Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 318.226
Filtrar
1.
Nat Commun ; 11(1): 4935, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004797

RESUMO

Gramicidin A (1) is a peptide antibiotic that disrupts the transmembrane ion concentration gradient by forming an ion channel in a lipid bilayer. Although long used clinically, it is limited to topical application because of its strong hemolytic activity and mammalian cytotoxicity, likely arising from the common ion transport mechanism. Here we report an integrated high-throughput strategy for discovering analogues of 1 with altered biological activity profiles. The 4096 analogue structures are designed to maintain the charge-neutral, hydrophobic, and channel forming properties of 1. Synthesis of the analogues, tandem mass spectrometry sequencing, and 3 microscale screenings enable us to identify 10 representative analogues. Re-synthesis and detailed functional evaluations find that all 10 analogues share a similar ion channel function, but have different cytotoxic, hemolytic, and antibacterial activities. Our large-scale structure-activity relationship studies reveal the feasibility of developing analogues of 1 that selectively induce toxicity toward target organisms.


Assuntos
Antibacterianos/farmacologia , Descoberta de Drogas/métodos , Gramicidina/análogos & derivados , Ensaios de Triagem em Larga Escala/métodos , Animais , Antibacterianos/química , Linhagem Celular Tumoral , Química Farmacêutica , Eritrócitos , Estudos de Viabilidade , Bactérias Gram-Positivas/efeitos dos fármacos , Gramicidina/química , Gramicidina/farmacologia , Hemólise/efeitos dos fármacos , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Coelhos , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
2.
Vestn Oftalmol ; 136(5): 77-86, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33056967

RESUMO

PURPOSE: To evaluate biocompatibility of the new keratoprosthesis supporting plates (KSP) in rabbits in vivo. MATERIAL AND METHODS: The study included 15 chinchilla rabbits. In the first group (5 rabbit eyes) KSP made of hydrophobic acryl with square penetrating holes of 220×220 micron (model 1) were inserted into rabbits' corneas. In the second group (5 eyes), KSP made of hydrophobic acryl were used that had trapezoidal fenestrations with size (from 170×130 micron to 180×70 microns) gradually changing from periphery to the center of KSP (model 2). The control group rabbits (5 eyes) had 1/2 of Fyodorov-Zuev KSP made of titanium implanted. All animals were observed for up to 3 months with biomicroscopy and optical coherence tomography of the anterior segment. The animals were then euthanized and had their corneo-scleral discs excised and then examined with optical microscopy and scanning electron microscopy (SEM). RESULTS: After 3 months, there was only one case of KSP protrusion in the first group. In the second group, thinning of the corneal layers above the central part of KSP occurred in one case. The presence of polymer KSP (of both models) in the corneal stroma was found not to cause formation of rough fibrotic tissue. At the same time, adhered cellular and fibrous elements were discovered on the surface and inside the holes of the polymer KSP, while on the surface of the titanium plate cellular elements were absent. CONCLUSION: Supporting plates made of hydrophobic acrylic material can potentially serve as a foundation for the new keratoprosthesis design.


Assuntos
Córnea , Próteses e Implantes , Animais , Córnea/diagnóstico por imagem , Córnea/cirurgia , Substância Própria , Coelhos , Tomografia de Coerência Óptica
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 414-417, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018016

RESUMO

Atrial Fibrillation (AF) is most common sustained cardiac arrhythmia and a precursor to many fatal cardiac conditions. Catheter ablation, which is a minimally invasive treatment, is associated with limited success rates in patients with persistent AF. Rotors are believed to maintain AF and core of rotors are considered to be robust targets for ablation. Recently, multiscale entropy (MSE) was proposed to identify the core of rotors in ex-vivo rabbit hearts. However, MSE technique is sensitive to intrinsic parameters, such as scale factor and template dimension, that may lead to an imprecise estimation of entropy measures. The purpose of this research is optimize MSE approach to improve its accuracy and sensitivity in rotor core identification using simulated EGMs from human atrial model. Specifically, we have identified the optimal time scale factor (τopt) and optimal template dimension (Τopt) that are needed for efficient rotor core identification. The τopt was identified to be 10, using a convergence graph, and the Τopt (~20 ms) remained the same at different sampling rates, indicating that optimized MSE will be efficient in identifying core of the rotor irrespective of the signal acquisition system.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Animais , Fibrilação Atrial/cirurgia , Técnicas Eletrofisiológicas Cardíacas , Entropia , Átrios do Coração , Humanos , Coelhos
4.
Vestn Oftalmol ; 136(6): 19-25, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33084275

