Role of oxidative stress in the pathology and management of human tuberculosis

Copyright © 2018 Madhur D. Shastri et al. Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S-oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptible and drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host's OS response

Design, fabrication and performance evaluation of a 22-channel direct reading atomic emission spectrometer using inductively coupled plasma as a source of excitation

The indigenous design, fabrication and performance evaluation of a polychromator, using inductively coupled plasma (ICP) as a source of excitation, are described. A concave holographic grating is used as the dispersing element and a Paschen-Runge mount is chosen to focus the spectra over a wide range along the Rowland circle. Twenty-two exit slits, mounted along the circle, precisely correspond to the wavelengths used for determination of up to twenty elements present in the plasma. Radiations emerging from the exit slits are detected by photomultiplier tubes placed behind them. The photomultiplier signal is recorded by an electronic system consisting of an integrator and a PC-based data acquisition system. The performance of the spectrometer has been evaluated with an ICP excitation source. Synthetic standards in deionized water containing a mixture of twenty impurities have been analysed. Typical determination limits observed for elements range from sub-ppm to ppm levels. All the elements present as impurities can be detected simultaneously. It is also observed that each element has a different emitting region in the ICP flame for which the maximum signal to the background is obtained. The determination limits obtained corresponding to these zones are the lowest. A study of the sensitive emitting zones for several elements has been carried out and the results are demonstrated by photographs of the ICP flame. The study will help in achieving the minimum value of determination limit for an impurity element

The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders.

Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome-induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress- and inflammasome-related inflammatory disorders

Effect of temperature anisotropy on various modes and instabilities for a magnetized non-relativistic bi-Maxwellian plasma

Using kinetic theory for homogeneous collisionless magnetized plasmas, we present an extended review of the plasma waves and instabilities and discuss the anisotropic response of generalized relativistic dielectric tensor and Onsager symmetry properties for arbitrary distribution functions. In general, we observe that for such plasmas only those electromagnetic modes whose magnetic field perturbations are perpendicular to the ambient magneticeld, i.e.,B1 \perp B0, are effected by the anisotropy. However, in oblique propagation all modes do show such anisotropic effects. Considering the non-relativistic bi-Maxwellian distribution and studying the relevant components of the general dielectric tensor under appropriate conditions, we derive the dispersion relations for various modes and instabilities. We show that only the electromagnetic R- and L- waves, those derived from them and the O-mode are affected by thermal anisotropies, since they satisfy the required condition B1\perpB0. By contrast, the perpendicularly propagating X-mode and the modes derived from it (the pure transverse X-mode and Bernstein mode) show no such effect. In general, we note that the thermal anisotropy modifies the parallel propagating modes via the parallel acoustic effect, while it modifies the perpendicular propagating modes via the Larmor-radius effect. In oblique propagation for kinetic Alfven waves, the thermal anisotropy affects the kinetic regime more than it affects the inertial regime. The generalized fast mode exhibits two distinct acoustic effects, one in the direction parallel to the ambient magnetic field and the other in the direction perpendicular to it. In the fast-mode instability, the magneto-sonic wave causes suppression of the firehose instability. We discuss all these propagation characteristics and present graphic illustrations

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO