Effect of selected drugs used in asthma treatment on morphology and elastic properties of red blood cells

Anna Zuk, Marta Targosz-Korecka, Marek SzymonskiResearch Centre for Nanometer-Scale Science and Advanced Materials, Faculty of Physics, Astronomy, and Applied Computer Science, Jagiellonian University, Reymonta 4, 30-059 Krakow, PolandBackground: The main function of red blood cells is to transport oxygen to all parts of the body with the help of hemoglobin. Other proteins of the cell membrane can attach xenobiotics (eg, drugs) from the blood and transport them throughout the body. Only drugs able to bind to the membrane of the red blood cell can modify its structure and elastic properties. The morphology and local elastic properties of living red blood cells incubated with drug solutions commonly used in the treatment of severe asthma were studied by atomic force microscopy and nanoindentation with an atomic force microscopy tip.Methods: The elasticity modules of native red blood cells, as well as those incubated with two types of drugs, ie, aminophylline and methylprednisolone, were determined from experimentally measured nanoindentation curves.Results: The elasticity modules of erythrocytes incubated with aminophylline were substantially higher than those obtained for nonincubated native, ie, healthy, red blood cells.Conclusion: The increase of the elasticity module obtained for aminophylline can reduce the cell's ability to bind oxygen and transport it through capillaries.Keywords: nanoindentation, atomic force microscopy, erythrocytes, elasticity, asthm

Thermodynamics of stationary states of the ideal gas in a heat flow

There is a long-standing question as to whether and to what extent it is possible to describe nonequilibrium systems in stationary states in terms of global thermodynamic functions. The positive answers have been obtained only for isothermal systems or systems with small temperature differences. We formulate thermodynamics of the stationary states of the ideal gas subjected to heat flow in the form of the zeroth, first, and second law. Surprisingly, the formal structure of steady state thermodynamics is the same as in equilibrium thermodynamics. We rigorously show that U satisfies the following equation dU= T* dS* -pdV for a constant number of particles, irrespective of the shape of the container, boundary conditions, size of the system, or mode of heat transfer into the system. We calculate S* and T* explicitly. The theory selects stable nonequilibrium steady states in a multistable system of ideal gas subjected to volumetric heating. It reduces to equilibrium thermodynamics when heat flux goes to zero

Continuous non-equilibrium transition driven by the heat flow

We discovered an out-of-equilibrium transition in the ideal gas between two walls, divided by an inner, adiabatic, movable wall. The system is driven out-of-equilibrium by supplying energy directly into the volume of the gas. At critical heat flux, we have found a continuous transition to the state with a low-density, hot gas on one side of the movable wall and a dense, cold gas on the other side. Molecular dynamic simulations of the soft-sphere fluid confirm the existence of the transition in the interacting system. We introduce a stationary state Helmholtz-like function whose minimum determines the stable positions of the internal wall. This transition can be used as a paradigm of transitions in stationary states and the Helmholtz-like function as a paradigm of the thermodynamic description of these states

Children and adolescents with pulmonary arterial hypertension : baseline and follow-up data from the polish registry of pulmonary hypertension (BNP-PL)

We present the results from the pediatric arm of the Polish Registry of Pulmonary Hypertension. We prospectively enrolled all pulmonary arterial hypertension (PAH) patients, between the ages of 3 months and 18 years, who had been under the care of each PAH center in Poland between 1 March 2018 and 30 September 2018. The mean prevalence of PAH was 11.6 per million, and the estimated incidence rate was 2.4 per million/year, but it was geographically heterogeneous. Among 80 enrolled children (females, n = 40; 50%), 54 (67.5%) had PAH associated with congenital heart disease (CHD-PAH), 25 (31.25%) had idiopathic PAH (IPAH), and 1 (1.25%) had portopulmonary PAH. At the time of enrolment, 31% of the patients had significant impairment of physical capacity (WHO-FC III). The most frequent comorbidities included shortage of growth (n = 20; 25%), mental retardation (n = 32; 40%), hypothyroidism (n = 19; 23.8%) and Down syndrome (n = 24; 30%). The majority of children were treated with PAH-specific medications, but only half of them with double combination therapy, which improved after changing the reimbursement policy. The underrepresentation of PAH classes other than IPAH and CHD-PAH, and the geographically heterogeneous distribution of PAH prevalence, indicate the need for building awareness of PAH among pediatricians, while a frequent coexistence of PAH with other comorbidities calls for a multidisciplinary approach to the management of PAH children

Current practice of care for adolescent and adult patients after Fontan surgery in Poland

Background: The growing number of adults patients after the Fontan operation requires regular surveillance tests in the specialized centers. Aims: Evaluation of current practice of care for Fontan patients in Poland based on a multicenter survey. Methods: Eight centers were included in the study-5 adult congenital heart disease (ACHD) and 3 pediatric centers for adolescents. To aim for a comparison between the centers and facilitate the interpretation of the results, the Fontan Surveillance Score (FSS) was developed. The higher score is consistent with better care, with a maximum of 19 points. Results: The number of 398 Fontan patients (243 adults and 155 adolescents [age 14-18 years]) was included in the study. The median FSS was 13 points with variability between the centers (interquartile range 7-14 points). Centers providing continuous care from the pediatric period until 18 years of age achieved a higher FSS compared to ACHD centers (median: 14 points vs 12 points, p< 0.001). Most of the patients, both in the ACHD (82.3%) and in pediatric centers (89%), were seen annually and had a physical examination, electrocardiogram, and echocardiogram performed at each visit. However, unsatisfactory utilization of tests identifying the early stages of Fontan circulation failure (cardiopulmonary exercise tests, cardiac magnetic resonance, liver biochemistry and imaging, detection of protein-losing enteropathy) was observed. Conclusions: The results of the study showed that there is no unified surveillance approach for Fontan patients in Poland. The practice of care for adults differs from that of adolescents

Transplanted human adipose tissue-derived stem cells engraft and induce regeneration in mice olfactory neuroepithelium in response to dichlobenil subministration

We used immunodeficient mice, whose dorsomedial olfactory region was permanently damaged by dichlobenil inoculation, to test the neuroregenerative properties of transplanted human adipose tissue-derived stem cells after 30 and 60 days. Analysis of polymerase chain reaction bands revealed that stem cells preferentially engrafted in the lesioned olfactory epithelium compared with undamaged mucosa of untreated transplanted mice. Although basal cell proliferation in untransplanted lesioned mice did not give rise to neuronal cells in the olfactory mucosa, we observed clusters of differentiating olfactory cells in transplanted mice. After 30 days, and even more at 60 days, epithelial thickness was partially recovered to normal values, as also the immunohistochemical properties. Functional reactivity to odorant stimulation was also confirmed through electroolfactogram recording in the dorsomedial epithelium. Furthermore, we demonstrated that engrafted stem cells fused with mouse cells in the olfactory organ, even if heterokaryons detected were too rare to hypothesize they directly repopulated the lesioned epithelium. The data reported prove that the migrating transplanted stem cells were able to induce a neuroregenerative process in a specific lesioned sensory area, enforcing the perspective that they could become an available tool for stem cell therapy. \ua9 The Author 2014. Published by Oxford University Press. All rights reserved

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London