematogenic and 40% for hemorrhagic activities). However, BAv poorly inhibited edema and hemorrhage in post-envenomation protocol, whilst, in contrast, AE was significantly active even when used after BeV injection. AE was able to inhibit all the tested enzymatic activities of BeV, while BAv was active only against hyaluronidase activity, which could justify the low effectiveness of BAv against BeV-induced local effects in vivo. Ouchterlony's test showed positive cross-reactivity against BeV, but the antibody titers were slightly higher against BjV. Together, these

Acidente vascular cerebral hemorrágico associado à acidente ofídico por serpente do gênero bothrops: relato de caso Hemorrhagic stroke related to snakebite by bothrops genus: a case report

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Amanda Silva Machado

2010-10-01

Full Text Available Este trabalho tem como objetivo relatar um caso de acidente vascular cerebral hemorrágico, associado à acidente ofídico por serpente do gênero bothrops e hipertensão arterial sistêmica grave. Apesar do ofidismo botrópico ser frequente no Estado do Pará, tais associações são incomuns, necessitando de uma abordagem especializada e precoce, visando menores complicações.This research reports a clinical case of hemorrhagic stroke due to envenomation by bothrops snakebite associated with severe hypertension. Although bothrops snakebites are frequent in the State of Pará, such associations are uncommon, requiring specialized and early management to avoid severe complications.

Biochemical and hematological study of goats envenomed with natural and 60Co-irradiated bothropic venom

International Nuclear Information System (INIS)

Lucas de Oliveira, P.C.; Madruga, R.A.; Barbosa, N.P.U.; Sakate, M.

2007-01-01

Venoms from snakes of the Bothrops genus are proteolytic, coagulant, hemorrhagic and nephrotoxic, causing edema, necrosis, hemorrhage and intense pain at the bite site, besides systemic alterations. Many adjuvants have been added to the venom used in the sensitization of antiserum-producer animals to increase antigenic induction and reduce the envenomation pathological effects. Gamma radiation from 60 Co has been used as an attenuating agent of the venoms toxic properties. The main objective was to study, comparatively, clinical and laboratory aspects of goats inoculated with bothropic (Bothrops jararaca) venom, natural and irradiated from a 60 Co source. Twelve goats were divided into two groups of six animals: GINV, inoculated with 0.5 mg/kg of natural venom; and GIIV, inoculated with 0.5 mg/kg of irradiated venom. Blood samples were collected immediately before and one, two, seven, and thirty days after venom injection. Local lesions were daily evaluated. The following exams were carried out: blood tests; biochemical tests of urea, creatinine, creatine kinase, aspartate amino-transferase and alanine amino-transferase; clotting time; platelets count; and total serum immunoglobulin measurement. In the conditions of the present experiment, irradiated venom was less aggressive and more immunogenic than natural venom. (author)

Antigenic cross-reactivity and immunogenicity of Bothrops venoms from snakes of the Amazon region.

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Furtado, Maria de Fátima D; Cardoso, Silvia Travaglia; Soares, Oscar Espellet; Pereira, Aparecida Pietro; Fernandes, Daniel Silva; Tambourgi, Denise Vilarinho; Sant'Anna, Osvaldo Augusto

2010-04-01

Snakebites are still a critical public health problem in developing countries or isolated areas. In Brazil, the North Region has a high distribution coefficient worsened by the significant number of eventually unreported cases, due to difficulties in access to health services, to the natural geographic barriers and the vast territory. In the Rio Negro area, the species Bothrops atrox, Bothrops brazili, Lachesis muta muta and Bothriopsis taeniata are thought to be the major species responsible for snakebites. The aim of this study was to qualitatively and quantitatively determine the antigenic cross-reactivity and expression of toxins and the immunogenicity of Bothrops venom species of the Amazon and to evaluate the general efficacy of the therapeutic sera. The in vivo assays demonstrated that the defibrinating activity of B. taeniata venom was absent but that the lethal and hemorrhagic properties were more intense than in the B. atrox venom. The results evidence venom variability among the two B. atrox populations from two distinct Amazonian regions, which may reveal a subjacent speciation process. The results point to new aspects that may guide the improvement of anti-Bothropic therapeutic serum. Copyright 2010 Elsevier Ltd. All rights reserved.

Isolation and Functional Characterization of an Acidic Myotoxic Phospholipase A2 from Colombian Bothrops asper Venom

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Silvia Posada Arias

2017-10-01

Full Text Available Myotoxic phospholipases A2 (PLA2 are responsible for many clinical manifestations in envenomation by Bothrops snakes. A new myotoxic acidic Asp49 PLA2 (BaCol PLA2 was isolated from Colombian Bothrops asper venom using reverse-phase high performance liquid chromatography (RP-HPLC. BaCol PLA2 had a molecular mass of 14,180.69 Da (by mass spectrometry and an isoelectric point of 4.4. The complete amino acid sequence was obtained by cDNA cloning (GenBank accession No. MF319968 and revealed a mature product of 124 amino acids with Asp at position 49. BaCol PLA2 showed structural homology with other acidic PLA2 isolated from Bothrops venoms, including a non-myotoxic PLA2 from Costa Rican B. asper. In vitro studies showed cell membrane damage without exposure of phosphatidylserine, an early apoptosis hallmark. BaCol PLA2 had high indirect hemolytic activity and moderate anticoagulant action. In mice, BaCol PLA2 caused marked edema and myotoxicity, the latter seen as an increase in plasma creatine kinase and histological damage to gastrocnemius muscle fibers that included vacuolization and hyalinization necrosis of the sarcoplasm.

Biochemical and hematological study of goats envenomed with natural and 60Co-irradiated bothropic venom

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Lucas de Oliveira, P.C.; Madruga, R.A.; Barbosa, N.P.U. [Uberaba School of Veterinary Medicine (UNIUBE), MG (Brazil)]. E-mail: pedrolucaso@uol.com.br; Sakate, M. [UNESP, Botucatu, SP (Brazil). School of Veterinary Medicine and Animal Husbandry

2007-07-01

Venoms from snakes of the Bothrops genus are proteolytic, coagulant, hemorrhagic and nephrotoxic, causing edema, necrosis, hemorrhage and intense pain at the bite site, besides systemic alterations. Many adjuvants have been added to the venom used in the sensitization of antiserum-producer animals to increase antigenic induction and reduce the envenomation pathological effects. Gamma radiation from {sup 60}Co has been used as an attenuating agent of the venoms toxic properties. The main objective was to study, comparatively, clinical and laboratory aspects of goats inoculated with bothropic (Bothrops jararaca) venom, natural and irradiated from a {sup 60}Co source. Twelve goats were divided into two groups of six animals: GINV, inoculated with 0.5 mg/kg of natural venom; and GIIV, inoculated with 0.5 mg/kg of irradiated venom. Blood samples were collected immediately before and one, two, seven, and thirty days after venom injection. Local lesions were daily evaluated. The following exams were carried out: blood tests; biochemical tests of urea, creatinine, creatine kinase, aspartate amino-transferase and alanine amino-transferase; clotting time; platelets count; and total serum immunoglobulin measurement. In the conditions of the present experiment, irradiated venom was less aggressive and more immunogenic than natural venom. (author)

Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

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Monique Silva Martines

Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

Topic utilization of sesquiterpene lactone from Milleria quinqueflora on treatment of bothropic envenomation in rabbits Uso tópico da lactona sesquiterpênica de Milleria quinqueflora no tratamento local da pele de coelhos após envenenamento botrópico experimental

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M.M. Melo

2005-08-01

Full Text Available Estudou-se o efeito terapêutico da lactona sesquiterpênica (SL, 4,15-Epoxy-miller-9-Z-enolide, na lesão local do envenenamento botrópico experimental. Utilizaram-se três grupos de coelhos inoculados com 1.0µg de veneno de Bothrops alternatus e tratados com solução NaCl (0,85% (grupo I, SL diluída em glicerol (0,5% (grupo II e SL diluída em vaselina (0,5% (grupo III. Todos os animais foram avaliados nos tempos 30min e 1, 2, 24, 30, 48, 54, 72, 96, 120 e 148h quanto ao grau de edema, diâmetro do halo hemorrágico e presença de necrose local. Os animais do grupo II apresentaram os menores valores de grau de edema e halo hemorrágico com desaparecimento em 54h. Apesar de a necrose ter ocorrido em todos os animais, o diâmetro também foi menor no grupo II, quando comparado com os outros grupos. A SL, extraída da Milleria quinqueflora, possui efeito antiinflamatório, que é importante no tratamento local do envenenamento botrópico.

Isotopic analysis of Bothrops atrox in Amazonian forest

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Martinez, M. G.; Silva, A. M.; Chalkidis, H.; de Oliveira Júnior, R. C.; Camargo, P. B.

2012-12-01

The poisoning of snakes is considered a public health problem, especially in populations from rural areas of tropical and subtropical countries. In Brazil, the 26,000 snakebites, 90% are of the genus Bothrops, and Bothrops atrox species predominant in the Amazon region including all the Brazilian Amazon. Research shows that using stable isotopes, we can verify the isotopic composition of tissues of animals that depend mainly on food, water ingested and inhaled gases. For this study, samples taken from Bothrops atrox (B. atrox), in forest using pitfall traps and fall ("Pitt-fall traps with drift fence"). The analyzes were performed by mass spectrometry, where the analytical error is 0.3‰ for carbon and 0.5‰ to nitrogen. The results of the forest animals are significantly different from results of animal vivarium. The average values of the tissues and venoms of snakes of the forest for carbon-13 and nitrogen-15 are: δ13C = -24.68‰ and δ15N = 14.22‰ and mean values of tissue and poisons snakes vivarium (Instituto Butantan) to carbon-13 and nitrogen-15 are δ13C = -20.47‰ and δ15N = 8.36‰, with a significantly different due to different sources of food animals. Based on all results isotopic δ13C and δ15N, we can suggest that changes as the power of the serpent, (nature and captivity), changes occur in relation to diet and environment as the means of the isotopic data are quite distinct, showing that these changes can also cause metabolic changes in the body of the animal itself and the different periods of turnover of each tissue analyzed.

Determination of inorganic elements in blood of mice immunized with Bothrops Snake venom using XRF and NAA

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Lopes da Silva, L. F. F.; Zamboni, C. B.; Bahovschi, V.; Metairon, S.; Suzuki, M. F.; Sant'Anna, O. A.; Rizzutto, M. A.

2015-07-01

In this work, mice genetically modified [HIII line] were immunized against different Bothrops snake venoms to produce anti-Bothrops serum (antivenom). The Neutron Activation Analysis (NAA) and Energy Dispersive X-Ray Fluorescence (EDXRF) techniques were used to evaluate Ca and Fe concentrations in blood of these immunized mice in order to establish a potential correlation between both phenotypes: antibody response and blood constituents after Bothrops venom administration. The results were compared with the control group (mice not immunized) and with human being estimative. These data are important for clinical screening of patients submitted to immunological therapy as well as the understanding of the envenoming mechanisms.

Determination of inorganic elements in blood of mice immunized with Bothrops Snake venom using XRF and NAA

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Da Silva, L F F Lopes; Zamboni, C B; Bahovschi, V; Metairon, S; Suzuki, M F; Sant' Anna, O A; Rizzutto, M A

2015-01-01

In this work, mice genetically modified [H III line] were immunized against different Bothrops snake venoms to produce anti-Bothrops serum (antivenom). The Neutron Activation Analysis (NAA) and Energy Dispersive X-Ray Fluorescence (EDXRF) techniques were used to evaluate Ca and Fe concentrations in blood of these immunized mice in order to establish a potential correlation between both phenotypes: antibody response and blood constituents after Bothrops venom administration. The results were compared with the control group (mice not immunized) and with human being estimative. These data are important for clinical screening of patients submitted to immunological therapy as well as the understanding of the envenoming mechanisms. (paper)

Venomics and antivenomics of Bothrops erythromelas from five geographic populations within the Caatinga ecoregion of northeastern Brazil.

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Jorge, Roberta Jeane B; Monteiro, Helena S A; Gonçalves-Machado, Larissa; Guarnieri, Míriam C; Ximenes, Rafael M; Borges-Nojosa, Diva M; Luna, Karla P de O; Zingali, Russolina B; Corrêa-Netto, Carlos; Gutiérrez, José María; Sanz, Libia; Calvete, Juan J; Pla, Davinia

2015-01-30

The Caatinga lancehead, Bothrops erythromelas, is a medically relevant species, responsible for most of the snakebite accidents in most parts of its distribution range in northeastern Brazil. The spectrum and geographic variability of its venom toxins were investigated applying a venomics approach to venom pools from five geographic areas within the Caatinga ecoregion. Despite its wide habitat, populations of B. erythromelas from Ceará, Pernambuco, Juazeiro, Paraiba, and Ilha de Itaparica exhibit highly conserved venom proteomes. Mirroring their compositional conservation, the five geographic venom pools also showed qualitatively and quantitatively overlapping antivenomic profiles against antivenoms generated in Vital Brazil (BR) and Clodomiro Picado (CR) Institutes, using different venoms in the immunization mixtures. The paraspecificity exhibited by the Brazilian SAB and the Costa Rican BCL antivenoms against venom toxins from B. erythromelas indicates large immunoreactive epitope conservation across genus Bothrops during the last ~14 million years, thus offering promise for the possibility of generating a broad-spectrum bothropic antivenom. Biological Significance Accidental snakebite envenomings represent an important public health hazard in Brazil. Ninety per cent of the yearly estimated 20-30,000 snakebite accidents are caused by species of the Bothrops genus. Bothrops erythromelas, a small, moderately stocky terrestrial venomous snake, is responsible for most of the snakebite accidents in its broad distribution range in the Caatinga, a large ecoregion in northeastern Brazil. To gain a deeper insight into the spectrum of medically important toxins present in the venom of the Caatinga lancehead, we applied a venomics approach to define the proteome and geographic variability of adult B. erythromelas venoms from five geographic regions. Although intraspecific compositional variation between venoms among specimens from different geographic regions has long been

An overview of Bothrops erythromelas venom

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Nery,Neriane Monteiro; Luna,Karla Patrícia; Fernandes,Carla Freire Celedônio; Zuliani,Juliana Pavan

2016-01-01

Abstract This review discusses studies on the venom of Bothrops erythromelas published over the past 36 years. During this period, many contributions have been made to understand the venomous snake, its venom, and its experimental and clinical effects better. The following chronological overview is based on 29 articles that were published between 1979 and 2015, with emphasis on diverse areas. The complexity of this task demands an integration of multidisciplinary research tools to study toxin...

Immunological assessment of mice hyperimmunized with native and Cobalt-60-irradiated Bothrops venoms

International Nuclear Information System (INIS)

Ferreira Junior, R.S.; Meira, D.A.; Martinez, J.C.

2005-01-01

ELISA was used to evaluate, accompany, and compare the humoral immune response of Swiss mice during hyperimmunization with native and Cobalt-60-irradiated ( 60 Co) venoms of Bothrops jararaca, Bothrops jararacussu and Bothrops moojeni. Potency and neutralization were evaluated by in vitro challenges. After hyperimmunization, immunity was observed by in vivo challenge, and the side effects were assessed. The animals immunization with one LD50 of each venom occurred on days 1, 15, 21, 30, and 45, when blood samples were collected; challenges happened on the 60th day. Results showed that ELISA was efficient in evaluating, accompanying and comparing mouse immune response during hyperimmunization. Serum titers produced with natural venom were similar to those produced with irradiated venom. Immunogenic capacity was maintained after 60 Co-irradiation. The sera produced with native venom showed neutralizing potency and capacity similar to those of the sera produced with irradiated venom. All antibodies were able to neutralize five LD50 from these venoms. Clinical alterations were minimum during hyperimmunization with irradiated venom, however, necrosis and death occurred in animals inoculated with native venom. (author)

Quantitative evaluation of blood elements by neutron activation analysis in mice immunized with Bothrops snake venoms

International Nuclear Information System (INIS)

Zamboni, C.B.; Metairon, S.; Suzuki, M.F.; Furtado, M.F.; Sant'Anna, O.A.; Tambourgi, D.V.

2009-01-01

Mice genetically selected for high antibody responsiveness (HIII) were immunized against different Bothrops species snake venoms from distinct region of Brazil. The Neutron Activation Analysis technique was used to evaluate the whole blood concentrations of elements of clinical relevance [Ca, Cl, K, Mg and Na] in order to establish a potential correlation between antibody response and blood constituents after Bothrops venom administration for clinical screening of envenomed patients. (author)

Trichomoniasis in Bothrops jararaca (serpentes, viperidae

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F. C. Vilela

2003-01-01

Full Text Available We describe a case of trichomoniasis in a Bothrops jararaca (Serpentes, Viperidae donated to the Center for the Study of Venoms and Venomous Animals - CEVAP/UNESP. The animal had diarrhea with great quantity of flagellated protozoa in the feces. Microscopic examination of fecal smears stained with Giemsa revealed the presence of trichomonads, morphologically similar to Trichomonas acosta. Trichomonads were not detected in fecal exams after treatment with a single dose of 40 mg/kg metronidazole (Flagyl®.

Variação anual do sistema reprodutor de fêmeas de Bothrops jararaca (Serpentes, Viperidae Annual variation of the reproductive system in females of Bothrops jararaca (Serpentes, Viperidae

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Thélia R. F. Janeiro-Cinquini

2004-09-01

Full Text Available The morphological changes of the ovary and oviduct of 238 tropical snakes Bothrops jararaca (Wied, 1824 were determined. The ovarian mass presented a remarkable decrease in October, after ovulation, staying in low levels from November to March, during the gestational period. From April to September, it increased because of the ovarian follicles maturation. A gradual increase in oviduct weight was observed from October to March due to stages of embryonic development. A significant difference was observed between right and left ovary weight, and oviduct length, independently of the months considered.

Unmasking Snake Venom of Bothrops leucurus: Purification and Pharmacological and Structural Characterization of New PLA2 Bleu TX-III

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Marangoni, Fábio André; Ponce-Soto, Luis Alberto; Marangoni, Sergio; Landucci, Elen Cristina Teizem

2013-01-01

Bleu TX-III was isolated from Bothrops leucurus snake venom on one-step analytical chromatography reverse phase HPLC, was homogeneous on SDS-PAGE, and was confirmed by Q-Tof Ultima API ESI/MS (TOF MS mode) mass spectrometry in 14243.8 Da. Multiple alignments of Bleu TX-III show high degree of homology with basic PLA2 myotoxins from other Bothrops venoms. Our studies on local and systemic myotoxicity “in vivo” reveal that Bleu TX-III is myotoxin with local but not systemic action due to the decrease in the plasmatic CK levels when Bleu TX-III is administrated by intravenous route in mice (dose 1 and 5 μg). And at a dose of 20 μg myotoxin behaves like a local and systemic action. Bleu TX-III induced moderate marked paw edema, evidencing the local increase in vascular permeability. The inflammatory events induced in the mice (I.M.) were investigated. The increase in the levels of IL-1, IL-6, and TNF-α was observed in the plasma. It is concluded that Bleu TX-III induces inflammatory events in this model. The enzymatic phospholipid hydrolysis may be relevant to these phenomena. Bothrops leucurus venom is still not extensively explored, and the knowledge of its toxins separately through the study of structure/function will contribute for a better understanding of its action mechanism. PMID:23509815

Antiparasitic effects induced by polyclonal IgY antibodies anti-phospholipase A2 from Bothrops pauloensis venom.

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Borges, Isabela Pacheco; Silva, Mariana Ferreira; Santiago, Fernanda Maria; de Faria, Lucas Silva; Júnior, Álvaro Ferreira; da Silva, Rafaela José; Costa, Mônica Soares; de Freitas, Vitor; Yoneyama, Kelly Aparecida Geraldo; Ferro, Eloísa Amália Vieira; Lopes, Daiana Silva; Rodrigues, Renata Santos; de Melo Rodrigues, Veridiana

2018-06-01

Activities of phospholipases (PLAs) have been linked to pathogenesis in various microorganisms, and implicated in cell invasion and so the interest in these enzymes as potential targets that could contribute to the control of parasite survival and proliferation. Chicken eggs immunized with BnSP-7, a Lys49 phospholipase A 2 (PLA 2 ) homologue from Bothrops pauloensis snake venom, represent an excellent source of polyclonal antibodies with potential inhibitory activity on parasite PLA s. Herein, we report the production, characterization and anti-parasitic effect of IgY antibodies from egg yolks of hens immunized with BnSP-7. Produced antibodies presented increasing avidity and affinity for antigenic toxin epitopes throughout immunization, attaining a plateau after 4weeks. Pooled egg yolks-purified anti-BnSP-7 IgY antibodies were able to specifically recognize different PLA 2 s from Bothrops pauloensis and Bothrops jararacussu venom. Antibodies also neutralized BnSP-7 cytotoxic activity in C2C12 cells. Also, the antibodies recognized targets in Leishmania (Leishmania) amazonensis and Toxoplasma gondii extracts by ELISA and immunofluorescence assays. Anti-BnSP-7 IgY antibodies were cytotoxic to T. gondii tachyzoite and L. (L.) amazonensis promastigotes, and were able to decrease proliferation of both parasites treated before infection. These data suggest that the anti-BnSP-7 IgY is an important tool for discovering new parasite targets and blocking parasitic effects. Copyright © 2018 Elsevier B.V. All rights reserved.

The distribution and elimination of Bothrops erythromelas venom labeled with 131 I after intravenous injection in mice

International Nuclear Information System (INIS)

Rocha, M.L.

1999-01-01

Pharmacokinetic studies can be used to study the systemic effects of snake venoms and to develop standard serotherapy protocols for envenomation. Bothrops erythromelas is probably responsible for most of the snakebite in Pernambuco. The objective of this study was to investigate the pharmacokinetics of B. erythromelas venom (BeV) in mice, and to evaluate the efficacy of bothropic antivenom. BeV showed bicompartmental distribution in the blood of the experimental animals. (author)

Naa Technique for Clinical Investigation of Mice Immunized with BOTHROP Venom

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Zamboni, C. B.; Aguiar, R. O.; Kovacs, L.; Suzuki, M.; Sant'Anna, O. A.

2009-06-01

In the present study Neutron Activation Analysis (NAA) technique was used to determine sodium concentration in whole blood of mice immunized with Bothrops venom. With this value it was possible to perform clinical investigation in this animal model using whole blood.

Purification of phospholipase A2 from Bothrops atrox venom

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B. Quevedo

1999-01-01

Full Text Available Phospholipase A2 (PLA2 from Bothrops atrox (Sensu lato venom, from Chiriguaná (Colombia was purified using exclusión chromatography on Sephadex G-75, obtaining five fractions one of which showed phospholipase A2 activity. After further purification on Mono S cationic exchange column, eight fractions with PLA2 activity, measured using the hemolytic method, were obtained.

Postprandial thermogenesis in Bothrops moojeni (Serpentes: Viperidae

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DR Stuginski

2011-01-01

Full Text Available Snakes that can ingest prey that are proportionally large have high metabolic rates during digestion. This great increase in metabolic rate (specific dynamic action - SDA may create a significant augment in the animal's body temperature. The present study investigated postprandial thermogenesis in Bothrops moojeni. Briefly, two groups of snakes were fed meals equivalent to 17 ± 3% and 32 ± 5% of their body weight and were observed for 72 hours, in which thermal images of each snake were taken with an infrared camera in a thermostable environment with a constant air temperature of 30°C. The results showed a significant increase in snake surface temperature, with a thermal peak between 33 and 36 hours after feeding. The meal size had a great impact on the intensity and duration of the thermogenic response. Such increase in temperature appears to be connected with the huge increase in metabolic rates during digestion of relatively large prey by snakes that feed infrequently. The ecologic implication of the thermogenic response is still not well understood; however, it is possible that its presence could affect behaviors associated with the snake digestion, such as postprandial thermophily.

Protistas "incerta sedis" de ofídios do Brasil: Toddia França, 1912 e Pirhemocyton Chatton & Blanc, 1914: estudo comparativo "Incerta sedis" Portists from Brazilian snakes: Toddia França, 1912 and Pirhemocyton Chatton & Blanc, 1914: comparative study

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Maria Auxiliadora de Sousa

1973-01-01

Full Text Available Dentre 683 serpentes procedentes de diferentes pontos do Brasil, 16 (2,4% apresentaram em seu sangue (em glóbulos vermelhos maturos e imaturos Toddia ou Pirhemocyton. Denominamos provisoriamente Toddia os parasitos encontrados em Bothrops moojeni, B. pradoi, B. jararaca e Chironius flavolineatus e Pirhemocyton os encontrados em B. alternatus; fornecemos a primeira referência nestes hospedeiros. Estes parasitos foram estudados comparativamente com o objetivo de estabelecermos a extensão de suas afinidades. Com Toddia de B. moojeni realizamos técnica citoquímica para caracterização de ácidos nucleicos e encontramos positividade apenas para DNA. As maiores afinidades entre os parasitos estudados residiam nas características dos corpúsculos cromáticos e alterações celulares que determinam; observarmos quase total identidade nas maneiras como os parasitos da mesma espécie de serpente se apresentaram. Constatamos a coexistência de inclusões globóides, cristalóides e formas intermediárias associada aos parasitos de B. pradoi e B. alternatus; em C. flavolineatus encotnramos além dos cristais, raríssimas formas intermediárias entre estes e globóides. Afinidades entre Toddia e Pirhemocyton abrangendo o tipo de inclusão contrariam as descrições originais, tornando pouco válida esta separação genérica. Discutimos também os fundamentos da criação das espécies e a possível natureza virótica destes parasitos.Among 683 snakes from several localities of Brazil, 16 (2,4% presented in their blood (in mature or immature red cells Toddia or Pirhemocyton. We named provisorily Toddia the parasites found in Bothrops moojeni, B. pradoi, B. jararaca and Chironius flavolineatus and Pirhemocyton those found in B. alternatus; we give the first reference in these hosts. These parasites were comparatively studied in view to establish the range of their relationship. With Toddia from B. moojeni we attempted nucleic acids by cytochemical

The distribution and elimination of Bothrops erythromelas venom labeled with {sup 131} I after intravenous injection in mice

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Rocha, M.L. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Zoologia]. E-mail: rocha@cascavel.uefs.br

1999-07-01

Pharmacokinetic studies can be used to study the systemic effects of snake venoms and to develop standard serotherapy protocols for envenomation. Bothrops erythromelas is probably responsible for most of the snakebite in Pernambuco. The objective of this study was to investigate the pharmacokinetics of B. erythromelas venom (BeV) in mice, and to evaluate the efficacy of bothropic antivenom. BeV showed bicompartmental distribution in the blood of the experimental animals. (author)

Características biológicas e inmunológicas del veneno de Bothrops cotiara (Serpentes: Viperidae

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Adolfo Rafael de Roodt

2006-09-01

Full Text Available Bothrops cotiara es una serpiente que se encuentra en la provincia de Misiones (Argentina, el Sur de Brasil y Paraguay. La información sobre las características clínicas de los accidentes por esta serpiente es muy escasa y existen pocos datos sobre su veneno y la capacidad neutralizante de las actividades tóxicas del mismo por antivenenos terapéuticos. En este trabajo se estudiaron características bioquímicas, actividades tóxicas y la reactividad inmunoquímica del veneno de B. cotiara. Seis antivenenos anti Viperinos Sudamericanos fueron estudiados frente a este veneno por el método ELISA y se probó la capacidad neutralizante de tres de estos frente a las actividades hemorrágica, necrotizante, procoagulante, trombina-símil, hemolítica indirecta y la potencia letal de veneno de ejemplares de B. cotiara de la provincia de Misiones. Los patrones cromatográficos y electroforéticos mostraron características similares a los de otros venenos de Bothrops. Las actividades tóxicas estuvieron dentro de los ámbitos descritos para los venenos botrópicos. Los seis antivenenos mostraron gran reactividad inmunoquímica por ELISA y las potencias neutralizantes de los tres estudiados fueron muy próximas para las actividades letal, hemorrágica, necrotizante, hemolítica indirecta, coagulante y trombina-símil. Los resultados de los estudios de neutralización indicarían que ante la mordedura de esta poco común especie de Bothrops, pueden usarse los diferentes tipos de antivenenos botrópicos o botrópico-crotálicos para uso terapéutico disponibles en esa región.Biological and immunological characteristics of the poison of Bothrops cotiara (Serpentes: Viperidae. Bothrops cotiara is a venomous snake sporadically found in the province of Misiones in Argentina, South of Brazil and Paraguay. Data on the clinics of the envenomation produced by its bite and on its venom are scarce. There is no information on the neutralizing capacity of the

Accidents caused by Bothrops and Bothropoides in the State of Paraiba: epidemiological and clinical aspects.

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Oliveira, Fagner Neves; Brito, Monalisa Taveira; Morais, Isabel Cristina Oliveira de; Fook, Sayonara Maria Lia; Albuquerque, Helder Neves de

2010-01-01

Bothrops and Bothropoides snakes cause 70% of the ophidic accidents in Brazil. The species that cause ophidic accidents in State of Paraíba are Bothropoides erythromelas, Bothrops leucurus and Bothropoides neuwiedi. This is a prospective and transverse study, following a quantitative approach of accidents involving Bothrops and Bothropoides admitted to the Toxicological Assistance and Information Centers of Campina Grande and João Pessoa (Ceatox-CG and Ceatox-JP), aimed at identifying the epidemiological and clinical profile of such accidents. All of the patients admitted had medical diagnoses and were monitored at Ceatox-CG or Ceatox-JP. The genera Bothrops and Bothropoides caused 91.7% of the ophidic accidents reported. Snake bites were frequent in men (75.1%), rural workers (65.1%), literate individuals (69%) between 11 and 20 years-old (21.7%), and toes the most common area attacked (52.7%). Most (86.6%) patients were admitted within 6 hours after the accident/bite, with a predominance of mild cases (64.6%). The annual occurrence in Paraíba was 5.5 accidents/100,000 inhabitants and lethality was 0.2%. Positive changes in the profiles of these accidents were verified, such as the non-application of inadequate solutions, including the use of tourniquet, coffee grounds, garlic, suction and/or cutting the bitten area. Moreover, the Itinerant Laboratory project, linked to Paraíba State University in partnership with Ceatox-CG, has contributed positively, providing several cities of the state with information regarding the prevention of accidents involving venomous animals. The local press has also contributed, reporting the educational work developed by the centers.

Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation.

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Nikele Nadur-Andrade

2016-10-01

Full Text Available Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv, as well as the mechanisms involved was investigated.Bmv (1 μg was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT.These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.

Inactivation and fragmentation of lectin from Bothrops leucurus snake venom by gamma irradiation

International Nuclear Information System (INIS)

Nunes, E.S.; Souza, M.A.A.; Vaz, A.F.M.; Coelho, L.C.B.B.; Aguiar, J.S.; Silva, T.G.; Guarnieri, M.C.; Melo, A.M.M.A.; Oliva, M.L.V.; Correia, M.T.S.

2012-01-01

Gamma radiation alters the molecular structure of biomolecules and is able to mitigate the action of snake venoms and their isolated toxins. The effect of γ-radiation on the folding of Bothrops lecurus venom lectin was measured by a hemagglutinating assay, intrinsic and bis-ANS fluorescence. Intrinsic and bis-ANS fluorescence analyses indicated that irradiation caused unfolding followed by aggregation of the lectin. Our results suggest that irradiation can lead to significant changes in the protein structure, which may promote the loss of its binding property and toxic action. - Highlights: ► Gamma radiation alters the molecular structure of biomolecules. ► The radiation has been able to mitigate snake venoms and its isolated toxins. ► Our aim was to evaluate the effects of radiation in Bothrops lecurus venom lectin. ► The irradiation acts as a detoxification strategy in snake venoms.

ENVENENAMIENTO OFIDICO POR EL GENERO Bothrops COMPLICADO CON MIOCARDIOPATIA TÓXICA: A PROPOSITO DE UN CASO.

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Sajar Abusaid Palomo

2014-12-01

Full Text Available El envenenamiento ofídico en Venezuela es un problema de salud pública, afectando a agricultores y mineros, implicada con mayor frecuencia la familia Viperidae, genero Bothrops. Presenta clínica variable, desde manifestaciones locales hasta sistémicas. Paciente femenina de 40 años, agricultora, consulta por dolor y aumento de volumen en cara lateral de pie izquierdo por envenenamiento ofídico. Acude a ambulatorio de su localidad, 24 horas después es trasladada al Hospital Universitario Ruiz y Páez, ingresando con diagnóstico de Envenenamiento Ofídico por Bothrops. Evoluciona tórpidamente presentando Insuficiencia Renal Aguda en terapia de hemodiálisis, Sepsis punto de partida respiratorio, Insuficiencia Respiratoria Aguda y Miocardiopatía Tóxica, por lo que ingresa a Unidad de Cuidados Intensivos y Cuidados Coronarios. Luego de marcada mejoría clínica es dada de alta. El envenenamiento ofídico por Bothrops corresponde 80% de los accidentes por mordeduras de serpientes, su pronóstico depende de la especie, atención medica-hospitalaria, el intervalo de tiempo ocurrido y el uso de la terapia antiofídica especifica.

Ocorrência de Hepatozoon spp. (Apicomplexa, Hepatozoidae em serpentes do gênero Bothrops de cativeiro Occurrence of Hepatozoon spp. (Apicomplexa, Hepatozoidae in snakes of genus Bothrops in captivity

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V. Glaser

2008-10-01

Full Text Available The occurrence of Hepatozoon gamont in the blood cells of Bothrops jararaca and B. jararacussu in captivity was analyzed. The prevalence of infection by Hepatozoon spp. was 50% and few erythrocytes contained the gamonts. Results suggest that the infection by Hepatozoon spp. occurred in the natural environment or after the captivity.

The influence of circadian rhythms on the metabolism of the snake Bothrops jararaca (Serpentes, Viperidae = A influência dos ritmos circadianos no metabolismo da serpente Bothrops jararaca (Serpentes, Viperidae

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José Geraldo Pereira da Cruz

2008-07-01

Full Text Available The thermoregulatory activity has led to an extensive search for correlations between physiological variables, including metabolic functions, and the ideal level of body temperature. Snakes were also often seen basking, when their body temperatures were relatively independent of ambient temperature, indicating successful thermoregulation. Bothrops jararaca were exposed to two different ambient temperatures (20 and 30oC over a time course of three weeks and oxygen consumption and body temperature were measured. The snakes exhibited a freerunning rhythm of body temperature. Metabolic rate wasincreased at the same circadian phase as the increase in body temperature in the 30oC. The increase of body temperature and oxygen consumption of B. jararaca occurs in the scotophase of the photoperiod, consistent with that of nocturnal species. However, prior to a scotophase period the snakes under 20oC maintain body temperature and oxygen consumption at higher levels during the day. These results demonstrate for the first time that ectothermic animals may display physiologically generated circadian rhythms of bodytemperature similar to those recorded in endotherms. Circadian rhythms allow animals to anticipate environmental changes: physiological parameters such as body temperature andmobilization of energy reserves have to be adjusted before the expected environmental changes actually take place.A atividade termorreguladora conduziu a uma busca extensiva para o entendimento das correlações entre as variáveis fisiológicas, incluindo as funções metabólicas e a temperatura corporal. Frequentes observações mostram que algumas serpentes podem se aquecer, sendo este aumento de temperatura independente da temperatura ambiente, indicando a termorregulação bem sucedida. Bothrops jararaca foramexpostas a dois ambientes com diferentes temperaturas (20 e 30oC durante três semanas, sendo mensuradas a temperatura corporal e o consumo de oxigênio. O aumento

Screening of Bothrops snake venoms for L-amino acid oxidase activity

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Pessati, M.L.; Fontana, J.D.; Guimaraes, M.F. [Federal Univ. of Parana, Curitiba (Brazil)

1995-12-31

Toxins, enzymes, and biologically active peptides are the main components of snake venoms from the genus Bothrops. Following the venom inoculation, the local effects are hemorrhage, edema, and myonecrosis. Nineteen different species of Brazilian Bothrops were screened for protein content and L-amino acid oxidase activity. B. cotiara, formerly found in the South of Brazil, is now threatened with extinction. Its venom contains a highly hemorrhagic fraction and, as expected from the deep yellow color of the corresponding lyophilized powder, a high L-amino acid oxidase (LAO) activity was also characterized. Flavin adenine dinucleotide (FAD) is its associate coenzyme. B. cotiara venom LAO catalyzed the oxidative deamination of several L-amino acids, and the best substrates were methionine, leucine, tryptophan, and phenylalanine, hence, its potential application for the use in biosensors for aspartame determination and for the removal of amino acids from plasma. High levels for LAO were also found in other species than B. cotiara. In addition, the technique of isoelectric focusing (IEF) was employed as a powerful tool to study the iso- or multi-enzyme distribution for LAO activity in the B. cotiara snake venom.

ACUTE KIDNEY INJURY CAUSED BY Crotalus AND Bothrops SNAKE VENOM: A REVIEW OF EPIDEMIOLOGY, CLINICAL MANIFESTATIONS AND TREATMENT

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Polianna L.M.M. Albuquerque

2013-09-01

Full Text Available SUMMARY Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents.

ACUTE KIDNEY INJURY CAUSED BY Crotalus AND Bothrops SNAKE VENOM: A REVIEW OF EPIDEMIOLOGY, CLINICAL MANIFESTATIONS AND TREATMENT

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Albuquerque, Polianna L.M.M.; Jacinto, Camilla N.; Silva, Geraldo B.; Lima, Juliana B.; Veras, Maria do Socorro B.; Daher, Elizabeth F.

2013-01-01

SUMMARY Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI) appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents. PMID:24037282

Occurrence of Hepatozoon spp. (Apicomplexa, Hepatozoidae) in snakes of genus Bothrops in captivity

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Glaser, V.; Boni, A.P.; Albuquerque, C.A.C.

2008-01-01

The occurrence of Hepatozoon gamont in the blood cells of Bothrops jararaca and B. jararacussu in captivity was analyzed. The prevalence of infection by Hepatozoon spp. was 50% and few erythrocytes contained the gamonts. Results suggest that the infection by Hepatozoon spp. occurred in the natural environment or after the captivity.

Insuficiencia renal aguda inducida por mordedura de serpiente Bothrops

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Gustavo A. Aroca Martínez

2014-01-01

Full Text Available Mujer de 58 años de edad, remitida a urgencias por presentar cuadro clínico de insuficiencia renal aguda (IRA secundaria a mordedura de serpiente (Bothrops Atrox. Ingresa hipotensa con elevación de azoados e hiperkalemia, ecografía renal dentro de parámetros normales. Se maneja terapia dialítica con lo cual presenta mejoría clínica. En este reporte se detallan aspectos del diagnóstico, manejo clínico y posibles mecanismos fisiopatológicos que explican el daño renal.

Snake Venomics and Antivenomics of Bothrops diporus, a Medically Important Pitviper in Northeastern Argentina

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Gay, Carolina; Sanz, Libia; Calvete, Juan J.; Pla, Davinia

2015-01-01

Snake species within genus Bothrops are responsible for more than 80% of the snakebites occurring in South America. The species that cause most envenomings in Argentina, B. diporus, is widely distributed throughout the country, but principally found in the Northeast, the region with the highest rates of snakebites. The venom proteome of this medically relevant snake was unveiled using a venomic approach. It comprises toxins belonging to fourteen protein families, being dominated by PI- and PIII-SVMPs, PLA2 molecules, BPP-like peptides, L-amino acid oxidase and serine proteinases. This toxin profile largely explains the characteristic pathophysiological effects of bothropic snakebites observed in patients envenomed by B. diporus. Antivenomic analysis of the SAB antivenom (Instituto Vital Brazil) against the venom of B. diporus showed that this pentabothropic antivenom efficiently recognized all the venom proteins and exhibited poor affinity towards the small peptide (BPPs and tripeptide inhibitors of PIII-SVMPs) components of the venom. PMID:26712790

Neuromuscular activity of Bothrops fonsecai snake venom in vertebrate preparations

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Fernandes, Carla T; Giaretta, Vânia MA; Prudêncio, Luiz S; Toledo, Edvana O; da Silva, Igor RF; Collaço, Rita CO; Barbosa, Ana M; Hyslop, Stephen; Rodrigues-Simioni, Léa; Cogo, José C

2014-01-01

The neuromuscular activity of venom from Bothrops fonsecai, a lancehead endemic to southeastern Brazil, was investigated. Chick biventer cervicis (CBC) and mouse phrenic nerve-diaphragm (PND) preparations were used for myographic recordings and mouse diaphragm muscle was used for membrane resting potential (RP) and miniature end-plate potential (MEPP) recordings. Creatine kinase release and muscle damage were also assessed. In CBC, venom (40, 80 and 160μg/ml) produced concentration- and time-dependent neuromuscular blockade (50% blockade in 85±9 min and 73±8 min with 80 and 160μg/ml, respectively) and attenuated the contractures to 110μM ACh (78–100% inhibition) and 40mM KCl (45–90% inhibition). The venom-induced decrease in twitch-tension in curarized, directly-stimulated preparations was similar to that in indirectly stimulated preparations. Venom (100 and 200μg/ml) also caused blockade in PND preparations (50% blockade in 94±13 min and 49±8 min with 100 and 200μg/ml, respectively) but did not alter the RP or MEPP amplitude. In CBC, venom caused creatine kinase release and myonecrosis. The venom-induced decrease in twitch-tension and in the contractures to ACh and K+ were abolished by preincubating venom with commercial antivenom. These findings indicate that Bothrops fonsecai venom interferes with neuromuscular transmission essentially through postsynaptic muscle damage that affects responses to ACh and KCl. These actions are effectively prevented by commercial antivenom. PMID:25028603

Bothrops jararaca venom metalloproteinases are essential for coagulopathy and increase plasma tissue factor levels during envenomation.

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Karine M Yamashita

2014-05-01

Full Text Available BACKGROUND/AIMS: Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF, resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a whether TF and protein disulfide isomerase (PDI, an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b the involvement and significance of snake venom metalloproteinases (SVMP and serine proteinases (SVSP to hemostatic disturbances. METHODS/PRINCIPAL FINDINGS: Crude Bothrops jararaca venom (BjV was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. CONCLUSIONS: SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in

Vellozia flavicans Mart. ex Schult. hydroalcoholic extract inhibits the neuromuscular blockade induced by Bothrops jararacussu venom.

Science.gov (United States)

Tribuiani, Natália; da Silva, Alexandro Mateus; Ferraz, Miriéle Cristina; Silva, Magali Glauzer; Bentes, Ana Paula Guerreiro; Graziano, Talita Signoreti; dos Santos, Marcio Galdino; Cogo, José Carlos; Varanda, Eliana Aparecida; Groppo, Francisco Carlos; Cogo, Karina; Oshima-Franco, Yoko

2014-02-08

Snakebite is a significant public health issue in tropical countries. In Brazil, some of the most common snake envenomations are from Bothrops. Bothrops bites trigger local and systemic effects including edema, pain, erythema, cyanosis, infections, and necrosis. Vellozia flavicans is a plant from the Brazilian "cerrado" (savanna) that is popularly used as an anti-inflammatory medicine. Since inflammation develops quickly after Bothrops bites, which can lead to infection, the aim of the present study was to observe possible anti-snake venom and antimicrobial activities of V. flavicans (Vf). The chromatographic profile of the main constituents from the Vf leaf hydroalcoholic extract was obtained by thin-layer chromatography (TLC). The anti-snake venom activity was measured by Vf's ability to neutralize the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu) in a mouse phrenic nerve-diaphragm model (PND). After a 20 min incubation, preparations of PND were added to Tyrode's solution (control); Vf (0.2, 0.5, 1, and 2 mg/mL); 40 μg/mL Bjssu; pre-incubation for 30 min with Bjssu and 1 mg/mL Vf; and a Bjssu pretreated preparation (for 10 min) followed by 1 mg/mL Vf. Myographic recording was performed, and the contractile responses were recorded. The antimicrobial activity (minimum inhibitory concentration [MIC] and minimum bactericidal concentration [MBC]) was obtained for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, using gentamicin and vancomycin as positive controls. TLC analysis yielded several compounds from Vf, such as flavonoids (quercetin) and phenolic acids (chlorogenic acid). Bjssu completely blocked the contractile responses of PND preparations, while Vf preserved 97% (±10%) of the contractile responses when incubated with Bjssu. In the PND pretreated with Bjssu, Vf was able to inhibit the neuromuscular blockade progress. MIC and MBC of Vf ranged from 2.5 to 5.0 mg/mL for P. aeruginosa

Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom

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S. F. Barros

1998-01-01

Full Text Available We have provided evidence that: (a lethality of mice to crude Bothrops venom varies according the isogenic strain (A/J > C57Bl/6 > A/Sn > BALB/c > C3H/ HePas > DBA/2 > C3H/He; (bBALB/c mice (LD50=100.0 μg were injected i.p. with 50 μg of venom produced IL-6, IL-10, INF-γ, TNF-α and NO in the serum. In vitro the cells from the mice injected and challenged with the venom only released IL-10 while peritoneal macrophages released IL-10, INF-γ and less amounts of IL-6; (c establishment of local inflammation and necrosis induced by the venom, coincides with the peaks of TNF-α, IFN-γ and NO and the damage was neutralized when the venom was incubated with a monoclonal antibody against a 60 kDa haemorrhagic factor. These results suggest that susceptibility to Bothrops a trox venom is genetically dependent but MHC independent; that IL-6, IL10, TNF-α, IFN-γ and NO can be involved in the mediation of tissue damage; and that the major venom component inducers of the lesions are haemorrhagins.

New findings from the first transcriptome of the Bothrops moojeni snake venom gland.

Science.gov (United States)

Amorim, Fernanda Gobbi; Morandi-Filho, Romualdo; Fujimura, Patricia Tieme; Ueira-Vieira, Carlos; Sampaio, Suely Vilela

2017-12-15

Snakebites are a serious health problem in tropical countries. In Brazil, the genus Bothrops (Viperidae family) causes most of the ophidic accidents, characterized by proteolysis and haemorrhage. Snake venoms are rich sources of toxins with great therapeutic and biotechnological potential and omics approaches is a valuable tool for identification of new bioactive components in the venom. In this study, we described the first transcriptome of the venom gland of Bothrops moojeni snake, using the next-generation sequencing with the Illumina platform. We identified: (i) 20 venom components classes, among which metalloproteases were the most expressed ones, followed by serine proteases and phospholipases; and (ii) the 33 full-length amino acid sequences of toxins that have never been reported before in B. moojeni venom, such as one cysteine-rich secretory protein (Moojin), two hyaluronidases (BmooHyal-1 and BmooHyal-2), and one three-finger toxin (Bmoo-3FTx). Altogether, the transcripts identified herein represent a starting point for the analysis of structure-function relationships of toxins, which shall help develop novel biological tools and therapeutic drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical poisoning in bovine the venom of Bothrops atrox the municipality of Oriximiná-Pará, Central Amazonia, Brazil - Case report

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Ubaldo de Almeida Farias Junior

2015-10-01

Full Text Available ABSTRACT. Farias Junior U. de A. & Chalkidis H.M. [Clinical poisoning in bovine the venom of Bothrops atrox the municipality of Oriximiná-Pará, Central Amazonia, Brazil - Case report.] Envenenamento clínico de bovino por peçonha de Bothrops atrox no município de Oriximiná-Pará, Amazô- nia Central, Brasil - Relato de caso. Revista Brasileira de Medicina Veterinária, 37(3:264-268, 2015. Laboratório de Pesquisas Zoológicas, Faculdades Integradas do Tapajós, Rua Rosa Vermelha, 335, Aeroporto Velho, Santarém, PA 68010-200, Brasil. E-mail: chalkidis@hotmail.com It explains a case of poisoning bovine by Bothrops atrox, abundant snake family Viperidae, prevalent in northern Brazil, assigned as the etiological agent of over 90% of cases of snakebite in the State of Pará. Report the examination semiological and the clinical symptoms observed due to its evolution as well. Clinical signs are confronted with the findings conferred in similar cases reported by veterinarians and ranchers in the region. The treatment in this particular case was not proceeded in order to examine symptoms presented by the accuracy of these reports.

Daño renal en ratas inducido por veneno de Bothrops neuwiedii diporus de Argentina Renal injury in rats poisoned by venom of Bothrops neuwiedii diporus from Argentina

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Patricia Koscinczuk

2004-08-01

Full Text Available La insuficiencia renal aguda es una de las complicaciones sistémicas más frecuentes después de un accidente ofídico. En este estudio se evalúan los efectos que el veneno de Bothrops neuwiedii diporus produce en el riñón de ratas machos de la cepa Wistar. La histopatología permitió comprobar el desarrollo de necrosis tubular aguda; las lesiones iniciales se observaron a las 3 horas de la inoculación de una dosis de 700 µg del veneno, observándose en corteza renal congestión y degeneración granulohialina de las células epiteliales tubulares, acompañadas de dilatación y cilindros hialinos en la luz tubular. A las 24 horas se presentó necrosis tubular aguda en una superficie extensa de la corteza sin daño de la membrana basal tubular. Las lesiones de degeneración turbia de células epiteliales tubulares, dilatación de la luz tubular y cilindros hialinos se mantuvieron presentes hasta las 4 semanas post-inoculación. Si bien los parámetros de la bioquímica clínica asociados con insuficiencia renal aguda aumentaron a las 6 horas de la administración del veneno (urea: 1.10±0.22 g/dl; creatinina: 19.60±1.51mg/dl, a la semana descendieron a valores normales. Las densidades urinarias, en cambio, a la semana se mantuvieron más bajas que lo normal, 1.005 ± 0.001 (pAcute renal failure is one of the systemic complications that can be found in bothropic accidents. In this study the effects on male Wistar rats induced by the venom of Bothrops neuwiedii diporus were evaluated. The histopathology revealed acute tubular necrosis, lesions firstly were observed 3 hours post inoculation of 700 µg of venom. Cortical kidney congestion and granulohialin degeneration of tubular epithelial cells were observed, these lesions achieved a maximum at 24 hours after inoculation. Tubular epithelial hidropic degeneration and dilatation of tubular lumen with hyalin casts were present inclusive up to 4 weeks after inoculation. Biochemical parameter

Filogenia e filogeografia do grupo Bothrops neuwiedi (Serpentes, Squamata)

OpenAIRE

Tais Machado

2015-01-01

O grupo Bothrops neuwiedi é composto por serpentes neotropicais que desempenham grande impacto na saúde pública, em decorrência de acidentes ofídicos. O grupo apresenta ampla distribuição ao longo da diagonal seca de formações abertas, desde o nordeste do Brasil até o noroeste da Argentina. A taxonomia atual, baseada principalmente em dados morfológicos qualitativos, não recupera as linhagens evolutivas apontadas pelas abordagens moleculares. O objetivo deste trabalho foi investigar o grupo B...

Proteomic identification of gender molecular markers in Bothrops jararaca venom.

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Zelanis, André; Menezes, Milene C; Kitano, Eduardo S; Liberato, Tarcísio; Tashima, Alexandre K; Pinto, Antonio F M; Sherman, Nicholas E; Ho, Paulo L; Fox, Jay W; Serrano, Solange M T

2016-04-29

Variation in the snake venom proteome is a well-documented phenomenon; however, sex-based variation in the venom proteome/peptidome is poorly understood. Bothrops jararaca shows significant sexual size dimorphism and here we report a comparative proteomic/peptidomic analysis of venoms from male and female specimens and correlate it with the evaluation of important venom features. We demonstrate that adult male and female venoms have distinct profiles of proteolytic activity upon fibrinogen and gelatin. These differences were clearly reflected in their different profiles of SDS-PAGE, two-dimensional electrophoresis and glycosylated proteins. Identification of differential protein bands and spots between male or female venoms revealed gender-specific molecular markers. However, the proteome comparison by in-solution trypsin digestion and label-free quantification analysis showed that the overall profiles of male and female venoms are similar at the polypeptide chain level but show striking variation regarding their attached carbohydrate moieties. The analysis of the peptidomes of male and female venoms revealed different contents of peptides, while the bradykinin potentiating peptides (BPPs) showed rather similar profiles. Furthermore we confirmed the ubiquitous presence of four BPPs that lack the C-terminal Q-I-P-P sequence only in the female venom as gender molecular markers. As a result of these studies we demonstrate that the sexual size dimorphism is associated with differences in the venom proteome/peptidome in B. jararaca species. Moreover, gender-based variations contributed by different glycosylation levels in toxins impact venom complexity. Bothrops jararaca is primarily a nocturnal and generalist snake species, however, it exhibits a notable ontogenetic shift in diet and in venom proteome upon neonate to adult transition. As is common in the Bothrops genus, B. jararaca shows significant sexual dimorphism in snout-vent length and weight, with females being

Microhabitat use by species of the genera Bothrops and Crotalus (Viperidae in semi-extensive captivity

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CA Gomes

2012-01-01

Full Text Available Many factors influence microhabitat including climate and the occurrence of predators, prey and suitable shelters. The influence of predators in a semi-extensive breeding system is minimized due to frequent monitoring of the area. This situation enables the independent analysis of such other variables as refuges and temperature. Some specimens of the Viperidae family are kept in a semi-extensive breeding system at the Butantan Institute for display and study. These animals are widely distributed in the Atlantic Forest and Cerrado, two biomes with distinct climatic characteristics. We compared the daily activity pattern and microhabitat use of the species Bothrops jararaca and Crotalus durissus terrificus. Our main questions were whether rattlesnakes and lancehead snakes respond to habitat selection differently in similar climatic conditions and if they choose similar microhabitats. Species of the genus Bothrops were frequently found under shelters regardless of the time of day. On the other hand, snakes of the genus Crotalus were frequently found sheltered during the early morning, then migrated to sunnier areas and returned to shelters in late afternoon.

Snake venomics of the Lesser Antillean pit vipers Bothrops caribbaeus and Bothrops lanceolatus: correlation with toxicological activities and immunoreactivity of a heterologous antivenom.

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Gutiérrez, José María; Sanz, Libia; Escolano, José; Fernández, Julián; Lomonte, Bruno; Angulo, Yamileth; Rucavado, Alexandra; Warrell, David A; Calvete, Juan J

2008-10-01

The venom proteomes of the snakes Bothrops caribbaeus and Bothrops lanceolatus, endemic to the Lesser Antillean islands of Saint Lucia and Martinique, respectively, were characterized by reverse-phase HPLC fractionation, followed by analysis of each chromatographic fraction by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. The venoms contain proteins belonging to seven ( B. caribbaeus) and five ( B. lanceolatus) types of toxins. B. caribbaeus and B. lanceolatus venoms contain phospholipases A 2, serine proteinases, l-amino acid oxidases and zinc-dependent metalloproteinases, whereas a long disintegrin, DC-fragments and a CRISP molecule were present only in the venom of B. caribbaeus, and a C-type lectin-like molecule was characterized in the venom of B. lanceolatus. Compositional differences between venoms among closely related species from different geographic regions may be due to evolutionary environmental pressure acting on isolated populations. The venoms of these two species differed in the composition and the relative abundance of their component toxins, but they exhibited similar toxicological and enzymatic profiles in mice, characterized by lethal, hemorrhagic, edema-forming, phospholipase A 2 and proteolytic activities. The venoms of B. caribbaeus and B. lanceolatus are devoid of coagulant and defibrinogenating effects and induce only mild local myotoxicity in mice. The characteristic thrombotic effect described in human envenomings by these species was not reproduced in the mouse model. The toxicological profile observed is consistent with the abundance of metalloproteinases, PLA 2s and serine proteinases in the venoms. A polyvalent (Crotalinae) antivenom produced in Costa Rica was able to immunodeplete approximately 80% of the proteins from both B. caribbaeus and B. lanceolatus venoms, and was effective in neutralizing the lethal, hemorrhagic, phospholipase

Eficacia experimental de anticuerpos IgY producidos en huevos, contra el veneno de la serpiente peruana Bothrops atrox Experimental efficacy of IgY antibodies produced in eggs against the venom of the Peruvian snake Bothrops atrox

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Julio C. Mendoza

2012-03-01

Full Text Available Objetivos. Desarrollar un protocolo de inmunización para producir inmunoglobulinas IgY de origen aviar contra el veneno de la serpiente peruana Bothrops atrox y evaluar la capacidad neutralizante. Materiales y métodos. Se inmunizaron seis gallinas de postura de la raza hy line brown con 500 μg/dosis de veneno de B. atrox en un periodo de dos meses. Cada semana, los huevos fueron colectados para el aislamiento de inmunoglobulinas IgY a partir de la yema, usando dos pasos consecutivos con αcido caprνlico y sulfato de amonio. La detecciσn de anticuerpos se realizσ por inmunodifusiσn doble mientras que el tνtulo y reactividad cruzada se determinaron por las técnicas de ELISA y Western blot. El cálculo de DL50 y de la DE50 del antiveneno IgY producido se realizó utilizando el método de Probits. Resultados. La masa de anticuerpos aislados fue de 8,5 ± 1,35 mg de IgY/mL de yema. Asimismo, la DE50 del antiveneno aviar fue calculada en 575 μL de antiveneno/mg de veneno. Adicionalmente, los ensayos de reactividad cruzada mostraron que el veneno de B. atrox comparte mas epνtopes comunes con el veneno de B. brazili (47% que con otros veneno del mismo género, en tanto que los venenos de Lachesis muta (19% y Crotalus durissus (12% mostraron una baja reactividad cruzada. Conclusiones. Se ha obtenido IgY purificada contra el veneno de B. atrox con capacidad neutralizante y se ha demostrado su utilidad como herramienta inmunoanalítica para evaluar la reactividad cruzada con venenos de otras especies.Objectives. To develop an immunization protocol in order to produce avian IgY immunoglobulins against Bothrops atrox Peruvian snake venom and to evaluate its neutralizing capacity. Materials and methods. Six Hy Line Brown hens were immunized each two weeks using 500μg/doses of B. atrox venom in a period of two months. Each week, eggs were collected for IgY isolation from yolk using two consecutive steps with caprilic acid and ammonium sulfate

Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart.

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Monteiro, D A; Kalinin, A L; Selistre-de-Araujo, H S; Vasconcelos, E S; Rantin, F T

2016-02-01

Alternagin-C (ALT-C) is a disintegrin-like protein purified from the venom of the snake, Rhinocerophis alternatus. Recent studies showed that ALT-C is able to induce vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, angiogenesis and to increase myoblast viability. This peptide, therefore, can play a crucial role in tissue regeneration mechanisms. The aim of this study was to evaluate the effects of a single dose of alternagin-C (0.5 mg kg(-1), via intra-arterial) on in vitro cardiac function of the freshwater fish traíra, Hoplias malabaricus, after 7 days. ALT-C treatment increased the cardiac performance promoting: 1) significant increases in the contraction force and in the rates of contraction and relaxation with concomitant decreases in the values of time to the peak tension and time to half- and 90% relaxation; 2) improvement in the cardiac pumping capacity and maximal electrical stimulation frequency, shifting the optimum frequency curve upward and to the right; 3) increases in myocardial VEGF levels and expression of key Ca(2+)-cycling proteins such as SERCA (sarcoplasmic reticulum Ca(2+)-ATPase), PLB (phospholamban), and NCX (Na(+)/Ca(2+) exchanger); 4) abolishment of the typical negative force-frequency relationship of fish myocardium. In conclusion, this study indicates that ALT-C improves cardiac function, by increasing Ca(2+) handling efficiency leading to a positive inotropism and chronotropism. The results suggest that ALT-C may lead to better cardiac output regulation indicating its potential application in therapies for cardiac contractile dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

ESI-MS/MS Identification of a Bradykinin-Potentiating Peptide from Amazon Bothrops atrox Snake Venom Using a Hybrid Qq-oaTOF Mass Spectrometer

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Coutinho-Neto, Antonio; Caldeira, Cleópatra A. S.; Souza, Gustavo H. M. F.; Zaqueo, Kayena D.; Kayano, Anderson M.; Silva, Rodrigo S.; Zuliani, Juliana P.; Soares, Andreimar M.; Stábeli, Rodrigo G.; Calderon, Leonardo A.

2013-01-01

A bradykinin-potentiating peptide (BPP) from Amazon Bothrops atrox venom with m/z 1384.7386 was identified and characterized by collision induced dissociation (CID) using an ESI-MS/MS spectra obtained in positive ion mode on a hybrid Qq-oaTOF mass spectrometer, Xevo G2 QTof MS (Waters, Manchester, UK). De novo peptide sequence analysis of the CID fragmentation spectra showed the amino acid sequence ZKWPRPGPEIPP, with a pyroglutamic acid and theoretical monoisotopic m/z 1384.7378, which is similar to experimental data, showing a mass accuracy of 0.6 ppm. The peptide is homologous to other BPP from Bothrops moojeni and was named as BPP-BAX12. PMID:23430539

Fatal bothropic snakebite in a horse: a case report

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NS Silva

2011-01-01

Full Text Available The present study reports a snakebite in a horse in the state of Pará, Brazil. At initial evaluation the animal was reluctant to walk and had tachycardia, tachypnea, severe lameness, bleeding on the pastern and swelling around the left hind leg. Blood samples from the bleeding sites, took on the first day, showed leukocytosis and neutrophilia, whereas biochemical values of urea and creatinine were significantly increased. The chosen treatment was snake antivenom, fluid therapy, antibiotics, anti-inflammatory agents and diuretic drugs. On the fourth day of therapy, the hematological values were within normal parameters. There was improvement related to the clinical lameness and swelling of the limb. However, a decrease in water intake and oliguria were observed. On the seventh day the animal died. Necropsy revealed areas of hemorrhagic edema in the left hind limb and ventral abdomen; the kidneys presented equimosis in the capsule, and when cut they were wet. Moreover, the cortex was pale, slightly yellow and the medullary striae had the same aspect. Based on these data, we concluded that the snakebite in the present study was caused by Bothrops spp. and that renal failure contributed to death.

Preliminary X-ray crystallographic studies of BthTX-II, a myotoxic Asp49-phospholipase A2 with low catalytic activity from Bothrops jararacussu venom

International Nuclear Information System (INIS)

Corrêa, L. C.; Marchi-Salvador, D. P.; Cintra, A. C. O.; Soares, A. M.; Fontes, M. R. M.

2006-01-01

A myotoxic Asp49-PLA 2 with low catalytic activity from B. jararacussu (BthTX-II) was crystallized in the monoclinic crystal system; a complete X-ray diffraction data set was collected and a molecular-replacement solution was obtained. The oligomeric structure of BthTX-II resembles those of the Asp49-PLA 2 PrTX-III and all bothropic Lys49-PLA 2 s. For the first time, a complete X-ray diffraction data set has been collected from a myotoxic Asp49-phospholipase A 2 (Asp49-PLA 2 ) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) and a molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resembles the myotoxin Asp49-PLA 2 PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA 2 s. In contrast, the oligomeric structure of BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA 2 from B. jararacussu). Thus, comparison between these structures should add insight into the catalytic and myotoxic activities of bothropic PLA 2 s

A importância dos acidentes ofídicos como causa de mortes em bovinos no Brasil The importance of snake bites as cause of cattle death in Brazil

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Carlos Hubinger Tokarnia

2006-06-01

Full Text Available A revisão da literatura pertinente indica que as opiniões sobre a importância dos acidentes ofídicos, como causa de mortes em bovinos no Brasil, são divergentes no meio veterinário. Enquanto alguns acreditam que são pouco importantes, ou que têm menor significado do que lhes é atribuído, outros são da opinião que esses acidentes são freqüentes. Verificou-se que só foi relatado diagnóstico fundamentado de dois casos fatais de envenenamento por Bothrops spp em bovinos, e de nenhum por Crotalus spp. Um questionário por nós submetido a patologistas e clínicos veterinários que atuam em diversos Estados do país, revelou apenas raros casos suspeitos de envenenamento ofídico fatal em bovinos no Brasil. Em nossas viagens de estudo e nos trabalhos de diagnóstico nunca estabelecemos o diagnóstico de morte por acidente ofídico em bovinos. Os casos tidos como envenenamento ofídico, na sua grande maioria, são apenas suposições, sem embasamento. Esses "diagnósticos", em geral, são feitos à distância dos animais que morreram, à revelia de exame clínico, necropsia e estudo histopatológico. Importante foi a constatação de que, no Brasil, embora algumas serpentes do gênero Bothrops possam, teoricamente, produzir quantidades suficientes de veneno para matar um bovino adulto, em experimentos realizados, apenas Bothrops alternatus foi capaz de levar a morte um dos três bovinos experimentalmente por ela picados; esse animal tinha apenas 279 kg. Já as serpentes do gênero Crotalus poderiam inocular quantidades letais de veneno para bovinos adultos. Mesmo assim, tanto para Bothrops spp, como para Crotalus spp, há que se considerar que as serpentes, em geral, só inoculam parte do veneno disponível. Esse estudo indica que é necessário melhor investigar as mortes suspeitas de terem sido causadas por acidente ofídico em bovinos no Brasil. O estabelecimento do diagnóstico de morte por envenenamento ofídico, porém, só é poss

Metabolic Profiling of Somatic Tissues from Monochamus alternatus (Coleoptera: Cerambycidae Reveals Effects of Irradiation on Metabolism

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Liangjian Qu

2014-06-01

Full Text Available A high-level of sexual sterility is of importance for the sterile insect technique (SIT. However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest.

In vitro and in vivo genotoxic evaluation of Bothrops moojeni snake venom.

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Novak Zobiole, Nathalia; Caon, Thiago; Wildgrube Bertol, Jéssica; Pereira, Cintia Alves de Souza; Okubo, Brunna Mary; Moreno, Susana Elisa; Cardozo, Francielle Tramontini Gomes de Sousa

2015-06-01

Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile. This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV). The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay. BMV displayed a 50% cytotoxic concentration (CC50) on Vero cells of 4.09 µg/mL. Vero cells treated with 4 µg/mL for 90 min and 6 h presented significant (p < 0.05, ANOVA/Newman-Keuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 µg/animal presented significant genotoxicity (p < 0.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 µg/animal. The results show that BMV presents cyto- and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.

Study of 60 Co gamma radiation effects on the biochemical, biological and immunological properties of the Bothrops jararaca venom

International Nuclear Information System (INIS)

Guarnieri, M.C.

