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The inclusion of antioxidants (AOXs) has been proposed in various protocols to conserve the normal physiology of spermatozoa during (cryo) preservation. The main aim of this review was to understand the necessity of AOXs inclusion in semen extenders of caprine and ovine semen samples and to decipher physico-chemical space of AOXs used in semen extenders till now. A total 27 full-text relevant articles were finally discussed here. This systematic review showed that the inclusion of AOXs may improve the success of semen cryopreservation although at least three studies could not support this finding. AOXs have been not added after assaying total antioxidant capacity of the sample of interest, and this is principal measurement bias of all papers. Furthermore, no rational dose-response curve and precise posology have been considered in comparable studies. Furthermore, new methodologies are requested to detect the oxidative status of semen specimens before AXOs fortification and new methodologies like imaging are also needed to detect various injuries of sperms during semen (cryo)preservation. Defining computational chemical and physical spaces of AOXs which used in semen (cryo)preservation would be an interdisciplinary effort to hasten deciphering epoch-making compounds. In conclusion, more in-depth analytical, toxicological and pharmacological methodologies should be pursued in supplementation or addition of AOXs during caprine and ovine semen (cryo)preservation after determining the oxidative status of semen samples.
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Antioxidantes/farmacologia , Criopreservação/veterinária , Preservação do Sêmen/veterinária , Animais , Antioxidantes/química , Criopreservação/métodos , Crioprotetores , Cabras , Masculino , Sêmen , Preservação do Sêmen/métodos , Ovinos , Espermatozoides/fisiologiaRESUMO
In this study, the frequency of different types of mammary masses and their relationship with cytohistopathologic changes was investigated and data on history, macroscopic description, clinical examination and treatment were collected. To determine the prevalence and types of cytohistopathologic changes, mammary glands from 12 female cats were evaluated. The mean age of cats at the time of diagnosis was 11.5 ± 1.9 years (range 4-14 years), the mean gross size of the masses was 3.1 ± 2.4 cm, 4/12 (33.3 %) masses were ≤3.0 cm in diameter, and the maximum diameter of the largest mass had a median of 5 cm, with a range of diameter of 6 × 5 × 4 cm. Moreover, the preferential localization of mammary masses was the abdominal lobes (%50) and thoracic lobes (%33.3), and inguinal lobes (%16.7 of cases). Furthermore, two cases of the inguinal masses affected the caudo-inguinal lobe, six cases caudo-abdominal lobe, and thoracic masses were found in four cases. Eventually, six cases (%50) of masses were found in the right mammary lobes and six cases (%50) in the left mammary lobes. The majority of the masses revealed elastic (%50 of cases), hard (%25 of cases), or soft (%25 of cases) consistency. In the present study, according to the criteria of the veterinary and the medical WHO classification system, of the 12 cats with the cytohistopathological features of six (50 %) cases qualified abscess, 3 (25 %) cases as cystic hyperplasia and 3 (25 %) cases were called situ carcinoma. Whereas, all hyperplastic lesions (case nos. 7-9 and ranging in size from, 1 to >4 cm(3)) and carcinomas in situ lesions (case nos. 10-12 and ranging in size from, 1 to >3 cm(3)) were found incidentally upon routine cytohistology. Other lesions were observed grossly and removed either at surgery (case nos. 1-6). Finally, the cats were treated with unilateral lumpectomy (3 cases) and also, nine (75 %) cases had subsequent drainage, 3 (25 %) of which showed cystic hyperplasia and 6 (50 %) showed abscess on subsequent histopathological evaluation. Therefore, a correct diagnosis must be established quickly, and treatment must be instituted rapidly when alteration is noted in the mammary glands.
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Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/diagnóstico , Neoplasias Mamárias Experimentais/terapia , Animais , Gatos , Modelos Animais de Doenças , Feminino , Humanos , Carga TumoralRESUMO
Oligoclonal mixtures of broadly-neutralizing antibodies can neutralize complex compositions of similar and dissimilar antigens, making them versatile tools for the treatment of e.g., infectious diseases and animal envenomations. However, these biotherapeutics are complicated to develop due to their complex nature. In this work, we describe the application of various strategies for the discovery of cross-neutralizing nanobodies against key toxins in coral snake venoms using phage display technology. We prepare two oligoclonal mixtures of nanobodies and demonstrate their ability to neutralize the lethality induced by two North American coral snake venoms in mice, while individual nanobodies fail to do so. We thus show that an oligoclonal mixture of nanobodies can neutralize the lethality of venoms where the clinical syndrome is caused by more than one toxin family in a murine challenge model. The approaches described may find utility for the development of advanced biotherapeutics against snakebite envenomation and other pathologies where multi-epitope targeting is beneficial.
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Anticorpos Neutralizantes , Cobras Corais , Anticorpos de Domínio Único , Animais , Anticorpos de Domínio Único/imunologia , Camundongos , Anticorpos Neutralizantes/imunologia , Cobras Corais/imunologia , Modelos Animais de Doenças , Antivenenos/imunologia , Venenos Elapídicos/imunologia , Feminino , Mordeduras de Serpentes/imunologia , Mordeduras de Serpentes/terapia , Epitopos/imunologia , Camundongos Endogâmicos BALB C , Técnicas de Visualização da Superfície CelularRESUMO
Immunoglobulin G (IgG) antibodies that bind their cognate antigen in a pH-dependent manner (acid-switched antibodies) can release their bound antigen for degradation in the acidic environment of endosomes, while the IgGs are rescued by the neonatal Fc receptor (FcRn). Thus, such IgGs can neutralize multiple antigens over time and therefore be used at lower doses than their non-pH-responsive counterparts. Here, we show that light-chain shuffling combined with phage display technology can be used to discover IgG1 antibodies with increased pH-dependent antigen binding properties, using the snake venom toxins, myotoxin II and α-cobratoxin, as examples. We reveal differences in how the selected IgG1s engage their antigens and human FcRn and show how these differences translate into distinct cellular handling properties related to their pH-dependent antigen binding phenotypes and Fc-engineering for improved FcRn binding. Our study showcases the complexity of engineering pH-dependent antigen binding IgG1s and demonstrates the effects on cellular antibody-antigen recycling.
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Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors (nAChRs) resulting in life-threatening neurotoxicity4. Currently, the only available treatments for snakebite consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5,6,7. Here, we use deep learning methods to de novo design proteins to bind short- and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtain protein designs with remarkable thermal stability, high binding affinity, and near-atomic level agreement with the computational models. The designed proteins effectively neutralize all three 3FTx sub-families in vitro and protect mice from a lethal neurotoxin challenge. Such potent, stable, and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective, and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our computational design methodology should help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for development of therapies to neglected tropical diseases.
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Ion channels play a crucial role in diverse physiological processes, including neurotransmission and muscle contraction. Venomous creatures exploit the vital function of ion channels by producing toxins in their venoms that specifically target these ion channels to facilitate prey capture upon a bite or a sting. Envenoming can therefore lead to ion channel dysregulation, which for humans can result in severe medical complications that often necessitate interventions such as antivenom administration. Conversely, the discovery of highly potent and selective venom toxins with the capability of distinguishing between different isoforms and subtypes of ion channels has led to the development of beneficial therapeutics that are now in the clinic. This review encompasses the historical evolution of electrophysiology methodologies, highlighting their contributions to venom and antivenom research, including venom-based drug discovery and evaluation of antivenom efficacy. By discussing the applications and advancements in patch-clamp techniques, this review underscores the profound impact of electrophysiology in unravelling the intricate interplay between ion channels and venom toxins, ultimately leading to the development of drugs for envenoming and ion channel-related pathologies.
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MicroRNAs (miRNAs) are small single-stranded RNAs belonging to a class of non-coding RNAs with an average length of 18-22 nucleotides. Although not able to encode any protein, miRNAs are vastly studied and found to play role in various human physiologic as well as pathological conditions. A huge number of miRNAs have been identified in human cells whose expression is straightly regulated with crucial biological functions, while this number is constantly increasing. miRNAs are particularly studied in cancers, where they either can act with oncogenic function (oncomiRs) or tumor-suppressors role (referred as tumor-suppressor/oncorepressor miRNAs). miR-382 is a well-studied miRNA, which is revealed to play regulatory roles in physiological processes like osteogenic differentiation, hematopoietic stem cell differentiation and normal hematopoiesis, and liver progenitor cell differentiation. Notably, miR-382 deregulation is reported in pathologic conditions, such as renal fibrosis, muscular dystrophies, Rett syndrome, epidural fibrosis, atrial fibrillation, amelogenesis imperfecta, oxidative stress, human immunodeficiency virus (HIV) replication, and various types of cancers. The majority of oncogenesis studies have claimed miR-382 downregulation in cancers and suppressor impact on malignant phenotype of cancer cells in vitro and in vivo, while a few studies suggest opposite findings. Given the putative role of this miRNA in regulation of oncogenesis, assessment of miR-382 expression is suggested in a several clinical investigations as a prognostic/diagnostic biomarker for cancer patients. In this review, we have an overview to recent studies evaluated the role of miR-382 in oncogenesis as well as its clinical potential.
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Current snakebite antivenoms are based on polyclonal animal-derived antibodies, which can neutralize snake venom toxins in envenomed victims, but which are also associated with adverse reactions. Therefore, several efforts within antivenom research aim to explore the utility of recombinant monoclonal antibodies, such as human immunoglobulin G (IgG) antibodies, which are routinely used in the clinic for other indications. In this study, the feasibility of using tobacco plants as bioreactors for expressing full-length human monoclonal IgG antibodies against snake toxins was investigated. We show that the plant-produced antibodies perform similarly to their mammalian cell-expressed equivalents in terms of in vitro antigen binding. Complete neutralization was achieved by both the plant and mammalian cell-produced anti-α-cobratoxin antibody. The feasibility of using plant-based expression systems may potentially make it easier for laboratories in resource-poor settings to work with human monoclonal IgG antibodies.
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Nicotiana , Mordeduras de Serpentes , Animais , Humanos , Venenos de Serpentes , Antivenenos , Anticorpos Monoclonais , Imunoglobulina G , MamíferosRESUMO
Recycling IgG antibodies bind to their target antigen at physiological pH in the blood stream and release them upon endocytosis when pH levels drop, allowing the IgG antibodies to be recycled into circulation via FcRn-mediated cellular pathways, while the antigens undergo lysosomal degradation. This enables recycling antibodies to achieve comparable therapeutic effect at lower doses than their non-recycling counterparts. The development of such antibodies is typically achieved by histidine doping of their variable regions or by performing in vitro antibody selection campaigns utilizing histidine doped libraries. Both are strategies that may introduce sequence liabilities. Here, we present a methodology that employs a naïve antibody phage display library, consisting of natural variable domains, to discover antibodies that bind α-cobratoxin from the venom of Naja kaouthia in a pH-dependent manner. As a result, an antibody was discovered that exhibits a 7-fold higher off-rate at pH 5.5 than pH 7.4 in bio-layer interferometry experiments. Interestingly, no histidine residues were found in its variable domains, and in addition, the antibody showed pH-dependent binding to a histidine-devoid antigen mutant. As such, the results demonstrate that pH-dependent antigen-antibody binding may not always be driven by histidine residues. By employing molecular dynamics simulations, different protonation states of titratable residues were found, which potentially could be responsible for the observed pH-dependent antigen binding properties of the antibody. Finally, given the typically high diversity of naïve antibody libraries, the methodology presented here can likely be applied to discover recycling antibodies against different targets ab initio without the need for histidine doping.
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Bacteriófagos , Histidina , Histidina/metabolismo , Antígenos/metabolismo , Imunoglobulina G/genética , Concentração de Íons de Hidrogênio , Bacteriófagos/metabolismo , Biblioteca de PeptídeosRESUMO
Snakebite envenoming was reintroduced as a Category A Neglected Tropical Disease by the World Health Organization in 2017. Since then, increased attention has been directed towards this affliction and towards the development of a deeper understanding of how snake venoms exert their toxic effects and how antivenoms can counter them. However, most of our in vivo generated knowledge stems from the use of animal models which do not always accurately reflect how the pathogenic effects of snake venoms manifest in humans. Moreover, animal experiments are associated with pain, distress, and eventually animal sacrifice due to the toxic nature of snake venoms. Related to this, the implementation of the 3Rs principle (Replacement, Reduction, and Refinement) in the use of experimental animals in snakebite envenoming research is recommended by the World Health Organization. Therefore, more humane experimental designs and new in vitro/ex vivo alternatives for experimental animals are sought after. Here, we report the use of an organotypic model of human skin to further elucidate the pathophysiology of the dermonecrotic effects caused by the venom of the black-necked spitting cobra, Naja nigricollis, in humans. The goal of this study is to expand the repertoire of available models that can be used to study the local tissue damages induced by cytotoxic venoms.
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Mordeduras de Serpentes , Animais , Humanos , Mordeduras de Serpentes/complicações , Proteômica , Venenos Elapídicos/toxicidade , Antivenenos/farmacologia , Naja , Venenos de SerpentesRESUMO
Venomous snakes are important parts of the ecosystem, and their behavior and evolution have been shaped by their surrounding environments over the eons. This is reflected in their venoms, which are typically highly adapted for their biological niche, including their diet and defense mechanisms for deterring predators. Sub-Saharan Africa is rich in venomous snake species, of which many are dangerous to humans due to the high toxicity of their venoms and their ability to effectively deliver large amounts of venom into their victims via their bite. In this study, the venoms of 26 of sub-Saharan Africa's medically most relevant elapid and viper species were subjected to parallelized toxicovenomics analysis. The analysis included venom proteomics and in vitro functional characterization of whole venom toxicities, enabling a robust comparison of venom profiles between species. The data presented here corroborate previous studies and provide biochemical details for the clinical manifestations observed in envenomings by the 26 snake species. Moreover, two new venom proteomes (Naja anchietae and Echis leucogaster) are presented here for the first time. Combined, the presented data can help shine light on snake venom evolutionary trends and possibly be used to further improve or develop novel antivenoms.
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Elapidae , Proteômica , Animais , Humanos , Ecossistema , Antivenenos/química , África SubsaarianaRESUMO
A major challenge in industrial pig production is the prevalence of post-weaning diarrhea (PWD) in piglets, often caused by enterotoxigenic Escherichia coli (ETEC). The increased use of antibiotics and zinc oxide to treat PWD has raised global concerns regarding antimicrobial resistance development and environmental pollution. Still, alternative treatments targeting ETEC and counteracting PWD are largely lacking. Here, we report the design of a pH, temperature, and protease-stable bivalent VHH-based protein BL1.2 that cross-links a F4+ ETEC model strain by selectively binding to its fimbriae. This protein inhibits F4+ ETEC adhesion to porcine epithelial cells ex vivo and decreases F4+ ETEC proliferation when administrated as a feed additive to weaned F4+ ETEC challenged piglets. These findings highlight the potential of a highly specific bivalent VHH-based feed additive in effectively delimiting pathogenic F4+ ETEC bacteria proliferation in piglets and may represent a sustainable solution for managing PWD while circumventing antimicrobial resistance development.
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Neurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration of nerve cells. Due to the complexity of conditions in neurodegenerative diseases, combination therapy, including cell and drug therapy is important as a new therapeutic strategy. Epidermal neural crest stem cells (EPI-NCSCs) are among the best choices in cell therapy for various neurological diseases. In this study, the effect of Lithium carbonate and Crocin, considering their effects on cellular signaling pathways and neuroprotective properties were investigated on the expression of neurotrophic factors BDNF and GDNF in EPI-NCSCs. EPI-NCSCs were isolated from the hair follicle and treated with different concentrations of drugs [Lithium, Crocin, and lithium + Crocin] for 72h. Then, trial concentrations were selected by MTT assay. The cells were treated with selected concentrations (Lithium 1 mM, Crocin 1.5 mM, and for co-treatment Lithium 1 mM and Crocin 1 mM) for 7 days. The Real-Time PCR results indicated an increasing in expression of BDNF and GDNF in treated cells as compared with control (* p < 0.05, ** p < 0.01 and *** p < 0.001). The results in this study confirmed and supported the neuroprotective/neurogenesis effects of Lithium and Crocin. It also showed that the proposed protocol could be used to increase EPI-NCSCs differentiation potential into neural cells in cell therapy and combination therapy of neurodegenerative diseases.
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OBJECTIVE: Transcranial direct current stimulation (tDCS) and mindfulness practices have been proposed as a potential approach to improve executive functions (EFs) and reduce craving in persons with substance use disorders. Based on the neural mechanisms of action of each of these interventions, the combination of both non-pharmacological interventions might have additive effects. In the current study, the effects of tDCS combined with mindfulness-based substance abuse treatment (MBSAT) to improve EFs and reduce craving were investigated in early abstinent methamphetamine abuse. METHODS: Eighty (youths aged between 18 and 21) early-abstinent methamphetamine users were randomly assigned to the research groups (tDCS group [n = 20], mindfulness group [n = 20], combined mindfulness-tDCS group [n = 20], and sham group [n = 20]). Active tDCS (1.5 mA,20 min, 12 sessions) or sham tDCS was appliedover the left dorsolateral prefrontal cortex and the MBSAT protocol was used over twelve 50-min sessions. RESULTS: Both in the post-test phase (immediately after the intervention) and follow-up phase (one month after the intervention), performance in most EFs tasks significantly improved in the combination group which received real tDCS ï¼ MBSAT, as compared to baseline values and sham stimulation group. Similarly, a significant reduction in craving was observed after intervention inall treatment groups, but not the sham stimulation group. Interestingly, the increase in EFs and the reduction in craving post versus pre tDCS ï¼ MBSAT intervention were correlated. CONCLUSION: Findings from the current study provide initial support for the clinical effectiveness of combination tDCS ï¼ MBSAT, possibly influencing cognitive/affective processes.
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The Middle East and Northern Africa, collectively known as the MENA region, are inhabited by a plethora of venomous animals that cause up to 420,000 bites and stings each year. To understand the resultant health burden and the key variables affecting it, this review describes the epidemiology of snake, scorpion, and spider envenomings primarily based on heterogenous hospital data in the MENA region and the pathologies associated with their venoms. In addition, we discuss the venom composition and the key medically relevant toxins of these venomous animals, and, finally, the antivenoms that are currently in use to counteract them. Unlike Asia and sub-Saharan Africa, scorpion stings are significantly more common (approximately 350,000 cases/year) than snakebites (approximately 70,000 cases/year) and present the most significant contributor to the overall health burden of envenomings, with spider bites being negligible. However, this review also indicates that there is a substantial lack of high-quality envenoming data available for the MENA region, rendering many of these estimates speculative. Our understanding of the venoms and the toxins they contain is also incomplete, but already presents clear trends. For instance, the majority of snake venoms contain snake venom metalloproteinases, while sodium channel-binding toxins and potassium channel-binding toxins are the scorpion toxins that cause most health-related challenges. There also currently exist a plethora of antivenoms, yet only few are clinically validated, and their high cost and limited availability present a substantial health challenge. Yet, some of the insights presented in this review might help direct future research and policy efforts toward the appropriate prioritization of efforts and aid the development of future therapeutic solutions, such as next-generation antivenoms.
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Picadas de Escorpião/fisiopatologia , Venenos de Escorpião/análise , Mordeduras de Serpentes/fisiopatologia , Venenos de Serpentes/análise , África do Norte , Animais , Antivenenos/uso terapêutico , Humanos , Oriente Médio , Picadas de Escorpião/tratamento farmacológico , Escorpiões , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/terapia , SerpentesRESUMO
This study reports the isolation, structural, biochemical, and functional characterization of a novel phosphodiesterase from Crotalus durissus collilineatus venom (CdcPDE). CdcPDE was successfully isolated from whole venom using three chromatographic steps and represented 0.7% of total protein content. CdcPDE was inhibited by EDTA and reducing agents, demonstrating that metal ions and disulfide bonds are necessary for its enzymatic activity. The highest enzymatic activity was observed at pH 8-8.5 and 37 °C. Kinetic parameters indicated a higher affinity for the substrate bis(p-nitrophenyl) phosphate compared to others snake venom PDEs. Its structural characterization was done by the determination of the protein primary sequence by Edman degradation and mass spectrometry, and completed by the building of molecular and docking-based models. Functional in vitro assays showed that CdcPDE is capable of inhibiting platelet aggregation induced by adenosine diphosphate in a dose-dependent manner and demonstrated that CdcPDE is cytotoxic to human keratinocytes. CdcPDE was recognized by the crotalid antivenom produced by the Instituto Butantan. These findings demonstrate that the study of snake venom toxins can reveal new molecules that may be relevant in cases of snakebite envenoming, and that can be used as molecular tools to study pathophysiological processes due to their specific biological activities.
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Venenos de Crotalídeos , Queratinócitos/efeitos dos fármacos , Diester Fosfórico Hidrolases , Animais , Células Cultivadas , Venenos de Crotalídeos/química , Crotalus , Humanos , Cinética , Diester Fosfórico Hidrolases/química , Diester Fosfórico Hidrolases/isolamento & purificação , Diester Fosfórico Hidrolases/toxicidade , Especificidade por SubstratoRESUMO
Rod-like mesoporous silica nanoparticles with pH-responsive amphiphilic hyperbranched polyester shells were prepared for doxorubicin (DOX) delivery. First, rod-shaped mesoporous silica nanoparticles (MSNs) were obtained, then hydrophobic hyperbranched polyester Boltorn H40 (H40) was grafted on their surface. The H40 coated MSNs were next treated with amine-functionalized polyethylene glycol (PEG) to achieve the hydrophilic and pH-responsive material denoted as PEG-H40-MSNs. The experimental results showed that PEG-H40-MSNs were successfully synthesized. BET analysis showed that rod MSNs exhibits a type IV standard isotherm. TEM revealed that the thin gray polymer layer was formed around the SBA-15 particle with a diameter of around 150 nm. DOX was effectively loaded, which can be released according to the ambient pH inside the cell as follow: at pH 7.4, only 9.7% of the DOX was released after 48 h; as the pH decreased to 5.5, the cumulative release reached to 49% at the same time. PEG-H40-MSNs showed less than 1.6% of hemolytic activity and a slight effect on the liver and kidney of treated mice were observed at a high disposal dosage implying negligible toxicities were caused by PEG-H40-MSNs in both in vitro hemolysis analysis and in vivo biochemical in mice. However, the in vitro cytotoxicity evaluation of the DOX-PEG-H40-MSNs showed that the cell cytotoxicity of both pure DOX and DOX-loaded PEG-H40-MSNs generally enhanced by increasing the concentration of DOX. Graphical abstract Schematic of cellular uptake and DOX release of PEG-H40-MSNs nanoparticle.
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Antibióticos Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Nanopartículas , Polietilenoglicóis , Dióxido de Silício , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Dióxido de Silício/administração & dosagem , Dióxido de Silício/químicaRESUMO
Broadly-neutralizing monoclonal antibodies are of high therapeutic utility against infectious diseases caused by bacteria and viruses, as well as different types of intoxications. Snakebite envenoming is one such debilitating pathology, which is currently treated with polyclonal antibodies derived from immunized animals. For the development of novel envenoming therapies based on monoclonal antibodies with improved therapeutic benefits, new discovery approaches for broadly-neutralizing antibodies are needed. Here, we present a methodology based on phage display technology and a cross-panning strategy that enables the selection of cross-reactive monoclonal antibodies that can broadly neutralize toxins from different snake species. This simple in vitro methodology is immediately useful for the development of broadly-neutralizing (polyvalent) recombinant antivenoms with broad species coverage, but may also find application in the development of broadly-neutralizing antibodies against bacterial, viral, and parasitic agents that are known for evading therapy via resistance mechanisms and antigen variation.
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Anticorpos Monoclonais/química , Anticorpos Neutralizantes/química , Antivenenos/química , Testes de Neutralização , Animais , Antígenos/química , Biotecnologia , Reações Cruzadas/imunologia , Desenho de Fármacos , Ensaio de Imunoadsorção Enzimática , Humanos , Fragmentos Fab das Imunoglobulinas/imunologia , Técnicas In Vitro , Concentração Inibidora 50 , Queratinócitos/imunologia , Espectrometria de Massas , Biblioteca de Peptídeos , Proteômica , Proteínas Recombinantes/química , Serpentes , PeçonhasRESUMO
BACKGROUND: Snakebite envenoming can be a life-threatening condition, for which emergency care is essential. The Bothrops (lancehead) genus is responsible for most snakebite-related deaths and permanent loss of function in human victims in Latin America. Bothrops spp. venom is a complex mixture of different proteins that are known to cause local necrosis, coagulopathy, and acute kidney injury. However, the long-term effects of these viper envenomings have remained largely understudied. CASE PRESENTATION: Here, we present a case report of a 46-years old female patient from Las Claritas, Venezuela, who was envenomed by a snake from the Bothrops genus. The patient was followed for a 10-year period, during which she presented oliguric renal failure, culminating in kidney failure 60 months after the envenoming. CONCLUSION: In Latin America, especially in Brazil, where there is a high prevalence of Bothrops envenoming, it may be relevant to establish long-term outpatient programs. This would reduce late adverse events, such as chronic kidney disease, and optimize public financial resources by avoiding hemodialysis and consequently kidney transplantation.