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1.
J Biomed Mater Res B Appl Biomater ; 112(6): e35434, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38874589

RESUMO

Bioactive degradable scaffolds that facilitate bone healing while fighting off initial bacterial infection have the potential to change established strategies of dealing with traumatic bone injuries. To achieve this a composite material made from calcium phosphate graphene (CaPG), and MXene was synthesized. CaPG was created by functionalizing graphene oxide with phosphate groups in the presence of CaBr with a Lewis acid catalyst. Through this transformation, Ca2+ and PO4 3- inducerons are released as the material degrades thereby aiding in the process of osteogenesis. The 2D MXene sheets, which have shown to have antibacterial properties, were made by etching the Al from a layered Ti3AlC2 (MAX phase) using HF. The hot-pressed scaffolds made of these materials were designed to combat the possibility of infection during initial surgery and failure of osteogenesis to occur. These two failure modes account for a large percentage of issues that can arise during the treatment of traumatic bone injuries. These scaffolds were able to retain induceron-eluting properties in various weight percentages and bring about osteogenesis with CaPG alone and 2 wt% MXene scaffolds demonstrating increased osteogenic activity as compared to no treatment. Additionally, added MXene provided antibacterial properties that could be seen at as little as 2 wt%. This CaPG and MXene composite provides a possible avenue for developing osteogenic, antibacterial materials for treating bone injuries.


Assuntos
Antibacterianos , Fosfatos de Cálcio , Grafite , Osteogênese , Alicerces Teciduais , Titânio , Osteogênese/efeitos dos fármacos , Grafite/química , Grafite/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Titânio/química , Titânio/farmacologia , Alicerces Teciduais/química , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Animais , Humanos , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
2.
Proc Natl Acad Sci U S A ; 120(45): e2309156120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37903261

RESUMO

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Prótese de Quadril/efeitos adversos , Ácido Hialurônico , Dimercaprol , Terapia por Quelação , Falha de Prótese , Artroplastia de Quadril/efeitos adversos , Metais , Cobalto , Quelantes/uso terapêutico , Íons
3.
ACS Appl Bio Mater ; 5(12): 5608-5616, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36383154

RESUMO

Wound dressings have been shifting toward a more active role in the wound-healing process. Hydrated environments with additives to aid in the healing process are currently being explored through the application of hydrocolloid dressings. However, these moist healing environments are also ideal for bacterial growth, leading to the widespread use of antibiotics with concerns of antibiotic resistance and toxicity. To overcome this concern, we present a hydrogel wound dressing consisting of hyaluronic acid (HA) cross-linked with gentamicin. This hydrogel treats bacterial infection locally, lowering the effective dose and reducing the concerns of antibiotic resistance and systemic exposure. Changing the cross-linking density, by using varied amounts of a cross-linker, created gels that provided a sustained release of gentamicin for up to 9 days with a range of adhesive and cohesive properties. Overall, this HA hydrogel could provide an important solution in treating local infection in burns and other dermal injuries.


Assuntos
Ácido Hialurônico , Hidrogéis , Hidrogéis/uso terapêutico , Ácido Hialurônico/farmacologia , Curativos Hidrocoloides , Antibacterianos/uso terapêutico , Gentamicinas
4.
Ochsner J ; 21(4): 419-424, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34984060

RESUMO

Background: Isosulfan blue dye, or Lymphazurin, is commonly used for sentinel lymph node biopsy during operative procedures for patients with breast cancer. Allergic reactions to Lymphazurin have been reported, ranging from mild dermatologic reactions to severe anaphylaxis. Case Series: We report 2 patients who experienced allergic reaction to Lymphazurin while admitted to our service. We also conducted a literature search for similar cases using national databases. Included studies were limited to retrospective studies, case series, or case reports. Patient characteristics, reaction observed, and hospital course were extracted. Of the patients we report, both had grade 3 anaphylactic reactions requiring vasopressors to achieve hemodynamic stability. One patient required intensive care unit monitoring for 18 hours, and the other required overnight monitoring in the postanesthesia care unit. The literature revealed 29 studies reporting 108 patients with confirmed allergic reactions to Lymphazurin. Including the 2 patients in this series (total study n=110), most reactions were grade 3 (57/110, 51.8%), followed by grade 1 (40/110, 36.4%) and grade 2 (13/110, 11.8%). Among the patients who had individual hospital course reported (n=34), 23 patients required admission to the surgical intensive care unit. Of studies that reported cancellation or progression of surgery after the reaction, the surgical procedure was canceled for 12 of 26 patients (46.1%). Conclusion: Although severe anaphylactic reactions are more commonly reported, mild reactions occur more frequently but are likely underreported. Although no fatalities were reported in the cases included in this review, anaphylactic reactions to Lymphazurin pose significant risks. Operating room personnel should be familiar with potential reactions to recognize and treat them early.

5.
Adv Mater ; 32(39): e2003310, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32820582

RESUMO

Peptide nanofibers are useful for many biological applications, including immunotherapy, tissue engineering, and drug delivery. The robust lengthwise assembly of these peptides into nanofibers is typically difficult to control, resulting in polydisperse fiber lengths and an incomplete understanding of how nanofiber length affects biological responses. Here, rationally designed capping peptides control the length of helical peptide nanofibers with unique precision. These designed peptides bind the tips of elongated nanofibers to shorten and narrow their length distributions. Demonstrating their use as immunotherapies, capped nanofibers are preferentially cross-presented by dendritic cells compared to uncapped nanofibers. Due to increased cross-presentation, these capped nanofibers trigger stronger CD8+ T-cell responses in mice than uncapped nanofibers. This strategy illustrates a means for controlling the length of supramolecular peptide nanofibers to modulate their immunogenicity in the context of immunotherapies.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Nanofibras/química , Peptídeos/química , Peptídeos/farmacologia , Animais , Linfócitos T CD8-Positivos/citologia , Camundongos , Conformação Proteica em alfa-Hélice
6.
Liver Transpl ; 18(8): 979-83, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22508549

RESUMO

This is the first report presenting a human immunodeficiency virus (HIV)-positive patient with fulminant hepatic failure receiving a liver graft from a Chagas disease-seropositive deceased donor. We describe the history of a 38-year-old HIV-positive female patient who developed fulminant hepatic failure of an autoimmune etiology with rapid deterioration of her clinical status and secondary multiorgan failure and, therefore, needed emergency liver transplantation (LT) as a lifesaving procedure. Because of the scarcity of organs and the high mortality rate for emergency status patients on the LT waiting list, we decided to accept a Chagas disease-seropositive deceased donor liver graft for this immunocompromised Chagas disease-seronegative patient. The recipient had a rapid postoperative recovery and was discharged on postoperative day 9 without prophylactic treatment for Chagas disease. Fifteen months after LT, she was still alive and had never experienced seroconversion on periodic screening tests for Chagas detection. Although there is an inherent risk of acute Chagas disease developing in seronegative recipients, our report suggests that these infected organs can be safely used as a lifesaving strategy for HIV patients with a high need for LT.


Assuntos
Doença de Chagas/sangue , Infecções por HIV/complicações , Transplante de Fígado/métodos , Doença Aguda , Adulto , Doença de Chagas/cirurgia , Doença de Chagas/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , Feminino , Sobrevivência de Enxerto , Infecções por HIV/sangue , Humanos , Fígado/virologia , Falência Hepática Aguda/complicações , Falência Hepática Aguda/cirurgia , Falência Hepática Aguda/terapia , Doadores de Tecidos , Resultado do Tratamento
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