不同浓度异氟醚对小鼠肺表面活性蛋白A表达的影响

目的 探讨异氟醚对小鼠肺表面活性蛋白A表达的影响。方法 将雄性昆明小鼠随机分为5组,吸入空气组、吸入1.0MAC异氟醚5min组、吸入3.0MAC异氟醚5min组、吸入1.0MAC异氟醚2h组、吸入3.0MAC异氟醚2h组;RT-PCR方法检测小鼠肺内SP-A mRNA的表达;免疫组化方法检测小鼠肺内SP-A蛋白的表达。结果 吸入异氟醚5min对小鼠肺内SP-A表达无影响,吸入异氟醚2h能降低小鼠肺内SP-A表达,而且随吸入浓度升高,SP-A表达呈负相关。结论 吸入高浓度异氟醚长时间能够降低小鼠肺内SP-A的表达。     

The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats

Introduction

To evaluate the effect of Ambroxol on the pulmonary surfactant (PS) in rat pneumonia induced by Pseudomonas aeruginosa (PA).

Material and methods

The pneumonic rats were obtained by injecting ATCC27853 intratracheally. One hundred and twenty SD rats were randomized into four groups: normal saline and Ambroxol was injected intraperitoneally following PA challenge in the PA/NS and PA/AM group; the other two groups were NS/AM and NS/NS. The wet/dry weight ratio (W/D), and pathological changes were assayed. Total proteins (TP), total phospholipid (TPL), and dipalmitoylphosphatidylcholine (DPPC) in bronchial alveolar lavage fluid (BALF) were analysed. Some BALF was cultured for colony counts. Ultrastructural change of the lung was observed by electron microscopy.

Results

The W/D ratio in the PA/AM group was lower than that in the PA/NS group; both were higher than that in the NS/NS group (p < 0.05). There were more neutrophils in the PA/NS group than in the PA/AM group (p < 0.05), and more in the PA/AM group than in the NS/NS group (p < 0.05). The ratio of DSPC/TPL and DSPC/TP in the BALF in PA/NS group was lower than that in the PA/AM group; DSPC/TPL and DSPC/TP ratios also increased in the NS/AM group. The PA colony numbers in the PA/AM group were lower than in the PA/NS group (p > 0.05). In the PA/NS group, vacuolation occurred in the lamellar body of alveolar type 2 cells (AT2) and the PS layer was rough and broken in some areas. In the PA/AM group, the degree of vacuolation of the lamellar body was less than in the PA/NS group.

Conclusions

Ambroxol could protect rats from pneumonia by improving the level of endogenous PS, especially DPPC.     

Amphicrine Differentiation in Bronchioloalveolar Cell Carcinoma

We report for the first time a classical bronchioloalveolar cell carcinoma with both exocrine and endocrine differentiation (amphicrine) in the same cell. At electron microscopy the tumor cells showed a mixed type II alveolar cell/Clara cell and mucous differentiation. In addition, there were many dense-core neurosecretory granules at the base of the majority of the cells. Immunocytochemically the tumor showed positivity for surfactant and a panel of neuroendocrine antibodies, including NSE, PGP9.5, synaptophysin, and chromogranin A. The presence of neuroendocrine differentiation was not hinted at by routine histology and did not indicate a more aggressive behavior in this case since the patient is well 3 years after the resection.     

Potential of biocompatible regenerated silk fibroin/sodium N-lauroyl sarcosinate hydrogels

Hydrogels are becoming widely used in biomaterial applications. The available methods for the preparation of these materials are continually growing. The gelation time (GT) of silk protein fibroin is difficult to control by physical methods. The cross-linkers used in available chemical techniques are likely to impact the biocompatibility of the resultant materials. In this paper, we demonstrate that the addition of sodium N-lauroyl sarcosinate (an amino-acid-based surfactant) accelerates the formation of hydrogels from fibroin. GT, turbidity variations, changes of viscoelasticity during the gelation process, and the mechanical properties of the products are measured. The secondary structure was probed by Fourier transform infrared spectroscopy, X-ray diffraction and the morphologies of the products were investigated by scanning electron microscopy. Transformations in the β-sheet content were monitored by the fluorescence of Thioflavine T and circular dichroism measurements. The relationship between the surface tension of sodium N-lauroyl sarcosinate and the GT was also explained. To investigate cell compatibility, fibroblast cells were seeded onto the surface of the hydrogels. The results indicate that the sodium N-lauroyl sarcosinate/fibroin GT can be controlled. This blend-hydrogel demonstrates excellent cell compatibility, good compression strength, and outstanding compression-recovery characteristics. Sodium N-lauroyl sarcosinate/silk fibroin hydrogels containing β-sheets have considerable potential as replacement materials in addressing the tissue defects involved with repair surgery.     

Chorioamnionitis decreased incidence of respiratory distress syndrome by elevating fetal interleukin-6 serum concentration

Respiratory distress syndrome (RDS) of newborns is one of the most important factors determining neonatal morbidity and mortality. The interleukin-6 (IL-6) titre in cord sera of RDS-free neonates born to mothers with histological chorioamnionitis was significantly higher than that in RDS-complicated neonates without chorioamnionitis. Maternal administration of glucocorticoid suppressed the IL-6 concentrations in the cord sera of fetuses with chorioamnionitis. The fetuses without chorioamnionitis who suffered from RDS even after maternal glucocorticoid administration showed a similar IL-6 titre to that of RDS-affected neonates without chorioamnionitis. Examination of the mechanism by which IL-6 decreased the incidence of fetal RDS revealed that H441-4, a human pulmonary adenocarcinoma cell line, stimulated with recombinant (r)-IL-6 started the synthesis of mRNA and protein of pulmonary surfactant protein (SP)-A. The present study shows that IL-6 elevation in fetuses with chorioamnionitis promotes fetal lung maturation by inducing SP-A synthesis, thereby decreasing the incidence of RDS in the preterm neonates.     

偏二甲基肼和四氧化二氮吸入性肺损伤中肺泡表面活性物质的变化

目的研究火箭液体推进剂偏二甲基肼（UDMH）和四氧化二氮（N2O4）吸入性急性肺损伤（ALI）中肺泡表面活性物质（PS）的变化及其与ALI的关系。方法84只大鼠分为对照组和5个实验组。实验组在静式染毒柜内分别吸入UDMH（0．98g／m^3）和N2O4（0．19g／ms）各10min，间隔10min。实验组在吸入后2、6、12、24、48h分别处死。测定各组大鼠常压下支气管肺泡灌洗液（BALF）的表面张力（γ）、加压下最低表面张力（γmin）、磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）。同时测定肺组织湿／于重比（W／D）、BALF中总蛋白和乳酸脱氢酶（LDH）等肺损伤指标，评价病理学改变。结果UDMH-N2O4吸入性ALI表现为肺W／D比值增加、BALF中总蛋白和LDH升高，以及肺水肿、肺间隔增厚等病理变化。PS的异常表现为：①在UDMH—N2O4吸入后2hBALF中γ和γmin。即明显升高，至24-48h尚未恢复到对照组水平；②吸入后24hBALF中PC明显低于对照组，PE含量明显高于对照组。以BALF中总蛋白作为肺损伤指标与PS异常的指标γ和γmin分别做直线相关分析，相关系数分别为0．435（P〈0．01）和0．419（P〈0．01）。结论UDMH—N2O4吸入性ALI中存在PS异常，PS异常可能参与了UDMH—N2O4吸入性ALI的发生发展过程。     

Surfactant does not improve survival rate in preterm infants with congenital diaphragmatic hernia

Background

Use of exogenous surfactant in congenital diaphragmatic hernia (CDH) patients is routine in many centers. The authors sought to determine the impact of surfactant use in the premature infant with CDH.

Methods

Data on liveborn infants with CDH from participating institutions were collected prospectively. Surfactant use and timing and outcome data were analyzed retrospectively. The authors evaluated the prenatal diagnosis patients as well. The outcome variable was survival to discharge. Odds ratios with confidence intervals were calculated.

Results

Five hundred ten infants less than 37 weeks’ gestation were entered in the CDH registry. Infants with severe anomalies (n = 80) were excluded. Information on surfactant use was available for 424 patients. Infants receiving surfactant (n = 209) had a greater odds of death than infants not receiving surfactant (n = 215, odds ratio, 2.17, 95% CI: 1.5 to 3.2; P < .01). In prenatally diagnosed infants with immediate distress, there was a trend toward worse survival rates among those receiving surfactant at 1 hour (52 patients) versus those that did not (93 patients; odds ratio, 1.93, 95% CI: 0.96 to 3.9; P < .07).

Conclusions

Surfactant, as currently used, is associated with a lower survival rate in preterm infants with CDH. The use of surfactant replacement in premature infants with CDH can be recommended only within the context of a randomized clinical trial.     

Innate immune molecule surfactant protein D attenuates sepsis‐induced acute kidney injury through modulating apoptosis and NFκB‐mediated inflammation

The objective of this study is to investigate the mechanism whereby innate immune molecule surfactant protein D (SP‐D) attenuates sepsis‐induced acute kidney injury (AKI) through modulating apoptosis and nuclear factor kappa‐B (NFκB)‐mediated inflammation. In the present study, a mouse sepsis model was established by cecal ligation and puncture in SP‐D knockout (KO) mice and wild‐type (WT) mice. A sham‐operated group was included as the control. The experimental materials were extracted 6 and 24 hours postoperatively. The plasma levels of tumour necrosis factor alpha (TNF‐α) and MCP‐1 were determined by enzyme‐linked immunosorbent assay (ELISA). Apoptosis was measured by double staining with Annexin V/propidium iodide and flow cytometry. The levels of NFκB in renal tissues were measured by ELISA and Western blotting assay. Apoptosis was detected by TUNEL assays. There were no significant differences in plasma TNF‐α levels between the WT sham group and the KO sham group at 6 and 24 hours postoperatively (P < .05), but the levels of TNF‐α in the WT sepsis and KO sepsis groups were significantly higher than those in controls (P < .05). The levels of TNF‐α in the KO sepsis group were significantly higher than those of the WT sepsis group (P < .05). TNF‐α levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The levels of MCP‐1 in the WT sepsis group and the KO sepsis group at 6 and 24 hours postoperatively were significantly higher than those in the control group (P < .05), and MCP‐1 levels in the KO sepsis group were significantly higher than those in the WT sepsis group (P < .05). MCP‐1 levels in the WT sepsis group and the KO sepsis group at 24 hours postoperatively were significantly higher than those at 6 hours postoperatively (P < .05). The expression of SP‐D in WT kidneys was significantly lower at 6 and 24 hours postoperatively (P < .05). The number of TUNEL‐positive cells in the kidneys from septic SP‐D KO mice was significantly higher (P < .05). The levels of NFκB in septic mice were significantly increased at 6 and 24 hours after induction of sepsis compared with the sham‐operated group compared with those of septic SP‐D KO mice and WT mice (P < .05). Innate immune molecule SP‐D significantly decreased plasma levels of inflammatory cytokines in mice and attenuated sepsis‐induced AKI by inhibiting NFκB activity and apoptosis.     

Efficacy of a topical concentrated surfactant gel on microbial communities in non‐healing diabetic foot ulcers with chronic biofilm infections: A proof‐of‐concept study

This proof‐of‐concept study sought to determine the effects of standard of care (SOC) and a topically applied concentrated surfactant gel (SG) on the total microbial load, community composition, and community diversity in non‐healing diabetic foot ulcers (DFUs) with chronic biofilm infections. SOC was provided in addition to a topical concentrated SG, applied every 2 days for 6 weeks. Wound swabs were obtained from the base of ulcers at baseline (week 0), week 1, mid‐point (week 3), and end of treatment (week 6). DNA sequencing and real‐time quantitative polymerase chain reaction (qPCR) were employed to determine the total microbial load, community composition, and diversity of patient samples. Tissue specimens were obtained at baseline and scanning electron microscopy and peptide nucleic acid fluorescent in situ hybridisation with confocal laser scanning microscopy were used to confirm the presence of biofilm in all 10 DFUs with suspected chronic biofilm infections. The application of SG resulted in 7 of 10 samples achieving a reduction in mean log10 total microbial load from baseline to end of treatment (0.8 Log10 16S copies, ±0.6), and 3 of 10 samples demonstrated an increase in mean Log10 total microbial load (0.6 log10 16S copies, ±0.8) from baseline to end of treatment. Composition changes in microbial communities were driven by changes to the most dominant bacteria. Corynebacterium sp. and Streptococcus sp. frequently reduced in relative abundance in patient samples from week 0 to week 6 but did not disappear. In contrast, Staphylococcus sp., Finegoldia sp., and Fusobacterium sp., relative abundances frequently increased in patient samples from week 0 to week 6. The application of a concentrated SG resulted in varying shifts to diversity (increase or decrease) between week 0 and week 6 samples at the individual patient level. Any shifts in community diversity were independent to changes in the total microbial loads. SOC and a topical concentrated SG directly affect the microbial loads and community composition of DFUs with chronic biofilm infections.     

鼻塞式持续气道正压通气联合肺表面活性物质治疗早产儿肺透明膜病对照研究

目的探讨鼻塞式持续气道正压通气(NCPAP)联合肺表面活性物质(PS)和NCPAP联合沐舒坦(MU)两种方法治疗早产儿肺透明膜病的疗效差异。方法将90例肺透明膜病(HMD)早产儿随机分为NCPAP联合PS(NC+PS治疗组)和NCPAP联合MU(NC+MU治疗组),分别进行治疗,并比较两组的疗效、动脉血气分析和近远期并发症的差异。结果 (NC+PS)组的总有效率显著高于(NC+MU)组,而在呼吸困难缓解时间、上呼吸机时间和平均住院时间方面均小于(NC+MU)组,两组间的差异具有统计学意义(P<0.05)。治疗前两组早产儿的pH、PaO2、PaCO2和PaO2/FiO2无统计学差异(P>0.05);治疗后,两组早产儿的pH、PaO2和PaO2/FiO2均逐渐升高,PaCO2逐渐降低,两组间的差异具有统计学意义(P<0.05)。近期并发症主要为肺炎、颅内出血和肺出血,远期并发症主要为脑性瘫痪、听力障碍和早产儿视网膜病,(NC+PS)组的早产儿在早期和远期并发症方面均显著低于(NC+MU)组(P<0.05)。结论 NCPAP联合PS能显著提高早产儿肺透明膜病疗效,近远期并发症低,疗效显著高于NCPAP联合MU的疗效。