RESUMEN
Dealing with wound related pain is an integral part of treatment. Systemic administration of analgesic and anesthetic agents is a common solution for providing pain relief to patients but comes at a risk of severe side effects as well as addiction. To overcome these issues, research efforts were madeto provide a platform for local controlled release of pain killers. We have developed a bilayer soy protein-based wound dressing for the controlled local release of bupivacaine to the wound site. The combination of a dense and a porous layer provides a platform for cell growth and proliferation as well as physical protection to the wound site. The current study focuses on the in vitro bupivacaine release profile from the dressing and the corresponding in vivo results of pain levels in a second-degree burn model on rats. The Rat Grimace Scale method and the Von Frey filaments method were used to quantify both, spontaneous pain and mechanically induced pain. A high burst release of 61.8 ± 1.9% of the loaded drug was obtained during the initial hour, followed by a slower release rate during the following day. The animal trials show that the RGS scores of the bupivacaine-treated group were significantly lower than these of the untreated group, proving a decrease of 51-68% in pain levels during days 1-3 after burn. Hence, successful pain reduction of spontaneous pain as well as mechanically induced pain, for at least three days after burn was achieved. It is concluded that our novel bupivacaine eluting soy protein wound dressings are a promising new concept in the field of local controlled drug release for pain management.
Asunto(s)
Quemaduras , Analgésicos/farmacología , Analgésicos/uso terapéutico , Anestésicos Locales/uso terapéutico , Animales , Vendajes , Bupivacaína/uso terapéutico , Quemaduras/tratamiento farmacológico , Preparaciones de Acción Retardada/uso terapéutico , Humanos , Dolor/tratamiento farmacológico , Dolor Postoperatorio/tratamiento farmacológico , Ratas , Proteínas de Soja/farmacología , Proteínas de Soja/uso terapéuticoRESUMEN
Nipple sparing mastectomy is gaining popularity in recent years, as it provides superior aesthetic results and has a positive impact on the psychological well-being of patients. However, patients with macromastia and high grade ptosis are not good candidates for nipple sparing mastectomy due to a high risk for nipple necrosis; for these patients, the free nipple grafting (FNG) is an excellent option following autologous reconstruction. We herein present our experience with FNG for women with large and ptotic breasts undergoing mastectomy and autologous reconstruction. We also present the option of splitting a single nipple-areolar complex to provide 2 grafts for bilateral nipple reconstruction. This retrospective study is based on data collected between 2014 and 2019 at a single institution. We report on 7 patients (13 grafts): 5 patients underwent FNG (4 bilateral, 1 unilateral) and 2 patients had a single nipple split into 2 parts to create 2 nipple-areolar complexes. Of the 13 grafts, 9 had complete take, 3 had almost complete take, and only 1 graft was lost. Overall patient satisfaction from the procedure was high. The use of FNG is an excellent reconstructive option, as it preserves the patient's own nipple in terms of color, shape, and texture. The procedure can be executed as part of a direct single-staged reconstruction for patients who are at a high risk for nipple necrosis.
RESUMEN
Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC), representing an advanced disease stage and independently predicting patient survival. Current nodal staging is inadequate preoperatively and even less so postoperatively, and molecular biomarkers are needed to improve prognostication and selection of therapy. Recent data have suggested important roles of miRNAs in PDAC tumorigenesis and progression. The aim of the present study was to identify miRNA expression signature for nodal spread in PDAC patients. Using PDAC human tissue specimens, we identified 39 miRNAs which were differently expressed in LN positive compared to LN negative PDAC samples. Of them, six miRNAs have been reported to play a role in cancer invasion and metastasis. A high versus low six- miRNA signature score was predictive of LN metastasis in the PDAC validation cohort. We demonstrated a similar expression pattern of four out of the six miRNAs in the plasma of PDAC patients. The results of our in-vitro studies revealed that miR-141 and miR-720 are involved in the process of epithelial to mesenchymal-transition in PDAC. These miRNAs significantly inhibited in vitro proliferation, migration and invasion of PDAC cells as evidence by gain- and loss- of function studies, specifically, via ZEB-1 and TWIST1 transcription factors, as well as through the activation of the MAP4K4/JNK signaling pathway.