1992-01-01

Gamma radiation, by including different modifications on the toxic, enzymatic and immunological activities of proteins, could be an useful implement for detoxification of snake venoms. The present work was done to study the mechanism of action and effects of gamma rays on the Bothrops jararaca venom, determining the radiation dose that attenuates the toxic and enzymatic activities maintaining the immunological properties of venom, and also the most important free radicals on this process. The results of immuno diffusion, immunoblotting, immunoprecipitation, immunization of mice and rabbits, and neutralization tests, showed the maintenance of antigenic and immunogenic properties and decrease of neutralizing capacity of antibodies induced by 3,000 and 4,000 Gy irradiated venom. Since the immunological properties were the most radioresistant, it was possible to determine the dose of 2,000 Gy, as the ideal radiation dose in the treatment of venoms aiming the improvement of the immunization schedule to obtain bothropic antisera. (author). 164 refs, 19 tabs, 54 figs

Variaciones en las actividades enzimáticas del veneno de la serpiente Bothrops atrox "jergón", de tres zonas geográficas del Perú Variation of the enzymatic activity of Bothrops atrox "jergon" snake venom from three geographic regions, Peru

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César Ortiz

2012-06-01

casein and by zymogram. Additionally, immunodiffusion and neutralization assays in vitro were done with a polyvalent botropic serum from the national institute of health of Peru. Results. The amidolytic, coagulant, hemorrhagic, proteolytic by zymogram, phospholipase A2, and indirect hemolytic activity were variable, demonstrating increased activity in the venoms from Amazonas, regarding proteolytic by zymogram, phospholipase A2, and indirect hemolytic activity. While the amount of protein electrophoretic bands and proteolytic activity on casein did not demonstrated differences. Regarding neutralization tests, a 0.5 dose of antivenom was sufficient to effectively neutralize (>50% the coagulant activity and phospholipase A2 of all samples analyzed. Conclusions. Some biological properties of the venom from adult Bothrops atrox of Peru are variable, without interference with the in vitro neutralization by the polyvalent botropic serum on coagulant and phospholipase A2 properties of the venom.

Inactivation and fragmentation of lectin from Bothrops leucurus snake venom by gamma irradiation

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Nunes, E. S.; Souza, M. A. A.; Vaz, A. F. M.; Coelho, L. C. B. B.; Aguiar, J. S.; Silva, T. G.; Guarnieri, M. C.; Melo, A. M. M. A.; Oliva, M. L. V.; Correia, M. T. S.

2012-04-01

Gamma radiation alters the molecular structure of biomolecules and is able to mitigate the action of snake venoms and their isolated toxins. The effect of γ-radiation on the folding of Bothrops lecurus venom lectin was measured by a hemagglutinating assay, intrinsic and bis-ANS fluorescence. Intrinsic and bis-ANS fluorescence analyses indicated that irradiation caused unfolding followed by aggregation of the lectin. Our results suggest that irradiation can lead to significant changes in the protein structure, which may promote the loss of its binding property and toxic action.

Alternagin-C (ALT-C), a Disintegrin-Like Cys-Rich Protein Isolated from the Venom of the Snake Rhinocerophis alternatus, Stimulates Angiogenesis and Antioxidant Defenses in the Liver of Freshwater Fish, Hoplias malabaricus.

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Monteiro, Diana Amaral; Selistre-de-Araújo, Heloisa Sobreiro; Tavares, Driele; Fernandes, Marisa Narciso; Kalinin, Ana Lúcia; Rantin, Francisco Tadeu

2017-09-28

Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg -1 , via intra-arterial) on oxidative stress biomarkers, histological alterations, vascular endothelial growth factor (VEGF) production, and the degree of vascularization in the liver of the freshwater fish traíra, Hoplias malabaricus , seven days after the initiation of therapy. ALT-C treatment increased VEGF levels and hepatic angiogenesis. ALT-C also enhanced hepatic antioxidant enzymes activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, decreasing the basal oxidative damage to lipids and proteins in the fish liver. These results indicate that ALT-C improved hepatic tissue and may play a crucial role in tissue regeneration mechanisms.

Immunogenicity of Bothrops atrox (Ophidia: Viperidae venom and its evaluation by immunoenzymatic methods Inmunogenicidad del veneno de Bothrops atrox (Ophidia: Viperidae y su evaluación por métodos inmunoenzimáticos

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Gustavo A. Sandoval

2012-02-01

Full Text Available The immunogenicity of Bothrops atrox, “jergón”, venom was studied using ELISA and Western Blot methods, as well as cross-reactivity patterns against venoms of Bothrops brazili, Lachesis muta and Crotalus durissus. For this purpose, New Zealand white rabbits (2 kg aprox were immunized with four 500 μg doses of B. atrox venom in a period of 90 days. Antibody production was followed using ELISA technique, and title of hiper-immune serum was determined at the end of immunization protocol. Additionally, electrophoretic patterns of venoms were analyzed by SDS-PAGE and venom reactivity against obtained serum by ELISA and Western Blot. Immunization schedule allowed a pronounced antibody production since day 20 of protocol. At the end of process, serum title was 256000, which demonstrated both efficacy and usefulness of the developed procedure. On the other hand, studied venoms showed a heterogenic protein composition according to their electrophoretic patterns, whereas cross-reactivity values of 23,7%, 4,0% and 1,8% were obtained between B. atrox venom and B. brazili, L. muta and C. durissus venoms, respectively, using immunoenzymatic methods. According to our results, this procedure constitutes an initial step for further assays directed to optimization in immunoserum production for envenoming treatment and development of kits for diagnosis and species identification of snakes.Se estudió la inmunogenicidad del veneno de la serpiente Bothrops atrox, “jergón”, utilizando los métodos inmunoenzimáticos de ELISA y Western Blot, así como los patrones de reactividad cruzada empleando los venenos de las serpientes Bothrops brazili, Lachesis muta y Crotalus durissus. Para este fin se inmunizaron conejos albinos Nueva Zelanda (2 kg aprox con cuatro dosis de 500 μg del veneno de B. atrox en un periodo de 90 días. La producción de anticuerpos fue monitoreada mediante la técnica de ELISA, determinándose el título del suero hiperinmune obtenido

A influência dos ritmos circadianos no metabolismo da serpente Bothrops jararaca (Serpentes, Viperidae - DOI: 10.4025/actascibiolsci.v30i3.5030 The influence of circadian rhythms on the metabolism of the snake Bothrops jararaca (Serpentes, Viperidae - DOI: 10.4025/actascibiolsci.v30i3.5030

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José Geraldo Pereira da Cruz

2008-10-01

Full Text Available A atividade termorreguladora conduziu a uma busca extensiva para o entendimento das correlações entre as variáveis fisiológicas, incluindo as funções metabólicas e a temperatura corporal. Frequentes observações mostram que algumas serpentes podem se aquecer, sendo este aumento de temperatura independente da temperatura ambiente, indicando a termorregulação bem sucedida. Bothrops jararaca foram expostas a dois ambientes com diferentes temperaturas (20 e 30oC durante três semanas, sendo mensuradas a temperatura corporal e o consumo de oxigênio. O aumento da temperatura corporal e consumo de oxigênio de Bothrops jararaca ocorreram na fase de escuro do fotoperíodo, consistente para espécies noturnas. Entretanto, antecedendo a fase de escuro, as serpentes em 20oC apresentaram os níveis mais elevados durante o dia para temperatura corporal e consumo de oxigênio. Estes resultados indicam pela primeira vez que animais termodependentes podem controlar a temperatura corporal por meio de ritmos fisiológicos circadianos, semelhante aos observados em termoindependentes. Os ritmos circadianos permitem que os animais antecipem as mudanças no ambiente: parâmetros fisiológicos como a temperatura corporal e as reservas de energia ou sua mobilização podem ser ajustadas antes que as mudanças ambientais previstas ocorram realmente.The thermoregulatory activity has led to an extensive search for correlations between physiological variables, including metabolic functions, and the ideal level of body temperature. Snakes were also often seen basking, when their body temperatures were relatively independent of ambient temperature, indicating successful thermoregulation. Bothrops jararaca were exposed to two different ambient temperatures (20 and 30ºC over a time course of three weeks and oxygen consumption and body temperature were measured. The snakes exhibited a freerunning rhythm of body temperature. Metabolic rate was increased at the same

Hemiparesia esquerda consecutiva a empeçonhamento: Por Bothrops Jararacussu

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Napoleão L. Teixeira

1944-09-01

Full Text Available O A. apresenta uma observação de hemiparesia esquerda, consecutiva a envenenamento por Bothrops Jararacussu. É o segundo caso que publica, com idêntica etiologia; além das suas, há duas outras observações semelhantes, de Octávio de Magalhães. Depois de discorrer sobre as hemiplegias cerebrais infantis - mais comuns - lembra que estas nem sempre se acompanham de espasticidade, podendo apresentar-se, raramente, com hipotonia muscular, ou mesmo de coréia, atetose, ou movimentos córeo-atetóticos que falam em favor de comprometimento extrapiramidal. Assinala, também, que crises epileptiformes - generalizadas ou parciais - podem ocorrer, o mesmo se podendo dizer de distúrbios psíquicos. Traduzir-se-iam, estes, por déficit intelectual marcado, podendo ir desde a debilidade mental até a idiotia; ou então, mesmo quando não há aparente comprometimento da esfera intelectual, por perturbações da afetividade, da vontade e do pragmatismo. Passando em revista as causas mais frequentes das hemiplegias cerebrais infantis, abre lugar, dentre elas, para os empeçonhamentos ofídico e escorpiônico (Magalhães e Guimarães. Estuda, a seguir, a patogenia das hemiplegias no decurso dos referidos empeçonhamentos, alinhando as hipóteses correntes, da preferência de conceituadas autoridades no assunto. Transcreve, finalmente, sua observação clínica, da qual se pode concluir, sem dúvida possível, haver, no caso "que apresenta, estreita e imediata ligação entre o envenenamento ofídico e a hemiparesia em estudo. O observado seria portador, além do mais, de crises epileptiformes generalizadas, aparecidas logo a seguir ao empeçonhamento. Além da fotografia do caso que apresenta, mostra-nos o A. outra, de caso anteriormente publicado, este, porém, de hemiplegia cerebral infantil típica, instalada aos 11 anos, após picada de Bothrops jararaca.

Evaluation of the interaction of surfactants with stratum corneum model membrane from Bothrops jararaca by DSC.

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Baby, André Rolim; Lacerda, Aurea Cristina Lemos; Velasco, Maria Valéria Robles; Lopes, Patrícia Santos; Kawano, Yoshio; Kaneko, Telma Mary

2006-07-06

The interaction of surfactants sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium chloride (CTAC) and lauryl alcohol ethoxylated (12 mol ethylene oxide) (LAE-12OE) was evaluated on the stratum corneum (SC) of shed snake skins from Bothrops jararaca, used as model membrane, and thermal characterized by differential scanning calorimetry (DSC). Surfactant solutions were employed above of the critical micellar concentration (CMC) with treatment time of 8h. The SDS interaction with the SC model membrane has increased the characteristic transition temperature of 130 degrees C in approximately 10 degrees C for the water loss and keratin denaturation, indicating an augmentation of the water content. Samples treated with CTAC have a decrease of the water loss temperature, while, for the LAE-12OE treated samples, changes on the transition temperature have not been observed.

The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo

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Miriéle Cristina Ferraz

2015-01-01

Full Text Available We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL, but only partial blockade (~30% in EPSTA (3.6 mg/kg, i.m. after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations. Preincubation of venom with betulin (200 μg/mL markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite.

The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo

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Ferraz, Miriéle Cristina; de Oliveira, Jhones Luiz; de Oliveira Junior, Joel Reis; Cogo, José Carlos; dos Santos, Márcio Galdino; Franco, Luiz Madaleno; Puebla, Pilar; Ferraz, Helena Onishi; Ferraz, Humberto Gomes; da Rocha, Marisa Maria Teixeira; Hyslop, Stephen

2015-01-01

We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite. PMID:26633987

Preparación toxoide a partir de la fracción hemorrágica del veneno de Bothrops asper (serpiente de América Central y del Sur) (Toxoid preparation from hemorrhagic fraction of the venom from Bothrops asper (snake from Central and South America).

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Rodríguez-Acosta, A; Aguilar, I; Girón, M E

1993-01-01

A technique is described for preparing a toxoid from the hemorrhagic fraction of the Bothrops asper venom. This method conserves a high degree of immunogenicity although it eliminates lethal effects. None of the animals vaccinated with the toxoid from this fraction had hemorrhagic lesions after they were injected the venom from the hemorrhagic fraction.

Spectroscopic and thermal characterization of alternative model biomembranes from shed skins of Bothrops jararaca and Spilotis pullatus

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André Rolim Baby

2009-09-01

Full Text Available Recently, there has been an interest in the use of shed snake skin as alternative model biomembrane for human stratum corneum. This research work presented as objective the qualitative characterization of alternative model biomembranes from Bothrops jararaca and Spilotis pullatus by FT-Raman, PAS-FTIR and DSC. The employed biophysical techniques permitted the characterization of the biomembranes from shed snake skin of B. jararaca and S. pullatus by the identification of vibrational frequencies and endothermic transitions that are similar to those of the human stratum corneum.Existe atualmente interesse no uso da muda de pele de cobra como modelos alternativos de biomembranas da pele humana. O presente trabalho apresentou como objetivo a caracterização qualitativa de modelos alternativos de biomembranas provenientes de mudas de pele de cobra da Bothrops jararaca e Spilotis pullatus por espectroscopia Raman (FT-Raman, espectroscopia fotoacústica no infravermelho (PAS-FTIR e calorimetria exploratória diferencial (DSC. As técnicas biofísicas FT-Raman, PAS-FTIR e DSC permitiram caracterizar qualitativamente os modelos alternativos de biomembranas provenientes das mudas de pele de cobra da B. jararaca e S. pullatus e identificar freqüências vibracionais e transições endotérmicas similares ao estrato córneo humano.

Venomics and antivenomics of Bothrops erythromelas from five geographic populations within the Caatinga ecoregion of northeastern Brazil

OpenAIRE

Jorge, Roberta Jeane B.; Monteiro, Helena S.A.; Gonçalves Machado, Larissa; Guarnieri, Míriam C.; Ximenes, Rafael M.; Borges Nojosa, Diva M.; de O. Luna, Karla P.; Zingali, Russolina B.; Corrêa Netto, Carlos; Gutiérrez, José María; Sanz, Libia; Calvete, Juan J.; Pla, Davinia

2015-01-01

The Caatinga lancehead, Bothrops erythromelas, is a medically relevant species, responsible for most of the snakebite accidents in most parts of its distribution range in northeastern Brazil. The spectrum and geographic variability of its venom toxins were investigated applying a venomics approach to venom pools from five geographic areas within the Caatinga ecoregion. Despite its wide habitat, populations of B. erythromelas from Ceará, Pernambuco, Juazeiro, Paraiba, and Ilha de Itaparica exh...

BjussuSP-I: a new thrombin-like enzyme isolated from Bothrops jararacussu snake venom.

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Sant' Ana, Carolina D; Ticli, Fabio K; Oliveira, Leandro L; Giglio, Jose R; Rechia, Carem G V; Fuly, André L; Selistre de Araújo, Heloisa S; Franco, João J; Stabeli, Rodrigo G; Soares, Andreimar M; Sampaio, Suely V

2008-11-01

A thrombin-like enzyme named BjussuSP-I, isolated from B. jararacussu snake venom, is an acidic single chain glycoprotein with approximately 6% sugar, Mr=61,000 under reducing conditions and pI approximately 3.8, representing 1.09% of the chromatographic A(280) recovery. BjussuSP-I is a glycosylated serine protease containing both N-linked carbohydrates and sialic acid in its structure. BjussuSP-I showed a high clotting activity upon human plasma, which was inhibited by PMSF, leupeptin, heparin and 1,10-phenantroline. This enzyme showed high stability regarding coagulant activity when analyzed at different temperatures (-70 to 37 degrees C), pHs (4.5 to 8.0), and presence of two divalent metal ions (Ca(2+) and Mg(2+)). It also displayed TAME esterase and proteolytic activities toward natural (fibrinogen and fibrin) and synthetic (BAPNA) substrates, respectively, being also inhibited by PMSF and leupeptin. BjussuSP-I can induce production of polyclonal antibodies able to inhibit its clotting activity, but unable to inhibit its proteolytic activity on fibrinogen. The enzyme also showed crossed immunoreactivity against 11 venom samples of Bothrops, 1 of Crotalus, and 1 of Calloselasma snakes, in addition of LAAO isolated from B. moojeni venom. It displayed neither hemorrhagic, myotoxic, edema-inducing profiles nor proteolytic activity on casein. BjussuSP-I showed an N-terminal sequence (VLGGDECDINEHPFLA FLYS) similar to other thrombin-like enzymes from snake venoms. Based on its biochemical, enzymatic and pharmacological characteristics, BjussuSP-I was identified as a new thrombin-like enzyme isoform from Bothrops jararacussu snake venom.

Molecular Cloning and Pharmacological Properties of an Acidic PLA2 from Bothrops pauloensis Snake Venom

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Ferreira, Francis Barbosa; Gomes, Mário Sérgio Rocha; Naves de Souza, Dayane Lorena; Gimenes, Sarah Natalie Cirilo; Castanheira, Letícia Eulalio; Borges, Márcia Helena; Rodrigues, Renata Santos; Yoneyama, Kelly Aparecida Geraldo; Homsi Brandeburgo, Maria Inês; Rodrigues, Veridiana M.

2013-01-01

In this work, we describe the molecular cloning and pharmacological properties of an acidic phospholipase A2 (PLA2) isolated from Bothrops pauloensis snake venom. This enzyme, denominated BpPLA2-TXI, was purified by four chromatographic steps and represents 2.4% of the total snake venom protein content. BpPLA2-TXI is a monomeric protein with a molecular mass of 13.6 kDa, as demonstrated by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis and its theoretical isoelectric point was 4.98. BpPLA2-TXI was catalytically active and showed some pharmacological effects such as inhibition of platelet aggregation induced by collagen or ADP and also induced edema and myotoxicity. BpPLA2-TXI displayed low cytotoxicity on TG-180 (CCRF S 180 II) and Ovarian Carcinoma (OVCAR-3), whereas no cytotoxicity was found in regard to MEF (Mouse Embryonic Fibroblast) and Sarcoma 180 (TIB-66). The N-terminal sequence of forty-eight amino acid residues was determined by Edman degradation. In addition, the complete primary structure of 122 amino acids was deduced by cDNA from the total RNA of the venom gland using specific primers, and it was significantly similar to other acidic D49 PLA2s. The phylogenetic analyses showed that BpPLA2-TXI forms a group with other acidic D49 PLA2s from the gender Bothrops, which are characterized by a catalytic activity associated with anti-platelet effects. PMID:24304676

Variação entre filhotes de representantes do complexo Bothrops newied (Serpentes, Viperidae, Crotalinae

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Vinícius Xavier

2002-01-01

Full Text Available External morphological characters of 141 young specimens (69 males and 72 femalesof the Bothrops newied complex were analyzed. Regression analysis was used in the study of morphometric characters and principal components analysis was used in the study of meristic and qualitative characters. Sexual dimorphism was confirmed in the meristic and morphometric characters. Males showed higher counts of subcaudals and longer tails. Females showed eventually higher number of ventrals and dorsal rows, and larger heads. Six different drawing patterns were diagnosed and can indicate the existence of different species. Ontogenetic variation was described.

Inhibition of the Myotoxicity Induced by Bothrops jararacussu Venom and Isolated Phospholipases A2 by Specific Camelid Single-Domain Antibody Fragments.

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Nidiane D R Prado

Full Text Available Antivenoms, produced using animal hyperimmune plasma, remains the standard therapy for snakebites. Although effective against systemic damages, conventional antivenoms have limited efficacy against local tissue damage. Additionally, the hypersensitivity reactions, often elicited by antivenoms, the high costs for animal maintenance, the difficulty of producing homogeneous lots, and the instability of biological products instigate the search for innovative products for antivenom therapy. In this study, camelid antibody fragments (VHH with specificity to Bothropstoxin I and II (BthTX-I and BthTX-II, two myotoxic phospholipases from Bothrops jararacussu venom, were selected from an immune VHH phage display library. After biopanning, 28 and 6 clones recognized BthTX-I and BthTX-II by ELISA, respectively. Complementarity determining regions (CDRs and immunoglobulin frameworks (FRs of 13 VHH-deduced amino acid sequences were identified, as well as the camelid hallmark amino acid substitutions in FR2. Three VHH clones (KF498607, KF498608, and KC329718 were capable of recognizing BthTX-I by Western blot and showed affinity constants in the nanomolar range against both toxins. VHHs inhibited the BthTX-II phospholipase A2 activity, and when tested for cross-reactivity, presented specificity to the Bothrops genus in ELISA. Furthermore, two clones (KC329718 and KF498607 neutralized the myotoxic effects induced by B. jararacussu venom, BthTX-I, BthTX-II, and by a myotoxin from Bothrops brazili venom (MTX-I in mice. Molecular docking revealed that VHH CDRs are expected to bind the C-terminal of both toxins, essential for myotoxic activity, and to epitopes in the BthTX-II enzymatic cleft. Identified VHHs could be a biotechnological tool to improve the treatment for snake envenomation, an important and neglected world public health problem.

Evaluation of platelet number and function and fibrinogen level in patients bitten by snakes of the Bothrops genus

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Fábio Cardoso Luan

1995-03-01

Full Text Available Platelet function and plasma fibrinogen levels were evaluated in 14 patients, 10 males and 4females, aged 13-59years bitten by Bothrops genus snakes. There was a statistical difference (p Foram avaliadas a função plaquetária e os níveis séricos de fibrinogênio em 14 doentes picados por serpentes do gênero Bothrops, sendo 10 do sexo masculino e 4 do sexo feminino, com idades compreendidas entre 13 e 59 anos. Houve diferença estatística (p < 0,05 entre os níveis séricos defibrinogênio avaliados 24 e 48 horas após o acidente. Houve tendência à normalização após 48 horas do tratamento. A plaquetopenia foi evidente nas avaliações de 24 e 48 horas. Houve tendência à nomalização no 8o dia após o tratamento (p <0,05. Os níveis de produtos de degradação defibrina (PDF mostraram-se alterados em 83,33 % dos pacientes avaliados. Os autores sugerem que a hipoagregação esteja relacionada com níveis baixos de fibrinogênio e elevados de PDF.

BOTHROPS JARARACUSSU: A NEW RECORD FOR THE MUNICIPALITY OF SÃO PAULO, BRAZIL

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Silara Fatima Batista

2016-10-01

Full Text Available Bothrops jararacussu is a terrestrial snake, predominantly nocturnal, and mainly found in forested areas. Our objective was to provide the first record of B.jararacussu for the municipality of São Paulo, in the highland of Parque Estadual da Serra do Mar (PESM, Núcleo Curucutu. The register ocurred through monthly samplings in the Núcleo Curucutu, during one year. The specimen was found in a transitional area of Atlantic upper montane forest and Pinus sp. reforestation. It represents a new altitude record (>800m in a well-preserved area, reiterating the importance of this park for the maintenance of biodiversity in this municipality and evinces the region potential to house rare species in São Paulo highland.

Effects of Co60 gamma radiation on the immunogenic and antigenic properties of Bothrops jararacussu venom

International Nuclear Information System (INIS)

Spencer, Patrick J.; Nascimento, Nanci do; Rogero, Jose R.

1997-01-01

Ionizing radiation has been successfully employed to attenuate animals toxins and venoms for immunizing antisera producing animals. However, the radiation effects on antigenicity and immunogenecity have not yet been elucidated. In the present work, we investigated the effects of gamma rays on the antigenic and immunogenicity have not yet been elucidated. In the present work, we investigated the effects of gamma rays on the antigenic and immunogenic behaviour of Bothrops jararacussu venon. Venom samples (2mg/ml in 150 mM NaCl) were irradiated with 500, 1000 and 2000 Gy of 60 Co gamma rays. These samples were submitted to antigen capture ELISA on plates coated with commercial bothropic antiserum. Results suggest a loss of reactivity of the 1000 and 2000 Gy irradiated samples. Antibodies against native and 2000 Gy irradiated venoms were produced in rabbits. Both sera able to bind native venom with a slightly higher titer for anti-irradiated serum. These data suggest that radiation promoted structural modification on the antigen molecules. However since the antibodies produced against irradiated antivenom were able to recognize native venom, there must have been preservation of some antigenic determinants. It has already been demosntrated that irradiation of proteins leads to structural modifications and unfolding of the molecules. Our data suggest that irradiation led to conformational epitopes destruction with preservation of linear epitopes and that the response against irradiated venom may be attributed to these linear antigenic determinants. (author). 8 refs., 3 figs

Molecular Cloning and Pharmacological Properties of an Acidic PLA2 from Bothrops pauloensis Snake Venom

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Francis Barbosa Ferreira

2013-12-01

Full Text Available In this work, we describe the molecular cloning and pharmacological properties of an acidic phospholipase A2 (PLA2 isolated from Bothrops pauloensis snake venom. This enzyme, denominated BpPLA2-TXI, was purified by four chromatographic steps and represents 2.4% of the total snake venom protein content. BpPLA2-TXI is a monomeric protein with a molecular mass of 13.6 kDa, as demonstrated by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF analysis and its theoretical isoelectric point was 4.98. BpPLA2-TXI was catalytically active and showed some pharmacological effects such as inhibition of platelet aggregation induced by collagen or ADP and also induced edema and myotoxicity. BpPLA2-TXI displayed low cytotoxicity on TG-180 (CCRF S 180 II and Ovarian Carcinoma (OVCAR-3, whereas no cytotoxicity was found in regard to MEF (Mouse Embryonic Fibroblast and Sarcoma 180 (TIB-66. The N-terminal sequence of forty-eight amino acid residues was determined by Edman degradation. In addition, the complete primary structure of 122 amino acids was deduced by cDNA from the total RNA of the venom gland using specific primers, and it was significantly similar to other acidic D49 PLA2s. The phylogenetic analyses showed that BpPLA2-TXI forms a group with other acidic D49 PLA2s from the gender Bothrops, which are characterized by a catalytic activity associated with anti-platelet effects.

The pharmacological effect of Bothrops neuwiedii pauloensis (jararaca-pintada snake venom on avian neuromuscular transmission

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C.R. Borja-Oliveira

2003-05-01

Full Text Available The neuromuscular effects of Bothrops neuwiedii pauloensis (jararaca-pintada venom were studied on isolated chick biventer cervicis nerve-muscle preparations. Venom concentrations of 5-50 µg/ml produced an initial inhibition and a secondary increase of indirectly evoked twitches followed by a progressive concentration-dependent and irreversible neuromuscular blockade. At venom concentrations of 1-20 µg/ml, the responses to 13.4 mM KCl were inhibited whereas those to 110 µM acetylcholine alone and cumulative concentrations of 1 µM to 10 mM were unaffected. At venom concentrations higher than 50 µg/ml, there was pronounced muscle contracture with inhibition of the responses to acetylcholine, KCl and direct stimulation. At 20-24ºC, the venom (50 µg/ml produced only partial neuromuscular blockade (30.7 ± 8.0%, N = 3 after 120 min and the initial inhibition and the secondary increase of the twitch responses caused by the venom were prolonged and pronounced and the response to KCl was unchanged. These results indicate that B.n. pauloensis venom is neurotoxic, acting primarily at presynaptic sites, and that enzyme activity may be involved in this pharmacological action.

Edema induced by Bothrops asper (Squamata: Viperidae snake venom and its inhibition by Costa Rican plant extracts

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Beatriz Badilla

2006-06-01

Full Text Available We tested the capacity of leaf (Urera baccifera, Loasa speciosa, Urtica leptuphylla, Chaptalia nutans, and Satureja viminea and root (Uncaria tomentosa extracts to inhibit edema induced by Bothrops asper snake venom. Edema-forming activity was studied plethysmographically in the rat hind paw model. Groups of rats were injected intraperitoneally with various doses of each extract and, one hour later, venom was injected subcutaneously in the right hind paw. Edema was assessed at various time intervals. The edematogenic activity was inhibited in those animals that received an injection U. tomentosa, C. nutans or L. speciosa extract. The extract of U. baccifera showed a slight inhibition of the venom effect. Extract from S. viminea and, to a lesser extent that of U. leptuphylla, induced a pro-inflammatory effect, increasing the edema at doses of 250 mg/kg at one and two hours. Rev. Biol. Trop. 54(2: 245-252. Epub 2006 Jun 01.Se investigó la capacidad de los extractos de las hojas de Urera baccifera, Loasa speciosa, Urtica leptuphylla, Chaptalia nutans, Satureja viminea y de la raíz de Uncaria tomentosa para inhibir el edema inducido por el veneno de Bothrops asper por métodos pletismométricos. Los grupos de ratas fueron inyectados intraperitonealmente con varias dosis de cada extracto y una hora mas tarde se inyectó veneno por vía subcutánea en la pata trasera derecha de la rata. Se evaluó el edema en distintos intervalos de tiempo. Los resultados muestran que la actividad edematogénica fue inhibida en los animales que recibieron los extractos de raíz de U. tomentosa, hojas de C. nutans y L. speciosa. Los extractos de hojas de U. baccifera mostraron leve inhibición del efecto del veneno. El extracto de hojas de S. viminea y en menor grado el de U. leptuphylla indujeron un efecto pro inflamatorio.

Estudio bioquímico del veneno de la serpiente Bothrops hyoprorus

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César Bonilla

1997-07-01

Full Text Available Se describe la purificación parcial de la enzima Fosfolipasa A del veneno de Bothrops hyoprorus y la caracterización de sus actividades hemolítica y citotóxica. La actividad fosfolipásica se detectó en dos fracciones de 23 y 12 Kd por cromatografía en Sephadex G-100 y G-50. Las actividades fosfolipásica y hemolítica fueron detectadas en las mismas fracciones. Los ensayos de Western-blot, sugieren que la fracción con 12 Kd es un producto de degradación, in-vitro, del polipéptido mayor. La actividad citotóxica de la fracción fue evidente sólo a elevadas concentraciones, sugiriéndose que moléculas diferentes a Fosfolipasa A serián responsables del efecto citotóxico del veneno

Características biológicas e inmunológicas del veneno de Bothrops cotiara (Serpentes: Viperidae)

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Adolfo Rafael de Roodt; Judith Estévez; Jorge Adrián Dolab; Marcelo Víctor Manzanelli; Nicolás Piñeiro; Jorge Francisco Paniagua; Alejandro Urs Vogt

2006-01-01

Bothrops cotiara es una serpiente que se encuentra en la provincia de Misiones (Argentina), el Sur de Brasil y Paraguay. La información sobre las características clínicas de los accidentes por esta serpiente es muy escasa y existen pocos datos sobre su veneno y la capacidad neutralizante de las actividades tóxicas del mismo por antivenenos terapéuticos. En este trabajo se estudiaron características bioquímicas, actividades tóxicas y la reactividad inmunoquímica del veneno de B. cotiara. Seis ...

Structural and biophysical studies with the MjTX-I, a Lys49-phospholipase A2 homologue from Bothrops moojeni venom

International Nuclear Information System (INIS)

Salvador, G.H.M.; Fernandes, C.A.H.; Fernandez, R.M.; Fontes, M.R.M.; Marchi-Salvador, D.P.; Soares, A.M.; Oliveira, C.L.P

2012-01-01

Full text: Phospholipases A 2 (PLA 2 ) are small proteins found in a great diversity of organisms and belong to a superfamily of proteins involved in many important pharmacological processes, such as neurotoxicity, myotoxicity, platelet aggregation, and anticoagulant activity. Ophidic accidents caused by snakes from Bothrops genus are not efficiently neutralized by conventional serum therapy, and then detailed studies with this class of proteins may be very important to supplement this conventional therapy. Miotoxin-I (MjTX-I) is a basic Lys49-PLA 2 , isolated from Bothrops moojeni snake venom, which induces a drastic local myonecrosis. Crystal structure of MjTX-I shows four molecules in the asymmetric unit, an unusually oligomeric conformation for snake venom Lys49-PLA 2 s. However, bioinformatics techniques indicate a dimer as the biological oligomeric conformation. To get additional information of its biological conformation, we also performed Dynamic Light Scattering, Size Exclusion Chromatography and Small Angle X-ray Scattering experiments. These techniques showed a monomer as the most probable biological conformation in water; however small changes in pH and ionic strength result in different oligomeric assemblies. These novel information for Lys49-PLA 2 s may result in important conclusions for this intriguing class of toxins. (author)

Referências hematológicas para a jararaca de rabo branco (Bothrops leucurus recém capturadas da natureza Hematological references for wild recently-caught white-tailed lancehead (Bothrops leucurus

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K.F. Grego

2006-12-01

Full Text Available The hematological values for the specie Bothrops leucurus, recently captured from nature, were determined from blood samples of 29 snakes (11 males and 18 females. The performed hematological tests were: total red blood cell count (TRBCC, total white blood cell count (TWBCC, total trombocyte blood cell count (TTBCC; packed cell volume (PCV; hemoglobin content; and mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH and mean corpuscular hemoglobin concentration (MCHC. The mean values for TRBCC was 4.23cellsx10(5/mm³, for TWRCC was 8.92cellsx10³/mm³ and for TTBCC was 8.60cellsx10³/mm³. The mean for packed cell volume was 22.3%. The intraerythrocytic hemoparasite Hepatozoon sp was found on 58.6% of the studied animals.

Circadian pattern of Bothrops moojeni in captivity (Serpentes: Viperidae

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DR Stuginski

2012-01-01

Full Text Available Members of the subfamily Crotalinae are considered to be essentially nocturnal and most of the data about these snakes have been collected from the field. Information on how nutritional status affects the movement rate and activity patterns is a key point to elucidating the ecophysiology of snakes. In this study, we distributed 28 lancehead Bothrops moojeni into three groups under distinct feeding regimens after a month of fasting. Groups were divided as follows: ingestion of meals weighing (A 40%, (B 20%, or (C 10% of the snake body mass. Groups were monitored for five days before and after food intake and the activity periods and movement rates were recorded. Our results show that B. moojeni is prevalently nocturnal, and the activity peak occurs in the first three hours of the scotophase. After feeding, a significant decrease in activity levels in groups A and B was detected. The current results corroborate previous field data that describe B. moojeni as a nocturnal species with low movement rates. The relationship between motion and the amount of food consumed by the snake may be associated with its hunting strategy.

Irradiation of the Crude Venom of Bothrops jararacussu to Obtain Toxoid

International Nuclear Information System (INIS)

Ferreira, Camila G.; Avalloni, Tania M.; Oshima-Franco, Yoko; Oliveira, Sara de J; Oliveira, Jose M. Jr. de; Cogo, Jose C.

2011-01-01

The aim of this work was to reduce the toxicity of Bothrops jararacussu venom using gamma-rays of low-energy coming from a source of Americium-241 (E = 59.6 keV and 3.7x10 9 Bq of activity) in order to obtain a toxoid. The radiation dose that each sample received was controlled by exposure time of the venom to the radiation beam. Mouse nerve phrenic-diaphragm preparation was used for testing the loss of venom toxicity, since the venom causes an irreversible neuromuscular blockade. In this condition, the several samples of irradiated venom, when assayed in neuromuscular preparation showed that with a dose of 0.051 Gy the paralysis caused by the irradiated venom was of 91%, at 0.360 Gy was of 79%, at 1.662 Gy was of 50% and at 2.448 Gy was of 42%. Therefore, it can be concluded that the irradiation model was able to induce a progressive loss of the venom toxicity.

Irradiation of the Crude Venom of Bothrops jararacussu to Obtain Toxoid

Science.gov (United States)

Ferreira, Camila G.; Avalloni, Tânia M.; Oshima-Franco, Yoko; de J. Oliveira, Sara; de Oliveira, José M.; Cogo, José C.

2011-08-01

The aim of this work was to reduce the toxicity of Bothrops jararacussu venom using gamma-rays of low-energy coming from a source of Americium-241 (E = 59.6 keV and 3.7×109 Bq of activity) in order to obtain a toxoid. The radiation dose that each sample received was controlled by exposure time of the venom to the radiation beam. Mouse nerve phrenic-diaphragm preparation was used for testing the loss of venom toxicity, since the venom causes an irreversible neuromuscular blockade. In this condition, the several samples of irradiated venom, when assayed in neuromuscular preparation showed that with a dose of 0.051 Gy the paralysis caused by the irradiated venom was of 91%, at 0.360 Gy was of 79%, at 1.662 Gy was of 50% and at 2.448 Gy was of 42%. Therefore, it can be concluded that the irradiation model was able to induce a progressive loss of the venom toxicity.

Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon.

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Sousa, Leijiane F; Portes-Junior, José A; Nicolau, Carolina A; Bernardoni, Juliana L; Nishiyama, Milton Y; Amazonas, Diana R; Freitas-de-Sousa, Luciana A; Mourão, Rosa Hv; Chalkidis, Hipócrates M; Valente, Richard H; Moura-da-Silva, Ana M

2017-04-21

Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-firme upland forest and várzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA 2 s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from várzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA 2 s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silico prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats. In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (várzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not

PROVENANCE SNAKES OF GENUS Bothrops AND Crotalus (VIPERIDAE CATALOGED IN SERPENTARIUM ZOO UNIVERSITY OF CAXIAS DO SUL (UCS

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Ezequiel Capeletti

2016-09-01

Full Text Available Snakes are reptiles that have large environmental adaptations, which favored it's distribution among the various ecosystems. In Brazil, there are found 392 species of snakes, while in Rio Grande do Sul (RS, this research field, 79 species have been described, of which there is the Viperidae family. The objective of this work is to verify the origin of snakes of genus Bothrops and Crotalus, according to the records of the last 15 years of the serpentarium the University of Caxias do Sul, representing the first survey in captivity of the northeastern region of RS. By extension, we seek to investigate whether there is a relationship between the amount of snakes records and abiotic factors: precipitation, temperature and humidity during the period. The research was developed at UCS's serpentarium, by documental analysis of notebook records describing serpents entries between the years 2000 and 2014, in addition to literature review that helped to understand the distribution of the species and gather of the environmental parameters at the Instituto Nacional de Metereologia for further analysis. It was found that the received species are distributed in 26 cities in the RS state, of which the highlights are the municities of Nova Petrópolis and Caxias do Sul, with 148 and 42 individuals respectively. Further, it was found that there was no relationship between the amount of animals and registered temperature, precipitation and humidity. Keywords: Geographic distribution; Bothrops; Crotalus; abiotic factors; northeastern RS.

Structural and biophysical studies with the MjTX-I, a Lys49-phospholipase A{sub 2} homologue from Bothrops moojeni venom

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Salvador, G.H.M.; Fernandes, C.A.H.; Fernandez, R.M.; Fontes, M.R.M. [UNESP, Universidade Estadual Paulista, Botucatu, SP (Brazil); Marchi-Salvador, D.P. [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil); Soares, A.M. [Universidade de Sao Paulo (USP-RP), Ribeirao Preto, SP (Brazil); Oliveira, C.L.P [Universidade de Sao Paulo (USP), SP (Brazil)

2012-07-01

Full text: Phospholipases A{sub 2} (PLA{sub 2}) are small proteins found in a great diversity of organisms and belong to a superfamily of proteins involved in many important pharmacological processes, such as neurotoxicity, myotoxicity, platelet aggregation, and anticoagulant activity. Ophidic accidents caused by snakes from Bothrops genus are not efficiently neutralized by conventional serum therapy, and then detailed studies with this class of proteins may be very important to supplement this conventional therapy. Miotoxin-I (MjTX-I) is a basic Lys49-PLA{sub 2}, isolated from Bothrops moojeni snake venom, which induces a drastic local myonecrosis. Crystal structure of MjTX-I shows four molecules in the asymmetric unit, an unusually oligomeric conformation for snake venom Lys49-PLA{sub 2}s. However, bioinformatics techniques indicate a dimer as the biological oligomeric conformation. To get additional information of its biological conformation, we also performed Dynamic Light Scattering, Size Exclusion Chromatography and Small Angle X-ray Scattering experiments. These techniques showed a monomer as the most probable biological conformation in water; however small changes in pH and ionic strength result in different oligomeric assemblies. These novel information for Lys49-PLA{sub 2}s may result in important conclusions for this intriguing class of toxins. (author)

Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the Brazilian Atlantic rainforest.

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Gonçalves-Machado, Larissa; Pla, Davinia; Sanz, Libia; Jorge, Roberta Jeane B; Leitão-De-Araújo, Moema; Alves, Maria Lúcia M; Alvares, Diego Janisch; De Miranda, Joari; Nowatzki, Jenifer; de Morais-Zani, Karen; Fernandes, Wilson; Tanaka-Azevedo, Anita Mitico; Fernández, Julián; Zingali, Russolina B; Gutiérrez, José María; Corrêa-Netto, Carlos; Calvete, Juan J

2016-03-01

Bothrops jararaca is a slender and semi-arboreal medically relevant pit viper species endemic to tropical and subtropical forests in southern Brazil, Paraguay, and northern Argentina (Misiones). Within its geographic range, it is often abundant and is an important cause of snakebite. Although no subspecies are currently recognized, geographic analyses have revealed the existence of two well-supported B. jararaca clades that diverged during the Pliocene ~3.8Mya and currently display a southeastern (SE) and a southern (S) Atlantic rainforest (Mata Atlântica) distribution. The spectrum, geographic variability, and ontogenetic changes of the venom proteomes of snakes from these two B. jararaca phylogroups were investigated applying a combined venom gland transcriptomic and venomic analysis. Comparisons of the venom proteomes and transcriptomes of B. jararaca from the SE and S geographic regions revealed notable interpopulational variability that may be due to the different levels of population-specific transcriptional regulation, including, in the case of the southern population, a marked ontogenetic venom compositional change involving the upregulation of the myotoxic PLA2 homolog, bothropstoxin-I. This population-specific marker can be used to estimate the proportion of venom from the southern population present in the B. jararaca venom pool used for the Brazilian soro antibotrópico (SAB) antivenom production. On the other hand, the southeastern population-specific D49-PLA2 molecules, BinTX-I and BinTX-II, lend support to the notion that the mainland ancestor of Bothrops insularis was originated within the same population that gave rise to the current SE B. jararaca phylogroup, and that this insular species endemic to Queimada Grande Island (Brazil) expresses a pedomorphic venom phenotype. Mirroring their compositional divergence, the two geographic B. jararaca venom pools showed distinct bioactivity profiles. However, the SAB antivenom manufactured in Vital Brazil

Intraspecific variation of Bothrops pubescens (cope, 1869 venom in Uruguay (serpentes: viperidae

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V. Morais

2006-01-01

Full Text Available In Uruguay, there was no information about the variations degree in Bothrops pubescens venoms until the present work, in which we investigated intraspecific venom variation using polyacrylamide gel electrophoresis (SDS-PAGE. We found some differences in the venom protein profile; however, they were not related to the parameters studied (geographic distribution, weight, sex, and captivity time. Moreover, we distinguished two different groups in relation to band densities at 49 and 57 kDa. Specimens with predominant density in the 49kDa band tend to be predominantly females. Weight distribution in this group extended for all the range (150-1500 g with an average weight of 720 g. The other group (57kDa predominant band showed restricted weight range (150-400 g with an average weight of 280 g. Cluster analysis was also performed. The variability observed in the venom profile probably corresponds to genetic variations.

Purification and Biochemical Characterization of Three Myotoxins from Bothrops mattogrossensis Snake Venom with Toxicity against Leishmania and Tumor Cells

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Andréa A. de Moura

2014-01-01

Full Text Available Bothrops mattogrossensis snake is widely distributed throughout eastern South America and is responsible for snakebites in this region. This paper reports the purification and biochemical characterization of three new phospholipases A2 (PLA2s, one of which is presumably an enzymatically active Asp49 and two are very likely enzymatically inactive Lys49 PLA2 homologues. The purification was obtained after two chromatographic steps on ion exchange and reverse phase column. The 2D SDS-PAGE analysis revealed that the proteins have pI values around 10, are each made of a single chain, and have molecular masses near 13 kDa, which was confirmed by MALDI-TOF mass spectrometry. The N-terminal similarity analysis of the sequences showed that the proteins are highly homologous with other Lys49 and Asp49 PLA2s from Bothrops species. The PLA2s isolated were named BmatTX-I (Lys49 PLA2-like, BmatTX-II (Lys49 PLA2-like, and BmatTX-III (Asp49 PLA2. The PLA2s induced cytokine release from mouse neutrophils and showed cytotoxicity towards JURKAT (leukemia T and SK-BR-3 (breast adenocarcinoma cell lines and promastigote forms of Leishmania amazonensis. The structural and functional elucidation of snake venoms components may contribute to a better understanding of the mechanism of action of these proteins during envenomation and their potential pharmacological and therapeutic applications.

Effect of Diterpenes Isolated of the Marine Alga Canistrocarpus cervicornis against Some Toxic Effects of the Venom of the Bothrops jararaca Snake

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Thaisa Francielle Souza Domingos

2015-02-01

Full Text Available Snake venoms are composed of a complex mixture of active proteins and peptides which induce a wide range of toxic effects. Envenomation by Bothrops jararaca venom results in hemorrhage, edema, pain, tissue necrosis and hemolysis. In this work, the effect of a mixture of two secodolastane diterpenes (linearol/isolinearol, previously isolated from the Brazilian marine brown alga, Canistrocarpus cervicornis, was evaluated against some of the toxic effects induced by B. jararaca venom. The mixture of diterpenes was dissolved in dimethylsulfoxide and incubated with venom for 30 min at room temperature, and then several in vivo (hemorrhage, edema and lethality and in vitro (hemolysis, plasma clotting and proteolysis assays were performed. The diterpenes inhibited hemolysis, proteolysis and hemorrhage, but failed to inhibit clotting and edema induced by B. jararaca venom. Moreover, diterpenes partially protected mice from lethality caused by B. jararaca venom. The search for natural inhibitors of B. jararaca venom in C. cervicornis algae is a relevant subject, since seaweeds are a rich and powerful source of active molecules which are as yet but poorly explored. Our results suggest that these diterpenes have the potential to be used against Bothropic envenomation accidents or to improve traditional treatments for snake bites.

Quadros clínico-patológicos do envenenamento ofídico por Crotalus durissus terrificus e Bothrops spp. em animais de produção

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Carlos Hubinger Tokarnia

2014-04-01

Full Text Available Foi realizada uma revisão dos quadros clínico-patológicos causados pelos venenos de Crotalus durissus terrificus e Bothrops spp. em bovinos, búfalos, ovinos equinos e suínos. Foram compilados os dados obtidos pela experimentação em animais de produção encontrados na literatura e os obtidos através de experimentação realizada por nossa equipe. Também foram revisados os casos naturais de envenenamento ofídico comunicados. Em dois Quadros foram lançados os mais importantes dados dessas revisões, que revelou diversos aspectos interessantes: 1 em nossos experimentos, o veneno de Crotalus durissus terrificus, quando injetado por via subcutânea em cavalos, causou um edema acentuado no local da aplicação, ao contrário do que tem sido observado em todas as outras espécies animais, aspecto não relatado na literatura; 2 em nossos experimentos, o veneno de diversas espécies de Bothrops, quando injetado por via subcutânea em bovinos, ovinos e equinos, não causou edema como em geral é relatado na literatura, e sim hemorragias subcutâneas acentuadas no local da aplicação. Nos casos não fatais este sangue era reabsorvido em poucos dias sem deixar sequelas. Exceção foi a reação ao veneno de Bothrops jararacussu, que causou edema nos ovinos experimentais, e tumefação acentuada que resultou em fístula com eliminação de líquido seroso nos equinos experimentais. O objetivo do presente estudo visa contribuir para o aperfeiçoamento do diagnóstico de acidentes ofídicos em animais de produção.

Snake population venomics and antivenomics of Bothrops atrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management

OpenAIRE

Calvete, Juan J.; Sanz, Libia; Pérez, Alicia; Borges, Adolfo; Vargas, Alba M.; Lomonte, Bruno; Angulo, Yamileth; Gutiérrez, José María; Chalkidis, Hipócrates M.; Mourão, Rosa H.V.; Furtado, María de Fátima; Moura Da Silva, Ana M.

2011-01-01

We describe two geographically differentiated venom phenotypes across the wide distribution range of Bothrops atrox, from the Colombian Magdalena Medio Valley through Puerto Ayacucho and El Paují, in the Venezuelan States of Amazonas and Orinoquia, respectively, and São Bento in the Brazilian State of Maranhão. Colombian and Venezuelan venoms show an ontogenetic toxin profile phenotype whereas Brazilian venoms exhibit paedomorphic phenotypes. Venoms from each of the 16 localities sampled cont...

Combined venomics, venom gland transcriptomics, bioactivities, and antivenomics of two Bothrops jararaca populations from geographic isolated regions within the Brazilian Atlantic rainforest

OpenAIRE

Gonçalves Machado, Larissa; Pla, Davinia; Sanz, Libia; Jorge, Roberta Jeane B.; Leitão De Araújo, Moema; Alves, Maria Lúcia M.; Alvares, Diego Janisch; De Miranda, Joari; Nowatzki, Jenifer; de Morais Zani, Karen; Fernandes, Wilson; Tanaka Azevedo, Anita Mitico; Fernández, Julián; Zingali, Russolina B.; Gutiérrez, José María

2016-01-01

Bothrops jararaca is a slender and semi-arboreal medically relevant pit viper species endemic to tropical and subtropical forests in southern Brazil, Paraguay, and northern Argentina (Misiones). Within its geographic range, it is often abundant and is an important cause of snakebite. Although no subspecies are currently recognized, geographic analyses have revealed the existence of two well-supported B. jararaca clades that diverged during the Pliocene ~ 3.8 Mya and currently display a southe...

Oral microbiota of Brazilian captive snakes

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MG Fonseca

2009-01-01

Full Text Available The present work aimed to determine the oral microbiotic composition of snakes from São José do Rio Preto city, São Paulo State, Brazil. Ten snake species, comprising the families Boidae, Colubridae, Elapidae and Viperidae, were submitted to microbiological examination of their oral cavity, which indicated positivity for all buccal samples. Gram-negative bacilli, gram-negative cocci bacilli, gram-positive bacilli and gram-positive cocci were isolated from the snakes. Among isolated bacterium species, the occurrence of coagulase-negative staphylococci in the buccal cavity of Crotalus durissus (Viperiade, Eunectes murinus (Boidae, Mastigodryas bifossatus (Colubridae and Bacillus subtilis, common to oral cavity of Bothrops alternatus (Viperidae and Phalotris mertensi (Colubridae, was detected. It was observed higher diversity of isolated bacteria from the oral cavity of Micrurus frontalis (Elapidae and Philodryas nattereri (Colubridae, as well as the prevalence of gram-positive baccillus and gram-positive cocci. The composition of the oral microbiota of the studied snakes, with or without inoculating fangs, is diverse and also related to the formation of abscesses at the bite site in the victims of the ophidian accidents, and to pathogenic processes in the snakes that host these microorganisms.

Data for a direct fibrinolytic metalloproteinase, barnettlysin-I from Bothrops barnetti (barnett,s pitviper) snake venom with anti-thrombotic effect

Science.gov (United States)

Sanchez, Eladio Flores; Richardson, Michael; Gremski, Luiza Helena; Veiga, Silvio Sanches; Yarleque, Armando; Niland, Stephan; Lima, Augusto Martins; Estevao-Costa, Maria Inácia; Eble, Johannes Andreas

2016-01-01

Initial association of platelets after vascular injury is mediated by glycoprotein (GP)Ib-IX-V binding to von Willebrand factor (vWf) immobilized on exposed collagens and eventually leads to thrombus formation. This article provides data about a new P-I class snake venom metalloproteinase (SVMP), barnettlysin-I (Bar-I), purified from the venom of Bothrops barnetti. This Data in Brief manuscript complements the main research article by providing additional data of the biochemical characterization of Bar-I 10.1016/j.bbagen.2015.12.021[1]. PMID:27222863

Neutralization of pharmacological and toxic activities of Bothrops jararacussu snake venom and isolated myotoxins by Serjania erecta methanolic extract and its fractions

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RS Fernandes

2011-01-01

Full Text Available Most of the snakebites recorded in Brazil are caused by the Bothrops genus. Given that the local tissue damage caused by this genus cannot be treated by antivenom therapy, numerous studies are focusing on supplementary alternatives, such as the use of medicinal plants. Serjania erecta has already demonstrated anti-inflammatory, antiseptic and healing properties. In the current study, the aerial parts of S. erecta were extracted with methanol, then submitted to chromatographic fractionation on a Sephadex LH20 column and eluted with methanol, which resulted in four main fractions. The crude extract and fractions neutralized the toxic activities of Bothrops jararacussu snake venom and isolated myotoxins (BthTX-I and II. Results showed that phospholipase A2, fibrinogenolytic, myotoxic and hemorrhagic activities were inhibited by the extract. Moreover, the myotoxic and edematous activities induced by BthTX-I, and phospholipase A2 activity induced by BthTX-II, were inhibited by the extract of S. erecta and its fraction. The clotting time on bovine plasma was significantly prolonged by the inhibitory action of fractions SF3 and SF4. This extract is a promising source of natural inhibitors, such as flavonoids and tannins, which act by forming complexes with metal ions and proteins, inhibiting the action of serineproteases, metalloproteases and phospholipases A2.

Comparative evaluation of adverse effects in the use of powder trivalent antivenom and liquid antivenoms in Bothrops snake bites

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Iran Mendonça da Silva

2012-08-01

Full Text Available INTRODUCTION: Snake bite, a problem in public health, generally occurs where there is no electric power. METHODS: A comparative clinical study was conducted with 102 victims of Bothrops snake bite, from the state of Amazonas, Brazil; 58 victims were treated with liofilizated trivalent antivenom serum (SATL and 44 victims treated with liquid bivalent and monovalent antivenom serum (SAMBL. RESULTS: 17% (10/58 of patients presented adverse effects with the SATL and 25% (11/44 with the SAMBL. CONCLUSIONS: There was no statistic difference in number of adverse effects between the two types of snake bite antivenom.

Extratos de Curcuma longa L. e Kalanchoe brasiliensis Camb. no tratamento local do envenenamento por Bothrops alternatus

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F. V. Fonseca

Full Text Available Este trabalho teve como objetivo a utilização dos extratos aquosos das plantas Curcuma longa e Kalanchoe brasiliensis na terapêutica tópica complementar do envenenamento botrópico experimental em camundongos, visando a antagonização dos efeitos locais (edema, hemorragia e necrose provocados pelo veneno. O experimento mostrou que os melhores resultados foram obtidos com o extrato de Kalanchoe brasiliensis.

PROVENANCE SNAKES OF GENUS Bothrops AND Crotalus (VIPERIDAE) CATALOGED IN SERPENTARIUM ZOO UNIVERSITY OF CAXIAS DO SUL (UCS)

OpenAIRE

Ezequiel Capeletti; Michel Mendes; Diezza Biondo; Marcia Maria Dosciatti de Oliveira

2016-01-01

Snakes are reptiles that have large environmental adaptations, which favored it's distribution among the various ecosystems. In Brazil, there are found 392 species of snakes, while in Rio Grande do Sul (RS), this research field, 79 species have been described, of which there is the Viperidae family. The objective of this work is to verify the origin of snakes of genus Bothrops and Crotalus, according to the records of the last 15 years of the serpentarium the University of Caxias do Sul, repr...

Neuromuscular activity of Bothrops neuwiedi pauloensis snake venom in mouse nerve-muscle preparations

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A. M. Durigon

2005-03-01

Full Text Available The pharmacological effects of Bothrops neuwiedi pauloensis venom on mouse phrenic nerve-diaphragm (PND preparations were studied. Venom (20 mug/ml irreversibly inhibited indirectly evoked twitches in PND preparations (60 ± 10% inhibition, mean ± SEM; p<0.05; n=6. At 50 mug/ml, the venom blocked indirectly and directly (curarized preparations evoked twitches in mouse hemidiaphragms. In the absence of Ca2+, venom (50 mug/ml, produced partial blockade only after an 80 min incubation, which reached 40.3 ± 7.8% (p<0.05; n=3 after 120 min. Venom (20 mug/ml increased (25 ± 2%, p< 0.05 the frequency of giant miniature end-plate potentials in 9 of 10 end-plates after 30 min and the number of miniature end-plate potentials which was maximum (562 ± 3%, p<0.05 after 120 min. During the same period, the resting membrane potential decreased from - 81 ± 1.4 mV to - 41.3 ± 3.6 mV 24 fibers; p<0.01; n=4 in the end-plate region and from - 77.4 ± 1.4 to -44.6 ± 3.9 mV (24 fibers; p<0.01; n=4 in regions distant from the end-plate. These results indicate that B. n. pauloensis venom acts primarily at presynaptic sites. They also suggest that enzymatic activity may be involved in this pharmacological action.

A new l-amino acid oxidase from Bothrops jararacussu snake venom: Isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities.

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Carone, Sante E I; Costa, Tássia R; Burin, Sandra M; Cintra, Adélia C O; Zoccal, Karina F; Bianchini, Francine J; Tucci, Luiz F F; Franco, João J; Torqueti, Maria R; Faccioli, Lúcia H; Albuquerque, Sérgio de; Castro, Fabíola A de; Sampaio, Suely V

2017-10-01

A new l-amino acid oxidase (LAAO) from Bothrops jararacussu venom (BjussuLAAO-II) was isolated by using a three-step chromatographic procedure based on molecular exclusion, hydrophobicity, and affinity. BjussuLAAO-II is an acidic enzyme with pI=3.9 and molecular mass=60.36kDa that represents 0.3% of the venom proteins and exhibits high enzymatic activity (4884.53U/mg/mim). We determined part of the primary sequence of BjussuLAAO-II by identifying 96 amino acids, from which 34 compose the N-terminal of the enzyme (ADDRNPLEECFRETDYEEFLEIARNGLSDTDNPK). Multiple alignment of the partial BjussuLAAO-II sequence with LAAOs deposited in the NCBI database revealed high similarity (95-97%) with other LAAOs isolated from Bothrops snake venoms. BjussuLAAO-II exerted a strong antiprotozoal effect against Leishmania amazonensis (IC 50 =4.56μg/mL) and Trypanosoma cruzi (IC 50 =4.85μg/mL). This toxin also induced cytotoxicity (IC 50 =1.80μg/mL) and apoptosis in MCF7 cells (a human breast adenocarcinoma cell line) by activating the intrinsic and extrinsic apoptosis pathways, but were not cytotoxic towards MCF10A cells (a non-tumorigenic human breast epithelial cell line). The results reported herein add important knowledge to the field of Toxinology, especially for the development of new therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Cross-reactivity and phospholipase A2 neutralization of anti-irradiated Bothrops jararaca venom antibodies

International Nuclear Information System (INIS)

Spencer, P.J.; Nascimento, N. do; Paula, R.A. de; Cardi, B.A.; Rogero, J.R.

1995-01-01

The detoxified Bothrops jararaca venom, immunized rabbits with the toxoid obtained and investigated cross-reactivity of the antibodies obtained against autologous and heterelogous venoms was presented. It was also investigated the ability of the IgGs, purified by affinity chromatography, from those sera to neutralize phospholipase. A 2 , an ubiquous enzyme in animal venoms. Results indicate that venom irradiation leads to an attenuation of toxicity of 84%. Cross-reactivity was investigated by ELISA and Western blot and all venoms were reactive to the antibodies. On what refers to phospholipase A 2 activity neutralization, the antibodies neutralized autologous venoms efficiently and, curiously, other venoms from the same genus were not neutralized, while Lachesis muta venom, a remote related specier, was neutralized by this serum. These data suggest that irradiation preserve important epitopes for induction of neutralizing antibodies and that these epitopes are not shared by all venoms assayed. (author). 8 refs, 2 figs, 3 tabs

Effect of Echinacea purpurea (Asteraceae aqueous extract on antibody response to Bothrops asper venom and immune cell response

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Fernando Chaves

2007-03-01

Full Text Available The effect of aqueous extract of Echinacea purpurea roots on the murine antibody response to Bothrops asper snake venom in vivo was studied. Three groups were used. Group #1, baseline control, was treated with snake venom plus PBS. Group #2 was treated with snake venom plus sodium alginate as adjuvant (routine method used at Instituto Clodomiro Picado, and group #3 or experimental group, was treated with snake venom plus aqueous extract of E. purpurea root as adjuvant. In all groups, the first inoculation was done with Freund’s complete adjuvant (FCA. By the time of the second bleeding, mice in group #3 showed a remarkable increment in the level of anti-venom antibodies compared with those in groups #1 or #2. In vitro immune cell proliferation as a response to aqueous extract of E. purpurea root was studied using human lymphocytes activated with different lectins (Con A, PHA and PWM. In all cases, increase in percentage of lymphoproliferation was greater when E. purpurea root extract was used in addition to individual lectins. Rev. Biol. Trop. 55 (1: 113-119. Epub 2007 March. 31.Se estudió in vivo, el efecto del extracto acuoso de las raíces de Echinacea purpurea en la respuesta de los anticuerpos murinos al veneno de la serpiente Bothrops asper. El grupo 1 control, fue tratado con el veneno y PBS. El grupo 2 con veneno y alginato de sodio (método utilizado en el Instituto Clodomiro Picado, y el grupo 3 o experimental, con veneno y extracto acuoso de las raíces de E. purpurea. En todos los grupos, la primera inmunización fue hecha con FCA (Freund’s Complete Adjuvant. En las muestras correspondientes a la segunda sangría, los ratones del grupo 3 mostraron un marcado incremento en el nivel de anticuerpos, en comparación con los ratones de los otros grupos. También se determinó la proliferación de células inmunes in vitro, como respuesta al extracto acuoso de la raíz de E. purpurea, utilizando linfocitos humanos activados con

Phylogeography of the Central American lancehead Bothrops asper (SERPENTES: VIPERIDAE)

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Parkinson, Christopher L.; Daza, Juan M.; Wüster, Wolfgang

2017-01-01

The uplift and final connection of the Central American land bridge is considered the major event that allowed biotic exchange between vertebrate lineages of northern and southern origin in the New World. However, given the complex tectonics that shaped Middle America, there is still substantial controversy over details of this geographical reconnection, and its role in determining biogeographic patterns in the region. Here, we examine the phylogeography of Bothrops asper, a widely distributed pitviper in Middle America and northwestern South America, in an attempt to evaluate how the final Isthmian uplift and other biogeographical boundaries in the region influenced genealogical lineage divergence in this species. We examined sequence data from two mitochondrial genes (MT-CYB and MT-ND4) from 111 specimens of B. asper, representing 70 localities throughout the species’ distribution. We reconstructed phylogeographic patterns using maximum likelihood and Bayesian methods and estimated divergence time using the Bayesian relaxed clock method. Within the nominal species, an early split led to two divergent lineages of B. asper: one includes five phylogroups distributed in Caribbean Middle America and southwestern Ecuador, and the other comprises five other groups scattered in the Pacific slope of Isthmian Central America and northwestern South America. Our results provide evidence of a complex transition that involves at least two dispersal events into Middle America during the final closure of the Isthmus. PMID:29176806

Thrombocytin, a serine protease from Bothrops atrox venom. 1. Purification and characterization of the enzyme

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Kirby, E.P. (Temple Univ. Health Sciences Center, Philadelphia, PA); Niewiarowski, S.; Stocker, K.; Kettner, C.; Shaw, E.; Brudzynsi, T.M.

1979-08-07

Thrombocytin, a platelet-activating enzyme from Bothrops atrox venom, has been purified to homogeneity by precipitation with sodium salicylate and chromatography on heparin-agarose. Thrombocytin is a single-chain glycoprotein with a molecular weight of 36,000 which contains 5.6% carbohydrate. It causes platelet aggregation, release of platelet serotonin, and activation of factor XIII. The most sensitive substrate for the amidolytic activity of thrombocytin was Tos-Gly-Pro-Arg-p-nitroanilide hydrochloride. The activity of thrombocytin on this substrate and on platelets was inhibited by diisopropyl fluorophosphate (DFP), soybean trypsin inhibitor, and several arginine chloromethyl ketones. Active site titration with nitrophenyl guanidinobenzoate demonstrated that approximately 86% of the preparation was in the active form. These experiments demonstrate the presence of serine and histidine in the active site of thrombocytin and suggest that thrombocytin is a classical serine protease with a platelet-activating activity similar to thrombin.

Immunoglobulin G and F(ab')2 polyvalent antivenoms do not differ in their ability to neutralize hemorrhage, edema and myonecrosis induced by Bothrops asper (terciopelo) snake venom

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León Montero, Guillermo; Rojas Céspedes, Gustavo; Lomonte, Bruno; Gutiérrez, José María

1997-01-01

The ability of whole immunoglobulin G (IgG) and F(ab')2 polyvalent (Crotalinae) antivenoms to neutralize the hemorrhagic, edema-forming and myotoxic activities of Bothrops asper venom was studied. Both antivenoms were adjusted to the same neutralizing potency against lethal and hemorrhagic activities in experiments where venom and antivenoms were incubated before injection. Thus, in these experimental conditions, differences in the neutralizing ability in experiments involving independent inj...

Individual variability in the venom proteome of juvenile Bothrops jararaca specimens.

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Dias, Gabriela S; Kitano, Eduardo S; Pagotto, Ana H; Sant'anna, Sávio S; Rocha, Marisa M T; Zelanis, André; Serrano, Solange M T

2013-10-04

Snake venom proteomes/peptidomes are highly complex and subject to ontogenetic changes. Individual variation in the venom proteome of juvenile snakes is poorly known. We report the proteomic analysis of venoms from 21 juvenile specimens of Bothrops jararaca of different geographical origins and correlate it with the evaluation of important venom features. Individual venoms showed similar caseinolytic activities; however, their amidolytic activities were significantly different. Rather intriguingly, plasma coagulant activity showed remarkable variability among the venoms but not the prothrombin-activating activity. LC-MS analysis showed significant differences between venoms; however, an interesting finding was the ubiquitous presence of the tripeptide ZKW, an endogenous inhibitor of metalloproteinases. Electrophoretic profiles of proteins submitted to reduction showed significant variability in total proteins, glycoproteins, and in the subproteomes of proteinases. Moreover, identification of differential bands revealed variation in most B. jararaca toxin classes. Profiles of venoms analyzed under nonreducing conditions showed less individual variability and identification of proteins in a conserved band revealed the presence of metalloproteinases and l-amino acid oxidase as common components of these venoms. Taken together, our findings suggest that individual venom proteome variability in B. jararaca exists from a very early animal age and is not a result of ontogenetic and diet changes.

Biochemical, biological and molecular characterization of an L-Amino acid oxidase (LAAO) purified from Bothrops pictus Peruvian snake venom.

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Lazo, Fanny; Vivas-Ruiz, Dan E; Sandoval, Gustavo A; Rodríguez, Edith F; Kozlova, Edgar E G; Costal-Oliveira, F; Chávez-Olórtegui, Carlos; Severino, Ruperto; Yarlequé, Armando; Sanchez, Eladio F

2017-12-01

An L-amino acid oxidase from Peruvian Bothrops pictus (Bpic-LAAO) snake venom was purified using a combination of size-exclusion and ion-exchange chromatography. Bpic-LAAO is a homodimeric glycosylated flavoprotein with molecular mass of ∼65 kDa under reducing conditions and ∼132 kDa in its native form as analyzed by SDS-PAGE and gel filtration chromatography, respectively. N-terminal amino acid sequencing showed highly conserved residues in a glutamine-rich motif related to binding substrate. The enzyme exhibited optimal activity towards L-Leu at pH 8.5, and like other reported SV-LAAOs, it is stable until 55 °C. Kinetic studies showed that the cations Ca 2+ , Mg 2+ and Mn 2+ did not alter Bpic-LAAO activity; however, Zn 2+ is an inhibitor. Some reagents such as β-mercaptoethanol, glutathione and iodoacetate had inhibitory effect on Bpic-LAAO activity, but PMSF, EDTA and glutamic acid did not affect its activity. Regarding the biological activities of Bpic-LAAO, this enzyme induced edema in mice (MED = 7.8 μg), and inhibited human platelet aggregation induced by ADP in a dose-dependent manner and showed antibacterial activity on Gram (+) and Gram (-) bacteria. Bpic-LAAO cDNA of 1494 bp codified a mature protein with 487 amino acid residues comprising a signal peptide of 11 amino acids. Finally, the phylogenetic tree obtained with other sequences of LAAOs, evidenced its similarity to other homologous enzymes, showing two well-established monophyletic groups in Viperidae and Elapidae families. Bpic-LAAO is evolutively close related to LAAOs from B. jararacussu, B. moojeni and B. atrox, and together with the LAAO from B. pauloensis, form a well-defined cluster of the Bothrops genus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identificación de Bacterias en Cavidad Oral y Valores Hematológicos en Bothrops asper en el Serpentario de la Universidad de Antioquia -resumen-

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C Martínez-Mejía; A Marín-Marín; Claudia Ceballos-Fonseca; Ana M Henao-Duque

2014-01-01

La flora bacteriana de la cavidad oral de las serpientes en cautiverio ha sido asociada a infecciones por estomatitis y abscesos secundarios por auto-mordedura. Igualmente‚ su identificación es importante debido a las infecciones secundarias que pueden causar los accidentes ofídicos en humanos y animales. En particular el veneno de la serpiente mapaná‚ Bothrops asper‚ responsable del 70% de los accidentes ofídicos en Colombia‚ genera efectos sistémicos y locales incluyendo dermonecrosis y mio...

Acción de la miotoxina del veneno de Bothrops brazili Hoge, 1953 (Ophidia: Viperidae

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Carmen Pantigoso

2013-06-01

Full Text Available Se ha estudiado el modo de acción de la miotoxina aislada del veneno de la serpiente Bothrops brazili. La inoculación de la miotoxina en el músculo gastrocnemius de ratones albinos produce durante la primera hora de acción la liberación de creatina kinasa y lactato deshidrogenasa, mientras que por PAGE-SDS, se revela que la incubación de la miotoxina con músculo gastrocnemius aislado, produce además la liberación de otras proteínas musculares. Asimismo, la miotoxina produce hipercontracción, lesiones delta e incrementa los niveles de calcio intramuscular, tanto in vivo como in vitro, lo cual no depende del ingreso de calcio extracelular vía receptores de dihidropiridina. Este incremento de calcio explicaría la hipercontracción observada y podría generar la activación de proteasas y lipasas endógenas dependientes de calcio, que conducirían a la necrosis muscular.

Bothrops asper snake venom and its metalloproteinase BaP–1 activate the complement system. Role in leucocyte recruitment

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Sandra H. P. Farsky

2000-01-01

Full Text Available The venom of the snake Bothrops asper, the most important poisonous snake in Central America, evokes an inflammatory response, the mechanisms of which are not well characterized. The objectives of this study were to investigate whether B. asper venom and its purified toxins – phospholipases and metalloproteinase – activate the complement system and the contribution of the effect on leucocyte recruitment. In vitro chemotaxis assays were performed using Boyden's chamber model to investigate the ability of serum incubated with venom and its purified toxins to induce neutrophil migration. The complement consumption by the venom was evaluated using an in vitro haemolytic assay. The importance of complement activation by the venom on neutrophil migration was investigated in vivo by injecting the venom into the peritoneal cavity of C5-deficient mice. Data obtained demonstrated that serum incubated with crude venom and its purified metalloproteinase BaP–1 are able to induce rat neutrophil chemotaxis, probably mediated by agent(s derived from the complement system. This hypothesis was corroborated by the capacity of the venom to activate this system in vitro. The involvement of C5a in neutrophil chemotaxis induced by venom-activated serum was demonstrated by abolishing migration when neutrophils were pre-incubated with antirat C5a receptor antibody. The relevance of the complement system in in vivo leucocyte mobilization was further demonstrated by the drastic decrease of this response in C5-deficient mice. Pre-incubation of serum with the soluble human recombinant complement receptor type 1 (sCR 1 did not prevent the response induced by the venom, but abolished the migration evoked by metalloproteinase-activated serum. These data show the role of the complement system in bothropic envenomation and the participation of metalloproteinase in the effect. Also, they suggest that the venom may contain other component(s which can cause direct activation

Evaluation of anti-Bothrops asper venom activity of ethanolic extract of Brownea rosademonte leaves

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Salazar Marcos

2014-12-01

Full Text Available Significant inhibition of the coagulant and hemorrhagic effects of Bothrops asper venom was demonstrated by ethanolic extract prepared from the leaves of Brownea rosademonte. In vitro experiments preincubating 5.5 mg of extract kg-1 b.m. for 30 min with a minimum hemorrhagic dose of venom (273.8 ± 16.1 μg of venom kg-1 b.m. lowered the hemorrhagic activity of the venom alone in CD-1 mice by 51.5 ± 2.6 %. Additionally, 1.7 mg extract L-1 plasma prolonged 5.1 times the plasma coagulation time. Fractionation of the extract led to the isolation of two compounds: ononitol (1 and quercetrin (2. The structure of compounds 1 and 2 was established by spectroscopic analyses, including APCI-HRMS and NMR (1H, 13C, HSQC, HMBC and COSY. A quercetrin concentration of 0.11 μmol L-1 prolonged the plasma coagulation time 2.6 times demonstrating that this compound was one of the active constituents of the Brownea rosademonte extract.

Isolation and characterization of a myotoxin from Bothrops brazili Hoge, 1953 Hoge, 1953 snake venom (Ophidia: Viperidae.

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Carmen Pantigoso

2014-06-01

Full Text Available A myotoxin from the venom of the snake Bothrops brazili has been purified by ion-exchange chromatography on CM-Sephadex C-50 with 0,05 M ammonium acetate buffer pH 7. The homogeneity was evaluated by PAGE with and without SDS, immunodiffusion and immunoelectrophoresis. The myotoxin is a basic protein with 15,6% of Lys+Arg; it is not a glicoprotein, has not enzymatic activity, and corresponds to 25% of the whole venom protein. The molecular weight of the myotoxin was determined by PAGE-SDS and gel filtration chromatography. The myotoxin has 30 KDa of molecular weight and two polypeptide chains of 15 KDa each. Myotoxin produces a severe necrosis on the gastrocnemius muscle of white mice. The myotoxin does not have hemolytic nor anticoagulant activity. However, produces edema with a DEM of 32,6 mg of protein.

Aislamiento y caracterización parcial de una miotoxina del veneno de la serpiente Bothrops atrox (Ophidia: Viperidae

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Sergio Huatuco

2013-06-01

Full Text Available Se ha purificado una miotoxina del veneno de la serpiente Bothrops atrox, empleando una columna de intercambio catiónico de CM-Sephadex C-50 equilibrada con buffer acetato de amonio 0,05M a pH 7. La miotoxina es una proteína básica, y por cromatografía de filtración y PAGE-SDS se ha determinado que tiene un peso molecular de 27 kDa, estando formada por dos cadenas polipeptídicas de 14 kDa cada una. La inoculación de la miotoxina en el músculo gastrocnemius de ratones albinos produce la liberación de creatina kinasa así como la necrosis del tejido. La miotoxina tiene actividad de fosfolipasa, anticoagulante y edemática, pero no hemolítica.

Caracterización toxinológica del veneno de Bothrops Atrox de Puerto Ayacucho, Edo. Amazonas (Venezuela) y su neutralización por un antiveneno venezolano

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Duque Zerpa, Carmen Teresa; Fernández, Irma; Vargas, Alba M.; López, Juan Carlos; Scannone, Héctor

2014-01-01

Bothrops atrox es reconocida por la Organización Mundial de la Salud (OMS) como una de las serpientes suramericanas, que comúnmente causa incapacidad física o muerte. En Venezuela, esta especie se localiza en los estados Amazonas, Bolívar y Delta Amacuro siendo responsable de un cuadro fisiopatológico caracterizado por edema, hemorragia, necrosis, incoagulabilidad sanguínea y hemólisis. Para el tratamiento del envenenamiento por esta especie, en Venezuela se produce un ...

A New Platelet-Aggregation-Inhibiting Factor Isolated from Bothrops moojeni Snake Venom

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Bruna Barbosa de Sousa

2017-01-01

Full Text Available This work reports the purification and functional characterization of BmooPAi, a platelet-aggregation-inhibiting factor from Bothrops moojeni snake venom. The toxin was purified by a combination of three chromatographic steps (ion-exchange on DEAE-Sephacel, molecular exclusion on Sephadex G-75, and affinity chromatography on HiTrap™ Heparin HP. BmooPAi was found to be a single-chain protein with an apparent molecular mass of 32 kDa on 14% SDS-PAGE, under reducing conditions. Sequencing of BmooPAi by Edman degradation revealed the amino acid sequence LGPDIVPPNELLEVM. The toxin was devoid of proteolytic, haemorrhagic, defibrinating, or coagulant activities and induced no significant oedema or hyperalgesia. BmooPAi showed a rather specific inhibitory effect on ristocetin-induced platelet aggregation in human platelet-rich plasma, whereas it had little or no effect on platelet aggregation induced by collagen and adenosine diphosphate. The results presented in this work suggest that BmooPAi is a toxin comprised of disintegrin-like and cysteine-rich domains, originating from autolysis/proteolysis of PIII SVMPs from B. moojeni snake venom. This toxin may be of medical interest because it is a platelet aggregation inhibitor, which could potentially be developed as a novel therapeutic agent to prevent and/or treat patients with thrombotic disorders.

Snake population venomics and antivenomics of Bothrops atrox: Paedomorphism along its transamazonian dispersal and implications of geographic venom variability on snakebite management.

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Calvete, Juan J; Sanz, Libia; Pérez, Alicia; Borges, Adolfo; Vargas, Alba M; Lomonte, Bruno; Angulo, Yamileth; Gutiérrez, José María; Chalkidis, Hipócrates M; Mourão, Rosa H V; Furtado, M Fatima D; Moura-Da-Silva, Ana M

2011-04-01

We describe two geographically differentiated venom phenotypes across the wide distribution range of Bothrops atrox, from the Colombian Magdalena Medio Valley through Puerto Ayacucho and El Paují, in the Venezuelan States of Amazonas and Orinoquia, respectively, and São Bento in the Brazilian State of Maranhão. Colombian and Venezuelan venoms show an ontogenetic toxin profile phenotype whereas Brazilian venoms exhibit paedomorphic phenotypes. Venoms from each of the 16 localities sampled contain both population-specific toxins and proteins shared by neighboring B. atrox populations. Mapping the molecular similarity between conspecific populations onto a physical map of B. atrox range provides clues for tracing dispersal routes that account for the current biogeographic distribution of the species. The proteomic pattern is consistent with a model of southeast and southwest dispersal and allopatric fragmentation northern of the Amazon Basin, and trans-Amazonian expansion through the Andean Corridor and across the Amazon river between Monte Alegre and Santarém. An antivenomic approach applied to assess the efficacy towards B. atrox venoms of two antivenoms raised in Costa Rica and Brazil using Bothrops venoms different than B. atrox in the immunization mixtures showed that both antivenoms immunodepleted very efficiently the major toxins (PIII-SVMPs, serine proteinases, CRISP, LAO) of paedomorphic venoms from Puerto Ayacucho (Venezuelan Amazonia) through São Bento, but had impaired reactivity towards PLA(2) and P-I SVMP molecules abundantly present in ontogenetic venoms. The degree of immunodepletion achieved suggests that each of these antivenoms may be effective against envenomations by paedomorphic, and some ontogenetic, B. atrox venoms. Copyright © 2010 Elsevier B.V. All rights reserved.

Neutralización del efecto hemorrágico inducido por veneno de Bothrops asper (Serpentes: Viperidae por extractos de plantas tropicales

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Oscar Castro

1999-09-01

Full Text Available Se evaluó la capacidad de extractos orgánicos de 48 especies de plantas costarricenses para neutralizar la actividad hemorrágica del veneno de la serpiente Bothrops asper (terciopelo. Los extractos se evaluaron mediante un bioensayo basado en inyecciones intradérmicas de veneno en ratones, o de mezclas veneno-extracto, seguidas de la cuantificación macroscópica de la hemorragia. Se observó una inhibición total de la hemorragia con los extractos etanólico, de acetato de etilo y acuoso de Bursera simaruba, Clusia torresii, C. palmana, Croton draco, Persea americana, Phoebe brenesii, Pimenta dioica, Sapindus saponaria, Smilax cuculmeca y Virola koschnyi. El análisis químico de estos extractos permitió identificar catequinas, flavonas, antocianinas y taninos condensados, los cuales podrían jugar un papel en la inhibición del efecto hemorrágico debido a la capacidad de quelar el ion zinc requerido por las metaloproteinasas hemorrágicas para su acción.Organic extracts representing 48 species included in 30 families of Costa Rican tropical plants were evaluated for their ability to neutralize hemorrhagic activity induced by the venom of the snake Bothrops asper. A bioassay in mice was used, based on intradermal injection of either venom or venom-extract mixtures followed by the measurement of hemorrhagic areas. Total inhibition of hemorrhage was observed with the ethanolic, ethyl acetate and aquous extracts of Bursera simaruba, Clusia torresii, C. palmana, Croton draco, Persea americana, Phoebe brenesii, Pimenta dioica, Sapindus saponaria, Smilax cuculmeca and Virola koschnyi. Chemical analysis of these extracts identified catequines, flavones, anthocyanines and condensated tannins, which may be responsible for the inhibitory effect observed, probably owing to the chelation of the zinc required for the catalytic activity of venom’s hemorrhagic metalloproteinases.

Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom.

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Olmedo, Hidekel; Herrera, María; Rojas, Leonardo; Villalta, Mauren; Vargas, Mariángela; Leiguez, Elbio; Teixeira, Catarina; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo; Montero, Mavis L

2014-01-01

The adjuvanticity of aluminum hydroxide and calcium phosphate on the antibody response in mice towards the venom of the snake Bothrops asper was studied. It was found that, in vitro, most of the venom proteins are similarly adsorbed by both mineral salts, with the exception of some basic phospholipases A2, which are better adsorbed by calcium phosphate. After injection, the adjuvants promoted a slow release of the venom, as judged by the lack of acute toxicity when lethal doses of venom were administered to mice. Leukocyte recruitment induced by the venom was enhanced when it was adsorbed on both mineral salts; however, venom adsorbed on calcium phosphate induced a higher antibody response towards all tested HPLC fractions of the venom. On the other hand, co-precipitation of venom with calcium phosphate was the best strategy for increasing: (1) the capacity of the salt to couple venom proteins in vitro; (2) the venom ability to induce leukocyte recruitment; (3) phagocytosis by macrophages; and (4) a host antibody response. These findings suggest that the chemical nature is not the only one determining factor of the adjuvant activity of mineral salts.

Effects of irradiated Bothropstoxin-1 and Bothrops jararacussu crude venom on the immune system; Acao da Bothropstoxina-1 e do veneno total de Bothrops jararacussu irradiados sobre o sistema imune

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Caproni, Priscila

2009-07-01

Ionizing radiation has been successfully employed to modify the immunological properties of biomolecules and has been proven to be a powerful tool to attenuate snake venoms toxicity without affecting and even increasing their immunogenic properties. Very promising results were obtained when crude animal venoms, as well as isolated toxins, were treated with {sup 60}Co gamma rays, yielding toxoids with good immunogenicity, however, little is known about the modifications that irradiated molecules undergo and even less about the immunological response that such antigens elicit. At the present work, we have evaluated the effects on immune system of B10.PL and BALB/c mice of Bothrops jararacussu crude venom and isolated bothropstoxin-1 (Bthx-1), before and after gamma radiation exposition. According to our data, irradiation process promoted structural modifications on both isolated toxin and crude venom, characterized by higher molecular weight protein (aggregates and oligomers) formation. Irradiated samples were immunogenic and the antibodies elicited by them were able to recognize the native toxin in ELISA. These results indicate that irradiation of toxic proteins can promote significant modifications in their structures, but still retain many of the original antigenic and immunological properties. Also, our data indicate that the irradiated protein induced higher titers of IgG2b, suggesting that Th1 cells were predominantly involved. Results from Western blot assay showed that antibodies raised against irradiated bothropstoxin-1 recognize both native isolated toxin or crude venom. Cytotoxicity assay showed that irradiated toxin and crude venom were less toxic than their native counterpart. Thus, the viability of the macrophages cultured in the presence of irradiated Bthx-1 or crude venom was higher if compared with their native forms. LDH Assay showed that irradiated Bthx-1 promotes less muscular damage than the native form. Our data confirm a potential use of

Envenenamento experimental por Bothropoides jararaca e Bothrops jararacussu em ovinos: aspectos clínico-patológicos e laboratoriais Experimental poisoning by Bothropoides jararaca and Bothrops jararacussu in sheep: clinic-pathological and laboratory aspects

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Ana Paula Aragão

2010-09-01

Bothropoides jararaca and Bothrops jararacussu venom to provide subsidies for the differential diagnosis of snake bites. The liofilized venoms were diluted in 1 ml saline and administrated subcutaneously to four sheep. Three of the animals died, and the one that received 0.5mg/kg (B. jararaca venom recovered. First symptoms were observed from 7 minutes to 1 hour after inoculation, and the clinical course varied from 7 hours and 9 minutes to 21 hours and 59 minutes. The symptoms, independent of the dosage, were swelling of the inoculation site, increased bleeding time and capillary filling, tachycardia, dyspnea, pale mucous membranes and diminished reaction to external stimuli. Laboratory tests revealed pronounced normocytic and normochromic anemia, trombocytopenia, slight reduction of fibrogen and total plasmatic protein, in two animals diminished hematocrit, besides pronounced increase of creatinaquinase and lactic dehydrogenase. At necropsy, the main findings at the inoculation site and adjacent tissues were extensive hemorrhages in the sheep inoculated with jararaca venom, and predominantly edema in the two animals inoculated with jararacussu venom. In two sheep which received jararacussu venom, acute pulmonary edema was observed. Hemorrhage and edema as the main histopathological changes, besides necrosis of muscle fibers and vessels at the inoculation site and adjacent tissue was observed. The renal tubular necrosis was attributed to shock. The volume increase at the inoculation site and surroundings was mainly due to hemorrhage (B. jararaca or edema (B. jararacussu.

Inhibitory Effects of Hydroethanolic Leaf Extracts of Kalanchoe brasiliensis and Kalanchoe pinnata (Crassulaceae) against Local Effects Induced by Bothrops jararaca Snake Venom.

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Fernandes, Júlia Morais; Félix-Silva, Juliana; da Cunha, Lorena Medeiros; Gomes, Jacyra Antunes Dos Santos; Siqueira, Emerson Michell da Silva; Gimenes, Luisa Possamai; Lopes, Norberto Peporine; Soares, Luiz Alberto Lira; Fernandes-Pedrosa, Matheus de Freitas; Zucolotto, Silvana Maria

2016-01-01

The species Kalanchoe brasiliensis and Kalanchoe pinnata, both known popularly as "Saião," are used interchangeably in traditional medicine for their antiophidic properties. Studies evaluating the anti-venom activity of these species are scarce. This study aims to characterize the chemical constituents and evaluate the inhibitory effects of hydroethanolic leaf extracts of K. brasiliensis and K. pinnata against local effects induced by Bothrops jararaca snake venom. Thin Layer Chromatography (TLC) and High Performance Liquid Chromatography coupled with Diode Array Detection and Electrospray Mass Spectrometry (HPLC-DAD-MS/MS) were performed for characterization of chemical markers of the extracts from these species. For antiophidic activity evaluation, B. jararaca venom-induced paw edema and skin hemorrhage in mice were evaluated. In both models, hydroethanolic extracts (125-500 mg/kg) were administered intraperitoneally in different protocols. Inhibition of phospholipase enzymatic activity of B. jararaca was evaluated. The HPLC-DAD-MS/MS chromatographic profile of extracts showed some particularities in the chemical profile of the two species. K. brasileinsis exhibited major peaks that have UV spectra similar to flavonoid glycosides derived from patuletin and eupafolin, while K. pinnata showed UV spectra similar to flavonoids glycosides derived from quercetin and kaempferol. Both extracts significantly reduced the hemorrhagic activity of B. jararaca venom in pre-treatment protocol, reaching about 40% of inhibition, while only K. pinnata was active in post-treatment protocol (about 30% of inhibition). In the antiedematogenic activity, only K. pinnata was active, inhibiting about 66% and 30% in pre and post-treatment protocols, respectively. Both extracts inhibited phospholipase activity; however, K. pinnata was more active. In conclusion, the results indicate the potential antiophidic activity of Kalanchoe species against local effects induced by B. jararaca snake

Inhibitory Effects of Hydroethanolic Leaf Extracts of Kalanchoe brasiliensis and Kalanchoe pinnata (Crassulaceae against Local Effects Induced by Bothrops jararaca Snake Venom.

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Júlia Morais Fernandes

Full Text Available The species Kalanchoe brasiliensis and Kalanchoe pinnata, both known popularly as "Saião," are used interchangeably in traditional medicine for their antiophidic properties. Studies evaluating the anti-venom activity of these species are scarce. This study aims to characterize the chemical constituents and evaluate the inhibitory effects of hydroethanolic leaf extracts of K. brasiliensis and K. pinnata against local effects induced by Bothrops jararaca snake venom. Thin Layer Chromatography (TLC and High Performance Liquid Chromatography coupled with Diode Array Detection and Electrospray Mass Spectrometry (HPLC-DAD-MS/MS were performed for characterization of chemical markers of the extracts from these species. For antiophidic activity evaluation, B. jararaca venom-induced paw edema and skin hemorrhage in mice were evaluated. In both models, hydroethanolic extracts (125-500 mg/kg were administered intraperitoneally in different protocols. Inhibition of phospholipase enzymatic activity of B. jararaca was evaluated. The HPLC-DAD-MS/MS chromatographic profile of extracts showed some particularities in the chemical profile of the two species. K. brasileinsis exhibited major peaks that have UV spectra similar to flavonoid glycosides derived from patuletin and eupafolin, while K. pinnata showed UV spectra similar to flavonoids glycosides derived from quercetin and kaempferol. Both extracts significantly reduced the hemorrhagic activity of B. jararaca venom in pre-treatment protocol, reaching about 40% of inhibition, while only K. pinnata was active in post-treatment protocol (about 30% of inhibition. In the antiedematogenic activity, only K. pinnata was active, inhibiting about 66% and 30% in pre and post-treatment protocols, respectively. Both extracts inhibited phospholipase activity; however, K. pinnata was more active. In conclusion, the results indicate the potential antiophidic activity of Kalanchoe species against local effects induced by B

Antivenom Effects of 1,2,3-Triazoles against Bothrops jararaca and Lachesis muta Snakes

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Domingos, Thaisa F. S.; Moura, Laura de A.; Carvalho, Carla; Campos, Vinícius R.; Jordão, Alessandro K.; Cunha, Anna C.; Ferreira, Vitor F.; de Souza, Maria Cecília B. V.; Sanchez, Eladio F.; Fuly, André L.

2013-01-01

Snake venoms are complex mixtures of proteins of both enzymes and nonenzymes, which are responsible for producing several biological effects. Human envenomation by snake bites particularly those of the viperid family induces a complex pathophysiological picture characterized by spectacular changes in hemostasis and frequently hemorrhage is also seen. The present work reports the ability of six of a series of 1,2,3-triazole derivatives to inhibit some pharmacological effects caused by the venoms of Bothrops jararaca and Lachesis muta. In vitro assays showed that these compounds were impaired in a concentration-dependent manner, the fibrinogen or plasma clotting, hemolysis, and proteolysis produced by both venoms. Moreover, these compounds inhibited biological effects in vivo as well. Mice treated with these compounds were fully protected from hemorrhagic lesions caused by such venoms. But, only the B. jararaca edema-inducing activity was neutralized by the triazoles. So the inhibitory effect of triazoles derivatives against some in vitro and in vivo biological assays of snake venoms points to promising aspects that may indicate them as molecular models to improve the production of effective antivenom or to complement antivenom neutralization, especially the local pathological effects, which are partially neutralized by antivenoms. PMID:23710441

Angiogenenic effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom.

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Castanheira, Letícia Eulalio; Lopes, Daiana Silva; Gimenes, Sarah Natalie Cirilo; Deconte, Simone Ramos; Ferreira, Bruno Antônio; Alves, Patricia Terra; Filho, Luiz Ricardo Goulart; Tomiosso, Tatiana Carla; Rodrigues, Renata Santos; Yoneyama, Kelly Aparecida Geraldo; Araújo, Fernanda de Assis; Rodrigues, Veridiana de Melo

2017-09-01

The present work reports the effects of a C-type lectin (BpLec) isolated from Bothrops pauloensis snake venom upon in vitro and in vivo angiogenesis models. Initially, we noted that BpLec was not cytotoxic to endothelial cells (tEnd) in doses up to 40μg/mL, but lower doses (2.5μg/mL, 5μg/mL, 10μg/mL and 20μg/mL) reduced tEnd cells adhesion to some extracellular matrix proteins and inhibited the in vitro vessel formation in Matrigel assay stimulated by bFGF. β-galactosides (d-lactose, N-acetyl-d-galactosamine and d-galactose) at 400mM reversed the effect of BpLec on tEnd cells adhesion, whereas d-galactose (400mM) partially reversed BpLec property of inhibiting vessel formation by tEnd cells in Matrigel. In vivo assays showed that BpLec increased hemoglobin content and capillary vessels number in polyether-polyurethane sponge discs subcutaneously implanted into dorsal skin mice. Additionally, BpLec also reduced collagen deposition and did not induce a pro-inflammatory response, as demonstrated by the decreased the secretion of some inflammatory cytokines, whereas myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities were not altered by BpLec. Taken together, our results indicate that BpLec might represent an interesting angiogenesis and inflammatory modulator that could also be used for searching possible therapeutic targets involved in these processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Digenetic trematodes infection in a Bothrops moojeni (Viperidae population from a fauna rescue in Porto Primavera, São Paulo State

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Barrella T.H.

2003-01-01

Full Text Available No presente estudo é descrita a infecção por trematódeos digenéticos parasitas da cavidade oral e esôfago em uma população de serpentes Bothrops moojeni provenientes de resgate de fauna em Porto Primavera, Estado de São Paulo. Foi observada prevalência de infecção de 68%. O grau de infecção (número de trematódeos por serpente variou de 2 a 51 helmintos. Os trematódeos encontrados foram Ophisthogonimus spp. e Sticholecitha serpentis. A alta prevalência de infecção foi associada com a drástica alteração ambiental e o estresse multi-fatorial aos quais os animais foram submetidos, que poderiam ter favorecido o ciclo dos parasitas.

Evaluación biológica preliminar de extractos vegetales utilizados en la medicina tradicional de la Sierra Nevada deSanta Marta contra el veneno de la Bothrops asper

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Willinton Barranco Pérez

2013-10-01

Full Text Available Title: Preliminary biological evaluation of plants extracts used in the Sierra Nevada de Santa Marta against the snake Bothrops asper venom.ResumenLa mordedura de serpientes constituye un problema de salubridad importante en muchos países tropicales y subtropicales, con un estimado de 2,5 millones de personas envenenadas cada año. En Colombia las especies Bothropsasper y Bothropsatrox son las causantes del 70 al 90 % de los accidentes registrados. Se estima que el 60% de estos accidentes son inicialmente tratados por curanderos tradicionales utilizando plantas medicinales en diferentes preparaciones. Este estudio evaluó la capacidad inhibitoria de cinco especies contra el efecto proteolítico y hemolítico indirecto inducido por el veneno de B. asper en ensayos in vitro.Las especies, que fueron seleccionadas de acuerdo a su uso en la medicina tradicional por parte de las comunidades campesinas de la Sierra Nevada de Santa Marta, fueron, Aristolochia máxima, Cissampelospareira, Equisetumbogotense, Mucunacfpruriens y una especie de la familia Asteraceae. La planta E. bogotense mostró los mayores porcentaje de inhibición contra la actividad de las fosfolipasas A2(42,29 %, así como la mayor precipitación de las proteínas en un rango de masas moleculares de 28,2 y 94,43 KDa. Al fraccionar el extracto de E. bogotense se obtuvieron cinco fracciones, las cuales presentaron un porcentaje de inhibición de 36,6 ± 1,07 a 46,1 ± 13,6. Adicionalmente se detectaron por métodos cualitativos núcleos como, alcaloides, esteroides y/o triterpenos, taninos, cumarinas y leucoantocianidinas. En estudio se reporta la actividad antiofídica en ensayos in vitro de la especie E. bogotense contra el veneno de la especie B.asper. (DUAZARY 2012 No. 2, 140 - 150AbstractIn Colombia the species Bothrops asper and Bothrops atrox are responsible for 70 to 90% of the snakebite accidents. Around 60% of these injuries are initially treated by traditional healers; they�

Sarcophagidae and Calliphoridae related to Rhinella schneideri (Anura, Bufonidae, Bothrops moojeni (Reptilia, Serpentes and Mabuya frenata (Reptilia, Lacertilia carcasses in Brasília, Brazil Sarcophagidae e Calliphoridae associados às carcaças de Rhinella schneideri (Anura, Bufonidae, Bothrops moojeni (Reptilia, Serpentes e Mabuya frenata (Reptilia, Lacertilia em Brasília, Distrito Federal, Brasil

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Roger Maia Dias Ledo

2012-09-01

Full Text Available Sarcophagidae and Calliphoridae related to Rhinella schneideri (Anura, Bufonidae, Bothrops moojeni (Reptilia, Serpentes and Mabuya frenata (Reptilia, Lacertilia carcasses in Brasília, Brazil. This paper presents a list of necrophagous insects associated with small size carrions of two reptiles and one amphibian, found in areas of riparian forests and Cerrado sensu stricto physiognomies in a Conservation Unit located in Brasilia, Distrito Federal. We found seven species of insects related to these carcasses, being five Sarcophagidae, one Calliphoridae and one Braconidae parasitoid wasp. Lucilia eximia and Peckia (Pattonella intermutans were the most abundant species in the study, corroborating with other studies that suggests that these species have specializations for colonization of small size animal carcasses.Sarcophagidae e Calliphoridae associados às carcaças de Rhinella schneideri (Anura, Bufonidae, Bothrops moojeni (Reptilia, Serpentes e Mabuya frenata (Reptilia, Lacertilia em Brasília, Distrito Federal, Brasil. Este trabalho apresenta uma lista de insetos decompositores associados a carcaças de pequeno porte de dois répteis e de um anfíbio, encontrados em áreas de matas de galeria e de cerrado sensu stricto em unidades de conservação do Distrito Federal. Foram encontradas sete espécies de insetos associados a essas carcaças, sendo cinco sarcofagídeos, um califorídeo e uma vespa parasitóide Braconidae. Lucilia eximia e Peckia (Pattonella intermutans foram as espécies mais abundantes, corroborando com outros estudos que sugerem que estas espécies apresentam especializações para a colonização de carcaças menores.

Pulsed ultrasound therapy accelerates the recovery of skeletal muscle damage induced by Bothrops jararacussu venom

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J. Saturnino-Oliveira

2012-06-01

Full Text Available We studied the effect of pulsed ultrasound therapy (UST and antibothropic polyvalent antivenom (PAV on the regeneration of mouse extensor digitorum longus muscle following damage by Bothrops jararacussu venom. Animals (Swiss male and female mice weighing 25.0 ± 5.0 g; 5 animals per group received a perimuscular injection of venom (1 mg/kg and treatment with UST was started 1 h later (1 min/day, 3 MHz, 0.3 W/cm², pulsed mode. Three and 28 days after injection, muscles were dissected and processed for light microscopy. The venom caused complete degeneration of muscle fibers. UST alone and combined with PAV (1.0 mL/kg partially protected these fibers, whereas muscles receiving no treatment showed disorganized fascicules and fibers with reduced diameter. Treatment with UST and PAV decreased the effects of the venom on creatine kinase content and motor activity (approximately 75 and 48%, respectively. Sonication of the venom solution immediately before application decreased the in vivo and ex vivo myotoxic activities (approximately 60 and 50%, respectively. The present data show that UST counteracts some effects of B. jararacussu venom, causing structural and functional improvement of the regenerated muscle after venom injury.

Envenomations by Bothrops and Crotalus snakes induce the release of mitochondrial alarmins.

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Irene Zornetta

Full Text Available Skeletal muscle necrosis is a common manifestation of viperid snakebite envenomations. Venoms from snakes of the genus Bothrops, such as that of B. asper, induce muscle tissue damage at the site of venom injection, provoking severe local pathology which often results in permanent sequelae. In contrast, the venom of the South American rattlesnake Crotalus durissus terrificus, induces a clinical picture of systemic myotoxicity, i.e., rhabdomyolysis, together with neurotoxicity. It is known that molecules released from damaged muscle might act as 'danger' signals. These are known as 'alarmins', and contribute to the inflammatory reaction by activating the innate immune system. Here we show that the venoms of B. asper and C. d. terrificus release the mitochondrial markers mtDNA (from the matrix and cytochrome c (Cyt c from the intermembrane space, from ex vivo mouse tibialis anterior muscles. Cyt c was released to a similar extent by the two venoms whereas B. asper venom induced the release of higher amounts of mtDNA, thus reflecting hitherto some differences in their pathological action on muscle mitochondria. At variance, injection of these venoms in mice resulted in a different time-course of mtDNA release, with B. asper venom inducing an early onset increment in plasma levels and C. d. terrificus venom provoking a delayed release. We suggest that the release of mitochondrial 'alarmins' might contribute to the local and systemic inflammatory events characteristic of snakebite envenomations.

Effects of irradiated Bothropstoxin-1 and Bothrops jararacussu crude venom on the immune system

International Nuclear Information System (INIS)

Caproni, Priscila

2009-01-01

Ionizing radiation has been successfully employed to modify the immunological properties of biomolecules and has been proven to be a powerful tool to attenuate snake venoms toxicity without affecting and even increasing their immunogenic properties. Very promising results were obtained when crude animal venoms, as well as isolated toxins, were treated with 60 Co gamma rays, yielding toxoids with good immunogenicity, however, little is known about the modifications that irradiated molecules undergo and even less about the immunological response that such antigens elicit. At the present work, we have evaluated the effects on immune system of B10.PL and BALB/c mice of Bothrops jararacussu crude venom and isolated bothropstoxin-1 (Bthx-1), before and after gamma radiation exposition. According to our data, irradiation process promoted structural modifications on both isolated toxin and crude venom, characterized by higher molecular weight protein (aggregates and oligomers) formation. Irradiated samples were immunogenic and the antibodies elicited by them were able to recognize the native toxin in ELISA. These results indicate that irradiation of toxic proteins can promote significant modifications in their structures, but still retain many of the original antigenic and immunological properties. Also, our data indicate that the irradiated protein induced higher titers of IgG2b, suggesting that Th1 cells were predominantly involved. Results from Western blot assay showed that antibodies raised against irradiated bothropstoxin-1 recognize both native isolated toxin or crude venom. Cytotoxicity assay showed that irradiated toxin and crude venom were less toxic than their native counterpart. Thus, the viability of the macrophages cultured in the presence of irradiated Bthx-1 or crude venom was higher if compared with their native forms. LDH Assay showed that irradiated Bthx-1 promotes less muscular damage than the native form. Our data confirm a potential use of ionizing

Radioiodination and biodistribution of Leucurolysin-B isolated from Bothrops Leucurus in mice bearing Ehrlich

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Gabriel, L.M.; Soares, M.A.; Bicalho, M.S.; Santos, R.G. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: marcellaaraugio@yahoo.com.br, e-mail: mbs@cdtn.br, e-mail: santosr@cdtn.br; Sanchez, E.O.F.; Silva, S.G. [Ezequiel Dias Foundation, Belo Horizonte, MG (Brazil)], e-mail: silea@funed.mg.gov.br, e-mail: eladio@funed.mg.gov.br

2009-07-01

Integrins are family of heterodimeric cell surface adhesion receptors able to recognize and bind to proteins in the extracellular matrix (ECM). This recognition is mainly through the RGD domain present in both the cell surface as the protein in the ECM. Various integrins have been identified as regulators of tumor progression. The RGD domain is also found in some snake venoms named disintegrins. Disintegrins inhibit cell-matrix and a cell-cell interaction mediated by integrin and has been shown that these proteins are able to inhibit metastasis in processes dependent on integrin. The disintegrin-like (ECD), as well as RGD-disintegrin are also able to bind to cell surface integrins and inhibit their adherence to the natural ligands. Leucurolysin-B (Leuc-B) is a metalloproteinase class P-III isolated from Bothrops leucurus (BLV) and possesses a disintegrin-like domain (ECD). The goals of this work were to synthesize a radioactive probe analog to Leuc-B using radioiodine {sup 125}I and evaluate the interaction of {sup 125}I-Leuc-B in tumor cells through the study of biodistribution in animals bearing Ehrlich tumor.125I-Leuc-B was synthesized using lactoperoxidase with high yield (90%) and specific activity of 1.2x10-7Bq/mmol. It was observed that {sup 125}I-Leuc-B had very fast clearance from the blood stream (T1/2= 0.01 h). Tumor uptake of 125I-Leuc-B gradually increased up to (2 min) and remained for a quite long period. The tumor/normal tissue uptake ratios of {sup 125}I-Leuc-B were 1.77 (tumor/normal paw) and 8.44 tumor/skeletal muscle. The results suggest that {sup 125}I-Leuc- B may constitute a good template for development of a tool for detection of solid tumors. (author)

Radioiodination and biodistribution of Leucurolysin-B isolated from Bothrops Leucurus in mice bearing Ehrlich

International Nuclear Information System (INIS)

Gabriel, L.M.; Soares, M.A.; Bicalho, M.S.; Santos, R.G.; Sanchez, E.O.F.; Silva, S.G.

2009-01-01

Integrins are family of heterodimeric cell surface adhesion receptors able to recognize and bind to proteins in the extracellular matrix (ECM). This recognition is mainly through the RGD domain present in both the cell surface as the protein in the ECM. Various integrins have been identified as regulators of tumor progression. The RGD domain is also found in some snake venoms named disintegrins. Disintegrins inhibit cell-matrix and a cell-cell interaction mediated by integrin and has been shown that these proteins are able to inhibit metastasis in processes dependent on integrin. The disintegrin-like (ECD), as well as RGD-disintegrin are also able to bind to cell surface integrins and inhibit their adherence to the natural ligands. Leucurolysin-B (Leuc-B) is a metalloproteinase class P-III isolated from Bothrops leucurus (BLV) and possesses a disintegrin-like domain (ECD). The goals of this work were to synthesize a radioactive probe analog to Leuc-B using radioiodine 125 I and evaluate the interaction of 125 I-Leuc-B in tumor cells through the study of biodistribution in animals bearing Ehrlich tumor.125I-Leuc-B was synthesized using lactoperoxidase with high yield (90%) and specific activity of 1.2x10-7Bq/mmol. It was observed that 125 I-Leuc-B had very fast clearance from the blood stream (T1/2= 0.01 h). Tumor uptake of 125I-Leuc-B gradually increased up to (2 min) and remained for a quite long period. The tumor/normal tissue uptake ratios of 125 I-Leuc-B were 1.77 (tumor/normal paw) and 8.44 tumor/skeletal muscle. The results suggest that 125 I-Leuc- B may constitute a good template for development of a tool for detection of solid tumors. (author)

Systemic effects induced by the venom of the snake Bothrops caribbaeus in a murine model.

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Herrera, Cristina; Rucavado, Alexandra; Warrell, David A; Gutiérrez, José María

2013-03-01

Snakebite envenoming by Bothrops caribbaeus, an endemic viperid from the Lesser Antillean island of Saint Lucia, is clinically characterized by local tissue damage and systemic thrombosis that can lead to cerebral, myocardial or pulmonary infarctions and venous thromboses. Systemic effects (lethality, pulmonary hemorrhage, thrombocytopenia and coagulopathy) induced by intravenous (i.v.) administration of B. caribbaeus venom were studied in mice. The role of snake venom metalloproteinases (SVMPs) in these systemic alterations was assessed by inhibition with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa(2)EDTA). A snake C-type lectin-like (snaclec) and a type P-III hemorrhagic SVMP were isolated and characterized from this venom, and the effect of venom and the isolated snaclec on human platelet aggregation was studied in vitro. Results indicate that SVMPs play an important role in the overall toxicity of B. caribbaeus venom, being responsible for systemic hemorrhage and lethality, but not thrombocytopenia, whereas the isolated snaclec is involved in the thrombocytopenic effect. Both venom and snaclec induce platelet aggregation/agglutination. Moreover, the snaclec binds directly to glycoprotein Ib (GPIb) and induces agglutination in washed fixed platelets. On the other hand, B. caribbaeus venom hydrolyzed fibrinogen in vitro and induced a partial drop of fibrinogen levels with an increase in fibrin/fibrinogen degradation products (FDP) levels in vivo. The negative result for D-dimer (DD) in plasma is consistent with the lack of microscopic evidence of pulmonary thrombosis and endothelial cell damage. Likewise, no increments in plasma sE-selectin levels were detected. The absence of thrombosis in this murine model suggests that this effect may be species-specific. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of the effect of Crotalus simus and Crotalus durissus ruruima venoms on the equine antibody response towards Bothrops asper venom: implications for the production of polyspecific snake antivenoms.

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Dos-Santos, Maria Cristina; Arroyo, Cynthia; Solano, Sergio; Herrera, María; Villalta, Mauren; Segura, Alvaro; Estrada, Ricardo; Gutiérrez, José María; León, Guillermo

2011-02-01

Antivenoms are preparations of immunoglobulins purified from the plasma of animals immunized with snake venoms. Depending on the number of venoms used during the immunization, antivenoms can be monospecific (if venom from a single species is used) or polyspecific (if venoms from several species are used). In turn, polyspecific antivenoms can be prepared by purifying antibodies from the plasma of animals immunized with a mixture of venoms, or by mixing antibodies purified from the plasma of animals immunized separately with single venom. The suitability of these strategies to produce polyspecific antibothropic-crotalic antivenoms was assessed using as models the venoms of Bothrops asper, Crotalus simus and Crotalus durissus ruruima. It was demonstrated that, when used as co-immunogen, C. simus and C. durissus ruruima venoms exert a deleterious effect on the antibody response towards different components of B. asper venom and in the neutralization of hemorrhagic and coagulant effect of this venom when compared with a monospecific B. asper antivenom. Polyspecific antivenoms produced by purifying immunoglobulins from the plasma of animals immunized with venom mixtures showed higher antibody titers and neutralizing capacity than those produced by mixing antibodies purified from the plasma of animals immunized separately with single venom. Thus, despite the deleterious effect of Crotalus sp venoms on the immune response against B. asper venom, the use of venom mixtures is more effective than the immunization with separate venoms for the preparation of polyspecific bothropic-crotalic antivenoms. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparison between IgG and F(ab′)2 polyvalent antivenoms: neutralization of systemic effects induced by Bothrops asper venom in mice, extravasation to muscle tissue, and potential for induction of adverse reactions

OpenAIRE

León Montero, Guillermo; Monge Monge, María; Rojas Umaña, Ermila; Lomonte, Bruno; Gutiérrez, José María

2001-01-01

Whole IgG and F(ab′)2 equine-derived polyvalent (Crotalinae) antivenoms, prepared from the same batch of hyperimmune plasma, were compared in terms of neutralization of the lethal and defibrinating activities induced by Bothrops asper venom, their ability to reach the muscle tissue compartment in envenomated mice, and their potential for the induction of adverse reactions. Both preparations were adjusted to the same potency against the lethal effect of B. asper venom in experiments involving ...

Sarcophagidae and Calliphoridae related to Rhinella schneideri (Anura, Bufonidae, Bothrops moojeni (Reptilia, Serpentes and Mabuya frenata (Reptilia, Lacertilia carcasses in Brasília, Brazil

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Roger Maia Dias Ledo

2012-09-01

Full Text Available Sarcophagidae and Calliphoridae related to Rhinella schneideri (Anura, Bufonidae, Bothrops moojeni (Reptilia, Serpentes and Mabuya frenata (Reptilia, Lacertilia carcasses in Brasília, Brazil. This paper presents a list of necrophagous insects associated with small size carrions of two reptiles and one amphibian, found in areas of riparian forests and Cerrado sensu stricto physiognomies in a Conservation Unit located in Brasilia, Distrito Federal. We found seven species of insects related to these carcasses, being five Sarcophagidae, one Calliphoridae and one Braconidae parasitoid wasp. Lucilia eximia and Peckia (Pattonella intermutans were the most abundant species in the study, corroborating with other studies that suggests that these species have specializations for colonization of small size animal carcasses.

A C-Type Lectin from Bothrops jararacussu Venom Disrupts Staphylococcal Biofilms

Science.gov (United States)

Klein, Raphael Contelli; Fabres-Klein, Mary Hellen; de Oliveira, Leandro Licursi; Feio, Renato Neves; Malouin, François; Ribon, Andréa de Oliveira Barros

2015-01-01

Bovine mastitis is a major threat to animal health and the dairy industry. Staphylococcus aureus is a contagious pathogen that is usually associated with persistent intramammary infections, and biofilm formation is a relevant aspect of the outcome of these infections. Several biological activities have been described for snake venoms, which led us to screen secretions of Bothrops jararacussu for antibiofilm activity against S. aureus NRS155. Crude venom was fractionated by size-exclusion chromatography, and the fractions were tested against S. aureus. Biofilm growth, but not bacterial growth, was affected by several fractions. Two fractions (15 and 16) showed the best activities and were also assayed against S. epidermidis NRS101. Fraction 15 was identified by TripleTOF mass spectrometry as a galactose-binding C-type lectin with a molecular weight of 15 kDa. The lectin was purified from the crude venom by D-galactose affinity chromatography, and only one peak was observed. This pure lectin was able to inhibit 75% and 80% of S. aureus and S. epidermidis biofilms, respectively, without affecting bacterial cell viability. The lectin also exhibited a dose-dependent inhibitory effect on both bacterial biofilms. The antibiofilm activity was confirmed using scanning electron microscopy. A pre-formed S. epidermidis biofilm was significantly disrupted by the C-type lectin in a time-dependent manner. Additionally, the lectin demonstrated the ability to inhibit biofilm formation by several mastitis pathogens, including different field strains of S. aureus, S. hyicus, S. chromogenes, Streptococcus agalactiae, and Escherichia coli. These findings reveal a new activity for C-type lectins. Studies are underway to evaluate the biological activity of these lectins in a mouse mastitis model. PMID:25811661

A C-type lectin from Bothrops jararacussu venom disrupts Staphylococcal biofilms.

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Raphael Contelli Klein

Full Text Available Bovine mastitis is a major threat to animal health and the dairy industry. Staphylococcus aureus is a contagious pathogen that is usually associated with persistent intramammary infections, and biofilm formation is a relevant aspect of the outcome of these infections. Several biological activities have been described for snake venoms, which led us to screen secretions of Bothrops jararacussu for antibiofilm activity against S. aureus NRS155. Crude venom was fractionated by size-exclusion chromatography, and the fractions were tested against S. aureus. Biofilm growth, but not bacterial growth, was affected by several fractions. Two fractions (15 and 16 showed the best activities and were also assayed against S. epidermidis NRS101. Fraction 15 was identified by TripleTOF mass spectrometry as a galactose-binding C-type lectin with a molecular weight of 15 kDa. The lectin was purified from the crude venom by D-galactose affinity chromatography, and only one peak was observed. This pure lectin was able to inhibit 75% and 80% of S. aureus and S. epidermidis biofilms, respectively, without affecting bacterial cell viability. The lectin also exhibited a dose-dependent inhibitory effect on both bacterial biofilms. The antibiofilm activity was confirmed using scanning electron microscopy. A pre-formed S. epidermidis biofilm was significantly disrupted by the C-type lectin in a time-dependent manner. Additionally, the lectin demonstrated the ability to inhibit biofilm formation by several mastitis pathogens, including different field strains of S. aureus, S. hyicus, S. chromogenes, Streptococcus agalactiae, and Escherichia coli. These findings reveal a new activity for C-type lectins. Studies are underway to evaluate the biological activity of these lectins in a mouse mastitis model.

Investigating possible biological targets of Bj-CRP, the first cysteine-rich secretory protein (CRISP) isolated from Bothrops jararaca snake venom.

Science.gov (United States)

Lodovicho, Marina E; Costa, Tássia R; Bernardes, Carolina P; Menaldo, Danilo L; Zoccal, Karina F; Carone, Sante E; Rosa, José C; Pucca, Manuela B; Cerni, Felipe A; Arantes, Eliane C; Tytgat, Jan; Faccioli, Lúcia H; Pereira-Crott, Luciana S; Sampaio, Suely V

2017-01-04

Cysteine-rich secretory proteins (CRISPs) are commonly described as part of the protein content of snake venoms, nevertheless, so far, little is known about their biological targets and functions. Our study describes the isolation and characterization of Bj-CRP, the first CRISP isolated from Bothrops jararaca snake venom, also aiming at the identification of possible targets for its actions. Bj-CRP was purified using three chromatographic steps (Sephacryl S-200, Source 15Q and C18) and showed to be an acidic protein of 24.6kDa with high sequence identity to other snake venom CRISPs. This CRISP was devoid of proteolytic, hemorrhagic or coagulant activities, and it did not affect the currents from 13 voltage-gated potassium channel isoforms. Conversely, Bj-CRP induced inflammatory responses characterized by increase of leukocytes, mainly neutrophils, after 1 and 4h of its injection in the peritoneal cavity of mice, also stimulating the production of IL-6. Bj-CRP also acted on the human complement system, modulating some of the activation pathways and acting directly on important components (C3 and C4), thus inducing the generation of anaphylatoxins (C3a, C4a and C5a). Therefore, our results for Bj-CRP open up prospects for better understanding this class of toxins and its biological actions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A C-type lectin from Bothrops jararacussu venom can adhere to extracellular matrix proteins and induce the rolling of leukocytes

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S. L. Elífio-Esposito

2007-01-01

Full Text Available Purification of a lectin from Bothrops jararacussu venom (BjcuL was carried out using agarose-D-galactose affinity gel. MALDI-TOF gave a major signal at m/z 32028, suggesting the presence of a dimmer composed of two identical subunits. Divalent cations were required for the lectin activity, as complete absence of such ions reduced hemagglutination. BjcuL was more effective at neutral pH and showed total loss of activity at pH values below 4.0 and above 9.0. Its agglutinating activity remained stable at 25°C until 60min, but increased when at 35°C for at least 15min. Adhesion assays to extracellular matrix (ECM glycoproteins showed that the biotinylated lectin (0.039-5.0µg/100µl was capable of binding to fibronectin and vitronectin in a dose-dependent manner. The binding was partially inhibited in the presence of D-galactose. BjcuL (1.25-10µg/30µl potential was investigated for leukocyte rolling and adhesion to endothelial cells in living microvessels using intravital microscopy, which showed that it induced a dose-dependent increase in rolling and adherence of leukocytes, acting directly on endothelial cells of postcapillary venules. The specific association between lectins and their ligands, either on the cell surface or on the ECM, is related to a variety of biological processes. The complementary characterization of BjcuL, shown here, is useful to further understand the venom effects and as a background for future investigation for therapeutic strategies.

The effects of low-level laser on muscle damage caused by Bothrops neuwiedi venom

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DM Dourado

2008-01-01

Full Text Available The present study aimed to assess the effects of low-level laser (660 nm on myonecrosis caused by the insertion of Bothrops neuwiedi venom in the gastrocnemius muscle of rats. Male Wistar rats were divided into three groups (n = 24 each: Group S (0.9% saline solution; Group V (venom and Group VLLL (venom plus low-level laser. These categories were subdivided into four additional groups (n = 6 based on the euthanasia timing (3 hours, 24 hours, 3 days and 7 days. The groups V and VLLL were inoculated with 100 µL of concentrated venom (40 µg/mL in the gastrocnemius muscle. The muscle was irradiated using a gallium-aluminum-arsenide laser (GaAlAs at 35 mW power and 4 J/cm² energy density for 3 hours, 24 hours, 3 days or 7 days after venom inoculation. To evaluate the myotoxic activity of the venom, CK activity was measured and the muscle was histologically analyzed. The low-level laser reduced venom-induced CK activity in the groups euthanized at 3 hours, 24 hours and 3 days (p < 0.0001. Histological analysis revealed that low-level laser reduced neutrophilic inflammation as well as myofibrillar edema, hemorrhage and myonecrosis following B. neuwiedi envenomation. These results suggest that low-level laser can be useful as an adjunct therapy following B. neuwiedi envenomation.

The effects of low-level laser on muscle damage caused by Bothrops neuwiedi venom

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Dourado, D.M.; Matias, R.; Almeida, M.F.; Paula, K.R. de; Carvalho, P.T.C. [University for the Development of the State and of the Region of Pantanal (UNIDERP), Campo Grande, MS (Brazil). Lab. of Experimental Histopathology]. E-mail: ccfi@uniderp.br; Vieira, R.P. [University of Sao Paulo (USP), SP (Brazil). School of Medicine. Dept. of Pathology and Physical Therapy; Oliveira, L.V.F. [Nove de Julho University (UNINOVE), Sao Paulo, SP (Brazil). Masters Program in Rehabilitation Sciences

2008-07-01

The present study aimed to assess the effects of low-level laser (660 nm) on myonecrosis caused by the insertion of Bothrops neuwiedi venom in the gastrocnemius muscle of rats. Male Wistar rats were divided into three groups (n = 24 each): Group S (0.9% saline solution); Group V (venom) and Group VLLL (venom plus low-level laser). These categories were subdivided into four additional groups (n = 6) based on the euthanasia timing (3 hours, 24 hours, 3 days and 7 days). The groups V and VLLL were inoculated with 100 {mu}L of concentrated venom (40 {mu}g/mL) in the gastrocnemius muscle. The muscle was irradiated using a gallium-aluminum-arsenide laser (GaAlAs) at 35 mW power and 4 J/cm{sup 2} energy density for 3 hours, 24 hours, 3 days or 7 days after venom inoculation. To evaluate the myotoxic activity of the venom, CK activity was measured and the muscle was histologically analyzed. The low-level laser reduced venom-induced CK activity in the groups euthanized at 3 hours, 24 hours and 3 days (p < 0.0001). Histological analysis revealed that low-level laser reduced neutrophilic inflammation as well as myofibrillar edema, hemorrhage and myonecrosis following B. neuwiedi envenomation. These results suggest that low-level laser can be useful as an adjunct therapy following B. neuwiedi envenomation. (author)

The effects of low-level laser on muscle damage caused by Bothrops neuwiedi venom

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Dourado, D.M.; Matias, R.; Almeida, M.F.; Paula, K.R. de; Carvalho, P.T.C.; Vieira, R.P.; Oliveira, L.V.F.

2008-01-01

The present study aimed to assess the effects of low-level laser (660 nm) on myonecrosis caused by the insertion of Bothrops neuwiedi venom in the gastrocnemius muscle of rats. Male Wistar rats were divided into three groups (n = 24 each): Group S (0.9% saline solution); Group V (venom) and Group VLLL (venom plus low-level laser). These categories were subdivided into four additional groups (n = 6) based on the euthanasia timing (3 hours, 24 hours, 3 days and 7 days). The groups V and VLLL were inoculated with 100 μL of concentrated venom (40 μg/mL) in the gastrocnemius muscle. The muscle was irradiated using a gallium-aluminum-arsenide laser (GaAlAs) at 35 mW power and 4 J/cm 2 energy density for 3 hours, 24 hours, 3 days or 7 days after venom inoculation. To evaluate the myotoxic activity of the venom, CK activity was measured and the muscle was histologically analyzed. The low-level laser reduced venom-induced CK activity in the groups euthanized at 3 hours, 24 hours and 3 days (p < 0.0001). Histological analysis revealed that low-level laser reduced neutrophilic inflammation as well as myofibrillar edema, hemorrhage and myonecrosis following B. neuwiedi envenomation. These results suggest that low-level laser can be useful as an adjunct therapy following B. neuwiedi envenomation. (author)

Study of the immune response by antibodies against the Bothrops asper venom for the elaboration of a antiophidic vaccine for bovines

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Gonzalez Rojas, Katherine

2014-01-01

Active immunization has determined against Bothrops asper snake venom (tested in murine and bovine models) a induced response by antibody able to prevent in immunized animals. A coagulopathy or death is developed after of be administered with adequate doses of poison. The amount of B. asper venom has defined the poisoning induced in bovine and murine models. The plasmatic concentration of equine antibodies against B. asper venom is specified to prevent coagulopathy and lethality induced by this venom in murine and bovine models. Murine and bovine models have verified the active immunization reached in a concentration of antibodies against B. asper venom equal or greater to the maximum concentration achieved by intravenous administration of antivenoms from equine origin. The concentration of antibodies induced by the active immunization is evaluated against B. asper venom to prevent the development of coagulopathy and lethality induced by the venom in murine and bovine models [es

Distribution of 131 I- labeled Bothrops erythromelas venom in mice

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Vasconcelos, C.M.L.; Valenca, R.C.; Araujo, E.A.; Modesto, J.C.A.; Pontes, M.M.; Guarnieri, M.C.; Brazil, T.K.

1998-01-01

Bothrops erythromelas is responsible for many snake bites in northeastern Brazil. In the present study we determined the in vivo distribution of the venom following its subcutaneous injection into mice. B. erythromelas venom and albumin were labeled individually with 131 I by the chloramine T method, and separated in a Sephacryl S-200 column. The efficiency of labeling was 68%.Male Swiss mice (40-45 g), which had been provided with drinking water containing 0.05% KI over a period of 10 days prior to the experiment, were inoculated dorsally (sc) with 0.3 ml (2.35 x 10 5 cpm/mouse) of 131 I-venom (N = 42), 131 -albumin or 131 I (controls, N = 28 each). Thirty minutes and 1,3, 6, 12, 18 and 24 h after inoculation, the animals were perfused with 0.85% Na Cl and skin and various organs were collected in order to determine radioactivity content. There was a high rate of venom absorption int he skin (51%) within the first 30 min compared to albumin (20.1%) and free iodine (8.2%). Up to the third hour after injection there was a tendency for venom and albumin to concentrate in the stomach ( 3 rd h),small intestine (3 rd h) and large intestine (6th h). Both control groups had more radioactivity in the digestive tract, especially in the stomach, but these levels decreased essentially to baseline by 12-18 h postinjection. In the kidneys, the distribution profiles of venom, albumin and iodine were similar. Counts at 30 min postinjection were low in all three groups (1.37, 1.86 and 0.77, respectively), and diminished to essentially 0% by 12-18 h. Albumin tended to concentrate in muscle until the 3 rd h postinjection (1.98%).There was a low binding of labeled venom in the liver (B. erythromelas venom does not specifically target most internal organs. That is, the systemic effects of envenomation ar mainly due to an indirect action. (author)

Snakebites by Bothrops spp in children in Campinas, São Paulo, Brazil Acidentes por serpentes do gênero Bothrops em crianças em Campinas, São Paulo, Brasil

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Fábio BUCARETCHI

2001-12-01

Full Text Available From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7% as moderate envenoming and 20.6% as severe envenoming. Two patients (2.7% showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5%, pain (94.5% ecchymosis (73.9% and blisters (11%. Local and/or systemic bleeding was observed in 28.8% of the patients. Before antivenom (AV administration, blood coagulation disorders were observed in 60.7% (incoagulable blood in 39.3% of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6% of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists. The main clinical complications observed were local infection (15.1%, compartment syndrome (4.1%, gangrene (1.4% and acute renal failure (1.4%. No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75 or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55. The frequency of local infection was significantly greater in severe cases (p De janeiro de 1984 a março de 1999, 73 crianças com menos de 15 anos de idade (1 a 14 anos, mediana = 9 anos foram admitidas após terem sido picadas por serpentes do gênero Bothrops. 26,0% das crianças foram classificadas como acidente leve, 50,7% como moderado e 20,6% como grave. Dois pacientes (2,7% não apresentaram sinais de envenenamento. A maioria dos pacientes apresentou manifestações locais, principalmente edema (94,5%, dor (94,5%, equimoses (73,9% e bolhas (11,0%. Sangramento local e/ou sist

Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Perú and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism.

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Núñez, Vitelbina; Cid, Pedro; Sanz, Libia; De La Torre, Pilar; Angulo, Yamileth; Lomonte, Bruno; Gutiérrez, José María; Calvete, Juan J

2009-11-02

The venom proteomes of Bothrops atrox from Colombia, Brazil, Ecuador, and Perú were characterized using venomic and antivenomic strategies. Our results evidence the existence of two geographically differentiated venom phenotypes. The venom from Colombia comprises at least 26 different proteins belonging to 9 different groups of toxins. PI-metalloproteinases and K49-PLA(2) molecules represent the most abundant toxins. On the other hand, the venoms from Brazilian, Ecuadorian, and Peruvian B. atrox contain predominantly PIII-metalloproteinases. These toxin profiles correlate with the venom phenotypes of adult and juvenile B. asper from Costa Rica, respectively, suggesting that paedomorphism represented a selective trend during the trans-Amazonian southward expansion of B. atrox through the Andean Corridor. The high degree of crossreactivity of a Costa Rican polyvalent (Bothrops asper, Lachesis stenophrys, Crotalus simus) antivenom against B. atrox venoms further evidenced the close evolutionary kinship between B. asper and B. atrox. This antivenom was more efficient immunodepleting proteins from the venoms of B. atrox from Brazil, Ecuador, and Perú than from Colombia. Such behaviour may be rationalized taking into account the lower content of poorly immunogenic toxins, such as PLA(2) molecules and PI-SVMPs in the paedomorphic venoms. The immunological profile of the Costa Rican antivenom strongly suggests the possibility of using this antivenom for the management of snakebites by B. atrox in Colombia and the Amazon regions of Ecuador, Perú and Brazil.