RESUMO

Palpebral eyelid weight implants are currently considered as the gold standard method for lagophthalmos correction. Manufactured from different precious metals, they have both benefits and drawbacks. The article presents the results of an experimental morphological study of biointegration of different eyelid weight implants used for correction of paralytic lagophthalmos. PURPOSE: To investigate biointegration properties of implants made of gold, platinum and platinum-gold alloy. MATERIAL AND METHODS: The study enrolled 4 Chinchilla rabbits (8 eyelids). Palpebral implants manufactured of gold, platinum and platinum-gold alloy were placed into the eyelids of the experimental animals. The morphological examination was performed 1 and 6 months after the implantation using paraffin sections. RESULTS: Light microscopy revealed that the implant beds were surrounded by pronounced fibrovascular capsule of uneven thickness over the whole follow-up. The capsule formed after the placement of an implant made of gold and platinum alloy was more loose. However, the emerging connective tissue bridges of the capsule contributed to its immobilization in the tissues and lower risk of extrusion. No signs of an inflammatory and/or allergic reaction were observed in any of the cases. CONCLUSION: The obtained results show that implants made of a 90/10% platinum-gold alloy and 999.9 fine platinum have similar biointegration in terms of morphological features during 6 months of the follow-up period.


Assuntos
Doenças Palpebrais , Paralisia Facial , Animais , Doenças Palpebrais/etiologia , Doenças Palpebrais/cirurgia , Pálpebras/cirurgia , Paralisia Facial/cirurgia , Próteses e Implantes , Implantação de Prótese , Coelhos
5.
Urologiia ; (4): 14-17, 2020 Sep.
Artigo em Russo | MEDLINE | ID: mdl-32897008

RESUMO

OBJECTIVES: the study of the nature and severity of the reorganization of the structural elements of the bladder wall on experimental models of IC / BPS at the optical and ultrastructural levels. MATERIALS AND METHODS: The experimental model of IC / SBMP was created on 22 white New Zealand female rabbits weighing 1500-2000 g. The animals were divided into 2 groups: group 1 - 15 rabbits, which were introduced into the bladder wall urine taken from the animals bladder; Group 2 (control) - 7 animals that were injected into the bladder wall with a 0.9% NaCl solution. The biomaterial was examined by electron microscopy. The structural elements of the lamina propria of the bladder mucosa were evaluated. RESULTS: In the bladder mucosa of the experimental model, perivascular infiltration by inflammatory cells, pronounced edema of the lamina propria of the bladder mucosa, and the presence of numerous plasma cells having close contacts with macrophages, fibroblasts, and lymphocytes were revealed. In the nucleus of lymphocytes of a peripherally located supercondensed heterochromatin showed their apoptotic state. Edematous fluid was determined, penetrating mainly through the fenestra, located in the peripheral parts of the endothelial cells of capillaries and postcapillary venules. CONCLUSION: The study of the structural elements of the lamina propria of the bladder mucosa in the experiment by the method of electron microscopy made it possible to identify changes caused by the inflammatory process, both of an acute and productive nature. The results obtained showed that toxic damage to the lamina propria of the bladder mucosa causes apoptosis of fibroblasts of the lamina propria, leads to loosening of collagen fibers and, ultimately, to a decrease in the protective factors of the mucous membrane.


Assuntos
Cistite Intersticial , Animais , Elétrons , Células Endoteliais , Feminino , Microscopia Eletrônica , Membrana Mucosa , Coelhos
6.
Urologiia ; (4): 27-35, 2020 Sep.
Artigo em Russo | MEDLINE | ID: mdl-32897011

RESUMO

INTRODUCTION: Reconstructive plastic surgery is the gold standard in the treatment of primary urethral strictures, but the effectiveness of these methods does not reach 100%. In cases of recurrent urethral strictures, the effectiveness of standard operations is lower than with primary strictures, which requires a search for methods to improve the results of surgical treatment. PURPOSE OF THE STUDY: To evaluate the structure of the intercellular matrix, the cellular composition and regenerative potential of a plasma enriched in platelets after performing urethroplasty on a biological model. MATERIALS AND METHODS: Experiment was carried out on male rabbits ("Burgundy" breed) weighting 3.0-4.5 kg (18 individuals). 18 animals were divided into two groups: an experimental one (contained 9 individuals) and a control one (contained 9 individuals). All animals in each group were subjected to end-to-end plastic surgery of the urethral bulbous region using standard procedures. In the control group 4 ml of 0.9% NaCl isotonic solution was injected along the perimeter of the suture into anastomotic zone of the spongy body. Autologous plasma was injected to the animals from the experimental group. Histopathological examination was made by using routine pathological assessment with hematoxylin-eosin staining. The study also assessed the distribution and orientation of collagen fibers with Van Gieson stain. In order to objectively detail inflammatory and regenerative changes an additional immunohistochemical analysis was performed for the following antibodie groups: CD79a, CD43, CD31 (PECAM1), MMP1, MMP9. Quantitative analysis of structural changes was carried out by counting B- and T-lymphocytes having a positive membrane reaction with CD79a and CD43, respectively, in 10 representative sites in view (HPF) with a lens aperture of 0.65 in the highest concentration areas ("hot spots"). The expression level of MMP1, MMP9 was estimated by counting positive cells in 10 representative sites in view with a lens aperture of 0.65 in the submucosal and muscle layers. The level of angiogenesis in micropreparations was evaluated by counting the number of vessels in 10 sites in view (objective aperture of 0.65), reliable endothelial visualization was performed using CD31 expression (PECAM1). RESULTS: In the analysis of histological material use of platelet-rich plasma in the suture zone helps to reduce the area of necrotic changes and the inflammation severity, accelerated migration of macrophage-histiocytic cells to the alteration site and increased blood supply due to enhanced angiogenesis. In experimental samples a higher expression of metalloproteinases (collagenases) types 1 and 9, decreased collagen production and the correct orientation of collagen fibers during repair processes were noticed. CONCLUSIONS: The use of platelet-rich plasma helps to accelerate the reparative processes in the spongy body after urethroplasty. Another important positive effect of platelet-rich plasma is an increase in the expression of metalloproteinases, which leads to a decrease in collagen production and the correct orientation of collagen fibers. This allows to reduce the amount of pathological fibro-scar tissue in the operation area.


Assuntos
Plasma Rico em Plaquetas , Estreitamento Uretral/cirurgia , Animais , Humanos , Masculino , Modelos Teóricos , Coelhos , Uretra , Procedimentos Cirúrgicos Urológicos Masculinos
7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(9): 1177-1183, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-32929913

RESUMO

Objective: To assess the effect of microfracture and biomimetic hydrogel scaffold on tendon-to-bone healing in a rabbit rotator cuff tear model. Methods: Gelatin and methacrylic anhydride were used to synthesize gelatin methacryloyl (GelMA). Then the GelMA were treated with ultraviolet rays and vacuum freeze-drying method to obtain a biomimetic hydrogel scaffold. The morphology of the scaffold was observed by gross observation and scanning electron microscope. Degradation of the scaffold was determined at different time points. Twenty-four adult New Zealand rabbits, weighting 2.8-3.5 kg and male or female, were surgically created the bilateral acute rotator cuff tear models. One shoulder was treated with microfractures on the footprint and transosseous suture (control group, n=24). The other shoulder was treated with the same way, except for putting the scaffold on the footprint before transosseous suture (experimental group, n=24). The general conditions of rabbits were observed postoperatively. Tendon-to-bone healing was evaluated by gross observation, Micro-CT, HE staining, and bio-mechanical testing at 4 and 8 weeks after operation. Results: The scaffold was white and has a porous structure with pore size of 31.7-89.9 µm, which degraded slowly in PBS solution. The degradation rate was about 95% at 18 days. All the rabbits survived to the completion of the experiment. Micro-CT showed that there was no obvious defect and re-tear at the tendon-to-bone interface in both groups. No difference was found in bone mineral density (BMD), tissue mineral density (TMD), and bone volume/total volume (BV/TV) between the two groups at 4 and 8 weeks postoperatively ( P>0.05). HE staining showed that the fibrous scar tissue was the main component at the tendon-to-bone interface in the control group at 4 and 8 weeks postoperatively; the disorderly arranged mineralized cartilage and fibrocartilage formation were observed at the tendon-to-bone interface in the experimental group at 4 weeks, and the orderly arranged cartilage formation was observed at 8 weeks. Besides, the tendon maturation scores of the experimental group were significantly higher than those of the control group at 4 and 8 weeks ( P<0.05). There was no significant difference in the ultimate load to failure and stiffness between the two groups at 4 weeks ( P>0.05); the ultimate load to failure at 8 weeks was significantly higher in the experiment group than in the control group ( t=4.162, P=0.009), and no significant difference was found in stiffness between the two groups at 8 weeks ( t=2.286, P=0.071). Conclusion: Compared with microfracture alone, microfracture combined with biomimetic hydrogel scaffold can enhance tendon-to-bone healing and improve the ultimate load to failure in rabbits.


Assuntos
Fraturas de Estresse , Lesões do Manguito Rotador , Animais , Fenômenos Biomecânicos , Biomimética , Hidrogéis , Masculino , Coelhos , Manguito Rotador , Tendões , Cicatrização
8.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(9): 1184-1189, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-32929914

RESUMO

Objective: To study the effect of chemical extraction of allogeneic tendon and allogeneic chondrocytes for reconstruction of anterior labrum of shoulder joint in rabbits. Methods: The body weight of 45 adult New Zealand white rabbits ranged from 2.5 to 3.0 kg. The Achilles tendons of 15 rabbits were taken and the allogeneic tendons were prepared by chemical extraction with antigen inactivation. The extracted tendons were compared with untreated tendons by HE and Masson stainings. Chondrocytes were isolated and cultured by trypsin method and identified by immunohistochemical staining of collagen type Ⅱ. The remaining 30 rabbits were used to prepare the model of anterior labrum defect of shoulder joint. After the allogeneic tendon was transplanted to the damaged labrum, the rabbits was randomly divided into two groups (15 in each group). In group A, the allogeneic chondrocytes were injected into the joint immediately after transplantation, while in group B, no treatment was made. At 4, 6, and 8 weeks after operation, 5 transplanted tendons of each group were taken. After general observation, HE staining was used to observe the number of nuclei, Masson staining was used to observe the expression of collagen fibers in muscle fiber tissues, and AB staining was used to detect the glycosaminoglycan level after transplantation, to evaluate the cell growth in the tissues of the two groups of allogeneic tendon. Results: By HE and Masson stainings, the allogeneic tendon antigen prepared by chemical extraction method was inactivated and the fibrous tissue structure was intact; collagen type Ⅱ immunohisto-chemistry staining showed that the cultured cells were chondrocytes. After tendon transplantation, the content of glycosaminoglycan in group A was significantly higher than that in group B ( P<0.05). At 6 weeks after operation, HE staining showed that the nuclear in tendon tissue of group A was significantly more than that of group B ( t=20.043, P=0.000). Masson staining showed that the number of nuclei in tendon tissue of group A was significantly increased, the muscle fibers and collagen fibers were interlaced, the tissue structure was more compact, and the tendon tissue was mainly blue stained; while the number of nuclei in group B was less, mainly collagen fibers of the original graft. Conclusion: The allogeneic tendon inactivated by chemical extraction can be used to reconstruct the defect of anterior labrum of shoulder joint in rabbits, and the combination of allogeneic chondrocytes can promote the healing of tendon transplantation.


Assuntos
Tendão do Calcâneo , Transplante de Células-Tronco Hematopoéticas , Articulação do Ombro , Animais , Condrócitos , Coelhos , Cicatrização
10.
PLoS Pathog ; 16(9): e1008871, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32936831

RESUMO

Deconvolution of syphilis pathogenesis and selection of candidate syphilis vaccinogens requires detailed knowledge of the molecular architecture of the Treponema pallidum outer membrane (OM). The T. pallidum OM contains a low density of integral OM proteins, while the spirochete's many lipoprotein immunogens are periplasmic. TP0751, a lipoprotein with a lipocalin fold, is reportedly a surface-exposed protease/adhesin and protective antigen. The rapid expansion of calycin/lipocalin structures in the RCSB PDB database prompted a comprehensive reassessment of TP0751. Small angle X-ray scattering analysis of full-length protein revealed a bipartite topology consisting of an N-terminal, intrinsically disordered region (IDR) and the previously characterized C-terminal lipocalin domain. A DALI server query using the lipocalin domain yielded 97 hits, 52 belonging to the calycin superfamily, including 15 bacterial lipocalins, but no Gram-negative surface proteins. Surprisingly, Tpp17 (TP0435) was identified as a structural ortholog of TP0751. In silico docking predicted that TP0751 can bind diverse ligands along the rim of its eight-stranded ß-barrel; high affinity binding of one predicted ligand, heme, to the lipocalin domain was demonstrated. qRT-PCR and immunoblotting revealed very low expression of TP0751 compared to other T. pallidum lipoproteins. Immunoblot analysis of immune rabbit serum failed to detect TP0751 antibodies, while only one of five patients with secondary syphilis mounted a discernible TP0751-specific antibody response. In opsonophagocytosis assays, neither TP0751 nor Tpp17 antibodies promoted uptake of T. pallidum by rabbit peritoneal macrophages. Rabbits immunized with intact, full-length TP0751 showed no protection against local or disseminated infection following intradermal challenge with T. pallidum. Our data argue that, like other lipoprotein lipocalins in dual-membrane bacteria, TP0751 is periplasmic and binds small molecules, and we propose that its IDR facilitates ligand binding by and offloading from the lipocalin domain. The inability of TP0751 to elicit opsonic or protective antibodies is consistent with a subsurface location.


Assuntos
Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Imunização , Lipoproteínas/imunologia , Sífilis/imunologia , Treponema pallidum/imunologia , Animais , Proteínas de Bactérias/genética , Vacinas Bacterianas/genética , Humanos , Lipoproteínas/genética , Domínios Proteicos , Dobramento de Proteína , Coelhos , Sífilis/genética , Sífilis/patologia , Sífilis/prevenção & controle , Treponema pallidum/genética , Treponema pallidum/patogenicidade
11.
Sci Rep ; 10(1): 15917, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985513

RESUMO

SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/veterinária , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos/genética , Animais , Gatos , Biologia Computacional/métodos , Infecções por Coronavirus/patologia , Cricetinae , Modelos Animais de Doenças , Cães , Furões , Furina/genética , Furina/metabolismo , Cobaias , Humanos , Macaca fascicularis , Camundongos , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/genética , Pneumonia Viral/patologia , Coelhos , Ratos , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo
12.
Int J Oral Maxillofac Implants ; 35(5): 879-887, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991637

RESUMO

PURPOSE: To evaluate the influence on healing of the bony window elevated inward in the sinus cavity as a cortical bone graft. MATERIALS AND METHODS: Eighteen rabbits were included in the experiment. At the test sites (bony window), the antrostomy was prepared and the remaining bony window was elevated together with the sinus mucosa. At the control sites, the bony window was gently detached before the sinus mucosa elevation and discarded. The space obtained was grafted with deproteinized bovine bone mineral (DBBM). A collagen membrane was positioned on the antrostomy at both sides. The rabbits were euthanized after 2, 4, and 8 weeks in groups of six each. Histologic analyses in different regions of the elevated space were carried out, and a Wilcoxon test was used to estimate differences. Microcomputed tomography (microCT) analyses were also performed. RESULTS: After 2 weeks of healing, higher proportions of new bone were found in the test group compared with the control group due to the higher amount of bone formed in the region subjacent to the sinus mucosa. In this region, higher amounts of new bone were also found in the test group after 4 (P = .028) and 8 weeks of healing (P = .345). After 8 weeks of healing, the percentage of new bone was higher at the control sites compared with the test sites, with the proportions being 25.4% ± 3.2% and 21.3% ± 6.1%, respectively. In this period of evaluation, the bony window contributed with 20.1% ± 5.3% of vital bone in the test group. A fraction of 60.4% ± 10.8% of its surface was surrounded by new bone. In the microCT analysis, after 8 weeks of healing, fractions of 22.3% ± 1.6% and 22.2% ± 0.7% of bone were found in the test and control groups, respectively. CONCLUSION: The presence of the bony window positively influenced the healing in the elevated space, especially in the submucosa region. The bony window was vital and incorporated into newly formed bone.


Assuntos
Levantamento do Assoalho do Seio Maxilar , Animais , Transplante Ósseo , Bovinos , Osso Cortical/diagnóstico por imagem , Osso Cortical/cirurgia , Coelhos , Cicatrização , Microtomografia por Raio-X
13.
Int J Oral Maxillofac Implants ; 35(5): 917-923, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991641

RESUMO

PURPOSE: Compaction of particulated grafts is done manually; thus, the effect of compression force on bone regeneration remains unclear. The aim of this study was to evaluate the impact of two different compression forces on the consolidation of particulated bovine hydroxyapatite. MATERIALS AND METHODS: Two titanium cylinders were fixed on the calvarium of eight New Zealand rabbits. Both defects were filled with particulated bovine hydroxyapatite subjected to a compression force of 0.7 kg/cm2 or 1.6 kg/cm2 before being covered with a resorbable collagen membrane. A handheld device that uses a spring to control the compression force applied by the plugger was used. At 6 weeks, histomorphometry of the area immediately adjacent to the calvaria bone and to the collagen membrane was performed. RESULTS: It was shown that next to the calvaria, the bone volume per tissue volume (BV/TV) was 29.0% ± 8.8% and 27.6% ± 8.2% at low and high compression force, respectively; the bone-to-biomaterial contact (BBC) was 58.2% ± 25.0% and 69.3% ± 22.9%, respectively (P > .05). In the corresponding area next to the collagen membrane, BV/TV was 4.9% ± 5.1% and 5.7% ± 4.7%, and the BBC was 18.3% ± 20.8% and 20.1% ± 15.9%, respectively (P > .05). In addition, the number and area of blood vessels were not significantly affected by compression force. CONCLUSION: Both compression forces applied resulted in similar consolidation of bovine hydroxyapatite expressed by new bone formation and vascularization based on a rabbit calvaria augmentation model.


Assuntos
Regeneração Óssea , Durapatita , Animais , Materiais Biocompatíveis , Bovinos , Colágeno , Coelhos , Crânio/cirurgia
14.
Adv Clin Exp Med ; 29(9): 1073-1081, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32886457

RESUMO

BACKGROUND: Inflammatory pseudotumor of the liver (IPTL) is misdiagnosed usually as a malignant tumor based on the imaging findings. Differential diagnosis should be established to avoid hepatic resection. At imaging, IPTL has been misdiagnosed usually as hepatocellular carcinoma (HCC). It is usually found firstly using conventional ultrasonic examination, which cannot give a definitive diagnosis. Because of its atypical clinical presentation and radiological appearance, a presumptive diagnosis of malignancy is frequently made. With the development of ultrasound systems and ultrasound contrast agents (UCA), contrast-enhanced ultrasound is widely used in diagnosing focal lesions of the liver. OBJECTIVES: To delineate the hemodynamic features of IPTL compared with hepatic VX2 tumor and normal liver using contrast-enhanced ultrasound. MATERIAL AND METHODS: Freund's complete adjuvant (FCA) was injected using a modified method into the desirable portion of the liver in rabbits. Two weeks after the injection, solitary IPTLs were formed (which was proved with pathological examination). Ten rabbits with IPTL, 10 rabbits with VX2 carcinoma and 10 healthy rabbits were studied using contrast-enhanced ultrasound with bolus injection of SonoVueTM through the peripheral vein. Corresponding parameters such as time to enhancement (ET), time to peak intensity (PIT), time to ascent (AT), and time to lighten (LT) were measured with wash-in/wash-out curve. RESULTS: Contrast-enhanced imaging clearly delineated the dynamic enhancement of the lesions and liver parenchyma during the whole phase. Inflammatory pseudotumor of the liver showed the same enhanced features as the liver parenchyma. In VX2 tumors, hyperechoic enhancement in arterial phase and hypoechoic enhancement was observed in the portal and delayed phase compared with the surrounding hepatic parenchyma. The normal liver showed whole of liver parenchyma enhanced in portal phase. CONCLUSIONS: The study showed that contrast-enhanced ultrasound provided useful information about perfusion in IPTL and VX2 carcinoma. Contrast-enhanced ultrasound is a useful technique in the differential diagnosis of focal liver lesions if combined with time-intensity curve.


Assuntos
Carcinoma Hepatocelular , Granuloma de Células Plasmáticas , Neoplasias Hepáticas , Animais , Meios de Contraste , Coelhos , Ultrassonografia
15.
Nat Commun ; 11(1): 4446, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895387

RESUMO

Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe3O4/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe3O4/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.


Assuntos
Nanopartículas de Magnetita/uso terapêutico , Micro-Ondas/uso terapêutico , Osteomielite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Tratamento Farmacológico/métodos , Óxido Ferroso-Férrico/uso terapêutico , Gentamicinas/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanotubos de Carbono , Osteomielite/microbiologia , Coelhos
16.
Acta Cir Bras ; 35(8): e202000801, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32901678

RESUMO

PURPOSE: To evaluate the use of demineralized bone matrix of caprine origin in experimental bone defects of the tibia in New Zealand rabbits. METHODS: Fragments of the tibia diaphysis were collected aseptically from clinically healthy goats. The bones were sectioned into 1 cm fragments and stored at -20°C for subsequent hydrochloric acid (HCL) demineralization. A 70 mg portion of DBMc was used to fill the experimental bone defects. Twenty-four female adult New Zealand rabbits were divided into 2 groups: the MG (matrix group, left tibia) and CG (control group, right tibia). Additionally, they were separated into 4 groups with 6 animals, according to the period of analysis (15, 30, 60 and 90 days postoperatively). Using microCT, volumetric parameters were evaluated: bone volume, relationship between bone volume and total volume, bone surface area, relationship between bone surface area and total volume, number of trabeculae, trabecular thickness and trabecular separation. RESULTS: There was a statistically significant difference (P<0.05) between groups considering bone volume (BV) and bone:total volume (BV/TV), on 15, 30 and 90 days postoperatively. Control group showed a statistically significant superiority (P < 0.05) considering the mean of the variables bone surface (BS), number of trabeculae (Tb.N) and between bone surface and total volume (BS/TV) at 15 and 90 days. CONCLUSIONS: Caprine demineralized bone matrix was safe and tolerable. No signs of material rejection were seen macroscopically. It is an alternative for the treatment of bone defects when autologous graft is not available or in insufficient quantities.


Assuntos
Transplante Ósseo , Cabras , Transplante Heterólogo , Animais , Matriz Óssea , Feminino , Xenoenxertos , Coelhos , Tíbia
17.
Sci Rep ; 10(1): 15917, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: covidwho-800800

RESUMO

SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/veterinária , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos/genética , Animais , Gatos , Biologia Computacional/métodos , Infecções por Coronavirus/patologia , Cricetinae , Modelos Animais de Doenças , Cães , Furões , Furina/genética , Furina/metabolismo , Cobaias , Humanos , Macaca fascicularis , Camundongos , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/genética , Pneumonia Viral/patologia , Coelhos , Ratos , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(6): 684-692, 2020 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879126

RESUMO

OBJECTIVES: To evaluate the repairing ability of nano-pearl powder bone substitute in rabbit with defect of distal femur bone. METHODS: Thirty-two New Zealand rabbits were randomly divided into four groups: a nano-pearl powder/recombinant human bone morphogenetic protein 2 (rhBMP-2)/hyaluronic acid group, a nano-pearl powder/hyaluronic acid group, a nano-pearl powder group and a blank control group (n=8 in each group). A defect with the diameter of 7 mm and height of 10 mm was prepared at the distal femoral metaphysis line of the rabbit.Different bone substitutes were planted, and the effect of repair was evaluated by macroscopic observation, imaging examination, and histopathological examination. RESULTS: The results of imageology showed that: the bone repairing effect in the nano-pearl powder/rhBMP-2/hyaluronic acid group was better than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group, and which in the 3 experimental groups was better than that in the blank control group; The results of histology showed that: at the 4th, 8th and 12th weeks after the modeling operation, the speed of bone repair in the nano-pearl powder/rhBMP-2/hyaluronic acid group was faster than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group, and which in the blank control group was far slower than that in the 3 experimental groups. The results of immunohistochemistry staining for osteocalcin antibody showed that: the osteogenic effect in the nano-pearl powder/rhBMP-2/hyaluronic acid group was better than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group (both P<0.05); there was no significant difference between the nano-pearl powder/hyaluronic acid group and the pure pearl powder group (P>0.05); however, there was significant difference between the pure pearl powder group and the blank control group (P<0.05). According to the staining results of Type I collagen antibody, there was no significant difference in the osteogenic effect between the nano-pearl powder/rhBMP-2/hyaluronic acid group and the nano-pearl powder/hyaluronic acid group (P>0.05), but the osteogenic effect in the nano-pearl powder/hyaluronic acid group was better than that in the pure pearl powder group and the blank control group (both P<0.05). CONCLUSIONS: Nano-pearl powder and its bone substitute can promote the repair of bone defect, and the nano-pearl powder which contains rhBMP-2 has better osteogenic and repairing effect on defect.


Assuntos
Substitutos Ósseos , Animais , Proteína Morfogenética Óssea 2 , Colágeno , Fêmur , Humanos , Osteogênese , Pós , Coelhos , Proteínas Recombinantes , Fator de Crescimento Transformador beta
20.
Yakugaku Zasshi ; 140(9): 1141-1150, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879246

RESUMO

Osteoarthritis is the most common joint disorder worldwide and one of the leading causes of disability in the elderly. We have reported that the novel sodium hyaluronate derivative chemically linked with diclofenac (DF), diclofenac etalhyaluronate (SI-613), exerted a potent and long-lasting analgesic effect in experimental arthritis models. In this study, we evaluated the properties of residual SI-613 in the knee joint after an intra-articular (IA) administration. After IA administration of fluorescent labeled SI-613 (FA-SI-613) or fluorescent labeled hyaluronic acid (FA-HA) to rabbits, fluorescence intensities in the synovial membrane and cartilage were higher in the FA-SI-613 group until 7 d after administration than in the FA-HA group. After IA administration of radiolabeled SI-613 (14C-SI-613) to rabbits, the radioactivity remained in the joint cavity and the joint tissues such as synovial membrane and cartilage until 84 d after administration. This residual radioactivity was identified mainly as HA linked with DF, since 14C-SI-613 was labeled at the benzene ring of DF and since more DF-linked HA oligomer was detected on metabolite analysis than free DF in the synovial membrane and synovial lavage fluid up to 28 d after administration. These results suggested that intra-articularly administered SI-613 remained for a longer time in the joint as HA linked with DF than when HA was administered. Therefore, SI-613 was considered to prolong the pharmacological effects of both HA and DF by remaining in the joint as HA linked with DF.


Assuntos
Diclofenaco/administração & dosagem , Diclofenaco/metabolismo , Ácido Hialurônico/análogos & derivados , Articulação do Joelho , Osteoartrite/tratamento farmacológico , Animais , Cartilagem/metabolismo , Modelos Animais de Doenças , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/metabolismo , Injeções Intra-Articulares , Articulação do Joelho/metabolismo , Masculino , Coelhos , Membrana Sinovial/metabolismo , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA