Leandro Norberto da Silva-Júnior, Lara de Souza Abreu, Caroline Fabri Bittencourt Rodrigues, Nathália da Costa Galizio, Weslei da Silva Aguiar, Caroline Serino-Silva, Valdomiro Souza Dos Santos, Isabella Alves Costa, Luis Vicente Franco Oliveira, Sávio Stefanini Sant'Anna, Kathleen Fernandes Grego, Anita Mitico Tanaka-Azevedo, Leandro Nascimento da Silva Rodrigues, Karen de Morais-Zani
{"title":"Geographic variation of individual venom profile of <i>Crotalus durissus</i> snakes.","authors":"Leandro Norberto da Silva-Júnior, Lara de Souza Abreu, Caroline Fabri Bittencourt Rodrigues, Nathália da Costa Galizio, Weslei da Silva Aguiar, Caroline Serino-Silva, Valdomiro Souza Dos Santos, Isabella Alves Costa, Luis Vicente Franco Oliveira, Sávio Stefanini Sant'Anna, Kathleen Fernandes Grego, Anita Mitico Tanaka-Azevedo, Leandro Nascimento da Silva Rodrigues, Karen de Morais-Zani","doi":"10.1590/1678-9199-JVATITD-2020-0016","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0016","url":null,"abstract":"<p><strong>Background: </strong>South American rattlesnakes are represented in Brazil by a single species, <i>Crotalus durissus</i>, which has public health importance due to the severity of its envenomation and to its wide geographical distribution. The species is subdivided into several subspecies, but the current classification is controversial. In Brazil, the venoms of <i>C. d. terrificus</i> and <i>C. d. collilineatus</i> are used for hyperimmunization of horses for antivenom production, even though the distinction of these two subspecies are mostly by their geographical distribution. In this context, we described a comparative compositional and functional characterization of individual <i>C. d. collilineatus</i> and <i>C. d. terrificus</i> venoms from three Brazilian states.</p><p><strong>Methods: </strong>We compared the compositional patterns of <i>C. d. terrificus</i> and <i>C. d. collilineatus</i> individual venoms by 1-DE and RP-HPLC. For functional analyzes, the enzymatic activities of PLA<sub>2</sub>, LAAO, and coagulant activity were evaluated. Finally, the immunorecognition of venom toxins by the crotalic antivenom produced at Butantan Institute was evaluated using Western blotting.</p><p><strong>Results: </strong>The protein profile of individual venoms from <i>C. d. collilineatus</i> and <i>C. d. terrificus</i> showed a comparable overall composition, despite some intraspecific variation, especially regarding crotamine and LAAO. Interestingly, HPLC analysis showed a geographic pattern concerning PLA<sub>2</sub>. In addition, a remarkable intraspecific variation was also observed in PLA<sub>2</sub>, LAAO and coagulant activities. The immunorecognition pattern of individual venoms from <i>C. d. collilineatus</i> and <i>C. d. terrificus</i> by crotalic antivenom produced at Butantan Institute was similar.</p><p><strong>Conclusions: </strong>The results highlighted the individual variability among the venoms of <i>C. durissus</i> ssp. specimens. Importantly, our data point to a geographical variation of <i>C. durissus</i> ssp. venom profile, regardless of the subspecies, as evidenced by PLA<sub>2</sub> isoforms complexity, which may explain the increase in venom neurotoxicity from Northeastern through Southern Brazil reported for the species.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200016"},"PeriodicalIF":2.4,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38374884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neisa Santos Carvalho Alves Pissurno, Lucas da Motta Esteves, Juliana Marques Benedito, Vanessa Ponsano Giglio, Lídia Raquel de Carvalho, Rinaldo Poncio Mendes, Anamaria Mello Miranda Paniago
{"title":"Impact of laryngeal sequelae on voice- and swallowing-related outcomes in paracoccidioidomycosis.","authors":"Neisa Santos Carvalho Alves Pissurno, Lucas da Motta Esteves, Juliana Marques Benedito, Vanessa Ponsano Giglio, Lídia Raquel de Carvalho, Rinaldo Poncio Mendes, Anamaria Mello Miranda Paniago","doi":"10.1590/1678-9199-JVATITD-2020-0008","DOIUrl":"10.1590/1678-9199-JVATITD-2020-0008","url":null,"abstract":"<p><strong>Background: </strong>The present study was carried out aiming to evaluate the impact of laryngeal sequelae on the quality of life of treated paracoccidioidomycosis (PCM) patients.</p><p><strong>Methods: </strong>This cross-sectional study was conducted at the Otorhinolaryngology Outpatient Clinic of the University Hospital, Federal University of Mato Grosso do Sul, Brazil. Thirty-two PCM patients considered clinically and immunologically cured were included: 16 with laryngeal involvement during the active phase of the disease (laryngeal PCM group) and 16 without laryngeal involvement (control group). They were submitted to structured interview, otorhinolaryngology examination, videolaryngoscopy, videoendoscopic swallowing study, completed two questionnaires for voice self-assessment - Voice-related Quality of Life (V-RQOL) and Voice Handicap Index (VHI) - and were asked to score their voices on a scale from zero to 10 (self-assessment of vocal quality).</p><p><strong>Results: </strong>Dysphonia was present in 50% of the cases. Patients with laryngeal PCM presented worse voice-related quality of life scores on the V-RQOL and poorer vocal quality self-assessment than the control group. No significant differences in the VHI were found between the groups. None of the participants developed dysphagic sequelae, although some minor changes were observed on videoendoscopic examination.</p><p><strong>Conclusion: </strong>There were no dysphagia complaints and only a few mild changes were found on the fiberoptic endoscopic evaluation of swallowing, suggesting that this evaluation should be performed only in specific cases. Patients with laryngeal involvement presented worse V-RQOL and self-assessment voice quality. This study contributes to the current knowledge of the functional assessment of the larynx affected by PCM and the impact of dysphonia on quality of life.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200008"},"PeriodicalIF":1.8,"publicationDate":"2020-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38421900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Venom peptides in association with standard drugs: a novel strategy for combating antibiotic resistance - an overview.","authors":"Ashish K Lamiyan, Ramkesh Dalal, Neelima R Kumar","doi":"10.1590/1678-9199-JVATITD-2020-0001","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0001","url":null,"abstract":"<p><p>Development of antibiotic resistance that leads to resurgence of bacterial infections poses a threat to disease-free existence for humankind and is a challenge for the welfare of the society at large. Despite research efforts directed towards treatment of pathogens, antibiotics within new improved classes have not emerged for years, a fact largely attributable to the pharmacological necessities compelling drug development. Recent reversion to the use of natural products alone or in combination with standard drugs has opened up new vistas for alternative therapeutics. The success of this strategy is evident in the sudden interest in plant extracts as additives/synergists for treatment of maladies caused by drug-resistant bacterial strains. Animal venoms have long fascinated scientists as sources of pharmacologically active components that can be exploited for the treatment of specific ailments and should be promoted further to clinical trials. In the present review, we outline the scope and possible methods for the applications of animal venoms in combination with commercial antibiotics to offer a better treatment approach against antibiotic-resistant infections.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200001"},"PeriodicalIF":2.4,"publicationDate":"2020-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38307819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Beatriz R Mayor, Leonardo A Guevarra, Myla R Santiago-Bautista, Librado A Santiago
{"title":"<i>Phlogiellus bundokalbo</i> spider venom: cytotoxic fractions against human lung adenocarcinoma (A549) cells.","authors":"Anna Beatriz R Mayor, Leonardo A Guevarra, Myla R Santiago-Bautista, Librado A Santiago","doi":"10.1590/1678-9199-JVATITD-2019-0104","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2019-0104","url":null,"abstract":"<p><strong>Background: </strong>Spider venom is a potential source of pharmacologically important compounds. Previous studies on spider venoms reported the presence of bioactive molecules that possess cell-modulating activities. Despite these claims, sparse scientific evidence is available on the cytotoxic mechanisms in relation to the components of the spider venom. In this study, we aimed to determine the cytotoxic fractions of the spider venom extracted from <i>Phlogiellus bundokalbo</i> and to ascertain the possible mechanism of toxicity towards human lung adenocarcinoma (A549) cells.</p><p><strong>Methods: </strong>Spider venom was extracted by electrostimulation. Components of the extracted venom were separated by reversed-phase high performance liquid chromatography (RP-HPLC) using a linear gradient of 0.1% trifluoroacetic acid (TFA) in water and 0.1% TFA in 95% acetonitrile (ACN). Cytotoxic activity was evaluated by the MTT assay. Apoptotic or necrotic cell death was assessed by microscopic evaluation in the presence of Hoechst 33342 and Annexin V, Alexa Fluor<sup>TM</sup> 488 conjugate fluorescent stains, and caspase activation assay. Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) activity of the cytotoxic fractions were also measured.</p><p><strong>Results: </strong>We observed and isolated six fractions from the venom of <i>P. bundokalbo</i> collected from Aurora, Zamboanga del Sur. Four of these fractions displayed cytotoxic activities. Fractions AT5-1, AT5-3, and AT5-4 were found to be apoptotic while AT5-6, the least polar among the cytotoxic components, was observed to induce necrosis. PLA<sub>2</sub> activity also showed cytotoxicity in all fractions but presented no relationship between specific activity of PLA<sub>2</sub> and cytotoxicity.</p><p><strong>Conclusion: </strong>The venom of <i>P. bundokalbo</i> spider, an endemic tarantula species in the Philippines, contains components that were able to induce either apoptosis or necrosis in A549 cells.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20190104"},"PeriodicalIF":2.4,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38260068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wesley L Fotoran, Nicole Kleiber, Thomas Müntefering, Eva Liebau, Gerhard Wunderlich
{"title":"Production of glycosylphosphatidylinositol-anchored proteins for vaccines and directed binding of immunoliposomes to specific cell types.","authors":"Wesley L Fotoran, Nicole Kleiber, Thomas Müntefering, Eva Liebau, Gerhard Wunderlich","doi":"10.1590/1678-9199-JVATITD-2020-0032","DOIUrl":"10.1590/1678-9199-JVATITD-2020-0032","url":null,"abstract":"<p><strong>Background: </strong>Liposomes are highly useful carriers for delivering drugs or antigens. The association of glycosylphosphatidylinositol (GPI)-anchored proteins to liposomes potentially enhances the immunogenic effect of vaccine antigens by increasing their surface concentration. Furthermore, the introduction of a universal immunoglobulin-binding domain can make liposomes targetable to virtually any desired receptor for which antibodies exist.</p><p><strong>Methods: </strong>We developed a system for the production of recombinant proteins with GPI anchors and histidine tags and Strep-tags for simplified purification from cells. This system was applied to i) the green fluorescent protein (GFP) as a reporter, ii) the promising <i>Plasmodium falciparum</i> vaccine antigen PfRH5 and iii) a doubled immunoglobulin Fc-binding domain termed ZZ from protein A of <i>Staphylococcus aureus</i>. As the GPI-attachment domain, the C-terminus of murine CD14 was used. After the recovery of these three recombinant proteins from Chinese hamster ovary (CHO) cells and association with liposomes, their vaccine potential and ability to target the CD4 receptor on lymphocytes in <i>ex vivo</i> conditions were tested.</p><p><strong>Results: </strong>Upon immunization in mice, the PfRH5-GPI-loaded liposomes generated antibody titers of 10<sup>3</sup> to 10<sup>4</sup>, and showed a 45% inhibitory effect on <i>in vitro</i> growth at an IgG concentration of 600 µg/mL in <i>P. falciparum</i> cultures. Using GPI-anchored ZZ to couple anti-CD4 antibodies to liposomes, we created immunoliposomes with a binding efficiency of 75% to CD4<sup>+</sup> cells in splenocytes and minimal off-target binding.</p><p><strong>Conclusions: </strong>Proteins are very effectively associated with liposomes via a GPI-anchor to form proteoliposome particles and these are useful for a variety of applications including vaccines and antibody-mediated targeting of liposomes. Importantly, the CHO-cell and GPI-tagged produced PfRH5 elicited invasion-blocking antibodies qualitatively comparable to other approaches.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200032"},"PeriodicalIF":1.8,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38260069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tihana Kurtović, Marija Brgles, Maja Lang Balija, Stephanie Steinberger, Dora Sviben, Martina Marchetti-Deschmann, Beata Halassy
{"title":"Streamlined downstream process for efficient and sustainable (Fab')<sub>2</sub> antivenom preparation.","authors":"Tihana Kurtović, Marija Brgles, Maja Lang Balija, Stephanie Steinberger, Dora Sviben, Martina Marchetti-Deschmann, Beata Halassy","doi":"10.1590/1678-9199-jvatitd-2020-0025","DOIUrl":"10.1590/1678-9199-jvatitd-2020-0025","url":null,"abstract":"<p><strong>Background: </strong>Antivenoms are the only validated treatment against snakebite envenoming. Numerous drawbacks pertaining to their availability, safety and efficacy are becoming increasingly evident due to low sustainability of current productions. Technological innovation of procedures generating therapeutics of higher purity and better physicochemical characteristics at acceptable cost is necessary. The objective was to develop at laboratory scale a compact, feasible and economically viable platform for preparation of equine F(ab')<sub>2</sub> antivenom against <i>Vipera ammodytes ammodytes</i> venom and to support it with efficiency data, to enable estimation of the process cost-effectiveness.</p><p><strong>Methods: </strong>The principle of simultaneous caprylic acid precipitation and pepsin digestion has been implemented into plasma downstream processing. Balance between incomplete IgG breakdown, F(ab')<sub>2</sub> over-digestion and loss of the active drug's protective efficacy was achieved by adjusting pepsin to a 1:30 substrate ratio (<i>w</i>/<i>w</i>) and setting pH at 3.2. Precipitation and digestion co-performance required 2 h-long incubation at 21 °C. Final polishing was accomplished by a combination of diafiltration and flow-through chromatography. <i>In vivo</i> neutralization potency of the F(ab')<sub>2</sub> product against the venom's lethal toxicity was determined.</p><p><strong>Results: </strong>Only three consecutive steps, performed under finely tuned conditions, were sufficient for preservation of the highest process recovery with the overall yield of 74%, comparing favorably to others. At the same time, regulatory requirements were met. Final product was aggregate- and pepsin-free. Its composition profile was analyzed by mass spectrometry as a quality control check. Impurities, present in minor traces, were identified mostly as IgG/IgM fragments, contributing to active drug. Specific activity of the F(ab')<sub>2</sub> preparation with respect to the plasma was increased 3.9-fold.</p><p><strong>Conclusion: </strong>A highly streamlined mode for production of equine F(ab')<sub>2</sub> antivenom was engineered. In addition to preservation of the highest process yield and fulfillment of the regulatory demands, performance simplicity and rapidity in the laboratory setting were demonstrated. Suitability for large-scale manufacturing appears promising.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200025"},"PeriodicalIF":2.4,"publicationDate":"2020-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38236811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Choo Hock Tan, Jia Lee Liew, Suerialoasan Navanesan, Kae Shin Sim, Nget Hong Tan, Kae Yi Tan
{"title":"Cytotoxic and anticancer properties of the Malaysian mangrove pit viper (<i>Trimeresurus purpureomaculatus</i>) venom and its disintegrin (purpureomaculin).","authors":"Choo Hock Tan, Jia Lee Liew, Suerialoasan Navanesan, Kae Shin Sim, Nget Hong Tan, Kae Yi Tan","doi":"10.1590/1678-9199-JVATITD-2020-0013","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0013","url":null,"abstract":"<p><strong>Background: </strong>The Asiatic pit vipers from the <i>Trimeresurus</i> complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of <i>Trimeresurus</i> spp.; however, hold great potential for the development of peptide-based anticancer drugs.</p><p><strong>Methods: </strong>This study investigated the cytotoxic effect of the venom from <i>Trimeresurus purpureomaculatus</i>, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue.</p><p><strong>Results: </strong>The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC<sub>50</sub>) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C<sub>18</sub> reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study.</p><p><strong>Conclusion: </strong>Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian <i>T. purpureomaculatus</i> venom and suggested its anticancer potential in drug discovery.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200013"},"PeriodicalIF":2.4,"publicationDate":"2020-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38227657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tuchakorn Lertwanakarn, Montamas Suntravat, Elda E Sanchez, Worakan Boonhoh, R John Solaro, Beata M Wolska, Jody L Martin, Pieter P de Tombe, Kittipong Tachampa
{"title":"Suppression of cardiomyocyte functions by β-CTX isolated from the Thai king cobra (<i>Ophiophagus hannah</i>) venom via an alternative method.","authors":"Tuchakorn Lertwanakarn, Montamas Suntravat, Elda E Sanchez, Worakan Boonhoh, R John Solaro, Beata M Wolska, Jody L Martin, Pieter P de Tombe, Kittipong Tachampa","doi":"10.1590/1678-9199-JVATITD-2020-0005","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2020-0005","url":null,"abstract":"<p><strong>Background: </strong>Beta-cardiotoxin (β-CTX), the three-finger toxin isolated from king cobra (<i>Ophiophagus hannah</i>) venom, possesses β-blocker activity as indicated by its negative chronotropy and its binding property to both β-1 and β-2 adrenergic receptors and has been proposed as a novel β-blocker candidate. Previously, β-CTX was isolated and purified by FPLC. Here, we present an alternative method to purify this toxin. In addition, we tested its cytotoxicity against different mammalian muscle cell types and determined the impact on cardiac function in isolated cardiac myocyte so as to provide insights into the pharmacological action of this protein.</p><p><strong>Methods: </strong>β-CTX was isolated from the crude venom of the Thai king cobra using reverse-phased and cation exchange HPLC. <i>In vitro</i> cellular viability MTT assays were performed on mouse myoblast (C2C12), rat smooth muscle (A7r5), and rat cardiac myoblast (H9c2) cells. Cell shortening and calcium transient dynamics were recorded on isolated rat cardiac myocytes over a range of β-CTX concentration.</p><p><strong>Results: </strong>Purified β-CTX was recovered from crude venom (0.53% w/w). MTT assays revealed 50% cytotoxicity on A7r5 cells at 9.41 ± 1.14 µM (n = 3), but no cytotoxicity on C2C12 and H9c2 cells up to 114.09 µM. β-CTX suppressed the extend of rat cardiac cell shortening in a dose-dependent manner; the half-maximal inhibition concentration was 95.97 ± 50.10 nM (n = 3). In addition, the rates of cell shortening and re-lengthening were decreased in β-CTX treated myocytes concomitant with a prolongation of the intracellular calcium transient decay, indicating depression of cardiac contractility secondary to altered cardiac calcium homeostasis.</p><p><strong>Conclusion: </strong>We present an alternative purification method for β-CTX from king cobra venom. We reveal cytotoxicity towards smooth muscle and depression of cardiac contractility by this protein. These data are useful to aid future development of pharmacological agents derived from β-CTX.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200005"},"PeriodicalIF":2.4,"publicationDate":"2020-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38227689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum: Antiproliferative activity of marine stingray <i>Dasyatis sephen</i> venom on human cervical carcinoma cell line.","authors":"","doi":"10.1590/s40409-015-0036-5er","DOIUrl":"https://doi.org/10.1590/s40409-015-0036-5er","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1186/s40409-015-0036-5.].</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20200101"},"PeriodicalIF":2.4,"publicationDate":"2020-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38194010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polianna Lemos Moura Moreira Albuquerque, José Hicaro Hellano Gonçalves Lima Paiva, Alice Maria Costa Martins, Gdayllon Cavalcante Meneses, Geraldo Bezerra da Silva, Nicholas Buckley, Elizabeth De Francesco Daher
{"title":"Clinical assessment and pathophysiology of <i>Bothrops</i> venom-related acute kidney injury: a scoping review.","authors":"Polianna Lemos Moura Moreira Albuquerque, José Hicaro Hellano Gonçalves Lima Paiva, Alice Maria Costa Martins, Gdayllon Cavalcante Meneses, Geraldo Bezerra da Silva, Nicholas Buckley, Elizabeth De Francesco Daher","doi":"10.1590/1678-9199-JVATITD-2019-0076","DOIUrl":"10.1590/1678-9199-JVATITD-2019-0076","url":null,"abstract":"<p><p><i>Bothrops</i> are one of the most common medically important snakes found in Latin America. Its venom is predominantly hemotoxic and proteolytic, which means that local lesion (edema and redness) and hemorrhagic symptoms are recurrent in envenoming by this snake. Although hemorrhage is usually the major cause of death, snakebite-related acute kidney injury is another potentially fatal clinical complication that may lead to chronic kidney disease. The present review highlights the main studies on <i>Bothrops</i> venom-related acute kidney injury, including observational, cross-sectional, case-control and cohort human studies available up to December 2019. The following descriptors were used according to Medical Subject Headings (MeSH): on Medline/Pubmed and Google Scholar \"acute kidney injury\" <i>or</i> \"kidney disease\" <i>and</i> \"<i>Bothrops</i>\"; on Lilacs and SciELO \"kidney disease\" <i>or</i> \"acute kidney injury\" <i>and</i> \"<i>Bothrops</i>\". Newcastle-Ottawa quality assessment scale was used to appraise the quality of the cross-sectional and cohort studies included. The selection of more severe patients who looked for health care units and tertiary centers is a risk of bias. Due to the methodological heterogeneity of the studies, a critical analysis of the results was performed based on the hypothesis that the design of the included studies influences the incidence of acute kidney injury. Fifteen human studies (total participants 4624) were included according to stablished criteria. The coagulation abnormalities (hemorrhagic symptoms, abnormal fibrinogen and activated partial thromboplastin time) were associated with acute kidney injury in the most recent studies reported. The findings observed in this review provide up-to-date evidence about the acute kidney injury pathogenesis following <i>Bothrops</i> syndrome. Studies pointed out that coagulation abnormalities comprise the major pathway for acute kidney injury development. This review may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment of <i>Bothrops</i> venom-related acute kidney injury.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":"26 ","pages":"e20190076"},"PeriodicalIF":2.4,"publicationDate":"2020-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38194011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}