Markers of Oxidative Stress in Generalized Anxiety Psychiatric Disorder: Therapeutic Implications

There is growing evidence that oxidative stress contributes to the pathogenesis of anxiety disorders. Our aim was to measure oxidative stress in anxiety disorders subjects, and assesses the potential confounding influences of anti anxiety therapy. Serum malondialdehyde and antioxidant levels were estimated in patients at the time of presentation and also after anti- anxiety therapy for 3 months. During the period of study no antioxidant/s was given to the patients and control subjects. Serum malondialdehyde levels were significantly higher in the anxiety disorders patients in comparison to control cases. Also, the antioxidant activity of enzymes super oxide dismutase, glutathione and non enzymatic antioxidant levels of vitamins E and C were significantly lower in patients compared to controls at the initial presentation. After 3 months of anti anxiety treatment all the above parameters showed reversal in the respective levels of serum malondialdehyde and antioxidant activity. Anti anxiety medications results in reduced oxidative stress which indicates that oxidative stress is not the cause, but rather a consequence, of anxiety disorders

Protein Damage and Antioxidant Status Alterations Caused by Oxidative Injury in Chronic Myeloid Leukemia

Objective: To evaluate the oxidative stress and antioxidant defense in patients with chronic myeloid leukemia.Background: Chronic myeloid leukemia is a myeloproliferative disorder associated with a characteristic chromosomal translocation called the Philadelphia chromosome. Reactive oxygen species and other free radicals mediate phenotypic and genotypic changes leading from mutation to neoplasia in all cancers, including chronic myeloid leukemia. We evaluated patients with chronic myeloid leukemia by observing their oxidative status and antioxidant defense.Methods: Using serum from 40 clinically diagnosed cases of chronic myeloid leukemia as well as 40 healthy controls, we measured the concentration of thiobarbituric acid, levels of protein carbonylation, total antioxidant status, catalase, superoxide dismutase, glutathione peroxidase, vitamins A and E, and the trace elements zinc, magnesium, and selenium. Results: We found significantly increased levels of serum malonyldialdehyde and protein carbonyl in patients with chronic myeloid leukemia in comparison to healthy individuals, and significantly decreased levels of the antioxidants and micronutrients thiobarbituric acid, catalase, superoxide dismutase, glutathione peroxidase, vitamins A and E, zinc, magnesium, and selenium. These data suggest cellular damage occurring at the level of lipids and proteins.Conclusion: These findings indicate a link between low levels of antioxidants and cellular damage in patients with chronic myeloid leukemia, supporting the idea that oxidative stress may play a role in the pathogenesis of chronic myeloid leukemia

A novel approach to study oxidative stress in neonatal respiratory distress syndrome

Background: Respiratory distress syndrome of the neonate (neonatal RDS) is still an important problem in treatment of preterm infants. It is accompanied by inflammatory processes with free radical generation and oxidative stress. The aim of study was to determine the role of oxidative stress in the development of neonatal RDS. Methods: Markers of oxidative stress and antioxidant activity in umbilical cord blood were studied in infants with neonatal respiratory distress syndrome with reference to healthy newborns. Results: Status of markers of oxidative stress (malondialdehyde, protein carbonyl and 8-hydroxy-2-deoxy guanosine) showed a significant increase with depleted levels of total antioxidant capacity in neonatal RDS when compared to healthy newborns. Conclusion: The study provides convincing evidence of oxidative damage and diminished antioxidant defenses in newborns with RDS. Neonatal RDS is characterized by damage of lipid, protein and DNA, which indicates the augmentation of oxidative stress. General significance: The identification of the potential biomarker of oxidative stress consists of a promising strategy to study the pathophysiology of neonatal RDS

Design and Synthesis of 2‑Pyridone Based Flexible Dimers and Their Conformational Study through X‑ray Diffraction and Density Functional Theory: Perspective of Cyclooxygenase‑2 Inhibition

This paper describes the results of X-ray crystallography of 4-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (<b>1</b>) and its propylene bridged dimers <b>2</b> and <b>3</b>. Influence of inter- and intramolecular interactions on the conformation of propylene linker have been studied through single crystal X-ray crystallography and density functional theory studies. Hirshfeld surface analysis has been employed for the study of intermolecular interactions. However, differential scanning calorimetry analysis of compounds <b>2</b> and <b>3</b>, and thermogravimetric analysis of compound <b>3</b> has been performed to determine the thermal stability. Along with molecular packing and thermal analysis, molecular docking has also been performed in the catalytic site of cyclooxygenase-2 to identify the potential anti-inflammatory activity of dimer <b>2</b> and <b>3</b>. The above results suggest that the supramolecular aggregate structures which are formed in solution are of lowest energy. However, cyclooxygenase-2 active site prefers the higher energy conformers

A monoclonal antibody cytolytic to androgen independent DU145 and PC3 human prostatic carcinoma cells

Background: While a range of therapeutic products is available for androgen-dependent prostatic cancer, no specific intervention modality exists for androgen-independent prostatic cancer. The objective of this research was to explore whether epitopes exist on androgen-independent prostatic DU145 cancer cells, which could be susceptible to cytotoxic action of specific antibodies. Methods: Hybrid cell clones were developed by immunization of mice with DU145 cells and tested for immunoreactivity by solid phase EIA and cytotoxicity in vitro on DU145 in the presence of the complement, employing colorimetric quantitation by MTS (3- (4-, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-(4-sulfophenyl)-2H-tetrazolium). Binding and cytotoxicity studies were also carried out by flow-cytometry. Results: Of 15 stabilized clones immunoreactive with DU145 cells, one monoclonal antibody (mAb 730) manifested cytotoxicity on DU145 cells. Approximately 80% of cells in the DU145 cell line were susceptible to lysis with this antibody at saturating levels. This figure corresponded quantitatively to the number of cells binding with this antibody as determined by Flow-cytometry. Staining with ethidium monoazide bromide (EMA) showed that the cell binding the antibody was also the one killed by the antibody in the presence of the complement. MAb 730 was also cytotoxic to PC3, another androgen-independent human prostatic cancer cell line. This antibody is devoid of classical autoantibody reactivities and does not react with normal human liver, thyroid, kidney, pancreas, and adrenal tissues, as determined by immunofluorescence. Also, it shows negative immuno-reactivity to benign glandular tissue but is observed to positively react with neoplastic prostate tissue. Conclusions: Epitopes exist on androgen-independent prostatic cancer cells that are susceptible to cytolysis by monoclonal antibodies and these could be investigated for potential immunotherapy