Analysis of protease-activated receptor-1 and -2 in human scar formation

Protease-activated receptor (PAR)-1 and PAR-2 are reported to contribute to the fibrotic process in a number of organs, including lung, liver, pancreas, and kidney. The aim of this study was to localize expression and biological activity of PAR-1 and PAR-2 in normal and pathological cutaneous scars. First, we investigated the immunohistochemical expression of PAR-1 and PAR-2 proteins in a series of human normal scars (NS, n = 10), hypertrophic scars (HS, n = 10), and keloids (K, n = 10). Expression of PAR-1 and PAR-2 was observed in all types of scar. Specifically, in HS and K, diffuse PAR-1 and PAR-2 positivity was found in dermal cellular areas composed of myofibroblasts, while no or minor staining was observed in the scattered fibroblasts embedded in abundant extracellular matrix in the context of the more collagenous nodules, irrespective of the type of scar. The hyperplastic epidermis overlying K was also found to be strongly PAR-1 and PAR-2 positive, whilst in most NS and HS the epidermis was faintly to moderately stained. Second, ribonuclease protection assay on paraffin-embedded specimens showed overexpression of PAR-1 and PAR-2 mRNA in K compared to NS and HS. Third, cultured human fibroblasts exposed to TGF-beta1 expressed a myofibroblast phenotype associated with overexpression of PAR-2, while PAR-1 expression was unaffected. Intracellular Ca(2+) mobilization by PAR-2 agonists in myofibroblasts was increased as compared to fibroblasts, whereas the effect of PAR-1 agonists was unchanged. Our in vivo study indicates that PAR-1 and PAR-2 are expressed in cells involved in physiological and pathological scar formation and suggests that in vitro overexpression and exaggerated functional response of PAR-2 may play a role in the function of myofibroblasts in scar evolution from a physiological repair process to a pathological tissue response.     

Comparatine analysis of cytophenotypes of cells of mesenchymal lineage isolated from human tissues

The expression of cytoplasmic and surface proteins in cultured human skin fibroblasts, human umbilical cord cells obtained after normal delivery on gestation week 38–40, and mesenchymal bone marrow stem cells was compared by the methods of immunocytochemistry and flow cytofluorometry. Bone marrow mesenchymal stem cells expressed a great variety of marker proteins typical of stem and progenitor cells and did not express proteins typical of differentiated cells. Fibroblast-like umbilical cord cells expressed markers of both stem cells and differentiated cells. Fibroblasts of dermal origin were characterized by intensive expression of proteins typical of differentiated cells. __________ Translated from Kletochnye Tehnologii v Biologii i Medicine, No. 1, pp. 38–45, January, 2007     

Children's skin conductance level and reactivity: Are these measures stable over time and across tasks?

The stability of children's skin conductance level during baselines (SCL-B) and SCL reactivity (SCL-R) were examined longitudinally. During two laboratory sessions (T1 and T2), 2 years apart, children participated in procedures during which they were exposed to two stressors namely exposure to an audiotaped conflict between two adults, and a problem solving task. Children ranged in age between 6 and 13 years at T1. Measures of SCL-B and SCL-R during the two stressors were obtained. Findings illustrated the temporal stability of SCL-B and SCL-R to the star-tracing task over 2 years. Results also indicated stability in SCL-R to the two stressors (argument and problem-solving) examined within the same session at either T1 or T2. These results support the proposition that SCL-B and SCL-R constitute stable individual differences at the ages examined, and build on the scant longitudinal literature on psychophysiological development in children.     

An energetically coherent lumped parameter model of the left ventricle specially developed for educational purposes

We present a Bond Graph model and simulation of the cardiac dynamics of the left ventricle (LV). It models all the levels from the mechanisms of contraction up to the hemodynamics of the LV. We validate our model by presenting several case studies. The goal is to build a model with a strong physiological basis that may be understood in physical terms but, in contrast with other existing models, may be simulated sufficiently fast to use it as a teaching tool in cardiovascular physiology and allow its integration as a boundary condition in more sophisticated 3D finite-element models.     

How Sensitive Are Transdermal Transport Predictions by Microscopic Stratum Corneum Models to Geometric and Transport Parameter Input?

While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g., compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and-mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations. In addition, these models rely on transport parameters obtained from pure theory, parameter fitting to match in vivo experiments, and time-intensive diffusion experiments for each compound. In this work, we develop a microscopic finite element model that allows us to probe model sensitivity to variations in geometry, transport pathway, and hydration level. Given the dearth of experimentally-validated transport data and the wide range in theoretically-predicted transport parameters, we examine the model's response to a variety of transport parameters reported in the literature. Results show that model predictions are strongly dependent on all aforementioned variations, resulting in order-of-magnitude differences in lag times and permeabilities for distinct structure, hydration, and parameter combinations. This work demonstrates that universally predictive models cannot fully succeed without employing experimentally verified transport parameters and individualized SC structures.     

Assessing the risk of epidemic dropsy from black salve use

Epidemic dropsy is a potentially life‐threatening condition resulting from the ingestion of argemone oil derived from the seeds of Argemone mexicana Linn. Exposure to argemone oil is usually inadvertent, arising from mustard cooking oil adulteration. Sanguinarine, an alkaloid present in argemone oil, has been postulated as a causative agent with the severity of epidemic dropsy correlating with plasma sanguinarine levels. Cases of epidemic dropsy have also been reported following the topical application of argemone containing massage oil. Black salve, a topical skin cancer therapy also contains sanguinarine, but at significantly higher concentrations than that reported for contaminated massage oil. Although not reported to date, a theoretical risk therefore exists of black salve inducing epidemic dropsy. This literature review explores the presentation and pathophysiology of epidemic dropsy and assesses the risk of it being induced by black salve.     

Vascular endothelial growth factor (VEGF) antibody significantly increases the risk of hand–foot skin reaction to multikinase inhibitors (MKIs): A systematic literature review and meta‐analysis

With the use of multikinase inhibitors (MKIs) having emerged in recent years, skin toxicities such as hand–foot skin reaction (HFSR) are primary side effects, and they lack effective prediction methods. Here, we updated a previous systematic review by establishing a meta‐analysis of the risk of developing HFSR among patients receiving MKIs and antivascular endothelial growth factor antibody. Publications from PubMed and abstracts presented at the American Society of Clinical Oncology Annual Meeting up to February 5, 2015, were searched to identify relevant studies, and a total of 236 patients with metastatic tumours in nine trials were included for analysis. In the meta‐analysis, the pooled incidence rates of all‐grade and high‐grade HFSR among patients who received the combination therapy were 56.9% [95% confidence interval (CI), 45%‐71.1%] and 14.3% (95% CI, 9%‐24.2%), respectively, with significant differences observed with MKI monotherapy (P < .05). Further subgroup analysis demonstrated that increasing the dosages of bevacizumab (77.8% vs 51.1%, P = .04) and MKIs (64.3% vs 52.6%, P = .02) significantly increased HFSR incidence. Moreover, combination with chemotherapy exerted a minimal effect on HFSR risk (61% vs 55.3%, P = .5). This updated review and meta‐analysis confirm the increased risk of HFSR incidence due to the use of MKIs and antivascular endothelial growth factor antibody. Thus, using these therapies requires safety standards.     

抗氧化肽AOP_1对小鼠皮肤烫伤创面愈合修复的影响

目的探究抗氧化肽AOP_1促进小鼠皮肤烫伤创面愈合修复的作用及机制。方法选用DCFH-DA检测细胞内活性氧(ROS)的变化;通过细胞增殖与迁移实验检测药物毒性及对创面愈合的影响。采用直径1 cm铜柱80℃水浴2min、紧贴小鼠皮肤10 s的方法制备烫伤模型,观察烫伤创面愈合情况;并用HE和Masson三色染色观察AOP_1对皮肤烫伤创面愈合修复的作用;检测小鼠全皮组织中MDA含量和SOD活性。结果在细胞水平上,抗氧化肽AOP_1能够明显降低HaCaT和L929细胞内ROS的含量,促进细胞迁移和增殖。与对照组相比,AOP_1组小鼠皮肤创面愈合时间短、愈合率高,结痂面积小,可明显降低烫伤创伤组织中炎症反应及MDA的含量;HE和Masson染色也证实了AOP_1对烫伤创面愈合修复的促进作用。结论具有天然活性的抗氧化肽AOP_1可能通过减轻烫伤引起的氧化应激,促进小鼠皮肤烫伤创面的愈合修复。     

重组人皮肤模型用于评价药品包装材料原发性皮肤刺激质量标准的建立

摘要 目的：建立重组人皮肤模型用于评价药品包装材料原发性皮肤刺激性的标准。方法：用Epikutis?模型和EpiSkinTM模型对药品包装材料进行检测,对浸提介质、浓度、时间以及浸提液与模型的接触时间等条件进行选择,建立可行的标准。结果：取平整部位表面积600cm2,剪碎,加入大豆油100ml,37℃放置24h。使用Epikutis?模型或EpiSkinTM模型,按重组人皮肤模型皮肤刺激检测方法检测,组织活力平均值应大于80%。结论：所建立的标准可用于药品包装材料原发性皮肤刺激检测。