ASSESMENT OF QUALITY OF LIFE AND OXIDATIVE STRESS IN TUBERCULOSIS PATIENTS VISITING DIRECTLY OBSERVED TREATMENT SHORT COURSE CENTRES OF WARANGAL

ABSTRACTObjectives: Tuberculosis (TB) is a disease associated with a wide range of respiratory symptoms. It remains a major public health problem worldwide.In TB, oxidative stress is a result of tissue inflammation, poor dietary intake of micronutrients due to illness, and free radical burst from activatedmacrophages. In recent years, efforts have been dedicated for assessing the health-related quality of life (HRQoL) in TB patients. The objectives of thestudy were to evaluate the impairment of HRQoL in TB patients using by DR-12 questionnaire and to estimate oxidative stress parameters such asmalondialdehyde (MDA), glutathione (GSH), vitamins A, and C in TB patients.Methods: A total of 142 patients meeting the study criteria were recruited in the study to evaluate HRQOL. The patients were administered withDR-12 questionnaire at 0 week, 4 weeks and at the end of intensive phase of the treatment. A paired t-test was applied and a p<0.05 was consideredas significant. 40 patients meeting the study criteria were recruited for assessment of oxidative stress parameters. The blood samples were assessedfor the concentration of MDA, GSH, vitamin A, and vitamin C using suitable methods.Results: A significantly higher HRQOL scores were observed at the end of intensive phase of the treatment for both pulmonary and extrapulmonaryTB patients. There was a significant improvement in their QOL (p<0.05). An increased oxidative stress was obtained in plasma of TB patients ascompared to normal healthy controls. There was a significant increase in the MDA levels of TB patients (7 times greater than control) when comparedto normal population. There was a double decrease in GSH and vitamin A concentrations in TB cases compared with controls. The plasma levels ofvitamin C in TB cases obtained thrice lesser in TB cases than the control population.Conclusion: The study showed that in TB patients free radical activity is quite high and antioxidant levels are low. A suitable antioxidant therapy mayimprove QoL and prove beneficial supplementation for fast recovery.Keywords: Tuberculosis, Health-related quality of life, Directly observed treatment short course, DR-12 score, Antioxidants, Free radicals

Colocalization of intranuclear lamin foci with RNA splicing factors

The lamins form a fibrous network underlying the inner nuclear membrane termed the nuclear lamina. In order to gain insights into the role of lamins in nuclear organization, we have characterized a monoclonal antibody (LA-2H10) raised against recombinant rat lamin A that labels nuclei in a speckled pattern in all cells of unsynchronized populations of HeLa and rat F-111 fibroblast cells, unlike the typical nuclear periphery staining by another monoclonal antibody to lamin A, LA-2B3. In immunolocalization studies the lamin A speckles or foci were found to colocalize with the RNA splicing factors SC-35 and U5-116 kD, but not with p80 coilin found in coiled bodies. Lamin B1 was also associated with these foci. These foci dispersed when cells entered mitosis and reformed during anaphase. The differential reactivity of LA-2H10 and LA-2B3 was retained after nuclei were extracted with detergents, nucleases and salt to disrupt interactions of lamins with chromatin and other nuclear proteins. Using deletion fragments of recombinant lamin A, the epitope recognized by LA-2H10 was located between amino acids 171 and 246. Our findings are consistent with a structural role for lamins in supporting nuclear compartments containing proteins involved in RNA splicing

Novel multicomponent B2-ordered aluminides: Compositional design, synthesis, characterization, and thermal stability

For the first time, multicomponent alloys belonging to a B2-ordered single phase were designed and fabricated by melting route. The design concept of high entropy alloys is applied to engineering the transition metal sublattice of binary B2 aluminide. The equiatomic substitution of transition metal elements in the Ni sublattice of binary AlNi followed to produce Al(CoNi), Al(FeNi), Al(CoFe), Al(CoFeNi), Al(CoFeMnNi), and Al(CoCuFeMnNi) multicomponent alloys. CALculation of PHAse Diagrams (CALPHAD) approach was used to predict the phases in these alloys. X-ray diffraction and transmission electron microscopy were used to confirm the B2 ordering in the alloys. Thermal stability of the B2 phase in these alloys was demonstrated by prolonged heat treatments at 1373 K and 1073 K up to 200 h. © 2020 by the author. Licensee MDPI, Basel, Switzerland

Novel Multicomponent B2-Ordered Aluminides: Compositional Design, Synthesis, Characterization, and Thermal Stability

For the first time, multicomponent alloys belonging to a B2-ordered single phase were designed and fabricated by melting route. The design concept of high entropy alloys is applied to engineering the transition metal sublattice of binary B2 aluminide. The equiatomic substitution of transition metal elements in the Ni sublattice of binary AlNi followed to produce Al(CoNi), Al(FeNi), Al(CoFe), Al(CoFeNi), Al(CoFeMnNi), and Al(CoCuFeMnNi) multicomponent alloys. CALculation of PHAse Diagrams (CALPHAD) approach was used to predict the phases in these alloys. X-ray diffraction and transmission electron microscopy were used to confirm the B2 ordering in the alloys. Thermal stability of the B2 phase in these alloys was demonstrated by prolonged heat treatments at 1373 K and 1073 K up to 200 h. © 2020 by the author. Licensee MDPI, Basel, Switzerland

Grain boundary diffusion and segregation of Cr in Ni Σ11(1̄13)[110] bicrystals: Decoding the role of grain boundary defects

Grain boundary diffusion of Cr in a near Σ11(1̄13)[110] Ni bicrystal is measured over a temperature interval between 503 K and 1203 K using the radiotracer technique. The grain boundary diffusion coefficients, Dgb, and the triple products, P=s⋅δ⋅Dgb, are determined in the C- and B-type kinetics regimes, respectively, with s being the segregation factor and δ the grain boundary width. Opposite to expectations, two distinct contributions to short-circuit diffusion along the nominally single interface are distinguished and related to the existence of two macroscopic facets with distinct grain boundary inclinations and, as a result, distinct structures. The experimental results indicate that the segregation factor of Cr in Ni is about unity, which is fully supported by ab initio calculations. Using classical atomistic simulations, Ni grain boundary self-diffusion coefficients are calculated for the symmetric and asymmetric facets. The computational simulations reveal accelerated self-diffusion kinetics along the asymmetric facet, attributing this phenomenon to the presence of disconnection-like defects. This elucidates the experimentally observed diffusion dynamics of chromium atoms, thereby corroborating the heterogeneous mechanisms governing atomic migration across distinct facets

The Level of Isoprostanes as a Non-invasive Marker for in vivo Lipid Peroxidation in Secondary Progressive Multiple Sclerosis

Oxidative stress leads to lipid peroxidation and may contribute to the pathogenesis of lesions in multiple sclerosis (MS), an autoimmune disease characterized by inflammatory as well as degenerative phenomena. Isoprostanes are prostaglandin-like compounds which are formed by free radical catalysed peroxidation of arachidonic acid esterified in membrane phospholipids. They are a new class of sensitive specific markers for in vivo lipid peroxidation. In this study 26 patients (15 females and 11 males; mean age 48.2 ± 15.2 year; mean disease duration 10.0 ± 6.5 year) with secondary progressive MS (SPMS) and 12 healthy controls were enrolled. In patients with multiple sclerosis the lipid peroxidation as the level of urine isoprostanes and the level of thiobarbituric acid reactive species (TBARS) in plasma were estimated. Moreover, we estimated the total antioxidative status (TAS) in plasma. It was found that the urine isoprostanes level was over 6-fold elevated in patients with SPMS than in control (P < 0.001). In SPMS patients TBARS level was also statistically higher than in controls (P < 0.01). However, we did not observed any difference of TAS level in serum between SPMS patients and controls (P > 0.05). In patients with SPMS the lipid peroxidation and oxidative stress measured as the increased level of isoprostanes was observed. Thus, we suggest that the level of isoprostanes may be used as non-invasive marker for a determination of oxidative stress what in turn, together with clinical symptoms, may determine an specific antioxidative therapy in SPMS patients

Identification of uPAR-positive Chemoresistant Cells in Small Cell Lung Cancer

BACKGROUND: The urokinase plasminogen activator (uPA) and its receptor (uPAR/CD87) are major regulators of extracellular matrix degradation and are involved in cell migration and invasion under physiological and pathological conditions. The uPA/uPAR system has been of great interest in cancer research because it is involved in the development of most invasive cancer phenotypes and is a strong predictor of poor patient survival. However, little is known about the role of uPA/uPAR in small cell lung cancer (SCLC), the most aggressive type of lung cancer. We therefore determined whether uPA and uPAR are involved in generation of drug resistant SCLC cell phenotype. METHODS AND FINDINGS: We screened six human SCLC cell lines for surface markers for putative stem and cancer cells. We used fluorescence-activated cell sorting (FACS), fluorescence microscopy and clonogenic assays to demonstrate uPAR expression in a subpopulation of cells derived from primary and metastatic SCLC cell lines. Cytotoxic assays were used to determine the sensitivity of uPAR-positive and uPAR-negative cells to chemotherapeutic agents. The uPAR-positive cells in all SCLC lines demonstrated multi-drug resistance, high clonogenic activity and co-expression of CD44 and MDR1, putative cancer stem cell markers. CONCLUSIONS: These data suggest that uPAR-positive cells may define a functionally important population of cancer cells in SCLC, which are resistant to traditional chemotherapies, and could serve as critical targets for more effective therapeutic interventions in SCLC

Intermittent Hypoxia-Induced Cognitive Deficits Are Mediated by NADPH Oxidase Activity in a Murine Model of Sleep Apnea

Background: In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction. Methods and Findings: The effect of IH during light period on two forms of spatial learning in the water maze and well as markers of oxidative stress was assessed in mice lacking NADPH oxidase activity (gp91phox _/Y) and wild-type littermates. On a standard place training task, gp91phox _/Y displayed normal learning, and were protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to IH as compared to room air (RA) controls, while no changes emerged in gp91phox _/Y mice. Additionally, wild-type mice, but not gp91phox _/Y mice had significantly elevated levels of NADPH oxidase expression and activity, as well as MDA and 8-OHDG in cortical and hippocampal lysates following IH exposures. Conclusions: The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by excessive NADPH oxidase activity, and thus pharmacological agents targeting NADPH oxidase may provid