RESUMEN
A new electron skin dosimetry model was developed for the VARSKIN 5 tissue dosimetry code. This model employs energy deposition kernels that provides for improved accuracy of energy deposition at the end of electron tracks. The Monte Carlo code EGSnrc was utilized to develop these energy deposition kernels such that scaling of electron energy loss is dependent on effective atomic number and density of the source material, electron range and conservation of energy. This work contrasts VARSKIN's electron dosimetry model to several existing deterministic and Monte Carlo dosimetry tools to determine the efficacy of these improvements. Comparison results are given for a wide range of scenarios that extend beyond the typical use of VARSKIN, including mono-energetic electrons and a homogenous water medium. For planar and point sources in contact with the skin, VARSKIN produces results equated to other dosimetry methods within 10%. However, it appears that VARSKIN is unable to account accurately for electron energy loss with the introduction of a cover material or an air gap. The comparisons herein confirm that VARSKIN provides accurate electron dose calculations for skin-contamination scenarios.
Asunto(s)
Electrones , Modelos Biológicos , Modelos Estadísticos , Dosis de Radiación , Radiometría/métodos , Fenómenos Fisiológicos de la Piel/efectos de la radiación , Simulación por Computador , Humanos , Método de MontecarloRESUMEN
PEGylated gold nanoparticles (AuNPs) have an extended circulation time after intravenous injection in vivo and exhibit favorable properties for biosensing, diagnostic imaging, and cancer treatment. No impact of PEGylated AuNPs on the barrier forming properties of endothelial cells (ECs) has been reported, but recent studies demonstrated that unexpected effects on erythrocytes are observed. Almost all studies to date have been with static-cultured ECs. Herein, ECs maintained under physiological cyclic stretch and flow conditions and used to generate a blood-brain barrier model were exposed to 20 nm PEGylated AuNPs. An evaluation of toxic effects, cell stress, the release profile of pro-inflammatory cytokines, and blood-brain barrier properties showed that even under physiological conditions no obvious effects of PEGylated AuNPs on ECs were observed. These findings suggest that 20 nm-sized, PEGylated AuNPs may be a useful tool for biomedical applications, as they do not affect the normal function of healthy ECs after entering the blood stream.
Asunto(s)
Células Endoteliales/efectos de los fármacos , Oro/metabolismo , Nanopartículas/metabolismo , Polietilenglicoles/metabolismo , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/patología , Oro/química , Oro/toxicidad , Células Endoteliales de la Vena Umbilical Humana , Humanos , Nanopartículas/química , Nanopartículas/toxicidad , Tamaño de la Partícula , Polietilenglicoles/química , Polietilenglicoles/toxicidad , PorcinosRESUMEN
OBJECTIVE: Propranolol-induced involution is a unique biological feature of some pediatric vascular tumors, for instance infantile hemangioma (IH), cerebral cavernoma or chorioangioma. Currently, the cellular origin of these distinct tumors is unclear. In this study, we tested the hypothesis that propranolol-responsive vascular tumors are derived from common vessel-forming CD15 + progenitor cells which occur in early gestation. The aim of this study was to identify the tumor-relevant CD15 + progenitors at the early stages of embryo-placental development. MATERIALS AND METHODS: Human embryo-placental units of 4-8 weeks gestation and pediatric vascular tumors were tested for expression of the tumor-relevant markers CD15, CD31 and CD34. RESULTS: Placental vessel-forming progenitors were characterized by immunostaining for CD15, CD31, and CD34. In embryonic tissue, a discontinuous CD15+/CD31+/CD34 + progenitors was detected in immature vessels of the skin, neural tube, spinal and cerebral meninges. Similarly, vessels in IH and chorioangioma exhibited a co-expression of CD15, CD31, and CD34. In contrast, the majority of embryonic vessels presented a CD31+/CD34+, but CD15-negative immunophenotypic pattern. DISCUSSION: Our results suggest the existence of a CD15+ "vasculogenic zones" in the embryo-placental unit as well as in IH and chorioangioma. A site-specific correlation between normal embryo-placental and tumoral vessel-forming CD15 + progenitors was demonstrated. CONCLUSION: Hence, site- and stage-specific CD15 + progenitors of vascular wall could be considered as propronalol-sensitive targets and source of pre- and postnatal vascular tumors. We propose, that the CD15+ "vasculogenic zones" are a site-specific reserve of multi-lineage progenitors that could be recruited in pre- and postnatal emergency situations.
Asunto(s)
Embrión de Mamíferos/citología , Células Endoteliales/patología , Antígeno Lewis X/metabolismo , Neoplasias de Tejido Vascular/patología , Células Madre Neoplásicas/patología , Placenta/citología , Edad de Inicio , Linaje de la Célula , Niño , Resistencia a Antineoplásicos , Embrión de Mamíferos/metabolismo , Células Endoteliales/metabolismo , Femenino , Hemangioma/metabolismo , Hemangioma/patología , Hemangioma Capilar/metabolismo , Hemangioma Capilar/patología , Humanos , Recién Nacido , Neoplasias de Tejido Vascular/epidemiología , Células Madre Neoplásicas/metabolismo , Síndromes Neoplásicos Hereditarios/metabolismo , Síndromes Neoplásicos Hereditarios/patología , Placenta/irrigación sanguínea , Placenta/metabolismo , Placentación , Embarazo , Primer Trimestre del Embarazo , Propranolol , Nicho de Células MadreRESUMEN
BACKGROUND: Wound healing depends on a well-balanced regulation of inflammation and angiogenesis. In chronic wounds the healing process is disturbed and inflammation persists. Regulation of wound closure is controlled by transmembrane and extracellular proteins, the folding and maturation of which occur in the endoplasmic reticulum (ER) by ER-resident chaperone machinery. OBJECTIVES: To study the role of the ER-resident chaperones BiP/Grp78, its cochaperone Mdg1/ERdJ4, and Grp94 in chronic, nonhealing wounds. METHODS: Immunohistochemical staining of these chaperones in individual human biopsies and investigation of the possible role of BiP and Mdg1 in endothelial cells, focusing on their inflammatory response and angiogenic potential. RESULTS: In all chronic wounds investigated, the levels of these ER-resident chaperones were elevated in endothelial cells and leucocytes. The proangiogenic role of BiP has been shown in tumour growth studies before and was confirmed in this study. Proangiogenic activity of the cochaperone Mdg1 has been postulated before but could not be confirmed in this study. The chemokine tumour necrosis factor (TNF)-α was shown to trigger the presentation of proinflammatory adhesion molecules and the release of proinflammatory cytokines. Here we show that TNF-α does not affect endogenous chaperone levels, but that the ER-resident chaperones BiP and Mdg1 modulate the cellular TNF-α-induced proinflammatory response. CONCLUSIONS: According to the presented data we assume that in chronic wounds upregulated levels of ER-resident chaperones might contribute to persistent inflammation in chronic wounds. Therapies to downregulate chaperone levels might provide a tool that switches the imbalanced chronic wound microenvironment from inflammation to healing.