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Africanized bees have spread across the Americas since 1956 and consequently resulted in human and animal deaths attributed to massive attacks related to exposure from Argentina to the USA. In Brazil, more than 100,000 accidents were registered in the last 5 years with a total of 303 deaths. To treat such massive attacks, Brazilian researchers developed the first specific antivenom against Africanized honey bee sting exposure. This unique product, the first of its kind in the world, has been safely tested in 20 patients during a Phase 2 clinical trial. To develop the antivenom, a standardized process was undertaken to extract primary venom antigens from the Africanized bees for immunization of serum-producing horses. This process involved extracting, purifying, fractionating, characterizing, and identifying the venom (apitoxin) employing mass spectrometry to generate standardized antigen for hyperimmunization of horses using the major toxins (melittin and its isoforms and phospholipase A2). The current guide describes standardization of the entire production chain of venom antigens in compliance with good manufacturing practices (GMP) required by regulatory agencies. Emphasis is placed upon the welfare of bees and horses during this process, as well as the development of a new biopharmaceutical to ultimately save lives.
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Venenos de Abelha , Mordeduras e Picadas de Insetos , Abelhas , Humanos , Animais , Antivenenos/uso terapêutico , Mordeduras e Picadas de Insetos/tratamento farmacológico , Venenos de Abelha/análise , Venenos de Abelha/química , Meliteno/análise , Meliteno/química , Fosfolipases A2 , AntígenosRESUMO
Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons.
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Adesivo Tecidual de Fibrina/administração & dosagem , Regeneração Nervosa/fisiologia , Recuperação de Função Fisiológica/fisiologia , Neuropatia Ciática/tratamento farmacológico , Animais , Animais Recém-Nascidos , Sobrevivência Celular/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Recuperação de Função Fisiológica/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/fisiologia , Neuropatia Ciática/patologia , Venenos de Serpentes , Fatores de TempoRESUMO
Biomaterials are used extensively in graft procedures to correct bone defects, interacting with the body without causing adverse reactions. The aim of this pre-clinical study was to analyze the effects of photobiomodulation therapy (PBM) with the use of a low-level laser in the repair process of bone defects filled with inorganic matrix (IM) associated with heterologous fibrin biopolymer (FB). A circular osteotomy of 4 mm in the left tibia was performed in 30 Wistar male adult rats who were randomly divided into three groups: G1 = IM + PBM, G2 = IM + FB and G3 = IM + FB + PBM. PBM was applied at the time of the experimental surgery and three times a week, on alternate days, until euthanasia, with 830 nm wavelength, in two points of the operated site. Five animals from each group were euthanized 14 and 42 days after surgery. In the histomorphometric analysis, the percentage of neoformed bone tissue in G3 (28.4% ± 2.3%) was higher in relation to G1 (24.1% ± 2.91%) and G2 (22.2% ± 3.11%) at 14 days and at 42 days, the percentage in G3 (35.1% ± 2.55%) was also higher in relation to G1 (30.1% ± 2.9%) and G2 (31.8% ± 3.12%). In the analysis of the birefringence of collagen fibers, G3 showed a predominance of birefringence between greenish-yellow in the neoformed bone tissue after 42 days, differing from the other groups with a greater presence of red-orange fibers. Immunohistochemically, in all experimental groups, it was possible to observe immunostaining for osteocalcin (OCN) near the bone surface of the margins of the surgical defect and tartrate-resistant acid phosphatase (TRAP) bordering the newly formed bone tissue. Therefore, laser photobiomodulation therapy contributed to improving the bone repair process in tibial defects filled with bovine biomaterial associated with fibrin biopolymer derived from snake venom.
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Envenoming resulting from Apis honeybee stings pose a neglected public health concern, with clinical complications ranging from mild local reactions to severe systemic manifestations. This review explores the mechanisms underlying envenoming by honeybee sting, discusses diagnostic approaches, and reviews current pharmacological interventions. This section explores the diverse clinical presentations of honeybee envenoming, including allergic and non-allergic reactions, emphasizing the need for accurate diagnosis to guide appropriate medical management. Mechanistic insights into the honeybee venom's impact on physiological systems, including the immune and cardiovascular systems, are provided to enhance understanding of the complexities of honeybee sting envenoming. Additionally, the article evaluates emerging diagnostic technologies and therapeutic strategies, providing a critical analysis of their potential contributions to improved patient outcomes. This article aims to provide current knowledge for healthcare professionals to effectively manage honeybee sting envenoming, thereby improving patient care and treatment outcomes.
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Venenos de Abelha , Mordeduras e Picadas de Insetos , Abelhas/imunologia , Animais , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/diagnóstico , Mordeduras e Picadas de Insetos/terapia , Humanos , Venenos de Abelha/imunologia , Venenos de Abelha/efeitos adversosRESUMO
Disintegrins are a class of peptides found in snake venom that inhibit the activity of integrins, which are essential cell adhesion receptors in tumor progression and development. In this work, moojecin, a RGD disintegrin, was isolated from Bothrops moojeni snake venom, and its antitumor potential in acute myeloid leukemia (AML) HL-60 and THP-1 cells was characterized. The isolation was performed using a C18 reverse-phase column in two chromatographic steps, and its molecular mass is 7417.84 Da. N-terminal and de novo sequencing was performed to identify moojecin. Moojecin did not show cytotoxic or antiproliferative activity in THP-1 and HL-60 at tested concentrations, but it exhibited significant antimigratory activity in both cell lines, as well as inhibition of angiogenesis in the tube formation assay on Matrigel in a dose-dependent manner. A stronger interaction with integrin αVß3 was shown in integrin interaction assays compared to α5ß1, and the platelet aggregation assay indicated an IC50 of 5.039 µg/mL. Preliminary evaluation of disintegrin toxicity revealed no incidence of hemolysis or cytotoxic effects on peripheral blood mononuclear cells (PBMCs) across the tested concentrations. Thus, this is the first study to report the isolation, functional and structural characterization of a disintegrin from B. moojeni venom and bring a new perspective to assist in AML treatment.
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Antineoplásicos , Bothrops , Desintegrinas , Leucemia Mieloide Aguda , Humanos , Desintegrinas/farmacologia , Desintegrinas/química , Desintegrinas/isolamento & purificação , Leucemia Mieloide Aguda/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Células HL-60 , Venenos de Crotalídeos/química , Agregação Plaquetária/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Serpentes PeçonhentasRESUMO
Biomaterials and biopharmaceuticals for correcting large bone defects are a potential area of translational science. A new bioproduct, purified from snake venom and fibrinogen from buffalo blood, aroused interest in the repair of venous ulcers. Expanding potential uses, it has also been used to form biocomplexes in combination with bone grafts, associated with physical therapies or used alone. The aim of this preclinical study was to evaluate low-level laser photobiomodulation (PBM) in critical defects in the calvaria of rats filled with nanohydroxyapatite (NH) associated with the heterologous fibrin biopolymer (HFB). Sixty animals were used, divided into six groups (n = 10 each): G1 (NH); G2 (HFB); G3 (NH + HFB); G4 (NH + PBM); G5 (HFB + PBM); G6 (NH + HFB + PBM). PBM simultaneously used red (R) and infrared (IR) light emission, applied intraoperatively and twice a week, until the end of the experiment at 42 days. Microtomography, bone formation can be seen initially at the margins of the defect, more evident in G5. Microscopically, bone formation demonstrated immature and disorganized trabeculation at 14 days, with remnants of grafting materials. At 42 days, the percentage of new bone formed was higher in all groups, especially in G5 (HFB, 45.4 ± 3.82), with collagen fibers at a higher degree of maturation and yellowish-green color in the birefringence analysis with Picrosirius-red. Therefore, it is concluded that the HFB + PBM combination showed greater effectiveness in the repair process and presents potential for future clinical studies.
