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Sample records for oxygenase-1 protects donor

  1. Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction

    International Nuclear Information System (INIS)

    Nakao, Atsunori; Kaczorowski, David J.; Zuckerbraun, Brian S.; Lei Jing; Faleo, Gaetano; Deguchi, Kentaro; McCurry, Kenneth R.; Billiar, Timothy R.; Kanno, Shinichi

    2008-01-01

    Galantamine, a reversible inhibitor of acetylcholine esterase (AChE), is a novel drug treatment for mild to moderate Alzheimer's disease and vascular dementia. Interestingly, it has been suggested that galantamine treatment is associated with more clinical benefit in patients with mild-to-moderate Alzheimer disease compared to other AChE inhibitors. We hypothesized that the protective effects of galantamine would involve induction of the protective gene, heme oxygenase-1 (HO-1), in addition to enhancement of the cholinergic system. Brain microvascular endothelial cells (mvECs) were isolated from spontaneous hypertensive rats. Galantamine significantly reduced H 2 O 2 -induced cell death of mvECs in association with HO-1 induction. These protective effects were completely reversed by nuclear factor-κB (NF-κB) inhibition or HO inhibition. Furthermore, galantamine failed to induce HO-1 in mvECs which lack inducible nitric oxide synthase (iNOS), supplementation of a nitric oxide (NO) donor or iNOS gene transfection on iNOS-deficient mvECs resulted in HO-1 induction with galantamine. These data suggest that the protective effects of galantamine require NF-κB activation and iNOS expression, in addition to HO-1. Likewise, carbon monoxide (CO), one of the byproducts of HO, up-regulated HO-1 and protected mvECs from oxidative stress in a similar manner. Our data demonstrate that galantamine mediates cytoprotective effects on mvECs through induction HO-1. This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease

  2. UVA-induced protection of skin through the induction of heme oxygenase-1.

    Science.gov (United States)

    Xiang, Yuancai; Liu, Gang; Yang, Li; Zhong, Julia Li

    2011-12-01

    UVA (320-400 nm) and UVB (290-320 nm) are the major components of solar UV irradiation, which is associated with various pathological conditions. UVB causes direct damage to DNA of epidermal cells and is mainly responsible for erythema, immunosuppression, photoaging, and skin cancer. UVA has oxidizing properties that can cause damage or enhance UVB damaging effects on skin. On the other hand, UVA can also lead to high levels of heme oxygenase-1 (HO-1) expression of cells that can provide an antioxidant effect on skin as well as anti-inflammatory properties in mammals and rodents. Therefore, this review focuses on the potential protection of UVA wavebands for the skin immune response, instead of mechanisms that underlie UVA-induced damage. Also, the role of HO-1 in UVA-mediated protection against UVB-induced immunosuppression in skin will be summarized. Thus, this review facilitates further understanding of potential beneficial mechanisms of UVA irradiation, and using the longer UVA (UVA1, 340-400 nm) in combination with HO-1 for phototherapy and skin protection against sunlight exposure.

  3. [Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

    Science.gov (United States)

    Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

    2010-12-14

    To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (PhHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

  4. Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase.

    Science.gov (United States)

    Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F

    2013-08-01

    The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.

  5. Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system.

    Science.gov (United States)

    Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

    2004-04-01

    Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, PhHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.

  6. Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals

    International Nuclear Information System (INIS)

    Lawal, Akeem O.; Zhang, Min; Dittmar, Michael; Lulla, Aaron; Araujo, Jesus A.

    2015-01-01

    Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4 h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25 μg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM. - Highlights: • We examined the role of HO-1 expression on diesel exhaust particle (DEP) in endothelial cells. • DEPs exert cytotoxic and inflammatory effects on human microvascular endothelial cells (HMECs). • DEPs induce HO-1 expression in HMECs. • HO-1 protects against the oxidative stress induced by DEps. • HO-1 attenuates the proinflammatory effects

  7. Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Lawal, Akeem O.; Zhang, Min; Dittmar, Michael [Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095 (United States); Lulla, Aaron [Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095 (United States); Molecular Toxicology Interdepartmental Program, University of California, Los Angeles (United States); Araujo, Jesus A., E-mail: JAraujo@mednet.ucla.edu [Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095 (United States); Molecular Toxicology Interdepartmental Program, University of California, Los Angeles (United States); Molecular Biology Institute, University of California, Los Angeles (United States)

    2015-05-01

    Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4 h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25 μg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM. - Highlights: • We examined the role of HO-1 expression on diesel exhaust particle (DEP) in endothelial cells. • DEPs exert cytotoxic and inflammatory effects on human microvascular endothelial cells (HMECs). • DEPs induce HO-1 expression in HMECs. • HO-1 protects against the oxidative stress induced by DEps. • HO-1 attenuates the proinflammatory effects

  8. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Chenglong [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zheng, Haining [Department of Hyperbaric Oxygen, Nanjing General Hospital of Nanjing Military Command, Nanjing (China); Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Ding, Dafa, E-mail: dingdafa2004@aliyun.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China); Lu, Yibing, E-mail: luyibing2004@126.com [Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2015-10-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK.

  9. Heme oxygenase-1 enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis

    International Nuclear Information System (INIS)

    Dong, Chenglong; Zheng, Haining; Huang, Shanshan; You, Na; Xu, Jiarong; Ye, Xiaolong; Zhu, Qun; Feng, Yamin; You, Qiang; Miao, Heng; Ding, Dafa; Lu, Yibing

    2015-01-01

    Injury and loss of podocytes play vital roles in diabetic nephropathy progression. Emerging evidence suggests autophagy, which is induced by multiple stressors including hyperglycemia, plays a protective role. Meanwhile, heme oxygenase-1 (HO-1) possesses powerful anti-apoptotic properties. Therefore, we investigated the impact of autophagy on podocyte apoptosis under diabetic conditions and its association with HO-1. Mouse podocytes were cultured in vitro; apoptosis was detected by flow cytometry. Transmission electron microscopy and biochemical autophagic flux assays were used to measure the autophagy markers microtubule-associated protein 1 light chain 3-II (LC3-II) and beclin-1. LC3-II and beclin-1 expression peaked 12–24 h after exposing podocytes to high glucose. Inhibition of autophagy with 3-methyladenine or Beclin-1 siRNAs or Atg 5 siRNAs sensitized cells to apoptosis, suggesting autophagy is a survival mechanism. HO-1 inactivation inhibited autophagy, which aggravated podocyte injury in vitro. Hemin-induced autophagy also protected podocytes from hyperglycemia in vitro and was abrogated by HO-1 siRNA. Adenosine monophosphate-activated protein kinase phosphorylation was higher in hemin-treated and lower in HO-1 siRNA-treated podocytes. Suppression of AMPK activity reversed HO-1-mediated Beclin-1 upregulation and autophagy, indicating HO-1-mediated autophagy is AMPK dependent. These findings suggest HO-1 induction and regulation of autophagy are potential therapeutic targets for diabetic nephropathy. - Highlights: • High glucose leads to increased autophagy in podocytes at an early stage. • The early autophagic response protects against high glucose-induced apoptosis. • Heme oxygenase-1 enhances autophagy and decreases high glucose -mediated apoptosis. • Heme oxygenase-1 induces autophagy through the activation of AMPK

  10. Effect of heme oxygenase-1 on the protection of ischemia reperfusion injury of bile duct in rats after liver transplantation.

    Science.gov (United States)

    Zhan, Xi; Zhang, Zhiqing; Huang, Hanfei; Zhang, Yujun; Zeng, Zhong

    2018-06-01

    To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic reperfusion injury (IRI) of bile duct in rat models after liver transplantation. 320 SD rats were equally and randomly divided into 5 groups, which were group A receiving injection of 3×10 8 /pfu/ml adenovirus (adv), group B with donor receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA and recipient receiving Adv-HO-1, and group E with donor and recipient both receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was stored in UW liquid at 4°C followed by measuring HO-1 level by western blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated for analysis of liver function, inflammatory cell infiltration by H&E staining, ultrastructure of liver by transmission electron microscopy as well as the expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. Compared with group D and E, group B and C displayed improved liver function as demonstrated by lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced inflammatory cells infiltration and liver injury. Our study demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage to bile duct and liver, and improved liver function, suggesting HO-1 might be a new therapeutic target in the treatment of IRI after liver transplantation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Epigallocatechin-3-gallate (EGCG) protects skin cells from ionizing radiation via heme oxygenase-1 (HO-1) overexpression

    International Nuclear Information System (INIS)

    Zhu Wei; Xu Jing; Ge Yangyang

    2014-01-01

    Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, is a potent antioxidant and free radical scavenger that may have therapeutic applications for the treatment of many disorders. Radiation therapy is widely used for the treatment of various types of cancers; however, radiation-induced skin injury remains a serious concern. EGCG has not yet been reported as protecting skin cells against ionizing radiation. In the present study, we investigated whether EGCG confers cytoprotection against ionizing radiation. We found that, compared with the control, pretreatment with EGCG significantly enhanced the viability of human skin cells that were irradiated with X-rays, and decreased apoptosis induced by X-ray irradiation. Mito-Tracker assay showed that EGCG suppressed the damage to mitochondria induced by ionizing radiation via upregulation of SOD2. Reactive oxygen species (ROS) in HaCaT cells were significantly reduced when pretreated with EGCG before irradiation. Radiation-induced γH2AX foci, which are representative of DNA double-strand breaks, were decreased by pretreatment with EGCG. Furthermore, EGCG induced the expression of the cytoprotective molecule heme oxygenase-1 (HO-1) in a dose-dependent manner via transcriptional activation. HO-1 knockdown or treatment with the HO-1 inhibitor tin protoporphyrin (SnPPIX) reversed the protective role of EGCG, indicating an important role for HO-1. These results suggest that EGCG offers a new strategy for protecting skin against ionizing radiation. (author)

  12. Heme oxygenase-1 dependant pathway contributes to protection by tetramethylpyrazine against chronic hypoxic injury on medulla oblongata in rats.

    Science.gov (United States)

    Ding, Yan; Hou, Xuefei; Chen, Li; Zhou, Hua; Gong, Yanju; Dai, Liqun; Zheng, Yu

    2016-02-15

    Tetramethylpyrazine (TMP), one of the active ingredients of the Chinese herb Lingusticum Wallichii (Chuan Xiong) has been proved to protect the medulla oblongata from chronic hypoxia injury. However, the underlying mechanism remains unclear. The purpose of this study was to determine whether the protective effects of TMP are associated with the heme oxygenase-1 (HO-1) dependant pathway in adult rats. The morphological changes of neurons in the hypoglossal nucleus (12N), the nucleus ambiguus (Amb), the nucleus tractus solitarius (NTS), and the pre-Bötzinger complex (pre-BötC) were investigated by Nissl staining; the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured to evaluate the anti-oxidant effect; some apoptosis parameters, Bax mRNA and Bcl-2 mRNA, were tested; and the double immunochemistry staining of active caspase-3/NeuN was performed. Meanwhile, the HO-1 protein expression and heme oxygenase (HO) activity were examined. Tin-protoporphyrin (SnPP), a potent inhibitor of HO, was used to further confirm the effect of HO-1. We found that TMP ameliorated the neuron loss in 12N, Amb and NTS, the decrease in SOD activity and the increase in MDA content, the decrease in Bcl-2 mRNA of medulla oblongata (Pmedulla oblongata in the rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1.

    Science.gov (United States)

    Zhang, Meijuan; Wang, Suping; Mao, Leilei; Leak, Rehana K; Shi, Yejie; Zhang, Wenting; Hu, Xiaoming; Sun, Baoliang; Cao, Guodong; Gao, Yanqin; Xu, Yun; Chen, Jun; Zhang, Feng

    2014-01-29

    Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.

  14. Heme oxygenase-1 expression protects melanocytes from stress-induced cell death: implications for vitiligo

    NARCIS (Netherlands)

    Elassiuty, Yasser E.; Klarquist, Jared; Speiser, Jodi; Yousef, Randa M.; El Refaee, Abdelaziz A.; Hunter, Nahla S.; Shaker, Olfat G.; Gundeti, Mohan; Nieuweboer-Krobotova, Ludmila; Caroline Le Poole, I.

    2011-01-01

    To study protection of melanocytes from stress-induced cell death by heme oxygenases during depigmentation and repigmentation in vitiligo, expression of isoforms 1 and 2 was studied in cultured control and patient melanocytes and normal skin explants exposed to UV or bleaching agent 4-TBP.

  15. Adenoviral transfer of the heme oxygenase-1 gene protects striatal astrocytes from heme-mediated oxidative injury.

    Science.gov (United States)

    Teng, Zhi-Ping; Chen, Jing; Chau, Lee-Young; Galunic, Nicholas; Regan, Raymond F

    2004-11-01

    Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is a neurotoxin that is present in intracranial hematomas. In a prior study, we observed that HO inhibitors increased the vulnerability of cultured cortical astrocytes to heme-mediated oxidative injury. To investigate the effect of HO more specifically, we used an adenoviral vector encoding the human HO-1 gene to specifically increase HO-1 expression. Incubation with 100 MOI of the HO-1 adenovirus (Adv-HHO-1) for 24 h increased both HO-1 protein and HO activity; a control adenovirus lacking the HO-1 gene had no effect. Using a DNA probe that was specific for human HO-1, 80.5 +/- 7.2% of astrocytes were observed to be infected by in situ hybridization. The cell death produced by 30-60 microM hemin was significantly reduced by pretreatment with 100 MOI Adv-HHO-1, as assessed by LDH release, propidium iodide exclusion, and MTT reduction assay. The threefold increase in cell protein oxidation produced by hemin was also attenuated in cultures pretreated with Adv-HHO-1. These results support the hypothesis that HO-1 protects astrocytes from heme-mediated oxidative injury. Specifically increasing astrocytic HO-1 by gene transfer may have a beneficial effect on hemorrhagic CNS injury.

  16. Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice

    Science.gov (United States)

    Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B.; Carter, A. Brent; Rowe, Steven M.; Matalon, Sadis; Thannickal, Victor J.; Agarwal, Anupam

    2015-01-01

    Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1+/+, HO-1−/−, and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1−/− mice exhibited more severe emphysema compared with HO-1+/+ or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1+/+, HO-1−/−, and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1−/− PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1+/+ PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema. PMID:26071551

  17. Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice.

    Science.gov (United States)

    Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B; Carter, A Brent; Rowe, Steven M; Matalon, Sadis; Thannickal, Victor J; Agarwal, Anupam; Antony, Veena B

    2015-08-01

    Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1(+/+), HO-1(-/-), and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1(-/-) mice exhibited more severe emphysema compared with HO-1(+/+) or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1(+/+), HO-1(-/-), and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1(-/-) PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1(+/+) PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema. Copyright © 2015 the American Physiological Society.

  18. Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS.

    Science.gov (United States)

    Pereira, Marcelo L M; Ortolan, Luana S; Sercundes, Michelle K; Debone, Daniela; Murillo, Oscar; Lima, Flávia A; Marinho, Claudio R F; Epiphanio, Sabrina

    2016-01-01

    Malaria is a serious disease, caused by the parasite of the genus Plasmodium , which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected with Plasmodium berghei ANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset of MA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans.

  19. Fibroblast growth factor 10 protects neuron against oxygen–glucose deprivation injury through inducing heme oxygenase-1

    International Nuclear Information System (INIS)

    Li, Yong-Hua; Yang, Li-Ye; Chen, Wei; Li, Ying-Ke; Yuan, Hong-Bin

    2015-01-01

    Highlights: • FGF10 attenuates OGD induced injury in cortical neuron. • FGF10 reduces OGD triggered ROS level in cortical neuron. • FGF10 induces HO-1 expression upon OGD stimuli in cortical neuron. • Knockdown of HO-1 impairs the neuroprotection of FGF10 in OGD model. - Abstract: Fibroblast growth factors (FGFs) are a family of structurally related heparin-binding proteins with diverse biological functions. FGFs participate in mitogenesis, angiogenesis, cell proliferation, development, differentiation and cell migration. Here, we investigated the potential effect of FGF10, a member of FGFs, on neuron survival in oxygen–glucose deprivation (OGD) model. In primary cultured mouse cortical neurons upon OGD, FGF10 treatment (100 and 1000 ng/ml) attenuated the decrease of cell viability and rescued the LDH release. Tuj-1 immunocytochemistry assay showed that FGF10 promoted neuronal survival. Apoptosis assay with Annexin V + PI by flow cytometry demonstrated that FGF10 treatment reduced apoptotic cell proportion. Moreover, immunoblotting showed that FGF10 alleviated the cleaved caspase-3 upregulation caused by OGD. FGF10 treatment also depressed the OGD-induced increase of caspase-3, -8 and -9 activities. At last, we found FGF10 triggered heme oxygenase-1 (HO-1) protein expression rather than hypoxia-inducible factor-1 (HIF-1), AMP-activated protein kinase (AMPK) signaling and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Knockdown of HO-1 by siRNA partly abolished the neuroprotection of FGF10 in OGD model. In summary, our observations provide the first evidence for the neuroprotective function of FGF10 against ischemic neuronal injury and suggest that FGF10 may be a promising agent for treatment of ischemic stroke

  20. Fibroblast growth factor 10 protects neuron against oxygen–glucose deprivation injury through inducing heme oxygenase-1

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yong-Hua; Yang, Li-Ye; Chen, Wei; Li, Ying-Ke, E-mail: liyingke6f@126.com; Yuan, Hong-Bin, E-mail: yuanhongbin6f@126.com

    2015-01-02

    Highlights: • FGF10 attenuates OGD induced injury in cortical neuron. • FGF10 reduces OGD triggered ROS level in cortical neuron. • FGF10 induces HO-1 expression upon OGD stimuli in cortical neuron. • Knockdown of HO-1 impairs the neuroprotection of FGF10 in OGD model. - Abstract: Fibroblast growth factors (FGFs) are a family of structurally related heparin-binding proteins with diverse biological functions. FGFs participate in mitogenesis, angiogenesis, cell proliferation, development, differentiation and cell migration. Here, we investigated the potential effect of FGF10, a member of FGFs, on neuron survival in oxygen–glucose deprivation (OGD) model. In primary cultured mouse cortical neurons upon OGD, FGF10 treatment (100 and 1000 ng/ml) attenuated the decrease of cell viability and rescued the LDH release. Tuj-1 immunocytochemistry assay showed that FGF10 promoted neuronal survival. Apoptosis assay with Annexin V + PI by flow cytometry demonstrated that FGF10 treatment reduced apoptotic cell proportion. Moreover, immunoblotting showed that FGF10 alleviated the cleaved caspase-3 upregulation caused by OGD. FGF10 treatment also depressed the OGD-induced increase of caspase-3, -8 and -9 activities. At last, we found FGF10 triggered heme oxygenase-1 (HO-1) protein expression rather than hypoxia-inducible factor-1 (HIF-1), AMP-activated protein kinase (AMPK) signaling and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Knockdown of HO-1 by siRNA partly abolished the neuroprotection of FGF10 in OGD model. In summary, our observations provide the first evidence for the neuroprotective function of FGF10 against ischemic neuronal injury and suggest that FGF10 may be a promising agent for treatment of ischemic stroke.

  1. Edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating heme oxygenase-1 expression.

    Science.gov (United States)

    Cheng, Baohua; Guo, Yunliang; Li, Chuangang; Ji, Bingyuan; Pan, Yanyou; Chen, Jing; Bai, Bo

    2014-08-15

    Oxidative stress is involved in the pathogenesis of Parkinson's disease (PD). Edaravone has been shown to have a neuroprotective effect. In the present work, we investigated the effect of edaravone on 1-methyl-4-phenylpyridinium (MPP(+))-treated PC12 cells. Edaravone inhibited the decrease of cell viability and apoptosis induced by MPP(+) in PC12 cells. In addition, edaravone alleviated intracellular reactive oxygen species (ROS) production. MPP(+) induced heme oxygenase-1 (HO-1) expression, which was further enhanced by edaravone. The inhibitor of HO-1 zinc protoporphyrin-IX attenuated the neuroprotection of edaravone. So edaravone protected PC12 cells against MPP(+)-cytoxicity via inhibiting oxidative stress and up-regulating HO-1 expression. The data showed that edaravone was neuroprotective and could be potentially therapeutics for PD in future. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The in vitro protection of human decay accelerating factor and hDAF/heme oxygenase-1 transgenes in porcine aortic endothelial cells against sera of Formosan macaques.

    Science.gov (United States)

    Tu, C-F; Tai, H-C; Wu, C-P; Ho, L-L; Lin, Y-J; Hwang, C-S; Yang, T-S; Lee, J-M; Tseng, Y-L; Huang, C-C; Weng, C-N; Lee, P-H

    2010-01-01

    To mitigate hyperacute rejection, pigs have been generated with alpha-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC), an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15% MS reduced survived to 40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However, comparing with 10% MS and HS in pAEC of nontransgenic pigs, the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Eriodictyol Protects Endothelial Cells against Oxidative Stress-Induced Cell Death through Modulating ERK/Nrf2/ARE-Dependent Heme Oxygenase-1 Expression.

    Science.gov (United States)

    Lee, Seung Eun; Yang, Hana; Son, Gun Woo; Park, Hye Rim; Park, Cheung-Seog; Jin, Young-Ho; Park, Yong Seek

    2015-06-26

    The pathophysiology of cardiovascular diseases is complex and may involve oxidative stress-related pathways. Eriodictyol is a flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-cancer, neurotrophic, and antioxidant effects in a range of pathophysiological conditions including vascular diseases. Because oxidative stress plays a key role in the pathogenesis of cardiovascular disease, the present study was designed to verify whether eriodictyol has therapeutic potential. Upregulation of heme oxygenase-1 (HO-1), a phase II detoxifying enzyme, in endothelial cells is considered to be helpful in cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with eriodictyol showed the upregulation of HO-1 through extracellular-regulated kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further, eriodictyol treatment provided protection against hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in cardiovascular disease.

  4. Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved.

    Science.gov (United States)

    Cao, Huifang; Feng, Ying; Ning, Yunye; Zhang, Zinan; Li, Weihao; Li, Qiang

    2015-01-01

    Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism. We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors. The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells. This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia-induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway.

  5. Heme oxygenase-1 mediates the protective effects of ischemic preconditioning on mitigating lung injury induced by lower limb ischemia-reperfusion in rats.

    Science.gov (United States)

    Peng, Tsui-Chin; Jan, Woan-Ching; Tsai, Pei-Shan; Huang, Chun-Jen

    2011-05-15

    Lower limb ischemia-reperfusion (I/R) imposes oxidative stress, elicits inflammatory response, and subsequently induces acute lung injury. Ischemic preconditioning (IP), a process of transient I/R, mitigates the acute lung injury induced by I/R. We sought to elucidate whether the protective effects of IP involve heme oxygenase-1 (HO-1). Adult male rats were randomized to receive I/R, I/R plus IP, I/R plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by reperfusion for 3 h. To achieve IP, three cycles of bilateral lower limb I/R (i.e., ischemia for 10 min followed by reperfusion for 10 min) were performed. IP was performed immediately before I/R. After sacrifice, degree of lung injury was determined. Histologic findings, together with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that I/R induced acute lung injury. I/R also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E(2) concentrations), imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations), and up-regulated HO-1 expression in lung tissues. IP significantly enhanced HO-1 up-regulation and, in turn, mitigated oxidative stress, inflammatory response, and acute lung injury induced by I/R. In addition, the protective effects of IP were counteracted by SnPP. The protective effects of IP on mitigating acute lung injury induced by lower limb I/R are mediated by HO-1. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. MAPK/JNK1 activation protects cells against cadmium-induced autophagic cell death via differential regulation of catalase and heme oxygenase-1 in oral cancer cells.

    Science.gov (United States)

    So, Keum-Young; Kim, Sang-Hun; Jung, Ki-Tae; Lee, Hyun-Young; Oh, Seon-Hee

    2017-10-01

    Antioxidant enzymes are related to oral diseases. We investigated the roles of heme oxygenase-1 (HO-1) and catalase in cadmium (Cd)-induced oxidative stress and the underlying molecular mechanism in oral cancer cells. Exposing YD8 cells to Cd reduced the expression levels of catalase and superoxide dismutase 1/2 and induced the expression of HO-1 as well as autophagy and apoptosis, which were reversed by N-acetyl-l-cysteine (NAC). Cd-exposed YD10B cells exhibited milder effects than YD8 cells, indicating that Cd sensitivity is associated with antioxidant enzymes and autophagy. Autophagy inhibition via pharmacologic and genetic modulations enhanced Cd-induced HO-1 expression, caspase-3 cleavage, and the production of reactive oxygen species (ROS). Ho-1 knockdown increased autophagy and apoptosis. Hemin treatment partially suppressed Cd-induced ROS production and apoptosis, but enhanced autophagy and CHOP expression, indicating that autophagy induction is associated with cellular stress. Catalase inhibition by pharmacological and genetic modulations increased Cd-induced ROS production, autophagy, and apoptosis, but suppressed HO-1, indicating that catalase is required for HO-1 induction. p38 inhibition upregulated Cd-induced phospho-JNK and catalase, but suppressed HO-1, autophagy, apoptosis. JNK suppression exhibited contrary results, enhancing the expression of phospho-p38. Co-suppression of p38 and JNK1 failed to upregulate catalase and procaspase-3, which were upregulated by JNK1 overexpression. Overall, the balance between the responses of p38 and JNK activation to Cd appears to have an important role in maintaining cellular homeostasis via the regulation of antioxidant enzymes and autophagy induction. In addition, the upregulation of catalase by JNK1 activation can play a critical role in cell protection against Cd-induced oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Jin; Kang, Hyung Kyung [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Song, Dong Keun [Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik; Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil, E-mail: hykwon@hallym.ac.kr [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2015-06-05

    Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner. PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction.

  8. Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

    International Nuclear Information System (INIS)

    Lee, Su Jin; Kang, Hyung Kyung; Song, Dong Keun; Eum, Won Sik; Park, Jinseu; Choi, Soo Young; Kwon, Hyeok Yil

    2015-01-01

    Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner. PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction

  9. Kidney injury and heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Hai-xing MAI

    2012-02-01

    Full Text Available     Heme oxygenase-1 (HO-1 is one of the main pathways to degrade heme in mammals, and the main degradation products are free iron (Fe2+, carbon monoxide (CO, and bilirubin. Heme plays an important role in promoting cell survival, circulation of intracellular substrates, and immune regulation. Previous studies suggest that HO-1 pathway is an important internal factor in determining the susceptibility and severity of acute kidney injury (AKI. The induction of HO-1 expression can attenuate the severity of renal ischemia-reperfusion injury (IRI, and the inhibition of HO-1 expression will aggravate IRI. The present article summarizes the latest advances in research abroad and at home on protective mechanism by which HO-1 prevents AKI to further deepen our understanding of the role of HO-1 in the treatment of AKI.   

  10. Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood.

    Science.gov (United States)

    Ahrens, Hellen E; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2015-07-01

    Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a (51)Chromium release assay and by ex vivo kidney perfusions with human blood. Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation.

  11. Red Yeast Rice Protects Circulating Bone Marrow-Derived Proangiogenic Cells against High-Glucose-Induced Senescence and Oxidative Stress: The Role of Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Jung-Tung Liu

    2017-01-01

    Full Text Available The inflammation and oxidative stress of bone marrow-derived proangiogenic cells (PACs, also named endothelial progenitor cells, triggered by hyperglycemia contributes significantly to vascular dysfunction. There is supporting evidence that the consumption of red yeast rice (RYR; Monascus purpureus-fermented rice reduces the vascular complications of diabetes; however, the underlying mechanism remains unclear. This study aimed to elucidate the effects of RYR extract in PACs, focusing particularly on the role of a potent antioxidative enzyme, heme oxygenase-1 (HO-1. We found that treatment with RYR extract induced nuclear factor erythroid-2-related factor nuclear translocation and HO-1 mRNA and protein levels in PACs. RYR extract inhibited high-glucose-induced (30 mM PAC senescence and the development of reactive oxygen species (ROS in a dose-dependent manner. The HO-1 inducer cobalt protoporphyrin IX also decreased high-glucose-induced cell senescence and oxidative stress, whereas the HO-1 enzyme inhibitor zinc protoporphyrin IX and HO-1 small interfering RNA significantly reversed RYR extract-caused inhibition of senescence and reduction of oxidative stress in high-glucose-treated PACs. These results suggest that RYR extract serves as alternative and complementary medicine in the treatment of these diseases, by inducing HO-1, thereby decreasing the vascular complications of diabetes.

  12. Heme oxygenase-1, oxidation, inflammation and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jesus A Araujo

    2012-07-01

    Full Text Available Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1 is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of heme oxygenase, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This article reviews the evidence that supports the antiatherogenic role of HO-1, potential pathways and mechanisms mediating

  13. Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells

    International Nuclear Information System (INIS)

    Hwang, Yong Pil; Jeong, Hye Gwang

    2010-01-01

    Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a popular traditional herbal medicine. Ginsenoside Rb1 (Rb1), an active component commonly found in ginseng root, is a phytoestrogen that exerts estrogen-like activity. In this study, we demonstrate that the phytoestrogen Rb1 inhibits 6-hydroxydopamine (6-OHDA)-induced oxidative injury via an ER-dependent Gβ1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of SH-SY5Y cells with Rb1 significantly reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. Rb1 also up-regulated HO-1 expression, which conferred cytoprotection against 6-OHDA-induced oxidative injury. Moreover, Rb1 induced both Nrf2 nuclear translocation, which is upstream of HO-1 expression and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Also, Rb1-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that Rb1 augments the cellular antioxidant defenses through ER-dependent HO-1 induction via the Gβ1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress. Thus our study indicates that Rb1 has a partial cytoprotective role in dopaminergic cell culture systems.

  14. Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats.

    Science.gov (United States)

    Yen, Ting-Lin; Chen, Ray-Jade; Jayakumar, Thanasekaran; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsu, Ming-Jen; Yang, Chih-Hao; Chang, Chao-Chien; Lin, Yen-Kuang; Lin, Kuan-Hung; Sheu, Joen-Rong

    2016-04-01

    Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years because of its various pharmacologic activities. We determined that andrographolide modulates the mitogen-activated protein kinase (MAPK)-Nrf2-HO-1 signaling cascade in primary cerebral endothelial cells (CECs) to provide positive protection against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in rats. In the present study, andrographolide (10 μM) increased HO-1 protein and messenger RNA expressions, Nrf2 phosphorylation, and nuclear translocation in CECs, and these activities were disrupted by a p38 MAPK inhibitor, SB203580, but not by the extracellular signal-regulated kinase inhibitor PD98059 or c-Jun amino-terminal kinase inhibitor SP600125. Similar results were observed in confocal microscopy analysis. Moreover, andrographolide-induced Nrf2 and HO-1 protein expressions were significantly inhibited by Nrf2 small interfering RNA. Moreover, HO-1 knockdown attenuated the protective effect of andrographolide against oxygen-glucose deprivation-induced CEC death. Andrographolide (0.1 mg/kg) significantly suppressed free radical formation, blood-brain barrier disruption, and brain infarction in MCAO-insulted rats, and these effects were reversed by the HO-1 inhibitor zinc protoporphyrin IX. The mechanism is attributable to HO-1 activation, as directly evidenced by andrographolide-induced pronounced HO-1 expression in brain tissues, which was highly localized in the cerebral capillary. In conclusion, andrographolide increased Nrf2-HO-1 expression through p38 MAPK regulation, confirming that it provides protection against MCAO-induced brain injury. These findings provide strong evidence that andrographolide could

  15. Heme oxygenase-1: a metabolic nike.

    Science.gov (United States)

    Wegiel, Barbara; Nemeth, Zsuzsanna; Correa-Costa, Matheus; Bulmer, Andrew C; Otterbein, Leo E

    2014-04-10

    Heme degradation, which was described more than 30 years ago, is still very actively explored with many novel discoveries on its role in various disease models every year. The heme oxygenases (HO) are metabolic enzymes that utilize NADPH and oxygen to break apart the heme moiety liberating biliverdin (BV), carbon monoxide (CO), and iron. Heme that is derived from hemoproteins can be toxic to the cells and if not removed immediately, it causes cell apoptosis and local inflammation. Elimination of heme from the milieu enables generation of three products that influences numerous metabolic changes in the cell. CO has profound effects on mitochondria and cellular respiration and other hemoproteins to which it can bind and affect their function, while BV and bilirubin (BR), the substrate and product of BV, reductase, respectively, are potent antioxidants. Sequestration of iron into ferritin and its recycling in the tissues is a part of the homeodynamic processes that control oxidation-reduction in cellular metabolism. Further, heme is an important component of a number of metabolic enzymes, and, therefore, HO-1 plays an important role in the modulation of cellular bioenergetics. In this review, we describe the cross-talk between heme oxygenase-1 (HO-1) and its products with other metabolic pathways. HO-1, which we have labeled Nike, the goddess who personified victory, dictates triumph over pathophysiologic conditions, including diabetes, ischemia, and cancer.

  16. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  17. Effect of a heme oxygenase-1 inducer on NADPH oxidase ...

    African Journals Online (AJOL)

    Effect of a heme oxygenase-1 inducer on NADPH oxidase expression in ... and immunohistochemistry of hepatic NOX1 and NOX4 were investigated in week 4. ... (HO-1 inhibitor) administration caused upregulation of NOX gene expression ...

  18. Immunolocalization of heme oxygenase-1 in periodontal diseases

    Directory of Open Access Journals (Sweden)

    G Gayathri

    2014-01-01

    Conclusion: The results of our study is an increasing evidence of involvement of antioxidant enzymes like heme oxygenase-1 in periodontal inflammation and their implication for treatment of chronic periodontitis.

  19. Metallothionein-III protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a PI3K and ERK/Nrf2-dependent manner

    International Nuclear Information System (INIS)

    Hwang, Yong Pil; Kim, Hyung Gyun; Han, Eun Hee; Jeong, Hye Gwang

    2008-01-01

    The zinc-binding protein metallothionein-III (MT-III) is associated with resistance to neuronal injury. However, the underlying mechanism for its effects is unclear. In this study, we demonstrate that MT-III prevents the accumulation of reactive oxygen species (ROS) in dopaminergic SH-SY5Y cells challenged with the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA) by a mechanism that involves phosphatidylinositol 3-kinase (PI3K) and ERK kinase/NF-E2-related factor 2 (Nrf2) dependent induction of the stress response protein heme oxygenase-1 (HO-1). Pretreatment of SH-SY5Y cells with MT-III significantly reduced 6-OHDA-induced generation of ROS, caspase-3 activation, and subsequent cell death. Also, MT-III up-regulates HO-1 expression and this expression confers neuroprotection against oxidative injury induced by 6-OHDA. Moreover, MT-III induces Nrf2 nuclear translocation, which is upstream of MT-III-induced HO-1 expression, and PI3K and ERK1/2 activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. Taken together, these results suggest that the PI3K and ERK/Nrf2 signaling pathway controls the intracellular levels of ROS by regulating the expression of the antioxidant enzyme HO-1

  20. Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Yong Son

    2013-01-01

    Full Text Available Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress, oxidative stress, and endoplasmic reticulum (ER stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1 plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

  1. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

    Science.gov (United States)

    Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

    2013-12-01

    Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

  2. Generation and characterization of human heme oxygenase-1 transgenic pigs.

    Directory of Open Access Journals (Sweden)

    Hye-Jung Yeom

    Full Text Available Xenotransplantation using transgenic pigs as an organ source is a promising strategy to overcome shortage of human organ for transplantation. Various genetic modifications have been tried to ameliorate xenograft rejection. In the present study we assessed effect of transgenic expression of human heme oxygenase-1 (hHO-1, an inducible protein capable of cytoprotection by scavenging reactive oxygen species and preventing apoptosis caused by cellular stress during inflammatory processes, in neonatal porcine islet-like cluster cells (NPCCs. Transduction of NPCCs with adenovirus containing hHO-1 gene significantly reduced apoptosis compared with the GFP-expressing adenovirus control after treatment with either hydrogen peroxide or hTNF-α and cycloheximide. These protective effects were diminished by co-treatment of hHO-1 antagonist, Zinc protoporphyrin IX. We also generated transgenic pigs expressing hHO-1 and analyzed expression and function of the transgene. Human HO-1 was expressed in most tissues, including the heart, kidney, lung, pancreas, spleen and skin, however, expression levels and patterns of the hHO-1 gene are not consistent in each organ. We isolate fibroblast from transgenic pigs to analyze protective effect of the hHO-1. As expected, fibroblasts derived from the hHO-1 transgenic pigs were significantly resistant to both hydrogen peroxide damage and hTNF-α and cycloheximide-mediated apoptosis when compared with wild-type fibroblasts. Furthermore, induction of RANTES in response to hTNF-α or LPS was significantly decreased in fibroblasts obtained from the hHO-1 transgenic pigs. These findings suggest that transgenic expression of hHO-1 can protect xenografts when exposed to oxidative stresses, especially from ischemia/reperfusion injury, and/or acute rejection mediated by cytokines. Accordingly, hHO-1 could be an important candidate molecule in a multi-transgenic pig strategy for xenotransplantation.

  3. Generation and characterization of human heme oxygenase-1 transgenic pigs.

    Science.gov (United States)

    Yeom, Hye-Jung; Koo, Ok Jae; Yang, Jaeseok; Cho, Bumrae; Hwang, Jong-Ik; Park, Sol Ji; Hurh, Sunghoon; Kim, Hwajung; Lee, Eun Mi; Ro, Han; Kang, Jung Taek; Kim, Su Jin; Won, Jae-Kyung; O'Connell, Philip J; Kim, Hyunil; Surh, Charles D; Lee, Byeong-Chun; Ahn, Curie

    2012-01-01

    Xenotransplantation using transgenic pigs as an organ source is a promising strategy to overcome shortage of human organ for transplantation. Various genetic modifications have been tried to ameliorate xenograft rejection. In the present study we assessed effect of transgenic expression of human heme oxygenase-1 (hHO-1), an inducible protein capable of cytoprotection by scavenging reactive oxygen species and preventing apoptosis caused by cellular stress during inflammatory processes, in neonatal porcine islet-like cluster cells (NPCCs). Transduction of NPCCs with adenovirus containing hHO-1 gene significantly reduced apoptosis compared with the GFP-expressing adenovirus control after treatment with either hydrogen peroxide or hTNF-α and cycloheximide. These protective effects were diminished by co-treatment of hHO-1 antagonist, Zinc protoporphyrin IX. We also generated transgenic pigs expressing hHO-1 and analyzed expression and function of the transgene. Human HO-1 was expressed in most tissues, including the heart, kidney, lung, pancreas, spleen and skin, however, expression levels and patterns of the hHO-1 gene are not consistent in each organ. We isolate fibroblast from transgenic pigs to analyze protective effect of the hHO-1. As expected, fibroblasts derived from the hHO-1 transgenic pigs were significantly resistant to both hydrogen peroxide damage and hTNF-α and cycloheximide-mediated apoptosis when compared with wild-type fibroblasts. Furthermore, induction of RANTES in response to hTNF-α or LPS was significantly decreased in fibroblasts obtained from the hHO-1 transgenic pigs. These findings suggest that transgenic expression of hHO-1 can protect xenografts when exposed to oxidative stresses, especially from ischemia/reperfusion injury, and/or acute rejection mediated by cytokines. Accordingly, hHO-1 could be an important candidate molecule in a multi-transgenic pig strategy for xenotransplantation.

  4. Spatiotemporal expression of heme oxygenase-1 detected by in vivo bioluminescence after hepatic ischemia in HO-1/luc mice

    NARCIS (Netherlands)

    Su, Huawei; van Dam, Gooitzen M.; Buis, Carlijn I.; Visser, Dorien S.; Hesselink, Jan Willem; Schuurs, Theo A.; Leuvenink, Henri G. D.; Contag, Christopher H.; Porte, Robert J.

    Upregulation of heme oxygenase-1 (HO-1) has been proposed as a critical mechanism protecting against cellular stress during liver transplantation, providing a potential target for new therapeutic interventions. We investigated the feasibility of in vivo bioluminescence imaging (BLI) to noninvasively

  5. Interaction of nitric oxide with human heme oxygenase-1.

    Science.gov (United States)

    Wang, Jinling; Lu, Shen; Moënne-Loccoz, Pierre; Ortiz de Montellano, Paul R

    2003-01-24

    NO and CO may complement each other as signaling molecules in some physiological situations. We have examined the binding of NO to human heme oxygenase-1 (hHO-1), an enzyme that oxidizes heme to biliverdin, CO, and free iron, to determine whether inhibition of hHO-1 by NO can contribute to the signaling interplay of NO and CO. An Fe(3+)-NO hHO-1-heme complex is formed with NO or the NO donors NOC9 or 2-(N,N-diethylamino)-diazenolate-2-oxide.sodium salt. Resonance Raman spectroscopy shows that ferric hHO-1-heme forms a 6-coordinated, low spin complex with NO. The nu(N-O) vibration of this complex detected by Fourier transform IR is only 4 cm(-1) lower than that of the corresponding metmyoglobin (met-Mb) complex but is broader, suggesting a greater degree of ligand conformational freedom. The Fe(3+)-NO complex of hHO-1 is much more stable than that of met-Mb. Stopped-flow studies indicate that k(on) for formation of the hHO-1-heme Fe(3+)-NO complex is approximately 50-times faster, and k(off) 10 times slower, than for met-Mb, resulting in K(d) = 1.4 microm for NO. NO thus binds 500-fold more tightly to ferric hHO-1-heme than to met-Mb. The hHO-1 mutations E29A, G139A, D140A, S142A, G143A, G143F, and K179A/R183A do not significantly diminish the tight binding of NO, indicating that NO binding is not highly sensitive to mutations of residues that normally stabilize the distal water ligand. As expected from the K(d) value, the enzyme is reversibly inhibited upon exposure to pathologically, and possibly physiologically, relevant concentrations of NO. Inhibition of hHO-1 by NO may contribute to the pleiotropic responses to NO and CO.

  6. Multi-donor Research Platform on Social Protection, Financial ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Multi-donor Research Platform on Social Protection, Financial Inclusion and ICTs ... been some experiments linking a financial inclusion component to CCT programs, ... Institution. Universidad de Chile. Pays d' institution. Chile. Site internet.

  7. Multi-donor Research Platform on Social Protection, Financial ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Multi-donor Research Platform on Social Protection, Financial Inclusion and ... There have been some experiments linking a financial inclusion component to CCT programs, ... Universidad de Chile. Institution Country. Chile. Institution Website.

  8. Epalrestat increases glutathione, thioredoxin, and heme oxygenase-1 by stimulating Nrf2 pathway in endothelial cells

    Directory of Open Access Journals (Sweden)

    Kaori Yama

    2015-04-01

    Full Text Available Epalrestat (EPS is the only aldose reductase inhibitor that is currently available for the treatment of diabetic neuropathy. Recently, we found that EPS at near-plasma concentration increases the intracellular levels of glutathione (GSH in rat Schwann cells. GSH plays a crucial role in protecting endothelial cells from oxidative stress, thereby preventing vascular diseases. Here we show that EPS increases GSH levels in not only Schwann cells but also endothelial cells. Treatment of bovine aortic endothelial cells (BAECs, an in vitro model of the vascular endothelium, with EPS caused a dramatic increase in intracellular GSH levels. This was concomitant with the up-regulation of glutamate cysteine ligase, an enzyme catalyzing the first and rate-limiting step in de novo GSH synthesis. Moreover, EPS stimulated the expression of thioredoxin and heme oxygenase-1, which have important redox regulatory functions in endothelial cells. Nuclear factor erythroid 2-related factor 2 (Nrf2 is a key transcription factor that regulates the expression of antioxidant genes. EPS increased nuclear Nrf2 levels in BAECs. Nrf2 knockdown by siRNA suppressed the EPS-induced glutamate cysteine ligase, thioredoxin-1, and heme oxygenase-1 expression. Interestingly, LY294002, an inhibitor of phosphatidylinositol 3-kinase, abolished the EPS-stimulated GSH synthesis, suggesting that the kinase is associated with Nrf2 activation induced by EPS. Furthermore, EPS reduced the cytotoxicity induced by H2O2 and tert-butylhydroperoxide, indicating that EPS plays a role in protecting cells from oxidative stress. Taken together, the results provide evidence that EPS exerts new beneficial effects on endothelial cells by increasing GSH, thioredoxin, and heme oxygenase-1 levels through the activation of Nrf2. We suggest that EPS has the potential to prevent several vascular diseases caused by oxidative stress.

  9. DNA Protecting Activities of Nymphaea nouchali (Burm. f Flower Extract Attenuate t-BHP-Induced Oxidative Stress Cell Death through Nrf2-Mediated Induction of Heme Oxygenase-1 Expression by Activating MAP-Kinases

    Directory of Open Access Journals (Sweden)

    Md Badrul Alam

    2017-09-01

    Full Text Available This study was performed to investigate the antioxidant activities of Nymphaea nouchali flower (NNF extract and the underlying mechanism using RAW 264.7 cells. The presence of gallic acid, catechin, epicatechin, epigallocatechin, epicatechin gallate, caffeic acid, quercetin, and apigenin in the NNF was confirmed by high-performance liquid chromatography (HPLC. The extract had a very potent capacity to scavenge numerous free radicals. NNF extract was also able to prevent DNA damage and quench cellular reactive oxygen species (ROS generation induced by tert-Butyl hydroperoxide (t-BHP with no signs of toxicity. The NNF extract was able to augment the expression of both primary and phase II detoxifying enzyme, resulting in combat the oxidative stress. This is accomplished by phosphorylation of mitogen-activated protein kinase (MAP kinase (p38 kinase and extracellular signal-regulated kinase (ERK followed by enhancing the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2. This attenuates cellular ROS generation and confers protection from cell death. Altogether, the results of current study revealed that Nymphaea nouchali flower could be a source of natural phytochemicals that could lead to the development of new therapeutic agents for preventing oxidative stress associated diseases and attenuating disease progression.

  10. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  11. Protecting the interests of the child bone marrow donor.

    Science.gov (United States)

    Terry, Louise M; Campbell, Anne

    2004-01-01

    At a time when designer babies have been created to act as cord blood donors to sick siblings, ethical debate has focused predominantly on the extent to which it is acceptable to create one human being to assist another. However, children are frequently used this way, by their families and doctors who extract their bone marrow, to try to save the life of another, usually a sibling. With any life-threatening illness, there is the possibility that the urgency of the sick sibling's need means that the short-term welfare of the donor child receives less attention than it should by parents and doctors. This article suggests ways to protect the interests of such children and empower them within the decision-making process and concludes that the drive to save life must be tempered by recognition of the intrinsic worth of donor children and their rights not to be exploited.

  12. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    International Nuclear Information System (INIS)

    Becker, Jan C.; Grosser, Nina; Waltke, Christian; Schulz, Stephanie; Erdmann, Kati; Domschke, Wolfram; Schroeder, Henning; Pohle, Thorsten

    2006-01-01

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection

  13. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Jan C [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Grosser, Nina [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Waltke, Christian [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schulz, Stephanie [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Erdmann, Kati [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Domschke, Wolfram [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schroeder, Henning [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Pohle, Thorsten [Department of Medicine B, University of Muenster, 48149 Muenster (Germany)

    2006-07-07

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.

  14. Serum heme oxygenase-1 levels in patients with primary dysmenorrhea.

    Science.gov (United States)

    Aksoy, Ayse Nur; Laloglu, Esra; Ozkaya, Alev Lazoglu; Yilmaz, Emsal Pınar Topdagi

    2017-04-01

    Primary dysmenorrhea effects the life-quality of women negatively. The aim of this study was to evaluate heme oxygenase-1 (HO1) activity together with malondialdehyde (MDA) and nitric oxide (NO) levels in patients with primary dysmenorrhea. A total of 28 nulliparous women with the diagnosis of primary dysmenorrhea and 26 healthy controls were included in this study. On the first day of menstruation, all patients underwent ultrasound examination to exclude pelvic pathology and the visual analogue scale was applied to patients. Patient's visual analogue scale (VAS) scores, age, body mass index (BMI), menstrual cycle length (day), length of bleeding (day) were recorded. In the same day, fasting blood samples were taken from each patient for biochemical analysis. Serum MDA, NO and HO1 levels were found to be higher in women with primary dysmenorrhea compared to healthy controls (p = 0.012, p = 0.009, p dysmenorrhea. Antioxidant support might be helpful to reduce pain severity in primary dysmenorrhea.

  15. Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis.

    Science.gov (United States)

    Chang, Ling-Chu; Chiang, Shih-Kai; Chen, Shuen-Ei; Yu, Yung-Luen; Chou, Ruey-Hwang; Chang, Wei-Chao

    2018-03-01

    Ferroptosis is a form of oxidative cell death and has become a chemotherapeutic target for cancer treatment. BAY 11-7085 (BAY), which is a well-known IκBα inhibitor, suppressed viability in cancer cells via induction of ferroptotic death in an NF-κB-independent manner. Reactive oxygen species scavenging, relief of lipid peroxidation, replenishment of glutathione and thiol-containing agents, as well as iron chelation, rescued BAY-induced cell death. BAY upregulated a variety of Nrf2 target genes related to redox regulation, particularly heme oxygenase-1 (HO-1). Studies with specific inhibitors and shRNA interventions suggested that the hierarchy of induction is Nrf2-SLC7A11-HO-1. SLC7A11 inhibition by erastin, sulfasalazine, or shRNA interference sensitizes BAY-induced cell death. Overexperession of SLC7A11 attenuated BAY-inhibited cell viability. The ferroptotic process induced by hHO-1 overexpression further indicated that HO-1 is a key mediator of BAY-induced ferroptosis that operates through cellular redox regulation and iron accumulation. BAY causes compartmentalization of HO-1 into the nucleus and mitochondrion, and followed mitochondrial dysfunctions, leading to lysosome targeting for mitophagy. In this study, we first discovered that BAY induced ferroptosis via Nrf2-SLC7A11-HO-1 pathway and HO-1 is a key mediator by responding to the cellular redox status. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Heme oxygenase-1 comes back to endoplasmic reticulum

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hong Pyo [School of Biological Sciences, Ulsan University (Korea, Republic of); Pae, Hyun-Ock [Department of Immunology, Wonkwang University School of Medicine (Korea, Republic of); Back, Sung Hun; Chung, Su Wol [School of Biological Sciences, Ulsan University (Korea, Republic of); Woo, Je Moon [Department of Opthalmology, Ulasn University Hospital (Korea, Republic of); Son, Yong [Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine (Korea, Republic of); Chung, Hun-Taeg, E-mail: chung@ulsan.ac.kr [School of Biological Sciences, Ulsan University (Korea, Republic of)

    2011-01-07

    Research highlights: {yields} Although multiple compartmentalization of HO-1 has been documented, the functional implication of this enzyme at these subcellular organelles is only partially elucidated. {yields} HO-1 expression at ER is induced by a diverse set of conditions that cause ER stressors. {yields} CO may induce HO-1 expression in human ECs by activating Nrf2 through PERK phosphorylation in a positive-feedback manner. {yields} ER-residing HO-1 and its cytoprotective activity against ER stress is discussed. -- Abstract: Originally identified as a rate-limiting enzyme for heme catabolism, heme oxygenase-1 (HO-1) has expanded its roles in anti-inflammation, anti-apoptosis and anti-proliferation for the last decade. Regulation of protein activity by location is well appreciated. Even though multiple compartmentalization of HO-1 has been documented, the functional implication of this enzyme at these subcellular organelles is only partially elucidated. In this review we discuss the endoplasmic reticulum (ER)-residing HO-1 and its cytoprotective activity against ER stress.

  17. Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

    Science.gov (United States)

    Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

    2016-08-01

    Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p brucellosis (r = 0.707, p brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

  18. Oxidative stress suppression by luteolin-induced heme oxygenase-1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Gui-bo; Sun, Xiao; Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Ye, Jing-xue [Jilin Agricultural University, No.2888, Xincheng Street, Changchun, 130021, Jilin (China); Si, Jian-yong [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Xu, Hui-bo [Academy of Chinese Medical Sciences of Jilin Province, Gongnongda road 1745, Changchun, 130021, Jiblin (China); Meng, Xiang-bao; Qin, Meng; Sun, Jing [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Wang, Hong-wei, E-mail: hwang@nju.edu.cn [Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093 (China); Sun, Xiao-bo, E-mail: sunsubmit@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China)

    2012-12-01

    Luteolin, a flavonoid that exhibits antioxidative properties, exerts myocardial protection effects. However, the underlying molecular mechanisms are not yet fully understood. To investigate the effects of luteolin on myocardial injury protection and its possible mechanisms, a myocardial injury model was established with intragastric administration of 4 mg/kg isoproterenol (ISO) to male Sprague–Dawley rats (200–220 g) daily for 2 days. We found that pretreatment of luteolin (160, 80 and 40 mg/kg, i.g., respectively) daily for 15 days can prevent ISO-induced myocardial damage, including decrease of serum cardiac enzymes, improvement electrocardiography and heart vacuolation. Luteolin also improved the free radical scavenging and antioxidant potential, suggesting one possible mechanism of luteolin-induced cardio-protection is mediated by blocking the oxidative stress. To clarify the mechanisms, we performed the in vitro study by hydrogen peroxide (H{sub 2}O{sub 2})-induced cytotoxicty model in H9c2 cells. We found that luteolin pretreatment prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1), and enhanced the binding of Nrf2 to the antioxidant response element, providing an adaptive survival response against H{sub 2}O{sub 2}-derived oxidative cytotoxicity. The addition of Znpp, a selective HO-1 competitive inhibitor, reduced the cytoprotective ability of luteolin, indicating the vital role of HO-1 on these effects. Luteolin also activated Akt and ERK, whereas the addition of LY294002 and U0126, the pharmacologic inhibitors of PI3K and ERK, attenuated luteolin-induced HO-1 expression and cytoprotective effect. Taken together, the above findings suggest that luteolin protects against myocardial injury and enhances cellular antioxidant defense capacity through the activation of Akt and ERK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction. -- Highlights: ► Luteolin prevents isoproterenol-induced myocardial damage.

  19. Oxidative stress suppression by luteolin-induced heme oxygenase-1 expression

    International Nuclear Information System (INIS)

    Sun, Gui-bo; Sun, Xiao; Wang, Min; Ye, Jing-xue; Si, Jian-yong; Xu, Hui-bo; Meng, Xiang-bao; Qin, Meng; Sun, Jing; Wang, Hong-wei; Sun, Xiao-bo

    2012-01-01

    Luteolin, a flavonoid that exhibits antioxidative properties, exerts myocardial protection effects. However, the underlying molecular mechanisms are not yet fully understood. To investigate the effects of luteolin on myocardial injury protection and its possible mechanisms, a myocardial injury model was established with intragastric administration of 4 mg/kg isoproterenol (ISO) to male Sprague–Dawley rats (200–220 g) daily for 2 days. We found that pretreatment of luteolin (160, 80 and 40 mg/kg, i.g., respectively) daily for 15 days can prevent ISO-induced myocardial damage, including decrease of serum cardiac enzymes, improvement electrocardiography and heart vacuolation. Luteolin also improved the free radical scavenging and antioxidant potential, suggesting one possible mechanism of luteolin-induced cardio-protection is mediated by blocking the oxidative stress. To clarify the mechanisms, we performed the in vitro study by hydrogen peroxide (H 2 O 2 )-induced cytotoxicty model in H9c2 cells. We found that luteolin pretreatment prevented apoptosis, increased the expression of heme oxygenase-1 (HO-1), and enhanced the binding of Nrf2 to the antioxidant response element, providing an adaptive survival response against H 2 O 2 -derived oxidative cytotoxicity. The addition of Znpp, a selective HO-1 competitive inhibitor, reduced the cytoprotective ability of luteolin, indicating the vital role of HO-1 on these effects. Luteolin also activated Akt and ERK, whereas the addition of LY294002 and U0126, the pharmacologic inhibitors of PI3K and ERK, attenuated luteolin-induced HO-1 expression and cytoprotective effect. Taken together, the above findings suggest that luteolin protects against myocardial injury and enhances cellular antioxidant defense capacity through the activation of Akt and ERK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction. -- Highlights: ► Luteolin prevents isoproterenol-induced myocardial damage. ► Luteolin

  20. Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia

    Science.gov (United States)

    Minamino, Tohru; Christou, Helen; Hsieh, Chung-Ming; Liu, Yuxiang; Dhawan, Vijender; Abraham, Nader G.; Perrella, Mark A.; Mitsialis, S. Alex; Kourembanas, Stella

    2001-07-01

    Chronic hypoxia causes pulmonary hypertension with smooth muscle cell proliferation and matrix deposition in the wall of the pulmonary arterioles. We demonstrate here that hypoxia also induces a pronounced inflammation in the lung before the structural changes of the vessel wall. The proinflammatory action of hypoxia is mediated by the induction of distinct cytokines and chemokines and is independent of tumor necrosis factor- signaling. We have previously proposed a crucial role for heme oxygenase-1 (HO-1) in protecting cardiomyocytes from hypoxic stress, and potent anti-inflammatory properties of HO-1 have been reported in models of tissue injury. We thus established transgenic mice that constitutively express HO-1 in the lung and exposed them to chronic hypoxia. HO-1 transgenic mice were protected from the development of both pulmonary inflammation as well as hypertension and vessel wall hypertrophy induced by hypoxia. Significantly, the hypoxic induction of proinflammatory cytokines and chemokines was suppressed in HO-1 transgenic mice. Our findings suggest an important protective function of enzymatic products of HO-1 activity as inhibitors of hypoxia-induced vasoconstrictive and proinflammatory pathways.

  1. Regulation of human heme oxygenase-1 gene expression under thermal stress.

    Science.gov (United States)

    Okinaga, S; Takahashi, K; Takeda, K; Yoshizawa, M; Fujita, H; Sasaki, H; Shibahara, S

    1996-06-15

    Heme oxygenase-1 is an essential enzyme in heme catabolism, and its human gene promoter contains a putative heat shock element (HHO-HSE). This study was designed to analyze the regulation of human heme oxygenase-1 gene expression under thermal stress. The amounts of heme oxygenase-1 protein were not increased by heat shock (incubation at 42 degrees C) in human alveolar macrophages and in a human erythroblastic cell line, YN-1-0-A, whereas heat shock protein 70 (HSP70) was noticeably induced. However, heat shock factor does bind in vitro to HHO-HSE and the synthetic HHO-HSE by itself is sufficient to confer the increase in the transient expression of a reporter gene upon heat shock. The deletion of the sequence, located downstream from HHO-HSE, resulted in the activation of a reporter gene by heat shock. These results suggest that HHO-HSE is potentially functional but is repressed in vivo. Interestingly, heat shock abolished the remarkable increase in the levels of heme oxygenase-1 mRNA in YN-1-0-A cells treated with hemin or cadmium, in which HSP70 mRNA was noticeably induced. Furthermore, transient expression assays showed that heat shock inhibits the cadmium-mediated activation of the heme oxygenase-1 promoter, whereas the HSP70 gene promoter was activated upon heat shock. Such regulation of heme oxygenase-1 under thermal stress may be of physiologic significance in erythroid cells.

  2. Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hanxia; Falgout, Barry; Takeda, Kazuyo [Food and Drug Administration, Silver Spring, MD (United States); Yamada, Kenneth M. [National Institutes of Health, Bethesda, MD (United States); Dhawan, Subhash, E-mail: subhash.dhawan@fda.hhs.gov [Food and Drug Administration, Silver Spring, MD (United States)

    2017-03-15

    We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of >90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retarding ZIKV replication. The inverse correlation between hemin-induced HO-1 levels and ZIKV replication provides a potentially useful therapeutic modality based on stimulation of an innate cellular response against Zika virus infection. - Highlights: •Hemin treatment protected monocyte-derived macrophages against Zika virus (ZIKV) infection. •Innate cellular protection against ZIKV infection correlated with Nrf2-dependent HO-1 expression. •Stimulation of innate cellular responses may provide a therapeutic strategy against ZIKV infection.

  3. Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

    International Nuclear Information System (INIS)

    Huang, Hanxia; Falgout, Barry; Takeda, Kazuyo; Yamada, Kenneth M.; Dhawan, Subhash

    2017-01-01

    We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of >90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retarding ZIKV replication. The inverse correlation between hemin-induced HO-1 levels and ZIKV replication provides a potentially useful therapeutic modality based on stimulation of an innate cellular response against Zika virus infection. - Highlights: •Hemin treatment protected monocyte-derived macrophages against Zika virus (ZIKV) infection. •Innate cellular protection against ZIKV infection correlated with Nrf2-dependent HO-1 expression. •Stimulation of innate cellular responses may provide a therapeutic strategy against ZIKV infection.

  4. The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

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    Jens Haugbølle Thomsen

    2013-01-01

    Full Text Available The haptoglobin- (Hp- CD163-heme oxygenase-1 (HO-1 pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO, biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6, but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.

