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Patients suffering from malignant diseases have a high risk of developing severe or critical forms of COVID-19 (Coronavirus Disease 2019). Chronic lymphocytic leukaemia (CLL) is characterized by dysregulated adaptive and innate immune responses, because both T and B cells, the function of phagocytes and the activity of the complement system may be affected. Severe SARS-CoV-2 infection also influences the immunological functions mainly via causing the depletion of CD4+ and CD8+ T cells. We present the cases of two patients, whose

of PhD thesis submitted in 2020 to the Archaeology Doctoral Programme, Doctoral School of History, Eötvös Loránd University, Budapest under the supervision of Gábor V. Szabó.

The Great Hungarian Plain (GHP) served as a geographic funnel for population mobility throughout prehistory. Genomic and isotopic research demonstrates non-linear genetic turnover and technological shifts between the Copper and Iron Ages of the GHP, which influenced the dietary strategies of numerous cultures that intermixed and overlapped through time. Given the complexities of these prehistoric cultural and demographic processes, this study aims to improve our understanding of diachronic and culture-specific dietary signatures. Here we report on stable carbon and nitrogen isotope values from 75 individuals from twenty sites in the GHP dating to a ~ 3000-year time span between the Early Bronze and Early Iron Ages. The samples broadly indicate a terrestrial C3 diet with nuanced differences amongst cultures, suggesting exogenous influences that manifested in subsistence strategies. Compared to the Iron Age, the Bronze Age samples have slightly elevated δ15N values implying higher reliance on protein. Interestingly, carbon values typical of C4 vegetation indicate the consumption of millet, or a grain with comparable δ13C values during the Middle Bronze Age. Overall, our results suggest a gradual transition in dietary patterns from the Early Bronze to Early Iron Age, demonstrating a relationship between subsistence and time periods, congruent with the archaeological record.

The development of olivine texture, or lattice preferred orientation (LPO), has been implemented in many numerical modelling tools to predict seismic anisotropy, which places constraints on mantle dynamics. However, a few recent studies have linked olivine texture development to its mechanical anisotropy, which in turn can affect deformation rates and also the resulting texture. To study the effect of anisotropic viscosity (AV) and LPO evolution in geodynamics processes, it is important to know the role of AV and LPO and the differences between the numerical methods that calculate them.The modified director method parameterizes the olivine LPO formation as relative rotation rates along the slip systems that participate in the rotation of olivine grains due to finite deformation. When it is coupled with a micromechanical model for olivine AV, it allows the anisotropic texture to modify the viscosity. We compare the olivine textures predicted by the modified director method both with and without a coupled micromechanical model and textures predicted by the D-Rex LPO evolution model. To do this, we recalculate the texture observed in simple 3D models such as a shear box model and two other well-understood models: a corner flow model and a subduction model. In general, we observed that the D-Rex models predict a stronger anisotropic texture compared to the texture predicted by the modified director method both with and without the micromechanical model, in agreement with previous studies. When including the micromechanical model, the anisotropic texture changes the observed strain rates, which allows for a slightly faster texture evolution that is more similar to the D-Rex predictions than it is to those produced by the modified director method alone. We found that even for the simplest settings there is an increase of 10~15% in strain rate during deformation until a strain of 2.5. When shearing the asthenosphere over ~10 Myr, such anisotropy could modify the effective viscosity of the mantle,causing an up to 40% increase in plate velocity for the same applied stress. The anisotropy can also induce deformation in planes other than the initial shear plane, which can change the direction of the primary deformation.Our ultimate goal is to understand the role of AV and LPO evolution in geodynamic processes by looking at deformation paths predicted by geodynamic models in ASPECTWith this initial test, we will gain a basic understanding of olivine AV behavior and LPO evolution under different deformation settings calculated with different numerical methods, which we will carry onto our next step of implementing anisotropic viscosity of olivine in 3D into ASPECT.

The last few years have been marked by a number of motivating novel ideas and methodological advancements in paleomagnetic analysis (e.g. trans-hierarchical uncertainty propagation), observational and theoretical geodynamics, and paleogeographical modeling (e.g. optimisation and Bayesian approaches). Many of these developments offer new insights on, and/or approaches to estimating, the past motions of tectonic plates—but so far these developments have largely unfolded in isolation of one another. In November 2021 an international group of 15 young scientists with highly complementary backgrounds (spanning the aforementioned fields) gathered to explore and discuss these exciting new developments and to brainstorm strategies that may enable their integration. We anticipate that the integration of these diverse new ideas and methods will open new frontiers in plate tectonic research, and notably lead to much better-constrained paleogeographic models. In this presentation, we will share some of the insights and strategies that emerged from the workshop, including the advantages of conducting paleomagnetic analysis at the site-level, the application of emerging paleomagnetic Euler pole analysis frameworks, and the use of insights extracted from Earth-like geodynamic models (which self-generate plate tectonic behavior) to further constrain the results of these paleomagnetic methods. We also present some preliminary results of early experiments putting these strategies into practice on a paleomagnetic dataset from North America.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared “predicted” genetic contributions to height from paleogenomic data and “achieved” adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

The article concentrates on the issue of Hungarian education reforms brought about by radical political changes, in particular, the country’s admittance to the European Union. The paper outlines priorities in educational process transformation, as well as risks emerging in the system of teacher education and lifelong learning. The challenges associated with our times transform the teacher’s consciousness, shiftingfocus to the mandatory use of information technology, the activation of students’ information mobility, and the detailed analysis of employers’ requirements. The study reveals the Hungarian government’s key activities in relation to the socialization of the Roma minority and other national minorities compactly residing in Ukraine. The research illustrated educational resources used to train teachers at educational institutions to instill tolerance and mutual respect. The 2020s’ are marked by powerful globalization and political factors penetrating all spheres of social life. The dynamic formation of the civilized information society is accompanied by a number of contradictions and conflicts, the strengthening of social ties, and changing living conditions (R.ti, 2009), (V.g. and Vass 2006). Despite numerous methodological and conceptual studies, the issues of updating the modern teacher’s training to enableteachers to train and educate students and adequately react to challenges imposed by digitalization remain open. In this respect, the experience of European states that successfully carried out a number of educational reforms is of great scientific interest and deserves to be systematically studied, popularized and introduced into the domestic educational system. One of such countries is Hungary, which borders on Ukraine both territorially and functionally (Transcarpathia is compactly inhabited by Hungarian national minorities). The aim of the article is to substantiate the essence of the key educational reforms in Hungary and to identify the risks and priorities brought about by transformational changes in the country.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ~12,000 years before present (BP). Subsistence shifts from hunting and gathering to agriculture are hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a simultaneous decline in physiological health as inferred from paleopathological analyses and stature reconstructions of skeletal remains. A key component of the health decline inference is that relatively shorter statures observed for early farmers may (at least partly) reflect higher childhood disease burdens and poorer nutrition. However, while such stresses can indeed result in growth stunting, height is also highly heritable, and substantial inter-individual variation in the height genetic component within a population is typical. Moreover, extensive migration and gene flow were characteristics of multiple agricultural transitions worldwide. Here, we consider both osteological and ancient DNA data from the same prehistoric individuals to comprehensively study the trajectory of human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared ‘predicted’ genetic contributions to height from paleogenomic data and ‘achieved’ adult osteological height estimated from long bone measurements on a per-individual basis for n=160 ancient Europeans from sites spanning the Upper Paleolithic to the Iron Age (~38,000-2,400 BP). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −4.47 cm relative to individuals from the Upper Paleolithic and Mesolithic (P=0.016). The average osteological vs. expected stature then increased relative to the Neolithic over the Copper (+2.67 cm, P=0.052), Bronze (+3.33 cm, P=0.032), and Iron Ages (+3.95 cm, P=0.094). These results were partly attenuated when we accounted for genome-wide genetic ancestry variation in our sample (which we note is partly duplicative with the individual polygenic score information). For example, in this secondary analysis Neolithic individuals were −3.48 cm shorter than expected on average relative to individuals from the Upper Paleolithic and Mesolithic (P=0.056). We also incorporated observations of paleopathological indicators of non-specific stress that can persist from childhood to adulthood in skeletal remains (linear enamel hypoplasia, cribra orbitalia, and porotic hyperostosis) into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

Dietary reconstruction is used to make inferences about the subsistence strategies of ancient human populations, but it may also serve as a proxy to characterise their diverse cultural and technological manifestations. Dental microwear and stable isotope analyses have been shown to be successful techniques for paleodietary reconstruction of ancient populations but, despite yielding complementary dietary information, these techniques have rarely been combined within the same study. Here we present for the first time a comprehensive approach to interpreting ancient lifeways through the results of buccal and occlusal microwear, and δ13C and δ15N isotope analyses applied to the same individuals of prehistoric populations of Hungary from the Middle Neolithic to the Late Bronze Age periods. This study aimed to (a) assess if the combination of techniques yields a more precise assessment of past dietary and subsistence practices, and (b) contribute to our understanding of the dietary patterns of the prehistoric Hungarian populations. Overall, no correlations between microwear and δ13C and δ15N isotope variables were observed, except for a relationship between nitrogen and the vertical and horizontal index. However, we found that diachronic differences are influenced by the variation within the period. Particularly, we found differences in microwear and isotope variables between Middle Neolithic sites, indicating that there were different dietary practices among those populations. Additionally, microwear results suggest no changes in the abrasiveness of the diet, neither food processing methods, despite higher C4 plant resource consumption shown by carbon isotopic signal. Thus, we demonstrate that the integration of dental microwear and carbon and nitrogen stable isotope methodologies can provide complementary information for making inferences about paleodietary habits.

Monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML) plays an important role in predicting relapse and outcome. The applicability of the leukemia-initiating nucleophosmin1 (NPM1) gene mutations in MRD detection is well-established, while that of isocitrate dehydrogenase1/2 (IDH1/2) mutations are matter of debate. The aim of this study was to investigate the stability of NPM1 and IDH1/2 mutations at diagnosis and relapse retrospectively in 916 adult AML patients. The prognostic value of MRD was evaluated by droplet digital PCR on the DNA level in a selected subgroup of patients in remission. NPM1 re-emerged at relapse in 91% (72/79), while IDH1/2 in 87% (20/23) of mutation-positive cases at diagnosis. NPM1 mutation did not develop at relapse, on the contrary novel IDH1/2 mutations occurred in 3% (3/93) of previously mutation-negative cases. NPM1 MRD-positivity after induction (n = 116) proved to be an independent, adverse risk factor (MRDpos 24-month OS: 39.3±6.2% versus MRDneg: 58.5±7.5%, p = 0.029; HR: 2.16; 95%CI: 1.25–3.74, p = 0.006). In the favorable subgroup of mutated NPM1 without fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) or with low allelic ratio, NPM1 MRD provides a valuable prognostic biomarker (NPM1 MRDpos versus MRDneg 24-month OS: 42.9±6.7% versus 66.7±8.6%; p = 0.01). IDH1/2 MRD-positivity after induction (n = 62) was also associated with poor survival (MRDpos 24-month OS: 41.3±9.2% versus MRDneg: 62.5±9.0%, p = 0.003; HR 2.81 95%CI 1.09–7.23, p = 0.032). While NPM1 variant allele frequency decreased below 2.5% in remission in all patients, IDH1/2 mutations (typically IDH2 R140Q) persisted in 24% of cases. Our results support that NPM1 MRD even at DNA level is a reliable prognostic factor, while IDH1/2 mutations may represent pre-leukemic, founder or subclonal drivers.

A common feature of tectonic reconstructions is the migration of subduction zones and their interactions, resulting in complex tectonic patterns. Reduced migration rates, uplift, strong rotations, and slab break-off are all tectonics features commonly associated with convergent margin interactions, showing that while subduction zones' motions fundamentally shape tectonics settings, their interactions hold the key to their complexities. Fundamental properties such as slab buoyancy, dip direction, and coupled mantle flow determine the motions of single hinge zones. When these zones approach, stress transfers between the slabs through the lithosphere and the mantle, thereby altering the subduction force balance, favoring, opposing, or diverting further motions. We illustrate the range of configurations reported in tectonic reconstructions and address their dynamics through the results of analog and numerical models of subduction dynamics in the upper mantle. The Cenozoic evolution of the Mediterranean provides relevant examples of such interactions, where the coeval activity of several subduction zones during the Africa-Europe convergence has strongly overprinted the current tectonics. A comparison of new analog models with the deep dynamics of the Mediterranean shows how the interactions among slabs and mantle may have shaped the distribution of basins and mountain belts, their uplift, and volcanism in this tectonic province.

Ancient DNA sampling methods—although optimized for efficient DNA extraction—are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but standard destructive sampling methods often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and 9 corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods.

Asthenospheric shear causes some minerals, particularly olivine, to develop anisotropic textures that can be detected seismically. In laboratory experiments, these textures are also associated with anisotropic viscous behavior, which should be important for geodynamic processes. To examine the role of anisotropic viscosity for asthenospheric deformation, we developed a numerical model of coupled anisotropic texture development and anisotropic viscosity, both calibrated with laboratory measurements of olivine aggregates. This model characterizes the time‐dependent coupling between large‐scale formation of lattice‐preferred orientation (i.e., texture) and changes in asthenospheric viscosity for a series of simple deformation paths that represent upper mantle geodynamic processes. We find that texture development beneath a moving surface plate tends to align the a axes of olivine into the plate motion direction, which weakens the effective viscosity in this direction and increases plate velocity for a given driving force. Our models indicate that the effective viscosity increases for shear in the horizontal direction perpendicular to the a axes. This increase should slow plate motions and new texture development in this perpendicular direction and could impede changes to the plate motion direction for tens of millions of years. However, the same well‐developed asthenospheric texture may foster subduction initiation perpendicular to the plate motion and deformations related to transform faults, as shearing on vertical planes seems to be favored across a sublithospheric olivine texture. These end‐member cases examining shear deformation in the presence of a well‐formed asthenospheric texture illustrate the importance of the mean olivine orientation, and its associated viscous anisotropy, for a variety of geodynamic processes.

Numerous studies have provided insights into one of the key problems of the Earth Sciences: subduction zone initiation (SZI). The insights into SZI are both numerous and diverse with evidence from multiple disciplines in Earth Sciences. SZI studies exploit the geological record, reconstruct regional or global plate motion back in time, interpret seismic tomography to identify the tip depth of sunken plate portions, and diagnose theoretical and numerical models of rock and plate deformation based on known physics.Getting and keeping an overview over the many discipline-specific advances is challenging for many reasons: one being the dispersed sources of information, another being the missing communication across the individual disciplines. The latter shortcoming also arises from the multiple incompatible scientific jargons currently in use.The SZI database now unifies the scientific jargon, and brings together old and new insights relating to SZI into a common, community-wide platform online (www.SZIdatabase.org). The SZI database builds bridges between individual communities, opening a community-wide discussion by making SZI data readily available and understandable. This keeps data and knowledge up-to-date, and can therefore provide the most complete picture of our current understanding of SZI.In this presentation, we outline where to find, how to use, and why to contribute to the SZI database. This community-wide project has already yielded interesting results regarding the fascinating question about how and where SZI occurs on present-day Earth and back to around 100 Ma. Work thus far suggests ‘subduction breeds subduction’, highlighting the beginning of crucial insights from these ongoing cross-disciplinary efforts.

Developing an appropriate characterization of upper mantle viscosity structure presents one of the biggest challenges for understanding geodynamic processes in the upper mantle. This is because different creep mechanisms become activated depending on depth, accumulated strain, and applied stress, and other factors such grain size and anisotropic fabric can change as the deformation develops, changing the effective viscosity. Here we focus on the relationship between anisotropic fabric development and viscous anisotropy.Under applied shear, olivine crystals, which form a large proportion of the asthenosphere, rotate towards the shear direction and accumulate a lattice preferred orientation (LPO) parallel to the macroscopic deformation. On a large scale, LPO can be observed through the propagation of seismic waves because of the anisotropic elastic properties of olivine. As olivine is anisotropic in its viscous properties, this developing texture within the asthenosphere can affect the macro-scale viscosity of the asthenosphere. This behavior has been detected in rock mechanics measurements on pure olivine aggregates, showing more than an order magnitude of viscosity change between shear parallel to the olivine aggregate’s LPO versus shear across this fabric (Hansen et al., EPSL 2016a, JGR 2016b).Here, we use numerical models developed first in MATLAB and then implemented into the mantle convection code ASPECT. These models incorporate both anisotropic fabric development and anisotropic viscosity, both calibrated according to laboratory measurements on slip system activities of olivine aggregates (Hansen et al., JGR 2016b), to better understand the coupling between the large-scale formation of LPO textures and changes in asthenospheric viscosity.The modeling results allows us to discuss the role of anisotropic viscosity on the processes of plate tectonics. An asthenosphere with a well-developed LPO becomes weak parallel to its texture, allowing for increasing plate velocity at the surface, for a given applied driving force. On the other hand, this fabric resists abrupt changes in the direction of plate motion because the effective viscosity is elevated for shear perpendicular to the developed LPO. This increased resistance to fabric-perpendicular shear also decreases strain rates, which slows texture development. This means that asthenospheric fabric can impede changes in plate motion direction for periods of over 10 Myrs. However, the same well-developed texture in the asthenosphere could enhance the initiation of subduction or lithospheric gravitational instabilities as vertical deformation is favored across a sub-lithospheric olivine fabric, and the sheared fabric can quickly rotate into a vertical LPO. These end-member cases examining shear-deformation across a formed asthenospheric fabric illustrate the importance of olivine fabrics, and their associated viscous anisotropy, for a variety of geodynamic processes.

The study of slab-slab interactions has come to the front of geodynamics researches to explain geological and geophysical observations from tectonically complex areas. Here we aim to better understand the geodynamics of the Central Mediterranean, where the Adria plate subducts on its two opposite sides. Additionally, the slab below the Central South Apennines has been progressively breaking off during the last 3 Myr. The role of a slab window in a single slab or in an outward dipping double-sided subduction system is addressed by analog models at the scale of the upper mantle, realized using glucose syrup and silicone putty, to model the interaction between the Earth's mantle and the lithosphere. Our results show that the presence of a slab window modifies the pattern of mantle circulation, as well as the trench geometry and kinematics. In particular, the opening of the slab window induces the formation of two arcs flanking the window, while the mantle flows through it and turns toward the arcs, creating a small-scale toroidal flow. The effect of a slab window is more pronounced on double subduction systems, as the outflow through the window is amplified, while internal deformation is induced in the plate by the opposite slab pull force. These experimental results suggest that the origin of the Apenninic and the Calabrian arcs is the result of the formation of a slab window, providing a new interpretation of the surface deformation and the SKS shear wave splitting pattern of the Adria microplate.Plain Language Summary The Adria microplate in the Central Mediterranean is an important part of the tectonic puzzle between the converging Africa and Eurasia plates. The heavy lithosphere sinks into the underlying mantle on two sides of the Adria plate, under the Apennines in the west and under the Dinarides in the east. During the most recent few millions of years, the lithosphere started to detach from the surface in the Central South Apennines while sinking into the mantle. This opened a slab window, an additional escape route for the mantle, which is squeezed by the two subducting lithospheres. We scaled down and simplified this setting in order to model and investigate the role of the dual subduction and the opening slab window in the evolution of the Central Mediterranean by means of analog models. Our results show that the two opposite subduction zones have a regional tectonics effect via the complex subduction-induced mantle circulation. Furthermore, the detaching lithosphere modifies the geometry of the subduction zone, which results in a double-arc geometry resembling the Northern Apennines and Calabria.

At the end of October 2018, nearly 30 experts – potters and archaeologists – met in the city of Mula (Murcia, Spain) to study Europe’s Bronze Age pottery-making techniques. Participants of the three-day workshop represented the Friends' Association of the Archaeological Site of La Bastida (ASBA) from Totana (Spain), the Mula Town Hall (Spain), the Autonomous University of Barcelona (Spain), the EXARC association (The Netherlands), the Halle State Museum of Prehistory (Germany), the Hometown Museum of Paraćin (Serbia), the Déri Museum of Debrecen, the Hungarian Academy of Sciences (Hungary) and the traditional ceramicists and potters of Totana (Spain).

Gaps within a subducting plate can alter the surrounding mantle flow field and the overall subduction zone dynamics by allowing hot sub-slab mantle to flow through the gaps and into the mantle wedge. This through-slab flow can produce melting of the slab gap edges as well as significant upwelling that can lead to anomalous alkaline volcanism and/or dynamic uplift in the overriding plate, while the altered mantle flow patterns affect the trench evolution. Numerous geodynamic models have investigated the processes that form slab gaps, but few studies have examined the dynamics of slab gap-altered mantle flow, its effects on trench morphology and kinematics, or the controlling parameters on these processes. Here, laboratory subduction models with a pre-cut gap in a subducting silicone plate are used to explore how slab gap size, and slab gap depth influence the surrounding mantle flow field and trench dynamics. Results suggest that both the vertical extent and the depth of the top (trailing edge) of the slab gap are crucial parameters for modulating overall subduction dynamics. They show that a slab gap, which occurs near the surface and initially comprises 30% of the subducting plate width, can extend enough vertically in the slab to produce significant vertical flow through the gap. Changes to the trench geometry and kinematics are also evident in the models, such that double- and triple-arc geometries are formed during subduction of a shallow slab gap. All of these results are consistent with observations of slab gaps and their induced surface expressions, or the lack thereof, in Eastern Anatolia, East Java, Italy, and Argentina.

Subduction-induced mantle circulation plays an important role in the dynamics of convergent margins. Different components of the flow, i.e. toroidal and poloidal, provide relevant driving forces for back-arc basin formation, overriding plate deformation, curvature of subduction zones and volcanic activity. Here, we investigate on the emergence and controls on the toroidal component of the subduction–induced mantle flow by means of numerical modeling. To characterize the toroidal cell's three-dimensional flow, size and length-scales and its disposing factors, we test separately a series of lithospheric and mantle parameters, such as the density difference and viscosity ratio between the slab and the mantle, the width of the slab, as opposed to the size, the stratification and the rheology of the mantle. Out of the tested parameters, the numerical results show that the strength of the flow depends on the mantle viscosity and the magnitude of the slab pull force, that is slab-mantle density difference and the mantle thickness, however the characteristic length, axis and the shape of the toroidal cell are almost independent of the slab's properties and mainly depend on the thickness of the convecting mantle.

Active and fossil subduction systems consisting of two adjacent plates with opposite retreating directions occur in several areas on Earth, as the Mediterranean or Western Pacific. The goal of this work is to better understand the first-order plate dynamics of these systems using the results of experimental models. The laboratory model is composed of two separate plates made of silicon putty representing the lithosphere, on top of a tank filled with glucose syrup representing the mantle. The set of experiments is designed to test the influence of the width of plates and the initial separation between them on the resulting trench velocities, deformation of plates, and mantle flow. Results show that the mantle flow induced by both plates is asymmetric relative to the axis of each plate causing a progressive merging of the toroidal cells that prevents a steady state phase of the subduction process and generates a net outward drag perpendicular to the plates. Trench velocities increase when trenches approach each other and decrease when they separate after their intersection. The trench curvature of both plates increases linearly with time during the entire evolution of the process regardless their width and initial separation. The interaction between the return flows associated with each retreating plate, particularly in the interplate region, is stronger for near plate configurations and correlates with variations of rollback velocities. We propose that the inferred first-order dynamics of the presented analog models can provide relevant clues to understand natural complex subduction systems. ©2018. American Geophysical Union. All Rights Reserved., The work of M. P., M. F., and J. V. is part of the projects ALPIMED (PIE-CSIC- 201530E082) and MITE (CGL2014- 59516-P) and partly financed by the Generalitat de Catalunya (2014-SGR-1471 and 2017-SGR-847). The work of S. Z. is funded by the Spanish Ministry of Economy and Competitiveness through grant CICYT DPI2017-85139-C2-2-R and Generalitat de Catalunya (2017-SGR-1278).

Slab‐slab interaction is a characteristic feature of tectonically complex areas. Outward dipping double‐sided subduction is one of these complex cases, which has several examples on Earth, most notably the Molucca Sea and Adriatic Sea. This study focuses on developing a framework for linking plate kinematics and slab interactions in an outward dipping subduction geometry. We used analog and numerical models to better understand the underlying subduction dynamics. Compared to a single subduction model, double‐sided subduction exhibits more time‐dependent and vigorous toroidal flow cells that are elongated (i.e., not circular). Because both the Molucca and Adriatic Sea exhibit an asymmetric subduction configuration, we also examine the role that asymmetry plays in the dynamics of outward dipping double‐sided subduction. We introduce asymmetry in two ways; with variable initial depths for the two slabs (“geometric” asymmetry), and with variable buoyancy within the subducting plate (“mechanical” asymmetry). Relative to the symmetric case, we probe how asymmetry affects the overall slab kinematics, whether asymmetric behavior intensifies or equilibrates as subduction proceeds. While initial geometric asymmetry disappears once the slabs are anchored to the 660 km discontinuity, the mechanical asymmetry can cause more permanent differences between the two subduction zones. In the most extreme case, the partly continental slab stops subducting due to the unequal slab pull force. The results show that the slab‐slab interaction is most effective when the two trenches are closer than 10–8 cm in the laboratory, which is 600–480 km when scaled to the Earth.

A tanulmány a 10–13. századi Észak- és Kelet-Európa egy jellegzetes tárgytípusának, a balta alakú amuletteknek a magyarországi leleteit, illetve azok kapcsolatrendszerét mutatja be. A lelettípusnak sokáig csak egy Kárpát-medencei példányát ismertük, az utóbbi években azonban ugrásszerűen megnőtt a hazánkban előkerült darabok száma, ami a legfrissebb kelet-európai elterjedési térképek alapján várható volt. A miniatürizált tárgyak, köztük a balta alakú amulettek használatának hagyománya valószínűleg Skandináviából indult ki a korai középkorban, de széles körű kelet-európai elterjedésük a 11. században egyértelműen a Rusz aktivitásához köthető. A tárgytípust a Kárpát-medence kora Árpád-kori hagyatékában a magyar kutatás eddig a Ruszból érkező zsoldosokhoz kötötte, mint importleletet. Jelen tanulmány minden eddiginél nagyobb adatbázis és nemzetközi szakirodalom alapján foglalja össze ismereteinket erről a korábban kissé egyoldalúan értékelt tárgyról. Az új darabok részletes közlése mellett dolgozatunk további értelmezési lehetőségeket is felvet a leletek interpretációja kapcsán.

Density anomalies beneath the lithosphere are expected to generate dynamic topography at the Earth's surface due to the induced mantle flow stresses which scale linearly with density anomalies, while the viscosity of the upper mantle is expected to control uplift rates. However, limited attention has been given to the role of the lithosphere. Here we present results from analogue modeling of the interactions between a density anomaly rising in the mantle and the lithosphere in a Newtonian system. We find that, for instabilities with wavelengths of the same order of magnitude as lithosphere thickness, the uplift rate and the geometry of the surface bulge are inversely correlated to the lithosphere thickness. We also show that a layered lithosphere may modulate the topographic signal. With respect to previous approaches our models represent a novel attempt to unravel the way normal stresses generated by mantle flow are transmitted through a rheologically stratified lithosphere and the resulting topographic signal. © 2017. American Geophysical Union. All Rights Reserved., T.W.B. was partially supported through NASA OSP 201601412-001.

Gastric-arterial partial CO(2) pressure gap (P(g-)(a)CO(2) gap) measured by gastric tonometry may detect the disturbance of splanchnic perfusion. As in the neonatal age it is very difficult to follow up the circulatory condition with frequent acid-base examinations, we wanted to compare the P(g-)(a)CO(2) gap with an alternative gap of P(g)CO(2) - end-tidal carbon dioxide (P(g)(-)(ET)CO(2) gap).A prospective study was performed on ventilated neonates requiring intensive therapy (n = 44, weight: 1813 ± 977 g). P(ET)CO(2) and P(g)CO(2) were measured with a side stream capnograph. We applied a newly developed gastric tonometric probe. Patients were divided into two groups: Group 1 of patients in stable condition (n = 35) and Group 2 of patients with severe condition (i.e. Clinical Risk Index for Babies [CRIB] score higher than 10; n = 9). For main statistical analysis a mixed model repeated measurements ANOVA, Bland-Altman analysis were applied.P(g)(-)(ET)CO(2) gap was higher than P(g-)(a)CO(2) gap (11.40 ± 7.79 versus 3.63 ± 7.98 mmHg, p0.01). Both gaps were higher in Group 2 (8.71 ± 10.89 and 18.27 ± 10.49 versus 2.53 ± 6.78 and 9.92 ± 6.22 mmHg, p0.01 and p0.05). Bland-Altman analysis of the two gaps showed an acceptable correspondence.P(g)(-)(ET)CO(2) gap may be used as a method for continuous estimation of splanchnic perfusion and a prognostic index also in critically ill neonates. However, the P(g-)(a)CO(2) gap should not be abandoned.

Summary Background: Important progress relating to the early prediction of postoperative complications was recently achieved through the combined use of endtidal PCO2 (PETCO2) and gastric tonometry. The aim of this article was to present results obtained with a new tonometric instrument, proving its feasibility and extending its use to the control of anesthetized infants and children. Methods: The new tonometric probe, which is balloon free, consists basically of silicone rubber tubing. The room air initially inside the tubes of the probe equilibrates with the PCO2 of the body cavity throughout its full length. The PCO2 content of the gastric cavity (PgCO2) and simultaneously PETCO2 were measured with a microcapnograph. A total of 108 measurements were performed intraoperatively on 25 infants and young children operated on at the Surgical Unit of the Department of Pediatrics. The patients were divided into elective surgery cases 2 years of age, group II; and acute surgery cases, independently of age, group III. To examine the degree of agreement between the measurements, Pearson’s correlation coefficients were determined and Bland–Altman analysis was performed. A mixed model repeated measurements anova was used to compare the differences between the groups. Results: PETCO2 and PgCO2 for groups I and II were nearly identical, and statistically not significantly different (mean difference 0.10 mmHg and 0.85 mmHg, P = 0.96 and 0.45, respectively), whereas the corresponding data for group III differed significantly from those for groups I and II (P = 0.03 and 0.001, respectively). On Bland–Altman analysis, the bias value for groups proved to be statistically significantly different (P = 0.001). Conclusions: The tested new probe worked very well in small children. The clinical implications of the large gaps found between PETCO2 and PgCO2 values in acutely ill children and children undergoing elective operations must be investigated further.

The interaction of neighboring subducting lithospheres is a characteristic feature of many tectonically complex areas. Here we use numerical modeling to study the interactions between two oppositely dipping, adjacent subducting lithospheres and to understand their impact on the subduction evolution, mantle flow, and stress propagation through the mantle. As slabs subduct, rollback, and approach, they strongly affect each other if plate edges are at distances

For hypertensive lower esophageal sphincter with dysphagia and chest pain, a laparoscopic cardiomyotomy is recommended. Recently, the role of gastroesophageal reflux in this abnormality has been recognized. A prospective study on six patients with manometrically proven hypertensive lower esophageal sphincter was performed. Laparoscopic floppy Nissen fundoplication was performed in all cases. The first follow up was performed 6 weeks after the operation. The mean follow up time was 56 months (range 50-61). Before the operation, all patients had abnormal esophageal acid exposure. Mean DeMeester score was 41.7 (range 16.7-86). Average LES pressure before the operation was 50.5 mmHg (range 35.6-81.3). Six weeks after operation, all patients were symptom free. DeMeester score returned to a normal level of 2.9. Furthermore, a marked decrease in the lower esophageal sphincter pressure (24.7 mmHg) was detected. At late follow up, all patients were symptom-free, and only two patients agreed to undergo functional testing. The mean DeMeester score of this two patients was 1.2. The pressure remained at normal value (15.7 mmHg). In our study, an antireflux operation normalized lower esophageal sphincter pressure suggesting that abnormal esophageal acid exposure may be an etiologic factor in the development of hypertensive lower esophageal sphincter.

Two achalasia patients with former complaints of heartburn were examined. Antisecretory drugs were used by the patients when dysphagia occurred. Barium X-ray and esophageal manometry were performed and achalasia was diagnosed in both patients. Twenty-four-hour pH-metry showed significant and long-lasting acid reflux during supine position. Prolonged reflux episodes can be explained not only by the swallow-unrelated transient relaxation of lower esophageal sphincter (LES) and mechanical damage of the esophageal body, but also by its chemical insensitivity. Thus preoperative detection of reflux should determinate either the operational procedure and the postoperative follow up of the patient.

Recent modeling shows that surface processes, such as erosion and deposition, may drive the deformation of the Earth's surface, interfering with deeper crustal and mantle signals. To investigate the coupling between the surface and deep process, we designed a three-dimensional laboratory apparatus, to analyze the role of erosion and sedimentation, triggered by deep mantle instability. The setup is constituted and scaled down to natural gravity field using a thin viscous sheet model, with mantle and lithosphere simulated by Newtonian viscous glucose syrup and silicon putty, respectively. The surface process is simulated assuming a simple erosion law producing the downhill flow of a thin viscous material away from high topography. The deep mantle upwelling is triggered by the rise of a buoyant sphere. The results of these models along with the parametric analysis show how surface processes influence uplift velocity and topography signals.

The physiologic importance of afferent sensory pathways in the esophageal motor functions has been recently recognised. Capsaicin-sensitive sensory afferents were shown to play a role in the maintenance of mucosal integrity of the GI tract, and regulation of human esophageal motility. The aim of this study was to investigate the effect of topical application of capsaicin-containing red pepper sauce (Tabasco, 25%v/v, pH:7.0) suspension on the phasic activity of the human esophagus of healthy volunteers and patients with Barrett’s esophagus. Methods : The diagnosis of Barrett’s esophagus was based on the findings of esophagoscopy and histology taken from the squamocolumnar junction of the esophagus. Esophageal motility was measured by perfusion manometry before and after application of red pepper sauce. Results : Capsaicin containing red pepper sauce increases the motility response (LES tone, contraction amplitude, propagation velocity) of the human esophagus in healthy volunteers. This response failed in patients with Barrett’s esophagus. Conclusion : Impaired esophageal sensorymotor function may serve as one etiologic role in the development of Barrett’s esophagus.

Background: Our laboratory group observed earlier that the gastric mucosal cytoprotective effect of prostacyclin (PGI 2 ) disappeared after surgical vagotomy in rats. Similarly to this, the beta-carotene induced gastric cytoprotection disappeared in adrenalectomized rats too. Aims: In these studies we aimed to investigate the possible role of vagal nerve and adrenals in the development of gastric mucosal lesions induced by exogenously administered chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers (vitamin A and β-carotene). Methods: The observations were carried out in fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH; 25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in intact, surgically bilaterally vagatomized, and adrenalectomized rats without or with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week). The gastric mucosal protective effect of antisecretory doses of atropine (0.1–0.5–1.0 mg/kg i.g.) and cimetidine (10–25–50 mg/kg i.g.), and vitamin A and β-carotene (0.01–0.1–1.0–10 mg/kg i.g.) was studied. The number and severity of mucosal gastric lesions was numerically or semiquantitatively measured. In other series of observations the gastric acid secretion and mucosal damage were studied in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy. Results: It was found that: (1) the chemical-induced gastric mucosal damage was enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous secretion of gastric acid, and the development of mucosal damage can be prevented by surgical vagotomy; (2) the gastric cyto- and general protection produced by the drugs and scavengers disappeared in vagotomized and adrenalectomized rats; (3) the gastric mucosal protective effects of drugs and of scavengers returned after sufficient glucocorticoid supplementation of the rats. Conclusion: It has been concluded that the intact vagal nerve and adrenals have a key role in the gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and general mucosal protection.

Visceral hyperalgesia has been suggested to play a role in the development of symptoms presented by irritable bowel syndrome patients. Otilonium bromide was developed to block smooth muscle Ca release to control cramping pain of these patients. Aims: to determine whether otilonium bromide can influence sensory thresholds of patients suffering from irritable bowel syndrome. Methods: 15 patients with Rome-II positive IBS were tested by Synectics Visceral Stimulator Barostat using rapid phasic distension (870 ml/min). The sensory threshold for first sensation, stool, pain and maximum tolerable volume and pressure were measured. All of the parameters were tested before and 1 week after the initiation of otilonium bromide (Spasmomen, Berlin Chemie, 3×40 mg) therapy. Results: The perceptual thresholds for first sensation, stool, pain and maximum tolerable distention were, 8.8±1.7 Hgmm, 19.2±2.1 Hgmm, 26.3±2.8 Hgmm, 28.7±2.8 Hgmm for pressure, 90±21 ml, 145±28 ml, 208±25 ml, 213±28 ml for volume, before treatment, respectively. Otilonium bromide treatment did not influence the thresholds for first sensation and stool, 7.4±1.4 Hgmm, 20.7±4.6 Hgmm and 83±21 ml, 178±35.8 ml, respectively. The pressure threshold of pain was significantly higher 1 week after treatment (26.3±2.8 Hgmm vs. 29.1±5.5 Hgmm, P

TRH analogue, RX 77368, injected intracisternally (i.c.) at high dose (3 microg/rat) produces gastric mucosal lesion formation through vagal-dependent pathway. The gastric mucosal hyperemia induced by i.c. RX 77368 was shown to be mediated by muscarinic vagal efferent fibres and mast cells. Furthermore, electrical vagal stimulation was observed to induce gastric mucosal mast cell degranulation. The aim of the study was to assess the influence of ketotifen, a mast cell stabilizer, on RX 77368-induced gastric lesion formation and gastric acid secretion. RX 77368 (3 microg, i.c.) or vehicle (10 microL, i.c.) was delivered 240 min prior to the sacrifice of the animals. Ketotifen or vehicle (0.9% NaCl, 0.5 mL) was injected intraperitoneally (i.p.) at a dose of 10 mg x kg(-1) 30 min before RX 77368 injection. The extent of mucosal damage was planimetrically measured by a video image analyzer (ASK Ltd., Budapest) device. In the gastric acid secretion studies, the rats were pretreated with ketotifen (10 mg x kg(-1), i.p.) or vehicle (0.9% NaCl, 0.5 mL, i.p.), 30 min later pylorus-ligation was performed and RX 77368 (3 microg, i.c.) or vehicle (0.9% NaCl, 10 microL, i.c.) was injected. The rats were killed 240 min after i.c. injection, and the gastric acid secretion was measured through the titration of gastric contents with 0.1 N NaOH to pH 7.0. RX 77368 (3 microg, i.c.) resulted in a gastric mucosal lesion formation involving 8.2% of the corpus mucosa (n = 7). Ketotifen elicited an 85% inhibition on the development of mucosal lesions (n = 7, P < 0.001) whereas ketotifen alone had no effect on the lesion formation in the mucosa (n = 7). The RX 77368 induced increase of gastric acid secretion was not influenced by ketotifen pretreatment in 4-h pylorus-ligated animals. Central vagal activation induced mucosal lesion formation is mediated by the activation of mucosal mast cells in the stomach. Mast cell inhibition by ketotifen does not influence gastric acid secretion induced by i.c. TRH analogue in 4-h pylorus-ligated rats.

INTRODUCTION: Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen((R))], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio((R)), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. METHODS: In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 x 5 mug) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. RESULTS: In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU((R)), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 x 10(6)/kg (2.22-57.07 x 10(6)/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 x 10(6)/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients. CONCLUSIONS: In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.

Gastric hyperemic and acid responses to the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a cytoprotective dose were investigated, as well as the underlying mechanisms of the responses. Gastric acid secretion (GAS), mucosal blood flow (GMBF; measured by the hydrogen gas clearance technique), and mucosal vascular resistance (GMVR) and mean arterial pressure (MAP) were assessed simultaneously for 30 min before and after RX-77368 (1.5 ng) administration in urethan-anesthetized rats. RX-77368 increased GMBF from 46.8 +/- 5.3 to 100.6 +/- 20.9 ml.min-1.100 g-1 and MAP from 70.3 +/- 2.1 to 84.3 +/- 5.9 mmHg and decreased GMVR from 1.50 +/- 0.33 to 0.84 +/- 0.08 mmHg.ml-1.min.100 g, whereas GAS was not significantly altered (1.8 +/- 0.4 vs. 4.7 +/- 1.7 mumol/30 min) in vehicle-pretreated rats. The GMBF, MAP, and GMVR responses to RX-77368 were not modified by indomethacin (5 mg/kg ip), whereas GAS was increased. In rats pretreated with capsaicin (125 mg/kg sc) or calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37), intracisternal RX-77368 did not increase GMBF or decrease GMVR but did stimulate GAS. These data show that vagal stimulation by the TRH analog RX-77368 injected intracisternally at a nonacid secretory dose increases GMBF. Gastric hyperemia is mediated by CGRP contained in capsaicin-sensitive afferent fibers, whereas acid secretion is under the inhibitory influence of prostaglandins and CGRP.

KirALy, A., G. SUTO, P. Guth and Y. TachE. Influence of [4Cl-D-Phe 6 ,Leu 17 ]VIP on VIP- and central TRH-induced gastric hyperemia. Peptides 18(9) 1321–1325, 1997.—The specific VIP receptor antagonist, [4Cl-D-Phe 6 ,Leu 17 ]VIP, infused iv blocked close-intra-arterial infusion of VIP-induced increase in gastric mucosal blood flow (GMBF, measured by the hydrogen gas clearance), and decrease in mean arterial blood pressure while not influencing basal levels in urethane-anesthetized rats. The thyrotropin-releasing hormone (TRH) stable analog, RX 77368, injected intracisternally (IC, 30 ng) increased GMBF and blood pressure. The VIP antagonist did not significantly reduce the GMBF response to IC RX 77368 while enhancing the rise in blood pressure. These findings indicate that [4Cl-D-Phe 6 ,Leu 17 ]VIP is an antagonist for exogenous VIP-induced gastric hyperemia and hypotension and that VIP modulates the systemic blood pressure response to IC RX 77368 at 30 ng while not playing a primary role in the increase of GMBF.

Prostacyclin (PGI2) and β-carotene have a key role in gastric mucosal defence against endogenous or exogenous noxious agents. Prostacyclin has appreciable protective effects on the gastrointestinal (GI) mucosa, while β-carotene (as one of the retinoid compounds) has oxyradical scavenging properties.

Cytokines are known to play a key role in regulation of gastric functions. Interferon-alpha (IFN-α) has been published to impair gastric motility. Aims of this study were to clarify effect of IFN-α on gastric acid secretion (GAS) and determine role of nitric oxide (NO) in the process. Both subcutaneous (1000, 10000, 100 000 IU, s.c.) and intracisternal (10, 100, 1000 IU, i.c.) injections of IFN-α dose-dependently inhibited GAS induced by pylorus ligation in male SD rats in 2 hrs (370±40, 233±39, 208±50 micromol vs control 415±59 micromol and 481±50, 249±75, 141±25 micromol vs control 485±65 micromol, respectively). Central doses inducing same level inhibition were 100 times lower. NOS inhibitor L-NAME (3 mg/kg, i.v.) blocked the inhibitory effect of i.c. ED50 dose 100 IU IFN-α (507±75 micromol/2 hrs), while L-arginine, the substrate of nitric oxide synthase (NOS) prevented L-NAME action (266±82 micromol/2 hrs). D-arginine failed to prevent L-NAME action on IFN-α-induced inhibition of GAS. Aminoguanidine, a selective inhibitor of inducible NOS (iNOS) failed to block IFN-α induced inhibition of GAS. Results suggest that IFN-α inhibits GAS centrally through nitric oxide pathways probably mediated by continuous isoform of NOS that can be important in regulation of GAS in healthy or pathological conditions.

Oxidative stress, observed in the asthmatic airways, is not localized only to the bronchial system. It would be a great advantage to monitor the oxidative stress markers from blood especially in childhood asthma following the inflammation. Our aim was to measure the levels of antioxidants and the oxidatively damaged biomolecules. We were also interested in the gene expression alterations of the free radical source gp91(phox) subunit (CYBB) of the NADPH oxidase system, and the antioxidant heme oxygenase-1 (HMOX-1) isoenzyme in the blood. Our findings were also examined in the context of medical treatment.Oxidative stress parameters via photometric methods, CYBB and HMOX-1 expressions via real-time PCR were measured in 58 asthmatic and 30 healthy children.Higher blood thiobarbituric acid reactive substances (TBARS) (p0.03) and carbonylated protein (p0.05) levels were found in the asthmatic children than in the controls. The relative expression of CYBB was significantly lower (p0.05) in patients treated with a low daily dose of inhaled corticosteroid (ICS), than in asthmatics not receiving ICS therapy. Higher ICS doses alone or combined with long acting β2-receptor agonists did not influence the expression significantly. No similar tendency was found as regards to HMOX-1 expression.Elevated levels of damaged lipid (TBARS) and protein (carbonylated) products corroborate the presence of oxidative stress in the blood during bronchial asthma and suggest the presence of chronic oxidative overload. Our findings also suggest that ICS treatment can influence the relative CYBB mRNA expression in circulating leukocytes in a dose dependent manner.

Karadi O, Bodis B, Kiraly A, Abdel-Salam OME, Sutō G, Vincze A, Mozsik Gy. Surgical vagotomy enhances the indomethacin-induced gastrointestinal mucosal damage in rats. Inflammopharmacology. 1994;2:389-399.

An essential role for an intact vagal nerve has been proven in the development of gastric mucosal cyto- and general protection. On the other hand, chemically-induced (ethanol, HCl, indomethacin) gastric mucosal damage is enhanced after acute surgical vagotomy. The aims of this paper were to study the possible mechanisms of the vagal nerve in the development of gastric mucosal defense. The following questions were addressed: 1) effect of surgical vagotomy on the development of ethanol- (ETOH), HCl-, and indomethacin (IND)-induced gastric mucosal damage: 2) changes in the gastric mucosal defense by scavengers, prostacyclin and other compounds (small doses of atropine and cimetidine; 3) changes in the gastric mucosal vascular permeability due to chemicals; 4) effect of indomethacin in the ETOH and HCl models with and without surgical vagotomy; 5) changes in the gastric mucosal content of prostacyclin and PGE2 in the ETOH and HCl models after surgical vagotomy; and 6) changes in the role of SH-groups in gastric mucosal defense after surgical vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Different chemicals (such as ethanol, HCl, drugs) produce gastric mucosal injury. A special type of gastric mucosal defense, which differed from the inhibition of gastric acid secretion, was discovered in response to small doses of prostaglandins. This phenomenon was termed "gastric cytoprotection". Later, the existence of gastric cytoprotection was proved using different compounds, such as vitamin A and other carotenoids, prostacyclin, small doses of anticholinergic and H2-blocking agents. These compounds produce cyto-protection by different mechanisms. In this study we tested the role of vagus nerve on the development of these different types of gastric cytoprotection. These compounds prevent ethanol-induced gastric mucosal injury in rats with intact vagus nerve, but their cyto- and mucosal protective effects disappear in surgically vagotomized rats. These results indicate that the intact vagus nerve is basically necessary for the overproduction of HCl and pepsin secretion, and for the development of gastric cytoprotection, produced by different compounds (e.g. prostacyclin, beta-carotene, small doses of atropine and cimetidine) acting without the presence of inhibition of gastric acid secretion.