Genotoxic damage to glioblastoma cells treated with 6 MV X-radiation in the presence or absence of methoxy estradiol, IUDR or topotecan

Objective: To explore the cumulative genotoxic damage to glioblastoma (GBM) cells, grown as multicellular spheroids, following exposure to 6 MV X-rays (2 Gy, 22 Gy) with or without, 2-methoxy estradiol (2ME2), iododeoxyuridine (IUDR) or topotecan (TPT), using the Picogreen assay. Materials and Methods: The U87MG cells cultured as spheroids were treated with 6 MV X-ray using linear accelerator. Specimens were divided into five groups and irradiated using X-ray giving the dose of 2 Gy after sequentially incubated with one of the following three drug combinations: TPT, 2-ME2/TPT, IUDR/TPT or 2ME2/IUDR/TPT. One specimen was used as the irradiated only sample (R). The last group was also irradiated with total dose of 22 Gy (each time 2 Gy) of 6 MV X-ray in 11 fractions and treated for three times. DNA damage was evaluated using the Picogreen method in the experimental study. Results: R/TPT treated group had more DNA damage double strand break (DSB)/single strand break (SSB) compared with the untreated group (P<0.05). Moreover the R/TPT group treated with 2ME2 followed by IUDR had maximum DNA damage in spheroid GBM indicating an augmented genotoxicity in the cells. The DNA damage was induced after seven fractionated irradiation and two sequential treatments with 2ME2/IUDR/TPT. To ensure accuracy of the slope of dose response curve the fractionated radiation was calculated as 7.36 Gy with respect to α/β ratio based on biologically effective dose (BED) formulae. Conclusion: Cells treated with 2ME2/IUDR showed more sensitivity to radiation and accumulative DNA damage. DNA damage was significantly increased when GBM cells treated with TPT ceased at S phase due to the inhibition of topoisomerase enzyme and phosphorylation of Chk1 enzyme. These results suggest that R/TPT-treated cells increase sensitivity to 2ME2 and IUDR especially when they are used together. Therefore, due to an increase in the level of DNA damage (SSB vs. DSB) and impairment of DNA repair machinery, more cell death will occur. This in turn may improve the treatment of GBM. © 2015, Royan Institute (ACECR). All rights reserved

A study of the oxidation-induced conformational and functional changes in neuroserpin

Background: Neuroserpin, a member of the Serine Proteinase Inhibitor (Serpin) superfamily, is known to be a neuroprotective factor in the focal ischemic stroke followed by reducing the microglial activation. Neuroserpin is a protein rich of methionine residues that can scavenge the free radical species which may increase its neuroprotective effect. On the other hand, the oxidative modifications of the amino acid residues in neuroserpin may lead to changes in its conformation and function. In this study, it was investigated the changes in the conformation and the function of the oxidized neuroserpin. Methods: Neuroserpin expressed in E. coli, BL21 or M15 harboring plasmid pQE81L containing neuroserpin cDNA. Expressed neuroserpin was purified by resin sulfopropyl A50 precharged with 0.1 M NiSO4 under denaturing condition. Neuroserpin was oxidized under oxidative stress condition in the presence of different concentration of hydrogen peroxide. The oxidation of neuroserpin was conveniently detected by a carbonyl content assay using 2, 4 dinitrophenylhydrazine. Changes in tertiary structure of neuroserpin were monitored by spectrofluorimeter to study the alteration of intrinsic fluorescence and also fluorescence of 8-anilinonaphthalin-1 sulfonic acid (ANS) in native and oxidized form of neuroserpin. Results: Total expressed neuroserpin was estimated 4-5 mg/lit in 2XYT culture media. SDS-PAGE analysis of purified neuroserpin showed a single band which reflects the efficiency of the resin SP A50 for purification of the proteins containing 6xHis tag. Carbonyl content of oxidized and native neuroserpin was estimated 12.3 ± 0.3 and 0.45 ± 0.05, respectively. The inhibitory activity of oxidized neuroserpin decreased up to 40-60 as compared with native form of neuroserpin. Intrinsic fluorescence and also the emission of ANS bind to the hydrophobic region of the protein altered from 380 to 85 and in the case of ANS from 105 to 150 in oxidized and native form of neuroserpin, respectively. Conclusion: The decreased intrinsic fluorescence intensity, an enhancement in the fluorescence of ANS, and loss of the inhibitory activity up to 40-60 in neuroserpin, all suggested a conformational modification in the protein under the oxidative stress condition. Remaining the inhibitory activity of neuroserpin reflects that the protein tolerates the oxidative stress condition effectively

Sex Differences in Severe Pulmonary Emphysema

Rationale: Limited data on sex differences in advanced COPD are available. Objectives: To compare male and female emphysema patients with severe disease. Methods: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Measurements and Main Results: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower bodymass index (BMI), shorter smoking history, less severe airflow obstruction, lower DLCO and arterial PO2, higher arterial PCO2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% predicted, age, number of packyears, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. Conclusions: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.The National Emphysema Treatment Trial (NETT) was supported by contracts with the National Heart, Lung, and Blood Institute (N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119); the Centers for Medicare and Medicaid Services (CMS; formerly the Health Care Financing Administration); and the Agency for Healthcare Research and Quality (AHRQ). J.L.C. is supported by funding from a Research Enhancement Award Program (REAP) from the Biomedical Laboratory Research & Development Service, Department of Veterans Affairs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91968/1/2007 Martinez AJRCCM Sex Differences in Empy.pd

Recombinant Lysyl Oxidase Propeptide Protein Inhibits Growth and Promotes Apoptosis of Pre-Existing Murine Breast Cancer Xenografts

Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations

ICAR: endoscopic skull‐base surgery

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The Effects of Second-hand Smoke Exposure on Breast Milk Cotinine and Infant Urinary Cotinine

Abstract: Background & Aims: Exposure to cigarette smoke affects the health of mothers and infants. The aim of this study was to examine the effects of second-hand smoke exposure on breast milk and infant urinary cotinine during breastfeeding. Methods: This cohort study was conducted on 45 breastfeeding mothers and infants exposed to second-hand cigarette smoke (exposed group), and 40 breastfeeding mothers and their infants not exposed to second-hand cigarette smoke (non-exposed group). The participants were chosen from mothers and infants who referred to one of the health centers affiliated with Tehran University of Medical Sciences, Tehran, Iran. Mothers’ breast milk and infant urine samples were collected twice at baseline (5–7 days after delivery) and 4 months after delivery. The cotinine levels in milk and urine were measured. Maternal nutritional status was assessed by 24-hour recall. All data were analyzed in SPSS. Results: There was a significant difference between the two groups regarding average level of cotinine in mothers’ breast milk, and urine of infants at baseline. This difference was also significant at 4 months postpartum (P < 0.001). Conclusion: The results showed that exposure to second-hand cigarette smoke during breastfeeding increases the cotinine level of mother's milk and infant urine at 4 months postpartum. Keywords: Second-hand smoke exposure, Breastfeeding, Cotinin

EFFECT OF HIGH TEMPERATURE OXIDATION ON THE CORROSION BEHAVIOR OF ALUMINIZED LOW CARBON STEEL IN MOLTEN ALUMINUM

Hot dip aluminizing was carried out on the low carbon steel rod under optimized conditions. The aluminized samples were further oxidized at 1000̊C in air atmosphere at two different times of 20 and 60 minutes. Microstructure study and phase analysis were studied by scanning electron microscopy and X-ray diffraction methods, respectively. The characterization of the coating showed that, Fe2 Al5 has been the major phase formed on the surface of specimen before heat treatment. Following the oxidation of the coating at high temperature, Al 2O3 was formed on the surface of coating while Fe 2 Al5 transformed into FeAl and Fe 3 Al which are favorable to the hot corrosion resistance of the coating. Corrosion resistance of aluminized samples before and after heat treatment was evaluated by rotating the samples in the molten aluminum at 700 ̊C for various times and the dissolution rate was determined. The obtained results showed that by oxidizing the coating at high temperature, the corrosion resistance of the samples in molten aluminum improves significantly

Effectiveness of mobilization with movement (Mulligan concept techniques) on low back pain: a systematic review

