Propanil (3,4-DCPA)-induced alterations of macrophage function

The pesticide 3,4-dichloropropionanilide (propanil or alternatively, DCPA) is a post-emergent herbicide predominantly used for the control of weeds on commercial rice crops worldwide. The US Environmental Protection Agency report on Pesticides Industry Sales and Usage in 2001 ranked propanil as the 17th most used herbicide in the US. It is applied on the fields via groundboom sprayers or aerial equipment suppressing photosynthesis and carbon fixation of a growing plant. The primary target of herbicide exposure is personnel working in the manufacturing and application who are required to wear personal protective equipment to minimize the exposure. The common routes of this exposure are inhalational and dermal, and to a lesser extent, oral. A number of toxic side effects are induced by propanil include hemolytic anemia, methemoglobinemia, and myelotoxicity. The majority of current knowledge about propanil\u27s toxic effects comes from animal studies. Liver and spleen were found to be the primary target organs, with many cell populations of the immune system affected, including T and B lymphocytes, NK cells and macrophages.;Macrophages play essential roles in both innate and adaptive immune responses. They recognize and destroy pathogens through phagocytosis and generation of reactive oxygen and nitrogen species (ROS and RNS). Macrophages can also function as antigen presenting cells in the initiation of an adaptive immune response and secrete a number of cytokines and inflammatory mediators thereby modulating the immune reaction at the inflamed site.;Previous studies have demonstrated that propanil was able to suppress interleukin (IL)-1beta, IL-6 and TNF-alpha cytokine production by LPS-activated murine macrophages. The analysis of nuclear factor-kappaB (NF-kappaB), responsible for TNF-alpha production, detected a decreased nuclear localization of NF-kappaB accompanied by a reduced, but not entirely abrogated binding to DNA activity.;The first study of this dissertation demonstrated the ability of propanil to inhibit TNF-alpha production by LPS-stimulated human monocytic cells line and suppress phagocytosis of fluorescent beads and Listeria monocytogenes . The ability to directly kill this bacterium and produce ROS and RNS was also assessed. The results demonstrate that DCPA has profound effects on macrophage function, and provide insight into the potential mechanisms of immunosuppression by DCPA. The second study focused on the mechanism of dramatic suppression of an inflammatory mediator secreted by activated macrophages, prostaglandin E2 (PGE2). Enzymatic activity and expression level of the proteins involved in PGE2 production were studied. However, the exact mechanism of propanil\u27s action is still unknown. The third study describes a novel behavior on NF-kappaB, called oscillations, in continuously LPS-stimulated macrophages. Binding activity of NF-kappaB was studied by two independent methods, and a mathematical model describing the oscillatory behavior was created based on experimental data. It demonstrated that propanil exposure potentiated the NF-kappaB activation process changing the oscillation behavior which could influence the transcription activity of the NF-kappaB-inducible genes.;Taken together our findings indicate that propanil exposure affects a number of important macrophage functions, such as phagocytosis, ROS and RNS production and inflammatory mediator\u27s secretion. Our studies also demonstrated a potential mechanism for the inhibition of a number of inflammatory cytokines through changes in NF-kappaB binding activity and oscillatory behavior

Feasibility of radiation dose range capable to cause subacute course of radiation syndrome

There had been analysed cases of radiation syndrome which clinical picture takes an intermediate place between the acute radiation syndrome (ARS) and the chronic radiation syndrome (CRS), and differs from them because of a subacute. This variant of disease can develop as a result of the fractioned or prolonged radiation lasting from several days to several weeks. Development of primary reaction took place only in the extremely hard cases which ends with an early fatality. After the general radiation the marrow failure was characterized by directly expressed formation and restoration period, specific features of which were defined by the radiation duration, a total dose and dose derivative. The most typical outcomes of a subacute radiation syndrome are death from infectious complications in the period of an eruptive phase or leukosis development in the remote period

On the anomalously large extension of the Pulsar Wind Nebula HESS J1825-137

The very high energy (VHE) gamma-ray emission reported from a number of pulsar wind nebulae (PWNe) is naturally explained by the inverse Compton scattering of multi-TeV electrons. However, the physical dimensions of some gamma-ray-emitting PWNe significantly exceed the scales anticipated by the standard hydrodynamical paradigm of PWN formation. The most "disturbing" case in this regard is HESS J1825-137, which extends to distances $r\approx70\rm\,pc$ from the central pulsar PSR J1826-1334. If the gamma-ray emission is indeed produced inside the PWN, but not by electrons that escaped the nebula and diffuse in the interstellar medium (ISM), the formation of such an anomalously extended plerion could be realized, in a diluted environment with the hydrogen number density $n_{ism}\le10^{-2}\rm\,cm^{-3}$. In this paper, we explore an alternative scenario assuming that the pulsar responsible for the formation of the nebula initially had a very short rotation period. In this case, the sizes of both the PWN and the surrounding supernova remnant depend on the initial pulsar period, the braking index, and the ISM density. To check the feasibility of this scenario, we study the parameter space that would reproduce the size of HESS J1825-137. We show that this demand can be achieved if the braking index is small, $n\leq2$ and the pulsar birth period is short, $P_{\rm b}\simeq1\rm\,ms$. This scenario can reproduce the wind termination position, which is expected at $R_{ts}\simeq0.03\rm\,pc$, only in a dense environment with $n_{ism}\geq\rm1\,cm^{-3}$. The requirement of the dense surrounding gas is supported by the presence of molecular clouds found in the source vicinity.Comment: 15 pages, 6 figures, ApJ accepte

Stability and structure of analytical MHD jet formation models with a finite outer disk radius

(Abridged) Finite radius accretion disks are a strong candidate for launching astrophysical jets from their inner parts and disk-winds are considered as the basic component of such magnetically collimated outflows. The only available analytical MHD solutions for describing disk-driven jets are those characterized by the symmetry of radial self-similarity. Radially self-similar MHD models, in general, have two geometrical shortcomings, a singularity at the jet axis and the non-existence of an intrinsic radial scale, i.e. the jets formally extend to radial infinity. Hence, numerical simulations are necessary to extend the analytical solutions towards the axis and impose a physical boundary at finite radial distance. We focus here on studying the effects of imposing an outer radius of the underlying accreting disk (and thus also of the outflow) on the topology, structure and variability of a radially self-similar analytical MHD solution. The initial condition consists of a hybrid of an unchanged and a scaled-down analytical solution, one for the jet and the other for its environment. In all studied cases, we find at the end steady two-component solutions.Comment: 14 pages, 15 figures, accepted for publication in A &

Propeller outflows from an MRI disc

We present the results of axisymmetric simulations of MRI-driven accretion onto a rapidly rotating, magnetized star accreting in the propeller regime. The stellar magnetosphere corotates with the star, forming a centrifugal barrier at the disc-magnetosphere boundary which inhibits matter accretion onto the star. Instead, the disc matter accumulates at the disc-magnetosphere interface and slowly diffuses into the inner magnetosphere where it picks up angular momentum and is quickly ejected from the system as an outflow. Due to the interaction of the matter with the magnetosphere, this wind is discontinuous and is launched as discrete plasmoids. If the ejection rate is lower than the disc accretion rate, the matter accumulates at the disc-magnetosphere boundary faster than it can be ejected. In this case, accretion onto the star proceeds through the episodic accretion instability in which episodes of matter accumulation are followed by simultaneous accretion and ejection. During the accretion phase of this instability in which matter flows onto the star in funnel streams, we observe a corresponding rise in the outflow rate. Both the accretion and ejection processes observed in our simulations are highly non-stationary. The stars undergo strong spin-down due to the coupling of the stellar field with the disc and corona and we measure the spin-down timescales of around 1 Myr for a typical CTTS in the propeller regime.Comment: 13 pages, 10 figures, submitted to MNRA

Hydrodynamics of interaction of pulsar and stellar winds and its impact on the high energy radiation of binary pulsar systems

The hydrodynamics of the interaction of pulsar and stellar winds in binary systems harboring a pulsar and its impact on the nonthermal radiation of the binary pulsar PSR B1259-63/SS2883 is discussed. The collision of an ultrarelativistic pulsar wind with a nonrelativistic stellar outflow results in significant bulk acceleration of the shocked material from the pulsar wind. Already at distances comparable to the size of the binary system, the Lorentz factor of the shocked flow can be as large as $\gamma$~4. This results in significant anisotropy of the inverse Compton radiation of accelerated electrons. Because of the Doppler boosting of the produced radiation, one should expect a variable gamma-ray signal from the system. In particular, this effect may naturally explain the reported tendency of a decrease of TeV gamma-ray flux close to the periastron. The modeling of the interaction of pulsar and stellar winds allows self-consistent calculations of adiabatic losses. Our results show that adiabatic losses dominate over the radiative losses. These results have direct impact on the orbital variability of radio, X-ray and gamma-ray signals detected from the binary pulsar PSR 1259-63/SS2883.Comment: 4 pages, 4 figures; based on poster presentation at "High Energy Phenomena in Relativistic Outflows", Dublin, Sept. 2007; accepted for publication in International Journal of Modern Physics