Study of nonenzymatic antioxidants in schizophrenic patients

Background: Schizophrenia is one of the most debilitating psychiatric disorders. There is now substantial evidence of increased free radical–mediated damage in schizophrenia. These mechanisms are critical role in etiopathogenesis of schizophrenia. The potential toxicity of reactive oxygen species (ROS) is counteracted by a large number of cytoprotective enzymes and nonenzymatic anti-oxidants. Endogenous substances like albumin, bilirubin and uric acid play very important defensive role against reactive oxygen species (ROS) produced in our body. The present study was undertaken to study nonenzymatic antioxidants i.e. serum albumin, bilirubin and uric acid in first episode and chronic schizophrenic patients.Methods: 50 patients of first episode schizophrenia and 50 patients of chronic schizophrenia were included in the study. 50 numbers of age and sex matched healthy and apparently normal controls were also selected for study. Blood samples were drawn and analysed for albumin, bilirubin and uric acid from all participants.Results: The study shows significant decrease in serum albumin, bilirubin and uric acid levels in both first episode schizophrenics and chronic schizophrenic patients as compared to controls. When we compared levels of these parameters in first episode schizophrenics and chronic schizophrenics, we did not find significant difference.Conclusions: Findings in our study is suggesting that decrease in the levels of nonenzymatic antioxidants occurs in attempting neutralization of ROS in schizophrenics. This study supports the defensive role of nonenzymatic antioxidants against ROS in our body

Study of malondialdehyde as an oxidative stress marker in schizophrenia

Background: Schizophrenia is characterized by distortions in thinking, perception, emotions, language, sense of self and behaviour. It has been demonstrated that free radical-mediated damage has an important role in the pathophysiology of schizophrenia. The present study was undertaken to study malondialdehyde as an oxidative stress marker in first episode and chronic schizophrenic patients.Methods: 50 patients of first episode schizophrenia and 50 patients of chronic schizophrenia were included in the study. 50 numbers of age and sex matched healthy and apparently normal controls were also selected for study. Blood samples were drawn and analysed for malondialdehyde (MDA) from all participants.Results: The study shows significant increase in plasma malondialdehyde (MDA) levels in both first episode schizophrenics and chronic schizophrenic patients as compared to controls. When we compared levels of these parameters in first episode schizophrenics and chronic schizophrenics, we did not find significant difference.Conclusions: Findings in our study is suggesting that increase in the levels of plasma malondialdehyde (MDA) occurs due to increased lipid peroxidation in schizophrenics.      

The association between isolated oligohydramnios at term and pregnancy outcome and perinatal outcome in case of isolated oligohydramnosis: a retrospective analysis

Background: Current study was carried out to assess the impact of isolated oligohydramnios on perinatal outcomes and mode of delivery.Methods: A retrospective observational cohort study was conducted at term pregnancy with sonographic finding of isolated oligohydramnios (AFI 5-25 cm).Results: When compared to the normal AFI, women with oligohydramnios had significantly lower birth weight babies and were delivered at a significantly earlier gestational age. However there was no difference in the APGAR scores at birth and NICU admissions between the two groups. Reactive NST had more chances of good APGAR score at 1 and 5 minute and that lower the AFI more the probability of nonreactive NST and abnormal Doppler. The number of inductions and caesareans done for foetal reasons were significantly higher in the exposed group.Conclusions: Obstetric and perinatal outcome remains similar in both isolated oligohydramnios with reactive NST as well as in patients with normal amniotic fluid index. Isolated oligohydramnios is not associated with adverse perinatal outcomes. However, it increases the risk for labour induction and caesarean section

Status report on the folded tandem ion accelerator at BARC

The folded tandem ion accelerator (FOTIA) facility set up at BARC has become operational. At present, it is used for elemental analysis studies using the Rutherford backscattering technique. The beams of 1H, 7Li, 12C, 16O and 19F have been accelerated up to terminal voltages of about 3 MV and are available for experiments. The terminal voltage is stable within ±2 kV. In this paper, present status of the FOTIA and future plans are discussed

Charge transport mechanisms in monovalent doped mixed valent manganites

Abstract In this communication, we report the results of the studies on structural and transport properties of monovalent Na + doped La 1-x Na x MnO 3 (LNMO; x = 0.00, 0.05, 0.10, 0.15, 0.20, 0.25 and 0.30) manganites synthesized by conventional ceramic method. X-ray diffraction (XRD) and Rietveld refinements reveal the single phasic nature of LNMO manganites without any detectable impurity within the measurement range. Temperature dependent resistivity, under different applied magnetic fields, has been performed on LNMO samples. Samples understudy exhibit metal to insulator (semiconductor) transition at temperature T P which is strongly influenced by the substitution of Na + at La 3+ site. -T plots also exhibit resistivity upturn behavior at low temperature well below 40K under all the applied fields. Variation in T P and resistivity has been discussed in the context of the competition between the transport favoring tolerance factor and zener double exchange (ZDE) mechanism and transport degrading Jahn-Teller (JT) and size variance effects. In order to understand the mechanisms responsible for the charge transport in metallic and semiconducting regions and to explore the possible electronic processes responsible for the observed low temperature resistivity minima in all the presently studied LNMO manganites, various models have been employed. It has been found that VRH mechanism gets successfully fitted to the resistivity data in the semiconducting region while ZDE polynomial law is responsible for the charge conduction in metallic region for all the presently studied LNMO samples. A strong dependence of activation energy on the Na + -content as well as applied magnetic field has been discussed in the context of variation and interrelations between the structural parameters. Charge conduction in metallic region has been discussed in the light of electron-phonon interactions which is influenced by the Na + -content and applied magnetic field. Electrostatic blockade model has been employed to understand the low temperature resistivity minima behavior. Blocking energy for the charge carriers shows a dependence on the magnetic energy provided to the charge carriers. Present study can be useful to understand and to control the charge conduction in the manganites and hence to design the manganite based thin film devices for various spintronic applications

Rb regulates fate choice and lineage commitment in vivo

February 1, 2011Mutation of the retinoblastoma gene (RB1) tumour suppressor occurs in one-third of all human tumours and is particularly associated with retinoblastoma and osteosarcoma[superscript 1]. Numerous functions have been ascribed to the product of the human RB1 gene, the retinoblastoma protein (pRb). The best known is pRb’s ability to promote cell-cycle exit through inhibition of the E2F transcription factors and the transcriptional repression of genes encoding cell-cycle regulators[superscript 1]. In addition, pRb has been shown in vitro to regulate several transcription factors that are master differentiation inducers[superscript 2]. Depending on the differentiation factor and cellular context, pRb can either suppress or promote their transcriptional activity. For example, pRb binds to Runx2 and potentiates its ability to promote osteogenic differentiation in vitro[superscript 3]. In contrast, pRb acts with E2F to suppress peroxisome proliferator-activated receptor γ subunit (PPAR-γ), the master activator of adipogenesis[superscript 4, 5]. Because osteoblasts and adipocytes can both arise from mesenchymal stem cells, these observations suggest that pRb might play a role in the choice between these two fates. However, so far, there is no evidence for this in vivo. Here we use mouse models to address this hypothesis in mesenchymal tissue development and tumorigenesis. Our data show that Rb status plays a key role in establishing fate choice between bone and brown adipose tissue in vivo.National Cancer Institute (U.S.) (Grant)National Institutes of Health (U.S.) (Grant

Detection and Characterization of CD133+ Cancer Stem Cells in Human Solid Tumours

Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of heterogeneous cell populations, which display different goals and roles in tumour economy. A rather small cell subset can hold or acquire stem potentials, gaining aggressiveness and increasing expectancy of recurrence. The CD133 antigen is a pentaspan membrane glycoprotein, which has been proposed as a cancer stem cell marker, since it has been previously demonstrated to be capable of identifying a cancer initiating subpopulation in brain, colon, melanoma and other solid tumours. Therefore, our aim was to observe the possible presence of cells expressing the CD133 antigen within solid tumour cell lines of osteosarcoma and, then, understand their biological characteristics and performances.In this study, using SAOS2, MG63 and U2OS, three human sarcoma cell lines isolated from young Caucasian subjects, we were able to identify and characterize, among them, CD133+ cells showing the following features: high proliferation rate, cell cycle detection in a G2\M phase, positivity for Ki-67, and expression of ABCG2 transporters. In addition, at the FACS, we were able to observe the CD133+ cell fraction showing side population profile and forming sphere-clusters in serum-free medium with a high clonogenic efficiency.Taken together, our findings lead to the thought that we can assume that we have identified, for the first time, CD133+ cells within osteosarcoma cell lines, showing many features of cancer stem cells. This can be of rather interest in order to design new therapies against the bone cancer

Amplicon-Dependent CCNE1 Expression Is Critical for Clonogenic Survival after Cisplatin Treatment and Is Correlated with 20q11 Gain in Ovarian Cancer

Genomic amplification of 19q12 occurs in several cancer types including ovarian cancer where it is associated with primary treatment failure. We systematically attenuated expression of genes within the minimally defined 19q12 region in ovarian cell lines using short-interfering RNAs (siRNA) to identify driver oncogene(s) within the amplicon. Knockdown of CCNE1 resulted in G1/S phase arrest, reduced cell viability and apoptosis only in amplification-carrying cells. Although CCNE1 knockdown increased cisplatin resistance in short-term assays, clonogenic survival was inhibited after treatment. Gain of 20q11 was highly correlated with 19q12 amplification and spanned a 2.5 Mb region including TPX2, a centromeric protein required for mitotic spindle function. Expression of TPX2 was highly correlated with gene amplification and with CCNE1 expression in primary tumors. siRNA inhibition of TPX2 reduced cell viability but this effect was not amplicon-dependent. These findings demonstrate that CCNE1 is a key driver in the 19q12 amplicon required for survival and clonogenicity in cells with locus amplification. Co-amplification at 19q12 and 20q11 implies the presence of a cooperative mutational network. These observations have implications for the application of targeted therapies in CCNE1 dependent ovarian cancers

Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS