Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds

Syntheses and Characterizations of Some New N-alkyl, Isoxazole and Dioxazole Derivatives of 5-Chloroisatin

N-alkyl and cycloadducts derivatives of 5-Chloroisatin were synthesized in good to excellent yields. The method evidences a selective N-alkylation when using 1,2-bis (2-chloroethoxy) ethane as efficient spacer at room temperature on the 5-Chloroisatin moiety. A general method for the 1,3-dipolar cycloaddition of 4-Chlorobenzaldoxime to alkynes provides a useful alternative route to get newisoxazole et dioxazole derivatives

Synthesis of 1,2,3-Triazole 5-Chloroisatin Derivatives via Copper-Catalyzed 1,3-Dipolar Cycloaddition Reactions

A facile and simple protocol for the ‘Click\u27 cycloaddition of organic azides with N-propargylchloroisatine catalyzed by CuI, produces in good yields novel of 1,4-disubstituted 1,2,3-triazoles were obtained. Compared to the uncatalyzed cycloaddition, the yields are significantly improved in the presence of CuI as catalyst, without alteration of the selectivity. The regio- and stereochemistry of the cycloadducts has been corroborated by 1H, 13C NMR spectroscopy

The reliability of the anterior pelvic plane for computer navigated acetabular component placement during total hip arthroplasty: Prospective study with the EOS imaging system

Introduction Computer navigated total hip arthroplasty is mostly based on the use of the anterior pelvic plane (APP) as a reference. EOS is a new imaging system that provides three-dimensional analysis of the pelvis in a functional position with a low dose of radiation. The aim of this study was to evaluate the reliability of the APP for placement of the cup during computer navigated THA using EOS. Hypothesis The reliability of the APP is limited for the placement of the acetabular cup during computer navigated THA. Materials and methods This was a prospective monocentric study using the EOS imaging system evaluating 44 patients in the standing position three months after computer navigated THA (Orthopilot™). Reproducibility of EOS measurements were analyzed using SterEOS software and the reliability of the navigation data for the position of the cup were assessed. Results Intra and interobserver reproducibility of the measurements of the orientation of the cup by EOS were good with correlation coefficients above 93% and 95% and confidence intervals of less than ± 5°. Mean cup inclination and anteversion were 41.3° and 20.9° and 44.3° and 29.5° respectively in operatively and post-operatively. The differences between measurements of operative cup inclination using computer assisted navigation and the post-operative EOS measurements were significant (P < 0.05) with a correlation coefficient of less than 40%. Discussion Our study confirms the lack of precision of the APP as a reference for positioning of the acetabular component, especially in relation to anteversion. Although for many years the APP was considered to be a global reference, in fact, it is subject to significant inter-individual variations and variations during changes in position. These factors, associated with the difficulty of determining the preoperative APP, explain the lack of reliability of this reference. Preoperative evaluation of the orientation of APP by EOS and its integration into the navigation system could help the operator position these components

Synthesis Characterization And Photopolymerization Of Novel Phosphonated Materials

New phosphonated cross-linked materials were synthesized from telomers obtained by reaction between 10-undecenol and dialkyl hydrogenphosphonates. Telomers were then converted to materials resins by methacrylation reactions. Finally, photopolymerization of the different materials synthesized was achieved and influence of the nature of the phosphonate group (diester, monoacid and diacid) was also evaluated.New phosphonated cross-linked materials were synthesized from telomers obtained by reaction between 10-undecenol and dialkyl hydrogenphosphonates. Telomers were then converted to materials resins by methacrylation reactions. Finally, photopolymerization of the different materials synthesized was achieved and influence of the nature of the phosphonate group (diester, monoacid and diacid) was also evaluated

Histological Evaluation of the Biocompatibility of Polyurea Crosslinked Silica Aerogel Implants in a Rat Model: A Pilot Study

Background: Aerogels are a versatile group of nanostructured/nanoporous materials with physical and chemical properties that can be adjusted to suit the application of interest. In terms of biomedical applications, aerogels are particularly suitable for implants such as membranes, tissue growth scaffolds, and nerve regeneration and guidance inserts. The mesoporous nature of aerogels can also be used for diffusion based release of drugs that are loaded during the drying stage of the material. From the variety of aerogels polyurea crosslinked silica aerogels have the most potential for future biomedical applications and are explored here. Methodology: This study assessed the short and long term biocompatibility of polyurea crosslinked silica aerogel implants in a Sprague-Dawley rat model. Implants were inserted at two different locations a) subcutaneously (SC), at the dorsum and b) intramuscularly (IM), between the gluteus maximus and biceps femoris of the left hind extremity. Nearby muscle and other internal organs were evaluated histologically for inflammation, tissue damage, fibrosis and movement (travel) of implant. Conclusion/Significance: In general polyurea crosslinked silica aerogel (PCSA) was well tolerated as a subcutaneous and an intramuscular implant in the Sprague-Dawley rat with a maximum incubation time of twenty months. In some cases a thin fibrous capsule surrounded the aerogel implant and was interpreted as a normal response to foreign material. No noticeable toxicity was found in the tissues surrounding the implants nor in distant organs. Comparison was made with control rats without any implants inserted, and animals with suture material present. No obvious or noticeable changes were sustained by the implants at either location. Careful necropsy and tissue histology showed age-related changes only. An effective sterilization technique for PCSA implants as well as staining and sectioning protocol has been established. These studies further support the notion that silica-based aerogels could be useful as biomaterials. © 2012 Sabri et al

A mathematical model for fibro-proliferative wound healing disorders

The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable. In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsenet al., J. theor. Biol. 177, 113–128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay. Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states—a central property of the model, which is evident from stability and bifurcation analyses. The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders

Lower-limb lengths and angles in children older than six years: Reliability and reference values by EOS® stereoradiography

Lower-limb alignment in children is classically assessed clinically or based on conventional radiography, which is associated with projection bias. Low-dose biplanar radiography was described recently as an alternative to conventional imaging. The primary objective of this study was to assess the reliability of length and angle values inferred from 3D reconstructions in children seen in everyday practice. The secondary objective was to obtain reference values for goniometry parameters in children. The paediatric reliability study was done in 18 volunteers who were divided into three groups based on whether they were typically developing (TD) children, had skeletal development abnormalities, or had cerebral palsy. The reference data were obtained in 129 TD children. Each study participant underwent biplanar radiography with 3D reconstruction performed by experts and radiology technicians. Goniometry parameters were computed automatically. Reproducibility was assessed based on the intra-class coefficient (ICC) and the ISO 5725 standard (standard deviation of reproducibility, SDR). For length parameters, the ICCs ranged from 0.94 to 1.00 and the SDR from 2.1 to 3.5 mm. For angle parameters, the ICC and SDR ranges were 0.60–0.95 and 0.9°–4.6°, respectively. No significant differences were found across experts or radiology technicians. Age-specific reference data are reported. These findings confirm the reliability of low-dose biplanar radiography for assessing lower-limb parameters in children seen in clinical practice. In addition, the study provides reference data for commonly measured parameters

Proteotypic classification of spontaneous and transgenic mammary neoplasms

INTRODUCTION: Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation. METHODS: Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV). RESULTS: On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1. CONCLUSIONS: Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm