The Stiffness of Three-dimensional Ionic Self-assembling Peptide Gels Affects the Extent of Capillary-like Network Formation

Improving our ability to control capillary morphogenesis has implications for not only better understanding of basic biology, but also for applications in tissue engineering and in vitro testing. Numerous biomaterials have been investigated as cellular supports for these applications and the biophysical environment biomaterials provide to cells has been increasingly recognized as an important factor in directing cell function. Here, the ability of ionic self-assembling peptide gels to support capillary morphogenesis and the effect of their mechanical properties is investigated. When placed in a physiological salt solution, these oligopeptides spontaneously self-assemble into gels with an extracellular matrix (ECM)-like microarchitecture. To evaluate the ability of three-dimensional (3D) self-assembled peptide gels to support capillary-like network formation, human umbilical vein endothelial cells (HUVECs) were embedded within RAD16-I ((RADA)₄) or RAD16-II ((RARADADA)₂) peptide gels with various stiffness values. As peptide stiffness is decreased cells show increased elongation and are increasingly able to contract gels. The observation that capillary morphogenesis is favored in more malleable substrates is consistent with previous reports using natural biomaterials. The structural properties of peptide gels and their ability to support capillary morphogenesis in vitro make them promising biomaterials to investigate for numerous biomedical applications.     

Association of IL-8-251A/T polymorphism with incidence of Acute Respiratory Distress Syndrome (ARDS) and IL-8 synthesis after multiple trauma

INTRODUCTION: Interleukin-8 (IL-8) is regarded as one of the most important mediators in the pathogenesis of Adult Respiratory Distress Syndrome (ARDS). However, knowledge regarding the influence of genetic variations within the IL-8 gene either on the development of ARDS or on IL-8 production in the traumatic setting is sparse. PATIENTS AND METHODS: In this prospective cohort study, patients were included if the following criteria were fulfilled: Injury Severity Score (ISS) >16, age 18-60 years and a survival >48 h after injury. Systemic IL-8 concentrations and the polymorphisms (IL-8-251A/T) were determined. Patients were separated according to the development of ARDS (group +ARDS vs. group -ARDS) and the genotypes of the IL-8-251A/T polymorphism (genotypes A/A, A/T and T/T). RESULTS: Group +ARDS demonstrated significantly higher IL-8 plasma concentrations from day 3 until the end of the observation period compared to group -ARDS. In addition, duration of mechanical ventilation and length of stay in the ICU were significantly longer in this group. Furthermore, a significant association between the IL-8-251A allele and IL-8 production (day 4-8) was observed. Genotype A/A showed a significantly longer duration of mechanical ventilation compared to genotype T/T. A trend towards an association between the IL-8-251A allele and an increased incidence of posttraumatic ARDS was observed (p=0.08). CONCLUSION: This data reaffirms a central role of IL-8 in the pathogenesis of ARDS. Furthermore, it points towards a genetic predisposition for posttraumatic IL-8 synthesis which might also be associated with the development of posttraumatic ARDS.     

机械通气相关性肺炎患者病原体分布及 抗生素停药指征

目的了解机械通气相关性肺炎患者病原体分布特征,探讨降钙素原(PCT)在机械通气相关性肺炎(VAP)中对抗生素停药的指导价值。方法以在ICU行机械通气并被诊断为VAP的患者为研究对象,依据患者入组日期将患者随机分为观察组(37例)与对照组(35例)。采集患者痰液进行病原菌分离与药敏试验。观察组患者依据PCT水平决定抗生素停用时间,对照组患者依据临床医师经验决定抗生素停用时间。观察患者抗生素使用时间、PCT水平、肺部感染复发率及二重感染发生率等指标。结果 72例患者累计检出病原菌84株,其中12株为革兰阳性菌(14.33%),72株为革兰阴性菌(85.7%)。病原菌以肺炎克雷伯菌与铜绿假单胞菌最为常见,检出率分别为34.5%与31.0%,二者多重耐药率分别为44.8%与57.6%。抗生素治疗第8天时检测显示观察组与对照组患者PCT0.5ng/mL的比例分别为72.9%与71.4%,差异无统计学意义(χ2=0.021,P=0.885)。观察组患者VAP抗生素治疗平均时间为(9.8±3.2)d,显著短于对照组的(14.3±3.6)d,二者差异有统计学意义(t=5.612,P0.001)。多元线性回归分析结果显示,依据PCT水平停药是VAP抗生素治疗开始后28d内抗生素使用时间的独立影响因素(β=-8.24,95%CI:-11.37～-5.11,P0.001)。结论 VAP患者的病原菌以革兰阴性菌最为常见,铜绿假单胞菌与肺炎克雷伯菌感染高发,且二者多重耐药比例较高。PCT水平可作为VAP患者抗生素治疗停药判断标准,可有效减少抗生素使用时间。     

COPD合并Ⅱ型呼吸衰竭患者血清磷、降钙素原、25-羟维生素D3水平与机械通气撤机结局的关系研究

摘要 目的：探讨慢性阻塞性肺疾病（COPD）合并Ⅱ型呼吸衰竭患者血清磷（P）、降钙素原（PCT）、25-羟维生素D3[25(OH)D3]水平对机械通气撤机结局的影响。方法：选取2020年3月-2021年3月我院收治的接受机械通气治疗的COPD合并Ⅱ型呼吸衰竭患者117例,根据撤机结局分为撤机成功组（n=91）和撤机失败组（n=26）,比较两组患者的临床资料、自主呼吸测试(SBT)前的血清P、PCT、25(OH)D3水平,多因素Logistic回归分析撤机失败的影响因素,受试者工作特征(ROC)曲线分析血清P、PCT、25(OH)D3水平对撤机失败的预测价值。结果：两组患者在机械通气时间、入住重症监护室（ICU）时间、急性生理学及慢性健康状况评分系统Ⅱ（APACHE II）评分方面差异有统计学意义（P＜0.05）;SBT前撤机成功组血清25(OH)D3、P水平高于撤机失败组,PCT水平低于撤机失败组（P＜0.05）;多因素Logistic 回归分析结果显示：PCT、25(OH)D3、P、机械通气时间均是撤机失败的影响因素（P＜0.05）;ROC曲线分析结果显示：血清PCT、25(OH)D3、P水平预测撤机失败的曲线下面积（AUC）分别为0.687、0.802、0.751,均低于三者联合应用的0.846。结论：血清P、PCT、25(OH)D3均是COPD合并Ⅱ型呼吸衰竭患者机械通气撤机结局的影响因素,检测以上指标水平有助于预测患者机械通气撤机结局。     

舒芬太尼与芬太尼对机械通气患者镇痛的效果比较

目的:比较舒芬太尼与芬太尼对机械通气(MV)患者镇痛的效果。方法:选择我院2012年1月至2014年1月收治的87例手术室MV患者,按随机数字表法分为两组,芬太尼组44例患者应用芬太尼镇痛,舒芬太尼组43例患者应用舒芬太尼镇痛,比较两组患者用药前后心率(HR)、自主呼吸频率(RR)、平均动脉血压(MAP)及脉搏氧饱和度(Sp O2)基本生命指征变化,同时记录两组患者芬太尼、舒芬太尼及咪达唑仑用量,MV时间,持续镇痛时间,手术室滞留时间,比较两组患者用药前后Ramsay评分。结果:1两组用药后1h(T1)及24 h(T2)HR、RR及MAP较用药前(T0)明显下降,Sp O2较T0明显升高,差异有统计学意义(P0.05);芬太尼组MAP在T1及T2时刻下降程度明显高于舒芬太尼组,差异有统计学意义(P0.05)。2两组患者在T1时刻Ramsay评分较T0时刻明显升高,且舒芬太尼组升高程度明显高于芬太尼组,差异有统计学意义(P0.05)。3达到较好镇痛效果水平时,舒芬太尼组患者镇痛药物用量及咪达唑仑用量均明显少于芬太尼组,且舒芬太尼组MV时间及手术室滞留时间明显短于芬太尼组,差异有统计学意义(P0.05),两组患者持续镇痛时间比较差异无统计学意义(P0.05)。结论:MV患者使用舒芬太尼的镇痛镇静效果优于芬太尼,可有效节省咪达唑仑的使用量,缩短MV及手术室滞留时间,值得临床推广应用。     

Mechanical stress induces DNA synthesis in PDL fibroblasts by a mechanism unrelated to autocrine growth factor action

Periodontal regeneration is thought to require the proliferation of stress-sensitive periodontal ligament (PDL) fibroblast cells. The influence of physiological amounts of mechanical stretching on the DNA synthesis potential of human PDL fibroblasts was examined by means of an established, simple in vitro system of stretch application. A significant increase in the relative levels of incorporation of tritiated thymidine was observed in cultures stretched for 1–6 h. Neutralising antibodies for platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) did not blunt the DNA synthesis induction. This mitogenic response to stretch appears to be independent of an autocrine mechanism involving growth factors in general, because stretch-conditioned medium, when transferred to non-stretched fibroblasts, did not mimic the mitogenic effect of stretch.     

Regeneration processes of biological soil crusts,macro-cryptogams and vascular plant species after fine-scale disturbance in a temperate region: Recolonization or successional replacement?

Open base-rich sandy habitats are often characterised by an extensive cover of biological soil crusts (BSCs). We studied the impact of mechanical disturbances on cyanobacteria/algae-dominated BSCs, macro-cryptogams (bryophytes, lichens), phanerogams and their regeneration processes in a 3-year field experiment in a temperate region. We compared controls with two fine-scale disturbance regimes, each based on 50 plots (20 cm×20 cm): 1. BSCs were raked (weak disturbance), 2. BSCs were completely removed (strong disturbance). We used a Sileno conicae-Cerastion semidecandri habitat as a model area for the field study and ask if the crusts are able to regenerate or will be replaced by macro-cryptogams and/or phanerogams.     

Fission of the bilayer lipid tube

The fusion of two black lipid membranes results in the formation of peculiar bilayer lipid tubes (‘cylindrical’) membranes (Neher, E. (1974) Biochim. Biophys. Acta 373, 328–336 and Melikyan, G.B., Abidor, L.G., Chernomordik, L.V. and Chailakhyan, L.M. (1983) Biochim. Biophys. Acta 730, 395–398). The mechanical stability of such tubes has been investigated experimentally and theoretically. With increasing hydrostatic pressure on the outside of the tube the radius of its middle part decreases. After this radius has reached a critical value, which constitutes 0.55 of the radius of the tube base, there occurs a collapse of the tube and its disintegration into two planar bilayers (fission). Expressions are obtained which relate the transmembrane difference of the hydrostatic pressure, causing the collapse, to the geometrical characteristics of the tube (its length and the radius of its base) and to the tension of the lipid bilayer. A method for measuring the membrane tension is proposed on the basis of the phenomenon considered.     

Structural heterogeneity of the basement membrane in the rat proximal tubule

Summary The ultrastructure of the basement membrane of the rat proximal tubule was observed by transmission electron microscopy after the use of a cold dehydration technique. The basement membrane of the P1 segment is thick and possesses several structural specializations that are rare in other basement membranes; these include intraepithelial ridges, dense bars, and basement membrane vesicles. The intraepithelial ridges are found in the intercellular spaces between interdigitating processes of the proximal tubule cells. The ridges and the interdigitating processes run circumferentially around the tubule. The dense bars are frequently found in the intraepithelial ridges. They are especially prominent on the concave side of the tubular bends and to a lesser extent near sites where intracellular actin filaments anchor onto the basal cell membranes. The basement membrane vesicles are bounded by unit membranes; they are variable in both their electron density and their size. They are usually found in association with dense bars, and the grade of their accumulation is positively correlated with the development of the dense bars. These three specializations have no topographical relationship with the interstitial structures, such as fibrobalasts and collagen fibrils. The specializations are best developed on the concave side of tubular bends where the circumferential stresses caused by the intraluminal hydraulic pressure are presumably the largest; we therefore propose that they are an adaptation to, or a manifestation of, the increased wall stress in the proximal tubule.