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1.
Medicine (Baltimore) ; 99(17): e19743, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332613

RESUMO

INTRODUCTION: The implantation of a gestational sac within the scar of a previous caesarean delivery is defined as caesarean scar pregnancy (CSP), which is classified into two types: CSP I and CSP II. CSP II is life threatening, and no clear consensus for CSP II management exists. PATIENT CONCERNS: A 31-year-old woman, gravida 1, para 1, with a previous caesarean delivery due to macrosomia, presented with an estimated 45 days of amenorrhea. The patient presented to the emergency department with vaginal bleeding for 1 day and no abdominal pain. DIAGNOSES: An ultrasound examination was performed demonstrating a viable fetus that was embedded in the caesarean scar area and was bulging through the wall of the uterus into the bladder without contact with the uterine cavity or cervical canal. A diagnosis of type II caesarean scar pregnancy was made. INTERVENTIONS: Local lauromacrogol was used to reduce the gestational sac blood supply. Suction curettage was performed under the guidance of abdominal ultrasound 24 h later, and the amount of bleeding was 20 mL. The response to the treatment was monitored by serial beta-human chorionic gonadotropin (ß-hCG). OUTCOMES: Patient was followed up with ß-hCG weekly levels which became <10 mIU/mL after 4 weeks of treatment. CONCLUSION: Ultrasound-guided local lauromacrogol injection combined with suction curettage may be a safer and novel therapeutic method.


Assuntos
Cesárea/efeitos adversos , Cicatriz/complicações , Curetagem a Vácuo/métodos , Adulto , Cesárea/métodos , Feminino , Humanos , Polidocanol/uso terapêutico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/cirurgia , Ultrassonografia/métodos
2.
Int J Nanomedicine ; 14: 6019-6033, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534334

RESUMO

OBJECTIVE: Icariin (IC) promotes osteogenic differentiation, and it may be a potential small molecule drug for local application in bone regeneration. Icariin-loaded hydroxyapatite/alginate (IC/HAA) porous composite scaffolds were designed in this study for the potential application of the sustainable release of icariin and subsequent bone regeneration. METHODS: An icariin-loaded hydroxyapatite/alginate porous composite scaffold was prepared and characterized by SEM and HPLC for morphology and release behavior, respectively. The mechanical properties, degradation in PBS and cytotoxicity on BMSCs were also evaluated by MTT assay, compression strength and calculation of weight remaining ratio, respectively. Rabbit BMSCs were cocultured with IC/HAA scaffolds, and ALP activity and Alizarin Red staining were performed to evaluate osteogenic differentiation induction. The mRNA and protein expression level of an osteogenic gene was detected by RT-PCR and Western blotting, respectively. In vivo animal models of critical bone defects in the radius of rabbit were used. Four and 12 weeks after the implantation of IC/HAA scaffolds in the bone defect, radiographic images of the radius were obtained and scored by using the Lane and Sandhu X-ray scoring system. Tissue samples were also evaluated using H&E and Masson staining, and an osteogenic gene and Wnt signaling pathway genes were detected. RESULTS: A hydroxyapatite/alginate (HAA) porous composite scaffold-loaded icariin was fabricated using a freeze-drying method. Our data indicated that the icariin was loaded in alginate scaffold without compromising the macro/microstructure or mechanical properties of the scaffold. Notably, the IC/HAA promoted the proliferation of rBMSCs without exerting cytotoxicity on rBMSCs. In vivo, rabbit radius bone defect experiments demonstrated that the IC/HAA scaffold exhibited better capacity for bone regeneration than HAA, and IC/HAA upregulated the relative expression levels of an osteogenic gene and the Wnt signaling pathway genes. Most notably, the IC/HAA scaffold also inhibited osteoclast activity in vivo. CONCLUSION: Our data suggests a promising application for the use of HAA scaffolds to load icariin and promote bone regeneration in situ through mediation of the coupling processes of osteogenesis induction and osteoclast activity inhibition.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Flavonoides/farmacologia , Osteoclastos/metabolismo , Osteogênese , Alicerces Teciduais/química , Alginatos/farmacologia , Animais , Materiais Biocompatíveis/farmacologia , Biomarcadores/metabolismo , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Durapatita/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Porosidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Rádio (Anatomia)/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
3.
Ann Biomed Eng ; 43(12): 2978-90, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26066056

RESUMO

Collagen makes up a large proportion of the human body, particularly the skin. As the body ages, collagen content decreases, resulting in wrinkled skin and decreased wound healing capabilities. This paper presents a method of delivering type I collagen into porcine and human skin utilizing a polyvinylpyrrolidone microneedle delivery system. The microneedle patches were made with concentrations of 1, 2, 4, and 8% type I collagen (w/w). Microneedle structures and the distribution of collagen were characterized using scanning electron microscopy and confocal microscopy. Patches were then applied on the porcine and human skin, and their effectiveness was examined using fluorescence microscopy. The results illustrate that this microneedle delivery system is effective in delivering collagen I into the epidermis and dermis of porcine and human skin. Since the technique presented in this paper is quick, safe, effective and easy, it can be considered as a new collagen delivery method for cosmetic and therapeutic applications.


Assuntos
Colágeno Tipo I/administração & dosagem , Sistemas de Liberação de Medicamentos , Agulhas , Administração Cutânea , Animais , Humanos , Técnicas In Vitro , Masculino , Microinjeções , Povidona , Pele/metabolismo , Suínos
4.
Acta Biomater ; 9(8): 7767-74, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23648574

RESUMO

We present a method of fabricating microneedles from polyvinylpyrrolidone (PVP) that enables delivery of intact proteins (or peptides) to the dermal layers of the skin. PVP is known to self-assemble into branched hollow fibers in aqueous and alcoholic solutions; we utilized this property to develop dissolvable patches of microneedles. Proteins were dissolved in concentrated PVP solution in both alcohol and water, poured into polydimethylsiloxane templates shaped as microneedles and, upon evaporation of solvent, formed into concentric, fibrous, layered structures. This approach of making PVP microneedles overcomes problems in dosage, uniform delivery and stability of protein formulation as compared to protein-coated metallic microneedles or photopolymerized PVP microneedles. Here we characterize the PVP microneedles and measure the delivery of proteins into skin. We show that our method of fabrication preserves the protein conformation. These microneedles can serve as a broadly useful platform for delivering protein antigens and therapeutic proteins to the skin, for example for allergen skin testing or immunotherapy.


Assuntos
Injeções Intradérmicas/instrumentação , Microinjeções/instrumentação , Agulhas , Povidona/química , Proteínas/administração & dosagem , Desenho de Equipamento , Análise de Falha de Equipamento , Miniaturização
5.
J Drug Target ; 20(8): 678-90, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22845840

RESUMO

DNA nanoparticles (DNA NPs), which self-assemble from DNA plasmids and poly-L-lysine (pLL)-polyethylene glycol (PEG) block copolymers, transfect several cell types in vitro and in vivo with minimal toxicity and immune response. To further enhance the gene transfer efficiency of DNA NP and control its tropism, we established a strategy to efficiently attach peptide ligands to DNA NPs. The non-covalent biotin-streptavidin (SA) interaction was used for ligand conjugation to overcome problems associated with covalent conjugation methods. A fusion protein of SA with the HIV-1 TAT peptide was cloned, expressed, purified and attached to biotinylated DNA NPs. A modified SA system with tetrameric structure but monovalent biotin binding capacity was adopted and shown to reduce the aggregation of biotinylated DNA NPs compared to neutravidin. Compared to unmodified DNA NPs, TAT modified DNA NPs significantly enhanced in vitro gene transfer, particularly at low DNA concentrations. Studies of cellular uptake and cellular distribution of the DNA NPs indicated that attaching TAT enhanced binding of DNA NPs to cell surface but not internalization at high DNA concentrations. In vivo studies showed that TAT modified DNA NPs mediated equal level of gene transfer to the mouse airways via the luminal route compared to unmodified DNA NPs.


Assuntos
Biotina/metabolismo , DNA/metabolismo , Nanopartículas/química , Peptídeos/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Estreptavidina/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Animais , Biotinilação/métodos , Células Cultivadas , DNA/genética , Técnicas de Transferência de Genes , Células HeLa , Humanos , Ligantes , Lisina/genética , Lisina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/genética , Polietilenoglicóis/metabolismo , Polímeros/metabolismo , Proteínas Recombinantes de Fusão/genética , Estreptavidina/genética , Transfecção/métodos , Produtos do Gene tat do Vírus da Imunodeficiência Humana/genética
6.
J Control Release ; 146(1): 118-27, 2010 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-20438780

RESUMO

We developed polylysine based DNA nanoparticles (DNA NPs) that contain disulfide linkage in the carrier and demonstrated that this reducible DNA NP enhances in vitro gene transfer via an extracellular mechanism. Polylysine was conjugated through an N-terminal cysteine to a polyethylene glycol chain (PEG) by either a disulfide bond (SS) or a thioether bond (CS), and the resulting PEG-peptide conjugates were used to compact plasmid DNA into reducible SS-DNA NPs or non-reducible CS-DNA NPs with identical physical properties. SS-DNA NPs mediated more than 10-fold higher in vitro gene transfer. Others have suggested that disulfide bonds in synthetic gene carriers undergo cleavage in the reducing environment inside the cell, allowing increased intracellular DNA release. In this study, however, both higher cellular uptake of SS-DNA NPs and inhibition of SS-DNA NP mediated in vitro gene transfer by blocking extracellular free thiols suggested an extracellular mechanism. DePEGylation of SS-DNA NPs by extracellular thiols caused aggregation which might lead to higher cellular uptake and higher transgene expression. A series of SS-DNA NPs prepared with stabilized disulfide bonds survived the extracellular environment without aggregation but lost the superior gene transfer ability, indicating that, in our system, intracellular mechanisms are not involved. These results provided further insight into the mechanisms of in vitro gene transfer enhancement by introducing reducible linkages, contributing to the rational design of more efficient non-viral gene delivery systems.


Assuntos
DNA/genética , Portadores de Fármacos/química , Espaço Extracelular/metabolismo , Técnicas de Transferência de Genes , Nanopartículas/química , Técnicas de Cultura de Células , Membrana Celular/metabolismo , Sobrevivência Celular , Cisteína/química , DNA/administração & dosagem , Eletroforese em Gel de Poliacrilamida , Citometria de Fluxo , Células HeLa , Humanos , Microscopia Eletrônica de Transmissão , Plasmídeos , Polietileno/química , Polilisina/química , Compostos de Sulfidrila/metabolismo , Transfecção
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