  5. Molecular mechanism and functional consequences of lansoprazole-mediated heme oxygenase-1 induction

    Science.gov (United States)

    Schulz-Geske, Stephanie; Erdmann, Kati; Wong, Ronald J; Stevenson, David K; Schröder, Henning; Grosser, Nina

    2009-01-01

    AIM: To investigate the molecular mechanism and functional consequences of heme oxygenase-1 (HO-1) activation by lansoprazole in endothelial cells and macrophages. METHODS: Expression of HO-1 mRNA was analyzed by Northern blotting. Western blotting was used to determine the HO-1 and ferritin protein levels. NADPH-dependent reactive oxygen species (ROS) formation was measured with lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of the reporter gene luciferase, was assessed using in vivo bioluminescence imaging. RESULTS: Lansoprazole increased HO-1 mRNA levels in endothelial cells and HO-1 protein levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1 and ferritin by lansoprazole was followed by a decrease in NADPH-mediated ROS formation. The radical scavenging properties of lansoprazole were diminished in the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene expression by lansoprazole was not related to oxidative stress or to the activation of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1 mRNA and promoter activity. CONCLUSION: Activation of HO-1 and ferritin may account for the gastric protection of lansoprazole and is dependent on a pathway blocked by LY294002. PMID:19764090

  6. Heme oxygenase-1 prevents hyperthyroidism induced hepatic damage via an antioxidant and antiapoptotic pathway.

    Science.gov (United States)

    Giriş, Murat; Erbil, Yeşim; Depboylu, Bilge; Mete, Ozgür; Türkoğlu, Umit; Abbasoğlu, Semra Doğru; Uysal, Müjdat

    2010-12-01

    The exact pathogenesis of hepatic dysfunction in hyperthyroidism is still unknown. We aimed to investigate the pathogenesis of liver dysfunction caused by hyperthyroidism through inducing heme oxygenase-1 (HO-1) expression, which has antioxidant and anti-apoptotic properties. Rats were divided into six groups: untreated (group 1), treated with zinc protoporphyrin (ZnPP) (group 2), treated with hemin (group 3), treated with tri-iodothyronine (T3) (group 4), treated with T3 and ZnPP (group 5), and treated with T3 and hemin (group 6). After 22 d, oxidative stress and antioxidant enzymes and the expression of HO-1, mitochondrial permeability transition, cytochrome c, Bax, Bcl-2, caspase-3, caspase-8, and caspase-3 activity, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay were examined. Hyperthyroidism induced oxidative stress of liver tissue was ameliorated by HO-1 induction. Administration of hemin (HO-1 inducer) increased Bcl-2 expression. Decreased expression of cytochrome c was accompanied by a decrease in caspase-3, caspase-8, Bax expression, and caspase-3 activity. The apoptotic activity and oxidative damage were found to be increased by the administration of ZnPP (HO-1 inhibitor). Immunohistochemistry findings supported these results. HO-1 induction plays a protective role in the pathogenesis of the liver dysfunction in hyperthyroidism. This effect is dependent on modulation of the antiapoptotic and antioxidative pathways by HO-1 expression. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats

    Science.gov (United States)

    Suttorp, Christiaan M.; Xie, Rui; Lundvig, Ditte M. S.; Kuijpers-Jagtman, Anne Marie; Uijttenboogaart, Jasper Tom; Van Rheden, René; Maltha, Jaap C.; Wagener, Frank A. D. T. G.

    2016-01-01

    Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, “fast” and “slow” tooth movers during orthodontic treatment. PMID:27486402

  8. Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats.

    Science.gov (United States)

    Suttorp, Christiaan M; Xie, Rui; Lundvig, Ditte M S; Kuijpers-Jagtman, Anne Marie; Uijttenboogaart, Jasper Tom; Van Rheden, René; Maltha, Jaap C; Wagener, Frank A D T G

    2016-01-01

    Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, "fast" and "slow" tooth movers during orthodontic treatment.

  9. Methamphetamine induces heme oxygenase-1 expression in cortical neurons and glia to prevent its toxicity

    International Nuclear Information System (INIS)

    Huang, Y.-N.; Wu, C.-H.; Lin, T.-C.; Wang, J.-Y.

    2009-01-01

    The impairment of cognitive and motor functions in humans and animals caused by methamphetamine (METH) administration underscores the importance of METH toxicity in cortical neurons. The heme oxygenase-1 (HO-1) exerts a cytoprotective effect against various neuronal injures; however, it remains unclear whether HO-1 is involved in METH-induced toxicity. We used primary cortical neuron/glia cocultures to explore the role of HO-1 in METH-induced toxicity. Exposure of cultured cells to various concentrations of METH (0.1, 0.5, 1, 3, 5, and 10 mM) led to cytotoxicity in a concentration-dependent manner. A METH concentration of 5 mM, which caused 50% of neuronal death and glial activation, was chosen for subsequent experiments. RT-PCR and Western blot analysis revealed that METH significantly induced HO-1 mRNA and protein expression, both preceded cell death. Double and triple immunofluorescence staining further identified HO-1-positive cells as activated astrocytes, microglia, and viable neurons, but not dying neurons. Inhibition of the p38 mitogen-activated protein kinase pathway significantly blocked HO-1 induction by METH and aggravated METH neurotoxicity. Inhibition of HO activity using tin protoporphyrine IX significantly reduced HO activity and exacerbated METH neurotoxicity. However, prior induction of HO-1 using cobalt protoporphyrine IX partially protected neurons from METH toxicity. Taken together, our results suggest that induction of HO-1 by METH via the p38 signaling pathway may be protective, albeit insufficient to completely protect cortical neurons from METH toxicity.

  10. Orthodontic forces induce the cytoprotective enzyme heme oxygenase-1 in rats

    Directory of Open Access Journals (Sweden)

    Christiaan M. Suttorp

    2016-07-01

    Full Text Available Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL, and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalization. Heme oxygenase-1 (HO-1 forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Ni-Ti 10 cN coil spring. The contralateral side served as control. After 6, 12, 72, 96 and 120 hrs rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of multinuclear osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in the mononuclear cell population within the PDL at both the apposition- and resorption side. Shortly after appliance placement HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 hours. Some osteoclasts were HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of cytoprotective enzymes as HO-1 in the PDL determines the level of hyalinization and, subsequently, fast and slow tooth movers during orthodontic treatment.

  11. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

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    Massimo Collino

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1 induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO. These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO activity, interleukin 1β (IL-1β production and tumor necrosis factor-α (TNFα production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  12. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

    Science.gov (United States)

    Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  13. Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice.

    Science.gov (United States)

    Ohta, Ryo; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Nakamae, Toshio; Izumi, Bunichiro; Fujioka, Yuki; Ochi, Mitsuo

    2012-09-01

    Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress. Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9-C10 caudal discs in 12-week-old Bach 1-/- and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1-/- and wild-type mice. In the age-related model, there were no significant differences between Bach 1-/- and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1-/- mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1-/- mice. Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

  14. Heme oxygenase-1 prevents non-alcoholic steatohepatitis through suppressing hepatocyte apoptosis in mice

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    Fu Na

    2010-10-01

    Full Text Available Abstract Objective Heme oxygenase-1 (HO-1, the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant properties. However, the role of HO-1 on hepatocyte apoptosis remains unclear. We aim to elucidate the effects of HO-1 on oxidative stress related hepatocellular apoptosis in nutritional steatohepatitis in mice. Methods C57BL/6J mice were fed with methionine-choline deficient (MCD diet for four weeks to induce hepatic steatohepatitis. HO-1 chemical inducer (hemin, HO-1 chemical inhibitor zinc protoporphyrin IX (ZnPP-IX and/or adenovirus carrying HO-1 gene (Ad-HO-1 were administered to mice, respectively. Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay, the mRNA and protein expression of apoptosis related genes were assayed by quantitative real-time PCR and Western blot. Results Hepatocyte signs of oxidative related apoptotic injury were presented in mice fed with MCD diet for 4 weeks. Induction of HO-1 by hemin or Ad-HO-1 significantly attenuated the severity of liver histology, which was associated with decreased hepatic lipid peroxidation content, reduced number of apoptotic cells by TUNEL staining, down-regulated expression of pro-apoptosis related genes including Fas/FasL, Bax, caspase-3 and caspase-9, reduced expression of cytochrome p4502E1 (CYP2E1, inhibited cytochrome c (Cyt-c release, and up-regulated expression of anti-apoptosis gene Bcl-2. Whereas, inhibition of HO-1 by ZnPP-IX caused oxidative stress related hepatic injury, which concomitant with increased number of TUNEL positive cells and up-regulated expression of pro-apoptosis related genes. Conclusions The present study provided evidences for the protective role of HO-1 in preventing nutritional steatohepatitis through suppressing hepatocyte apoptosis in mice.

  15. Heme oxygenase-1 regulates the progression of K/BxN serum transfer arthritis.

    Directory of Open Access Journals (Sweden)

    Rita Brines

    Full Text Available Heme oxygenase-1 (HO-1 is induced in many cell types as a defense mechanism against stress. We have investigated the possible role of endogenous HO-1 in the effector phase of arthritis using the K/BxN serum transfer model of arthritis in HO-1 heterozygous and homozygous knock-out mice.Arthritis was induced in C57/Black-6 xFVB (HO-1(+/+, HO-1(+/- and HO-1(-/- mice by intraperitoneal injection of 150 µl serum from arthritic K/BxN mice at days 0 and 2. Blood was collected and animals were sacrificed at day 10. Histological analysis was performed in ankle sections. The levels of inflammatory mediators were measured in serum and paw homogenates by enzyme-linked immunosorbent assay or Multiplex technology. The incidence of arthritis was higher in HO-1(+/- and HO-1(-/- groups compared with HO-1(+/+. The inflammatory response was aggravated in HO-1(+/- mice as shown by arthritic score and the migration of inflammatory cells that could be related to the enhancement of CXCL-1 production. In addition, the HO-1(+/- group showed proteoglycan depletion significantly higher than HO-1(+/+ mice. Serum levels of matrix metalloproteinase-3, monocyte chemotactic protein-1, plasminogen activator inhibitor-1, E-selectin and intercellular adhesion molecule-1 were increased in arthritic HO-1(-/- mice, whereas vascular endothelial growth factor and some cytokines such as interferon-γ showed a reduction compared to HO-1(+/+ or HO-1(+/- mice. In addition, down-regulated gene expression of ferritin, glutathione S-reductase A1 and superoxide dismutase-2 was observed in the livers of arthritic HO-1(+/- animals.Endogenous HO-1 regulates the production of systemic and local inflammatory mediators and plays a protective role in K/BxN serum transfer arthritis.

  16. Heme-Oxygenase-1 Expression Contributes to the Immunoregulation Induced by Fasciola hepatica and Promotes Infection

    Directory of Open Access Journals (Sweden)

    Paula Carasi

    2017-07-01

    Full Text Available Fasciola hepatica, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T immune response by immunomodulating dendritic cell (DC maturation and alternative activation of macrophages. In this paper, we show that F. hepatica infection in mice induces the upregulation of heme-oxygenase-1 (HO-1, the rate-limiting enzyme in the catabolism of free heme that regulates the host inflammatory response. We show and characterize two different populations of antigen presenting cells that express HO-1 during infection in the peritoneum of infected animals. Cells that expressed high levels of HO-1 expressed intermediate levels of F4/80 but high expression of CD11c, CD38, TGFβ, and IL-10 suggesting that they correspond to regulatory DCs. On the other hand, cells expressing intermediate levels of HO-1 expressed high levels of F4/80, CD68, Ly6C, and FIZZ-1, indicating that they might correspond to alternatively activated macrophages. Furthermore, the pharmacological induction of HO-1 with the synthetic metalloporphyrin CoPP promoted F. hepatica infection increasing the clinical signs associated with the disease. In contrast, treatment with the HO-1 inhibitor SnPP protected mice from parasite infection, indicating that HO-1 plays an essential role during F. hepatica infection. Finally, HO-1 expression during F. hepatica infection was associated with TGFβ and IL-10 levels in liver and peritoneum, suggesting that HO-1 controls the expression of these immunoregulatory cytokines during infection favoring parasite survival in the host. These results contribute to the elucidation of the immunoregulatory mechanisms induced by F. hepatica in the host and provide alternative checkpoints to control fasciolosis.

  17. In vitro studies on heme oxygenase-1 and P24 antigen HIV-1 level ...

    African Journals Online (AJOL)

    Background: Heme oxygenase-1 (HO-1) is a protein secreted by immune cells as a part of immune response mechanism.HO-1 can be induced by variety agents that causingoxidative stress, such as exposure to 100% oxygenat2,4 ATA pressure.It plays a vital role in maintaining cellular homeostasis.This study was ...

  18. Rapamycin Induces Heme Oxygenase-1 in Liver but Inhibits Bile Flow Recovery after Ischemia

    NARCIS (Netherlands)

    Kist, Alwine; Wakkie, Joris; Madu, Max; Versteeg, Ruth; ten Berge, Judith; Nikolic, Andrej; Nieuwenhuijs, Vincent B.; Porte, Robert J.; Padbury, Robert T. A.; Barritt, Greg J.

    Background/Aims. Rapamycin, which is employed in the management of patients undergoing liver surgery, induces the synthesis of heme oxygenase-1 (HO-1) in some non-liver cell types. The aim was to investigate whether rapamycin can induce HO-1 expression in the liver, and to test the effects of

  19. The haptoglobin-CD163-heme oxygenase-1 pathway for hemoglobin scavenging

    DEFF Research Database (Denmark)

    Thomsen, Jens Haugbølle; Etzerodt, Anders; Svendsen, Pia

    2013-01-01

    The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex...

  20. Keeping mum about dad: "contracts" to protect gamete donor anonymity.

    Science.gov (United States)

    Rees, Anne

    2012-06-01

    This article considers the legal status of so-called contracts for anonymity between fertility clinics and donors of gametes that were made in the period before legislation authorising disclosure. It notes that while clinics frequently cite the existence of these "contracts" to argue against retrospective legislation authorising disclosure of the donor's identity, they may be nothing more than one-sided statements of informed consent. However, the article notes that even if an agreement between a donor and a clinic is not contractual, it does not follow that a person conceived through assisted reproductive technology has any right of access to the identity of the donor. The writer has not been able to locate examples of written promises by the clinics promising anonymity. There are written promises by the donors not to seek the identity of the recipients. These promises do not bind the resulting offspring nor do they appear to be supported by consideration. The article suggests that the basis for any individual donor to restrain a clinic from revealing their identity may be found in promissory estoppel. Nevertheless, there is no real issue in Australia concerning clinics revealing these details absent legislative authority. The issue is whether parliaments will legislate to authorise the disclosure. The article notes that it would be rare for parliaments to legislate to overturn existing legal contracts but suggests that the contract argument may not be as strong as has been thought.

  1. Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy

    Directory of Open Access Journals (Sweden)

    Christiano Machado

    2013-04-01

    Full Text Available OBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1 the control group, recipients of open donor nephrectomy (n = 29, and 2 the study group, recipients of laparoscopic donor nephrectomy (n = 26. Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047 and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01. CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic donor nephrectomy and open donor nephrectomy. These findings ensure

  2. Involvement of heme oxygenase-1 in β-cyclodextrin-hemin complex-induced cucumber adventitious rooting process.

    Science.gov (United States)

    Lin, Yuting; Li, Meiyue; Huang, Liqin; Shen, Wenbiao; Ren, Yong

    2012-09-01

    Our previous results showed that β-cyclodextrin-hemin complex (CDH) exhibited a vital protective role against cadmium-induced oxidative damage and toxicity in alfalfa seedling roots by the regulation of heme oxygenase-1 (HO-1) gene expression. In this report, we further test whether CDH exhibited the hormonal-like response. The application of CDH and an inducer of HO-1, hemin, were able to induce the up-regulation of cucumber HO-1 gene (CsHO1) expression and thereafter the promotion of adventitious rooting in cucumber explants. The effect is specific for HO-1 since the potent HO-1 inhibitor zinc protoporphyrin IX (ZnPP) blocked the above responses triggered by CDH, and the inhibitory effects were reversed further when 30% saturation of CO aqueous solution was added together. Further, molecular evidence showed that CDH triggered the increases of the HO-1-mediated target genes responsible for adventitious rooting, including one DnaJ-like gene (CsDNAJ-1) and two calcium-dependent protein kinase (CDPK) genes (CsCDPK1 and CsCDPK5), and were inhibited by ZnPP and reversed by CO. The calcium (Ca2+) chelator ethylene glycol-bis (2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) and the Ca2+ channel blocker lanthanum chloride (LaCl3) not only compromised the induction of adventitious rooting induced by CDH but also decreased the transcripts of above three target genes. However, the application of ascorbic acid (AsA), a well-known antioxidant in plants, failed to exhibit similar inducible effect on adventitious root formation. In short, above results illustrated that the response of CDH in the induction of cucumber adventitious rooting might be through HO-1-dependent mechanism and calcium signaling. Physiological, pharmacological and molecular evidence showed that β-cyclodextrin-hemin complex (CDH) was able to induce cucumber adventitious rooting through heme oxygenase-1 (HO-1)-dependent mechanism and calcium signaling.

  3. Role of the Nrf2-heme oxygenase-1 pathway in silver nanoparticle-mediated cytotoxicity

    International Nuclear Information System (INIS)

    Kang, Su Jin; Ryoo, In-geun; Lee, Young Joon; Kwak, Mi-Kyoung

    2012-01-01

    Silver nanoparticles (nano-Ag) have been widely used in various commercial products including textiles, electronic appliances and biomedical products. However, there remains insufficient information on the potential risk of nano-Ag to human health and environment. In the current study, we have investigated the role of NF-E2-related factor 2 (Nrf2) transcription factor in nano-Ag-induced cytotoxicity. When Nrf2 expression was blocked using interring RNA expression in ovarian carcinoma cell line, nano-Ag treatment showed a substantial decrease in cell viability with concomitant increases in apoptosis and DNA damage compared to the control cells. Target gene analysis revealed that the expression of heme oxygenase-1 (HO-1) was highly elevated by nano-Ag in nonspecific shRNA expressing cells, while Nrf2 knockdown cells (NRF2i) did not increase HO-1 expression. The role of HO-1 in cytoprotection against nano-Ag was reinforced by results using pharmacological inducer of HO-1: cobalt protoporphyrin-mediated HO-1 activation in the NRF2i cells prevented nano-Ag-mediated cell death. Similarly, pharmacological or genetic inhibition of HO-1 in nonspecific control cells exacerbated nano-Ag toxicity. As the upstream signaling mechanism, nano-Ag required the phosphoinositide 3-kinase (PI3K) and p38MAPK signaling cascades for HO-1 induction. The treatment with either PI3K inhibitor or p38MAPK inhibitor suppressed HO-1 induction and intensified nano-Ag-induced cell death. Taken together, these results suggest that Nrf2-dependent HO-1 up-regulation plays a protective role in nano-Ag-induced DNA damage and consequent cell death. In addition, nano-Ag-mediated HO-1 induction is associated with the PI3K and p38MAPK signaling pathways. -- Highlights: ► Role of Nrf2 signaling in silver nanoparticle toxicity. ► Silver nanoparticle toxicity is increased by Nrf2 blockade. ► Nrf2-dependent HO-1 induction protects cells from silver nanoparticle toxicity. ► PI3K and p38MAPK cascades are

  4. Heme oxygenase-1 induction improves cardiac function following myocardial ischemia by reducing oxidative stress.

    Directory of Open Access Journals (Sweden)

    Yossi Issan

    Full Text Available Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1, a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation.In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP and tin protoporphyrin (SnPP prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured.HO-1 induction lowered release of lactate dehydrogenase (LDH and creatine phospho kinase (CK, decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05. CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01, reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively. CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05. The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05. CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05 in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects.HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by the increased levels of pAKT with

  5. Adenovirus-mediated heme oxygenase-1 gene transfer into rabbit ocular tissues.

    Science.gov (United States)

    Abraham, N G; da Silva, J L; Lavrovsky, Y; Stoltz, R A; Kappas, A; Dunn, M W; Schwartzman, M L

    1995-10-01

    Heme oxygenase-1 (HO-1) is a stress protein induced up to 100-fold within a few hours after exposure to oxidative stress, and it has been shown to counteract oxidative injury induced by ultraviolet light or free radicals. The current study was undertaken to determine whether the HO-1 gene can be introduced into adult rabbit ocular tissues by microinjection of a recombinant replication-deficient adenovirus human HO-1 cDNA (Adv-HHO). Human HO-1 gene was used for transfection studies to differentiate endogenous from transfected HO. The purified Adv-HHO construct (10(8) pfu/ml) was mixed with lipofectamine and microinjected into the anterior chamber, vitreous cavity, and subretinal space of New Zealand rabbit eyes. After 2 weeks, total RNA was extracted from different ocular tissues, reverse transcription-polymerase chain reaction was performed using specific human HO-1 primers, and amplification products were subjected to Southern hybridization. Transfection with the Adv-HHO construct into rabbit corneal epithelial cells in culture resulted in a functional expression of the human HO-1 gene; the human HO-1 mRNA was detected, and enzyme activity increased threefold. Human HO-1 mRNA was detected in the retina after microinjection of the Adv-HHO construct into the subretinal space. Microinjection into the vitreous resulted in HO-1 mRNA expression in the corneal endothelium, iris, lens, and retina; after intracameral injection of the Adv-HHO construct, human HO-1 mRNA was detected in corneal epithelium and endothelium, ciliary body, lens, and iris. Regardless of the injection site, transfected human HO-1 mRNA was undetectable in tissues outside the eye, that is, brain, liver, and kidney. These results demonstrated a tissue-selective functional transfer of the human HO-1 gene into rabbit ocular tissues in vivo. This technique may be a promising means for delivering HO-1 gene in vivo as a protective mechanism against oxidative stress that contributes to the pathogenesis of

  6. Relationship of Heme Oxygenase-1 (HO-1 Level with Onset and Severity in Normotensive Pregnancy and Severe Preeclampsia

    Directory of Open Access Journals (Sweden)

    John Johannes Wantania

    2016-08-01

    Full Text Available Background: Preeclampsia still becomes a major problem in pregnancies. Various evidences showed that heme oxygenase-1 (HO-1 is very important in pregnancy. This study aims to understand the relationship of heme oxygenase-1 level with onset and severity in normotensive pregnancy and severe preeclampsia. Methods: This is a cross sectional analytic comparative study, the subjects consisted of 26 patients with normotensive pregnancies and 26 patients with severe preeclampsia. Blood samples from women with < 34 / ≥ 34 weeks’ normotensive pregnancies and women with severe preeclampsia were taken. HO-1 ELISA kit used to quantitate heme oxygenase-1 level in samples. Results: The level of heme oxygenase-1 in normotensive pregnant women < 34 weeks lower than severe preeclampsia pregnant women < 34 weeks (3.28 ± 0.46 ng/mL vs 4.20 ± 0.64 ng/mL, p=0.003, respectively. The median level of heme oxygenase-1 in normotensive pregnant women ≥ 34 weeks was 2.96 (2.41–4.39 ng/mL, while severe preeclampsia pregnant women ≥ 34 weeks was 3.52 (2.88–5.43 ng/mL, (p=0.040. The median level of heme oxygenase-1 in normotensive pregnant women was 3.04 (2.41–4.39 ng/mL, while severe preeclampsia pregnant women was 3.68 (2.88–5.67 ng/mL, (p=0.001. Conclusions: There is correlation between the incidence of severe preeclampsia with heme oxygenase-1 level in < 34 and ≥ 34 weeks of pregnancy. There is a significant difference between the level of heme oxygenase-1 in pregnant women with severe preeclampsia and in women with normotensive pregnancy. 

  7. Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis

    Directory of Open Access Journals (Sweden)

    Guoliang Meng

    2015-01-01

    Full Text Available Hydrogen sulfide (H2S is a gasotransmitter which regulates multiple cardiovascular functions. However, the precise roles of H2S in modulating myocardial fibrosis in vivo and cardiac fibroblast proliferation in vitro remain unclear. We investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial fibrosis. Spontaneously hypertensive rats (SHR were administrated with GYY4137 by intraperitoneal injection daily for 4 weeks. GYY4137 decreased systolic blood pressure and inhibited myocardial fibrosis in SHR as evidenced by improved cardiac collagen volume fraction (CVF in the left ventricle (LV, ratio of perivascular collagen area (PVCA to lumen area (LA in perivascular regions, reduced hydroxyproline concentration, collagen I and III mRNA expression, and cross-linked collagen. GYY4137 also inhibited angiotensin II- (Ang II- induced neonatal rat cardiac fibroblast proliferation, reduced the number of fibroblasts in S phase, decreased collagen I and III mRNA expression and protein synthesis, attenuated oxidative stress, and suppressed α-smooth muscle actin (α-SMA, transforming growth factor-β1 (TGF-β1 expression as well as Smad2 phosphorylation. These results indicate that GYY4137 improves myocardial fibrosis perhaps by a mechanism involving inhibition of oxidative stress, blockade of the TGF-β1/Smad2 signaling pathway, and decrease in α-SMA expression in cardiac fibroblasts.

  8. 4-Hydroxyestradiol induces mammary epithelial cell transformation through Nrf2-mediated heme oxygenase-1 overexpression

    OpenAIRE

    Park, Sin-Aye; Lee, Mee-Hyun; Na, Hye-Kyung; Surh, Young-Joon

    2016-01-01

    Estrogen (17?-estradiol, E2) undergoes oxidative metabolism by CYP1B1 to form 4-hydroxyestradiol (4-OHE2), a putative carcinogenic metabolite of estrogen. Our previous study showed that 4-OHE2-induced production of reactive oxygen species contributed to neoplastic transformation of human breast epithelial (MCF-10A) cells. In this study, 4-OHE2, but not E2, increased the expression of heme oxygenase-1 (HO-1), a sensor and regulator of oxidative stress, in MCF-10A cells. Silencing the HO-1 gene...

  9. 2,4-dimethoxybenzyl: An amide protecting group for 2-acetamido glycosyl donors

    DEFF Research Database (Denmark)

    Kelly, N.M.; Jensen, Knud Jørgen

    2001-01-01

    2,4-Dimethoxybenzyl (Dmob) was used as an amide protecting group for 2-acetamido glycosyl donors. The N-Dmob group was introduced by imine formation between 2,4-dimethoxybenzaldehyde and d-glucosamine, followed by per-O-acylation, reduction to form the amine, and finally N-acetylation to give 1...

  10. Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Diego L. Costa

    2016-10-01

    Full Text Available Heme oxygenase-1 (HO-1 is a stress response antioxidant enzyme which catalyzes the degradation of heme released during inflammation. HO-1 expression is upregulated in both experimental and human Mycobacterium tuberculosis infection, and in patients it is a biomarker of active disease. Whether the enzyme plays a protective versus pathogenic role in tuberculosis has been the subject of debate. To address this controversy, we administered tin protoporphyrin IX (SnPPIX, a well-characterized HO-1 enzymatic inhibitor, to mice during acute M. tuberculosis infection. These SnPPIX-treated animals displayed a substantial reduction in pulmonary bacterial loads comparable to that achieved following conventional antibiotic therapy. Moreover, when administered adjunctively with antimycobacterial drugs, the HO-1 inhibitor markedly enhanced and accelerated pathogen clearance. Interestingly, both the pulmonary induction of HO-1 expression and the efficacy of SnPPIX treatment in reducing bacterial burden were dependent on the presence of host T lymphocytes. Although M. tuberculosis expresses its own heme-degrading enzyme, SnPPIX failed to inhibit its enzymatic activity or significantly restrict bacterial growth in liquid culture. Together, the above findings reveal mammalian HO-1 as a potential target for host-directed monotherapy and adjunctive therapy of tuberculosis and identify the immune response as a critical regulator of this function.

  11. Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Laura Foucault-Fruchard

    2018-01-01

    Full Text Available Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days. Western blot assay results showed that the expression of heme oxygenase-1 (HO-1, the key component of the cholinergic anti-inflammatory pathway, in the right striatum of rat models of Huntington's disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water, and that the increase in HO-1 expression was independent of change in α7nAChR expression. These findings suggest that HO-1 expression is unrelated to α7nAChR density and the increase in HO-1 expression likely contributes to α7nAChR activation-related neuroprotective effect in early-stage Huntington's disease.

  12. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    International Nuclear Information System (INIS)

    Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen; Catalano, Jennifer; Yamada, Kenneth M.; Dhawan, Subhash

    2014-01-01

    Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection

  13. Management of oxidative stress by heme oxygenase-1 in cisplatin-induced toxicity in renal tubular cells.

    Science.gov (United States)

    Schaaf, G J; Maas, R F M; de Groene, E M; Fink-Gremmels, J

    2002-08-01

    Induction of heme oxygenase-1 (HO-1) may serve as an immediate protective response during treatment with the cytostatic drug cisplatin (CDDP). Oxidative pathways participate in the characteristic nephrotoxicity of CDDP. In the present study, cultured tubular cells (LLC-PK1) were used to investigate whether induction of HO provided protection against CDDP by maintaining the cellular redox balance. The antioxidants, alpha-tocopherol (TOCO) and N-acetylcysteine (NAC), were used to demonstrate that elevation of ROS levels contribute to the development of CDDP-induced cytotoxicity. Chemical modulators of HO activity were used to investigate the role of HO herein. Hemin was used to specifically induce HO-1, while exposure of the cells to tin-protoporphyrin (SnPP) was shown to inhibit HO activity. Hemin treatment prior to CDDP-exposure significantly decreased the generation of ROS to control levels, while inhibition of HO increased the ROS levels beyond the levels measured in cells treated with CDDP alone. Furthermore, HO induction protected significantly against the cytotoxicity of CDDP, although this protection was limited. Similar results were obtained when the cells were preincubated with TOCO, suggesting that mechanisms other than impairment of the redox ratio are important in CDDP-induced loss of cell viability in vitro. In addition, SnPP treatment exacerbated the oxidative response and cytotoxicity of CDDP, especially at low CDDP concentrations. We therefore conclude that HO is able to directly limit the CDDP-induced oxidative stress response and thus serves as safeguard of the cellular redox balance.

  14. Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages

    International Nuclear Information System (INIS)

    Zhou, Zhao-Hua; Kumari, Namita; Nekhai, Sergei; Clouse, Kathleen A.; Wahl, Larry M.; Yamada, Kenneth M.; Dhawan, Subhash

    2013-01-01

    Highlights: •Lipopolysaccharide stimulation of heme oxygenase-1 (HO-1) ameliorated HIV-1 infection of primary human macrophages. •The partial protection by HO-1 against HIV infection was associated with induction of chemokines such as MIP1α and MIP1β. •This mechanism explains lipopolysaccharide-stimulated HO-1-mediated inhibition of HIV-1 infection of macrophages. -- Abstract: We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1α and MIP1β) by LPS-activated MDM, significantly decreased surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1α, MIP1β, and LD78β chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM

  15. Proteção funcional da enzima heme-oxigenase-1 na lesão renal aguda isquêmica e tóxica Protección funcional de la enzima heme-oxigenasa-1 en la lesión renal aguda isquémica y tóxica Functional protection of heme-oxygenase-1 enzyme in ischemic and toxic acute kidney injury

    Directory of Open Access Journals (Sweden)

    Cassiane Dezoti

    2009-01-01

    estudio demuestran que la isquemia y la PmxB inducen AKL por la elevación de los peróxidos urinarios. El inductor de HO-1 atenuó la lesión en ambos modelos por atenuación del mecanismo redox.OBJECTIVE: To investigate the functional protection of heme-oxygenase-1 enzyme (HO-1 when using its inducer (Hemin and inhibitor (zinc protoporphyrin-ZnPP in ischemic and toxic acute kidney injury by Polymixin B in mice. MATERIALS: Adult male Wistar mice divided into 8 groups were used: SHAM (control, Ischemic (Isq, Isq+Hemin (Inducer of H0-1, Isq+ZnPP (inhibitor of H0-1, SALINA (control, Polimyxin B (PmxB, PmxB+Hemin, PmxB+ZnPP. METHOD: Analysis consists of Jaffé (creatinine clearance [crCl] and FOX-2 (urinary peroxides [UP]. RESULTS: Thirty minutes renal ischemia and its treatment with PmxB reduced the crCl and maintained urinary output. Urinary peroxide levels increased in both injuries. The administration of the inducer of H0-1 resulted in improvement in renal function and reduction in the levels of urinary peroxide. CONCLUSIONS: Findings indicated that ischemia and PmxB induce LAR (acute kidney injury [AKI] by elevating the levels of urinary peroxide. The HO-1 inducer ameliorated the injury in both animal models through redox mechanism.

  16. A Heme Oxygenase-1 Transducer Model of Degenerative and Developmental Brain Disorders

    Directory of Open Access Journals (Sweden)

    Hyman M. Schipper

    2015-03-01

    Full Text Available Heme oxygenase-1 (HO-1 is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In “stressed” astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders.

  17. Structure prediction and activity analysis of human heme oxygenase-1 and its mutant.

    Science.gov (United States)

    Xia, Zhen-Wei; Zhou, Wen-Pu; Cui, Wen-Jun; Zhang, Xue-Hong; Shen, Qing-Xiang; Li, Yun-Zhu; Yu, Shan-Chang

    2004-08-15

    To predict wild human heme oxygenase-1 (whHO-1) and hHO-1 His25Ala mutant (delta hHO-1) structures, to clone and express them and analyze their activities. Swiss-PdbViewer and Antheprot 5.0 were used for the prediction of structure diversity and physical-chemical changes between wild and mutant hHO-1. hHO-1 His25Ala mutant cDNA was constructed by site-directed mutagenesis in two plasmids of E. coli DH5alpha. Expression products were purified by ammonium sulphate precipitation and Q-Sepharose Fast Flow column chromatography, and their activities were measured. rHO-1 had the structure of a helical fold with the heme sandwiched between heme-heme oxygenase-1 helices. Bond angle, dihedral angle and chemical bond in the active pocket changed after Ala25 was replaced by His25, but Ala25 was still contacting the surface and the electrostatic potential of the active pocket was negative. The mutated enzyme kept binding activity to heme. Two vectors pBHO-1 and pBHO-1(M) were constructed and expressed. Ammonium sulphate precipitation and column chromatography yielded 3.6-fold and 30-fold higher purities of whHO-1, respectively. The activity of delta hHO-1 was reduced 91.21% after mutation compared with whHO-1. Proximal His25 ligand is crucial for normal hHO-1 catalytic activity. delta hHO-1 is deactivated by mutation but keeps the same binding site as whHO-1. delta hHO-1 might be a potential inhibitor of whHO-1 for preventing neonatal hyperbilirubinemia.

  18. Heme Oxygenase-1 and breast cancer resistance protein protect against heme-induced toxicity

    NARCIS (Netherlands)

    Wagener, Frank A D T G; Dankers, Anita C A; van Summeren, Frank; Scharstuhl, Alwin; van den Heuvel, Jeroen J M W; Koenderink, Jan B; Pennings, Sebastiaan W C; Russel, Frans G M; Masereeuw, R.

    2013-01-01

    Heme is the functional group of diverse hemoproteins and crucial for many cellular processes. However, heme is increasingly recognized as a culprit for a wide variety of pathologies, including sepsis, malaria, and kidney failure. Excess of free heme can be detrimental to tissues by mediating

  19. Heme Oxygenase-1 Induction by Carbon Monoxide Releasing Molecule-3 Suppresses Interleukin-1β-Mediated Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Chih-Chung Lin

    2017-11-01

    Full Text Available Neurodegenerative disorders and brain damage are initiated by excessive production of reactive oxygen species (ROS, which leads to tissue injury, cellular death and inflammation. In cellular anti-oxidant systems, heme oxygenase-1 (HO-1 is an oxidative-sensor protein induced by ROS generation or carbon monoxide (CO release. CO releasing molecules (CORMs, including CORM-3, exert anti-oxidant and anti-inflammatory effects. However, the molecular mechanisms of CORM-3-induced HO-1 expression and protection against interleukin (IL-1β-induced inflammatory responses have not been fully elucidated in rat brain astrocytes (RBA-1. To study the regulation of CORM-3-induced HO-1 expression, signaling pathways, promoter activity, mRNA and protein expression were assessed following treatment with pharmacological inhibitors and gene-specific siRNA knockdown. We found that CORM-3 mediated HO-1 induction via transcritional and translational processes. Furthermore, CORM-3-induced HO-1 expression was mediated by phosphorylation of several protein kinases, such as c-Src, Pyk2, protein kinase Cα (PKCα and p42/p44 mitogen-activated protein kinase (MAPK, which were inhibited by respective pharmacological inhibitors or by gene-specific knockdown with siRNA transfections. Next, we found that CORM-3 sequentially activated the c-Src/Pyk2/PKCα/p42/p44 MAPK pathway, thereby up-regulating mRNA for the activator protein (AP-1 components c-Jun and c-Fos; these effects were attenuated by an AP-1 inhibitor (Tanshinone IIA; TSIIA and other relevant inhibitors. Moreover, CORM-3-induced upregulation of HO-1 attenuated the IL-1β-induced cell migration and matrix metallopeptidase-9 mRNA expression in RBA-1 cells. These effects were reversed by an matrix metalloproteinase (MMP2/9 inhibitor or by transfection with HO-1 siRNA.

  20. Who should donate blood? Policy decisions on donor deferral criteria should protect recipients and be fair to donors.

    Science.gov (United States)

    Brailsford, S R; Kelly, D; Kohli, H; Slowther, A; Watkins, N A

    2015-08-01

    An important element in the development of voluntary blood donation schemes throughout the world has been the attention given to minimising the risk to recipients of donated blood, primarily the risk of transfusion transmitted infections. In response to the appearance of human immunodeficiency virus (HIV) in the 1980s a range of national policies emerged that excluded populations at high risk of contracting HIV from donating blood, with a particular focus on men who have sex with men (MSM), the primary reason being the protection of recipients of donated blood. Recently some countries, including the UK, have revised their policies, informed by advances in screening tests, epidemiological evidence of transmission rates and an increasing concern about unfair discrimination of specific groups in society. Policy makers face a difficult task of balancing safety of recipients; an adequate blood supply for those who require transfusion; and societal/legal obligations to treat everyone fairly. Given that no transfusion is risk free, the question is what degree of risk is acceptable in order to meet the needs of recipients and society. Decisions about acceptance of risk are complex and policy makers who set acceptable risk levels must provide ethically justifiable reasons for their decisions. We suggest it is possible to provide a set of reasons that stakeholders could agree are relevant based on careful evaluation of the evidence of all relevant risks and explicit acknowledgement of other morally relevant values. We describe using such a process in the Safety of Blood Tissue and Organs (SaBTO) review of donor deferral criteria related to sexual behaviour. © 2015 British Blood Transfusion Society.

  1. Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats

    International Nuclear Information System (INIS)

    Morio, Lisa A.; Leone, Angelique; Sawant, Sharmilee P.; Nie, Alex Y.; Brandon Parker, J.; Taggart, Peter; Barron, Alfred M.; McMillian, Michael K.; Lord, Peter

    2006-01-01

    Heme oxygenase-1 (HO-1) is one of several enzymes induced by hepatotoxicants, and is thought to have an important protective role against cellular stress during liver inflammation and injury. The objective of the present study was to evaluate the role of HO-1 in estradiol-induced liver injury. A single dose of ethinyl estradiol (500 mg/kg, po) resulted in mild liver injury. Repeated administration of ethinyl estradiol (500 mg/kg/day for 4 days, po) resulted in no detectable liver injury or dysfunction. Using RT-PCR analysis, we demonstrate that HO-1 gene expression in whole liver tissue is elevated (> 20-fold) after the single dose of ethinyl estradiol. The number and intensity of HO-1 immunoreactive macrophages were increased after the single dose of ethinyl estradiol. HO-1 expression was undetectable in hepatic parenchymal cells from rats receiving Methocel control or a single dose of ethinyl estradiol, however cytosolic HO-1 immunoreactivity in these cells after repeated dosing of ethinyl estradiol was pronounced. The increases in HO-1 mRNA and HO-1 immunoreactivity following administration of a single dose of ethinyl estradiol suggested that this enzyme might be responsible for the observed protection of the liver during repeated dosing. To investigate the effect of HO-1 expression on ethinyl estradiol-induced hepatotoxicity, rats were pretreated with hemin (50 μmol/kg, ip, a substrate and inducer of HO-1), with tin protoporphyrin IX (60 μmol/kg, ip, an HO-1 inhibitor), or with gadolinium chloride (10 mg/kg, iv, an inhibitor/toxin of Kupffer cells) 24 h before ethinyl estradiol treatment. Pretreatment with modulators of HO-1 expression and activity had generally minimal effects on ethinyl estradiol-induced liver injury. These data suggest that HO-1 plays a limited role in antioxidant defense against ethinyl estradiol-induced oxidative stress and hepatotoxicity, and suggests that other coordinately induced enzymes are responsible for protection observed with

  2. Effect of heme oxygenase-1 on radiation-induced skin injury

    International Nuclear Information System (INIS)

    Song Chuanjun; Meng Xingjun; Xie Ling; Chen Qing; Zhou Jundong; Zhang Shuyu; Wu Jinchang

    2012-01-01

    Objective: To investigate the effect of heme oxygenase-1 (HO-1) on the acute radiation-induced skin injury by gene transfer. Methods: Thirty-three male SD rats were randomly divided into three groups as PBS-injected group, Ad-EGFP-injected group and Ad-HO-1-injected group (n=11). In each group, three rats were used for determining the expression of target gene and the other rats were irradiated on the buttock skin with 40 Gy electron beam generated by a linear accelerator. Immediately after irradiation, rats were administered with a subcutaneous injection of PBS, Ad-EGFP or Ad-HO-1, respectively. Subsequently, the skin reactions were measured twice a week using the semi-quantitative skin injury scale. Results: The strong positive expression of HO-1 was observed in subcutaneous dermal tissue after injection of Ad-HO-1. Compared to the PBS-injected group or the Ad-EGFP-injected group, a significant mitigation of skin injury was observed in Ad-HO-1-injected mice 14 d after irradiation (q=0.000-0.030, P<0.05). Conclusions: HO-1 could significantly mitigate radiation-induced acute skin injury and Ad-HO-1 could be used to treat radiation-induced skin injury. (authors)

  3. Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

    International Nuclear Information System (INIS)

    Noh, Sang Jae; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun; Bae, Jun Sang; Jamiyandorj, Urangoo; Park, Ho Sung; Kwon, Keun Sang; Jung, Sung Hoo; Youn, Hyun Jo; Lee, Ho; Park, Byung-Hyun

    2013-01-01

    Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

  4. Fructose during pregnancy provokes fetal oxidative stress: The key role of the placental heme oxygenase-1.

    Science.gov (United States)

    Rodrigo, Silvia; Rodríguez, Lourdes; Otero, Paola; Panadero, María I; García, Antonia; Barbas, Coral; Roglans, Núria; Ramos, Sonia; Goya, Luis; Laguna, Juan C; Álvarez-Millán, Juan J; Bocos, Carlos

    2016-12-01

    One of the features of metabolic syndrome caused by liquid fructose intake is an impairment of redox status. We have investigated whether maternal fructose ingestion modifies the redox status in pregnant rats and their fetuses. Fructose (10% wt/vol) in the drinking water of rats throughout gestation, leads to maternal hepatic oxidative stress. However, this change was also observed in glucose-fed rats and, in fact, both carbohydrates produced a decrease in antioxidant enzyme activity. Surprisingly, mothers fed carbohydrates displayed low plasma lipid oxidation. In contrast, fetuses from fructose-fed mothers showed elevated levels of plasma lipoperoxides versus fetuses from control or glucose-fed mothers. Interestingly, a clearly augmented oxidative stress was observed in placenta of fructose-fed mothers, accompanied by a lower expression of the transcription factor Nuclear factor-erythroid 2-related factor-2 (Nrf2) and its target gene, heme oxygenase-1 (HO-1), a potent antioxidant molecule. Moreover, histone deacetylase 3 (HDAC3) that has been proposed to upregulate HO-1 expression by stabilizing Nrf2, exhibited a diminished expression in placenta of fructose-supplemented mothers. Maternal fructose intake provoked an imbalanced redox status in placenta and a clear diminution of HO-1 expression, which could be responsible for the augmented oxidative stress found in their fetuses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The role of heme oxygenase-1 in systemic-onset juvenile idiopathic arthritis.

    Science.gov (United States)

    Takahashi, Akitaka; Mori, Masaaki; Naruto, Takuya; Nakajima, Shoko; Miyamae, Takako; Imagawa, Tomoyuki; Yokota, Shumpei

    2009-01-01

    We have determined the serum levels of heme oxygenase-1 (HO-1) in 56 patients with systemic-onset juvenile idiopathic arthritis (s-JIA) and compared these with serum HO-1 levels in healthy controls and patients with other pediatric rheumatic diseases. Serum HO-1 levels were measured by the sandwich enzyme-linked immunosorbent assay. The mean serum HO-1 level in s-JIA patients during the active phase was 123.6 +/- 13.83 ng/ml, which was significantly higher than that in patients with polyarticular juvenile idiopathic arthritis (p-JIA), Kawasaki disease, systemic lupus erythematosus or mixed connective tissue disease (P < 0.0005). The serum levels of HO-1, cytokines and cytokine receptors in patients with s-JIA were also assessed at both the active and inactive phases. The serum HO-1 level in patients with s-JIA in the active phase was found to be significantly greater than that in patients with the disease in the inactive phase (P < 0.0001). An assessment of the relationships between serum HO-1 levels and other laboratory parameters or cytokines in patients with s-JIA did not reveal any strong correlations. These results suggest that the serum level of HO-1 may be a useful marker for the differential diagnosis of s-JIA. Further study will be necessary to elucidate the mechanism of HO-1 production and to clarify the role of HO-1 in the disease process.

  6. Impact of heme oxygenase-1 on cholesterol synthesis, cholesterol efflux and oxysterol formation in cultured astroglia.

    Science.gov (United States)

    Hascalovici, Jacob R; Song, Wei; Vaya, Jacob; Khatib, Soliman; Fuhrman, Bianca; Aviram, Michael; Schipper, Hyman M

    2009-01-01

    Up-regulation of heme oxygenase-1 (HO-1) and altered cholesterol (CH) metabolism are characteristic of Alzheimer-diseased neural tissues. The liver X receptor (LXR) is a molecular sensor of CH homeostasis. In the current study, we determined the effects of HO-1 over-expression and its byproducts iron (Fe(2+)), carbon monoxide (CO) and bilirubin on CH biosynthesis, CH efflux and oxysterol formation in cultured astroglia. HO-1/LXR interactions were also investigated in the context of CH efflux. hHO-1 over-expression for 3 days ( approximately 2-3-fold increase) resulted in a 30% increase in CH biosynthesis and a two-fold rise in CH efflux. Both effects were abrogated by the competitive HO inhibitor, tin mesoporphyrin. CO, released from administered CORM-3, significantly enhanced CH biosynthesis; a combination of CO and iron stimulated CH efflux. Free iron increased oxysterol formation three-fold. Co-treatment with LXR antagonists implicated LXR activation in the modulation of CH homeostasis by heme degradation products. In Alzheimer's disease and other neuropathological states, glial HO-1 induction may transduce ambient noxious stimuli (e.g. beta-amyloid) into altered patterns of glial CH homeostasis. As the latter may impact synaptic plasticity and neuronal repair, modulation of glial HO-1 expression (by pharmacological or other means) may confer neuroprotection in patients with degenerative brain disorders.

  7. Overexpressed human heme Oxygenase-1 decreases adipogenesis in pigs and porcine adipose-derived stem cells.

    Science.gov (United States)

    Park, Eun Jung; Koo, Ok Jae; Lee, Byeong Chun

    2015-11-27

    Adipose-derived mesenchymal stem cells (ADSC) are multipotent, which means they are able to differentiate into several lineages in vivo and in vitro under proper conditions. This indicates it is possible to determine the direction of differentiation of ADSC by controlling the microenvironment. Heme oxygenase 1 (HO-1), a type of antioxidant enzyme, attenuates adipogenicity and obesity. We produced transgenic pigs overexpressing human HO-1 (hHO-1-Tg), and found that these animals have little fatty tissue when autopsied. To determine whether overexpressed human HO-1 suppresses adipogenesis in pigs, we analyzed body weight increases of hHO-1-Tg pigs and wild type (WT) pigs of the same strain, and induced adipogenic differentiation of ADSC derived from WT and hHO-1-Tg pigs. The hHO-1-Tg pigs had lower body weights than WT pigs from 16 weeks of age until they died. In addition, hHO-1-Tg ADSC showed reduced adipogenic differentiation and expression of adipogenic molecular markers such as PPARγ and C/EBPα compared to WT ADSC. These results suggest that HO-1 overexpression reduces adipogenesis both in vivo and in vitro, which could support identification of therapeutic targets of obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance.

    Science.gov (United States)

    Zeng, Bin; Chen, Honglei; Zhu, Chengang; Ren, Xiaofeng; Lin, Guosheng; Cao, Feng

    2008-10-01

    Bone marrow mesenchymal stem cells (MSCs) have the potential to repair the infarcted myocardium and improve cardiac function. However, this approach is limited by its poor viability after transplantation, and controversy still exists over the mechanism by which MSCs contribute to the tissue repair. The human heme oxygenase-1 (hHO-1) was transfected into cultured MSCs using an adenoviral vector. 1 x 10(6) Ad-hHO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS only (PBS group) were injected intramyocardially into rat hearts 1h after myocardial infarction. HO-1-MSCs survived in the infarcted myocardium, and expressed hHO-1 mRNA. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was significantly enhanced in HO-1-MSCs-treated hearts. At the same time, there were significant reduction of TNF-alpha, IL-1-beta and IL-6 mRNA, and marked increase of IL-10 mRNA in HO-1-MSCs-treated hearts. Moreover, a further downregulation of proapoptotic protein, Bax, and a marked increase in microvessel density were observed in HO-1-MSCs-treated hearts. The infarct size and cardiac performance were also significantly improved in HO-1-MSCs-treated hearts. The combined approach improves MSCs survival and is superior to MSCs injection alone.

  9. The binding sites on human heme oxygenase-1 for cytochrome p450 reductase and biliverdin reductase.

    Science.gov (United States)

    Wang, Jinling; de Montellano, Paul R Ortiz

    2003-05-30

    Human heme oxygenase-1 (hHO-1) catalyzes the NADPH-cytochrome P450 reductase-dependent oxidation of heme to biliverdin, CO, and free iron. The biliverdin is subsequently reduced to bilirubin by biliverdin reductase. Earlier kinetic studies suggested that biliverdin reductase facilitates the release of biliverdin from hHO-1 (Liu, Y., and Ortiz de Montellano, P. R. (2000) J. Biol. Chem. 275, 5297-5307). We have investigated the binding of P450 reductase and biliverdin reductase to truncated, soluble hHO-1 by fluorescence resonance energy transfer and site-specific mutagenesis. P450 reductase and biliverdin reductase bind to truncated hHO-1 with Kd = 0.4 +/- 0.1 and 0.2 +/- 0.1 microm, respectively. FRET experiments indicate that biliverdin reductase and P450 reductase compete for binding to truncated hHO-1. Mutation of surface ionic residues shows that hHO-1 residues Lys18, Lys22, Lys179, Arg183, Arg198, Glu19, Glu127, and Glu190 contribute to the binding of cytochrome P450 reductase. The mutagenesis results and a computational analysis of the protein surfaces partially define the binding site for P450 reductase. An overlapping binding site including Lys18, Lys22, Lys179, Arg183, and Arg185 is similarly defined for biliverdin reductase. These results confirm the binding of biliverdin reductase to hHO-1 and define binding sites of the two reductases.

  10. Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression

    International Nuclear Information System (INIS)

    Choi, Byung-Min; Pae, Hyun-Ock; Jeong, Young-Ran; Kim, Young-Myeong; Chung, Hun-Taeg

    2005-01-01

    Foxp3, which encodes the transcription factor scurfin, is indispensable for the development and function of CD4 + CD25 + regulatory T cells (Treg). Recent data suggest conversion of peripheral CD4 + CD25 - naive T cells to CD4 + CD25 + Treg by acquisition of Foxp3 through costimulation with TCR and TGF-β or forced expression of the gene. One critical question is how Foxp3 causes T cells to become regulatory. In the present work, we demonstrate that Foxp3 can induce heme oxygenase-1 (HO-1) expression and subsequently such regulatory phenotypes as the suppression of nontransfected cells in a cell-cell contact-dependent manner as well as impaired proliferation and production of cytokines upon stimulation in Jurkat T cells. Moreover, we confirm the expression of both Foxp3 and HO-1 in peripheral CD4 + CD25 + Treg and suppressive function of the cells are relieved by the inhibition of HO-1 activity. In summary, we demonstrate that Foxp3 induces HO-1 expression and HO-1 engages in Foxp3-mediated immune suppression

  11. Hormonal fluctuations during the estrous cycle modulate Heme Oxygenase-1 expression in the uterus

    Directory of Open Access Journals (Sweden)

    Maria Laura Zenclussen

    2014-03-01

    Full Text Available Deletion of the Heme Oxygenase-1 (Hmox1 locus in mice results in intrauterine lethality. The expression of the heme catabolyzing enzyme encoded by this gene, namely HO 1, is required to successfully support reproductive events. We have previously observed that HO-1 acts at several key events in reproduction ensuring pregnancy. HO-1 defines ovulation, positively influences implantation and placentation and ensures fetal growth and survival. Here, we embarked on a study aimed to determine whether hormonal changes during the estrous cycle in the mouse define HO-1 expression, thus influencing receptivity. We analyzed the serum levels of progesterone and estrogen by ELISA and HO-1 mRNA expression in uterus by real time RT-PCR at the metestrus, proestrus, estrus and diestrus phases of the estrous cycle. Further, we studied the HO-1 protein expression by Western Blot upon hormone addition to cultured uterine AN3 cells. We observed that HO-1 variations in uterine tissue correlated to changes in hormonal levels at different phases of the estrus cycle. In vitro, HO-1 protein levels in AN3 cells augmented after the addition of physiological concentrations of progesterone and estradiol, which confirmed our in vivo observations. Our data suggest an important role for hormones in HO-1 regulation in uterus that has a significant impact in receptivity and later on blastocyst implantation.

  12. Myeloid Heme Oxygenase-1 Regulates the Acute Inflammatory Response to Zymosan in the Mouse Air Pouch

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    Rita Brines

    2018-01-01

    Full Text Available Heme oxygenase-1 (HO-1 is induced by many stimuli to modulate the activation and function of different cell types during innate immune responses. Although HO-1 has shown anti-inflammatory effects in different systems, there are few data on the contribution of myeloid HO-1 and its role in inflammatory processes is not well understood. To address this point, we have used HO-1M-KO mice with myeloid-restricted deletion of HO-1 to specifically investigate its influence on the acute inflammatory response to zymosan in vivo. In the mouse air pouch model, we have shown an exacerbated inflammation in HO-1M-KO mice with increased neutrophil infiltration accompanied by high levels of inflammatory mediators such as interleukin-1β, tumor necrosis factor-α, and prostaglandin E2. The expression of the degradative enzyme matrix metalloproteinase-3 (MMP-3 was also enhanced. In addition, we observed higher levels of serum MMP-3 in HO-1M-KO mice compared with control mice, suggesting the presence of systemic inflammation. Altogether, these findings demonstrate that myeloid HO-1 plays an anti-inflammatory role in the acute response to zymosan in vivo and suggest the interest of this target to regulate inflammatory processes.

  13. Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells

    International Nuclear Information System (INIS)

    Lee, Bok-Soo; Heo, JungHee; Kim, Yong-Man; Shim, Sang Moo; Pae, Hyun-Ock; Kim, Young-Myeong; Chung, Hun-Taeg

    2006-01-01

    Carbon monoxide (CO) and nitric oxide (NO) are two gas molecules which have cytoprotective functions against oxidative stress and inflammatory responses in many cell types. Currently, it is known that NO produced by nitric oxide synthase (NOS) induces heme oxygenase 1 (HO1) expression and CO produced by the HO1 inhibits inducible NOS expression. Here, we first show CO-mediated HO1 induction and its possible mechanism in human hepatocytes. Exposure of HepG2 cells or primary hepatocytes to CO resulted in dramatic induction of HO1 in dose- and time-dependent manner. The CO-mediated HO1 induction was abolished by MAP kinase inhibitors (MAPKs) but not affected by inhibitors of PI3 kinase or NF-κB. In addition, CO induced the nuclear translocation and accumulation of Nrf2, which suppressed by MAPKs inhibitors. Taken together, we suggest that CO induces Nrf2 activation via MAPKs signaling pathways, thereby resulting in HO1 expression in HepG2 cells

  14. Effect of dimethyl fumarate on heme oxygenase-1 expression in experimental allergic encephalomyelitis in rats

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    Kaja Kasarełło

    2017-12-01

    Full Text Available Multiple sclerosis (MS is an autoimmunological disease leading to neurodegeneration. The etiology of the disease remains unknown, which strongly impedes the development of effective therapy. Most MS treatments focus on modulating the activity of the immune system. Dimethyl fumarate (DMF exerts a broad spectrum of action, such as modulating immune cell differentiation towards anti-inflammatory subtypes, influencing cytokine production, regulating immune cell migration into the central nervous system, and activating intracellular antioxidant mechanisms. It is well established that activation of the nuclear factor E2 (Nrf2-dependent pathway, leading to expression of the second-phase antioxidant enzymes, is influenced by DMF. In our experiments we used female Lewis rats in an animal model of MS – experimental allergic encephalomyelitis (EAE. The rats were fed with dimethyl fumarate to test the expression of heme oxygenase-1 (HO-1, one of the second-phase antioxidant enzymes, at specific time points of the symptomatic phases of the disease: on the first day of the occurrence of clinical symptoms (10th day post immunization, DPI; at the peak of clinical symptoms (14th DPI; and at the end of the relapse (21st DPI. The results showed that HO-1 expression, at both the mRNA and protein level, is influenced by DMF administration only at the very beginning of the symptomatic phase of EAE, and not at the peak of clinical symptoms, nor at the end of the relapse. This indicates that the regulation of the Nrf2-dependent antioxidant pathway by DMF occurs at a certain time interval (early EAE/MS and strongly underlines the importance of the earliest introduction of the therapy to the patient.

  15. Heme Oxygenase-1/Carbon Monoxide System and Embryonic Stem Cell Differentiation and Maturation into Cardiomyocytes

    Science.gov (United States)

    Suliman, Hagir B.; Zobi, Fabio

    2016-01-01

    Abstract Aims: The differentiation of embryonic stem (ES) cells into energetically efficient cardiomyocytes contributes to functional cardiac repair and is envisioned to ameliorate progressive degenerative cardiac diseases. Advanced cell maturation strategies are therefore needed to create abundant mature cardiomyocytes. In this study, we tested whether the redox-sensitive heme oxygenase-1/carbon monoxide (HO-1/CO) system, operating through mitochondrial biogenesis, acts as a mechanism for ES cell differentiation and cardiomyocyte maturation. Results: Manipulation of HO-1/CO to enhance mitochondrial biogenesis demonstrates a direct pathway to ES cell differentiation and maturation into beating cardiomyocytes that express adult structural markers. Targeted HO-1/CO interventions up- and downregulate specific cardiogenic transcription factors, transcription factor Gata4, homeobox protein Nkx-2.5, heart- and neural crest derivatives-expressed protein 1, and MEF2C. HO-1/CO overexpression increases cardiac gene expression for myosin regulatory light chain 2, atrial isoform, MLC2v, ANP, MHC-β, and sarcomere α-actinin and the major mitochondrial fusion regulators, mitofusin 2 and MICOS complex subunit Mic60. This promotes structural mitochondrial network expansion and maturation, thereby supporting energy provision for beating embryoid bodies. These effects are prevented by silencing HO-1 and by mitochondrial reactive oxygen species scavenging, while disruption of mitochondrial biogenesis and mitochondrial DNA depletion by loss of mitochondrial transcription factor A compromise infrastructure. This leads to failure of cardiomyocyte differentiation and maturation and contractile dysfunction. Innovation: The capacity to augment cardiomyogenesis via a defined mitochondrial pathway has unique therapeutic potential for targeting ES cell maturation in cardiac disease. Conclusion: Our findings establish the HO-1/CO system and redox regulation of mitochondrial biogenesis as

  16. Pharmacological Induction of Heme Oxygenase-1 Impairs Nuclear Accumulation of Herpes Simplex Virus Capsids upon Infection

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    Francisco J. Ibáñez

    2017-10-01

    Full Text Available Heme oxygenase-1 (HO-1 is an inducible enzyme that is expressed in response to physical and chemical stresses, such as ultraviolet radiation, hyperthermia, hypoxia, reactive oxygen species (ROS, as well as cytokines, among others. Its activity can be positively modulated by cobalt protoporphyrin (CoPP and negatively by tin protoporphirin (SnPP. Once induced, HO-1 degrades iron-containing heme into ferrous iron (Fe2+, carbon monoxide (CO and biliverdin. Importantly, numerous products of HO-1 are cytoprotective with anti-apoptotic, anti-oxidant, anti-inflammatory, and anti-cancer effects. The products of HO-1 also display antiviral properties against several viruses, such as the human immunodeficiency virus (HIV, influenza, hepatitis B, hepatitis C, and Ebola virus. Here, we sought to assess the effect of modulating HO-1 activity over herpes simplex virus type 2 (HSV-2 infection in epithelial cells and neurons. There are no vaccines against HSV-2 and treatment options are scarce in the immunosuppressed, in which drug-resistant variants emerge. By using HSV strains that encode structural and non-structural forms of the green fluorescent protein (GFP, we found that pharmacological induction of HO-1 activity with CoPP significantly decreases virus plaque formation and the expression of virus-encoded genes in epithelial cells as determined by flow cytometry and western blot assays. CoPP treatment did not affect virus binding to the cell surface or entry into the cytoplasm, but rather downstream events in the virus infection cycle. Furthermore, we observed that treating cells with a CO-releasing molecule (CORM-2 recapitulated some of the anti-HSV effects elicited by CoPP. Taken together, these findings indicate that HO-1 activity interferes with the replication cycle of HSV and that its antiviral effects can be recapitulated by CO.

  17. Genetic analyses of heme oxygenase 1 (HMOX1 in different forms of pancreatitis.

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    Sebastian Weis

    Full Text Available Heme oxygenase 1 (HMOX1 is the rate limiting enzyme in heme degradation and a key regulator of inflammatory processes. In animal models the course of pancreatitis was ameliorated by up-regulation of HMOX1 expression. Additionally, carbon monoxide released during heme breakdown inhibited proliferation of pancreatic stellate cells and might thereby prevent the development of chronic pancreatitis (CP. Transcription of HMOX1 in humans is influenced by a GT-repeat located in the promoter. As such, HMOX1 variants might be of importance in the pathogenesis of pancreatitis.The GT-repeat and SNP rs2071746 were investigated with fluorescence labelled primers and by melting curve analysis in 285 patients with acute pancreatitis, 208 patients with alcoholic CP, 207 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and in 289 controls, respectively. GT-repeat analysis was extended to a total of 446 alcoholic CP patients. In addition, we performed DNA sequencing in 145 patients with alcoholic CP, 138 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and 151 controls. Exon 3 screening was extended to additional patients and controls.S- and L-alleles of the GT-repeat, genotypes and alleles of SNP rs2071746 and non-synonymous variants detected by sequencing were found with similar frequencies in all groups.Although functional data implicate a potential influence of HMOX1 variants on the pathogenesis of pancreatitis, we did not find any association. As rare non-synonymous HMOX1 variants were found in patients and controls, it is rather unlikely that they will have functional consequences essential for pancreatitis development.

  18. Plasma heme oxygenase-1 concentration is elevated in individuals with type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Wei Bao

    Full Text Available BACKGROUND: Circulating concentrations of heme oxygenase-1 (HO-1 have been recently reported to be elevated in several chronic disorders. However, no study has ever examined the association between circulating HO-1 concentrations and type 2 diabetes mellitus (T2DM. METHODS AND FINDINGS: 581 cases with newly-diagnosed T2DM (New-T2DM and 611 comparison controls were recruited in this two-phase case-control study, comprising 420 cases and 429 controls collected in the first phase study and 161 cases and 182 controls in the second phase replication study. Analyses, using both separated data and combined data from the two-phase studies, show that plasma HO-1 concentrations were significantly increased in New-T2DM cases compared to controls (P<0.001. Plasma HO-1 concentrations were significantly correlated with plasma glucose concentrations, HOMA-beta and HOMA-IR (P<0.001. After adjustment for age, sex, BMI and family history of diabetes, the ORs for New-T2DM in the highest quartile of plasma HO-1 concentrations, compared with the lowest, was 8.23 (95% CI 5.55-12.21; P for trend <0.001. The trend remained significant after additional adjustment for fasting plasma glucose/insulin, HOMA-beta/HOMA-IR, TC/TG, smoking, drinking and history of hypertension, and even in further stratification analysis by age, sex, BMI, smoking, drinking and history of hypertension. CONCLUSIONS: Elevated plasma HO-1 concentrations are associated with higher ORs for New-T2DM, which add more knowledge regarding the important role of oxidative stress in T2DM. More consequent studies were warranted to confirm the clinical utility of plasma HO-1, especially in diagnosis and prognosis of T2DM and its complications.

  19. Astroglia overexpressing heme oxygenase-1 predispose co-cultured PC12 cells to oxidative injury.

    Science.gov (United States)

    Song, Linyang; Song, Wei; Schipper, Hyman M

    2007-08-01

    The mechanisms responsible for the progressive degeneration of dopaminergic neurons and pathologic iron deposition in the substantia nigra pars compacta of patients with Parkinson's disease (PD) remain unclear. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the oxidative degradation of heme to ferrous iron, carbon monoxide, and biliverdin, is upregulated in affected PD astroglia and may contribute to abnormal mitochondrial iron sequestration in these cells. To determine whether glial HO-1 hyper-expression is toxic to neuronal compartments, we co-cultured dopaminergic PC12 cells atop monolayers of human (h) HO-1 transfected, sham-transfected, or non-transfected primary rat astroglia. We observed that PC12 cells grown atop hHO-1 transfected astrocytes, but not the astroglia themselves, were significantly more susceptible to dopamine (1 microM) + H(2)O(2) (1 microM)-induced death (assessed by nuclear ethidium monoazide bromide staining and anti-tyrosine hydroxylase immunofluorescence microscopy) relative to control preparations. In the experimental group, PC12 cell death was attenuated significantly by the administration of the HO inhibitor, SnMP (1.5 microM), the antioxidant, ascorbate (200 microM), or the iron chelators, deferoxamine (400 microM), and phenanthroline (100 microM). Exposure to conditioned media derived from HO-1 transfected astrocytes also augmented PC12 cell killing in response to dopamine (1 microM) + H(2)O(2) (1 microM) relative to control media. In PD brain, overexpression of HO-1 in nigral astroglia and accompanying iron liberation may facilitate the bioactivation of dopamine to neurotoxic free radical intermediates and predispose nearby neuronal constituents to oxidative damage. (c) 2007 Wiley-Liss, Inc.

  20. Over-expression of heme oxygenase-1 promotes oxidative mitochondrial damage in rat astroglia.

    Science.gov (United States)

    Song, Wei; Su, Haixiang; Song, Sisi; Paudel, Hemant K; Schipper, Hyman M

    2006-03-01

    Glial heme oxygenase-1 is over-expressed in the CNS of subjects with Alzheimer disease (AD), Parkinson disease (PD) and multiple sclerosis (MS). Up-regulation of HO-1 in rat astroglia has been shown to facilitate iron sequestration by the mitochondrial compartment. To determine whether HO-1 induction promotes mitochondrial oxidative stress, assays for 8-epiPGF(2alpha) (ELISA), protein carbonyls (ELISA) and 8-OHdG (HPLC-EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole-cell compartments derived from cultured rat astroglia engineered to over-express human (h) HO-1 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [3H] thymidine incorporation and total cell counts. In rat astrocytes, hHO-1 over-expression (x 3 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 microM tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up-regulation of HO-1 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme-derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO-1 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. Copyright 2005 Wiley-Liss, Inc.

  1. Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

    Science.gov (United States)

    Liu, Xiaoli; Pachori, Alok S; Ward, Christopher A; Davis, J Paul; Gnecchi, Massimiliano; Kong, Deling; Zhang, Lunan; Murduck, Jared; Yet, Shaw-Fang; Perrella, Mark A; Pratt, Richard E; Dzau, Victor J; Melo, Luis G

    2006-02-01

    We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction.

  2. Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA.

    Science.gov (United States)

    Xia, Zhen-Wei; Li, Chun-E; Jin, You-Xin; Shi, Yi; Xu, Li-Qing; Zhong, Wen-Wei; Li, Yun-Zhu; Yu, Shan-Chang; Zhang, Zi-Li

    2007-04-01

    Neonatal hyperbilirubinemia is a common clinical condition caused mainly by the increased production and decreased excretion of bilirubin. Current treatment is aimed at reducing the serum levels of bilirubin. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that generates bilirubin. In this study we intended to suppress HO-1 using the RNA interference technique. Small interfering RNA (siRNA)-A, -B, and -C were designed based on human HO-1 (hHO-1) mRNA sequences. siRNA was transfected into a human hepatic cell line (HL-7702). hHO-1 transcription and protein levels were then determined. In addition, the inhibitory effect of siRNA on hHO-1 was assessed in cells treated with hemin or transfected with an hHO-1 plasmid. siRNA-C showed the most potent suppressive effect on hHO-1. This inhibition is dose and time dependent. Compared with control, both hemin and hHO-1 plasmids up-regulated hHO-1 expression in HL-7702 cells. However, the up-regulation was significantly attenuated by siRNA-C. Furthermore, the decrease in hHO-1 activity was coincident with the suppression of its transcription. Finally, siRNA-C was shown to reduce hHO-1 enzymatic activity and bilirubin levels. Thus, this study provides a novel therapeutic rationale by blocking bilirubin formation via siRNA for preventing and treating neonatal hyperbilirubinemia and bilirubin encephalopathy at an early clinical stage.

  3. Heme oxygenase-1: A new druggable target in the management of chronic and acute myeloid leukemia.

    Science.gov (United States)

    Salerno, Loredana; Romeo, Giuseppe; Modica, Maria N; Amata, Emanuele; Sorrenti, Valeria; Barbagallo, Ignazio; Pittalà, Valeria

    2017-12-15

    Heme oxygenase-1 (HO-1) is the enzyme catalyzing the rate-limiting oxidative degradation of cellular heme into free iron, carbon monoxide (CO), and biliverdin, which is then rapidly converted into bilirubin. By means of these catabolic end-products and by removal of pro-oxidant heme, HO-1 exerts antioxidant, antiapoptotic, and immune-modulating effects, leading to overall cytoprotective and beneficial functions in mammalian cells. Therefore, HO-1 is considered a survival molecule in various stress-related conditions. By contrast, growing evidence suggests that HO-1 is a survival-enhancing molecule also in various solid and blood cancers, such as various types of leukemia, promoting carcinogenesis, tumor progression, and chemo-resistance. Among leukemias, chronic myeloid leukemia (CML) is currently therapeutically well treated with tyrosine kinase inhibitors (TKIs) such as Imatinib (IM) and its congeners; nevertheless, resistance to all kinds of current drugs persist in a number of patients. Moreover, treatment outcomes for acute myeloid leukemia (AML) remain unsatisfactory, despite progress in chemotherapy and hematopoietic stem cell transplantation. Therefore, identification of new eligible targets that may improve leukemias therapy is of general interest. Several recent papers prove that inhibition of HO-1 through HO-1 inhibitors as well as modulation of other pathways involving HO-1 by a number of different new or known molecules, are critical for leukemia treatment. This review summarizes the current understanding of the pro-tumorigenic role of HO-1 and its potential as a molecular target for the treatment of leukemias. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Effect of heme oxygenase-1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro.

    Science.gov (United States)

    Cao, Yi; Wu, Ben-Juan; Zheng, Wei-Ping; Yin, Ming-Li; Liu, Tao; Song, Hong-Li

    2017-07-01

    In this study, we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase-1 (HO-1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO-1 recombinant adenovirus (HO-MSCs) for stable expression of HO-1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor-α (TNF-α) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad-MSCs, Ad-HO + MSCs or HO-MSCs. mRNA and protein expression of Zona occludens-1 (ZO-1) and human HO-1 and the release of cytokines were measured. ZO-1 and human HO-1 in Caco2 were significantly decreased after treatment with TNF-α; and this effect was reduced when coculture with MSCs from bone marrow. Expression of ZO-1 was not significantly affected by Caco2 treatment with TNF-α, Ad-HO, and MSCs. In contrast, ZO-1 and human HO-1 increased significantly when the damaged Caco2 was treated with HO-MSCs. HO-MSCs showed the strongest effect on the expression of ZO-1 in colon epithelial cells. Coculture with HO-MSCs showed the most significant effects on reducing the expression of IL-2, IL-6, IFN-γ and increasing the expression of IL-10. HO-MSCs protected the intestinal epithelial barrier, in which endogenous HO-1 was involved. HO-MSCs play an important role in the repair process by reducing the release of inflammatory cytokines and increasing the release of anti-inflammatory factors. These results suggested that HO-MSCs from bone marrow were more effective in repairing the damaged intestinal epithelial barrier, and the effectiveness of MSCs was improved by HO-1 gene transduction, which provides favorable support for the application of stem cell therapy in the intestinal diseases. © 2017 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

  5. Iron depletion in HCT116 cells diminishes the upregulatory effect of phenethyl isothiocyanate on heme oxygenase-1

    International Nuclear Information System (INIS)

    Bolloskis, Michael P.; Carvalho, Fabiana P.; Loo, George

    2016-01-01

    Some of the health-promoting properties of cruciferous vegetables are thought to be partly attributed to isothiocyanates. These phytochemicals can upregulate the expression of certain cytoprotective stress genes, but it is unknown if a particular nutrient is involved. Herein, the objective was to ascertain if adequate iron is needed for enabling HCT116 cells to optimally express heme oxygenase-1 (HO-1) when induced by phenethyl isothiocyanate (PEITC). PEITC increased HO-1 expression and also nuclear translocation of Nrf2, which is a transcription factor known to activate the HO-1 gene. However, in HCT116 cells that were made iron-deficient by depleting intracellular iron with deferoxamine (DFO), PEITC was less able to increase HO-1 expression and nuclear translocation of Nrf2. These suppressive effects of DFO were overcome by replenishing the iron-deficient cells with the missing iron. To elucidate these findings, it was found that PEITC-induced HO-1 upregulation can be inhibited with thiol antioxidants (glutathione and N-acetylcysteine). Furthermore, NADPH oxidase inhibitors (diphenyleneiodonium and apocynin) and a superoxide scavenger (Tiron) each inhibited PEITC-induced HO-1 upregulation. In doing so, diphenyleneiodonium was the most potent and also inhibited nuclear translocation of redox-sensitive Nrf2. Collectively, the results imply that the HO-1 upregulation by PEITC involves an iron-dependent, oxidant signaling pathway. Therefore, it is concluded that ample iron is required to enable PEITC to fully upregulate HO-1 expression in HCT116 cells. As such, it is conceivable that iron-deficient individuals may not reap the full health benefits of eating PEITC-containing cruciferous vegetables that via HO-1 may help protect against multiple chronic diseases. - Highlights: • PEITC increased HO-1 expression in HCT116 cells. • PEITC-induced HO-1 upregulation was impaired in iron-depleted HCT116 cells. • Impairment of PEITC-induced HO-1 upregulation was

  6. Transgenic expression of human heme oxygenase-1 in pigs confers resistance against xenograft rejection during ex vivo perfusion of porcine kidneys.

    Science.gov (United States)

    Petersen, Björn; Ramackers, Wolf; Lucas-Hahn, Andrea; Lemme, Erika; Hassel, Petra; Queisser, Anna-Lisa; Herrmann, Doris; Barg-Kues, Brigitte; Carnwath, Joseph W; Klose, Johannes; Tiede, Andreas; Friedrich, Lars; Baars, Wiebke; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

    2011-01-01

    The major immunological hurdle to successful porcine-to-human xenotransplantation is the acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and perturbation of coagulation. Heme oxygenase-1 (HO-1) and its derivatives have anti-apoptotic, anti-inflammatory effects and protect against reactive oxygen species, rendering HO-1 a promising molecule to control AVR. Here, we report the production and characterization of pigs transgenic for human heme oxygenase-1 (hHO-1) and demonstrate significant protection in porcine kidneys against xenograft rejection in ex vivo perfusion with human blood and transgenic porcine aortic endothelial cells (PAEC) in a TNF-α-mediated apoptosis assay. Transgenic and non-transgenic PAEC were tested in a TNF-α-mediated apoptosis assay. Expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was measured by real-time PCR. hHO-1 transgenic porcine kidneys were perfused with pooled and diluted human AB blood in an ex vivo perfusion circuit. MHC class-II up-regulation after induction with IFN-γ was compared between wild-type and hHO-1 transgenic PAEC. Cloned hHO-1 transgenic pigs expressed hHO-1 in heart, kidney, liver, and in cultured ECs and fibroblasts. hHO-1 transgenic PAEC were protected against TNF-α-mediated apoptosis. Real-time PCR revealed reduced expression of adhesion molecules like ICAM-1, VCAM-1, and E-selectin. These effects could be abrogated by the incubation of transgenic PAECs with the specific HO-1 inhibitor zinc protoporphorine IX (Zn(II)PPIX, 20 μm). IFN-γ induced up-regulation of MHC class-II molecules was significantly reduced in PAECs from hHO-1 transgenic pigs. hHO-1 transgenic porcine kidneys could successfully be perfused with diluted human AB-pooled blood for a maximum of 240 min (with and without C1 inh), while in wild-type kidneys, blood flow ceased after ∼60 min. Elevated levels of d-Dimer and TAT were detected, but no significant consumption of fibrinogen and

  7. Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis

    Science.gov (United States)

    Gibbons, Simon J.; Grover, Madhusudan; Choi, Kyoung Moo; Wadhwa, Akhilesh; Zubair, Adeel; Wilson, Laura A.; Wu, Yanhong; Abell, Thomas L.; Hasler, William L.; Koch, Kenneth L.; McCallum, Richard W.; Nguyen, Linda A. B.; Parkman, Henry P.; Sarosiek, Irene; Snape, William J.; Tonascia, James; Hamilton, Frank A.; Pasricha, Pankaj J.

    2017-01-01

    Background Idiopathic and diabetic gastroparesis in Homo sapiens cause significant morbidity. Etiology or risk factors have not been clearly identified. Failure to sustain elevated heme oxygenase-1 (HO1) expression is associated with delayed gastric emptying in diabetic mice and polymorphisms in the HO1 gene (HMOX1, NCBI Gene ID:3162) are associated with worse outcomes in other diseases. Aim Our hypothesis was that longer polyGT alleles are more common in the HMOX1 genes of individuals with gastroparesis than in controls without upper gastrointestinal motility disorders. Methods Repeat length was determined in genomic DNA. Controls with diabetes (84 type 1, 84 type 2) and without diabetes (n = 170) were compared to diabetic gastroparetics (99 type 1, 72 type 2) and idiopathic gastroparetics (n = 234). Correlations of repeat lengths with clinical symptom sub-scores on the gastroparesis cardinal symptom index (GCSI) were done. Statistical analyses of short (32) repeat alleles and differences in allele length were used to test for associations with gastroparesis. Results The distribution of allele lengths was different between groups (P = 0.016). Allele lengths were longest in type 2 diabetics with gastroparesis (29.18±0.35, mean ± SEM) and longer in gastroparetics compared to non-diabetic controls (28.50±0.14 vs 27.64±0.20 GT repeats/allele, P = 0.0008). Type 2 diabetic controls had longer alleles than non-diabetic controls. In all gastroparetic groups, allele lengths were longer in African Americans compared to other racial groups, differences in the proportion of African Americans in the groups accounted for the differences between gastroparetics and controls. Diabetic gastroparetics with 1 or 2 long alleles had worse GCSI nausea sub-scores (3.30±0.23) as compared to those with 0 long alleles (2.66±0.12), P = 0.022. Conclusions Longer poly-GT repeats in the HMOX1 gene are more common in African Americans with gastroparesis. Nausea symptoms are worse in

  8. Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis.

    Science.gov (United States)

    Gibbons, Simon J; Grover, Madhusudan; Choi, Kyoung Moo; Wadhwa, Akhilesh; Zubair, Adeel; Wilson, Laura A; Wu, Yanhong; Abell, Thomas L; Hasler, William L; Koch, Kenneth L; McCallum, Richard W; Nguyen, Linda A B; Parkman, Henry P; Sarosiek, Irene; Snape, William J; Tonascia, James; Hamilton, Frank A; Pasricha, Pankaj J; Farrugia, Gianrico

    2017-01-01

    Idiopathic and diabetic gastroparesis in Homo sapiens cause significant morbidity. Etiology or risk factors have not been clearly identified. Failure to sustain elevated heme oxygenase-1 (HO1) expression is associated with delayed gastric emptying in diabetic mice and polymorphisms in the HO1 gene (HMOX1, NCBI Gene ID:3162) are associated with worse outcomes in other diseases. Our hypothesis was that longer polyGT alleles are more common in the HMOX1 genes of individuals with gastroparesis than in controls without upper gastrointestinal motility disorders. Repeat length was determined in genomic DNA. Controls with diabetes (84 type 1, 84 type 2) and without diabetes (n = 170) were compared to diabetic gastroparetics (99 type 1, 72 type 2) and idiopathic gastroparetics (n = 234). Correlations of repeat lengths with clinical symptom sub-scores on the gastroparesis cardinal symptom index (GCSI) were done. Statistical analyses of short (32) repeat alleles and differences in allele length were used to test for associations with gastroparesis. The distribution of allele lengths was different between groups (P = 0.016). Allele lengths were longest in type 2 diabetics with gastroparesis (29.18±0.35, mean ± SEM) and longer in gastroparetics compared to non-diabetic controls (28.50±0.14 vs 27.64±0.20 GT repeats/allele, P = 0.0008). Type 2 diabetic controls had longer alleles than non-diabetic controls. In all gastroparetic groups, allele lengths were longer in African Americans compared to other racial groups, differences in the proportion of African Americans in the groups accounted for the differences between gastroparetics and controls. Diabetic gastroparetics with 1 or 2 long alleles had worse GCSI nausea sub-scores (3.30±0.23) as compared to those with 0 long alleles (2.66±0.12), P = 0.022. Longer poly-GT repeats in the HMOX1 gene are more common in African Americans with gastroparesis. Nausea symptoms are worse in subjects with longer alleles.

  9. Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis.

    Directory of Open Access Journals (Sweden)

    Simon J Gibbons

    Full Text Available Idiopathic and diabetic gastroparesis in Homo sapiens cause significant morbidity. Etiology or risk factors have not been clearly identified. Failure to sustain elevated heme oxygenase-1 (HO1 expression is associated with delayed gastric emptying in diabetic mice and polymorphisms in the HO1 gene (HMOX1, NCBI Gene ID:3162 are associated with worse outcomes in other diseases.Our hypothesis was that longer polyGT alleles are more common in the HMOX1 genes of individuals with gastroparesis than in controls without upper gastrointestinal motility disorders.Repeat length was determined in genomic DNA. Controls with diabetes (84 type 1, 84 type 2 and without diabetes (n = 170 were compared to diabetic gastroparetics (99 type 1, 72 type 2 and idiopathic gastroparetics (n = 234. Correlations of repeat lengths with clinical symptom sub-scores on the gastroparesis cardinal symptom index (GCSI were done. Statistical analyses of short (32 repeat alleles and differences in allele length were used to test for associations with gastroparesis.The distribution of allele lengths was different between groups (P = 0.016. Allele lengths were longest in type 2 diabetics with gastroparesis (29.18±0.35, mean ± SEM and longer in gastroparetics compared to non-diabetic controls (28.50±0.14 vs 27.64±0.20 GT repeats/allele, P = 0.0008. Type 2 diabetic controls had longer alleles than non-diabetic controls. In all gastroparetic groups, allele lengths were longer in African Americans compared to other racial groups, differences in the proportion of African Americans in the groups accounted for the differences between gastroparetics and controls. Diabetic gastroparetics with 1 or 2 long alleles had worse GCSI nausea sub-scores (3.30±0.23 as compared to those with 0 long alleles (2.66±0.12, P = 0.022.Longer poly-GT repeats in the HMOX1 gene are more common in African Americans with gastroparesis. Nausea symptoms are worse in subjects with longer alleles.

  10. Identification of heme oxygenase-1 stimulators by a convenient ELISA-based bilirubin quantification assay.

    Science.gov (United States)

    Rücker, Hannelore; Amslinger, Sabine

    2015-01-01

    The upregulation of heme oxygenase-1 (HO-1) has proven to be a useful tool for fighting inflammation. In order to identify new HO-1 inducers, an efficient screening method was developed which can provide new lead structures for drug research. We designed a simple ELISA-based HO-1 enzyme activity assay, which allows for the screening of 12 compounds in parallel in the setting of a 96-well plate. The well-established murine macrophage cell line RAW264.7 is used and only about 26µg of protein from whole cell lysates is needed for the analysis of HO-1 activity. The quantification of HO-1 activity is based on an indirect ELISA using the specific anti-bilirubin antibody 24G7 to quantify directly bilirubin in the whole cell lysate, applying a horseradish peroxidase-tagged antibody together with ortho-phenylenediamine and H2O2 for detection. The bilirubin is produced on the action of HO enzymes by converting their substrate heme to biliverdin and additional recombinant biliverdin reductase together with NADPH at pH 7.4 in buffer. This sensitive assay allows for the detection of 0.57-82pmol bilirubin per sample in whole cell lysates. Twenty-three small molecules, mainly natural products with an α,β-unsaturated carbonyl unit such as polyphenols, including flavonoids and chalcones, terpenes, an isothiocyanate, and the drug oltipraz were tested at typically 6 or 24h incubation with RAW264.7 cells. The activity of known HO-1 inducers was confirmed, while the chalcones cardamonin, flavokawain A, calythropsin, 2',3,4'-trihydroxy-4-methoxychalcone (THMC), and 2',4'-dihydroxy-3,4-dimethoxychalcone (DHDMC) were identified as new potent HO-1 inducers. The highest inductive power after 6h incubation was found at 10µM for DHDMC (6.1-fold), carnosol (3.9-fold), butein (3.1-fold), THMC (2.9-fold), and zerumbone (2.5-fold). Moreover, the time dependence of HO-1 protein production for DHDMC was compared to its enzyme activity, which was further evaluated in the presence of

  11. The Anti-Inflammatory Effects of Dimethyl Fumarate in Astrocytes Involve Glutathione and Haem Oxygenase-1

    Directory of Open Access Journals (Sweden)

    Shao Xia Lin

    2011-03-01

    Full Text Available DMF (dimethyl fumarate exerts anti-inflammatory and prometabolic effects in a variety of cell types, and a formulation (BG-12 is being evaluated for monotherapy in multiple sclerosis patients. DMF modifies glutathione (GSH levels that can induce expression of the anti-inflammatory protein HO-1 (haem oxygenase-1. In primary astrocytes and C6 glioma cells, BG-12 dose-dependently suppressed nitrite production induced by either LI [LPS (lipopolysaccharide at 1 μg/ml plus IFNγ (interferon γ at 20 units/ml] or a mixture of proinflammatory cytokines, with greater efficacy in C6 cells. BG-12 reduced NOS2 (nitric oxide synthase 2 mRNA levels and activation of a NOS2 promoter, reduced nuclear levels of NF-κB (nuclear factor κB p65 subunit and attenuated loss of |κBα (inhibitory κBα in both cell types, although with greater effects in astrocytes. In astrocytes, LI decreased mRNA levels for GSHr (GSH reductase and GCL (c-glutamylcysteine synthetase, and slightly suppressed GSHs (GSH synthetase mRNAs. Co-treatment with BG-12 prevented those decreased and increased levels above control values. In contrast, LI reduced GSHp (GSH peroxidase and GCL in C6 cells, and BG-12 had no effect on those levels. BG-12 increased nuclear levels of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2, an inducer of GSH-related enzymes, in astrocytes but not C6 cells. In astrocytes, GSH was decreased by BG-12 at 2 h and increased at 24 h. Prior depletion of GSH using buthionine-sulfoximine increased the ability of BG-12 to reduce nitrites. In astrocytes, BG-12 increased HO-1 mRNA levels and effects on nitrite levels were blocked by an HO-1 inhibitor. These results demonstrate that BG-12 suppresses inflammatory activation in astrocytes and C6 glioma cells, but with distinct mechanisms, different dependence on GSH and different effects on transcription factor activation.

  12. 50 Hz electric field effects on protein carbonyl (PCO), heme oxygenase-1 (HO-1) and hydroxyproline levels

    International Nuclear Information System (INIS)

    Ozgur, Elcin; Goknur, Guler; Seyhan, Nesrin

    2008-01-01

    Full text: Non-ionizing electromagnetic field (EMF) radiation sources, such as power lines and other Extremely Low Frequency (ELF) sources have become one of the most ubiquitous components of the spectrum of the human environment, and the possibility that they may have hazardous effects on human health is a major a public concern. Although it is well documented that EMFs have biological effects, the degree to which these exposures constitute a human health hazard is not clear yet. Today relation between production of oxidative stress resulted by reactive oxygen species and electrical stimulus, also the protective effects of antioxidant treatments are mentioned in many researches. In this study, it was aimed to determine both oxidation of proteins and protein collagen levels under 50 Hz 12 kV/m vertical Electric (E) Field exposure and the N-Acetylcysteine (NAC) administration which is a well-known antioxidant. To this end, protein carbonyl levels (PCO) as bio-markers of oxidative stress and Heme oxygenase-1 (HO-1), an enzyme that catalyzes the degradation of heme analyzed to figure out the protein oxidation. Hydroxyproline level, a major component of the protein collagen was measured in order to express the level of collagen in lung tissue. Guinea pigs, weighted 250-300 g, were used in the study. A total forty male guinea pigs were randomly divided into four groups which are composed of 10 guinea pigs each for groups: 1) Group I (Sham); 2) Group II (NAC-administrated group); 3) Group III (E Field Exposure group); 4) Group IV (NAC administrated + E Field exposed group). One week exposure period for 8 hours per daily was conducted for each exposure groups (Group III, Group IV ). The electric field exposure period was from 9 a.m. to 5 p.m. After the last exposure day, the guinea pigs were anesthetized by the injection of ketamine and xylazine. The guinea pigs were killed by decapitation. Statistical analyses were carried out using SPSS software (SPSS 11.5 for windows

  13. Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Villamor-Martínez, Eduardo; Pierro, Maria; Cavallaro, Giacomo; Mosca, Fabio; Kramer, Boris W; Villamor, Eduardo

    2018-02-20

    Bronchopulmonary dysplasia (BPD) is the most common complication after preterm birth. Pasteurized donor human milk (DHM) has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF) if the mother's own milk (MOM) is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCTs could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (three studies, risk ratio (RR) 0.89, 95% confidence interval (CI) 0.60-1.32). However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67-0.90). An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (three studies, RR 0.80, 95% CI 0.68-0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (two studies, RR 0.77, 95% CI 0.62-0.96). In conclusion, our data suggest that DHM protects against BPD in very preterm infants.

  14. Donor Human Milk Protects against Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Eduardo Villamor-Martínez

    2018-02-01

    Full Text Available Bronchopulmonary dysplasia (BPD is the most common complication after preterm birth. Pasteurized donor human milk (DHM has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF if the mother’s own milk (MOM is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCTs could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (three studies, risk ratio (RR 0.89, 95% confidence interval (CI 0.60–1.32. However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67–0.90. An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (three studies, RR 0.80, 95% CI 0.68–0.95. Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (two studies, RR 0.77, 95% CI 0.62–0.96. In conclusion, our data suggest that DHM protects against BPD in very preterm infants.

  15. Heme oxygenase-1 delays gibberellin-induced programmed cell death of rice aleurone layers subjected to drought stress by interacting with nitric oxide

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    Huangming eWu

    2016-01-01

    Full Text Available Cereal aleurone layers undergo a gibberellin (GA-regulated process of programmed cell death (PCD following germination. Heme oxygenase-1 (HO-1 is known as a rate-liming enzyme in the degradation of heme to biliverdin IXα (BV, carbon monoxide (CO, and free iron ions (Fe2+. It is a critical component in plant development and adaptation to environment stresses. Our previous studies confirmed that HO-1 inducer hematin (Ht promotes the germination of rice seeds in drought (20% polyethylene glycol-6000, PEG conditions, but the corresponding effects of HO-1 on the alleviation of germination-triggered PCD in GA-treated rice aleurone layers remain unknown. The present study has determined that GA co-treated with PEG results in lower HO-1 transcript levels and HO activity, which in turn results in the development of vacuoles in aleurone cells, followed by PCD. The pharmacology approach illustrated that up- or down-regulated HO-1 gene expression and HO activity delayed or accelerated GA-induced PCD. Furthermore, the application of the HO-1 inducer hematin and nitric oxide (NO donor sodium nitroprusside (SNP not only activated HO-1 gene expression, HO activity, and endogenous NO content, but also blocked GA-induced rapid vacuolation and accelerated aleurone layers PCD under drought stress. However, both HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX and NO scavenger 2-(4-carboxyphenyl0-4, 4, 5, 5-tetramethylimidazoline-l-oxyl-3-oxide potassium salt (cPTIO reserved the effects of hematin and SNP on rice aleurone layer PCD under drought stress by down-regulating endogenous HO-1 and NO, respectively. The inducible effects of hematin and SNP on HO-1 gene expression, HO activity, and NO content were blocked by cPTIO. Together, these results clearly suggest that HO-1 is involved in the alleviation of GA-induced PCD of drought-triggered rice aleurone layers by associating with NO.

  16. Postneonatal Mortality and Liver Changes in Cloned Pigs Associated with Human Tumor Necrosis Factor Receptor I-Fc and Human Heme Oxygenase-1 Overexpression.

    Science.gov (United States)

    Kim, Geon A; Jin, Jun-Xue; Lee, Sanghoon; Taweechaipaisankul, Anukul; Oh, Hyun Ju; Hwang, Joing-Ik; Ahn, Curie; Saadeldin, Islam M; Lee, Byeong Chun

    2017-01-01

    Soluble human tumor necrosis factor (shTNFRI-Fc) and human heme oxygenase 1 (hHO-1) are key regulators for protection against oxidative and inflammatory injury for xenotransplantation. Somatic cells with more than 10 copy numbers of shTNFRI-Fc and hHO-1 were employed in somatic cell nuclear transfer to generate cloned pigs, thereby resulting in seven cloned piglets. However, produced piglets were all dead within 24 hours after birth. Obviously, postnatal death with liver apoptosis was reported in the higher copy number of shTNFRI-Fc and hHO-1 piglets. In liver, the transcript levels of ferritin heavy chain, light chain, transferrin, and inducible nitric oxide synthase were significantly highly expressed compared to those of lower copy number of shTNFRI-Fc and hHO-1 piglets ( P hHO-1 piglets ( P hHO-1 overexpression may apparently induce free iron in the liver and exert oxidative stress by enhancing reactive oxygen species production and block normal postneonatal liver metabolism.

  17. Postneonatal Mortality and Liver Changes in Cloned Pigs Associated with Human Tumor Necrosis Factor Receptor I-Fc and Human Heme Oxygenase-1 Overexpression

    Directory of Open Access Journals (Sweden)

    Geon A. Kim

    2017-01-01

    Full Text Available Soluble human tumor necrosis factor (shTNFRI-Fc and human heme oxygenase 1 (hHO-1 are key regulators for protection against oxidative and inflammatory injury for xenotransplantation. Somatic cells with more than 10 copy numbers of shTNFRI-Fc and hHO-1 were employed in somatic cell nuclear transfer to generate cloned pigs, thereby resulting in seven cloned piglets. However, produced piglets were all dead within 24 hours after birth. Obviously, postnatal death with liver apoptosis was reported in the higher copy number of shTNFRI-Fc and hHO-1 piglets. In liver, the transcript levels of ferritin heavy chain, light chain, transferrin, and inducible nitric oxide synthase were significantly highly expressed compared to those of lower copy number of shTNFRI-Fc and hHO-1 piglets (P<0.05. Also, H2O2 contents were increased, and superoxide dismutase was significantly lower in the higher copy number of shTNFRI-Fc and hHO-1 piglets (P<0.05. These results indicate that TNFRI-Fc and hHO-1 overexpression may apparently induce free iron in the liver and exert oxidative stress by enhancing reactive oxygen species production and block normal postneonatal liver metabolism.

  18. A role for heme oxygenase-1 in the antioxidant and antiapoptotic effects of erythropoietin: the start of a good news/bad news story?

    Science.gov (United States)

    Calò, Lorenzo A; Davis, Paul A; Piccoli, Antonio; Pessina, Achille C

    2006-01-01

    Erythropoietin (EPO) is the major regulator of erythropoiesis. EPO's actions have been shown to be antiapoptotic and dependent on JAK2 signaling and Akt phosphorylation. These effects serve as link between EPO and heme oxygenase-1 (HO-1). HO-1 is an inducible enzyme with potent antioxidant and antiapoptotic activities which are regulated by Akt signaling. EPO's ability to alter cellular systems that involve apoptosis and oxidants suggests that EPO treatments are likely to have multiple and different effects which may start a good news/bad news story. Recombinant human EPO is the recognized treatment of choice to address anemia and to stimulate erythropoiesis in chronic renal failure patients, through its antiapoptotic action which likely involves HO-1. On the other hand, EPO treatment to address anemia in cancer patients, while providing significant improvements in cancer patients' quality of life, its effects on survival are equivocal, likely due to its linkage with HO-1. Two clinical trials of EPO in patients with solid tumors have, in fact, shown specific negative effects on survival. However, EPO's effect on tumor growth and survival is not uniformily pro growth and pro survival, as EPO may act synergistically with chemotherapy to induce apoptosis. Finally, compounds have been synthesized that do not trigger EPO receptor and thus may allow experimental distinction and, therefore, at least potentially affect at the clinical level the tissue-protective effects of EPO (e.g., antiapoptosis) without provoking its other potentially detrimental effects. Copyright 2006 S. Karger AG, Basel

  19. Chinese herbal medicine compound Yi-Zhi-Hao pellet inhibits replication of influenza virus infection through activation of heme oxygenase-1

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    Jinqiu Yin

    2017-11-01

    Full Text Available As a leading cause of respiratory disease, influenza A virus (IAV presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet (CYZH is a famous traditional Chinese medicine (TCM used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2 (Nrf2 and nuclear factor kappa B (NF-κB, which subsequently upregulated heme oxygenase-1 (HO-1 expression. Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions, CYZH inhibits IAV replication in vitro, at least partly by activating expression of the Nrf2/HO-1 pathway.

  20. Epigallocatechin Gallate Attenuates Proliferation and Oxidative Stress in Human Vascular Smooth Muscle Cells Induced by Interleukin-1β via Heme Oxygenase-1

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    Po-Len Liu

    2014-01-01

    Full Text Available Proliferation of vascular smooth muscle cells (VSMCs triggered by inflammatory stimuli and oxidative stress contributes importantly to atherogenesis. The association of green tea consumption with cardiovascular protection has been well documented in epidemiological observations, however, the underlying mechanisms remain unclear. This study aimed to elucidate the effects of the most active green tea catechin derivative, (−-epigallocatechin-3-gallate (EGCG, in human aortic smooth muscle cells (HASMCs, focusing particularly on the role of a potent anti-inflammatory and antioxidative enzyme heme oxygenase-1 (HO-1. We found that pretreatment of EGCG dose- and time-dependently induced HO-1 protein levels in HASMCs. EGCG inhibited interleukin- (IL-1β-induced HASMC proliferation and oxidative stress in a dose-dependent manner. The HO-1 inducer CoPPIX decreased IL-1β-induced cell proliferation, whereas the HO-1 enzyme inhibitor ZnPPIX significantly reversed EGCG-caused growth inhibition in IL-1β-treated HASMCs. At the molecular level, EGCG treatment significantly activated nuclear factor erythroid-2-related factor (Nrf2 transcription activities. These results suggest that EGCG might serve as a complementary and alternative medicine in the treatment of these pathologies by inducing HO-1 expression and subsequently decreasing VSMC proliferation.

  1. Physalis peruviana L. inhibits airway inflammation induced by cigarette smoke and lipopolysaccharide through inhibition of extracellular signal-regulated kinase and induction of heme oxygenase-1.

    Science.gov (United States)

    Park, Hyun Ah; Lee, Jae-Won; Kwon, Ok-Kyoung; Lee, Gilhye; Lim, Yourim; Kim, Jung Hee; Paik, Jin-Hyub; Choi, Sangho; Paryanto, Imam; Yuniato, Prasetyawan; Kim, Doo-Young; Ryu, Hyung Won; Oh, Sei-Ryang; Lee, Seung Jin; Ahn, Kyung-Seop

    2017-11-01

    Physalis peruviana L. (PP) is a medicinal herb that has been confirmed to have several biological activities, including anticancer, antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the protective effect of PP on cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced pulmonary inflammation. Treatment with PP significantly reduced the influx of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung of mice with CS- and LPS-induced pulmonary inflammation. PP also decreased the levels of reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF. PP effectively attenuated the expression of monocyte chemoattractant protein-1 (MCP-1) and the activation of extracellular signal-regulated kinase (ERK) in the lung. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) activation and heme oxygenase-1 (HO-1) expression were increased by PP treatment. In an in vitro experiment, PP reduced the mRNA expression of TNF-α and MCP-1, and the activation of ERK in CS extract-stimulated A549 epithelial cells. Furthermore, PP increased the activation of Nrf2 and the expression of HO-1 in A549 cells. These findings suggest that PP has a therapeutic potential for the treatment of pulmonary inflammatory diseases, such as chronic obstructive pulmonary disease.

  2. How nitric oxide donors can protect plants in a changing environment: what we know so far and perspectives

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    Amedea B. Seabra

    2016-12-01

    Full Text Available The free radical nitric oxide (NO plays important roles in plant growth and defense. Owing to its small size and lipophilicity, NO acts as a crucial signaling molecule in plants, crossing cell membranes and enhancing cell communication. Indeed, NO donors have been shown to modulate a variety of physiological processes, such as plant greening, seed germination, iron homeostasis and mitochondrial respiration. Recently, several papers have reported the protective actions upon application of low molecular weight NO donors in plants under abiotic stress. Exogenous NO is able to improve plant tolerance to several abiotic stresses, such as drought, salinity, metal toxicity, and extreme temperatures. This protection is assigned to the NO-mediated redox signaling in plants, which involves interplay with reactive oxygen species and modulation of gene expression and protein function. This review reports and discusses the recent advantages, pitfalls, challenges, and perspectives in the applications of low molecular weight NO donors in plants under abiotic stress. The combination of nanotechnology and NO donors as an efficient approach to protect plants under challenging environments is also discussed.

  3. BTB and CNC homolog 1 (Bach1) deficiency ameliorates TNBS colitis in mice: role of M2 macrophages and heme oxygenase-1.

    Science.gov (United States)

    Harusato, Akihito; Naito, Yuji; Takagi, Tomohisa; Uchiyama, Kazuhiko; Mizushima, Katsura; Hirai, Yasuko; Higashimura, Yasuki; Katada, Kazuhiro; Handa, Osamu; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Ichikawa, Hiroshi; Muto, Akihiko; Igarashi, Kazuhiko; Yoshikawa, Toshikazu

    2013-01-01

    BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1), which plays an important role in the protection of cells and tissues against acute and chronic inflammation. However, the role of Bach1 in the gastrointestinal mucosal defense system remains little understood. HO-1 supports the suppression of experimental colitis and localizes mainly in macrophages in colonic mucosa. This study was undertaken to elucidate the Bach1/HO-1 system's effects on the pathogenesis of experimental colitis. This study used C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice in which colonic damage was induced by the administration of an enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Subsequently, they were evaluated macroscopically, histologically, and biochemically. Peritoneal macrophages from the respective mice were isolated and analyzed. Then, wild-type mice were injected with peritoneal macrophages from the respective mice. Acute colitis was induced similarly. TNBS-induced colitis was inhibited in Bach1-deficient mice. TNBS administration increased the expression of HO-1 messenger RNA and protein in colonic mucosa in Bach1-deficient mice. The expression of HO-1 mainly localized in F4/80-immunopositive and CD11b-immunopositive macrophages. Isolated peritoneal macrophages from Bach1-deficient mice highly expressed HO-1 and also manifested M2 macrophage markers, such as Arginase-1, Fizz-1, Ym1, and MRC1. Furthermore, TNBS-induced colitis was inhibited by the transfer of Bach1-deficient macrophages into wild-type mice. Deficiency of Bach1 ameliorated TNBS-induced colitis. Bach1-deficient macrophages played a key role in protection against colitis. Targeting of this mechanism is applicable to cell therapy for human inflammatory bowel disease.

  4. Methane-rich water induces cucumber adventitious rooting through heme oxygenase1/carbon monoxide and Ca(2+) pathways.

    Science.gov (United States)

    Cui, Weiti; Qi, Fang; Zhang, Yihua; Cao, Hong; Zhang, Jing; Wang, Ren; Shen, Wenbiao

    2015-03-01

    Methane-rich water triggered adventitious rooting by regulating heme oxygenase1/carbon monoxide and calcium pathways in cucumber explants. Heme oxygenase1/carbon monoxide (HO1/CO) and calcium (Ca(2+)) were reported as the downstream signals in auxin-induced cucumber adventitious root (AR) formation. Here, we observed that application of methane-rich water (MRW; 80% saturation) obviously induced AR formation in IAA-depleted cucumber explants. To address the universality, we checked adventitious rooting in soybean and mung bean explants, and found that MRW (50 and 10% saturation, respectively) exhibited the similar inducing results. To further determine if the HO1/CO system participated in MRW-induced adventitious rooting, MRW, HO1 inducer hemin, its activity inhibitor zinc protoporphyrin IX (ZnPP), and its catalytic by-products CO, bilirubin, and Fe(2+) were used to detect their effects on cucumber adventitious rooting in IAA-depleted explants. Subsequent results showed that MRW-induced adventitious rooting was blocked by ZnPP and further reversed by 20% saturation CO aqueous solution. However, the other two by-products of HO1, bilirubin and Fe(2+), failed to induce AR formation. Above responses were consistent with the MRW-induced increases of HO1 transcript and corresponding protein level. Further molecular evidence indicted that expression of marker genes, including auxin signaling-related genes and cell cycle regulatory genes, were modulated by MRW alone but blocked by the cotreatment with ZnPP, the latter of which could be significantly rescued by the addition of CO. By using the Ca(2+)-channel blocker and Ca(2+) chelator, the involvement of Ca(2+) pathway in MRW-induced adventitious rooting was also suggested. Together, our results indicate that MRW might serve as a stimulator of adventitious rooting, which was partially mediated by HO1/CO and Ca(2+) pathways.

  5. GT-repeat polymorphism in the heme oxygenase-1 gene promoter is associated with cardiovascular mortality risk in an arsenic-exposed population in northeastern Taiwan

    International Nuclear Information System (INIS)

    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Wang, Yuan-Hung; Hsieh, Yi-Chen; Lien, Li-Ming; Lee, Te-Chang; Chen, Chien-Jen

    2010-01-01

    Inorganic arsenic has been associated with increased risk of atherosclerotic vascular disease and mortality in humans. A functional GT-repeat polymorphism in the heme oxygenase-1 (HO-1) gene promoter is inversely correlated with the development of coronary artery disease and restenosis after clinical angioplasty. The relationship of HO-1 genotype with arsenic-associated cardiovascular disease has not been studied. In this study, we evaluated the relationship between the HO-1 GT-repeat polymorphism and cardiovascular mortality in an arsenic-exposed population. A total of 504 study participants were followed up for a median of 10.7 years for occurrence of cardiovascular deaths (coronary heart disease, cerebrovascular disease, and peripheral arterial disease). Cardiovascular risk factors and DNA samples for determination of HO-1 GT repeats were obtained at recruitment. GT repeats variants were grouped into the S (< 27 repeats) or L allele (≥ 27 repeats). Relative mortality risk was estimated using Cox regression analysis, adjusted for competing risk of cancer and other causes. For the L/L, L/S, and S/S genotype groups, the crude mortalities for cardiovascular disease were 8.42, 3.10, and 2.85 cases/1000 person-years, respectively. After adjusting for conventional cardiovascular risk factors and competing risk of cancer and other causes, carriers with class S allele (L/S or S/S genotypes) had a significantly reduced risk of cardiovascular mortality compared to non-carriers (L/L genotype) [OR, 0.38; 95% CI, 0.16-0.90]. In contrast, no significant association was observed between HO-1 genotype and cancer mortality or mortality from other causes. Shorter (GT)n repeats in the HO-1 gene promoter may confer protective effects against cardiovascular mortality related to arsenic exposure.

  6. A novel compound derived from danshensu inhibits apoptosis via upregulation of heme oxygenase-1 expression in SH-SY5Y cells.

    Science.gov (United States)

    Pan, Li-Long; Liu, Xin-Hua; Jia, Yao-Ling; Wu, Dan; Xiong, Qing-Hui; Gong, Qi-Hai; Wang, Yang; Zhu, Yi-Zhun

    2013-04-01

    Heme oxygenase-1 (HO-1) has potential anti-apoptotic properties. A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2- ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)] was synthesized by joining danshensu and cysteine through an appropriate linker. This study investigated if the cytoprotective properties of DSC involved the induction of HO-1. We evaluated the cytoprotective effects of DSC on H2O2-induced cell damage, apoptosis, intracellular and mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm) loss, and apoptosis-related proteins expression and its underlying mechanisms. DSC concentration-dependently attenuated cell death, lactate dehydrogenase release, intracellular and mitochondrial ROS production, and ΔΨm collapse, modulated apoptosis-related proteins (Bcl-2, Bax, caspase-3, p53, and cleaved PARP) expression, and inhibited phosphorylation of extracellular signal-regulated kinase 1/2 in SH-SY5Y cells induced by H2O2. In addition, DSC concentration-dependently induced HO-1 expression associated with nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2), while the effect of DSC was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Furthermore, the protective effect of DSC on H2O2-induced cell death was abolished by HO-1 inhibitor ZnPP, but was mimicked by carbon monoxide-releasing moiety CORM-3 or HO-1 by-product bilirubin. Finally, DSC inhibited H2O2-induced changes of Bcl-2, Bax, and caspase-3 expression, and all of these effects were reversed by HO-1 silencing. Induction of HO-1 may be, at least in part, responsible for the anti-apoptotic property of DSC, an effect that involved the activation of PI3K/Akt/Nrf-2 axis. DSC might have the potential for beneficial therapeutic interventions for neurodegenerative diseases. Copyright © 2013. Published by Elsevier B.V.

  7. A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.

    Science.gov (United States)

    Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian

    2005-12-01

    The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

  8. Glomerular Epithelial Cells-Targeted Heme Oxygenase-1 Over Expression in the Rat: Attenuation of Proteinuria in Secondary But Not Primary Injury.

    Science.gov (United States)

    Atsaves, Vassilios; Makri, Panagiota; Detsika, Maria G; Tsirogianni, Alexandra; Lianos, Elias A

    2016-01-01

    Induction of heme oxygenase 1 (HO-1) in glomerular epithelial cells (GEC) in response to injury is poor and this may be a disadvantage. We, therefore, explored whether HO-1 overexpression in GEC can reduce proteinuria induced by puromycin aminonucleoside (PAN) or in anti-glomerular basement membrane (GBM) antibody (Ab)-mediated glomerulonephritis (GN). HO-1 overexpression in GEC (GECHO-1) of Sprague-Dawley rats was achieved by targeting a FLAG-human (h) HO-1 using transposon-mediated transgenesis. Direct GEC injury was induced by a single injection of PAN. GN was induced by administration of an anti-rat GBM Ab and macrophage infiltration in glomeruli was assessed by immunohistochemistry and western blot analysis, which was also used to assess glomerular nephrin expression. In GECHO-1 rats, FLAG-hHO-1 transprotein was co-immunolocalized with nephrin. Baseline glomerular HO-1 protein levels were higher in GECHO-1 compared to wild type (WT) rats. Administration of either PAN or anti-GBM Ab to WT rats increased glomerular HO-1 levels. Nephrin expression markedly decreased in glomeruli of WT or GECHO-1 rats treated with PAN. In anti-GBM Ab-treated WT rats, nephrin expression also decreased. In contrast, it was preserved in anti-GBM Ab-treated GECHO-1 rats. In these, macrophage infiltration in glomeruli and the ratio of urine albumin to urine creatinine (Ualb/Ucreat) were markedly reduced. There was no difference in Ualb/Ucreat between WT and GECHO-1 rats treated with PAN. Depending on the type of injury, HO-1 overexpression in GEC may or may not reduce proteinuria. Reduced macrophage infiltration and preservation of nephrin expression are putative mechanisms underlying the protective effect of HO-1 overexpression following immune injury. © 2016 S. Karger AG, Basel.

  9. Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of carbon monoxide

    NARCIS (Netherlands)

    Dijkstra, Gerard; Blokzijl, Hans; Bok, Lisette; Homan, Manon; van Goor, Harry; Faber, Klaas Nico; Jansen, Peter L. M.; Moshage, Han

    2004-01-01

    Inducible nitric oxide synthase (iNOS) is expressed in intestinal epithelial cells (IEC) of patients with active inflammatory bowel disease (IBD) and in IEC of endotoxaemic rats. The induction of iNOS in IEC is an element of the NF-kappaB-mediated survival pathway. Haem oxygenase-1 (HO-1) is an

  10. Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction.

    Science.gov (United States)

    Fetoni, Anna R; Eramo, Sara L M; Paciello, Fabiola; Rolesi, Rolando; Podda, Maria Vittoria; Troiani, Diana; Paludetti, Gaetano

    2014-06-01

    To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1. Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities. In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection. Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression. This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.

  11. Polymorphisms in the Haem Oxygenase-1 promoter are not associated with severity of Plasmodium falciparum malaria in Ghanaian children.

    Science.gov (United States)

    Hansson, Helle H; Maretty, Lasse; Balle, Christina; Goka, Bamenla Q; Luzon, Elisa; Nkrumah, Francis N; Schousboe, Mette L; Rodrigues, Onike P; Bygbjerg, Ib Christian; Kurtzhals, Jørgen A L; Alifrangis, Michael; Hempel, Casper

    2015-04-11

    Haem oxygenase-1 (HO-1) catabolizes haem and has both cytotoxic and cytoprotective effects. Polymorphisms in the promoter of the Haem oxygenase-1 (HMOX1) gene encoding HO-1 have been associated with several diseases including severe malaria. The objective of this study was to determine the allele and genotype frequencies of two single nucleotide polymorphisms; A(-413)T and G(-1135)A, and a (GT)n repeat length polymorphism in the HMOX1 promoter in paediatric malaria patients and controls to determine possible associations with malaria disease severity. Study participants were Ghanaian children (n=296) admitted to the emergency room at the Department of Child Health, Korle-Bu Teaching Hospital, Accra, Ghana during the malaria season from June to August in 1995, 1996 and 1997, classified as having uncomplicated malaria (n=101) or severe malaria (n=195; defined as severe anaemia (n=63) or cerebral malaria (n=132)). Furthermore, 287 individuals without a detectable Plasmodium infection or asymptomatic carriers of the parasite were enrolled as controls. Blood samples from participants were extracted for DNA and allele and genotype frequencies were determined with allele-specific PCR, restriction fragment length analysis and microsatellite analysis. The number of (GT)n repeats in the study participants varied between 21 and 46 with the majority of alleles having lengths of 26 (8.1%), 29/30 (13.2/17.9%) and 39/40 (8.0/13.8%) repeats, and was categorized into short, medium and long repeats. The (-413)T allele was very common (69.8%), while the (-1135)A allele was present in only 17.4% of the Ghanaian population. The G(-1135)A locus was excluded from further analysis after failing the Hardy-Weinberg equilibrium test. No significant differences in allele or genotype distribution of the A(-413)T and (GT)n repeat polymorphisms were found between the controls and the malaria patients, or between the disease groups, for any of the analysed polymorphisms and no associations with

  12. Andrographolide induces Nrf2 and heme oxygenase 1 in astrocytes by activating p38 MAPK and ERK.

    Science.gov (United States)

    Wong, Siew Ying; Tan, Michelle G K; Wong, Peter T H; Herr, Deron R; Lai, Mitchell K P

    2016-09-23

    Andrographolide is the major labdane diterpenoid originally isolated from Andrographis paniculata and has been shown to have anti-inflammatory and antioxidative effects. However, there is a dearth of studies on the potential therapeutic utility of andrographolide in neuroinflammatory conditions. Here, we aimed to investigate the mechanisms underlying andrographolide's effect on the expression of anti-inflammatory and antioxidant heme oxygenase-1 (HO-1) in primary astrocytes. Measurements of the effects of andrograholide on antioxidant HO-1 and its transcription factor, Nrf2, include gene expression, protein turnover, and activation of putative signaling regulators. Andrographolide potently activated Nrf2 and also upregulated HO-1 expression in primary astrocytes. Andrographolide's effects on Nrf2 seemed to be biphasic, with acute (within 1 h) reductions in Nrf2 ubiquitination efficiency and turnover rate, followed by upregulation of Nrf2 mRNA between 8 and 24 h. The acute regulation of Nrf2 by andrographolide seemed to be independent of Keap1 and partly mediated by p38 MAPK and ERK signaling. These data provide further insights into the mechanisms underlying andrographolide's effects on astrocyte-mediated antioxidant, and anti-inflammatory responses and support the further assessment of andrographolide as a potential therapeutic for neurological conditions in which oxidative stress and neuroinflammation are implicated.

  13. Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis.

    Science.gov (United States)

    Liu, Shu-Ling; Deng, Jeng-Shyan; Chiu, Chuan-Sung; Hou, Wen-Chi; Huang, Shyh-Shyun; Lin, Wang-Ching; Liao, Jung-Chun; Huang, Guan-Jhong

    2012-01-01

    Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT) were used in lipopolysaccharide (LPS-)stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-)induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE(2)) levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and elevated heme oxygenase-1 (HO-1), significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products.

  14. Involvement of Heme Oxygenase-1 Participates in Anti-Inflammatory and Analgesic Effects of Aqueous Extract of Hibiscus taiwanensis

    Directory of Open Access Journals (Sweden)

    Shu-Ling Liu

    2012-01-01

    Full Text Available Anti-inflammatory effects of the aqueous extract of Hibiscus taiwanensis (AHT were used in lipopolysaccharide (LPS-stimulated mouse macrophage RAW264.7 cells and carrageenan (Carr-induced mouse paw edema model. When RAW264.7 macrophages were treated with AHT together with LPS, a concentration-dependent inhibition of nitric oxide (NO, tumor necrosis factor (TNF-α, and prostaglandin E2 (PGE2 levels productions were detected. Western blotting revealed that AHT blocked protein expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2, and elevated heme oxygenase-1 (HO-1, significantly. In the animal test, AHT decreased the paw edema at the 4th and the 5th h after Carr administration, and it increased the activities of catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx in the paw tissue. We also demonstrated AHT decreased the NO, TNF-α, and PGE2 levels on the serum level at the 5th h after the Carr injection. Western blotting revealed that AHT decreased Carr-induced iNOS, and COX-2, and increased HO-1 expressions at the 5th h in the edema paw. These findings demonstrated that AHT has excellent anti-inflammatory activities in vitro and in vivo and thus it has great potential to be used as a source for natural health products.

  15. Covalent heme attachment to the protein in human heme oxygenase-1 with selenocysteine replacing the His25 proximal iron ligand.

    Science.gov (United States)

    Jiang, Yongying; Trnka, Michael J; Medzihradszky, Katalin F; Ouellet, Hugues; Wang, Yongqiang; Ortiz de Montellano, Paul R

    2009-03-01

    To characterize heme oxygenase with a selenocysteine (SeCys) as the proximal iron ligand, we have expressed truncated human heme oxygenase-1 (hHO-1) His25Cys, in which Cys-25 is the only cysteine, in the Escherichia coli cysteine auxotroph strain BL21(DE3)cys. Selenocysteine incorporation into the protein was demonstrated by both intact protein mass measurement and mass spectrometric identification of the selenocysteine-containing tryptic peptide. One selenocysteine was incorporated into approximately 95% of the expressed protein. Formation of an adduct with Ellman's reagent (DTNB) indicated that the selenocysteine in the expressed protein was in the reduced state. The heme-His25SeCys hHO-1 complex could be prepared by either (a) supplementing the overexpression medium with heme, or (b) reconstituting the purified apoprotein with heme. Under reducing conditions in the presence of imidazole, a covalent bond is formed by addition of the selenocysteine residue to one of the heme vinyl groups. No covalent bond is formed when the heme is replaced by mesoheme, in which the vinyls are replaced by ethyl groups. These results, together with our earlier demonstration that external selenolate ligands can transfer an electron to the iron [Y. Jiang, P.R. Ortiz de Montellano, Inorg. Chem. 47 (2008) 3480-3482 ], indicate that a selenyl radical is formed in the hHO-1 His25SeCys mutant that adds to a heme vinyl group.

  16. Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1.

    Science.gov (United States)

    Zhou, Wen-Pu; Zhong, Wen-Wei; Zhang, Xue-Hong; Ding, Jian-Ping; Zhang, Zi-Li; Xia, Zhen-Wei

    2009-03-01

    Human heme oxygenase-1 (hHO-1) is a rate-limiting enzyme in heme metabolism. It regulates serum bilirubin level. Site-directed mutagenesis studies indicate that the proximal residue histidine 25 (His25) plays a key role in hHO-1 activity. A highly purified hHO-1 His25Ala mutant was generated and crystallized with a new expression system. The crystal structure of the mutant was determined by X-ray diffraction technology and molecular replacement at the resolution of 2.8 A, and the model of hHO-1 His25Ala mutant was refined. The final crystallographic and free R factors were 0.245 and 0.283, respectively. The standard bond length deviation was 0.007 A, and the standard bond angle deviation was 1.3 degrees . The mutation of His25 to Ala led to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Although this did not cause an overall structural change, the enzymatic activity of the mutant hHO-1 was reduced by 90%. By supplementing imidazole, the HO-1 activity was restored approximately 90% to its normal level. These data suggest that Ala25 remains unchanged in the structure compared to His25, but the important catalytic function of hHO-1 is lost. Thus, it appears that His25 is a crucial residue for proper hHO-1 catalysis.

  17. An improved method for purification of recombinant truncated heme oxygenase-1 by expanded bed adsorption and gel filtration.

    Science.gov (United States)

    Hu, Hong-Bo; Wang, Wei; Han, Ling; Zhou, Wen-Pu; Zhang, Xue-Hong

    2007-03-01

    Recombinant truncated human heme oxygenase-1 (hHO-1) expressed in Escherichia coli was efficiently separated and purified from feedstock by DEAE-ion exchange expanded bed adsorption. Protocol optimization of hHO-1 on DEAE adsorbent resulted in adsorption in 0 M NaCl and elution in 150 mM NaCl at a pH of 8.5. The active enzyme fractions separated from the expanded bed column were further purified by a Superdex 75 gel filtration step. The specific hHO-1 activity increased from 0.82 +/- 0.05 to 24.8 +/- 1.8 U/mg during the whole purification steps. The recovery and purification factor of truncated hHO-1 of the whole purification were 72.7 +/- 4.7 and 30.2 +/- 2.3%, respectively. This purification process can decrease the demand on the preparation of feedstock and simplify the purification process.

  18. L-ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1.

    Science.gov (United States)

    Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

    2012-12-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ya-Ni [Department of Nursing, Hsin Sheng College of Medical Care and Management, Taoyuan, Taiwan (China); Wang, Jiz-Yuh [Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Lee, Ching-Tien [Department of Nursing, Hsin Sheng College of Medical Care and Management, Taoyuan, Taiwan (China); Lin, Chih-Hung [Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Lai, Chien-Cheng [Far Eastern Memorial Hospital, Department of Surgery, Taipei, Taiwan (China); Wang, Jia-Yi, E-mail: jywang2010@tmu.edu.tw [Graduate Institute of Medical Sciences and Department of Physiology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2012-12-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by

  20. L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

    International Nuclear Information System (INIS)

    Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

    2012-01-01

    Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by

  1. Exogenous nitric oxide donor protects Artemisia annua from oxidative stress generated by boron and aluminium toxicity.

    Science.gov (United States)

    Aftab, Tariq; Khan, M Masroor A; Naeem, M; Idrees, Mohd; Moinuddin; Teixeira da Silva, Jaime A; Ram, M

    2012-06-01

    Nitric oxide (NO) is an important signal molecule modulating the response of plants to environmental stress. Here we report the effects of boron (B) and aluminium (Al) contamination in soil, carried out with or without application of exogenous SNP (NO donor), on various plant processes in Artemisia annua, including changes in artemisinin content. The addition of B or Al to soil medium significantly reduced the yield and growth of plants and lowered the values of net photosynthetic rate, stomatal conductance, internal CO(2) concentration and total chlorophyll content. The follow-up treatment of NO donor favoured growth and improved the photosynthetic efficiency in stressed as well as non-stressed plants. Artemisinin content was enhanced by 24.6% and 43.8% at 1mmole of soil-applied B or Al. When SNP was applied at 2mmole concentration together with either 1mmole of B and/or Al, it further stimulated artemisinin biosynthesis compared to the control. Application of B+Al+SNP proved to be the best treatment combination for the artemisinin content in Artemisia annua leaves. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Impact of Bariatric Surgery on Heme Oxygenase-1, Inflammation, and Insulin Resistance in Morbid Obesity with Obstructive Sleep Apnea.

    Science.gov (United States)

    Tirado, Raquel; Masdeu, Maria José; Vigil, Laura; Rigla, Mercedes; Luna, Alexis; Rebasa, Pere; Pareja, Rocío; Hurtado, Marta; Caixàs, Assumpta

    2017-09-01

    Morbid obesity and obstructive sleep apnea (OSA) interact at an inflammatory level. Bariatric surgery reduces inflammatory responses associated with obesity. Heme oxygenase-1 (HO-1) is an enzyme with anti-inflammatory properties, which might be increased in morbid obesity or OSA. We studied morbidly obese patients with OSA to determine: (a) HO-1 plasma concentrations according to OSA severity and their relationship with insulin resistance and inflammation and (b) the impact of bariatric surgery on HO-1 and parameters of insulin resistance and inflammation. We analyzed the homeostasis model insulin resistance index (HOMA) and plasma concentrations of HO-1, tumor necrosis factor alpha, interleukin-6, interleukin-1-beta, C reactive protein (CRP), and adiponectin according to polysomnography findings in 66 morbidly obese patients before bariatric surgery and 12 months after surgery. Before surgery, HO-1 plasma concentrations were similar in three groups of patients with mild, moderate, and severe OSA, and correlated with HOMA (r = 0.27, p = 0.02). Twelve months after surgery, low-grade inflammation and insulin resistance had decreased in all the groups, but HO-1 plasma concentration had decreased only in the severe OSA group (p = 0.02). In this group, the reduction in HO-1 correlated with a reduction in CRP concentrations (r = 0.43, p = 0.04) and with improved HOMA score (r = 0.37, p = 0.03). Bariatric surgery decreases HO-1 concentrations in morbid obesity with severe OSA, and this decrease is associated with decreases in insulin resistance and in inflammation.

  3. Identification of Heme Oxygenase-1 as a Novel Predictor of Hematopoietic Stem Cell Transplantation Outcomes in Acute Leukemia

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    Yinghao Lu

    2016-09-01

    Full Text Available Objective: The main aim of this study was to determine the correlation between clinical outcome and heme oxygenase-1 (HO-1 expression before and after hematopoietic stem cell transplantation (HSCT in acute leukemia. Methods: HO-1 mRNA levels in 83 patients were measured using qRT-PCR. In a comparative analysis of HO-1 levels in relation to different post-transplant outcomes, the HO-1 threshold, determined via the receiver operating characteristic (ROC curve, was effectively used to predict clinical relapse and acute graft-versus-host disease (aGVHD. The correlations among clinical relapse, aGVHD and HO-1 expression were analyzed based on this threshold. Results: Leukemia risk stratification and relative expression of HO-1 before pretreatment had significant effects on clinical relapse. Leukemia risk stratification, relative expression of HO-1 after HSCT and the interval from diagnosis to transplantation had a significant influence on aGVHD. Both relapse and aGVHD appeared to be associated with relative HO-1 expression. The relative expression rate of HO-1 was 1.131-1.186 before pretreatment, and strongly associated with post-transplantation relapse. The relative expression rate of HO-1 was 1.102-1.144 after transplantation, and closely related to aGVHD. ROC curve analysis revealed high specificity and sensitivity of HO-1 expression in predicting relapse and aGVHD after allo-HSCT. Conclusions: HO-1 expression can be effectively used as a predictor of relapse as well as a diagnostic factor of aGVHD after transplantation for allo-HSCT patients with acute leukemia.

  4. Heme oxygenase-1 (HO-1 expression in prostate cancer cells modulates the oxidative response in bone cells.

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    Mercedes Ferrando

    Full Text Available Prostate cancer (PCa is a leading cause of death among males. It is currently estimated that inflammatory responses are linked to 15-20% of all deaths from cancer worldwide. PCa is dominated by complications arising from metastasis to the bone where the tumor cells interact with the bone microenvironment impairing the balance between bone formation and degradation. However, the molecular nature of this interaction is not completely understood. Heme oxygenase-1 (HO-1 counteracts oxidative damage and inflammation. Previous studies from our laboratory showed that HO-1 is implicated in PCa, demonstrating that endogenous HO-1 inhibits bone derived-prostate cancer cells proliferation, invasion and migration and decreases tumor growth and angiogenesis in vivo. The aim of this work was to analyze the impact of HO-1 modulated PCa cells on osteoblasts proliferation in vitro and on bone remodeling in vivo. Using a co-culture system of PC3 cells with primary mice osteoblasts (PMOs, we demonstrated that HO-1 pharmacological induction (hemin treatment abrogated the diminution of PMOs proliferation induced by PCa cells and decreased the expression of osteoclast-modulating factors in osteoblasts. No changes were detected in the expression of genes involved in osteoblasts differentiation. However, co-culture of hemin pre-treated PC3 cells (PC3 Hem with PMOs provoked an oxidative status and activated FoxO signaling in osteoblasts. The percentage of active osteoblasts positive for HO-1 increased in calvarias explants co-cultured with PC3 Hem cells. Nuclear HO-1 expression was detected in tumors generated by in vivo bone injection of HO-1 stable transfected PC3 (PC3HO-1 cells in the femur of SCID mice. These results suggest that HO-1 has the potential to modify the bone microenvironment impacting on PCa bone metastasis.

  5. Microsatellite polymorphism in the heme oxygenase-1 gene promoter and the risk of atrial fibrillation in Taiwanese.

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    Lung-An Hsu

    Full Text Available Atrial fibrillation (AF is associated with increased oxidative stress. Emerging evidence suggests that heme oxygenase-1 (HO-1 is a potent antioxidant system against various oxidative stress-related diseases. The human HO-1 promoter has a GT-repeat length polymorphism that can determine the level of gene transcription.The aim of this study is to assess the role of the GT-repeat polymorphism in the promoter region of the HO-1 gene in Chinese-Taiwanese patients with AF.This study enrolled 200 AF patients and 240 controls, comparable for age and gender. In each subject, the length of GT-repeat polymorphism in the HO-1 promoter region was examined by polymerase chain reactions. The frequencies of long GT-repeat alleles (≧32 were significantly higher in AF patients than in controls. Multivariate analysis showed that the presence of long allele was significantly and independently associated with AF (odds ratio: 1.91, 95% CI 1.07-3.72; P = 0.028. Right atrial tissues from patients with chronic AF were investigated with immunoconfocal microscopy. Patients homozygous for shorter GT-repeat alleles exhibited greater HO-1 expression in their atria than those homozygous for longer alleles, which was reflected by less oxidative stress, myofibril degradation, and fibrosis in the atria of patients with shorter GT-repeat. In vitro, transient transfection assay in HL-1 atrial myocytes showed that the responsiveness of HO-1 transcriptional activity to tachypacing was inversely correlated with the length of the GT-repeats.Our results suggest that the HO-1 microsatellite polymorphism may contribute to the genetic background of AF in Chinese-Taiwanese patients.

  6. Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by reducing inflammation, oxidative stress, apoptosis and enhancing autophagy.

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    Yanli Zhao

    Full Text Available Heme oxygenase-1 (HO-1 has been implicated in cardiac dysfunction, oxidative stress, inflammation, apoptosis and autophagy associated with heart failure, and atherosclerosis, in addition to its recognized role in metabolic syndrome and diabetes. Numerous studies have presented contradictory findings about the role of HO-1 in diabetic cardiomyopathy (DCM. In this study, we explored the role of HO-1 in myocardial dysfunction, myofibril structure, oxidative stress, inflammation, apoptosis and autophagy using a streptozotocin (STZ-induced diabetes model in mice systemically overexpressing HO-1 (Tg-HO-1 or mutant HO-1 (Tg-mutHO-1. The diabetic mouse model was induced by multiple peritoneal injections of STZ. Two months after injection, left ventricular (LV function was measured by echocardiography. In addition, molecular biomarkers related to oxidative stress, inflammation, apoptosis and autophagy were evaluated using classical molecular biological/biochemical techniques. Mice with DCM exhibited severe LV dysfunction, myofibril structure disarray, aberrant cardiac oxidative stress, inflammation, apoptosis, autophagy and increased levels of HO-1. In addition, we determined that systemic overexpression of HO-1 ameliorated left ventricular dysfunction, myofibril structure disarray, oxidative stress, inflammation, apoptosis and autophagy in DCM mice. Furthermore, serine/threonine-specific protein kinase (Akt and AMP-activated protein kinase (AMPK phosphorylation is normally inhibited in DCM, but overexpression of the HO-1 gene restored the phosphorylation of these kinases to normal levels. In contrast, the functions of HO-1 in DCM were significantly reversed by overexpression of mutant HO-1. This study underlines the unique roles of HO-1, including the inhibition of oxidative stress, inflammation and apoptosis and the enhancement of autophagy, in the pathogenesis of DCM.

  7. Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

    Science.gov (United States)

    Kaartokallio, Tea; Utge, Siddheshwar; Klemetti, Miira M; Paananen, Jussi; Pulkki, Kari; Romppanen, Jarkko; Tikkanen, Ilkka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

    2018-01-01

    Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes. © 2017 American Heart Association, Inc.

  8. Mycobacterium tuberculosis Induction of Heme Oxygenase-1 Expression Is Dependent on Oxidative Stress and Reflects Treatment Outcomes

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    Neesha Rockwood

    2017-05-01

    Full Text Available The antioxidant enzyme heme oxygenase-1 (HO-1 is implicated in the pathogenesis of tuberculosis (TB and has been proposed as a biomarker of active disease. Nevertheless, the mechanisms by which Mycobacterium tuberculosis (Mtb induces HO-1 as well as how its expression is affected by HIV-1 coinfection and successful antitubercular therapy (ATT are poorly understood. We found that HO-1 expression is markedly increased in rabbits, mice, and non-human primates during experimental Mtb infection and gradually decreased during ATT. In addition, we examined circulating concentrations of HO-1 in a cohort of 130 HIV-1 coinfected and uninfected pulmonary TB patients undergoing ATT to investigate changes in expression of this biomarker in relation to HIV-1 status, radiological disease severity, and treatment outcome. We found that plasma levels of HO-1 were elevated in untreated HIV-1 coinfected TB patients and correlated positively with HIV-1 viral load and negatively with CD4+ T cell count. In both HIV-1 coinfected and Mtb monoinfected patients, HO-1 levels were substantially reduced during successful TB treatment but not in those who experienced treatment failure or subsequently relapsed. To further delineate the molecular mechanisms involved in induction of HO-1 by Mtb, we performed a series of in vitro experiments using mouse and human macrophages. We found that Mtb-induced HO-1 expression requires NADPH oxidase-dependent reactive oxygen species production induced by the early-secreted antigen ESAT-6, which in turn triggers nuclear translocation of the transcription factor NRF-2. These observations provide further insight into the utility of HO-1 as a biomarker of both disease and successful therapy in TB monoinfected and HIV-TB coinfected patients and reveal a previously undocumented pathway linking expression of the enzyme with oxidative stress.

  9. Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein.

    Science.gov (United States)

    Wu, C C; Hsieh, C W; Lai, P H; Lin, J B; Liu, Y C; Wung, B S

    2006-08-01

    Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde that is present in cigarette smoke. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by various such electrophilic compounds. In this study, the regulatory effects of acrolein upon the expression of HO-1 were investigated in endothelial cells (ECs). We demonstrate that acrolein induces the elevation of HO-1 protein levels, and subsequent enzyme activity, at non-cytotoxic concentrations. An additional alpha,beta-unsaturated aldehyde, cinnamaldehyde, was also found to increase HO-1 expression and have less cytotoxicity than acrolein. Moreover, acrolein-mediated HO-1 induction is abrogated in the presence of actinomycin D and cycloheximide. Nrf2 is a transcription factor involved in the induction of HO-1 through an antioxidant response element (ARE) in the promoter region of the HO-1 gene. We show that acrolein induces Nrf2 translocation and ARE-luciferase reporter activity. Acrolein was also found to induce the production of both superoxide and H2O2 at levels greater than 100 microM. However, with the exception of NAC, no antioxidant generated any effect upon acrolein-dependent HO-1 expression in ECs. Our present findings suggest that reactive oxygen species (ROS) may not be a major modulator for HO-1 induction. Using buthionine sulfoximine to deplete the intracellular GSH levels further enhanced the effects of acrolein. We also found that cellular GSH level was rapidly reduced after both 10 and 100 microM acrolein treatment. However, after 6 h of exposure to ECs, only 10 microM acrolein treatment increases GSH level. In addition, only the JNK inhibitor SP600125 and tyrosine kinase inhibitor genistein had any significant inhibitory impact upon the upregulation of HO-1 by acrolein. Pretreatment with a range of other PI3 kinase inhibitors, including wortmannin and LY294002, showed no effects. Hence, we show in our current experiments that a sublethal concentration of acrolein is in fact a

  10. Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein

    International Nuclear Information System (INIS)

    Wu, C.C.; Hsieh, C.W.; Lai, P.H.; Lin, J.B.; Liu, Y.C.; Wung, B.S.

    2006-01-01

    Acrolein is a highly electrophilic α,β-unsaturated aldehyde that is present in cigarette smoke. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by various such electrophilic compounds. In this study, the regulatory effects of acrolein upon the expression of HO-1 were investigated in endothelial cells (ECs). We demonstrate that acrolein induces the elevation of HO-1 protein levels, and subsequent enzyme activity, at non-cytotoxic concentrations. An additional α,β-unsaturated aldehyde, cinnamaldehyde, was also found to increase HO-1 expression and have less cytotoxicity than acrolein. Moreover, acrolein-mediated HO-1 induction is abrogated in the presence of actinomycin D and cycloheximide. Nrf2 is a transcription factor involved in the induction of HO-1 through an antioxidant response element (ARE) in the promoter region of the HO-1 gene. We show that acrolein induces Nrf2 translocation and ARE-luciferase reporter activity. Acrolein was also found to induce the production of both superoxide and H 2 O 2 at levels greater than 100 μM. However, with the exception of NAC, no antioxidant generated any effect upon acrolein-dependent HO-1 expression in ECs. Our present findings suggest that reactive oxygen species (ROS) may not be a major modulator for HO-1 induction. Using buthionine sulfoximine to deplete the intracellular GSH levels further enhanced the effects of acrolein. We also found that cellular GSH level was rapidly reduced after both 10 and 100 μM acrolein treatment. However, after 6 h of exposure to ECs, only 10 μM acrolein treatment increases GSH level. In addition, only the JNK inhibitor SP600125 and tyrosine kinase inhibitor genistein had any significant inhibitory impact upon the upregulation of HO-1 by acrolein. Pretreatment with a range of other PI3 kinase inhibitors, including wortmannin and LY294002, showed no effects. Hence, we show in our current experiments that a sublethal concentration of acrolein is in fact a novel HO-1 inducer

  11. The role of heme oxygenase-1 in drug metabolizing dysfunction in the alcoholic fatty liver exposed to ischemic injury

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Won [Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 52727 (Korea, Republic of); Kang, Jung-Woo [School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419 (Korea, Republic of); Lee, Sun-Mee, E-mail: sunmee@skku.edu [School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419 (Korea, Republic of)

    2016-02-01

    This study was designed to investigate the role of heme oxygenase-1 (HO-1) in hepatic drug metabolizing dysfunction after ischemia/reperfusion (IR) in alcoholic fatty liver (AFL). Rats were fed a Lieber–DeCarli diet for five weeks to allow for development of AFL and were then subjected to 90 min of hepatic ischemia and 5 h of reperfusion. Rats were pretreated with hemin (HO-1 inducer) or ZnPP (HO-1 inhibitor) for 16 h and 3 h before hepatic ischemia. After hepatic IR, ethanol diet (ED)-fed rats had higher serum aminotransferase activities and more severe hepatic necrosis compared to the control diet (CD)-fed rats. These changes were attenuated by hemin and exacerbated by ZnPP. The activity and gene expression of HO-1 and its transcription factor (Nrf2) level increased significantly after 5 h of reperfusion in CD-fed rats but not in ED-fed rats. After reperfusion, cytochrome P450 (CYP) 1A1, 1A2, and 2B1 activities were reduced to levels lower than those observed in sham group, whereas CYP2E1 activity increased. The decrease in CYP2B1 activity and the increase in CYP2E1 activity were augmented after hepatic IR in ED-fed animals. These changes were significantly attenuated by hemin but aggravated by ZnPP. Finally, CHOP expression and PERK phosphorylation, microsomal lipid peroxidation, and levels of proinflammatory mediators increased in ED-fed rats compared to CD-fed rats after reperfusion. These increases were attenuated by hemin. Our results suggest that AFL exacerbates hepatic drug metabolizing dysfunction during hepatic IR via endoplasmic reticulum stress and lipid peroxidation and this is associated with impaired HO-1 induction. - Highlights: • Endogenous HO-1 is generated in insufficient quantities in steatotic ischemic injury. • Impaired HO-1 induction leads to excessive ER stress response and lipid peroxidation. • Alcoholic steatosis exacerbates IR-induced hepatic drug-metabolizing dysfunction. • HO-1 induction is required for appropriate medication

  12. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

    Science.gov (United States)

    Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

    2005-02-01

    Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

  13. Blockade of Inflammation and Apoptosis Pathways by siRNA Prolongs Cold Preservation Time and Protects Donor Hearts in a Porcine Model

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    Jia Wei

    2017-12-01

    Full Text Available In donor hearts from mini pigs, overtime cold preservation and ischemia-reperfusion injury cause poor graft quality and impaired heart function. Blockage of complement, apoptosis, and inflammation is considered a strategy for attenuating ischemia-reperfusion injury and protecting cardiac function. Minipig donor hearts were perfused and preserved in Celsior solution or transfection reagent containing Celsior solution with scramble siRNA or siRNAs targeting complement 3, caspase-8, caspase-3, and nuclear factor κB-p65 genes at 4°C and subsequently hemo-reperfused ex vivo (38°C or transplanted into recipients. The protective effect of the siRNA solution was evaluated by measuring cell apoptosis, structural alteration, protein markers for tissue damage and oxidative stress, and cardiac function. We found a reduction in cell apoptosis, myocardial damage, and tissue inflammation by reduced biochemistry and markers and protein expression of proinflammatory cytokines and improvement in cardiac function, as shown by the improved hemodynamic indices in 12-hr-preserved siRNA-treated hearts of both ex vivo and orthotopic transplantation models. These findings demonstrate that blockade of inflammation and apoptosis pathways using siRNA can prolong cold preservation time and better protect donor heart function in cardiac transplantation of large animals, which may be beneficial for human heart preservation.

  14. Cadmium-induced heme-oxygenase-1 expression plays dual roles in autophagy and apoptosis and is regulated by both PKC-δ and PKB/Akt activation in NRK52E kidney cells

    International Nuclear Information System (INIS)

    So, Keum-Young; Oh, Seon-Hee

    2016-01-01

    Heme oxygenase-1 (HO-1) protects cells against cadmium (Cd)-induced oxidative stress. However, the mechanism underlying this protection is not well understood. In this study, we elucidated the role of HO-1 in Cd-induced cytotoxicity. Exposure of NRK52E cells to Cd induced protein kinase B (PKB)/Akt, protein kinase C (PKC)-δ, and glycogen synthase kinase (GSK) 3αb phosphorylation, and eukaryotic initiation factor (eIF) 2α dephosphorylation. Pharmacological inhibition of Akt resulted in HO-1 suppression and eIF2α activation, which partially suppressed CHOP and PARP-1 cleavage, but promoted autophagy and decreased cell viability. Pharmacological inactivation of PKC-δ markedly suppressed Cd-induced phospho-serine (p-Ser) GSK3αβ, and HO-1, and partially inhibited PARP-1 cleavage, but massively induced autophagy and decreased cell viability. Pharmacological upregulation of p-Ser GSK3αβ enhanced Cd-induced HO-1, CHOP, and PARP-1 cleavage, but decreased autophagy. Genetic deficiency of GSK3β suppressed HO-1 and PARP-1 cleavage and increased autophagy. Genetic suppression of HO-1 reduced Cd-induced PARP-1 cleavage, but increased LC3-II. Cd exposure led to accumulation of p-PKC-δ, p-Ser GSK3αβ, and HO-1 in the nucleus and particulate fractions, suggesting that they have dual functions in response to Cd. N-acetylcysteine treatment suppressed Cd-induced activation of PKC-δ and Akt. These results indicate that HO-1 induced by Cd exposure is regulated by PKC-δ, p-Ser GSK3αβ, and PKB/Akt, which restrain autophagic cell death, but mildly induce apoptosis in NRK52E cells. Together, the results suggest that HO-1 expression in response to Cd maintains cellular homeostasis during oxidative stress.

  15. Hyperglycemia in Streptozotocin-Induced Diabetes Leads to Persistent Inflammation and Tissue Damage Following Uveitis Due to Reduced Levels of Ciliary Body Heme Oxygenase-1

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available This study investigated the heme oxygenase-1 (HO-1 and the endotoxin-induced uveitis (EIU in diabetic streptozotocin (STZ-hyperglycemic rats. STZ-hyperglycemic rats had impaired levels of the enzyme HO-1 within the ciliary bodies if compared with the nondiabetic rats. STZ-hyperglycemic rats also predisposed the eye to produce high levels of both the cytokines IL-1 β and CXCL8. Subsequent EIU further and significantly P<.01 increased the cytokines production, an effect partly prevented by hemin treatment. Most importantly, hemin, an inducer of heme oxygenase expression and activity, recovered the huge number of infiltrated polymorphonuclear leukocytes PMN within the ciliary bodies associated with STZ-hyperglycemic state and EIU damage. Impairment of the stress-sensitive enzyme HO-1 in STZ-hyperglycemic rats increases and prolongs the inflammatory response to EIU.

  16. Anti-inflammatory effect of transduced PEP-1-heme oxygenase-1 in Raw 264.7 cells and a mouse edema model

    International Nuclear Information System (INIS)

    Kwon, Soon Won; Sohn, Eun Jeong; Kim, Dae Won; Jeong, Hoon Jae; Kim, Mi Jin; Ahn, Eun Hee; Kim, Young Nam; Dutta, Suman; Kim, Duk-Soo; Park, Jinseu; Eum, Won Sik; Hwang, Hyun Sook; Choi, Soo Young

    2011-01-01

    Highlights: → Recombinant PEP-1 heme oxygenase-1 expression vector was constructed and overexpressed. → We investigated transduction efficiency of PEP-1-HO-1 protein in Raw 264.7 cells. → PEP-1-HO-1 was efficiently transduced into Raw 264.7 cells in a dose and time dependent manner. → PEP-1-HO-1 exerted anti-inflammatory activity in Raw 264.7 cells and in a mice edema model. → PEP-1-HO-1 could be used as a therapeutic drug against inflammatory diseases. -- Abstract: Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to biliverdin, carbon monoxide (CO), and free iron (Fe 2+ ), is up-regulated by several cellular stress and cell injuries, including inflammation, ischemia and hypoxia. In this study, we examined whether fusion of HO-1 with PEP-1, a protein transduction domain that is able to deliver exogenous molecules to living cells or tissues, would facilitate HO-1 delivery to target cells and tissues, and thereby effectively exert a therapeutically useful response against inflammation. Western blot analysis demonstrated that PEP-1-HO-1 fusion proteins were transduced into Raw 264.7 cells in time- and dose-dependent manners, and were stably maintained in the cells for about 60 h. In addition, fluorescence analysis revealed that only PEP-1-HO-1 fusion proteins were significantly transduced into the cytoplasm of cells, while HO-1 proteins failed to be transduced. In lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse edema model, transduced PEP-1-HO-1 fusion proteins effectively inhibited the overexpression of pro-inflammatory mediators and cytokines. Also, histological analysis demonstrated that PEP-1-HO-1 remarkably suppressed ear edema. The results suggest that the PEP-1-HO-1 fusion protein can be used as a therapeutic molecule against reactive oxygen species-related inflammatory diseases.

  17. Regulation of heme oxygenase-1 expression and MAPK pathways in response to kaempferol and rhamnocitrin in PC12 cells

    International Nuclear Information System (INIS)

    Hong, J.-T.; Yen, J.-H.; Wang Lisu; Lo, Y.-H.; Chen, Z.-T.; Wu, M.-J.

    2009-01-01

    Oxidative stress has been considered as a major cause of cellular injuries in a variety of clinical abnormalities, especially neural diseases. Our aim of research is to investigate the protective effects and mechanisms of kaempferol and rhamnocitrin (kaempferol-7-methyl ether) on oxidative damage in rat pheochromocytoma PC12 cells induced by a limited supply of serum and hydrogen peroxide (H 2 O 2 ). The current result demonstrated that kaempferol protected PC12 cells from serum deprivation-induced apoptosis. Pretreatment of cells with kaempferol also diminished intracellular generation of reactive oxygen species (ROS) in response to H 2 O 2 and strongly elevated cell viability. RT-Q-PCR and Western blotting revealed that kaempferol and rhamnocitrin significantly induced heme oxygenase (HO)-1 gene expression. Addition of zinc protoporphyrin (Znpp), a HO-1 competitive inhibitor, significantly attenuated their protective effects in H 2 O 2 -treated cells, indicating the vital role of HO-1 in cell resistance to oxidative injury. While investigating the signaling pathways responsible for HO-1 induction, we observed that kaempferol induced sustained extracellular signal-regulated protein kinase 1/2 (ERK1/2) in PC12 cells grown in low serum medium; while rhamnocitrin only stimulated transient ERK cascade. Addition of U0126, a highly selective inhibitor of MEK1/2, which is upstream of ERK1/2, had no effect on kaempferol- or rhamnocitrin-induced HO-1 mRNA expression, indicating no direct cross-talk between these two pathways. Furthermore, both kaempferol and rhamnocitrin were able to persistently attenuate p38 phosphorylation. Taking together, the above findings suggest that kaempferol and rhamnocitrin can augment cellular antioxidant defense capacity, at least in part, through regulation of HO-1 expression and MAPK signal transduction.

  18. Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model.

    Science.gov (United States)

    Hinkel, Rabea; Lange, Philipp; Petersen, Björn; Gottlieb, Elena; Ng, Judy King Man; Finger, Stefanie; Horstkotte, Jan; Lee, Seungmin; Thormann, Michael; Knorr, Maike; El-Aouni, Chiraz; Boekstegers, Peter; Reichart, Bruno; Wenzel, Philip; Niemann, Heiner; Kupatt, Christian

    2015-07-14

    Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear. This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model. Murine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed. Human microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP-1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals. Whereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model. Copyright © 2015 American

  19. Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Solip [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701 (Korea, Republic of); Nguyen, Van Thu [College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702 (Korea, Republic of); Tae, Nara; Lee, Suhyun [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701 (Korea, Republic of); Ryoo, Sungwoo [Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701 (Korea, Republic of); Min, Byung-Sun [College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702 (Korea, Republic of); Lee, Jeong-Hyung, E-mail: jhlee36@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 200-701 (Korea, Republic of)

    2014-11-01

    Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE{sub 2}, butyl lucidenateD{sub 2} (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting the involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum. - Highlights: • The anti-inflammatory effects of selected triterpenes from Ganoderma lucidum are demonstrated. • Heme oxygenase-1 induction is attributable to the anti-inflammatory properties of these

  20. Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells

    International Nuclear Information System (INIS)

    Choi, Solip; Nguyen, Van Thu; Tae, Nara; Lee, Suhyun; Ryoo, Sungwoo; Min, Byung-Sun; Lee, Jeong-Hyung

    2014-01-01

    Ganoderma lucidum is a popular medicinal mushroom used in traditional medicine for preventing or treating a variety of diseases. In the present study, we investigated the anti-inflammatory and heme oxygenase (HO)-1 inducing effects of 12 lanostane triterpenes from G. lucidum in RAW264.7 cells. Of these, seven triterpenes, butyl lucidenateE 2 , butyl lucidenateD 2 (GT-2), butyl lucidenate P, butyl lucidenateQ, Ganoderiol F, methyl ganodenate J and butyl lucidenate N induced HO-1 expression and suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Inhibiting HO-1 activity abrogated the inhibitory effects of these triterpenes on the production of NO in LPS-stimulated RAW264.7 cells, suggesting the involvement of HO-1 in the anti-inflammatory effects of these triterpenes. We further studied the anti-inflammatory and HO-1 inducing effects of GT-2. Mitogen-activated protein kinase inhibitors or N-acetylcysteine, an antioxidant, did not suppress GT-2-mediated HO-1 induction; however, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, blocked GT-2-induced HO-1 mRNA and protein expression. GT-2 increased nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and knockdown of Nrf2 by small interfering RNA blocked GT-2-mediated HO-1 induction, suggesting that GT-2 induced HO-1 expression via the PI3K/AKT-Nrf2 pathway. Consistent with the notion that HO-1 has anti-inflammatory properties, GT-2 inhibited the production of tumor necrosis factor-α and interleukin-6, as well as inducible nitric oxide synthase and cyclooxygenase-2 expression. These findings suggest that HO-1 inducing activities of these lanostane triterpenes may be important in the understanding of a novel mechanism for the anti-inflammatory activity of G. lucidum. - Highlights: • The anti-inflammatory effects of selected triterpenes from Ganoderma lucidum are demonstrated. • Heme oxygenase-1 induction is attributable to the anti-inflammatory properties of these triterpenes

  1. Evidence for hydroxyl radical scavenging action of nitric oxide donors in the protection against 1-methyl-4-phenylpyridinium-induced neurotoxicity in rats.

    Science.gov (United States)

    Banerjee, Rebecca; Saravanan, Karuppagounder S; Thomas, Bobby; Sindhu, Kizhake M; Mohanakumar, Kochupurackal P

    2008-06-01

    In the present study we provide evidence for hydroxyl radical (*OH) scavenging action of nitric oxide (NO*), and subsequent dopaminergic neuroprotection in a hemiparkinsonian rat model. Reactive oxygen species are strongly implicated in the nigrostriatal dopaminergic neurotoxicity caused by the parkinsonian neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). Since the role of this free radical as a neurotoxicant or neuroprotectant is debatable, we investigated the effects of some of the NO* donors such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine hydrochloride (SIN-1), sodium nitroprusside (SNP) and nitroglycerin (NG) on in vitro *OH generation in a Fenton-like reaction involving ferrous citrate, as well as in MPP+-induced *OH production in the mitochondria. We also tested whether co-administration of NO* donor and MPP+ could protect against MPP+-induced dopaminergic neurotoxicity in rats. While NG, SNAP and SIN-1 attenuated MPP+-induced *OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up to 18-fold increase in *OH production in the latter reaction. Striatal dopaminergic depletion following intranigral infusion of MPP+ in rats was significantly attenuated by NG, SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP and SIN-1, exposed to air for 48 h to remove NO*, when administered similarly failed to attenuate MPP+-induced neurotoxicity in vivo. Conversely, long-time air-exposed SNP solution when administered in rats intranigrally, caused a dose-dependent depletion of the striatal dopamine. These results confirm the involvement of *OH in the nigrostriatal degeneration caused by MPP+, indicate the *OH scavenging ability of NO*, and demonstrate protection by NO* donors against MPP+-induced dopaminergic neurotoxicity in rats.

  2. Heme Oxygenase-1 Activity as a Correlate to Exercise-Mediated Amelioration of Cognitive Decline and Neuropathological Alterations in an Aging Rat Model of Dementia

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    Andrea Kurucz

    2018-01-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder with cognitive impairment. Physical exercise has long been proven to be beneficial in the disorder. The present study was designed to examine the effect of voluntary exercise on spatial memory, imaging, and pathological abnormalities. Particular focus has been given to the role of heme oxygenase-1 (HO-1—an important cellular cytoprotectant in preserving mental acuity—using an aging rat model of dementia. Male and female Wistar rats were segregated into six groups—namely, (i aged sedentary (control females (ASF, n=8; (ii aged sedentary (control males (ASM, n=8; (iii aged running females (ARF, n=8; (iv aged running males (ARM, n=8; (v young control females (YCF, n=8; and (vi young control males (YCM, n=8. Rats in the ARF and ARM groups had free access to a standardized inbuilt running wheel during the 3-month evaluation period. Spatial memory was investigated using the Morris Water Test, imaging and pathological alterations were assessed using positron emission tomography (PET imaging and histopathological examinations (H&E, Congo red staining, respectively, and HO-1 enzyme activity assays were also conducted. The outcomes suggest that voluntary physical exercise mitigates impaired spatial memory and neuropathological changes exhibited by the aging sedentary group, via elevated HO-1 activity, contributing to the antioxidant capacity in the aging brain.

  3. Involvement of Heme Oxygenase-1 Induction in the Cytoprotective and Immunomodulatory Activities of Viola patrinii in Murine Hippocampal and Microglia Cells

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    Bin Li

    2012-01-01

    Full Text Available A number of diseases that lead to injury of the central nervous system are caused by oxidative stress and inflammation in the brain. In this study, NNMBS275, consisting of the ethanol extract of Viola patrinii, showed potent antioxidative and anti-inflammatory activity in murine hippocampal HT22 cells and BV2 microglia. NNMBS275 increased cellular resistance to oxidative injury caused by glutamate-induced neurotoxicity and reactive oxygen species generation in HT22 cells. In addition, the anti-inflammatory effects of NNMBS275 were demonstrated by the suppression of proinflammatory mediators, including proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2 and cytokines (tumor necrosis factor-α and interleukin-1β. Furthermore, we found that the neuroprotective and anti-inflammatory effects of NNMBS275 were linked to the upregulation of nuclear transcription factor-E2-related factor 2-dependent expression of heme oxygenase-1 in HT22 and BV2 cells. These results suggest that NNMBS275 possesses therapeutic potential against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.

  4. Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

    Science.gov (United States)

    Qin, Jun; He, Yue; Duan, Ming; Luo, Meng

    2017-05-01

    We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Crocin Suppresses LPS-Stimulated Expression of Inducible Nitric Oxide Synthase by Upregulation of Heme Oxygenase-1 via Calcium/Calmodulin-Dependent Protein Kinase 4

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    Ji-Hee Kim

    2014-01-01

    Full Text Available Crocin is a water-soluble carotenoid pigment that is primarily used in various cuisines as a seasoning and coloring agent, as well as in traditional medicines for the treatment of edema, fever, and hepatic disorder. In this study, we demonstrated that crocin markedly induces the expression of heme oxygenase-1 (HO-1 which leads to an anti-inflammatory response. Crocin inhibited inducible nitric oxide synthase (iNOS expression and nitric oxide production via downregulation of nuclear factor kappa B activity in lipopolysaccharide- (LPS- stimulated RAW 264.7 macrophages. These effects were abrogated by blocking of HO-1 expression or activity. Crocin also induced Ca2+ mobilization from intracellular pools and phosphorylation of Ca2+/calmodulin-dependent protein kinase 4 (CAMK4. CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling. Moreover, crocin-mediated suppression of iNOS expression was blocked by CAMK4 inhibition. Overall, these results suggest that crocin suppresses LPS-stimulated expression of iNOS by inducing HO-1 expression via Ca2+/calmodulin-CAMK4-PI3K/Akt-Nrf2 signaling cascades. Our findings provide a novel molecular mechanism for the inhibitory effects of crocin against endotoxin-mediated inflammation.

  6. Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

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    Young-Man Lee

    2013-01-01

    Full Text Available Although previous studies have shown that mollugin, a bioactive phytochemical isolated from Rubia cordifolia L. (Rubiaceae, exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs. Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G1 phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-κB and NF-κB-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl, invasion (MMP-9 and ICAM-1, and angiogenesis (FGF-2 and VEGF. Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1 and nuclear factor E2–related factor 2 (Nrf2. Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-κB.

  7. Induction of Protective Genes Leads to Islet Survival and Function

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    Hongjun Wang

    2011-01-01

    Full Text Available Islet transplantation is the most valid approach to the treatment of type 1 diabetes. However, the function of transplanted islets is often compromised since a large number of β cells undergo apoptosis induced by stress and the immune rejection response elicited by the recipient after transplantation. Conventional treatment for islet transplantation is to administer immunosuppressive drugs to the recipient to suppress the immune rejection response mounted against transplanted islets. Induction of protective genes in the recipient (e.g., heme oxygenase-1 (HO-1, A20/tumor necrosis factor alpha inducible protein3 (tnfaip3, biliverdin reductase (BVR, Bcl2, and others or administration of one or more of the products of HO-1 to the donor, the islets themselves, and/or the recipient offers an alternative or synergistic approach to improve islet graft survival and function. In this perspective, we summarize studies describing the protective effects of these genes on islet survival and function in rodent allogeneic and xenogeneic transplantation models and the prevention of onset of diabetes, with emphasis on HO-1, A20, and BVR. Such approaches are also appealing to islet autotransplantation in patients with chronic pancreatitis after total pancreatectomy, a procedure that currently only leads to 1/3 of transplanted patients being diabetes-free.

  8. Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells.

    Science.gov (United States)

    Lee, Jin-Ching; Tseng, Chin-Kai; Young, Kung-Chia; Sun, Hung-Yu; Wang, Shainn-Wei; Chen, Wei-Chun; Lin, Chun-Kuang; Wu, Yu-Hsuan

    2014-01-01

    This study aimed to evaluate the anti-hepatitis C virus (HCV) activity of andrographolide, a diterpenoid lactone extracted from Andrographis paniculata, and to identify the signalling pathway involved in its antiviral action. Using HCV replicon and HCVcc infectious systems, we identified anti-HCV activity of andrographolide by measuring protein and RNA levels. A reporter activity assay was used to determine transcriptional regulation of anti-HCV agents. A specific inhibitor and short hairpin RNAs were used to investigate the mechanism responsible for the effect of andrographolide on HCV replication. In HCV replicon and HCVcc infectious systems, andrographolide time- and dose-dependently suppressed HCV replication. When combined with IFN-α, an inhibitor targeting HCV NS3/4A protease (telaprevir), or NS5B polymerase (PSI-7977), andrographolide exhibited a significant synergistic effect. Andrographolide up-regulated the expression of haeme oxygenase-1 (HO-1), leading to increased amounts of its metabolite biliverdin, which was found to suppress HCV replication by promoting the antiviral IFN responses and inhibiting NS3/4A protease activity. Significantly, these antiviral effects were attenuated by an HO-1-specific inhibitor or HO-1 gene knockdown, indicating that HO-1 contributed to the anti-HCV activity of andrographolide. Andrographolide activated p38 MAPK phosphorylation, which stimulated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated HO-1 expression, and this was found to be associated with its anti-HCV activity. Our results demonstrate that andrographolide has the potential to control HCV replication and suggest that targeting the Nrf2-HO-1 signalling pathway might be a promising strategy for drug development. © 2013 The British Pharmacological Society.

  9. IN VITRO STUDIES ON HEME OXYGENASE-1 AND P24 ANTIGEN HIV-1 LEVEL AFTERHYPERBARIC OXYGEN TREATMENTOFHIV-1 INFECTED ON PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMCS).

    Science.gov (United States)

    Budiarti, Retno; Kuntaman; Nasronudin; Suryokusumo; Khairunisa, Siti Qamariyah

    2018-01-01

    Heme oxygenase-1 (HO-1) is a protein secreted by immune cells as a part of immune response mechanism.HO-1 can be induced by variety agents that causingoxidative stress, such as exposure to 100% oxygenat2,4 ATA pressure.It plays a vital role in maintaining cellular homeostasis.This study was conducted to identify the effect of hyperbaric oxygen exposure in cultured ofPBMCthat infected by HIV-1. Primary culture of PBMCs were isolated from 16 healthy volunteers and HIV-1 infected MT4 cell line by co-culture. The PBMCs were aliquoted into two wells as control group and treatment group. The 16 samples of HIV-1 infected PBMCwere exposed to oxygen at 2,4 ATA in animal hyperbaric chamber forthree times in 30 minutes periods with 5 minutes spacing period, that called 1 session.The Treatment done on 5 sessions within 5 days. 16 samples of HIV-1 infected PMBCs that have no hyperbaric treatment became control group.The supernatant were measured the HO-1 production by ELISA andmRNA expression of HO-1 by real time PCR and the number ofantigen p24 HIV-1by ELISA. The result showed that there was no increasing of HO-1 at both mRNA level and protein level, there was a decreasing number of antigen p24 HIV-1 at the treatment group. In addition, hyperbaric exposure could not increase the expression of HO-1, more over the viral replication might be reduced by other mechanism. Hyperbaric oxygen could increases cellular adaptive response of PBMCs infected HIV-1 through increased expression of proteins that can inhibit HIV viralreplication.

  10. Transforming growth factor β1 enhances heme oxygenase 1 expression in human synovial fibroblasts by inhibiting microRNA 519b synthesis.

    Directory of Open Access Journals (Sweden)

    Shu-Jui Kuo

    Full Text Available Osteoarthritis (OA is manifested by synovial inflammation and cartilage destruction that is directly linked to synovitis, joint swelling and pain. In the light of the role of synovium in the pathogenesis and the symptoms of OA, synovium-targeted therapy is a promising strategy to mitigate the symptoms and progression of OA. Transforming growth factor beta 1 (TGF-β1, a secreted homodimeric protein, possesses unique and potent anti-inflammatory and immune-regulatory properties in many cell types. Heme oxygenase 1 (HO-1 is an inducible anti-inflammatory and stress responsive enzyme that has been proven to prevent injuries caused by many diseases. Despite the similar anti-inflammatory profile and their involvement in the pathogenesis of arthritic diseases, no studies have as yet explored the possibility of any association between the expression of TGF-β1 and HO-1.TGF-β1-induced HO-1 expression was examined by HO-1 promoter assay, qPCR, and Western blotting. The siRNAs and enzyme inhibitors were utilized to determine the intermediate involved in the signal transduction pathway. We showed that TGF-β1 stimulated the synthesis of HO-1 in a concentration- and time-dependent manner, which can be mitigated by blockade of the phospholipase (PLCγ/protein kinase C alpha (PKCα pathway. We also showed that the expression of miRNA-519b, which blocks HO-1 transcription, is inhibited by TGF-β1, and the suppression of miRNA 519b could be reversed via blockade of the PLCγ/PKCα pathway.TGF-β1 stimulated the expression of HO-1 via activating the PLCγ/PKCα pathway and suppressing the downstream expression of miRNA-519b. These results may shed light on the pathogenesis and treatment of OA.

  11. Characterization of Nrf2 activation and heme oxygenase-1 expression in NIH3T3 cells exposed to aqueous extracts of cigarette smoke.

    Science.gov (United States)

    Knörr-Wittmann, Constanze; Hengstermann, Arnd; Gebel, Stephan; Alam, Jawed; Müller, Thomas

    2005-12-01

    Cigarette smoke (CS) is a complex chemical mixture estimated to be composed of up to 5000 different chemicals, many of which are prooxidant. Here we show that, at least in vitro, the cellular response designed to combat oxidative stress resulting from CS exposure is primarily controlled by the transcription factor Nrf2, a principal inducer of antioxidant and phase II-related genes. The prominent role of Nrf2 in the cellular response to CS is substantiated by the following observations: In NIH3T3 cells exposed to aqueous extracts of CS (i) Nrf2 is strongly stabilized and becomes detectable in nuclear extracts. (ii) Nuclear localization of Nrf2 coincides with increased DNA binding of a putative Nrf2/MafK heterodimer to its cognate cis-regulatory site, i.e., the antioxidant-responsive element (ARE). (iii) Studies on the regulatory elements of the oxidative stress-inducible gene heme oxygenase-1 (hmox1) using various hmox1 promoter/luciferase reporter constructs revealed that the strong CS-dependent expression of this gene is primarily governed by the distal enhancers 1 ("E1") and 2 ("E2"), which both contain three canonical ARE-like stress-responsive elements (StREs). Notably, depletion of Nrf2 levels caused by RNA interference significantly compromised CS-induced hmox1 promoter activation, based on the distinct Nrf2 sensitivity exhibited by E1 and E2. Finally, (iv) siRNA-dependent knock-down of Nrf2 completely abrogated CS-induced expression of phase II-related genes. Taken together, these results confirm the outstanding role of Nrf2 both in sensing (oxidant) stress and in orchestrating an efficient transcriptional response aimed at resolving the stressing conditions.

  12. Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells.

    Science.gov (United States)

    Yang, Po-Min; Chen, Huang-Zhi; Huang, Yu-Ting; Hsieh, Chia-Wen; Wung, Being-Sun

    2017-06-01

    The endothelial expression of cell adhesion molecules plays a leading role in atherosclerosis. Lycopene, a carotenoid with 11 conjugated double bonds, has been shown to have anti-inflammatory properties. In the present study, we demonstrate a putative mechanism for the anti-inflammatory effects of lycopene. We demonstrate that lycopene inhibits the adhesion of tumor necrosis factor α (TNFα)-stimulated monocytes to endothelial cells and suppresses the expression of intercellular cell adhesion molecule-1 (ICAM-1) at the transcriptional level. Moreover, lycopene was found to exert its inhibitory effects by blocking the degradation of the inhibitory protein, IκBα, following 6 h of pre-treatment. In TNFα-stimulated endothelial cells, nuclear factor-κB (NF-κB) nuclear translocation and transcriptional activity were abolished by up to 12 h of lycopene pre-treatment. We also found that lycopene increased the intracellular glutathione (GSH) level and glutamate-cysteine ligase expression. Subsequently, lycopene induced nuclear factor-erythroid 2 related factor 2 (Nrf2) activation, leading to the increased expression of downstream of heme oxygenase-1 (HO-1). The use of siRNA targeting HO-1 blocked the inhibitory effects of lycopene on IκB degradation and ICAM-1 expression. The inhibitory effects of lycopene thus appear to be mediated through its induction of Nrf2-mediated HO-1 expression. Therefore, the findings of the present study indicate that lycopene suppresses the activation of TNFα-induced signaling pathways through the upregulation of Nrf2-mediated HO-1 expression.

  13. Transition between acute and chronic hepatotoxicity in mice is associated with impaired energy metabolism and induction of mitochondrial heme oxygenase-1.

    Directory of Open Access Journals (Sweden)

    Aniket Nikam

    Full Text Available The formation of protein inclusions is frequently associated with chronic metabolic diseases. In mice, short-term intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC leads to hepatocellular damage indicated by elevated serum liver enzyme activities, whereas only minor morphological changes are observed. Conversely, chronic administration of DDC for several weeks results in severe morphological damage, characterized by hepatocellular ballooning, disruption of the intermediate filament cytoskeleton, and formation of Mallory-Denk bodies consisting predominantly of misfolded keratins, Sqstm1/p62, and heat shock proteins. To evaluate the mechanistic underpinnings for this dichotomy we dissected the time-course of DDC intoxication for up to 10 weeks. We determined body weight change, serum liver enzyme activities, morphologic alterations, induction of antioxidant response (heme oxygenase-1, HO-1, oxidative damage and ATP content in livers as well as respiration, oxidative damage and the presence and activity of HO-1 in endoplasmic reticulum and mitochondria (mtHO-1. Elevated serum liver enzyme activity and oxidative liver damage were already present at early intoxication stages without further subsequent increase. After 2 weeks of intoxication, mice had transiently lost 9% of their body weight, liver ATP-content was reduced to 58% of controls, succinate-driven respiration was uncoupled from ATP-production and antioxidant response was associated with the appearance of catalytically active mtHO-1. Oxidative damage was associated with both acute and chronic DDC toxicity whereas the onset of chronic intoxication was specifically associated with mitochondrial dysfunction which was maximal after 2 weeks of intoxication. At this transition stage, adaptive responses involving mtHO-1 were induced, indirectly leading to improved respiration and preventing further drop of ATP levels. Our observations clearly demonstrate principally different

  14. Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

    Science.gov (United States)

    Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

    2009-01-01

    Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

  15. Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

    Science.gov (United States)

    Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

    2014-01-01

    The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

  16. Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

    International Nuclear Information System (INIS)

    Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy

    2016-01-01

    Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner. siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H 2 O 2 ) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H 2 O 2 levels. Furthermore, H 2 O 2 independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H 2 O 2 levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H 2 O 2 -independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H 2 O 2 - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. - Highlights: • Omeprazole induces HO-1 in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of HO-1. • Nrf2 knockdown abrogates omeprazole-mediated HO-1 induction in human lung cells. • Hydrogen peroxide depletion augments omeprazole-mediated induction of HO-1.

  17. The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes-associated osteoarthritis.

    Science.gov (United States)

    Vaamonde-Garcia, Carlos; Courties, Alice; Pigenet, Audrey; Laiguillon, Marie-Charlotte; Sautet, Alain; Houard, Xavier; Kerdine-Römer, Saadia; Meijide, Rosa; Berenbaum, Francis; Sellam, Jérémie

    2017-09-01

    Epidemiological findings support the hypothesis that type 2 diabetes mellitus (T2DM) is a risk factor for osteoarthritis (OA). Moreover, OA cartilage from patients with T2DM exhibits a greater response to inflammatory stress, but the molecular mechanism is unclear. To investigate whether the antioxidant defense system participates in this response, we examined here the expression of nuclear factor-erythroid 2-related factor (Nrf-2), a master antioxidant transcription factor, and of heme oxygenase-1 (HO-1), one of its main target genes, in OA cartilage from T2DM and non-T2DM patients as well as in murine chondrocytes exposed to high glucose (HG). Ex vivo experiments indicated that Nrf-2 and HO-1 expression is reduced in T2DM versus non-T2DM OA cartilage (0.57-fold Nrf-2 and 0.34-fold HO-1), and prostaglandin E 2 (PGE 2 ) release was increased in samples with low HO-1 expression. HG-exposed, IL-1β-stimulated chondrocytes had lower Nrf-2 levels in vitro , particularly in the nuclear fraction, than chondrocytes exposed to normal glucose (NG). Accordingly, HO-1 levels were also decreased (0.49-fold) in these cells. The HO-1 inducer cobalt protoporphyrin IX more efficiently attenuated PGE 2 and IL-6 release in HG+IL-1β-treated cells than in NG+IL-1β-treated cells. Greater reductions in HO-1 expression and increase in PGE 2 /IL-6 production were observed in HG+IL-1β-stimulated chondrocytes from Nrf-2 -/- mice than in chondrocytes from wild-type mice. We conclude that the Nrf-2/HO-1 axis is a critical pathway in the hyperglucidic-mediated dysregulation of chondrocytes. Impairments in this antioxidant system may explain the greater inflammatory responsiveness of OA cartilage from T2DM patients and may inform treatments of such patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2016-11-15

    Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner. siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H{sub 2}O{sub 2}) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H{sub 2}O{sub 2} levels. Furthermore, H{sub 2}O{sub 2} independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H{sub 2}O{sub 2} levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H{sub 2}O{sub 2}-independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H{sub 2}O{sub 2} - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. - Highlights: • Omeprazole induces HO-1 in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of HO-1. • Nrf2 knockdown abrogates omeprazole-mediated HO-1 induction in human lung cells. • Hydrogen peroxide depletion augments

  19. Daily exercise prevents diastolic dysfunction and oxidative stress in a female mouse model of western diet induced obesity by maintaining cardiac heme oxygenase-1 levels.

    Science.gov (United States)

    Bostick, Brian; Aroor, Annayya R; Habibi, Javad; Durante, William; Ma, Lixin; DeMarco, Vincent G; Garro, Mona; Hayden, Melvin R; Booth, Frank W; Sowers, James R

    2017-01-01

    Obesity is a global epidemic with profound cardiovascular disease (CVD) complications. Obese women are particularly vulnerable to CVD, suffering higher rates of CVD compared to non-obese females. Diastolic dysfunction is the earliest manifestation of CVD in obese women but remains poorly understood with no evidence-based therapies. We have shown early diastolic dysfunction in obesity is associated with oxidative stress and myocardial fibrosis. Recent evidence suggests exercise may increase levels of the antioxidant heme oxygenase-1 (HO-1). Accordingly, we hypothesized that diastolic dysfunction in female mice consuming a western diet (WD) could be prevented by daily volitional exercise with reductions in oxidative stress, myocardial fibrosis and maintenance of myocardial HO-1 levels. Four-week-old female C57BL/6J mice were fed a high-fat/high-fructose WD for 16weeks (N=8) alongside control diet fed mice (N=8). A separate cohort of WD fed females was allowed a running wheel for the entire study (N=7). Cardiac function was assessed at 20weeks by high-resolution cardiac magnetic resonance imaging (MRI). Functional assessment was followed by immunohistochemistry, transmission electron microscopy (TEM) and Western blotting to identify pathologic mechanisms and assess HO-1 protein levels. There was no significant body weight decrease in exercising mice, normalized body weight 14.3g/mm, compared to sedentary mice, normalized body weight 13.6g/mm (p=0.38). Total body fat was also unchanged in exercising, fat mass of 6.6g, compared to sedentary mice, fat mass 7.4g (p=0.55). Exercise prevented diastolic dysfunction with a significant reduction in left ventricular relaxation time to 23.8ms for exercising group compared to 33.0ms in sedentary group (pstress and myocardial fibrosis with improved mitochondrial architecture. HO-1 protein levels were increased in the hearts of exercising mice compared to sedentary WD fed females. This study provides seminal evidence that exercise

  20. Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways

    International Nuclear Information System (INIS)

    Do, Minh Truong; Kim, Hyung Gyun; Khanal, Tilak; Choi, Jae Ho; Kim, Dong Hee; Jeong, Tae Cheon; Jeong, Hye Gwang

    2013-01-01

    Resistance to therapy is the major obstacle to more effective cancer treatment. Heme oxygenase-1 (HO-1) is often highly up-regulated in tumor tissues, and its expression is further increased in response to therapies. It has been suggested that inhibition of HO-1 expression is a potential therapeutic approach to sensitize tumors to chemotherapy and radiotherapy. In this study, we tested the hypothesis that the anti-tumor effects of metformin are mediated by suppression of HO-1 expression in cancer cells. Our results indicate that metformin strongly suppresses HO-1 mRNA and protein expression in human hepatic carcinoma HepG2, cervical cancer HeLa, and non-small-cell lung cancer A549 cells. Metformin also markedly reduced Nrf2 mRNA and protein levels in whole cell lysates and suppressed tert-butylhydroquinone (tBHQ)-induced Nrf2 protein stability and antioxidant response element (ARE)-luciferase activity in HepG2 cells. We also found that metformin regulation of Nrf2 expression is mediated by a Keap1-independent mechanism and that metformin significantly attenuated Raf-ERK signaling to suppress Nrf2 expression in cancer cells. Inhibition of Raf-ERK signaling by PD98059 decreased Nrf2 mRNA expression in HepG2 cells, confirming that the inhibition of Nrf2 expression is mediated by an attenuation of Raf-ERK signaling in cancer cells. The inactivation of AMPK by siRNA, DN-AMPK or the pharmacological AMPK inhibitor compound C, revealed that metformin reduced HO-1 expression in an AMPK-independent manner. These results highlight the Raf-ERK-Nrf2 axis as a new molecular target in anticancer therapy in response to metformin treatment. - Highlights: • Metformin inhibits HO-1 expression in cancer cells. • Metformin attenuates Raf-ERK-Nrf2 signaling. • Suppression of HO-1 by metformin is independent of AMPK. • HO-1 inhibition contributes to anti-proliferative effects of metformin

  1. Prisoners as Living Donors: A Vulnerabilities Analysis.

    Science.gov (United States)

    Ross, Lainie Friedman; Thistlethwaite, J Richard

    2018-01-01

    Although national guidelines exist for evaluating the eligibility of potential living donors and for procuring their informed consent, no special protections or considerations exist for potential living donors who are incarcerated. Human research subject protections in the United States are codified in the Federal Regulations, 45 CFR 46, and special protections are given to prisoners. Living donor transplantation has parallels with human subject research in that both activities are performed with the primary goal of benefiting third parties. In this article, we describe what special considerations should be provided to prisoners as potential living donors using a vulnerabilities approach adapted from the human research subject protection literature.

  2. Prediction of Protection against Asian Enterovirus 71 Outbreak Strains by Cross-neutralizing Capacity of Serum from Dutch Donors, The Netherlands

    Science.gov (United States)

    Koen, Gerrit; van Eijk, Hetty; Koekkoek, Sylvie M.; de Jong, Menno D.; Wolthers, Katja C.

    2016-01-01

    Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from donors in the Netherlands against EV-71 strains isolated in Europe and in Asia. All IVIg batches and 41%, 79%, and 65% of serum samples from children ≤5 years of age, women of childbearing age, and HIV-positive men, respectively, showed high neutralizing activity against a Dutch C1 strain, confirming widespread circulation of EV-71 in the Netherlands. Asian B3–4 and C4 strains were efficiently cross-neutralized, predicting possible protection against extensive circulation and associated outbreaks of those types in Europe. However, C2 and C5 strains that had few mutations in the capsid region consistently escaped neutralization, emphasizing the importance of monitoring antigenic diversity among circulating EV-71 strains. PMID:27533024

  3. Prediction of Protection against Asian Enterovirus 71 Outbreak Strains by Cross-neutralizing Capacity of Serum from Dutch Donors, The Netherlands.

    Science.gov (United States)

    van der Sanden, Sabine M G; Koen, Gerrit; van Eijk, Hetty; Koekkoek, Sylvie M; de Jong, Menno D; Wolthers, Katja C

    2016-09-01

    Outbreaks of human enterovirus 71 (EV-71) in Asia are related to high illness and death rates among children. To gain insight into the potential threat for the population of Europe, we determined the neutralizing activity in intravenous immunoglobulin (IVIg) batches and individual serum samples from donors in the Netherlands against EV-71 strains isolated in Europe and in Asia. All IVIg batches and 41%, 79%, and 65% of serum samples from children ≤5 years of age, women of childbearing age, and HIV-positive men, respectively, showed high neutralizing activity against a Dutch C1 strain, confirming widespread circulation of EV-71 in the Netherlands. Asian B3-4 and C4 strains were efficiently cross-neutralized, predicting possible protection against extensive circulation and associated outbreaks of those types in Europe. However, C2 and C5 strains that had few mutations in the capsid region consistently escaped neutralization, emphasizing the importance of monitoring antigenic diversity among circulating EV-71 strains.

  4. Recruitment of feces donors among blood donors

    DEFF Research Database (Denmark)

    Dahl Jørgensen, Simon Mark; Erikstrup, Christian; Dinh, Khoa Manh

    2018-01-01

    As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we...... investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire...... to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58...

  5. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation.

    Directory of Open Access Journals (Sweden)

    Rehan Mujeeb Faridi

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT.The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs and 'validation' (146 pairs cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD, chronic GVHD needing systemic therapy (cGVHD and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS, cGVHD & relapse free survival (cGRFS and overall survival (OS] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17 and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11. High incidence of cGVHD associated with KIR genotype mismatching was

  6. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Faridi, Rehan Mujeeb; Kemp, Taylor J; Dharmani-Khan, Poonam; Lewis, Victor; Tripathi, Gaurav; Rajalingam, Raja; Daly, Andrew; Berka, Noureddine; Storek, Jan; Masood Khan, Faisal

    2016-01-01

    Allogeneic hematopoietic cell transplantation (HCT) can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD) and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR)-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG) is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT. The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs) and 'validation' (146 pairs) cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD), chronic GVHD needing systemic therapy (cGVHD) and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS), cGVHD & relapse free survival (cGRFS) and overall survival (OS)] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa) and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17) and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11). High incidence of cGVHD associated with KIR genotype mismatching was applicable

  7. Identification of danthron as an isoform-specific inhibitor of HEME OXYGENASE-1/cytochrome P450 reductase interaction with anti-tumor activity.

    Science.gov (United States)

    Chou, Yi-Tai; Hsu, Fu-Fei; Hu, Dun-Yao; Chen, Ying-Chih; Hsu, Yuan-Hao; Hsu, John T-A; Chau, Lee-Young

    2018-01-23

    Heme oxygenase (HO) catalyzes NADPH-dependent degradation of heme to liberate iron, carbon monoxide and biliverdin. The interaction between HO and cytochrome P450 reductase (CPR), an electron donor, is essential for HO activity. HO-1 is a stress-inducible isoform whereas HO-2 is constitutively expressed. HO-1 induction is commonly seen in cancers and impacts disease progression, supporting the possibility of targeting HO-1 for cancer therapy. We employed a cell-based bioluminescence resonance energy transfer assay to screen compounds with ability to inhibit HO-1/CPR interaction. The effect of the identified compound on HO-1/CPR interaction was confirmed by pull down assay. Moreover, the anti-tumorigenic activity of the identified compound on HO-1-enhanced tumor growth and migration was assessed by trypan blue exclusion method and wound healing assay. Danthron was identified as an effective small molecule able to interfere with the interaction between HO-1 and CPR but not HO-2 and CPR. Additional experiments with structural analogues of danthron revealed that the positions of hydroxyl moieties significantly affected the potency of inhibition on HO-1/CPR interaction. Pull-down assay confirmed that danthron inhibited the interaction of CPR with HO-1 but not HO-2. Danthron suppressed growth and migration of HeLa cells with stable HO-1 overexpression but not mock cells. In contrast, anthrarufin, a structural analog with no ability to interfere HO-1/CPR interaction, exhibited no significant effect on HO-1-overexpressing HeLa cells. These findings demonstrate that danthron is an isoform-specific inhibitor for HO-1/CPR interaction and may serve as a lead compound for novel anticancer drug.

  8. [Lack of donor organs as an argument for living donors?].

    Science.gov (United States)

    Kirste, G

    2010-09-01

    In Germany more than 12,000 patients are presently waiting for an organ donation. Living donation makes sense for the long waiting time for a kidney, but it is not a permanent solution for the lack of organ donations. In the future topics which should be discussed are intensified public relations, a better family care and the allocation of rights and duties at the German coordinating agency. For all the prospects of success after a living donation the high standards of quality and security, which are targeted by the German donor organization in recipient protection, responsible evaluation of the expanded donor criteria and immunosuppressive therapy are all in favor of post-mortem organ donation. For all the phenomenal chance of success the priority of the post-mortem organ donation is regulated by law. The living donation remains an individual decision of the donor and the personal situation of life.

  9. Nyretransplantation med levende donor

    DEFF Research Database (Denmark)

    Kamper, A L; Løkkegaard, H; Rasmussen, F

    2000-01-01

    In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associate...... in cadaver transplantation. The ethical and psychological aspects related to transplantation from a living donor are complex and need to be carefully evaluated when this treatment is offered to the patients....

  10. The evaluation of blood donor deferral causes in Zimbabwe

    NARCIS (Netherlands)

    Mafirakureva, N.; Khoza, S.; Van Hulst, M.; Postma, M.J.; Mvere, D.A.

    2013-01-01

    Background: Donor selection is one of the first steps in blood donation aimed at improving the safety of blood and blood products. It is the only line of protection for donors and against certain infections for which testing is not performed. There is paucity of published data on reasons for donor

  11. Prediction models for hemoglobin deferral in whole blood donors

    NARCIS (Netherlands)

    Baart, A.M.

    2013-01-01

    Each year, a relevant proportion of the invited blood donors is eventually deferred from donation because of low hemoglobin (Hb) levels. Deferrals are meant to protect donors from developing iron deficiency anemia after a blood donation, however, they may increase the risk of donor lapse, even

  12. Psidium guajava extract inhibits thymus and activation-regulated chemokine (TARC/CCL17) production in human keratinocytes by inducing heme oxygenase-1 and blocking NF-κB and STAT1 activation.

    Science.gov (United States)

    Han, Eun Hee; Hwang, Yong Pil; Choi, Jae Ho; Yang, Ji Hye; Seo, Jong Kwon; Chung, Young Chul; Jeong, Hye Gwang

    2011-09-01

    Psidium guajava (P. guajava) is a food and medicinal plant with antioxidant, anti-inflammatory, and anti-allergic activities that support its traditional uses. The aim of this study was to determine the effects of P. guajava ethyl acetate extract (PGEA) on atopic dermatitis and to investigate the possible mechanisms by which PGEA inhibits cytokine-induced Th2 chemokine expression in HaCaT human keratinocyte cells. We found that PGEA suppressed the IFN-γ/TNF-α-co-induced production of thymus and activation-regulated chemokine (TARC) protein and mRNA in HaCaT cells. Additionally, PGEA inhibited the TNF-α/IFN-γ-co-induced activation of NF-κB and STAT1 and increased the expression of heme oxygenase-1 (HO-1) protein and mRNA. HO-1 inhibitor enhanced the suppressive effects of PGEA on TNF-α/IFN-γ-co-induced TARC production and gene expression. Collectively, these data demonstrate that PGEA inhibits chemokine expression in keratinocytes by inducing HO-1 expression and it suggests a possible therapeutic application in atopic dermatitis and other inflammatory skin diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line.

    Science.gov (United States)

    Takahashi, Shigeru; Matsuura, Naomi; Kurokawa, Takako; Takahashi, Yuji; Miura, Takashi

    2002-11-01

    We reported previously that the 5'-flanking region (nucleotides -1976 to -1655) of the human haem oxygenase-1 ( hHO-1 ) gene enhances hHO-1 promoter activity in human hepatoma HepG2 cells, but not in HeLa cells [Takahashi, Takahashi, Ito, Nagano, Shibahara and Miura (1999) Biochim. Biophys. Acta 1447, 231-235]. To define more precisely the regulatory elements involved, in the present study we have functionally dissected this region and localized the enhancer to a 50 bp fragment (-1793 to -1744). Site-direct mutagenesis analysis revealed that two regions were responsible for this enhancer activity, i.e. a hepatocyte nuclear factor-4 (HNF-4) homologous region and a GC box motif homologous region. Mutation in either region alone moderately decreased enhancer activity. However, mutations in both regions reduced promoter activity to the basal level. Electrophoretic mobility-shift assays demonstrated that the P5-2 fragment (-1793 to -1744) interacted with at least two nuclear factors, i.e. HNF-4 and Sp1/Sp3. Co-transfection experiments using Drosophila SL2 cells revealed that HNF-4 and Sp1/Sp3 synergistically stimulated the enhancer activity of the P5-2 fragment. These results indicate that co-operation of HNF-4 with Sp1 or Sp3 leads to the activation of hHO-1 gene expression in hepatoma cells.

  14. Hemin inhibits NO production by IL-1β-stimulated human astrocytes through induction of heme oxygenase-1 and reduction of p38 MAPK activation

    Directory of Open Access Journals (Sweden)

    Sheng Wen S

    2010-09-01

    NOS expression and thereby NO production, an effect that involves the p38 MAPK signaling pathway, which suggests that this glial cell response could play an important protective role against oxidative stress in the brain.

  15. High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiaowen Kang

    2015-02-01

    Full Text Available Background: Growing evidence indicates that heme oxygenase-1 (HO-1 is up-regulated in malignancies and subsequently alters tumor aggressiveness and various cancer-related factors, such as high glucose (HG levels. HO-1 expression can be induced when glucose concentrations are above 25 mM; however, the role of HO-1 in lung cancer patients with diabetes remains unknown. Therefore, in this study we investigated the promotion of tumor cell invasion and the expression of metastasis-associated proteins by inducing the up-regulation of HO-1 expression by HG treatment in A549 human lung epithelial cells. Methods: The expression of HO-1and metastasis-associated protein expression was explored by western blot analysis. HO-1 enzymatic activity, reactive oxygen species (ROS production and TGF-β1 production were examined by ELISA. Invasiveness was analyzed using a Transwell chamber. Results: HG treatment of A549 cells induced an increase in HO-1 expression, which was mediated by the HG-induced generation of reactive oxygen species (ROS and transforming growth factor-β1 (TGF-β1 in a concentration- and time-dependent manner. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in HG-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC or with phosphatidylinositol 3-kinase (PI3K/Akt inhibitors attenuated the HG-induced increase in HO-1 expression. HG treatment of A549 cells enhanced the invasion potential of these cells, as shown with a Transwell assay, and increased metastasis-associated protein expression. However, HO-1 siRNA transfection significantly decreased these capabilities. Conclusion: this study is the first to demonstrate that HG treatment of A549 human lung epithelial cells promotes tumor cell invasion and increases metastasis-associated protein expression by up-regulating HO-1 expression via ROS or the TGF-β1/PI3K/Akt signaling pathway.

  16. Inhibitory Effects of Benzaldehyde Derivatives from the Marine Fungus Eurotium sp. SF-5989 on Inflammatory Mediators via the Induction of Heme Oxygenase-1 in Lipopolysaccharide-Stimulated RAW264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Kyoung-Su Kim

    2014-12-01

    Full Text Available Two benzaldehyde derivatives, flavoglaucin (1 and isotetrahydro-auroglaucin (2, were isolated from the marine fungus Eurotium sp. SF-5989 through bioassay- and 1H NMR-guided investigation. In this study, we evaluated the anti-inflammatory effects of these compounds in lipopolysaccharide (LPS-stimulated RAW264.7 macrophages. We demonstrated that compounds 1 and 2 markedly inhibited LPS-induced nitric oxide (NO and prostaglandin E2 (PGE2 production by suppressing inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 protein expression without affecting cell viability. We also demonstrated that the compounds reduced the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β and interleukin-6 (IL-6. Furthermore, compounds 1 and 2 inhibited LPS-induced nuclear factor-κB (NF-κB activation by suppressing phosphorylation of IkappaB (IκB. These results indicated that the anti-inflammatory effects of these benzaldehyde derivatives in LPS-stimulated RAW264.7 macrophages were due to the inactivation of the NF-κB pathway. In addition, compounds 1 and 2 induced heme oxygenase-1 (HO-1 expression through the nuclear transcription factor-E2–related factor 2 (Nrf2 translocation. The inhibitory effects of compounds 1 and 2 on the production of pro-inflammatory mediators and on NF-κB binding activity were reversed by HO-1 inhibitor tin protoporphyrin (SnPP. Thus, the anti-inflammatory effects of compounds 1 and 2 also correlated with their ability of inducing HO-1 expression.

  17. Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation.

    Science.gov (United States)

    Wang, Shuai; Hannafon, Bethany N; Wolf, Roman F; Zhou, Jundong; Avery, Jori E; Wu, Jinchang; Lind, Stuart E; Ding, Wei-Qun

    2014-05-01

    The effect of docosahexaenoic acid (DHA) on heme oxygenase-1 (HO-1) expression in cancer cells has never been characterized. This study examines DHA-induced HO-1 expression in human cancer cell model systems. DHA enhanced HO-1 gene expression in a time- and concentration-dependent manner, with maximal induction at 21 h of treatment. This induction of HO-1 expression was confirmed in vivo using a xenograft nude mouse model fed a fish-oil-enriched diet. The increase in HO-1 gene transcription induced by DHA was significantly attenuated by the antioxidant N-acetyl cysteine, suggesting the involvement of oxidative stress. This was supported by direct measurement of lipid peroxide levels after DHA treatment. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediate the DHA-induced increase in HO-1 gene transcription. Knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression compromised the DHA-induced increase in HO-1 gene transcription, indicating the importance of the Nrf2 pathway in this event. However, the nuclear protein levels of Nrf2 remained unchanged upon DHA treatment. Further studies demonstrated that DHA reduces nuclear Bach1 protein expression by promoting its degradation and attenuates Bach1 binding to the AREs in the HO-1 gene promoter. In contrast, DHA enhanced Nrf2 binding to the AREs without affecting nuclear Nrf2 expression levels, indicating a new cellular mechanism that mediates DHA's induction of HO-1 gene transcription. To our knowledge, this is the first characterization of DHA-induced HO-1 expression in human malignant cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Expanding the live kidney donor pool: ethical considerations regarding altruistic donors, paired and pooled programs.

    Science.gov (United States)

    Patel, Shaneel Rajendra; Chadha, Priyanka; Papalois, Vassilios

    2011-06-01

    In renal transplant, there is a well-known deficiency in organ supply relative to demand. Live donation provides superior results when compared with deceased donation including a better rate of graft success and fewer immunologic complications. This deficiency in organs leads to significant morbidity and mortality rates. Alternative avenues have been extensively explored that may expand the live donor pool. They include altruistic donation as well as paired and pooled exchange programs. Altruistic donation is a truly selfless act from a donor unknown to the recipient. Kidney paired donation involves 2 incompatible donor-recipient pairs swapping donors to produce compatibility. Pooled donation involves at least 2 pairs, and can take the form of domino chains in which altruistic input sets up a chain of transplants, in which each recipient's incompatible donor makes a donation for the next recipient. Despite application of these various methods, there lie extensive ethical issues surrounding them. Misconceptions frequently occur; for instance, the perceived benefit that donating an organ to a loved one is greater for a related donor than for an altruistic one. Additionally, it is frequently believed that immunologic incompatibility offers coerced donors liberation from surgery, and that overcoming these barriers by introducing exchange programs provides vulnerable donors less protection. This article explores these and other complex ethical issues surrounding the various methods of expanding the donor pool. The authors offer opinions that challenge the ethical issues and attempt to overcome those views that hinder progress in the field.

  19. Laparoscopic donor nephrectomy

    Directory of Open Access Journals (Sweden)

    Gupta Nitin

    2005-01-01

    Full Text Available Of the various options for patients with end stage renal disease, kidney transplantation is the treatment of choice for a suitable patient. The kidney for transplantation is retrieved from either a cadaver or a live donor. Living donor nephrectomy has been developed as a method to address the shortfall in cadaveric kidneys available for transplantation. Laparoscopic living donor nephrectomy (LLDN, by reducing postoperative pain, shortening convalescence, and improving the cosmetic outcome of the donor nephrectomy, has shown the potential to increase the number of living kidney donations further by removing some of the disincentives inherent to donation itself. The technique of LLDN has undergone evolution at different transplant centers and many modifications have been done to improve donor safety and recipient outcome. Virtually all donors eligible for an open surgical procedure may also undergo the laparoscopic operation. Various earlier contraindications to LDN, such as right donor kidney, multiple vessels, anomalous vasculature and obesity have been overcome with increasing experience. Laparoscopic live donor nephrectomy can be done transperitoneally or retroperitoneally on either side. The approach is most commonly transperitoneal, which allows adequate working space and easy dissection. A review of literature and our experience with regards to standard approach and the modifications is presented including a cost saving model for the developing countries. An assessment has been made, of the impact of LDN on the outcome of donor and the recipient.

  20. Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase.

    Science.gov (United States)

    Huber, Warren J; Backes, Wayne L

    2007-10-30

    Heme oxygenase-1 (HO-1) is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. In the process of heme degradation, HO-1 receives the electrons necessary for catalysis from the flavoprotein NADPH cytochrome P450 reductase (CPR), releasing free iron and carbon monoxide. Much of the recent research involving heme oxygenase has been done using a 30 kDa soluble form of the enzyme, which lacks the membrane binding region (C-terminal 23 amino acids). The goal of this study was to express and purify a full-length human HO-1 (hHO-1) protein; however, due to the lability of the full-length form, a rapid purification procedure was required. This was accomplished by use of a glutathione-s-transferase (GST)-tagged hHO-1 construct. Although the procedure permitted the generation of a full-length HO-1, this form was contaminated with a 30 kDa degradation product that could not be eliminated. Therefore, attempts were made to remove a putative secondary thrombin cleavage site by a conservative mutation of amino acid 254, which replaces arginine with lysine. This mutation allowed the expression and purification of a full-length hHO-1 protein. Unlike wild type (WT) HO-1, the R254K mutant could be purified to a single 32 kDa protein capable of degrading heme at the same rate as the WT enzyme. The R254K full-length form had a specific activity of approximately 200-225 nmol of bilirubin h-1 nmol-1 HO-1 as compared to approximately 140-150 nmol of bilirubin h-1 nmol-1 for the WT form, which contains the 30 kDa contaminant. This is a 2-3-fold increase from the previously reported soluble 30 kDa HO-1, suggesting that the C-terminal 23 amino acids are essential for maximal catalytic activity. Because the membrane-spanning domain is present, the full-length hHO-1 has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other endoplasmic reticulum resident enzymes.

  1. Isorhamnetin inhibits Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages via anti-inflammatory heme oxygenase-1 induction and inhibition of nuclear factor-κB and signal transducer and activator of transcription 1 activation.

    Science.gov (United States)

    Jin, J Y; Choi, E Y; Park, H R; Choi, J I; Choi, I S; Kim, S J

    2013-12-01

    Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits. Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling. Although further research is required to clarify the detailed mechanism of action, we propose

  2. Biluminescence via Fluorescence and Persistent Phosphorescence in Amorphous Organic Donor(D4)-Acceptor(A) Conjugates, and Application in Data Security Protection.

    Science.gov (United States)

    Bhatia, Harsh; Bhattacharjee, Indranil; Ray, Debdas

    2018-06-25

    Purely organic biluminescent materials are of great interest due to the involvement of both singlet and long-lived triplet emissions, which have been used in bio-imaging and organic light-emitting diodes. We show two molecules 3,4,5,6-tetraphenyloxy-phthlonitrile (POP) and 3,4,5,6-tetrakis-p-tolyloxy-phthalonitrile (TOP), in which POP was found to exhibit fluorescence and persistent room-temperature green phosphorescence (pRTGP) in the amorphous and crystal states. Both POP and TOP show aggregation induced emission in tetrahydrofuran-water mixture. We found in single crystal X-ray analysis that intra-and inter molecular lp(O)•••π interactions along with (π(C=C)•••π(C≡N), hydrogen bond (H-B), and C-H•••π interactions induce head-to-tail slipped-stacked arrangement in POP. In addition, X-ray structure of TOP with slipped-stack arrangement induced by only (π(C=C)•••π(C≡N) and H-B interactions, shows dim afterglow only in crystals. These indicate that more number of non-covalent interactions may reinforce relatively efficient inter system crossing that leads to pRTGP even in the amorphous state of POP. Given the unique green afterglow feature in amorphous state of POP, document security protection application is achievable.

  3. Donor Telomere Length SAA

    Science.gov (United States)

    A new NCI study has found that, among patients with severe aplastic anemia who received a hematopoietic cell transplant from an unrelated donor, those whose donor white blood cells had longer telomeres had higher survival rates five-years after transplant

  4. Systems of donor transfer

    NARCIS (Netherlands)

    F.T. de Charro (Frank); J.E.M. Akveld (Hans); E. Hessing (Ellen)

    1993-01-01

    textabstractThe development of medical knowledge has resulted in a demand in society for donor organs, but the recruitment of donor organs for transplantation is difficult. This paper aims to provide some general insights into the complex interaction processes involved. A laissez-faire policy, in

  5. Lung Focused Resuscitation at a Specialized Donor Care Facility Improves Lung Procurement Rates.

    Science.gov (United States)

    Chang, Stephanie H; Kreisel, Daniel; Marklin, Gary F; Cook, Lindsey; Hachem, Ramsey; Kozower, Benjamin D; Balsara, Keki R; Bell, Jennifer M; Frederiksen, Christine; Meyers, Bryan F; Patterson, G Alexander; Puri, Varun

    2018-05-01

    Lung procurement for transplantation occurs in approximately 20% of brain dead donors and is a major impediment to wider application of lung transplantation. We investigated the effect of lung protective management at a specialized donor care facility on lung procurement rates from brain dead donors. Our local organ procurement organization instituted a protocol of lung protective management at a freestanding specialized donor care facility in 2008. Brain dead donors from 2001 to 2007 (early period) were compared with those from 2009 to 2016 (current period) for lung procurement rates and other solid-organ procurement rates using a prospectively maintained database. An overall increase occurred in the number of brain dead donors during the study period (early group, 791; late group, 1,333; p procurement rate (lung donors/all brain dead donors) improved markedly after the introduction of lung protective management (early group, 157 of 791 [19.8%]; current group, 452 of 1,333 [33.9%]; p procurement rate (total number of organs procured/donor) also increased during the study period (early group, 3.5 organs/donor; current group, 3.8 organs/donor; p = 0.006). Lung protective management in brain dead donors at a specialized donor care facility is associated with higher lung utilization rates compared with conventional management. This strategy does not adversely affect the utilization of other organs in a multiorgan donor. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Increasing the supply of kidneys for transplantation by making living donors the preferred source of donor kidneys.

    Science.gov (United States)

    Testa, Giuliano; Siegler, Mark

    2014-12-01

    At the present time, increasing the use of living donors offers the best solution to the organ shortage problem. The clinical questions raised when the first living donor kidney transplant was performed, involving donor risk, informed consent, donor protection, and organ quality, have been largely answered. We strongly encourage a wider utilization of living donation and recommend that living donation, rather than deceased donation, become the first choice for kidney transplantation. We believe that it is ethically sound to have living kidney donation as the primary source for organs when the mortality and morbidity risks to the donor are known and kept extremely low, when the donor is properly informed and protected from coercion, and when accepted national and local guidelines for living donation are followed.

  7. Marginal kidney donor

    Directory of Open Access Journals (Sweden)

    Ganesh Gopalakrishnan

    2007-01-01

    Full Text Available Renal transplantation is the treatment of choice for a medically eligible patient with end stage renal disease. The number of renal transplants has increased rapidly over the last two decades. However, the demand for organs has increased even more. This disparity between the availability of organs and waitlisted patients for transplants has forced many transplant centers across the world to use marginal kidneys and donors. We performed a Medline search to establish the current status of marginal kidney donors in the world. Transplant programs using marginal deceased renal grafts is well established. The focus is now on efforts to improve their results. Utilization of non-heart-beating donors is still in a plateau phase and comprises a minor percentage of deceased donations. The main concern is primary non-function of the renal graft apart from legal and ethical issues. Transplants with living donors outnumbered cadaveric transplants at many centers in the last decade. There has been an increased use of marginal living kidney donors with some acceptable medical risks. Our primary concern is the safety of the living donor. There is not enough scientific data available to quantify the risks involved for such donation. The definition of marginal living donor is still not clear and there are no uniform recommendations. The decision must be tailored to each donor who in turn should be actively involved at all levels of the decision-making process. In the current circumstances, our responsibility is very crucial in making decisions for either accepting or rejecting a marginal living donor.

  8. Donor milk: current perspectives

    Directory of Open Access Journals (Sweden)

    Giuliani F

    2014-07-01

    Full Text Available Francesca Giuliani,1 Ilaria Rovelli,1 Chiara Peila,1 Stefania Alfonsina Liguori,2 Enrico Bertino,1 Alessandra Coscia1 1SCDU Neonatologia, Dipartimento di Scienze Pediatriche e dell'Adolescenza, Università degli Studi di Torino, Torino, Italy; 2SC Neonatologia, Ospedale Maria Vittoria, Torino, Italy Abstract: Mother's own milk is widely recognized as the optimal feeding for term infants, but increasing evidence exists of its benefits also for sick and preterm infants in neonatal intensive care units. However, the nutritional needs for appropriate growth and neurodevelopmental outcomes of such a particular population of infants should be attentively evaluated, considering also the indication to an appropriate fortification of human milk. The target is to achieve growth potential for preterm newborns while ensuring good metabolic outcomes and normal neurological development. When mother's milk is unavailable or in short supply, donor human milk (DHM represents the second best choice and, although somewhat modified by the Holder pasteurization process, it preserves many benefits when compared to formula, as documented by more and more reports, randomized controlled trials, and meta-analyses published in the past few years. Evidence exists of the protection exerted by DHM from necrotizing enterocolitis, while further studies are required to look at possible beneficial effects regarding infections, bronchopulmonary dysplasia, long-term cardiovascular risk factors, feeding tolerance, neurological outcome, and allergy. Finally, the concern that the use of DHM might decrease preterm infant breastfeeding is being raised. Conversely, publications exist showing that the use of DHM in the neonatal unit increases breastfeeding rates at discharge for infants of very low birth weight. Keywords: human milk, preterm infant feeding, milk bank, breast milk, mother's own milk, pasteurized human milk, fortification

  9. How to optimize the lung donor.

    Science.gov (United States)

    Sales, Gabriele; Costamagna, Andrea; Fanelli, Vito; Boffini, Massimo; Pugliese, Francesco; Mascia, Luciana; Brazzi, Luca

    2018-02-01

    Over the last two decades, lung transplantation emerged as the standard of care for patients with advanced and terminal lung disease. Despite the increment in lung transplantation rates, in 2016 the overall mortality while on waiting list in Italy reached 10%, whereas only 39% of the wait-list patients were successfully transplanted. A number of approaches, including protective ventilatory strategy, accurate management of fluid balance, and administration of a hormonal resuscitation therapy, have been reported to improve lung donor performance before organ retrieval. These approaches, in conjunction with the use of ex-vivo lung perfusion technique contributed to expand the lung donor pool, without affecting the harvest of other organs and the outcomes of lung recipients. However, the efficacy of issues related to the ex-vivo lung perfusion technique, such as the optimal ventilation strategy, the ischemia-reperfusion induced lung injury management, the prophylaxis of germs transmission from donor to recipient and the application of targeted pharmacologic therapies to treat specific donor lung injuries are still to be explored. The main objective of the present review is to summarize the "state-of-art" strategies to optimize the donor lungs and to present the actual role of ex-vivo lung perfusion in the process of lung transplant. Moreover, different approaches about the technique reported in literature and several issues that are under investigation to treat specific donor lung injury will be discussed.

  10. National Marrow Donor Program

    National Research Council Canada - National Science Library

    Setterholm, Michelle

    2008-01-01

    ... a nationwide contingency response plan. 2. Rapid Identification of Matched Donors : Increase operational efficiencies that accelerate the search process and increase patient access are key to preparedness in a contingency event. pa 3...

  11. Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress.

    Science.gov (United States)

    Kim, Jung Wha; Yang, Heejung; Kim, Hyeon Woo; Kim, Hong Pyo; Sung, Sang Hyun

    2017-01-01

    Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

  12. Protective

    Directory of Open Access Journals (Sweden)

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  13. Management to optimize organ procurement in brain dead donors.

    Science.gov (United States)

    Mascia, L; Mastromauro, I; Viberti, S; Vincenzi, M; Zanello, M

    2009-03-01

    The demand for donor organs continues to exceed the number of organs available for transplantation. Many reasons may account for this discrepancy, such as the lack of consent, the absence of an experienced coordinator team able to solve logistical problems, the use of strict donor criteria, and suboptimal, unstandardized critical care management of potential organ donors. This has resulted in efforts to improve the medical care delivered to potential organ donors, so as to reduce organ shortages, improve organ procurement, and promote graft survival. The physiological changes that follow brain death entail a high incidence of complications jeopardizing potentially transplantable organs. Adverse events include cardiovascular changes, endocrine and metabolic disturbances, and disruption of internal homeostasis. Brain death also upregulates the release of pro-inflammatory molecules. Recent findings support the hypothesis that a preclinical lung injury characterized by an enhanced inflammatory response is present in potential donors and may predispose recipients to an adverse clinical prognosis following lung transplantation. In clinical practice, hypotension, diabetes insipidus, relative hypothermia, and natremia are more common than disseminated intravascular coagulation, cardiac arrhythmias, pulmonary oedema, acute lung injury, and metabolic acidosis. Strategies for the management of organ donors exist and consist of the normalization of donor physiology. Management has been complicated by the recent use of ''marginal'' donors and donors of advanced age or with ''extended'' criteria. Current guidelines suggest that the priority of critical care management for potential organ donors should be shifted from a ''cerebral protective'' strategy to a multimodal strategy aimed to preserve peripheral organ function.

  14. BLOOD DONORS CAMPAIGN

    CERN Document Server

    Medical Service

    2002-01-01

    Tuesday 19 March 2002 in restaurant nr 2, from 9.00 to 16.30 hrs A blood donors campaign, organized by the Centre de Transfusion sanguine of Geneva If you already have a card giving your blood group, please bring this with you.

  15. BLOOD DONORS CAMPAIGN

    CERN Multimedia

    2001-01-01

    A blood donors campaign, organized by the Centre de Transfusion Sanguine of Geneva will be held at CERN on Tuesday 13 March 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  16. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2002-01-01

    Wednesday 13 November 2002 in restaurant nr 2, from 8.30 to 16.30 hrs will be held a blood donors campaign, organized by the Etablissement de Transfusion de Haute-Savoie If you already have a card giving your blood group, please bring this with you.

  17. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2000-01-01

    A blood donors campaign, organized by the Établissement de Transfusion de Rhône-Alpes will be held at CERN on Tuesday 14 November 2000 in restaurant nr 2, from 8.30 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  18. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2001-01-01

    A blood donors campaign, organized by the Centre de Transfusion d'Annemasse will be held at CERN on Tuesday 14 November 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  19. Donor transplant programme

    International Nuclear Information System (INIS)

    Abu Bakar Sulaiman

    1999-01-01

    The transplantation of organs and tissues from one human to another human has become an essential and well established form of therapy for many types of organ and tissue failure. In Malaysia, kidney, cornea and bone marrow transplantation are well established. Recently, liver, bone and heart transplanation have been performed. Unfortunately, because of the lack of cadaveric organ donation, only a limited number of solid organ transplantation have been performed. The cadaveric organ donor rate in Malaysia is low at less than one per million population. The first tissue transplanted in Malaysia was the cornea which was performed in the early 1970s. At that time and even now the majority of corneas came from Sri Lanka. The first kidney transplant was performed in 1975 from a live related donor. The majority of the 629 kidney transplants done at Hospital Kuala Lumpur to date have been from live related donors. Only 35 were from cadaver donors. Similarly, the liver transplantation programme which started in 1995 are from live related donors. A more concerted effort has been made recently to increase the awareness of the public and the health professionals on organ and tissue donation. This national effort to promote organ and tissue donation seems to have gathered momentum in 1997 with the first heart transplant successfully performed at the National Heart Institute. The rate of cadaveric donors has also increased from a previous average of I to 2 per year to 6 per year in the last one year. These developments are most encouraging and may signal the coming of age of our transplantati on programme. The Ministry of Health in conjunction with various institutions, organizations and professional groups, have taken a number of proactive measures to facilitate the development of the cadaveric organ donation programme. Efforts to increase public awareness and to overcome the negative cultural attitude towards organ donation have been intensified. Equally important are efforts

  20. Are drowned donors marginal donors? A single pediatric center experience.

    Science.gov (United States)

    Kumm, Kayla R; Galván, N Thao N; Koohmaraie, Sarah; Rana, Abbas; Kueht, Michael; Baugh, Katherine; Hao, Liu; Yoeli, Dor; Cotton, Ronald; O'Mahony, Christine A; Goss, John A

    2017-09-01

    Drowning, a common cause of death in the pediatric population, is a potentially large donor pool for OLT. Anecdotally, transplant centers have deemed these organs high risk over concerns for infection and graft dysfunction. We theorized drowned donor liver allografts do not portend worse outcomes and therefore should not be excluded from the donation pool. We reviewed our single-center experience of pediatric OLTs between 1988 and 2015 and identified 33 drowned donor recipients. These OLTs were matched 1:2 to head trauma donor OLTs from our center. A chart review assessed postoperative peak AST and ALT, incidence of HAT, graft and recipient survival. Recipient survival at one year between patients with drowned donor vs head trauma donor allografts was not statistically significant (94% vs 97%, P=.63). HAT incidence was 6.1% in the drowned donor group vs 7.6% in the control group (P=.78). Mean postoperative peak AST and ALT was 683 U/L and 450 U/L for drowned donors vs 1119 U/L and 828 U/L in the matched cohort. These results suggest drowned donor liver allografts do not portend worse outcomes in comparison with those procured from head trauma donors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Iron deficiency in blood donors

    Directory of Open Access Journals (Sweden)

    Rodolfo Delfini Cançado

    Full Text Available CONTEXT: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. OBJECTIVE: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors, and the frequency of donations per year. DESIGN: From September 20 to October 5, 1999, three hundred blood donors from Santa Casa Hemocenter of São Paulo were studied. DIAGNOSTIC TESTS: Using a combination of biochemical measurements of iron status: serum iron, total iron-binding capacity, transferrin saturation index, serum ferritin and the erythrocyte indices. RESULTS: The frequency of iron deficiency in blood donors was 11.0%, of whom 5.5% (13/237 were male and 31.7% (20/63 female donors. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, for male blood donors (7.6% versus 0.0%, P < 0.05 and female ones (41.5% versus 18.5%, P < 0.05. The frequency of iron deficiency found was higher among the male blood donors with three or more donations per year (P < 0.05 and among the female blood donors with two or more donations per year (P < 0.05. CONCLUSIONS: We conclude that blood donation is a very important factor for iron deficiency in blood donors, particularly in multi-time donors and especially in female donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia.

  2. Meet the donors

    DEFF Research Database (Denmark)

    Olejaz, Maria; Hoeyer, Klaus

    2016-01-01

    motivations, but rather as something made meaningful in the light of how donors understand their bodies; their social relations; and their societal position and experiences as patients in the healthcare system. The article thus contributes to the field by investigating the nature of the relationship between......For centuries, gross anatomy teaching and anatomical dissection have been fundamental elements in the training of medical doctors and surgeons across the world. Anatomy education and research rely on a stable and reliable supply of bodies in order to take place. Based on qualitative in...

  3. Iron deficiency among blood donors

    DEFF Research Database (Denmark)

    Rigas, A S; Pedersen, O B; Magnussen, K

    2017-01-01

    Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation...... and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark...

  4. Being Sherlock Holmes: the Internet as a tool for assessing live organ donors.

    Science.gov (United States)

    Bramstedt, Katrina A; Katznelson, Steven

    2009-01-01

    Donor advocacy is a critical feature of live donor transplantation. Donor Advocates and Donor Advocate Teams (DAT) are now routine to the practice of live donor evaluation in the USA. Multidisciplinary in nature, DATs gather both medical and psychosocial information about potential live organ donors and then render a decision as to whether or not these individuals are suitable to participate. Because of the critical ethical and psychosocial concerns about live donation, thorough donor evaluations are essential. Additionally, the information gathered must be accurate, and this requires honest disclosure by the donor candidate. In this paper, we describe how DATs can use various forms of free, public content available on the Internet to aid live donor assessments. In this way, the DAT assumes somewhat of an investigative role; however, this is ethically justified in light of the DAT duty to protect the donor. The protective effect can also spread to the transplant program, in general, when inappropriate donors are excluded from the donation process.

  5. The doctor-patient relationship in living donor kidney transplantation.

    Science.gov (United States)

    Danovitch, Gabriel M

    2007-11-01

    A therapeutic and effective doctor-patient relationship and patient-doctor relationship is at the core of all successful medical care. The medical and psychological evaluation of a potential kidney donor serves to protect the long-term health of both the donor and the potential recipient. Careful assessment of risk and donor education is at the core of donor evaluation and the decision to progress with donation requires refined clinical judgment by the medical team and critical thinking by the donor. Increasing pressure to increase the numbers of living donor transplants and suggestions by some that the process should be commercialized make it timely to consider the nature of the relationship between the doctor and the patient in the unusual circumstance of living donation. A high rate of complications in recipients of purchased kidneys and a lack of knowledge of the fate of paid donors have been reported. Commercialization of transplantation undermines the therapeutic doctor-patient relationship and threatens the healthy development of the international transplant endeavor.

  6. Involvement of heme oxygenase-1 expression in neuroprotection by piceatannol, a natural analog and a metabolite of resveratrol, against glutamate-mediated oxidative injury in HT22 neuronal cells.

    Science.gov (United States)

    Son, Yong; Byun, Seung Jae; Pae, Hyun-Ock

    2013-08-01

    Neuronal cell death caused by oxidative stress is common in a variety of neural diseases and can be investigated in detail in cultured HT22 neuronal cells, where the amino acid glutamate at high concentrations causes glutathione depletion by inhibition of the glutamate/cystine antiporter system, intracellular accumulation of reactive oxygen species (ROS) and eventually oxidative stress-induced neuronal cell death. Using this paradigm, we have previously reported that resveratrol (3,5,4'-trans-trihydroxystilbene) protects HT22 neuronal cells from glutamate-induced oxidative stress by inducing heme oxygenase (HO)-1 expression. Piceatannol (3,5,4',3'-trans-trihydroxystilbene), which is a hydroxylated resveratrol analog and one of the resveratrol metabolites, is estimated to exert neuroprotective effect similar to that of resveratrol. The aim of this study, thus, is to determine whether piceatannol, similarly to resveratrol, would protect HT22 neuronal cells from glutamate-induced oxidative stress. Glutamate at high concentrations induced neuronal cell death and ROS formation. Piceatannol reduced glutamate-induced cell death and ROS formation. The observed cytoprotective effect was much higher when HT22 neuronal cells were pretreated with piceatannol for 6 or 12 h prior to glutamate treatment than when pretreated for 0.5 h. Piceatannol also increased HO-1 expression and HO activity via its activation of nuclear factor-E2-related factor 2 (Nrf2). Interestingly, neuroprotective effect of piceatannol was partly (but not completely) abolished by either down-regulation of HO-1 expression or blockage of HO-1 activity. Taken together, our results suggest that piceatannol, similar to resveratrol, is capable of protecting HT22 neuronal cells against glutamate-induced cell death, at least in part, by inducing Nrf2-dependent HO-1 expression.

  7. Protective effect of hemin against cadmium-induced testicular damage in rats

    International Nuclear Information System (INIS)

    Fouad, Amr A.; Qureshi, Habib A.; Al-Sultan, Ali Ibrahim; Yacoubi, Mohamed T.; Ali, Abdellah Abusrie

    2009-01-01

    The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2 mg/kg). Hemin was given for three consecutive days (40 μmol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium

  8. Donor selection criteria and procurement

    International Nuclear Information System (INIS)

    Agcaoili, N.R.

    1999-01-01

    Donor selection is one of the most important aspects of tissue banking practice. Without a good donor selection criteria, the results of any effort of trying to preserve tissues will have disastrous outcome for the recipient of these tissues. While with a very good and strict donor selection the Tissue Bank can guarantee safe and effective tissue allografts. There are significant aspects in the history and physical examination of the donor that must be emphasized. A donor exclusion criteria has also been formulated together with a list of all the needed laboratory examinations to eliminate possible diseases that may be transferred from the donor. The methods of procurement of tissue allografts from living and cadaver donors will be described. The limitations and advantages of each will be taken.There are also special restrictions that are important in the practice of removing the tissues from the donors. All the necessary equipment should be ready and the potential risk on the personnel should be known to all doing Tissue Banking

  9. The Dirt on the Donors.

    Science.gov (United States)

    Walker, Mary Margaret

    1996-01-01

    A discussion of donor records in college and university fund-raising programs looks at a variety of issues, including who sees them (administrators, donors, volunteers, and members of the legal profession), how access to them is controlled, and what is kept in them. Suggestions are offered for managing such records, and the experiences of a number…

  10. Heart transplantation from older donors

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2017-01-01

    Full Text Available In the current situation of the shortage of suitable donor organs, heart transplantation from older donors is one of the ways to increase the performance of more heart transplants, particularly, in patients with urgent need of transplantation. While planning a heart transplantation from older donor one should consider increased risk of early cardiac allograft dysfunction, preexisting coronary artery disease, accelerated transplant vasculopathy which may adversely affect early and long-term survival of recipients. Subject to careful selection of donor–recipient pairs, effective prevention and treatment of early cardiac allograft dysfunction, pre-existing atherosclerosis and transplant vasculopathy the early and long-term survival of heart transplant recipients from older donors is comparable to heart transplantation from young donors.

  11. DISAL glycosyl donors for the synthesis of a linear hexasaccharide under mild conditions

    DEFF Research Database (Denmark)

    Petersen, Lars; Laursen, Jane B.; Larsen, K.

    2003-01-01

    The new class of glycosyl donors with a methyl 3,5-dinitrosalicylate (DISAL) anomeric leaving group has proved efficient for glycosylation under strictly neutral, mildly basic, or mildly acidic conditions. Here, we report the synthesis of novel DISAL disaccharide glycosyl donors prepared by easy...... nucleophilic aromatic substitution. These DISAL donors proved efficient in the synthesis of a starch-related hexasaccharide under very mild conditions. Glycosylations proceeded with alpha-selectivity and were compatible with Trt protecting groups....

  12. Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals.

    Science.gov (United States)

    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Hsu, Ling-I; Lien, Li-Ming; Wang, Chih-Hao; Hsieh, Yi-Chen; Wang, Yuan-Hung; Hsueh, Yu-Mei; Lee, Te-Chang; Cheng, Wen-Fang; Chen, Chien-Jen

    2011-12-01

    Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (accounting for CV covariates. Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles. HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. Fisetin inhibits TNF-α-induced inflammatory action and hydrogen peroxide-induced oxidative damage in human keratinocyte HaCaT cells through PI3K/AKT/Nrf-2-mediated heme oxygenase-1 expression.

    Science.gov (United States)

    Seo, Seung-Hee; Jeong, Gil-Saeng

    2015-12-01

    Oxidative skin damage and skin inflammation play key roles in the pathogenesis of skin-related diseases. Fisetin is a naturally occurring flavonoid abundantly found in several vegetables and fruits. Fisetin has been shown to exert various positive biological effects, such as anti-cancer, anti-proliferative, neuroprotective and anti-oxidative effects. In this study, we investigate the skin protective effects and anti-inflammatory properties of fisetin in hydrogen peroxide- and TNF-α-challenged human keratinocyte HaCaT cells. When HaCaT cells were treated with non-cytotoxic concentrations of fisetin (1-20μM), heme oxygenase (HO)-1 mRNA and protein expression increased in a dose-dependent manner. Furthermore, fisetin dose-dependently increased cell viability and reduced ROS production in hydrogen peroxide-treated HaCaT cells. Fisetin also inhibited the production of NO, PGE2 IL-1β, IL-6, expression of iNOS and COX-2, and activation of NF-κB in HaCaT cells treated with TNF-α. Fisetin induced Nrf2 translocation to the nuclei. HO-1 siRNA transient transfection reversed the effects of fisetin on cytoprotection, ROS reduction, NO, PGE2, IL-1β, IL-6, and TNF-α production, and NF-κB DNA-binding activity. Moreover, fisetin increased Akt phosphorylation and a PI3K pathway inhibitor (LY294002) abolished fisetin-induced cytoprotection and NO inhibition. Taken together, these results provide evidence for a beneficial role of fisetin in skin therapy. Copyright © 2015. Published by Elsevier B.V.

  14. Anti-inflammatory effect of a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor via the stimulation of heme oxygenase-1 in LPS-activated mice and J774.1 murine macrophages

    Directory of Open Access Journals (Sweden)

    Sung Bum Park

    2016-08-01

    Full Text Available 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1 converts inactive cortisone to the active cortisol. 11β-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344, a selective 11β-HSD1 inhibitor, in lipopolysaccharide (LPS-activated C57BL/6J mice and macrophages. LPS increased 11β-HSD1 activity and expression in macrophages, which was inhibited by KR-66344. In addition, KR-66344 increased survival rate in LPS treated C57BL/6J mice. HO-1 mRNA expression level was increased by KR-66344, and this effect was reversed by the HO competitive inhibitor, ZnPP, in macrophages. Moreover, ZnPP reversed the suppression of ROS formation and cell death induced by KR-66344. ZnPP also suppressed animal survival rate in LPS plus KR-66344 treated C57BL/6J mice. In the spleen of LPS-treated mice, KR-66344 prevented cell death via suppression of inflammation, followed by inhibition of ROS, iNOS and COX-2 expression. Furthermore, LPS increased NFκB-p65 and MAPK phosphorylation, and these effects were abolished by pretreatment with KR-66344. Taken together, KR-66344 protects against LPS-induced animal death and spleen injury by inhibition of inflammation via induction of HO-1 and inhibition of 11β-HSD1 activity. Thus, we concluded that the selective 11β-HSD1 inhibitor may provide a novel strategy in the prevention/treatment of inflammatory disorders in patients.

  15. Anesthesia Management of Organ Donors.

    Science.gov (United States)

    Xia, Victor W; Braunfeld, Michelle

    2017-09-01

    The shortage of suitable organs is the biggest obstacle for transplants. At present, most organs for transplant in the United States are from donation after neurologic determination of death (brain death). Potential organs for transplant need to maintain their viability during a series of insults, including the original disease, physiologic derangements during the dying process, ischemia, and reperfusion. Proper donor management before, during, and after procurement has potential to increase the number and quality of organs from donors. Anesthesiologists need to understand the physiologic derangements associated with brain death and the updated donor management during the periprocurement period. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. New hydrogen donors in germanium

    International Nuclear Information System (INIS)

    Pokotilo, Yu.M.; Petukh, A.N.; Litvinov, V.V.

    2003-01-01

    The electrophysical properties of the n-type conductivity germanium, irradiated through protons, is studied by the volt-farad method. It is shown that the heat treatment of the implanted germanium at the temperature of 200-300 deg C leads to formation of the fast-diffusing second-rate donors. It is established that the diffusion coefficient of the identified donors coincides with the diffusion coefficient of the atomic hydrogen with an account of the capture on the traps. The conclusion is made, that the atomic hydrogen is the second-rate donor center in germanium [ru

  17. Sexual behaviour and practices among adolescent blood donors in ...

    African Journals Online (AJOL)

    Nevertheless, they also reported on the acceptability of unprotected sex with sexual partners perceived to be HIV negative. Social status ascribed to blood donors, and mandatory HIV screening of donated blood, were protective against risky sexual behaviour. However, socio-economic and cultural factors may override this.

  18. Governance, resource curse and donor

    OpenAIRE

    Wiig, Arne

    2008-01-01

    Plan Part 1. Governance What is good governance? Why is it important? How can we measure good governance? Part 2. The resource curse and the importance of governance in resource rich countries Focus on political economy (PE) models of the resource curse Policy implications Some donor initiatives Transparency and the EITI Petroleum related aid - Window dressing initiatives or research based? Conclusion Governance, resource curse and donor

  19. Philanthropic Motivations of Community College Donors

    Science.gov (United States)

    Carter, Linnie S.; Duggan, Molly H.

    2011-01-01

    This descriptive study surveyed current, lapsed, and major gift donors to explore the impact of college communications on donors' decisions to contribute to the college, the likelihood of donor financial support for various college projects, and the philanthropic motivation profiles of the donors of a midsized, multicampus community college in…

  20. Kidney transplant outcomes from older deceased donors

    DEFF Research Database (Denmark)

    Pippias, Maria; Jager, Kitty J; Caskey, Fergus

    2018-01-01

    As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor...

  1. Living related donor liver transplantation.

    Science.gov (United States)

    Chen, C L; Chen, Y S; Liu, P P; Chiang, Y C; Cheng, Y F; Huang, T L; Eng, H L

    1997-10-01

    Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. According to the International Living Donor Registry, 521 transplants had been performed in 515 patients between December 8 1988 and January 19 1996 in 30 centres worldwide. The overall actuarial patient and graft survival rates were 82.7 and 80%, respectively. Between June 17 1994 and November 30 1996, the authors performed 11 LRLT at the Chung Gung Memorial Hospital. The living donors consisted of 10 mothers and one father. The mean graft weight was 303 g and the mean graft recipient weight ratio was 2.2%. Donor hepatectomy was performed without vascular inflow occlusion. The intra-operative blood loss ranged from 30 mL to 120 mL with an average of 61 mL, and blood transfusion was not required in all donors both intra-operatively and during the postoperative period. Underlying diseases of the recipients were biliary atresia (n = 10) and glycogen storage disease (n = 1). The mean graft cold ischaemia time was 106 min, the mean second warm ischaemia time was 51 min and the mean interval between portal and arterial reperfusion was 81 min. The initial LRLT results were promising with all donors having been discharged without complication. The recipients experienced a few complications, all of which were manageable with early intervention. All 11 recipients are alive and well. These are encouraging results and the authors hope to expand the use of live donors for liver transplantation to cope with demand.

  2. Why Should Donors Care about Corruption?

    OpenAIRE

    Kolstad, Ivar

    2008-01-01

    Corruption is bad for donor business. Corruption reduces popular support for aid in donor countries. However, aid agencies should pay attention to corruption because it is the right thing to do, rather than just the smart thing to do. Donor anti-corruption policies require a strong grounding in ethics. Corruption produces bad development outcomes. This is the reasoning largely underlying donor anti-corruption efforts. The focus on consequences of corruption makes donor anticorruptioneffo...

  3. Host heme oxygenase-1: Friend or foe in tackling pathogens?

    Science.gov (United States)

    Singh, Nisha; Ahmad, Zeeshan; Baid, Navin; Kumar, Ashwani

    2018-05-14

    Infectious diseases are a major challenge in management of human health worldwide. Recent literature suggests that host immune system could be modulated to ameliorate the pathogenesis of infectious disease. Heme oxygenase (HMOX1) is a key regulator of cellular signaling and it could be modulated using pharmacological reagents. HMOX1 is a cytoprotective enzyme that degrades heme to generate carbon monoxide (CO), biliverdin, and molecular iron. CO and biliverdin (or bilirubin derived from it) can restrict the growth of a few pathogens. Both of these also induce antioxidant pathways and anti-inflammatory pathways. On the other hand, molecular iron can induce proinflammatory pathway besides making the cellular environment oxidative in nature. Since microbial infections often induce oxidative stress in host cells/tissues, role of HMOX1 has been analyzed in the pathogenesis of number of infections. In this review, we have described the role of HMOX1 in pathogenesis of bacterial infections caused by Mycobacterium species, Salmonella and in microbial sepsis. We have also provided a succinct overview of the role of HMOX1 in parasitic infections such as malaria and leishmaniasis. In the end, we have also elaborated the role of HMOX1 in viral infections such as AIDS, hepatitis, dengue, and influenza. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  4. Effect of a heme oxygenase-1 inducer on NADPH oxidase ...

    African Journals Online (AJOL)

    Acute alcohol consumption leads to fatty liver. Although fatty liver is a reversible injury, its progression can develop into more severe liver problems including steatohepatitis and cirrhosis [1]. Previous studies showed that oxidative stress is an important factor contributing to the development of alcohol-induced liver injury [2].

  5. Functional imaging: monitoring heme oxygenase-1 gene expression in vivo

    Science.gov (United States)

    Zhang, Weisheng; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

    1999-07-01

    The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

  6. Function following Living Donor Nephrectomy

    Directory of Open Access Journals (Sweden)

    Jonathan Heldt

    2011-01-01

    Full Text Available Background. While tobacco use by a renal transplant recipient has been shown to negatively affect graft and patient survival, the effect of smoking on the part of the kidney donor remains unknown. Methods. 29 smoking donors (SD and their recipients (SD-R as well as 71 non-smoking donors (ND and their recipients (ND-R were retrospectively reviewed. Preoperative demographics and perioperative variables including serum creatinine (Cr and glomerular filtration rate (GFR were calculated and stratified by amount of tobacco exposure in pack-years. Clinical outcomes were analyzed with a Student's t-test, chi-square, and multiple linear regression analysis (=0.05. Results. At most recent followup, SD-R's had a significantly smaller percent decrease in postoperative Cr than ND-R's (−57% versus −81%; =0.015 and lower calculated GFR's (37.0 versus 53.0 mL/min per 1.73 m2; <0.001. SD's had a larger percent increase in Cr than ND's at most recent followup (57% versus 40%; <0.001, with active smokers having a larger increase than those who quit, although this difference was not statistically significant (68% versus 52%; =0.055. Conclusions. Use of tobacco by kidney donors is associated with decreased posttransplant renal function, although smoking cessation can improve outcomes. Kidneys from donors who smoke should be used with caution.

  7. Dengue antibodies in blood donors.

    Science.gov (United States)

    Ribas-Silva, Rejane Cristina; Eid, Andressa Ahmad

    2012-01-01

    Dengue is an urban arbovirus whose etiologic agent is a virus of the genus Flavorius with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. The Campo Mourão region in Brazil is endemic for dengue fever. OBTECTIVE: The aim of this study was to evaluate the presence of IgG and IgM antibodies specific to the four serotypes of dengue in donors of the blood donor service in the city of Campo Mourão. Epidemiological records were evaluated and 4 mL of peripheral blood from 213 blood donors were collected in tubes without anticoagulant. Serum was then obtained and immunochromatographic tests were undertaken (Imuno-Rápido Dengue IgM/IgG(TM)). Individuals involved in the study answered a social and epidemiological questionnaire on data which included age, gender and diagnosis of dengue. Only three (1.4%) of the 213 blood tests were positive for IgG anti-dengue antibodies. No donors with IgM antibody, which identifies acute infection, were identified. The results of the current analysis show that the introduction of quantitative or molecular serological methods to determine the presence of anti-dengue antibodies or the detection of the dengue virus in blood donors in endemic regions should be established so that the quality of blood transfusions is guaranteed.

  8. Donor Outcomes in Living Donor Liver Transplantation-Analysis of 275 Donors From a Single Centre in India.

    Science.gov (United States)

    Narasimhan, Gomathy; Safwan, Mohamed; Kota, Venugopal; Reddy, Mettu S; Bharathan, Anand; Dabora, Abderrhaim; Kaliamoorthy, Ilankumaran; Kanagavelu, Rathnavel G; Srinivasan, Vijaya; Rela, Mohamed

    2016-06-01

    Live donor liver transplantation is the predominant form of liver transplantation in India and in most Asian countries. Donor outcome reports are an important source of information to be shared with prospective donors at the time of informed consent. This is the first donor outcome series from India. Analysis of donor characteristics and morbidity of 275 live donors from a single large volume center is documented. Two hundred seventy-five patients donated from November 2009 to October 2014, 144 were women and 131 were men, 180 donated to adults and 95 donated to children. Right lobe donors were majority at 62.2% followed by left lateral segment 28%. Two thirds of the live donors did not have any morbidity; 114 complications were encountered in 85 patients. The complications were graded as per Clavien 5 tier grading and major morbidity (grade III b, grade IV grade V) was 4.36%. Postoperative biliary complication was seen in 3 donors. This large single-center study is the first donor outcome report from India, and the results are comparable to other published donor series. Documentation and regular audit of donor outcomes is important to help improve the safety of donor hepatectomy and to provide a database for informed consent of prospective donors.

  9. Gamete donation: parents' experiences of searching for their child's donor siblings and donor.

    Science.gov (United States)

    Freeman, T; Jadva, V; Kramer, W; Golombok, S

    2009-03-01

    This study investigates the new phenomenon of parents of donor offspring searching for and contacting their child's 'donor siblings' (i.e. donor offspring conceived by the same donor) and donor. Online questionnaires were completed by 791 parents (39% lone-mother, 35% lesbian-couple, 21% heterosexual-couple, 5% non-specified) recruited via the Donor Sibling Registry; a US-based international registry that facilitates contact between donor conception families who share the same donor. Data were collected on parents' reasons for searching for their child's donor siblings and/or donor, the outcome of these searches and parents' and their child's experiences of any resulting contact. Parents' principal motivation for searching for their child's donor siblings was curiosity and for their donor, enhancing their child's sense of identity. Some parents had discovered large numbers of donor siblings (maximum = 55). Most parents reported positive experiences of contacting and meeting their child's donor siblings and donor. This study highlights that having access to information about a child's donor origins is important for some parents and has potentially positive consequences. These findings have wider implications because the removal of donor anonymity in the UK and elsewhere means that increasing numbers of donor offspring are likely to seek contact with their donor relations in the future.

  10. Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor.

    Science.gov (United States)

    Malinoski, Darren J; Daly, Michael C; Patel, Madhukar S; Oley-Graybill, Chrystal; Foster, Clarence E; Salim, Ali

    2011-10-01

    There is a national shortage of organs available for transplantation. Implementation of preset donor management goals (DMGs) to improve outcomes is recommended, but uniform practices and data are lacking. We hypothesized that meeting DMGs before organ procurement would result in more organs transplanted per donor (OTPD). The eight organ procurement organization in United Network for Organ Sharing Region 5 selected 10 critical care end points as DMGs. Each organ procurement organization submitted retrospective data from 40 standard criteria donors. "DMGs met" was defined as achieving any eight DMGs before procurement. The primary outcome was ≥4 OTPD. Binary logistic regression was used to determine independent predictors of ≥4 OTPD with a pdonors had 3.6±1.6 OTPD. Donors with DMGs met had more OTPD (4.4 vs. 3.3, p50% (OR=4.0), Pao2:FIO2>300 (OR=4.6), and serum sodium 135 to 160 mEq/L (OR=3.4). Meeting DMGs before procurement resulted in more OTPD. Donor factors and critical care end points are independent predictors of organ yield. Prospective studies are needed to determine the true impact of each DMG on the number and function of transplanted organs.

  11. Bone density in apheresis donors and whole blood donors

    NARCIS (Netherlands)

    Boot, C.L.; Luken, J.S.; van den Burg, P.J.M.; de Kort, W.L.A.M.; Koopman, M.M.W.; Vrielink, H.; van Schoor, N.M.; den Heijer, M.; Lips, P.

    2015-01-01

    Apheresis donation using citrate causes acute decrease in serum calcium and increase in serum parathyroid hormone. Long-term consequences, such as decrease in bone mineral density (BMD), are not known. In this study, we compared the BMD of 20 postmenopausal apheresis donors (mean donation number 115

  12. Suicidal hanging donors for lung transplantation

    Science.gov (United States)

    Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

    2018-01-01

    Abstract In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group. Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed. No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation. PMID:29620623

  13. Donor human milk for preterm infants

    DEFF Research Database (Denmark)

    Arslanoglu, Sertac; Corpeleijn, Willemijn; Moro, Guido

    2013-01-01

    guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research......The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge...... and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding...

  14. Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

    Directory of Open Access Journals (Sweden)

    Irene Riezzo

    2017-01-01

    Full Text Available Allogenic hematopoietic progenitor cell transplantation (allo-HSCT is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA- identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.

  15. For Donors Who Have Everything.

    Science.gov (United States)

    Shubeck, Theresa

    1990-01-01

    Most major donors don't need another plaque or formal dinner. Development officers need to be more imaginative and less materialistic in expressing their institution's thanks, personalizing them by tying the gesture in with something distinctive about the institution or the gift. Development office teamwork and care help promote donor…

  16. Being a Living Donor: Risks

    Science.gov (United States)

    ... to know FAQ Living donation What is living donation? Organs Types Being a living donor First steps Being ... are considering one of these types of living donation, please talk to your transplant center about the organ-specific risks. Psychological concerns You may also have ...

  17. Associations of health status with subsequent blood donor behavior-An alternative perspective on the Healthy Donor Effect from Donor InSight

    NARCIS (Netherlands)

    van den Hurk, Katja; Zalpuri, Saurabh; Prinsze, Femmeke J.; Merz, Eva-Maria; de Kort, Wim L. A. M.

    2017-01-01

    In donor health research, the 'Healthy Donor Effect' (HDE) often biases study results and hampers their interpretation. This refers to the fact that donors are a selected 'healthier' subset of a population due to both donor selection procedures and self-selection. Donors with long versus short donor

  18. Influence of donor-donor transport on excitation energy transfer

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, K K; Joshi, H C; Pant, T C [Kumaun University, Nainital (India). Department of Physics

    1989-01-01

    Energy migration and transfer from acriflavine to rhodamine B and malachite green in poly (methylmethacrylate) have been investigated using the decay function analysis. It is found that the influence of energy migration in energy transfer can be described quite convincingly by making use of the theories of Loring, Andersen and Fayer (LAF) and Huber. At high acceptor concentration direct donor-acceptor transfer occurs through Forster mechanism. (author). 17 refs., 5 figs.

  19. Establishment of an oocyte donor program. Donor screening and selection.

    Science.gov (United States)

    Quigley, M M; Collins, R L; Schover, L R

    1991-01-01

    IVF with donated oocytes, followed by embryo placement in the uterus of a recipient who has been primed with exogenous steroids, is a successful treatment for special cases of infertility. Preliminary results indicate that the success rate in this situation is even greater than that usually seen with normal IVF (with placement of the embryos back into the uteri of the women from whom the oocytes were recovered). Although different sources for donated oocytes have been identified, the use of "excess" oocytes from IVF cycles and the attempted collection of oocytes at the time of otherwise indicated pelvic surgery have ethical and practical problems associated with their use. We have herein described the establishment of a successful program relying on anonymous volunteers who go through ovarian stimulation, monitoring, and oocyte recovery procedures solely to donate oocytes. The potential donors go through an exhaustive screening and education process before they are accepted in the program. Psychological evaluation of our potential donors indicated a great degree of turmoil in their backgrounds and a wide variety of motivations for actually participating. Despite the extensive educational and screening process, a substantial percentage of the donors did not complete a donation cycle, having either voluntarily withdrawn or been dropped because of lack of compliance. Further investigation of the psychological aspects of participating in such a program is certainly warranted. The use of donated oocytes to alleviate specific types of infertility is quite successful, but the application of this treatment is likely to be limited by the relative unavailability of suitable oocyte donors.

  20. Live donor transplantation--the incompetent donor: comparative law.

    Science.gov (United States)

    Wolfman, Samuel; Shaked, Tali

    2008-12-01

    Informed consent of the patient to medical treatment is an essential prerequisite for any invasive medical procedure. However in emergency cases, when the patient is unable to sign a consent form due to unconsciousness or to psychotic state, than the primary medical consideration shall take place. In such a case, in order to save life or even prevent a major medical hazard to the patient, doctors are allowed, in certain cases and in accordance with well accepted medical practice, to perform invasive procedures, major surgery or risky pharmacological treatment, without the explicit consent of the patient. All the above refers to the cases when avoidance of such non-consented treatment may harm severely the health and wellbeing of the patient and there is no doubt that such treatment is for the ultimate benefit of the patient. The question, however, shall arise when such a medical procedure is not necessarily for the benefit of the patient, but rather for the benefit of somebody else. Such is the case in the transplantation area and the question of living donor-donee relationship. This paper shall analyze the legal situation in cases of non competent donors whose consent cannot be considered legal consent given in full understanding and out of free will. It will also compare three legal systems, the Israeli, the American and the traditional Jewish law, with regard to the different approaches to this human problem, where the autonomy of the donor may be sacrificed for the purpose of saving life of another person.

  1. Association of Complement C3 Gene Variants with Renal Transplant Outcome of Deceased Cardiac Dead Donor Kidneys

    NARCIS (Netherlands)

    Damman, J.; Daha, M. R.; Leuvenink, H. G.; van Goor, H.; Hillebrands, J. L.; van Dijk, M. C.; Hepkema, B. G.; Snieder, H.; van den Born, J.; de Borst, M. H.; Bakker, S. J.; Navis, G. J.; Ploeg, R. J.; Seelen, M. A.

    Local renal complement activation by the donor kidney plays an important role in the pathogenesis of renal injury inherent to kidney transplantation. Contradictory results were reported about the protective effects of the donor C3F allotype on renal allograft outcome. We investigated the influence

  2. Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors.

    Science.gov (United States)

    Cairo, Mitchell S; Rocha, Vanderson; Gluckman, Eliane; Hale, Gregory; Wagner, John

    2008-01-01

    Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.

  3. Blood donor: nursing care plan

    OpenAIRE

    Marco Antonio Zapata Sampedro; Laura Castro Varela

    2008-01-01

    The standardized nursing care plan can be used as a means through which the nurse will assess and identify the particular needs of the blood donor.To draw up the care plan, we have conducted the evaluation on the basis of the Marjory Gordon’s functional health patterns.The more prevailing diagnosis according to the NANDA taxonomy have been identified, results have been established according to the NOC (Nursing Outcomes Classification) taxonomy, and nursing interventions have been suggested ac...

  4. Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors

    Directory of Open Access Journals (Sweden)

    Ramachandra Lakshmi

    2011-08-01

    Full Text Available Abstract Background While influenza vaccination results in protective antibodies against primary infections, clearance of infection is primarily mediated through CD8+ T cells. Studying the CD8+ T cell response to influenza epitopes is crucial in understanding the disease associated morbidity and mortality especially in at risk populations such as the elderly. We compared the CD8+ T cell response to immunodominant and subdominant influenza epitopes in HLA-A2+ control, adult donors, aged 21-42, and in geriatric donors, aged 65 and older. Results We used a novel artificial Antigen Presenting Cell (aAPC based stimulation assay to reveal responses that could not be detected by enzyme-linked immunosorbent spot (ELISpot. 14 younger control donors and 12 geriatric donors were enrolled in this study. The mean number of influenza-specific subdominant epitopes per control donor detected by ELISpot was only 1.4 while the mean detected by aAPC assay was 3.3 (p = 0.0096. Using the aAPC assay, 92% of the control donors responded to at least one subdominant epitopes, while 71% of control donors responded to more than one subdominant influenza-specific response. 66% of geriatric donors lacked a subdominant influenza-specific response and 33% of geriatric donors responded to only 1 subdominant epitope. The difference in subdominant response between age groups is statistically significant (p = 0.0003. Conclusion Geriatric donors lacked the broad, multi-specific response to subdominant epitopes seen in the control donors. Thus, we conclude that aging leads to a decrease in the subdominant influenza-specific CTL responses which may contribute to the increased morbidity and mortality in older individuals.

  5. Renal Transplantation from Elderly Living Donors

    Directory of Open Access Journals (Sweden)

    Jacob A. Akoh

    2013-01-01

    Full Text Available Acceptance of elderly living kidney donors remains controversial due to the higher incidence of comorbidity and greater risk of postoperative complications. This is a review of publications in the English language between 2000 and 2013 about renal transplantation from elderly living donors to determine trends and effects of donation, and the outcomes of such transplantation. The last decade witnessed a 50% increase in living kidney donor transplants, with a disproportionate increase in donors >60 years. There is no accelerated loss of kidney function following donation, and the incidence of established renal failure (ERF and hypertension among donors is similar to that of the general population. The overall incidence of ERF in living donors is about 0.134 per 1000 years. Elderly donors require rigorous assessment and should have a predicted glomerular filtration rate of at least 37.5 mL/min/1.73 m2 at the age of 80. Though elderly donors had lower glomerular filtration rate before donation, proportionate decline after donation was similar in both young and elderly groups. The risks of delayed graft function, acute rejection, and graft failure in transplants from living donors >65 years are significantly higher than transplants from younger donors. A multicentred, long-term, and prospective database addressing the outcomes of kidneys from elderly living donors is recommended.

  6. Development of Organ-Specific Donor Risk Indices

    OpenAIRE

    Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

    2012-01-01

    Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in devel...

  7. IMPACT OF SEVOFLURANE AND ACETYLCYSTEINE ON ISCHEMIA-REPERFUSION INJURY OF THE LIVER FROM BRAIN-DEAD DONOR

    Directory of Open Access Journals (Sweden)

    A. E. Shcherba

    2013-01-01

    Full Text Available Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury. 

  8. Providing Coverage for the Unique Lifelong Health Care Needs of Living Kidney Donors Within the Framework of Financial Neutrality.

    Science.gov (United States)

    Gill, J S; Delmonico, F; Klarenbach, S; Capron, A M

    2017-05-01

    Organ donation should neither enrich donors nor impose financial burdens on them. We described the scope of health care required for all living kidney donors, reflecting contemporary understanding of long-term donor health outcomes; proposed an approach to identify donor health conditions that should be covered within the framework of financial neutrality; and proposed strategies to pay for this care. Despite the Affordable Care Act in the United States, donors continue to have inadequate coverage for important health conditions that are donation related or that may compromise postdonation kidney function. Amendment of Medicare regulations is needed to clarify that surveillance and treatment of conditions that may compromise postdonation kidney function following donor nephrectomy will be covered without expense to the donor. In other countries lacking health insurance for all residents, sufficient data exist to allow the creation of a compensation fund or donor insurance policies to ensure appropriate care. Providing coverage for donation-related sequelae as well as care to preserve postdonation kidney function ensures protection against the financial burdens of health care encountered by donors throughout their lives. Providing coverage for this care should thus be cost-effective, even without considering the health care cost savings that occur for living donor transplant recipients. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Laparoscopic nephrectomy in live donor

    Directory of Open Access Journals (Sweden)

    Mitre Anuar I.

    2004-01-01

    Full Text Available OBJECTIVE: To present the initial experience of videolaparoscopic nephrectomy in live renal donor. MATERIALS AND METHODS: In the period from April 2000 to August 2003, 50 left nephrectomies in live donor were performed by videolaparoscopy for transplantation. Twenty-eight patients were male (56% and 22 female (44%. Mean age was 37.2 years, and the mean body mass index (BMI was 27.1 kg/m². RESULTS: Mean surgical time was 179.5 minutes, and warm ischemia time of the graft was 3.79 minutes. The mean estimated bleeding was 141 mL. There was no need of blood transfusion or conversion to open surgery. In 42 cases (84%, the vascular portion of the graft was considered good by the recipient's surgical team and in all cases, the ureter was considered of proper size, though in one of them (2% its vascularization was considered improper. The transplanted kidneys produced urine still in the surgical room in 46 of the 50 transplantations considered. In only 2 cases opioid was required for analgesia. In average, 3.1 doses of dipyrone were used for each patient during hospital stay, and hospital discharge occurred, in average, after 3.2 days post-operatively. Two patients required re-operations and one of them evolved to death. CONCLUSIONS: The laparoscopic nephrectomy in live donor for renal transplantation is an alternative to conventional open surgery. In relation to the graft, no alteration, either anatomic or functional, was detected. Though there is already a large documentation in the international literature regarding this procedure, in our setting a prospective randomized study with the usual surgical study is still necessary in order to prove the advantages and disadvantages of the method.

  10. Laparoscopic nephrectomy in live donor

    Directory of Open Access Journals (Sweden)

    Anuar I. Mitre

    2004-02-01

    Full Text Available OBJECTIVE: To present the initial experience of videolaparoscopic nephrectomy in live renal donor. MATERIALS AND METHODS: In the period from April 2000 to August 2003, 50 left nephrectomies in live donor were performed by videolaparoscopy for transplantation. Twenty-eight patients were male (56% and 22 female (44%. Mean age was 37.2 years, and the mean body mass index (BMI was 27.1 kg/m². RESULTS: Mean surgical time was 179.5 minutes, and warm ischemia time of the graft was 3.79 minutes. The mean estimated bleeding was 141 mL. There was no need of blood transfusion or conversion to open surgery. In 42 cases (84%, the vascular portion of the graft was considered good by the recipient's surgical team and in all cases, the ureter was considered of proper size, though in one of them (2% its vascularization was considered improper. The transplanted kidneys produced urine still in the surgical room in 46 of the 50 transplantations considered. In only 2 cases opioid was required for analgesia. In average, 3.1 doses of dipyrone were used for each patient during hospital stay, and hospital discharge occurred, in average, after 3.2 days post-operatively. Two patients required re-operations and one of them evolved to death. CONCLUSIONS: The laparoscopic nephrectomy in live donor for renal transplantation is an alternative to conventional open surgery. In relation to the graft, no alteration, either anatomic or functional, was detected. Though there is already a large documentation in the international literature regarding this procedure, in our setting a prospective randomized study with the usual surgical study is still necessary in order to prove the advantages and disadvantages of the method.

  11. Decision making on organ donation: the dilemmas of relatives of potential brain dead donors.

    Science.gov (United States)

    de Groot, Jack; van Hoek, Maria; Hoedemaekers, Cornelia; Hoitsma, Andries; Smeets, Wim; Vernooij-Dassen, Myrra; van Leeuwen, Evert

    2015-09-17

    This article is part of a study to gain insight into the decision-making process by looking at the views of the relatives of potential brain dead donors. Alongside a literature review, focus interviews were held with healthcare professionals about their role in the request and decision-making process when post-mortal donation is at stake. This article describes the perspectives of the relatives. A content-analysis of 22 semi-structured in-depth interviews with relatives involved in an organ donation decision. Three themes were identified: 'conditions', 'ethical considerations' and 'look back'. Conditions were: 'sense of urgency', 'incompetence to decide' and 'agreement between relatives'. Ethical considerations result in a dilemma for non-donor families: aiding people or protecting the deceased's body, especially when they do not know his/her preference. Donor families respect the deceased's last will, generally confirmed in the National Donor Register. Looking back, the majority of non-donor families resolved their dilemma by justifying their decision with external arguments (lack of time, information etc.). Some non-donor families would like to be supported during decision-making. The discrepancy between general willingness to donate and the actual refusal of a donation request can be explained by multiple factors, with a cumulative effect. Firstly, half of the participants (most non-donor families) stated that they felt that they were not competent to decide in such a crisis and they seem to struggle with utilitarian considerations against their wish to protect the body. Secondly, non-donor families refused telling that they did not know the deceased's wishes or contesting posthumous autonomy of the eligible. Thirdly, the findings emphasise the importance of Donor Registration, because it seems to prevent dilemmas in decision-making, at least for donor families. Discrepancies between willingness to consent to donate and refusal at the bedside can be attributed

  12. Molecular blood grouping of donors.

    Science.gov (United States)

    St-Louis, Maryse

    2014-04-01

    For many decades, hemagglutination has been the sole means to type blood donors. Since the first blood group gene cloning in the early 1990s, knowledge on the molecular basis of most red blood cell, platelet and neutrophil antigens brought the possibility of using nucleotide-based techniques to predict phenotype. This review will summarized methodologies available to genotype blood groups from laboratory developed assays to commercially available platforms, and how proficiency assays become more present. The author will also share her vision of the transfusion medicine future. The field is presently at the crossroads, bringing new perspectives to a century old practice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Donor free radical explosive composition

    Science.gov (United States)

    Walker, Franklin E. [15 Way Points Rd., Danville, CA 94526; Wasley, Richard J. [4290 Colgate Way, Livermore, CA 94550

    1980-04-01

    An improved explosive composition is disclosed and comprises a major portion of an explosive having a detonation velocity between about 1500 and 10,000 meters per second and a minor amount of a donor additive comprising an organic compound or mixture of organic compounds capable of releasing low molecular weight free radicals or ions under mechanical or electrical shock conditions and which is not an explosive, or an inorganic compound or mixture of inorganic compounds capable of releasing low molecular weight free radicals or ions under mechanical or electrical shock conditions and selected from ammonium or alkali metal persulfates.

  14. Heme oxygenase and carbon monoxide protect from muscle dystrophy.

    Science.gov (United States)

    Chan, Mun Chun; Ziegler, Olivia; Liu, Laura; Rowe, Glenn C; Das, Saumya; Otterbein, Leo E; Arany, Zoltan

    2016-11-28

    Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children worldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high side-effect profile. New therapeutic approaches are urgently needed. Here, we leverage PGC-1α, a powerful transcriptional coactivator known to protect against dystrophy in the mdx murine model of DMD, to search for novel mechanisms of protection against dystrophy. We identify heme oxygenase-1 (HO-1) as a potential novel target for the treatment of DMD. Expression of HO-1 is blunted in the muscles from the mdx murine model of DMD, and further reduction of HO-1 by genetic haploinsufficiency worsens muscle damage in mdx mice. Conversely, induction of HO-1 pharmacologically protects against muscle damage. Mechanistically, HO-1 degrades heme into biliverdin, releasing in the process ferrous iron and carbon monoxide (CO). We show that exposure to a safe low dose of CO protects against muscle damage in mdx mice, as does pharmacological treatment with CO-releasing molecules. These data identify HO-1 and CO as novel therapeutic agents for the treatment of DMD. Safety profiles and clinical testing of inhaled CO already exist, underscoring the translational potential of these observations.

  15. Control of charge transfer by conformational and electronic effects: Donor-donor and donor-acceptor phenyl pyrroles

    International Nuclear Information System (INIS)

    Neubauer, Antje; Bendig, Juergen; Rettig, Wolfgang

    2009-01-01

    Derivatives of N-pyrrolobenzene with a para-donor and a para-acceptor substituent on the benzene ring are compared. It is shown that by a suitable increase of the donor strength of the pyrrolo group, CT fluorescence can be achieved even for donor-donor-substituted benzenes. The ICT emission for sterically hindered compounds is more forbidden than that of unhindered phenyl pyrroles. This suggests conformational effects which induce a narrower twist angle distribution around a perpendicular minimum in the excited state.

  16. Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!

    Science.gov (United States)

    Kindwall-Keller, Tamila L; Ballen, Karen K

    2017-09-01

    Hematopoietic stem cell transplant (HSCT) is potentially curative for a wide variety of malignant diseases, including acute and leukemias, lymphoma, and myelodysplasia. Choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Current sources of stem cell donation for HSCT are matched sibling donors (MSDs), matched unrelated donors (MUDs), 1-antigen mismatched unrelated donors (MMUDs), haploidentical donors (haplo), and umbilical cord blood (UCB) units. Historically, preferred donors for HSCT have been human leukocyte antigen (HLA)-matched sibling donors; however, only about 30% of U.S. patients will have a MSD available. The majority of patients referred for HSCT will require an alternative donor graft: MUD, MMUD, UCB, or haplo. The likelihood of finding a MUD varies depending on the ethnicity of the recipient. White Caucasians of European descent have the greatest chance of finding a MUD. Chances of finding a MUD are significantly less for African-American or Hispanic recipients due to HLA polymorphisms. Therefore, MMUD, UCB, and haplo donor graft sources expand the donor pool for recipients who do not have a MSD or MUD available. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic HSCT has a potential donor in 2017. All transplant-eligible patients with hematologic malignancies should be evaluated by a transplant center to determine if HSCT is a viable treatment option for their underlying disease process. The goal of this review is to increase the awareness of oncology practitioners to the availability of alternative donor stem cell transplants for patients with hematologic malignancies. Despite new agents, stem cell transplant remains the only curative therapy for many patients with acute and chronic leukemia, myelodysplasia, and lymphoma. Given the variety of different donor stem cell sources available today

  17. Economic crisis and blood donation: How are donors' motivations changing?

    Science.gov (United States)

    Alfieri, Sara; Guiddi, Paolo; Marta, Elena; Saturni, Vincenzo

    2016-06-01

    The economic crisis has exasperated people's feelings of loneliness; job instability often does not allow people to commit to voluntary work. The present work proposes to examine whether the motivations to donate blood have changed before and during the period of economic crisis, taking into consideration donors' gender. We adopted Omoto & Snyder's functionalist approach, which states that blood donation serves different functions for any one person, who may have different motivations from those held by other people. We compared six-year pre-post (t1 "pre-crisis": 2008 - t2 "during the crisis": 2014) data on a sample of blood donors in a single blood donation center situated in Northern Italy. T-test was used for data analysis. Three hundred thirty donors (age range 18-60, M = 32.6, SD = 9.53; 54.5% male) were administered a survey at t1 and 444 (age range 18-60, M = 37.8, SD = 10.16; 68% male) six years later at t2. In both surveys, participants were administered a questionnaire with socio-demographic items and a version of Omoto & Snyder's Motivations to Volunteer scale adapted to blood donation. Donors' motivation priorities did not vary over time. Values and Self-enhancement motivations are the most prevalent. Knowledge and Ego-protection motivations decreased with the upsurge of the crisis. Women, in general, report higher mean values than men do for Values and Ego-protection motivations. These results can offer valuable clues for the agencies that manage blood collection. Copyright © 2016. Published by Elsevier Ltd.

  18. Imaging evaluation of potential donors in living-donor liver transplantation

    International Nuclear Information System (INIS)

    Low, G.; Wiebe, E.; Walji, A.H.; Bigam, D.L.

    2008-01-01

    Liver transplants, originally obtained from deceased donors, can now be harvested from living donors as well. This technique, called living-donor liver transplantation (LDLT), provides an effective alternative means of liver transplantation and is a method of expanding the donor pool in light of the demand and supply imbalance for organ transplants. Imaging plays an important role in LDLT programmes by providing robust evaluation of potential donors to ensure that only anatomically suitable donors with no significant co-existing pathology are selected and that crucial information that allows detailed preoperative planning is available. Imaging evaluation helps to improve the outcome of LDLT for both donors and recipients, by improving the chances of graft survival and reducing the postoperative complication rate. In this review, we describe the history of LDLT and discuss in detail the application of imaging in donor assessment with emphasis on use of modern computed tomography (CT) and magnetic resonance imaging (MRI) techniques

  19. Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment

    Directory of Open Access Journals (Sweden)

    Brend Ray-Sea Hsu

    2017-01-01

    Full Text Available The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b mice to construct donor chimerism in conditioned diabetic BALB/c (H2d mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05 for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.

  20. Differences in social representation of blood donation between donors and non-donors: an empirical study.

    Science.gov (United States)

    Guarnaccia, Cinzia; Giannone, Francesca; Falgares, Giorgio; Caligaris, Aldo Ozino; Sales-Wuillemin, Edith

    2015-11-04

    Both donors and non-donors have a positive image of blood donation, so donors and non-donors do not differ regarding their views on donation but do differ in converting their opinion into an active deed of donation. Several studies have identified altruism and empathy as the main factors underlying blood donation. However, a mixture of various motivational factors mould the complex behaviour of donation. This paper presents an exploratory study on differences of social representations of blood donation between blood donors and non-donors, in order to understand the reasons that bring someone to take the decision to become a blood donor. Participants filled in the Adapted Self-Report Altruism Scale, Toronto Empathy Questionnaire and answered a test of verbal association. Descriptive and correlation analyses were carried out on quantitative data, while a prototypic analysis was used for qualitative data. The study was carried out on a convenience sample of 786 individuals, 583 donors (mean age: 35.40 years, SD: 13.01 years; 39.3% female) and 203 non-donors (mean age: 35.10 years, SD: 13.30 years; 67.5% female). Social representations of donors seem to be more complex and articulated than those of non-donors. The terms that appear to be central were more specific in donors (life, needle, blood, help, altruism were the words most associated by non-donors; life, aid, altruism, solidarity, health, love, gift, generosity, voluntary, control, needed, useful, needle were the words most associated by donors). Furthermore, non-donors associated a larger number of terms referring to negative aspects of blood donation. Aspects related to training and the accuracy of any information on blood donation seem to be important in the decision to become a donor and stabilise the behaviour of donation over time, thus ensuring the highest levels of quality and safety in blood establishments.

  1. Experiences of offspring searching for and contacting their donor siblings and donor.

    Science.gov (United States)

    Jadva, Vasanti; Freeman, Tabitha; Kramer, Wendy; Golombok, Susan

    2010-04-01

    This study investigates a new phenomenon whereby individuals conceived by donor insemination are searching for and contacting their donor and/or 'donor siblings' (i.e. donor offspring conceived by the same donor who are their genetic half siblings). On-line questionnaires were completed by members of the Donor Sibling Registry (DSR), a US-based registry that facilitates contact between donor conception families who share the same donor. Of the 165 donor offspring who completed the survey, 15% were searching for their donor siblings, 13% were searching for their donor, and 64% were searching for both. Differences were found according to family type and age of disclosure. Fewer offspring from heterosexual couple families had told their father about their search when compared with offspring from lesbian couple families who had told their co-parent. Offspring who had found out about their conception after age 18 were more likely to be searching for medical reasons, whereas those who had found out before age 18 tended to be searching out of curiosity. Some offspring had discovered large numbers of half siblings (maximum=13). The majority of offspring who had found their donor relations reported positive experiences and remained in regular contact with them. Copyright (c) 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  2. BLOODR: blood donor and requester mobile application.

    Science.gov (United States)

    Tatikonda, Vamsi Krishna; El-Ocla, Hosam

    2017-01-01

    With rapid increase in the usage of social networks sites across the world, there is also a steady increase in blood donation requests as being noticed in the number of posts on these sites such as Facebook and twitter seeking blood donors. Finding blood donor is a challenging issue in almost every country. There are some blood donor finder applications in the market such as Blood app by Red Cross and Blood Donor Finder application by Neologix. However, more reliable applications that meet the needs of users are prompted. Several software technologies including languages and framework are used to develop our blood-donor web application known as BLOODR application. These technologies comprise Ruby programming language (simply known as Ruby) along with JavaScript and PostgreSQL for database are used. Ruby on Rails (simply known as Rails) is an open source Web framework that makes it possible to quickly and easily create data-based web applications. We show screenshots for the BLOODR application for different types of users including requester, donor, and administrator. Various features of the application are described and their needs of use are analyzed. If a patient needs a blood at a clinic, blood donors in vicinity can be contacted through using a clinic management service provided in this application. Registered donors will get notification for the blood requests only if their blood group is compatible with the requested blood type and in the same city/region. Then matching blood donors can go to the requesting clinic and donate. BLOODR application provides a reliable platform to connect local blood donors with patients. BLOODR creates a communication channel through authenticated clinics whenever a patient needs blood donation. It is a useful tool to find compatible blood donors who can receive blood request posts in their local area. Clinics can use this web application to maintain the blood donation activity. Future improvement of the BLOODR is explained.

  3. Genetic factors influencing ferritin levels in 14,126 blood donors

    DEFF Research Database (Denmark)

    Sørensen, Erik; Rigas, Andreas S; Thørner, Lise W

    2015-01-01

    BACKGROUND: Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN...... AND METHODS: The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain...... with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION: Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron...

  4. Development of Organ-Specific Donor Risk Indices

    Science.gov (United States)

    Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

    2012-01-01

    Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in developing new kidney allocation algorithms. The Liver Donor Risk Index allows for greater appreciation of the importance of donor factors, particularly for hepatitis C-positive recipients; as the donor risk index increases, rates of allograft and patient survival among these recipients decrease disproportionately. Use of livers with high donor risk index is associated with increased hospital costs independent of recipient risk factors, and transplanting livers with high donor risk index into patients with Model for End-Stage Liver Disease scores Donor Risk Index has limited this practice. Significant regional variation in donor quality, as measured by the Liver Donor Risk Index, remains in the United States. We also review other potential indices for liver transplant, including donor-recipient matching and the retransplant donor risk index. While substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. PMID:22287036

  5. Normothermic machine perfusion for donor liver preservation

    NARCIS (Netherlands)

    Tolboom, H.

    2012-01-01

    Currently, liver transplantation is the only treatment for end-stage liver failure. Unfortunately, a sever shortage of donor organs causes significant mortality amongst patients awaiting transplantation. The donor organ shortage could be alleviated by using organs that are normally not accepted for

  6. Predictors of hemoglobin in Danish blood donors

    DEFF Research Database (Denmark)

    Kotzé, Sebastian R; Pedersen, Ole B; Petersen, Mikkel S

    2015-01-01

    BACKGROUND: It is well known that blood donors are at increased risk of iron deficiency and subsequent development of iron deficiency anemia. We aimed to investigate the effect of factors influencing hemoglobin (Hb) levels. STUDY DESIGN AND METHODS: Initiated in 2010, the Danish Blood Donor Study...

  7. True HIV seroprevalence in Indian blood donors.

    Science.gov (United States)

    Choudhury, N; Ayagiri, A; Ray, V L

    2000-03-01

    The National AIDS Control Organization (NACO), the apex body for controlling AIDS in India, projected that HIV seroprevalence would increase from 7/1000 in 1995 to 21.2/1000 in 1997. A high incidence (8.2%) of HIV was observed in blood donors. This study was carried out to find out the true HIV positivity in Indian blood donors. Blood donors from our centre were followed for more than 5 years to determine the true HIV seroprevalence and our result was compared with similar studies from India. Voluntary and relative blood donors who visited the SGPGIMS, Lucknow, since 1993 to June 1998 were included. They were screened for HIV 1/2 by ELISA kits (WHO approved). First-time HIV-positive samples were preserved frozen for further study (stage-I). They were repeated in duplicate and retested with other kits. If found positive, the sample was labelled as ELISA positive (stage-II). ELISA-positive samples were confirmed by Western Blot (WB) at stage-III. A total of 65 288 donors were included and 834 (12.8/1000) were reactive at stage-I. But 1.1/1000 donors were found to be ELISA positive at stage-II, and 0.28/1000 donors were positive by WB at stage-III. The 'seropositivity' rate from the NACO was significantly (P commercial blood banks. The HIV prevalence of blood donors (and national prevalence) is to be reassessed.

  8. Negotiating boundaries: Accessing donor gametes in India.

    Science.gov (United States)

    Widge, A; Cleland, J

    2011-01-01

    This paper documents how couples and providers access donor materials for conception in the Indian context and perceptions about using them. The objective is to facilitate understanding of critical issues and relevant concerns. A postal survey was conducted with a sample of 6000 gynaecologists and in-depth interviews were -conducted with 39 gynaecologists in four cities. Donor gametes are relatively more acceptable than a few years ago, especially if confidentiality can be -maintained, though lack of availability of donor materials is sometimes an impediment to infertility treatment. Donor sperms are usually accessed from in-house or commercial sperm banks, pathology laboratories, IVF centres, -professional donors, relatives or friends. There is scepticism about screening procedures of sperm banks. Donor eggs are usually accessed from voluntary donors, friends, relatives, egg sharing programmes, donation from other patients, advertising and commercial donors. There are several concerns regarding informed consent for using donated gametes, using -relatives and friends gametes, the unregulated use of gametes and embryos, record keeping and documentation, -unethical and corrupt practices and commercialisation. These issues need to be addressed by patients, providers and regulatory authorities by providing -information, counselling, ensuring informed consent, addressing exploitation and commercialisation, ensuring -monitoring, proper documentation and transparency.

  9. Posttransplantation Disseminated Coccidioidomycosis Acquired from Donor Lungs

    OpenAIRE

    Miller, Melissa B.; Hendren, Ryan; Gilligan, Peter H.

    2004-01-01

    A North Carolinian developed fatal coccidioidomycosis immediately after bilateral lung transplantation. The donor had previously traveled to Mexico, and the recipient had no travel history to an area where Coccidioides immitis is endemic. Immunosuppresive therapy of the transplant recipient likely reactivated latent Coccidioides infection in the donor lungs, leading to posttransplant coccidioidomycosis.

  10. Psychosocial counselling in donor sperm treatment

    NARCIS (Netherlands)

    Visser, M.

    2018-01-01

    For decades, donor sperm treatment is offered to men and women to build a family. In daily life, parents, children and donors have to deal with the consequences of this treatment. The studies of this thesis show that there are gaps in knowledge about specialist psychosocial counselling and guidance

  11. Organ donors: deceased or alive? Quo vadis?

    Science.gov (United States)

    Rozental, R

    2006-01-01

    Irrespectively of universal shortage of donor organs there is a tendency of increasing the number of transplantations from living and deceased donors. Each of these two methods has positive and negative features. The main obstacles using living donors are health hazard, necessity to solve certain donor's social and psychological problems, possibility of organ trade and moving. The main problems connected with organ retrieval from deceased donors are possible conflicts with public opinion: difficulties in interpretation of brain death, legislation, obtaining of informed consent from donor's relatives, etc. Future progress in organ transplantation may take place through activation of organ retrieval from deceased donors. The most perspective ways are change to presumed consent in all countries, establishing of centralized system of donor detection and registration, intensification of transplant coordination, active contacts with mass-media, etc. It is necessary to increase (enhance) participation of the members of the public in organ donation process, to develop solidarity among the public members and to involve public authorities to deal with this problem. Bioethical standards should be put in accordance with common progress and some ethical traditions should be changed.

  12. Potential organ donor audit in Ireland.

    LENUS (Irish Health Repository)

    Hegarty, M

    2010-11-01

    As increasing demand for organs is a challenge for transplant services worldwide it is essential to audit the process of organ donation. To address this, a national audit of potential organ donors was undertaken across hospitals with Intensive Care Units (N = 36). Questionnaires were returned on all patients (n = 2073) who died in these units from 1\\/9\\/07-31\\/8\\/08; 200 (10%) of these patients were considered for Brain Stem Testing (BST), 158 patients (79%) were diagnosed Brain Stem Dead (BSD) and 138 patients (87%) became potential donors. Consent for donation was given by 92 (69%) next of kin and 90 potential donors (65%) became organ donors. There was no evidence of a large number of potential organ donors being missed. Recommendations included completion of BSTs on all appropriate patients, development of support on BST, referral of all BSD patients to the Organ Procurement Service; enhanced co-ordination within hospitals and sustained information\\/education campaigns.

  13. PATHOMORPHOLOGY OF ZERO BIOPSIES OF DONOR KIDNEYS

    Directory of Open Access Journals (Sweden)

    M. L. Arefjev

    2011-01-01

    Full Text Available There is well known fact that kidney transplants from Extended Criteria Donors may increase risk of De- layed Graft Function and Primary Non-Function of transplants. We have collected and tested 65 «zero» kidney biopsies from cadaver donors aged from 19 to 71 years old. In the pool of elderly donors who died from cerebrovascular accident the frequency of nephrosclerosis presentation was higher than in donors of yonger age who died from craniocephalic trauma. Nevertheless in the general donor pool the number of sclerosed glomeruli was no more than 12%. We did not meet at all in the whole volume of material any bi- opsy with the severe degree of arteriosclerosis. The «zero» biopsies of cadaver kidneys is quite usable and unexpensive tool to measure the degree of nephrosclerosis in order to exclude kidneys which are not fitable for transplantation. 

  14. Glucosamine derived DISAL donors for stereoselective glycosylations under neutral conditions

    DEFF Research Database (Denmark)

    Grathe, S.; Thygesen, M.B.; Larsen, K.

    2005-01-01

    DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report the synthe......DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report...... the synthesis of new glucosamine DISAL donors, carrying N-TCP, -Troc, or -TFAc protecting groups, and their use in beta-(1,2-trans) selective glycosylations, primarily in NMP in the absence of any added Lewis acids, or in CH3NO2 with LiClO4. Finally, precise microwave heating proved effective in promoting...

  15. Donor, dad, or…? Young adults with lesbian parents' experiences with known donors.

    Science.gov (United States)

    Goldberg, Abbie E; Allen, Katherine R

    2013-06-01

    In this exploratory qualitative study of 11 young adults, ages 19-29 years, we examine how young people who were raised by lesbian parents make meaning out of and construct their relationships with known donors. In-depth interviews were conducted to examine how participants defined their family composition, how they perceived the role of their donors in their lives, and how they negotiated their relationships with their donors. Findings indicate that mothers typically chose known donors who were family friends, that the majority of participants always knew who their donors were, and that their contact with donors ranged from minimal to involved. Further, participants perceived their donors in one of three ways: as strictly donors and not members of their family; as extended family members but not as parents; and as fathers. The more limited role of donors in participants' construction of family relationships sheds light on how children raised in lesbian, gay, and bisexual families are contributing to the redefinition and reconstruction of complex kinship arrangements. Our findings hold implications for clinicians who work with lesbian-mother families, and suggest that young adulthood is an important developmental phase during which interest in and contact with the donor may shift, warranting a transfer of responsibility from mother to offspring in terms of managing the donor-child relationship. © FPI, Inc.

  16. Correlation between donor age and organs transplanted per donor: our experience in Japan.

    Science.gov (United States)

    Ashikari, J; Omiya, K; Konaka, S; Nomoto, K

    2014-05-01

    The shortage of available organs for transplantation is a worldwide issue. To maximize the number of transplantations, increasing the number of organs transplanted per donor (OTPD) is widely recognized as an important factor for improving the shortage. In Japan, we have had 211 donors, 1112 organs transplanted, and 924 recipients receiving the transplants, resulting in 4.4 ± 1.4 recipients receiving transplants per donor and 5.3 ± 1.6 OTPD as of February 2013. Because donor age is a well-recognized factor of donor suitability, we analyzed the correlation between donor age group and OTPD. Only the age group 60 to 69 years and the age group 70 to 79 years were significantly different (P donor under age 70 years has the potential to donate 4.6 to 6.7 organs. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Adult-to-Adult Living Donor Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Shimul A Shah

    2006-01-01

    Full Text Available The present review outlines the principles of living donor liver transplantation, donor workup, procedure and outcomes. Living donation offers a solution to the growing gap between the need for liver transplants and the limited availability of deceased donor organs. With a multidisciplinary team focused on donor safety and experienced surgeons capable of performing complex resection/reconstruction procedures, donor morbidity is low and recipient outcomes are comparable with results of deceased donor transplantation.

  18. The impact of disclosure on donor gamete participants: donors, intended parents and offspring.

    Science.gov (United States)

    Greenfeld, Dorothy A

    2008-06-01

    The present review examines recent publications that provide insight into how the trend toward nonanonymity and disclosure in gamete donation impacts donors, intended parents, and their donor-conceived children. Recent findings show an increase in donor programs that offer open-identity between donors and offspring. The psychological needs of gamete donors and their attitudes toward disclosure are increasingly given consideration. Qualitative research on how parents of donor gamete offspring make decisions about disclosure reveals that even when couples initially disagree about disclosing to offspring, most ultimately come to a united disclosure decision. The literature on the impact of disclosure on donor gamete offspring has extended to include children conceived through embryo donation and children born as a result of surrogacy. The absence of genetic or gestational link between parents and their child does not have a negative impact on parent-child relationships. Parents through surrogacy tend to disclose the method of family creation to their child, whereas parents through embryo donation tend to be secretive about their child's origins. The trend toward greater openness in gamete donation has been accompanied by an increase in programs offering open-identity donation. In addition, the psychological needs of gamete donors and their attitudes toward disclosure are increasingly being given consideration. Parents of donor gamete offspring give careful thought to their disclosure decisions, and the psychological well being of donor-conceived children does not seem to be impacted by those decisions.

  19. Inter- and Intrapersonal Barriers to Living Donor Kidney Transplant among Black Recipients and Donors.

    Science.gov (United States)

    Davis, LaShara A; Grogan, Tracy M; Cox, Joy; Weng, Francis L

    2017-08-01

    End-stage renal disease (ESRD) is more common among Blacks, but Blacks are less likely to receive a live donor kidney transplant (LDKT). The objective of this study is to identify barriers and coping mechanisms that Black LDKT recipients and donors experienced while receiving or donating a kidney. A qualitative study was conducted using structured interviews. Thematic analysis was used for data interpretation. All 20 participants identified as Black, with two participants identifying themselves as multiracial. The mean age for the 14 recipients was 60, and the average age for the 6 living donors was 47. Themes emerging from the data suggest both recipients and donors faced barriers in the LDKT experience. Recipients faced barriers associated with their denial and avoidance of the severity of their ESRD, their desire to maintain the privacy of their health status, and their refusal to approach potential donors. Donors encountered negative responses from others about the donors' desire to donate and the initial refusal of recipients to accept a LDKT offer. Recipients identified faith as a coping mechanism, while donors identified normalization of donation as their method of coping. Various types of social support helped donors and recipients navigate the transplant process. Black LDKT recipients and donors must overcome barriers prior to receiving or donating a kidney. Most of these barriers arise from communication and interactions with others that are either lacking or undesirable. Future interventions to promote LDKT among Blacks may benefit by specifically targeting these barriers.

  20. Donor Retention in Online Crowdfunding Communities: A Case Study of DonorsChoose.org.

    Science.gov (United States)

    Althoff, Tim; Leskovec, Jure

    2015-05-01

    Online crowdfunding platforms like DonorsChoose.org and Kick-starter allow specific projects to get funded by targeted contributions from a large number of people. Critical for the success of crowdfunding communities is recruitment and continued engagement of donors. With donor attrition rates above 70%, a significant challenge for online crowdfunding platforms as well as traditional offline non-profit organizations is the problem of donor retention. We present a large-scale study of millions of donors and donations on DonorsChoose.org, a crowdfunding platform for education projects. Studying an online crowdfunding platform allows for an unprecedented detailed view of how people direct their donations. We explore various factors impacting donor retention which allows us to identify different groups of donors and quantify their propensity to return for subsequent donations. We find that donors are more likely to return if they had a positive interaction with the receiver of the donation. We also show that this includes appropriate and timely recognition of their support as well as detailed communication of their impact. Finally, we discuss how our findings could inform steps to improve donor retention in crowdfunding communities and non-profit organizations.

  1. Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

    Science.gov (United States)

    Taniguchi, K; Yoshihara, S; Maruya, E; Ikegame, K; Kaida, K; Hayashi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Onuma, T; Fujii, N; Kusunoki, Y; Soma, T; Saji, H; Ogawa, H

    2012-10-01

    Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

  2. Responses to recipient and donor B cells by genetically donor T cells from human haploidentical chimeras

    International Nuclear Information System (INIS)

    Schiff, S.; Sampson, H.; Buckley, R.

    1986-01-01

    Following administration of haploidentical stem cells to infants with severe combined immunodeficiency (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-versus-host disease. To investigate the effect of the host environment on the responsiveness of these genetically donor T cells, blood B and T lymphocytes from 6 SCID recipients, their parental donors and unrelated controls were purified by double SRBC rosetting. T cells were stimulated by irradiated B cells at a 1:1 ratio in 6 day cultures. Engrafted T cells of donor karyotype gave much smaller responses to irradiated genetically recipient B cells than did fresh donor T cells. Moreover, engrafted T cells of donor karyotype from two of the three SCIDs who are longest post-transplantation responded more vigorously (14,685 and 31,623 cpm) than fresh donor T cells (5141 and 22,709 cpm) to donor B cells. These data indicate that T lymphocytes which have matured from donor stem cells in the recipient microenvironment behave differently from those that have matured in the donor

  3. Being a haematopoietic stem cell donor for a sick sibling: Adult donors' experiences prior to donation.

    Science.gov (United States)

    Kisch, Annika; Bolmsjö, Ingrid; Lenhoff, Stig; Bengtsson, Mariette

    2015-10-01

    There is a lack of knowledge about sibling stem cell donors' experiences pre-donation and the waiting period before the donation might have been long. The donors and their corresponding sibling recipients were simultaneously included in two different interview studies. The results from the recipient study have been presented in a separate paper. The aim was to explore the experiences of being a stem cell donor for a sibling, prior to donation. Ten adult sibling donors were interviewed prior to stem cell donation. The interviews were digitally recorded, transcribed verbatim and subjected to qualitative content analysis. The main theme Being a cog in a big wheel describes the complex process of being a sibling donor prior to donation, covering a mixture of emotions and thoughts. The four subthemes Being available, Being anxious, Being concerned and Being obliged cover the various experiences. The sibling donors' experiences are influenced by the quality of the relationship with the sick sibling. Sibling stem cell donors go through a complex process once they have accidentally got involved in. They have been asked to become a donor; it was not a voluntary choice. In caring for sibling stem cell donors the nurses should be aware of the complexity of the process they experience and take into consideration their personal situation and needs. Providing optimal care for both sibling donors and their corresponding recipients is a challenge, and further improvement and exploration are needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Shallow hydrogen-related donors in silicon

    International Nuclear Information System (INIS)

    Hartung, J.; Weber, J.

    1993-01-01

    Photothermal ionization spectroscopy on neutron-irradiated and subsequently hydrogen-plasma-treated silicon reveals the existence of new shallow donors. The binding energies of the observed effective-mass-like donors are between 34 and 53 meV. The optical dipole transitions of the different donors are shifted towards higher energies by ΔE=0.1--0.2 cm -1 , when deuterium is used in the plasma instead of hydrogen. This isotope shift of the optical dipole transitions between the electronic levels of the defects is direct proof of the incorporation of hydrogen in these defects

  5. Donor policy rules and aid effectiveness

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars

    2008-01-01

    The present paper examines the macroeconomic impact of aid, by introducing endogenous aid allocations into a neoclassical growth framework. On this basis it is shown that donor policies can have important implications for the trajectory of recipients' GDP per capita. Depending on specific donor...... policy choices, aid disbursements may lead to faster transitional growth, stagnation or cyclical growth. Moreover, the analysis also suggests that donor policies may be part of the reason why foreign aid is not found to be uniformly effective in raising long-run productivity across recipients...

  6. Kidney for sale by live donor.

    Science.gov (United States)

    Brahams, D

    1989-02-04

    The capacity to consent to bodily harm is explored in relation to the trade in kidneys obtained from impoverished healthy live donors for cash. The British medical profession has unambiguously condemned the practice, but the law in Britain allows a donor to consent to serious injury where the act had some social purpose, recognized by the law as valid. Allegations against the private Humana Hospital Wellington that indigent Turks were brought to Britain to be paid kidney donors, and similar practices elsewhere, are discussed. Questions are raised about the illegality of such contracts in Britain and the possibility of a Parliamentary Act making brokerage and involvement with such cash transactions a criminal offense.

  7. Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

    Directory of Open Access Journals (Sweden)

    Christopher A Smith

    Full Text Available To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC. BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1 concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

  8. Informed consent in research to improve the number and quality of deceased donor organs.

    Science.gov (United States)

    Rey, Michael M; Ware, Lorraine B; Matthay, Michael A; Bernard, Gordon R; McGuire, Amy L; Caplan, Arthur L; Halpern, Scott D

    2011-02-01

    Improving the management of potential organ donors in the intensive care unit could meet an important public health goal by increasing the number and quality of transplantable organs. However, randomized clinical trials are needed to quantify the extent to which specific interventions might enhance organ recovery and outcomes among transplant recipients. Among several barriers to conducting such studies are the absence of guidelines for obtaining informed consent for such studies and the fact that deceased organ donors are not covered by extant federal regulations governing oversight of research with human subjects. This article explores the underexamined ethical issues that arise in the context of donor management studies and provides ethical guidelines and suggested regulatory oversight mechanisms to enable such studies to be conducted ethically. We conclude that both the respect that is traditionally accorded to the prior wishes of the dead and the possibility of postmortem harm support a role for surrogate consent of donors in such randomized controlled trials. Furthermore, although recipients will often be considered human subjects under federal regulations, several ethical arguments support waiving requirements for recipient consent in donor management randomized controlled trials. Finally, we suggest that new regulatory mechanisms, perhaps linked to existing regional and national organ donation and transplantation infrastructures, must be established to protect patients in donor management studies while limiting unnecessary barriers to the conduct of this important research.

  9. Cost and Cost-Effectiveness of Donor Human Milk to Prevent Necrotizing Enterocolitis: Systematic Review.

    Science.gov (United States)

    Buckle, Abigail; Taylor, Celia

    2017-11-01

    Necrotizing enterocolitis (NEC) is a costly gastrointestinal disorder that mainly affects preterm and low-birth-weight infants and can lead to considerable morbidity and mortality. Mother's own milk is protective against NEC but is not always available. In such cases, donor human milk has also been shown to be protective (although to a lesser extent) compared with formula milk, but it is more expensive. This systematic review aimed at evaluating the cost of donor milk, the cost of treating NEC, and the cost-effectiveness of exclusive donor milk versus formula milk feeding to reduce the short-term health and treatment costs of NEC. We systematically searched five relevant databases to find studies with verifiable costs or charges of donor milk and/or treatment of NEC and any economic evaluations comparing exclusive donor milk with exclusive formula milk feeding. All search results were double screened. Seven studies with verifiable donor milk costs and 17 with verifiable NEC treatment costs were included. The types of cost or charge included varied considerably across studies, so quantitative synthesis was not attempted. Estimates of the incremental length of stay associated with NEC were ∼18 days for medical NEC and 50 days for surgical NEC. Two studies claimed to report economic evaluations but did not do so in practice. It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC. Future studies should provide more details on cost components included and a full economic evaluation, including long-term outcomes, should be undertaken.

  10. Laparoscopic donor nephrectomy increases the supply of living donor kidneys: a center-specific microeconomic analysis.

    Science.gov (United States)

    Kuo, P C; Johnson, L B

    2000-05-27

    A tenet of microeconomics is that new technology will shift the supply curve to the right. Laparoscopic donor nephrectomy (LDN) is a new technique for removal of living donor kidneys. Centers performing this procedure have noted an increased number of patients presenting for donor evaluation. This has not been previously studied. The records of all LDN performed from May 1998 to February 1999 were reviewed. The following variables were examined: sex, age, related vs. unrelated donation, estimated blood loss, i.v. analgesia, length of stay, and time out of work. Donors undergoing traditional open donor nephrectomy during January 1997 to May 1998 served as the control group. A composite cost index was constructed. LDN significantly decreased length of stay, pain, and time out of work; the supply function shifted to the right. Telephone interviews revealed that 47% donated solely because of the LDN procedure. LDN increases the supply of living donor kidneys.

  11. Donor-Derived Myeloid Sarcoma in Two Kidney Transplant Recipients from a Single Donor

    Directory of Open Access Journals (Sweden)

    Amudha Palanisamy

    2015-01-01

    Full Text Available We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

  12. A simplified donor risk index for predicting outcome after deceased donor kidney transplantation.

    Science.gov (United States)

    Watson, Christopher J E; Johnson, Rachel J; Birch, Rhiannon; Collett, Dave; Bradley, J Andrew

    2012-02-15

    We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, Pinformed consent.

  13. RESULTS OF THE SPECIAL BLOOD DONOR DAY

    CERN Document Server

    SC Unit

    2008-01-01

    Responding to the HUG (Hôpitaux Universitaires de Genève) hospitals’ urgent appeal for blood donations during this summer season, the CERN medical staff organised a day of blood donations for the Swiss bloodbank CTS on 30 July. They were supported by NOVAE (Restaurant No. 1), who provided donors with a free snack. This specially arranged campaign was a success, as the 135 volunteers included 66 first-time donors, and a total of 99 standard bags of blood was collected. (Swiss hospitals need 1300 bags every day!) The CTS and CERN’s medical staff want to thank the donors and all others who helped make the event a success. Upcoming blood donor days at CERN: 12 November 2008 and 10 March 2009.

  14. RESULTS OF THE SPECIAL BLOOD DONOR DAY

    CERN Document Server

    SC Unit

    2008-01-01

    Responding to the HUG (Hôpitaux Universitaires de Genève) hospitals’ urgent appeal for blood donations during this summer season, the CERN medical staff organised a day of blood donations for the Swiss bloodbank CTS on 30 July. They were supported by NOVAE (Restaurant No. 1), who provided donors with a free snack. This specially arranged campaign was a success, as the 135 volunteers included 66 first-time donors, and a total of 99 standard bags of blood were collected. (Swiss hospitals need 1300 bags every day!) The CTS and CERN’s medical staff wish to thank the donors and all others who helped make the event a success. Upcoming blood donor days at CERN: 12 November 2008 and 10 March 2009.

  15. FORUM Paediatric living donor liver transplantation

    African Journals Online (AJOL)

    879 November 2012, Vol. 102, No. 11 SAMJ. REVIEW. Paediatric living donor liver transplantation ... been excellent after left lateral segmentectomy, with a usually quoted ... has led to the development of new surgical techniques to increase.

  16. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    International Nuclear Information System (INIS)

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-01-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells

  17. [Psychological specificities of living donor kidney transplantation].

    Science.gov (United States)

    Papeloux-Heitzmann, Élodie

    2016-12-01

    For people with end-stage kidney disease, a transplant is the promise of a future without dialysis. Living donor kidney transplantation comprises many specificities and is distinct from cadaveric donor transplantation. Some psychological aspects explain these specificities. They may be subconscious and difficult to access, but it is essential to decipher them in order to adapt the support provided to these people. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Promoting Organ Donor Registries Through Public Education: What Is the Cost of Securing Organ Donors?

    Science.gov (United States)

    Razdan, Manik; Smith, Kenneth J; Bryce, Cindy L; Degenholtz, Howard B

    2016-06-01

    Transplant medicine's impact on America's public health is seriously limited by acute shortage of transplantable organs. Consequently, the United Sates has witnessed considerable investment in the promotion of organ donor registries. Although there is no evidence to support that donor registry promotion alleviates organ shortage, this belief continues to drive investments into registry promotion. In this study, return on investment in donor registry promotion was examined using cost-outcomes analysis. Cost of promoting the donor registry was estimated in US dollars whereas the outcome was measured as the number of individuals who join the registry (registrants) and their value in terms of organ donors. The study was conducted from the perspective of a regional Organ Procurement Organization (OPO). Costs were directly obtained from the OPO. The number of new registrants was obtained from the OPO and the departments of motor vehicles that maintain the donor registry. The value of registrants in terms of organ donors was computed based on a registrant's age-dependent risk of dying and age-dependent probability of becoming an organ donor. Six thousand seven hundred eight individuals joined the organ donor registry (95% confidence interval [95% CI], 5429-7956) at a cost of $455 per registrant (95% CI, US $383-US $562). These individuals result in 4.2 present-day donors (95% CI, 2.5-6.6) at a cost of US $726 000 (95% CI, US $462000-US $1.2 million). Because the cost per registrant and cost per donor is less than society's willingness to pay, donor registry promotion offers positive return on investment. Investment in registry promotion should at the minimum be maintained at current levels.

  19. Determination of Eligibility in Related Pediatric Hematopoietic Cell Donors: Ethical and Clinical Considerations. Recommendations from a Working Group of the Worldwide Network for Blood and Marrow Transplantation Association.

    Science.gov (United States)

    Bitan, Menachem; van Walraven, Suzanna M; Worel, Nina; Ball, Lynne M; Styczynski, Jan; Torrabadella, Marta; Witt, Volker; Shaw, Bronwen E; Seber, Adriana; Yabe, Hiromasa; Greinix, Hildegard T; Peters, Christina; Gluckman, Eliane; Rocha, Vanderson; Halter, Joerg; Pulsipher, Michael A

    2016-01-01

    Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Secrets and disclosure in donor conception.

    Science.gov (United States)

    Frith, Lucy; Blyth, Eric; Crawshaw, Marilyn; van den Akker, Olga

    2018-01-01

    This article considers the disclosure, sharing and exchange of information on being donor conceived within families, drawing on data from a study undertaken with donor-conceived adults registered with UK Donor Link (a voluntary DNA-linking register). This paper considers the narratives of how respondents found out they were donor-conceived and what events triggered disclosure of this information. This paper then goes on to examine the role secrecy played in their family life and uses the concept of 'display' to explore how secrecy affected their relationships with their immediate and extended family. Secrets are notoriously 'leaky' and we found complex patterns of knowing and uncertainty about whom in the family knew that the person was donor-conceived. We argue that what is kept secret and from whom provides insights into the multifaceted web of social relationships that can be created by donor-conception, and how knowledge can be managed and controlled in attempts to display and maintain family narratives of biogenetic connection. © 2017 Foundation for the Sociology of Health & Illness.

  1. Influence of kinship on donors' mental burden in living donor liver transplantation.

    Science.gov (United States)

    Erim, Yesim; Beckmann, Mingo; Kroencke, Sylvia; Sotiropoulos, Georgios C; Paul, Andreas; Senf, Wolfgang; Schulz, Karl-Heinz

    2012-08-01

    In the context of living donor liver transplantation (LDLT), German transplantation law stipulates that donor candidates should primarily be relatives of the recipients or persons with distinct and close relationships. In this study, we investigated the influence of the relationship between the donor and the recipient on the donor's emotional strain before transplantation. Donors were categorized according to the following subgroups: (1) parents donating for their children, (2) children donating for their parents, (3) siblings, (4) spouses, (5) other relatives, and (6) nonrelatives. The sample consisted of 168 donor candidates. Anxiety (F = 2.8, P = 0.02), depression (F = 2.6, P = 0.03), and emotional quality of life (F = 3.1, P = 0.01) differed significantly according to the relationship between the donor and the recipient. In comparison with healthy controls, parents donating for their children were significantly less stressed before LDLT and demonstrated fewer anxiety (P depression symptoms (P < 0.05). Adult children donating for their parents demonstrated the highest mental burden and the lowest emotional quality of life. However, this was not due to the responsibility of these children for their own families because differences between donors with children and donors without children could not be ascertained. This group should be given special attention before LDLT and during follow-up visits, and psychological help should be provided when it is necessary. Copyright © 2012 American Association for the Study of Liver Diseases.

  2. Prevalence of malaria parasitaemia among blood donors in Owerri ...

    African Journals Online (AJOL)

    A study of the prevalence of malaria parasitaemia among blood donors in the Federal Medical Centre, Owerri, Imo State, was carried out between December, 2003 and April, 2004. A total of 500 blood samples were collected from blood donors consisting of 262 commercial donors and 238 relation-donors, using ...

  3. Parvovirus B19 viraemia in Dutch blood donors

    NARCIS (Netherlands)

    Zaaijer, H. L.; Koppelman, M. H. G. M.; Farrington, C. P.

    2004-01-01

    Blood, donated by asymptomatic donors, may contain and transmit parvovirus B19. To investigate the dynamics of parvovirus viraemia in asymptomatic blood donors, we studied the amounts of parvovirus DNA in pools of donor plasma, the prevalence of parvovirus antibodies among blood donors in relation

  4. Adult-to-adult living donor liver transplantation

    OpenAIRE

    Shah, Shimul A; Levy, Gary A; Adcock, Lesley D; Gallagher, Gary; Grant, David R

    2006-01-01

    The present review outlines the principles of living donor liver transplantation, donor workup, procedure and outcomes. Living donation offers a solution to the growing gap between the need for liver transplants and the limited availability of deceased donor organs. With a multidisciplinary team focused on donor safety and experienced surgeons capable of performing complex resection/reconstruction procedures, donor morbidity is low and recipient outcomes are comparable with results of decease...

  5. Gamete donors' reasons for, and expectations and experiences of, registration with a voluntary donor linking register.

    Science.gov (United States)

    Blyth, Eric; Crawshaw, Marilyn; Frith, Lucy; van den Akker, Olga

    2017-12-01

    This paper reports on a study of the views and experiences of 21 sperm donors and five egg donors registered with UK DonorLink (UKDL), a voluntary DNA-based contact register established to facilitate contact between adults who wish to identify and locate others to whom they are genetically related following donor conception. Specifically, the paper examines donors' reasons for searching for, or making information about themselves available to donor-conceived offspring. Their expectations of registration with UKDL, experiences of being registered and finally, the experiences of those who had contacted donor-conceived offspring and other genetic relatives are investigated. While most respondents reported largely positive experiences of registration, the study found significant issues relating to concerns about donation, DNA testing, possible linking with offspring and expectations of any relationship that might be established with offspring that have implications for support, mediation and counselling. Research that puts the experiences, perceptions and interests of gamete donors as the central focus of study is a relatively recent phenomenon. This study contributes to this debate and highlights directions for future research in this area.

  6. Oocyte cryopreservation for donor egg banking.

    Science.gov (United States)

    Cobo, Ana; Remohí, José; Chang, Ching-Chien; Nagy, Zsolt Peter

    2011-09-01

    Oocyte donation is an efficient alternative to using own oocytes in IVF treatment for different indications. Unfortunately, 'traditional' (fresh) egg donations are challenged with inefficiency, difficulties of synchronization, very long waiting periods and lack of quarantine measures. Given the recent improvements in the efficiency of oocyte cryopreservation, it is reasonable to examine if egg donation through oocyte cryopreservation has merits. The objective of the current manuscript is to review existing literature on this topic and to report on the most recent outcomes from two established donor cryobank centres. Reports on egg donation using slow freezing are scarce and though results are encouraging, outcomes are not yet comparable to a fresh egg donation treatment. Vitrification on the other hand appears to provide high survival rates (90%) of donor oocytes and comparable fertilization, embryo development, implantation and pregnancy rates to traditional (fresh) egg donation. Besides the excellent outcomes, the ease of use for both donors and recipients, higher efficiency, lower cost and avoiding the problem of synchronization are all features associated with the benefit of a donor egg cryobank and makes it likely that this approach becomes the future standard of care. Oocyte donation is one of the last resorts in IVF treatment for couples challenged with infertility problems. However, traditional (fresh) egg donation, as it is performed today, is not very efficient, as typically all eggs from one donor are given to only one recipient, it is arduous as it requires an excellent synchronization between the donor and recipient and there are months or years of waiting time. Because of the development of an efficient oocyte cryopreservation technique, it is now possible to cryo-store donor (as well as non-donor) eggs, maintaining their viability and allowing their use whenever there is demand. Therefore, creating a donor oocyte cryobank would carry many advantages

  7. Development of organ-specific donor risk indices.

    Science.gov (United States)

    Akkina, Sanjeev K; Asrani, Sumeet K; Peng, Yi; Stock, Peter; Kim, W Ray; Israni, Ajay K

    2012-04-01

    Because of the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival with various combinations of donor and recipient characteristics. Here we review the kidney donor risk index (KDRI) and the liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The KDRI has a potential role in developing new kidney allocation algorithms. The LDRI allows a greater appreciation of the importance of donor factors, particularly for hepatitis C virus-positive recipients; as the donor risk index increases, the rates of allograft and patient survival among these recipients decrease disproportionately. The use of livers with high donor risk indices is associated with increased hospital costs that are independent of recipient risk factors, and the transplantation of livers with high donor risk indices into patients with Model for End-Stage Liver Disease scores indices for liver transplantation, including donor-recipient matching and the retransplant donor risk index. Although substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. Copyright © 2012 American Association for the Study of Liver Diseases.

  8. Are live kidney donors at risk

    International Nuclear Information System (INIS)

    Kamran, T.; Zaheer, K.; Hussain, S.W.; Zahid, K.H.; Akhtar, M.S.

    2003-01-01

    Objective: To share experience of live donor nephrectomy (including intraoperative variables, morbidity and ethical aspects) and to give an overview of surgical technique being practiced. Results: Majority of the donors (58.5%) were 31-50 years old and 70.6% were first-degree relatives. Left sided kidney was taken in 96.5% cases. Mean operative time was 145 minutes. Mean renal warm ischemia time from cross clamping of renal vessels to cold perfusion on the bench was 1.5 minutes per operation. Operative complications encountered were injury to lumbar veins in 5.1 % cases, slipping of satinsky clamp on vena cava stump in 1.7 % and accidental pleural damage in 5.1 % cases. Postoperative morbid complications found were urinary retention in 6.4 % cases, epididymo-orchitis in 1.7 %, prolonged lymph drain in 3.4 %, stitch infection in 1.7 % and prolonged wound discomfort in 5.1 % patients. Conclusions: Open live donor nepherectomy appears to be safe procedure for harvesting kidney. Related or emotionally related donors must be the choice in all cases. Non-related donors may be entertained in selected cases despite the probability of organ vending in our society. (author)

  9. Breast milk donation: women's donor experience.

    Science.gov (United States)

    Alencar, Lucienne Christine Estevez de; Seidl, Eliane Maria Fleury

    2009-02-01

    To describe the characteristics of donation behavior and identify reasons, beliefs and feelings relative to this practice, based on the reports of donor women. Personal and social-environmental aspects, which seem to affect donation behavior in donors and former donors, were also investigated. An exploratory, descriptive and cross-sectional study was carried out with women donors at two breast-milk banks within the public health system of the Brazilian Federal District. Data was collected from July to September 2005. The participants were 36 women, aged 14 to 33 years (average=24.78; SD=5.22), with different levels of schooling, 58.3% of which were first-time mothers. Data gathering was based on interviews carried out during home visits. In addition to descriptive statistical analyses of quantitative data, a qualitative data categorical analysis was also performed. The most frequently reported reasons for donating breast milk were altruism and excess milk production. The most frequent time interval for donation was 13 days after delivery. Contact by phone with the milk bank was the most common means of communication used by the majority of participants (n=22) to obtain information that enabled the donating process. Psychosocial aspects identified and the experience of donors can contribute to the empowerment of the formal and informal social donation-support network, in addition to serving as a driver for the implementation of technical and policy strategies in promoting future donation practices.

  10. Donor insemination: eugenic and feminist implications.

    Science.gov (United States)

    Hanson, F A

    2001-09-01

    One concern regarding developments in genetics is that, when techniques such as genetic engineering become safe and affordable, people will use them for positive eugenics: to "improve" their offspring by enpowering them with exceptional qualities. Another is whether new reproductive technologies are being used to improve the condition of women or as the tools of a patriarchal system that appropriates female functions to itself and exploits women to further its own ends. Donor insemination is relevant to both of these issues. The degree to which people have used donor insemination in the past for positive eugenic purposes may give some insight into the likelihood of developing technologies being so used in the future. Donor insemination provides women with the opportunity to reproduce with only the most remote involvement of a man. To what degree do women take advantage of this to liberate themselves from male dominance? Through questionnaires and interviews, women who have used donor insemination disclosed their criteria for selecting sperm donors. The results are analyzed for the prevalence of positive eugenic criteria in the selection process and women's attitudes toward minimizing the male role in reproduction.

  11. Ex-vivo partial nephrectomy after living donor nephrectomy: Surgical technique for expanding kidney donor pool

    Directory of Open Access Journals (Sweden)

    Yaw A Nyame

    2017-01-01

    Full Text Available Renal transplantation has profound improvements in mortality, morbidity, and overall quality of life compared to renal replacement therapy. This report aims to illustrate the use of ex-vivo partial nephrectomy in a patient with a renal angiomyolipoma prior to living donor transplantation. The surgical outcomes of the donor nephrectomy and recipient transplantation are reported with 2 years of follow-up. Both the donor and recipient are healthy and without any significant comorbidities. In conclusion, urologic techniques such as partial nephrectomy can be used to expand the living donor pool in carefully selected and well informed transplant recipients. Our experience demonstrated a safe and positive outcome for both the recipient and donor, and is consistent with other reported outcomes in the literature.

  12. Energy status of pig donor organs after ischemia is independent of donor type.

    Science.gov (United States)

    Stadlbauer, Vanessa; Stiegler, Philipp; Taeubl, Philipp; Sereinigg, Michael; Puntschart, Andreas; Bradatsch, Andrea; Curcic, Pero; Seifert-Held, Thomas; Zmugg, Gerda; Stojakovic, Tatjana; Leopold, Barbara; Blattl, Daniela; Horki, Vera; Mayrhauser, Ursula; Wiederstein-Grasser, Iris; Leber, Bettina; Jürgens, Günther; Tscheliessnigg, Karlheinz; Hallström, Seth

    2013-04-01

    Literature is controversial whether organs from living donors have a better graft function than brain dead (BD) and non-heart-beating donor organs. Success of transplantation has been correlated with high-energy phosphate (HEP) contents of the graft. HEP contents in heart, liver, kidney, and pancreas from living, BD, and donation after cardiac death in a pig model (n=6 per donor type) were evaluated systematically. BD was induced under general anesthesia by inflating a balloon in the epidural space. Ten hours after confirmation, organs were retrieved. Cardiac arrest was induced by 9V direct current. After 10min of ventricular fibrillation without cardiac output, mechanical and medical reanimation was performed for 30min before organ retrieval. In living donors, organs were explanted immediately. Freeze-clamped biopsies were taken before perfusion with Celsior solution (heart) or University of Wisconsin solution (abdominal organs) in BD and living donors or with Histidine-Tryptophan-Ketoglutaric solution (all organs) in non-heart-beating donors, after perfusion, and after cold ischemia (4h for heart, 6h for liver and pancreas, and 12h for kidney). HEPs (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and phosphocreatine), xanthine, and hypoxanthine were measured by high-performance liquid chromatography. Energy charge and adenosine triphosphate-to-adenosine diphosphate ratio were calculated. After ischemia, organs from different donor types showed no difference in energy status. In all organs, a decrease of HEP and an increase in hypoxanthine contents were observed during perfusion and ischemia, irrespective of the donor type. Organs from BD or non-heart-beating donors do not differ from living donor organs in their energy status after average tolerable ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. The effect of whole-blood donor adverse events on blood donor return rates.

    Science.gov (United States)

    Newman, Bruce H; Newman, Daniel T; Ahmad, Raffat; Roth, Arthur J

    2006-08-01

    Some blood donation-related adverse events (AEs) can negatively impact the blood donor return rate (BDRR) and decrease donor retention. One-thousand randomly selected whole-blood donors were interviewed 3 weeks after a 525-mL index whole-blood donation for seven AEs. The number of return visits and duration of follow-up were recorded for each of the 1000 donors. A negative binomial regression analysis was used to determine the contribution of the four most common AEs to the BDRR, and interactions between these AEs were also evaluated. The four most common AEs were bruise alone (15.1%), sore arm "alone" (7.0%), fatigue "alone" (5.1%), and donor reaction "alone" (4.2%), where "alone" is defined to also include donors who had a bruise but no other AE. The estimated BDRR for donations without AEs was 1.32 visits per year. The estimated BDRRs for the four most common AEs were: bruise alone, 1.32 visits per year; sore arm alone, 1.30 visits per year (2% reduction in BDRR); fatigue alone, 1.06 visits per year (20% reduction in BDRR); and donor reaction alone, 0.87 visits per year (34% reduction in BDRR). The BDRR for donor reaction, fatigue, and sore arm together was 0.20 visits per year (85% reduction in BDRR). Donor reaction had the most negative impact on the BDRR. There appears to be a synergistic effect between donor reaction, fatigue, and sore arm. Theoretically, amelioration of some AEs has the potential to improve BDRRs.

  14. The Psychosocial and Independent Living Donor Advocate Evaluation and Post-surgery Care of Living Donors.

    Science.gov (United States)

    Rudow, Dianne LaPointe; Swartz, Kathleen; Phillips, Chelsea; Hollenberger, Jennifer; Smith, Taylor; Steel, Jennifer L

    2015-09-01

    Solid organ transplantation as a treatment for end stage organ failure has been an accepted treatment option for decades. Despite advances in medicine and technology, and increased awareness of organ donation and transplantation, the gap between supply and demand continues to widen. Living donation has been an option that has increased the number of transplants despite the continued shortage of deceased organs. In the early 2000s live donor transplantation reached an all-time high in the United States. As a result, a consensus meeting was convened in 2000 to increase the oversight of living donor transplantation. Both the Centers for Medicare and Medicaid Services and the United Network for Organ Sharing developed regulations that transplant programs performing live donor transplantation. These regulations and guidelines involve the education, evaluation, informed consent process and living donor follow-up care. Two areas in which had significant changes included the psychosocial and the independent living donor advocate (ILDA) evaluation. The purpose of this paper was to outline the current regulations and guidelines associated with the psychosocial and ILDA evaluation as well as provide further recommendations for the administration of a high quality evaluation of living donors. The goals and timing of the evaluation and education of donors; qualifications of the health care providers performing the evaluation; components of the evaluation; education provided to donors; documentation of the evaluation; participation in the selection committee meeting; post-decline and post-donation care of donors is described. Caveats including the paired donor exchange programs and non-directed and directed donation are also considered.

  15. Blood donor deferral: time for change? An evidence-based analysis

    Directory of Open Access Journals (Sweden)

    Borra V

    2016-05-01

    Full Text Available Vere Borra,1 Giovani Vandewalle,1 Hans Van Remoortel,1 Veerle Compernolle,1,2 Emmy De Buck,1 Philippe Vandekerckhove1–31Belgian Red Cross-Flanders, Mechelen, 2Faculty of Medicine, University of Ghent, Ghent, 3Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven, Leuven, BelgiumAbstract: Donor selection remains an important part in the safety of the blood supply all over the world. Yet, donor deferral criteria seem to be strongly based on the precautionary principle protecting safety and quality, and on supply and expense considerations. This review therefore provides an overview of the available evidence on donor exclusion criteria, as well as on their cost-effectiveness, for the most frequent reasons of donor deferral in our region. PubMed was queried to retrieve primary research studies, systematic reviews, and health technology assessments (HTAs concerning donor exclusion criteria. With a similar approach, HTAs about the different blood-banking safety interventions were included. Reasons for donor deferral were recorded via the blood bank information system of the Belgian Red Cross-Flanders. Seven systematic reviews were identified: four on donor safety (hypotension, hypertension/type 2 diabetes, epilepsy, and higher age and three on recipient safety (hemochromatosis, men who have sex with men, and endoscopy. Forty-three low-quality observational studies were included, as well as 16 HTAs: three about donor exclusion criteria and 13 cost-utility analyses about blood-banking safety interventions. In general, the available evidence for deferral reasons was of low quality, and for 60% of the top 30 reasons for excluding donors, no evidence was found. Blood banking shows its unique position as many safety measures far exceed the normally accepted cost of €50,000/quality-adjusted life-years. The historical model based on the precautionary principle and on supply and expense considerations provides adequate supplies of

  16. Eye bank procedures: donor selection criteria.

    Science.gov (United States)

    Sousa, Sidney Júlio de Faria E; Sousa, Stella Barretto de Faria E

    2018-01-01

    Eye banks use sterile procedures to manipulate the eye, antiseptic measures for ocular surface decontamination, and rigorous criteria for donor selection to minimize the possibility of disease transmission due to corneal grafting. Donor selection focuses on analysis of medical records and specific post-mortem serological tests. To guide and standardize procedures, eye bank associations and government agencies provide lists of absolute and relative contraindications for use of the tissue based on donor health history. These lists are guardians of the Hippocratic principle "primum non nocere." However, each transplantation carries risk of transmission of potentially harmful agents to the recipient. The aim of the procedures is not to eliminate risk, but limit it to a reasonable level. The balance between safety and corneal availability needs to be maintained by exercising prudence without disproportionate rigor.

  17. Syntheses of donor-acceptor-functionalized dihydroazulenes

    DEFF Research Database (Denmark)

    Broman, Søren Lindbæk; Jevric, Martyn; Bond, Andrew

    2014-01-01

    The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has been of interest for use in molecular electronics and advanced materials. The switching between the two isomers has previously been found to depend strongly on the presence of donor and acceptor groups. The fine-tuning of opt......The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has been of interest for use in molecular electronics and advanced materials. The switching between the two isomers has previously been found to depend strongly on the presence of donor and acceptor groups. The fine...

  18. Radioimmunological determination of neopterin in blood donors

    International Nuclear Information System (INIS)

    Haas, R.; Gerstner, L.

    1985-01-01

    In 518 sera from blood donors below 30 years of age neopterin was determined by radioimmunoassay. 21 of these patients (4.05%) showed elevated serum levels for neopterin. By clinical investigation of these cases viral infections of the upper airways were found. Furthermore after elimination of elevated values significant differences in normal neopterin serum levels could be demonstrated for female and male blood donors (p < 0.01). Because elevated neopterin serum levels indicate immune responses to several antigens, determination of neopterin from serum may be useful for detection of infectious blood samples. (author)

  19. Initial experience with purely laparoscopic living-donor right hepatectomy.

    Science.gov (United States)

    Hong, S K; Lee, K W; Choi, Y; Kim, H S; Ahn, S W; Yoon, K C; Kim, H; Yi, N J; Suh, K S

    2018-05-01

    There may be concerns about purely laparoscopic donor right hepatectomy (PLDRH) compared with open donor right hepatectomy, especially when performed by surgeons accustomed to open surgery. This study aimed to describe technical tips and pitfalls in PLDRH. Data from donors who underwent PLDRH at Seoul National University Hospital between December 2015 and July 2017 were analysed retrospectively. Endpoints analysed included intraoperative events and postoperative complications. All operations were performed by a single surgeon with considerable experience in open living donor hepatectomy. A total of 26 donors underwent purely laparoscopic right hepatectomy in the study interval. No donor required transfusion during surgery, whereas two underwent reoperation. In two donors, the dissection plane at the right upper deep portion of the midplane was not correct. One donor experienced portal vein injury during caudate lobe transection, and one developed remnant left hepatic duct stenosis. One donor experienced remnant portal vein angulation owing to a different approach angle, and one experienced arterial damage associated with the use of a laparoscopic energy device. One donor had postoperative bleeding due to masking of potential bleeding foci owing to intra-abdominal pressure during laparoscopy. Two donors experienced right liver surface damage caused by a xiphoid trocar. Purely laparoscopic donor hepatectomy differs from open donor hepatectomy in terms of angle and caudal view. Therefore, surgeons experienced in open donor hepatectomy must gain adequate experience in laparoscopic liver surgery and make adjustments when performing PLDRH. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

  20. Peer-to-peer milk donors' and recipients' experiences and perceptions of donor milk banks.

    Science.gov (United States)

    Gribble, Karleen D

    2013-07-01

    To explore the intersection of peer-to-peer milk sharing and donor milk banks. A descriptive survey design containing closed and open-ended questions was used to examine women's perceptions of peer-to-peer milk sharing and milk banking. Closed-ended questions were analyzed using descriptive statistics and conventional qualitative content analysis was used to analyze open-ended responses. Participants were recruited via the Facebook sites of two online milk-sharing networks (Human Milk 4 Human Babies and Eats on Feet). Ninety-eight milk donors and 41 milk recipients who had donated or received breast milk in an arrangement that was facilitated via the Internet. One half of donor recipients could not donate to a milk bank because there were no banks local to them or they did not qualify as donors. Other respondents did not donate to a milk bank because they viewed the process as difficult, had philosophical objections to milk banking, or had a philosophical attraction to peer sharing. Most donor respondents felt it was important to know the circumstances of their milk recipients. No recipient respondents had obtained milk from a milk bank; it was recognized that they would not qualify for banked milk or that banked milk was cost prohibitive. Peer-to-peer milk donors and recipients may differ from milk bank donors and recipients in significant ways. Cooperation between milk banks and peer sharing networks could benefit both groups. © 2013 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

  1. Moorfields technique of donor cornea mounting for femtosecond-assisted keratoplasty: use of viscoelastic in the artificial anterior chamber.

    Science.gov (United States)

    Iovieno, Alfonso; Chowdhury, Vivek; Stevens, Julian D; Maurino, Vincenzo

    2012-07-01

    Appropriate mounting and cutting of the donor sclero-corneal cap is often cumbersome during femtosecond laser-assisted keratoplasty. The authors describe a technique for donor cornea femtosecond laser cutting using ophthalmic viscoelastic devices. The donor sclero-corneal cap is mounted on the artificial anterior chamber using a dispersive ophthalmic viscoelastic device instead of saline solution. The chances of artificial anterior chamber pressure loss, inadequate applanation, and fluid leaks are consistently reduced with the use of dispersive ophthalmic viscoelastic devices. The speed of donor femtosecond laser cutting is increased. The viscosity and elasticity of dispersive ophthalmic viscoelastic devices greatly assist the procedure with regard to ease of applanation, corneal endothelium protection, and decreased distortion of the applanated cornea. Copyright 2012, SLACK Incorporated.

  2. Comparison of donor, and early and late recipient outcomes following hand assisted and laparoscopic donor nephrectomy.

    Science.gov (United States)

    Lucas, Steven M; Liaw, Aron; Mhapsekar, Rishi; Yelfimov, Daniel; Goggins, William C; Powelson, John A; Png, Keng Siang; Sundaram, Chandru P

    2013-02-01

    While laparoscopic donor nephrectomy has encouraged living kidney donation, debate exists about the safest laparoscopic technique. We compared purely laparoscopic and hand assisted laparoscopic donor nephrectomies in terms of donor outcome, early graft function and long-term graft outcome. We reviewed the records of consecutive laparoscopic and hand assisted laparoscopic donor nephrectomies performed by a single surgeon from 2002 to 2011. Donor operative time and perioperative morbidity were compared. Early graft function for kidneys procured by each technique was evaluated by rates of delayed graft function, need for dialysis and recipient discharge creatinine. Long-term outcomes were evaluated by graft function. A total of 152 laparoscopic donor nephrectomies were compared with 116 hand assisted laparoscopic donor nephrectomies. Hand assisted procedures were more often done for the right kidney (41.1% vs 17.1%, p recipient outcomes were also similar. Delayed function occurred after 0% hand assisted vs 0.9% purely laparoscopic nephrectomies, dialysis was required in 0.9% vs 1.7% and rejection episodes developed in 9.7% vs 18.4% (p >0.05). At last followup the organ was nonfunctioning in 6.1% of hand assisted and 7.7% of purely laparoscopic cases (p >0.05). The recipient glomerular filtration rate at discharge home was similar in the 2 groups. Hand assisted laparoscopic donor nephrectomy had shorter warm ischemia time but perioperative donor morbidity and graft outcome were comparable. The choice of technique should be based on patient and surgeon preference. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. Frequency and risk factors for donor reactions in an anonymous blood donor survey.

    Science.gov (United States)

    Goldman, Mindy; Osmond, Lori; Yi, Qi-Long; Cameron-Choi, Keltie; O'Brien, Sheila F

    2013-09-01

    Adverse donor reactions can result in injury and decrease the likelihood of donor return. Reaction reports captured in the blood center's database provide an incomplete picture of reaction rates and risk factors. We performed an anonymous survey, mailed to 40,000 donors in 2008, including questions about symptoms, height, weight, sex, and donation status. Reaction rates were compared to those recorded in our database. Possible risk factors were assessed for various reactions. The response rate was 45.5%. A total of 32% of first-time and 14% of repeat donors reported having any adverse symptom, most frequently bruising (84.9 per 1000 donors) or feeling faint or weak (66.2 per 1000). Faint reactions were two to eight times higher than reported in our database, although direct comparison was difficult. Younger age, female sex, and first-time donation status were risk factors for systemic and arm symptoms. In females, low estimated blood volume (EBV) was a risk factor for systemic symptoms. Only 51% of donors who consulted an outside physician also called Canadian Blood Services. A total of 10% of first-time donors with reactions found adverse effects information inadequate. This study allowed us to collect more information about adverse reactions, including minor symptoms and delayed reactions. Based on our findings of the risk factors and frequency of adverse reactions, we are implementing more stringent EBV criteria for younger donors and providing more detailed information to donors about possible adverse effects and their management. © 2012 American Association of Blood Banks.

  4. [Survey of blood donors on the topic of "reimbursement for blood donors"].

    Science.gov (United States)

    Zeiler, T; Kretschmer, V

    1995-02-01

    Remuneration for blood donors, in the way as presently handled by governmental and communal blood transfusion services in Germany, is not generally accepted. It is feared that donors are recruited with increased risk to transmit infectious diseases, especially AIDS. Alternative incentives are discussed. After the so-called AIDS scandal in Germany, a change in the donor motivation was to be expected, associated with an increased willingness to renounce remuneration. Therefore, we performed the present survey, in which we evaluated the donor's willingness to renounce remuneration, possibilities of cashless remuneration and other alternative incentives. During March and April 1994, a total of 1,157 blood donors of the University Blood Bank Marburg were questioned anonymously by a questionnaire in the framework of whole-blood donations. Beside the above-mentioned aspects demoscopic data were included (age, sex, profession, journey). Cutting of remuneration without any other compensation was refused by 86.1% of the donors, 77% would not want to further donate blood in this case. Transfer of money to a bank account instead of cash payment was accepted by 78.6%, the use of non-negotiable cheques by 68.7%. Alternative compensation by tickets for theater, concert, cinema or coupons for restaurants met with the approval of only 27.3%; under these circumstances, 36.9% would be willing to continue blood donation. With increasing age and number of donations, but largely independent of social status, donors attached greater importance to retention of remuneration. Cutting of remuneration would result in a considerable reduction of the willingness to donate blood within the population of donors of the governmental and communal blood transfusion services. However, an increase of virus safety of the blood products would not be reached in this way, since especially the long-term donors would be driven away. Considerable bottlenecks, particularly in the specific blood supply of

  5. Electrostatically defined silicon quantum dots with counted antimony donor implants

    Energy Technology Data Exchange (ETDEWEB)

    Singh, M., E-mail: msingh@sandia.gov; Luhman, D. R.; Lilly, M. P. [Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States); Center for Integrated Nanotechnologies, Sandia National Laboratories, Albuquerque, New Mexico 87175 (United States); Pacheco, J. L.; Perry, D.; Garratt, E.; Ten Eyck, G.; Bishop, N. C.; Wendt, J. R.; Manginell, R. P.; Dominguez, J.; Pluym, T.; Bielejec, E.; Carroll, M. S. [Sandia National Laboratories, Albuquerque, New Mexico 87185 (United States)

    2016-02-08

    Deterministic control over the location and number of donors is crucial to donor spin quantum bits (qubits) in semiconductor based quantum computing. In this work, a focused ion beam is used to implant antimony donors in 100 nm × 150 nm windows straddling quantum dots. Ion detectors are integrated next to the quantum dots to sense the implants. The numbers of donors implanted can be counted to a precision of a single ion. In low-temperature transport measurements, regular Coulomb blockade is observed from the quantum dots. Charge offsets indicative of donor ionization are also observed in devices with counted donor implants.

  6. Marrow donor registry and cord blood bank in Taiwan.

    Science.gov (United States)

    Lee, Tsung Dao

    2002-08-01

    Unrelated Bone marrow transplant was initiated thirty years ago. Though there are over millions of donors registered with the bone marrow registries worldwide, Asian patients rarely find a match with all these donors. Tzu Chi Marrow Donor Registry was established to meet this need. It has become the largest Asian marrow donor registry in the world. With the introduction of high technology to test the HLA of the donors and recipients, the success rate of bone marrow transplant is greatly improved among Asian countries. 50% of blood disease Asian patients who cannot find a bone marrow matched donor will be complemented by the establishment of cord blood banks in Taiwan.

  7. Compliance with donor age recommendations in oocyte donor recruitment advertisements in the USA.

    Science.gov (United States)

    Alberta, Hillary B; Berry, Roberta M; Levine, Aaron D

    2013-04-01

    IVF using donated oocytes offers benefits to many infertile patients, yet the technique also raises a number of ethical concerns, including worries about potential physical and psychological risks to oocyte donors. In the USA, oversight of oocyte donation consists of a combination of federal and state regulations and self-regulatory guidelines promulgated by the American Society for Reproductive Medicine. This study assesses compliance with one of these self-regulatory guidelines - specifically, ASRM's preferred minimum age for donors of 21. To assess compliance, 539 oocyte donor recruitment advertisements from two recruitment channels (Craigslist and college newspapers) were collected and evaluated. Of these, 61% in the Craigslist dataset and 43% in the college newspaper dataset listed minimum ages between 18 and 20, which is inconsistent with ASRM's preferred minimum age recommendation of 21. Advertisements placed by oocyte donor recruitment agencies were more likely than advertisements placed by clinics to specify minimum ages between 18 and 20. These results indicate that ASRM should evaluate and consider revising its donor age guidelines. IVF using donated human eggs can help many patients who have difficulty having children. However, the technique also raises ethical concerns, including concerns about potential physical and psychological harms to egg donors. In the USA, oversight of egg donation relies on a combination of federal and state regulation and professional self-regulation. Governmental regulations address only limited aspects of egg donation, such as the potential spread of infectious diseases and the reporting of success rates, leaving voluntary guidelines developed by an association of medical professionals to address most issues, including ethical concerns raised by the practice. One of these voluntary guidelines recommends that egg donors should be at least 21 years of age. In this article, we analysed 539 egg donor recruitment advertisements

  8. Criteria for selecting organ donors and recipients.

    Science.gov (United States)

    Michielsen, P

    1990-11-01

    As there is a world-wide shortage of organs for transplantation, the selection of the patients is more defined by the availability of transplantable organs than by the medical condition of the potential recipient. This shortage of cadaveric organs is mainly responsible for the use of living donors. With HLA identical sibling donors the results are better than with cadaveric organs, but the ethical problems are usually underestimated. For the parent-to-child donation, the HLA compatibility is less than what could be achieved with well-matched cadaveric donors. The use of genetically unrelated donors is unacceptable from the ethical as well as from the medical point of view. The short- and long-term risk of donation has been insufficiently documented. The experience with the introduction of an opting-out legislation in Belgium in 1987 demonstrates that the shortage of cadaveric organs can be overcome. Harmonization of the legislation is, however, necessary so as to achieve comparable organ retrieval rates between countries participating in organ-exchange organisations.

  9. Properties of Excitons Bound to Ionized Donors

    DEFF Research Database (Denmark)

    Skettrup, Torben; Suffczynski, M.; Gorzkowski, W.

    1971-01-01

    Binding energies, interparticle distances, oscillator strengths, and exchange corrections are calculated for the three-particle complex corresponding to an exciton bound to an ionized donor. The results are given as functions of the mass ratio of the electron and hole. Binding of the complex is o...

  10. Non-organ donors' attitudes toward incentives.

    Science.gov (United States)

    Tumin, Makmor; Noh, Abdillah; Chong, Chin-Sieng; Lim, Soo-Kun; Abdullah, Nawi; Ng, Kok-Peng

    2013-01-01

    Malaysians indicating that they did not intend to become organ donors upon their death were surveyed regarding interest in non-fungible financial incentives to be granted to surviving family members. Among the 730 (56% of the total sample of 1311) indicating unwillingness to be donors, 29.6% (216/730) subsequently indicated that they would be willing donors if the government introduced policies that, upon their death, "rewarded your (their) family with incentives for your (their) deeds." Among the 69% (504/730) who insisted that they would not become organ donor even with incentive, nearly 80% (404/501) of them were able to identify relevant incentives they thought should be provided by the state to those who make organ donations upon death. The majority of both groups preferred the state provide medical benefits to a surviving family member, suggesting this may be an attractive policy option for the state to raise the deceased organ donation pool. © 2013 John Wiley & Sons A/S.

  11. [Outcome of living kidney donors for transplantation].

    Science.gov (United States)

    Lanot, Antoine; Bouvier, Nicolas; Chatelet, Valérie; Lecouf, Angélique; Tillou, Xavier; Hurault de Ligny, Bruno

    2017-11-01

    Nowadays, several treatments exist to treat terminal chronic renal failure. Best results for the recipients are obtained with kidney transplantation concerning mortality and quality of life. Transplantation is also the cheaper option for society. Living kidney donation raises the issue of the becoming of the donor, an absolutely healthy subject who gets to a surgical procedure. The becoming of living kidney donors has been compared with the one of controls subjects in several studies. The evaluations focused on the complications of nephrectomy in the short and long-term: kidney failure, hypertension, proteinuria, possibility of pregnancy, quality of life, and mortality. The first results did not show any risk linked to kidney donation, compared to general population. However, since 2013, kidney donors were found at higher risk for kidney failure and even for mortality, compared with controls selected like donor candidates. The risk of kidney donation is nevertheless acceptable and minimal, on the condition of rigorous selection of candidates and regular follow-up. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

  12. BLOOD DONOR HAEMATOLOGY PARAMETERS IN TWO ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-03

    Mar 3, 2005 ... determine distribution frequencies (including mean and median) and 95% percentile ranges (defined as the mean ± 2SD). These were determined individually for Kisumu and Nairobi, and comparisons between the two donor groups were made using the independent samples t-test. RESULTS. Red blood ...

  13. Electron Donor Acceptor Interactions. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Ana L. [Arizona State Univ., Tempe, AZ (United States)

    2002-08-16

    The Gordon Research Conference (GRC) on Electron Donor Acceptor Interactions was held at Salve Regina University, Newport, Rhode Island, 8/11-16/02. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  14. Predictors of Donor Heart Utilization for Transplantation in United States.

    Science.gov (United States)

    Trivedi, Jaimin R; Cheng, Allen; Gallo, Michele; Schumer, Erin M; Massey, H Todd; Slaughter, Mark S

    2017-06-01

    Optimum use of donor organs can increase the reach of the transplantation therapy to more patients on waiting list. The heart transplantation (HTx) has remained stagnant in United States over the past decade at approximately 2,500 HTx annually. With the use of the United Network of Organ Sharing (UNOS) deceased donor database (DCD) we aimed to evaluate donor factors predicting donor heart utilization. UNOS DCD was queried from 2005 to 2014 to identify total number of donors who had at least one of their organs donated. We then generated a multivariate logistic regression model using various demographic and clinical donor factors to predict donor heart use for HTx. Donor hearts not recovered due to consent or family issues or recovered for nontransplantation reasons were excluded from the analysis. During the study period there were 80,782 donors of which 23,606 (29%) were used for HTx, and 38,877 transplants (48%) were not used after obtaining consent because of poor organ function (37%), donor medical history (13%), and organ refused by all programs (5%). Of all, 22,791 donors with complete data were used for logistic regression (13,389 HTx, 9,402 no-HTx) which showed significant predictors of donor heart use for HTx. From this model we assigned probability of donor heart use and identified 3,070 donors with HTx-eligible unused hearts for reasons of poor organ function (28%), organ refused by all programs (15%), and recipient not located (9%). An objective system based on donor factors can predict donor heart use for HTx and may help increase availability of hearts for transplantation from existing donor pool. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Seropositive abdominal and thoracic donor organs are largely underutilized.

    Science.gov (United States)

    Taylor, R M; Pietroski, R E; Hagan, M; Eisenbrey, A B; Fontana, R J

    2010-12-01

    The aim of this study was to describe the epidemiology and utilization of anti-hepatitis B core protein(+) and anti-hepatitis C virus(+) organ donor referrals in a large organ procurement organization. Between 1995 and 2006, 3,134 deceased organ donor referrals were tested for anti-HBc and anti-HCV using commercial assays. The prevalence of anti-HCV(+) organ donor referrals significantly increased from 3.4% in 1994-1996 to 8.1% in 2003-2005 (P organ donor referrals remained unchanged at 3%-4% (P = .20). The 112 anti-HBc(+) (3.5%) and 173 anti-HCV(+) (5.5%) organ donor referrals were significantly older and more likely to be noncaucasian than seronegative organ donor referrals (P donor organs were significantly lower compared with seronegative organ donors (P donors over time (21% vs 46%; P = .026), whereas utilization of anti-HCV(+) liver donors remained unchanged over time (5% vs 18%; P = .303). In summary, the proportion of anti-HCV(+) organ donor referrals has significantly increased and the proportion of anti-HBc(+) organ donor referrals has remained stable. Both thoracic and abdominal organs from seropositive donors are largely underutilized. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Donor-derived aspergillosis from use of a solid organ recipient as a multiorgan donor.

    Science.gov (United States)

    Mueller, N J; Weisser, M; Fehr, T; Wüthrich, R P; Müllhaupt, B; Lehmann, R; Imhof, A; Aubert, J-D; Genoni, M; Kunz, R; Weber, M; Steiger, J

    2010-02-01

    The growing need for organs and the scarcity of donors has resulted in an increased use of extended criteria donors. We report a case where a recipient of a cardiac graft was used as an organ donor. Death of the recipient occurred 9 days after transplantation and was attributed to presumed cerebral hemorrhage, which post mortem was diagnosed as invasive aspergillosis of the brain. One recipient of a kidney transplant lost the graft due to infection with Aspergillus fumigatus, whereas prompt initiation of therapy successfully prevented disseminated aspergillosis in the other recipients. Despite the pressure to extend the use of organs by lowering the acceptance criteria, organs should only be accepted if the cause of death of the donors is unequivocally explained.

  17. 75 FR 58400 - Donor Management Research: Improvements in Clinical Management of Deceased Organ Donors

    Science.gov (United States)

    2010-09-24

    ... needed. Upon review of research possibilities being discussed in meetings and in the literature, HRSA... their experiences and opinions regarding the importance of further study into donor management and its...

  18. Blood donation and blood donor mortality after adjustment for a healthy donor effect

    DEFF Research Database (Denmark)

    Ullum, Henrik; Rostgaard, Klaus; Kamper-Jørgensen, Mads

    2015-01-01

    BACKGROUND: Studies have repeatedly demonstrated that blood donors experience lower mortality than the general population. While this may suggest a beneficial effect of blood donation, it may also reflect the selection of healthy persons into the donor population. To overcome this bias, we...... investigated the relation between blood donation frequency and mortality within a large cohort of blood donors. In addition, our analyses also took into consideration the effects of presumed health differences linked to donation behavior. STUDY DESIGN AND METHODS: Using the Scandinavian Donation...... and mortality. The magnitude of the association was reduced after adjustment for an estimate of self-selection in the donor population. Our observations indicate that repeated blood donation is not associated with premature death, but cannot be interpreted as conclusive evidence of a beneficial health effect....

  19. Bursopentin (BP5 protects dendritic cells from lipopolysaccharide-induced oxidative stress for immunosuppression.

    Directory of Open Access Journals (Sweden)

    Tao Qin

    Full Text Available Dendritic cells (DCs play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5, a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD, were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1 was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.

  20. ِAnalysis of donor motivations in living donor liver transplantation

    Directory of Open Access Journals (Sweden)

    Hesham eAbdeldayem

    2014-07-01

    Full Text Available Objectives: The introduction of the living donor liver transplantation (LDLT in Egypt as in elsewhere, has raised important psychological conflicts and ethical questions. The objective of this study was to get better understanding of the potential donors’ motives towards LDLT.Methods:This study was conducted on consecutive 193 living –liver donors who underwent partial hepatectomy as donors for LDLT during the period between April 2003 and January 2013, at the National Liver Institute Menoufeyia University, Egypt. Potential donors were thoroughly evaluated preoperatively through a screening questionnaire and interviews as regard their demographic data, relationship to the potential recipient and motives towards proceeding to surgery. They were assured that the information shared between them and the transplant centre is confidential. Results.The donors’ mean age was 25.53± 6.39 years with a range of 18-45 years. Males represented 64.7 % and females were 35.3%. The most common donors (32.1%, n_62, were sons and daughters to their parents (sons: n_43, daughters: n_19 while parents to their offsprings represent 15% (mothers: n_21, fathers: n_8. Brothers and sisters represent 16.5 % (brothers: n_22, sisters: n_10. Nephews & nieces giving their uncles or aunts were 14%. The number of wives donating to their husbands was 11 (5.7%. Interestingly, there was no single husband who donated his wife. Among the remaining donors, there were 11 cousins & one uncle. Unrelated donors were 20 (10.4%. Several factors seemed to contribute to motivation for donation: the seriousness of the potential recipient condition, the relationship and personal history of the donor to the potential recipient, the religious beliefs, the trust in the health care system, and family dynamics and obligations.Conclusions. Absolute absence of coercion on the living-liver donor’s motives may not be realistic because of the serious condition of the potential recipient. It is

  1. Retroperitoneoscopic live donor nephrectomy: Review of the first 50 ...

    African Journals Online (AJOL)

    but the working space in the initial stages of the operation is ... To evaluate donor safety and graft outcomes for the first 50 retroperitoneoscopic ... maintained during the early learning curve of the transition to minimalaccess donor nephrectomy ...

  2. Anaesthesia and peri-operative care for laparoscopic donor nephrectomy

    NARCIS (Netherlands)

    I.R.A.M. Mertens Zur Borg (Ingrid)

    2008-01-01

    textabstractA successful renal transplant for patients with kidney failure reduces mortality rate when compared to patients who continue dialysis. Organ donation from living donors has significant better results over organ donation from deceased donors. Traditionally the surgical

  3. Computer Algorithms in the Search for Unrelated Stem Cell Donors

    Directory of Open Access Journals (Sweden)

    David Steiner

    2012-01-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a medical procedure in the field of hematology and oncology, most often performed for patients with certain cancers of the blood or bone marrow. A lot of patients have no suitable HLA-matched donor within their family, so physicians must activate a “donor search process” by interacting with national and international donor registries who will search their databases for adult unrelated donors or cord blood units (CBU. Information and communication technologies play a key role in the donor search process in donor registries both nationally and internationaly. One of the major challenges for donor registry computer systems is the development of a reliable search algorithm. This work discusses the top-down design of such algorithms and current practice. Based on our experience with systems used by several stem cell donor registries, we highlight typical pitfalls in the implementation of an algorithm and underlying data structure.

  4. Trends in organ donor management: 2002 to 2012.

    Science.gov (United States)

    Callahan, Devon S; Kim, Dennis; Bricker, Scott; Neville, Angela; Putnam, Brant; Smith, Jennifer; Bongard, Frederic; Plurad, David

    2014-10-01

    Refinements in donor management have resulted in increased numbers and quality of grafts after neurologic death. We hypothesize that the increased use of hormone replacement therapy (HRT) has been accompanied by improved outcomes over time. Using the Organ Procurement and Transplant Network donor database, all brain-dead donors procured from July 1, 2001 to June 30, 2012 were studied. Hormone replacement therapy was identified by an infusion of thyroid hormone. An expanded criteria donor was defined as age 60 years or older. Incidence of HRT administration and number of donors and organs recovered were calculated. Using the Organ Procurement and Transplant Network thoracic recipient database transplant list, wait times were examined. There were 74,180 brain-dead donors studied. Hormone replacement therapy use increased substantially from 25.6% to 72.3% of donors. However, mean number of organs procured per donor remained static (3.51 to 3.50; p = 0.083), and the rate of high-yield donors decreased (46.4% to 43.1%; p donors decreased (42.1% to 33.9%; p donors (22.1% to 26%). Despite this, there has been an increase in the raw number of donors (20,558 to 24,308; p organs (5,857 to 6,945; p organs per traumatic brain injury donor (4.02 to 4.12; p = 0.002) and a decrease in days on the waiting list (462.2 to 170.4 days; p donors has been accompanied by increased organ availability overall. Potential mechanisms might include successful conversion of previously unacceptable donors and improved recovery in certain subsets of donors. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Synthesis of all eight L-glycopyranosyl donors using C-H activation

    DEFF Research Database (Denmark)

    Frihed, Tobias; Pedersen, Christian Marcus; Bols, Mikael

    2014-01-01

    by an intramolecular C-H activation of the methyl group in g-position; both steps were catalyzed by iridium. The following Fleming-Tamao oxidation and acetylation gave the suitably protected L-hexoses. This is the first general method for the preparation of all eight L-hexoses as their thioglycosyl donors ready...... for glycosylation and the first example of an iridium-catalyzed C(sp3)-H activation on sulfide-containing compounds....

  6. Viral Infectivity Markers in Donor Blood: A Retrospective Study of ...

    African Journals Online (AJOL)

    A total of 12,540 homologous donors seen between 1993 and 1999 at the University of Maiduguri Teaching Hospital (U.M.T.H) blood bank were analysed with respect to the frequency of viral infectivity markers (HBsAg and HIV antibodies) as it relates to donor categories. Fifteen percent and 4.07% of voluntary donors were ...

  7. Explaining differences between hospitals in number of organ donors.

    NARCIS (Netherlands)

    Friele, R.D.; Coppen, R.; Marquet, R.L.; Gevers, J.K.M.

    2006-01-01

    The shortage of donor organs calls for a careful examination of all improvement options. In this study, 80 Dutch hospitals were compared. They provided 868 donors in a 5-year period, constituting 91% of all donors in that period in The Netherlands. Multilevel regression analysis was used to explain

  8. [Towards the development of living donor kidney transplantation].

    Science.gov (United States)

    Macher, Marie-Alice

    2016-12-01

    Living donor kidney transplantation has been increasing since 2008. Living donors represent a significant potential for organ transplants, in a context where the needs outstrip the availability of organs from deceased donors. However, patients are still poorly informed regarding the conditions in which these transplants are possible. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Prevalence and intensity of malaria in blood donors at Nnamdi ...

    African Journals Online (AJOL)

    Prevalence and intensity of malaria in blood donors at Nnamdi Azikiwe University Teaching Hospital (NAUTH) Nnewi, Anambra State, Nigeria. ... Apprentices and primary school dropouts constituted the most frequent donors. These differences were between the two donor-groups statistically significant (p<0.05). Screening ...

  10. 20 CFR 401.200 - Blood donor locator service.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Blood donor locator service. 401.200 Section... AND INFORMATION Disclosure of Official Records and Information § 401.200 Blood donor locator service... donors whose blood donations show that they are or may be infected with the human immunodeficiency virus...

  11. Donors and archives a guidebook for successful programs

    CERN Document Server

    Purcell, Aaron D

    2015-01-01

    Donors and Archives: A Guidebook for Successful Programs highlights the importance of development and fundraising for archives, while focusing on the donor and potential donor. Their interest, their support, their enthusiasm, and their stuff are vital to the success of archival programs.

  12. Grandparents’ Stories of Family Life After Donor Conception (Parents of heterosexual couples with children conceived using donor sperm or eggs)

    OpenAIRE

    Burke, Hazel; Nordqvist, Petra; Smart, Carol

    2015-01-01

    This leaflet is written for the parents of heterosexual couples who have, or are planning, children using donor conception. It is based on many hours of research interviews, during which parents and grandparents of donor-conceived children told usabout their experiences of family life after donor conception.This leaflet is one of a series of four, written for parents and grandparents with donor-conceived children. They are based on research from the Relative Strangers project.

  13. South Korea as an emerging donor

    DEFF Research Database (Denmark)

    Chun, Hong-Min; Munyi, Elijah Nyaga; Lee, Heejin

    2010-01-01

    South Korea's official development assistance (ODA) has been increasing rapidly and will continue to do so. Korea is one of the few countries which have successfully transitioned from a recipient to a donor. It became a member of DAC (development assistance committee), OECD in November 2009. Korea......'s ODA policy, along with its growth in quantity, is at a crossroads for the enhancement of its quality. Discussions and debates are going on regarding the reforms in Korea's ODA activities, and this paper examines key issues raised. It first reviews the past and present of Korea's ODA, and identifies...... like the objective of ODA, positioning of Korea's ODA as an emerging donor and the nature of aid to North Korea. We also argue that a shift of ODA policy is required to promote reform, based on a thorough reflection on the role of ODA in the alleviation of poverty and promoting sustainable development...

  14. Diet and Asthma: Vitamins and Methyl Donors

    Science.gov (United States)

    Han, Yueh-Ying; Blatter, Josh; Brehm, John M.; Forno, Erick; Litonjua, Augusto A; Celedón, Juan C.

    2014-01-01

    SUMMARY Dietary changes may partly explain the high burden of asthma in industrialized nations. Experimental studies have motivated a significant number of observational studies of the relation between vitamins (A, C, D, and E) or nutrients acting as methyl donors (folate, vitamin B12, and choline) and asthma. Because observational studies are susceptible to several sources of bias, well-conducted randomized controlled trials (RCTs) remain the “gold standard” to determine whether a vitamin or nutrient has an effect on asthma. Evidence from observational studies and/or relatively few RCTs most strongly justify ongoing and future RCTs of: 1) vitamin D to prevent or treat asthma, 2) choline supplementation as adjuvant treatment for asthma, and 3) vitamin E to prevent the detrimental effects of air pollution in subjects with asthma. At this time, there is insufficient evidence to recommend supplementation with any vitamin or nutrient acting as a methyl donor to prevent or treat asthma. PMID:24461761

  15. Deceased donor organ transplantation with expanded criteria donors: a single-center experience from India.

    Science.gov (United States)

    Goplani, K R; Firoz, A; Ramakrishana, P; Shah, P R; Gumber, M R; Patel, H V; Vanikar, A V; Trivedi, H L

    2010-01-01

    Deceased donor organ transplantation (DDOT) accounts for DKT) and 19 single (SKT). Fourteen donors had hypertension, a cerebrovascular accident as the cause of death, 9 had both, and 4 had diabetes. Mean donor age was 70.3 +/- 8.9 years. Decisions on the procedure were based upon frozen section biopsy in 13 of 21 donors. Mean DKT donor age was 76 +/- 9.7 years versu 64 +/- 5.7 years of SKT donors. The native kidney diseases were chronic glomerulonephritis (n = 14), diabetic nephropathy (n = 7), tubulointerstitial nephritis (n = 4) and polycystic kidney disease, focal segmental glomerulosclerosis, lupus nephritis and patchy cortical necrosis, (n = 1 each). Mean recipient age of DKT versus SKT was 43.5 versus 42.3 years. All recipients received rabbit anti-thymocyte globulin, followed by steroid, mycophenolate mofetil/calcinueurin inhibitor. Over a mean follow-up of 341 days, the mean serum creatinine (SCr) of 25/29 patients was 1.60 mg/dL (range, 1.0-2.6). The mean SCr of SKT patients was 1.59 +/- 0.63 mg/dL and of DKT, 1.62 +/- 0.48 mg/dL. Ten patients had delayed graft function and 11 had biopsy proven acute tubular necrosis. Seven (24%) patients had rejection (grade 3 Banff update '05, type IA; 4, type 2A); 6 responded to antirejection; 1 graft was lost at 7 months due to chronic rejection. Three (10.3%) patients were lost, 1 each due to AMI, sepsis, and CMV disease. In the circumstances of organ shortage, DDOT with expanded criteria donor is a feasible option.

  16. Donor conversion and procurement failure: the fate of our potential organ donors.

    Science.gov (United States)

    Branco, Bernardino C; Inaba, Kenji; Lam, Lydia; Salim, Ali; Barmparas, Galinos; Teixeira, Pedro G R; Talving, Peep; Demetriades, Demetrios

    2011-02-01

    Donor availability remains the primary limiting factor for organ transplantation today. The purpose of this study was to examine the causes of procurement failure amongst potential organ donors. After Institutional Review Board approval, all surgical intensive care unit (SICU) patients admitted to the LAC+USC Medical Center from 01/2006 to 12/2008 who became potential organ donors were identified. Demographics, clinical data, and procurement data were abstracted. In non-donors, the causes of procurement failure were documented. During the 3-year study period, a total of 254 patients were evaluated for organ donation. Mean age was 44.8±18.7 years; 191 (75.2%) were male, 136 (53.5%) were Hispanic, and 148 (58.3%) were trauma patients. Of the 254 patients, 116 (45.7%) were not eligible for donation: 34 had multi-system organ failure, 24 did not progress to brain death and had support withdrawn, 18 had uncontrolled sepsis, 15 had malignancy, 6 had human immunodeficiency virus or hepatitis B or C, and 19 patients had other contraindications to organ donation. Of the remaining 138 eligible patients, 83 (60.2%) did not donate: 56 because the family denied consent, 9 by their own choice. In six, next of kin could not be located, five died because of hemodynamic instability before organ procurement was possible, four had organs that could not be placed, and three had their organs declined by the organ procurement organization. The overall consent rate was 57.5% (n=67). From the 55 donors, 255 organs were procured (yield 4.6 organs/donor). Of all patients screened for organ donation, only a fifth actually donated. Denial of consent was the major potentially preventable cause of procurement failure, whereas hemodynamic instability accounted for only a small percentage of donor losses. With such low conversion rates, the preventable causes of procurement failure warrant further study.

  17. The effect of World Blood Donor Day on digital information seeking and donor recruitment.

    Science.gov (United States)

    Kranenburg, Floris J; Kreuger, Aukje L; Arbous, M Sesmu; Laeijendecker, Daphne; van Kraaij, Marian G J

    2017-10-01

    The purpose of World Blood Donor Day (WBDD) is to raise awareness for the importance of blood donation. The aim of this study was to quantify the impact of WBDD on digital information seeking and donor recruitment. Google Trends data were used to quantify seeking behavior on "blood donation" and "blood donor." Differences in relative search volume (RSV) between the 3 weeks surrounding WBDD and the rest of the year were calculated. Second, mean differences in RSV were compared to assess the additional effect of hosting using translated search terms. Third, we compared the period around WBDD with the control period regarding page views of the Sanquin website and Facebook likes and number of newly registered donors in 2016. The mean RSV for "blood donation" in the period of interest was 78.6, compared to 72.1 in the control period (difference, 6.5; 95% confidence interval [95% CI], 1.2-11.8). For "blood donor" this was 78.9 compared to 65.9 (difference, 12.9; 95% CI, 8.1-17.8). We found no additional effect of hosting. In the period of interest, the website of Sanquin was visited 6862 times a day and 4293 times in the control period (difference, 2569; 95% CI, 1687-3451). In June 2016, 54.6% (95% CI, 53.0-56.2) more new donors were registered compared to the control period. An international campaign like WBDD raises the awareness of blood donation and is effective in convincing people to register as blood donors. © 2017 AABB.

  18. [Ethics and kidney transplants with living donors].

    Science.gov (United States)

    Mamzer Bruneel, Marie-France

    2016-12-01

    The ethical debate surrounding transplant practices questions our societies. International recommendations set out numerous precautions which must be taken to ensure that donors act with their free will. While in most countries, including France, organ donation is a voluntary and non-commercial act, a black market exists in the world resulting in the trafficking of organs and tragic transplant tourism. Copyright © 2016. Publié par Elsevier Masson SAS.

  19. Hemochromatosis Patients as Voluntary Blood Donors

    Directory of Open Access Journals (Sweden)

    Tara E Power

    2004-01-01

    Full Text Available The present study was designed to investigate hemochromatosis patients' suitability as blood donors as well as their perceptions and experience with the current public donation system. Participants were gathered from a list of current hemochromatosis patients (n=120 and members of the Canadian Hemochromatosis Society (n=1000. Of the 1120 surveys mailed out to these groups, 801 surveys were returned completed. The sample respondents had a mean age of 57.44 years (SD=12.73; range 19 to 87 years, and 57% were men. It was found that 20% (160 of the respondents have donated blood since their diagnosis; however, only 12% of the respondents indicated that they use voluntary blood donation as a means of maintaining their iron levels. Forty per cent of the respondents indicated that they had been refused from voluntary donation. Despite the fact that in May 2001 the Canadian Blood Services, in collaboration with the Canadian Hemochromatosis Society, began a promotion campaign to encourage hemochromatosis patients to become voluntary blood donors, the present study found that 15% of the respondents reported having been refused from the voluntary blood donation service due to the diagnosis of hemochromatosis. With respect to quality of life, it was found that individuals who donate blood were generally healthier with respect to physical functioning and bodily pain, however, these findings may indicate that hemochromatosis patients who are healthier are better able to donate at public blood banks, rather than that voluntary blood donation has an effect on the donors' physical functioning over phlebotomy clinic users. These study findings suggest that although there may be other medical factors limiting individuals from donating, hemochromatosis patients are interested in being voluntary blood donors and this potential resource is currently under-used.

  20. Higher refusal rates for organ donation among older potential donors in the Netherlands: impact of the donor register and relatives.

    NARCIS (Netherlands)

    Leiden, H.A. van; Jansen, N.E.; Haase-Kromwijk, B.J.; Hoitsma, A.J.

    2010-01-01

    BACKGROUND: The availability of donor organs is considerably reduced by relatives refusing donation after death. There is no previous large-scale evaluation of the influence of the Donor Register (DR) consultation and the potential donor's age on this refusal in The Netherlands. METHODS: This study

  1. Contrasting roles of donor and recipient TGFB1 and IFNG gene polymorphic variants in chronic kidney transplant rejection.

    Science.gov (United States)

    Coelho, Verônica Porto Carreiro de Vasconcellos; Ioschpe, Rafael; Caldas, Cristina; Spadafora-Ferreira, Monica; Fonseca, João Americo; Cardoso, Maria Regina Alves; Palacios, Selma Aliotti; Kalil, Jorge; Goldberg, Anna Carla

    2011-03-01

    To assess the long-term impact (minimum of 3 years follow-up) of polymorphisms in cytokine genes in donor:recipient pairs on the results of the transplant. We compared genetic cytokine polymorphisms and the primary factors of risk for the development of chronic rejection in paired groups of renal transplant patients with and without chronic allograft nephropathy [CAN]. Multivariate analysis indicated that the presence of the high-production TT genotype (codon 10) of the transforming growth factor beta-1 (TGFB1) was protective in receptors (p=0.017), contrasting with the increased risk when present in donor samples (p=0.049). On the other hand, in the case of the gamma interferon studied, the greater frequency of the high production allele was protective in the analysis of the donor group (p=0.013), increasing the risk of chronic nephropathy of the allograft when present in the recipients (p=0.036). Our results highlight the importance of TGFB1 genotyping in donors, and indicate that polymorphisms in the gene of this cytokine in donor cells might contribute to the development of chronic allograft nephropathy.

  2. Slow graft function and related risk factors in living donor kidney transplantation

    Directory of Open Access Journals (Sweden)

    Lesan Pezeshki M.

    2008-03-01

    Full Text Available Background: While excellent organ quality and ideal transplant conditions eliminate many of the known factors that compromise initial graft function (IGF, slow graft function (SGF, still occurs after living donor kidney transplantation (LDKT. The aim of our current study is determination SGF frequency and its risk factors in LDKT Methods: In this prospective study, between April 2004 and March 2006, data were collected on 340 LDKT, in Baghiyattallah Hospital, Tehran. Recipients were analyzed in two groups based on initial graft function (IGF: Creatinine <3 mg/dl 5 day after transplantation, SGF: Creatinine ≥ 3 mg/dl 5 day after transplantation with out dialysis in the first week. Donors' and recipients' characteristics and recipient lab. data were compared in two groups by chi-square, Mann-whitney & independent samples T-test.Results: The incidence of SGF was 22 (6.2% and IGF 318 (89.8%, Recipients' BMI in IGF were 22.1±3.9 and in SGF were 25.3±3.8 (P=0.001 95% Cl 1.097-1.401 OR= 1.24. SGF relative frequency in female donors is more than male donors. A multivariate analysis model confirms this significant difference. (P=0.044 95% Cl 1.028-7.971 OR= 2.862. SGF relative frequency in PRA (Panel Reactive Antibody positive recipients are more than negative ones. A multivariate analysis model confirms this significant difference. (P=0.007 95%Cl 1.755-35.280 OR= 7.849. Recipients' age and donors' BMI are significant in univariate analysis (P=0.002 & P=0.029 respectively but multivariate analysis model dose not confirm those significance. Serum ca & P & PTH levels don't have significant difference between IGF & SGF. Using calcium channels blockers have not a protective effect. Conclusions: We conclude that negative PRA and lower recipient BMI have protective effects on SGF. Recipients with female donors have higher chance to develop SGF. We recommend recipients reduce their BMI before transplantation. The male donors

  3. Anonymous living liver donation: donor profiles and outcomes.

    Science.gov (United States)

    Reichman, T W; Fox, A; Adcock, L; Wright, L; Abbey, S E; Levy, G; Grant, D R

    2010-09-01

    There are no published series of the assessment process, profiles and outcomes of anonymous, directed or nondirected live liver donation. The outcomes of 29 consecutive potential anonymous liver donors at our center were assessed. We used our standard live liver assessment process, augmented with the following additional acceptance criteria: a logical rationale for donation, a history of social altruism, strong social supports and a willingness to maintain confidentiality of patient information. Seventeen potential donors were rejected and 12 donors were ultimately accepted (six male, six female). All donors were strongly motivated by a desire and sense of responsibility to help others. Four donations were directed toward recipients who undertook media appeals. The donor operations included five left lateral segmentectomies and seven right hepatectomies. The overall donor morbidity was 40% with one patient having a transient Clavien level 3 complication (a pneumothorax). All donors are currently well. None expressed regret about their decision to donate, and all volunteered the opinion that donation had improved their lives. The standard live liver donor assessment process plus our additional requirements appears to provide a robust assessment process for the selection of anonymous live liver donors. Acceptance of anonymous donors enlarges the donor liver pool. © 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Factors influencing the virological testing of cornea donors.

    Science.gov (United States)

    Röck, Tobias; Beck, Robert; Jürgens, Stefan; Bartz-Schmidt, Karl Ulrich; Bramkamp, Matthias; Thaler, Sebastian; Röck, Daniel

    2017-11-01

    To assess the influence of donor, environment, and logistical factors on the results of virological testing of blood samples from cornea donors.Data from 670 consecutive cornea donors were analyzed retrospectively. Logistic regression analysis was used to assess the influence of different factors on the results of virological testing of blood samples from cornea donors.The mean annual rate of donors with serology-reactive or not evaluable result was 14.8% (99 of 670) (range 11.9%-16.9%). The cause of donor death by cancer increased the risk of serology-reactive or not evaluable result (P = .0300). Prolonged time between death and post mortem blood removal was associated with a higher rate of serology-reactive or not evaluable result (P donors, sex, and donor age had no significant impact on the results of virological testing of blood samples from cornea donors.The cause of donor death by cancer and a prolonged time between death and post mortem blood removal seem to be mainly responsible for serology-reactive or not evaluable result of blood samples from cornea donors. The percentage of discarded corneas caused by serology-reactive or not evaluable result may be reduced by shortening the period of time between death and post mortem blood removal. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  5. Transplantation and differentiation of donor cells in the cloned pigs

    International Nuclear Information System (INIS)

    Shimada, Arata; Tomii, Ryo; Kano, Koichiro; Nagashima, Hiroshi

    2006-01-01

    The application of nuclear transfer technology is an interesting approach to investigate stem and progenitor cell transplantation therapy. If stem cells are used as a nuclear donor, donor cells can engraft into cloned animals without histocompatible problems. However, it is still uncertain whether donor cells can engraft to cloned animal and differentiate in vivo. To address this problem, we transplanted donor cells to dermal tissues of cloned pigs developed by using preadipocytes as donor cells. Preadipocytes are adipocytic progenitor which can differentiate to mature adipocytes in vitro. We showed that the donor preadipocytes were successfully transplanted into the cloned pigs without immune rejection and they differentiated into mature adipocytes in vivo 3 weeks after transplantation. In contrast, allogenic control preadipocytes, which can differentiate in vitro, did not differentiate in vivo. These results indicate that donor progenitor cells can differentiate in cloned animal

  6. Whole-blood donation: blood donor suitability and adverse events.

    Science.gov (United States)

    Newman, Bruce H

    2004-11-01

    Approximately 3% to 3.5% of the US population donates whole blood each year. Physicians might be approached by a blood donor because of a donor suitability issue, a positive postdonation test, or a donation-related complication. Approximately 83% of blood donors successfully donate; but 13% are rejected because of a donor suitability issue; 1% have a positive test, which is often nonspecific or false-positive; and 2% to 4% of the phlebotomies are not successful. The most common adverse physical events based on donor interviews are bruise (23%), sore arm (10%), fatigue (8%), and vasovagal reaction (7%), while uncommon events include nerve irritation (0.9%), syncope (0.1-0.3%), and arterial puncture (0.01%). One in 3400 donors (0.033%) report seeking outside medical care. Serious injuries occur but are very rare. More often, blood donors do well and feel satisfied with the blood donation experience.

  7. Whistleblower Protection

    Science.gov (United States)

    The Whistleblower Protection Enhancement Act of 2012 (WPA) and the Whistleblower Protection Act of 1989 Enhanced by the Act of 2012 provides protection rights for Federal employees against retaliation for whistleblowing activities.

  8. Activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

    Science.gov (United States)

    Xu, Jun; Wu, Liang; Zhang, Yiming; Gu, Huijie; Huang, Zhongyue; Zhou, Kaifeng; Yin, Xiaofan

    2017-12-22

    The present study tested the potential effect of OSU53, a novel AMPK activator, against hydrogen peroxide (H2O2)-induced spinal cord neuron damages. Treatment with OSU53 attenuated H2O2-induced death and apoptosis of primary murine spinal cord neurons. OSU53 activated AMPK signaling, which is required for its actions in spinal cord neurons. The AMPK inhibitor Compound C or AMPKα1 siRNA almost abolished OSU53-mediated neuroprotection against H2O2. On the other hand, sustained-activation of AMPK by introducing the constitutive-active AMPKα1 mimicked OSU53's actions, and protected spinal cord neurons from oxidative stress. OSU53 significantly attenuated H2O2-induced reactive oxygen species production, lipid peroxidation and DNA damages in spinal cord neurons. Additionally, OSU53 increased NADPH content and heme oxygenase-1 mRNA expression in H2O2-treated spinal cord neurons. Together, we indicate that targeted-activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

  9. Intramolecular Charge-Transfer Interaction of Donor-Acceptor-Donor Arrays Based on Anthracene Bisimide.

    Science.gov (United States)

    Iwanaga, Tetsuo; Ogawa, Marina; Yamauchi, Tomokazu; Toyota, Shinji

    2016-05-20

    We designed anthracene bisimide (ABI) derivatives having two triphenylamine (TPA) groups as donor units at the 9,10-positions to form a novel π-conjugated donor-acceptor system. These compounds and their analogues with ethynylene linkers were synthesized by Suzuki-Miyaura and Sonogashira coupling reactions, respectively. In UV-vis spectra, the linker-free derivatives showed broad absorption bands arising from intramolecular charge-transfer interactions. Introducing ethynylene linkers resulted in a considerable red shift of the absorption bands. In fluorescence spectra, the ethynylene derivatives showed intense emission bands at 600-650 nm. Their photophysical and electrochemical properties were compared with those of the corresponding mono TPA derivatives on the basis of theoretical calculations and cyclic voltammetry to evaluate the intramolecular electronic interactions between the donor and acceptor units.

  10. Emergency department referral for organ donation: more organ donors and more organs per donor.

    Science.gov (United States)

    Miller, Lisabeth D; Gardiner, Stuart K; Gubler, K Dean

    2014-05-01

    This study sought to determine whether early referral from the emergency department (ED) would increase the number of organ donors and the number of organs transplanted per donor (OTPD). This is a retrospective cohort analysis of all patients referred to a single organ procurement organization for a period of 60 months. Patients referred for organ donation evaluation from the ED were more likely to become organ donors than patients referred from the intensive care unit (19.3% vs 5.2%, P organ donation from the ED is associated with an increased likelihood of organ recovery and with an increased number of OTPD. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Why search for a sperm donor online? The experiences of women searching for and contacting sperm donors on the internet.

    Science.gov (United States)

    Jadva, Vasanti; Freeman, Tabitha; Tranfield, Erika; Golombok, Susan

    2018-06-01

    Whilst studies have examined the experiences of women who use clinic donors, to date there has been limited research investigating women's motivations and experiences of searching for a sperm donor online. A total of 429 women looking for a sperm donor on Pride Angel (a website that facilitates contact between donors and recipients) completed an online survey. Fifty-eight percent (249) saw advantages of obtaining donated sperm online with the most common advantage reported as being able to connect with and meet the donor (n = 50 (24%)). A third (n = 157 (37%)) of the participants gave disadvantages, the most common reported was encountering 'dishonest donors' (n = 63 (40%)). Most recipients (n = 181 (61%)) wanted the donor to be 'just a donor' (i.e. to provide sperm and have no further contact). Whilst it was important for recipients to know the identity of the donor, some did not see this as important for the child and thus the level of information that parents have about the donor, and that which the child has, can differ. Finding a donor online blurs the distinction between categories of 'anonymous', 'known' and 'identity release' donations. Whilst the survey had a large sample size, the representativeness of the sample is not known.

  12. Radiation protection

    International Nuclear Information System (INIS)

    Koelzer, W.

    1975-01-01

    Physical and radiological terms, quantities, and units. Basic principles of radiation protection (ICRP, IAEA, EURATOM, FRG). Biological effects of ionizing radiation. Objectives of practical radiation protection. (HP) [de

  13. Is portal venous pressure modulation still indicated for all recipients in living-donor liver transplantation?

    Science.gov (United States)

    Yao, Siyuan; Kaido, Toshimi; Uozumi, Ryuji; Yagi, Shintaro; Miyachi, Yosuke; Fukumitsu, Ken; Anazawa, Takayuki; Kamo, Naoko; Taura, Kojiro; Okajima, Hideaki; Uemoto, Shinji

    2018-04-30

    There is a consensus that portal venous pressure (PVP) modulation prevents portal hypertension (PHT) and consequent complications after adult living donor liver transplantation (ALDLT). However, PVP-modulation strategies need updating based on most recent findings. We examined our 10-year experience of PVP modulation and reevaluate whether it is necessary for all recipients or selected recipients in ALDLT. In this retrospective study, 319 patients who underwent ALDLT from 2007 to 2016 were divided into three groups according to the necessity and results of PVP modulation: not indicated (n=189), indicated and successful (n=92), and indicated but failed (n=38). Graft survival and associations with various clinical factors were investigated. PVP modulation was performed mainly by splenectomy to lower final PVP to ≤15 mmHg. Successful PVP modulation improved prognosis that was equivalent to that of patients who did not need modulation, whereas failed modulation was associated with increased incidence of small-for-size syndrome (SFSS) (p=0.003), and early graft loss (EGL) (p=0.006). Among patients with failed modulation, donor age ≥45 years (hazard ratio [HR], 3.67; p=0.02) and ABO incompatibility (HR, 3.90; p=0.01) were independent risk factors for graft loss. Survival analysis showed that PVP >15 mmHg was related to poor prognosis in grafts from either ABO-incompatible or older donor aged ≥45 years (pmodulation is not necessarily required in all recipients. While grafts from both ABO-compatible/identical and young donor can tolerate PHT, lowering PVP to ≤15 mmHg is a key to preventing SFSS and consequent EGL with grafts from either ABO-incompatible or older donors. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  14. Techniques used for the screening of hemoglobin levels in blood donors: current insights and future directions

    Directory of Open Access Journals (Sweden)

    Chaudhary R

    2017-07-01

    Full Text Available Rajendra Chaudhary,1 Anju Dubey,2 Atul Sonker3 1Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, 2Department of Transfusion Medicine, T.S. Misra Medical College and Hospital, 3Department of Transfusion Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Abstract: Blood donor hemoglobin (Hb estimation is an important donation test that is performed prior to blood donation. It serves the dual purpose of protecting the donors’ health against anemia and ensuring good quality of blood components, which has an implication on recipients’ health. Diverse cutoff criteria have been defined world over depending on population characteristics; however, no testing methodology and sample requirement have been specified for Hb screening. Besides the technique, there are several physiological and methodological factors that affect accuracy and reliability of Hb estimation. These include the anatomical source of blood sample, posture of the donor, timing of sample and several other biological factors. Qualitative copper sulfate gravimetric method has been the archaic time-tested method that is still used in resource-constrained settings. Portable hemoglobinometers are modern quantitative devices that have been further modified to reagent-free cuvettes. Furthermore, noninvasive spectrophotometry was introduced, mitigating pain to blood donor and eliminating risk of infection. Notwithstanding a tremendous evolution in terms of ease of operation, accuracy, mobility, rapidity and cost, a component of inherent variability persists, which may partly be attributed to pre-analytical variables. Hence, blood centers should pay due attention to validation of test methodology, competency of operating staff and regular proficiency testing of the outputs. In this article, we have reviewed various regulatory guidelines, described the variables that affect the measurements and compared the validated

  15. The Protective Effect of Lavender Essential Oil and Its Main Component Linalool against the Cognitive Deficits Induced by D-Galactose and Aluminum Trichloride in Mice

    Directory of Open Access Journals (Sweden)

    Pan Xu

    2017-01-01

    Full Text Available Lavender essential oil (LO is a traditional medicine used for the treatment of Alzheimer’s disease (AD. It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO and its active component, linalool (LI, against cognitive impairment induced by D-galactose (D-gal and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg or LI (100 mg/kg significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test. The mechanisms study demonstrated that LO and LI significantly protected the decreased activity of superoxide dismutase (SOD, glutathione peroxidase (GPX, and protected the increased activity of acetylcholinesterase (AChE and content of malondialdehyde (MDA. Besides, they protected the suppressed nuclear factor-erythroid 2-related factor 2 (Nrf2 and heme oxygenase-1 (HO-1 expression significantly. Moreover, the decreased expression of synapse plasticity-related proteins, calcium-calmodulin-dependent protein kinase II (CaMKII, p-CaMKII, brain-derived neurotrophic factor (BDNF, and TrkB in the hippocampus were increased with drug treatment. In conclusion, LO and its active component LI have protected the oxidative stress, activity of cholinergic function and expression of proteins of Nrf2/HO-1 pathway, and synaptic plasticity. It suggest that LO, especially LI, could be a potential agent for improving cognitive impairment in AD.

  16. Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

    Directory of Open Access Journals (Sweden)

    Youichi Kawano

    Full Text Available Along with the increasing need for living-donor liver transplantation (LDLT, the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH. The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038, demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001. Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

  17. Genetic predisposition of donors affects the allograft outcome in kidney transplantation; polymorphisms of stromal-derived factor-1 and CXC receptor 4.

    Directory of Open Access Journals (Sweden)

    Jung Pyo Lee

    Full Text Available Genetic interaction between donor and recipient may dictate the impending responses after transplantation. In this study, we evaluated the role of the genetic predispositions of stromal-derived factor-1 (SDF1 [rs1801157 (G>A] and CXC receptor 4 (CXCR4 [rs2228014 (C>T] on renal allograft outcomes. A total of 335 pairs of recipients and donors were enrolled. Biopsy-proven acute rejection (BPAR and long-term graft survival were traced. Despite similar allele frequencies between donors and recipients, minor allele of SDF1 rs1801157 (GA+AA from donor, not from recipients, has a protective effect on the development of BPAR compared to wild type donor (GG (P  = 0.005. Adjustment for multiple covariates did not affect this result (odds ratio 0.39, 95% C.I 0.20-0.76, P = 0.006. CXCR4 rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. SDF1 was differentially expressed in renal tubular epithelium with acute rejection according to genetic variations of donor rs1801157 showing higher expressions in the grafts from GG donors. Contrary to the development of BPAR, the presence of minor allele rs1801157 A, especially homozygocity, predisposed poor graft survival (P = 0.001. This association was significant after adjusting for several risk factors (hazard ratio 3.01; 95% C.I = 1.19-7.60; P = 0.020. The allelic variation of recipients, however, was not associated with graft loss. A donor-derived genetic polymorphism of SDF1 has influenced the graft outcome. Thus, the genetic predisposition of donor should be carefully considered in transplantation.

  18. Physical protection

    International Nuclear Information System (INIS)

    Myers, D.A.

    1989-01-01

    Physical protection is defined and its function in relation to other functions of a State System of Accounting for and Control of Nuclear Materials is described. The need for a uniform minimum international standard for physical protection as well as the need for international cooperation in physical protection is emphasized. The IAEA's INFCIRC/225/Rev. 1 (Annex 1) is reviewed. The Convention on the Physical Protection of Nuclear Material (Annex 2) is discussed. Photographs show examples of typical physical protection technology (Annex 3)

  19. Diplomatic Protection

    OpenAIRE

    Režná, Jana

    2006-01-01

    Final thesis Topic: Diplomatic protection Thesis supervisor: JUDr. Vladimír Balaš, CSc. Student: Marek Čermák Thesis on the topic of diplomatic protection deals with the granting of exercise of diplomatic protection by the states and is divided into seven chapters which follow each other. The first chapter describes the diplomatic protection and its historical foundations. The second chapter focuses on the possibility of exercise of diplomatic protection in respect of natural persons and the ...

  20. The Willed Body Donor Interview Project: Medical Student and Donor Expectations

    Science.gov (United States)

    Bohl, Michael; Holman, Alexis; Mueller, Dean A.; Gruppen, Larry D.; Hildebrandt, Sabine

    2013-01-01

    The Anatomical Donations Program at the University of Michigan Medical School (UMMS) has begun a multiphase project wherein interviews of donors will be recorded and later shown to medical students who participate in the anatomical dissection course. The first phase of this project included surveys of both current UMMS medical students and donors…

  1. Donor Motivations and Decision Making: Understanding the Major Gift Development Process from a Donor's Perspective

    Science.gov (United States)

    Morrison, Anna Lee

    2015-01-01

    Higher education is faced with a challenge to its traditional funding structure. As a result, academic programs must seek alternative sources of support. Chief among these sources is philanthropy in the form of major gifts. Insight into donor motivations and decision making when approached to consider a major gift may help to maximize the success…

  2. Variation in semen parameters derived from computer-aided semen analysis, within donors and between donors

    NARCIS (Netherlands)

    Wijchman, JG; De Wolf, BTHM; Graaff, R; Arts, EGJM

    2001-01-01

    The development of computer-aided semen analysis (CASA) has made it possible to study sperm motility characteristics objectively and longitudinally. In this 2-year study of 8 sperm donors, we used CASA to measure 7 semen parameters (concentration, percentage of motile spermatozoa, curvilinear

  3. Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance

    International Nuclear Information System (INIS)

    Weiden, P.L.; Storb, R.; Tsoi, M.S.; Graham, T.C.; Lerner, K.G.; Thomas, E.D.

    1976-01-01

    Canine radiation chimeras were used to investigate further mechanism(s) responsible for maintaining the stable chimeric state. In an attempt to elucidate the nature of this postulated active mechanism, the cytotoxicity of donor lymphocytes for fibroblasts of the chimera and the presence or absence of serum-blocking factors were assessed in vitro by using a cellular inhibition (CI) assay. The presence of serum-blocking factors did not protect against the development of significant GVHD in two chimeras (fatal in one). GVHD did not occur in four other chimeras after infusion of cytotoxic donor lymphocytes despite the absence of serum-blocking factors. These and previous results suggest that serum-blocking factors are not the mechanism suppressing the development of GVHD in canine radiation chimeras, and raise the possibility that a suppressor cell population may be responsible for preventing GVHD

  4. Improving Photoconductance of Fluorinated Donors with Fluorinated Acceptors

    Energy Technology Data Exchange (ETDEWEB)

    Garner, Logan E.; Larson, Bryon; Oosterhout, Stefan; Owczarczyk, Zbyslaw; Olson, Dana C.; Kopidakis, Nikos; Boltalina, Olga V.; Strauss, Steven H.; Braunecker, Wade A.

    2016-11-21

    This work investigates the influence of fluorination of both donor and acceptor materials on the generation of free charge carriers in small molecule donor/fullerene acceptor BHJ OPV active layers. A fluorinated and non-fluorinated small molecule analogue were synthesized and their optoelectronic properties characterized. The intrinsic photoconductance of blends of these small molecule donors was investigated using time-resolved microwave conductivity. Blends of the two donor molecules with a traditional non-fluorinated fullerene (PC70BM) as well as a fluorinated fullerene (C60(CF3)2-1) were investigated using 5% and 50% fullerene loading. We demonstrate for the first time that photoconductance in a 50:50 donor:acceptor BHJ blend using a fluorinated fullerene can actually be improved relative to a traditional non-fluorinated fullerene by fluorinating the donor molecule as well.

  5. Donor level of interstitial hydrogen in GaAs

    International Nuclear Information System (INIS)

    Dobaczewski, L.; Bonde Nielsen, K.; Nylandsted Larsen, A.; Peaker, A.R.

    2006-01-01

    The first data evidencing the existence of the donor level of the interstitial hydrogen in GaAs are presented. The abundant formation of the (0/+) donor level after in situ low-temperature implantation of hydrogen into the depletion layer of GaAs Schottky diodes has been observed and the activation energy and annealing properties have been determined by Laplace DLTS. The activation energy for electron emission of this donor state is 0.14eV. Above 100K the hydrogen deep donor state is unstable, converting to a more stable form when there are electrons available for the capture process. A slightly perturbed form of the hydrogen donor in its neutral charge state can be recovered by illuminating the sample. This process releases twice as many electrons as the ionisation process of the hydrogen donor state itself. This fact, by analogy with the silicon case, evidences the negative-U behaviour of hydrogen in GaAs

  6. Counted Sb donors in Si quantum dots

    Science.gov (United States)

    Singh, Meenakshi; Pacheco, Jose; Bielejec, Edward; Perry, Daniel; Ten Eyck, Gregory; Bishop, Nathaniel; Wendt, Joel; Luhman, Dwight; Carroll, Malcolm; Lilly, Michael

    2015-03-01

    Deterministic control over the location and number of donors is critical for donor spin qubits in semiconductor based quantum computing. We have developed techniques using a focused ion beam and a diode detector integrated next to a silicon MOS single electron transistor to gain such control. With the diode detector operating in linear mode, the numbers of ions implanted have been counted and single ion implants have been detected. Poisson statistics in the number of ions implanted have been observed. Transport measurements performed on samples with counted number of implants have been performed and regular coulomb blockade and charge offsets observed. The capacitances to various gates are found to be in agreement with QCAD simulations for an electrostatically defined dot. This work was performed, in part, at the Center for Integrated Nanotechnologies, a U.S. DOE Office of Basic Energy Sciences user facility. The work was supported by Sandia National Laboratories Directed Research and Development Program. Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the U. S. Department of Energy under Contract No. DE-AC04-94AL85000.

  7. Human body donation in Thailand: Donors at Khon Kaen University.

    Science.gov (United States)

    Techataweewan, N; Panthongviriyakul, C; Toomsan, Y; Mothong, W; Kanla, P; Chaichun, A; Amarttayakong, P; Tayles, N

    2018-03-01

    Culture, society and spirituality contribute to variability in the characteristics of human body donors and donation programmes worldwide. The donors and the body donation programme at Khon Kaen University, northeast Thailand, reflect all these aspects of Thailand, including the status accorded to the donors and the ceremonial acknowledgement of the donors and their families. Data from the programme records and from surveys of samples of currently registering donors and recently received donor bodies are analysed to define the characteristics of both registering and received donors, including motivation, demography, socio-economic status, health, and use of the bodies. The body donation programme at Khon Kaen University currently has a very high rate of registration of body donors, with gender and age differences in the patterns of donation. Registrants include more females than males, a long-standing pattern, and are an average age of 50 years. The bodies of 12% of registrants are received after death and include more males than females. Both sexes are of an average age of 69 years. Males had registered their donation eight years prior to death and females ten years prior. Current registrants identified altruistic motives for their decision to donate, although the coincidence of body donation by a highly revered monk with a surge in donations in 2015 suggests that Buddhism plays a primary role in motivation. The opportunity to make merit for donors and their families, and respect shown to donors and the nature of the ceremonies acknowledging the donors and their families, including the use of the Royal Flame at the cremation ceremony, all contribute to decisions to donate. The characteristics of body donors and the body donation programme at Khon Kaen University are reflective of Thai society and the centrality of Buddhism to Thai culture. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Thalassemia and Hemoglobin E in Southern Thai Blood Donors

    OpenAIRE

    Nuinoon, Manit; Kruachan, Kwanta; Sengking, Warachaya; Horpet, Dararat; Sungyuan, Ubol

    2014-01-01

    Thalassemia and hemoglobin E (Hb E) are common in Thailand. Individuals with thalassemia trait usually have a normal hemoglobin concentration or mild anemia. Therefore, thalassemic individuals who have minimum acceptable Hb level may be accepted as blood donors. This study was aimed at determining the frequency of α-thalassemia 1 trait, β-thalassemia trait, and Hb E-related syndromes in Southern Thai blood donors. One hundred and sixteen voluntary blood donors, Southern Thailand origin, were ...

  9. [Is there an age limit for cadaveric kidney donors currently?].

    Science.gov (United States)

    Cofán Pujol, F; Oppenheimer Salinas, F; Talbot-Wright, R; Carretero González, P

    1996-12-01

    The insufficient number of kidney transplants has gradually raised the age limit to the cadaver kidney donor. The use of grafts harvested from older donors has been debated due to the existing structural and functional changes that might influence renal function and long-term graft survival. The foregoing aspects are discussed herein. The anatomical, histological and functional changes in the kidney associated with ageing are analyzed. The clinical experience with renal grafts from older donors before and after cyclosporine became available are reviewed. The ethical issues on whether grafts from very old donors should be used and who should receive these grafts are discussed. The use of grafts from donors over 60 years old had no significant short and medium term differences in comparison with younger donors in terms of graft survival, although a higher incidence of acute tubular necrosis and poor renal function have been observed. There are no conclusive studies on the long-term effects on graft survival when kidneys from donors aged over 65 are utilized. In our experience, the results achieved with grafts from donors over 70 has been unsatisfactory. The guidelines utilized in the selection of grafts derived from older donors are presented. Grafts from donors aged 60 to 70 may be utilized in renal transplantation following precise selection criteria. Graft survival has been satisfactory, although a higher incidence of acute tubular necrosis and higher creatinine levels have been observed. We do not advocate the use of grafts from donors over 70, except in very exceptional cases. Long-term multicenter studies on grafts from very old donors and trials using alternative immunosuppressor modalities that might permit optimal use of these grafts are warranted.

  10. Cigarette smoke causes caspase-independent apoptosis of bronchial epithelial cells from asthmatic donors.

    Directory of Open Access Journals (Sweden)

    Fabio Bucchieri

    Full Text Available Epidemiologic studies have demonstrated important links between air pollution and asthma. Amongst these pollutants, environmental cigarette smoke is a risk factor both for asthma pathogenesis and exacerbation. As the barrier to the inhaled environment, the bronchial epithelium is a key structure that is exposed to cigarette smoke.Since primary bronchial epithelial cells (PBECs from asthmatic donors are more susceptible to oxidant-induced apoptosis, we hypothesized that they would be susceptible to cigarette smoke-induced cell death.PBECs from normal and asthmatic donors were exposed to cigarette smoke extract (CSE; cell survival and apoptosis were assessed by fluorescence-activated cell sorting, and protective effects of antioxidants evaluated. The mechanism of cell death was evaluated using caspase inhibitors and immunofluorescent staining for apoptosis-inducing factor (AIF.Exposure of PBEC cultures to CSE resulted in a dose-dependent increase in cell death. At 20% CSE, PBECs from asthmatic donors exhibited significantly more apoptosis than cells from non-asthmatic controls. Reduced glutathione (GSH, but not ascorbic acid (AA, protected against CSE-induced apoptosis. To investigate mechanisms of CSE-induced apoptosis, caspase-3 or -9 inhibitors were tested, but these failed to prevent apoptosis; in contrast, CSE promoted nuclear translocation of AIF from the mitochondria. GSH reduced the number of nuclear-AIF positive cells whereas AA was ineffective.Our results show that PBECs from asthmatic donors are more susceptible to CSE-induced apoptosis. This response involves AIF, which has been implicated in DNA damage and ROS-mediated cell-death. Epithelial susceptibility to CSE may contribute to the impact of environmental tobacco smoke in asthma.

  11. Factors affecting the serological testing of cadaveric donor cornea

    Directory of Open Access Journals (Sweden)

    Anuradha Raj

    2018-01-01

    Full Text Available Purpose: The purpose of this study was to evaluate the serological profile of the eye donors and to study the influence of various factors on serological test results. Methods: A cross-sectional, observational study was conducted, and data of 509 donors were reviewed from the records of eye bank from December 2012 to June 2017. Various details of donors analyzed included the age, sex of the donor, cause of death, source of tissue, time since blood collection after death, macroscopic appearance of blood sample, and details of discarded tissues. Serological examination of blood was performed for human immunodeficiency virus (HIV, hepatitis B virus, hepatitis C virus (HCV, venereal disease research laboratory (VDRL, and serology reports reactive or nonreactive were analyzed. Results: Among the 509 donors, 295 (58% were male, and 420 (82.50% belonged to age group ≥60 years. Most donors (354, 69.5% died due to cardiac arrest. Macroscopically, sera were normal in the majority of 488 (95.9% cases. Among 509 donors, 475 (93.3% were nonreactive, 12 (2.4% donors were found to be reactive to hepatitis B surface antigen (HBsAg, and 1 (0.2% was reactive to HCV, but no donor serology was reactive to HIV or VDRL. Twenty-one (4.12% donors' sera were not fit for serological testing. Among all donors, 475 (93.32% donors were accepted and 34 (6.67% were rejected or discarded on the basis of serological testing. Cause of death and macroscopic aspect of sera influenced the serological results in a highly significant manner (P = 0.00. Acceptance or rejection of the donor was significantly influenced by the serological results of the donor (P = 0.00. Conclusion: The seroprevalence among eye donor for HBsAg and HCV was 12 (2.4% and 1 (0.2%, respectively. Factors such as cause of death and macroscopic aspect of sera influence the serological results. Time since blood collection or sampling will not show any impact on viral serological results if postmortem sampling

  12. Donor management parameters and organ yield: single center results.

    Science.gov (United States)

    Marshall, George Ryne; Mangus, Richard S; Powelson, John A; Fridell, Jonathan A; Kubal, Chandrashekhar A; Tector, A Joseph

    2014-09-01

    Management of organ donors in the intensive care unit is an emerging subject in critical care and transplantation. This study evaluates organ yield outcomes for a large number of patients managed by the Indiana Organ Procurement Organization. This is a retrospective review of intensive care unit records from 2008-2012. Donor demographic information and seven donor management parameters (DMP) were recorded at admission, consent, 12 h after consent, and before procurement. Three study groups were created: donors meeting 0-3, 4, or 5-7 DMP. Active donor Organ Procurement Organization management began at consent; so, data analysis focuses on the 12-h postconsent time point. Outcomes included organs transplanted per donor (OTPD) and transplantation of individual solid organs. Complete records for 499 patients were reviewed. Organ yield was 1415 organs of 3992 possible (35%). At 12 h, donors meeting more DMP had more OTPD: 2.2 (0-3) versus 3.0 (4) versus 3.5 (5-7) (P organ except intestine. Oxygen tension, vasopressor use, and central venous pressure were the most frequent independent predictors of organ usage. There were significantly more organs transplanted for donors meeting all three of these parameters (4.5 versus 2.7, P organs, with analysis of individual parameters suggesting that appropriate management of oxygenation, volume status, and vasopressor use could lead to more organs procured per donor. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Kidney transplantation from donors with rhabdomyolysis and acute renal failure.

    Science.gov (United States)

    Chen, Chuan-Bao; Zheng, Yi-Tao; Zhou, Jian; Han, Ming; Wang, Xiao-Ping; Yuan, Xiao-Peng; Wang, Chang-Xi; He, Xiao-Shun

    2017-08-01

    Rhabdomyolysis in deceased donors usually causes acute renal failure (ARF), which may be considered a contraindication for kidney transplantation. From January 2012 to December 2016, 30 kidneys from 15 deceased donors with severe rhabdomyolysis and ARF were accepted for transplantation at our center. The peak serum creatinine (SCr) kinase, myoglobin, and SCr of the these donors were 15 569±8597 U/L, 37 092±42 100 μg/L, and 422±167 μmol/L, respectively. Two donors received continuous renal replacement therapy due to anuria. Six kidneys exhibited a discolored appearance (from brown to glossy black) due to myoglobin casts. The kidney transplant results from the donors with rhabdomyolysis donors were compared with those of 90 renal grafts from standard criteria donors (SCD). The estimated glomerular filtration rate at 2 years was similar between kidney transplants from donors with rhabdomyolysis and SCD (70.3±14.6 mL/min/1.73 m 2 vs 72.3±15.1 mL/min/1.73 m 2 ). We conclude that excellent graft function can be achieved from kidneys donors with ARF caused by rhabdomyolysis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Quality of life of elderly live kidney donors.

    Science.gov (United States)

    Klop, Karel W J; Dols, Leonienke F C; Weimar, Willem; Dooper, Ine M; IJzermans, Jan N M; Kok, Niels F M

    2013-10-15

    Expanding the use of elderly live donors may help meet the demand for kidney transplants. The aim of this study was to quantify the effect of the surgical procedure on the quality of life (QOL) of elderly donors compared with younger donors. Alongside three prospective studies (two randomized) running between May 2001 and October 2010, we asked 501 live donors to fill out the Short Form-36 questionnaire preoperatively and at 1, 3, 6, and 12 months postoperatively. We defined live donors 60 years or older as elderly. Between-group analyses regarding QOL were adjusted for baseline values and gender. One hundred thirty-five donors were older and 366 donors were younger than 60 years. The response rate was high, with 87% at 12 months postoperatively. Elderly donors less often scored as American Society of Anaesthesiology classification 1 (60% vs. 81%; Pvitality" (5 points; P=0.008). At 3 months, "bodily pain" (3 points, P=0.04) and "role physical" (8 points, P=0.02) were still in favor of the older group. At 6 and 12 months, "physical function" was in favor of the younger group (3 and 5 points, respectively; P=0.04 and P<0.001). This study demonstrates that elderly donors recover relatively fast. The perspective of excellent postoperative QOL may help convince elderly individuals to donate.

  15. Scar evaluation of split thickness skin graft donor site

    Directory of Open Access Journals (Sweden)

    Jani Muha

    2014-12-01

    Full Text Available BACKGROUND. Split thickness skin graft harvesting causes a certain degree of scaring on the donor site. Donor site scar can cause aesthetic and functional sequelae on the patient's body. Our goal was to study the process of donor site selection, and then evaluate donor site scars and their impact on patients. PATIENTS AND METHODS. This retrospective study included 45 patients aged 5 to 61 years (in average 36, who have been treated with STSG in the 2004–2010 period. 57.8% of them were men. On a follow-up visit, we photographed healed skin defects and donor sites. We then determined and compared the surface areas of skin defect and the donor site using the Adobe® Illustrator® CS5 computer program. Donor site scars were assessed according to the Vancouver scar scale (VSS. We examined scar’s light touch sensitivity with monofilaments and skin colouring compared to adjacent healthy skin using colorimeter. Patients were also interviewed about their treatment course in a form of a standardized questionnaire. RESULTS. Our research has revealed that 20.0% of patients participated in the decision making process of choosing the donor site, while in 80.0% the donor site was chosen by the surgeon himself. 6.7% of patients were not satisfied with their donor site. Most of the patients (37/45 had donor sites on their thighs. In average, the donor site surface area was 94% bigger than the skin defect area. We found statistically significant differences in VSS values, light touch sensitivity and skin colouring between donor site scaring and adjacent healthy skin. CONCLUSIONS. Donor site scar can represent a lasting aesthetic and functional disability for patients. Our research has shown that most of the patients do not participate in the donor site selection process, but are satisfied with their donor site. In most cases, STGSs are harvested from the thigh, other anatomical regions, where scarring would be aesthetically less obtrusive, are underused

  16. Factors affecting the serological testing of cadaveric donor cornea.

    Science.gov (United States)

    Raj, Anuradha; Mittal, Garima; Bahadur, Harsh

    2018-01-01

    The purpose of this study was to evaluate the serological profile of the eye donors and to study the influence of various factors on serological test results. A cross-sectional, observational study was conducted, and data of 509 donors were reviewed from the records of eye bank from December 2012 to June 2017. Various details of donors analyzed included the age, sex of the donor, cause of death, source of tissue, time since blood collection after death, macroscopic appearance of blood sample, and details of discarded tissues. Serological examination of blood was performed for human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus (HCV), venereal disease research laboratory (VDRL), and serology reports reactive or nonreactive were analyzed. Among the 509 donors, 295 (58%) were male, and 420 (82.50%) belonged to age group ≥60 years. Most donors (354, 69.5%) died due to cardiac arrest. Macroscopically, sera were normal in the majority of 488 (95.9%) cases. Among 509 donors, 475 (93.3%) were nonreactive, 12 (2.4%) donors were found to be reactive to hepatitis B surface antigen (HBsAg), and 1 (0.2%) was reactive to HCV, but no donor serology was reactive to HIV or VDRL. Twenty-one (4.12%) donors' sera were not fit for serological testing. Among all donors, 475 (93.32%) donors were accepted and 34 (6.67%) were rejected or discarded on the basis of serological testing. Cause of death and macroscopic aspect of sera influenced the serological results in a highly significant manner (P = 0.00). Acceptance or rejection of the donor was significantly influenced by the serological results of the donor (P = 0.00). The seroprevalence among eye donor for HBsAg and HCV was 12 (2.4%) and 1 (0.2%), respectively. Factors such as cause of death and macroscopic aspect of sera influence the serological results. Time since blood collection or sampling will not show any impact on viral serological results if postmortem sampling will be done in donor cornea.

  17. [Vascular anatomy of donor and recipient in living kidney transplantation].

    Science.gov (United States)

    Zhang, Jiqing; Zhang, Xiaodong

    2009-09-01

    To review the vascular anatomy of the donor and the recipient for the living kidney transplantation. The recent literature about the vessels of donor and recipient in clinical applications was extensively reviewed. The pertinent vascular anatomy of the donor and recipient was essential for the screening of the proper candidates, surgical planning and long-term outcome. Early branching and accessory renal artery of the donor were particularly important to deciding the side of nephrectomy, surgical technique and anastomosing pattern, and their injuries were the most frequent factor of the conversion from laparoscopic to open surgery. With increase of laparoscopic nephrectomy in donors, accurate venous anatomy was paid more and more attention to because venous bleeding could also lead to conversion to open nephrectomy. Multidetector CT (MDCT) could supplant the conventional excretory urography and renal catheter angiography and could accurately depict the donors' vessels, vascular variations. In addition, MDCT can excellently evaluate the status of donor kidney, collecting system and other pertinent anatomy details. Accurate master of related vascular anatomy can facilitate operation plan and success of operation and can contribute to the rapid development of living donor kidney transplantation. MDCT has become the choice of preoperative one-stop image assessment for living renal donors.

  18. Embryo donation parents' attitudes towards donors: comparison with adoption.

    Science.gov (United States)

    MacCallum, Fiona

    2009-03-01

    Embryo donation produces a family structure where neither rearing parent is genetically related to the child, as in adoption. It is not known how embryo donation parents view the donors compared with how adoptive parents view the birth parents. 21 couples with an embryo donation child aged 2-5 years were compared with 28 couples with an adopted child. Parents were administered a semi-structured interview, assessing knowledge of the donors/birth parents, frequency of thoughts and discussions about the donors/birth parents and disclosure of the donor conception/adoption to the child. Comparisons were made between mothers and fathers to examine gender differences. Embryo donation parents generally knew only the donors' physical characteristics, and thought about and talked about the donors less frequently than adoptive parents thought about and talked about the birth parents. Embryo donation fathers tended to think about the donors less often than did mothers. Disclosure of the child's origins in embryo donation families was far less common than in adoptive families (P parents' views on the donors differ from adoptive parents' views on the birth parents, with donors having little significance in family life once treatment is successful.

  19. On the effect of nuclear bridge modes on donor-acceptor electronic coupling in donor-bridge-acceptor molecules

    International Nuclear Information System (INIS)

    Davis, Daly; Toroker, Maytal Caspary; Speiser, Shammai; Peskin, Uri

    2009-01-01

    We report a theoretical study of intra-molecular electronic coupling in a symmetric DBA (donor-bridge-acceptor) complex, in which a donor electronic site is coupled to an acceptor site by way of intervening orbitals of a molecular bridge unit. In the off-resonant (deep tunneling) regime of electronic transport, the lowest unoccupied molecular orbitals (MO's) of the DBA system are split into distinguishable donor/acceptor and bridge orbitals. The effect of geometrical changes at the bridge on the donor/acceptor electronic energy manifold is studied for local stretching and bending modes. It is demonstrated that the energy splitting in the manifold of donor/acceptor unoccupied MOs changes in response to such changes, as assumed in simple McConnell-type models. Limitations of the simple models are revealed where the electronic charging of the bridge orbitals correlates with increasing donor/acceptor orbital energy splitting only for stretching but not for bending bridge modes.

  20. Liver transplantation from maastricht category 2 non-heart-beating donors: a source to increase the donor pool?

    Science.gov (United States)

    Otero, A; Gómez-Gutiérrez, M; Suárez, F; Arnal, F; Fernández-García, A; Aguirrezabalaga, J; García-Buitrón, J; Alvarez, J; Máñez, R

    2004-04-01

    The demand for liver transplantation has increasingly exceeded the supply of cadaver donor organs. Non-heart-beating donors (NHBDs) may be an alternative to increase the cadaver donor pool. The outcome of 20 liver transplants from Maastricht category 2 NHBD was compared with that of 40 liver transplants from heart-beating donors (HBDs). After unsuccessful cardiopulmonary resuscitation (CPR), cardiopulmonary support with simultaneous application of chest and abdominal compression (CPS; n = 6) or cardiopulmonary bypass (CPB; n = 14) was used to maintain the donors. At a minimum follow-up of 2 years, actuarial patient and graft survival rates with livers from Maastricht category 2 NHBD were 80% and 55%, respectively. Transplantation of organs from these donors was associated with a significantly higher incidence of primary nonfunction, biliary complications, and more severe initial liver dysfunction compared with organs from HBDs. The graft survival rates was 83% for livers from NHBDs preserved with CPS and 42% in those maintained with CPB.

  1. Reproducing whiteness and enacting kin in the Nordic context of transnational egg donation: Matching donors with cross-border traveller recipients in Finland.

    Science.gov (United States)

    Homanen, Riikka

    2018-04-01

    The multimillion-euro fertility industry increasingly tailors its treatments to infertile people who are willing to travel across national borders for treatments inaccessible at home, especially reproductive tissue donor treatments. Finland is the Nordic destination for access to donor eggs, particularly for Swedes and Norwegians hoping for a donor match that will achieve a child of phenotypically plausible biological descent. Finns are seen as Nordic kin, and the inheritability of "Nordicness" is reinforced at clinics. Drawing on ethnographic material from three fertility clinics in Finland during 2015-2017, this article discusses how Nordic relatedness and whiteness are enacted in the practices of matching of donors with recipient parents. The analysis shows a selective and exclusionary rationale to matching built around whiteness: matches between donors with dark skin tone and recipients with fair skin tone are rejected, but a match of a donor with fair skin and recipients with dark skin may be made. Within the context of transnational egg donation, the whiteness or Nordicness of Finns is not questioned as it has been in other historical circumstances. Even the establishment of a state donor register offers a guarantee of kin-ness, especially non-Russian kin-ness. It is concluded that the logics of matching protect the "purity" of whiteness but not browness or blackness, enacting Nordic(kin)ness in ways that are part of broader intra-European histories of racism and post-socialist Othering. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

    Science.gov (United States)

    Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

    2015-11-01

    Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

  3. Individual, contextual and network characteristics of blood donors and non-donors: a systematic review of recent literature

    Science.gov (United States)

    Piersma, Tjeerd W.; Bekkers, René; Klinkenberg, Elisabeth F.; de Kort, Wim L.A.M.; Merz, Eva-Maria

    2017-01-01

    Background The ageing population and recent migration flows may negatively affect the blood supply in the long term, increasing the importance of targeted recruitment and retention strategies to address donors. This review sought to identify individual, network and contextual characteristics related to blood donor status and behaviour, to systematically discuss differences between study results, and to identify possible factors to target in recruitment and retention efforts. Methods The systematic review was conducted in accordance with a predefined PROSPERO protocol (CRD42016039591). After quality assessments by multiple independent raters, a final set of 66 peer-reviewed papers, published between October 2009 and January 2017, were included for review. Results Individual and contextual characteristics of blood donor status and behaviour were categorised into five main lines of research: donor demographics, motivations and barriers, adverse reactions and deferral, contextual factors, and blood centre factors. Results on donor demographics, motivations and barriers, and contextual factors were inconclusive, differing between studies, countries, and sample characteristics. Adverse reactions and deferral were negatively related to blood donor behaviour. Blood centre factors play an important role in donor management, e.g., providing information, reminders, and (non-)monetary rewards. No studies were found on network characteristics of (non-)donors. Discussion Although individual and contextual characteristics strongly relate to blood donor status and behaviour, mechanisms underlying these relations have not been studied sufficiently. We want to stress the importance of longitudinal studies in donor behaviour, exploring the role of life events and network characteristics within blood donor careers. Increased understanding of donor behaviour will assist policy makers of blood collection agencies, with the ultimate goal of safeguarding a sufficient and matching blood

  4. Individual, contextual and network characteristics of blood donors and non-donors: a systematic review of recent literature.

    Science.gov (United States)

    Piersma, Tjeerd W; Bekkers, René; Klinkenberg, Elisabeth F; De Kort, Wim L A M; Merz, Eva-Maria

    2017-09-01

    The ageing population and recent migration flows may negatively affect the blood supply in the long term, increasing the importance of targeted recruitment and retention strategies to address donors. This review sought to identify individual, network and contextual characteristics related to blood donor status and behaviour, to systematically discuss differences between study results, and to identify possible factors to target in recruitment and retention efforts. The systematic review was conducted in accordance with a predefined PROSPERO protocol (CRD42016039591). After quality assessments by multiple independent raters, a final set of 66 peer-reviewed papers, published between October 2009 and January 2017, were included for review. Individual and contextual characteristics of blood donor status and behaviour were categorised into five main lines of research: donor demographics, motivations and barriers, adverse reactions and deferral, contextual factors, and blood centre factors. Results on donor demographics, motivations and barriers, and contextual factors were inconclusive, differing between studies, countries, and sample characteristics. Adverse reactions and deferral were negatively related to blood donor behaviour. Blood centre factors play an important role in donor management, e.g., providing information, reminders, and (non-)monetary rewards. No studies were found on network characteristics of (non-)donors. Although individual and contextual characteristics strongly relate to blood donor status and behaviour, mechanisms underlying these relations have not been studied sufficiently. We want to stress the importance of longitudinal studies in donor behaviour, exploring the role of life events and network characteristics within blood donor careers. Increased understanding of donor behaviour will assist policy makers of blood collection agencies, with the ultimate goal of safeguarding a sufficient and matching blood supply.

  5. Diaphragmatic herniation following donor hepatectomy for living donor liver transplantation: a serious complication not given due recognition.

    Science.gov (United States)

    Lochan, Rajiv; Saif, Rehan; Ganjoo, Naveen; Sakpal, Mallikarjun; Panackal, Charles; Raja, Kaiser; Reddy, Jayanth; Asthana, Sonal; Jacob, Mathew

    2017-11-01

    A clear appreciation of benefits and risks associated with living donor hepatectomy is important to facilitate counselling for the donor, family, and recipient in preparation for living donor liver transplant (LDLT). We report a life-threatening complication occurring in one of our live liver donors at 12 weeks following hemi-liver donation. We experienced five donor complications among our first 50 LDLT: Clavien Grade 1, n=1; Clavien grade 2, n=3; and Clavien grade 3B, n=1. The one with Clavien grade 3B had a life-threatening diaphragmatic hernia occurring 12 weeks following hepatectomy. This was promptly recognized and emergency surgery was performed. The donor is well at 1-year follow-up. Here we provide a review of reported instances of diaphragmatic hernia following donor hepatectomy with an attempt to elucidate the pathophysiology behind such occurrence. Life-threatening donor risk needs to be balanced with recipient benefit and risk on a tripartite basis during the counselling process for LDLT. With increasing use of LDLT, we need to be aware of such life-threatening complication. Preventive measures in this regard and counselling for such complication should be incorporated into routine work-up for potential live liver donor.

  6. The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy.

    Science.gov (United States)

    Dietrich, Nadine; Kolibabka, Matthias; Busch, Stephanie; Bugert, Petra; Kaiser, Ulrike; Lin, Jihong; Fleming, Thomas; Morcos, Michael; Klein, Thomas; Schlotterer, Andrea; Hammes, Hans-Peter

    2016-01-01

    Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear. Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks), DPP4 activity (fluorometric assay), GLP-1 (ELISA), methylglyoxal (LC-MS/MS), acellular capillaries and pericytes (quantitative retinal morphometry), SDF-1a and heme oxygenase-1 (ELISA), HMGB-1, Iba1 and Thy1.1 (immunohistochemistry), nuclei in the ganglion cell layer, GFAP (western blot), and IL-1beta, Icam1, Cxcr4, catalase and beta-actin (quantitative RT-PCR) were determined. In C. elegans, neuronal function was determined using worm tracking software. Linagliptin decreased DPP4 activity by 77% and resulted in an 11.5-fold increase in active GLP-1. Blood glucose and HbA1c were reduced by 13% and 14% and retinal methylglyoxal by 66%. The increase in acellular capillaries was diminished by 70% and linagliptin prevented the loss of pericytes and retinal ganglion cells. The rise in Iba-1 positive microglia was reduced by 73% with linagliptin. In addition, the increase in retinal Il1b expression was decreased by 65%. As a functional correlate, impairment of motility (body bending frequency) was significantly prevented in C. elegans. Our data suggest that linagliptin has a protective effect on the microvasculature of the diabetic retina, most likely due to a combination of neuroprotective and antioxidative effects of linagliptin on the neurovascular unit.

  7. The DPP4 Inhibitor Linagliptin Protects from Experimental Diabetic Retinopathy.

    Directory of Open Access Journals (Sweden)

    Nadine Dietrich

    Full Text Available Dipeptidyl peptidase 4 (DPP4 inhibitors improve glycemic control in type 2 diabetes, however, their influence on the retinal neurovascular unit remains unclear.Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats (diabetes duration of 24 weeks, DPP4 activity (fluorometric assay, GLP-1 (ELISA, methylglyoxal (LC-MS/MS, acellular capillaries and pericytes (quantitative retinal morphometry, SDF-1a and heme oxygenase-1 (ELISA, HMGB-1, Iba1 and Thy1.1 (immunohistochemistry, nuclei in the ganglion cell layer, GFAP (western blot, and IL-1beta, Icam1, Cxcr4, catalase and beta-actin (quantitative RT-PCR were determined. In C. elegans, neuronal function was determined using worm tracking software.Linagliptin decreased DPP4 activity by 77% and resulted in an 11.5-fold increase in active GLP-1. Blood glucose and HbA1c were reduced by 13% and 14% and retinal methylglyoxal by 66%. The increase in acellular capillaries was diminished by 70% and linagliptin prevented the loss of pericytes and retinal ganglion cells. The rise in Iba-1 positive microglia was reduced by 73% with linagliptin. In addition, the increase in retinal Il1b expression was decreased by 65%. As a functional correlate, impairment of motility (body bending frequency was significantly prevented in C. elegans.Our data suggest that linagliptin has a protective effect on the microvasculature of the diabetic retina, most likely due to a combination of neuroprotective and antioxidative effects of linagliptin on the neurovascular unit.

  8. Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

    Science.gov (United States)

    Stratta, Robert J; Farney, Alan C; Orlando, Giuseppe; Farooq, Umar; Al-Shraideh, Yousef; Palanisamy, Amudha; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; El-Hennawy, Hany; Khan, Muhammad; Rogers, Jeffrey

    2016-04-01

    The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for

  9. Environmental protection

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    In this chapter environmental protection in the Slovak Republic in 1997 are reviewed. The economics of environmental protection, state budget, Slovak state environmental fund, economic instruments, environmental laws, environmental impact assessment, environmental management systems, and environmental education are presented

  10. The triumph of good over evil: protection by the sickle gene against malaria.

    Science.gov (United States)

    Bunn, H Franklin

    2013-01-03

    The mechanisms underlying Plasmodium falciparum resistance in persons with sickle trait have been under active investigation for more than a half century. This Perspective reviews progress in solving this challenging problem, including recent studies that have exploited the genomics and proteomics of the parasite. The formation of Hb S polymer in the parasitized AS RBC leads to impaired parasite growth and development along with enhanced clearance from the circulation and reduced deposition in deep postcapillary vascular beds. Enhanced generation of reactive oxygen species in sickled AS RBCs is a pathogenetic feature shared by parasitized thalassemic and G6PD-deficient RBCs, triggering abnormal topology of the RBC plasma membrane with decreased and disordered display of PfEMP-1, a P falciparum adhesion protein critical for endothelial adherence. A mouse model of Hb S confers host tolerance to P berghei, through inhibition of pathogenic CD8(+) T cells and induction of heme oxygenase-1. An additional and apparently independent mode of protection is provided by the selective expression in AS RBCs of 2 species of microRNA that integrate into P falciparum mRNAs and inhibit translation and parasite growth.

  11. Protective effects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes.

    Science.gov (United States)

    Chen, Mingcang; Gu, Honggang; Ye, Yiyi; Lin, Bing; Sun, Lijuan; Deng, Weiping; Zhang, Jingzhe; Liu, Jianwen

    2010-10-01

    Increasing evidence regarding free radical generating agents and the inflammatory process suggest that accumulation of reactive oxygen species (ROS) could involve hepatotoxicity. Hesperidin, a naturally occurring flavonoid presents in fruits and vegetables, has been reported to exert a wide range of pharmacological effects that include antioxidant, anti-inflammatory, antihypercholesterolemic, and anticarcinogenic actions. However, the cytoprotection and mechanism of hesperidin to neutralize oxidative stress in human hepatic L02 cells remain unclear. In this work, we assessed the capability of hesperidin to prevent tert-butyl hydroperoxide (t-BuOOH)-induced cell damage by augmenting cellular antioxidant defense. Hesperidin significantly protected hepatocytes against t-BuOOH-induced cell cytotoxicity, such as mitochondrial membrane potential (MMP) deplete and lactate dehydrogenase (LDH) release. Hesperidin also remarkably prevented indicators of oxidative stress, such as the ROS and lipid peroxidation level in a dose-dependent manner. Western blot showed that hesperidin facilitated ERK/MAPK phosphorylation which appeared to be responsible for nuclear translocation of Nrf2, thereby inducing cytoprotective heme oxygenase-1 (HO-1) expression. Based on the results described above, it suggested that hesperidin has potential as a therapeutic agent in the treatment of oxidative stress-related hepatocytes injury and liver dysfunctions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.

    Science.gov (United States)

    Zeng, Bin; Ren, Xiaofeng; Lin, Guosheng; Zhu, Chengang; Chen, Honglei; Yin, Jiechao; Jiang, Hong; Yang, Bo; Ding, Danhua

    2008-10-01

    The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-beta, VEGF and IL-1beta, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators.

  13. Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses.

    Science.gov (United States)

    Schriner, Samuel E; Avanesian, Agnesa; Liu, Yanxia; Luesch, Hendrik; Jafari, Mahtab

    2009-09-01

    Rhodiola rosea root has been long used in traditional medical systems in Europe and Asia as an adaptogen to increase an organism's resistance to physical stress. Recent research has demonstrated its ability to improve mental and physical stamina, to improve mood, and to help alleviate high-altitude sickness. We have also recently found that R. rosea is able to extend the life span of Drosophila melanogaster. The mode of action of R. rosea is currently unknown; it has been suggested by some to act as an antioxidant, whereas others have argued that it may actually be a pro-oxidant and act through a hormetic mechanism. We found that R. rosea supplementation could protect cultured cells against ultraviolet light, paraquat, and H(2)O(2). However, it did not alter the levels of the major antioxidant defenses nor did it markedly activate the antioxidant response element or modulate heme-oxygenase-1 expression levels at relevant concentrations. In addition, R. rosea extract was not able to significantly degrade H(2)O(2) in vitro. These results suggest that in human cultured cells R. rosea does not act as an antioxidant and that its mode of action cannot be sufficiently explained through a pro-oxidant hormetic mechanism.

  14. Supplemental dietary phytosterin protects against 4-nitrophenol-induced oxidative stress and apoptosis in rat testes

    Directory of Open Access Journals (Sweden)

    Yonghui Zhang

    2015-01-01

    Full Text Available 4-Nitrophenol (PNP, is generally regarded as an environmental endocrine disruptor (EED. Phytosterin (PS, a new feed additive, possesses highly efficient antioxidant activities. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf2, is an important regulator of cellular oxidative stress. Using rats, this study examined PNP-induced testicular oxidative damage and PS-mediated protection against that damage. The generation of MDA and H2O2 upon PNP and PS treatment was milder than that upon treatment with PNP alone. This mitigation was accompanied by partially reversed changes in SOD, CAT, GSH and GSH-Px. Moreover, PNP significantly reduced the caudal epididymal sperm counts and serum testosterone levels. Typical morphological changes were also observed in the testes of PNP-treated animals. PNP reduced the transcriptional level of Nrf2, as evaluated by RT-PCR, but it promoted the dissociation from the Nrf2 complex, stabilization and translocation into the nucleus, as evaluated by immunohistochemistry and Western blotting. In addition, PNP enhanced the Nrf2-dependent gene expression of heme oxygenase-1 (HO-1 and glutamate–cysteine ligase catalytic subunit (GCLC. These results suggest that the Nrf2 pathway plays an important role in PNP-induced oxidative damage and that PS possesses modulatory effects on PNP-induced oxidative damage in rat testes.

  15. The impact of meeting donor management goals on the number of organs transplanted per donor: results from the United Network for Organ Sharing Region 5 prospective donor management goals study.

    Science.gov (United States)

    Malinoski, Darren J; Patel, Madhukar S; Daly, Michael C; Oley-Graybill, Chrystal; Salim, Ali

    2012-10-01

    Many organ procurement organizations have implemented critical care end points as donor management goals in efforts to increase organs transplanted per donor after neurologic determination of death. Although retrospective studies have demonstrated an association between meeting donor management goals and organ yield, prospective studies are lacking. In June 2008, nine donor management goals were prospectively implemented as a checklist and every donor after neurologic determination of death was managed to meet them. The donor management goals represented normal cardiovascular, pulmonary, renal, and endocrine end points. Data were collected for 7 months. Donor management goals "met" was defined a priori as achieving any seven of the nine donor management goals, and this was recorded at the time of consent, 12-18 hrs later, and prior to organ recovery. The primary outcome measure was ≥4 organs transplanted per donor, and binary logistic regression was used to identify independent predictors of this outcome with a porgan procurement organizations in the five Southwestern United States (United Network for Organ Sharing Region 5). All standard criteria donors after neurologic determination of deaths. Prospective implementation of a donor management goal checklist. There were 380 standard criteria donors with 3.6±1.7 organs transplanted per donor. Fifteen percent had donor management goals met at the time of consent, 33% at 12-18 hrs, and 38% prior to organ recovery. Forty-eight percent had ≥4 organs transplanted per donor. Donors with ≥4 organs transplanted per donor had significantly more individual donor management goals met at all three time points. Independent predictors of ≥4 organs transplanted per donor were age (odds ratio=0.95 per year), final creatinine (odds ratio=0.75 per 1-unit increase), donor management goals "met" at consent (odds ratio=2.03), donor management goals "met" prior to organ recovery (odds ratio=2.34), and a change in the number of

  16. Enzymatic O-Galactosylation of Selected Free as Well as Partially Protected Ketohexoses

    DEFF Research Database (Denmark)

    Eder, B.; Lundt, Inge; Stütz, A. E.

    2001-01-01

    A range of partially protected ketoses was O-galactosylated with P-galactosidase from Aspergillus oryzae employing (4-nitro)phenyl beta -D-galactopyranoside as the donor. This enzyme also accepted free D-tagatose as a substrate.......A range of partially protected ketoses was O-galactosylated with P-galactosidase from Aspergillus oryzae employing (4-nitro)phenyl beta -D-galactopyranoside as the donor. This enzyme also accepted free D-tagatose as a substrate....

  17. Haemoglobin variants among voluntary blood donors in Jos, Nigeria ...

    African Journals Online (AJOL)

    This study aimed to determine the haemoglobin variants among voluntary blood donors in Jos. METHOD: Records of the age, sex, Haemoglobin level, and the haemoglobin genotype of all voluntary blood donors who donated blood at the National Blood Transfusion Service Centre, Jos, Nigeria between January 2011 and ...

  18. Settlement Ends Dispute between Princeton and Donors' Heirs

    Science.gov (United States)

    Masterson, Kathryn; Gose, Ben

    2009-01-01

    This article reports that Princeton University has settled a long-running dispute with the heirs of a major donor by agreeing to pay $50-million to the heirs' foundation and approximately the same amount for their legal fees. The case has been closely watched as a test of how strictly institutions must adhere to donors' wishes. The settlement…

  19. Seroprevalence of hiv and hepatitis viruses in directed blood donors ...

    African Journals Online (AJOL)

    Aims: To determine the seroprevalence of HIV and Hepatitis B viruses in directed blood donors in Nguru and also to see if there is co-infection of these viruses in this category of donor population. Method: This is a prospective study carried out at the blood bank of the Federal Medical Centre Nguru, Yobe State between ...

  20. Optimal screening and donor management in a public stool bank.

    Science.gov (United States)

    Kazerouni, Abbas; Burgess, James; Burns, Laura J; Wein, Lawrence M

    2015-12-17

    Fecal microbiota transplantation is an effective treatment for recurrent Clostridium difficile infection and is being investigated as a treatment for other microbiota-associated diseases. To facilitate these activities, an international public stool bank has been created, which screens donors and processes stools in a standardized manner. The goal of this research is to use mathematical modeling and analysis to optimize screening and donor management at the stool bank. Compared to the current policy of screening active donors every 60 days before releasing their quarantined stools for sale, costs can be reduced by 10.3 % by increasing the screening frequency to every 36 days. In addition, the stool production rate varies widely across donors, and using donor-specific screening, where higher producers are screened more frequently, also reduces costs, as does introducing an interim (i.e., between consecutive regular tests) stool test for just rotavirus and C. difficile. We also derive a donor release (i.e., into the system) policy that allows the supply to approximately match an exponentially increasing deterministic demand. More frequent screening, interim screening for rotavirus and C. difficile, and donor-specific screening, where higher stool producers are screened more frequently, are all cost-reducing measures. If screening costs decrease in the future (e.g., as a result of bringing screening in house), a bottleneck for implementing some of these recommendations may be the reluctance of donors to undergo serum screening more frequently than monthly.

  1. Increasing the pool of deceased donor organs for kidney transplantation.

    Science.gov (United States)

    Schold, Jesse D; Segev, Dorry L

    2012-03-27

    Expanding the pool of available deceased donor kidneys is critical for improving the outcomes of prospective and current renal transplant candidates. A number of interventions have been proposed that may increase the pool of donors in the US. However, these interventions have variable levels of empirical evidence supporting their potential beneficial impact. Proposed interventions include the instigation of policies for presumed donor consent, the expansion of donor registration, increased quality oversight of transplant providers, financial incentives for donors, increased reimbursement for higher risk donors, alterations in organ allocation policies and distribution, and the selective use of donors with potential or known risk for disease transmission. Many of these interventions have contentious elements that may have delayed or impeded their implementation; however, these options should be considered in the context of the diminishing prognoses for prospective transplant patients, given the increasing scarcity of donor organs relative to the population need. In this Review, we outline the proposed interventions and briefly discuss salient issues that characterize the debates concerning their implementation and effectiveness. Ultimately, any intervention must be based on the best evidence available, with consideration of numerous stakeholders and in conjunction with a careful evaluation of long-term and potential unintended consequences.

  2. Optimization of IVF pregnancy outcomes with donor spermatozoa.

    Science.gov (United States)

    Wang, Jeff G; Douglas, Nataki C; Prosser, Robert; Kort, Daniel; Choi, Janet M; Sauer, Mark V

    2009-03-01

    To identify risk factors for suboptimal IVF outcomes using insemination with donor spermatozoa and to define a lower threshold that may signal a conversion to fertilization by ICSI rather than insemination. Retrospective, age-matched, case-control study of women undergoing non-donor oocyte IVF cycles using either freshly ejaculated (N=138) or cryopreserved donor spermatozoa (N=69). Associations between method of fertilization, semen sample parameters, and pregnancy rates were analyzed. In vitro fertilization of oocytes with donor spermatozoa by insemination results in equivalent fertilization and pregnancy rates compared to those of freshly ejaculated spermatozoa from men with normal semen analyses when the post-processing motility is greater than or equal to 88%. IVF by insemination with donor spermatozoa when the post-processing motility is less than 88% is associated with a 5-fold reduction in pregnancy rates when compared to those of donor spermatozoa above this motility threshold. When the post-processing donor spermatozoa motility is low, fertilization by ICSI is associated with significantly higher pregnancy rates compared to those of insemination. While ICSI does not need to be categorically instituted when using donor spermatozoa in IVF, patients should be counseled that conversion from insemination to ICSI may be recommended based on low post-processing motility.

  3. Fermilab Friends for Science Education | Programs | Past Donors

    Science.gov (United States)

    Fermilab Friends for Science Education FFSE Home About Us Join Us Support Us Contact Us Our Donors Testimonials Our Donors Board of Directors Board Tools Calendar Join Us Donate Now Get FermiGear! Education DuPage Area Occupational Education Systems Technology Center DuPage/Kane Educational Service Center Fermi

  4. Crowd Around: Expanding Your Donor Pool with Crowdfunding

    Science.gov (United States)

    Jarrell, Andrea

    2013-01-01

    At most institutions, annual fund-giving is down. Crowdfunding sites allow people with a great idea or worthy cause to bypass traditional funding methods and take their case directly to web-savvy investors and donors. This article describes how higher education institutions are expanding their donor pool through such crowdfunding sites as USEED,…

  5. 21 CFR 640.3 - Suitability of donor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Suitability of donor. 640.3 Section 640.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... determination shall be made on the day of collection from the donor by means of medical history, a test for...

  6. 21 CFR 640.63 - Suitability of donor.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Suitability of donor. 640.63 Section 640.63 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... determination shall be made on the day of collection from the donor by means of a medical history, tests, and...

  7. Digging up Classroom Dollars on DonorsChoose

    Science.gov (United States)

    Curriculum Review, 2006

    2006-01-01

    Back in 2000, Charles Best was teaching at Wings Academy, an alternative high school in the Bronx, when he got the idea for a Web site where teachers could solicit donations for class projects. With help from his students, DonorsChoose.org soon was born. Last year, the site won Amazon.com's Nonprofit Innovation Award. So far, DonorsChoose has…

  8. Parasitological profile of perstans filariasis among blood donors in ...

    African Journals Online (AJOL)

    The study was conducted at Ile – Ife, in Osun State Southwest Nigeria between March and September, 2009 with a view to determine the prevalence of blood filariasis among blood donors. The blood samples of 250 blood donors were parasitologically examined directly with wet preparation, while the thick and thin films ...

  9. You...as Blood Donor: Teacher Strategies and Student Worksheets.

    Science.gov (United States)

    Degroat, Diane Zagare; And Others

    This curriculum guide for teaching about blood donation was prepared to improve school-community participation in the New York City Blood Donor Program. It contains plans for five lessons on the following topics: (1) the nature of blood; (2) blood and technology--modern-day advances; (3) blood and your personal health; (4) the blood donor as good…

  10. Unconfirmed reactive screening tests and their impact on donor management

    International Nuclear Information System (INIS)

    Rahman, M.; Khan, S.A.

    2008-01-01

    To determine the percentage of false positive testing for transfusion transmitted infections (TTIs) using immunochromatographic test (ICT) as first line of screening tests and its effect on loss of volunteer blood donors. Over a period of three months, samples from blood bags of donors undergoing phlebotomy at teaching hospital blood banks in Lahore were screened for human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) by immunochromatographic tests. Those found positive on initial screening were re-tested by ELISA method at the screening laboratory of the Institute of Haematology and Blood Transfusion Service, Punjab. Lahore. Out of a total of 62090 voluntary blood donors, 469 donors were found to be initially reactive for either HIV, HBV or HCV. Amongst these 96 (0.15%) blood donors were found to have tested falsely positive for HIV, HBV or HCV as compared to testing by ELISA. False positive testing rate of 0.15% or 96 out of a total of 62090 donors is rather small in terms of loss of voluntary donors and appropriate utilization of available resources. Although immunochromatographic testing is not the gold standard, however it serves an important purpose of initial donor screening. (author)

  11. Modeling charge transfer at organic donor-acceptor semiconductor interfaces

    NARCIS (Netherlands)

    Cakir, Deniz; Bokdam, Menno; de Jong, Machiel Pieter; Fahlman, M.; Brocks, G.

    2012-01-01

    We develop an integer charge transfer model for the potential steps observed at interfaces between donor and acceptor molecular semiconductors. The potential step can be expressed as the difference between the Fermi energy pinning levels of electrons on the acceptor material and holes on the donor

  12. Prevalence of HIV positive blood donors among screened ...

    African Journals Online (AJOL)

    Two thousand five hundred and thirty two (2,532) males, aged 25 – 50 years potential blood donors were randomly selected from the total number of volunteer blood donors who satisfied the initial screening criteria for donating blood, and were screened for HIV using Immunocomb II (HIV 1 and 2 Bispot) and Recombigen ...

  13. Current status of malaria parasite among blood donors in Port ...

    African Journals Online (AJOL)

    This study was carried out to determine the prevalence of malaria parasite among blood donors at the Police Clinic Port Harcourt, Rivers State, Nigeria. The standard parasitological techniques using both thick and thin blood films from the donors for the detection of malaria parasite was followed. Venous blood was ...

  14. Prevalence of HIV among blood donors at Juba Teaching Hospital ...

    African Journals Online (AJOL)

    Male. 85. (99%). 193. (99%). 34. (100%). 102. (97%). 414. Female. 1(1%). 2(1%). 0. 3(3%). 6. Total. 86. 195. 34. 105. 420. Figure 1. Distribution (percent) of HIV, HBV, HCV and syphilis among blood donors. Table 3. Distribution of blood groups among blood donors. Blood group. Frequency. Percentage (%). A+ve. 270. 24.7.

  15. Prevalence of HIV positive blood donors among screened ...

    African Journals Online (AJOL)

    hope&shola

    2006-04-03

    Apr 3, 2006 ... Department of Physiology, Obafemi Awolowo College of Health Sciences, Olabisi Onabanjo University Teaching. Hospital ... screening volunteer donors by initial criteria alone does not fully eliminate all HIV positive donors. The prevalence of HIV ... HIV test criteria alone to qualify for blood donation in the.

  16. Prevalence of haemolysins in blood donors in Nnamdi Azikiwe ...

    African Journals Online (AJOL)

    Background: The presence of high titres of haemolysins (lytic antibodies) in the sera of donors could predispose to adverse blood transfusion reactions. Objective: To evaluate the prevalence of haemolysins among blood donors at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State. Methodology: A ...

  17. Seroprevalence of Treponema Pallidum in Donor Blood at the ...

    African Journals Online (AJOL)

    Objectives: To determine the Seroprevalence of Treponema pallidum in Donor blood at University of Benin Teaching Hospital Benin City. Materials and Method: This is a descriptive hospital based study. Donor blood supplied to the hospital blood bank was screened for syphilis. The study was conducted between February ...