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1.
AAPS PharmSciTech ; 22(5): 170, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34085150

RESUMO

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.


Assuntos
Resinas Acrílicas/química , Administração Oftálmica , Quitosana/química , Nanofibras/química , Ofloxacino/química , Álcool de Polivinil/química , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/farmacocinética , Animais , Antibacterianos/química , Química Farmacêutica/métodos , Quitosana/administração & dosagem , Quitosana/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Nanofibras/administração & dosagem , Ofloxacino/administração & dosagem , Ofloxacino/farmacocinética , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/farmacocinética , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(2): 229-238, 2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-34137224

RESUMO

To establish a rabbit model of proprotein convertase subtilisin/kexin type9 () point mutation with CRISPR/Cas9 gene editing technique. According to the PubMed gene protein data, the PCSK9 protein functional regions of human and rabbit were analyzed by Blast. The 386S (Ser) amino acid functional region of human gene was homologous to the 485S of rabbit gene. Three small guide RNAs and one single-stranded donor oligonucleotide were designed according to the 485S base substitution position and sequence analysis of rabbit gene. The synthetic small guide RNAs, Cas9 mRNA and single-stranded donor oligonucleotide were co-injected into the cytoplasm of rabbit fertilized eggs and the embryos were transferred into the pregnant rabbits. PCR, TA cloning and off-target analysis were performed on the F0 rabbits to identify whether the PCSK9 mutation was successful. Fifteen F0 rabbits were obtained. The sequencing results showed that one of them was PCSK9 point mutation homozygote and two of them were PCSK9 point mutation heterozygotes, and the mutation could be stably inherited. The rabbit model of PCSK9 point mutation was successfully constructed by CRISPR/Cas9 technique, which provides an animal model for exploring the molecular mechanism of impaired PCSK9 function and developing reliable and effective diagnosis and treatment measures.


Assuntos
Sistemas CRISPR-Cas , Pró-Proteína Convertase 9 , Animais , Sistemas CRISPR-Cas/genética , Mutação , Mutação Puntual , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Coelhos
3.
Acta Cir Bras ; 36(4): e360406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076083

RESUMO

PURPOSE: To evaluate the effects of controlled decompression and rapid decompression, explore the potential mechanism, provide the theoretical basis for the clinical application, and explore the new cell death method in intracranial hypertension. METHODS: Acute intracranial hypertension was triggered in rabbits by epidural balloon compression. New Zealand white rabbits were randomly put into the sham group, the controlled decompression group, and the rapid decompression group. Brain water content, etc., was used to evaluate early brain injury. Western blotting and double immunofluorescence staining were used to detect necroptosis and apoptosis. RESULTS: Brain edema, neurological dysfunction, and brain injury appeared after traumatic brain injury (TBI). Compared with rapid decompression, brain water content was significantly decreased, neurological scores were improved by controlled decompression treatment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining showed neuron death decreased in the controlled decompression group. Compared with rapid decompression, it was also found that apoptosis-related protein caspase-3/ tumor necrosis factor (TNF)-a was reduced markedly in the brain cortex and serum, and the expression levels of necroptosis-related protein, receptor-interacting protein 1 (RIP1)/receptor-interacting protein 1 (RIP3) reduced significantly in the controlled decompression group. CONCLUSIONS: Controlled decompression can effectively reduce neuronal damage and cerebral edema after craniocerebral injury and, thus, protect the brain tissue by alleviating necroptosis and apoptosis.


Assuntos
Lesões Encefálicas , Hipertensão Intracraniana , Animais , Apoptose , Descompressão , Necroptose , Coelhos , Ratos , Ratos Sprague-Dawley
4.
J Biomed Nanotechnol ; 17(5): 901-909, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082875

RESUMO

Alginate/Silk fibroin/hyaluronic acid (ALG/SF/HA) nanocomposites were synthesised using blending, inter-linking, and lyophilization methods. We investigated the physicochemical properties of the resulting nanocomposites, including their water retention, weight loss, porosity and cytocompatibility. The optimum ratios of the ALG/SF/HA scaffolding were 3:6.5:0.5. Nanocomposites with optimum ratios were then prepared by integrating pilose antler polypeptides (PAPS) to poly(lactic-co-glycolic acid) (PLGA) microspheres, and the performance was investigated. PAPS-ALG/SF/HA nanocomposites exhibited desirable adhesions and proliferations. Rabbit cartilage deficiencies was developed by the animal model. The cartilage repair effects deficiencies were detected and analyzed between PAPS-SF/ALG/ALG/SF/HA, and control activity classes. The deficiencies were virtually fully remedied after 13 weeks in the presence of PAPS-ALG/SF/HA class, suggesting that the PAPS-ALG/SF/HA nanocomposites had a positive effects on joint cartilage repair.


Assuntos
Alginatos , Cartilagem Articular , Engenharia Tecidual , Animais , Ácido Hialurônico , Microesferas , Peptídeos , Coelhos , Regeneração , Seda , Tecidos Suporte
5.
Int J Nanomedicine ; 16: 3613-3631, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079253

RESUMO

Purpose: Anti-inflammation is essential for dry eye disease. Traditional anti-inflammation agent corticosteroids applied in dry eye disease (DED) treatment could result in high intraocular pressure, especially in long-term treatment. Thus, we have prepared a liposome loading 1-bromoheptadecafluorooctane and tetrandrine (PFOB@LIP-Tet) to treat DED via anti-inflammation that hardly affects intraocular pressure in this study, which provided another therapy strategy for dry eye disease. Methods: We firstly detected the physicochemical properties of PFOB@LIP-Tet. Next, we tested the biosafety of synthesized liposomes for corneal epithelium. Then, we explored the accumulations and distribution of PFOB@LIP-Tet both in cellular and animal models. And then, we assessed the therapeutic effects of PFOB@LIP-Tet formulations by laboratory and clinical examinations. Last, we examined the changes in eye pressure before and after treatment. Results: PFOB@LIP-Tet and Tet showed a characteristic absorption peak at 282 nm while PFOB@LIP did not. Large amounts of PFOB@LIP-Tet remained on the ocular surface and accumulated in the corneal epithelial cells in DED rabbits. Corneal staining scores of DED rabbits respectively treated by ATS, PFOB@LIP-ATS, Tet-ATS and PFOB@LIP-Tet-ATS for seven days were 3.7±0.5, 3.2±0.4, 1.5±0.5 and 0.5±0.5. The expressions of related cytokines were correspondingly downregulated significantly, indicating that the inflammation of DED was successfully suppressed. The intraocular pressure changes of DED rabbits before and after treatment by PFOB@LIP-Tet showed no statistical significance. Conclusion: We successfully synthesized PFOB@LIP-Tet, and it could effectively treat dry eye disease via anti-inflammation but hardly affected the intraocular pressure.


Assuntos
Síndromes do Olho Seco/tratamento farmacológico , Nanomedicina , Animais , Benzilisoquinolinas/administração & dosagem , Benzilisoquinolinas/efeitos adversos , Benzilisoquinolinas/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Interações Medicamentosas , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Epitélio Anterior/efeitos dos fármacos , Epitélio Anterior/patologia , Pressão Intraocular/efeitos dos fármacos , Lipossomos , Coelhos
6.
Nat Commun ; 12(1): 3303, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083518

RESUMO

Peri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.


Assuntos
Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Peri-Implantite/prevenção & controle , Peri-Implantite/terapia , Titânio/farmacologia , Aminas/administração & dosagem , Aminas/química , Aminas/farmacologia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Materiais Revestidos Biocompatíveis/administração & dosagem , Materiais Revestidos Biocompatíveis/química , Implantes Dentários , Estabilidade de Medicamentos , Humanos , Técnicas In Vitro , Masculino , Teste de Materiais , Osseointegração/efeitos dos fármacos , Peri-Implantite/microbiologia , Porosidade , Coelhos , Propriedades de Superfície , Titânio/administração & dosagem , Titânio/química
7.
Acta Cir Bras ; 36(4): e360402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978094

RESUMO

PURPOSE: To assess the influence of prolonged cyclosporine use on the macro- and microscopic morphology of the spleen. METHODS: 16 adult rabbits were divided into two groups (n = 8): group 1 - a placebo group, which was followed-up over a period of nine months; group 2 - which had taken an oral dose of cyclosporine (10 mg·kg-1·day-1) over nine months. At the end of this period, the splenic histoarchitecture of all animals was evaluated and the splenic corpuscles were measured. RESULTS: The spleens of the first group presented normal characteristics and dimensions. The second group, however, had a reduction in all dimensions and its tissue texture had become soft. The white pulp and the perivascular sheath had become reduced in size and the number of lymphoid follicles had also fallen (p = 0.002), manifesting less splenic corpuscles (p = 0.0012) and lymphocyte nuclear pigments (p = 0.03). CONCLUSIONS: Prolonged use of cyclosporine reduces the spleen size, transforming it into a soft organ associated with a decrease in white pulp, perivascular sheath, lymphoid follicles and nuclear pigments in rabbits.


Assuntos
Ciclosporina , Baço , Animais , Ciclosporina/farmacologia , Coelhos
8.
Nat Commun ; 12(1): 2633, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976149

RESUMO

Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1C modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1C exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display.


Assuntos
Vacinas contra Ebola/administração & dosagem , Glicoproteínas/administração & dosagem , Doença pelo Vírus Ebola/terapia , Proteínas Virais/administração & dosagem , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Antígenos Virais/administração & dosagem , Antígenos Virais/genética , Antígenos Virais/imunologia , Antígenos Virais/ultraestrutura , Linfócitos B/imunologia , Cristalografia por Raios X , Modelos Animais de Doenças , Vacinas contra Ebola/genética , Vacinas contra Ebola/imunologia , Ebolavirus/genética , Ebolavirus/imunologia , Epitopos de Linfócito T/administração & dosagem , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/ultraestrutura , Feminino , Glicoproteínas/genética , Glicoproteínas/imunologia , Glicoproteínas/ultraestrutura , Doença pelo Vírus Ebola/sangue , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/virologia , Humanos , Camundongos , Nanopartículas/química , Domínios Proteicos/genética , Domínios Proteicos/imunologia , Engenharia de Proteínas , Multimerização Proteica/genética , Multimerização Proteica/imunologia , Estabilidade Proteica , Coelhos , Linfócitos T Auxiliares-Indutores/imunologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia , Proteínas Virais/ultraestrutura
9.
Adv Exp Med Biol ; 1269: 387-391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33966247

RESUMO

The gene expression of Prox-1 and Hif-1a for the isolated primo vessels (PVs) and composite lymphatic vessels (LVs) containing PVs (LVs + PVs) was investigated by RNA-sequencing (Seq) and quantitative polymerase chain reaction (qRT-PCR) analysis. RNA-Seq on the passed 10 samples on RNA-QC for two experimental groups with PVs and PVs + LVs proceeded to the library construction stage automatically and analyzed differentially expressed genes (DEGs). From the real-time qRT-PCR analysis data, we found the marker genes of Prox-1 and Hif-1a were enriched and decreased in an isolated PVs compared to LVs, respectively. Based on mRNA transcriptional data, Prox-1 and Hif-1a were increased and decreased in PVs compared to LVs + PVs under lipopolysaccharide (LPS) treatment and relieved by acupuncture electric stimulation (AES), respectively. This finding indicates that high and low levels of Prox-1 and Hif-1a may be involved in the function of PVs and that pathophysiological and physiological condition could progress into inflamed lymphatic endothelial cells expanding the PV within the LV.


Assuntos
Células Endoteliais , Vasos Linfáticos , Animais , Expressão Gênica , Proteínas de Homeodomínio , Subunidade alfa do Fator 1 Induzível por Hipóxia , Lipopolissacarídeos , Coelhos , Análise de Sequência de RNA
10.
Acta Cir Bras ; 36(4): e360404, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037081

RESUMO

PURPOSE: To use a 3D printed poly (L-lactide) acid (PLLA) and hydroxyapatite (HA) composite as a bone substitute for reconstruction of a critical bone defect in the radius of rabbits. METHODS: A 1.5 cm ostectomy was performed in the radial diaphysis of 60 New Zealand white rabbits. The rabbits were divided into three groups according to surgical treatment of the bone defect (group I - control, group II - bone graft, group III - 3D PLLA). Each group was divided into four subgroups with different radiographic and histopathologic evaluation times (T1 - 15 days, T2 - 30 days, T3 - 60 days, T4 - 90 days). RESULTS: The implant group had greater clinically lameness (p = 0.02), edema (p = 0.007), pain (p = 0.04) and more complications at the surgical site (p = 0.03). Histologically, this group showed greater congestion (p = 0.04), hemorrhage (p = 0.04) and inflammation. Osteogenesis was microscopically similar between days (p = 0.54) and treatments (p = 0.17), even though radiographically, more effective bone healing occurred in the graft group (II), with more callus and bone bridge formation. CONCLUSIONS: The customization of a 3D PLLA/HA scaffold was successful. However, in animals receiving the polymer-ceramic composite less bone callus and bone bridge was formed compared to the graft group.


Assuntos
Substitutos Ósseos , Durapatita , Animais , Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Dioxanos , Osteogênese , Poliésteres , Coelhos , Tecidos Suporte
11.
Sci Total Environ ; 779: 146461, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34030245

RESUMO

In industrialized countries, biodiversity is threatened by high atmospheric N deposition. In coastal dunes, blowouts can mitigate this through deposition of fresh sand, but lime-rich and lime-poor dunes may differ in blowout activity. We studied natural blowout activity and explanatory factors in 2000 and 2014 in up to 51 sites along the Dutch coast, representative for other parts of Europe. We further analyzed plant and soil characteristics related to P nutrition in seven sites in 2019 and found that blowout activity was intrinsically linked to interactions between the geosphere, pedosphere and biosphere. Blowout activity was higher in lime-rich than in lime-poor dunes, especially in 2014. This difference could not be explained by wind velocity and only partly by position in the landscape, but was associated with pH, critical N load and rabbit density. At high pH, P availability to the vegetation was low. Arbuscular mycorrhizal (AM) plant species thus predominated, which belong to the most characteristic dune plants and may provide rabbit food of better quality than nonmycorrhizal (NM) or ericoid mycorrhizal (ErM) plants. Root biomass was also low at high pH, which may reduce cohesion of the sand and increase blowout activity, especially in areas with high rabbit density. At low pH, P availability increased, which favored NM and ErM rather than AM plants, and root biomass increased, which increased stability of the blowouts. As a restoration measure, (re)activation of blowouts may improve buffer capacity, characteristic biodiversity and conservation status of coastal dune grasslands. However, lime-poor dunes are more vulnerable to acidification, increase in P availability and blowout stabilization than lime-rich dunes. In extremely lime-poor dunes, it may even be better to let vegetation develop towards Dune heathlands, which are also EU priority habitats.


Assuntos
Ecossistema , Solo , Animais , Compostos de Cálcio , Europa (Continente) , Óxidos , Plantas , Coelhos
12.
Parasite ; 28: 40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33944773

RESUMO

Eimeria tenella is an obligate intracellular parasite that actively invades cecal epithelial cells of chickens. This parasite encodes a genome of more than 8000 genes. However, more than 70% of the gene models for this species are currently annotated as hypothetical proteins. In this study, a conserved hypothetical protein gene of E. tenella, designated EtCHP18905, was cloned and identified, and its immune protective effects were evaluated. The open reading frame of EtCHP18905 was 1053bp and encoded a protein of 350 amino acids with a molecular weight of 38.7kDa. The recombinant EtCHP18905 protein (rEtCHP18905) was expressed in E. coli. Using western blot, the recombinant protein was successfully recognized by anti GST-Tag monoclonal antibody and anti-sporozoites protein rabbit serum. Real-time quantitative PCR analysis revealed that the EtCHP18905 mRNA levels were higher in sporozoites than in unsporulated oocysts, sporulated oocysts and second-generation merozoites. Western blot analysis showed that EtCHP18905 protein expression levels were lower in sporozoites than in other stages. Immunofluorescence analysis indicated that the EtCHP18905 protein was located on the surface of sporozoites and second-generation merozoites. Inhibition experiments showed that the ability of sporozoites to invade host cells was significantly decreased after treatment with the anti-rEtCHP18905 polyclonal antibody. Vaccination with rEtCHP18905 protein was able to significantly decrease mean lesion scores and oocyst outputs as compared to non-vaccinated controls. The results suggest that the rEtCHP18905 protein can induce partial immune protection against infection with E. tenella and could be an effective candidate for the development of new vaccines.


Assuntos
Eimeria tenella , Animais , Galinhas , Clonagem Molecular , Eimeria tenella/genética , Escherichia coli/genética , Proteínas de Protozoários/genética , Coelhos
13.
AAPS PharmSciTech ; 22(4): 153, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33982230

RESUMO

Large volumes of protein solutions are commonly stored in a frozen state before further drug product fill and finish. This study aimed to establish a design space to perform large-scale freeze-thaw (F/T) processes of biotherapeutics without inducing protein destabilization. A response surface model was designed to evaluate the following main factors and interactions: fill volume of the protein solution in 1-L containers, distance among nine containers during both F/T, freezer set temperature, and a novel forced air flow methodology during thawing. The analysis from 46 experimental runs indicated over 4-fold increase in the freezing rate by lowering the freezing temperature from -20 to -80°C, and the forced air flow at 98 fpm doubled the thawing rate. Furthermore, multivariate linear regression modeling revealed the significant impact of all main factors investigated on lactate dehydrogenase (LDH) quality attributes. The factor that most strongly affected the retention of LDH activity was the loading distance: ≥ 5 cm among containers positively affected the LDH activity response in 50.6%. The factor that most strongly retained the LDH tetramers was the set freezer temperature towards the lower range of -80°C (2.2% higher tetramer retention compared to -20°C freezing, due to faster freezing rate). In summary, this DoE-based systematic analysis increased F/T process understanding at large scale, identified critical F/T process parameters, and confirmed the feasibility of applying faster freezing and forced air thawing procedures to maintain the stability of LDH solutions subject to large-scale F/T.


Assuntos
Produtos Biológicos/síntese química , Química Farmacêutica/métodos , Congelamento , L-Lactato Desidrogenase/síntese química , Animais , Produtos Biológicos/metabolismo , L-Lactato Desidrogenase/metabolismo , Coelhos , Projetos de Pesquisa
14.
BMC Ophthalmol ; 21(1): 226, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016081

RESUMO

BACKGROUND: Glaucoma is a leading cause of global blindness, especially preventable blindness. The increased prevalence of glaucoma has led to a growing demand for newer, safer, more rapid, and simpler treatments for the reduction of intraocular pressure (IOP). In this study, we evaluated the safety and feasibility of performing filtration glaucoma surgery with an Ab-Interno Er:YAG laser in rabbits. METHODS: Nine New Zealand White rabbits age 16 weeks were studied. After subconjunctival injection of mitomycin C (MMC), a novel Ab-Interno Er:YAG laser probe was inserted into the anterior chamber (AC) through a clear corneal 1 mm paracentesis and directed at the trabecular meshwork adjacent to the MMC injection area. A pulsed laser beam was applied to create a patent sclerostomy connecting the AC to the subconjuctival space, resulting in a filtering bleb. The laser system used was the Er:YAG laser system - LAS25-FCU, (Pantec Biosolutions AG, Liechtenstein). Parameters used: Wave lengh: 2940 nm, Pulse length: 100-400 µsec,frequency: 250 Hz. Average laser power in accordance to the fiber tip diameter: 0.85 W(range 0.8-0.92 W). Complete ocular exams, including IOP measurements, were performed on 1, 7, 14, and 23 days postoperatively. Three rabbits were sacrificed on days 1, 14, and 23, and histological examinations were performed on all nine eyes. RESULTS: All procedures resulted in a functional medium-large superior bleb without significant complications. The bleb was sustained in all rabbits by day 14 and in one of the three rabbits that reached the last follow-up at 23 days. No cases of postoperative hypotony were observed. There was a transient significant reduction in mean IOP on postoperative days 5 and 7 (P = 0.028). Histopathological analysis revealed a patent full-thickness scleral tunnel with only a minor degree of surrounding coagulation necrosis. CONCLUSIONS: The Ab-Interno laser sclerostomy procedure is potentially safe and effective based on initial experience in an in-vivo rabbit animal model.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Esclerostomia , Animais , Humanos , Pressão Intraocular , Lasers de Estado Sólido/uso terapêutico , Coelhos , Esclera , Malha Trabecular/cirurgia
15.
Undersea Hyperb Med ; 48(2): 127-147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33975403

RESUMO

Multiday hyperbaric exposure has been shown to reduce the incidence of decompression sickness (DCS) of compressed-air workers. This effect, termed acclimatization, has been addressed in a number of studies, but no comprehensive review has been published. This systematic review reports the findings of a literature search. PubMed, Ovid Embase, The Cochrane Library and Rubicon Research Repository were searched for studies reporting DCS incidence, venous gas embolism (VGE) or subjective health reports after multiday hyperbaric exposure in man and experimental animals. Twenty-nine studies fulfilled inclusion criteria. Three epidemiological studies reported statistically significant acclimatization to DCS in compressed-air workers after multiday hyperbaric exposure. One experimental study observed less itching after standardized simulated dives. Two human experimental studies reported lower DCS incidence after multiday immersed diving. Acclimatization to DCS has been observed in six animal species. Multiday diving had less consistent effect on VGE after hyperbaric exposure in man. Four studies observed acclimatization while no statistically significant acclimatization was reported in the remaining eight studies. A questionnaire study did not report any change in self-perceived health after multiday diving. This systematic review has not identified any study suggesting a sensitizing effect of multiday diving, and there is a lack of data supporting benefit of a day off diving after a certain number of consecutive diving days. The results suggest that multiday hyperbaric exposure probably will have an acclimatizing effect and protects from DCS. The mechanisms causing acclimatization, extent of protection and optimal procedure for acclimatization has been insufficiently investigated.


Assuntos
Aclimatação/fisiologia , Doença da Descompressão/prevenção & controle , Mergulho/fisiologia , Embolia Aérea/prevenção & controle , Oxigenação Hiperbárica , Doenças Profissionais/prevenção & controle , Animais , Pressão Atmosférica , Gatos , Doença da Descompressão/epidemiologia , Autoavaliação Diagnóstica , Mergulho/efeitos adversos , Mergulho/estatística & dados numéricos , Cães , Embolia Aérea/epidemiologia , Cabras , Humanos , Incidência , Doenças Profissionais/epidemiologia , Coelhos , Ratos , Ratos Sprague-Dawley , Valores de Referência , Ovinos , Fatores de Tempo
16.
Vaccine ; 39(23): 3197-3206, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33965258

RESUMO

Despite widespread utilization of pneumococcal conjugate vaccines (PCVs) and the resultant disease reduction, the development of PCVs containing additional serotypes remains a public health priority due to serotype replacement and the resultant shift to non-vaccine containing serotypes. However, incorporating additional serotypes to existing PCVs using conventional technologies has proven problematic. Immune responses to individual serotypes have consistently decreased as more polysaccharide-conjugates are added due to carrier suppression. Using our proprietary cell-free protein synthesis (CFPS) platform, we have successfully produced eCRM® based on the CRM197 sequence for use as an enhanced carrier protein to develop a 24-valent PCV. The eCRM carrier protein contains multiple non-native amino acids (nnAAs) located outside of the primary T-cell epitope regions, thereby enabling site-specific covalent conjugation of the pneumococcal polysaccharides to the nnAAs to consistently expose the critical T-cell epitopes. eCRM also serves to reduce structural heterogeneity associated with classic reductive-amination conjugation while promoting formation of the conjugate matrix structures, the hallmark of PCVs. This process serves to increase the overall polysaccharide:protein ratio, enabling the inclusion of more serotypes while minimizing carrier-mediated immunological interference. The aim of this non-clinical study was to construct a 24-valent PCV and evaluate its immunogenicity. Using the XPressCF® CFPS platform, the eCRM carrier protein was separately conjugated through nnAAs to each of the 24 pneumococcal polysaccharides through click chemistry and mixed with aluminum phosphate to produce VAX-24, Vaxcyte's proprietary PCV preclinical candidate. VAX-24, Prevnar13® and Pneumovax®23 were administered to New Zealand White rabbits to compare the resulting opsonophagocytic activity (OPA) and anti-capsular IgG antibodies. VAX-24 showed conjugate-like immune responses to all 24 serotypes based on comparable OPA and IgG responses to Prevnar13 and higher responses than Pneumovax 23. This study demonstrates the utility of site-specific conjugation technology in a preclinical setting and the potential for a PCV with improved serotype coverage.


Assuntos
Proteínas de Transporte , Infecções Pneumocócicas , Animais , Anticorpos Antibacterianos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Coelhos , Padrão de Cuidado , Streptococcus pneumoniae , Vacinas Conjugadas
17.
An Acad Bras Cienc ; 93(2): e20190274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33950150

RESUMO

The present study investigated the effects of dietary supplementation of Saccharomyces cerevisiae (SC) on growth performance, carcass traits, blood biochemical parameters, histological changes in intestinal wall and economic indices in two breeds of weanling rabbits (V-Line and Rex). One-hundred and twenty weaned male rabbits were allotted randomly into four groups in factorial arrangement. The results could be summarized as follows: dietary supplementation of SC significantly accelerated body weight gain (BWG), reduced feed conversion ratio (FCR) and increased profit. The highest BWG and the lowest FCR were noticed in each breed when interacted with SC. There were non-significant differences in carcass traits due to the studied factors, except in loin and dressing percentages. The highest percentages of loin and dressing were obtained from V-line when fed diet supplemented with SC. The treated rabbits with yeast were characterized by an increase in Brunner`s gland and villi. Dietary Supplementation of SC decreased blood total glycerides and cholesterol and increased blood total protein, albumin and A/G ratio. The treated group showed higher profitability than the control. Conclusively, dietary supplementation of SC provided beneficial effects in growth performance and profitability of rabbits. Finally, dietary supplementation of SC is highly recommended in growing rabbits.


Assuntos
Ração Animal , Saccharomyces cerevisiae , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta , Suplementos Nutricionais , Masculino , Coelhos , Ganho de Peso
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(4): 426-431, 2021 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33967091

RESUMO

Rotator cuff injuries are the most common cause of shoulder pain and dysfunction. Ideal animal shoulder models should have similar shoulder anatomy and function as human, and are able to replicate the microenvironment change after tendon injury. At present, a variety of animal models including rat, mouse, rabbit, sheep, canine, bovine, and primate have been used to study the mechanism of rotator cuff injury, effects of different repair techniques, and factors affecting tendon to bone healing. Although large animal models are more anatomically similar to humans, small animal models are more convenient in revealing the biological mechanism of rotator cuff injury and healing. Choosing appropriate animal models based on research objectives and establishing new small animal models play a critical role in revealing the mechanism of rotator cuff diseases and developing novel treating strategies.


Assuntos
Lesões do Manguito Rotador , Traumatismos dos Tendões , Animais , Bovinos , Modelos Animais de Doenças , Cães , Camundongos , Coelhos , Ratos , Manguito Rotador , Ovinos , Cicatrização
19.
Nat Commun ; 12(1): 2875, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001908

RESUMO

Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.


Assuntos
Corticosteroides/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Dexametasona/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Corticosteroides/química , Corticosteroides/farmacocinética , Animais , Células Cultivadas , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Dexametasona/química , Dexametasona/farmacocinética , Dimerização , Modelos Animais de Doenças , Implantes de Medicamento , Liberação Controlada de Fármacos , Polímeros/química , Coelhos , Ratos , Uveíte/metabolismo , Uveíte/prevenção & controle
20.
J Med Microbiol ; 70(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34038343

RESUMO

Introduction. In vitro experimentation is intentionally contrived to isolate specific phenomena in the context of profound biological complexity. Mycoplasmas in the upper airway likely contribute to this complexity and play a largely unknown role in both health and disease. Similarly, the presence and role of mycoplasma in in vitro investigation are largely unknown.Hypothesis. We hypothesize mycoplasma in human vocal fold fibroblasts (VFF) will affect both basal gene-expression patterns as well as the cell response to exogenous stimuli.Aim. We sought to determine mycoplasma presence across vocal fold fibroblast cultures, basal transcriptional changes as a function of mycoplasma, and responsiveness to exogenous glucocorticoids in mycoplasma-positive and -negative VFF.Methodology. PCR-based mycoplasma detection was performed in an immortalized human VFF line as well as rat and rabbit primary VFF cultures and extracted rat laryngeal tissue. RNA sequencing was performed in mycoplasma-positive and -negative human cells at baseline and in response to dexamethasone.Results. Mycoplasma was identified in the human cell line as well as primary culture from rabbits. Mycoplasma was not detected in tissue or primary culture from rat vocal folds. Basal mRNA expression in human VFF differed significantly following mycoplasma treatment. In addition, differential responses to dexamethasone were observed across multiple pathways as a function of mycoplasma presence in these cells. Pathways including apoptosis, DNA damage repair, and G1 to S cell cycle signalling were significantly enriched in mycoplasma-positive cells.Conclusion. Variability of mycoplasma presence across culture conditions and differential responses to exogenous stimuli as a function of mycoplasma presence are potentially problematic for the translation of in vitro experimentation in the upper aerodigestive tract. It remains unclear if these findings represent contamination or the baseline state of this specialized tissue.


Assuntos
Fibroblastos , Glucocorticoides/farmacologia , Infecções por Mycoplasma , Prega Vocal , Animais , Apoptose , Ciclo Celular , Células Cultivadas , Reparo do DNA , Fibroblastos/efeitos dos fármacos , Fibroblastos/microbiologia , Expressão Gênica , Humanos , Mycoplasma , Infecções por Mycoplasma/metabolismo , Coelhos , Ratos , Ratos Sprague-Dawley , Prega Vocal/metabolismo , Prega Vocal/patologia
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