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21.
Galijasevic S Saed GM Diamond MP Abu-Soud HM 《The Journal of biological chemistry》2004,279(38):39465-39470
Heme reduction of ferric lactoperoxidase (LPO) into its ferrous form initially leads to the accumulation of the unstable form of LPO-Fe(II), which spontaneously converts to a more stable species, the two of which can be identified by Soret peaks at 440 and 434 nm, respectively. Our data demonstrate that both LPO-Fe(II) species are capable of binding O(2) at a similar rate to generate the ferrous-dioxy complex. Its formation with respect to O(2) was first order and monophasic and with rate constants of k(on) = 3.8 x 10(4) m(-1) s(-1) and k(off) = 11.2 s(-1). The dissociation rate constant for the formation of LPO-Fe(II)-O(2) is relatively high, in contrast to hemoprotein model compounds. This high dissociation rate can be attributed to a combination of effects that include the positive trans effect of the proximal ligand, the heme pocket environment, and the geometry of the Fe-O(2) linkage. Our results have also shown that the decay of the LPO-Fe(II)-O(2) complex occurs by two sequential O(2)-independent steps. The first step involves formation of a short-lived intermediate that can be characterized by its Soret absorption peak at 416 nm and may be attributed to the weakening of the Fe(II)-O(2) linkage with a rate constant of 0.5 s(-1). The second step is spontaneous conversion of this intermediate to generate the native enzyme and presumably superoxide as end products with a rate constant of 0.03 s(-1). A comprehensive kinetic model that links LPO-Fe(II)-O(2) complex formation to the LPO catalase-like activity, combined with the classic catalytic cycle, is presented here. 相似文献
22.
Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus 总被引:2,自引:0,他引:2
Uncontrolled diabetes mellitus (DM) adversely affects oocyte maturation and embryo development via mechanisms that are yet unclear. Nonetheless, DM may cause uncoupling of nitric oxide synthases (NOSs) with reduction in the bioavailability of nitric oxide (NO), which is critical to maintain oocyte viability and prevent aging. The current study investigates the role of NO-mediated signaling related to oocyte aging in diabetic and nondiabetic mice. Age-related alterations in the oocytes, including ooplasmic microtubule dynamics (OMD), cortical granule (CG) status, and zona pellucida (ZP) hardening as well as the integrity of the spindle/chromatin were studied using confocal microscopy. Oocytes obtained from diabetic mice exhibited accelerated aging compared to that from nondiabetic mice. Moreover, oocytes from diabetic animals were exquisitely sensitive to NOS and guanylate cyclase (GC) inhibitors (L-NAME, ODQ), which induced aging and relatively resistant to its delay by the cGMP derivative (8-Br-cGMP). Oocytes from nondiabetic control mice displayed similar sensitivity to L-NAME in older oocytes, although to a significantly lower extent than that of DM (P < 0.04-0.0001). Despite the differences in response between DM and nonDM mice, the activation of cGMP pathway is essential to maintain the integrity of oocytes and delay oocyte aging. These findings not only indicate the role of NO signaling in the prevention of oocyte aging but also suggest enhanced aging and NO insufficiency in oocytes from diabetic mice. A comprehensive model incorporating our current findings with NOS, GC, and G kinase cycles is presented. 相似文献
23.
Abu-Soud HM Maitra D Byun J Souza CE Banerjee J Saed GM Diamond MP Andreana PR Pennathur S 《Free radical biology & medicine》2012,52(3):616-625
Overproduction of hypochlorous acid (HOCl) has been associated with the development of a variety of disorders such as inflammation, heart disease, pulmonary fibrosis, and cancer through its ability to modify various biomolecules. HOCl is a potent oxidant generated by the myeloperoxidase-hydrogen peroxide-chloride system. Recently, we have provided evidence to support the important link between higher levels of HOCl and heme destruction and free iron release from hemoglobin and RBCs. Our current findings extend this work and show the ability of HOCl to mediate the destruction of metal-ion derivatives of tetrapyrrole macrocyclic rings, such as cyanocobalamin (Cobl), a common pharmacological form of vitamin B12. Cyanocobalamin is a water-soluble vitamin that plays an essential role as an enzyme cofactor and antioxidant, modulating nucleic acid metabolism and gene regulation. It is widely used as a therapeutic agent and supplement, because of its efficacy and stability. In this report, we demonstrate that although Cobl can be an excellent antioxidant, exposure to high levels of HOCl can overcome the beneficial effects of Cobl and generate proinflammatory reaction products. Our rapid kinetic, HPLC, and mass spectrometric analyses showed that HOCl can mediate corrin ring destruction and liberate cyanogen chloride (CNCl) through a mechanism that initially involves α-axial ligand replacement in Cobl to form a chlorinated derivative, hydrolysis, and cleavage of the phosphonucleotide moiety. Additionally, it can liberate free Co, which can perpetuate metal-ion-induced oxidant stress. Taken together, these results are the first report of the generation of toxic molecular products through the interaction of Cobl with HOCl. 相似文献
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25.
J Al Suwaidi K Al Habib N Asaad R Singh A Hersi H Al Falaeh S Al Saif A Al-Motarreb W Almahmeed K Sulaiman H Amin J Al-Lawati NQ Al-Sagheer AA Alsheikh-Ali AM Salam 《BMC cardiovascular disorders》2012,12(1):64
ABSTRACT: BACKGROUND: Stroke is a potential complication of acute coronary syndrome (ACS). The aim of this study was to identify the prevalence, risk factors predisposing to stroke, in-hospital and 1-year mortality among patients presenting with ACS in the Middle East. METHODS: For a period of 9 months in 2008 to 2009, 7,930 consecutive ACS patients were enrolled from 65 hospitals in 6 Middle East countries. RESULTS: The prevalence of in-hospital stroke following ACS was 0.70%. Most cases were ST segment elevation MI-related (STEMI) and ischemic stroke in nature. Patients with in-hospital stroke were 5 years older than patients without stroke and were more likely to have hypertension (66% vs. 47.6%, P = 0.001). There were no differences between the two groups in regards to gender, other cardiovascular risk factors, or prior cardiovascular disease. Patients with stroke were more likely to present with atypical symptoms, advanced Killip class and less likely to be treated with evidence-based therapies. Independent predictors of stroke were hypertension, advanced killip class, ACS type --STEMI and cardiogenic shock. Stroke was associated with increased risk of in-hospital (39.3% vs. 4.3%) and one-year mortality (52% vs. 12.3%). CONCLUSION: There is low incidence of in-hospital stroke in Middle-Eastern patients presenting with ACS but with very high in-hospital and one-year mortality rates. Stroke patients were less likely to be appropriately treated with evidence-based therapy. Future work should be focused on reducing the risk and improving the outcome of this devastating complication. 相似文献
26.
Cook MB Graubard BI Quraishi SM Yeager M Chanock SJ Crenshaw A Erickson RL Rubertone MV Thomas G McGlynn KA 《Human genetics》2008,123(4):409-418
Much evidence supports the premise that population genetic variation contributes significantly to the risk of testicular germ-cell
tumor (TGCT). However, investigations of the association between genomic markers and TGCT susceptibility are scarce. Single
nucleotide polymorphisms (SNPs) at the locus 8q24 have recently been found to be associated with prostate, colorectal and
breast cancer. The US Servicemen’s testicular tumor environmental and endocrine determinants (STEED) study was used to investigate
the association of 15 specific 8q24 SNPs with TGCT and its two main histologic groups of seminoma and nonseminoma. Conditional
and unconditional logistic regression models, adjusted for the matching variables of year of birth, race/ethnicity and serum
date, were utilized to produce odds ratios (OR) and 95% confidence intervals (95%CI). The analysis included 680 controls and
568 TGCT cases. In the TGCT analysis, no SNP was associated with risk in both heterozygotes and variant homozygotes. When
stratified by histology the seminoma analysis also showed no association with the 8q24 SNPs. Conversely, the analysis of nonseminomas
had three tentative associations (rs6470494, ORgenotype AG = 1.15, 95%CI: 0.86–1.54; ORgenotype GG = 1.68, 95%CI: 1.04–2.73; p for trend = 0.04) (rs13254738, ORgenotype GT = 1.04, 95%CI: 0.77–1.40; ORgenotype TT = 1.62, 95%CI: 1.06–2.49; p for trend = 0.07) (rs10505476, ORgenotype CT = 0.67, 95%CI: 0.50, 0.91; ORgenotype TT = 0.81, 95%CI: 0.47–1.39; p for trend = 0.04). There was no linkage disequilibrium between any of the 8q24 SNPs analyzed in this population. In conclusion,
this study has found little evidence for an association between the reported 8q24 SNPs and TGCTs, although the findings for
nonseminoma may be worth further investigation. 相似文献
27.
Development and Optimization of a Novel Immunomagnetic Separation- Bacteriophage Assay for Detection of Salmonella enterica Serovar Enteritidis in Broth 总被引:1,自引:0,他引:1
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Salmonella is the second-leading cause of food-borne illness in most developed countries, causing diarrhea, cramps, vomiting, and often fever. Many rapid methods are available for detection of Salmonella in foods, but these methods are often insensitive or expensive or require a high degree of technical ability to perform. In this paper we describe development and characterization of a novel assay that utilizes the normal infection cycle of bacteriophage SJ2 for detection of Salmonella enterica serovar Enteritidis in broth. The assay consists of four main stages: (i) capture and concentration of target cells by using immunomagnetic separation (IMS); (ii) infection of the target bacterium with phage; (iii) amplification and recovery of progeny phage; and (iv) assay of progeny phage on the basis of their effect on a healthy population of host cells (signal-amplifying cells). The end point of the assay can be determined by using either fluorescence or optical density measurements. The detection limit of the assay in broth is less than 104 CFU/ml, and the assay can be performed in 4 to 5 h. The results of this study demonstrate that the IMS-bacteriophage assay is a rapid, simple, and sensitive technique for detection of Salmonella serovar Enteritidis in broth cultures which can be applied to preenriched food samples. 相似文献
28.
29.
The present study explores the role of the meteorological variability in the pollen production and the timing of the airborne pollen season by analysis of the correlation between precipitation, insolation and temperature and the main standardised airborne pollen parameters of 22 taxa collected at 6 localities in Catalonia (NE Spain). The pollen parameters included in the study were: Annual Pollen Integral and the Start, End and Length of the Main Pollen Season. Considering that the Main Pollen Season of most of the taxa in Catalonia lasts from spring to summer or autumn, correlations between the pollen parameters and winter (from December to March) values of meteorological variables were calculated. Correlations between Monthly Pollen Integral and monthly values of the meteorological variables were also calculated. The results obtained report the synchronism registered in the variations of pollen concentration with precipitation (negative), insolation (positive) and temperature (positive). Temperature was the meteorological variable that showed a greater influence in the pollen production and the timing of the pollen season, being insolation the least one. The Start of the Main Pollen Season was the pollen parameter more correlated with the meteorological variables, especially with winter temperatures. 相似文献
30.
Qiu Jiang Narendra Kurra Mohamed Alhabeb Yury Gogotsi Husam N. Alshareef 《Liver Transplantation》2018,8(13)
2D transition metal carbides and nitrides, known as MXenes, are an emerging class of 2D materials with a wide spectrum of potential applications, in particular in electrochemical energy storage. The hydrophilicity of MXenes combined with their metallic conductivity and surface redox reactions is the key for high‐rate pseudocapacitive energy storage in MXene electrodes. However, symmetric MXene supercapacitors have a limited voltage window of around 0.6 V due to possible oxidation at high anodic potentials. In this study, the fact that titanium carbide MXene (Ti3C2Tx) can operate at negative potentials in acidic electrolyte is exploited, to design an all‐pseudocapacitive asymmetric device by combining it with a ruthenium oxide (RuO2) positive electrode. This asymmetric device operates at a voltage window of 1.5 V, which is about two times wider than the operating voltage window of symmetric MXene supercapacitors, and is the widest voltage window reported to date for MXene‐based supercapacitors. The complementary working potential windows of MXene and RuO2, along with proton‐induced pseudocapacitance, significantly enhance the device performance. As a result, the asymmetric devices can deliver an energy density of 37 µW h cm?2 at a power density of 40 mW cm?2, with 86% capacitance retention after 20 000 charge–discharge cycles. These results show that pseudocapacitive negative MXene electrodes can potentially replace carbon‐based materials in asymmetric electrochemical capacitors, leading to an increased energy density. 相似文献