The antioxidant properties of serum albumin

Free radicals are a normal component of cellular oxygen metabolism in mammals. However, free radical-associated damage is an important factor in many pathological processes. Glycation and oxidative damage cause protein modifications, frequently observed in numerous diseases. Albumin represents a very abundant and important circulating antioxidant. This review brings together recent insights on albumin antioxidant properties. First, it focuses on the different activities of albumin concerning protein antioxidation. In particular, we describe the role of albumin in ligand binding and free radical-trapping activities. In addition, physiological and pathological situations that modify the antioxidant properties of albumin are reported.     

Current perspectives in pulmonary surfactant — Inhibition, enhancement and evaluation

Pulmonary surfactant (PS) is a complicated mixture of approximately 90% lipids and 10% proteins. It plays an important role in maintaining normal respiratory mechanics by reducing alveolar surface tension to near-zero values. Supplementing exogenous surfactant to newborns suffering from respiratory distress syndrome (RDS), a leading cause of perinatal mortality, has completely altered neonatal care in industrialized countries. Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but with only limited success. Biophysical studies suggest that surfactant inhibition is partially responsible for this unsatisfactory performance. This paper reviews the biophysical properties of functional and dysfunctional PS. The biophysical properties of PS are further limited to surface activity, i.e., properties related to highly dynamic and very low surface tensions. Three main perspectives are reviewed. (1) How does PS permit both rapid adsorption and the ability to reach very low surface tensions? (2) How is PS inactivated by different inhibitory substances and how can this inhibition be counteracted? A recent research focus of using water-soluble polymers as additives to enhance the surface activity of clinical PS and to overcome inhibition is extensively discussed. (3) Which in vivo, in situ, and in vitro methods are available for evaluating the surface activity of PS and what are their relative merits? A better understanding of the biophysical properties of functional and dysfunctional PS is important for the further development of surfactant therapy, especially for its potential application in ARDS.     

Anti-inflammatory effect of chemically modified chitin

Anti-inflammatory effects of the three types of chitin derivatives namely phosphated chitin (P-chitin), phosphated–sulfated chitin (PS-chitin), and sulfated chitin (S-chitin) were investigated using a canine model of chitosan-induced pneumonia. After simultaneous administration of chitosan with or without each chitin derivative (chitosan alone: n=6, chitosan and P-chitin: n=6, chitosan and PS-chitin: n=1, and chitosan and S-chitin: n=3), hematological examination and X-ray image processing were performed for up to 24 h. Then the lungs were recovered and were evaluated by softex imaging after inflation and fixation. The hematological findings showed that PS-chitin and S-chitin did not prevent the decrease in white blood cell (WBC) count as seen in dogs administered chitosan, while P-chitin prevented such decrease in WBC count. The surface of the inflated and fixed lung specimens was hemorrhagic in the PS- and S-chitin groups as well as in the chitosan group, while the lung looked like normal in the P-chitin group. The pulmonary blood vessels of the chitosan group showed severe change while the P-chitin group showed no changes with softex findings. Furthermore, the pattern of histogram density obtained with image processing of thoracic X-ray in P-chitin group did not change among pre and post administration while chitosan group showed rightward movement and significant changes on parameters. The cause of which is attribured to an attenuation of X-ray permeability by angiectasis of the lung.     

Drugs to cure avian influenza infection – multiple ways to prevent cell death

New treatments and new drugs for avian influenza virus (AIV) infection are developed continually, but there are still high mortality rates. The main reason may be that not all cell death pathways induced by AIV were blocked by the current therapies. In this review, drugs for AIV and associated acute respiratory distress syndrome (ARDS) are summarized. The roles of antioxidant (vitamin C) and multiple immunomodulators (such as Celecoxib, Mesalazine and Eritoran) are discussed. The clinical care of ARDS may result in ischemia reperfusion injury to poorly ventilated alveolar cells. Cyclosporin A should effectively inhibit this kind of damages and, therefore, may be the key drug for the survival of patients with virus-induced ARDS. Treatment with protease inhibitor Ulinastatin could also protect lysosome integrity after the infection. Through these analyses, a large drug combination is proposed, which may hypothetically greatly reduce the mortality rate.     

Harm to Others Acts as a Negative Reinforcer in Rats

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Inside Back Cover: Development of a 3‐dimensional tissue lung phantom of a preterm infant for optical measurements of oxygen—Laser‐detector position considerations (J. Biophotonics 3/2018)

The picture depicts the different 3d‐printed organs, thorax, lungs, heart and bone. Assembled it is used as an optical phantom of a preterm infant for performing percutaneous optical measurements of the gas content in the lungs. In order to simulate the optical properties of the tissue, the heart and thorax can be filled with liquid phantoms, a mixture of Intralipid and Indian Ink. Further details can be found in the article by Jim Larsson et al. ( e201700097 ).

     

Effect of surfactant protein A on the physical properties and surface activity of KL4-surfactant

SP-A, the major protein component of pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice. However, it is thought that therapeutic properties of natural surfactants improve after enrichment with SP-A. The objective of this study was to determine SP-A effects on physical properties and surface activity of a new synthetic lung surfactant based on a cationic and hydrophobic 21-residue peptide KLLLLKLLLLKLLLLKLLLLK, KL(4). We have analyzed the interaction of SP-A with liposomes consisting of DPPC/POPG/PA (28:9:5.6, w/w/w) with and without 0.57 mol % KL(4) peptide. We found that SP-A had a concentration-dependent effect on the surface activity of KL(4)-DPPC/POPG/PA membranes but not on that of an animal-derived LES. The surface activity of KL(4)-surfactant significantly improved after enrichment with 2.5-5 wt % SP-A. However, it worsened at SP-A concentrations > or =10 wt %. This was due to the fluidizing effect of supraphysiological SP-A concentrations on KL(4)-DPPC/POPG/PA membranes as determined by fluorescence anisotropy measurements, calorimetric studies, and confocal fluorescence microscopy of GUVs. High SP-A concentrations caused disappearance of the solid/fluid phase coexistence of KL(4)-surfactant, suggesting that phase coexistence might be important for the surface adsorption process.     

Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies in type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns.     

共聚焦激光扫描对呼吸窘迫综合症大鼠肺组织的观察

目的：为了更直观地观察和显示呼吸窘迫综合症(acute respiratory distress syndrom,ARDS)典型的病理变化(肺泡内形成一层蛋白质透明膜)。方法：利用百草枯(Paraqual)染毒SD大鼠复制ARDS实验动物模型,取肺病理组织,切片,试剂Goat—Anti-Rat—FITC IgM IgG染色,共聚焦激光扫描显微镜(confocal laser scarming microscope,CLSM)观察。结果：CLSM能清晰到样品内不同层面的病理变化。结论：共聚焦激光扫描显微镜能清晰观察样品内不同层面的结构,相比于传统的光学显微镜,其观察到的图像更直观、更具立体感,能更好表达ARDS的病理变化特征。