Ontogenetic variations in the venom proteome of the Amazonian snake Bothrops atrox

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Sousa Marcelo V

2006-05-01

Full Text Available Abstract Background Bothrops atrox is responsible for the majority of snakebite accidents in the Brazilian Amazon region. Previous studies have demonstrated that the biological and pharmacological activities of B. atrox venom alter with the age of the animal. Here, we present a comparative proteome analysis of B. atrox venom collected from specimens of three different stages of maturation: juveniles, sub-adults and adults. Results Optimized conditions for two-dimensional gel electrophoresis (2-DE of pooled venom samples were achieved using immobilized pH gradient (IPG gels of non-linear 3–10 pH range during the isoelectric focusing step and 10–20% gradient polyacrylamide gels in the second dimension. Software-assisted analysis of the 2-DE gels images demonstrated differences in the number and intensity of spots in juvenile, sub-adult and adult venoms. Although peptide mass fingerprinting (PMF failed to identify even a minor fraction of spots, it allowed us to group spots that displayed similar peptide maps. The spots were subjected to a combination of tandem mass spectrometry and Mascot and MS BLAST database searches that identified several classes of proteins, including metalloproteinases, serine proteinases, lectins, phospholipases A2, L-amino oxidases, nerve growth factors, vascular endothelial growth factors and cysteine-rich secretory proteins. Conclusion The analysis of B. atrox samples from specimens of different ages by 2-DE and mass spectrometry suggested that venom proteome alters upon ontogenetic development. We identified stage specific and differentially expressed polypeptides that may be responsible for the activities of the venom in each developmental stage. The results provide insight into the molecular basis of the relation between symptomatology of snakebite accidents in humans and the venom composition. Our findings underscore the importance of the use of venoms from individual specimen at various stages of maturation for

Características bioquímicas y capacidad neutralizante de cuatro antivenenos polivalentes frente a los efectos farmacológicos y enzimáticos del veneno de Bothrops asper y Porthidium nasutum de Antioquia y Chocó

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Mónica Saldarriaga

2002-01-01

Full Text Available En Colombia, el 90-95% de las 3000 mordeduras de serpientes informadas cada año, son ocasionadas por Bothrops spp, con una elevada mortalidad y secuelas. Siguiendo recomendaciones de la OMS, se evaluó la capacidad neutralizante de los efectos farmacológicos y enzimáticos de los venenos de Bothrops asper y Porthidium nasutum de Antioquia y Chocó por cuatro antivenenos; 2 de ellos de IgG completa (polivalente antibothrópico, anticrotálico del Instituto Nacional de Salud INS -Colombia; polivalente antibothrópico, anticrotálico, antilachésico de Laboratorios Probiol -Colombia y 2 antivenenos de fragmentos F(ab’2 (polivalente antibothrópico, anticrotálico del Centro de Biotecnología de la Universidad Central de Venezuela; y el polivalente antibothrópico, anticrotálico Antivipmyn® del Instituto Bioclón -México. Se determinó la actividad letal, hemorrágica, desfibrinante, edematizante, mionecrosante y hemolítica indirecta de cada veneno, siguiendo métodos ya estandarizados. Las pruebas de neutralización in vitro e in vivo se realizaron por el método de preincubación a 370C de dosis fijas de veneno y dosis variables de antiveneno. Los antivenenos Antivipmyn® de México y polivalente INS de Colombia tuvieron la mayor potencia neutralizante de todos los efectos farmacológicos y enzimáticos del veneno de B. asper y P. nasutum. El antiveneno polivalente Probiol fue el de menor capacidad neutralizante y mayor concentración de proteínas. Los antivenenos de fragmentos F(ab’2 tuvieron más baja concentración de proteínas y solo cantidades menores de proteínas no inmunes por electroforesis. Ninety to 95% of the snakebites reported yearly in Colombia are inflicted by Bothrops spp with high mortality and sequelae. Following recommendations of the World Health Organization, the neutralizing ability of four polyvalent antivenoms against several pharmacological and enzymatic effects of Bothrops asper and Porthidium nasutum snake

Differential transcript profile of inhibitors with potential anti-venom role in the liver of juvenile and adult Bothrops jararaca snake

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Cícera Maria Gomes

2017-04-01

Full Text Available Background Snakes belonging to the Bothrops genus are vastly distributed in Central and South America and are responsible for most cases of reported snake bites in Latin America. The clinical manifestations of the envenomation caused by this genus are due to three major activities—proteolytic, hemorrhagic and coagulant—mediated by metalloproteinases, serine proteinases, phospholipases A2 and other toxic compounds present in snake venom. Interestingly, it was observed that snakes are resistant to the toxic effects of its own and other snake’s venoms. This natural immunity may occur due the absence of toxin target or the presence of molecules in the snake plasma able to neutralize such toxins. Methods In order to identify anti-venom molecules, we construct a cDNA library from the liver of B. jararaca snakes. Moreover, we analyzed the expression profile of four molecules—the already known anti-hemorrhagic factor Bj46a, one gamma-phospholipase A2 inhibitor, one inter-alpha inhibitor and one C1 plasma protease inhibitor—in the liver of juvenile and adult snakes by qPCR. Results The results revealed a 30-fold increase of gamma-phospholipase A2 inhibitor and a minor increase of the inter-alpha inhibitor (5-fold and of the C1 inhibitor (3-fold in adults. However, the Bj46a factor seems to be equally transcribed in adults and juveniles. Discussion The results suggest the up-regulation of different inhibitors observed in the adult snakes might be a physiological adaptation to the recurrent contact with their own and even other snake’s venoms throughout its lifespan. This is the first comparative analysis of ontogenetic variation of expression profiles of plasmatic proteins with potential anti-venom activities of the venomous snake B. jararaca. Furthermore, the present data contributes to the understanding of the natural resistance described in these snakes.

Biochemical and functional characterization of Bothropoidin: the first haemorrhagic metalloproteinase from Bothrops pauloensis snake venom.

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Gomes, Mário Sérgio R; Naves de Souza, Dayane L; Guimarães, Denise O; Lopes, Daiana S; Mamede, Carla C N; Gimenes, Sarah Natalie C; Achê, David C; Rodrigues, Renata S; Yoneyama, Kelly A G; Borges, Márcia H; de Oliveira, Fábio; Rodrigues, Veridiana M

2015-03-01

We present the biochemical and functional characterization of Bothropoidin, the first haemorrhagic metalloproteinase isolated from Bothrops pauloensis snake venom. This protein was purified after three chromatographic steps on cation exchange CM-Sepharose fast flow, size-exclusion column Sephacryl S-300 and anion exchange Capto Q. Bothropoidin was homogeneous by SDS-PAGE under reducing and non-reducing conditions, and comprised a single chain of 49,558 Da according to MALDI TOF analysis. The protein presented an isoelectric point of 3.76, and the sequence of six fragments obtained by MS (MALDI TOF\\TOF) showed a significant score when compared with other PIII Snake venom metalloproteinases (SVMPs). Bothropoidin showed proteolytic activity on azocasein, Aα-chain of fibrinogen, fibrin, collagen and fibronectin. The enzyme was stable at pH 6-9 and at lower temperatures when assayed on azocasein. Moreover, its activity was inhibited by EDTA, 1.10-phenanthroline and β-mercaptoethanol. Bothropoidin induced haemorrhage [minimum haemorrhagic dose (MHD) = 0.75 µg], inhibited platelet aggregation induced by collagen and ADP, and interfered with viability and cell adhesion when incubated with endothelial cells in a dose and time-dependent manner. Our results showed that Bothropoidin is a haemorrhagic metalloproteinase that can play an important role in the toxicity of B. pauloensis envenomation and might be used as a tool for studying the effects of SVMPs on haemostatic disorders and tumour metastasis. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

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Carolina Alves Nicolau

2018-02-01

Full Text Available Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7 followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic, and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1 antimicrobial activity; (2 treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy; (3 treatment of cardiovascular diseases, and (4 anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.

Isolation of bothrasperin, a disintegrin with potent platelet aggregation inhibitory activity, from the venom of the snake Bothrops asper

International Nuclear Information System (INIS)

Pinto, A.; Angulo, Y.; Jimenez, R.; Lomonte, B.

2003-01-01

The venom of Bothrops asper induces severe coagulation disturbances in accidentally envenomed humans. However, only few studies have been conducted to identify components that interact with the hemostatic system in this venom. In the present work, we fractionated B. asper venom in order to investigate the possible presence of inhibitors of platelet aggregation. Using a combination of gel filtration, anion-exchange chromatography, and reverse-phase high performance liquid chromatography, we isolated an acidic protein which shows a single chain composition, with a molecular mass of ∼8 kDa, estimated by SDS-polyacrylamide gel electrophoresis. Its N-terminal sequence has high similarity to disintegrins isolated from different snake venoms, which are known to bind to cellular integrins such as the GPIIb/IIIa fibrinogen receptor on platelets. The purified protein exerted potent aggregation inhibitory activity on ADP-stimulated human platelets in vitro, with an estimated IC 50 of 50 nM. This biological activity, together with the biochemical characteristics observed, demonstrate that the protein isolated from B. asper venom is a disintegrin, hereby named bothrasperin. This is the first disintegrin isolated from Central American viperid snake species. (Author)

The ratio and concentration of two monoterpenes mediate fecundity of the pinewood nematode and growth of its associated fungi.

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Hongtao Niu

Full Text Available The pinewood nematode (PWN Bursaphelenchus xylophilus, vectored primarily by the sawyer beetle, Monochamus alternatus, is an important invasive pest and causal agent of pine wilt disease of Chinese Masson pine, Pinus massoniana. Previous work demonstrated that the ratios and concentrations of α-pinene:β-pinene differed between healthy trees and those trees containing blue-stain fungus (and M. alternatus pupae. However, the potential influence of the altered monoterpene ratios and concentrations on PWN and associated fungi remained unknown. Our current results show that low concentrations of the monoterpenes within petri dishes reduced PWN propagation, whereas the highest concentration of the monoterpenes increased PWN propagation. The propagation rate of PWN treated with the monoterpene ratio representative of blue-stain infected pine (α-pinene:β-pinene = 1:0.8, 137.6 mg/ml was significantly higher than that (α-pinene:β-pinene = 1:0.1, 137.6 mg/ml representative of healthy pines or those damaged by M. alternatus feeding, but without blue stain. Furthermore, inhibition of mycelial growth of associated fungi increased with the concentration of the monoterpenes α-pinene and β-pinene. Additionally, higher levels of β-pinene (α-pinene:β-pinene = 1:0.8 resulted in greater inhibition of the growth of the associated fungi Sporothrix sp.2 and Ophiostoma ips strains, but had no significant effects on the growth of Sporothrix sp.1, which is the best food resource for PWN. These results suggest that host monoterpenes generally reduce the reproduction of PWN. However, PWN utilizes high monoterpene concentrations and native blue-stain fungus Sporothrix sp.1 to improve its own propagation and overcome host resistance, which may provide clues to understanding the ecological mechanisms of PWN's successful invasion.

Isolation of bothrasperin, a disintegrin with potent platelet aggregation inhibitory activity, from the venom of the snake Bothrops asper

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Adrián Pinto

2003-03-01

Full Text Available The venom of Bothrops asper induces severe coagulation disturbances in accidentally envenomed humans. However, only few studies have been conducted to identify components that interact with the hemostatic system in this venom. In the present work, we fractionated B. asper venom in order to investigate the possible presence of inhibitors of platelet aggregation. Using a combination of gel filtration, anion-exchange chromatography, and reverse-phase high performance liquid chromatography, we isolated an acidic protein which shows a single chain composition, with a molecular mass of ~8 kDa, estimated by SDS-polyacrylamide gel electrophoresis. Its N-terminal sequence has high similarity to disintegrins isolated from different snake venoms, which are known to bind to cellular integrins such as the GPIIb/IIIa fibrinogen receptor on platelets. The purified protein exerted potent aggregation inhibitory activity on ADP-stimulated human platelets in vitro, with an estimated IC50 of 50 nM. This biological activity, together with the biochemical characteristics observed, demonstrate that the protein isolated from B. asper venom is a disintegrin, hereby named "bothrasperin". This is the first disintegrin isolated from Central American viperid snake species.El veneno de la serpiente Bothrops asper induce graves alteraciones de la coagulación en los humanos accidentalmente envenenados. Sin embargo, se han realizado pocos estudios para identificar los componentes del veneno que interactúan con el sistema hemostático. En el presente trabajo, fraccionamos el veneno de B. asper para investigar la posible presencia de inhibidores de la agregación plaquetaria. Empleando una combinación de técnicas cromatográficas (filtración en gel, intercambio aniónico y cromatografía líquida de alto desempeño en fase reversa, aislamos una proteína acídica de cadena simple, con una masa molecular de ~8 kDa, estimada mediante electroforesis en gel de poliacrilamida con

Crystallization and preliminary X-ray diffraction analysis of three myotoxic phospholipases A2 from Bothrops brazili venom

International Nuclear Information System (INIS)

Fernandes, Carlos A. H.; Gartuzo, Elaine C. G.; Pagotto, Ivan; Comparetti, Edson J.; Huancahuire-Vega, Salomón; Ponce-Soto, Luis Alberto; Costa, Tássia R.; Marangoni, Sergio; Soares, Andreimar M.; Fontes, Marcos R. M.

2012-01-01

Two myotoxic and noncatalytic Lys49-phospholipases A 2 (braziliantoxin-II and MT-II) and a myotoxic and catalytic phospholipase A 2 (braziliantoxin-III) from B. brazili were crystallized. X-ray diffraction data sets were collected and molecular-replacement solutions were obtained. Two myotoxic and noncatalytic Lys49-phospholipases A 2 (braziliantoxin-II and MT-II) and a myotoxic and catalytic phospholipase A 2 (braziliantoxin-III) from the venom of the Amazonian snake Bothrops brazili were crystallized. The crystals diffracted to resolutions in the range 2.56–2.05 Å and belonged to space groups P3 1 21 (braziliantoxin-II), P6 5 22 (braziliantoxin-III) and P2 1 (MT-II). The structures were solved by molecular-replacement techniques. Both of the Lys49-phospholipases A 2 (braziliantoxin-II and MT-II) contained a dimer in the asymmetric unit, while the Asp49-phospholipase A 2 braziliantoxin-III contained a monomer in its asymmetric unit. Analysis of the quaternary assemblies of the braziliantoxin-II and MT-II structures using the PISA program indicated that both models have a dimeric conformation in solution. The same analysis of the braziliantoxin-III structure indicated that this protein does not dimerize in solution and probably acts as a monomer in vivo, similar to other snake-venom Asp49-phospholipases A 2

Sexual dimorphism in development and venom production of the insular threatened pit viper Bothrops insularism (Serpentes: Viperidae of Queimada Grande Island, Brazil

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S.R. Travaglia-Cardoso

2010-09-01

Full Text Available Bothrops insularis is a threatened snake endemic to Queimada Grande Island, southern coast of São Paulo, Brazil, and the occurrence of sexual abnormalities in females (females with functional ovaries and rudimentary hemipenis has been reported in this population. To date there are few data regarding developmental features of this particular species. The aim of this study was to follow some developmental features in specimens maintained in captivity for seven years in the Herpetology Laboratory at Instituto Butantan, São Paulo, Brazil. We verified a pronounced sexual dimorphism in development and venom production in the specimens analyzed. In this regard, females showed greater length, mass and amount of venom in comparison to males. Our results suggest a possible niche partitioning between the sexes that reduces (or minimizes intraspecific disharmonic interactions (eg. competition on their small living area (Queimada Grande Island. Taken together, our data suggest that males and females probably are divergent in their diets, with females feeding preferentially on endothermic prey (such as migratory birds, while males maintain the juvenile diet (with the major items being ectothermic prey.

Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

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Cristina Herrera

2016-04-01

Full Text Available The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM and other extracellular matrix (ECM proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

An in-depth snake venom proteopeptidome characterization: Benchmarking Bothrops jararaca.

Science.gov (United States)

Nicolau, Carolina A; Carvalho, Paulo C; Junqueira-de-Azevedo, Inácio L M; Teixeira-Ferreira, André; Junqueira, Magno; Perales, Jonas; Neves-Ferreira, Ana Gisele C; Valente, Richard H

2017-01-16

A large-scale proteomic approach was devised to advance the understanding of venom composition. Bothrops jararaca venom was fractionated by OFFGEL followed by chromatography, generating peptidic and proteic fractions. The latter was submitted to trypsin digestion. Both fractions were separately analyzed by reversed-phase nanochromatography coupled to high resolution mass spectrometry. This strategy allowed deeper and joint characterizations of the peptidome and proteome (proteopeptidome) of this venom. Our results lead to the identification of 46 protein classes (with several uniquely assigned proteins per class) comprising eight high-abundance bona fide venom components, and 38 additional classes in smaller quantities. This last category included previously described B. jararaca venom proteins, common Elapidae venom constituents (cobra venom factor and three-finger toxin), and proteins typically encountered in lysosomes, cellular membranes and blood plasma. Furthermore, this report is the most complete snake venom peptidome described so far, both in number of peptides and in variety of unique proteins that could have originated them. It is hypothesized that such diversity could enclose cryptides, whose bioactivities would contribute to envenomation in yet undetermined ways. Finally, we propose that the broad range screening of B. jararaca peptidome will facilitate the discovery of bioactive molecules, eventually leading to valuable therapeutical agents. Our proteopeptidomic strategy yielded unprecedented insights into the remarkable diversity of B. jararaca venom composition, both at the peptide and protein levels. These results bring a substantial contribution to the actual pursuit of large-scale protein-level assignment in snake venomics. The detection of typical elapidic venom components, in a Viperidae venom, reinforces our view that the use of this approach (hand-in-hand with transcriptomic and genomic data) for venom proteomic analysis, at the specimen

Avaliação da influência de tensoativos na pele de muda de cobra (Bothrops jararaca e Spilotis pullatus) por espectroscopia fatoacústica no infravermelho, calorimetria exploratória diferencial e espectroscopia Raman

OpenAIRE

Aurea Cristina Lemos Lacerda

2004-01-01

A influência dos tensoativos lauril sulfato de sódio, cloreto de cetil trimetil amônio e álcool láurico etoxilado com 12 moles de óxido de etileno sobre o stratum corneum da pele de muda das cobras Bothrops jararaca e Spilotis pullatus foi avaliada através das técnicas biofísicas de PAS-FTIR, FT-Raman e DSC. Foram utilizadas soluções dos tensoativos em concentrações acima e abaixo da cmc e tratamentos por 4 e 8 horas (stratum corneum íntegro) e por 12 horas (stratum corneum após a remoção mec...

Isolation and characterization of a serine proteinase with thrombin-like activity from the venom of the snake Bothrops asper

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A.V Pérez

2008-01-01

Full Text Available A serine proteinase with thrombin-like activity was isolated from the venom of the Central American pit viper Bothrops asper. Isolation was performed by a combination of affinity chromatography on aminobenzamidine-Sepharose and ion-exchange chromatography on DEAE-Sepharose. The enzyme accounts for approximately 0.13% of the venom dry weight and has a molecular mass of 32 kDa as determined by SDS-PAGE, and of 27 kDa as determined by MALDI-TOF mass spectrometry. Its partial amino acid sequence shows high identity with snake venom serine proteinases and a complete identity with a cDNA clone previously sequenced from this species. The N-terminal sequence of the enzyme is VIGGDECNINEHRSLVVLFXSSGFL CAGTLVQDEWVLTAANCDSKNFQ. The enzyme induces clotting of plasma (minimum coagulant dose = 4.1 µg and fibrinogen (minimum coagulant dose = 4.2 µg in vitro, and promotes defibrin(ogenation in vivo (minimum defibrin(ogenating dose = 1.0 µg. In addition, when injected intravenously in mice at doses of 5 and 10 µg, it induces a series of behavioral changes, i.e., loss of the righting reflex, opisthotonus, and intermittent rotations over the long axis of the body, which closely resemble the `gyroxin-like' effect induced by other thrombin-like enzymes from snake venoms.

Purification and Characterization of BmooAi: A New Toxin from Bothrops moojeni Snake Venom That Inhibits Platelet Aggregation

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Mayara Ribeiro de Queiroz

2014-01-01

Full Text Available In this paper, we describe the purification/characterization of BmooAi, a new toxin from Bothrops moojeni that inhibits platelet aggregation. The purification of BmooAi was carried out through three chromatographic steps (ion-exchange on a DEAE-Sephacel column, molecular exclusion on a Sephadex G-75 column, and reverse-phase HPLC chromatography on a C2/C18 column. BmooAi was homogeneous by SDS-PAGE and shown to be a single-chain protein of 15,000 Da. BmooAi was analysed by MALDI-TOF Spectrometry and revealed two major components with molecular masses 7824.4 and 7409.2 as well as a trace of protein with a molecular mass of 15,237.4 Da. Sequencing of BmooAi by Edman degradation showed two amino acid sequences: IRDFDPLTNAPENTA and ETEEGAEEGTQ, which revealed no homology to any known toxin from snake venom. BmooAi showed a rather specific inhibitory effect on platelet aggregation induced by collagen, adenosine diphosphate, or epinephrine in human platelet-rich plasma in a dose-dependent manner, whereas it had little or no effect on platelet aggregation induced by ristocetin. The effect on platelet aggregation induced by BmooAi remained active even when heated to 100°C. BmooAi could be of medical interest as a new tool for the development of novel therapeutic agents for the prevention and treatment of thrombotic disorders.

Inhibition of proteases and phospholipases A2 from Bothrops atrox and Crotalus durissus terrificus snake venoms by ascorbic acid, vitamin E, and B-complex vitamins.

Science.gov (United States)

Oliveira, Carlos H M; Simão, Anderson A; Trento, Marcus V C; César, Pedro H S; Marcussi, Silvana

2016-01-01

The enzyme inhibition by natural and/ or low-cost compounds may represent a valuable adjunct to traditional serotherapy performed in cases of snakebite, mainly with a view to mitigate the local effects of envenoming. The objective of this study was to evaluate possible interactions between vitamins and enzymes that comprise Bothrops atrox and Crotalus durissus terrificus venoms, in vitro. Proteolysis inhibition assays (substrates: azocasein, collagen, gelatin and fibrinogen), hemolysis, coagulation, hemagglutination were carried out using different proportions of vitamins in face of to inhibit minimum effective dose of each venom. The vitamins were responsible for reducing 100% of breaking azocasein by C.d.t. venom, thrombolysis induced by B. atrox and fibrinogenolysis induced by both venoms. It is suggested the presence of interactions between vitamin and the active site of enzymes, for example the interactions between hydrophobic regions present in the enzymes and vitamin E, as well as the inhibitions exercised by antioxidant mechanism.

Structural and binding studies of a C-type galactose-binding lectin from Bothrops jararacussu snake venom.

Science.gov (United States)

Sartim, Marco A; Pinheiro, Matheus P; de Pádua, Ricardo A P; Sampaio, Suely V; Nonato, M Cristina

2017-02-01

BJcuL is a snake venom galactoside-binding lectin (SVgalL) isolated from Bothrops jararacussu and is involved in a wide variety of biological activities including triggering of pro-inflammatory response, disruption of microbial biofilm structure and induction of apoptosis. In the present work, we determined the crystallographic structure of BJcuL, the first holo structure of a SVgalL, and introduced the fluorescence-based thermal stability assay (Thermofluor) as a tool for screening and characterization of the binding mechanism of SVgalL ligands. BJcuL structure revealed the existence of a porous and flexible decameric arrangement composed of disulfide-linked dimers related by a five-fold symmetry. Each monomer contains the canonical carbohydrate recognition domain, a calcium ion required for BJcuL lectinic activity and a sodium ion required for protein stabilization. BJcuL thermostability was found to be induced by calcium ion and galactoside sugars which exhibit hyperbolic saturation profiles dependent on ligand concentration. Serendipitously, the gentamicin group of aminoglycoside antibiotics (gAGAs) was also identified as BJcuL ligands. On contrast, gAGAs exhibited a sigmoidal saturation profile compatible with a cooperative mechanism of binding. Thermofluor, hemagglutination inhibition assay and molecular docking strategies were used to identify a distinct binding site in BJcuL localized at the dimeric interface near the fully conserved intermolecular Cys86-Cys86 disulfide bond. The hybrid approach used in the present work provided novel insights into structural behavior and functional diversification of SVgaLs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Isolation: analysis and properties of three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom.

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Ferreira, L A; Galle, A; Raida, M; Schrader, M; Lebrun, I; Habermehl, G

1998-04-01

In the course of systematic investigations on low-molecular-weight compounds from the venom of Crotalidae and Viperidae, we have isolated and characterized at least three bradykinin-potentiating peptides (BPP-II, BPP-III, and BPP-V) from Bothrops neuwiedi venom by gel filtration on Sephadex G-25 M, Sephadex G-10 followed by HPLC. The peptides showed bradykinin-potentiating action on isolated guinea-pig ileum, for which the BPP-V was more active than of BPP-II, and BPP-III, rat arterial blood pressure, and a relevant angiotensin-converting enzyme (ACE) competitive inhibiting activity. The kinetic studies showed a Ki of the order of 9.7 x 10(-3) microM to BPP-II, 7 x 10(-3) microM to BPP-III, and 3.3 x 10(-3) microM to BPP-V. The amino acid sequence of the BPP-III has been determined to be pGlu-Gly-Gly-Trp-Pro-Arg-Pro-Gly-Pro-Glu-Ile-Pro-Pro, and the amino acid compositions of the BPP-II and BPP-V by amino acid analysis were 2Glu-2Gly-1Arg-4Pro-1Ile and 2Glu-2Gly-1Ser-3Pro-2Val-1Ile, with molecular weight of 1372, 1046, and 1078, respectively.

Complete amino-acid sequence, crystallization and preliminary X-ray diffraction studies of leucurolysin-a, a nonhaemorrhagic metalloproteinase from Bothrops leucurus snake venom

International Nuclear Information System (INIS)

Ferreira, Rodrigo Novaes; Rates, Breno; Richardson, Michael; Guimarães, Beatriz Gomes; Sanchez, Eládio Oswaldo Flores; Castro Pimenta, Adriano Monteiro de; Nagem, Ronaldo Alves Pinto

2009-01-01

Leucurolysin-a, a nonhaemorrhagic metalloproteinase from B. leucurus snake venom, has been crystallized in a free form and in a complexed form. Leucurolysin-a (leuc-a) is a class P-I snake-venom metalloproteinase isolated from the venom of the South American snake Bothrops leucurus (white-tailed jararaca). The mature protein is composed of 202 amino-acid residues in a single polypeptide chain. It contains a blocked N-terminus and is not glycosylated. In vitro studies revealed that leuc-a dissolves clots made either from purified fibrinogen or from whole blood. Unlike some other venom fibrinolytic metalloproteinases, leuc-a has no haemorrhagic activity. Leuc-a was sequenced and was crystallized using the hanging-drop vapour-diffusion technique. Crystals were obtained using PEG 6000 or PEG 1500. Diffraction data to 1.80 and 1.60 Å resolution were collected from two crystals (free enzyme and the endogenous ligand–protein complex, respectively). They both belonged to space group P2 1 2 1 2 1 , with very similar unit-cell parameters (a = 44.0, b = 56.2, c = 76.3 Å for the free-enzyme crystal)

Gamma radiation affects the anti-Leishmania activity of Bothrops moojeni venom and correlates with L-amino acid oxidase activity

International Nuclear Information System (INIS)

Tempone, A.G.; Lourenco, C.O.; Spencer, P.J.; Rogero, J.R.; Nascimento, N.; Andrade Junior, H.F.

1999-01-01

Leishmania causes human disfiguring skin disease in endemic areas of Amazon and North Eastern Brazil. Those parasites present a remarkable resistance to most treatments, except those using toxic antimonial salts. We detected a specific anti-Leishmania activity in snake venoms, using an in vitro promastigote assay. In this report, we analyzed the activity of Bothrops moojeni venom against L. Amazonensis, using whole venom or fractions of L-amino acid oxidase (L-AO). Crude venom of B.moojeni, was fractionated by molecular exclusion chromatography. Activity against promastigotes was detected by respiratory oxidative conversion of MTT in a colorimetric assay and L-AO activity was detected by a colorimetric assay with peroxidase and OPD as revealing reagents. Crude venom was irradiated with 500, 1000, and 2000 Gy in a 60 Co gamma radiation source. The venom had an anti-Leishmania activity of 33 pg/promastigote and the active fraction migrates as 100-150 kDa, close to the size described for L-AOs, and also presented L-AO activity. The radiation reduces both the L-AO and anti-Leishmania activity in a dose dependent effect. Those data suggests the anti-Leishmania activity in this venom is closely related to the L-amino acid oxidase activity and also that radiation could be used as a tool to detect specific activities reduction in water solutions, similarly to observed in dry preparations. (author)

Crystal structure of pira toxin-I: a calcium-independent, myotoxic phospholipase A2 - homologue from Bothrops pirajai venom

International Nuclear Information System (INIS)

Canduri, R.J.; Ward, R.J.; Azevedo Junior, G.W.F. de; Arni, R.K.; Soares, A.M.; Giglio, J.R.

1997-01-01

Full text. Phospho lipases A2 (PLA 2 ) are small enzymes that specifically hydrolysed the sn-2 ester bond of phospholipids, preferentially in lamellar or micellar aggregates at membrane surfaces. These enzymes are widely distributed in nature and have been extensively studied. Toxic proteins from venoms from Bothrops species include catalytically active PLA 2 s and calcium independent PLA 2L ys 49 homologues. The substitution of Asp49 by Lys greatly diminishes the ability of these PLA 2 to bind calcium, an ion that plays a critical role in the stabilization of the tetrahedral transition state intermediate in the catalytic mechanism. The Lys 49 PLA 2 homologues and therefore catalytically inactive yet maintain cytolytic and myotoxic activities and furthermore retain the ability to disrupt the integrity of both plasma membranes and model lipid bilayers by a poorly understood Ca 2+ independente mechanism. Lys49 PLA 2 homologues demonstrate a specific toxic activity against skeletal muscle, affecting only muscle fibers and leaving other tissue structure such as connective tissue, nerves and vessels essentially unharmed. In order to improve our understanding of the molecular basis of the myotoxic and Ca 2+ -independent membrane damaging activities, we have determined the crystal structure of Pr TX-I, a Lys49 variant from the venom of B. pirajai. The model presented has been determined at 2.8 angstrom resolution and refined to a crystallographic residual of 19.7% (R free =29.7%). (author)

Canopy Venom: Proteomic Comparison among New World Arboreal Pit-Viper Venoms.

Science.gov (United States)

Debono, Jordan; Cochran, Chip; Kuruppu, Sanjaya; Nouwens, Amanda; Rajapakse, Niwanthi W; Kawasaki, Minami; Wood, Kelly; Dobson, James; Baumann, Kate; Jouiaei, Mahdokht; Jackson, Timothy N W; Koludarov, Ivan; Low, Dolyce; Ali, Syed A; Smith, A Ian; Barnes, Andrew; Fry, Bryan G

2016-07-08

Central and South American pitvipers, belonging to the genera Bothrops and Bothriechis, have independently evolved arboreal tendencies. Little is known regarding the composition and activity of their venoms. In order to close this knowledge gap, venom proteomics and toxin activity of species of Bothriechis, and Bothrops (including Bothriopsis) were investigated through established analytical methods. A combination of proteomics and bioactivity techniques was used to demonstrate a similar diversification of venom composition between large and small species within Bothriechis and Bothriopsis. Increasing our understanding of the evolution of complex venom cocktails may facilitate future biodiscoveries.

Purification and partial characterization of phospholipases A2 from Bothrops asper (barba amarilla snake venom from Chiriguaná (Cesar, Colombia

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J. Ramírez-Avila

2004-01-01

Full Text Available Components with phospholipase A2 activity were isolated by gel filtration and cationic exchange chromatography from the venom of Bothrops asper snakes from Chiriguaná, Colombia (9°22´N; 73°37´W. Five fractions were obtained by the gel filtration, and PLA2 activity was found in fraction 3 (F3. In the cationic exchange chromatography, F3 showed eight components with PLA2 activity. Six of these components appeared as one band in polyacrylamide gel electrophoresis (SDS-PAGE. Fractions II and VII exhibited an optimal activity at pH 9 and 52ºC. The optimum calcium concentration for fraction II was 48 mM and for fraction VII, 384 mM. Both fractions showed thermal stability. Fraction II was stable at pH values between 2.5 and 9, and fraction VII, between 2.5 and 8. The Michaelis Menten constant (K M was 3.5x10-3 M for fraction II and 1.6x10-3 M for fraction VII. The molecular weight was 16,000 Dalton for fraction II and 17,000 Dalton for fraction VII. Both isoenzymes did not show any toxic activity (DL50 at 5.3 and 4 µg/g. The two fractions showed different kinetic constant (K M, calcium requirement, and substrate specificity for haemolytic activity.

SISTEMA FIBRINOLÍTICO: MÉTODOS DE ESTUDIO Y HALLAZGOS EN VENENOS DE SERPIENTES DE LOS GENEROS Bothrops, Crotalus, Micrurus EN VENEZUELA | FIBRINOLYTIC SYSTEM: METHODS OF STUDY AND FINDINGS IN Bothrops, Crotalus, Micrurus SNAKE VENOMS IN VENEZUELA

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Alexis Rodríguez-Acosta,

2016-10-01

Full Text Available En la presente revisión se muestran resultados relevantes de actividades hemostáticas, con especial énfasis a las relacionadas con la fibrinólisis, presentes en venenos de serpientes venezolanas de los géneros Bothrops, Crotalus y Micrurus, que existen en diversas localidades geográficas. Con esta descripción, se presenta además una revisión de diversos ensayos que se utilizan en investigación para estos estudios. Se han evidenciado importantes diferencias inter e intra-especies, e incluso entre ejemplares de distintos espacios geográficos, lo que debe influir en los mecanismos de acción de sus venenos y la sintomatología clínica. Estas diferencias en composición y concentración de componentes activos, deben estar asociadas a variaciones estacionales o geográficas, dieta, sexo, hábitat, edad, e inclusive variabilidades genéticas. Ello podría explicar las discrepancias en los cuadros clínicos de las víctimas y también ayudar a determinar mecanismos de acción que faciliten una mejor orientación a los médicos tratantes. Estas variables ayudarían al seguimiento y tratamiento de los pacientes, orientando a los especialistas en antivenenos, en la escogencia del inóculo, con una mezcla amplia de venenos de diferentes especies, géneros, edad, sexo y procedencia, así como con toxinas de relevancia, para la preparación y obtención de estos antivenenos con valores de gran eficacia y amplio espectro. Los componentes bioactivos aislados, como las colombienasas y la tenerplasminina-1, por sus características biológicas, representan asimismo moléculas con un uso potencial como trombolíticos y antifibrinolíticos, respectivamente.

Gamma radiation affects the anti-Leishmania activity of Bothrops moojeni venom and correlates with L-amino acid oxidase activity

Energy Technology Data Exchange (ETDEWEB)

Tempone, A.G.; Lourenco, C.O.; Spencer, P.J.; Rogero, J.R.; Nascimento, N. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil). Div. de Radiobiologia; Andrade Junior, H.F. [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Inst. de Medicina Tropical

1999-11-01

Leishmania causes human disfiguring skin disease in endemic areas of Amazon and North Eastern Brazil. Those parasites present a remarkable resistance to most treatments, except those using toxic antimonial salts. We detected a specific anti-Leishmania activity in snake venoms, using an in vitro promastigote assay. In this report, we analyzed the activity of Bothrops moojeni venom against L. Amazonensis, using whole venom or fractions of L-amino acid oxidase (L-AO). Crude venom of B.moojeni, was fractionated by molecular exclusion chromatography. Activity against promastigotes was detected by respiratory oxidative conversion of MTT in a colorimetric assay and L-AO activity was detected by a colorimetric assay with peroxidase and OPD as revealing reagents. Crude venom was irradiated with 500, 1000, and 2000 Gy in a {sup 60} Co gamma radiation source. The venom had an anti-Leishmania activity of 33 pg/promastigote and the active fraction migrates as 100-150 kDa, close to the size described for L-AOs, and also presented L-AO activity. The radiation reduces both the L-AO and anti-Leishmania activity in a dose dependent effect. Those data suggests the anti-Leishmania activity in this venom is closely related to the L-amino acid oxidase activity and also that radiation could be used as a tool to detect specific activities reduction in water solutions, similarly to observed in dry preparations. (author) 13 refs., 3 figs.

Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia

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V. Núñez

2004-07-01

Full Text Available We determined the neutralizing activity of 12 ethanolic extracts of plants against the edema-forming, defibrinating and coagulant effects of Bothrops asper venom in Swiss Webster mice. The material used consisted of the leaves and branches of Bixa orellana (Bixaceae, Ficus nymphaeifolia (Moraceae, Struthanthus orbicularis (Loranthaceae and Gonzalagunia panamensis (Rubiaceae; the stem barks of Brownea rosademonte (Caesalpiniaceae and Tabebuia rosea (Bignoniaceae; the whole plant of Pleopeltis percussa (Polypodiaceae and Trichomanes elegans (Hymenophyllaceae; rhizomes of Renealmia alpinia (Zingiberaceae, Heliconia curtispatha (Heliconiaceae and Dracontium croatii (Araceae, and the ripe fruit of Citrus limon (Rutaceae. After preincubation of varying amounts of each extract with either 1.0 µg venom for the edema-forming effect or 2.0 µg venom for the defibrinating effect, the mixture was injected subcutaneously (sc into the right foot pad or intravenously into the tail, respectively, to groups of four mice (18-20 g. All extracts (6.2-200 µg/mouse partially neutralized the edema-forming activity of venom in a dose-dependent manner (58-76% inhibition, with B. orellana, S. orbicularis, G. panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten extracts (3.9-2000 µg/mouse also showed 100% neutralizing ability against the defibrinating effect of venom, and nine prolonged the coagulation time induced by the venom. When the extracts were administered either before or after venom injection, the neutralization of the edema-forming effect was lower than 40% for all extracts, and none of them neutralized the defibrinating effect of venom. When they were administered in situ (sc at the same site 5 min after venom injection, the neutralization of edema increased for six extracts, reaching levels up to 64% for C. limon.

Accidente bothrópico en Colombia: estudio multicéntrico de la eficacia y seguridad de Antivipmyn-Tri®, un antiveneno polivalente producido en México Bothrops bites in Colombia: a multicenter study on the efficacy and safety of Antivipmyn-Tri®, a polyvalent antivenom produced in Mexico

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Oscar Fernando Jaramillo Delgado

2007-08-01

Full Text Available Introducción: Colombia es un país con dos productores de antivenenos de IgG, pero hay un mercado insatisfecho por diferentes razones técnicas. Objetivos: evaluar la eficacia y la seguridad de un antiveneno F(ab´2 polivalente (Antivipmyn-Tri® producido en México, y un nuevo esquema de dosis en accidente bothrópico en Colombia. Métodos: se realizaron durante 9 meses un ensayo clínico-terapéutico y cuantificaciones de veneno y antiveneno sérico (ELISA en 53 pacientes. Resultados: cuarenta y cuatro pacientes fueron mordidos por Bothrops asper en Antioquia y Chocó y 9 por B. atrox en Amazonas; todos tenían sangre incoagulable al ingreso, 30 (56,6% con sangrado local y 24 (45,3% con sangrado sistémico. El grado final de envenenamiento fue leve en 13 (24,5%, moderado en 30 (56,6% y grave en 10 pacientes (18,9%. A las dosis recomendadas de 5 frascos para los casos leves o moderados y 10 para los graves, Antivipmyn-Tri® fue 100% eficaz para disminuir significativamente las concentraciones séricas de veneno en la primera hora de tratamiento y para detener el sangrado en las primeras 6-12 horas, 96,2% eficaz para normalizar la coagulación en 24 horas y 100% en 48 horas. Hubo 2 casos (3,8% de recurrencia de coagulopatía sin sangrado y 12 recurrencias de antigenemia sin implicaciones clínicas. Diez pacientes (18,9% presentaron reacciones tempranas adversas (leves a la faboterapia. No hubo muertes, y cuatro pacientes (7,5% tuvieron secuelas. Conclusión: a las dosis utilizadas en este estudio, Antivipmyn-Tri® fue eficaz y seguro para el tratamiento del envenenamiento bothrópico en Colombia. Introduction: Colombia is a country with two whole IgG antivenom producers, but the expectancy of all the market are not fulfilled by different technical reasons. Objectives: To evaluate the efficacy and safety of a F(ab´2 polyvalent antivenom produced in Mexico and of a new dosage regimen for Bothrops bites in Colombia. Methods: A clinical trial

Crystallization and preliminary X-ray crystallographic studies of a Lys49-phospholipase A2 homologue from Bothrops pirajai venom complexed with rosmarinic acid

International Nuclear Information System (INIS)

Santos, Juliana I. dos; Santos-Filho, Norival A.; Soares, Andreimar M.; Fontes, Marcos R. M.

2010-01-01

PrTX-I, a noncatalytic and myotoxic Lys49-phospholipase A 2 from B. pirajai venom, was cocrystallized with the inhibitor rosmarinic acid from C. verbenacea. The crystals diffracted X-rays to 1.8 Å resolution and the structure was solved, indicating a remarkable electronic density for the ligand at the entrance to the hydrophobic channel. PrTX-I, a noncatalytic and myotoxic Lys49-phospholipase A 2 from Bothrops pirajai venom, was crystallized in the presence of the inhibitor rosmarinic acid (RA). This is the active compound in the methanolic extract of Cordia verbenacea, a plant that is largely used in Brazilian folk medicine. The crystals diffracted X-rays to 1.8 Å resolution and the structure was solved by molecular-replacement techniques, showing electron density that corresponds to RA molecules at the entrance to the hydrophobic channel. The crystals belong to space group P2 1 2 1 2 1 , indicating conformational changes in the structure after ligand binding: the crystals of all apo Lys49-phospholipase A 2 structures belong to space group P3 1 21, while the crystals of complexed structures belong to space groups P2 1 or P2 1 2 1 2 1

Crystal structure of myotoxin-II: a myotoxic phospholipase A2 - homologue from Bothrops moojeni venom

International Nuclear Information System (INIS)

Azevedo, W.F.; Ward, R.J.; Lombardi, F.R.; Arni, R.K.; Soares, A.M.; Giglio, J.R.; Fontes, M.R.M.

1997-01-01

Full text. Phospho lipases A2 (PLA 2 ; E C 3.1.1.4, phosphatides s n-2 acyl hydrolases) hydrolysis the s n-2 ester bond of phospholipids showing enhanced activity at lamellar or membrane surfaces. Intracellular PLA 2 s are involved at phospholipid metabolism and signal transduction, whereas extracellular PLA 2 s are found in mammalian pancreatic juices, the venoms of snakes, lizards and insects. Based on their high primary sequence similarity, extracellular PLA 2 s are separated into Classes I, II and III. Class II PLA 2 s are found in snake venoms of Crotalidae an Viperidae species, and include the sub-family of Lys PLA 2 s homologue. he coordination of the Ca 2+ ion in the PLA 2 calcium-binding loop includes and aspartate at position 49. In the catalytically active PLA 2 s, this calcium ion plays a critical role in the stabilization of the tetrahedral transition state intermediate in the catalytic mechanism. The conservative substitution Asp49-Lys results in a decreased calcium affinity with a concomitant loss of catalytic activity, and naturally occurring PLA 2 s-homologues showing the same substitution are catalytically inactive. However, the Lys PLA 2 s possess cytolytic and myotoxic activities and furthermore retain the ability to disrupt the integrity of both plasma membranes and model lipid layers by a ca 2+ -independent mechanism for which there is no evidence of lipid hydrolysis. Lys 49 PLA 2 homologues have been isolated from several Bothrops spp. venoms including B. moojeni. Therefore, in order to improve our understanding of the molecular basis of the myotoxic and Ca 2+ independent membrane damaging activities we have determined the crystal structure of MjTX-II, a Lys 49 homologue from the venom of B. moojeni. The model presented has been determined at 2.0 A resolution and refined to a crystallographic residual of 19.7% (R f ree=28.1%). (author)

Discovery of human scFvs that cross-neutralize the toxic effects of B. jararacussu and C. d. terrificus venoms.

Science.gov (United States)

Silva, Luciano C; Pucca, Manuela B; Pessenda, Gabriela; Campos, Lucas B; Martinez, Edson Z; Cerni, Felipe A; Barbosa, José E

2018-01-01

Accidents involving venomous snakes are a public health problem worldwide, causing a large number of deaths per year. In Brazil, the majority of accidents are caused by the Bothrops and Crotalus genera, which are responsible for approximately 80% of severe envenoming cases. The cross-neutralization of snake venoms by antibodies is an important issue for development of more effective treatments. Our group has previously reported the construction of human monoclonal antibody fragments towards Bothrops jararacussu and Crotalus durissus terrificus' venoms. This study aimed to select human single-chain variable fragments (scFvs) that recognize both bothropic and crotalic crude venoms following venoms neutralizing capacity in vitro and in vivo. The cross-reactivity of Cro-Bothrumabs were demonstrated by ELISA and in vitro and in vivo experiments showed that a combination of scFvs neutralizes in vitro toxic activities (e.g. indirect hemolysis and plasma-clotting) of crotalic and bothropic venoms as well as prolonged survival time of envenomed animals. Our results may contribute to the development of the first human polyvalent antivenom against Bothrops jararacussu and Crotalus durissus terrificus venoms, overcoming some undesirable effects caused by conventional serotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Crystallization and preliminary X-ray crystallographic studies of a Lys49-phospholipase A{sub 2} homologue from Bothrops pirajai venom complexed with rosmarinic acid

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Santos, Juliana I. dos [Departamento de Física e Biofísica, Instituto de Biociências, UNESP - Universidade Estadual Paulista, Botucatu-SP (Brazil); Instituto Nacional de Ciência e Tecnologia em Toxinas, CNPq (Brazil); Santos-Filho, Norival A.; Soares, Andreimar M. [Instituto Nacional de Ciência e Tecnologia em Toxinas, CNPq (Brazil); Departamento de Análizes Clínicas, Toxicológicas e Bromatológicas, FCFRP, USP, Ribeirão Preto-SP (Brazil); Fontes, Marcos R. M., [Departamento de Física e Biofísica, Instituto de Biociências, UNESP - Universidade Estadual Paulista, Botucatu-SP (Brazil); Instituto Nacional de Ciência e Tecnologia em Toxinas, CNPq (Brazil)

2010-06-01

PrTX-I, a noncatalytic and myotoxic Lys49-phospholipase A{sub 2} from B. pirajai venom, was cocrystallized with the inhibitor rosmarinic acid from C. verbenacea. The crystals diffracted X-rays to 1.8 Å resolution and the structure was solved, indicating a remarkable electronic density for the ligand at the entrance to the hydrophobic channel. PrTX-I, a noncatalytic and myotoxic Lys49-phospholipase A{sub 2} from Bothrops pirajai venom, was crystallized in the presence of the inhibitor rosmarinic acid (RA). This is the active compound in the methanolic extract of Cordia verbenacea, a plant that is largely used in Brazilian folk medicine. The crystals diffracted X-rays to 1.8 Å resolution and the structure was solved by molecular-replacement techniques, showing electron density that corresponds to RA molecules at the entrance to the hydrophobic channel. The crystals belong to space group P2{sub 1}2{sub 1}2{sub 1}, indicating conformational changes in the structure after ligand binding: the crystals of all apo Lys49-phospholipase A{sub 2} structures belong to space group P3{sub 1}21, while the crystals of complexed structures belong to space groups P2{sub 1} or P2{sub 1}2{sub 1}2{sub 1}.

Bothrops pirajai snake venom L-amino acid oxidase: in vitro effects on infection of Toxoplasma gondii in human foreskin fibroblasts

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Luiz F. M. Izidoro

2011-06-01

Full Text Available The effect of an L-amino acid oxidase isolated from Bothrops pirajai snake venom (BpirLAAO-I was investigated on infection of Toxoplasma gondii in human foreskin fibroblasts (HFF. The cytotoxic activity of BpirLAAO-I on HFF cells showed a dose-dependent toxicity with median cytotoxic dose (TD50 of 11.8 µg/mL. BpirLAAO-I induced considerable dose-dependent decrease in the T. gondii infection index under two different conditions, treatment of tachyzoites before infection or treatment of HFF cells after infection. A maximal inhibition of infection (56% was found for treatment before infection, with a median inhibitory dose (ID50 at 1.83 µg/mL and selectivity index (SI at 6.45. For treatment after infection, it was observed a maximal inhibition of infection at 65%, ID50 of 1.20 µg/mL and SI of 9.83. The treatment before infection was also effective to reduce intracellular parasitism up to 62%, although presenting higher values of ID50 (3.14 µg/mL and lower values of SI (3.76. However, treatment after infection was not effective, suggesting that the enzyme seems to have no effect on the parasite intracellular replication for this condition. In conclusion, BpirLAAO-I was more effective to inhibit the infection of neighboring cells and consequently parasite dissemination than primary infection and parasite replication. Thus, the effect of BpirLAAO-I described herein could be taken into account for the development of new synthetic anti-parasite therapeutic agents.

Purificación y caracterización de la l-amino ácido oxidasa del veneno de la serpiente Bothrops brazili "jergón shushupe"

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Christian Solís

2014-06-01

Full Text Available Se ha purificado y caracterizado parcialmente la L-aminoácido oxidasa de la serpiente Bothrops brazili. El aislamiento se realizó usando técnicas cromatográficas en Sephadex G-100 y CM-Sephadex C-50, utilizando como eluyente buffer acetato de amonio 0,1M pH 6. La enzima fue purificada 29,3 veces con un rendimiento de 30,9%. Usando electroforesis en gel de poliacrilamida con dodecil sulfato de sodio (PAGE-SDS en condiciones reductoras y no reductoras, así como las técnicas de inmunodifusión e inmunoelectroforesis, se demostró la presencia de una sola banda proteica. La enzima fue caracterizada como una glicoproteína ácida con un peso molecular de 125,7 kd formada por dos subunidades de 59,9 kd unidas por enlaces débiles, con un pH óptimo entre 7,5 y 9, dependiendo del aminoácido usado como substrato; siendo termoestable hasta los 550 C y lábil a pH alcalino. Asimismo, los ensayos por el método del cilindro en placa de Grove demostraron el efecto antibacteriano de la proteína aislada en cepas estandarizadas de Staphylococcus aureus, Vibrio cholerae y Streptococcus faecalis.

Interaction between TNF and BmooMP-Alpha-I, a Zinc Metalloprotease Derived from Bothrops moojeni Snake Venom, Promotes Direct Proteolysis of This Cytokine: Molecular Modeling and Docking at a Glance

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Maraisa Cristina Silva

2016-07-01

Full Text Available Tumor necrosis factor (TNF is a major cytokine in inflammatory processes and its deregulation plays a pivotal role in several diseases. Here, we report that a zinc metalloprotease extracted from Bothrops moojeni venom (BmooMP-alpha-I inhibits TNF directly by promoting its degradation. This inhibition was demonstrated by both in vitro and in vivo assays, using known TLR ligands. These findings are supported by molecular docking results, which reveal interaction between BmooMP-alpha-I and TNF. The major cluster of interaction between BmooMP-alpha-I and TNF was confirmed by the structural alignment presenting Ligand Root Mean Square Deviation LRMS = 1.05 Å and Interactive Root Mean Square Deviation IRMS = 1.01 Å, this result being compatible with an accurate complex. Additionally, we demonstrated that the effect of this metalloprotease on TNF is independent of cell cytotoxicity and it does not affect other TLR-triggered cytokines, such as IL-12. Together, these results indicate that this zinc metalloprotease is a potential tool to be further investigated for the treatment of inflammatory disorders involving TNF deregulation.

Isotopic change in the tissues of Bothrops atrox in captivity collected from environments of the eastern Amazon

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Martinez, M. G.; Chalkidis, H. D.; Amazonas, D. R.; da Silva, A. M.; De Oliveira, R., Jr.; Camargo, P. B.

2013-12-01

The Bothrops atrox is little studied because it is sympatric Amazonian animals, and very little is known about the ecology and natural history of this species. It has a generalist diet and the distribution of this species is very wide. The adult animals forage mostly on the ground, while the younger animals prefer to stay on the vegetation. They are easily find in the rainy months in areas near lakes and seasonally flooded and are difficult to find in the driest months, a period where there is less availability of preys in these environments. Due to its aggressiveness, is considered one of the most feared snakes in South America and in the eastern Amazon, being responsible for the largest number of snakebites in the region. Through stable isotope carbon-13 and nitrogen-15, is intended to characterize the variations of the feeding habits of these collected animals in different environments and also when they are kept in captivity, feeding the animal's bioterium. The serpents were collected in environments with different land uses, such as native forest, savannah, pasture and have been brought to the serpentarium Integrated College Tapajos (FIT), being retained in order to Samplings throughout the experiment with feeding mice's own bioterium. When these snakes came from different locations, samples were collected scales and blood (T0), before receiving the new supply (captive), and every time we fed the mice the vivarium, new tissue samples were collected, (T1, T2, T3) to exchange all the nature of food for the food captivity.Based on the results of δ13C and δ15N, the samples collected in the tissues of snakes of different environments (nature and captivity), it was observed that changes in food sources reflect changes in tissues (blood and scales), also reflecting the production of poison different periods of turnover of absorbed material in those tissues, contributing to the study of animal ecology and behavior in relation to habitat.

BmajPLA2-II, a basic Lys49-phospholipase A2 homologue from Bothrops marajoensis snake venom with parasiticidal potential.

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Grabner, Amy N; Alfonso, Jorge; Kayano, Anderson M; Moreira-Dill, Leandro S; Dos Santos, Ana Paula de A; Caldeira, Cleópatra A S; Sobrinho, Juliana C; Gómez, Ana; Grabner, Fernando P; Cardoso, Fabio F; Zuliani, Juliana Pavan; Fontes, Marcos R M; Pimenta, Daniel C; Gómez, Celeste Vega; Teles, Carolina B G; Soares, Andreimar M; Calderon, Leonardo A

2017-09-01

Snake venoms contain various proteins, especially phospholipases A 2 (PLA 2 s), which present potential applications in diverse areas of health and medicine. In this study, a new basic PLA 2 from Bothrops marajoensis with parasiticidal activity was purified and characterized biochemically and biologically. B. marajoensis venom was fractionated through cation exchange followed by reverse phase chromatographies. The isolated toxin, BmajPLA 2 -II, was structurally characterized with MALDI-TOF (Matrix-assisted laser desorption/ionization-time of flight) mass spectrometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), followed by two-dimensional electrophoresis, partial amino acid sequencing, an enzymatic activity assay, circular dichroism, and dynamic light scattering assays. These structural characterization tests presented BmajPLA 2 -II as a basic Lys49 PLA 2 homologue, compatible with other basic snake venom PLA 2 s (svPLA 2 ), with a tendency to form aggregations. The in vitro anti-parasitic potential of B. marajoensis venom and of BmajPLA 2 -II was evaluated against Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes, showing significant activity at a concentration of 100μg/mL. The venom and BmajPLA 2 -II presented IC 50 of 0.14±0.08 and 6.41±0.64μg/mL, respectively, against intraerythrocytic forms of Plasmodium falciparum with CC 50 cytotoxicity values against HepG2 cells of 43.64±7.94 and >150μg/mL, respectively. The biotechnological potential of these substances in relation to leishmaniasis, Chagas disease and malaria should be more deeply investigated. Copyright © 2017. Published by Elsevier B.V.

Venom-related transcripts from Bothrops jararaca tissues provide novel molecular insights into the production and evolution of snake venom.

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Junqueira-de-Azevedo, Inácio L M; Bastos, Carolina Mancini Val; Ho, Paulo Lee; Luna, Milene Schmidt; Yamanouye, Norma; Casewell, Nicholas R

2015-03-01

Attempts to reconstruct the evolutionary history of snake toxins in the context of their co-option to the venom gland rarely account for nonvenom snake genes that are paralogous to toxins, and which therefore represent important connectors to ancestral genes. In order to reevaluate this process, we conducted a comparative transcriptomic survey on body tissues from a venomous snake. A nonredundant set of 33,000 unigenes (assembled transcripts of reference genes) was independently assembled from six organs of the medically important viperid snake Bothrops jararaca, providing a reference list of 82 full-length toxins from the venom gland and specific products from other tissues, such as pancreatic digestive enzymes. Unigenes were then screened for nontoxin transcripts paralogous to toxins revealing 1) low level coexpression of approximately 20% of toxin genes (e.g., bradykinin-potentiating peptide, C-type lectin, snake venom metalloproteinase, snake venom nerve growth factor) in body tissues, 2) the identity of the closest paralogs to toxin genes in eight classes of toxins, 3) the location and level of paralog expression, indicating that, in general, co-expression occurs in a higher number of tissues and at lower levels than observed for toxin genes, and 4) strong evidence of a toxin gene reverting back to selective expression in a body tissue. In addition, our differential gene expression analyses identify specific cellular processes that make the venom gland a highly specialized secretory tissue. Our results demonstrate that the evolution and production of venom in snakes is a complex process that can only be understood in the context of comparative data from other snake tissues, including the identification of genes paralogous to venom toxins. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

A novel fibrinolytic metalloproteinase, barnettlysin-I from Bothrops barnetti (Barnett´s pitviper) snake venom with anti-platelet properties.

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Sanchez, Eladio Flores; Richardson, Michael; Gremski, Luiza Helena; Veiga, Silvio Sanches; Yarleque, Armando; Niland, Stephan; Lima, Augusto Martins; Estevao-Costa, Maria Inácia; Eble, Johannes Andreas

2016-03-01

Viperid snake venoms contain active components that interfere with hemostasis. We report a new P-I class snake venom metalloproteinase (SVMP), barnettlysin-I (Bar-I), isolated from the venom of Bothrops barnetti and evaluated its fibrinolytic and antithrombotic potential. Bar-I was purified using a combination of molecular exclusion and cation-exchange chromatographies. We describe some biochemical features of Bar-I associated with its effects on hemostasis and platelet function. Bar-I is a 23.386 kDa single-chain polypeptide with pI of 6.7. Its sequence (202 residues) shows high homology to other members of the SVMPs. The enzymatic activity on dimethylcasein (DMC) is inhibited by metalloproteinase inhibitors e.g. EDTA, and by α2-macroglobulin. Bar-I degrades fibrin and fibrinogen dose- and time-dependently by cleaving their α-chains. Furthermore, it hydrolyses plasma fibronectin but not laminin nor collagen type I. In vitro Bar-I dissolves fibrin clots made either from purified fibrinogen or from whole blood. In contrast to many other P-I SVMPs, Bar-I is devoid of hemorrhagic activity. Also, Bar-I dose- and time-dependently inhibits aggregation of washed human platelets induced by vWF plus ristocetin and collagen (IC50=1.3 and 3.2 μM, respectively), presumably Bar-I cleaves both vWF and GPIb. Thus, it effectively inhibits vWF-induced platelet aggregation. Moreover, this proteinase cleaves the collagen-binding α2-A domain (160 kDa) of α2β1-integrin. This explains why it additionally inhibits collagen-induced platelet activation. A non-hemorrhagic but fibrinolytic metalloproteinase dissolves fibrin clots in vitro and impairs platelet function. This study provides new opportunities for drug development of a fibrinolytic agent with antithrombotic effect. Copyright © 2015 Elsevier B.V. All rights reserved.

Alkylation of histidine residues of Bothrops jararacussu venom proteins and isolated phospholipases A2: a biotechnological tool to improve the production of antibodies.

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Guimarães, C L S; Andrião-Escarso, S H; Moreira-Dill, L S; Carvalho, B M A; Marchi-Salvador, D P; Santos-Filho, N A; Fernandes, C A H; Fontes, M R M; Giglio, J R; Barraviera, B; Zuliani, J P; Fernandes, C F C; Calderón, L A; Stábeli, R G; Albericio, F; da Silva, S L; Soares, A M

2014-01-01

Crude venom of Bothrops jararacussu and isolated phospholipases A2 (PLA2) of this toxin (BthTX-I and BthTX-II) were chemically modified (alkylation) by p-bromophenacyl bromide (BPB) in order to study antibody production capacity in function of the structure-function relationship of these substances (crude venom and PLA2 native and alkylated). BthTX-II showed enzymatic activity, while BthTX-I did not. Alkylation reduced BthTX-II activity by 50% while this process abolished the catalytic and myotoxic activities of BthTX-I, while reducing its edema-inducing activity by about 50%. Antibody production against the native and alkylated forms of BthTX-I and -II and the cross-reactivity of antibodies to native and alkylated toxins did not show any apparent differences and these observations were reinforced by surface plasmon resonance (SPR) data. Histopathological analysis of mouse gastrocnemius muscle sections after injection of PBS, BthTX-I, BthTX-II, or both myotoxins previously incubated with neutralizing antibody showed inhibition of the toxin-induced myotoxicity. These results reveal that the chemical modification of the phospholipases A2 (PLA2) diminished their toxicity but did not alter their antigenicity. This observation indicates that the modified PLA2 may provide a biotechnological tool to attenuate the toxicity of the crude venom, by improving the production of antibodies and decreasing the local toxic effects of this poisonous substance in animals used to produce antivenom.

The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom: pathophysiological mechanisms, prophylactic analgesia, and a surrogate in vitro assay.

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Chacón, Francisco; Oviedo, Andrea; Escalante, Teresa; Solano, Gabriela; Rucavado, Alexandra; Gutiérrez, José María

2015-01-01

The potency of antivenoms is assessed by analyzing the neutralization of venom-induced lethality, and is expressed as the Median Effective Dose (ED50). The present study was designed to investigate the pathophysiological mechanisms responsible for lethality induced by the venom of Bothrops asper, in the experimental conditions used for the evaluation of the neutralizing potency of antivenoms. Mice injected with 4 LD50s of venom by the intraperitoneal route died within ∼25 min with drastic alterations in the abdominal organs, characterized by hemorrhage, increment in plasma extravasation, and hemoconcentration, thus leading to hypovolemia and cardiovascular collapse. Snake venom metalloproteinases (SVMPs) play a predominat role in lethality, as judged by partial inhibition by the chelating agent CaNa2EDTA. When venom was mixed with antivenom, there was a venom/antivenom ratio at which hemorrhage was significantly reduced, but mice died at later time intervals with evident hemoconcentration, indicating that other components in addition to SVMPs also contribute to plasma extravasation and lethality. Pretreatment with the analgesic tramadol did not affect the outcome of the neutralization test, thus suggesting that prophylactic (precautionary) analgesia can be introduced in this assay. Neutralization of lethality in mice correlated with neutralization of in vitro coagulant activity in human plasma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Action of Bothrops moojeni venom and its L-amino acid oxidase fraction, treated with {sup 60}Co gamma rays, in Leishmania spp; Acao do veneno de Bothrops moojeni e sua fracao L-aminoacido oxidase, submetida ao tratamento com raios gama de {sup 60}Co, em Leishmania spp

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Cardoso, Andre Gustavo Tempone

1999-07-01

Bothrops moojeni venom showed an anti leishmania activity in vitro, as determined by a cell viability assay using the reduction of MTT. After venom purification, by chromatography techniques, the fractions with anti leishmania and L-amino acid oxidase activities, eluted in the same positions. The molecular weight of the enzyme was estimated to be 140 kDa by molecular exclusion chromatography, and 69 kDa, by SDS-PAGE, migrating as a single band, with an isoelectric point of 4.8 as determined by isoelectric focusing. The purified LAO from B. moojeni venom, 135-fold more active than crude venom, showed homo dimeric constitution, and was active against Leishmania spp from the New World, with an effective concentration against L(L). amazonensis of 1.80 {mu}g/ml (EC{sub 50}), L.(V.) panamensis (0.78 |{mu}g/ml) and L.(L.) chagasi (0.63 ({mu}g/ml). Ultrastructural studies of promastigotes affected by LAO demonstrated cell death, with edema in several organelles such as mitochondria and nuclear membrane, before cell disruption and necrosis. The action of LAO was demonstrated to be hydrogen peroxide-dependent. Studies with LLCMK-2 cells, treated with LAO, showed a toxic effect, with an EC{sub 50} of 11|{mu}g/ml. Irradiation of LAO with 6{sup 0C}o gamma rays, did not affect its whole oxidative activity, neither detoxified the enzyme. Amastigotes treated with LAO were not affected by its hydrogen peroxide, otherwise, the exogenous product, killed amastigotes with an EC{sub 50} of 0.67mM. These data could be of help in the development of alternative therapeutic approaches to the treatment of leishmaniasis. (author)

Action of Bothrops moojeni venom and its L-amino acid oxidase fraction, treated with 60Co gamma rays, in Leishmania spp

International Nuclear Information System (INIS)

Cardoso, Andre Gustavo Tempone

1999-01-01

Bothrops moojeni venom showed an anti leishmania activity in vitro, as determined by a cell viability assay using the reduction of MTT. After venom purification, by chromatography techniques, the fractions with anti leishmania and L-amino acid oxidase activities, eluted in the same positions. The molecular weight of the enzyme was estimated to be 140 kDa by molecular exclusion chromatography, and 69 kDa, by SDS-PAGE, migrating as a single band, with an isoelectric point of 4.8 as determined by isoelectric focusing. The purified LAO from B. moojeni venom, 135-fold more active than crude venom, showed homo dimeric constitution, and was active against Leishmania spp from the New World, with an effective concentration against L(L). amazonensis of 1.80 μg/ml (EC 50 ), L.(V.) panamensis (0.78 |μg/ml) and L.(L.) chagasi (0.63 (μg/ml). Ultrastructural studies of promastigotes affected by LAO demonstrated cell death, with edema in several organelles such as mitochondria and nuclear membrane, before cell disruption and necrosis. The action of LAO was demonstrated to be hydrogen peroxide-dependent. Studies with LLCMK-2 cells, treated with LAO, showed a toxic effect, with an EC 50 of 11|μg/ml. Irradiation of LAO with 6 0C o gamma rays, did not affect its whole oxidative activity, neither detoxified the enzyme. Amastigotes treated with LAO were not affected by its hydrogen peroxide, otherwise, the exogenous product, killed amastigotes with an EC 50 of 0.67mM. These data could be of help in the development of alternative therapeutic approaches to the treatment of leishmaniasis. (author)

Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of the haemorrhagic effect of Bothrops atrox venom.

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Otero, R; Núñez, V; Barona, J; Fonnegra, R; Jiménez, S L; Osorio, R G; Saldarriaga, M; Díaz, A

2000-11-01

Thirty-one of 75 extracts of plants used by traditional healers for snakebites, had moderate or high neutralizing ability against the haemorrhagic effect of Bothrops atrox venom from Antioquia and Chocó, north-western Colombia. After preincubation of several doses of every extract (7.8-4000 microg/mouse) with six minimum haemorrhagic doses (10 microg) of venom, 12 of them demonstrated 100% neutralizing capacity when the mixture was i.d. injected into mice (18-20 g). These were the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plants of Pleopeltis percussa (Polypodiaceae), Trichomanes elegans (Hymenophyllaceae) and Senna dariensis (Caesalpiniaceae); rhizomes of Heliconia curtispatha (Heliconiaceae); leaves and branches of Bixa orellana (Bixaceae), Philodendron tripartitum (Araceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the ripe fruits of Citrus limon (Rutaceae); leaves, branches and stem of Ficus nymphaeifolia (Moraceae). Extracts of another 19 species showed moderate neutralization (21-72%) at doses up to 4 mg/mouse, e.g. the whole plants of Aristolochia grandiflora (Aristolochiaceae), Columnea kalbreyeriana (Gesneriaceae), Sida acuta (Malvaceae), Selaginella articulata (Selaginellaceae) and Pseudoelephantopus spicatus (Asteraceae); rhizomes of Renealmia alpinia (Zingiberaceae); the stem of Strychnos xinguensis (Loganiaceae); leaves, branches and stems of Hyptis capitata (Lamiaceae), Ipomoea cairica (Convolvulaceae), Neurolaena lobata (Asteraceae), Ocimum micranthum (Lamiaceae), Piper pulchrum (Piperaceae), Siparuna thecaphora (Monimiaceae), Castilla elastica (Moraceae) and Allamanda cathartica (Apocynaceae); the macerated ripe fruits of Capsicum frutescens (Solanaceae); the unripe fruits of Crescentia cujete (Bignoniaceae); leaves and branches of Piper arboreum (Piperaceae) and Passiflora quadrangularis (Passifloraceae). When the extracts were independently administered

Increments in cytokines and matrix metalloproteinases in skeletal muscle after injection of tissue-damaging toxins from the venom of the snake Bothrops asper

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Alexandra Rucavado

2002-01-01

Full Text Available Envenomations by the snake Bothrops asper are characterized by prominent local tissue damage (i.e. myonecrosis, blistering, hemorrhage and edema. Various phospholipases A2 and metalloproteinases that induce local pathological alterations have been purified from this venom. Since these toxins induce a conspicuous inflammatory response, it has been hypothesized that inflammatory mediators may contribute to the local pathological alterations described. This study evaluated the local production of cytokines and matrix metalloproteinases (MMPs as a consequence of intramuscular injections of an Asp-49 myotoxic phospholipase A2 (myotoxin III (MT-III and a P-I type hemorrhagic metalloproteinase (BaP1 isolated from B. asper venom. Both enzymes induced prominent tissue alterations and conspicuous increments in interleukin (IL-1β, IL-6 and a number of MMPs, especially gelatinase MMP-9, rapidly after injection. In contrast, no increments in tumor necrosis factor-α (TNF-α and interferon-γ were detected. In agreement, MT-III and BaP1 did not induce the synthesis of TNF-α by resident peritoneal macrophages in vitro. Despite the conspicuous expression of latent forms of MMPs in muscle, evidenced by zymography, there were no increments in activated MMP-2 and only a small increase in activated MMP-9, as detected by a functional enzymatic assay. This suggests that MMP activity was regulated by a highly controlled activation of latent forms and, probably, by a concomitant synthesis of MMP inhibitors. Since no hemorrhage nor dermonecrosis were observed after injection of MT-III, despite a prominent increase in MMP expression, and since inflammatory exudate did not enhance hemorrhage induced by BaP1, it is suggested that endogenous MMPs released in the tissue are not responsible for the dermonecrosis and hemorrhage characteristic of B. asper envenomation. Moreover, pretreatment of mice with the peptidomimetic MMP inhibitor batimastat did not reduce myotoxic nor

Neutralizing activities of ethanolic extracts of six plants traditionally used in Guatemala as antidotes for the envenomation caused by the snake Bothrops asper

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Patricia Saravia-Otten

2015-07-01

Full Text Available Many plants are reported to be used in Guatemalan traditional medicine as antidotes against various effects of the snakebite; however, very few attempts have been made to evaluate their neutralizing capacity in controlled experiments. Six plants (Acacia hindsii, Cissampelos pareira; Hamelia patens, Piper peltatum, Sansevieria hyacinthoides and Aristolochia maxima were evaluated in vitro for their ability to neutralize phospholipase A2(PLA2 and proteolytic effects of the venom of Bothrops asper, the snake responsible for approximately half of the snakebite envenomations in Central America. These effects are indicatives of the ability of B. asper venom to produce myotoxicity, hemorrhage and inflammation. Plants were collected, dried and extracted by maceration with ethanol. After pre-incubation of several amounts of each extract with a challenge dose of venom, S. hyacinthoides demonstrated a low neutralizing capacity (< DE 50 of the PLA2 effect (13.90 ± 6.41%; C. pareira (32.98 ± 5.51% and P. peltatum (24.52 ± 7.45% neutralized less than 50% of the proteolytic effect. The results suggest that neither of the tested plants should be used individually to treat the main effects of B. asper envenomation. However, the three low-active extracts might be potentiated when used in mixtures composed of several plants, as prepared by traditional healers. Given the complexity of the venom components and the multiple pathologic effects produced by B. asper envenomation, more tests are required to fully investigate the ability of this plants to neutralize the coagulant, fibrin(ogenolytic, edematizing and myotoxic effects of the venom.

Biotechnological application of protein Leuc-B isolated from Bothrops leucurus venom as a prototype for antitumoral radiopharmaceutical;Aplicacao biotecnologica da proteina Leuc-B isolada da peconha de Bothrops leucurus como prototipo de radiofarmaco antitumoral

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Gabriel, Lucilene Marcia

2010-07-01

According to the report of the International Agency for Research on Cancer, the growth of this disease implies the death of 17 million people a year by 2030. Although the knowledge on development of cancer is growing considerably, just a few advances in the diagnosis and therapy has been achieved. Faced with this scenario, it is clear the need for new substances more specifics with low toxicity to the patient, which can be used for diagnosis and treatment of cancer. Membrane receptors over expressed in tumor cells are promising target candidates for development of diagnostic and therapeutical tools. Integrins are a family of hetero dimeric cell surface adhesion receptors able to recognize and bind to proteins in the extracellular matrix (ECM). This recognition is mainly through the RGD domains presents in both the cell surface as in the protein from the ECM. Various integrins have been identified as regulators of tumor progression. The RGD domain is also found in some snake venoms named disintegrins. Disintegrins inhibit cell-matrix and a cell-cell interactions mediated by integrins and it has been shown that these proteins are able to inhibit metastasis in processes dependent on integrin. The disintegrin-like (ECD), as well as RGD-disintegrin are also able to bind to cell surface integrins and inhibit their adhesion to the natural ligands. In this work it was purified from Bothrops leucurus venom (VBL), a metalloproteinase-class P-III with disintegrin-like domain (ECD), Leucurolisina B (Leuc-B). This metalloproteinase and the crude venom were used to evaluate their applicability in the differential detection of tumors. In vitro results demonstrated that both VBL and Leuc-B have potent antitumoral effect on several cancer cell lines: U87, T98, RT2 (glioblastoma), MCF7 (breast), Ehrlich and UACC (melanoma) with IC{sub 50} values of approximately 0.6 muM. The morphological changes observed in these strains when treated with Leuc-B, and data from the DAPI staining

Structural and Functional Studies of a Bothropic Myotoxin Complexed to Rosmarinic Acid: New Insights into Lys49-PLA2 Inhibition

Science.gov (United States)

dos Santos, Juliana I.; Cardoso, Fábio F.; Soares, Andreimar M.; dal Pai Silva, Maeli; Gallacci, Márcia; Fontes, Marcos R. M.

2011-01-01

Snakebite envenoming is an important public health problem in many tropical and subtropical countries, and is considered a neglected tropical disease by the World Health Organization. Most severe cases are inflicted by species of the families Elapidae and Viperidae, and lead to a number of systemic and local effects in the victim. One of the main problems regarding viperidic accidents is prominent local tissue damage whose pathogenesis is complex and involves the combined actions of a variety of venom components. Phospholipases A2 (PLA2s) are the most abundant muscle-damaging components of these venoms. Herein, we report functional and structural studies of PrTX-I, a Lys49-PLA2 from Bothops pirajai snake venom, and the influence of rosmarinic acid (RA) upon this toxin's activities. RA is a known active component of some plant extracts and has been reported as presenting anti-myotoxic properties related to bothopic envenomation. The myotoxic activity of Lys49-PLA2s is well established in the literature and although no in vivo neurotoxicity has been observed among these toxins, in vitro neuromuscular blockade has been reported for some of these proteins. Our in vitro studies show that RA drastically reduces both the muscle damage and the neuromuscular blockade exerted by PrTX-I on mice neuromuscular preparations (by ∼80% and ∼90%, respectively). These results support the hypothesis that the two effects are closely related and lead us to suggest that they are consequences of the muscle membrane-destabilizing activity of the Lys49-PLA2. Although the C-terminal region of these proteins has been reported to comprise the myotoxic site, we demonstrate by X-ray crystallographic studies that RA interacts with PrTX-I in a different region. Consequently, a new mode of Lys49-PLA2 inhibition is proposed. Comparison of our results with others in the literature suggests possible new ways to inhibit bothropic snake venom myotoxins and improve serum therapy. PMID:22205953

Crystallization and preliminary X-ray diffraction studies of BmooPLA2-I, a platelet-aggregation inhibitor and hypotensive phospholipase A2 from Bothrops moojeni venom

International Nuclear Information System (INIS)

Salvador, Guilherme H. M.; Marchi-Salvador, Daniela P.; Silveira, Lucas B.; Soares, Andreimar M.; Fontes, Marcos R. M.

2011-01-01

BmooPLA 2 -I, an acidic, catalytic and nontoxic phospholipase A 2 from B. moojeni venom that is able to inhibit platelet aggregation and induce a hypotensive effect, has been crystallized. An X-ray diffraction data set was collected to 1.6 Å resolution and a molecular-replacement solution was obtained. Phospholipases A 2 (PLA 2 s) are enzymes that cause the liberation of fatty acids and lysophospholipids by the hydrolysis of membrane phospholipids. In addition to their catalytic action, a wide variety of pharmacological activities have been described for snake-venom PLA 2 s. BmooPLA 2 -I is an acidic, nontoxic and catalytic PLA 2 isolated from Bothrops moojeni snake venom which exhibits an inhibitory effect on platelet aggregation, an immediate decrease in blood pressure, inducing oedema at a low concentration, and an effective bactericidal effect. BmooPLA 2 -I has been crystallized and X-ray diffraction data have been collected to 1.6 Å resolution using a synchrotron-radiation source. The crystals belonged to space group C222 1 , with unit-cell parameters a = 39.7, b = 53.2, c = 89.2 Å. The molecular-replacement solution of BmooPLA 2 -I indicated a monomeric conformation, which is in agreement with nondenaturing electrophoresis and dynamic light-scattering experiments. A comparative study of this enzyme with the acidic PLA 2 from B. jararacussu (BthA-I) and other toxic and nontoxic PLA 2 s may provide important insights into the functional aspects of this class of proteins

Efficacy and safety of two whole IgG polyvalent antivenoms, refined by caprylic acid fractionation with or without beta-propiolactone, in the treatment of Bothrops asper bites in Colombia.

Science.gov (United States)

Otero, Rafael; León, Guillermo; Gutiérrez, José María; Rojas, Gustavo; Toro, María Fabiola; Barona, Jacqueline; Rodríguez, Verónica; Díaz, Abel; Núñez, Vitelbina; Quintana, Juan Carlos; Ayala, Shirley; Mosquera, Diana; Conrado, Lesdy L; Fernández, Diego; Arroyo, Yobana; Paniagua, Carlos A; López, Mercedes; Ospina, Carlos E; Alzate, Claudia; Fernández, Jorge; Meza, Jazmín J; Silva, Juan F; Ramírez, Patricia; Fabra, Patricia E; Ramírez, Eugenio; Córdoba, Elkin; Arrieta, Ana B; Warrell, David A; Theakston, R David G

2006-12-01

The efficacy and safety of two whole IgG polyvalent antivenoms (A and B) were compared in a randomised, blinded clinical trial in 67 patients systemically envenomed by Bothrops asper in Colombia. Both antivenoms were fractionated by caprylic acid precipitation and had similar neutralising potencies, protein concentrations and aggregate contents. Antivenom B was additionally treated with beta-propiolactone to lower its anticomplementary activity. Analysing all treatment regimens together, there were no significant differences between the two antivenoms (A=34 patients; B=33 patients) in the time taken to reverse venom-induced bleeding and coagulopathy, to restore physiological fibrinogen concentrations and to clear serum venom antigenaemia. Blood coagulability was restored within 6-24 h in 97% of patients, all of whom had normal coagulation and plasma fibrinogen levels 48 h after the start of antivenom treatment. Two patients (3.0%) had recurrent coagulopathy and eight patients suffered recurrence of antigenaemia within 72 h of treatment. None of the dosage regimens of either antivenom used guaranteed resolution of venom-induced coagulopathy within 6 h, nor did they prevent recurrences. A further dose of antivenom at 6 h also did not guarantee resolution of coagulopathy within 12-24 h in all patients. The incidence of early adverse reactions (all mild) was similar for both antivenoms (15% and 24%; P>0.05).

Serpentes da área urbana de Cuiabá, Mato Grosso: aspectos ecológicos e acidentes ofídicos associados Snakes from the urban area of Cuiabá, Mato Grosso: ecological aspects and associated snakebites

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Marcos André de Carvalho

1998-10-01

Full Text Available São apresentadas informações sobre as serpentes da área urbana do Município de Cuiabá, Mato Grosso, potencialmente causadoras de acidentes ofídicos. As informações estão baseadas em exemplares doados por populares ao Núcleo de Ofiologia Regional de Mato Grosso (Normat entre 1986 e 1993 e em registros efetuados pelo Centro de Informações Anti-Veneno (Ciave entre 1988 e 1993, que não fazem referência ao animal causador. Foram catalogadas 37 espécies de serpentes, em 25 gêneros e 3 famílias, com hábitos predominantemente diurnos, terrestres e com dietas baseadas em anfíbios e/ou lagartos. Dentre os 307 acidentes ofídicos registrados, 56% foram causados por serpentes sem interesse médico e 44% constituíram acidentes de importância médica. Cerca de 99% dos acidentes de importância médica foram atribuídos ao gênero Bothrops (Bothrops moojeni e Bothrops neuwiedi seriam as principais causadoras. Dentre as espécies sem interesse médico, Philodryas olfersii e Waglerophis merremii provavelmente foram as principais responsáveis pela maior parte dos acidentes.This study presents data on snakes recorded in the urban area of Cuiabá, Mato Grosso, Brazil. Sources of information included specimens captured by local residents (1986-1993 and turned over to the Mato Grosso Regional Ophiological Center (Normat, and data from the Anti-Venom Information Center (Ciave, regarding urban snakebites (1988-1993. Thirty-seven species of snakes from 25 genera and three families were recorded. Diurnal and terrestrial habits predominated, as well as a diet based on amphibians and/or lizards. From a total of 307 snakebites recorded, some 56% were of no clinical importance, caused by non-venomous snakes, whereas 44% were clinically relevant. Approximately 99% of the latter were attributed to vipers of the genus Bothrops, and especially the Bothrops moojeni and Bothrops neuwiedi species The colubrids Philodryas olfersii and Waglerophis merremii were

Identificación molecular y actividad sobre sustratos cromogénicos de la venombina A del veneno de la serpiente peruana Bothrops atrox

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Gustavo A. Sandoval

2011-05-01

Full Text Available En el presente trabajo se ha realizado la identificación molecular de la enzima similar a trombina (EST del veneno de Bothrops atrox y se ha evaluado su actividad enzimática sobre diversos sustratos sintéticos. La enzima fue purificada utilizando tres pasos cromatrográficos, sobre Sephadex G-75, CM-Sephadex C-50 y Agarosa-PAB, determinándose su peso molecular por PAGE-SDS. La identificación molecular de la enzima aislada se realizó por la técnica de peptide mass fingerprinting basada en espectrometría de masas MALDI-TOF y posterior análisis in silico. Las actividades fibrinocoagulante y amidolítica fueron ensayadas sobre fibrinó- geno bovino y BApNA, respectivamente, así como la hidrólisis sobre los sustratos cromogénicos específicos S-2238, S-2251 y S-2266. Como resultado de los ensayos bioquímicos y estructurales, la EST del veneno de B. atrox, presentó un peso molecular de 29,6 kDa. El análisis mediante espectrometría de masas de los péptidos obtenidos, permitió identificar a esta enzima como una venombina A, presentando una identidad del 75%. Del análisis de actividad enzimática, se obtuvo que la EST de B. atrox produjo coagulación del fibrinógeno bovino y presentó actividad sobre BApNA, S-2238 y S-2266, siendo incapaz de hidrolizar el sustrato S-2251. El empleo de estas aproximaciones estructurales y funcionales ha permitido lograr la identificación molecular del principal componente del veneno de B. atrox relacionado con su acción coagulante, así como evaluar en detalle la naturaleza de su actividad enzimática sobre diversos sustratos.

Analysis of Brazilian snake venoms by neutron activation analysis

International Nuclear Information System (INIS)

Saiki, M.; Vasconcellos, M.B.A.; Rogero, J.R.; Cruz, M.C.G.

1991-01-01

Instrumental neutron activation analysis (INAA) has been applied to multielemental determinations of Brazilian snake venoms from the species: Bothrops jararacussu, Crotalus durissus terrificus and Bothrops jararaca. Concentrations of Br, Ca, Cl, Cs, K, Mg, Na, Rb, Sb, Se and Zn have been determined in lyophilized venoms by using short and long irradiations in the IEA-RI nuclear reactor under a thermal neutron flux of 10 11 to 10 13 n · cm -2 · s -1 . The reference materials NIST Bovine Liver 1577 and IUPAC Bowen's Kale were also analyzed simultaneously with the venoms to evaluate the accuracy and the reproducibility of the method. The concentrations of the elements found in snake venoms from different species were compared. The Crotalus durissus terrificus venoms presented high concentration of Se but low concentrations of Zn when these results are compared with those obtained from genera Bothrops venoms. (author) 9 refs.; 2 tabs

Biochemical and biological characterization of Bothriechis schlegelii snake venoms from Colombia and Costa Rica.

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Prezotto-Neto, José P; Kimura, Louise F; Alves, André F; Gutiérrez, José María; Otero, Rafael; Suárez, Ana M; Santoro, Marcelo L; Barbaro, Katia C

2016-12-01

Snakebites inflicted by the arboreal viperid snake Bothriechis schlegelii in humans are characterized by pain, edema, and ecchymosis at the site of the bite, rarely with blisters, local necrosis, or defibrination. Herein, a comparative study of Bothriechis schlegelii snake venoms from Colombia (BsCo) and Costa Rica (BsCR) was carried out in order to compare their main activities and to verify the efficacy of Bothrops antivenom produced in Brazil to neutralize them. Biochemical (SDS-PAGE and zymography) and biological parameters (edematogenic, lethal, hemorrhagic, nociceptive, and phospholipase A 2 activities) induced by BsCo and BsCR snake venoms were evaluated. The presence of antibodies in Bothrops antivenom that recognize BsCo and BsCR snake venoms by enzyme-linked immunosorbent assay and Western blotting, as well as the ability of this antivenom to neutralize the toxic activities were also verified. SDS-PAGE showed differences between venoms. Distinctive caseinolytic and hyaluronidase patterns were detected by zymography. BsCo and BsCR showed similar phospholipase A 2 activity. Strong cross-reactivity between BsCo and BsCR was detected using Bothrops antivenom with many components located between 150 and 35 kDa. BsCR was more edematogenic and almost fourfold more hemorrhagic than BsCo, and both venoms induced nociception. BsCR (LD 50 5.60 mg/kg) was more lethal to mice than BsCo (LD 50 9.24 mg/kg). Bothrops antivenom was effective in the neutralization of lethal and hemorrhagic activities of BsCo and BsCR and was partially effective in the neutralization of edematogenic and nociceptive activities. In conclusion, geographic distribution influences the composition and activities of Bothriechis schlegelii venoms. Bothrops antivenom cross-reacted with these venoms and was partially effective in neutralizing some toxic activities of BsCo and BsCR.

A novel synthetic quinolinone inhibitor presents proteolytic and hemorrhagic inhibitory activities against snake venom metalloproteases.

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Baraldi, Patrícia T; Magro, Angelo J; Matioli, Fábio F; Marcussi, Silvana; Lemke, Ney; Calderon, Leonardo A; Stábeli, Rodrigo G; Soares, Andreimar M; Correa, Arlene G; Fontes, Marcos R M

2016-02-01

Metalloproteases play a fundamental role in snake venom envenomation inducing hemorrhagic, fibrigen(ogen)olytic and myotoxic effects in their victims. Several snake venoms, such as those from the Bothrops genus, present important local effects which are not efficiently neutralized by conventional serum therapy. Consequently, these accidents may result in permanent sequelae and disability, creating economic and social problems, especially in developing countries, leading the attention of the World Health Organization that considered ophidic envenomations a neglected tropical disease. Aiming to produce an efficient inhibitor against bothropic venoms, we synthesized different molecules classified as quinolinones - a group of low-toxic chemical compounds widely used as antibacterial and antimycobacterial drugs - and tested their inhibitory properties against hemorrhage caused by bothropic venoms. The results from this initial screening indicated the molecule 2-hydroxymethyl-6-methoxy-1,4-dihydro-4-quinolinone (Q8) was the most effective antihemorrhagic compound among all of the assayed synthetic quinolinones. Other in vitro and in vivo experiments showed this novel compound was able to inhibit significantly the hemorrhagic and/or proteolytic activities of bothropic crude venoms and isolated snake venom metalloproteases (SVMPs) even at lower concentrations. Docking and molecular dynamic simulations were also performed to get insights into the structural basis of Q8 inhibitory mechanism against proteolytic and hemorrhagic SVMPs. These structural studies demonstrated that Q8 may form a stable complex with SVMPs, impairing the access of substrates to the active sites of these toxins. Therefore, both experimental and structural data indicate that Q8 compound is an interesting candidate for antiophidic therapy, particularly for the treatment of the hemorrhagic and necrotic effects induced by bothropic venoms. Copyright © 2015 Elsevier B.V. and Société Française de

Variaciones ontogénicas y geográficas en los efectos tóxicos y en las características inmunoquímicas del veneno de serpientes del grupo Bothrops atrox del Meta y Antioquia

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María Fabiola Toro

2000-02-01

Full Text Available

El accidente ofídico es un problema de salud pública frecuente en algunos lugares del mundo. En Latinoamérica, el género Bothrops es el causante del 90% de los accidentes ofídicos y en Colombia el grupo Bothrops atrox es responsable del 50% o más de los casos que se reportan anualmente (2000 casos. Este grupo se encuentra distribuido en la mayor parte del territorio nacional colombiano, incluyendo el este y oeste de los Andes, vertiente Pacífica y Atlántica, además de los valles interandinos.

El veneno del grupo Bothrops atrox induce un complejo cuadro de alteraciones fisiopatológicas locales y sistémicas, como mionecrosis, dermonecrosis, edema, hemorragia, dolor, coagulopatías, choque cardiovascular, nefrotoxicidad, actividad proteolítica y hemolítica indirecta.

En diversos países se han realizado estudios sobre la variabilidad de los venenos de diferentes especies de serpientes. Se han encontrado diferencias en todos los niveles taxonómicos, siendo de mayor importancia la variabilidad intraespecífica. Con este estudio se pretende determinar la variabilidad ontogénica y geográfica del veneno de Bothrops atrox procedente de dos regiones colombianas, mediante pruebas biológicas e inmunoquímicas. Los resultados previos muestran que existe una variación ontogénica en el veneno de la especie Bothrops atrox del departamento del Meta con respecto a la letalidad, y a las actividades hemorrágica, coagulante y edematizante. Las serpientes recién nacidas tienen una mayor letalidad (DL50 = 51.8 ± 5.6 mg de veneno con respecto a los adultos (81.4±

Factors underlying the natural resistance of animals against snake venoms

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H. Moussatché

1989-01-01

Full Text Available The existence of mammals and reptilia with a natural resistance to snake venoms is known since a long time. This fact has been subjected to the study by several research workers. Our experiments showed us that in the marsupial Didelphis marsupialis, a mammal highly resistant to the venom of Bothrops jararaca, and other Bothrops venoms, has a genetically origin protein, a alpha-1, acid glycoprotein, now highly purified, with protective action in mice against the jararaca snake venom.

The inhibitory potential of the condensed-tannin-rich fraction of Plathymenia reticulata Benth. (Fabaceae) against Bothrops atrox envenomation.

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de Moura, Valéria Mourão; da Silva, Wania Cristina Rodrigues; Raposo, Juliana D A; Freitas-de-Sousa, Luciana A; Dos-Santos, Maria Cristina; de Oliveira, Ricardo Bezerra; Veras Mourão, Rosa Helena

2016-05-13

Ethnobotanical studies have shown that Plathymenia reticulata Benth. (Fabaceae) has been widely used in cases of snake envenomation, particularly in Northern Brazil. In light of this, the aim of this study was to evaluate the inhibitory potential of the condensed-tannin-rich fraction obtained from the bark of P. reticulata against the main biological activities induced by Bothrops atrox venom (BaV). The chemical composition of the aqueous extract of P. reticulata (AEPr) was first investigated by thin-layer chromatography (TLC) and the extract was then fractionated by column chromatography on Sephadex LH-20. This yielded five main fractions (Pr1, Pr2, Pr3, Pr4 and Pr5), which were analyzed by colorimetry to determine their concentrations of total phenolics, total tannins and condensed tannins and to assess their potential for blocking the phospholipase activity of BaV. The Pr5 fraction was defined as the fraction rich in condensed tannins (CTPr), and its inhibitory potential against the activities of the venom was evaluated. CTPr was evaluated in different in vivo and in vitro experimental protocols. The in vivo protocols consisted of (1) pre-incubation (venom:CTPr, w/w), (2) pre-treatment (orally administered) and (3) post-treatment (orally administered) to evaluate the effect on the hemorrhagic and edematogenic activities of BaV; in the in vitro protocol the effect on phospholipase and coagulant activity using pre-incubation in both tests was evaluated. There was statistically significant inhibition (p<0.05) of hemorrhagic activity by CTPr when the pre-incubation protocol was used [55% (1:5, w/w) and 74% (1:10, w/w)] and when pre-treatment with doses of 50 and 100mg/kg was used (19% and 13%, respectively). However, for the concentrations tested, there was no statistically significant inhibition in the group subjected to post-treatment administered orally. CTPr blocked 100% of phospholipase activity and 63.3% (1:10, w/w) of coagulant activity when it was pre

Moojenactivase, a novel pro-coagulant PIIId metalloprotease isolated from Bothrops moojeni snake venom, activates coagulation factors II and X and induces tissue factor up-regulation in leukocytes.

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Sartim, Marco A; Costa, Tassia R; Laure, Helen J; Espíndola, Milena S; Frantz, Fabiani G; Sorgi, Carlos A; Cintra, Adélia C O; Arantes, Eliane C; Faccioli, Lucia H; Rosa, José C; Sampaio, Suely V

2016-05-01

Coagulopathies following snakebite are triggered by pro-coagulant venom toxins, in which metalloproteases play a major role in envenomation-induced coagulation disorders by acting on coagulation cascade, platelet function and fibrinolysis. Considering this relevance, here we describe the isolation and biochemical characterization of moojenactivase (MooA), a metalloprotease from Bothrops moojeni snake venom, and investigate its involvement in hemostasis in vitro. MooA is a glycoprotein of 85,746.22 Da, member of the PIIId group of snake venom metalloproteases, composed of three linked disulfide-bonded chains: an N-glycosylated heavy chain, and two light chains. The venom protease induced human plasma clotting in vitro by activating on both blood coagulation factors II (prothrombin) and X, which in turn generated α-thrombin and factor Xa, respectively. Additionally, MooA induced expression of tissue factor (TF) on the membrane surface of peripheral blood mononuclear cells (PBMC), which led these cells to adopt pro-coagulant characteristics. MooA was also shown to be involved with production of the inflammatory mediators TNF-α, IL-8 and MCP-1, suggesting an association between MooA pro-inflammatory stimulation of PBMC and TF up-regulation. We also observed aggregation of washed platelets when in presence of MooA; however, the protease had no effect on fibrinolysis. Our findings show that MooA is a novel hemostatically active metalloprotease, which may lead to the development of coagulopathies during B. moojeni envenomation. Moreover, the metalloprotease may contribute to the development of new diagnostic tools and pharmacological approaches applied to hemostatic disorders.

Actividad in vitro de los venenos de Lachesis muta y Bothrops atrox sobre la viabilidad y desarrollo embrionario de los huevos de Ascaris suum

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Claudia Paredes

2014-06-01

Full Text Available Los venenos de serpientes son concentrados polienzimáticos cuya actividad biológica sobre algunas bacterias y protozoos ha sido comprobada. El objetivo principal del presente trabajo fue estudiar la actividad in vitro de los venenos totales de las serpientes Lachesis muta y Bothrops atrox sobre la viabilidad y el desarrollo embrionario de los huevos de Ascaris suum. Se emplearon los venenos totales en concentraciones de 2, 4, 8 y 16 mg/mL sobre huevos no embrionados y larvados in vitro. Se comparó la actividad de los venenos con la de otras sustancias como el hipoclorito de sodio al 5,25%, Albendazol (solución comercial y solución salina. Ambos venenos, en concentraciones de 4, 8 y 16 mg/mL, inhibieron la blastulación de estos huevos; hasta el sexto día de incubación; en cambio en concentración de 2 mg/mL la inhibición se dio hasta el cuarto día. Posteriormente iniciaron un proceso de embrionación aparentemente normal hasta la formación del estadio infectante. El veneno de B. atrox fue el que presentó el mayor efecto inhibitorio en concentración de 16 mg/mL. El hipoclorito de sodio destruyó el 100% de los huevos, mientras el albendazol ocasionó que los huevos iniciaran un proceso de segmentación anormal que originó su degeneración. Se concluye que los venenos de L. muta y B. atrox muestran actividad inhibitoria al inicio de la blastulación de los huevos de A. suum y no ejercen ningún efecto en los huevos larvados.

Biotechnological application of protein Leuc-B isolated from Bothrops leucurus venom as a prototype for antitumoral radiopharmaceutical

International Nuclear Information System (INIS)

Gabriel, Lucilene Marcia

2010-01-01

According to the report of the International Agency for Research on Cancer, the growth of this disease implies the death of 17 million people a year by 2030. Although the knowledge on development of cancer is growing considerably, just a few advances in the diagnosis and therapy has been achieved. Faced with this scenario, it is clear the need for new substances more specifics with low toxicity to the patient, which can be used for diagnosis and treatment of cancer. Membrane receptors over expressed in tumor cells are promising target candidates for development of diagnostic and therapeutical tools. Integrins are a family of hetero dimeric cell surface adhesion receptors able to recognize and bind to proteins in the extracellular matrix (ECM). This recognition is mainly through the RGD domains presents in both the cell surface as in the protein from the ECM. Various integrins have been identified as regulators of tumor progression. The RGD domain is also found in some snake venoms named disintegrins. Disintegrins inhibit cell-matrix and a cell-cell interactions mediated by integrins and it has been shown that these proteins are able to inhibit metastasis in processes dependent on integrin. The disintegrin-like (ECD), as well as RGD-disintegrin are also able to bind to cell surface integrins and inhibit their adhesion to the natural ligands. In this work it was purified from Bothrops leucurus venom (VBL), a metalloproteinase-class P-III with disintegrin-like domain (ECD), Leucurolisina B (Leuc-B). This metalloproteinase and the crude venom were used to evaluate their applicability in the differential detection of tumors. In vitro results demonstrated that both VBL and Leuc-B have potent antitumoral effect on several cancer cell lines: U87, T98, RT2 (glioblastoma), MCF7 (breast), Ehrlich and UACC (melanoma) with IC 50 values of approximately 0.6 μM. The morphological changes observed in these strains when treated with Leuc-B, and data from the DAPI staining solution

Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites.

Science.gov (United States)

Zelanis, André; Huesgen, Pitter F; Oliveira, Ana Karina; Tashima, Alexandre K; Serrano, Solange M T; Overall, Christopher M

2015-01-15

Many snake venom toxins are serine proteases but their specific in vivo targets are mostly unknown. Various act on components of the coagulation cascade, and fibrinolytic and kallikrein-kinin systems to trigger various pathological effects observed in the envenomation. Despite showing high similarity in terms of primary structure snake venom serine proteinases (SVSPs) show exquisite specificity towards macromolecular substrates. Therefore, the characterization of their peptide bond specificity is important for understanding the active site preference associated with effective proteolysis as well as for the design of peptide substrates and inhibitors. Bothrops jararaca contains various SVSPs among which Bothrops protease A is a specific fibrinogenolytic agent and PA-BJ is a platelet-activating enzyme. In this study we used proteome derived peptide libraries in the Proteomic Identification of protease Cleavage Sites (PICS) approach to explore the peptide bond specificity of Bothrops protease A and PA-BJ in order to determine their individual peptide cleavage sequences. A total of 371 cleavage sites (208 for Bothrops protease A and 163 for PA-BJ) were detected and both proteinases displayed a clear preference for arginine at the P1 position. Moreover, the analysis of the specificity profiles of Bothrops protease A and PA-BJ revealed subtle differences in the preferences along P6-P6', despite a common yet unusual preference for Pro at P2. Taken together, these results map the subsite specificity of both SVSPs and shed light in the functional differences between these proteinases. Proteolysis is key to various pathological effects observed upon envenomation by viperid snakes. The use of the Proteomic Identification of protease Cleavage Sites (PICS) approach for the easy mapping of proteinase subsite preferences at both the prime- and non-prime sides concurrently gives rise to a fresh understanding of the interaction of the snake venom serine proteinases with peptide and

Comparison of venoms from wild and long-term captive Bothrops atrox snakes and characterization of Batroxrhagin, the predominant class PIII metalloproteinase from the venom of this species.

Science.gov (United States)

Freitas-de-Sousa, L A; Amazonas, D R; Sousa, L F; Sant'Anna, S S; Nishiyama, M Y; Serrano, S M T; Junqueira-de-Azevedo, I L M; Chalkidis, H M; Moura-da-Silva, A M; Mourão, R H V

2015-11-01

Comparisons between venoms from snakes kept under captivity or collected at the natural environment are of fundamental importance in order to obtain effective antivenoms to treat human victims of snakebites. In this study, we compared composition and biological activities of Bothrops atrox venom from snakes collected at Tapajós National Forest (Pará State, Brazil) or maintained for more than 10 years under captivity at Instituto Butantan herpetarium after have been collected mostly at Maranhão State, Brazil. Venoms from captive or wild snakes were similar except for small quantitative differences detected in peaks correspondent to phospholipases A2 (PLA2), snake venom metalloproteinases (SVMP) class PI and serine proteinases (SVSP), which did not correlate with fibrinolytic and coagulant activities (induced by PI-SVMPs and SVSPs). In both pools, the major toxic component corresponded to PIII-SVMPs, which were isolated and characterized. The characterization by mass spectrometry of both samples identified peptides that matched with a single PIII-SVMP cDNA characterized by transcriptomics, named Batroxrhagin. Sequence alignments show a strong similarity between Batroxrhagin and Jararhagin (96%). Batroxrhagin samples isolated from venoms of wild or captive snakes were not pro-coagulant, but inhibited collagen-induced platelet-aggregation, and induced hemorrhage and fibrin lysis with similar doses. Results suggest that in spite of environmental differences, venom variability was detected only among the less abundant components. In opposition, the most abundant toxin, which is a PIII-SVMP related to the key effects of the venom, is structurally conserved in the venoms. This observation is relevant for explaining the efficacy of antivenoms produced with venoms from captive snakes in human accidents inflicted at distinct natural environments. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

P-I Snake Venom Metalloproteinase Is Able to Activate the Complement System by Direct Cleavage of Central Components of the Cascade

Science.gov (United States)

Pidde-Queiroz, Giselle; Magnoli, Fábio Carlos; Portaro, Fernanda C. V.; Serrano, Solange M. T.; Lopes, Aline Soriano; Paes Leme, Adriana Franco; van den Berg, Carmen W.; Tambourgi, Denise V.

2013-01-01

Background Snake Venom Metalloproteinases (SVMPs) are amongst the key enzymes that contribute to the high toxicity of snake venom. We have recently shown that snake venoms from the Bothrops genus activate the Complement system (C) by promoting direct cleavage of C-components and generating anaphylatoxins, thereby contributing to the pathology and spread of the venom. The aim of the present study was to isolate and characterize the C-activating protease from Bothrops pirajai venom. Results Using two gel-filtration chromatography steps, a metalloproteinase of 23 kDa that activates Complement was isolated from Bothrops pirajai venom. The mass spectrometric identification of this protein, named here as C-SVMP, revealed peptides that matched sequences from the P-I class of SVMPs. C-SVMP activated the alternative, classical and lectin C-pathways by cleaving the α-chain of C3, C4 and C5, thereby generating anaphylatoxins C3a, C4a and C5a. In vivo, C-SVMP induced consumption of murine complement components, most likely by activation of the pathways and/or by direct cleavage of C3, leading to a reduction of serum lytic activity. Conclusion We show here that a P-I metalloproteinase from Bothrops pirajai snake venom activated the Complement system by direct cleavage of the central C-components, i.e., C3, C4 and C5, thereby generating biologically active fragments, such as anaphylatoxins, and by cleaving the C1-Inhibitor, which may affect Complement activation control. These results suggest that direct complement activation by SVMPs may play a role in the progression of symptoms that follow envenomation. PMID:24205428

Acción del antiveneno botrópico polivalente sobre las actividades proteolíticas presentes en los venenos de serpientes peruanas

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Armando Yarlequé

2008-04-01

Full Text Available Los venenos de las serpientes peruanas causantes de la mayoría de accidentes ofídicos, contienen enzimas proteolíticas que pueden degradar proteínas tisulares y plasmáticas, así como causar hipotensión y coagulación sanguínea. Objetivos. Evaluar la capacidad inhibitoria del antiveneno botrópico polivalente al estado líquido producido por el Instituto Nacional de Salud del Perú (INS sobre las actividades caseinolítica, coagulante y amidolítica de los venenos de Bothrops atrox, Bothrops brazili, Bothrops pictus y Bothrops barnetti. Materiales y métodos. Se usaron en cada caso sustratos como caseína, fibrinógeno bovino y el cromógeno benzoil-arginil-p-nitroanilida (BApNA respectivamente, y se midieron los cambios en los valores de la actividad enzimática a ½, 1 y 2 dosis del antiveneno tanto al estado natural como calentado a 37 °C durante cinco días. Resultados. La actividad caseinolítica es la más resistente a la inhibición especialmente por el suero no calentado en tanto que, la actividad amidolítica fue severamente inhibida principalmente en los venenos de B. pictus y B. atrox. Así mismo la actividad coagulante fue totalmente inhibida en el veneno de B. pictus, mostrándose a su vez una elevada inhibición sobre los venenos de B. brazili y B. atrox. Para las actividades coagulante y amidolítica, los sueros calentados fueron menos efectivos que aquellos al estado natural. Conclusiones. El suero antibotrópico polivalente producido por el INS es efectivo para inhibir las actividades proteolíticas de los venenos de las serpientes peruanas ensayadas.

Evaluation of an antimicrobial L-amino acid oxidase and peptide derivatives from Bothropoides mattogrosensis pitviper venom.

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Brunna M Okubo

Full Text Available Healthcare-associated infections (HAIs are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3 were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms.

Serpentes da área urbana de Cuiabá, Mato Grosso: aspectos ecológicos e acidentes ofídicos associados

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Carvalho Marcos André de

1998-01-01

Full Text Available São apresentadas informações sobre as serpentes da área urbana do Município de Cuiabá, Mato Grosso, potencialmente causadoras de acidentes ofídicos. As informações estão baseadas em exemplares doados por populares ao Núcleo de Ofiologia Regional de Mato Grosso (Normat entre 1986 e 1993 e em registros efetuados pelo Centro de Informações Anti-Veneno (Ciave entre 1988 e 1993, que não fazem referência ao animal causador. Foram catalogadas 37 espécies de serpentes, em 25 gêneros e 3 famílias, com hábitos predominantemente diurnos, terrestres e com dietas baseadas em anfíbios e/ou lagartos. Dentre os 307 acidentes ofídicos registrados, 56% foram causados por serpentes sem interesse médico e 44% constituíram acidentes de importância médica. Cerca de 99% dos acidentes de importância médica foram atribuídos ao gênero Bothrops (Bothrops moojeni e Bothrops neuwiedi seriam as principais causadoras. Dentre as espécies sem interesse médico, Philodryas olfersii e Waglerophis merremii provavelmente foram as principais responsáveis pela maior parte dos acidentes.

Epidemiologia dos acidentes ofídicos notificados pelo Centro de Assistência e Informação Toxicológica de Campina Grande (Ceatox-CG, Paraíba Epidemiologic profile of snakebites reported by the Poison Information Center of Campina Grande, Paraíba

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Josiverton de Carvalho Lemos

2009-03-01

Full Text Available Os acidentes causados por animais peçonhentos ainda constituem problema de Saúde Pública no Brasil. Embora a produção e a distribuição dos soros no país encontrem-se estabilizadas, há problemas relacionados à notificação de acidentes deste tipo em várias regiões. Considerando esta realidade, foi realizado um estudo transversal entre janeiro e dezembro de 2005, utilizando documentação indireta sobre os acidentes ofídicos ocorridos em Campina Grande e 80 municípios adjacentes à região, com o objetivo de conhecer o perfil epidemiológico e clínico deste tipo de caso. Todos os pacientes atendidos tiveram diagnóstico médico de acidente por serpentes realizado pelo Centro de Atendimento Toxicológico de Campina Grande (Ceatox-CG. Os dados foram coletados através da ficha de notificação do Sinan (Sistema Nacional de Notificação de Agravo do Ministério da Saúde. Para análise dos dados, foi utilizada estatística descritiva e os dados foram tabulados no programa Microsoft Excel 2003. Dos 1.443 atendimentos no Centro, 737 foram causados por animais peçonhentos e, destes, 277 foram provocados por serpentes peçonhentas e não peçonhentas. Os acidentes predominaram no sexo masculino, na faixa etária de 10 a 29 anos, principalmente em agricultores na zona rural, entre maio e novembro de 2005. O gênero Bothrops foi responsável pelo maior número de casos (71,5%, e as extremidades superior e inferior do corpo foram os locais de maior predominância de ataques. Na extremidade inferior, foi atingido principalmente o pé. Em relação à gravidade, foram mais frequentes os acidentes classificados como leves causados pelo gênero Bothrops e apenas um paciente evoluiu para óbito. A média do tempo de atendimento, em horas, foi superior a 12 horas nos acidentes considerados graves, causados pelos gêneros Bothrops e Crotalus. Nossos resultados concordam com o perfil epidemiológico nacional dos acidentes ofídicos, atingindo com

Ação de venenos de serpentes brasileiras sôbre a alexina ou complemento

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F. da Rocha Lagôa

1947-06-01

Full Text Available O autor estudou a ação inativante, sôbre o complemento de cobaia, alguns venenos de serpentes brasileiras pertencentes às famílias dos Elapideos e Crotalideos. Da primeira, foi utilizado veneno de Micrurus frontalis, da segunda, foram usados venenos de espécies pertencentes aos gêneros Crotalus (C. terrificus e Bothrops (B. atrox, B. neuwiedii, B. jararaca, B. ja-raracussú, B. cotiara e B. alternata. O venenos de M. frontalis e C. terri¬ficus se revelaram incapazes de inativar o complemento, ao passo que os diversos de Bothrops empregados se mostraram altamente inativantes, destruindo sempre o 4.° componente do complemento (C4, fração idêntica à afetada pela ação da amônea.The author shows in this paper the results of the inactivation of com¬plement or alexin by some Brazilian snakes venoms of the Elapideae and Cro¬talideae families. The venom of Micrurus frontalis (Elapideae family and of Crotalus terrificus (Crotalideae family did not destroy the complement; but the venoms of Bothrops generus (B. atrox, B. neuwiedii, B. jararaca, B. jararacussú, B. cotiara e B. alternata, (Crotalideae family are highly active in the inactivation complement, always destroing the fourth component, whichis exactly the same component that is detroyed by ammonia.

Cases of human envenoming caused by Philodryas olfersii and Philodryas patagoniensis (serpentes: Colubridae

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Maria Elisabeth de Araújo

1997-12-01

Full Text Available The present paper reports two cases of human envenoming by colubrid snakes of Philodryas, considered as not poisonous, showing evidence of the clinical aspects and the evolution of the symptoms of envenoming. The similarity of these cases with those caused by Bothrops suggests a more careful evaluation on the victims considering the medical treatment to be adopted.O presente trabalho é um relato de dois casos de acidentes com colubrídeos (Philodryas olfersii e P. patagoniensis considerados não peçonhentos, que destaca as manifestações clínicas e as suas evoluções. A semelhança de tais acidentes com aqueles causados por serpentes Bothrops indica a necessidade de uma melhor avaliação dos pacientes quanto à terapêutica a ser adotada.

Comparative study of anticoagulant and procoagulant properties of 28 snake venoms from families Elapidae, Viperidae, and purified Russell's viper venom-factor X activator (RVV-X).

Science.gov (United States)

Suntravat, Montamas; Nuchprayoon, Issarang; Pérez, John C

2010-09-15

Snake venoms consist of numerous molecules with diverse biological functions used for capturing prey. Each component of venom has a specific target, and alters the biological function of its target. Once these molecules are identified, characterized, and cloned; they could have medical applications. The activated clotting time (ACT) and clot rate were used for screening procoagulant and anticoagulant properties of 28 snake venoms. Crude venoms from Daboia russellii siamensis, Bothrops asper, Bothrops moojeni, and one Crotalus oreganus helleri from Wrightwood, CA, had procoagulant activity. These venoms induced a significant shortening of the ACT and showed a significant increase in the clot rate when compared to the negative control. Factor X activator activity was also measured in 28 venoms, and D. r. siamensis venom was 5-6 times higher than those of B. asper, B. moojeni, and C. o. helleri from Wrightwood County. Russell's viper venom-factor X activator (RVV-X) was purified from D. r. siamensis venom, and then procoagulant activity was evaluated by the ACT and clot rate. Other venoms, Crotalus atrox and two Naja pallida, had anticoagulant activity. A significant increase in the ACT and a significant decrease in the clot rate were observed after the addition of these venoms; therefore, the venoms were considered to have anticoagulant activity. Venoms from the same species did not always have the same ACT and clot rate profiles, but the profiles were an excellent way to identify procoagulant and anticoagulant activities in snake venoms.

Photobiomodulation Protects and Promotes Differentiation of C2C12 Myoblast Cells Exposed to Snake Venom.

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Luciana Miato Gonçalves Silva

Full Text Available Snakebites is a neglected disease and in Brazil is considered a serious health problem, with the majority of the snakebites caused by the genus Bothrops. Antivenom therapy and other first-aid treatments do not reverse local myonecrose which is the main sequel caused by the envenomation. Several studies have shown the effectiveness of low level laser (LLL therapy in reducing local myonecrosis induced by Bothropic venoms, however the mechanism involved in this effect is unknown. In this in vitro study, we aimed to analyze the effect of LLL irradiation against cytotoxicity induced by Bothrops jararacussu venom on myoblast C2C12 cells.C2C12 were utilized as a model target and were incubated with B. jararacussu venom (12.5 μg/mL and immediately irradiated with LLL at wavelength of red 685 nm or infrared 830 nm with energy density of 2.0, 4.6 and 7.0 J/cm2. Effects of LLL on cellular responses of venom-induced cytotoxicity were examined, including cell viability, measurement of cell damage and intra and extracellular ATP levels, expression of myogenic regulatory factors, as well as cellular differentiation.In non-irradiated cells, the venom caused a decrease in cell viability and a massive release of LDH and CK levels indicating myonecrosis. Infrared and red laser at all energy densities were able to considerably decrease venom-induced cytotoxicity. Laser irradiation induced myoblasts to differentiate into myotubes and this effect was accompanied by up regulation of MyoD and specially myogenin. Moreover, LLL was able to reduce the extracellular while increased the intracellular ATP content after venom exposure. In addition, no difference in the intensity of cytotoxicity was shown by non-irradiated and irradiated venom.LLL irradiation caused a protective effect on C2C12 cells against the cytotoxicity caused by B. jararacussu venom and promotes differentiation of these cells by up regulation of myogenic factors. A modulatory effect of ATP synthesis may

Crystallization and preliminary X-ray diffraction analysis of a Lys49-phospholipase A2 complexed with caffeic acid, a molecule with inhibitory properties against snake venoms

International Nuclear Information System (INIS)

Shimabuku, Patrícia S.; Fernandes, Carlos A. H.; Magro, Angelo J.; Costa, Tássia R.; Soares, Andreimar M.; Fontes, Marcos R. M.

2011-01-01

Piratoxin I, a noncatalytic and myotoxic Lys49-phospholipase A 2 from B. pirajai venom, was cocrystallized with the inhibitor caffeic acid and a data set was collected to a resolution of 1.65 Å. The electron-density map unambiguously indicated that three inhibitor molecules interact with the C-terminus of the protein. Phospholipases A 2 (PLA 2 s) are one of the main components of bothropic venoms; in addition to their phospholipid hydrolysis action, they are involved in a wide spectrum of pharmacological activities, including neurotoxicity, myotoxicity and cardiotoxicity. Caffeic acid is an inhibitor that is present in several plants and is employed for the treatment of ophidian envenomations in the folk medicine of many developing countries; as bothropic snake bites are not efficiently neutralized by conventional serum therapy, it may be useful as an antivenom. In this work, the cocrystallization and preliminary X-ray diffraction analysis of the Lys49-PLA 2 piratoxin I from Bothrops pirajai venom in the presence of the inhibitor caffeic acid (CA) are reported. The crystals diffracted X-rays to 1.65 Å resolution and the structure was solved by molecular-replacement techniques. The electron-density map unambiguously indicated the presence of three CA molecules that interact with the C-terminus of the protein. This is the first time a ligand has been observed bound to this region and is in agreement with various experiments previously reported in the literature

The interaction of the antitoxin DM43 with a snake venom metalloproteinase analyzed by mass spectrometry and surface plasmon resonance

DEFF Research Database (Denmark)

Brand, Guilherme D; Salbo, Rune; Jørgensen, Thomas J D

2012-01-01

DM43 is a circulating dimeric antitoxin isolated from Didelphis aurita, a South American marsupial naturally immune to snake envenomation. This endogenous inhibitor binds non-covalently to jararhagin, the main hemorrhagic metalloproteinase from Bothrops jararaca snake venom, and efficiently...

VARIACIONES EN L COMPOSICIÓN PROTEICA, ACTIVIDADES ENZIMÁTICAS Y BIOLÓGICAS DEL VENENO DE LA SERPIENTE BOTHROPS ATROX (VIPEREIDAE EN RELACIÓN CON LA EDAD

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O. Málaga

2014-06-01

Full Text Available La serpiente Bothrops atrox, que habita en la Selva Amazónica del Perú, es responsable del mayor número de accidentes ofídicos y constituye un problema de salud pública. Por esta razón, se ha realizado un estudio de las variaciones en la composición y actividad del veneno en tres grupos de especimenes en cautiverio, que corresponden a juveniles de 1 y 2 años, así como ejemplares adultos mayores de 5 años. Los venenos obtenidos fueron liofilizados para su conservación y diluidos en concentraciones iniciales de 1 mg/ml en solución salina o en el buffer apropiado. Con estas muestras se efectuaron los análisis de concentración de proteína por D. 0. 280 nm y por el método de Lowry, determinándose además el número de bandas proteicas por electroforesis en gel de poliacrilamida con dodecil sulfato de sodio (PAGE-SIDS. Con las mismas muestras se hicieron ensayos para medir las siguientes actividades enzimáticas: caseinolítica, amidolftica, coagulante, hialuronidasa, L-aminocácido oxidasa (LAO y fosfolipasa A, adicionalmente se determinó la actividad hemorrágica y el efecto edemático con ratones albinos. Los resultados mostraron que la mayor concentración proteica (0,938mg de proteína/mg de veneno así como el número máximo de bandas proteicas (8 bandas se obtuvieron con los venenos de juveniles de 2 años. Asimismo se encontró que algunas actividades enzimáticas como la amidolítica, fosfolipásica y L-aminoácido oxidasa fueron más altas en los juveniles de 2 años, además de los efectos hemorrágico y edemático. En cambio, las actividades coagulante y proteolítica sobre caseína se elevaron progresivamente con la edad de los ejemplares. Sin embargo, la enzima hialuronidasa tuvo su máximo valor en los juveniles de 1 año, decreciendo notablemente en los adultos. Es interesante señalar también que fosfolipasa A2 en los adultos sólo tuvo una actividad de 6,4% con respecto al valor más alto encontrado en el veneno

Ethnobotanic study of Randia aculeata (Rubiaceae in Jamapa, Veracruz, Mexico, and its anti-snake venom effects on mouse tissue

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CA Gallardo-Casas

2012-01-01

Full Text Available In Mexico, medicinal plants are widely used. The use of Randia aculeata by healers against snakebites has never been scientifically tested in relation to possible effects on blood parameters and muscle tissue damage. Interviews were carried out in Jamapa, Veracuz, Mexico, with local residents to collect information about the traditional use of Randia aculeata. In this locality, seven pieces of fruit from the plant are mixed in a liter of alcohol, and then administered orally against snakebites. By using histological techniques and a murine model, we explored its cytoprotective properties against the effects of Crotalus simus and Bothrops asper venoms. Possible protections provided by the plant against tissue damage to skeletal and cardiac muscles and against the typical loss of red blood cells were analyzed. Randia aculeata caused an increase in microhematocrit and total hemoglobin, parameters that are often decremented in association with the loss of red blood cells, which is a characteristic effect of animal venom. Randia aculeata was also shown to protect against the lowering of platelet levels caused by Bothrops asper venom. Finally, Randia aculeata produced a partial inhibition of necrosis following administration of snake venom in skeletal and myocardial muscles. The present results provide solid evidence for the traditional use of Randia aculeata against snakebites, as demonstrated by protection against muscular tissue damage and the diminution of red blood cells.

Prevalence of Hepatozoon spp. (Apicomplexa, Hepatozoidae among recently captured Brazilian snakes Prevalência de Hepatozoon spp. (Apicomplexa, Hepatozoidae em serpentes recém-capturadas no Brasil

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L.H. O'Dwyer

2003-06-01

Full Text Available The goal of this study was to determine the prevalence of Hepatozoon spp. infection in recently captured snakes from Botucatu, São Paulo State, Brazil. Blood was collected from all snakes by ventral tail venipuncture. Blood smears were air dried, fixed with methanol, and stained with 10% Giemsa solution. The slides were microscopically examined for detection of hemoparasites by light microscopy at 250x magnification. A total of 238 snakes from 23 species were examined, of which 135 (56.7% were venomous and 103 (43.3% non-venomous snakes. The more numerous venomous species sampled were Crotalus durissus terrificus (n=108 and Bothrops jararaca (n=17 and non-venomous snakes were Oxyrhopus guibei (n=35, Boa constrictor amarali (n=18, and Waglerophis merremi (n=13. Hepatozoon spp. infection was detected in 39 (16.4% snakes. The prevalence in venomous and non-venomous snakes was 20.0% and 11.7%, respectively. The highest prevalences observed were 38.9% for Boa constrictor amarali, 35.3% for Bothrops jararaca, and 19.4% for Crotalus durissus terrificus.O presente estudo teve como objetivo determinar a prevalência da infecção por Hepatozoon spp. em serpentes recém-capturadas da região de Botucatu, São Paulo. O sangue foi coletado de todas as serpentes por punção da veia caudal. Os esfregaços foram secos ao ar, fixados com metanol e corados com solução de Giemsa a 10%. Examinaram-se 238 serpentes pertencentes a 23 espécies, das quais 135 (56,7% eram venenosas e 103 (43,3% não venenosas. As espécies venenosas mais representativas foram Crotalus durissus terrificus (n=108 e Bothrops jararaca (n=17 e as não venenosas foram Oxyrhopus guibei (n=35, Boa constrictor amarali (n=18 e Waglerophis merremi (n=13. A infecção por Hepatozoon spp. foi detectada em 39 (16,4% serpentes. As prevalências em serpentes venenosas e não venenosas foram 20,0% e 11,7%, respectivamente. As maiores prevalências foram 38,9% para Boa constrictor amarali, 35

Screening for Proteolytic Activities in Snake Venom by Means of a Multiplexing ESI-MS Assay Scheme

NARCIS (Netherlands)

Liesener, A.; Perchuc, Anna-Maria; Schöni, Reto; Wilmer, Marianne; Karst, U.

2005-01-01

A multiplexed mass spectrometry based assay scheme for the simultaneous determination of five different substrate/product pairs was developed as a tool for screening of proteolytic activities in snake venom fractions from Bothrops moojeni. The assay scheme was employed in the functional

Evaluación comparativa de dos métodos para determinar la actividad de fosfolipasa A en venenos de serpientes

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Fanny Lazo

2014-06-01

Full Text Available Se ha evaluado la actividad de fosfolipasa A en seis venenos de serpientes comparando las ventajas de un método espectrofotométrico, previamente adaptado a nuestras condiciones de laboratorio, frente al método macroscópico de retardo en la coagulación de una emulsión lipoproteica. En ambos casos, la actividad de fosfolipasa A estuvo presente en los venenos de Micrurus spixii, Crotalus durissus, Bothrops brazili, Lachesis muta y Bothrops atrox y la actividad decreció en orden. En cambio, la actividad de la enzima en el veneno de Micrurus surinamensis sólo fue detectada por el método espectrofotométrico. Así mismo, los resultados basados en la cantidad de veneno utilizado para medir la actividad, mostraron una mayor sensibilidad con el método espectrofotométrico en comparación con el método macroscópico ya que se requirieron cantidades menores en el orden de 2 a 10 veces.

Activity evaluation from different native or irradiated with {sup 60} Co gamma rays snake venoms and their inhibitory effect on Leishmania (Leishmania) amazonensis; Avaliacao da atividade de diferentes venenos de serpentes, nativos ou irradiados, com radiacao gama de {sup 60} Co, quanto ao poder inibitorio do crescimento de Leishmania (Leishmania) amazonensis

Energy Technology Data Exchange (ETDEWEB)

Lourenco, Cecilia de Oliveira

2000-07-01

Cutaneous leishmaniasis is a disease, caused by Leishmania parasites, that occurs frequently in tropical and sub-tropical regions of the world. Skin lesions that could results in disfiguring aspect characterize it. The treatment is based on few drugs as antimony salts or pentamidine that are toxic with increasing resistance by the parasite. Alternative forms of disease treatment are in constant search, including natural components as snake venoms. Previous studies demonstrate that some components of snake venoms have an inhibitory effect against those parasites, including Leishmania species. Although snake venoms presented high toxicity, several methods have been described to detoxify most or some of their toxic components, with favorable results by the use of gamma irradiation. In this report we tested several native and irradiated snake venoms for inhibitory effect against Leishmania (Leishmania) amazonensis parasite and LLCMK{sub 2} mammalian cells, with enzymatic tests and electrophoresis. There are significant activity in Acanthophis antarcticus, Agkistrodon bilineatus, Bothrops moojeni, Bothrops jararaca, Hoplocephalus stephensi, Naja melanoleuca, Naja mossambica, Pseudechis australis, Pseudechis colletti, Pseudechis guttatus and Pseudechis porphyriacus, venom being inactive Pseudonaja textilis, Notechis ater niger, Notechis scutatus. Oxyuranus microlepidotus and Oxyuranus scutellatus venoms. After 2 KGy of {sup 60}Co irradiation most venom loses significantly their activity. Venoms with antileishmanial activity presented L-amino acid oxidase (L-AO) activity and showed common protein with a molecular weight about 60kDa in SDS-PAGE. These results indicate that L-AO activity in those venoms are probably related with antileishmanial effect. (author)

Activity evaluation from different native or irradiated with 60 Co gamma rays snake venoms and their inhibitory effect on Leishmania (Leishmania) amazonensis

International Nuclear Information System (INIS)

Lourenco, Cecilia de Oliveira

2000-01-01

Cutaneous leishmaniasis is a disease, caused by Leishmania parasites, that occurs frequently in tropical and sub-tropical regions of the world. Skin lesions that could results in disfiguring aspect characterize it. The treatment is based on few drugs as antimony salts or pentamidine that are toxic with increasing resistance by the parasite. Alternative forms of disease treatment are in constant search, including natural components as snake venoms. Previous studies demonstrate that some components of snake venoms have an inhibitory effect against those parasites, including Leishmania species. Although snake venoms presented high toxicity, several methods have been described to detoxify most or some of their toxic components, with favorable results by the use of gamma irradiation. In this report we tested several native and irradiated snake venoms for inhibitory effect against Leishmania (Leishmania) amazonensis parasite and LLCMK 2 mammalian cells, with enzymatic tests and electrophoresis. There are significant activity in Acanthophis antarcticus, Agkistrodon bilineatus, Bothrops moojeni, Bothrops jararaca, Hoplocephalus stephensi, Naja melanoleuca, Naja mossambica, Pseudechis australis, Pseudechis colletti, Pseudechis guttatus and Pseudechis porphyriacus, venom being inactive Pseudonaja textilis, Notechis ater niger, Notechis scutatus. Oxyuranus microlepidotus and Oxyuranus scutellatus venoms. After 2 KGy of 60 Co irradiation most venom loses significantly their activity. Venoms with antileishmanial activity presented L-amino acid oxidase (L-AO) activity and showed common protein with a molecular weight about 60kDa in SDS-PAGE. These results indicate that L-AO activity in those venoms are probably related with antileishmanial effect. (author)

Influence of gamma-radiation on the biological activity of snake venoms in Peru

International Nuclear Information System (INIS)

Yarleque Ch, A.

1986-03-01

Effects of Co-60 gamma radiation on enzymatic, haemorragic and necrotic activities of Lachesis muta and Bothrops atrox venoms was studied at several ranges of irradiation lower than 1.0 Mrad. The radiation produced changes on its enzymatic activities. Irradiation at 0.1 Mrad resulted in the partial or complete inactivation of the following enzymes that are listed in order of increasing sensitivity: exonuclease, phospholipase A, caseinolytic enzyme, thrombinolytic enzyme, fibrinolytic enzyme, 5'-nucleotidase and endonuclease. The enzymatic inactivation was increased with 0.5 and 1.0 Mrad although not in a linear manner. Exonuclease was found to be the most radioresistant. The haemorragic activity was decreased to a greater extent than the necrotic activity. The probable mechanism for the changes in the enzymatic, haemorragic and necrotic activities are discussed

Blood Evaluation Of Cl and Na Concentration In Crioulo Breed Horses Using NAA: Comparison With Humans Levels

International Nuclear Information System (INIS)

Baptista, Tatyana S.; Zamboni, Cibele B.; Medeiros, Jose Agostinho G. de; Marcelino, Jose R.; Higashi, Hisako G.; Freitas, Monica G.

2009-01-01

Neutron Activation Analysis was utilized for determining the concentration of chlorine and sodium in blood of Crioulo breed horses used for hyperimmune sera production (Bothrops, Diphtheria and Tetanus) at Butantan Institute (Sao Paulo city, Brasil). These data are an important support for a toxicological control of adverse reactions in patients who will receive the hyperimmune serum.

Seasonal, daily activity, and habitat use by three sympatric pit vipers (Serpentes, Viperidae) from southern Brazil.

Science.gov (United States)

Rocha, Marcelo C; Hartmann, Paulo A; Winck, Gisele R; Cechin, Sonia Z

2014-04-25

Viperid snakes are widely distributed in the South America and the greater distribution range of the family is found at the Crotalinae subfamily. Despite the abundance of this snakes along their geographic distribution, some ecological aspects remain unknown, principally at subtropical areas. In the present study, we evaluated the activity (daily and seasonal) and the use of the habitat by Bothrops diporus, B. jararaca and B. jararacussu, in an Atlantic Forest area at southern Brazil. We observed higher incidence of viperid snakes during the months with higher temperatures, while no snakes were found during the months with lower temperatures. The data suggest the minimum temperature as environmental variable with the greatest influence on the seasonal activity of this species. Considering the daily activity, we observed a tendency of snakes to avoid the warmest hours. Bothrops jararacussu tend to avoid open areas, being registered only inside and at the edges of the forest. We compared our results with previous studies realized at tropical areas and we suggest the observed seasonal activity as an evolutive response, despite the influence of the different environmental variables, according to the occurence region.

Seasonal, daily activity, and habitat use by three sympatric pit vipers (Serpentes, Viperidae from southern Brazil

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MARCELO C. ROCHA

2014-06-01

Full Text Available Viperid snakes are widely distributed in the South America and the greater distribution range of the family is found at the Crotalinae subfamily. Despite the abundance of this snakes along their geographic distribution, some ecological aspects remain unknown, principally at subtropical areas. In the present study, we evaluated the activity (daily and seasonal and the use of the habitat by Bothrops diporus, B. jararaca andB. jararacussu, in an Atlantic Forest area at southern Brazil. We observed higher incidence of viperid snakes during the months with higher temperatures, while no snakes were found during the months with lower temperatures. The data suggest the minimum temperature as environmental variable with the greatest influence on the seasonal activity of this species. Considering the daily activity, we observed a tendency of snakes to avoid the warmest hours. Bothrops jararacussu tend to avoid open areas, being registered only inside and at the edges of the forest. We compared our results with previous studies realized at tropical areas and we suggest the observed seasonal activity as an evolutive response, despite the influence of the different environmental variables, according to the occurence region.

Disseminated intravascular coagulation caused by moojenactivase, a procoagulant snake venom metalloprotease.

Science.gov (United States)

Sartim, Marco A; Cezarette, Gabriel N; Jacob-Ferreira, Anna L; Frantz, Fabiani G; Faccioli, Lucia H; Sampaio, Suely V

2017-10-01

Snake venom toxins that activate coagulation factors are key players in the process of venom-induced coagulopathy, and account for severe clinical manifestations. The present study applies a variety of biochemical, hematological, and histopathological approaches to broadly investigate the intravascular and systemic effects of moojenactivase (MooA), the first described PIIId subclass metalloprotease isolated from Bothrops sp. venom that activates coagulation factors. MooA induced consumption coagulopathy with high toxic potency, characterized by prolongation of prothrombin and activated partial thromboplastin time, consumption of fibrinogen and the plasma coagulation factors X and II, and thrombocytopenia. MooA promoted leukocytosis and expression of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, accompanied by tissue factor-dependent procoagulant activity in peripheral blood mononuclear cells. This metalloprotease also caused intravascular hemolysis, elevated plasma levels of creatine kinase-MB, aspartate transaminase, and urea/creatinine, and induced morphopathological alterations in erythrocytes, heart, kidney, and lungs associated with thrombosis and hemorrhage. Diagnosis of MooA-induced disseminated intravascular coagulation represents an important approach to better understand the pathophysiology of Bothrops envenomation and develop novel therapeutic strategies targeting hemostatic disturbances. Copyright © 2017. Published by Elsevier B.V.

Unraveling the distinctive features of hemorrhagic and non-hemorrhagic snake venom metalloproteinases using molecular simulations

Science.gov (United States)

de Souza, Raoni Almeida; Díaz, Natalia; Nagem, Ronaldo Alves Pinto; Ferreira, Rafaela Salgado; Suárez, Dimas

2016-01-01

Snake venom metalloproteinases are important toxins that play fundamental roles during envenomation. They share a structurally similar catalytic domain, but with diverse hemorrhagic capabilities. To understand the structural basis for this difference, we build and compare two dynamical models, one for the hemorrhagic atroxlysin-I from Bothrops atrox and the other for the non-hemorraghic leucurolysin-a from Bothrops leucurus. The analysis of the extended molecular dynamics simulations shows some changes in the local structure, flexibility and surface determinants that can contribute to explain the different hemorrhagic activity of the two enzymes. In agreement with previous results, the long Ω-loop (from residue 149 to 177) has a larger mobility in the hemorrhagic protein. In addition, we find some potentially-relevant differences at the base of the S1' pocket, what may be interesting for the structure-based design of new anti-venom agents. However, the sharpest differences in the computational models of atroxlysin-I and leucurolysin-a are observed in the surface electrostatic potential around the active site region, suggesting thus that the hemorrhagic versus non-hemorrhagic activity is probably determined by protein surface determinants.

Heterologous expression of the antimyotoxic protein DM64 in Pichia pastoris.

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Saulo Martins Vieira

2017-07-01

Full Text Available Snakebite envenomation is a neglected condition that constitutes a public health problem in tropical and subtropical countries, including Brazil. Interestingly, some animals are resistant to snake envenomation due to the presence of inhibitory glycoproteins in their serum that target toxic venom components. DM64 is an acidic glycoprotein isolated from Didelphis aurita (opossum serum that has been characterized as an inhibitor of the myotoxicity induced by bothropic toxins bearing phospholipase A2 (PLA2 structures. This antitoxic protein can serve as an excellent starting template for the design of novel therapeutics against snakebite envenomation, particularly venom-induced local tissue damage. Therefore, the aim of this work was to produce a recombinant DM64 (rDM64 in the methylotrophic yeast Pichia pastoris and to compare its biological properties with those of native DM64. Yeast fermentation in the presence of Pefabloc, a serine protease inhibitor, stimulated cell growth (~1.5-fold, increased the rDM64 production yield approximately 10-fold and significantly reduced the susceptibility of rDM64 to proteolytic degradation. P. pastoris fermentation products were identified by mass spectrometry and Western blotting. The heterologous protein was efficiently purified from the culture medium by affinity chromatography (with immobilized PLA2 myotoxin and/or an ion exchange column. Although both native and recombinant DM64 exhibit different glycosylation patterns, they show very similar electrophoretic mobilities after PNGase F treatment. rDM64 formed a noncovalent complex with myotoxin II (Lys49-PLA2 from Bothrops asper and displayed biological activity that was similar to that of native DM64, inhibiting the cytotoxicity of myotoxin II by 92% at a 1:1 molar ratio.

Ochetosoma heterocoelium (Digenea: Plagiorchiidae in snakes from Colombia Ochetosoma heterocoelium (Digenea: Plagiorchiidae en ofidios de Colombia

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Carolina Lenis

2009-12-01

Full Text Available Ochetosoma heterocoelium Travassos, 1921 is a parasite that has been identified in snakes from different locations in Colombia and is considered of veterinary importance. Here, we present a redescription based on morphological traits of juveniles and adults. Parasite burden of O. heterocoelium in the host varied between 3-207 individuals which were localized in the oral cavity of snakes, causing damage that range from small infections to mechanical obstruction of the esophagus and Jacobson's organ. The low levels of abundance and prevalence in the snakes Leptodeira septentrionalis, Bothriechis schlegelli, Bothrops asper and Porthidium nasutum coming from the localities of Maceo, Vegachí and Acandí regions, suggest that the parasite is not a threat to the snakes of Colombia. We propose a treatment program that consists of manual removal of Digenea as well as treating snakes with antihelminthics, the applaying of soft antiseptics and monitoring recovery. The prevalence of O. heterocoelium was established in new regions, namely Middle Magdalena, Valle de Aburrá, Urabá Chocoano and northern Colombia. This extends the known geographical distribution from Brazil and Venezuela. New hosts were also identified: Atractus lasallei, Bothriechis schlegelli, Bothrops asper, Chironius carinatus, Leptodeira septentrionalis, Leptophis ahaetulla and Porthidium nasutum.Se identifica Ochetosoma heterocoelium Travassos, 1921 como un parásito de importancia veterinaria en ofidios de diferentes localidades de Colombia y se redescribe con base en las características morfológicas de individuos juveniles y adultos. La carga parasitaria de O. heterocoelium varió de 3-207 individuos alojados en la cavidad bucal de los ofidios, causando desde infecciones leves hasta obstrucción mecánica en el esófago y órgano de Jacobson. Los bajos valores de abundancia y prevalencia en las localidades de Maceo, Vegachí y Acandí y en los ofidios Leptodeira septentrionalis

New records of snakes (Reptilia: Squamata) in Minas Gerais, Brazil

OpenAIRE

Moura, Mario; Pirani, Renata; Silva, Vinícius

2013-01-01

We report new records of three poorly-known species of snakes in Minas Gerais: Bothrops lutzi (Miranda- Ribeiro, 1915), Psomophis joberti (Sauvage, 1884), and Trilepida brasiliensis (Laurent, 1949). The new records represent important filling gaps for all three species or even southern extensions in the geographic distribution of B. lutzi and P. joberti. The new records are located in areas indicated as priority regions for biodiversity conservation in Cerrado. Maps of known records of these ...

Serpentes peçonhentas e ofidismo em Cruzeiro do Sul, Alto Juruá, Estado do Acre, Brasil Venomous snakes and ophidism in Cruzeiro do Sul, Alto Juruá, State of Acre, Brazil

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Paulo Sérgio Bernarde

2012-03-01

Full Text Available Apesar da importância dos acidentes ofídicos na Saúde Pública, são relativamente poucas as pesquisas realizadas sobre esse tema no Brasil. Devido aos poucos estudos sobre ofidismo na Amazônia e especialmente no estado do Acre, trabalhos epidemiológicos são de grande relevância. Esse estudo apresenta a lista de serpentes peçonhentas e aspectos epidemiológicos dos acidentes ofídicos em Cruzeiro do Sul, região do Alto Juruá (Acre, verificando quais gêneros de serpentes são responsáveis pelos envenenamentos e aspectos que envolvem o acidente e o atendimento hospitalar. Os dados epidemiológicos foram coligidos a partir do SINAN (Sistema de Informações de Agravos de Notificação, no setor de vigilância epidemiológica do Hospital Regional do Juruá, no município de Cruzeiro do Sul. Sete espécies de serpentes peçonhentas foram registradas nesse município: três viperídeos (Bothrops atrox, Bothriopsis bilineata e Lachesis muta e quatro elapídeos (Micrurus hemprichii, M. lemniscatus, M. remotus and M. surinamensis. Durante o período de dois anos (agosto de 2007 a julho de 2009 foram registrados 195 casos de acidentes ofídicos. Cinquenta e um por cento dos acidentes foi classificado como laquético (Lachesis, seguido pelo botrópico (Bothrops e Bothriopsis com 38% e crotálico (Crotalus com 2%. Em 9% dos casos o gênero da serpente envolvida não foi informado. A maioria dos acidentes envolveu indivíduos adultos do gênero masculino em área rural, afetados principalmente nos membros inferiores. Os casos ocorreram mais frequentemente nos meses de novembro a abril, coincidindo com os maiores níveis pluviométricos. A maioria dos acidentes foi atribuída equivocadamente à serpente L. muta, tendo sido provavelmente causados por B. atrox.Despite the importance of accidents involving snakebites, research on this theme in Brazil is relatively rare, especially in the Amazon region. Due to the poor number of studies about ophidism

Biochemical and biological characterization of Bothriechis schlegelii snake venoms from Colombia and Costa Rica

OpenAIRE

Prezotto-Neto, Jos�� P; Kimura, Louise F; Alves, Andr�� F; Guti��rrez, Jos�� Mar��a; Otero, Rafael; Su��rez, Ana M; Santoro, Marcelo L; Barbaro, Katia C

2016-01-01

Snakebites inflicted by the arboreal viperid snake Bothriechis schlegelii in humans are characterized by pain, edema, and ecchymosis at the site of the bite, rarely with blisters, local necrosis, or defibrination. Herein, a comparative study of Bothriechis schlegelii snake venoms from Colombia (BsCo) and Costa Rica (BsCR) was carried out in order to compare their main activities and to verify the efficacy of Bothrops antivenom produced in Brazil to neutralize them. Biochemical (SDS-PAGE and z...

Seasonal, daily activity, and habitat use by three sympatric pit vipers (Serpentes, Viperidae) from southern Brazil

OpenAIRE

ROCHA, MARCELO C.; HARTMANN, PAULO A.; WINCK, GISELE R.; CECHIN, SONIA Z.

2014-01-01

Viperid snakes are widely distributed in the South America and the greater distribution range of the family is found at the Crotalinae subfamily. Despite the abundance of this snakes along their geographic distribution, some ecological aspects remain unknown, principally at subtropical areas. In the present study, we evaluated the activity (daily and seasonal) and the use of the habitat by Bothrops diporus, B. jararaca andB. jararacussu, in an Atlantic Forest area at southern Brazil. We obser...

Epidemiology of snakebite accidents in the municipalities of the state of Paraíba, Brazil Epidemiologia dos acidentes ofídicos ocorridos nos municípios do Estado da Paraíba, Brasil

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Rafaella Moreno Barros

2013-05-01

Full Text Available Accidents involving venomous animals represent an important, albeit neglected, public health issue worldwide. A descriptive study was made of snakebite cases attended and recorded between 2007 and 2010 in the health units of the municipalities of Cariri, State of Paraíba, northeastern Brazil. Data was collected from the Injury Notification Information System data banks of the Health Ministry and a total of 351 records of snakebite victims were reviewed. Victims were predominantly male farm workers over 50. The highest incidence of snakebites occurred in rural areas, between April and June of 2007 and 2010. Snakes of the genus Bothrops were responsible for most cases, and victims were mostly bitten on the feet. The majority of the victims received medical assistance within 1 to 3 hours after being bitten. The most common clinical manifestations were pain, edema and ecchymosis, which were mainly classified as mild or moderate. Two deaths were reported. It was concluded that there is a significant impact of seasonality in snakebites, the prevalence of attacks caused by Bothrops, affecting the lower limbs of adult male farmers in rural areas. The findings of this study may contribute to identify the conditions that increase the risk of snake attacks in the northeastern region.Acidentes por animais peçonhentos representam um importante, embora negligenciado, problema de saúde pública mundial. Neste sentido, foi realizado um estudo descritivo dos acidentes ofídicos atendidos e registrados, entre 2007 e 2010, nas unidades de saúde dos municípios do Cariri, Estado da Paraíba, Nordeste do Brasil. As informações foram coletadas do banco de dados do Sistema de Informação de Agravos de Notificação do Ministério da Saúde. Um total de 351 registros de vítimas de ataques por serpentes peçonhentas foram analisados. As vítimas foram predominantemente trabalhadores rurais do sexo masculino com mais de 50 anos. As maiores incidências de

Efficacy of IgG and F(ab′)2 Antivenoms to Neutralize Snake Venom-induced Local Tissue Damage as Assessed by the Proteomic Analysis of Wound Exudate

OpenAIRE

Rucavado, Alexandra; Escalante Muñoz, Teresa; Shannon, John D.; Ayala Castro, Carla N.; Villalta, Mauren; Gutiérrez, José María; Fox, Jay W.

2012-01-01

2082-01 Embargo por política editorial Proteomic analysis of wound exudates represents a valuable tool to investigate tissue pathology and to assess the therapeutic success of various interventions. In this study, the ability of horse-derived IgG and F(ab0)2 antivenoms to neutralize local pathological effects induced by the venom of the snake Bothrops asper in mouse muscle was investigated by the proteomic analysis of exudates collected in the vicinity of affected tissue. In experiments...

Analysis of Cl and Na in Hyperimmune Sera by NAA

International Nuclear Information System (INIS)

Baptista, T. S.; Zamboni, C. B.; Marcelino, J. R.

2011-01-01

The Cl and Na concentration values in four types of hyperimmune sera (anti-Bothrops, anti-Diphtheria, anti-Rabies and anti-Tetanus) used for immunological therapy were determined using Neutron Activation Analysis (NAA). These data were compatible with the specifications established by the Word Health Organization (WHO-OMS) and with the Brazilian Official Pharmacopea (Pharmaceutical Code Official of the Country). These data are an important support for quality control of hyperimmune sera production at Butantan Institute (Sao Paulo city, Brazil), responsible for supplying the Brazilian market.

Involvement of Nitric Oxide on Bothropoides insularis Venom Biological Effects on Murine Macrophages In Vitro.

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Ramon R P P B de Menezes

Full Text Available Viperidae venom has several local and systemic effects, such as pain, edema, inflammation, kidney failure and coagulopathy. Additionally, bothropic venom and its isolated components directly interfere on cellular metabolism, causing alterations such as cell death and proliferation. Inflammatory cells are particularly involved in pathological envenomation mechanisms due to their capacity of releasing many mediators, such as nitric oxide (NO. NO has many effects on cell viability and it is associated to the development of inflammation and tissue damage caused by Bothrops and Bothropoides venom. Bothropoides insularis is a snake found only in Queimada Grande Island, which has markedly toxic venom. Thus, the aim of this work was to evaluate the biological effects of Bothropoides insularis venom (BiV on RAW 264.7 cells and assess NO involvement. The venom was submitted to colorimetric assays to identify the presence of some enzymatic components. We observed that BiV induced H2O2 production and showed proteolytic and phospholipasic activities. RAW 264.7 murine macrophages were incubated with different concentrations of BiV and then cell viability was assessed by MTT reduction assay after 2, 6, 12 and 24 hours of incubation. A time- and concentration-dependent effect was observed, with a tendency to cell proliferation at lower BiV concentrations and cell death at higher concentrations. The cytotoxic effect was confirmed after lactate dehydrogenase (LDH measurement in the supernatant from the experimental groups. Flow cytometry analyses revealed that necrosis is the main cell death pathway caused by BiV. Also, BiV induced NO release. The inhibition of both proliferative and cytotoxic effects with L-NAME were demonstrated, indicating that NO is important for these effects. Finally, BiV induced an increase in iNOS expression. Altogether, these results demonstrate that B. insularis venom have proliferative and cytotoxic effects on macrophages, with

Somatic pairing, endomitosis and chromosome aberrations in snakes (Viperidae and Colubridae

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Beçak Maria Luiza

2003-01-01

Full Text Available The positioning of macrochromosomes of Bothrops jararaca and Bothrops insularis (Viperidae was studied in undistorted radial metaphases of uncultured cells (spermatogonia and oogonia not subjected to spindle inhibitors. Colchicinized metaphases from uncultured (spleen and intestine and cultured tissues (blood were also analyzed. We report two antagonic non-random chromosome arrangements in untreated premeiotic cells: the parallel configuration with homologue chromosomes associated side by side in the metaphase plate and the antiparallel configuration having homologue chromosomes with antipolar distribution in the metaphase ring. The antiparallel aspect also appeared in colchicinized cells. The spatial chromosome arrangement in both configurations is groupal size-dependent and maintained through meiosis. We also describe, in untreated gonia cells, endomitosis followed by reductional mitosis which restores the diploid number. In B. jararaca males we observed that some gonad regions present changes in the meiotic mechanism. In this case, endoreduplicated cells segregate the diplochromosomes to opposite poles forming directly endoreduplicated second metaphases of meiosis with the suppression of first meiosis. By a successive division, these cells form nuclei with one set of chromosomes. Chromosome doubling in oogonia is known in hybrid species and in parthenogenetic salamanders and lizards. This species also presented chromosome rearrangements leading to aneuploidies in mitosis and meiosis. It is suggested that somatic pairing, endomitosis, meiotic alterations, and chromosomal aberrations can be correlated processes. Similar aspects of nuclei configurations, endomitosis and reductional mitosis were found in other Viperidae and Colubridae species.

Aspects of the immune response against proteic antigens submitted to the effects of 60Co gamma radiation

International Nuclear Information System (INIS)

Alves, Janaina Baptista.

2004-01-01

Considering the effects of gamma radiation on proteins and the capacity of the immune system to recognize modified macromolecules, we decided to evaluate some immunological aspects of B10.PL mice exposed to native or irradiated ovalbumin and bothrops toxin-1 (BthTx-1). In order to evaluate possible structural modifications of the molecules after being irradiated ( 60 Co gamma rays), bothrops toxin-1 was analysed by electrophoresis, while ovalbumin was submitted to analytical size exclusion chromatography. The toxin was also analysed by ESI-mass spectrometry. Our results indicate that radiation promoted modifications on both the molecules. Aiming to compare the toxicity of the native and irradiated forms of the toxin, an in vitro cytotoxicity assay, using CHO cells, was performed. According to our results, the modified toxin was 5 folds less toxic than its native counterpart. Sera of animals immunized with the native and irradiated proteins were analyzed in order to evaluate levels of IgG, as well as to quantify specific isotopes. While the native proteins induced a predominant Th2 response, the irradiated molecules apparently promoted a switch towards a Th1 pattern. We also performed a cell proliferation assay with splenocytes from mice immunized with either the native or the irradiated proteins, cultured in the presence of the antigens. Our results indicate that both the forms of the proteins induced a similar proliferative response. These data indicate a potential use of detoxified proteins as antigens for immunization. (author)

Social Perception and Encounters with Snakes in Costa Rica: An Analysis through the Social Network Facebook

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Katherine Sánchez-Paniagua

2017-12-01

Full Text Available Snakes are among the animals most affected by the ignorance of humans towards wildlife In Costa Rica, little effort has been made to know how snakes are affected by human actions. In the present study, we used information supplied to the Serpientes de Costa Rica page of the social network Facebook to find out: which species are reported most frequently? Which of these suffer the greatest number of deaths? and what ability to recognize them have those who send the reports? A total of 484 reports were obtained, 389 of which were non —venomous snakes and 95 were venomous, with 66 species being identified. The most frequent species were Ninia maculata, Senticolis triaspis, Leptodeira rhombifera, Boa imperator, Bothrops asper, Bothriechis schlegelii and Mastigodryas melanolomus. The genera with higher mortality were Mastigodryas, Bothrops, Senticolis, Geophis and Leptodeira. People killed one in four snakes, regardless of whether it was venomous or not. Species of the genera Mastigodryas, Geophis, Senticolis, Ninia and Leptodeira were among the least identified. The best identified species were B. imperator, B. asper and B. schlegelii. Only one in five people could correctly recognize whether a snake was poisonous or not. The reports were given with a small group of species, which seem to be the ones that are in closest contact with the studied population; education for the conservation of these animals can start with those species that seem to be more frequent and so people will gradually recognize and protect the wild life that surrounds them.

Contribuição à biologia de serpentes da Bahia, Brasil: I. vivíparas Contribution to reproductive biology of snakes in Bahia, Brazil: I. viviparous

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Rejane Maria Lira-da-Silva

1994-01-01

Full Text Available Great part of lhe avaiable data about snakes reprodution refers to species coming from subtropical and temperate regions. In Brazil, the data is rather rare and can be found in various works where information is restricted. Results from studies developed with five viviparous snakes - Crotalus durissus cascavella (Wagler, 1824. Bothrops erythromelas(Amaral, 1923, B. leucurus (Wagler, 1824, Helicops leopardinus (Schlegel, 1873 and Thamnodynastes strigilis (Thiinberg, 1787 - which come from the Northeast of Brazil (Bahia are described. Data about pregnancy and birth, number, sex ratio, length and weight of neonates is given and discussed.

Inorganic elements in blood of mice immunized with snake venom using NAA and XRF techniques

International Nuclear Information System (INIS)

Metairon, S.; Zamboni, C.B.; Suzuki, M.F.; Lopes da Silva, L.F.F.; Rizzutto, M.A.

2016-01-01

Brazil has the greatest diversity of snakes in the world and a large portion of them are venomous. Nowadays, Instituto Butantan (research center, at Brazil) produces various types of antivenom to meet the large number of incidences. In this investigation, mice were immunized with different species of Bothrops snake venom to evaluate the inorganic elements concentration in their blood by using NAA and XRF techniques. The results were compared with the control group (mice not immunized) and with human estimative. The data allows to evaluate the toxicity of these elements, important for clinical screening of patients submitted to immunological therapy. (author)

Avaliação das pressões venosa e arterial em cães submetidos a diferentes tipos de hipotensão Evaluation of venous and arterial blood pressures in dogs submitted to hypotension

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R.C. Rabelo

2005-12-01

Full Text Available Estabeleceram-se a pressão venosa periférica (PVP, a pressão venosa central (PVC, a pressão arterial invasiva (PAI e a pressão arterial não invasiva (PANI em cães após diferentes eventos de hipotensão. Foram utilizados 15 cães adultos, distribuídos aleatoriamente em três grupos (G com cinco animais cada, submetidos aos seguintes eventos hipotensores: GI - cloridrato de xilazina a 2%, GII - choque hipovolêmico agudo e GIII - veneno da serpente Bothrops moojeni. Os animais, avaliados durante 30 minutos após o início do evento hipotensor, foram tratados com cloridrato de ioimbina (GI, amido hidroxietílico a 6% (GII e cetoprofeno (GIII e reavaliados por mais 30 minutos. Somente os animais do GII apresentaram redução da PVP após o evento hipotensor e aumento, 25 minutos após tratamento. Os cães dos grupos II e III mostraram redução da PVC após o evento hipotensor, e somente os animais do GII exibiram discreto aumento cinco minutos imediatamente após o tratamento. Houve diminuição da PAI e PANI nos dos grupos II e III após o evento hipotensor, com recuperação gradativa imediata, após o tratamento, somente da PAI.The peripheral venous pressure (PVP, the central venous pressure (CVP, the invasive (IAP and non-invasive blood pressure (NIAP in dogs submitted to different hypotensive events were studied. Fifteen adult mongrel dogs were randomly divided in three groups with five animals each, and submitted to hypotensive event as follow: GI - xylazine chloride 2%, GII - acute hypovolemic shock and GIII - snake venom (Bothrops moojeni. All animals were evaluated for 30 minutes after starting hypotensive event, treated with yoimbine chloride (GI, colloid hetastarch 6% (GII and ketoprofen (GIII and reevaluated for more 30 minutes. Only the group II dogs showed PVP decrease after hypotensive event, and increase 25 minutes after treatment. In animals of groups II and III, the CVP decreased after hypotensive event and only in GII

DNA barcoding for biosecurity: case studies from the UK plant protection program.

Science.gov (United States)

Hodgetts, Jennifer; Ostojá-Starzewski, Jozef C; Prior, Thomas; Lawson, Rebecca; Hall, Jayne; Boonham, Neil

2016-11-01

Since its conception, DNA barcoding has seen a rapid uptake within the research community. Nevertheless, as with many new scientific tools, progression towards the point of routine deployment within diagnostic laboratories has been slow. In this paper, we discuss the application of DNA barcoding in the Defra plant health diagnostic laboratories, where DNA barcoding is used primarily for the identification of invertebrate pests. We present a series of case studies that demonstrate the successful application of DNA barcoding but also reveal some potential limitations to expanded use. The regulated plant pest, Bursephalenchus xylophilus, and one of its vectors, Monochamus alternatus, were found in dining chairs. Some traded wood products are potentially high risk, allowing the movement of longhorn beetles; Trichoferus campestris, Leptura quadrifasciata, and Trichoferus holosericeus were found in a wooden cutlery tray, a railway sleeper, and a dining chair, respectively. An outbreak of Meloidogyne fallax was identified in Allium ampeloprasum and in three weed species. Reference sequences for UK native psyllids were generated to enable the development of rapid diagnostics to be used for monitoring following the release of Aphalara itadori as a biological control agent for Fallopia japonica.

Design of Fab-based chimeric antibodies against Bothrops asper toxins

DEFF Research Database (Denmark)

M. Haack, Aleksander; B. Hallgren, Malte; U. W. Friis, Rasmus

Snakebite is one of the world’s most neglected tropical diseases, with an estimated 5 million bites per year, resulting in about 125.000 deaths. The only current treatment for snakebite envenoming is antiserum derived from the blood of immunized mammals(typically horses). These antisera are expen...

Envenenamento ofídico em crianças: frequência de reações precoces ao antiveneno em pacientes que receberam pré-tratamento com antagonistas H1 e H2 da histamina e hidrocortisona Snake envenomation in children: early reactions frequency at antivenom in patients pretreated with histamine antagonists HI and H2 and hydrocortisone

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Fábio Bucarethi

1994-10-01

Full Text Available Foram estudadas 24 crianças, com idade entre 2 a 14 anos, de 1989 a 1993, vítimas de acidentes ofídicos, submetidas a pré-tratamento com antagonistas H1 (dextroclorfeniramina e H2 (cimetidine ou ranitidina da histamina e hidrocortisona, com objetivo de avaliar a frequência e o tipo de reações precoces (RP ao antiveneno (AV. Em nenhum paciente havia antecedente de atopia ou uso prévio de algum tipo de antiveneno ou antitoxina heteróloga. Das 24 crianças 15 receberam AV botrópico (RP em 5, 7 AV crotálico (RP em 5, 1 AV crotálico e AV botrópico-crotálico e 1 AV elapídico (RP. Foram observadas RP graves em 3 crianças, as 3 classificadas como acidente crotálico grave. A análise dos resultados sugere que o pré-tratamento realizado não ofereceu uma proteção segura quanto ao aparecimento de RP.Type and frequency of early reactions (ER were studied in 24 children aging 2-14 years victims of snake bites who received pretreatment with histamine antagonists H1 (dextrochlorfenirarnine and H2 (cimetidine or ranitidine and hydrocortisone from 1989 to 1993. None of them had atopy nor received any type of anti-venoms(AV and antitoxins before. Of 24 children, 15 received bothropic AV (ER in 5, 7 crotalic AV (ER in 5, 1 crotalic plus crotalic-bothropic AV, and 1 elapidic AV (ER in 1. In 3 children severe early reactions were observed and they were classified as severe crotalic accident. Results suggest that pre-treatment did not offer safety protection at the appearance of early reactions.

Noteworthy records of reptiles from natural open vegetation areas in plateau and coastal areas of the state of Santa Catarina, southern Brazil

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Ivo Rohling Ghizoni-Jr.

2009-09-01

Full Text Available The composition and geographic distribution of reptiles in Santa Catarina are little known, particularly in the open areas of its plateau (covered with ombrophylous steppe and Atlantic littoral (coastal dunes with thin, low, and predominant herbaceous vegetation known as restinga. Aiming to contribute to the knowledge of reptiles that inhabit these areas, this paper presents sixteen records of previously unknown or uncommon species in Santa Catarina: Acanthochelys spixii, Anops kingii, Cnemidophorus lacertoides, C. vacariensis, Leptotyphlops munoai, Mastigodryas b. bifossatus, Tantilla aff. melanocephala, Atractus reticulatus, Gomesophis brasiliensis, Lygophis flavifrenatus, Oxyrhopus r. rhombifer, Phalotris reticulatus, Philodryas agassizii, Xenodon dorbignyi, Micrurus altirostris and Bothrops pubescens. Aspects of the distribution and conservation of these species are discussed briefly.

Requests for body computed tomography: increasing workload, increasing indications and increasing age

International Nuclear Information System (INIS)

Toms, A.P.; Cash, C.J.C.; Dixon, A.K.; Linton, S.J.

2001-01-01

Increasing numbers of increasingly elderly patients were being examined in our Body CT department. At the same time, some of our clinical colleagues perceived that their patients might be discriminated against on the basis of their age when allocating CT time. We therefore studied the population trends in our department over a 10-year period. The ages of patients attending the Body CT department were collected from the hospital's computer information system from 1995 to 2000 and from handwritten logbooks for the months of September 1988 and 1998. Comparison was made with population trends within the hospital and local demographic data. There has been an average increase of 11% per annum in the number of examinations performed in the Body CT unit. The average age of patients examined increased from 52.7 years in 1988 to 58.9 years in 1998. The largest increase occurred in the over 75-year population (18% rise per annum). Hospital and local demographic population profiles changed little during the same period. We are performing increasing numbers of body CT examinations on increasingly elderly patients. This is probably due to an increased willingness to investigate and treat elderly patients, rather than changes in the local population. There is no evidence of a general discriminatory policy on the basis of age. (orig.)

Methemoglobinemia associated with loxoscelism Meta-hemoglobinemia associada ao loxoscelismo

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Orlando C. de O. Barreto

1990-02-01

Full Text Available In twenty five patients who presented the cutaneous form of loxoscelism, serum haptoglobin and lactic dehydrogenase, erythrocyte glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, methemoglobin, bilirubin and reticulocytes were investigated after bite. No hemolysis was detected but an increase in methemoglobin was found in 54% of the cases; in 7% it was between 1.1% and 2%, in 27% it ranged from 2.1% to 4%, and in 20% from 4.1% to 8%. Blood samples of a normal, blood group 0 individual and of a patient who exhibited methemoglobinemia after Loxosceles bite were incubated separately with antisera against Loxosceles gaucho, Crotalus terrificus, Bothrops jararaca, with Loxosceles gaucho venom and 0.3% phenol. No methemoglobin was found after 1, 4,8 and 15 days in both sets of samples. At the 25th day all the samples, including the controls, exhibited similar methemoglobin reductase decrease. The data suggest that the methemoglobinemia which occurs in 50% of the patients probably arises from in vivo venom metabolism, inasmuch as the crude venom does not induce methemoglobinemia.Vinte e cinco pacientes que apresentaram a forma cutânea do loxoscelismo foram estudados após a picada, determinando-se a glicose-6-fosfato desidrogenase, glutationa redutase e glutationa peroxidase eritrocitárias, haptoglobina e latico desidrogenase séricas, bilirrubina, reticulócitos e meta-hemoglobina. Não foi observada hemólise aumentada, mas foi detectado aumento da meta-hemoglobina em 54% dos casos: em 7% entre 1,1% e 2%, em 27% variou de 2,1% a 4%, e em 20% de 4,1 a 8%. Amostras de sangue de um indivíduo normal do grupo 0 de uma paciente que exibiu meta-hemoglobina após picada por Loxosceles foram incubadas separadamente com anti-soros contra Loxosceles gancho, Crotalus terrificus e Bothrops jararaca, com veneno de Loxosceles gaucho e fenol a 3%, e não se detectou aumento de meta-hemoglobina depois de 1, 4, 8 e 15 dias em todas

Increasing instruction time in school does increase learning

DEFF Research Database (Denmark)

Andersen, Simon Calmar; Humlum, Maria; Nandrup, Anne Brink

2016-01-01

Increasing instruction time in school is a central element in the attempts of many governments to improve student learning, but prior research—mainly based on observational data—disputes the effect of this approach and points out the potential negative effects on student behavior. Based on a large......-scale, cluster-randomized trial, we find that increasing instruction time increases student learning and that a general increase in instruction time is at least as efficient as an expert-developed, detailed teaching program that increases instruction with the same amount of time. These findings support the value...... of increased instruction time....

A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules

Science.gov (United States)

2013-01-01

Background The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. Results The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without

A bradykinin-potentiating peptide (BPP-10c) from Bothrops jararaca induces changes in seminiferous tubules.

Science.gov (United States)

Gilio, Joyce M; Portaro, Fernanda Cv; Borella, Maria I; Lameu, Claudiana; Camargo, Antonio Cm; Alberto-Silva, Carlos

2013-11-06

The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure-activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs - including BPP-10c - are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability

Role of collagens and perlecan in microvascular stability: exploring the mechanism of capillary vessel damage by snake venom metalloproteinases.

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Teresa Escalante

Full Text Available Hemorrhage is a clinically important manifestation of viperid snakebite envenomings, and is induced by snake venom metalloproteinases (SVMPs. Hemorrhagic and non-hemorrhagic SVMPs hydrolyze some basement membrane (BM and associated extracellular matrix (ECM proteins. Nevertheless, only hemorrhagic SVMPs are able to disrupt microvessels; the mechanisms behind this functional difference remain largely unknown. We compared the proteolytic activity of the hemorrhagic P-I SVMP BaP1, from the venom of Bothrops asper, and the non-hemorrhagic P-I SVMP leucurolysin-a (leuc-a, from the venom of Bothrops leucurus, on several substrates in vitro and in vivo, focusing on BM proteins. When incubated with Matrigel, a soluble extract of BM, both enzymes hydrolyzed laminin, nidogen and perlecan, albeit BaP1 did it at a faster rate. Type IV collagen was readily digested by BaP1 while leuc-a only induced a slight hydrolysis. Degradation of BM proteins in vivo was studied in mouse gastrocnemius muscle. Western blot analysis of muscle tissue homogenates showed a similar degradation of laminin chains by both enzymes, whereas nidogen was cleaved to a higher extent by BaP1, and perlecan and type IV collagen were readily digested by BaP1 but not by leuc-a. Immunohistochemistry of muscle tissue samples showed a decrease in the immunostaining of type IV collagen after injection of BaP1, but not by leuc-a. Proteomic analysis by LC/MS/MS of exudates collected from injected muscle revealed higher amounts of perlecan, and types VI and XV collagens, in exudates from BaP1-injected tissue. The differences in the hemorrhagic activity of these SVMPs could be explained by their variable ability to degrade key BM and associated ECM substrates in vivo, particularly perlecan and several non-fibrillar collagens, which play a mechanical stabilizing role in microvessel structure. These results underscore the key role played by these ECM components in the mechanical stability of

Some new species of Caryospora (Apicomplexa: Eimeriidae from brazilian snakes, and a re-description of C. jararacae Carini, 1939

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Ralph Lainson

1991-09-01

Full Text Available The mature ooxysts of six new species of Caryospora are described from the faeces of Brazilian snakes. They are differentiated from other species previously recorded from reptiles, largely on the size and shape of the oocyst and sporocyst, structure of the oocyst wall, and presence or absence of a polar body. C. paraensis n. sp., and C. carajasensis n. sp., are from the "false coral", Oxyrhopus petola digitalis; C. pseustesi n. sp., from the "egg-eater", Pseustes sulphureus sulphureus; C. epicratesi n. sp., from the "red boa", Epicrates cenchria cenchria; and C. micruri n. sp., and C. constancieae n. sp., from the "coral snake", Micrurus spixii spixii. A re-description is given of C. jararacae Carini, 1939, from the "jararaca" Bothrops atrox, embodying some additional morphological features.

Envenomation by the neotropical colubrid Boiruna maculata (Boulenger, 1896: a case report Envenenamento por Colubrídeo Neotropical Boiruna maculata (Boulenger, 1896: registro de um caso

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Maria Cristina dos SANTOS-COSTA

2000-10-01

Full Text Available This is a case report of a Boiruna maculata snake bite in a child admitted to the Hospital Municipal de Pronto Socorro de Porto Alegre, Porto Alegre, RS, Brazil. The patient was bitten on the lower left limb, and exhibited pronounced local manifestations of envenomation. She was treated with Bothrops antivenom and was discharged from the hospital five days later with marked improvement of envenomation.Este trabalho relata o envenenamento por serpente do gênero Boiruna maculata em criança admitida e posteriormente hospitalizada no Hospital Municipal de Pronto Socorro de Porto Alegre, RS, Brasil. A paciente foi mordida no membro inferior esquerdo e apresentou sinais de envenenamento local pronunciado, foi tratada como acidente botrópico e permaneceu no hospital por cinco dias, recebendo alta após melhora.

Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

NARCIS (Netherlands)

de Sain-van der Velden, M; Kaysen, GA; Barrett, HA; Stellaard, F; Gadellaa, MM; Voorbij, HA; Reijngoud, DJ; Rabelink, TJ

Increased very low density lipoprotein (VLDL) in nephrotic patients results from a decreased catabolism while increased low density lipoprotein (LDL) results from increased synthesis. Hyperlipidemias a hallmark of nephrotic syndrome that has been associated with increased risk for ischemic heart

The effective control of a bleeding injury using a medical adhesive containing batroxobin

International Nuclear Information System (INIS)

You, Kyung Eun; Koo, Min-Ah; Lee, Dae-Hyung; Kwon, Byeong-Ju; Lee, Mi Hee; Park, Jong-Chul; Hyon, Suong-Hyu; Seomun, Young; Kim, Jong-Tak

2014-01-01

Many types of hemostatic agents have been studied for the effective control of bleeding. In this study, a powdery medical adhesive composed of aldehyded dextran and ε-poly (L-lysine) was used with the recombinant batroxobin. Batroxobin is a venomous component from the snake Bothrops atrox moojeni and catalyzes fibrinogen conversion to form soluble fibrin clots. This research aims to examine the performance of the batroxobin-containing adhesive for hemostasis, and evaluate its potential as a novel hemostatic adhesive. The fibrinogen conversion ability of batroxobin was evaluated by a fibrinogen clotting assay and a whole blood clotting assay. Both experiments demonstrated the effectiveness of the batroxobin-containing adhesive for blood clot formation. Animal experiments were also conducted. After a pricking wound was made in an ICR (imprinting control region) mouse liver, the adhesive and various concentrations of batroxobin were applied. The total amount of blood loss was reduced with increasing concentrations of batroxobin. For excessive bleeding conditions, the femoral artery wound model of SD (Sprague-Dawley) rats was adopted. With higher concentrations of batroxobin, hemostasis was more rapidly achieved. Histological analysis of the liver model also supports the hemostatic effects through fibrin clot formation. In conclusion, batroxobin and medical adhesive effectively facilitate blood coagulation, and could be developed for clinical use. (paper)

Gamma radiation effect on biological activity and enzymatic properties of snake venoms

International Nuclear Information System (INIS)

Herrera, E.; Yarleque, A.; Campos, S.; Zavaleta, A.

1986-01-01

The effect of gamma radiation, from Co-60, on the biological activity and on some enzymatic activities, present in the venoms of Lachesis muta and Bothrops atrox, using samples of dried venom that had been irradiated at a dose of 0.1, 0.5 and 1.0 Mrad have been studied. Variations in the degree of hemorrhage and local necrosis were observed in albino mice injected subcutaneously with venoms of both types. The reduction of the biological activity was greater for the local hemorrhagic effect and was dependent on the doses of irradiation. The specific activity of various enzymes, present in both venoms, is affected by the gamma radiation, at a dose of 0.1 Mrad the order of increasing inactivation being: exonuclease (4%), phospholipase (24%), caseinolytic enzyme (20%), tamesterase (33%), a thrombine-like enzyme (40%), fibrinolytic enzyme (41%), 5'-nucleotidase (50%) and endonuclease (55%). The enzymatic inactivation was augmented by 0.5 and 1.0 Mrad, without maintaining an arithmetic relation. The enzyme of major resistance to the radiation was exonuclease, whereas 5'-nucleotidase and endonuclease were the most sensitive. No significant changes were observed in the spectrum of UV absorbtion (range 260 to 290 nm) nor in the contents of L-tyrosine in the irradiated venoms

LATE DEVONIAN-CARBONIFEROUS CONODONTS FROM EASTERN IRAN

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MEHDI YAZDI

1999-07-01

Full Text Available Conodont data from acid-leaching 110 samples from two Late Devonian-Carboniferous areas in the Shotori Range (Tabas region of eastern Iran are presented. At Howz-e-Dorah, a section (88 samples commencing high in the Bahram Formation (Givetian-early Frasnian extended through the Shishtu Formation (Frasnian, Early hassi Zone or older, to latest Tournaisian, anchoralis-latus Zone and the Sardar Formation (earliest Visean, texanus Zone, to late Namurian, sinuatus-corrugatus-sulcatus Zone and into the Jamal Formation (Permian. Four less exhaustively sampled sections (22 samples show the Kale Sardar area to be tectonically more complicated than the Howz-e-Dorah area. Useful marker horizons in the Howz-e-Dorah section, well constrained by conodont data, are: the early Frasnian (no older than Early hassi Zone biostromal beds of the Shishtu Formation, an early Famennian (Late triangularis to Early crepida interval of oolitic limestone, a cyclothem sequence straddling the Early Carboniferous-Late Carboniferous boundary, and an Early Permian interval of siliceous sand ("the white quartzite" of previous authors. Additionally, several iron-rich horizons, readily traceable from locality to locality, are well constrained by conodont ages. Eighty-five conodont species/subspecies are documented representing 24 genera.. Two new species, Polygnathus capollocki and Polygnathus ratebi and one new subspecies, Icriodus alternatus mawsonae are described. 

Increasing Public Expenditure

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Ammar Ben Zaed

2017-04-01

Full Text Available This article aims to analyze and interpret the phenomenon of increased public expenditures and test explanatory theories as well as to analyze Abstract the relationship between public spending and GDP in the short and long term where you see the Wagner hypothesis that causal heading of GDP to government spending while there is a causal relationship analysis positive trending of government spending to GDP according to the Keynesian hypothesis in this study will be used descriptive analytical method to validate these hypotheses. Results in the short and long term made it clear that there is a difference in the outcome of Applied Studies where we find that each supports a relationship Wagner in the sense that the causal trending of real GDP to government spending and more precisely to increase the economic growth lead to increased aggregate demand which leads in turn increasing the need to increase government spending and to increase the resources available to the government sector to finance the increase in spending by the additional resources resulting from the economic growth while others opines opposes the existence of the relationship.

Increased SRP reactor power

International Nuclear Information System (INIS)

MacAfee, I.M.

1983-01-01

Major changes in the current reactor hydraulic systems could be made to achieve a total of about 1500 MW increase of reactor power for P, K, and C reactors. The changes would be to install new, larger heat exchangers in the reactor buildings to increase heat transfer area about 24%, to increase H 2 O flow about 30% per reactor, to increase D 2 O flow 15 to 18% per reactor, and increase reactor blanket gas pressure from 5 psig to 10 psig. The increased reactor power is possible because of reduced inlet temperature of reactor coolant, increased heat removal capacity, and increased operating pressure (larger margin from boiling). The 23% reactor power increase, after adjustment for increased off-line time for reactor reloading, will provide a 15% increase of production from P, K, and C reactors. Restart of L Reactor would increase SRP production 33%

Price increase

CERN Multimedia

2006-01-01

Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

Price increase

CERN Multimedia

2005-01-01

Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

Increasing tobacco taxes : A cheap tool to increase public health

NARCIS (Netherlands)

van Baal, Pieter H. M.; Brouwer, Werner B. F.; Hoogenveen, Rudolf T.; Feenstra, Talitha L.

Introduction: Several studies have estimated health effects resulting from tobacco tax increases. However, studies on the cost effectiveness of tobacco taxes are scarce. The aim of this study was to estimate the cost effectiveness of tobacco tax increases from a health care perspective, explicitly

Chemical constituents and antiedematogenic activity of Peltodon radicans (Lamiaceae); Constituintes quimicos e atividade antiedematogenica de Peltodon radicans (Lamiaceae)

Energy Technology Data Exchange (ETDEWEB)

Costa, Habdel Nasser Rocha da [Universidade Federal de Roraima, Boa Vista, RR (Brazil). Centro de Ciencias e Tecnologia. Dept. de Quimica; Santos, Maria Cristina dos [Universidade Federal do Amazonas, Manaus, AM (Brazil). Inst. de Ciencias Biologicas. Dept. de Parasitologia; Alcantara, Antonio Flavio de Carvalho; Silva, Marilda Conceicao; Franca, Roberta Cabral; Pilo-Veloso, Dorila [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Exatas. Dept. de Quimica]. E-mail: aalcantara@zeus.qui.ufmg.br

2008-07-01

Most of the snakebite incidents in the Amazon region involve Bothrops atrox, whose venom presents the most potent edematogenic and necrotic activities in the genus. This work describes the studies of isolation of the chemical constituents and antiedematogenic activity of the species Peltodon radicans (Lamiaceae), which is used in the treatment of snakebites and scorpion stings in the region. The extracts presented aliphatic hydrocarbons, 3{beta}-OH,{beta}-amirin (1), 3{beta}-OH,a-amirin (2), {beta}-sitosterol (3), stigmasterol (4), ursolic acid (5), 2{alpha},3{beta},19{alpha}- trihydroxy-urs-12-en-28-oic acid (tormentic acid, 6), methyl 3{beta}-hydroxy,28-methyl-ursolate (7), sitosterol-3-O-{beta}-D-glucopyranoside (8), and stigmasterol-3-O-{beta}-D-glucopyranoside (9). The flower extracts presented the higher antiedematogenic activity. This is the first report on the study of the flowers, stem, and roots of this plant. (author)

Body size, reproductive biology and abundance of the rare pseudoboini snakes genera Clelia and Boiruna (Serpentes, Colubridae in Brazil

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Lígia Pizzatto

2005-12-01

Full Text Available Pseudoboini snakes of the genera Clelia and Boiruna are apparently rare in nature and certainly rare in collections. This work presents data on body size, reproduction and abundance of five Brazilian species of these genera, in the largest collection of snakes in Latin America, the Instituto Butantan. Despite scarcity of data, follicular cycle seems to be continuous in most species, except Clelia rustica, which occurs in highlands. Females are largerthan males in all species, and fecundity is low when compared to other pseudoboini. Abundance is very low for all species even considering 100 years of collecting, and it is decreasing in recent decades when compared to other snakes (Bothrops jararaca, Oxyrhopus guibei, O. clathratus, Philodryas patagoniensis, Sibynomorphus mikanii, and Spilotes pullatus. The studied species present at least five traits of commonly threatened species and require more attention in researches and conservation policies.

Bradykinin-potentiating PEPTIDE-10C, an argininosuccinate synthetase activator, protects against H2O2-induced oxidative stress in SH-SY5Y neuroblastoma cells.

Science.gov (United States)

Querobino, Samyr Machado; Ribeiro, César Augusto João; Alberto-Silva, Carlos

2018-05-01

Bradykinin-potentiating peptides (BPPs - 5a, 7a, 9a, 10c, 11e, and 12b) of Bothrops jararaca (Bj) were described as argininosuccinate synthase (AsS) activators, improving l-arginine availability. Agmatine and polyamines, which are l-arginine metabolism products, have neuroprotective properties. Here, we investigated the neuroprotective effects of low molecular mass fraction from Bj venom (LMMF) and two synthetic BPPs (BPP-10c, BPP-12b, BPP-10c showed higher protective capacity than BPP-12b. LMMF pretreatment was unable to prevent the reduction of cell viability caused by H 2 O 2 . The neuroprotective mechanism of BPP-10c against oxidative stress was investigated. BPP-10c reduced ROS generation and lipid peroxidation in relation to cells treated only with H 2 O 2 . BBP-10c increased AsS expression and was not neuroprotective in the presence of MDLA, a specific inhibitor of AsS. BPP-10c reduced iNOS expression and nitrate levels but decreased NF-kB expression. Furthermore, BPP-10c protected the mitochondrial membrane against oxidation. Overall, we demonstrated for the first time neuroprotective mechanisms of BPPs against oxidative stress, opening new perspectives to the study and application of these peptides for the treatment of neurodegenerative diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessment of the impact of solvent/detergent treatment on the quality and potency of a whole IgG equine antivenom.

Science.gov (United States)

Segura, Alvaro; León, Guillermo; Su, Chen-Yao; Gutiérrez, José-María; Burnouf, Thierry

2009-10-01

We have evaluated for the first time the impact of a solvent/detergent (S/D) treatment on the quality and in vivo neutralization potency of horse-derived whole IgG antivenom used in the treatment of viperid snake bite envenoming in Central America. The S/D treatment by 1% tri (n-butyl) phosphate (TnBP) - 1% Triton X-45 at 22-25 degrees C was applied either on starting plasma or on purified immunoglobulins. The S/D agents were removed from both fractions by extractions with oil. S/D-treated plasma was subjected to caprylic acid precipitation to purify the immunoglobulins. Products were formulated, sterile-filtered, and filled into 10-mL vials, stored at 5+/-3 degrees C, and subjected to routine quality controls, SDS-PAGE, determination of anti-Bothrops asper venom antibody titre by ELISA, in vivo B. asper venom-neutralization potency tests, and safety test, comparatively with an antivenom manufactured by caprylic acid fractionation without S/D treatment. Results indicate that these conditions of S/D treatment on purified immunoglobulin yielded an antivenom of high turbidity that induced weight loss in animals. In contrast, antivenom fractionated from the S/D-treated plasma had physico-chemical and biological characteristics indistinguishable from those of the non-S/D-treated antivenom. S/D treatment of horse plasma may be considered to increase the viral safety of antivenoms.

The renal effects and initial characterization of venom from Philodryas nattereri Steindachner, 1870

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Marinetes Dantas de Aquino Nery

2014-01-01

Full Text Available The venom of the snake Philodryas nattereri is a mixture of proteins and toxic peptides with several important local and systemic actions, which are similar to those occurring in Bothrops snake bites. The mechanisms involved in the local and systemic actions of this venom are unknown. The aims of the work were to initial characterization of P. nattereri venom and investigate the effects of the poison in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin–Darby canine kidney. The P. nattereri venom is composed majority of proteins (86.3% and this poison promoted changes in all the evaluated renal parameters, mainly decreasing renal perfusion pressure (PP and renal vascular resistance (RVR and increasing urine flow (UF and glomerular filtration rate (GFR. The most relevant result was that this venom was highly detrimental to the renal tubules independent of the PP reduction, which was shown by a decrease in sodium (Na+, potassium (K+ and chloride (Cl− electrolyte transport in the studied concentrations. The glomeruli and tubules contain protein bodies and blood extravasation, which were observed by histological analysis. The venom of P. nattereri reduced viability of the MDCK cells only at high concentrations (50 and 100 μg/mL with an IC50 of 169.5 μg/mL.

Seizing an opportunity: increasing use of cessation services following a tobacco tax increase.

Science.gov (United States)

Keller, Paula A; Greenseid, Lija O; Christenson, Matthew; Boyle, Raymond G; Schillo, Barbara A

2015-04-10

Tobacco tax increases are associated with increases in quitline calls and reductions in smoking prevalence. In 2013, ClearWay Minnesota(SM) conducted a six-week media campaign promoting QUITPLAN® Services (QUITPLAN Helpline and quitplan.com) to leverage the state's tax increase. The purpose of this study was to ascertain the association of the tax increase and media campaign on call volumes, web visits, and enrollments in QUITPLAN Services. In this observational study, call volume, web visits, enrollments, and participant characteristics were analyzed for the periods June-August 2012 and June-August 2013. Enrollment data and information about media campaigns were analyzed using multivariate regression analysis to determine the association of the tax increase on QUITPLAN Services while controlling for media. There was a 160% increase in total combined calls and web visits, and an 81% increase in enrollments in QUITPLAN Services. Helpline call volumes and enrollments declined back to prior year levels approximately six weeks after the tax increase. Visits to and enrollments in quitplan.com also declined, but increased again in mid-August. The tax increase and media explained over 70% of variation in enrollments in the QUITPLAN Helpline, with media explaining 34% of the variance and the tax increase explaining an additional 36.1% of this variance. However, media explained 64% of the variance in quitplan.com enrollments, and the tax increase explained an additional 7.6% of this variance. Since tax increases occur infrequently, these policy changes must be fully leveraged as quickly as possible to help reduce prevalence.

Meeting increased demand.

Science.gov (United States)

Blair, Andrew

2004-07-01

New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

The Frasnian-Famennian boundary (Upper Devonian) within the Hanover-Dunkirk transition, northern Appalachian basin, western New York state

Energy Technology Data Exchange (ETDEWEB)

Over, D.J. (State Univ. of New York, Geneseo, NY (United States))

1993-03-01

In western New York State interbedded pyritic silty green and dark grey shales and siltstone of the Hanover Member, Java Formation, West Falls Group, are overlain by thick pyritic dark grey-black shale of the Dunkirk Member of the Canadaway formation. The dark shales in the upper Hanover and Dunkirk contain a diverse and well preserved conodont fauna which allows precise placement of the Frasnian-Famennian boundary at several described sections. At Pt. Gratiot, in far western New York State, the contact between the Hanover and Dunkirk is disconformable. The Frasnian-Famennian boundary is marked by a pyritic lag deposit at the base of the Dunkirk which contains Palmatolepis triangularis and Pa. subperlobata. The underlying upper Hanover is characterized by Pa. bogartensis , Pa. cf. Pa. rhenana, Pa. winchelli, and Ancyrognathus (asymmetricus/calvini) Eastward, in the direction of the paleo-source area, the Frasnian-Famennian boundary is within the upper Hanover Member. At Irish Gulf the boundary is recognized within a 10 cm thick laminated pyritic dark grey shale bed 3.0 m below the base of the Dunkirk. Palmatolepis triangularis and Pa. subperlobata occur below a conodont-rich lag layer in the upper 2 cm of the bed. Palmatolepis bogartensis , Pa. cf. Pa. rhenana, Ancyrodella curvata, and Icriodus alternatus occur in the underlying 8 cm. Palmatolepis triangularis and Pa. winchelli occur in an underlying dark shale bed separated from the boundary bed by a hummocky cross-bedded siltstone layer.

Reclassification of the Indo-Pacific Hawkfish Cirrhitus pinnulatus (Forster).

Science.gov (United States)

Gaither, Michelle R; Randall, John E

2013-01-04

The hawkfish Cirrhitus pinnulatus Forster (in Bloch & Schneider 1801) was regarded as one wide-ranging Indo-Pacific species, from the Red Sea and east coast of Africa to the Hawaiian Islands and the islands of French Polynesia. Schultz (1950) resurrected the name C. alternatus Gill for the population in the Hawaiian Islands and Johnston Atoll, and described the Red Sea population as a new species, C. spilotoceps, based on morphological data. Randall (1963) confirmed the differences that Schultz used to separate Cirrhitus pinnulatus into three species, but preferred to regard them as subspecies. We examined more specimens, colour photographs, and used genetic comparisons to determine the validity of the three species recognized by Schultz (1950). Combining mitochondrial cytochrome oxidase I and cytochrome b sequence data from specimens of C. pinnulatus pinnulatus from the Indo-Pacific, C. spilotoceps from the Red Sea, and C. pinnulatus maculosus from Hawai'i, we detected levels of sequence divergence (5-12%) that support the species-level designation of C. spilotoceps. We detected no genetic differentiation but maintain the subspecies designation of the Hawaiian form based on morphological and colour differences. We found a third genetic lineage in the Indian Ocean and Western Pacific that is 5% divergent from C. spilotoceps. We refrain from designating this group as a separate subspecies until further morphological and genetic study can be completed.

Increasing muscle extensibility: a matter of increasing length or modifying sensation?

DEFF Research Database (Denmark)

Weppler, Cynthia Holzman; Magnusson, S Peter; Weppler, Cynthia Holzman

2010-01-01

in muscle extensibility are due to a modification of sensation only. Studies that evaluated the biomechanical effect of stretching showed that muscle length does increase during stretch application due to the viscoelastic properties of muscle. However, this length increase is transient, its magnitude...

Isolation and characterization of a novel bradykinin potentiating peptide (BPP) from the skin secretion of Phyllomedusa hypochondrialis.

Science.gov (United States)

Conceição, Katia; Konno, Katsuhiro; de Melo, Robson Lopes; Antoniazzi, Marta M; Jared, Carlos; Sciani, Juliana M; Conceição, Isaltino M; Prezoto, Benedito C; de Camargo, Antônio Carlos Martins; Pimenta, Daniel C

2007-03-01

Bradykinin potentiating peptides (BPPs) from Bothrops jararaca venom were first described in the middle of 1960s and were the first natural inhibitors of the angiotensin-converting enzyme (ACE). BPPs present a classical motif and can be recognized by their typical pyroglutamyl (Pyr)/proline rich sequences presenting, invariably, a proline residue at the C-terminus. In the present study, we describe the isolation and biological characterization of a novel BPP isolated from the skin secretion of the Brazilian tree-frog Phyllomedusa hypochondrialis. This new BPP, named Phypo Xa presents the sequence Pyr-Phe-Arg-Pro-Ser-Tyr-Gln-Ile-Pro-Pro and is able to potentiate bradykinin activities in vivo and in vitro, as well as efficiently and competitively inhibit ACE. This is the first canonical BPP (i.e. Pyr-Aaa(n)-Gln-Ile-Pro-Pro) to be found not only in the frog skin but also in any other natural source other than the snake venoms.

Distribution of the herpetofauna community associated to four areas with different interference degree in Gorgona Island, Colombian pacific

International Nuclear Information System (INIS)

Urbina C, Jose Nicolas; Londono M, Maria Cecilia

2003-01-01

A total of 1840 individuals from 28 species (19 reptiles and 9 amphibians) were found in Gorgona Island, during June and July 2001. Based on 32 transects placed in four areas with different antropic perturbation degree (Prison, palm plantations, secondary forest and primary forest) it was found that the species richness was higher at the secondary forest. The species registered at primary and secondary forest where very similar as well as the species present at the prison and the palm plantations. A Canonical Correspondence Analysis (CCA) showed that Boa constricto1; Basiliscus galeritus. Ameiva bridgesii and Epipedobates boulengeri were found to be associated to open areas and their distribution was hardly affected by the environmental temperature. From the following species associated with forested areas, the canopy cover over the micro habitat influenced the distribution of Eleutherodactylus gularis. Eleutherodactylus achatinus and Bothrops atrox. While the understory cover influenced the distribution of Atelopus elegans. Bufo typhonius. Micrurus mipartitus y Enyalioides heterolepis

Professor José Roberto Giglio and toxinnology in Brazil: 48 years in research

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A. M. Soares

2007-01-01

Full Text Available This work succinctly describes the professional and scientific life of Dr. José R. Giglio, one of the most outstanding Brazilian researchers in the field of Toxinology. During his long and successful career, he has made major contributions, especially in elucidating the function, structure, and mechanisms of action of animal venom proteins (from snakes, scorpions and spiders as well as the characterization of antibodies and several inhibitors of venoms and toxins. We present here a brief history of Dr. Giglio’s personal and professional life, also reporting some of his numerous published scientific articles on venoms from snakes (Bothrops, Crotalus, and other genera, scorpions (Tityus sp, spiders (Phoneutria sp, their isolated toxins and natural inhibitors. Thus, this work is a tribute to Dr. Giglio in his 73rd birthday, having devoted 48 years of his life studying animal venoms, an effort that has continued even after his formal retirement from university duties.

Registros notáveis de répteis de áreas abertas naturais do planalto e litoral do Estado de Santa Catarina, sul do Brasil

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Ivo Rohling Ghizoni-Junior

2009-06-01

Full Text Available http://dx.doi.org/10.5007/2175-7925.2009v22n3p129 A composição e a distribuição dos répteis em Santa Catarina são pouco conhecidas, particularmente em suas áreas abertas naturais do planalto (estepe ombrófila e do litoral (faixa litorânea de restingas com dunas. Visando contribuir com o conhecimento dos répteis nestas áreas, são apresentados registros de dezesseis espécies anteriormente desconhecidas ou com poucos registros para Santa Catarina: Acanthochelys spixii, Anops kingii, Cnemidophorus lacertoides, C. vacariensis, Leptotyphlops munoai, Mastigodryas b. bifossatus, Tantilla aff. melanocephala, Atractus reticulatus, Gomesophis brasiliensis, Lygophis flavifrenatus, Oxyrhopus r. rhombifer, Phalotris reticulatus, Philodryas agassizii, Xenodon dorbignyi, Micrurus altirostris e Bothrops pubescens. São discutidos brevemente aspectos sobre a distribuição e a conservação destas espécies.

Increasing income inequality

DEFF Research Database (Denmark)

Frederiksen, Anders; Poulsen, Odile

In recent decades most developed countries have experienced an increase in income inequality. In this paper, we use an equilibrium search framework to shed additional light on what is causing an income distribution to change. The major benefit of the model is that it can accommodate shocks...... that shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....

Increasing Northern Hemisphere water deficit

Science.gov (United States)

McCabe, Gregory J.; Wolock, David M.

2015-01-01

A monthly water-balance model is used with CRUTS3.1 gridded monthly precipitation and potential evapotranspiration (PET) data to examine changes in global water deficit (PET minus actual evapotranspiration) for the Northern Hemisphere (NH) for the years 1905 through 2009. Results show that NH deficit increased dramatically near the year 2000 during both the cool (October through March) and warm (April through September) seasons. The increase in water deficit near 2000 coincides with a substantial increase in NH temperature and PET. The most pronounced increases in deficit occurred for the latitudinal band from 0 to 40°N. These results indicate that global warming has increased the water deficit in the NH and that the increase since 2000 is unprecedented for the 1905 through 2009 period. Additionally, coincident with the increase in deficit near 2000, mean NH runoff also increased due to increases in P. We explain the apparent contradiction of concurrent increases in deficit and increases in runoff.

Increased P diffusion as an explanation of increased P availability in flooded rice soils

International Nuclear Information System (INIS)

Turner, F.T.; Gilliam, J.W.

1976-01-01

Phosphorus supply factors (capacity, kinetic, intensity, and diffusivity) and plant growth were the approaches used to assess P supply of flooded rice soils. Increases in the capacity, intensity and kinetic factors, as measured by E-value, solution P concentration, and soil P release rate to a distilled water 'sink' respectively, were unpronounced and infrequent upon water-saturation of ten soils. However, increases in the diffusivity factor, as measured by 32 P diffusion coefficients, were at least ten-fold as soil moisture increased. The greatest increases in P diffusion occurred as soil moisture increased beyond one-third bar. Using a P-fertilized soil or P treated powdered cellulose as the P source and a minus P nutrient solution to nourish a split root system with water and nutrients, data were obtained which suggested that P uptake and rice shoot growth (indicators of P availability) increased with increasing moisture level. Phosphorus uptake and rice-shoot growth were greatest when the soil or P treated cellulose were water-saturated. These data indicate that increased soil P availability upon flooding can be attributed to an increase in the diffusivity factor

Study of possibility of increasing the catchment's retention capacity by groundwater accumulation increase

International Nuclear Information System (INIS)

Baranovicova, L.

2004-01-01

In this presentation author deals with the possibility of increasing the catechumen's retention capacity by groundwater accumulation increase. This presentation solves possibilities of increasing of the retention capacity of ground waters on the dependence of surface water outflow on upper parts of Podluzianka River (Hron River Basin) and Predmieranka River (Kysuce River basin)

A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

Science.gov (United States)

Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

2016-09-01

Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influenza em animais heterotérmicos Influenza in heterothermics

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Dalva Assunção Portari Mancini

2004-06-01

Full Text Available O objetivo foi pesquisar Ortomyxovirus em animais heterotérmicos. Coletou-se sangue de serpentes dos gêneros Bothrops e Crotalus e de sapo e rãs dos gêneros Bufo e Rana, para a detecção dos receptores de hemácias e anticorpos específicos, ao vírus influenza, pelos testes de hemaglutinação e inibição da hemaglutinação, respectivamente. Pelo teste de hemaglutinação, verificou-se que serpentes e sapos em cativeiro apresentaram receptores em suas hemácias para o vírus influenza, humano e eqüino do tipo A e tipo B. O mesmo ocorreu com serpentes recém chegadas. Quanto ao teste de inibição da hemaglutinação dos soros dos répteis observou-se títulos protetores de anticorpos aos vírus influenza tipo A (origens humana e eqüina e tipo B. Com soro de sapo não se observou reação de inibição da hemaglutinação porém, 83,3% das rãs obtiveram médias de 40UIH para algumas cepas. Conclui-se que animais heterotérmicos podem oferecer condições de hospedeiros aos vírus influenza, assim como susceptibilidade à infecção.The objective was to study Orthomyxovirus in heterothermic animals. Blood samples from snakes (genus Bothrops and Crotalus and from toads and frogs (genus Bufo and Rana were collected to evaluate the red cell receptors and antibodies specific to influenza virus by the hemagglutination and hemagglutination inhibition tests, respectively. Both snakes and toads kept in captivity presented receptors in their red cells and antibodies specific to either influenza virus type A (human and equine origin or influenza type B. The same was observed with recently captured snakes. Concerning the influenza hemagglutination inhibition antibodies protective levels were observed in the reptiles' serum, against influenza type A and type B. Unlike the toads, 83.3% of the frogs presented mean levels of Ab 40HIU for some influenza strains. It was concluded that heterothermic animals could offer host conditions to the influenza

Ofidismo: Estudio de 30 casos en Brasil Ophidism: Study of 30 cases in Brazil

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Moisés Morejón García

2006-06-01

Full Text Available Se realizó un estudio de 30 pacientes ingresados por mordedura de cobras, en el Hospital Municipal de Paraiso de Tocantins, Estado de Tocantins, Brasil, en el período comprendido entre 1998-2001. Los resultados arrojaron un predominio del accidente ofídico en pacientes masculinos (76,6 %, con edades entre los 15 y 50 años (80 %. Hubo una participación mayoritaria de reptiles del género Bothrops (63,3 %, que provocó la mayor parte de las mordeduras en los miembros inferiores (80 %. Las manifestaciones clínicas más evidentes fueron el edema y el dolor (93,3 %, de moderado a severo en 63,3 % de ellos, por lo que la dosis media de suero antiofídico utilizada fue de 10 ámpulas en dosis única. El coagulograma reflejó alteración de la coagulación en el 70 % de los pacientes, pero se recuperó totalmente en 48 h. La complicación que más se presentó fue el fallo renal en 9 pacientes, de los cuales 5 se recuperaron en nuestro hospital y 4 fueron remitidos a unidad de terapia intensiva. Fallecieron 2 pacientes (6,6 %, ambos por fallo renal y shock . Del total de pacientes, 25 (83,3 % tuvieron evolución satisfactoria.Thirty patients admitted in the Municipal Hospital of Paraiso de Tocantins, State of Tocantins , Brazil , due to cobra bite, were studied between 1998 and 2001 . According to the results, there was a predominance of ophidic accidents in male patients (76.6 % aged 15-50 (80 %. Most of the reptiles corresponded to Bothrops genus (63.3 %, and the greatest number of bites occurred in the lower limbs (80 %. The most evident clinical manifestations were edema and pain (93.3 %, which were from moderate to severe in 63.3 % of them. Therefore, the mean dose of anti-ophidic serum used was 10 ampules in a single dose. The coagulogram showed coagulation alteration in 70 % of the patients, but it was totally recovered in 48 hrs. The most frequent complication observed was a renal failure in 9 patients, of whom 5 had a complete recovery in

Increased NMDA receptor inhibition at an increased Sevoflurane MAC

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Brosnan Robert J

2012-06-01

Full Text Available Abstract Background Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Methods Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL plus 0.4 mg/mL dizocilpine (MK-801 was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Results Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P  Conclusions Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.

Increase of Internal CO2 of Cotton Plants by Methanol Application to Increase Yield

International Nuclear Information System (INIS)

Badron Zakaria; Darmawan; Nurlina Kasim; Joseph Saepuddin

2004-01-01

A field experiment has been conducted to increase internal CO 2 and Rubisco activity detected by 14 C and to determinate which factors influence this activities. Plant material used was cotton plants which internal CO 2 concentrations and Rubisco activity was observed at 35, 50, 65, 80 days after planting (DAP). Treatments applied were methanol with concentrations of 0%, 10%,20% and 30% at available water (AW) at 25-50% AW, 50-75% AW, 75-100% AW. Results obtained showed that application of methanol at concentration of 20% at 75-100% AW, increase internal CO 2 from 266.60 ppm to 295.10 ppm (11 % increase) and this will also increase Rubisco activity from 3.81 to 14.28 (μmol. CO 2 menit -1 (μmol. Rubisco -1 ). This increase is expected to push photosynthesis rate and result in increase cotton yield. The use of 14 C was satisfactorily detected the amount of carbon. (author)

Increased Baseline C-Reactive Protein Concentrations Are Associated with Increased Risk of Infections

DEFF Research Database (Denmark)

Zacho, Jeppe; Benfield, Thomas; Tybjærg-Hansen, Anne

2016-01-01

BACKGROUND: The acute-phase reactant C-reactive protein (CRP) increases rapidly during an infection. We tested the hypothesis that chronic low-level increases in CRP are associated with an increased risk of infectious disease. METHODS: We studied 9660 individuals from a prospective general...... population cohort, including 3592 in whom infectious disease developed, and another 60 896 individuals from a cross-sectional general population study, of whom 13 332 developed infectious disease; 55% were women, and the mean age was 57 years. Hospital diagnoses of infections in 1977-2010 were based....... RESULTS: Individuals with CRP >3 mg/L had 1.2 and 1.7 times increased risk of infectious disease, in the prospective general population cohort and the cross-sectional general population study, respectively, compared with individuals with CRP

Integrated engineering increases flexibility

International Nuclear Information System (INIS)

Smith, Ray

1991-01-01

Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author)

The Frasnian-Famennian boundary (Upper Devonian) in black shale sequences: US Southern Midcontinent, Illinois Basin, and northern Appalachian Basin

Energy Technology Data Exchange (ETDEWEB)

Over, D.J. (State Univ. of New York, Geneseo, NY (United States). Dept. of Geological Sciences)

1994-04-01

The Frasnian-Famennian (F/F) boundary in the Woodford Shale of the US southern Midcontinent, Sweetland Creek Shale of the Illinois Basin, and the Hanover Shale of the northern Appalachian Basin is recognized to a discrete horizon. In each locality the boundary is marked by evidence of a disconformity: phosphate nodules, concentration of conodonts, or coated and corroded grains. The Woodford Shale consists of finely laminated pyritic organic-rich shale containing interbeds of greenish shale and chert. The F/F boundary horizon is marked by a concentration of conodonts and phosphatic nodules. The boundary lag horizon contains Pa. linguliformis, Pa. subperlobtata, Pa. delicatula delicatula, and Pa. triangularis. Underlying laminations contain Ancyrognathus ubiquitus and Pa. triangularis indicating that the disconformity is within the uppermost MN Zone 13 or Lower triangularis Zone. The upper portion of the Type Sweetland Creek Shale consists of dark organic-rich shales. The F/F boundary is located within an interval containing three green shale interbeds. Palmatolepis triangularis in the absence of Frasnian species first occurs in the middle green shale. In the thick Upper Devonian clastic sequence of the northern Appalachian Basin the F/F boundary is within an interval of interbedded pyritic green and organic-rich silty shales of the Hanover Shale. At Irish Gulf strata containing Pa. triangularis overlie finely laminated dark shales containing Pa. bogartensis, Pa. triangularis, Pa. winchell, Ancyrodella curvata, and Icriodus alternatus. The conodont fauna transition is below a conodont-rich laminae containing a Famennian fauna that marks the boundary horizon.

Biostratigraphy and biofacies of the Devonian deposits of the Kuh-e-Shorab section (southwest Damghan based on conodont fauna

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Mehdi Hoveida

2016-09-01

Full Text Available The studied section located in the Djam-Semnan area 55 kms south west Damghan, at the vicinity of the Amrovan rail way station, in the northern flank of Shorab unassymetric anticline. The section is 440 meters thick, including limestone, dolomitic limestone and sandstone with rich fossils contents (e.g.: trilobite, coral, brachiopod, crinoid segments and vertebrate remains. The lower boundary is covered with the recent alluvial and the upper boundary disconformably overlain by the red marls and sandstones of the Permian Dorud formation. In order to determine biostratigraphy and bifacies of the deposits of Bahram formation in Shorab section, twenty five samples (4-6 kgs were collected and processed with conventional actic/formic acid. Nineteen samples were prolific and totally yielded 340 conodont elements. The extracted conodont elements mainly separated out of the carbonate units. Thirty-one species belong to four genera (Polygnathus, Icriodus, Pelecysgnathus and Ancyrodella were discriminated as: Icriodus excavatus, I. expansus, I. cedarensis, I. subterminus, I. iowaensis, I. alternatus, I. tafilaltensis, I. brevis, I. cf. expansus, I. sp., Polygnathus brevilaminus, Poly. angustidiscus, Poly. pollocki, Poly. cf. webbi, Poly. aspelundi, Poly. politus, Poly. alatus, Poly. webbi, Poly. cf. olgae, Poly. dubius, Poly. xylus, Poly. zinaidae, Poly. sp., Pelekeygnathus inclinathus, Pele. serradentatus, Pele. sp., Ancyrodella pristina, Acny. cf. pristina, Ancy. aff. binodosa, Ancy. sp. Based on the frequency and distribution of the collected elements Late Givetian to Early Famennian age were suggested to the studied interval. Conodonts biofacies (icriodid-polygnathid confirm the deposition of the Bahram formation of the Shorab section in the shallow carbonate condition.

Increased neural responses to empathy for pain might explain how acute stress increases prosociality

OpenAIRE

Tomova, L.; Majdand?i?, J.; Hummer, A.; Windischberger, C.; Heinrichs, M.; Lamm, C.

2016-01-01

Abstract Recent behavioral investigations suggest that acute stress can increase prosocial behavior. Here, we investigated whether increased empathy represents a potential mechanism for this finding. Using functional magnetic resonance imaging, we assessed the effects of acute stress on neural responses related to automatic and regulatory components of empathy for pain as well as subsequent prosocial behavior. Stress increased activation in brain areas associated with the automatic sharing of...

Cross-sectional area of the murine aorta linearly increases with increasing core body temperature.

Science.gov (United States)

Crouch, A Colleen; Manders, Adam B; Cao, Amos A; Scheven, Ulrich M; Greve, Joan M

2017-11-06

The cardiovascular (CV) system plays a vital role in thermoregulation. To date, the response of core vasculature to increasing core temperature has not been adequately studied in vivo. Our objective was to non-invasively quantify the arterial response in murine models due to increases in body temperature, with a focus on core vessels of the torso and investigate whether responses were dependent on sex or age. Male and female, adult and aged mice were anaesthetised and underwent magnetic resonance imaging (MRI). Data were acquired from the circle of Willis (CoW), heart, infrarenal aorta and peripheral arteries at core temperatures of 35, 36, 37 and 38 °C (±0.2 °C). Vessels in the CoW did not change. Ejection fraction decreased and cardiac output (CO) increased with increasing temperature in adult female mice. Cross-sectional area of the aorta increased significantly and linearly with temperature for all groups, but at a diminished rate for aged animals (p temperature are biologically important because they may affect conductive and convective heat transfer. Leveraging non-invasive methodology to quantify sex and age dependent vascular responses due to increasing core temperature could be combined with bioheat modelling in order to improve understanding of thermoregulation.

Employee benefits or wage increase?

Directory of Open Access Journals (Sweden)

Jiří Duda

2011-01-01

Full Text Available The paper comes from a survey done during the years 2007–2009. It focused on employee satisfaction with the provision of employee benefits. The research included 21 companies, 7 companies were from the engineering sector, 7 companies from the food industry, 3 companies represented the budgetary sphere, 3 companies the services sector and one company operates in pharmaceutical industry.The questionnaire survey consisted of 14 questions, including 5 identification-questions. The paper presents results of the questions on dealing with employees’ awareness of employee benefits and on choosing between employees’ preferences of wage increase or increase in value of benefits provided.Employees are informed about all options of providing employee benefits. Only in 3 cases employees stated dissatisfaction with information. This answer was related with the responses to the second monitored question. Employees of these companies preferred pay increases before benefits’ increases. There was no effect of gender of the respondents, neither the influence of the sector of operation, in the preference of increases in wages or in benefits. Exceptions were the employees of companies operating in the financial sector, who preferred employee benefits before a wage increase. It was found that employees of companies who participated in research in 2009, preferred wage increases before the extension of employee benefits, although the value of the net wage increase is lower than the monetary value of benefits increase.The paper is a part of solution of the research plan MSM 6215648904 The Czech economy in the process of integration and globalization, and the development of agricultural sector and the sector of services under the new conditions of the integrated European market.

Increasing Access to Special Collections

Directory of Open Access Journals (Sweden)

Ricky Erway

2012-01-01

Full Text Available In an environment where we increasingly have access to a collective collection of digitized books, special collections will become increasingly invisible if they are not accessible online. In an era of increasing expectations and decreasing budgets, finding ways to streamline some of our processes is the best way to enable us to do more with less. This report details a number of investigations into how access to special collections can be increased. It includes guidance running the gamut from digitization and rights management to policies and procedures.

Increasing work-time influence

DEFF Research Database (Denmark)

Nabe-Nielsen, Kirsten; Garde, Anne Helene; Aust, Birgit

2012-01-01

This quasi-experimental study investigated how an intervention aiming at increasing eldercare workers' influence on their working hours affected the flexibility, variability, regularity and predictability of the working hours. We used baseline (n = 296) and follow-up (n = 274) questionnaire data......), or discussion of working hours (subgroup C). Only computerised self-scheduling changed the working hours and the way they were planned. These changes implied more flexible but less regular working hours and an experience of less predictability and less continuity in the care of clients and in the co...... that while increasing the individual flexibility, increasing work-time influence may also result in decreased regularity of the working hours and less continuity in the care of clients and co-operation with colleagues....

Strong increase of solar panels

International Nuclear Information System (INIS)

Segers, R.; Janssen, S.

2012-01-01

The number of installed solar panels in 2011 has increased again. 40 megawatt of new panels have been installed. This increase is twice as high as the year before. The production of solar power increased to 90 million kWh in 2011 as a result of this expansion. However, the share of solar power in total energy use is still very limited. [nl

Increased neural responses to empathy for pain might explain how acute stress increases prosociality.

Science.gov (United States)

Tomova, L; Majdandžic, J; Hummer, A; Windischberger, C; Heinrichs, M; Lamm, C

2017-03-01

Recent behavioral investigations suggest that acute stress can increase prosocial behavior. Here, we investigated whether increased empathy represents a potential mechanism for this finding. Using functional magnetic resonance imaging, we assessed the effects of acute stress on neural responses related to automatic and regulatory components of empathy for pain as well as subsequent prosocial behavior. Stress increased activation in brain areas associated with the automatic sharing of others' pain, such as the anterior insula, the anterior midcingulate cortex, and the primary somatosensory cortex. In addition, we found increased prosocial behavior under stress. Furthermore, activation in the anterior midcingulate cortex mediated the effects of stress on prosocial behavior. However, stressed participants also displayed stronger and inappropriate other-related responses in situations which required them to take the perspective of another person, and to regulate their automatic affective responses. Thus, while acute stress may increase prosocial behavior by intensifying the sharing of others' emotions, this comes at the cost of reduced cognitive appraisal abilities. Depending on the contextual constraints, stress may therefore affect empathy in ways that are either beneficial or detrimental. © The Author (2016). Published by Oxford University Press.

Multidecadal Increase in North Atlantic Coccolithophores and Potential Role of Increasing CO2

Science.gov (United States)

Rivero-Calle, S.; Gnanadesikan, A.; del Castillo, C. E.; Balch, W. M.; Guikema, S.

2016-02-01

As anthropogenic CO2 emissions acidify the oceans, calcifiers are expected to be negatively impacted. Using data from the Continuous Plankton Recorder, we show that coccolithophore occurrence in the North Atlantic has increased from 2 to over 20% from 1965 through 2010. We used Random Forest models to examine more than 20 possible environmental drivers of this change. CO2 and the Atlantic Multidecadal Oscillation were the best predictors. Since coccolithophore photosynthesis is strongly carbon-limited, we hypothesize that higher CO2 levels might be encouraging growth. A compilation of 41 independent laboratory studies supports our hypothesis. Our study shows a long-term basin-scale increase in coccolithophores and suggests that increasing pCO2 and temperature accelerated the growth rate of a key phytoplankton group for carbon cycling.

Anti-Inflammatory and Antibothropic Properties of Jatropha Elliptica, a Plant from Brazilian Cerrado Biome

Directory of Open Access Journals (Sweden)

Sára Costa Ferreira-Rodrigues

2016-12-01

Full Text Available Purpose: The aim of this study was to evaluate the antibothropic and anti-inflammatory properties of J. elliptica. Methods: Phytochemical screening and thin-layer chromatography (TLC assays were performed on J. elliptica hydroalcoholic extract (TE in order to observe its main constituents. The antibothropic activity of TE was evaluated by the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu, in a mouse phrenic nerve-diaphragm model (PND. A quantitative histological study was carried out to observe a possible protection of TE against the venom myotoxicity. The anti-inflammatory activity was also evaluated in two models, Bjssu-induced paw edema, and carrageenan-induced neutrophils migration in the peritoneal cavity. Results: TLC analysis revealed several compounds in TE, such as saponins, alkaloids, and phenolic constituents. TE was able to neutralize the blockade and the myotoxicity induced by venom, when it was pre-incubated for 30 min with venom. In addition, it showed anti-inflammatory activity, inducing less neutrophils migration and reducing paw edema. Conclusion: J. elliptica showed both antibothropic and anti-inflammatory properties.

Immune response against antigens irradiated with 60Co gamma-rays

International Nuclear Information System (INIS)

Baptista, J.A.; Spencer, P.J.; Oliveira, J.E.; Casare, M.S.; Nascimento, N.

2006-01-01

In the present work, we investigated the immunological behavior of bothropstoxin-1, a K49 phospholipase from Bothrops jararacussu, and of ovalbumin before and after irradiation with 60 Co γ-rays. Isogenic mice were immunized with either native or irradiated proteins. The circulating antibodies were isotyped and titrated by ELISA. Results indicate that irradiated proteins were immunogenic and the antibodies elicited by them were able to recognize the native proteins in ELISA. Data also indicate that the irradiated protein induced higher titers of IgG2a and IgG2b, suggesting that Th1 cells were predominantly involved in the immune response. Structural modifications of the proteins were investigated by SDSPAGE, mass spectrometry and size exclusion chromatography. According to our data, irradiation promoted structural modifications on both proteins, characterized by higher molecular weight forms (aggregates and oligomers). When analyzed by mass spectrometry, the irradiated bothropstoxin appeared in several oxidized forms. These results indicate that irradiation of toxic proteins can promote significant modifications in their structures, but still retain many of the original antigenic and immunological properties of native form. (author)

Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

DEFF Research Database (Denmark)

Sjøberg, Kim Anker; Frøsig, Christian; Kjøbsted, Rasmus

2017-01-01

and increased similarly in both legs during the clamp and L-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4...... and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand....

Increasing diversity in radiologic technology.

Science.gov (United States)

Carwile, Laura

2003-01-01

Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity.

Pulsed electric field increases reproduction.

Science.gov (United States)

Panagopoulos, Dimitris J

2016-01-01

Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated.

Increased chromosome radiosensitivity during pregnancy

International Nuclear Information System (INIS)

Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard

1997-01-01

It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions

Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

DEFF Research Database (Denmark)

Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif

2012-01-01

were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R (2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.......002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P ......We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...

Assessing and Increasing Physical Activity

Science.gov (United States)

Van Camp, Carole M.; Hayes, Lynda B.

2012-01-01

Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

Increased muscle glucose uptake during contractions

DEFF Research Database (Denmark)

Ploug, Thorkil; Galbo, Henrik; Richter, Erik

1984-01-01

We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

Snakebites as a largely neglected problem in the Brazilian Amazon: highlights of the epidemiological trends in the State of Amazonas

Directory of Open Access Journals (Sweden)

Esaú Samuel Feitosa

2015-06-01

Full Text Available Envenoming snakebites are thought to be a particularly important threat to public health worldwide, especially in rural areas of tropical and subtropical countries. The true magnitude of the public health threat posed by snakebites is unknown, making it difficult for public health officials to optimize prevention and treatment. The objective of this work was to conduct a systematic review of the literature to gather data on snakebite epidemiology in the Amazon region and describe a case series of snakebites from epidemiological surveillance in the State of Amazonas (1974-2012. Only 11 articles regarding snakebites were found. In the State of Amazonas, information regarding incidents involving snakes is scarce. Historical trends show an increasing number of cases after the second half of the 1980s. Snakebites predominated among adults (20-39 years old; 38%, in the male gender (78.9% and in those living in rural areas (85.6%. The predominant snake envenomation type was bothropic. The incidence reported by the epidemiological surveillance in the State of Amazonas, reaching up to 200 cases/100,000 inhabitants in some areas, is among the highest annual snakebite incidence rates of any region in the world. The majority of the cases were reported in the rainy season with a case-fatality rate of 0.6%. Snakebite envenomation is a great disease burden in the State of Amazonas, representing a challenge for future investigations, including approaches to estimating incidence under-notification and case-fatality rates as well as the factors related to severity and disabilities.

Crop diversity for yield increase.

Directory of Open Access Journals (Sweden)

Chengyun Li

2009-11-01

Full Text Available Traditional farming practices suggest that cultivation of a mixture of crop species in the same field through temporal and spatial management may be advantageous in boosting yields and preventing disease, but evidence from large-scale field testing is limited. Increasing crop diversity through intercropping addresses the problem of increasing land utilization and crop productivity. In collaboration with farmers and extension personnel, we tested intercropping of tobacco, maize, sugarcane, potato, wheat and broad bean--either by relay cropping or by mixing crop species based on differences in their heights, and practiced these patterns on 15,302 hectares in ten counties in Yunnan Province, China. The results of observation plots within these areas showed that some combinations increased crop yields for the same season between 33.2 and 84.7% and reached a land equivalent ratio (LER of between 1.31 and 1.84. This approach can be easily applied in developing countries, which is crucial in face of dwindling arable land and increasing food demand.

Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

Science.gov (United States)

West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

2010-11-01

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

High population increase rates.

Science.gov (United States)

1991-09-01

In addition to its economic and ethnic difficulties, the USSR faces several pressing demographic problems, including high population increase rates in several of its constituent republics. It has now become clear that although the country's rigid centralized planning succeeded in covering the basic needs of people, it did not lead to welfare growth. Since the 1970s, the Soviet economy has remained sluggish, which as led to increase in the death and birth rates. Furthermore, the ideology that held that demography could be entirely controlled by the country's political and economic system is contradicted by current Soviet reality, which shows that religion and ethnicity also play a significant role in demographic dynamics. Currently, Soviet republics fall under 2 categories--areas with high or low natural population increase rates. Republics with low rates consist of Christian populations (Armenia, Moldavia, Georgia, Byelorussia, Russia, Lithuania, Estonia, Latvia, Ukraine), while republics with high rates are Muslim (Tadzhikistan, Uzbekistan, Turkmenistan, Kirgizia, Azerbaijan Kazakhstan). The later group has natural increase rates as high as 3.3%. Although the USSR as a whole is not considered a developing country, the later group of republics fit the description of the UNFPA's priority list. Another serious demographic issue facing the USSR is its extremely high rate of abortion. This is especially true in the republics of low birth rates, where up to 60% of all pregnancies are terminated by induced abortions. Up to 1/5 of the USSR's annual health care budget is spent on clinical abortions -- money which could be better spent on the production of contraceptives. Along with the recent political and economic changes, the USSR is now eager to deal with its demographic problems.

Nuclear programs see a qualified increase

International Nuclear Information System (INIS)

Anon.

1995-01-01

This March 1995 Nuclear News article is a review of the proposed DOE budget for nuclear energy activities. This proposed budget increases spending by 32.7% and includes increases in nearly every individual program except civilian reactor development. Isotope production and distribution receive the largest increase, followed by termination costs for certain federal reactor projects. There is a 61.9% proposed increase (to $199M) for waste management activities, but with funding from other Departments, the actual budget would be $612M. The majority of this money would go toward Yucca Mountain activities. Except for the cancellation of the Advanced Neutron Source, the Science and Technology portion of the budget shows an overall small increase

increases in cross-sectional samples

African Journals Online (AJOL)

1971-03-27

Mar 27, 1971 ... TABLE Ill. PERCE 'TAGE INCREASES IN BODY M EASU REM ENTS .... population means (polynomials) for calculating total per- ... with age in males, except for very small increases in Bantu. ..... this applies at high levels of energy expenditure is another .... available for adults of all 4 populations studied.

Do increases in cigarette prices lead to increases in sales of cigarettes with high tar and nicotine yields?

Science.gov (United States)

Farrelly, Matthew C; Loomis, Brett R; Mann, Nathan H

2007-10-01

We used scanner data on cigarette prices and sales collected from supermarkets across the United States from 1994 to 2004 to test the hypothesis that cigarette prices are positively correlated with sales of cigarettes with higher tar and nicotine content. During this period the average inflation-adjusted price for menthol cigarettes increased 55.8%. Price elasticities from multivariate regression models suggest that this price increase led to an increase of 1.73% in sales-weighted average tar yields and a 1.28% increase in sales-weighted average nicotine yields for menthol cigarettes. The 50.5% price increase of nonmenthol varieties over the same period yielded an estimated increase of 1% in tar per cigarette but no statistically significant increase in nicotine yields. An ordered probit model of the impact of cigarette prices on cigarette strength (ultra-light, light, full flavor, unfiltered) offers an explanation: As cigarette prices increase, the probability that stronger cigarette types will be sold increases. This effect is larger for menthol than for nonmenthol cigarettes. Our results are consistent with earlier population-based cross-sectional and longitudinal studies showing that higher cigarette prices and taxes are associated with increasing consumption of higher-yield cigarettes by smokers.

Aspectos clínico-patológicos do envenenamento botrópico experimental em equinos

Directory of Open Access Journals (Sweden)

Melina Garcia de Sousa

2011-09-01

Full Text Available Estudou-se as alterações clínico-patológicas e laboratoriais em equinos, inoculados experimentalmente com a peçonha de Bothropoides jararaca, Bothrops jararacussu, Bothrops moojeni e Bothropoides neuwiedi, com a finalidade de fornecer subsídios para o diagnóstico do envenenamento pela picada dessas. Os venenos liofilizados foram diluídos em 1ml de solução fisiológica e administrados a seis equinos, por via subcutânea, nas doses de 0,5 e 1mg/kg (B. jararaca, 0,8 e 1,6mg/kg (B. jararacussu, 0,205mg/kg (B. moojeni e 1mg/kg (B. neuwiedi. Todos os equinos, menos os que receberam o veneno de B. jararacussu, morreram Os sinais clínicos iniciaram-se entre 8min e 2h10min após a inoculação. O período de evolução variou, nos quatro casos de êxito letal, de 24h41min a 70h41min, e nos dois equinos que se recuperaram foi de 16 dias. O quadro clínico, independente do tipo de veneno e das doses, caracterizou-se por aumento de volume no local da inoculação, arrastar da pinça do membro inoculado no solo, inquietação, apatia, diminuição da resposta aos estímulos externos, mucosas pálidas e hemorragias. Os exames laboratoriais revelaram anemia normocítica normocrômica com progressiva diminuição no número de hemácias, da hemoglobina e do hematócrito, e leucocitose por neutrofilia. Houve aumento de alamina aminotransferase, creatinaquinase, dehidrogenase láctica, ureia e glicose, bem como aumento do tempo de ativação da protrombina e do tempo de tromboplastina parcial ativada. Os achados de necropsia foram extensas hemorragias no tecido subcutâneo, com presença de sangue não coagulado e em boa parte associadas a edema (edema hemorrágico, que se estendia desde o local da inoculação até as regiões cervical, torácica, escapular e membro. Na periferia das áreas hemorrágicas havia predominantemente edema gelatinoso. Havia ainda presença de grande quantidade de líquido sanguinolento nas cavidades torácica, peric

Increase of COP for heat transformer in water purification systems. Part I - Increasing heat source temperature

International Nuclear Information System (INIS)

Siqueiros, J.; Romero, R.J.

2007-01-01

The integration of a water purification system in a heat transformer allows a fraction of heat obtained by the heat transformer to be recycled, increasing the heat source temperature. Consequently, the evaporator and generator temperatures are also increased. For any operating conditions, keeping the condenser and absorber temperatures and also the heat load to the evaporator and generator, a higher value of COP is obtained when only the evaporator and generator temperatures are increased. Simulation with proven software compares the performance of the modeling of an absorption heat transformer for water purification (AHTWP) operating with water/lithium bromide, as the working fluid-absorbent pair. Plots of enthalpy-based coefficients of performance (COP ET ) and the increase in the coefficient of performance (COP) are shown against absorber temperature for several thermodynamic operating conditions. The results showed that proposed (AHTWP) system is capable of increasing the original value of COP ET more than 120%, by recycling part of the energy from a water purification system. The proposed system allows to increase COP values from any experimental data for water purification or any other distillation system integrated to a heat transformer, regardless of the actual COP value and any working fluid-absorbent pair

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

Science.gov (United States)

Simopoulos, Artemis P.

2016-01-01

In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

Directory of Open Access Journals (Sweden)

Artemis P. Simopoulos

2016-03-01

Full Text Available In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity.

Medicaid prospective payment: Case-mix increase

Science.gov (United States)

Baker, Samuel L.; Kronenfeld, Jennie J.

1990-01-01

South Carolina Medicaid implemented prospective payment by diagnosis-related group (DRG) for inpatient care. The rate of complications among newborns and deliveries doubled immediately. The case-mix index for newborns increased 66.6 percent, which increased the total Medicaid hospital expenditure 5.5 percent. Outlier payments increased total expenditure further. DRG distribution change among newborns has a large impact on spending because newborn complication DRGs have high weights. States adopting a DRG-based payment system for Medicaid should anticipate a greater increase in case mix than Medicare experienced. PMID:10113463

Food allergy: is prevalence increasing?

Science.gov (United States)

Tang, Mimi L K; Mullins, Raymond J

2017-03-01

It is generally accepted that the prevalence of food allergy has been increasing in recent decades, particularly in westernised countries, yet high-quality evidence that is based on challenge confirmed diagnosis of food allergy to support this assumption is lacking because of the high cost and potential risks associated with conducting food challenges in large populations. Accepting this caveat, the use of surrogate markers for diagnosis of food allergy (such as nationwide data on hospital admissions for food anaphylaxis or clinical history in combination with allergen-specific IgE (sIgE) measurement in population-based cohorts) has provided consistent evidence for increasing prevalence of food allergy at least in western countries, such as the UK, United States and Australia. Recent reports that children of East Asian or African ethnicity who are raised in a western environment (Australia and United States respectively) have an increased risk of developing food allergy compared with resident Caucasian children suggest that food allergy might also increase across Asian and African countries as their economies grow and populations adopt a more westernised lifestyle. Given that many cases of food allergy persist, mathematical principles would predict a continued increase in food allergy prevalence in the short to medium term until such time as an effective treatment is identified to allow the rate of disease resolution to be equal to or greater than the rate of new cases. © 2017 Royal Australasian College of Physicians.

Shopper marketing nutrition interventions: Social norms on grocery carts increase produce spending without increasing shopper budgets

Directory of Open Access Journals (Sweden)

Collin R. Payne

2015-01-01

Conclusions: Descriptive and provincial social norm messages (i.e., on grocery cart placards may be an overlooked tool to increase produce demand without decreasing store profitability and increasing shopper budgets.

DETECTING FORESTS DAMAGED BY PINE WILT DISEASE AT THE INDIVIDUAL TREE LEVEL USING AIRBORNE LASER DATA AND WORLDVIEW-2/3 IMAGES OVER TWO SEASONS

Directory of Open Access Journals (Sweden)

Y. Takenaka

2017-10-01

Full Text Available Pine wilt disease is caused by the pine wood nematode (Bursaphelenchus xylophilus and Japanese pine sawyer (Monochamus alternatus. This study attempted to detect damaged pine trees at different levels using a combination of airborne laser scanning (ALS data and high-resolution space-borne images. A canopy height model with a resolution of 50 cm derived from the ALS data was used for the delineation of tree crowns using the Individual Tree Detection method. Two pan-sharpened images were established using the ortho-rectified images. Next, we analyzed two kinds of intensity-hue-saturation (IHS images and 18 remote sensing indices (RSI derived from the pan-sharpened images. The mean and standard deviation of the 2 IHS images, 18 RSI, and 8 bands of the WV-2 and WV-3 images were extracted for each tree crown and were used to classify tree crowns using a support vector machine classifier. Individual tree crowns were assigned to one of nine classes: bare ground, Larix kaempferi, Cryptomeria japonica, Chamaecyparis obtusa, broadleaved trees, healthy pines, and damaged pines at slight, moderate, and heavy levels. The accuracy of the classifications using the WV-2 images ranged from 76.5 to 99.6 %, with an overall accuracy of 98.5 %. However, the accuracy of the classifications using the WV-3 images ranged from 40.4 to 95.4 %, with an overall accuracy of 72 %, which suggests poorer accuracy compared to those classes derived from the WV-2 images. This is because the WV-3 images were acquired in October 2016 from an area with low sun, at a low altitude.

The increased importance of sector switching

DEFF Research Database (Denmark)

Frederiksen, Anders; Hansen, Jesper Rosenberg

2017-01-01

Sector switching is an important phenomenon that casts light on public–private differences. Yet our knowledge about its prevalence and trends is limited. We study sector switching using unique Danish register-based employer–employee data covering more than 25 years. We find that sector switching...... constitutes 18.5% of all job-to-job mobility, and the trend is increasing both from public to private and from private to public. Sector switching is also generally increasing for middle managers, but for administrative professionals only the flows from private to public increase and for top managers only...... the flows from public to private increase....

Exercising self-control increases approach motivation.

Science.gov (United States)

Schmeichel, Brandon J; Harmon-Jones, Cindy; Harmon-Jones, Eddie

2010-07-01

The present research tested the hypothesis that exercising self-control causes an increase in approach motivation. Study 1 found that exercising (vs. not exercising) self-control increases self-reported approach motivation. Study 2a identified a behavior--betting on low-stakes gambles--that is correlated with approach motivation but is relatively uncorrelated with self-control, and Study 2b observed that exercising self-control temporarily increases this behavior. Last, Study 3 found that exercising self-control facilitates the perception of a reward-relevant symbol (i.e., a dollar sign) but not a reward-irrelevant symbol (i.e., a percent sign). Altogether, these results support the hypothesis that exercising self-control temporarily increases approach motivation. Failures of self-control that follow from prior efforts at self-control (i.e., ego depletion) may be explained in part by increased approach motivation.

Are increases in cigarette taxation regressive?

Science.gov (United States)

Borren, P; Sutton, M

1992-12-01

Using the latest published data from Tobacco Advisory Council surveys, this paper re-evaluates the question of whether or not increases in cigarette taxation are regressive in the United Kingdom. The extended data set shows no evidence of increasing price-elasticity by social class as found in a major previous study. To the contrary, there appears to be no clear pattern in the price responsiveness of smoking behaviour across different social classes. Increases in cigarette taxation, while reducing smoking levels in all groups, fall most heavily on men and women in the lowest social class. Men and women in social class five can expect to pay eight and eleven times more of a tax increase respectively, than their social class one counterparts. Taken as a proportion of relative incomes, the regressive nature of increases in cigarette taxation is even more pronounced.

Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: a randomized controlled trial.

Science.gov (United States)

Koopman, Karin E; Caan, Matthan W A; Nederveen, Aart J; Pels, Anouk; Ackermans, Mariette T; Fliers, Eric; la Fleur, Susanne E; Serlie, Mireille J

2014-08-01

American children consume up to 27% of calories from high-fat and high-sugar snacks. Both sugar and fat consumption have been implicated as a cause of hepatic steatosis and obesity but the effect of meal pattern is largely understudied. We hypothesized that a high meal frequency, compared to consuming large meals, is detrimental in the accumulation of intrahepatic and abdominal fat. To test this hypothesis, we randomized 36 lean, healthy men to a 40% hypercaloric diet for 6 weeks or a eucaloric control diet and measured intrahepatic triglyceride content (IHTG) using proton magnetic resonance spectroscopy ((1) H-MRS), abdominal fat using magnetic resonance imaging (MRI), and insulin sensitivity using a hyperinsulinemic euglycemic clamp with a glucose isotope tracer before and after the diet intervention. The caloric surplus consisted of fat and sugar (high-fat-high-sugar; HFHS) or sugar only (high-sugar; HS) and was consumed together with, or between, the three main meals, thereby increasing meal size or meal frequency. All hypercaloric diets similarly increased body mass index (BMI). Increasing meal frequency significantly increased IHTG (HFHS mean relative increase of 45%; P = 0.016 and HS mean relative increase of 110%; P = 0.047), whereas increasing meal size did not (2-way analysis of variance [ANOVA] size versus frequency P = 0.03). Abdominal fat increased in the HFHS-frequency group (+63.3 ± 42.8 mL; P = 0.004) and tended to increase in the HS-frequency group (+46.5 ± 50.7 mL; P = 0.08). Hepatic insulin sensitivity tended to decrease in the HFHS-frequency group while peripheral insulin sensitivity was not affected. A hypercaloric diet with high meal frequency increased IHTG and abdominal fat independent of caloric content and body weight gain, whereas increasing meal size did not. This study suggests that snacking, a common feature in the Western diet, independently contributes to hepatic steatosis and obesity. ( www

Atrial natriuretic factor increases vascular permeability

International Nuclear Information System (INIS)

Lockette, W.; Brennaman, B.

1990-01-01

An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness

A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake).

Science.gov (United States)

Lopes, Denise M; Junior, Norberto E G; Costa, Paula P C; Martins, Patrícia L; Santos, Cláudia F; Carvalho, Ellaine D F; Carvalho, Maria D F; Pimenta, Daniel C; Cardi, Bruno A; Fonteles, Manassés C; Nascimento, Nilberto R F; Carvalho, Krishnamurti M

2014-11-01

Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops jararaca and captopril. BPP-Cdc (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated. Copyright © 2014 Elsevier Ltd. All rights reserved.

Isoflurane increases cardiorespiratory coordination in rats

Science.gov (United States)

Kabir, Muammar M.; Beig, Mirza I.; Nalivaiko, Eugene; Abbott, Derek; Baumert, Mathias

2008-12-01

Anesthetics such as isoflurane adversely affect heart rate. In this study we analysed the interaction between heart rhythm and respiration at different concentrations of isoflurane and ventilation rates. In two rats, the electrocardiogram (ECG) and respiratory signals were recorded under the influence of isoflurane. For the assessment of cardiorespiratory coordination, we analysed the phase locking between heart rate, computed from the R-R intervals of body surface ECG, and respiratory rate, computed from impedance changes, using Hilbert transform. The changes in heart rate, percentage of synchronization and duration of synchronized epochs at different isoflurane concentrations and ventilation rates were assessed using linear regression model. From this study it appears that the amount of phase locking between cardiac and respiratory rates increases with the increase in concentration of isoflurane. Heart rate and duration of synchronized epochs increased significantly with the increase in the level of isoflurane concentration while respiratory rate was not significantly affected. Cardiorespiratory coordination also showed a considerable increase at the ventilation rates of 50- 55 cpm in both the rats, suggesting that the phase-locking between the cardiac and respiratory oscillators can be increased by breathing at a particular respiratory frequency.

Wind increases leaf water use efficiency.

Science.gov (United States)

Schymanski, Stanislaus J; Or, Dani

2016-07-01

A widespread perception is that, with increasing wind speed, transpiration from plant leaves increases. However, evidence suggests that increasing wind speed enhances carbon dioxide (CO2 ) uptake while reducing transpiration because of more efficient convective cooling (under high solar radiation loads). We provide theoretical and experimental evidence that leaf water use efficiency (WUE, carbon uptake per water transpired) commonly increases with increasing wind speed, thus improving plants' ability to conserve water during photosynthesis. Our leaf-scale analysis suggests that the observed global decrease in near-surface wind speeds could have reduced WUE at a magnitude similar to the increase in WUE attributed to global rise in atmospheric CO2 concentrations. However, there is indication that the effect of long-term trends in wind speed on leaf gas exchange may be compensated for by the concurrent reduction in mean leaf sizes. These unintuitive feedbacks between wind, leaf size and water use efficiency call for re-evaluation of the role of wind in plant water relations and potential re-interpretation of temporal and geographic trends in leaf sizes. © 2015 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.

Platelet-Rich Plasma Increases Pigmentation.

Science.gov (United States)

Uysal, Cagri A; Ertas, Nilgun Markal

2017-11-01

Platelet-rich plasma (PRP) is an autologous solution of plasma containing 4 to 7 times the baseline concentration of human platelets. Platelet-rich plasma has been widely popular in facial rejuvenation to attenuate wrinkles and has been practically used. The authors have been encountering various patients of increased hiperpigmentation following PRP applications that were performed to attenuate the postinflammatory hiperpigmentation especially after laser treatment. The authors have been using PRP for facial rejuvenation in selected patients and in 1 patient the authors have encountered increased pigmentation over the pigmented skin lesions that were present before the application. The authors recommend that the PRP might increase pigmentation especially in the face region and precautions might be taken before and after the application. Platelet-rich plasma should not be used for the treatment of post inflammatory hiperpigmentation.

Responding to bioterror concerns by increasing milk pasteurization temperature would increase estimated annual deaths from listeriosis.

Science.gov (United States)

Stasiewicz, Matthew J; Martin, Nicole; Laue, Shelley; Gröhn, Yrjo T; Boor, Kathryn J; Wiedmann, Martin

2014-05-01

In a 2005 analysis of a potential bioterror attack on the food supply involving a botulinum toxin release into the milk supply, the authors recommended adopting a toxin inactivation step during milk processing. In response, some dairy processors increased the times and temperatures of pasteurization well above the legal minimum for high temperature, short time pasteurization (72 °C for 15 s), with unknown implications for public health. The present study was conducted to determine whether an increase in high temperature, short time pasteurization temperature would affect the growth of Listeria monocytogenes, a potentially lethal foodborne pathogen normally eliminated with proper pasteurization but of concern when milk is contaminated postpasteurization. L. monocytogenes growth during refrigerated storage was higher in milk pasteurized at 82 °C than in milk pasteurized at 72 °C. Specifically, the time lag before exponential growth was decreased and the maximum population density was increased. The public health impact of this change in pasteurization was evaluated using a quantitative microbial risk assessment of deaths from listeriosis attributable to consumption of pasteurized fluid milk that was contaminated postprocessing. Conservative estimates of the effect of pasteurizing all fluid milk at 82 °C rather than 72 °C are that annual listeriosis deaths from consumption of this milk would increase from 18 to 670, a 38-fold increase (8.7- to 96-fold increase, 5th and 95th percentiles). These results exemplify a situation in which response to a rare bioterror threat may have the unintended consequence of putting the public at increased risk of a known, yet severe harm and illustrate the need for a paradigm shift toward multioutcome risk benefit analyses when proposing changes to established food safety practices.

Human preference and acceptance of increased air velocity to offset warm sensation at increased room temperatures

DEFF Research Database (Denmark)

Cattarin, Giulio; Simone, Angela; Olesen, Bjarne W.

. The present climatic chamber study examined energy performance and achievable thermal comfort of traditional and bladeless desk fans. Different effects of mechanical and simulated-natural airflow patterns were also investigated. 32 Scandinavians, performing office activities and wearing light clothes , were......Previous studies have demonstrated that in summertime increased air velocities can compensate for higher room temperatures to achieve comfortable conditions. In order to increase air movement, windows opening, ceiling or desk fans can be used at the expense of relatively low energy consumption...... exposed to a increased air movement generated by a personal desk fan. The subjects could continuously regulate the fans under three fixed environmental conditions (operative temperatures equal to 26 °C, 28 °C, or 30 °C, and same absolute humidity 12.2 g/m3). The experimental study showed that increased...

Increased Materialistic Trends among Youth

Directory of Open Access Journals (Sweden)

Afsheen Masood

2016-12-01

Full Text Available The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among youth nowadays. Because thought patterns of youth and societal demands have changed totally. Factors that are increasing materialism include social media, brand consciousness; self-centeredness; fake personality development and desire to be socially accepted. The implications indicate that materialistic trend should stop by controlling the social media possession among youth which is the primary source of enhancing materialism among youth.

Use of flax seed mucilage or its active component for increasing suppression of hunger, increasing reduction of prospective consumption, increasing reduction of appetite in a subject during or between meals or feedings

DEFF Research Database (Denmark)

2017-01-01

The present invention relates to methods for increasing the suppression of hunger and/or increasing the reduction of prospective consumption and/or increasing the reduction of appetite and/or increasing the feeling of satiety and/or reducing non-fat energy uptake in the gastrointestinal tract...... intervention comprises mucilage such as flax seed mucilage and/or one or more active compounds of mucilage useful for increasing the suppression of hunger and/or increasing the reduction of prospective consumption and/or increasing the reduction of appetite and/or increasing the feeling of satiety and...

Increasing sales by reducing procrastination

OpenAIRE

Gjedrem, William Gilje

2012-01-01

Master's thesis in Finance In this paper I analyze whether an intervention program increases productivity and sales, by reducing potential procrastination problems that employees face at work. The intervention was introduced to stores in a large retail chain in Norway, and contained different tools that could lead to lower perceived costs of higher effort. In a difference-in-differences analysis I find that the intervention increases sales after a 14 weeks long implementation period. Fu...

Increased Materialistic Trends Among Youth

OpenAIRE

Shama Mazahir, Afsheen Masood, Rubab Musarrat

2016-01-01

The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among...

Increased Materialistic Trends among Youth

OpenAIRE

Afsheen Masood; Rubab Musarrat; Shama Mazahir

2016-01-01

The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among...

Increasing incidence of pyogenic spondylodiscitis

DEFF Research Database (Denmark)

Kehrer, Michala; Pedersen, Court; Jensen, Thøger G

2014-01-01

Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008.......Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008....

Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact

Science.gov (United States)

Taylor, Jared F.; Khattab, Omar S.; Chen, Yu-Han; Chen, Yumay; Jacobsen, Steven E.; Wang, Ping H.

2015-01-01

Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp) and end (115 bp) of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer. PMID:26308346

Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact.

Directory of Open Access Journals (Sweden)

Puya G Yazdi

Full Text Available Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp and end (115 bp of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer.

Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

International Nuclear Information System (INIS)

Godar, D. E.

2011-01-01

The incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290-320 nm) exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321-400 nm) passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to∼ 50 degree N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

Directory of Open Access Journals (Sweden)

Dianne E. Godar

2011-01-01

Full Text Available The incidence of cutaneous malignant melanoma (CMM has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

Increased sternocleidomastoid, but not trapezius, muscle activity in response to increased chewing load.

Science.gov (United States)

Häggman-Henrikson, Birgitta; Nordh, Erik; Eriksson, Per-Olof

2013-10-01

Previous findings, during chewing, that boluses of larger size and harder texture result in larger amplitudes of both mandibular and head-neck movements suggest a relationship between increased chewing load and incremental recruitment of jaw and neck muscles. The present report evaluated jaw (masseter and digastric) and neck [sternocleidomastoid (SCM) and trapezius] muscle activity during the chewing of test foods of different sizes and textures by 10 healthy subjects. Muscle activity was recorded by surface electromyography and simultaneous mandibular and head movements were recorded using an optoelectronic technique. Each subject performed continuous jaw-opening/jaw-closing movements whilst chewing small and large boluses of chewing gum and rubber silicone (Optosil). For jaw opening/jaw closing without a bolus, SCM activity was recorded for jaw opening concomitantly with digastric activity. During chewing, SCM activity was recorded for jaw closing concomitantly with masseter activity. Trapezius activity was present in some, but not all, cycles. For the masseter and SCM muscles, higher activity was seen with larger test foods, suggesting increased demand and recruitment of these muscles in response to an increased chewing load. This result reinforces the previous notion of a close functional connection between the jaw and the neck motor systems in jaw actions and has scientific and clinical significance for studying jaw function and dysfunction. © 2013 Eur J Oral Sci.

Increasing portion sizes of fruits and vegetables in an elementary school lunch program can increase fruit and vegetable consumption.

Science.gov (United States)

Miller, Nicole; Reicks, Marla; Redden, Joseph P; Mann, Traci; Mykerezi, Elton; Vickers, Zata

2015-08-01

Increasing portion size can increase children's consumption of food. The goal of this study was to determine whether increasing the portion sizes of fruits and vegetables in an elementary school cafeteria environment would increase children's consumption of them. We measured each child's consumption of the fruit and vegetables served in a cafeteria line on a control day (normal cafeteria procedures) and on two intervention days. When we increased the portion size of 3 of the 4 fruits and vegetables by about 50%, children who took those foods increased their consumption of them. Although this was an effective strategy for increasing fruit and vegetable consumption among students who took those foods, many children chose not to take any fruits or vegetables. Further efforts are needed to increase children's selection and consumption of fruits and vegetables in an environment of competing foods of higher palatability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased Body Weight Reduces Voluntary Movement to Maintain Energy Expenditure of Rats Exposed to Increases in Gravity

Science.gov (United States)

Wade, C. E.; Moran, M. M.; Stein, T. P.; Sin, Sidney (Technical Monitor)

2001-01-01

With the increase in obesity related diseases there is heightened interest in mechanisms regulating body weight. To assess the influence of increases in body weight on energy expenditure and intake in rats we employed variable levels of gravity. Our approach afforded the means to measure interactions of energy expenditure and intake in response to increases in body weight (body mass x gravity level). We found a dose relationship between rapid elevation of body weight and reduction of voluntary movement, such that the energy requirements for activity are unchanged, and total energy expenditure and intake maintained. Reduction of movement appears to be a response to increased body weight, rather than a contributing factor, suggesting a new regulatory pathway.

11 CFR 110.17 - Price index increase.

Science.gov (United States)

2010-01-01

... 11 Federal Elections 1 2010-01-01 2010-01-01 false Price index increase. 110.17 Section 110.17... PROHIBITIONS § 110.17 Price index increase. (a) Price index increases for party committee expenditure... 11 CFR 109.32 and 110.8 shall be increased by the percent difference between the price index, as...

Increasing inhibitory input increases neuronal firing rate: why and when? Diffusion process cases

Energy Technology Data Exchange (ETDEWEB)

Feng Jianfeng [COGS, Sussex University (United Kingdom)]. E-mail: jf218@cam.ac.uk; Wei Gang [Department of Mathematics, Hong Kong Baptist University, Hong Kong (China)]. E-mail gwei@math.hkbu.edu.hk

2001-09-21

Increasing inhibitory input to single neuronal models, such as the FitzHugh-Nagumo model and the Hodgkin-Huxley model, can sometimes increase their firing rates, a phenomenon which we term inhibition-boosted firing (IBF). Here we consider neuronal models with diffusion approximation inputs, i.e. they share the identical first- and second-order statistics of the corresponding Poisson process inputs. Using the integrate-and-fire model and the IF-FHN model, we explore theoretically how and when IBF can happen. For both models, it is shown that there is a critical input frequency at which the efferent firing rate is identical when the neuron receives purely excitatory inputs or exactly balanced inhibitory and excitatory inputs. When the input frequency is lower than the critical frequency, IBF occurs. (author)

Angiotensin-converting enzyme inhibitors of Bothrops jararaca snake venom affect the structure of mice seminiferous epithelium.

Science.gov (United States)

Alberto-Silva, Carlos; Gilio, Joyce M; Portaro, Fernanda C V; Querobino, Samyr M; Camargo, Antonio C M

2015-01-01

Considering the similarity between the testis-specific isoform of angiotensin-converting enzyme and the C-terminal catalytic domain of somatic ACE as well as the structural and functional variability of its natural inhibitors, known as bradykinin-potentiating peptides (BPPs), the effects of different synthetic peptides, BPP-10c (

Vulnerability Assessment of Housing Damage in the Philippines Due to an Increase Increase in Typhoon Intensity

Science.gov (United States)

Esteban, Miguel; Stromberg, Per; Gasparatos, Alexandros

2010-05-01

It is currently feared that the increase in surface sea temperature resulting from increasing level of greenhouse gases in the atmosphere could result in higher tropical cyclone intensity in the future. Although the vulnerability of infrastructure and economic systems have been studied for a number of developed countries, very little work has been done on developing countries. The present work first attempts to evaluate the vulnerability of different regions in the Philippines to the passage of tropical cyclones. To this effect a total of 22 typhoons and tropical storms that affected the Philippines were analysed for the period 2003-2008. The data used was collected by the National Disaster Coordinating Council of the Philippines, who issue "SitRep" NDCC Reports after each major storm. This agency provides damage data for each region, including number of casualties, affected people, damaged and destroyed houses, and losses in the infrastructure and agriculture. The likely economic effects of increased typhoon intensity by using a Monte Carlo Simulation that magnifies the intensity of historical tropical cyclones between the years 1978 and 2008 to simulate the economic damage by 2085. The methodology used is based on the work of Esteban et al. (2009), which in turn uses the results of Knutson and Tuleya (2004) for the estimation of the increase in tropical cyclone intensity in 2085. The results show that downtime could increase from a national 1% to 1.3% by 2050 if economic and population growth are taken into account (29 to 36bn USD, from a total GDP of 2,757bn USD by 2050). If these are ignored the time lost each year can be estimated to cost around 630m USD (PPP) for the control scenario, which could increase to between 766m or 945mm USD by the year 2085 for the two different scenarios considered. This indirect damage depends on the geographical location and is for example higher in some areas of the northern island of Luzon, while the island of Mindanao in the

3 Ways to Increase Positive Emotions

Science.gov (United States)

... Search English Español 3 Ways to Increase Positive Emotions KidsHealth / For Teens / 3 Ways to Increase Positive ... to give yourself a boost. Track Your Positive Emotions Name the positive emotions you're already familiar ...

Increasing millet production in South Asia

International Development Research Centre (IDRC) Digital Library (Canada)

Asia, which has put the emphasis on cash crops and cereals ... aims to increase production and consumption of minor ... practices. They will then develop sustainable agriculture tool kits to help farmers to increase millet production in these.

Employee responses to health insurance premium increases.

Science.gov (United States)

Goldman, Dana P; Leibowitz, Arleen A; Robalino, David A

2004-01-01

To determine the sensitivity of employees' health insurance decisions--including the decision to not choose health maintenance organization or fee-for-service coverage--during periods of rapidly escalating healthcare costs. A retrospective cohort study of employee plan choices at a single large firm with a "cafeteria-style" benefits plan wherein employees paid all the additional cost of purchasing more generous insurance. We modeled the probability that an employee would drop coverage or switch plans in response to employee premium increases using data from a single large US company with employees across 47 states during the 3-year period of 1989 through 1991, a time of large premium increases within and across plans. Premium increases induced substantial plan switching. Single employees were more likely to respond to premium increases by dropping coverage, whereas families tended to switch to another plan. Premium increases of 10% induced 7% of single employees to drop or severely cut back on coverage; 13% to switch to another plan; and 80% to remain in their existing plan. Similar figures for those with family coverage were 11%, 12%, and 77%, respectively. Simulation results that control for known covariates show similar increases. When faced with a dramatic increase in premiums--on the order of 20%--nearly one fifth of the single employees dropped coverage compared with 10% of those with family coverage. Employee coverage decisions are sensitive to rapidly increasing premiums, and single employees may be likely to drop coverage. This finding suggests that sustained premium increases could induce substantial increases in the number of uninsured individuals.

Warming-related increases in soil CO2 efflux are explained by increased below-ground carbon flux

Science.gov (United States)

Christian P. Giardina; Creighton M. Litton; Susan E. Crow; Gregory P Asner

2014-01-01

The universally observed exponential increase in soil-surface CO2 effux (‘soil respiration’; FS) with increasing temperature has led to speculation that global warming will accelerate soil organic carbon (SOC) decomposition, reduce SOC storage, and drive a positive feedback to future warming. However, interpreting temperature–FS relationships,...

A Work Schedule to Increase Productivity.

Science.gov (United States)

Atwood, Caleb S.

1979-01-01

Outlines a technique for making a tight economy and energy shortages more palatable by supplementing employee wage increases with benefits such as alternative three and four day "weekends" without loss of regular pay and by enabling business to increase profits. (Author/IRT)

Reading Instruction That Increases Thinking Abilities.

Science.gov (United States)

Collins, Cathy

1991-01-01

Analyzes the effects of eight reading and writing lessons designed to increase adolescent thinking ability. Finds that the lessons increased thinking abilities and scholastic achievement of middle school students. Notes that the lessons positively affect students' self-esteem and communication skills. (RS)

Antibiotic resistance increases with local temperature

Science.gov (United States)

MacFadden, Derek R.; McGough, Sarah F.; Fisman, David; Santillana, Mauricio; Brownstein, John S.

2018-06-01

Bacteria that cause infections in humans can develop or acquire resistance to antibiotics commonly used against them1,2. Antimicrobial resistance (in bacteria and other microbes) causes significant morbidity worldwide, and some estimates indicate the attributable mortality could reach up to 10 million by 20502-4. Antibiotic resistance in bacteria is believed to develop largely under the selective pressure of antibiotic use; however, other factors may contribute to population level increases in antibiotic resistance1,2. We explored the role of climate (temperature) and additional factors on the distribution of antibiotic resistance across the United States, and here we show that increasing local temperature as well as population density are associated with increasing antibiotic resistance (percent resistant) in common pathogens. We found that an increase in temperature of 10 °C across regions was associated with an increases in antibiotic resistance of 4.2%, 2.2%, and 2.7% for the common pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The associations between temperature and antibiotic resistance in this ecological study are consistent across most classes of antibiotics and pathogens and may be strengthening over time. These findings suggest that current forecasts of the burden of antibiotic resistance could be significant underestimates in the face of a growing population and climate change4.

Smoking prevalence increases following Canterbury earthquakes.

Science.gov (United States)

Erskine, Nick; Daley, Vivien; Stevenson, Sue; Rhodes, Bronwen; Beckert, Lutz

2013-01-01

A magnitude 7.1 earthquake hit Canterbury in September 2010. This earthquake and associated aftershocks took the lives of 185 people and drastically changed residents' living, working, and social conditions. To explore the impact of the earthquakes on smoking status and levels of tobacco consumption in the residents of Christchurch. Semistructured interviews were carried out in two city malls and the central bus exchange 15 months after the first earthquake. A total of 1001 people were interviewed. In August 2010, prior to any earthquake, 409 (41%) participants had never smoked, 273 (27%) were currently smoking, and 316 (32%) were ex-smokers. Since the September 2010 earthquake, 76 (24%) of the 316 ex-smokers had smoked at least one cigarette and 29 (38.2%) had smoked more than 100 cigarettes. Of the 273 participants who were current smokers in August 2010, 93 (34.1%) had increased consumption following the earthquake, 94 (34.4%) had not changed, and 86 (31.5%) had decreased their consumption. 53 (57%) of the 93 people whose consumption increased reported that the earthquake and subsequent lifestyle changes as a reason to increase smoking. 24% of ex-smokers resumed smoking following the earthquake, resulting in increased smoking prevalence. Tobacco consumption levels increased in around one-third of current smokers.

BPP-5a produces a potent and long-lasting NO-dependent antihypertensive effect.

Science.gov (United States)

Ianzer, Danielle; Xavier, Carlos Henrique; Fraga, Fabiana Costa; Lautner, Roberto Queiroga; Guerreiro, Juliano Rodrigo; Machado, Leonor Tapias; Mendes, Elizabeth Pereira; de Camargo, Andônio Carlos Martins; Santos, Robson Augusto Souza

2011-12-01

The bradykinin potentiating peptides (BPPs) are oligopeptides found in different animal venoms. BPPs isolated from Bothrops jararaca venom were the first natural inhibitors described for somatic angiotensin I-converting enzyme (ACE). They were used in the structural modeling for captopril development, a classical ACE inhibitor widely used to treat human hypertension. We evaluated the effect of BPP-5a on cardiovascular parameters of conscious Wistar (WTs) and spontaneously hypertensive rats (SHRs). In SHR, BPP-5a showed potent cardiovascular effects, at doses ranging from 0.47 to 710 nmol/kg. The maximal changes in mean arterial pressure (MAP) and heart rate (HR) were found at the dose of 2.37 nmol/kg (Δ MAP: -38 ± 4 mmHg, p BPP-5a upon argininosuccinate synthetase and B(1), B(2), AT(1), AT(2) or Mas receptors. Ex vivo assays showed that BPP-5a induced endothelium-dependent vasorelaxation in isolated aortic rings of SHRs and WTs. Although the BPP-5a is considered an ACE inhibitor, our results indicate that its antihypertensive effect is exerted via a unique target, a nitric-oxide-dependent mechanism.

Phospholipase a properties of several snake venom preparations.

Science.gov (United States)

Nutter, L J; Privett, O S

1966-07-01

The hydrolytic properties of the venoms of seven species of snakes,Crotalus adamanteus, Ancistrodon contortrix, Naja naja, Bothrops atrox, Ophiophagus hannah, Crotalus atrox andVipera russeli, were studied with purified lecithins and mixtures of lecithins of known fatty acid and class composition as substrates.The relative rates of hydrolysis of the fatty acids by the above venoms were studied by analysis of the products of the reaction at intervals during the course of the reaction. Of the seven venoms studied, that ofOphiophagus hannah was the only one which did not give some degree of preferential rate of hydrolysis of individual fatty acids.In general, saturated fatty acids were liberated faster than unsaturated fatty acids; differences in the rates of the hydrolysis of individual saturate and unsaturated fatty acids were also observed. Individual classes of lecithin were also hydrolyzed at different rates. For the determination of the distribution of the fatty acids between the alpha- and beta-position of lecithin, the reaction should be carried to completion. If the reaction requires a prolonged time to go to completion, it should be carried out under nitrogen to prevent autoxidation.

The use of ecological niche modeling to infer potential risk areas of snakebite in the Mexican state of Veracruz.

Directory of Open Access Journals (Sweden)

Carlos Yañez-Arenas

Full Text Available Many authors have claimed that snakebite risk is associated with human population density, human activities, and snake behavior. Here we analyzed whether environmental suitability of vipers can be used as an indicator of snakebite risk. We tested several hypotheses to explain snakebite incidence, through the construction of models incorporating both environmental suitability and socioeconomic variables in Veracruz, Mexico.Ecological niche modeling (ENM was used to estimate potential geographic and ecological distributions of nine viper species' in Veracruz. We calculated the distance to the species' niche centroid (DNC; this distance may be associated with a prediction of abundance. We found significant inverse relationships between snakebites and DNCs of common vipers (Crotalus simus and Bothrops asper, explaining respectively 15% and almost 35% of variation in snakebite incidence. Additionally, DNCs for these two vipers, in combination with marginalization of human populations, accounted for 76% of variation in incidence.Our results suggest that niche modeling and niche-centroid distance approaches can be used to mapping distributions of environmental suitability for venomous snakes; combining this ecological information with socioeconomic factors may help with inferring potential risk areas for snakebites, since hospital data are often biased (especially when incidences are low.

The use of ecological niche modeling to infer potential risk areas of snakebite in the Mexican state of Veracruz.

Science.gov (United States)

Yañez-Arenas, Carlos; Peterson, A Townsend; Mokondoko, Pierre; Rojas-Soto, Octavio; Martínez-Meyer, Enrique

2014-01-01

Many authors have claimed that snakebite risk is associated with human population density, human activities, and snake behavior. Here we analyzed whether environmental suitability of vipers can be used as an indicator of snakebite risk. We tested several hypotheses to explain snakebite incidence, through the construction of models incorporating both environmental suitability and socioeconomic variables in Veracruz, Mexico. Ecological niche modeling (ENM) was used to estimate potential geographic and ecological distributions of nine viper species' in Veracruz. We calculated the distance to the species' niche centroid (DNC); this distance may be associated with a prediction of abundance. We found significant inverse relationships between snakebites and DNCs of common vipers (Crotalus simus and Bothrops asper), explaining respectively 15% and almost 35% of variation in snakebite incidence. Additionally, DNCs for these two vipers, in combination with marginalization of human populations, accounted for 76% of variation in incidence. Our results suggest that niche modeling and niche-centroid distance approaches can be used to mapping distributions of environmental suitability for venomous snakes; combining this ecological information with socioeconomic factors may help with inferring potential risk areas for snakebites, since hospital data are often biased (especially when incidences are low).

Increased urinary orosomucoid excretion

DEFF Research Database (Denmark)

Christiansen, M S; Iversen, K; Larsen, C T

2009-01-01

, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy...

Increased greenhouse effect substantiated through measurements

International Nuclear Information System (INIS)

Skartveit, Arvid

2001-01-01

The article presents studies on the greenhouse effect which substantiates the results from satellite measurements during the period 1970 - 1997. These show an increased effect due to increase in the concentration of the climatic gases CO 2 , methane, CFC-11 and CFC-12 in the atmosphere

Integrated engineering increases flexibility. [At BNFL

Energy Technology Data Exchange (ETDEWEB)

Smith, Ray [British Nuclear Fuels plc, London (UK)

1991-05-01

Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author).

PEG-albumin plasma expansion increases expression of MCP-1 evidencing increased circulatory wall shear stress: an experimental study.

Directory of Open Access Journals (Sweden)

C Makena Hightower

Full Text Available Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS, decreasing endothelial nitric oxide (NO production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer's lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1, a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity.

Shopper marketing nutrition interventions: Social norms on grocery carts increase produce spending without increasing shopper budgets☆

Science.gov (United States)

Payne, Collin R.; Niculescu, Mihai; Just, David R.; Kelly, Michael P.

2015-01-01

Objectives We assessed the efficacy of an easy-to-implement shopper marketing nutrition intervention in a pilot and two additional studies to increase produce demand without decreasing store profitability or increasing shopper budgets. Methods We created grocery cart placards that detailed the number of produce items purchased (i.e., descriptive norm) at particular stores (i.e., provincial norm). The effect of these placards on produce spending was assessed across 971,706 individual person grocery store transactions aggregated by day. The pilot study designated a baseline period (in both control and intervention store) followed by installation of grocery cart placards (in the intervention store) for two weeks. The pilot study was conducted in Texas in 2012. In two additional stores, we designated baseline periods followed by 28 days of the same grocery cart placard intervention as in the pilot. Additional interventions were conducted in New Mexico in 2013. Results The pilot study resulted in a significant difference between average produce spending per day per person across treatment periods (i.e., intervention versus same time period in control) (16%) and the difference between average produce spending per day per person across stores in the control periods (4%); Furthermore, the same intervention in two additional stores resulted in significant produce spending increases of 12.4% and 7.5% per day per person respectively. In all stores, total spending did not change. Conclusions Descriptive and provincial social norm messages (i.e., on grocery cart placards) may be an overlooked tool to increase produce demand without decreasing store profitability and increasing shopper budgets. PMID:26844084

Can increasing adult vaccination rates reduce lost time and increase productivity?

Science.gov (United States)

Rittle, Chad

2014-12-01

This article addresses limited vaccination coverage by providing an overview of the epidemiology of influenza, pertussis, and pneumonia, and the impact these diseases have on work attendance for the worker, the worker's family, and employer profit. Studies focused on the cost of vaccination programs, lost work time, lost employee productivity and acute disease treatment are discussed, as well as strategies for increasing vaccination coverage to reduce overall health care costs for employers. Communicating the benefits of universal vaccination for employees and their families and combating vaccine misinformation among employees are outlined. Copyright 2014, SLACK Incorporated.

A Model-Free Definition of Increasing Uncertainty

NARCIS (Netherlands)

Grant, S.; Quiggin, J.

2001-01-01

We present a definition of increasing uncertainty, independent of any notion of subjective probabilities, or of any particular model of preferences.Our notion of an elementary increase in the uncertainty of any act corresponds to the addition of an 'elementary bet' which increases consumption by a

Taurine increases hippocampal neurogenesis in aging mice

Directory of Open Access Journals (Sweden)

Elias Gebara

2015-05-01

Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

Increased migration of monocytes in essential hypertension is associated with increased transient receptor potential channel canonical type 3 channels

DEFF Research Database (Denmark)

Zhao, Zhigang; Ni, Yinxing; Chen, Jing

2012-01-01

Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performe...

Human preference and acceptance of increased air velocity to offset warm sensation at increased room temperatures

OpenAIRE

Cattarin, Giulio; Simone, Angela; Olesen, Bjarne W.

2012-01-01

Previous studies have demonstrated that in summertime increased air velocities can compensate for higher room temperatures to achieve comfortable conditions. In order to increase air movement, windows opening, ceiling or desk fans can be used at the expense of relatively low energy consumption. The present climatic chamber study examined energy performance and achievable thermal comfort of traditional and bladeless desk fans. Different effects of mechanical and simulated-natural airflow patte...

Effective Strategies for Increasing Citation Frequency

Science.gov (United States)

Ebrahim, Nader Ale; Salehi, Hadi; Embi, Mohamed Amin; Tanha, Farid Habibi; Gholizadeh, Hossein; Motahar, Seyed Mohammad; Ordi, Ali

2013-01-01

Due to the effect of citation impact on The Higher Education (THE) world university ranking system, most of the researchers are looking for some helpful techniques to increase their citation record. This paper by reviewing the relevant articles extracts 33 different ways for increasing the citations possibilities. The results show that the article…

Cyberbullying: An Increasing Challenge for Schools

Science.gov (United States)

von Marees, Nandoli; Petermann, Franz

2012-01-01

The use of information and communication technology (ICT) has not only brought advantages to mankind. One downside is the emergence and increase of cyberbullying in schools. Affecting students of all ages, teachers, parents, and other educators, this special form of bullying is an increasing challenge for schools. This article offers an overview…

ORIC Beam Energy Increase

CERN Document Server

Mallory, Merrit L; Dowling, Darryl; Hudson, Ed; Lord, Dick; Tatum, Alan

2005-01-01

The detection of and solution to a beam interference problem in the Oak Ridge Isochronous Cyclotron (ORIC) extraction system has yielded a 20% increase in the proton beam energy. The beam from ORIC was designed to be extracted before the nu r equal one resonance. Most cyclotrons extract after the nu r equal one resonance, thus getting more usage of the magnetic field for energy acceleration. We have now determined that the electrostatic deflector septum interferes with the last accelerated orbit in ORIC, with the highest extraction efficiency obtained near the maximum nu r value. This nu r provides a rotation in the betatron oscillation amplitude that is about the same length as the electrostatic septum thus allowing the beam to jump over the interference problem with the septum. With a thinned septum we were able to tune the beam through the nu r equal one resonance and achieve a 20% increase in beam energy. This nu r greater than one extraction method may be desirable for very high field cyclotrons since it...

Increase of the blocking temperature of Fe–Ag granular multilayers with increasing number of the layers

Energy Technology Data Exchange (ETDEWEB)

Balogh, Judit [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, Hungarian Academy of Sciences, P.O. Box 49, H-1525 Budapest (Hungary); Kaptás, Dénes, E-mail: kaptas.denes@wigner.mta.hu [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, Hungarian Academy of Sciences, P.O. Box 49, H-1525 Budapest (Hungary); Kiss, László F. [Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, Hungarian Academy of Sciences, P.O. Box 49, H-1525 Budapest (Hungary); Dézsi, István [Institute for Particle and Nuclear Physics, Wigner Research Centre for Physics, Hungarian Academy of Sciences, P.O. Box 49, H-1525 Budapest (Hungary); Nakanishi, Akio [Department of Physics, Shiga University of Medical Science, Shiga 520-2192 (Japan); Devlin, Eamonn; Vasilakaki, Marianna; Margaris, George; Trohidou, Kalliopi N. [Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”, Aghia Paraskevi, 15310 Athens (Greece)

2016-03-01

Multilayers of 0.4 nm Fe and 5 nm Ag with repetition number, n=1, 2, 5, 10 and 20 were prepared by vacuum evaporation onto Si wafer. The blocking temperature was determined by measuring the field cooled and zero field cooled magnetization curves with a SQUID magnetometer and it was found to increase by almost an order of magnitude from around 20 K for the single Fe layer sample up to around 160 K for n=20. Significant increase of the average size of the superparamagnetic Fe grains by increasing the number of the Fe layers was excluded by conversion electron Mössbauer spectroscopy measurements of the paramagnetic state. The role of the dipole–dipole interactions and their interplay with the out-of-plain magnetic anisotropy in the variation of the blocking temperature has been investigated by Monte-Carlo simulations. - Highlights: • Multilayers of [0.4 nm Fe/5 nm Ag]{sub n} (n=1,2,5,10, and 20) were grown over Si. • Large increase of the superparamagnetic blocking temperature up to n=10 is observed. • The average Fe grain size does not change in the subsequent layers. • Perpendicular anisotropy enhances the dipolar coupling and the blocking temperature.

High Heels Increase Women's Attractiveness.

Science.gov (United States)

Guéguen, Nicolas

2015-11-01

Research has found that the appearance of women's apparel helps increase their attractiveness as rated by men and that men care more about physical features in potential opposite-sex mates. However, the effect of sartorial appearance has received little interest from scientists. In a series of studies, the length of women's shoe heels was examined. A woman confederate wearing black shoes with 0, 5, or 9 cm heels asked men for help in various circumstances. In Study 1, she asked men to respond to a short survey on gender equality. In Study 2, the confederate asked men and women to participate in a survey on local food habit consumption. In Study 3, men and women in the street were observed while walking in back of the female confederate who dropped a glove apparently unaware of her loss. It was found that men's helping behavior increased as soon as heel length increased. However, heel length had no effect on women's helping behavior. It was also found that men spontaneously approached women more quickly when they wore high-heeled shoes (Study 4). Change in gait, foot-size judgment, and misattribution of sexiness and sexual intent were used as possible explanations.

Increase nuclear safety of WWER-440

International Nuclear Information System (INIS)

Nochev, T.; Sabinov, S.

2000-01-01

A complete program for increasing nuclear safety has been made at NPP Kozloduy with the participation of German, French, Russian and American specialists. This effort cost greater than 100 mil $. This report includes the methods of increasing nuclear safety. The style of management in NPP Kozloduy has been changed for the last seven years. (authors)

Increased burnup of fuel elements

International Nuclear Information System (INIS)

Ahlf, J.

1983-01-01

The specialists' group for fuel elements of the Kerntechnische Gesellschaft e.V. held a meeting on ''Increased Burnup of Fuel Elements'' on 9th and 10th of November 1982 at the GKSS Research Center Geesthacht. Most papers dealt with the problems of burnup increase of fuel elements for light water reactors with respect to fuel manufacturing, power plant operation and reprocessing. Review papers were given on the burnup limits for high temperature gas cooled reactors and sodium fast breeder reactors. The meeting ended with a presentation of the technical equipment of the hot laboratory of the GKSS and the programs which are in progress there. (orig.) [de

Does Increased Access Increase Equality? Gender and Child Health Investments in India

OpenAIRE

Emily Oster

2006-01-01

Policymakers often argue that increasing access to health care is one crucial avenue for decreasing gender inequality in the developing world. Although this is generally true in the cross section, time series evidence does not always point to the same conclusion. This paper analyzes the relationship between access to child health investments and gender inequality in those health investments in India. A simple theory of gender-biased parental investment suggests that gender inequality may actu...

Increasing plant diversity with border crops reduces insecticide use and increases crop yield in urban agriculture.

Science.gov (United States)

Wan, Nian-Feng; Cai, You-Ming; Shen, Yan-Jun; Ji, Xiang-Yun; Wu, Xiang-Wen; Zheng, Xiang-Rong; Cheng, Wei; Li, Jun; Jiang, Yao-Pei; Chen, Xin; Weiner, Jacob; Jiang, Jie-Xian; Nie, Ming; Ju, Rui-Ting; Yuan, Tao; Tang, Jian-Jun; Tian, Wei-Dong; Zhang, Hao; Li, Bo

2018-05-24

Urban agriculture is making an increasing contribution to food security in large cities around the world. The potential contribution of biodiversity to ecological intensification in urban agricultural systems has not been investigated. We present monitoring data collected from rice fields in 34 community farms in mega-urban Shanghai, China, from 2001 to 2015, and show that the presence of a border crop of soybeans and neighboring crops (maize, eggplant and Chinese cabbage), both without weed control, increased invertebrate predator abundance, decreased the abundance of pests and dependence on insecticides, and increased grain yield and economic profits. Two 2 year randomized experiments with the low and high diversity practices in the same locations confirmed these results. Our study shows that diversifying farming practices can make an important contribution to ecological intensification and the sustainable use of associated ecosystem services in an urban ecosystem. © 2018, Wan et al.

E-cigarettes: Comparing the Possible Risks of Increasing Smoking Initiation with the Potential Benefits of Increasing Smoking Cessation.

Science.gov (United States)

Warner, Kenneth E; Mendez, David

2018-03-29

The public health community is divided regarding electronic cigarettes. Skeptics emphasize potential vaping-induced increases in smoking among children and possible health hazards for adults. Enthusiasts consider e-cigarettes much less dangerous than smoking and believe they increase adult smoking cessation. We compare potential health benefits and costs to put these two perspectives in context. Using a dynamic model that tracks the US adult population's smoking status and smoking-related deaths over time, we simulate the effects of vaping-induced smoking initiation and cessation on life-years saved or lost to the year 2070. The base case assumes that vaping annually increases smoking initiation by 2% and smoking cessation by 10%. Sensitivity analyses raise the initiation rate increase to 6% while decreasing the cessation rate increase to 5%. Sensitivity analyses also test vaping's reducing the health benefits of quitting smoking by 10%. With base-case assumptions, the population gains almost 3.3 million life-years by 2070. If all people who quit smoking by vaping lose 10% of the benefit of quitting smoking, the net life-year gain falls to 2.4 million. Under worst-case assumptions, in which vaping increases smoking initiation by 6% and cessation by 5%, and vaping-induced quitters lose 10% of the health benefits, the population gains over 580,000 life-years. Potential life-years gained as a result of vaping-induced smoking cessation are projected to exceed potential life-years lost due to vaping-induced smoking initiation. These results hold over a wide range of plausible parameters. Our analysis strongly suggests that the upside health benefit associated with e-cigarettes, in terms of their potential to increase adult smoking cessation, exceeds their downside risk to health as a result of their possibly increasing the number of youthful smoking initiators. Public messaging and policy should continue to strive to reduce young people's exposure to all nicotine and

Precipitation variability increases in a warmer climate.

Science.gov (United States)

Pendergrass, Angeline G; Knutti, Reto; Lehner, Flavio; Deser, Clara; Sanderson, Benjamin M

2017-12-21

Understanding changes in precipitation variability is essential for a complete explanation of the hydrologic cycle's response to warming and its impacts. While changes in mean and extreme precipitation have been studied intensively, precipitation variability has received less attention, despite its theoretical and practical importance. Here, we show that precipitation variability in most climate models increases over a majority of global land area in response to warming (66% of land has a robust increase in variability of seasonal-mean precipitation). Comparing recent decades to RCP8.5 projections for the end of the 21 st century, we find that in the global, multi-model mean, precipitation variability increases 3-4% K -1 globally, 4-5% K -1 over land and 2-4% K -1 over ocean, and is remarkably robust on a range of timescales from daily to decadal. Precipitation variability increases by at least as much as mean precipitation and less than moisture and extreme precipitation for most models, regions, and timescales. We interpret this as being related to an increase in moisture which is partially mitigated by weakening circulation. We show that changes in observed daily variability in station data are consistent with increased variability.

Insulin Increases Ceramide Synthesis in Skeletal Muscle

Directory of Open Access Journals (Sweden)

M. E. Hansen

2014-01-01

Full Text Available Aims. The purpose of this study was to determine the effect of insulin on ceramide metabolism in skeletal muscle. Methods. Skeletal muscle cells were treated with insulin with or without palmitate for various time periods. Lipids (ceramides and TAG were isolated and gene expression of multiple biosynthetic enzymes were quantified. Additionally, adult male mice received daily insulin injections for 14 days, followed by muscle ceramide analysis. Results. In muscle cells, insulin elicited an increase in ceramides comparable to palmitate alone. This is likely partly due to an insulin-induced increase in expression of multiple enzymes, particularly SPT2, which, when knocked down, prevented the increase in ceramides. In mice, 14 days of insulin injection resulted in increased soleus ceramides, but not TAG. However, insulin injections did significantly increase hepatic TAG compared with vehicle-injected animals. Conclusions. This study suggests that insulin elicits an anabolic effect on sphingolipid metabolism in skeletal muscle, resulting in increased ceramide accumulation. These findings reveal a potential mechanism of the deleterious consequences of the hyperinsulinemia that accompanies insulin resistance and suggest a possible novel therapeutic target to mitigate its effects.

Environmental effects of increased atmospheric carbon dioxide

International Nuclear Information System (INIS)

Soon, W.; Baliunas, S.L.; Robinson, A.B.; Robinson, Z.W.

1999-01-01

A review of the literature concerning the environmental consequences of increased levels of atmospheric carbon dioxide leads to the conclusion that increases during the 20th century have produced no deleterious effects upon global climate or temperature. Increased carbon dioxide has, however, markedly increased plant growth rates as inferred from numerous laboratory and field experiments. There is no clear evidence, nor unique attribution, of the global effects of anthropogenic CO 2 on climate. Meaningful integrated assessments of the environmental impacts of anthropogenic CO 2 are not yet possible because model estimates of global and regional climate changes on interannual, decadal and centennial timescales remain highly uncertain.(author)

Is surgical workforce diversity increasing?

Science.gov (United States)

Andriole, Dorothy A; Jeffe, Donna B; Schechtman, Kenneth B

2007-03-01

We sought to determine the extent to which recent increases in levels of gender and racial diversity in the overall resident-physician workforce were evident among core-surgical specialty resident workforces. Chi-square tests for trend assessed the importance of changes from 1996 to 2004 in proportions of women and African Americans in the surgery-resident workforce. Surgery-resident trends were compared with overall resident workforce trends using two-tailed t-tests to compare regression slopes that quantified rates of change over time. Chi-square tests assessed differences between proportions of women and African Americans in the current overall board-certified workforce and their proportions in the surgery board-certified workforce. From 1996 to 2004, proportions of women increased in all seven surgical specialties studied. Compared with the overall trend toward increasing proportions of women in the resident workforce, the trend in one surgical specialty was larger (obstetrics/gynecology, p 0.05), and two were smaller (each p 0.05). Proportions of African Americans decreased in three specialties (each p workforce, except obstetrics/gynecology, remained lower than in the overall board-certified workforce (each p workforces have persisted since 1996 and will likely perpetuate ongoing surgery board-certified workforce disparities.

Increasing trends of herpes zoster in Australia.

Directory of Open Access Journals (Sweden)

Raina MacIntyre

Full Text Available Increasing trends in incidence of herpes zoster (HZ have been reported in Australia and internationally. This may reflect the impact of childhood VZV vaccination programs introduced universally in Australia in late 2005. The objective of this study was to evaluate changes in incidence of HZ and PHN in Australia over time, and associated healthcare resource utilisation.Australian data on general practice (GP encounters for HZ, specific antiviral prescribing data from the pharmaceutical benefits scheme, emergency department presentations from the states of NSW and Victoria and national hospitalisation data for HZ were analysed for time trends using regression models. Two time periods (2000-2006 and 2006-2013 were compared which correspond broadly with the pre- and post- universal VZV vaccination period.All data sources showed increasing rates of HZ with age and over time. The GP database showed a significant annual increase in encounters for HZ of 2.5 per 100,000 between 1998 and 2013, and the rates of prescriptions for HZ increased by 4.2% per year between 2002 and 2012. In the 60+ population HZ incidence was estimated to increase from 11.9 to 15.4 per 1,000 persons using GP data or from 12.8 to 14.2 per 1,000 persons using prescription data (p<0.05, between the two periods. Hospitalisation data did not show the same increasing trend over time, except for the age group ≥80 years. Most emergency visits for HZ were not admitted, and showed significant increases over time.The burden of HZ in Australia is substantial, and continues to increase over time. This increase is seen both pre- and post-universal VZV vaccination in 2005, and is most prominent in the older population. The substantial burden of HZ, along with ageing of the Australian population and the importance of healthy ageing, warrants consideration of HZ vaccination for the elderly.

Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

NARCIS (Netherlands)

Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.

2014-01-01

The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of

Increased ionization rate in laser enrichment

International Nuclear Information System (INIS)

Janes, G.S.; Pike, G.T.

1977-01-01

A system employing multiple, upper excitation levels in a technique for isotopically selective ionization to improve the ionization efficiency is described. Laser radiation is employed to excite particles with isotopic selectivity. Excitation is produced to a plurality of excited states below the ionization level with the result of increasing the number of available excited particles for ionization and thereby increasing the ionization cross section for improved system efficiency

Do childcare policies increase maternal employment?

OpenAIRE

Vuri, Daniela

2016-01-01

Women’s labor force participation has rapidly increased in most countries, but mothers still struggle to achieve a satisfactory work−life balance. Childcare allows the primary caregiver, usually the mother, to take time away from childrearing for employment. Family policies that subsidize childcare and increase its availability have different effects on female labor supply across countries. For policymakers to determine how well these policies work, they should consider that policy effectiven...

Increasing the Brightness of Light Sources

OpenAIRE

Fu, Ling

2006-01-01

In modern illumination systems, compact size and high brightness are important features. Light recycling allows an increase of the spectral radiance (brightness) emitted by a light source for the price of reducing the total radiant power. Light recycling means returning part of the emitted light to the source where part of it will escape absorption. As a result, the output brightness can be increased in a restricted phase space, ...

Do levels of perceived stress increase with increasing age after age 65? A population-based study.

Science.gov (United States)

Osmanovic-Thunström, Almira; Mossello, Enrico; Åkerstedt, Torbjörn; Fratiglioni, Laura; Wang, Hui-Xin

2015-09-01

psychological and health-related stressors often occur in advanced ages, but little is known about perceived stress in adults aged 65 and over. This study aimed to test the hypothesis that levels of perceived stress increase with increasing age and to detect factors that may account for the association. a dementia-free cohort of 1,656 adults aged 66-97 years living at home or in institutions, participating in the Swedish National Aging and Care study, Kungsholmen (SNAC-K) was assessed for levels of perceived stress using the 10-item perceived stress scale (PSS). prevalence of high stress according to the top tertile of the population (PSS score 20+) was 7.8% in adults aged 81+ years, 7.5% in adults aged 72-78 and 6.2% in adults aged 66 years (P = 0.020). More women than men reported high stress, 8.3 versus 5.4% (P = 0.001). Levels of stress increased with increasing age (P = 0.001) in the linear regression model. This association remained after adjustment for demographic and psychosocial factors, but no longer was present after adjusting for health-related factors. health-related stress is highly prevalent in older adults and seems to play an important role in the association between levels of perceived stress and age in older adults. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Age Increases Monocyte Adhesion on Collagen

Science.gov (United States)

Khalaji, Samira; Zondler, Lisa; Kleinjan, Fenneke; Nolte, Ulla; Mulaw, Medhanie A.; Danzer, Karin M.; Weishaupt, Jochen H.; Gottschalk, Kay-E.

2017-05-01

Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin αx showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin αxβ2. Surprisingly, we find no significant age-dependent difference in gene expression of integrin αx or integrin β2. However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.

Soil amendment with biochar increases the competitive ability of legumes via increased potassium availability

NARCIS (Netherlands)

Oram, N.J.; Van de Voorde, T.F.J.; Ouwehand, G.J.; Bezemer, T.M.; Mommer, Liesje; Jeffery, S.; van Groeningen, J.W.

2014-01-01

Soil amendment with biochar is currently proposed as a management strategy to improve soil quality and enhance plant productivity. Relatively little is known about how biochar affects plant competition, although it has been suggested that it can increase the competitive ability of legumes. This

Increased transvascular lipoprotein transport in diabetes

DEFF Research Database (Denmark)

Jensen, Jan Skov; Feldt-Rasmussen, Bo; Borch-Johnsen, Knut

2005-01-01

CONTEXT: Diabetes is associated with a highly increased risk of atherosclerosis, especially if hypertension or albuminuria is present. OBJECTIVE: We hypothesized that the increased transvascular lipoprotein transport in diabetes may be further accelerated if hypertension or albuminuria is present...... of transvascular transport. RESULTS: Transvascular LDL transport was 1.8 (1.6-2.0), 2.3 (2.0-2.6), and 2.6 (1.3-4.0)%/[h x (liter/m2)] in healthy controls, diabetic controls, and diabetes patients with systolic hypertension or albuminuria, respectively (P = 0.013; F = 4.5; df =2; ANOVA). These differences most...... likely were not caused by altered hepatic LDL receptor expression, glycosylation of LDL, small LDL size, or medicine use. CONCLUSIONS: Transvascular LDL transport is increased in patients with diabetes mellitus, especially if systolic hypertension or albuminuria is present. Accordingly, lipoprotein flux...

Linear increases in BOLD response associated with increasing proportion of incongruent trials across time in a colour Stroop task.

Science.gov (United States)

Mitchell, Rachel L C

2010-05-01

Selective attention is popularly assessed with colour Stroop tasks in which participants name the ink colour of colour words, whilst resisting interference from the natural tendency to read the words. Prior studies hinted that the key brain regions (dorsolateral prefrontal (dlPFC) and anterior cingulate cortex (ACC)) may vary their degree of involvement, dependent on attentional demand. This study aimed to determine whether a parametrically varied increase in attentional demand resulted in linearly increased activity in these regions, and/or whether additional regions would be recruited during high attentional demand. Twenty-eight healthy young adults underwent fMRI whilst naming the font colour of colour words. Linear increases in BOLD response were assessed with increasing percentage incongruent trials per block (0, 20, 40, 60, 80, and 100%). Whilst ACC activation increased linearly according to incongruity level, dlPFC activity appeared constant. Together with behavioural evidence of reduced Stroop interference, these data support a load-dependent conflict-related response in ACC, but not dlPFC.

Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

Science.gov (United States)

Moon, Shinje; Yoo, Hyung-Joon; Ahn, You-Hern; Kim, Gheun-Ho; Yu, Jae Myung; Park, Joon-Sung

2018-01-01

The association of mild increase in urinary albumin excretion with diabetic retinopathy (DR) in clinical studies is controversial. The aim of this study is to clarify the interaction between increased glycemic exposure and mild increase in urinary albumin excretion on risk of DR.Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. Overall, data from 953 participants without microalbuminuria (477 men and 476 women) were assessed. Logistic regression analysis was constructed to evaluate the association between DR and related clinical parameters, including urinary albumin-creatinine ratio (UACR, mg/g creatinine). The biological interaction of glycemic status and UACR on DR was evaluated by 3 indices: RERI, the relative excess risk due to the interaction; AP, the attributable proportion due to the interaction; and S, the additive interaction index of synergy.We found that UACR, glycated hemoglobin (HbA1c), and diabetic duration were deeply associated with increased risk of DR (UACR, odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.02-1.07; HbA1c, OR = 1.16, 95% CI = 1.04-1.30; diabetic duration, OR = 1.06, 95% CI = 1.04-1.07). Furthermore, our interaction analysis demonstrated that synergistic interaction between HbA1c and UACR on development of DR was prominent in participants with diabetic duration of ≥10 years (adjusted RERI = 0.92, 95% CI = 0.10-1.74; adjusted AP = 0.29, 95% CI = -0.82-1.41; adjusted S = 1.76, 95% CI = 1.27-2.25), but not subjects with shorter diabetic duration.These findings imply that there is the interaction between prolonged hyperglycemic exposure and increased urinary albumin excretion may exert additive synergistic effect on vascular endothelial dysfunction in the eye, even before the appearance of overt diabetic nephropathy. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Does milk increase mucus production?

Science.gov (United States)

Bartley, Jim; McGlashan, Susan Read

2010-04-01

Excessive milk consumption has a long association with increased respiratory tract mucus production and asthma. Such an association cannot be explained using a conventional allergic paradigm and there is limited medical evidence showing causality. In the human colon, beta-casomorphin-7 (beta-CM-7), an exorphin derived from the breakdown of A1 milk, stimulates mucus production from gut MUC5AC glands. In the presence of inflammation similar mucus overproduction from respiratory tract MUC5AC glands characterises many respiratory tract diseases. beta-CM-7 from the blood stream could stimulate the production and secretion of mucus production from these respiratory glands. Such a hypothesis could be tested in vitro using quantitative RT-PCR to show that the addition of beta-CM-7 into an incubation medium of respiratory goblet cells elicits an increase in MUC5AC mRNA and by identifying beta-CM-7 in the blood of asthmatic patients. This association may not necessarily be simply cause and effect as the person has to be consuming A1 milk, beta-CM-7 must pass into the systemic circulation and the tissues have to be actively inflamed. These prerequisites could explain why only a subgroup of the population, who have increased respiratory tract mucus production, find that many of their symptoms, including asthma, improve on a dairy elimination diet. (c) 2009 Elsevier Ltd. All rights reserved.

Calming Meditation Increases Altruism, Decreases Parochialism

OpenAIRE

Frost, Karl

2017-01-01

It has been proposed that cultivating calm will increase altruism and decrease parochialism, where altruism is defined as self-sacrifice in support of others, regardless of group affiliation or identity, and parochialism is defined as prosocial self-sacrifice restricted to fellow members of a group. Such could be the case with a calming meditation practice. An alternate hypothesis, coming from the study of ritual, proposes that shared practices lead to bonding, increasing parochialism, but no...

Seasonal differences in human responses to increasing temperatures

DEFF Research Database (Denmark)

Kitazawa, Sachie; Andersen, Rune Korsholm; Wargocki, Pawel

2014-01-01

to be sleepier. Heart rate slightly increased during exposure, and SpO2 and ETCO2 began to decrease while core temperature started to increase. Performance of Tsai-partington test and addition test improved during exposures due to learning though lesser in winter. Results show negative effects of the temperature......Experiments were conducted in late summer and winter with 80 young and elderly Danish subjects exposed for 3.5 hours in a climate chamber to the temperature increasing from 24°C to 35.2°C at a rate of 3.7K/h. Psychological and physiological measurements were performed during exposure and subjects...... assessed comfort and acute health symptoms. Thermal sensation increased with increasing chamber temperature and did not differ during late summer and winter exposures. Skin temperature increased with increasing temperature and was slightly but significantly higher in the late summer in the first half...

Energy in China: Coping with increasing demand

International Nuclear Information System (INIS)

Sandklef, Kristina

2004-11-01

Sustaining the increasing energy consumption is crucial to future economic growth in China. This report focuses on the current and future situation of energy production and consumption in China and how China is coping with its increasing domestic energy demand. Today, coal is the most important energy resource, followed by oil and hydropower. Most energy resources are located in the inland, whereas the main demand for energy is in the coastal areas, which makes transportation and transmission of energy vital. The industrial sector is the main driver of the energy consumption in China, but the transport sector and the residential sector will increase their share of consumption in China, but the transport sector and the residential sector will increase their share of consumption by 2020. China's energy intensity decreased during the 1990s, but it is still high in a global comparison. China is projected to increase its energy consumption at least two times between 2000 and 2025. The government has an equal focus on energy conservation and to develop the current energy resources. Coal will continue to be the most important fuel, but the demand for oil, hydropower, natural gas and nuclear power will also increase. The main future challenges are transportation of energy resources within China and securing oil supply, both domestic and imports

Increase of internal energy due to measurement

International Nuclear Information System (INIS)

Daboul, J.

1991-01-01

We argue that the internal energy E=(H) of a macroscopic system in thermal equilibrium must increase, if we measure an observable A which does not commute with the Hamiltonian H. We derive an expression for calculating a lower bound for this increase in E. We then generalize the above result, and show that under certain conditions the expectation value (C) of an observable C should increase by the measurement of another observable A, if A and C do not commute. (author)

Poor Semen Quality Predicts Increased Mortality

DEFF Research Database (Denmark)

Jensen, Tina Kold; Bostofte, Erik; Jacobsen, Rune

Objective: Over recent decades a possible decrease in semen quality and an increase in the incidence of testicular cancer have been reported. In addition, men with poor semen quality have been reported to be at increased risk of developing testicular cancer whereas the risk of other cancers...... is not increased. The long-term survival of men with poor semen quality is, however, unknown. We therefore studied the associations between semen characteristics and subsequent mortality. Back to Top Material and Methods: The Copenhagen Sperm Analysis Laboratory is one of several public semen analysis laboratories...... in Denmark and examines semen samples mostly from men in the area of Copenhagen. Men are referred to the clinic by general practitioners and urologists, and the investigations are paid for through the public health system. A total of 34.442 men had a semen analysis done at the laboratory during 1963 to 1995...

Increased power supplied to the shelf from land

International Nuclear Information System (INIS)

2002-01-01

The report analyses how increasing the power supply from land to the offshore installations will affect the emissions of carbon dioxide from the power production on land. For the time being the CO 2 emissions from the production in existing power plants outside Norway will increase. Since the power price also rises, this checks the rise in consumption. This means that the total emission of carbon dioxide does not increase as much as it would have done if the power supply to the shelf had been covered entirely by increased production in existing coal power plants. If in the long term new conventional gas power capacity can be developed commercially, then increased power supply to the shelf will cause the CO 2 emission from power production on land in Norway to increase. Should conventional gas power plants not be granted concession, then the effect will be to increase the power production in existing plants in other countries and to check the rise in consumption. The net rise in consumption increases the emission of carbon dioxide from production in coal, oil, or gas power plants in Denmark, Finland, Germany or Poland

Idaho Power's reverses decline with employee increase

International Nuclear Information System (INIS)

Anon.

1990-01-01

Following several years of decline, the number of full-time Idaho Power employees increased to 1,528 at the end of 1989, up from 1,500 in 1988. The increase reversed a steady decline that began in 1984 when the company had a peak employment of 1,725. Last year's increase in the work force in part reflects recent additions in customers served and the electric demands of an expanding economy in the service area, as well as new regulatory requirements, the company said

Who Benefits from a Minimum Wage Increase?

OpenAIRE

John W. Lopresti; Kevin J. Mumford

2015-01-01

This paper addresses the question of how a minimum wage increase affects the wages of low-wage workers. Most studies assume that there is a simple mechanical increase in the wage for workers earning a wage between the old and the new minimum wage, with some studies allowing for spillovers to workers with wages just above this range. Rather than assume that the wages of these workers would have remained constant, this paper estimates how a minimum wage increase impacts a low-wage worker's wage...

TSA increases C/EBP‑α expression by increasing its lysine acetylation in hepatic stellate cells.

Science.gov (United States)

Tao, Li-Li; Ding, Di; Yin, Wei-Hua; Peng, Ji-Ying; Hou, Chen-Jian; Liu, Xiu-Ping; Chen, Yao-Li

2017-11-01

CCAAT enhancer binding protein‑α (C/EBP‑α) is a transcription factor expressed only in certain tissues, including the liver. It has been previously demonstrated that C/EBP‑α may induce apoptosis in hepatic stellate cells (HSCs), raising the question of whether acetylation of C/EBP‑α is associated with HSCs, and the potential associated mechanism. A total of three histone deacetylase inhibitors (HDACIs), including trichostatin A (TSA), suberoylanilide hydroxamic acid and nicotinamide, were selected to determine whether acetylation affects C/EBP‑α expression. A Cell Counting Kit‑8 assay was used to determine the rate of proliferation inhibition following treatment with varying doses of the three HDACIs in HSC‑T6 and BRL‑3A cells. Western blot analysis was used to examine Caspase‑3, ‑8, ‑9, and ‑12 levels in HSC‑T6 cells treated with adenoviral‑C/EBP‑α and/or TSA. Following treatment with TSA, a combination of reverse transcription‑quantitative polymerase chain reaction and western blot analyses was used to determine the inherent C/EBP‑α mRNA and protein levels in HSC‑T6 cells at 0, 1, 2, 4, 8, 12, 24, 36 and 48 h. Nuclear and cytoplasmic proteins were extracted to examine C/EBP‑α distribution. Co‑immunoprecipitation analysis was used to examine the lysine acetylation of C/EBP‑α. It was observed that TSA inhibited the proliferation of HSC‑T6 cells to a greater extent compared with BRL‑3A cells, following treatment with the three HDACIs. TSA induced apoptosis in HSC‑T6 cells and enhanced the expression of C/EBP‑α. Following treatment of HSC‑T6 cells with TSA, inherent C/EBP‑α expression increased in a time‑dependent manner, and its lysine acetylation simultaneously increased. Therefore, the results of the present study suggested that TSA may increase C/EBP‑α expression by increasing its lysine acetylation in HSCs.

Does Movie Violence Increase Violent Crime?

OpenAIRE

Gordon Dahl; Stefano DellaVigna

2007-01-01

Laboratory experiments in psychology find that media violence increases aggression in the short run. We analyze whether media violence affects violent crime in the field. We exploit variation in the violence of blockbuster movies from 1995 to 2004, and study the effect on same-day assaults. We find that violent crime decreases on days with larger theater audiences for violent movies. The effect is partly due to voluntary incapacitation: between 6PM and 12AM, a one million increase in the audi...

Fuel-consumption reflects increasing export

International Nuclear Information System (INIS)

TREND

2003-01-01

Fuel consumption in Slovakia has been substantially rising during the first three months of this year. During January and February about 6 percent more petrol and 15 percent more diesel fuel were sold compared to last year. Retail sales were growing even faster, informed president of Slovak Association of Petroleum Industry and Trade (SAPPO), Karoly Robak. He considers this an evidence of a substantial economic growth. The export is executed in form of freight transport (lorries), as this, together with agriculture, is the largest diesel fuel consumer. K. Robak, who at the same time is the Deputy General Manager For Retail at Slovnaft, a.s., Bratislava, expects the sales of fuel to grow by about 8 percent this year. Low prices due to a weaker US dollar should only support these tendencies. Last year the sales grew by 8,3 percent and in retail business the increase exceeded 10 percent. At the moment there are about 700 petrol stations in Slovakia (SAPPO) and over 330 out of them are owned by Slovnaft. The sale of fuel is now moving more to the retail business - to petrol stations as the price difference between retail and wholesale is decreasing. Last year for instance the wholesale recorded an increase in sales of diesel by 6,5 percent whereas retail sales grew by 17 percent. With petrol the situation was similar - 6,4 increase in retail sales and 2,5 percent in wholesale. (Author)

Increasing vaccine production using pulsed ultrasound waves.

Directory of Open Access Journals (Sweden)

Jida Xing

Full Text Available Vaccination is a safe and effective approach to prevent deadly diseases. To increase vaccine production, we propose that a mechanical stimulation can enhance protein production. In order to prove this hypothesis, Sf9 insect cells were used to evaluate the increase in the expression of a fusion protein from hepatitis B virus (HBV S1/S2. We discovered that the ultrasound stimulation at a frequency of 1.5 MHz, intensity of 60 mW/cm2, for a duration of 10 minutes per day increased HBV S1/S2 by 27%. We further derived a model for transport through a cell membrane under the effect of ultrasound waves, tested the key assumptions of the model through a molecular dynamics simulation package, NAMD (Nanoscale Molecular Dynamics program and utilized CHARMM force field in a steered molecular dynamics environment. The results show that ultrasound waves can increase cell permeability, which, in turn, can enhance nutrient / waste exchange thus leading to enhanced vaccine production. This finding is very meaningful in either shortening vaccine production time, or increasing the yield of proteins for use as vaccines.

Reduced Dietary Sodium Intake Increases Heart Rate

DEFF Research Database (Denmark)

Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

2016-01-01

Reduced dietary sodium intake (sodium reduction) increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side......-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs) published in the period 1973-2014. Sixty-three of the RCTs including 72 study...... populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction...

Development of inertia-increased reactor internal pump

International Nuclear Information System (INIS)

Tanaka, Masaaki; Matsumura, Seiichi; Kikushima, Jun; Kawamura, Shinichi; Yamashita, Norimichi; Kurosaki, Toshikazu; Kondo, Takahisa

2000-01-01

The Reactor Internal Pump (RIP) was adopted for the Reactor Recirculation System (RRS) of Advanced Boiling Water Reactor (ABWR) plants, and ten RIPs are located at the bottom of the reactor pressure vessel. In order to simplify the power supply system for the RIPs, a new inertia-increased RIP was developed, which allows to eliminate the Motor-Generator (M-G) sets. The rotating inertia was increased approximately 2.5 times of current RIP inertia by addition of flywheel on its main shaft. A full scale proving test of the inertia-increased RIP under actual plant operating conditions using full scale test loop was performed to evaluate vibration characteristics and coast down characteristics. From the results of this proving test, the validity of the new inertia-increased RIP and its power supply system (without M-G sets) was confirmed. (author)

Osteoinductive potential of demineralized rat bone increases with increasing donor age from birth to adulthood

DEFF Research Database (Denmark)

Pinholt, E M; Solheim, E

1998-01-01

Demineralized allogenic bone implanted in the subcutis or muscle of rodents causes formation of heterotopic bone by osteoinduction. The osteoinductive response may be weaker in primates than in rodents. It was suggested that the osteoinductive response of demineralized bone for clinical use could...... be enhanced by using young donors, because studies have indicated that the osteoinductive response is reduced in demineralized bone of old versus young donors. However, these findings may not represent a gradual decline in the osteoinductive property of bone matrix throughout the life span. We evaluated...... quantitatively, by uptake of strontium 85, the osteoinductive effect of demineralized bone matrix from newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats implanted in the abdominal muscles of 8-week-old male Wistar rats. The osteoinductive response increased significantly with increasing...

Online Mathematics Homework Increases Student Achievement

Directory of Open Access Journals (Sweden)

Jeremy Roschelle

2016-10-01

Full Text Available In a randomized field trial with 2,850 seventh-grade mathematics students, we evaluated whether an educational technology intervention increased mathematics learning. Assigning homework is common yet sometimes controversial. Building on prior research on formative assessment and adaptive teaching, we predicted that combining an online homework tool with teacher training could increase learning. The online tool ASSISTments (a provides timely feedback and hints to students as they do homework and (b gives teachers timely, organized information about students’ work. To test this prediction, we analyzed data from 43 schools that participated in a random assignment experiment in Maine, a state that provides every seventh-grade student with a laptop to take home. Results showed that the intervention significantly increased student scores on an end-of-the-year standardized mathematics assessment as compared with a control group that continued with existing homework practices. Students with low prior mathematics achievement benefited most. The intervention has potential for wider adoption.

Nutrient enrichment increases mortality of mangroves.

Directory of Open Access Journals (Sweden)

Catherine E Lovelock

Full Text Available Nutrient enrichment of the coastal zone places intense pressure on marine communities. Previous studies have shown that growth of intertidal mangrove forests is accelerated with enhanced nutrient availability. However, nutrient enrichment favours growth of shoots relative to roots, thus enhancing growth rates but increasing vulnerability to environmental stresses that adversely affect plant water relations. Two such stresses are high salinity and low humidity, both of which require greater investment in roots to meet the demands for water by the shoots. Here we present data from a global network of sites that documents enhanced mortality of mangroves with experimental nutrient enrichment at sites where high sediment salinity was coincident with low rainfall and low humidity. Thus the benefits of increased mangrove growth in response to coastal eutrophication is offset by the costs of decreased resilience due to mortality during drought, with mortality increasing with soil water salinity along climatic gradients.

Increasing Product Confidence-Shifting Paradigms.

Science.gov (United States)

Phillips, Marla; Kashyap, Vishal; Cheung, Mee-Shew

2015-01-01

Leaders in the pharmaceutical, medical device, and food industries expressed a unilateral concern over product confidence throughout the total product lifecycle, an unsettling fact for these leaders to manage given that their products affect the lives of millions of people each year. Fueled by the heparin incident of intentional adulteration in 2008, initial efforts for increasing product confidence were focused on improving the confidence of incoming materials, with a belief that supplier performance must be the root cause. As in the heparin case, concern over supplier performance extended deep into the supply chain to include suppliers of the suppliers-which is often a blind spot for pharmaceutical, device, and food manufacturers. Resolved to address the perceived lack of supplier performance, these U.S. Food and Drug Administration (FDA)-regulated industries began to adopt the supplier relationship management strategy, developed by the automotive industry, that emphasizes "management" of suppliers for the betterment of the manufacturers. Current product and supplier management strategies, however, have not led to a significant improvement in product confidence. As a result of the enduring concern by industry leaders over the lack of product confidence, Xavier University launched the Integrity of Supply Initiative in 2012 with a team of industry leaders and FDA officials. Through a methodical research approach, data generated by the pharmaceutical, medical device, and food manufacturers surprisingly pointed to themselves as a source of the lack of product confidence, and revealed that manufacturers either unknowingly increase the potential for error or can control/prevent many aspects of product confidence failure. It is only through this paradigm shift that manufacturers can work collaboratively with their suppliers as equal partners, instead of viewing their suppliers as "lesser" entities needing to be controlled. The basis of this shift provides manufacturers

Impact on Smoking Behavior of the New Zealand Annual Increase in Tobacco Tax: Data for the Fifth and Sixth Year of Increases.

Science.gov (United States)

Li, Judy; Newcombe, Rhiannon; Guiney, Hayley; Walton, Darren

2017-11-07

New Zealand has implemented a series of seven annual increases in tobacco tax since 2010. All tax increases, except for the first in the series, were preannounced. It is unusual for governments to introduce small, persistent, and predictable increases in tobacco tax, and little is known about the impact of such a strategy. This paper evaluates the impact of the fifth and sixth annual increases. Smokers' behaviors were self-reported during the 3-month period before, and the 3-month period after, the two annual increases. Responses to the two increases were analyzed separately, and generalized estimating equations models were used to control for sociodemographic variables, recent quit attempts, and the research design. Findings were consistent across years. The proportion of participants who made a smoking-related (54%-56% before and after each tax increase) or product-related change (fifth tax increase: 17%-19%; sixth tax increase: 21%-22%) did not significantly alter from before to after each tax increase. However, it should be noted that the proportion of participants making smoking-related changes was generally high, even prior to each increase. For example, before the 2015 tax increase, 1% reported quitting completely, 21% trying to quit, and 53% cutting down. In New Zealand, with its series of annual tobacco tax increases since 2010, there were no significant changes in smoking- or product-related behavior associated with the fifth and sixth increases. Nevertheless, overall cessation-related activity was high, with a majority of participants reporting either quitting and/or cutting down recently. Little is known about the impact of small, persistent, predictable tobacco tax increases on smoking behavior. This study evaluated the impact of the fifth (in 2014) and sixth (2015) tax increases in an annual series implemented in New Zealand. Although there were no detectable changes in smoking behaviors from before to after each tax increase, self-reported cessation

Effect of increasing truck weight on bridges.

Science.gov (United States)

2010-09-01

Legislation has been proposed that will allow a 17,000 lb increase in the maximum gross vehicle : weight on the Interstate Highway System. This projects main goal is quantify the effect of this : increase on the internal forces to which typical sl...

Exponential increase in postprandial blood-glucose exposure with increasing carbohydrate loads using a linear carbohydrate-to-insulin ratio.

Science.gov (United States)

Marran, K J; Davey, B; Lang, A; Segal, D G

2013-04-10

Postprandial glucose excursions contribute significantly to average blood glucose, glycaemic variability and cardiovascular risk. Carbohydrate counting is a method of insulin dosing that balances carbohydrate load to insulin dose using a fixed ratio. Many patients and current insulin pumps calculate insulin delivery for meals based on a linear carbohydrate-to-insulin relationship. It is our hypothesis that a non-linear relationship exists between the amounts of carbohydrate consumed and the insulin required to cover it. To document blood glucose exposure in response to increasing carbohydrate loads on fixed carbohydrate-to-insulin ratios. Five type 1 diabetic subjects receiving insulin pump therapy with good control were recruited. Morning basal rates and carbohydrate- to-insulin ratios were optimised. A Medtronic glucose sensor was used for 5 days to collect data for area-under-the-curve (AUC) analysis, during which standardised meals of increasing carbohydrate loads were consumed. Increasing carbohydrate loads using a fixed carbohydrate-to-insulin ratio resulted in increasing glucose AUC. The relationship was found to be exponential rather than linear. Late postprandial hypoglycaemia followed carbohydrate loads of >60 g and this was often followed by rebound hyperglycaemia that lasted >6 hours. A non-linear relationship exists between carbohydrates consumed and the insulin required to cover them. This has implications for control of postprandial blood sugars, especially when consuming large carbohydrate loads. Further studies are required to look at the optimal ratios, duration and type of insulin boluses required to cover increasing carbohydrate loads.

Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running.

Science.gov (United States)

Johnson, R A; Rhodes, J S; Jeffrey, S L; Garland, T; Mitchell, G S

2003-01-01

Voluntary wheel running in rats increases hippocampal brain-derived neurotrophic factor (BDNF) expression, a neurochemical important for neuronal survival, differentiation, connectivity and synaptic plasticity. Here, we report the effects of wheel running on BDNF and neurotrophin-3 (NT-3) protein levels in normal control mice, and in mice selectively bred (25 generations) for increased voluntary wheel running. We hypothesized that increased voluntary wheel running in selected (S) mice would increase CNS BDNF and NT-3 protein levels more than in control (C) mice. Baseline hippocampal BDNF levels (mice housed without running wheels) were similar in S and C mice. Following seven nights of running, hippocampal BDNF increased significantly more in S versus C mice, and levels were correlated with distance run (considering C and S mice together). Spinal and cerebellar BDNF and hippocampal NT-3 levels were not significantly affected by wheel running in any group, but there was a small, positive correlation between spinal C3-C6 BDNF levels and distance run (considering C and S mice together). This is the first study to demonstrate that mice which choose to run more have greater elevations in hippocampal BDNF, suggesting enhanced potential for exercise-induced hippocampal neuroplasticity.

Increasing nursing treatment for pediatric procedural pain.

Science.gov (United States)

Bice, April A; Gunther, Mary; Wyatt, Tami

2014-03-01

Procedural pain management is an underused practice in children. Despite the availability of efficacious treatments, many nurses do not provide adequate analgesia for painful interventions. Complementary therapies and nonpharmacologic interventions are additionally essential to managing pain. Owing to the increasing awareness of inadequate nursing utilization of pharmacologic measures for procedural pain, this paper focuses only on analgesic treatments. The aim of this review was to examine how varying degrees of quality improvement affect nursing utilization of treatments for routine pediatric procedural pain. A comprehensive search of databases including Cinahl, Medline/Pubmed, Web of Science, Google Scholar, Psycinfo, and Cochrane Library was performed. Sixty-two peer-reviewed research articles were examined. Ten articles focusing on quality improvement in pediatric pain management published in English from 2001 to 2011 were included. Three themes emerged: 1) increasing nursing knowledge; 2) nursing empowerment; and 3) protocol implementation. Research critique was completed with the use of guidelines and recommendations from Creswell (2009) and Garrard (2011). The literature reveals that nurses still think that pediatric pain management is essential. Quality improvement increases nursing utilization of procedural pain treatments. Although increasing nursing knowledge improves pediatric pain management, it appears that nursing empowerment and protocol implementation increase nursing compliance more than just education alone. Nurses providing pain management can enhance their individual practice with quality improvement measures that may increase nursing adherence to institutional and nationally recommended pediatric procedural pain management guidelines. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

INCREASED RELIABILITY OF ELECTRIC BLASTING

OpenAIRE

Kashuba, Oleh Ivanovych; Skliarov, L I; Skliarov, A L

2017-01-01

The problems of improving reliability of an electric blasting method using electric detonators with nichrome filament bridges. It was revealed that in the calculation of the total resistance of the explosive network it is necessary to increase to 24% of the nominal value

Economic inequality increases risk taking.

Science.gov (United States)

Payne, B Keith; Brown-Iannuzzi, Jazmin L; Hannay, Jason W

2017-05-02

Rising income inequality is a global trend. Increased income inequality has been associated with higher rates of crime, greater consumer debt, and poorer health outcomes. The mechanisms linking inequality to poor outcomes among individuals are poorly understood. This research tested a behavioral account linking inequality to individual decision making. In three experiments ( n = 811), we found that higher inequality in the outcomes of an economic game led participants to take greater risks to try to achieve higher outcomes. This effect of unequal distributions on risk taking was driven by upward social comparisons. Next, we estimated economic risk taking in daily life using large-scale data from internet searches. Risk taking was higher in states with greater income inequality, an effect driven by inequality at the upper end of the income distribution. Results suggest that inequality may promote poor outcomes, in part, by increasing risky behavior.

Strangers With Benefits: Attraction to Outgroup Men Increases as Fertility Increases Across the Menstrual Cycle.

Science.gov (United States)

Salvatore, Joseph F; Meltzer, Andrea L; March, David S; Gaertner, Lowell

2017-02-01

Research typically reveals that outgroups are regarded with disinterest at best and hatred and enmity at worst. Working from an evolutionary framework, we identify a unique pattern of outgroup attraction. The small-group lifestyle of pre-human ancestors plausibly limited access to genetically diverse mates. Ancestral females may have solved the inbreeding dilemma while balancing parental investment pressures by mating with outgroup males either via converting to an outgroup or cuckolding the ingroup. A vestige of those mating strategies might manifest in human women as a cyclic pattern of attraction across the menstrual cycle, such that attraction to outgroup men increases as fertility increases across the cycle. Two studies, one using a longitudinal method and the other an experimental method, evidenced the hypothesized linear relationship between attraction to outgroup men and fertility in naturally cycling women.

The Aging Kidney: Increased Susceptibility to Nephrotoxicity

Science.gov (United States)

Wang, Xinhui; Bonventre, Joseph V.; Parrish, Alan R.

2014-01-01

Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair. PMID:25257519

Increasing atmospheric carbon dioxide and its consequences

Energy Technology Data Exchange (ETDEWEB)

Lockwood, J G

1982-09-16

The effects of increasing CO/sub 2/ concentrations in the atmosphere are estimated using general circulation models (GCMs), which have the ability to portray many of the nonlinear feedback processes which serve to regulate atmospheric (and hence climatic) changes. GCMs predict that a doubling of atmospheric CO/sub 2/ would result in a 2-3 k increase of globally averaged surface air temperature. The largest warming will occur in the winter in high latitudes. Detection studies are now being directed towards isolating those parts of observed climate fluctuations that are attributable to increasing atmospheric CO/sub 2/. (KRM)

Alanine increases blood pressure during hypotension

Science.gov (United States)

Conlay, L. A.; Maher, T. J.; Wurtman, R. J.

1990-01-01

The effect of L-alanine administration on blood pressure (BP) during haemorrhagic shock was investigated using anesthetized rats whose left carotid arteries were cannulated for BP measurement, blood removal, and drug administration. It was found that L-alanine, in doses of 10, 25, 50, 100, and 200 mg/kg, increased the systolic BP of hypotensive rats by 38 to 80 percent (while 100 mg/kg pyruvate increased BP by only 9.4 mmhg, not significantly different from saline). The results suggest that L-alanine might influence cardiovascular function.

Analysis of sharpness increase by image noise

Science.gov (United States)

Kurihara, Takehito; Aoki, Naokazu; Kobayashi, Hiroyuki

2009-02-01

Motivated by the reported increase in sharpness by image noise, we investigated how noise affects sharpness perception. We first used natural images of tree bark with different amounts of noise to see whether noise enhances sharpness. Although the result showed sharpness decreased as noise amount increased, some observers seemed to perceive more sharpness with increasing noise, while the others did not. We next used 1D and 2D uni-frequency patterns as stimuli in an attempt to reduce such variability in the judgment. The result showed, for higher frequency stimuli, sharpness decreased as the noise amount increased, while sharpness of the lower frequency stimuli increased at a certain noise level. From this result, we thought image noise might reduce sharpness at edges, but be able to improve sharpness of lower frequency component or texture in image. To prove this prediction, we experimented again with the natural image used in the first experiment. Stimuli were made by applying noise separately to edge or to texture part of the image. The result showed noise, when added to edge region, only decreased sharpness, whereas when added to texture, could improve sharpness. We think it is the interaction between noise and texture that sharpens image.

Electromigration early resistance increase measurements

NARCIS (Netherlands)

Niehof, J.; Flinn, P.A.; Maloney, T.J.

1993-01-01

An early resistance change measurement set-up, using an AC bridge technique, has been developed, and measurements have been performed. Large sample-to-sample variations occur. The characteristic time for the resistance change curve is shorter for resistance increase (under current stress) than for

How To Increase Advertising Revenue.

Science.gov (United States)

Mitchell, Carmen

1995-01-01

Describes advertising sales strategies to help faculty advisers of community college newspapers increase revenues. Argues that sales representatives should know their product well and maintain demographic information on the paper's readership. Includes strategies for organizing advertising staff, searching for potential clients, and taking charge…

SIRTF thermal design modifications to increase lifetime

Science.gov (United States)

Petrick, S. W.

1993-01-01

An effort was made to increase the predicted lifetime of the SIRTF dewar by lowering the exterior shell temperature, increasing the radiated energy from the vapor cooled shields and reconfiguring the vapor cooled shields. The lifetime increases can be used to increase the scientific return from the mission and as a trade-off against mass and cost. This paper describes the configurations studied, the steady state thermal model used, the analytical methods and the results of the analysis. Much of the heat input to the outside dewar shell is radiative heat transfer from the solar panel. To lower the shell temperature, radiative cooled shields were placed between the solar panel and the dewar shell and between the bus and the dewar shell. Analysis showed that placing a radiator on the outer vapor cooled shield had a significant effect on lifetime. Lengthening the distance between the outer shell and the point where the vapor cooled shields are attached to the support straps also improved lifetime.

Clusters - Tourism Activity Increase Competitiveness Support

Directory of Open Access Journals (Sweden)

Carmen IORDACHE

2010-05-01

Full Text Available Tourism represents one of those areas with the greatest potential of global expansion. Tourism development strategy in terms of maximizing its positive effects on regional economic increase and implicitly on the national one starts from the premise that in global economy value is created in regions which are defined as particular geographical entities, separated by geographical reasons and not as political-administrative structures, and economic increase is centrally cumulated and valued according to the economic policy and the national legal system.Regional economic system approach based on “cluster” concept is explained by the fact that the regional activities portfolio is based on an inter and intra-industry networking grouped by cluster, in which is created the value that increases as the activity results are leading to the final consumers.This type of communication aims to highlight the tourism role as a factor in regional development, the clustering process significance in obtaining some competitiveness advantages, clusters development in tourism beginnings, and also the identification methodology used to select one touristic area to create the cluster.

Increasing cardiac interventions among the aged.

LENUS (Irish Health Repository)

Groarke, J D

2010-11-01

Ireland\\'s over 65 year population is growing. As incidence of coronary events rises with age, there is a growing population of elderly patients with cardiac disease. The changing age profile of patients treated by a tertiary hospital\\'s Cardiology service was quantified using Hospital Inpatient Enquiry data. 53% of CCU admissions were aged > or = 65 years, with admissions aged > or = 85 years in 2008 four times greater than in 2002. Percentages of patients undergoing diagnostic coronary angiography and percutaneous coronary interventions in 1997 aged > or = 70 years were 19% and 18% respectively. By 2007, these percentages had risen to 31% and 34% respectively--greatest increases were in the very elderly age categories. The proportion of ICD recipients aged > 70 years increased from 8% in 2003 to 25% by 2008. The proportion of elderly patients receiving advanced cardiac care is increasing. This trend will continue and has clear resource implications. Outcomes of interventions in the very old need further investigation, since the \\'old old\\' are under-represented in clinical trials.

D-serine increases adult hippocampal neurogenesis

Directory of Open Access Journals (Sweden)

Sebastien eSultan

2013-08-01

Full Text Available Adult hippocampal neurogenesis results in the continuous formation of new neurons and is a process of brain plasticity involved in learning and memory. The neurogenic niche regulates the stem cell proliferation and the differentiation and survival of new neurons and a major contributor to the neurogenic niche are astrocytes. Among the molecules secreted by astrocytes, D-serine is an important gliotransmitter and is a co-agonist of the glutamate, N-methyl-D-aspartate (NMDA receptor. D-serine has been shown to enhance the proliferation of neural stem cells in vitro, but its effect on adult neurogenesis in vivo is unknown. Here, we tested the effect of exogenous administration of D-serine on adult neurogenesis in the mouse dentate gyrus. We found that 1 week of treatment with D-serine increased cell proliferation in vivo and in vitro and increased the density of neural stem cells and transit amplifying progenitors. Furthermore, D-serine increased the survival of newborn neurons. Together, these results indicate that D-serine treatment resulted in the improvement of several steps of adult neurogenesis in vivo.

Increased exposure to community-based education and 'below the line' social marketing results in increased fruit and vegetable consumption.

Science.gov (United States)

Glasson, Colleen; Chapman, Kathy; Wilson, Tamara; Gander, Kristi; Hughes, Clare; Hudson, Nayerra; James, Erica

2013-11-01

To determine if localised programmes that are successful in engaging the community can add value to larger fruit and vegetable mass-media campaigns by evaluating the results of the Eat It To Beat It programme. The Eat It To Beat It programme is a multi-strategy intervention that uses community-based education and ‘below the line’ social marketing to increase fruit and vegetable consumption in parents. This programme was evaluated by a controlled before-and-after study with repeat cross-sectional data collected via computer-assisted telephone interviews with 1403 parents before the intervention (2008) and 1401 following intervention delivery (2011). The intervention area was the Hunter region and the control area was the New England region of New South Wales, Australia. Parents of primary school-aged children (Kindergarten to Year 6). The programme achieved improvements in knowledge of recommended intakes for fruit and vegetables and some positive changes in knowledge of serving size for vegetables. Exposure to the programme resulted in a net increase of 0.5 servings of fruit and vegetables daily for those who recalled the programme compared with those who did not (P = 0.004). Increased intake of fruit and vegetables was significantly associated with increasing exposure to programme strategies. The Eat It To Beat It programme demonstrates that an increase in consumption of fruit and vegetables can be achieved by programmes that build on the successes of larger mass-media and social-marketing campaigns.This suggests that funding for localised, community-based programmes should be increased.

76 FR 29963 - Rate Increase Disclosure and Review

Science.gov (United States)

2011-05-23

... for the product associated with the rate increase; and (8) employee and executive compensation data... 154 Rate Increase Disclosure and Review; Final Rule #0;#0;Federal Register / Vol. 76 , No. 99 / Monday... CFR Part 154 [CMS-9999-FC] RIN 0938-AQ68 Rate Increase Disclosure and Review AGENCY: Center for...

Carbohydrase and protease supplementation increased ...

African Journals Online (AJOL)

A trial was conducted to evaluate whether the addition of commercial enzyme preparations containing carbohydrases and a protease would increase the available metabolizable energy (ME) of maize-soya-based broiler diets. Seven thousand five hundred and sixty (7560) day-old Ross 788 chicks were randomly allocated ...

Heavier smoking increases coffee consumption

DEFF Research Database (Denmark)

Bjørngaard, Johan H; Nordestgaard, Ask Tybjærg; Taylor, Amy E

2017-01-01

Background: There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods: We performed Mendelian randomization analyses in the UK...... Biobank ( N  = 114 029), the Norwegian HUNT study ( N  = 56 664) and the Copenhagen General Population Study (CGPS) ( N  = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS....... Analyses were conducted using linear regression and meta-analysed across studies. Results: Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per...

FEASIBILITY OF INCREASING THE ENERGY OF RHIC

International Nuclear Information System (INIS)

MACKAY, W.W.; JAIN, A.; LUCCIO, A.U.; PILAT, F.; ROSER, T.; TEPIKIAN, S.; TROBOJEVIC, D.

2001-01-01

In this paper we discuss the possibility of increasing the energy of beams in RHIC by as much as 30% with a modest trade-off in luminosity. The arc dipoles and quadrupoles were designed with considerable margin. For higher energies (>100 GeV/nucleon) the minimum β* may be required to increase as the interaction region triplets saturate. The separator magnets (DX) have the least margin for increased field, so we consider three scenarios: allowing for a small crossing angle with the present DX magnets, upgrading the DX magnets to higher strength, and permitting a crossing angle of ∼1degree by removing the DX magnets altogether

Africa: rapid population increase retards development.

Science.gov (United States)

1993-10-01

The Organization of African Unity (OAU), the African Development Bank (ADB) and the UN Economic Commission for Africa (ECA) have criticized African governments for not taking the problem of unchecked population growth seriously enough. "Until recently most African governments did not view rapid population growth as a matter for concern," said the OAU assistant secretary-general for political affairs, Machivenyika Mapuranga, at a seminar on 'population and development'. The OAU estimates that an annual average population increase of 3.1% far outstrips Africa's economic growth, which in 1992 was less than 1%. Mapuranga acknowledged that cutting the population increase is an uphill struggle, especially among rural communities. African agriculture is largely labor intensive, sustained by smallholders, which encourages farmers to have more children. Like other wage earners, African farmers look to support from their family when they grow old and, for that reason, the number of children also counts. But with agricultural production growing at an average annual rate of 2.5%, self-sufficiency in food remains an elusive goal. Cities in sub-Saharan Africa are growing much faster than the overall rate of population increase of 3.1% per year. Between 1980 and 1988 the region's urban population increased at the rate of 6.9% a year. Urban areas now account for nearly 30% of the sub-Saharan Africa population, currently put at 680 million. By 2025, approximately 700 million people are expected to live in urban areas. Despite migration to towns, the rural population is expected to rise more than 68%, reaching over 590 million. full text

Aspirin increases mitochondrial fatty acid oxidation

International Nuclear Information System (INIS)

Uppala, Radha; Dudiak, Brianne; Beck, Megan E.; Bharathi, Sivakama S.; Zhang, Yuxun; Stolz, Donna B.; Goetzman, Eric S.

2017-01-01

The metabolic effects of salicylates are poorly understood. This study investigated the effects of aspirin on fatty acid oxidation. Aspirin increased mitochondrial long-chain fatty acid oxidation, but inhibited peroxisomal fatty acid oxidation, in two different cell lines. Aspirin increased mitochondrial protein acetylation and was found to be a stronger acetylating agent in vitro than acetyl-CoA. However, aspirin-induced acetylation did not alter the activity of fatty acid oxidation proteins, and knocking out the mitochondrial deacetylase SIRT3 did not affect the induction of long-chain fatty acid oxidation by aspirin. Aspirin did not change oxidation of medium-chain fatty acids, which can freely traverse the mitochondrial membrane. Together, these data indicate that aspirin does not directly alter mitochondrial matrix fatty acid oxidation enzymes, but most likely exerts its effects at the level of long-chain fatty acid transport into mitochondria. The drive on mitochondrial fatty acid oxidation may be a compensatory response to altered mitochondrial morphology and inhibited electron transport chain function, both of which were observed after 24 h incubation of cells with aspirin. These studies provide insight into the pathophysiology of Reye Syndrome, which is known to be triggered by aspirin ingestion in patients with fatty acid oxidation disorders. - Highlights: • Aspirin increases mitochondrial—but inhibits peroxisomal—fatty acid oxidation. • Aspirin acetylates mitochondrial proteins including fatty acid oxidation enzymes. • SIRT3 does not influence the effect of aspirin on fatty acid oxidation. • Increased fatty acid oxidation is likely due to altered mitochondrial morphology and respiration.

5 CFR 9701.342 - Performance pay increases.

Science.gov (United States)

2010-01-01

... increases, the Secretary or designee must take into account the average value of within-grade and quality... pay pool controls to allocate pay increases based on performance points that are directly linked to... function of the amount of money in the performance pay pool, the relative point value placed on ratings...

Import of electric power increased by 19 %

International Nuclear Information System (INIS)

Anon.

2000-01-01

The import of electric power increased by 19% in 1999. Due to the decrease in the electric power export the net import of electric power increased even more. Electric power import from Sweden was 6000 GWh, import from Russia 5200 GWh and import from Norway 100 GWh. The electric power export in 1999 was only 200 GWh. The generation of nuclear power increased 5% and the consumption of wood-based fuels by 3%. The increase in nuclear power generation is based on increment of the power output capacities of the power plants. The consumption of peat decreased by 12% and the production of hydroelectric power by 15%. The decrement of the peat consumption is based on the changes in energy taxation. The production of hydroelectric power decreased to the normal level after the rainy year 1998. Oil consumption remained nearly the same as in 1998 even though the national product increased in 1999 by 3.5%. The wind power generation was doubled in 1999. The share of it is still only about 0.01% of the total energy consumption. Carbon dioxide emissions from coal and peat, decreased by 1.0 million tons, down to 56 million tons. The present emissions are now only about 2 million tons higher than during the reference year 1990. The emissions have decreased by 5 million tons since 1996 when they were at their highest

Increased Mercury Bioaccumulation Follows Water Quality Improvement

Energy Technology Data Exchange (ETDEWEB)

Bogle, M.A.; Peterson, M.J.; Smith, J.G.; Southworth, G.R.

1999-09-15

Changes in physical and chemical characteristics of aquatic habitats made to reduce or eliminate ecological risks can sometimes have unforeseen consequences. Environmental management activities on the U.S. Dept. of Energy reservation in Oak Ridge, Tennessee,have succeeded in improving water quality in streams impacted by discharges fi-om industrial facilities and waste disposal sites. The diversity and abundance of pollution-sensitive components of the benthic macroinvertebrate communities of three streams improved after new waste treatment systems or remedial actions reduced inputs of various toxic chemicals. Two of the streams were known to be mercury-contaminated from historical spills and waste disposal practices. Waterborne mercury concentrations in the third were typical of uncontaminated systems. In each case, concentrations of mercury in fish, or the apparent biological availability of mercury increased over the period during which ecological metrics indicated improved water quality. In the system where waterborne mercury concentrations were at background levels, increased mercury bioaccumulation was probably a result of reduced aqueous selenium concentrations; however, the mechanisms for increased mercury accumulation in the other two streams remain under investigation. In each of the three systems, reduced inputs of metals and inorganic anions was followed by improvements in the health of aquatic invertebrate communities. However, this reduction in risk to aquatic invertebrates was accompanied by increased risk to humans and piscivorous wildlife related to increased mercury concentrations in fish.

Increased Mercury Bioaccumulation Follows Water Quality Improvement

International Nuclear Information System (INIS)

Bogle, M.A.; Peterson, M.J.; Smith, J.G.; Southworth, G.R.

1999-01-01

Changes in physical and chemical characteristics of aquatic habitats made to reduce or eliminate ecological risks can sometimes have unforeseen consequences. Environmental management activities on the U.S. Dept. of Energy reservation in Oak Ridge, Tennessee,have succeeded in improving water quality in streams impacted by discharges fi-om industrial facilities and waste disposal sites. The diversity and abundance of pollution-sensitive components of the benthic macroinvertebrate communities of three streams improved after new waste treatment systems or remedial actions reduced inputs of various toxic chemicals. Two of the streams were known to be mercury-contaminated from historical spills and waste disposal practices. Waterborne mercury concentrations in the third were typical of uncontaminated systems. In each case, concentrations of mercury in fish, or the apparent biological availability of mercury increased over the period during which ecological metrics indicated improved water quality. In the system where waterborne mercury concentrations were at background levels, increased mercury bioaccumulation was probably a result of reduced aqueous selenium concentrations; however, the mechanisms for increased mercury accumulation in the other two streams remain under investigation. In each of the three systems, reduced inputs of metals and inorganic anions was followed by improvements in the health of aquatic invertebrate communities. However, this reduction in risk to aquatic invertebrates was accompanied by increased risk to humans and piscivorous wildlife related to increased mercury concentrations in fish

Big increase in US ethanol

Energy Technology Data Exchange (ETDEWEB)

1981-07-10

US ethanol capacity is expected to reach 600 million US gal/year by the end of 1982, according to a report from the AIChE. Although this is a six-fold increase over capacity installed in 1979 it is still less than 1% of US domestic motor fuel supply.