Journal of Venomous Animals and Toxins Including Tropical Diseases最新文献

{"title":"A scoping study of pulmonary paracoccidioidomycosis: severity classification based on radiographic and tomographic evaluation.","authors":"Sergio Marrone Ribeiro,&nbsp;Thiago Franchi Nunes,&nbsp;Ricardo de Souza Cavalcante,&nbsp;Anamaria Mello Miranda Paniago,&nbsp;Beatriz Aparecida Soares Pereira,&nbsp;Rinaldo Poncio Mendes","doi":"10.1590/1678-9199-JVATITD-2022-0053","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0053","url":null,"abstract":"<p><p>The lungs have great importance in patients with paracoccidioidomycosis since they are the portal of entry for the infecting fungi, the site of quiescent foci, and one of the most frequently affected organs. Although they have been the subject of many studies with different approaches, the severity classification of the pulmonary involvement, using imaging procedures, has not been carried out yet. This study aimed to classify the active and the residual pulmonary damage using radiographic and tomographic evaluations, according to the area involved and types of lesions.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9704082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35344054","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":"New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A₂.","authors":"Jeane do Nascimento Moraes,&nbsp;Aleff Ferreira Francisco,&nbsp;Leandro Moreira Dill,&nbsp;Rafaela Souza Diniz,&nbsp;Claudia Siqueira de Oliveira,&nbsp;Tainara Maiane Rodrigues da Silva,&nbsp;Cleópatra Alves da Silva Caldeira,&nbsp;Edailson de Alcântara Corrêa,&nbsp;Antônio Coutinho-Neto,&nbsp;Fernando Berton Zanchi,&nbsp;Marcos Roberto de Mattos Fontes,&nbsp;Andreimar Martins Soares,&nbsp;Leonardo de Azevedo Calderon","doi":"10.1590/1678-9199-JVATITD-2022-0002","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0002","url":null,"abstract":"<p><strong>Background: </strong>Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme.</p><p><strong>Methods: </strong>An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A₂ (svPLA₂), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA₂. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA₂ was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques.</p><p><strong>Conclusion: </strong>The present study suggests the versatility of human CatD and svPLA₂, showing that these enzymes can form a fully functional new enzymatic complex.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9647731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40697626","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":"Late peripheral facial paralysis after COVID-19: a rapid systematic review and two case reports.","authors":"Thalitta Mendes Cavalcante,&nbsp;Vanessa Terezinha Gubert,&nbsp;Carolina de Deus Lima,&nbsp;Larissa Anjos Luciano,&nbsp;Mariana Garcia Croda,&nbsp;James Venturini,&nbsp;Antonio Luiz Dal Bello Gasparoto,&nbsp;Wellyngton Matheus Souza Santiago,&nbsp;Ana Rita Coimbra Motta-Castro,&nbsp;Fernanda Paes Reis,&nbsp;Ana Paula da Costa Marques,&nbsp;Aline Pedroso Lorenz,&nbsp;Wellington Santos Fava,&nbsp;Marina Castilhos Souza Umaki Zardin,&nbsp;Cláudia Elizabeth Volpe Chaves,&nbsp;Gabriel Pereira Braga,&nbsp;Anamaria Mello Miranda Paniago,&nbsp;Sandra Maria do Valle Leone de Oliveira","doi":"10.1590/1678-9199-JVATITD-2022-0020","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0020","url":null,"abstract":"<p><p>Peripheral facial paralysis (PFP) has been shown to be a neurological manifestation of COVID-19. The current study presents two cases of PFP after COVID-19, along with a rapid review of known cases in the literature. Both case reports were conducted following CARE guidelines. We also performed a systematic review of PFP cases temporally related to COVID-19 using PubMed, Embase, and Cochrane Library databases on August 30, 2021, using a rapid review methodology. The two patients experienced PFP 102 and 110 days after COVID-19 symptom onset. SARS-CoV-2 RNA was detected in nasal samples through reverse-transcription real-time polymerase chain reaction (RT-qPCR) testing. Anosmia was the only other neurological manifestation. PFP was treated with steroids in both cases, with complete subsequent recovery. In the rapid review, we identified 764 articles and included 43 studies. From those, 128 patients with PFP were analyzed, of whom 42.1% (54/128) were male, 39.06% (50/128) female, and in 23 cases the gender was not reported. The age range was 18 to 59 (54.68%). The median time between COVID-19 and PFP was three days (ranging from the first symptom of COVID-19 to 40 days after the acute phase of infection). Late PFP associated with COVID-19 presents mild symptoms and improves with time, with no identified predictors. Late PFP should be added to the spectrum of neurological manifestations associated with the long-term effects of SARS-CoV-2 infection as a post COVID-19 condition.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9581522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40431099","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":"Inhibitory activities of propolis, nisin, melittin and essential oil compounds on <i>Paenibacillus alvei</i> and <i>Bacillus subtilis</i>.","authors":"Alessandra Aguirra Sani,&nbsp;Ana Flávia Marques Pereira,&nbsp;Alessandra Furlanetto,&nbsp;Débora Silva Marques de Sousa,&nbsp;Tatiane Baptista Zapata,&nbsp;Vera Lucia Mores Rall,&nbsp;Ary Fernandes","doi":"10.1590/1678-9199-JVATITD-2022-0025","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0025","url":null,"abstract":"<p><strong>Background: </strong>Natural products represent important sources of antimicrobial compounds. Propolis and compounds from essential oils comprise good examples of such substances because of their inhibitory effects on bacterial spores, including bee pathogens.</p><p><strong>Methods: </strong>Ethanol extracts of propolis (EEP) from <i>Apis mellifera</i> were prepared using different methods: double ultrasonication, double maceration and maceration associated with ultrasonication. Together with the antimicrobial peptides nisin and melittin, and compounds present in the essential oils of clove (<i>Syzygium aromaticum</i>) and cinnamon (<i>Cinnamomum zeylanicum</i>), assays were carried out on one <i>Bacillus subtilis</i> isolate and <i>Paenibacillus alvei</i> (ATCC 6344) against vegetative and sporulated forms, using the resazurin microtiter assay. Synergism with all the antimicrobials in association with tetracycline was verified by the time-kill curve method. Potassium and phosphate efflux, release of proteins and nucleic acids were investigated.</p><p><strong>Results: </strong>EEPs showed the same MIC, 156.25 µg/mL against <i>B. subtilis</i> and 78.12 µg/mL against <i>P. alvei</i>. The peptides showed better activities against <i>B. subtilis</i> (MIC of 12 µg/mL for melittin and 37.50 µg/mL for nisin). Antimicrobials showed similar inhibitory effects, but cinnamaldehyde (39.06 µg/mL) showed the best action against <i>P. alvei</i>. Melittin and nisin showed the greatest capacity to reduce spores, regarding <i>B. subtilis</i> there was a 100% reduction at 6.25 and 0.78 µg/mL, respectively. Concerning <i>P. alvei</i>, the reduction was 93 and 98% at concentrations of 80 µg/mL of melittin and 15 µg/mL of nisin. EEPs showed the highest effects on the protein release against <i>B. subtilis</i> and <i>P. alvei</i>. Nucleic acid release, phosphate and potassium efflux assays indicated bacterial cell membrane damage. Synergism between antimicrobials and tetracycline was demonstrated against both bacteria.</p><p><strong>Conclusion: </strong>All antimicrobials tested showed antibacterial activities against vegetative and sporulated forms of <i>P. alvei</i> and <i>B. subtilis</i>, especially nisin and melittin. Synergism with tetracycline and damage on bacterial cell membrane also occurred.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40364937","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":"Antifungal activity of liriodenine on clinical strains of <i>Cryptococcus neoformans</i> and <i>Cryptococcus gattii</i> species complexes.","authors":"Adriele Dandara Levorato-Vinche,&nbsp;Marcia de Souza Carvalho Melhem,&nbsp;Lucas Xavier Bonfietti,&nbsp;Iván de-la-Cruz-Chacón,&nbsp;Carmen Sílvia Fernandes Boaro,&nbsp;Alexandre Todorovic Fabro,&nbsp;Gisela Ferreira,&nbsp;Julhiany de Fátima da Silva,&nbsp;Daniela Carvalho Dos Santos,&nbsp;Beatriz Aparecida Soares Pereira,&nbsp;Camila Marçon,&nbsp;Lariza Maza,&nbsp;Lídia Raquel de Carvalho,&nbsp;Rinaldo Poncio Mendes","doi":"10.1590/1678-9199-JVATITD-2022-0006","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0006","url":null,"abstract":"<p><strong>Background: </strong>Cryptoccocal meningitis continues to present high incidence among AIDS patients. The treatment of choice is the synergistic combination of flucytosine (5-FC) with amphotericin B deoxycholate (AmBd) or its lipid formulations. However, 5-FC is unavailable in many countries and AmB demands hospitalization. The combination of AmB with the fungistatic fluconazole (FLC) or the use of high FLC daily doses alone became the choice. Nonetheless, sterilization of cerebrospinal fluid is delayed with FLC monotherapy, mainly with high fungal burden. These findings suggest the search for new antifungal compounds, such as liriodenine.</p><p><strong>Methods: </strong>Liriodenine antifungal activity was evaluated by three procedures: determining the minimum inhibitory concentration (MIC) on 30 strains of the <i>Cryptococcus neoformans</i> (<i>C. neoformans</i>) complex and 30 of the <i>Cryptococcus gattii</i> (<i>C. gattii</i>) complex, using EUCAST methodology and amphotericin B deoxycholate as control; performing the time-kill methodology in two strains of the <i>C. neoformans</i> complex and one of the <i>C. gattii</i> complex; and injury to cryptococcal cells, evaluated by transmission electron microscopy (TEM). Liriodenine absorption and safety at 0.75 and 1.50 mg.kg^-1 doses were evaluated in BALB/c mice.</p><p><strong>Results: </strong>Liriodenine MICs ranged from 3.9 to 62.5 μg.mL^-1 for both species complexes, with no differences between them. Time-kill methodology confirmed its concentration-dependent fungicidal effect, killing all the strains below the limit of detection (33 CFU.mL^-1) at the highest liriodenine concentration (32-fold MIC), with predominant activity during the first 48 hours. Liriodenine induced severe <i>Cryptococcus</i> alterations - cytoplasm with intense rarefaction and/or degradation, injury of organelles, and presence of vacuoles. Liriodenine was better absorbed at lower doses, with no histopathological alterations on the digestive tract.</p><p><strong>Conclusion: </strong>The fungicidal activity confirmed by time-kill methodology, the intense <i>Cryptococcus</i> injury observed by TEM, the absorption after gavage administration, and the safety at the tested doses indicate that the liriodenine molecule is a promising drug lead for development of anticryptococcal agents.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40364938","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":"Hemolymph of triatomines presents fungistatic activity against <i>Cryptococcus neoformans</i> and improves macrophage function through MCP-I/TNF-α increase.","authors":"Luísa Menezes-Silva, Jonatas da Silva Catarino, Laura Caroline de Faria, Bárbara Cristina Pizzolante, Leonardo Eurípedes Andrade-Silva, Marcos Vinicius da Silva, Virmondes Rodrigues, Helioswilton Sales-Campos, Carlo José Freire Oliveira","doi":"10.1590/1678-9199-JVATITD-2021-0124","DOIUrl":"10.1590/1678-9199-JVATITD-2021-0124","url":null,"abstract":"<p><strong>Background: </strong>Triatomines are blood-feeding arthropods belonging to the subfamily Triatominae (Hemiptera; Reduviidae), capable of producing immunomodulatory and water-soluble molecules in their hemolymph, such as antimicrobial peptides (AMPs). In this work, we evaluated the antifungal and immunomodulatory activity of the hemolymph of <i>Meccus pallidipennis</i> (MPH) and <i>Rhodnius prolixus</i> (RPH) against <i>Cryptococcus neoformans</i>.</p><p><strong>Methods: </strong>We assessed the activity of the hemolymph of both insects on fungal growth by a minimum inhibitory concentration (MIC) assay. Further, RAW 264.7 macrophages were cultivated with hemolymph and challenged with <i>C. neoformans</i>. Then, their phagocytic and killing activities were assessed. The cytokines MCP-1, IFN-γ, TNF-α, IL-10, IL-12, and IL-6 were measured in culture supernatants 4- and 48-hours post-infection.</p><p><strong>Results: </strong>Both hemolymph samples directly affected the growth rate of the fungus in a dose-dependent manner. Either MPH or RPH was capable of inhibiting fungal growth by at least 70%, using the lowest dilution (1:20). Treatment of RAW 264.7 macrophages with hemolymph of both insects was capable of increasing the production of MCP-I and TNF-α. In addition, when these cells were stimulated with hemolymph in the presence of <i>C. neoformans</i>, a 2- and a 4-fold increase in phagocytic rate was observed with MPH and RPH, respectively, when compared to untreated cells. For the macrophage killing activity, MPH decreased in approximately 30% the number of viable yeasts inside the cells compared to untreated control; however, treatment with RPH could not reduce the total number of viable yeasts. MPH was also capable of increasing MHC-II expression on macrophages. Regarding the cytokine production, MCP-I and TNF-α, were increased in the supernatant of macrophages treated with both hemolymphs, 4 and 48 hours after stimulation.</p><p><strong>Conclusion: </strong>These results suggested that hemolymph of triatomines may represent a source of molecules capable of presenting antifungal and immunomodulatory activity in macrophages during fungal infection.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2022-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40670905","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":"Back to <i>Tityus serrulatus</i> Lutz & Mello, 1922 (Scorpiones: Buthidae): new comments about an old species.","authors":"Wilson R Lourenço","doi":"10.1590/1678-9199-JVATITD-2022-0016","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0016","url":null,"abstract":"<p><p>A synopsis on the historical, geographical and ecological aspects related to the most conspicuous scorpion species of the genus <i>Tityus</i> known from Brazil is proposed. <i>Tityus serrulatus</i> Lutz & Mello, 1922 was described precisely one century ago, nevertheless many questions related to its ecological adaptations and geographical expansion remain without a precise response. This species, well known for its infamous reputation of noxious species, is also known for its capacity to reproduce asexually, by parthenogenesis. Although the individuals of a given population are considered clones, a new hypothesis could suggest the occurrence of mutations within isolated individuals, leading to distinct subpopulations that could present better phenotypic performances in ecological habitats distinct from those of the original area of distribution of the species.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40670906","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 composition of <i>Trimeresurus albolabris, T. insularis, T. puniceus</i> and <i>T. purpureomaculatus</i> from Indonesia.","authors":"Syahfitri Anita,&nbsp;Arif Rahman Sadjuri,&nbsp;Latri Rahmah,&nbsp;Herjuno Ari Nugroho,&nbsp;Mulyadi,&nbsp;Wahyu Trilaksono,&nbsp;Wiwit Ridhani,&nbsp;Nabila Safira,&nbsp;Hariman Bahtiar,&nbsp;Maharani,&nbsp;Amir Hamidy,&nbsp;Adriansjah Azhari","doi":"10.1590/1678-9199-JVATITD-2021-0103","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2021-0103","url":null,"abstract":"<p><strong>Background: </strong>Several studies have been published on the characterization of <i>Trimeresurus</i> venoms. However, there is still limited information concerning the venom composition of <i>Trimeresurus</i> species distributed throughout Indonesia, which contributes to significant snakebite envenomation cases. The present study describes a comparative on the composition of <i>T. albolabris, T. insularis, T. puniceus,</i> and <i>T. purpureomaculatus</i> venoms originated from Indonesia.</p><p><strong>Methods: </strong>Protein content in the venom of four <i>Trimeresurus</i> species was determined using Bradford assay, and the venom proteome was elucidated using one-dimension SDS PAGE nano-ESI- LCMS/MS shotgun proteomics.</p><p><strong>Results: </strong>The venom of <i>T. albolabris</i> contained the highest protein content of 11.1 mg/mL, followed by <i>T. puniceus</i>, <i>T. insularis</i> and <i>T. purpureomaculatus</i> venom with 10.7 mg/mL, 8.9 mg/mL and 5.54 mg/mL protein, respectively. In total, our venomic analysis identified 65 proteins belonging to 16 protein families in <i>T. purpureomaculatus</i>; 64 proteins belonging to 18 protein families in <i>T. albolabris</i>; 58 different proteins belonging to 14 protein families in <i>T. puniceus</i>; and 48 different proteins belonging to 14 protein familiesin <i>T. insularis.</i> Four major proteins identified in all venoms belonged to snake venom metalloproteinase, C-type lectin, snake venom serine protease, and phospholipase A2. There were 11 common proteins in all venoms, and <i>T. puniceus</i> venom has the highest number of unique proteins compared to the other three venoms. Cluster analysis of the proteins and venoms showed that <i>T. puniceus</i> venom has the most distinct venom composition.</p><p><strong>Conclusions: </strong>Overall, the results highlighted venom compositional variation of four <i>Trimeresurus</i> spp. from Indonesia. The venoms appear to be highly similar, comprising at least four protein families that correlate with venom's toxin properties and function. This study adds more information on venom variability among <i>Trimeresurus</i> species within the close geographic origin and may contribute to the development of optimum heterologous antivenom.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40535136","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":"<i>In vitro</i> and <i>in silico</i> evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools.","authors":"Isabella Maria Monteiro de Souza,&nbsp;Romulo Dias Novaes,&nbsp;Reggiani Vilela Gonçalves,&nbsp;Felipe Leonardo Bley Fialho,&nbsp;Diogo Teixeira Carvalho,&nbsp;Thiago Belarmino de Souza,&nbsp;Danielle Ferreira Dias,&nbsp;Stefânia Neiva Lavorato,&nbsp;Raquel Lopes Martins Souza,&nbsp;Marcos José Marques,&nbsp;Aline Pereira Castro","doi":"10.1590/1678-9199-JVATITD-2021-0108","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2021-0108","url":null,"abstract":"<p><strong>Background: </strong>Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome.</p><p><strong>Methods: </strong>The <i>in vitro</i> activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from <i>Schistosoma mansoni</i> were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na⁺/K⁺-ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na⁺/K⁺-ATPase, while <i>in silico</i> analysis identified potential Na⁺/K⁺-ATPase binding sites.</p><p><strong>Results: </strong>The compounds showed effective doses (ED₅₀) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED_50, ED₉₀ and ED₁₀₀ (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 <i>versus</i> 72 hours) and FB9 (192 <i>versus</i> 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited Na⁺/K⁺-ATPase activity according to <i>in silico</i> analysis but FB4 did not show a time-dependent relationship and may act on targets other than the parasite Na+/K+-ATPase.</p><p><strong>Conclusion: </strong>Eugenol derivatives, mainly FB4 when compared to FB1 and FB9, seem to act more effectively on the integument of adult <i>S. mansoni</i> worms.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40607922","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":"Launching a CDMO in Brazil aiming to develop biopharmaceuticals for clinical trials.","authors":"Rui Seabra Ferreira,&nbsp;Marcelo Marcos Morales,&nbsp;Pasqual Barretti,&nbsp;Benedito Barraviera","doi":"10.1590/1678-9199-JVATITD-2022-0017","DOIUrl":"https://doi.org/10.1590/1678-9199-JVATITD-2022-0017","url":null,"abstract":"<p><p>The innovation timeline is expensive, risky, competitive, time-consuming, and labor-intensive. In order to overcome such challenges and optimize financial resources, pharmaceutical companies nowadays hire contract development and manufacturing organizations (CDMO) to help them. Based on the experience acquired first from the development of two biopharmaceuticals, the Heterologous Fibrin Sealant and the Apilic Antivenom, and more recently, during their respective clinical trials; the Center for the Study of Venoms and Venomous Animals (CEVAP) proposed to the Ministry of Health the creation of the first Brazilian CDMO. This groundbreaking venture will assist in converting a candidate molecule - from its discovery, proof of concept, product development, up to pilot batch production - into a product. The CDMO impact and legacy will be immense, offering service provision to the public and private sector by producing validated samples for clinical trials and academic training on translational research for those seeking a position in pharmaceutical industries and manufacturing platforms.</p>","PeriodicalId":17565,"journal":{"name":"Journal of Venomous Animals and Toxins Including Tropical Diseases","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40041266","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}