Inhaled Interleukin-10 before and after induction of experimental endotoxemia in the rat : effects on the inflammatory response

To determine the effects of inhaled IL-10 at different doses and different time points on the pulmonary and systemic inflammatory response during endotoxemia, 48 ventilated, anaesthetized rats (mean body weight ± standard deviation, 500 ± 33g) were randomly assigned to six groups (n = 8, each). Interleukin-10 was nebulised either prior to or following the intravenous injection of LPS (5mg/kg) at two doses (5.0 mycro-g or 0.5 mycro-g) in our groups. Eight rats received the same insult with no further treatment (LPS-only group). Another eight rats served as controls without endotoxemia but with aerosolized phosphate-buffered saline, the solvent of IL-10 (Sham group). Concentrations of TNF-alpha, IL-1beta, IL-6, and IFN-gamma were analyzed in plasma and bronchoalveolar lavage fluid (BALF). In addition, the nitrite release from ex-vivo cultured alveolar macrophages was determined. As compared to the LPS-only group, the concentrations of the proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IFN-gamma in plasma were significantly reduced in the group, which inhaled 5 mycro-g IL-10 before LPS injection (p< 0.0125). Spontaneous nitrite release from exvivo cultured alveolar macrophages was suppressed in this group (p< 0.0125). Inhalation of 0.5 mycro-g IL-10 before LPS injection and both dosages of IL-10 inhalation (5 mycro-g or 0.5 mycro-g) after LPS injection did not significantly influence either inflammatory cytokine concentrations in BALF, in plasma or the nitrite release from ex-vivo cultured alveolar macrophages. In this study, inhaled IL-10 only demonstrated anti-inflammatory effects when it was administered at 5 mycro-g prior to the induction of experimental endotoxemia. Interleukin-10 aerosol had no effect when it was given either following induction of endotoxemia or given at a lower dosage (which here was 0.5 mycro-g) either before or following injection of lipopolysaccharide.Das "Acute Respiratory Distress Syndrome" (ARDS) ist eine akut auftretende, überwiegend Sepsis-induzierte, inflammatorische Erkrankung der Lunge mit hoher Letalität. Ein komplexes Netzwerk aus Zytokinen und anderen proinflammatorischen Mediatoren unterhält die pulmonale Entzündungreaktion. Dem Zytokin Interleukin-10 (IL-10) könnte in diesem Zusammenhang aufgrund seines spezifisch antiinflammatorischen und immunmodulierenden Wirkspektrums eine therapeutische Bedeutung zukommen. In tierexperimentellen Untersuchungen konnten die protektiven Wirkungen von systemisch appliziertem Interleukin-10 bezüglich verringerter Wirkspiegel proinflammatorischer Mediatoren sowie des Überlebens der Versuchstiere bei Sepsis belegt werden. In einer Untersuchung an ARDS-Erkrankten wiesen Patienten, deren bronchoalveoläre Lavage (BAL) hohe Konzentrationen an Interleukin-10 enthielt, eine signifikant niedrigere Letalität auf als Patienten mit niedriger IL-10-Konzentration. Die Inhalation von IL-10 über den Luftweg könnte lokal in der Lunge die Freisetzung von Entzündungsmediatoren verringern und so den Verlauf eines ARDS positiv beeinflussen. Im Rahmen einer bereits durchgeführten Studie der eigenen Arbeitsgruppe konnte gezeigt werden, dass die Inhalation von IL-10 (0.19 mycro-g/Tier) vor Induktion einer experimentellen Endotoxinämie (Beobachtungszeitraum 6h) zur signifikanten Reduktion proinflammatorischer Zytokine im Plasma sowie der BAL führte. Daneben bewirkte IL-10 Aerosol eine signifikante Verringerung der Nitritproduktion aus ex vivo kultivierten Alveolarmakrophagen (AM). Mit der vorliegenden Studie sollte untersucht werden, ob vernebeltes IL-10 auch in einer geringeren Dosierung als in der ersten Studie angewandt antiinflammatorisch wirksam ist. Daneben sollte geklärt werden, ob der Zeitpunkt der Applikation des IL-10 Aerosol relevant ist. Konkret sollte untersucht werden, ob die Inhalation von IL-10 erst nach Induktion der experimentellen Endotoxinämie ebenfalls antinflammatorisches Potential besitzt. Die Generierung und Verneblung des IL-10 Aerosols erfolgte in der vorliegenden Untersuchung mittels eines speziell für diesen Einsatz von der eigenen Arbeitsgruppe entwickelten und charakterisierten Verneblersystems. Der Vernebler produziert stabil Aerosopartikel, deren Größenverteilung (rund 2 mycro-m) mit hoher Wahrscheinlichkeit in alvelären Bereichen deponiert. Die alveoläre Depositionsfraktion des Verneblers beträgt rund 4% und liegt damit in einem Bereich, der aus der Humanmedizin für die Verneblung bei intubierten Patienten bekannt ist. An 48 narkotisierten, kontrolliert beatmeten Ratten wurde die antiinflammatorische Wirkung eines IL-10-Aerosols untersucht. Die Induktion des experimentellen Lungenschadens erfolgte durch intravenöse Injektion von Endotoxin (Lipopolysaccharid; LPS, in einer Dosierung von 5mg/kg). Als löslicher Bestandteil der Membran gram-negativer Bakterien führt LPS über die Freisetzung proinflammatorischer Substanzen zu entzündlichen Reaktionen, die lokal beschränkt oder auch systemisch auftreten können. Bei Versuchstieren unterschiedlicher Spezies bewirkt die systemische Applikation von LPS pulmonale Veränderungen, die denen des septisch bedingten ARDS des Menschen qualitativ entsprechen. Die Tiere wurden zufällig in eine der sechs Versuchsgruppen eingeteilt (je n=8): Die LPS-Gruppe erhielt eine LPS-Injektion (5 mg/kg/KG) ohne anschließende therapeutische Intervention. Die mit IL-10 behandelten Tiere erhielten das IL-10-Aerosol entweder vor oder nach Induktion der experimentellen Endotoxinämie nach unten genanntem Protokoll. In einer Kontroll (Sham)-Gruppe wurde die Auswirkung von Narkose, chirurgischer Präparation, Beatmung und Aerosolapplikation (IL-10-Trägerlösung; phosphatgepufferte Kochsalzlösung) evaluiert. Neben der in vivo Beobachtung von Hämodynamik (Herzfrequenz, mittlerer arterieller Blutdruck), Lungenmechanik, arteriellen Blutgasen und Blutbild, untersuchten wir anhand von Blutproben und einer Bronchoalveolären Lavage (BAL) die systemische und pulmonale Inflammation (inflammatorische Zytokine TNFalpha, IL-1beta, IL-6 und IFNgamma in Plasma und BAL). Die Verneblung von IL-10 erfolgte in zwei Dosierungen und zu zwei Zeitpunkten: in einer Gruppe wurde IL-10 in einer Dosierung von 5.0 mycro-g (0.19 mycro-g/Tier) vor, und in einer weiteren Gruppe nach Induktion der experimentellen Endotoxinämie vernebelt. In zwei weiteren Versuchgruppen wurde IL-10 in einer Dosierung von 0.5 mycro-g (0.019 mycro-g/Tier) ebenfalls vor sowie nach Injektion von LPS vernebelt. Die Endotoxinämie führte nur zu geringen Verschlechterungen der klinischen Parameter, aber sowohl pulmonal (BAL) als auch systemisch (Plasma) zeigte sich ein Anstieg proinflammatorischer Mediatoren. Gegenüber den Tieren, deren Endotoxinämie unbehandelt blieb, bewirkte nur die Inhalation von IL-10 in der höheren Dosierung (5 mycro-g) das signifikante Abfallen der proinflammatorischen Zytokine TNFalpha, IL-1beta, IL-6 und IFNgamma im Plasma sowie der Freisetzung von Nitrit aus kultivierten AM. IL-10 Aerosol hatte in keiner Dosierung respektive zu keinem Applikationszeitpunkt antiinflammatorische Effekte auf die Zytokinkonzentrationen in der BAL. Die präemptive Vernebelung von IL-10 in einer Dosierung von 5 mycro-g (0.19 mycro-g/Tier) vor Induktion einer experimentellen Endotoxinämie zeigte sowohl auf die AM Kultur als auch systemisch (Plasma) antinflammatorisches Wirkprofil. Demgegenüber zeigte IL-10 keine antinflammatorische Effekte, wenn es erst nach Injektion von LPS oder aber in geringerer Dosierung vernebelt wurde. Zur antiinflammatorischen Therapie der experimentellen Endotoxinämie durch LPS Injektion in der Spezies Ratte erscheint IL-10 Aerosol nur wirksam, wenn es in ausreichender Dosierung (5 mycro-g) sowie vor Injektion von LPS appliziert wird

The variable elasticity of substitution function and endogenous growth : an empirical evidence from Vietnam

Purpose: To specify a Variable Elasticity of Substitution function (VES), in which the estimated Elasticity of Substitution (ES) can give some implications for the tendency of economic growth in the Vietnames manufacturing sector. Design/Methodology/Approach: The contribution and the relevant methodology is based on the Bayesian approach having some advantages over the frequentist method: (i) the simulation and prediction results are more reliable in Bayesian analysis due to combining prior knowledge about parameters with obverved data to compose a posterior model, whereas the frequentist approach is based only on available data; (ii) in probability sense, Bayesian credible intervals have a straightforward interpretation compared to frequentist confidence intervals. The Bayesian nonlinear regresion performed is suitable for fitting production functions and depicting economic growth. Findings: The specified VES function has the ES greater than one and this finding contradicts many previous empirical studies in the growth theory. This result points to the possibility of unbounded endogenous growth in the Vietnamese manufacturing sector. Practical implications: Based on the empirical results, in order to realize the possibility of endogenous growth for the studied Vietnamese manufacturing sector, policies of enforcing investment are needed. To raise the level of science and technique, as well as human capital of the Vietnamese enterprises, at the same time, there is great necessity to encourage R&D activities in both the private and public sectors. Originality/Value: Although this study organically builds upon recent studies about the link between the VES, the elasticity of factor subsitution and economic growth, its results proved that the VES is more appropriate than the Cobb-Douglas and the Constant Elasticity of Substitution (CES) to explain economic growth in the view of capital-labor relationship.peer-reviewe

Case Study “XYZ Commercial Joint-Stock Bank”, Conversion of Financial Statements from Vietnam’s Accounting Standard into International Financing Reporting Standard

The aim of this study is to update significant differences between Vietnam’s accounting standards (VAS) and International financial report standards (IFRS). Case study “XYZ Commercial Joint-Stock Bank”, conversion of financial statements from VAS into IFRS. Analyzed the case study and status of conversion financial statements from VAS into IFRS of Vietnam listed Joint Stock Companies (JSCs) , author found and discussed impediments &amp; challenges to convert IFRS financial statements in Vietnam and suggest to enhance roles of Vietnam Government and listed JSCs on the Vietnam stock market in an effort to convert and adopt IFRS financial statements as well as suggest to establish an IFRS conversion project to have an overview of  conversion processes financial statements from VAS into IFRS for Vietam listed JSCs Keywords: Conversion financial statement, International financial reporting standard, Vietnamese account standar

POPULATION GENETIC DIVERSITY OF CAMELLIA DILINHENSIS ON THE DI LINH PLATEAU OF VIETNAM REVEALED BY ISSR AND SCOT MARKERS

Genetic diversity of naturally distributed Camellia dilinhensis populations on the Di Linh plateau of Vietnam was assessed by the inter-simple sequence repeat (ISSR) and start codon targeted (SCoT) techniques separately and then by combining data from both techniques for satisfactory results. The genetic diversity parameters and genetic distances among individuals found with the ISSR technique (HeI = 0.1420, II = 0.2092, PPBI = 35.22%, GSCsI = 0.765–0.988, and AGSCI = 0.915) are lower than those found with the SCoT technique (HeS = 0.2100, IS = 0.381, PPBS = 52.27%, GSCsS = 0.644–0.985, and AGSCS = 0.866). Based on the combined data from both techniques, the level of genetic diversity of the investigated population is PPB = 43.77%, He = 0.1720, I = 0.2582, and the genetic similarities among individuals are GSCs = 0.764–0.973 with an average of AGSC = 0.894. The SCoT technique differentiated between individuals better and reflected a higher level of genetic diversity in the population than the ISSR technique, but the ISSR technique revealed more loci in Camellia dilinhensis plants than did the SCoT technique

On initial value and terminal value problems for subdiffusive stochastic Rayleigh-Stokes equation

In this paper, we study two stochastic problems for time-fractional RayleighStokes equation including the initial value problem and the terminal value problem. Here, two problems are perturbed by Wiener process, the fractional derivative are taken in the sense of Riemann-Liouville, the source function and the time-spatial noise are nonlinear and satisfy the globally Lipschitz conditions. We attempt to give some existence results and regularity properties for the mild solution of each problem

On stochastic nonclassical diffusion equation with standard and fractional Brownian motion

This paper is concerned with the mathematical analysis of terminal value problems for a stochastic non-classical diffusion equation, where the source is assumed to be driven by classical and fractional Brownian motions. Our two problems are to study in the sense of well-posedness and ill-posedness meanings. Here, a terminal value problem is a problem of determining the statistical properties of the initial data from the final time data. In the case 0 < β ≤ 1, where β is the fractional order of a Laplace operator, we show that these are well-posed under certain assumptions. We state a definition of ill-posedness and obtain the ill-poseness results for the problems when β > 1. The major analysis tools in this paper are based on properties of stochastic integrals with respect to the fractional Brownian motion

On terminal value problems for bi-parabolic equations driven by Wiener process and fractional Brownian motions

In this paper, we study two terminal value problems (TVPs) for stochastic bi-parabolic equations perturbed by standard Brownian motion and fractional Brownian motion with Hurst parameter h ∈ ( 1/2 , 1) separately. For each problem, we provide a representation for the mild solution and find the space where the existence of the solution is guaranteed. Additionally, we show clearly that the solution of each problem is not stable, which leads to the ill-posedness of each problem. Finally, we propose two regularization results for both considered problems by using the filter regularization method

LEARNING AWARENESS LEVEL OF NURSING STUDENTS AT TRA VINH UNIVERSITY ON CLINICAL PRACTICE ENVIRONMENT AT HOSPITAL

The purpose of the study was to examine the level of awareness about the clinical practice environment at the hospital among nursing students of Tra Vinh University in 2021. A descriptive cross-sectional study was applied to analyze the data of 205 students selected. The study results showed a positive level of awareness with an average score of 130.83±8.73. ’Interaction and participation’ had an average score of 41.6±2.99, ’Student-centered’ had an average score of 45.92±3.56, ’Allow individual participation’ had an average score of 10.53±1.82, ’Nursing work value’ had an average score of 9.11±1.11, ’Promoting learning at work’ had an average score of 16.42±2.80, and ’Lack of creativity’ had an average score of 7.23±1.48. The research results  provide implications for the further improvement of nursing training at Tra Vinh University in particular and universities and colleges with nursing training in general