Objective: To evaluate evidence on the effectiveness of Mulligan techniques on low back pain. Data sources: PubMed/Medline, Scopus, Ovid, CINAHL, Embase, PEDro, Google Scholar, and Cochrane Library were searched from inception to 31 March 2018 for randomized clinical trials reporting outcomes of pain or disability in adult patients (⩾18 years) with low back pain. Review methods: Two authors screened the results and extracted data for use in this review. The risk of bias was evaluated using the Cochrane criteria. Basic information and treatment protocols were also extracted. In addition, the level of evidence of each study and strength of conclusion for pain and disability were determined. Results: A total of 20 studies with 693 patients were included. Nine trials focused on sustained natural apophyseal glide, three on spinal mobilization with limb movement and seven on bent leg raise. The results showed that Mulligan techniques can decrease pain and disability and increase range of motion in patients with low back pain; however, the strength of conclusion for pain and disability was moderate. Furthermore, inconclusive results were observed for the effectiveness of Mulligan techniques on movement speed. In this review, eight studies were categorized as low risk of bias, while 12 studies had high risk of bias. Level of evidence analysis revealed that 17 studies were classified as level of evidence B, while three studies were classified as level of evidence A2. Conclusion: Current evidence is insufficient in supporting the benefits of Mulligan techniques on pain, disability, and range of motion in low back pain patients. © 2018, The Author(s) 2018

Effectiveness of mobilization with movement (Mulligan concept techniques) on low back pain: a systematic review

Objective: To evaluate evidence on the effectiveness of Mulligan techniques on low back pain. Data sources: PubMed/Medline, Scopus, Ovid, CINAHL, Embase, PEDro, Google Scholar, and Cochrane Library were searched from inception to 31 March 2018 for randomized clinical trials reporting outcomes of pain or disability in adult patients (⩾18 years) with low back pain. Review methods: Two authors screened the results and extracted data for use in this review. The risk of bias was evaluated using the Cochrane criteria. Basic information and treatment protocols were also extracted. In addition, the level of evidence of each study and strength of conclusion for pain and disability were determined. Results: A total of 20 studies with 693 patients were included. Nine trials focused on sustained natural apophyseal glide, three on spinal mobilization with limb movement and seven on bent leg raise. The results showed that Mulligan techniques can decrease pain and disability and increase range of motion in patients with low back pain; however, the strength of conclusion for pain and disability was moderate. Furthermore, inconclusive results were observed for the effectiveness of Mulligan techniques on movement speed. In this review, eight studies were categorized as low risk of bias, while 12 studies had high risk of bias. Level of evidence analysis revealed that 17 studies were classified as level of evidence B, while three studies were classified as level of evidence A2. Conclusion: Current evidence is insufficient in supporting the benefits of Mulligan techniques on pain, disability, and range of motion in low back pain patients. © 2018, The Author(s) 2018

Relationship between self-reported exposure to passive smoking and maternal urinary cotinine level in pregnant women

Background and Objective: Passive smoking during pregnancy increases the risk of pregnancy complications. The purpose of this study was to determine the relationship between self-reported exposure to passive smoking and urinary cotinine level of the pregnant women. Materials and Methods: This cross-sectional study was done on 108 non-smoker pregnant women referred to Arash hospital in Tehran, Iran for delivery during 2010. A questionnaire including smoke exposure during pregnancy was completed for all the participants. Urine samples were collected from the mothers in the delivery room. The urinary cotinine levels was measured by ELISA method. Data were analyzed using SPSS-16, Student t-test, Chi-Square and one-way ANOVA tests. The Kappa test was used to evaluate the variability of mothers which report exposure to passive smoking with maternal urinary cotinine level. Results: The geometric mean cotinine of the maternal urine in the exposed group (27.4±29.96 ng/ml) was significantly higher than the non-exposed group (0.75±2.29 ng/ml) (P<0.05). There was a significant association between maternal reports of cigarette smoke exposure and urinary cotinine (Kappa=96%) (P<0.05). Conclusion: This study indicated that there is a relationship between maternal self-reporting and urinary cotinine level during pregnancy