Oxidative stress and increased type-IV collagenase levels in bronchoalveolar lavage fluid from newborn babies

Oxidative stress may increase lung permeability by upregulation of matrix-metalloproteinase-9 (MMP-8), a type-IV collagenase that can disrupt alveolar basement membranes. We have compared a marker of oxidative stress (protein carbonyl residues) with levels of MMP-8 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in bronchoalveolar lavage samples from newborn babies. Bronchoalveolar lavage samples (n = 87, two from each time point) were taken in the first 6 postnatal days from 41 ventilated babies: 18 of

Lipopolysaccharide-binding protein and CD14 are increased in the bronchoalveolar lavage fluid of smokers

Lipopolysaccharide-binding protein (LBP) and CD14 contribute to the recognition of pathogens by cells, which triggers the activation of defence responses. Smoking is a risk factor for the development of chronic obstructive pulmonary disease (COPD) and respiratory infections. The current authors theorised that levels of LBP and CD14 in the lungs of smokers would be higher than those in the lungs of never-smokers. These elevated levels could affect host responses upon infection. LBP, soluble CD14 (sCD14) and interleukin (IL)-8 were detected by ELISA. Nuclear factor (NF)- ?B, p38 and the inhibitor I?Ba were studied by immunoassays. Gene expression was assessed by RT-PCR. Bronchoalveolar lavage levels of LBP and CD14 were significantly higher in smokers and COPD patients than in never-smokers, whereas levels of both proteins were not significantly different between smokers and COPD patients. IL-6, IL-1ß5 and cigarette smoke condensate induced the expression of LBP and CD14 by airway epithelial cells. LBP and sCD14 inhibited the nontypeable Haemophilus influenzae (NTHi)-dependent secretion of IL-8 and the activation of NF-?B and p38 mitogen-activated protein kinase signalling pathways but they increased the internalisation of NTHi by airway epithelial cells. Thus, in the inflamed airways of smokers both proteins could contribute to inhibit bacteria-dependent cellular activation without compromising the internalisation of pathogens by airway cells. Copyright©ERS Journals Ltd 2009.

Demarcation laser therapy in the management of macular-sparing persistent subretinal fluid after scleral buckling procedures

Background: Persistent or recurrent macular-sparing subretinal fluid (SRF) can sometimes occur following scleral buckling procedures. Observation and reoperation have been used in the management of such cases. Demarcation laser therapy (DLT) has been used to treat macular-sparing retinal detachments in the context of cytomegalovirus retinitis and as primary treatment for selected rhegmatogenous retinal detachments. There are, however, scarce data in the literature regarding its use following primary scleral buckling procedures. The current study explores the use of DLT under the latter circumstances. Methods: The medical records of all consecutive patients with persistent SRF sparing the macula following primary rhegmatogenous retinal detachment repair using a scleral buckling procedure were retrospectively reviewed. Only those patients in whom the breaks were localised to the area of indentation and, thus, seemed to be well supported by the buckle were included. Demographics, clinical characteristics of the retinal detachment prior to scleral buckling, extension of the residual SRF observed postoperatively, details of the laser procedure, anatomical and functional outcomes and complications were evaluated. Results: Seven patients, all females, with a mean age of 47.9 years (range: 20-81) were included in the study. The retinal detachments were superior (n=3), inferior (n=3) and subtotal, affecting both superior and inferior retina (n=1). Scleral buckling procedures were used to treat the retinal detachments in all cases. Following demarcation laser therapy, the area of SRF remained stable in two patients, and flattened in four. In one patient, extension of SRF occurred requiring further surgery. Conclusions: Demarcation laser therapy appears to be a reasonable option in the management of patients with persistent or recurrent SRF sparing the macula following scleral buckling surgery. © Springer-Verlag 2006.

Fluid Shear Induces Conformation Change in Human Blood Protein von Willebrand Factor in Solution

Many of the physiological functions of von Willebrand Factor (VWF), including its binding interaction with blood platelets, are regulated by the magnitude of applied fluid/hydrodynamic stress. We applied two complementary strategies to study the effect of fluid forces on the solution structure of VWF. First, small-angle neutron scattering was used to measure protein conformation changes in response to laminar shear rates (G) up to 3000/s. Here, purified VWF was sheared in a quartz Couette cell and protein conformation was measured in real time over length scales from 2-140 nm. Second, changes in VWF structure up to 9600/s were quantified by measuring the binding of a fluorescent probe 1,1'-bis(anilino)-4-,4'-bis(naphtalene)-8,8'-disulfonate (bis-ANS) to hydrophobic pockets exposed in the sheared protein. Small angle neutron scattering studies, coupled with quantitative modeling, showed that VWF undergoes structural changes at G < 3000/s. These changes were most prominent at length scales <10 nm (scattering vector (q) range >0.6/nm). A mathematical model attributes these changes to the rearrangement of domain level features within the globular section of the protein. Studies with bis-ANS demonstrated marked increase in bis-ANS binding at G > 2300/s. Together, the data suggest that local rearrangements at the domain level may precede changes at larger-length scales that accompany exposure of protein hydrophobic pockets. Changes in VWF conformation reported here likely regulate protein function in response to fluid shear.

