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  1. Article ; Online: Lapachol and synthetic derivatives

    Marcelo A Strauch / Marcelo Amorim Tomaz / Marcos Monteiro-Machado / Bruno Lemos Cons / Fernando Chagas Patrão-Neto / Jhonatha da Mota Teixeira-Cruz / Matheus da Silva Tavares-Henriques / Pâmella Dourila Nogueira-Souza / Sara L S Gomes / Paulo R R Costa / Edgar Schaeffer / Alcides J M da Silva / Paulo A Melo

    PLoS ONE, Vol 14, Iss 1, p e

    in vitro and in vivo activities against Bothrops snake venoms.

    2019  Volume 0211229

    Abstract: BACKGROUND:It is known that local tissue injuries incurred by snakebites are quickly instilled causing extensive, irreversible, tissue destruction that may include loss of limb function or even amputation. Such injuries are not completely neutralized by ... ...

    Abstract BACKGROUND:It is known that local tissue injuries incurred by snakebites are quickly instilled causing extensive, irreversible, tissue destruction that may include loss of limb function or even amputation. Such injuries are not completely neutralized by the available antivenins, which in general are focused on halting systemic effects. Therefore it is prudent to investigate the potential antiophidic effects of natural and synthetic compounds, perhaps combining them with serum therapy, to potentially attenuate or eliminate the adverse local and systemic effects of snake venom. This study assessed a group of quinones that are widely distributed in nature and constitute an important class of natural products that exhibit a range of biological activities. Of these quinones, lapachol is one of the most important compounds, having been first isolated in 1882 from the bark of Tabebuia avellanedae. METHODOLOGY/PRINCIPAL FINDINGS:It was investigated the ability of lapachol and some new potential active analogues based on the 2-hydroxi-naphthoquinone scaffold to antagonize important activities of Bothrops venoms (Bothrops atrox and Bothrops jararaca) under different experimental protocols in vitro and in vivo. The bioassays used to test the compounds were: procoagulant, phospholipase A2, collagenase and proteolytic activities in vitro, venom-induced hemorrhage, edematogenic, and myotoxic effects in mice. Proteolytic and collagenase activities of Bothrops atrox venom were shown to be inhibited by lapachol and its analogues 3a, 3b, 3c, 3e. The inhibition of these enzymatic activities might help to explain the effects of the analogue 3a in vivo, which decreased skin hemorrhage induced by Bothrops venom. Lapachol and the synthetic analogues 3a and 3b did not inhibit the myotoxic activity induced by Bothrops atrox venom. The negative protective effect of these compounds against the myotoxicity can be partially explained by their lack of ability to effectively inhibit phospholipase A2 venom activity. Bothrops atrox venom also ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 540
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Polyclonal F(ab’)2 fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency

    Luis Eduardo R. Cunha / Adilson A. Stolet / Marcelo A. Strauch / Victor A.R. Pereira / Carlos H. Dumard / Andre M.O. Gomes / Fábio L. Monteiro / Luiza M. Higa / Patrícia N.C. Souza / Juliana G. Fonseca / Francisco E. Pontes / Leonardo G.R. Meirelles / José W.M. Albuquerque / Carolina Q. Sacramento / Natalia Fintelman-Rodrigues / Tulio M. Lima / Renata G.F. Alvim / Federico F. Marsili / Marcella Moreira Caldeira /
    Russolina B. Zingali / Guilherme A.P. de Oliveira / Thiago M.L. Souza / Alexandre S. Silva / Rodrigo Muller / Daniela del Rosário Flores Rodrigues / Luciana Jesus da Costa / Arthur Daniel R. Alves / Marcelo Alves Pinto / Andréa C. Oliveira / Herbert L.M. Guedes / Amilcar Tanuri / Leda R. Castilho / Jerson L. Silva

    iScience, Vol 24, Iss 11, Pp 103315- (2021)

    2021  

    Abstract: Summary: We used the recombinant trimeric spike (S) glycoprotein in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by ELISA were above 1:106, and the ... ...

    Abstract Summary: We used the recombinant trimeric spike (S) glycoprotein in the prefusion conformation to immunize horses for the production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by ELISA were above 1:106, and the neutralizing antibody titer against authentic virus (WT) was 1:14,604 (average PRNT90). Plasma from immunized animals was pepsin digested to remove the Fc portion and purified, yielding an F(ab’)2 preparation with PRNT90 titers 150-fold higher than the neutralizing titers in human convalescent plasma. Challenge studies were carried out in hamsters and showed the in vivo ability of equine F(ab’)2 to reduce viral load in the pulmonary tissues and significant clinical improvement determined by weight gain. The neutralization curve by F(ab’)2 was similar against the WT and P.2 variants, but displaced to higher concentrations by 0.39 log units against the P.1 (Gamma) variant. These results support the possibility of using equine F(ab’)2 preparation for the clinical treatment of COVID patients.
    Keywords Immunology ; Equine immunology ; Biological sciences ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Counteraction of Bothrops snake venoms by Combretum leprosum root extract and arjunolic acid

    Fernandes, Fabrício F.A / Adélia C.O. Cintra / Bruno L. Cons / Camila Z. El-Kik / Marcelo A. Strauch / Marcelo A. Tomaz / Marcos Monteiro-Machado / Matheus S. Tavares-Henriques / Paulo A. Melo / Valdir A. Facundo

    Journal of ethnopharmacology. 2014 Aug. 08, v. 155, no. 1

    2014  

    Abstract: Serotherapy against snakebite is often unavailable in some regions over Brazil, where people make use of plants from folk medicine to deal with ophidic accidents. About 10% of Combretum species have some ethnopharmacological use, including treatment of ... ...

    Abstract Serotherapy against snakebite is often unavailable in some regions over Brazil, where people make use of plants from folk medicine to deal with ophidic accidents. About 10% of Combretum species have some ethnopharmacological use, including treatment of snakebites.We evaluated the ability of the extract of Combretum leprosum and its component arjunolic acid to reduce some in vivo and in vitro effects of Bothrops jararacussu and Bothrops jararaca venoms. The protocols investigated include phospholipase, proteolytic, collagenase, hyaluronidase, procoagulant, hemorrhagic, edematogenic, myotoxic and lethal activities induced by these venoms in Swiss mice.Oral pre-treatment with arjunolic acid reduced the Bothrops jararacussu lethality in up to 75%, while preincubation prevented the death of all the animals. Hemoconcentration effect of Bothrops jararacussu venom was confirmed two hours after i.p. injection, while preincubation with arjunolic acid preserved the hematocrit levels. Both Combretum leprosum extract and arjunolic acid abolished the myotoxic action of Bothrops jararacussu venom. Preincubation of Bothrops jararacussu venom with the extract or arjunolic acid prevented the increase of plasma creatine kinase activity in mice. The hemorrhagic activity of Bothrops jararaca crude venom was reduced down to about 90% and completely inhibited by preincubation with 10mg/kg or 100mg/kg Combretum leprosum extract, respectively, while the preincubation and the pretreatment with 30mg/kg of arjunolic acid reduced the venom hemorrhagic activity down to about 12% and 58%, respectively. The preincubation of the venom with both extract and 30mg/kg arjunolic acid significantly reduced the bleeding amount induced by Bothrops jararacussu venom. The extract of Combretum leprosum decreased the edema formation induced by Bothrops jararacussu venom both in preincubation and pretreatment, but not in posttreatment. Similarly, arjunolic acid preincubated with the venom abolished edema formation, while pre- and posttreatment have been partially effective. Some enzymatic activities of Bothrops jararacussu and Bothrops jararaca venoms, i.e. phospholipase A2, collagenase, proteolytic and hyaluronidase activities, were to some extent inhibited by the extract and arjunolic acid in a concentration-dependent manner.Altogether, our results show that Combretum leprosum extract can inhibit different activities of two important Brazilian snake venoms, giving support for its popular use in folk medicine in the management of venomous snakebites.
    Keywords accidents ; Bothrops jararaca ; collagenase ; Combretum leprosum ; creatine kinase ; death ; edema ; enzyme activity ; hematocrit ; hemorrhage ; hyaluronoglucosaminidase ; mice ; mortality ; phospholipase A2 ; phospholipases ; proteolysis ; protocols ; snake bites ; snake venoms ; traditional medicine ; Brazil
    Language English
    Dates of publication 2014-0808
    Size p. 552-562.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2014.05.056
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response.

    Valdirene S Muniz / Renata Baptista-Dos-Reis / Claudia F Benjamim / Hilton A Mata-Santos / Alexandre S Pyrrho / Marcelo A Strauch / Paulo A Melo / Amanda R R Vicentino / Juliana Silva-Paiva / Christianne Bandeira-Melo / Peter F Weller / Rodrigo T Figueiredo / Josiane S Neves

    PLoS ONE, Vol 10, Iss 10, p e

    2015  Volume 0139805

    Abstract: Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression ... ...

    Abstract Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5'-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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