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The concept of pain encompasses a complex interplay of sensory and emotional experiences associated with actual or potential tissue damage. Accurately describing and localizing pain, whether acute or chronic, mild or severe, poses a challenge due to its diverse manifestations. Understanding the underlying origins and mechanisms of these pain variations is crucial for effective management and pharmacological interventions. Derived from a wide spectrum of species, including snakes, arthropods, mollusks, and vertebrates, animal venoms have emerged as abundant repositories of potential biomolecules exhibiting analgesic properties across a broad spectrum of pain models. This review focuses on highlighting the most promising venom-derived toxins investigated as potential prototypes for analgesic drugs. The discussion further encompasses research prospects, challenges in advancing analgesics, and the practical application of venom-derived toxins. As the field continues its evolution, tapping into the latent potential of these natural bioactive compounds holds the key to pioneering approaches in pain management and treatment. Therefore, animal toxins present countless possibilities for treating pain caused by different diseases. The development of new analgesic drugs from toxins is one of the directions that therapy must follow, and it seems to be moving forward by recommending the composition of multimodal therapy to combat pain.
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Specific and sensitive tools for the diagnosis and monitoring of accidents by venomous animals are urgently needed. Several diagnostic and monitoring assays have been developed; however, they have not yet reached the clinic. This has resulted in late diagnoses, which represents one of the main causes of progression from mild to severe disease. Human blood is a protein-rich biological fluid that is routinely collected in hospital settings for diagnostic purposes, which can translate research progress from the laboratory to the clinic. Although it is a limited view, blood plasma proteins provide information about the clinical picture of envenomation. Proteome disturbances in response to envenomation by venomous animals have been identified, allowing mass spectrometry (MS)-based plasma proteomics to emerge as a tool in a range of clinical diagnostics and disease management that can be applied to cases of venomous animal envenomation. Here, we provide a review of the state of the art on routine laboratory diagnoses of envenomation by snakes, scorpions, bees, and spiders, as well as a review of the diagnostic methods and the challenges encountered. We present the state of the art on clinical proteomics as the standardization of procedures to be performed within and between research laboratories, favoring a more excellent peptide coverage of candidate proteins for biomarkers. Therefore, the selection of a sample type and method of preparation should be very specific and based on the discovery of biomarkers in specific approaches. However, the sample collection protocol (e.g., collection tube type) and the processing procedure of the sample (e.g., clotting temperature, time allowed for clotting, and anticoagulant used) are equally important to eliminate any bias.
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Proteômica , Serpentes , Animais , Humanos , Proteômica/métodos , Proteínas Sanguíneas/análise , Biomarcadores , Proteoma , Plasma/químicaRESUMO
Spinal cord injuries result in severe neurological deficits and neuronal loss, with poor functional recovery. Mesenchymal stem cells have shown promising results; therefore the present objective of this work was to compare motor recovery after treatment with human dental pulp stem cells (hDPSC) cultivated in monolayer (2D) or as spheroids (3D), following avulsion and reimplantation of spinal motor roots in adult rats. Thus, 72 adult female Lewis rats were divided into 4 groups: avulsion (AV); avulsion followed by reimplantation (AR); avulsion associated with reimplant and 2D cell therapy (AR + 2D), and avulsion associated with reimplant and 3D cell therapy (AR + 3D). The application of the cells in 2D and 3D was performed by microsurgery, with subsequent functional assessment using a walking track test (Catwalk system), immunohistochemistry, neuronal survival, and qRT-PCR in 1-, 4-, and 12-weeks post-injury. The animals in the AR + 2D and AR + 3D groups showed the highest neuronal survival rates, and immunofluorescence revealed downregulation of GFAP, and Iba-1, with preservation of synaptophysin, indicating a reduction in glial reactivity, combined with the maintenance of pre-synaptic inputs. There was an increase in anti-inflammatory (IL-4, TGFß) and a reduction of pro-inflammatory factors (IL-6, TNFα) in animals treated with reimplantation and hDPSC. As for the functional recovery, in all analyzed parameters, the AR + 2D group performed better and was superior to the avulsion alone. Overall, our results indicate that the 2D and 3D cell therapy approaches provide successful immunomodulation and motor recovery, consistent with advanced therapies after spinal cord injury.
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Traumatismos da Medula Espinal , Medula Espinal , Adulto , Animais , Feminino , Humanos , Ratos , Polpa Dentária , Neurônios Motores/fisiologia , Ratos Endogâmicos Lew , Traumatismos da Medula Espinal/terapia , Raízes Nervosas Espinhais/lesões , Raízes Nervosas Espinhais/fisiologia , Células-Tronco , Técnicas de Cultura de CélulasRESUMO
Peripheral nerve injuries impair the patient's functional capacity, including those occurring in the facial nerve, which require effective medical treatment. Thus, we investigated the use of heterologous fibrin biopolymer (HFB) in the repair of the buccal branch of the facial nerve (BBFN) associated with photobiomodulation (PBM), using a low-level laser (LLLT), analyzing the effects on axons, muscles facials, and functional recovery. This experimental study used twenty-one rats randomly divided into three groups of seven animals, using the BBFN bilaterally (the left nerve was used for LLLT): Control group-normal and laser (CGn and CGl); Denervated group-normal and laser (DGn and DGl); Experimental Repair Group-normal and laser (ERGn and ERGl). The photobiomodulation protocol began in the immediate postoperative period and continued for 5 weeks with a weekly application. After 6 weeks of the experiment, the BBFN and the perioral muscles were collected. A significant difference (p < 0.05) was observed in nerve fiber diameter (7.10 ± 0.25 µm and 8.00 ± 0.36 µm, respectively) and axon diameter (3.31 ± 0.19 µm and 4.07 ± 0.27 µm, respectively) between ERGn and ERGl. In the area of muscle fibers, ERGl was similar to GC. In the functional analysis, the ERGn and the ERGI (4.38 ± 0.10) and the ERGI (4.56 ± 0.11) showed parameters of normality. We show that HFB and PBM had positive effects on the morphological and functional stimulation of the buccal branch of the facial nerve, being an alternative and favorable for the regeneration of severe injuries.
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There are several treatment methods available for bone repair, although the effectiveness becomes limited in cases of large defects. The objective of this pre-clinical protocol was to evaluate the grafting of hydroxyapatite/tricalcium phosphate (BCP) ceramic biomaterial (B; QualyBone BCP®, QualyLive, Amadora, Portugal) together with the heterologous fibrin biopolymer (FB; CEVAP/UNESP Botucatu, Brazil) and with photobiomodulation (PBM; Laserpulse®, Ibramed, Amparo, Brazil) in the repair process of bone defects. Fifty-six rats were randomly divided into four groups of seven animals each: the biomaterial group (G1/B), the biomaterial plus FB group (G2/BFB); the biomaterial plus PBM group (G3/B + PBM), and the biomaterial plus FB plus PBM group (G4/BFB + PBM). After anesthesia, a critical defect was performed in the center of the rats' parietal bones, then filled and treated according to their respective groups. The rats were euthanized at 14 and 42 postoperative days. Histomorphologically, at 42 days, the G4/BFB + PBM group showed a more advanced maturation transition, with more organized and mature bone areas forming concentric lamellae. A birefringence analysis of collagen fibers also showed a more advanced degree of maturation for the G4/BFB + PBM group. In the comparison between the groups, in the two experimental periods (14 and 42 days), in relation to the percentage of formation of new bone tissue, a significant difference was found between all groups (G1/B (5.42 ± 1.12; 21.49 ± 4.74), G2/BFB (5.00 ± 0.94; 21.77 ± 2.83), G3/B + PBM (12.65 ± 1.78; 29.29 ± 2.93), and G4/BFB + PBM (12.65 ± 2.32; 31.38 ± 2.89)). It was concluded that the use of PBM with low-level laser therapy (LLLT) positively interfered in the repair process of bone defects previously filled with the biocomplex formed by the heterologous fibrin biopolymer associated with the synthetic ceramic of hydroxyapatite and tricalcium phosphate.
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The characteristics of the denture base surface, in combination with the oral environment, promote the colonization and development of Candida albicans biofilm, which is the main cause of denture stomatitis. This study evaluated the effectiveness of fibrin biopolymer with digluconate chlorhexidine or Punica granatum alcoholic extract to prevent C. albicans biofilm. Conventional heat polymerized and pre-polymerized poly(methyl methacrylate) (PMMA) circular specimens (10 × 2 mm) were fabricated (n = 504) and randomly divided into groups: no treatment (control-CT), fibrin biopolymer coating (FB), fibrin biopolymer with P. granatum (FBPg), or digluconate of chlorhexidine (FBCh) coating. The specimens were inoculated with C. albicans SC5314 (1 × 107 cells/mL) and incubated for 24, 48, and 72 h. Crystal violet and colony-forming unit assays were used to quantify the total biofilm biomass and biofilm-living cells. A qualitative analysis was performed using confocal laser scanning microscopy. Data obtained are expressed as means and standard deviations and were statistically analyzed using a three-way analysis of variance (α = 0.05). The FBPg and FBCh groups inhibited the growth of C. albicans biofilm in both PMMA materials analyzed, with FBCh performing better in all periods evaluated (p < 0.0001). The colony forming unit (CFU) assay showed that the FB group favored the C. albicans biofilm growth at 24 h and 48 h (p < 0.0001), with no differences with CT group at 72 h (p = 0.790). All groups showed an enhancement in biofilm development up to 72 h (p < 0.0001), except the FBCh group (p = 0.100). No statistical differences were found between the PMMA base materials (p > 0.050), except in the FB group (p < 0.0001). Fibrin biopolymer, albeit a scaffold for the growth of C. albicans, when combined with chlorhexidine digluconate or P. granatum, demonstrated excellent performance as a drug delivery system, preventing and controlling the formation of denture biofilm.
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Acute kidney injury pathogenesis in envenoming by snakes is multifactorial and involves immunologic reactions, hemodynamic disturbances, and direct nephrotoxicity. Sildenafil (SFC), a phosphodiesterase 5 inhibitor, has been reported to protect against pathological kidney changes. OBJECTIVE: This study aimed to investigate the protective effect of sildenafil against Bothrops alternatus snake venom (BaV)-induced nephrotoxicity. METHODS: Kidneys from Wistar rats (n = 6, weighing 260-300 g) were isolated and divided into four groups: (1) perfused with a modified Krebs-Henseleit solution (MKHS) containing 6 g% of bovine serum albumin; (2) administered 3 µg/mL SFC; (3) perfused with 3 µg/mL BaV; and (4) administered SFC + BaV, both at 3 µg/mL. Subsequently, the perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF), glomerular filtration rate (GFR), and percentage of electrolyte tubular sodium and chloride transport (%TNa+, %TCl-, respectively) were evaluated. The cyclic guanosine monophosphate (cGMP) levels were analyzed in the perfusate, and the kidneys were removed to perform oxidative stress and histopathological analyses. RESULTS: All renal parameters evaluated were reduced with BaV. In the SFC + BaV group, SFC restored PP to normal values and promoted a significant increase in %TNa+ and %TCl-. cGMP levels were increased in the SFC + BaV group. The oxidative stress biomarkers, malondialdehyde (MDA) and glutathione (GSH), were reduced by BaV. In the SFC + BaV group, a decrease in MDA without an increase in GSH was observed. These findings were confirmed by histological analysis, which showed improvement mainly in tubulis. CONCLUSION: Our data suggest the involvement of phosphodiesterase-5 and cGMP in BaV-induced nephrotoxicity since its effects were attenuated by the administration of SFC.
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Bothrops , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Rim , Inibidores da Fosfodiesterase 5/uso terapêutico , Ratos , Ratos Wistar , Citrato de Sildenafila/uso terapêutico , Venenos de Serpentes/toxicidadeRESUMO
Fibrin sealant (FS) is a biomaterial that exhibits hemostatic and repairing properties. It has been successfully used as scaffolds and adhesives to improve repair and regeneration of tissues. The objective of this study was to evaluate the effect of FS in the regeneration process of bone defects in male rat tibias through macroscopic, microscopic and mechanical analysis. A bone defect of 2.9 mm was performed on the medial face of the proximal third of the tibia of 40 rats and implanted FS and autologous bone graft (AG). The animals were divided into four groups: animals with bone defect without any treatment (CON), animals treated with fibrin sealant (TFS), animals treated with autologous graft (TAG) and animals treated with fibrin sealant and autologous graft (FSAG). The animals were euthanized 42 days after surgery. Macroscopic analysis showed no difference between the groups (p > 0.05) in relation to tibial weight, but a statistically significant difference (p = 0.005) was observed for their length. Micro-computed tomography (micro-CT) revealed tendentious values regarding bone microarchitecture and FS. Bone mineral densitometry (BMD) showed significance between the FSAG (p = 0.009) and TFS (p = 0.007) groups. The bone mineral content (BMC) presented a significant difference between all groups (p = 0.020). Maximum strength showed a significant difference between the FSAG group (p = 0.007) and the others. The results obtained in relation to the relative stiffness also present a significant difference (p = 0.023). Newly formed bone showed significant differences between groups (p = 0.035). We conclude that bone defect regeneration was directly influenced by the use of FS and AG.
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Adesivo Tecidual de Fibrina , Tíbia , Animais , Regeneração Óssea , Transplante Ósseo , Adesivo Tecidual de Fibrina/farmacologia , Masculino , Ratos , Tíbia/diagnóstico por imagem , Microtomografia por Raio-XRESUMO
Bone defects cause aesthetic and functional changes that affect the social, economic and especially the emotional life of human beings. This complication stimulates the scientific community to investigate strategies aimed at improving bone reconstruction processes using complementary therapies. Photobiomodulation therapy (PBMT) and the use of new biomaterials, including heterologous fibrin biopolymer (HFB), are included in this challenge. The objective of the present study was to evaluate the influence of photobiomodulation therapy on bone tibial reconstruction of rats with biomaterial consisting of lyophilized bovine bone matrix (BM) associated or not with heterologous fibrin biopolymer. Thirty male rats were randomly separated into three groups of 10 animals. In all animals, after the anesthetic procedure, a noncritical tibial defect of 2 mm was performed. The groups received the following treatments: Group 1: BM + PBMT, Group 2: BM + HFB and Group 3: BM + HFB + PBMT. The animals from Groups 1 and 3 were submitted to PBMT in the immediate postoperative period and every 48 h until the day of euthanasia that occurred at 14 and 42 days. Analyses by computed microtomography (µCT) and histomorphometry showed statistical difference in the percentage of bone formation between Groups 3 (BM + HB + PBMT) and 2 (BM + HFB) (26.4% ± 1.03% and 20.0% ± 1.87%, respectively) at 14 days and at 42 days (38.2% ± 1.59% and 31.6% ± 1.33%, respectively), and at 42 days there was presence of bone with mature characteristics and organized connective tissue. The µCT demonstrated BM particles filling the defect and the deposition of new bone in the superficial region, especially in the ruptured cortical. It was concluded that the association of PBMT with HFB and BM has the potential to assist in the process of reconstructing bone defects in the tibia of rats.
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Materiais Biocompatíveis , Matriz Óssea , Regeneração Óssea , Fibrina , Terapia com Luz de Baixa Intensidade , Tíbia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Matriz Óssea/química , Matriz Óssea/transplante , Bovinos , Fibrina/química , Fibrina/farmacologia , Masculino , Ratos , Ratos Wistar , Tíbia/lesões , Tíbia/fisiologiaRESUMO
INTRODUCTION: We evaluated the epidemiological and clinical profile of reported cases of bee sting incidents in Santa Catarina, Brazil. METHODS: This retrospective cohort study included all reported cases of bee sting incidents among the population of Santa Catarina from 2007 to 2017. RESULTS: In total, 8,912 cases were reported, corresponding to an overall rate of 12.3/100,000 population. The mean age was 29,8 years with 60.2% men. The lethality rate was 0.2%. CONCLUSIONS: Santa Catarina has a high incidence rate of bee stings, which is higher than the national average. The data presented in this study may be underestimated.
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Venenos de Abelha/intoxicação , Abelhas , Mordeduras e Picadas de Insetos/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Notificação de Doenças , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise Espacial , Adulto JovemRESUMO
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.(AU)
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Produtos Biológicos/análise , Proposta de Concorrência/organização & administração , Protocolo de Ensaio Clínico , Brasil , Boas Práticas de FabricaçãoRESUMO
Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity two weeks post lesion. Then, qRT-PCR was used to assess gene expression of ß2-microglobulin (ß2m), TNFα, IL1ß, IL6 and IL10 in the spinal cord in vivo and FGF2 mRNA levels in hESC in vitro. The results indicate that hESC overexpressing FGF2 significantly rescued avulsed motoneurons, preserving synaptic covering and reducing astroglial reactivity. The cells were also shown to express BDNF and GDNF at the site of injury. Additionally, engraftment of hESC led to a significant reduction in mRNA levels of TNFα at the spinal cord ventral horn, indicating their immunomodulatory properties. Overall, the present data suggest that hESC overexpressing FGF2 are neuroprotective and can shift gene expression towards an anti-inflammatory environment.
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Células-Tronco Embrionárias Humanas/transplante , Radiculopatia/cirurgia , Raízes Nervosas Espinhais/patologia , Animais , Movimento Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Modelos Animais de Doenças , Doxiciclina/uso terapêutico , Feminino , Adesivo Tecidual de Fibrina/toxicidade , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Vetores Genéticos/fisiologia , Células-Tronco Embrionárias Humanas/metabolismo , Humanos , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Radiculopatia/induzido quimicamente , Ratos , Ratos Endogâmicos Lew , Adesivos Teciduais/toxicidadeRESUMO
The proteomic approach has aroused the interest of veterinary medicine researchers, especially regarding the production of biopharmaceuticals and diagnosis of diseases in farm animals. Water buffaloes have gained prominence in the world economy due to the quality of their milk, meat, and leather, in addition to being an important donor of blood components. This work aimed to identify and characterize the proteins present in the blood plasma of Murrah buffaloes (Bubalus bubalis) through 2D electrophoresis, in gel protein digestion followed by mass spectrometry technique and for albumin depletion, in solution protein digestion followed by shotgun analysis. Our results showed the identification of 112 protein spots and 35 individual proteins, respectively. The abundant proteins were represented by albumin, fibrinogen-α, fibrinogen-ß, fibrinogen-γ, immunoglobulins in general, α-1-antiproteinase, α-1B-glycoprotein, α-2-HS-glycoprotein, α-macroglobulin, apolipoprotein A1, antithrombin-III, endopin 2B, fetuin-B, retinol-binding protein, serotransferrin, transthyretin and vitamin D-binding protein. Most of these proteins are related to the signaling pathways of the complement system and coagulation cascade. The results allowed a better understanding of the protein composition of these blood components, thus promoting studies on animal health in the search for molecular markers of zoonotic diseases in buffaloes.
Assuntos
Proteínas Sanguíneas/metabolismo , Búfalos/sangue , Búfalos/metabolismo , Proteômica , AnimaisRESUMO
OBJECTIVE: Evaluate the efficacy of low-level laser therapy (LLLT) on qualitative, quantitative, and functional aspects in the facial nerve regeneration process. MATERIALS AND METHODS: Forty-two male Wistar rats were used, randomly divided into a control group (CG; n = 10), in which the facial nerve without lesion was collected, and four experimental groups: (1) suture experimental group (SEG) and (2) fibrin experimental group (FEG), consisting of 16 animals in which the buccal branch of the facial nerve was sectioned on both sides of the face; an end-to-end epineural suture was performed on the right side, and a fibrin sealant was used on the left side for coaptation of the stumps; and (3) laser suture experimental group (LSEG) and (4) laser fibrin experimental group (LFEG), consisting of 16 animals that underwent the same surgical procedures as SEG and FEG with the addition of laser application at three different points along the surgical site (pulsed laser of 830 nm wavelength, optical output power of 30 mW, power density of 0.2586 W/cm2, energy density of 6.2 J/cm2, beam area of 0.116 cm2, exposure time of 24 sec per point, total energy per session of 2.16 J, and cumulative dose of 34.56 J). The animals were submitted to functional analysis (subjective observation of whisker movement) and the data obtained were compared using Fisher's exact test. Euthanasia was performed at 5 and 10 weeks postoperative. The total number and density of regenerated axons were analyzed using the unpaired t-test (p < 0.05). RESULTS: Laser therapy resulted in a significant increase in the number and density of regenerated axons. The LSEG and LFEG presented better scores in functional analysis in comparison with the SEG and FEG. CONCLUSIONS: LLLT enhanced axonal regeneration and accelerated functional recovery of the whiskers, and both repair techniques allowed the growth of axons.