Semiclassical relativistic fluid theory for electrostatic envelope modes in dense electron-positron-ion plasmas:Modulational instability and rogue waves

A fluid model is used to describe the propagation of envelope structures in an ion plasma under the influence of the action of weakly relativistic electrons and positrons. A multiscale perturbative method is used to derive a nonlinear Schrödinger equation for the envelope amplitude. Criteria for modulational instability, which occurs for small values of the carrier wavenumber (long carrier wavelengths), are derived. The occurrence of rogue waves is briefly discussed. © Cambridge University Press 2013.

Pepsin in bronchoalveolar lavage fluid:a specific and sensitive method of diagnosing gastro-oesophageal reflux-related pulmonary aspiration

Gastro-oesophageal reflux (GOR)-related aspiration is associated with respiratory disease, but the current "gold standard" investigation, the lipid-laden macrophage index (LLMI), is flawed. A specific marker of GOR-related aspiration should originate in the stomach, but not the lung. An assay to detect gastric pepsin in the bronchoalveolar lavage (BAL) of children was developed and validated.

Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation

The lack of suitable donors for all solid-organ transplant programs is exacerbated in lung transplantation by the low utilization of potential donor lungs, due primarily to donor lung injury and dysfunction, including pulmonary edema. The current studies were designed to determine if intravenous clinical-grade human mesenchymal stem (stromal) cells (hMSCs) would be effective in restoring alveolar fluid clearance (AFC) in the human ex vivo lung perfusion model, using lungs that had been deemed unsuitable for transplantation and had been subjected to prolonged ischemic time. The human lungs were perfused with 5% albumin in a balanced electrolyte solution and oxygenated with continuous positive airway pressure. Baseline AFC was measured in the control lobe and if AFC was impaired (defined as

Learning fluid prescription skills: why is it so challenging?

IIt is well recognised that medical students and junior doctors find fluid prescription a challenging topic. This study was designed to gain a greater understanding of the experiences that medical students face related to learning about fluid prescribing. Methods: A qualitative approach, using focus groups, was employed in this research. Final-year medical students in academic year 2011-12 at Queen's University Belfast were invited to participate during their 'Assistantship' placement in March 2012. Discussions in focus groups, consisting of between six and eight students, were recorded and transcribed verbatim. The research team, consisting of three separate investigators, conducted thematic analysis independently. A final consensus regarding emerging themes was reached by discussion within the whole research team. Medical students and junior doctors find fluid prescription a challenging topic Results: Five prominent themes emerged: 'Teaching experience: a disruptive variation'; 'Curricular disconnections'; 'The driving test: Theory-practice transformation'; 'Role modelling: which standard to aspire to?'; and finally 'Reconciling the perceived risk'. Discussion: This re search provided insights into medical students' opinions of the teaching practices and learning experiences related to fluid prescribing. The learning of prescribing skills is complex andcontextual. In the development of such skills, medical students are often exposed to conflicting educational experiences that challenge the novicelearner in making judgements on best prescribing practice. This study adds to the body of evidence that fluid prescription is a difficult topic, and has generated a number of multifaceted and strategic recommendations to potentially improve fluid prescription teaching.

Better understanding of mechanochemical reactions: Raman monitoring reveals surprisingly simple 'pseudo-fluid' model for a ball milling reaction

Quantitative monitoring of a mechanochemical reaction by Raman spectroscopy leads to a surprisingly straightforward second-order kinetic model in which the rate is determined simply by the frequency of reactive collisions between reactant particles.

Evaluation of Corrosion Fatigue Behaviour of Laser-welded NiTi Alloys using Bending Rotation Fatigue Test in Simulated Body Fluid

Shape memory NiTi alloys have been used extensively for medical device applications such as orthopedic, dental, vascular and cardiovascular devices on account of their unique shape memory effect (SME) and super-elasticity (SE). Laser welding is found to be the most suitable method used to fabricate NiTi-based medical components. However, the performance of laser-welded NiTi alloys under corrosive environments is not fully understood and a specific focus on understanding the corrosion fatigue behaviour is not evident in the literature. This study reveals a comparison of corrosion fatigue behaviour of laser-welded and bare NiTi alloys using bending rotation fatigue (BRF) test which was integrated with a specifically designed corrosion cell. The testing environment was Hanks’ solution (simulated body fluid) at 37.5oC. Electrochemical impedance spectroscopic (EIS) measurement was carried out to monitor the change of corrosion resistance at different periods during the BRF test. Experiments indicate that the laser-welded NiTi alloy would be more susceptible to the corrosion fatigue attack than the bare NiTi alloy. This finding can serve as a benchmark for the product designers and engineers to determine the factor of safety of NiTi medical devices fabricated using laser welding.

Automotive waste heat recovery: Working fluid selection and related boundary conditions

This paper presents the rational for the selection of fluids for use in a model based study of sub and supercritical Waste Heat Recovery (WHR) Organic Rankine Cycle (ORC). The study focuses on multiple vehicle heat sources and the potential of WHR ORC’s for its conversion into useful work. The work presented on fluid selection is generally applicable to any waste heat recovery system, either stationary or mobile and, with careful consideration, is also applicable to single heat sources. The fluid selection process presented reduces the number of potential fluids from over one hundred to a group of under twenty fluids for further refinement in a model based WHR ORC performance study. The selection process uses engineering judgement, legislation and, where applicable, health and safety as fluid selection or de-selection criteria. This paper also investigates and discusses the properties of specific ORC fluids with regard to their impact on the theoretical potential for delivering efficient WHR ORC work output. The paper concludes by looking at potential temperature and pressure WHR ORC limits with regard to fluid properties thereby assisting with the generation of WHR ORC simulation boundary conditions.