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We have demonstrated in previous studies that a single amino acid change can alter the activity of the recombinant disintegrin r-Moj. In this study, four r-Moj recombinants containing single mutations (r-Moj-WL, r-Moj-WM, r-Moj-WP, r-Moj-MN) and two containing double mutations (r-Moj-MP and r-Moj-NM) at the binding loop were produced, purified, and tested. All r-Moj-W_, r-Moj-M_, and r-Moj-NM mutant...
Disintegrins are small peptides produced in viper venom that act as integrin antagonists. When bound to integrins, disintegrins induce altered cellular behaviors, such as apoptotic induction. Disintegrins with RGDDL or RGDDM motifs induce apoptosis of normal and cancer cells. We hypothesized that a second aspartate (D) carboxyl to the RGD is sufficient to induce apoptosis. Five recombinant mojastin...
Disintegrins are low molecular weight peptides isolated from viper venom. These peptides bind to integrin receptors using a conserved binding motif sequence containing an RGD or similar motif. As a consequence, disintegrins can inhibit platelet aggregation and inhibit cell migration, proliferation, and initiate apoptosis in cancer cell lines. Rubistatin is a MVD disintegrin cloned from a Crotalus...
Accidents by Thalassophryne nattereri fish venom are characterised by severe local symptoms and signs including pain of fast onset, oedema and necrosis with impaired muscle regeneration. These effects have been related to alterations in hemostatic mechanisms and cytolytic effects rather than to conventional inflammatory pathways. In this work we evaluated the effects induced by the venom on microcirculatory...
Bothrops asper is responsible for approximately half of the snakebite envenomations in Central America. Despite its medical relevance, only the venom of Costa Rican populations of this species has been studied to some detail, and there is very little information on intraspecies variability in venom composition and toxicity. Venom of B. asper from Guatemala was analyzed by sodium dodecyl sulphate-polyacrylamide...
A comparative study was performed on the pharmacology and biochemistry of venoms from three subspecies of Lachesis muta (L. m. stenophrys, L. m. muta and L. m. rhombeata) from Brazil, Colombia and Costa Rica. All venoms induced lethal, hemorrhagic, edema-forming, myotoxic, coagulant and defibrinating effects, showing also proteolytic and indirect hemolytic activities. The venoms of L. m. stenophrys...
The pharmacological modulation of edema-forming activity of Bothrops asper myotoxins II and III, Lys-49 and Asp-49 phospholipases A 2 , respectively, was studied plethysmographically in the mouse foot pad model. Myotoxin III had phospholipase A 2 activity, whereas myotoxin II was devoid of enzymatic activity when tested on egg yolk phosphatidylcholine. Both toxins induced a dose-dependent...
The mortality rate due to snakebite envenomation in Costa Rica was estimated from 1952 to 1993. The highest mortality was observed during the 1950s and 1960s, with the highest rate of 4.83 per 100,000 population in 1953. In contrast, a rate of 0.2 per 100,000 population per year was estimated from 1990 to 1993. The most conspicuous decline in mortality occurred after 1970. The highest mortality...
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...
Lysine and histidine residues of two myotoxic phospholipases A 2 , Bothrops asper myotoxin III and Bothrops godmani myotoxin I, were chemically modified in order to study the effects of these treatments on enzymatic and pharmacological properties. After lysine acetylation the overall basicity of these toxins was lost and their enzymatic activity was significantly reduced, although a residual...
Six horses were immunized with the venoms of Bothrops asper, Crotalus durissus durissus andLachesis muta stenophrys for the production of polyvalent (Crotalinae) antivenom. During the immunization, clinical and laboratory alterations were evaluated in these animals, and the development of humoral immune response was followed. Only moderate local tissue changes (edema, abscesses, fistules and fibrosis)...
Several myotoxins have been isolated from Bothrops snake venoms during the last 10 years. All of them are group II basic phospholipases A 2 , although some lack enzymatic activity (i.e. Lys-49 variants). These myotoxins appear as an antigenically related family of proteins occurring in many, but not all, Bothrops venoms, bearing a close structural and antigenic relationship to toxins found...
Incubation of BaH1, the main hemorrhagic toxin purified from the venom of Bothrops asper, with endothelial cells caused the appearance of spaces among the cells. This effect became more noticeable with increasing hemorrhagin concentration and longer incubation time. Later, the cells became rounded and detached from the substrate into the medium. Augmentation of Trypan blue did not stain the detached...
We studied the ability of four commercially available antivenoms to neutralize several toxic and enzymatic activities ofBothrops asper (terciopelo) venom from Costa Rica. Experiments with preincubation of venom and antivenom were carried out to test the neutralization of lethal, hemorrhagic, coagulant and indirect hemolytic activities. In addition, antibody titers against crude venom and myotoxin...
No immunological cross-reactivity was observed between BaH1 and BaP1, two hemorrhagic metalloproteinases isolated from B. asper venom, by gel immunodiffusion, Western blotting and neutralization studies. Cross-reactivity was detected with antisera against these toxins in several crotaline and viperine snake venoms by ELISA, whereas no reactivity was observed with either antiserum against the venoms...
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