Neprilysin inhibitors as a new approach in the treatment of right heart failure in the course of chronic obstructive pulmonary disease.

The aim of this paper was to review scientific evidence on the possible use of the combined angiotensin II receptor antagonistand neprilysin inhibitors (ARNI) in patients with right heart failure (RHF) in the course of chronic obstructive pulmonary disease(COPD). It has been proven that a lack of neprilysin or its reduced expression in hypoxia leads to exacerbation of pulmonaryarterial remodelling (PAR) or pulmonary hypertension (PH) in the mechanism related to the platelet-derived growth factor (PDGF)resulting in the proliferation and migration of pulmonary artery smooth muscle cells and endothelial-to-mesenchymal transition.Such action in the course of COPD can lead to RHF, which would signify noxious effect of this group of drugs. However, theinhibition of neprilysin also hinders natriuretic peptide metabolism. The representative of this group — brain natriuretic peptide(BNP) — acts as a vasodilator and also exerts an antiproliferative activity through the cGMP-dependent protein kinase G pathway.Additionally, it causes bronchodilation by inducing the release of acetylcholine from bronchial epithelial cells. This suggests thatnatriuretic peptides may appear to be a potential treatment agent in patients with cardiac complications and COPD. Their effectsassociated with the immunosuppression capacity by reducing the release of inflammatory mediators — IL-6, IL-1b, and TNF-acan bring benefits to patients with acute lung injury caused by pulmonary inflammation during COPD exacerbations. Consideringthe potentially positive effect of natriuretic peptides in this group of patients, further research is required in this area, which canprovide strong scientific data demonstrating the need for introducing ARNI drugs to the treatment of patients with COPD

DOŚWIADCZENIA ZWIĄZANE Z MIĘDZYNARODOWĄ EMIGRACJĄ ZAROBKOWĄ NA PRZYKŁADZIE STUDENTÓW UNIWERSYTETU EKONOMICZNEGO WE WROCŁAWIU

Article briefly presents the phenomenon of migration and classifies it according to certain criteria. Moreover, in his work the author has used some of the results of research carried out among students of Wroclaw University of Economics. Data obtained from the survey allowed to determine the size of the existing international labour migration of students, its direction, and the motives of this type of emigration. The article discusses the financial issues associated with this trip and trying to determine other benefits of these journeys.Artykuł pokrótce przedstawia zjawisko migracji oraz klasyfikuje ją według wybranych kryteriów. Ponadto w swojej pracy autor wykorzystał część wyników badań, które zostały przeprowadzone wśród studentów Uniwersytetu Ekonomicznego we Wrocławiu w roku akademickim 2009/2010. Uzyskane w wyniku badania ankietowego dane pozwoliły ustalić wielkość dotychczasowej międzynarodowej emigracji zarobkowej, jej kierunek, a także motywy kierujące polskimi studentami decydującymi się na taki rodzaj emigracji. Artykuł porusza również kwestie finansowe związane z takim wyjazdem oraz próbuje ustalić, jakie inne korzyści z takich podróży, oprócz finansowych, wynosiła kształcąca się młodzież

Inhibitory neprylizyny jako nowe podejście w leczeniu prawokomorowej niewydolności serca w przebiegu przewlekłej obturacyjnej choroby płuc

Celem niniejszej pracy było znalezienie danych naukowych na temat tego, czy stosowanie połączenia antagonistów receptorów angiotensyny II i inhibitorów neprylizyny (ARNI) byłoby uzasadnione u osób chorych na prawokomorową niewydolność serca (PNS) w przebiegu przewlekłej obturacyjnej choroby płuc (POChP). Wykazano że w warunkach hipoksji brak neprylizyny bądź jej zmniejszona ekspresja prowadzi do nasilenia remodelingu naczyń płucnych (PAR) oraz nadciśnienia płucnego (NP) w mechanizmie zależnym od płytkopochodnego czynnika wzrostu, powodującym proliferację i migrację komórek mięśni gładkich tętnic płucnych oraz transformację śródbłonkowo-mezenchymalną (EndoMT). Takie działanie w przebiegu POChP może prowadzić do PNS, co przemawiałoby za szkodliwym działaniem tej grupy leków. Jednak inhibicja neprylizyny powoduje także zahamowanie metabolizmu peptydu natriuretycznego. Przedstawiciel tej grupy — mózgowy peptyd natriuretyczny — działa antyproliferacyjne poprzez szlak zależny od cGMP i kinazę białkową G, a także wazodylatacyjnie. Dodatkowo wywołuje bronchodylatację poprzez indukcję uwalniania acetylocholiny z komórek nabłonka oskrzeli. Sugeruje to, że peptydy natiuretyczne mogą zaistnieć jako potencjalne leczenie u chorych na POChP z powikłaniami sercowymi. Ich działanie związane ze zdolnością do immunosupresji poprzez obniżenie uwalniania mediatorów reakcji zapalnej — IL-6, IL-1b oraz TNF-a może przynieść korzyści pacjentom z ostrym uszkodzeniem płuc spowodowanym ich zapaleniem w zaostrzeniach POChP. Biorąc pod uwagę potencjalnie pozytywne działanie peptydów natriuretycznych w tej grupie pacjentów, konieczne są dalsze badania w tym zakresie, które mogą dostarczyć silnych danych naukowych przemawiających za koniecznością włączenia leków z grupy ARNI do terapii pacjentów z POChP.Celem niniejszej pracy było znalezienie danych naukowych na temat tego, czy stosowanie połączenia antagonistów receptorów angiotensyny II i inhibitorów neprylizyny (ARNI) byłoby uzasadnione u osób chorych na prawokomorową niewydolność serca (PNS) w przebiegu przewlekłej obturacyjnej choroby płuc (POChP). Wykazano że w warunkach hipoksji brak neprylizyny bądź jej zmniejszona ekspresja prowadzi do nasilenia remodelingu naczyń płucnych (PAR) oraz nadciśnienia płucnego (NP) w mechanizmie zależnym od płytkopochodnego czynnika wzrostu, powodującym proliferację i migrację komórek mięśni gładkich tętnic płucnych oraz transformację śródbłonkowo-mezenchymalną (EndoMT). Takie działanie w przebiegu POChP może prowadzić do PNS, co przemawiałoby za szkodliwym działaniem tej grupy leków. Jednak inhibicja neprylizyny powoduje także zahamowanie metabolizmu peptydu natriuretycznego. Przedstawiciel tej grupy — mózgowy peptyd natriuretyczny — działa antyproliferacyjne poprzez szlak zależny od cGMP i kinazę białkową G, a także wazodylatacyjnie. Dodatkowo wywołuje bronchodylatację poprzez indukcję uwalniania acetylocholiny z komórek nabłonka oskrzeli. Sugeruje to, że peptydy natiuretyczne mogą zaistnieć jako potencjalne leczenie u chorych na POChP z powikłaniami sercowymi. Ich działanie związane ze zdolnością do immunosupresji poprzez obniżenie uwalniania mediatorów reakcji zapalnej — IL-6, IL-1b oraz TNF-a może przynieść korzyści pacjentom z ostrym uszkodzeniem płuc spowodowanym ich zapaleniem w zaostrzeniach POChP. Biorąc pod uwagę potencjalnie pozytywne działanie peptydów natriuretycznych w tej grupie pacjentów, konieczne są dalsze badania w tym zakresie, które mogą dostarczyć silnych danych naukowych przemawiających za koniecznością włączenia leków z grupy ARNI do terapii pacjentów z POChP

Selected bone morphogenetic proteins — the possibility of their use in the diagnostics and therapy of severe asthma

  Asthma is a chronic heterogeneous illness of the lower airway with an inflammatory basis, developing from hyperresponsiveness and bronchial obstruction. One of the more unfavourable processes occurring in the airway are the long-term changes of the respiratory tract known as remodelling, resulting in complete irreversible obstruction. Bone morphogenetic protein (BMP) is a member of the Transforming Growth Factor beta (TGF-b) superfamily, which regulates processes in embryonic and post-embryonic development. The role played by BMP is regulation of degradation and remodelling of the extracellular matrix, which is one of the elements involved in the reconstruction of the structure of the bronchi in severe asthma. This paper presents the antagonistic properties of BMP against TGF-b, anti-inflammatory and counteracting fibrosis in the respiratory tract. The current state of knowledge indicates that this group of cytokines are potential new markers of remodelling in severe asthma, and further studies on their therapeutic value are necessary.

Evaluation of interdental spacing in patients with shortened dental arch in relationship with prosthetic treatment needs

Aim of the study. The aim of the study was to analyze the interdental spacing in patients with different amount of dental arch reduction in relationship with prosthetic treatment needs. Material and methods. The study group included 120 individuals of both gender, aged 41–65, selected from the patients admitted to The Department of Prosthodontics, Wrocław Medical University and Academic Dental Policlinic, Krakowska Street 26, Wrocław, in years 2007–2009. Patients were divided into two study groups depending on amount of dental arch reduction and control group including individuals with complete natural dentition. All patients underwent interview and general oral cavity examination according to the protocol worked out in The Department of Prosthodontics, Wrocław Medical University. Assessment of interdental spacing was carried out with metal gauges by Pol-Intech, 0,05 milimeters thickness. The obtained data underwent statistic analysis. Results. The results of study on interdental spacing revealed more spacing with reduction of dental arch. Conclusions. Individuals with extremely shortened dental arches revealed the largest loss of dental arch integrity, thus this group of patients has the highest treatment needs

Long Term Trends and Correlates of Antler Anomalies in Roe Deer

Length and structural complexity of antlers provide an indication of individual quality in many ungulates in the context of female mate choice and trophy hunting. Selectivity of hunters for individuals with various antler sizes may have bearing on the population structure. It is less well understood, however, whether and how antler anomalies may signal individual characteristics. We used data on 2,461 roe deer (Capreolus capreolus) males harvested by stalking during 1966–2011 in western Poland to test hypotheses explaining probability of occurrence of accessory, broken, and malformed antlers. By employing a multinomial logistic regression, we showed that the probability of occurrence of broken and malformed antlers increased in males older than 2 years. Probability of occurrence of accessory and, in young males, broken antlers was higher in individuals with increased body weight. Occurrence of malformed antlers decreased over the study period. Contrary to our prediction, we did not detect an effect of distance to forest on the probability of malformed antlers occurring. We conclude that the main premise of compensatory culling is not supported in roe dee

Na-P1 zeolite synthesis and its crystalline structure ripening through hydrothermal process using coal combustion by-products as substrates

Energy industry sector is one of the major environment pollutants. This branch also generates significant amounts of by-products such as slugs, slug-ash mixtures, ashes and microspheres, which can be very harmful for the earth ecosystems. Statistically the microspheres (MIC) constitute from 0.6% to 2.5% of the total amount of post combustion wastes. MIC occurs mainly in fly ashes (less often in slugs) as the smallest, hollow, spherical particles. MIC is composed mainly of crystalline and amorphous aluminosilicate phases. The combustion conditions have strong influence on MIC composition. Mineral and chemical composition of MIC is very similar to F type of fly ashes; consequently there is a possibility to use them as substrates for zeolite synthesis. Zeolites are minerals from microporous, aluminosilicate group (Szala et al. 2015). Among others, they are characterized by specific channels and chambers occurrence in their structure, which results in a number of important features like: ion exchange, sorption, molecular sieve or catalytic properties. This is the reason for wide use of zeolites in numerous industrial sectors (Ahmaruzzaman 2010). The aim of this study is a synthesis of Na-P1 zeolite at semi-technical scale by conversion of microspheres under hydrothermal conditions in an alkaline medium. This study involves also research of Na-P1 zeolite structure ripening in order to optimize the synthesis conditions. Microspheres from Stalowa Wola Power Plant (Poland) were used as a substrate. For the synthesis of Na-P1 phase the following conditions were applied: 90 dm 3 of water, 15 kg of microsphere, 11 kg of sodium hydroxide (3 mol/dm 3 ), temperature: 80°C, and reaction time up to 26 h (Franus et al. 2014). The zeolite conversion was performed on semi-technical scale installation (Wdowin et al. 2014). During the conversion, samples were collected from the reactor after 2, 4, 6, 10, 14, 26 hours. To investigate the influence of time for zeolitization process efficiency these samples were analyzed in terms of chemical and mineral composition, structural and textural properties. The main attention was paid to the evolution of the Na-P1 unit cell parameters observed as a function of time (calculations and models were performed for every sample). The phase’s composition was determined with powder X-ray diffraction (XRD) method using a PANalytical X’pert MPD diffractometer (with a PW 3050/60 goniometer), Cu lamp, and a graphite monochromator. The analysis was performed within the angle range of 5–65 2θ. PANalytical X’Pert Highscore software was used to process the diffraction data. The identification of mineral phases was based on the PDF-2 release 2010 database formalized by the ICD and IZA-SC Database of Zeolite Structures. The experimental calculations of the unit cell parameters were performed using UnitCell software. The spatial model of Na-P1 zeolite cell was prepared using Mercury 3.7 Windows software. The morphological forms and the chemical composition of the main mineral components were determined with scanning electron microscope (SEM) FEI Quanta 250 FEG equipped with the SE detector and a system of chemical composition analysis based on energy dispersive X-ray-EDS of EDAX company. N 2 adsorption-desorption measurements were carried out at 77 K using ASAP 2020 volumetric adsorption analyzer (Micromeritics). The specific surface areas (S BET ) of the samples were evaluated using the standard Brunauer–Emmett–Teller (BET) method for nitrogen adsorption data in the range of relative pressure p / p 0 from 0.06 to 0.3. The total pore volumes were estimated from single-point adsorption at a relative pressure of 0.98. XRD data indicates that main phases in microsphere are amorphous aluminosilicate glass, mullite and quartz. The obtained product is dominated by Na-P1 phase. Experimental calculations of cell parameters and fabricated models confirm crystallographic similarity to Na-P1 pattern. Noteworthy is the fact that the unit cell parameters depend on reaction time. Calculations indicate that the cell parameters (walls length: a , b , c and cell volume) increase with time towards to pattern values. This phenomenon may be interpreted as a ripening of crystalline structure. An in-depth look at this matter can lead to better estimation of synthesis conditions, which have a significant impact to the total cost of zeolites production – especially at a larger scale. SEM shows progressive dissolution (also as a function of time) of aluminosilicate glass in favor of crystallization of zeolite phase. EDS analysis confirms similarity of chemical composition of the obtained samples to a standard Na-P1 zeolite. Calculated textural properties indicate increase of S BET with the reaction time. Simultaneously, the average pore diameters decrease. The S BET of synthetized Na-P1 was 4.62 m 2 /g after 2 h but it increased to 47.92 m 2 /g after 26 h. This is an effect of growing contribution of zeolite phase in relation to the initial substrates in the sample during the reaction time. The experimental conditions allowed synthesizing Na-P1 zeolite from microsphere particles in the prototype installation. Zeolitization process strongly influences the textural properties by increasing S BET and improving pore structure. The microsphere from Stalowa Wola Power Plant is a promising material for the synthesis of Na-P1 zeolite in the prototype installation. Still, the reaction parameters should be reconsidered, basing on the obtained results, in order to reduce the cost of the zeolite production as much as possible. This is required before proceeding to the full technical production scale. To observe increase of zeolite amount in entirety synthesis batch (and to link it with cell behavior) the Rietveld analysis will be provided

Biologic drugs in the treatment of chronic inflammatory pulmonary diseases: recent developments and future perspectives

Chronic inflammatory diseases of the lung are some of the leading causes of mortality and significant morbidity worldwide. Despite the tremendous burden these conditions put on global healthcare, treatment options for most of these diseases remain scarce. Inhaled corticosteroids and beta-adrenergic agonists, while effective for symptom control and widely available, are linked to severe and progressive side effects, affecting long-term patient compliance. Biologic drugs, in particular peptide inhibitors and monoclonal antibodies show promise as therapeutics for chronic pulmonary diseases. Peptide inhibitor-based treatments have already been proposed for a range of diseases, including infectious disease, cancers and even Alzheimer disease, while monoclonal antibodies have already been implemented as therapeutics for a range of conditions. Several biologic agents are currently being developed for the treatment of asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and pulmonary sarcoidosis. This article is a review of the biologics already employed in the treatment of chronic inflammatory pulmonary diseases and recent progress in the development of the most promising of those treatments, with particular focus on randomised clinical trial outcomes

The role of the TGF-SMAD signalling pathway in the etiopathogenesis of severe asthma

Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling.Asthma is a chronic inflammatory heterogeneous disease of the lower respiratory tract characterised by the occurrence of bronchial hyper-responsiveness and paroxysmal, changeable bronchial obstruction. Transforming growth factor-beta (TGF-b) is one of the cytokines involved in mediating airway inflammation and remodelling. The level of TGF-b1 gene expression correlates with severity of symptoms. Alterations in the main SMAD signal transmission, overexpression of TGF-b genes and changes in the transcriptome cause excessive secretion of TGF-b and its increased expression in target cells, which clinically induces a moderate-severe or severe course of asthma as well as an earlier and faster disease progression. Knowledge of these processes allows clinicians to assess immune responses in patients, which affects adequate disease control and prevention of remodelling