Sample records for gadolinium decreases inflammation

  1. Are gadolinium-based contrast media nephrotoxic? A renal biopsy study.

    PubMed

    Akgun, Hulya; Gonlusen, Gulfiliz; Cartwright, Joiner; Suki, Wadi N; Truong, Luan D

    2006-09-01

    Gadolinium-based contrast media were originally introduced as alternatives to iodinated media for magnetic resonance imaging. Although originally thought to be nonnephrotoxic, gadolinium-based contrast media have recently been reported to be associated with acute renal failure; the mechanism and the underlying renal injury are not completely understood. We report what is, to our knowledge, the first renal biopsy in this context. A 56-year-old patient underwent 2 consecutive vascular imaging procedures in conjunction with gadolinium-based contrast medium administration. A few days later, the patient developed acute renal failure. A renal biopsy showed acute tubular cell injury including patchy tubular cell necrosis, tubular cell degeneration, and marked proliferation of tubular cells, together with mild interstitial edema and interstitial inflammation, but without significant glomerular or vascular changes. During supportive therapy, renal function was partially regained. This case emphasizes the potential nephrotoxicity of gadolinium-based contrast media and suggests that the nephrotoxicity is related to potentially reversible acute tubular cell injury.

  2. Gadolinium toxicity and treatment.

    PubMed

    Ramalho, Joana; Ramalho, Miguel; Jay, Michael; Burke, Lauren M; Semelka, Richard C

    2016-12-01

    Gadolinium based contrast agents (GBCAs) play an important role in the diagnostic evaluation of many patients. The safety of these agents has been once again questioned after gadolinium deposits were observed and measured in brain and bone of patients with normal renal function. This retention of gadolinium in the human body has been termed "gadolinium storage condition". The long-term and cumulative effects of retained gadolinium in the brain and elsewhere are not as yet understood. Recently, patients who report that they suffer from chronic symptoms secondary to gadolinium exposure and retention created gadolinium-toxicity on-line support groups. Their self-reported symptoms have recently been published. Bone and joint complaints, and skin changes were two of the most common complaints. This condition has been termed "gadolinium deposition disease". In this review we will address gadolinium toxicity disorders, from acute adverse reactions to GBCAs to gadolinium deposition disease, with special emphasis on the latter, as it is the most recently described and least known. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Nephrogenic Systemic Fibrosis Manifesting a Decade After Exposure to Gadolinium.

    PubMed

    Larson, Krista N; Gagnon, Amy L; Darling, Melissa D; Patterson, James W; Cropley, Thomas G

    2015-10-01

    Nephrogenic systemic fibrosis (NSF) is a fibrosing skin disorder that develops in patients with kidney failure and has been linked to exposure to gadolinium-containing contrast agents. The time between exposure to gadolinium and the initial presentation of NSF is typically weeks to months but has been documented to be as long as 3½ years. We report a case of NSF developing 10 years after exposure to gadolinium. A long-term hemodialysis patient was exposed to gadolinium several times between 1998 and 2004 during magnetic resonance angiography of his abdominal vessels and arteriovenous fistula. In 2014, he was seen at our clinic with new dermal papules and plaques. Biopsy of affected skin showed thickening of collagen, CD34+ spindle cells, and increased mucin in the dermis, supporting the diagnosis of NSF. The clinical history and histopathological features of this case support the diagnosis of NSF 10 years after exposure to gadolinium. Although the use of gadolinium contrast agents in patients with kidney failure has markedly decreased, patients with exposure to gadolinium years to decades previously may manifest the disease.

  4. Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation.

    PubMed

    Xue, Peng; Li, Bei; An, Ying; Sun, Jin; He, Xiaoning; Hou, Rui; Dong, Guangying; Fei, Dongdong; Jin, Fang; Wang, Qintao; Jin, Yan

    2016-11-01

    The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis.

  5. Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

    PubMed

    Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

    2006-12-11

    In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection.

  6. Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

    DOE PAGES

    Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; ...

    2014-11-07

    High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperaturemore » of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.« less

  7. Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.

    High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperaturemore » of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.« less

  8. Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

    NASA Astrophysics Data System (ADS)

    Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; Vohra, Yogesh K.

    2014-10-01

    High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Sm-type → dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GPa and a temperature of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.

  9. Iron Supplementation Decreases Severity of Allergic Inflammation in Murine Lung

    PubMed Central

    Hale, Laura P.; Kant, Erin Potts; Greer, Paula K.; Foster, W. Michael

    2012-01-01

    The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans. PMID:23029172

  10. Synthesis of gadolinium doped titanium(IV) oxide and their photocatalytic activity to decrease chemical oxygen demand (COD) value of water pollutants

    NASA Astrophysics Data System (ADS)

    Eddy, Diana Rakhmawaty; Dwiyanti, Dina; Rahayu, Iman; Hastiawan, Iwan; Bahti, Husein H.

    2017-05-01

    Pesticides are widely used for the control of plant disease. Unfortunately they are highly toxic to terraneous and aquatic life; this is a particular problem in agricultural areas. TiO2 is widely used for pesticide control because of its photocatalytic activity, but it still has inadequacy in its wide band gap. Alternatively, the wide band gap of TiO2 could be narrowed by modification with rare earth element such as gadolinium, so the photocatalytic activity of TiO2could be significantly enhanced. The purpose of this experiment is to synthesize Gd/TiO2 and its application to reduce COD of water pollutants such as carbosulfan pesticide. This experiment is done by doping gadolinium oxide into titanium tetra isopropoxide by sol-gel method. The crystal structure is characterized by using XRD, shown anatase successfully obtained with the smallest crystallite size is 37.655 nm, indicated optimum calcination time is 4 hours. SEM-EDX result shown morphology of crystal is big aggregates. Photocatalytic activity is tested to carbosulfan pesticide, obtained the COD percent decreases up to 87.88%.

  11. Subcellular SIMS imaging of gadolinium isotopes in human glioblastoma cells treated with a gadolinium containing MRI agent

    NASA Astrophysics Data System (ADS)

    Smith, Duane R.; Lorey, Daniel R.; Chandra, Subhash

    2004-06-01

    Neutron capture therapy is an experimental binary radiotherapeutic modality for the treatment of brain tumors such as glioblastoma multiforme. Recently, neutron capture therapy with gadolinium-157 has gained attention, and techniques for studying the subcellular distribution of gadolinium-157 are needed. In this preliminary study, we have been able to image the subcellular distribution of gadolinium-157, as well as the other six naturally abundant isotopes of gadolinium, with SIMS ion microscopy. T98G human glioblastoma cells were treated for 24 h with 25 mg/ml of the metal ion complex diethylenetriaminepentaacetic acid Gd(III) dihydrogen salt hydrate (Gd-DTPA). Gd-DTPA is a contrast enhancing agent used for MRI of brain tumors, blood-brain barrier impairment, diseases of the central nervous system, etc. A highly heterogeneous subcellular distribution was observed for gadolinium-157. The nuclei in each cell were distinctly lower in gadolinium-157 than in the cytoplasm. Even within the cytoplasm the gadolinium-157 was heterogeneously distributed. The other six naturally abundant isotopes of gadolinium were imaged from the same cells and exhibited a subcellular distribution consistent with that observed for gadolinium-157. These observations indicate that SIMS ion microscopy may be a viable approach for subcellular studies of gadolinium containing neutron capture therapy drugs and may even play a major role in the development and validation of new gadolinium contrast enhancing agents for diagnostic MRI applications.

  12. MRI of normal and abnormal duodenum using Half-Fourier Single-Shot RARE and gadolinium-enhanced spoiled gradient echo sequences.

    PubMed

    Marcos, H B; Semelka, R C; Noone, T C; Woosley, J T; Lee, J K

    1999-07-01

    The objective of this research was two-fold: First, to describe the normal and abnormal MR appearances of the duodenum using combined Half-Fourier Acquisition Single Shot RARE (HASTE) and gadolinium-enhanced standard and fat suppressed spoiled gradient echo (SGE) sequences. The second objective was to assess the ability of these combined sequences to detect and characterize duodenal diseases. MR examinations were performed on fifty consecutive patients with no clinical history of duodenal diseases, who were 1) imaged with HASTE and gadolinium-enhanced standard and fat suppressed SGE sequences and 2) referred to MR examination for reasons other than duodenal diseases, and were reviewed retrospectively to determine the normal MR appearances of the duodenum. A second population of patients with abnormal duodenum who were imaged with the same MR sequences were included in the second part of this study. This population was composed of 20 consecutive patients with subsequently proven duodenal abnormalities, including: malrotation (2), diverticula (4), intussusception (1), sprue (1), polyps (2), neurofibroma (1), lymphoma (1), Zollinger Ellison syndrome (1), metastatic disease (1), Crohn's disease (1), and wall thickening and duodenitis (5). Normal measurements of the duodenum are described. Abnormalities of wall thickness and duodenal masses required combined HASTE and gadolinium-enhanced SGE images to evaluate well. Abnormalities of the bowel lumen (e.g., diverticula and intussusception), and developmental variants (e.g., malrotation), were sufficiently visualized on HASTE images alone. Bowel inflammation was best shown on gadolinium-enhanced fat suppressed SGE images. HASTE and gadolinium-enhanced fat suppressed SGE sequences are complementary techniques for the demonstration of normal and abnormal duodenum. The combined use of both sequences allows evaluation of different aspects of bowel diseases; abnormalities of position, lumen, and contents are well shown on HASTE

  13. Surfactant protein C dampens inflammation by decreasing JAK/STAT activation during lung repair.

    PubMed

    Jin, Huiyan; Ciechanowicz, Andrzej K; Kaplan, Alanna R; Wang, Lin; Zhang, Ping-Xia; Lu, Yi-Chien; Tobin, Rachel E; Tobin, Brooke A; Cohn, Lauren; Zeiss, Caroline J; Lee, Patty J; Bruscia, Emanuela M; Krause, Diane S

    2018-05-01

    Surfactant protein C (SPC), a key component of pulmonary surfactant, also plays a role in regulating inflammation. SPC deficiency in patients and mouse models is associated with increased inflammation and delayed repair, but the key drivers of SPC-regulated inflammation in response to injury are largely unknown. This study focuses on a new mechanism of SPC as an anti-inflammatory molecule using SPC-TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein C knockout) mice, which represent a novel sterile injury model that mimics clinical acute respiratory distress syndrome (ARDS). SPC-TK mice express the inducible suicide gene thymidine kinase from by the SPC promoter, which targets alveolar type 2 (AT2) cells for depletion in response to ganciclovir (GCV). We compared GCV-induced injury and repair in SPC-TK mice that have normal endogenous SPC expression with SPC-TK/SPC-KO mice lacking SPC expression. In contrast to SPC-TK mice, SPC-TK/SPC-KO mice treated with GCV exhibited more severe inflammation, resulting in over 90% mortality; there was only 8% mortality of SPC-TK animals. SPC-TK/SPC-KO mice had highly elevated inflammatory cytokines and granulocyte infiltration in the bronchoalveolar lavage (BAL) fluid. Consistent with a proinflammatory phenotype, immunofluorescence revealed increased phosphorylated signal transduction and activation of transcription 3 (pSTAT3), suggesting enhanced Janus kinase (JAK)/STAT activation in inflammatory and AT2 cells of SPC-TK/SPC-KO mice. The level of suppressor of cytokine signaling 3, an anti-inflammatory mediator that decreases pSTAT3 signaling, was significantly decreased in the BAL fluid of SPC-TK/SPC-KO mice. Hyperactivation of pSTAT3 and inflammation were rescued by AZD1480, a JAK1/2 inhibitor. Our findings showing a novel role for SPC in regulating inflammation via JAK/STAT may have clinical applications.

  14. Decreased serum hepcidin, inflammation, and improved functional iron status six-months post-restrictive bariatric surgery.

    USDA-ARS?s Scientific Manuscript database

    Excess adiposity is associated with low-grade inflammation and decreased iron status. Iron depletion (ID) in obesity is thought to be mediated by an inflammation-induced increase in the body’s main regulator of iron homeostasis, hepcidin. Elevated hepcidin can result in ID as it prevents the release...

  15. Dietary Supplementation with Fresh Pineapple Juice Decreases Inflammation and Colonic Neoplasia in IL-10-deficient Mice with Colitis

    PubMed Central

    Hale, Laura P.; Chichlowski, Maciej; Trinh, Chau T.; Greer, Paula K.

    2010-01-01

    Background Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of pro-inflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10−/− mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10−/− mice with chronic colitis as compared with bromelain derived from stem. Results Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 16 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (p = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% vs. 66%; p< 0.02), with fewer neoplastic lesions/colon (p = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. Conclusions These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of inflammatory bowel disease. PMID:20848493

  16. Bromelain treatment decreases neutrophil migration to sites of inflammation.

    PubMed

    Fitzhugh, David J; Shan, Siqing; Dewhirst, Mark W; Hale, Laura P

    2008-07-01

    Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.

  17. Bromelain Treatment Decreases Neutrophil Migration to Sites of Inflammation

    PubMed Central

    Fitzhugh, David J.; Shan, Siqing; Dewhirst, Mark W.; Hale, Laura P.

    2008-01-01

    Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50 – 85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action. PMID:18482869

  18. Removal of gadolinium by peritoneal dialysis.

    PubMed

    Murashima, M; Drott, H R; Carlow, D; Shaw, L M; Milone, M; Bachman, M; Tsai, D E; Yang, S-L; Bloom, R D

    2008-05-01

    An association between gadolinium-containing contrast and the development of nephrogenic systemic fibrosis (NSF) has been increasingly recognized. For patients receiving hemodialysis (HD) who are exposed to gadolinium, the Federal Drug Administration (FDA) recommends HD to remove this contrast agent in order to minimize the risk of NSF. This study examines if gadolinium can be removed by frequent exchanges by peritoneal dialysis (PD). Following administration of 0.1 mmol/kg of gadodiamide to a patient with end-stage renal disease, the serum clearance of this contrast agent by automated PD was examined. 10 and 15 exchanges of PD using an automated cycler were respectively performed during the first and second 24-hour periods after gadolinium exposure. Serum gadolinium levels were measured 1 hour after the gadolinium administration, then at 24 and 48 hours after PD was initiated. 90% of the gadolinium was removed from the circulation in 2 days with a regimen of 10-15 exchanges per day of PD. For patients on chronic maintenance PD who receive gadolinium, our case suggests that a temporary intensive automated PD regimen, aimed at maximizing clearance of this contrast agent immediately after exposure, could be an effective alternative when institution of HD is problematic.

  19. Dietary supplementation with fresh pineapple juice decreases inflammation and colonic neoplasia in IL-10-deficient mice with colitis.

    PubMed

    Hale, Laura P; Chichlowski, Maciej; Trinh, Chau T; Greer, Paula K

    2010-12-01

    Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of proinflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10(-/-) mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10(-/-) mice with chronic colitis as compared with bromelain derived from stem. Colitis was triggered in Il10(-/-) mice by exposure to the non-steroidal anti-inflammatory drug piroxicam. Mice with colitis were supplemented with fresh vs. boiled pineapple juice or bromelain purified from stem for up to 6 months. Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 14 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (P = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% versus 66%; P < 0.02), with fewer neoplastic lesions/colon (P = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly

  20. Structural, optical and magnetic properties of gadolinium sesquioxide nanobars synthesized via thermal decomposition of gadolinium oxalate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Manigandan, R.; Giribabu, K.; Suresh, R.

    2013-10-15

    Graphical abstract: - Highlights: • The cubic Gd{sub 2}O{sub 3} nanobars are synthesized by decomposition of C{sub 6}H{sub 20}Gd{sub 2}O{sub 22}. • The nanoparticles are rectangular bar shape with high porous surface. • The combination of magnetic and optical properties within a single particle. • The Gd{sub 2}O{sub 3} nanobars have tailorable nanostructure, wide bandgap and are paramagnetic. - Abstract: Gadolinium oxide nanobars were obtained by thermal decomposition of gadolinium oxalate, which was synthesized by the chemical precipitation method along with glycerol. The functional group analysis and formation of gadolinium oxide from gadolinium oxalate were characterized by the Fourier transformmore » infrared spectroscopy and thermo gravimetric analyzer. The crystal structure, average crystallite size, and lattice parameter were analyzed by X-ray diffraction technique. Moreover, Raman shifts, elemental composition and morphology of the gadolinium oxide was widely investigated by the laser Raman microscope, X-ray photoelectron spectroscopy, FE-SEM-EDAX and HR-TEM, respectively. Furthermore, the optical properties like band gap, absorbance measurement of the gadolinium oxide were extensively examined. In addition, the paramagnetic property of gadolinium oxide nanobars was explored by the vibrating sample magnetometer.« less

  1. Low-grade inflammation decreases emotion recognition - Evidence from the vaccination model of inflammation.

    PubMed

    Balter, Leonie J T; Hulsken, Sasha; Aldred, Sarah; Drayson, Mark T; Higgs, Suzanne; Veldhuijzen van Zanten, Jet J C S; Raymond, Jane E; Bosch, Jos A

    2018-05-06

    The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment. Hence, an experimental inflammation manipulation was applied that avoided this confound, isolating effects of inflammation and social interaction. Forty healthy male participants (mean age = 25, SD = 5 years) participated in this double-blind placebo-controlled crossover trial. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK); saline-injection was used as a control. About 6 h 30 m after injection in each condition, participants completed the Reading the Mind in the Eyes Test (RMET), a validated test for assessing how well the mental states of others can be inferred through observation of the eyes region of the face. Vaccination induced systemic inflammation, elevating IL-6 by +419% (p < .001), without fever, sickness symptoms (e.g., nausea, light-headedness), or mood changes (all p's > .21). Importantly, compared to placebo, vaccination significantly reduced RMET accuracy (p < .05). RMET stimuli selected on valence (positive, negative, neutral) provided no evidence of a selective impact of treatment. By utilizing an inflammation-induction procedure that avoided concurrent sicknesses or symptoms in a double-blinded design, the present study provides further support for the hypothesis that immune activation impairs ToM. Such impairment may provide a mechanistic link explaining social-cognitive deficits in psychopathologies that exhibit low-grade inflammation, such as major depression. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Pathophysiology of gadolinium-associated systemic fibrosis

    PubMed Central

    Drel, Viktor; Gorin, Yves

    2016-01-01

    Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis. PMID:27147669

  3. The dosimetric impact of gadolinium-based contrast media in GBM brain patient plans for a MRI-Linac

    NASA Astrophysics Data System (ADS)

    Bilal Ahmad, Syed; Paudel, Moti Raj; Sarfehnia, Arman; Kim, Anthony; Pang, Geordi; Ruschin, Mark; Sahgal, Arjun; Keller, Brian M.

    2017-08-01

    Dosimetric effects of gadolinium based contrast media (Gadovist) were evaluated for the Elekta MRI linear accelerator using the research version of the Monaco treatment planning system (TPS). In order to represent a gadolinium uptake, the contrast was manually assigned to a phantom as well as to the gross tumour volume (GTV) of 6 glioblastoma multiforme (GBM) patients. A preliminary estimate of the dose enhancement, due to gadolinium, was performed using the phantom irradiated with a single beam. A more complicated assessment was performed for the GBM patients using a 7 field IMRT technique. The material table in Monaco was modified in order to identify the presence of a non-biological material. The dose distribution was modelled using GPUMCD (MC algorithm in Monaco) for an unmodified (or default) material table (DMT) as well as for a modified (or custom) material table (CMT) for both the phantom and patients. Various concentrations ranging between 8 and 157 mg ml-1 were used to represent the gadolinium uptake in the patient’s GTV. It was assumed that the gadolinium concentration remained the same for the entire course of radiation treatment. Results showed that at the tissue-Gadovist interface, inside the phantom, dose scored using the DMT was 7% lower compared to that using the CMT for 157 mg ml-1 concentration of gadolinium. Dosimetric differences in the case of the patient study were measured using the DVH parameters. D 50% was higher by 6% when the DMT was used compared to the CMT for dose modelling for a gadolinium concentration of 157 mg ml-1. This difference decreased gradually with decreasing concentration of gadolinium. It was concluded that dosimetric differences can be quantified in Monaco if the tumour-gadolinium concentration is more than 23 mg ml-1. If the gadolinium concentration is lower than 23 mg ml-1, then a correction for the presence of gadolinium may not be necessary in the TPS.

  4. The dosimetric impact of gadolinium-based contrast media in GBM brain patient plans for a MRI-Linac.

    PubMed

    Ahmad, Syed Bilal; Paudel, Moti Raj; Sarfehnia, Arman; Kim, Anthony; Pang, Geordi; Ruschin, Mark; Sahgal, Arjun; Keller, Brian M

    2017-08-01

    Dosimetric effects of gadolinium based contrast media (Gadovist) were evaluated for the Elekta MRI linear accelerator using the research version of the Monaco treatment planning system (TPS). In order to represent a gadolinium uptake, the contrast was manually assigned to a phantom as well as to the gross tumour volume (GTV) of 6 glioblastoma multiforme (GBM) patients. A preliminary estimate of the dose enhancement, due to gadolinium, was performed using the phantom irradiated with a single beam. A more complicated assessment was performed for the GBM patients using a 7 field IMRT technique. The material table in Monaco was modified in order to identify the presence of a non-biological material. The dose distribution was modelled using GPUMCD (MC algorithm in Monaco) for an unmodified (or default) material table (DMT) as well as for a modified (or custom) material table (CMT) for both the phantom and patients. Various concentrations ranging between 8 and 157 mg ml -1 were used to represent the gadolinium uptake in the patient's GTV. It was assumed that the gadolinium concentration remained the same for the entire course of radiation treatment. Results showed that at the tissue-Gadovist interface, inside the phantom, dose scored using the DMT was 7% lower compared to that using the CMT for 157 mg ml -1 concentration of gadolinium. Dosimetric differences in the case of the patient study were measured using the DVH parameters. D 50% was higher by 6% when the DMT was used compared to the CMT for dose modelling for a gadolinium concentration of 157 mg ml -1 . This difference decreased gradually with decreasing concentration of gadolinium. It was concluded that dosimetric differences can be quantified in Monaco if the tumour-gadolinium concentration is more than 23 mg ml -1 . If the gadolinium concentration is lower than 23 mg ml -1 , then a correction for the presence of gadolinium may not be necessary in the TPS.

  5. Inhibition of intestinal cholesterol absorption decreases atherosclerosis but not adipose tissue inflammation

    PubMed Central

    Umemoto, Tomio; Subramanian, Savitha; Ding, Yilei; Goodspeed, Leela; Wang, Shari; Han, Chang Yeop; Teresa, Antonio Sta.; Kim, Jinkyu; O'Brien, Kevin D.; Chait, Alan

    2012-01-01

    Adipose tissue inflammation is associated with insulin resistance and increased cardiovascular disease risk in obesity. We previously showed that addition of cholesterol to a diet rich in saturated fat and refined carbohydrate significantly worsens dyslipidemia, insulin resistance, adipose tissue macrophage accumulation, systemic inflammation, and atherosclerosis in LDL receptor-deficient (Ldlr−/−) mice. To test whether inhibition of intestinal cholesterol absorption would improve metabolic abnormalities and adipose tissue inflammation in obesity, we administered ezetimibe, a dietary and endogenous cholesterol absorption inhibitor, to Ldlr−/− mice fed chow or high-fat, high-sucrose (HFHS) diets without or with 0.15% cholesterol (HFHS+C). Ezetimibe blunted weight gain and markedly reduced plasma lipids in the HFHS+C group. Ezetimibe had no effect on glucose homeostasis or visceral adipose tissue macrophage gene expression in the HFHS+C fed mice, although circulating inflammatory markers serum amyloid A (SSA) and serum amyloid P (SSP) levels decreased. Nevertheless, ezetimibe treatment led to a striking (>85%) reduction in atherosclerotic lesion area with reduced lesion lipid and macrophage content in the HFHS+C group. Thus, in the presence of dietary cholesterol, ezetimibe did not improve adipose tissue inflammation in obese Ldlr−/− mice, but it led to a major reduction in atherosclerotic lesions associated with improved plasma lipids and lipoproteins. PMID:22956784

  6. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice

    PubMed Central

    Pineton de Chambrun, G; Body-Malapel, M; Frey-Wagner, I; Djouina, M; Deknuydt, F; Atrott, K; Esquerre, N; Altare, F; Neut, C; Arrieta, M C; Kanneganti, T-D; Rogler, G; Colombel, J-F; Cortot, A; Desreumaux, P; Vignal, C

    2014-01-01

    The increasing incidence of inflammatory bowel diseases (IBDs) in developing countries has highlighted the critical role of environmental pollutants as causative factors in their pathophysiology. Despite its ubiquity and immune toxicity, the impact of aluminum in the gut is not known. This study aimed to evaluate the effects of environmentally relevant intoxication with aluminum in murine models of colitis and to explore the underlying mechanisms. Oral administration of aluminum worsened intestinal inflammation in mice with 2,4,6-trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis and chronic colitis in interleukin 10-negative (IL10−/−) mice. Aluminum increased the intensity and duration of macroscopic and histologic inflammation, colonic myeloperoxidase activity, inflammatory cytokines expression, and decreased the epithelial cell renewal compared with control animals. Under basal conditions, aluminum impaired intestinal barrier function. In vitro, aluminum induced granuloma formation and synergized with lipopolysaccharide to stimulate inflammatory cytokines expression by epithelial cells. Deleterious effects of aluminum on intestinal inflammation and mucosal repair strongly suggest that aluminum might be an environmental IBD risk factor. PMID:24129165

  7. Use of gadolinium-based magnetic resonance imaging contrast agents and awareness of brain gadolinium deposition among pediatric providers in North America.

    PubMed

    Mithal, Leena B; Patel, Payal S; Mithal, Divakar; Palac, Hannah L; Rozenfeld, Michael N

    2017-05-01

    Numerous recent articles have reported brain gadolinium deposition when using linear but not macrocyclic gadolinium-based contrast agents (GBCAs). To determine the current landscape of gadolinium use among pediatric institutions and the knowledge base of radiologists and referring providers with regard to GBCAs and brain gadolinium deposition. We e-mailed voluntary closed surveys to 5,390 physicians in various pediatric professional societies between January 2016 and March 2016. We used chi-square and Fisher exact tests to compare response distributions among specialties. We found that 80% of surveyed pediatric hospitals use macrocyclic contrast agents. In the last year, 58% switched their agent, most commonly to gadoterate meglumine, with the most common reason being brain gadolinium deposition. Furthermore, surveys indicated that 23% of hospitals are considering switching, and, of these, 83% would switch to gadoterate meglumine; the most common reasons were brain gadolinium deposition and safety. Radiologists were more aware of brain gadolinium deposition than non-radiologist physicians (87% vs. 26%; P<0.0001). Radiologists and referring providers expressed similar levels of concern (95% and 89%). Twelve percent of radiologists and 2% of referring providers reported patients asking about brain gadolinium deposition. Radiologists were significantly more comfortable addressing patient inquiries than referring pediatric physicians (48% vs. 6%; P<0.0001). The number of MRIs requested by referring pediatric physicians correlated with their knowledge of brain gadolinium deposition, contrast agent used by their hospital, and comfort discussing brain gadolinium deposition with patients (P<0.0001). Since the discovery of brain gadolinium deposition, many pediatric hospitals have switched to or plan to switch to a more stable macrocyclic MR contrast agent, most commonly gadoterate meglumine. Despite this, there is need for substantial further education of radiologists and

  8. High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease

    PubMed Central

    Raj Krishnamurthy, Vidya M.; Wei, Guo; Baird, Bradley C.; Murtaugh, Maureen; Chonchol, Michel B.; Raphael, Kalani L.; Greene, Tom; Beddhu, Srinivasan

    2016-01-01

    Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m2) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease. PMID:22012132

  9. Upregulation of autophagy decreases chlorine-induced mitochondrial injury and lung inflammation.

    PubMed

    Jurkuvenaite, Asta; Benavides, Gloria A; Komarova, Svetlana; Doran, Stephen F; Johnson, Michelle; Aggarwal, Saurabh; Zhang, Jianhua; Darley-Usmar, Victor M; Matalon, Sadis

    2015-08-01

    The mechanisms of toxicity during exposure of the airways to chlorinated biomolecules generated during the course of inflammation and to chlorine (Cl2) gas are poorly understood. We hypothesized that lung epithelial cell mitochondria are damaged by Cl2 exposure and activation of autophagy mitigates this injury. To address this, NCI-H441 (human lung adenocarcinoma epithelial) cells were exposed to Cl2 (100 ppm/15 min) and bioenergetics were assessed. One hour after Cl2, cellular bioenergetic function and mitochondrial membrane potential were decreased. These changes were associated with increased MitoSOX signal, and treatment with the mitochondrial redox modulator MitoQ attenuated these bioenergetic defects. At 6h postexposure, there was significant increase in autophagy, which was associated with an improvement of mitochondrial function. Pretreatment of H441 cells with trehalose (an autophagy activator) improved bioenergetic function, whereas 3-methyladenine (an autophagy inhibitor) resulted in increased bioenergetic dysfunction 1h after Cl2 exposure. These data indicate that Cl2 induces bioenergetic dysfunction, and autophagy plays a protective role in vitro. Addition of trehalose (2 vol%) to the drinking water of C57BL/6 mice for 6 weeks, but not 1 week, before Cl2 (400 ppm/30 min) decreased white blood cells in the bronchoalveolar lavage fluid at 6h after Cl2 by 70%. Acute administration of trehalose delivered through inhalation 24 and 1h before the exposure decreased alveolar permeability but not cell infiltration. These data indicate that Cl2 induces bioenergetic dysfunction associated with lung inflammation and suggests that autophagy plays a protective role. Published by Elsevier Inc.

  10. Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

    PubMed

    Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

    2017-05-01

    Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Gadolinium Distribution in Cerebrospinal Fluid after Administration of a Gadolinium-based MR Contrast Agent in Humans.

    PubMed

    Berger, Florian; Kubik-Huch, Rahel A; Niemann, Tilo; Schmid, Hans Ruedi; Poetzsch, Michael; Froehlich, Johannes M; Beer, Jürg H; Thali, Michael J; Kraemer, Thomas

    2018-05-08

    Purpose To evaluate whether gadolinium penetrates human cerebrospinal fluid (CSF) after MR imaging (MRI) with a gadolinium-based contrast agent (GBCA). Materials and Methods For this retrospective study, the authors analyzed 60 CSF samples from 57 patients (median age, 50 years; range, 3-92 years) who underwent one contrast material-enhanced MRI examination with gadoterate meglumine within 60 days of CSF extraction between January and December 2016. CSF samples from patients who underwent MRI without contrast material administration (n = 22) or those who underwent contrast-enhanced MRI at least 1 year before extraction (n = 2) were analyzed and used as control samples. CSF measurements were performed with inductively coupled plasma mass spectrometry by monitoring the gadolinium 158 isotope. Statistical analyses were performed by using a preliminary Kruskal-Wallis test. Results Higher CSF gadolinium concentrations were detected within the first 8 hours after GBCA administration (mean concentration, 1152 ng/mL ± 734.6). Concentrations were lower between 8 and 48 hours (872 ng/mL ± 586). After 48 hours, gadolinium was almost completely cleared from CSF (121 ng/mL ± 296.3). All but two samples from the 24 control patients (median age, 60.5 years; range, 19-79 years) were negative for the presence of gadolinium. Those samples were from patients who had undergone GBCA-enhanced MRI examination more than a year before CSF extraction (0.1 and 0.2 ng/mL after 1 and 3 years, respectively). The concentrations in patients with chronic renal insufficiency (n = 3), cerebral toxoplasmosis (n = 1), and liver cirrhosis (n = 1) were higher than the mean concentrations. Conclusion Gadoterate meglumine can be detected in human CSF after intravenous administration. © RSNA, 2018.

  12. Gadolinium-hydrogen ion exchange of zirconium phosphate

    NASA Technical Reports Server (NTRS)

    Liu, D. C.; Power, J. L.

    1972-01-01

    The Gd(+3)/H(+) ion exchange on a commercial zirconium phosphate ion exchanger was investigated in chloride, sulfate, and phosphate solutions of Gd(+3) at gadolinium concentrations of 0.001 to 1 millimole per cc and in the pH range of 0 to 3.5. Relatively low Gd(+3) capacities, in the range of 0.01 to 0.1 millimole per g of ion exchanger were found at room temperature. A significant difference in Gd(+3) sorption was observed, depending on whether the ion exchanger was converted from initial conditions of greater or lesser Gd(+3) sorption than the specific final conditions. Correlations were found between decrease in Gd(+3) capacity and loss of exchanger phosphate groups due to hydrolysis during washing and between increase in capacity and treatment with H3PO4. Fitting of the experimental data to ideal ion exchange equilibrium expressions indicated that each Gd(+3) ion is sorbed on only one site of the ion exchanger. The selectivity quotient was determined to be 2.5 + or - 0.4 at room temperature on gadolinium desorption in chloride solutions.

  13. Gadolinium accumulation in organs of Sprague-Dawley® rats after implantation of a biodegradable magnesium-gadolinium alloy.

    PubMed

    Myrissa, Anastasia; Braeuer, Simone; Martinelli, Elisabeth; Willumeit-Römer, Regine; Goessler, Walter; Weinberg, Annelie Martina

    2017-01-15

    Biodegradable magnesium implants are under investigation because of their promising properties as medical devices. For enhancing the mechanical properties and the degradation resistance, rare earth elements are often used as alloying elements. In this study Mg10Gd pins were implanted into Sprague-Dawley® rats. The pin volume loss and a possible accumulation of magnesium and gadolinium in the rats' organs and blood were investigated in a long-term study over 36weeks. The results showed that Mg10Gd is a fast disintegrating material. Already 12weeks after implantation the alloy is fragmented to smaller particles, which can be found within the intramedullary cavity and the cortical bones. They disturbed the bone remodeling until the end of the study. The results concerning the elements' distribution in the animals' bodies were even more striking, since an accumulation of gadolinium could be observed in the investigated organs over the whole time span. The most affected tissue was the spleen, with up to 3240μgGd/kg wet mass, followed by the lung, liver and kidney (up to 1040, 685 and 207μgGd/kg). In the brain, muscle and heart, the gadolinium concentrations were much smaller (less than 20μg/kg), but an accumulation could still be detected. Interestingly, blood serum samples showed no accumulation of magnesium and gadolinium. This is the first time that an accumulation of gadolinium in animal organs was observed after the application of a gadolinium-containing degradable magnesium implant. These findings demonstrate the importance of future investigations concerning the distribution of the constituents of new biodegradable materials in the body, to ensure the patients' safety. In the last years, biodegradable Mg alloys are under investigation due to their promising properties as orthopaedic devices used for bone fracture stabilization. Gadolinium as Rare Earth Element enhances the mechanical properties of Mg-Gd alloys but its toxicity in humans is still questionable

  14. Emodin up-regulates glucose metabolism, decreases lipolysis, and attenuates inflammation in vitro.

    PubMed

    Zhang, Xiaoyan; Zhang, Rong; Lv, Pengfei; Yang, Jian; Deng, Yujie; Xu, Jun; Zhu, Rongfeng; Zhang, Di; Yang, Ying

    2015-05-01

    Emodin, the major bioactive component of Rheum palmatum, has many different activities, including antitumor, anti-inflammatory, and antidiabetes effects. Recently, emodin was reported to regulate energy metabolism. In the present study, we further explored the effects of emodin on glucose and lipid metabolism. Differentiated C2C12 myotubes and 3T3-L1 adipocytes were treated with or without different concentrations of emodin (6.25, 12.5, 25 or 50 μmol/L) for different time (1 h, 3 h, 12 h, 24 h or 48 h). Glucose metabolism, oxygen consumption, lactic acid levels, glycerol levels, and inflammation pathways were then evaluated. Cells were collected for quantitative polymerase chain reaction (PCR) and western blot analysis. Emodin upregulated glucose uptake and consumption in both C2C12 myotubes and 3T3-L1 adipocytes, with glycolysis increased. Furthermore, emodin inhibited lipolysis under basal conditions (as well as in the presence of 10 ng/ml tumor necrosis factor (TNF-)-α in 3T3-L1 adipocytes) and significantly decreased phosphorylated perilipin. Moreover, emodin inhibited the nuclear factor-κB and extracellular signal-regulated kinase pathways in C2C12 myotubes and 3T3-L1 adipocytes. Emodin upregulates glucose metabolism, decreases lipolysis, and inhibits inflammation in C2C12 myotubes and 3T3-L1 adipocytes. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  15. Gadolinium photoionization process

    DOEpatents

    Paisner, J.A.; Comaskey, B.J.; Haynam, C.A.; Eggert, J.H.

    1993-04-13

    A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

  16. Gadolinium photoionization process

    DOEpatents

    Paisner, Jeffrey A.; Comaskey, Brian J.; Haynam, Christopher A.; Eggert, Jon H.

    1993-01-01

    A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

  17. The Effect of Pressure and Temperature on Separation of Free Gadolinium(III) From Gd-DTPA Complex by Nanofiltration-Complexation Method

    NASA Astrophysics Data System (ADS)

    Rahayu, Iman; Anggraeni, Anni; Ukun, MSS; Bahti, Husein H.

    2017-05-01

    Nowdays, the utilization of rare earth elements has been carried out widely in industry and medicine, one of them is gadolinium in Gd-DTPA complex is used as a contrast agent in a magnetic resonance imaging (MRI) diagnostic to increase the visual contrast between normal tissue and diseased. Although the stability of a given complex may be high enough, the complexation step couldnot have been completed, so there is possible to gadolinium(III) in the complex compound. Therefore, the function of that compounds should be dangerous because of the toxicity of gadolinium(III) in human body. So, it is necessarry to separate free gadolinium(III) from Gd-DTPA complex by nanofiltration-complexation. The method of this study is complexing of Gd2O3 with DTPA ligand by reflux and separation of Gd-DTPA complex from gadolinium(III) with a nanofiltration membrane on the variation of pressures(2, 3, 4, 5, 6 bars) and temperature (25, 30, 35, 40 °C) and determined the flux and rejection. The results of this study are the higher of pressures and temperatures, permeation flux are increasing and ion rejections are decreasing and gave the free gadolinium(III) rejection until 86.26%.

  18. Gadolinium-Induced Fibrosis.

    PubMed

    Todd, Derrick J; Kay, Jonathan

    2016-01-01

    Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

  19. Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure.

    PubMed

    Prola-Netto, Joao; Woods, Mark; Roberts, Victoria H J; Sullivan, Elinor L; Miller, Christina Ann; Frias, Antonio E; Oh, Karen Y

    2018-01-01

    Purpose To determine whether gadolinium remains in juvenile nonhuman primate tissue after maternal exposure to intravenous gadoteridol during pregnancy. Materials and Methods Gravid rhesus macaques and their offspring (n = 10) were maintained, as approved by the institutional animal care and utilization committee. They were prospectively studied as part of a pre-existing ongoing research protocol to evaluate the effects of maternal malnutrition on placental and fetal development. On gestational days 85 and 135, they underwent placental magnetic resonance imaging after intravenous gadoteridol administration. Amniocentesis was performed on day 135 prior to administration of the second dose of gadoteridol. After delivery, the offspring were followed for 7 months. Tissue samples from eight different organs and from blood were harvested from each juvenile macaque. Gadolinium levels were measured by using inductively coupled plasma mass spectrometry. Results Gadolinium concentration in the amniotic fluid was 0.028 × 10 -5 %ID/g (percentage injected dose per gram of tissue) 50 days after administration of one gadoteridol dose. Gadolinium was most consistently detected in the femur (mean, 2.5 × 10 -5 %ID/g; range, [0.81-4.1] × 10 -5 %ID/g) and liver (mean, 0.15 × 10 -5 %ID/g; range, [0-0.26] × 10 -5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 × 10 -5 %ID/g), one juvenile spleen sample (0.039 × 10 -5 %ID/g), and one juvenile brain (0.095 × 10 -5 %ID/g) and kidney (0.13 × 10 -5 %ID/g) sample. Conclusion The presence of gadoteridol in the amniotic fluid after maternal injection enables confirmation that it crosses the placenta. Extremely low levels of gadolinium are found in juvenile macaque tissues after in utero exposure to two doses of gadoteridol, indicating that a very small amount of gadolinium persists after delivery. © RSNA, 2017.

  20. Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms.

    PubMed

    Rogosnitzky, Moshe; Branch, Stacy

    2016-06-01

    Gadolinium chelates are widely used as contrast media for magnetic resonance imaging. The approved gadolinium-based contrast agents (GBCAs) have historically been considered safe and well tolerated when used at recommended dosing levels. However, for nearly a decade, an association between GBCA administration and the development of nephrogenic systemic fibrosis (NSF) has been recognized in patients with severe renal impairment. This has led to modifications in clinical practices aimed at reducing the potential and incidence of NSF development. Newer reports have emerged regarding the accumulation of gadolinium in various tissues of patients who do not have renal impairment, including bone, brain, and kidneys. Despite the observations of gadolinium accumulation in tissues regardless of renal function, very limited clinical data regarding the potential for and mechanisms of toxicity is available. This significant gap in knowledge warrants retrospective cohort study efforts, as well as prospective studies that involve gadolinium ion (Gd(3+)) testing in patients exposed to GBCA. This review examines the potential biochemical and molecular basis of gadolinium toxicity, possible clinical significance of gadolinium tissue retention and accumulation, and methods that can limit gadolinium body burden.

  1. Inflammation-induced decrease in voluntary wheel running in mice: a nonreflexive test for evaluating inflammatory pain and analgesia.

    PubMed

    Cobos, Enrique J; Ghasemlou, Nader; Araldi, Dionéia; Segal, David; Duong, Kelly; Woolf, Clifford J

    2012-04-01

    Inflammatory pain impacts adversely on the quality of life of patients, often resulting in motor disabilities. Therefore, we studied the effect of peripheral inflammation induced by intraplantar administration of complete Freund's adjuvant (CFA) in mice on a particular form of voluntary locomotion, wheel running, as an index of mobility impairment produced by pain. The distance traveled over 1 hour of free access to activity wheels decreased significantly in response to hind paw inflammation, peaking 24 hours after CFA administration. Recovery of voluntary wheel running by day 3 correlated with the ability to support weight on the inflamed limb. Inflammation-induced mechanical hypersensitivity, measured with von Frey hairs, lasted considerably longer than the impaired voluntary wheel running and is not driving; therefore, the change in voluntary behavior. The CFA-induced decrease in voluntary wheel running was dose-dependently reversed by subcutaneous administration of antiinflammatory and analgesic drugs, including naproxen (10-80 mg/kg), ibuprofen (2.5-20mg/kg), diclofenac (1.25-10mg/kg), celecoxib (2.5-20mg/kg), prednisolone (0.62-5mg/kg), and morphine (0.06-0.5mg/kg), all at much lower doses than reported in most rodent models. Furthermore, the doses that induced recovery in voluntary wheel running did not reduce CFA-induced mechanical allodynia, indicating a greater sensitivity of the former as a surrogate measure of inflammatory pain. We conclude that monitoring changes in voluntary wheel running in mice during peripheral inflammation is a simple, observer-independent objective measure of functional changes produced by inflammation, likely more aligned to the global level of pain than reflexive measures, and much more sensitive to analgesic drug effects. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis.

    PubMed

    Baker, DeAnna A; Barth, Jeremy; Chang, Raymond; Obeid, Lina M; Gilkeson, Gary S

    2010-08-15

    Sphingosine kinase 1 (SphK1) is an enzyme that converts sphingosine to bioactive sphingosine-1-phosphate. Recent in vitro data suggest a potential role of SphK1 in TNF-alpha-mediated inflammation. Our aims in this study were to determine the in vivo significance of SphK1 in TNF-alpha-mediated chronic inflammation and to define which pathogenic mechanisms induced by TNF-alpha are SphK1 dependent. To pursue these aims, we studied the effect of SphK1 deficiency in an in vivo model of TNF-alpha-induced chronic inflammatory arthritis. Transgenic hTNF-alpha mice, which develop spontaneous inflammatory erosive arthritis beginning at 14-16 wk, were crossed with SphK1 null mice (SphK1(-/-)), on the C57BL6 genetic background. Beginning at 4 mo of age, hTNF/SphK1(-/-) mice had significantly less severe clinically evident paw swelling and deformity, less synovial and periarticular inflammation, and markedly decreased bone erosions as measured quantitatively through micro-CT images. Mechanistically, the mice lacking SphK1 had less articular cyclooxygenase 2 protein and fewer synovial Th17 cells than did hTNF/SphK1(+/+) littermates. Microarray analysis and real-time RT-PCR of the ankle synovial tissue demonstrated that hTNF/SphK1(-/-) mice had increased transcript levels of suppressor of cytokine signaling 3 compared with hTNF/SphK1(+/+) mice, likely also contributing to the decreased inflammation in the SphK1-deficient mice. Finally, significantly fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1(-/-) mice compared with hTNF/SphK1(+/+) mice. These data indicate that SphK1 plays a key role in hTNF-alpha-induced inflammatory arthritis via impacting synovial inflammation and osteoclast number.

  3. Room temperature ferromagnetic gadolinium silicide nanoparticles

    DOEpatents

    Hadimani, Magundappa Ravi L.; Gupta, Shalabh; Harstad, Shane; Pecharsky, Vitalij; Jiles, David C.

    2018-03-06

    A particle usable as T1 and T2 contrast agents is provided. The particle is a gadolinium silicide (Gd5Si4) particle that is ferromagnetic at temperatures up to 290 K and is less than 2 .mu.m in diameter. An MRI contrast agent that includes a plurality of gadolinium silicide (Gd.sub.5Si.sub.4) particles that are less than 1 .mu.m in diameter is also provided. A method for creating gadolinium silicide (Gd5Si4) particles is also provided. The method includes the steps of providing a Gd5Si4 bulk alloy; grinding the Gd5Si4 bulk alloy into a powder; and milling the Gd5Si4 bulk alloy powder for a time of approximately 20 minutes or less.

  4. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes

    PubMed Central

    2012-01-01

    Background Obesity is a state of subclinical inflammation resulting in loss of function of insulin receptors and decreased insulin sensitivity. Inhibition of the inflammatory enzymes, matrix metalloproteinases (MMPs), for 6 months in rodent models restores insulin receptor function and insulin sensitivity. Methods This 12-week double-blind, randomized, placebo (PL)-controlled proof-of-concept study was performed to determine if the MMP inhibitor (MMPI), doxycycline, decreased global markers of inflammation and enhanced muscle insulin sensitivity in obese people with type 2 diabetes (DM2). The study included non-DM2 controls (n = 15), and DM2 subjects randomized to PL (n = 13) or doxycycline 100 mg twice daily (MMPI; n = 11). All participants were evaluated on Day 1; MMPI and PL groups were also evaluated after 84 days of treatment. Results There was a significant decrease in inflammatory markers C-reactive protein (P < 0.05) and myeloperoxidase (P = 0.01) in the MMPI but not PL group. The MMPI also significantly increased skeletal muscle activated/total insulin signaling mediators: 3’phosphoinositide kinase-1 (PDK1) (p < 0.03), protein kinase B (PKB/Akt) (p < 0.004), and glycogen synthase kinase 3ß (GSK3ß) (p < 0.03). Conclusions This study demonstrated short term treatment of people with diabetes with an MMPI resulted in decreased inflammation and improved insulin sensitivity. Larger, longer studies are warranted to determine if doxycycline can improve glucose control in people with diabetes. Trial Registration Clinicaltrials.gov NCT01375491 PMID:23025537

  5. Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply

    PubMed Central

    Krehl, Susanne; Loewinger, Maria; Florian, Simone; Kipp, Anna P.; Banning, Antje; Wessjohann, Ludger A.; Brauer, Martin N.; Iori, Renato; Esworthy, Robert S.; Chu, Fong-Fong; Brigelius-Flohé, Regina

    2012-01-01

    Chronic inflammation and selenium deficiency are considered as risk factors for colon cancer. The protective effect of selenium might be mediated by specific selenoproteins, such as glutathione peroxidases (GPx). GPx-1 and -2 double knockout, but not single knockout mice, spontaneously develop ileocolitis and intestinal cancer. Since GPx2 is induced by the chemopreventive sulforaphane (SFN) via the nuclear factor E2-related factor 2 (Nrf2)/Keap1 system, the susceptibility of GPx2-KO and wild-type (WT) mice to azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis was tested under different selenium states and SFN applications. WT and GPx2-KO mice were grown on a selenium-poor, -adequate or -supranutritional diet. SFN application started either 1 week before (SFN4) or along with (SFN3) a single AOM application followed by DSS treatment for 1 week. Mice were assessed 3 weeks after AOM for colitis and Nrf2 target gene expression and after 12 weeks for tumorigenesis. NAD(P)H:quinone oxidoreductases, thioredoxin reductases and glutathione-S-transferases were upregulated in the ileum and/or colon by SFN, as was GPx2 in WT mice. Inflammation scores were more severe in GPx2-KO mice and highest in selenium-poor groups. Inflammation was enhanced by SFN4 in both genotypes under selenium restriction but decreased in selenium adequacy. Total tumor numbers were higher in GPx2-KO mice but diminished by increasing selenium in both genotypes. SFN3 reduced inflammation and tumor multiplicity in both Se-adequate genotypes. Tumor size was smaller in Se-poor GPx2-KO mice. It is concluded that GPx2, although supporting tumor growth, inhibits inflammation-mediated tumorigenesis, but the protective effect of selenium does not strictly depend on GPx2 expression. Similarly, SFN requires selenium but not GPx2 for being protective. PMID:22180572

  6. Glutathione peroxidase-2 and selenium decreased inflammation and tumors in a mouse model of inflammation-associated carcinogenesis whereas sulforaphane effects differed with selenium supply.

    PubMed

    Krehl, Susanne; Loewinger, Maria; Florian, Simone; Kipp, Anna P; Banning, Antje; Wessjohann, Ludger A; Brauer, Martin N; Iori, Renato; Esworthy, Robert S; Chu, Fong-Fong; Brigelius-Flohé, Regina

    2012-03-01

    Chronic inflammation and selenium deficiency are considered as risk factors for colon cancer. The protective effect of selenium might be mediated by specific selenoproteins, such as glutathione peroxidases (GPx). GPx-1 and -2 double knockout, but not single knockout mice, spontaneously develop ileocolitis and intestinal cancer. Since GPx2 is induced by the chemopreventive sulforaphane (SFN) via the nuclear factor E2-related factor 2 (Nrf2)/Keap1 system, the susceptibility of GPx2-KO and wild-type (WT) mice to azoxymethane and dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis was tested under different selenium states and SFN applications. WT and GPx2-KO mice were grown on a selenium-poor, -adequate or -supranutritional diet. SFN application started either 1 week before (SFN4) or along with (SFN3) a single AOM application followed by DSS treatment for 1 week. Mice were assessed 3 weeks after AOM for colitis and Nrf2 target gene expression and after 12 weeks for tumorigenesis. NAD(P)H:quinone oxidoreductases, thioredoxin reductases and glutathione-S-transferases were upregulated in the ileum and/or colon by SFN, as was GPx2 in WT mice. Inflammation scores were more severe in GPx2-KO mice and highest in selenium-poor groups. Inflammation was enhanced by SFN4 in both genotypes under selenium restriction but decreased in selenium adequacy. Total tumor numbers were higher in GPx2-KO mice but diminished by increasing selenium in both genotypes. SFN3 reduced inflammation and tumor multiplicity in both Se-adequate genotypes. Tumor size was smaller in Se-poor GPx2-KO mice. It is concluded that GPx2, although supporting tumor growth, inhibits inflammation-mediated tumorigenesis, but the protective effect of selenium does not strictly depend on GPx2 expression. Similarly, SFN requires selenium but not GPx2 for being protective.

  7. Magnetic resonance characteristics and susceptibility weighted imaging of the brain in gadolinium encephalopathy.

    PubMed

    Samardzic, Dejan; Thamburaj, Krishnamoorthy

    2015-01-01

    To report the brain imaging features on magnetic resonance imaging (MRI) in inadvertent intrathecal gadolinium administration. A 67-year-old female with gadolinium encephalopathy from inadvertent high dose intrathecal gadolinium administration during an epidural steroid injection was studied with multisequence 3T MRI. T1-weighted imaging shows pseudo-T2 appearance with diffusion of gadolinium into the brain parenchyma, olivary bodies, and membranous labyrinth. Nulling of cerebrospinal fluid (CSF) signal is absent on fluid attenuation recovery (FLAIR). Susceptibility-weighted imaging (SWI) demonstrates features similar to subarachnoid hemorrhage. CT may demonstrate a pseudo-cerebral edema pattern given the high attenuation characteristics of gadolinium. Intrathecal gadolinium demonstrates characteristic imaging features on MRI of the brain and may mimic subarachnoid hemorrhage on susceptibility-weighted imaging. Identifying high dose gadolinium within the CSF spaces on MRI is essential to avoid diagnostic and therapeutic errors. Copyright © 2013 by the American Society of Neuroimaging.

  8. Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats

    PubMed Central

    Martins, Conceição S.; Leitão, Renata F. C.; Costa, Deiziane V. S.; Melo, Iracema M.; Santos, Glaylton S.; Lima, Vilma; Baldim, Victor; Wong, Deysi V. T.; Bonfim, Luana E.; Melo, Cíntia B.; Brito, Gerly A. C.

    2016-01-01

    S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease. PMID:27116554

  9. Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats.

    PubMed

    Martins, Conceição S; Leitão, Renata F C; Costa, Deiziane V S; Melo, Iracema M; Santos, Glaylton S; Lima, Vilma; Baldim, Victor; Wong, Deysi V T; Bonfim, Luana E; Melo, Cíntia B; G de Oliveira, Marcelo; Brito, Gerly A C

    2016-01-01

    S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease.

  10. Density of Gadolinium Nitrate Solutions for the High Flux Isotope Reactor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Taylor, Paul Allen; Lee, Denise L

    2009-05-01

    In late 1992, the High Flux Isotope Reactor (HFIR) was planning to switch the solution contained in the poison injection tank from cadmium nitrate to gadolinium nitrate. The poison injection system is an emergency system used to shut down the reactor by adding a neutron poison to the cooling water. This system must be able to supply a minimum of 69 pounds of gadolinium to the reactor coolant system in order to guarantee that the reactor would become subcritical. A graph of the density of gadolinium nitrate solutions over a concentration range of 5 to 30 wt% and a temperaturemore » range of 15 to 40{sup o}C was prepared. Routine density measurements of the solution in the poison injection tank are made by HFIR personnel, and an adaptation of the original graph is used to determine the gadolinium nitrate concentration. In late 2008, HFIR personnel decided that the heat tracing that was present on the piping for the poison injection system could be removed without any danger of freezing the solution; however, the gadolinium nitrate solution might get as cold as 5{sup o}C. This was outside the range of the current density-concentration correlation, so the range needed to be expanded. This report supplies a new density-concentration correlation that covers the extended temperature range. The correlation is given in new units, which greatly simplifies the calculation that is required to determine the pounds of gadolinium in the tank solution. The procedure for calculating the amount of gadolinium in the HFIR poison injection system is as follows: (1) Calculate the usable volume in the system; (2) Measure the density of the solution; (3) Calculate the gadolinium concentration using the following equation: Gd(lb/ft{sup 3}) = measured density (g/mL) x 34.681 - 34.785; (4) Calculate the amount of gadolinium in the system using the following equation: Amount of Gd(lb) = Gd concentration (lb/ft{sup 3}) x usable volume (ft{sup 3}). The equation in step 3 is exact for a

  11. Direct Targeting of Macrophages with Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology

    PubMed Central

    Walker, Joshua A.; Miller, Andrew D.; Burdo, Tricia H.; McGrath, Michael S.; Williams, Kenneth C.

    2017-01-01

    Background Despite effective combination antiretroviral therapy (cART) HIV infected individuals develop co-morbidities including cardiovascular disease (CVD), where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages. Methods We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima-media thickness (cIMT), and fibrosis in a SIV infection model of AIDS. Eleven SIV-infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 dpi. Animals were time sacrificed (49 dpi), sacrificed when matched placebos controls developed AIDS (63, 70, 77, 80), or at the study endpoint (84 dpi). Aorta, carotid artery and cardiac tissues were analyzed. Quantitative analysis of macrophage populations and T-lymphocytes were done and correlated with cIMT and fibrosis. Results MGBG treatment resulted in a 2.19 (CD163+), 1.86 (CD68+), 2.31 (CD206+), and 2.12-fold (MAC387+) decrease in macrophages in carotid arteries and significant 2.07 (CD163+), 1.61 (CD68+), 1.95 (MAC387+) and 1.62-fold (CD206+) decrease in macrophages in cardiac tissues. CIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and CIMT, and cardiac macrophages and fibrosis was found. Conclusions These data demonstrate directly targeting macrophages with MGBG can reduce cardiovascular inflammation, CIMT, and fibrosis. They suggest therapies targeting macrophages with HIV could be used in conjunction with cART. PMID:28141779

  12. Direct Targeting of Macrophages With Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology.

    PubMed

    Walker, Joshua A; Miller, Andrew D; Burdo, Tricia H; McGrath, Michael S; Williams, Kenneth C

    2017-04-15

    Despite effective combination antiretroviral therapy, HIV-infected individuals develop comorbidities, including cardiovascular disease, where activated macrophages play a key role. To date, few therapies target activated monocytes and macrophages. We evaluated a novel oral form of the polyamine biosynthesis inhibitor methylglyoxal-bis-guanylhydrazone (MGBG) on cardiovascular inflammation, carotid artery intima-media thickness (cIMT), and fibrosis in a simian immunodeficiency virus infection model of AIDS. Eleven simian immunodeficiency virus-infected animals received MGBG (30 mg/kg) once daily and 8 received a placebo control both beginning at 21 days postinfection (dpi). Animals were time sacrificed at 49 days post infection (dpi), when their matched placebo controls developed AIDS (63, 70, 77, 80), or at the study end-point (84 dpi). Aorta, carotid artery, and cardiac tissues were analyzed. Quantitative analyses of macrophage populations and T lymphocytes were done and correlated with cIMT and fibrosis. MGBG treatment resulted in 2.19-fold (CD163), 1.86-fold (CD68), 2.31-fold (CD206), and 2.12-fold (MAC387) decreases in macrophages in carotid arteries and significant 2.07-fold (CD163), 1.61-fold (CD68), 1.95-fold (MAC387), and 1.62-fold (CD206) decreases in macrophages in cardiac tissues. cIMT (1.49-fold) and fibrosis (2.05-fold) also were significantly decreased with MGBG treatment. Numbers of macrophage and the degree of fibrosis in treated animals were similar to uninfected animals. A positive correlation between decreased macrophage in the carotid artery and cIMT, and cardiac macrophages and fibrosis was found. These data demonstrate that directly targeting macrophages with MGBG can reduce cardiovascular inflammation, cIMT, and fibrosis. They suggest that therapies targeting macrophages with HIV could be used in conjunction with combination antiretroviral therapy.

  13. Synthesis and evaluation of gadolinium complexes based on PAMAM as MRI contrast agents.

    PubMed

    Yan, Guo-Ping; Hu, Bin; Liu, Mai-Li; Li, Li-Yun

    2005-03-01

    Diethylenetriaminepentaacetic acid (DTPA) and pyridoxamine (PM) were incorporated into the amine groups on the surface of ammonia-core poly(amidoamine) dendrimers (PAMAM, Generation 2.0-5.0) to obtain dendritic ligands. These dendritic ligands were reacted with gadolinium chloride to yield the corresponding dendritic gadolinium (Gd) complexes. The dendritic ligands and their gadolinium complexes were characterized by(1)HNMR, IR, UV and elemental analysis. Relaxivity studies showed that the dendritic gadolinium complexes possessed higher relaxation effectiveness compared with the clinically used Gd-DTPA. After administration of the dendritic gadolinium complexes (0.09 mmol kg(-1) ) to rats, magnetic resonance imaging of the liver indicated that the dendritic gadolinium complexes containing pyridoxamine groups enhanced the contrast of the MR images of the liver, provided prolonged intravascular duration and produced highly contrasted visualization of blood vessels.

  14. Helium defectoscopy of cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the impurity disorder region

    NASA Astrophysics Data System (ADS)

    Koromyslov, A. V.; Zhiganov, A. N.; Kovalenko, M. A.; Kupryazhkin, A. Ya.

    2013-12-01

    The concentration of impurity anion vacancies formed upon the dissociation of gadolinium-vacancy complexes has been determined using helium defectoscopy of the cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the temperature range T = 740-1123 K and at saturation pressures ranging from 0.05 to 15 MPa. It has been found that the energy of dissociation of gadoliniumvacancy complexes is E {eff/ D }= 0.26 ± 0.06 eV, and the energy of dissolution of helium in anion vacancies in the impurity disorder region is E P = -0.31 ± 0.09 eV. The proposed mechanism of dissolution has been confirmed by the investigation of the electrical conductivity of the cerium gadolinium ceramics, as well as by the high-speed molecular dynamics simulation of the dissociation of gadolinium-vacancy complexes. It has been assumed that a decrease in the effective dissolution energy in comparison with the results of the previously performed low-temperature investigations is caused by the mutual repulsion of vacancies formed upon the dissociation of gadolinium-vacancy complexes in highly concentrated solutions of gadolinium in CeO2 with increasing temperature.

  15. Identification and characterization of gadolinium(III) complexes in biological tissue extracts.

    PubMed

    Kahakachchi, Chethaka L; Moore, Dennis A

    2010-07-01

    The gadolinium species present in a rat kidney following intravenous administration of a gadolinium-based magnetic resonance contrast agent (Optimark™, Gadoversetamide injection) to a rat was examined in the present study. The major gadolinium species in the supernatant of the rat kidney tissue extracts was determined by reversed-phase liquid chromatography with online inductively coupled plasma optical emission spectrometry (HPLC-ICP-OES). The identity of the compound was established by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) detection. The principal gadolinium(III) complex in a rat kidney tissue extract was identified as Gd-DTPA-BMEA 24 Hrs and 7 days after a single intravenous injection of Optimark™ (gadoversetamide; Gd-DTPA-BMEA) at a dose of 5 mmol Gd/kg body weight. The study demonstrated for the first time the feasibility of the use of two complementary techniques, HPLC-ICP-OES and HPLC-ESI-MS to study the in vivo behavior of gadolinium-based magnetic resonance contrast media.

  16. Alkali metal and alkali earth metal gadolinium halide scintillators

    DOEpatents

    Bourret-Courchesne, Edith; Derenzo, Stephen E.; Parms, Shameka; Porter-Chapman, Yetta D.; Wiggins, Latoria K.

    2016-08-02

    The present invention provides for a composition comprising an inorganic scintillator comprising a gadolinium halide, optionally cerium-doped, having the formula A.sub.nGdX.sub.m:Ce; wherein A is nothing, an alkali metal, such as Li or Na, or an alkali earth metal, such as Ba; X is F, Br, Cl, or I; n is an integer from 1 to 2; m is an integer from 4 to 7; and the molar percent of cerium is 0% to 100%. The gadolinium halides or alkali earth metal gadolinium halides are scintillators and produce a bright luminescence upon irradiation by a suitable radiation.

  17. Gadolinium-enhanced computed tomographic angiography: current status.

    PubMed

    Rosioreanu, Alex; Alberico, Ronald A; Litwin, Alan; Hon, Man; Grossman, Zachary D; Katz, Douglas S

    2005-01-01

    This article reviews the research to date, as well as our clinical experience from two institutions, on gadolinium-enhanced computed tomographic angiography (gCTA) for imaging the body. gCTA may be an appropriate examination for the small percentage of patients who would benefit from noninvasive vascular imaging, but who have contraindications to both iodinated contrast and magnetic resonance imaging. gCTA is more expensive than CTA with iodinated contrast, due to the dose of gadolinium administered, and gCTA has limitations compared with CTA with iodinated contrast, in that parenchymal organs are not optimally enhanced at doses of 0.5 mmol/kg or lower. However, in our experience, gCTA has been a very useful problem-solving examination in carefully selected patients. With the advent of 16-64 detector CT, in combination with bolus tracking, we believe that the overall dose of gadolinium needed for diagnostic CTA examinations, while relatively high, can be safely administered.

  18. Gadolinium-based magnetic resonance imaging contrast agents in interventional radiology.

    PubMed

    Atar, Eli

    2004-07-01

    Gadolinium-based agents are widely used in magnetic resonance imaging as contrast agents. These agents are radio-opaque enough for diagnostic imaging of the vascular tree by using digitally subtracted images as well as for imaging of the biliary system and the urinary tract. The recommended doses for gadolinium do not impair renal function or cause adverse reactions in patients with iodine sensitivity; thus patients with such conditions can safely undergo diagnostic angiography, either by MRI angiography or by catheterization using gadolinium as contrast agent, for diagnostic and therapeutic purposes.

  19. Asthma causes inflammation of human pulmonary arteries and decreases vasodilatation induced by prostaglandin I2 analogs.

    PubMed

    Foudi, Nabil; Badi, Aouatef; Amrane, Mounira; Hodroj, Wassim

    2017-12-01

    Asthma is a chronic inflammatory disease associated with increased cardiovascular events. This study assesses the presence of inflammation and the vascular reactivity of pulmonary arteries in patients with acute asthma. Rings of human pulmonary arteries obtained from non-asthmatic and asthmatic patients were set up in organ bath for vascular tone monitoring. Reactivity was induced by vasoconstrictor and vasodilator agents. Protein expression of inflammatory markers was detected by western blot. Prostanoid releases and cyclic adenosine monophosphate (cAMP) levels were quantified using specific enzymatic kits. Protein expression of cluster of differentiation 68, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and cyclooxygenase-2 was significantly increased in arteries obtained from asthmatic patients. These effects were accompanied by an alteration of vasodilatation induced by iloprost and treprostinil, a decrease in cAMP levels and an increase in prostaglandin (PG) E 2 and PGI 2 synthesis. The use of forskolin (50 µmol/L) has restored the vasodilatation and cAMP release. No difference was observed between the two groups in reactivity induced by norepinephrine, angiotensin II, PGE 2 , KCl, sodium nitroprusside, and acetylcholine. Acute asthma causes inflammation of pulmonary arteries and decreases vasodilation induced by PGI 2 analogs through the impairment of cAMP pathway.

  20. Man with a Swollen Eye: Nonspecific Orbital Inflammation in an Adult in the Emergency Department.

    PubMed

    Zhang, Xiao Chi; Statler, Brittney; Suner, Selim; Lloyd, Maureen; Curley, David; Migliori, Michael E

    2018-07-01

    Nonspecific orbital inflammation (NSOI) is a rare idiopathic ocular pathology characterized by unilateral, painful orbital swelling without identifiable infectious or systemic disorders, which can be complicated by optic nerve compromise. A 50-year-old man presented to the Emergency Department with recurring, progressive painless left eye swelling, decreased visual acuity, and binocular diplopia in the absence of trauma, infection, or known malignancy. His physical examination was notable for left-sided decreased visual acuity, an afferent pupillary defect, severe left eye proptosis and chemosis, and restricted extraocular movements; his dilatated funduscopic examination was notable for ipsilateral retinal folds within the macula, concerning for a disruption between the sclera and the retina. Ocular examination of the right eye was unremarkable. Laboratory data were unrevealing. Gadolinium-enhanced magnetic resonance imaging showed marked thickening of the left extraocular muscles associated with proptosis, dense inflammatory infiltration of the orbital fat, and characteristics consistent with perineuritis. The patient was diagnosed with NSOI with optic neuritis and admitted for systemic steroid therapy; he was discharged on hospital day 2 after receiving high-dose intravenous (i.v.) methylprednisolone with significant improvement. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: NSOI is a rare and idiopathic ocular emergency, with clinical mimicry resembling a broad spectrum of systemic diseases such as malignancy, autoimmune diseases, endocrine disorders, and infection. Initial work-up for new-onset ocular proptosis should include comprehensive laboratory testing and gadolinium-enhanced magnetic resonance imaging. Timely evaluation by an ophthalmologist is crucial to assess for optic nerve involvement. Signs of optic nerve compromise include decreased visual acuity, afferent pupillary defect, or decreased color saturation. Patients with optic nerve compromise

  1. FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study

    PubMed Central

    2012-01-01

    Background Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation. Study design and methodology Blood samples from an iron supplementation study in children (n=79) were collected at baseline and after 3 months supplementation with iron sulphate. The children were from a rural Gambian population where rates of iron deficiency and infection/inflammation are high. This study identified cross-sectional and longitudinal relationships between FGF23, inflammation (C-reactive protein (CRP)) and iron status (ferritin, haemoglobin, and zinc protoporphyrin). CRP ≥ 5 mg/dL was used to indicate inflammation and FGF23 ≥ 125 RU/mL was considered elevated. Results FGF23 was not significantly correlated with CRP. At baseline, all markers of iron status were significantly correlated with FGF23. Ferritin was the strongest independent inverse predictor of FGF23 in subjects with and without elevated CRP (coefficient (SE)): All subjects=−0.57 (0.12), R2=22.3%, P≤0.0001; subjects with CRP < 5 mg/dL=−0.89 (0.14), R2=38.9%, P≤0.0001. FGF23 was elevated in 28% of children at baseline and 16% post supplementation (P=0.1). Improved iron status was associated with a decrease in FGF23 concentration in univariate (ferritin =−0.41 (0.11), R2=14.1%, P=0.0004; haemoglobin=−2.22 (0.64), R2=12.5%, P=0.0008; zinc protoporphyrin=1.12 (0.26), R2=18.6%, P≤0.0001) and multivariate analysis (R2=33.1%; ferritin=−0.36 (0.10), P=0.0007, haemoglobin = −1.83 (0.61), P=0.004, zinc protoporphyrin=0.62 (0.26), P=0.02). Conclusions Iron status rather than inflammation is a

  2. Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation

    PubMed Central

    Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K.

    2013-01-01

    Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1–5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet. PMID:23008064

  3. Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.

    PubMed

    Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K; Varani, James

    2012-12-01

    Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5 μM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

  4. Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys

    NASA Astrophysics Data System (ADS)

    Maltsev, Dmitry S.; Volkovich, Vladimir A.; Yamshchikov, Leonid F.; Chukin, Andrey V.

    2016-09-01

    Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys were studied. Temperature dependences of gadolinium activity in the studied alloys were determined at 573-1073 K employing the EMF method. Solubility of gadolinium in the Ga-Sn and Ga-Zn alloys was measured at 462-1073 K using IMCs sedimentation method. Activity coefficients as well as partial and excess thermodynamic functions of gadolinium in the studied alloys were calculated on the basis of the obtained experimental data.

  5. Decreased expression levels of Nurr1 are associated with chronic inflammation in patients with type 2 diabetes.

    PubMed

    Xu, Ying; Huang, Qi; Zhang, Wenfang; Wang, Yaping; Zeng, Qingling; He, Chunyan; Xue, Junli; Chen, Jin; Hu, Xuemei; Xu, Yancheng

    2015-10-01

    Chronic inflammation is associated with insulin resistance, a characteristic of type 2 diabetes (T2D). Nuclear receptor‑related protein 1 (Nurr1) can regulate inflammation, dependent on the nature of individual diseases. However, whether Nurr1 regulates chronic inflammation during the pathogenic process of T2D in humans remains to be fully elucidated. The present study aimed to investigate the potential association between the expression of Nurr1 in peripheral blood mononuclear cells (PBMCs) and inflammation in patients with T2D. The levels of plasma tumor necrosis factor (TNF)α and interleukin (IL)‑6, the relative expression levels of Nurr1, and glycogen synthase kinase (GSK)‑3β phosphorylation in PBMCs from 40 patients with T2D and 40 healthy controls (HC group) were examined, and their potential association with clinical measures were analyzed. The expression levels of Nurr1, induced by high glucose and palmitic acid, were assessed in the PBMCs from the HC group. Compared with the HC group, significantly higher levels of plasma TNFα and IL‑6 were correlated positively with the degree of insulin resistance in the T2D patients. However, significantly lower expression levels of Nurr1 and GSK‑3β phosphorylation in the PBMCs were correlated negatively with the levels of TNFα, IL‑6, fasting insulin and insulin resistance in the T2D patients. Treatment of the PBMCs with high glucose or palmitic acid inhibited the expression of Nurr1 in a dose‑ and time‑dependent manner. Therefore, decreased expression levels of Nurr1 were associated with chronic inflammation and insulin resistance in patients with T2D.

  6. Simple method for quantification of gadolinium magnetic resonance imaging contrast agents using ESR spectroscopy.

    PubMed

    Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

    2012-01-01

    To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.

  7. The novel selective PPARα modulator (SPPARMα) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis.

    PubMed

    Hennuyer, Nathalie; Duplan, Isabelle; Paquet, Charlotte; Vanhoutte, Jonathan; Woitrain, Eloise; Touche, Véronique; Colin, Sophie; Vallez, Emmanuelle; Lestavel, Sophie; Lefebvre, Philippe; Staels, Bart

    2016-06-01

    Atherosclerosis is characterized by lipid accumulation and chronic inflammation in the arterial wall. Elevated levels of apolipoprotein (apo) B-containing lipoproteins are a risk factor for cardiovascular disease (CVD). By contrast, plasma levels of functional high-density lipoprotein (HDL) and apoA-I are protective against CVD by enhancing reverse cholesterol transport (RCT). Activation of peroxisome proliferator-activated receptor-α (PPARα), a ligand-activated transcription factor, controls lipid metabolism, cellular cholesterol trafficking in macrophages and influences inflammation. To study whether pharmacological activation of PPARα with a novel highly potent and selective PPARα modulator, pemafibrate, improves lipid metabolism, macrophage cholesterol efflux, inflammation and consequently atherosclerosis development in vitro and in vivo using human apolipoprotein E2 Knock-In (apoE2KI) and human apoA-I transgenic (hapoA-I tg) mice. Pemafibrate treatment decreases apoB secretion in chylomicrons by polarized Caco-2/TC7 intestinal epithelium cells and reduces triglyceride levels in apoE2KI mice. Pemafibrate treatment of hapoA-I tg mice increases plasma HDL cholesterol, apoA-I and stimulates RCT to feces. In primary human macrophages, pemafibrate promotes macrophage cholesterol efflux to HDL and exerts anti-inflammatory activities. Pemafibrate also reduces markers of inflammation and macrophages in the aortic crosses as well as aortic atherosclerotic lesion burden in western diet-fed apoE2KI mice. These results demonstrate that the novel selective PPARα modulator pemafibrate exerts beneficial effects on lipid metabolism, RCT and inflammation resulting in anti-atherogenic properties. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration.

    PubMed

    Ramalho, Joana; Ramalho, Miguel; AlObaidy, Mamdoh; Semelka, Richard C

    2016-12-01

    Over the last 2years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Decreased baroreflex sensitivity is linked to the atherogenic index, retrograde inflammation, and oxidative stress in subclinical hypothyroidism.

    PubMed

    Syamsunder, Avupati Naga; Pal, Pravati; Pal, Gopal Krushna; Kamalanathan, Chandrakasan Sadishkumar; Parija, Subhash Chandra; Nanda, Nivedita; Sirisha, Allampalli

    2017-02-01

    Purpose/aim of the study: The present study investigated the link of hyperlipidemia, inflammation and oxidative stress (OS) to cardiovascular (CV) risks in subclinical hypothyroidism (SCH). We enrolled 81 subclinical hypothyroid patients and 80 healthy subjects as control. Their CV and autonomic functions were assessed by spectral analysis of heart rate variability (HRV), continuous blood pressure variability (BPV) measurement and conventional autonomic function testing. Thyroid profile, lipid profile, immunological, inflammatory and OS markers were estimated and correlated with the baro-reflex sensitivity (BRS), the marker of sympathovagal imbalance (SVI) & CV risk. Mean arterial pressure (MAP, P<0.0001), total peripheral resistance (TPR, P<0.0001), ratio of low-frequency to high-frequency power of HRV (LF-HF ratio) (P<0.0001) were significantly higher and BRS (P<0.0001) was significantly lower in SCH group than the control group. BRS significantly correlated with heart rate, MAP, LF-HF ratio, lipid risk factors, anti-thyroperoxidase antibody, thyroid-stimulating hormone, high-sensitive C-reactive protein (hsCRP), malondialdehyde (MDA) and SCH. It was concluded that SVI is associated with SCH. Though dyslipidemia, inflammation and OS contributed to decreased BRS, SCH per se contributed maximally to it. Decreased BRS could be a physiological basis of increased CV risks in patients with SCH.

  10. Compensated gadolinium-loaded plastic scintillators for thermal neutron detection (and counting)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dumazert, Jonathan; Coulon, Romain; Bertrand, Guillaume H. V.

    2015-07-01

    Plastic scintillator loading with gadolinium-rich organometallic complexes shows a high potential for the deployment of efficient and cost-effective neutron detectors. Due to the low-energy photon and electron signature of thermal neutron capture by gadolinium-155 and gadolinium-157, alternative treatment to Pulse Shape Discrimination has to be proposed in order to display a trustable count rate. This paper discloses the principle of a compensation method applied to a two-scintillator system: a detection scintillator interacts with photon radiation and is loaded with gadolinium organometallic compound to become a thermal neutron absorber, while a non-gadolinium loaded compensation scintillator solely interacts with the photon partmore » of the incident radiation. Posterior to the nonlinear smoothing of the counting signals, a hypothesis test determines whether the resulting count rate after photon response compensation falls into statistical fluctuations or provides a robust image of a neutron activity. A laboratory prototype is tested under both photon and neutron irradiations, allowing us to investigate the performance of the overall compensation system in terms of neutron detection, especially with regards to a commercial helium-3 counter. The study reveals satisfactory results in terms of sensitivity and orientates future investigation toward promising axes. (authors)« less

  11. Aβ-related angiitis: comparison with CAA without inflammation and primary CNS vasculitis.

    PubMed

    Salvarani, Carlo; Hunder, Gene G; Morris, Jonathan M; Brown, Robert D; Christianson, Teresa; Giannini, Caterina

    2013-10-29

    To analyze the clinical findings, response to therapy, and outcomes of patients with cerebral vascular amyloid-β (Aβ) deposition with and without inflammatory vascular infiltration. We report 78 consecutive patients with cerebral vascular Aβ deposition examined at Mayo Clinic Rochester over 25 years (1987 through 2011). Specimens reviewed by a neuropathologist showed 40 with vascular Aβ peptide without inflammation (cerebral amyloid angiopathy [CAA]), 28 with granulomatous vasculitis (Aβ-related angiitis or ABRA), and 10 with perivascular CAA-related inflammation. We also matched findings in 118 consecutive patients with primary CNS vasculitis (PCNSV) without Aβ seen over 25 years (1983 through 2007). Compared to the 40 with CAA, the 28 with ABRA were younger at diagnosis (p = 0.05), had less altered cognition (p = 0.02), fewer neurologic deficits (p = 0.02), and fewer intracranial hemorrhages (<0.001), but increased gadolinium leptomeningeal enhancement (p = 0.01) at presentation, and less mortality and disability at last follow-up (p < 0.001). Compared with PCNSV, the 28 patients with ABRA were older at diagnosis (p < 0.001), had a higher frequency of altered cognition (p = 0.05), seizures/spells (p = 0.006), gadolinium leptomeningeal enhancement (p < 0.001), and intracerebral hemorrhage (p = 0.02), lower frequency of hemiparesis (p = 0.01), visual symptoms (p = 0.04), and MRI evidence of cerebral infarction (p = 0.003), but higher CSF protein levels (p = 0.03). Results of treatment and outcomes in ABRA and PCNSV were similar. ABRA appears to represent a distinct subset of PCNSV.

  12. Stability of Gadolinium-Doped Liquid Organic Scintillators

    NASA Astrophysics Data System (ADS)

    Gromov, M. B.; Kuznetsov, D. S.; Murchenko, A. E.; Novikova, G. Ya.; Obinyakov, B. A.; Oralbaev, A. Yu.; Plakitina, K. V.; Skorokhvatov, M. D.; Sukhotin, S. V.; Chepurnov, A. S.; Etenko, A. V.

    2018-03-01

    The technology of preparing a linear-alkylbenzene-based gadolinium-doped liquid organic scintillator (Gd-LOS) as a target material in reactor antineutrino detectors has been developed. Results of longterm measurements of the light yield of Gd-LOS in contact with acryl and stainless steel are presented, which confirm the compatibility of Gd-LOS with these materials. The measurements were performed for two otherwise identical LOS detectors only differing in wall materials of the sensitive volume: acryl versus stainless steel. The results of measurements over about one year showed almost the same, relatively small decreases in the light yield of both detectors. It is concluded that both structural materials can be used in detector parts contacting with Gd-doped scintillator. Such a long-term parallel comparative test was carried out for the first time.

  13. Dielectric properties and activation behavior of gadolinium doped nanocrystalline yttrium chromite

    NASA Astrophysics Data System (ADS)

    Sinha, R.; Basu, S.; Meikap, A. K.

    2018-04-01

    Gadolinium doped Yttrium Chromite nanoparticles are synthesized following sol-gel method. The formation of the nanoparticles are confirmed by XRD and TEM measurements. Dielectric permittivity and dielectric loss are estimated within the temperature range 298K to 523K and in the frequency range 20 Hz to 1 MHz. Dielectric permittivity follows the power law ɛ'(f) ∝ Tm. It is observed that the temperature exponent m increases with the decreasing frequency. The temperature variation of resistivity shows that the samples have semiconducting behavior. The activation energy is also measured.

  14. Randomized Trial of Plaque-Identifying Toothpaste: Decreasing Plaque and Inflammation.

    PubMed

    Fasula, Kim; Evans, Carla A; Boyd, Linda; Giblin, Lori; Belavsky, Benjamin Z; Hetzel, Scott; McBride, Patrick; DeMets, David L; Hennekens, Charles H

    2017-06-01

    Randomized data are sparse about whether a plaque-identifying toothpaste reduces dental plaque and nonexistent for inflammation. Inflammation is intimately involved in the pathogenesis of atherosclerosis and is accurately measured by high-sensitivity C-reactive protein (hs-CRP), a sensitive marker for cardiovascular disease. The hypotheses that Plaque HD (TJA Health LLC, Joliet, Ill), a plaque-identifying toothpaste, produces statistically significant reductions in dental plaque and hs-CRP were tested in this randomized trial. Sixty-one apparently healthy subjects aged 19 to 44 years were assigned at random to this plaque-identifying (n = 31) or placebo toothpaste (n = 30) for 60 days. Changes from baseline to follow-up in dental plaque and hs-CRP were assessed. In an intention-to-treat analysis, the plaque-identifying toothpaste reduced mean plaque score by 49%, compared with a 24% reduction in placebo (P = .001). In a prespecified subgroup analysis of 38 subjects with baseline levels >0.5 mg/L, the plaque-identifying toothpaste reduced hs-CRP by 29%, compared with a 25% increase in placebo toothpaste (P = .041). This plaque-identifying toothpaste produced statistically significant reductions in dental plaque and hs-CRP. The observed reduction in dental plaque confirms and extends a previous observation. The observed reduction in inflammation supports the hypothesis of a reduction in risks of cardiovascular disease. The direct test of this hypothesis requires a large-scale randomized trial of sufficient size and duration designed a priori to do so. Such a finding would have major clinical and public health implications. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. [Rapid imaging in orbito-ocular pathology. Contribution of gadolinium].

    PubMed

    Pigeau, I; Legeais, J M; D'Hermies, F; Fayet, B; Leport, M; Abenhaim, A; Guinet, C; Levy, C; Renard, G; Vadrot, D

    1990-01-01

    To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology.

  16. Distribution and chemical forms of gadolinium in the brain: a review.

    PubMed

    Kanda, Tomonori; Nakai, Yudai; Hagiwara, Akifumi; Oba, Hiroshi; Toyoda, Keiko; Furui, Shigeru

    2017-11-01

    In the 3 years since residual gadolinium-based contrast agent (GBCA) in the brain was first reported, much has been learned about its accumulation, including the pathway of GBCA entry into the brain, the brain distribution of GBCA and its excretion. Here we review recent progress in understanding the routes of gadolinium deposition in brain structures.

  17. Feasibility and accuracy of dual-layer spectral detector computed tomography for quantification of gadolinium: a phantom study.

    PubMed

    van Hamersvelt, Robbert W; Willemink, Martin J; de Jong, Pim A; Milles, Julien; Vlassenbroek, Alain; Schilham, Arnold M R; Leiner, Tim

    2017-09-01

    The aim of this study was to evaluate the feasibility and accuracy of dual-layer spectral detector CT (SDCT) for the quantification of clinically encountered gadolinium concentrations. The cardiac chamber of an anthropomorphic thoracic phantom was equipped with 14 tubular inserts containing different gadolinium concentrations, ranging from 0 to 26.3 mg/mL (0.0, 0.1, 0.2, 0.4, 0.5, 1.0, 2.0, 3.0, 4.0, 5.1, 10.6, 15.7, 20.7 and 26.3 mg/mL). Images were acquired using a novel 64-detector row SDCT system at 120 and 140 kVp. Acquisitions were repeated five times to assess reproducibility. Regions of interest (ROIs) were drawn on three slices per insert. A spectral plot was extracted for every ROI and mean attenuation profiles were fitted to known attenuation profiles of water and pure gadolinium using in-house-developed software to calculate gadolinium concentrations. At both 120 and 140 kVp, excellent correlations between scan repetitions and true and measured gadolinium concentrations were found (R > 0.99, P < 0.001; ICCs > 0.99, CI 0.99-1.00). Relative mean measurement errors stayed below 10% down to 2.0 mg/mL true gadolinium concentration at 120 kVp and below 5% down to 1.0 mg/mL true gadolinium concentration at 140 kVp. SDCT allows for accurate quantification of gadolinium at both 120 and 140 kVp. Lowest measurement errors were found for 140 kVp acquisitions. • Gadolinium quantification may be useful in patients with contraindication to iodine. • Dual-layer spectral detector CT allows for overall accurate quantification of gadolinium. • Interscan variability of gadolinium quantification using SDCT material decomposition is excellent.

  18. Effect of Cu2+ substitution on the structural, magnetic and electrical properties of gadolinium orthoferrite

    NASA Astrophysics Data System (ADS)

    Sai Vandana, C.; Hemalatha Rudramadevi, B.

    2018-04-01

    The pure and copper (Cu) substituted Gadolinium orthoferrites, GdFeO3, GdCu0.1Fe0.9O3, GdCu0.2Fe0.8O3 and GdCu0.3Fe0.7O3 were synthesized by conventional solid state method. The structural, morphological, dielectric, magnetic and impedance properties of Cu substituted Gadolinium orthoferrites have been investigated. The crystallographic phase as well as the substitution of Cu2+ ions in the lattice of GdFeO3 is confirmed from the x-ray diffraction patterns. The Fourier transform infrared spectra exhibit two prominent fundamental absorption peaks at ∼417 cm‑1 and 545 cm‑1. These bands are related to inherent stretching vibrations of metals at octahedral and tetrahedral sites respectively. The coercivity (Hc) and saturation magnetization (Ms) of the synthesized samples at different temperatures were determined from the hysteresis plots. Higher coercive values, 598 Oe and 600 Oe were achieved in GdCu0.1Fe0.9O3 ferrites compared to 527 Oe and 360 Oe in pure GdFeO3 at room temperature (300 K) and low temperature (20 k) respectively. Dielectric dispersion has been observed for gadolinium ferrite samples with Maxwell–Wagner type interfacial polarization. The decrease of dielectric constant and dielectric loss tangent with an increase in frequency was observed. The conduction due to charge hopping between localized states was confirmed from AC conductivity measurements. The composition dependent cationic distributions estimated from XRD, magnetic and electrical studies are in good agreement with each other. The achieved results indicate that the substitution of Cu in gadolinium orthoferrite strongly influences the crystal structure, magnetic and electrical properties thereby making them suitable as multiple state memory devices, transducers, electronic field controlled ferromagnetic resonance devices and spintronic devices.

  19. Type of MRI contrast, tissue gadolinium, and fibrosis.

    PubMed

    Do, Catherine; Barnes, Jeffrey L; Tan, Chunyan; Wagner, Brent

    2014-10-01

    It has been presupposed that the thermodynamic stability constant (K(therm)) of gadolinium-based MRI chelates relate to the risk of precipitating nephrogenic systemic fibrosis. The present study compared low-K(therm) gadodiamide with high-K(therm) gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor-β production, and expression of activated myofibroblast stress fiber protein α-smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in the spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appeared to be limited to the skin and kidney. These findings support the hypothesis that low-K(therm) chelates have a greater propensity to elicit nephrogenic systemic fibrosis and demonstrate that certain tissues are resistant to these effects.

  20. Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Dongkyu; Maeng, Inhee; Son, Joo-Hiuk

    2009-04-19

    The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRImore » technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.« less

  1. Hyperenhancement of the Pericardium on Cardiac Magnetic Resonance Imaging: A Marker of Acute Inflammation and Neovascularization or a Chronic Fibrotic State.

    PubMed

    Mullen, Liam; Chew, Pei Gee; Frost, Frederick; Ahmed, Ayesha; Khand, Aleem

    2016-01-01

    In cardiac magnetic resonance imaging, hyperenhancement of the pericardium post gadolinium administration in acute chest pain often signifies pericarditis with an acute inflammatory response and neovascularization. In the context of constrictive pericarditis, case series have indicated that the intensity of hyperenhancement and the thickness of the pericardium imply reversibility of the physiology of the constrictive pericarditis. We present a case of intense hyperenhancement and marked thickening of the pericardium in a patient with constrictive pericarditis with antecedent chest pain. Surgical resection of the pericardium and microscopy revealed a chronic fibrotic state with no evidence of inflammation or neovascularization, thus clarifying the failure of initial medical/anti-inflammatory treatment. Our case highlights the fact that hyperenhancement of the pericardium post gadolinium is non-specific for histology and does not necessarily imply the reversibility of pericardial constriction. © 2016 S. Karger AG, Basel.

  2. Neuroprotective effect of gadolinium: a stretch-activated calcium channel blocker in mouse model of ischemia-reperfusion injury.

    PubMed

    Gulati, Puja; Muthuraman, Arunachalam; Jaggi, Amteshwar S; Singh, Nirmal

    2013-03-01

    The present study was designed to investigate the potential of gadolinium, a stretch-activated calcium channel blocker in ischemic reperfusion (I/R)-induced brain injury in mice. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was given to induce cerebral injury in male Swiss mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using Morris water maze test and motor incoordination was evaluated using rota-rod, lateral push, and inclined beam walking tests. In addition, total calcium, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were also estimated in brain tissue. I/R injury produced a significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Furthermore, I/R injury also produced a significant increase in levels of TBARS, total calcium, AChE activity, and a decrease in GSH levels. Pretreatment of gadolinium significantly attenuated I/R-induced infarct size, behavioral and biochemical changes. On the basis of the present findings, we can suggest that opening of stretch-activated calcium channel may play a critical role in ischemic reperfusion-induced brain injury and that gadolinium has neuroprotective potential in I/R-induced injury.

  3. Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension.

    PubMed

    Subha, M; Pal, Pravati; Pal, G K; Habeebullah, S; Adithan, C; Sridhar, M G

    Pregnancy-induced hypertension (PIH) has been reported as a cardiovascular (CV) risk. We assessed the sympathovagal imbalance (SVI) and the association of inflammation and oxidative stress (OS) with CV risks in PIH. A total of 125 pregnant women having a risk factor for PIH were followed till term and the incidence of PIH was observed. Retrospectively, they were divided into two groups: Group I (those who did not develop PIH, n = 82) and Group II (those who developed PIH, n = 43). Blood pressure variability (BPV) parameters including baroreflex sensitivity (BRS), spectral heart rate variability (HRV), autonomic function tests (AFTs), inflammatory markers (interleukin-6, TNF-α, interferon-γ), and OS markers were measured in both the groups. Alterations in parasympathetic and sympathetic components of AFTs were analyzed. Link of various parameters to BRS was assessed by correlation and multiple regression analysis. Parasympathetic components of AFTs were decreased from the early part of pregnancy and sympathetic components were increased toward the later part of pregnancy. Decreased BRS, the marker of CV risk, was more prominent in Group II subjects. Independent contribution of interleukin-6 (β = 0.276, P = 0.020), TNF-α (β = 0.408, P = 0.002), interferon-γ (β = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (β = 0.287, P = 0.015) to BRS was found to be significant. It was concluded that sympathetic overactivity that develops more in the later part (third trimester) of pregnancy contributes to SVI and genesis of PIH. In PIH women, CV risks are present from the beginning of pregnancy that intensifies in the later part of pregnancy. Retrograde inflammation and oxidative stress contribute to the decreased BRS in PIH.

  4. Gadolinium-enhanced cardiovascular magnetic resonance: administered dose in relationship to United States Food and Drug Administration (FDA) guidelines.

    PubMed

    Nacif, Marcelo S; Arai, Andrew E; Lima, Joao A C; Bluemke, David A

    2012-02-29

    Myocardial late gadolinium enhancement was originally validated using higher than label-recommended doses of gadolinium chelate. The objective of this study was to evaluate available evidence for various gadolinium dosing regimens used for CMR. The relationship of gadolinium dose warnings (due to nephrogenic systemic fibrosis) announced in 2008 to gadolinium dosing regimens was also examined. We conducted a meta-analysis of peer reviewed publications from January, 2004 to December, 2010. Major subject search headings (MeSh) terms from the National Library of Medicine's PubMed were: contrast media, gadolinium, heart, magnetic resonance imaging; searches were limited to human studies with abstracts published in English. Case reports, review articles, editorials, MRA related papers and all reports that did not indicate gadolinium type or weight-based dose were excluded. For all included references, full text was available to determine the total administered gadolinium dose on a per kg basis. Average and median dose values were weighted by the number of subjects in each study. 399 publications were identified in PubMed; 233 studies matched the inclusion criteria, encompassing 19,934 patients with mean age 54.2 ± 11.4 (range 9.3 to 76 years). 34 trials were related to perfusion testing and 199 to myocardial late gadolinium enhancement. In 2004, the weighted-median and weighted-mean contrast dose were 0.15 and 0.16 ± 0.06 mmol/kg, respectively. Median contrast doses for 2005-2010 were: 0.2 mmol/kg for all years, respectively. Mean contrast doses for the years 2005-2010 were: 0.19 ± 0.03, 0.18 ± 0.04, 0.18 ± 0.10, 0.18 ± 0.03, 0.18 ± 0.04 and 0.18 ± 0.04 mmol/kg, respectively (p for trend, NS). Gadopentetate dimeglumine was the most frequent gadolinium type [114 (48.9%) studies]. No change in mean gadolinium dose was present before, versus after the Food and Drug Administration (FDA) black box warning (p > 0.05). Three multi-center dose ranging trials have been

  5. Turpentine oil induced inflammation decreases absorption and increases distribution of phenacetin without altering its elimination process in rats.

    PubMed

    Prasad, V G N V; Vivek, Ch; Anand Kumar, P; Ravi Kumar, P; Rao, G S

    2015-03-01

    Plasma concentrations and pharmacokinetics of phenacetin, a CYP1A2 substrate were determined in normal and experimentally induced inflamed rats by turpentine oil to know the role of inflammation on the pharmacokinetics of phenacetin and formation of its active metabolite (paracetamol) by CYP1A2 in wistar albino rats, weighing about 200-250 g that were randomly divided into two groups consisting six in each group. Rats in group I (control) received phenacetin (150 mg kg(-1), PO) where as group II received phenacetin 12 h after induction of inflammation by turpentine oil (0.4 mL, i.m). Blood samples were collected from retro orbital plexus at pre-determined time intervals prior to and at 0.166, 0.33, 0.67, 1.5, 2, 4, 8 and 12 h post-administration of phenacetin. Plasma was separated and analyzed for phenacetin and its metabolite paracetamol by HPLC assay. Based on plasma concentrations of phenacetin and its metabolite paracetamol, the pharmacokinetic parameters were determined by compartmental methods. C(max) of phenacetin was significantly (p < 0.01) decreased to 19.50 ± 2.74 μg mL(-1) in inflamed conditions compared to 38.13 ± 2.20 μg mL(-1) obtained in normal rats. Except, for significant (p < 0.001) increase in volume of distribution at steady state (V(dss)) from 2.87 ± 0.37 to 8.03 ± 1.26 L kg(-1) and increased the rate of absorption with shorter absorption half-life (t(1/2ka)) for phenacetin in inflammation. None of the pharmacokinetic parameters of either phenacetin or its metabolite paracetamol were affected. It can be concluded that turpentine oil induced inflammation has no role on the activity of CYP1A2 in rats, as the plasma concentrations and pharmacokinetic parameters of paracetamol were found unaltered.

  6. Method of separating and purifying gadolinium-153

    DOEpatents

    Bray, Lane A [Richland, WA; Corneillie, Todd M [Davis, CA

    2001-01-01

    The present invention is an improvement to the method of separating and purifying gadolinium from a mixture of gadolinium and europium having the steps of (a) dissolving the mixture in an acid; (b) reducing europium+3 to europium+2; and (c) precipitating the europium+2 with a sulfate ion in a superstoichiometric amount; wherein the improvement is achieved by using one or more of the following: (i) the acid is an anoic acid; (ii) the reducing is with zinc metal in the absence of a second metal or with an amount of the second metal that is ineffective in the reducing; (iii) adding a group IIA element after step (c) for precipitating the excess sulfate prior to repeating step (c); (iv) the sulfate is a sulfate salt with a monovalent cation; (v) adding cold europium+3 prior to repeating step (c).

  7. Modification of the crystal structure of gadolinium gallium garnet by helium ion irradiation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ostafiychuk, B. K.; Yaremiy, I. P., E-mail: yaremiy@rambler.ru; Yaremiy, S. I.

    2013-12-15

    The structure of gadolinium gallium garnet (GGG) single crystals before and after implantation by He{sup +} ions has been investigated using high-resolution X-ray diffraction methods and the generalized dynamic theory of X-ray scattering. The main types of growth defects in GGG single crystals and radiation-induced defects in the ion-implanted layer have been determined. It is established that the concentration of dislocation loops in the GGG surface layer modified by ion implantation increases and their radius decreases with an increase in the implantation dose.

  8. Gadolinium: Central Metal of the Lanthanoids

    ERIC Educational Resources Information Center

    Laing, Michael

    2009-01-01

    The physical and chemical properties of gadolinium are compared with those of the other lanthanoids. Some properties are intermediate between those of lanthanum and lutetium; some between those of barium and hafnium; and others (unexpectedly) between those of ytterbium and lutetium. Both the remarkably high molar heat capacity of the metal and the…

  9. Gadolinium Use in Spine Pain Management Procedures for Patients with Contrast Allergies: Results in 527 Procedures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Safriel, Yair; Ang, Roberto; Ali, Muhammed

    2008-03-15

    Introduction. To review the safety and efficacy of gadolinium in spine pain management procedures in patients at high risk for a contrast reaction and who are not suitable candidates for the use of standard non-ionic contrast. Methods. We reviewed records over a 61-month period of all image-guided spinal pain management procedures where patients had allergies making them unsuitable candidates for standard non-ionic contrast and where gadolinium was used to confirm needle tip placement prior to injection of medication. Results. Three hundred and four outpatients underwent 527 procedures. A spinal needle was used in all but 41 procedures. Gadolinium was visualizedmore » using portable C-arm fluoroscopy in vivo allowing for confirmation of needle tip location. The gadolinium dose ranged from 0.2 to 10 ml per level. The highest dose received by one patient was 15.83 ml intradiscally during a three-level discogram. Three hundred and one patients were discharged without complication or known delayed complications. One patient had documented intrathecal injection but without sequelae and 2 patients who underwent cervical procedures experienced seizures requiring admission to the intensive care unit. Both the latter patients were discharged without any further complications. Conclusion. Based on our experience we recommend using gadolinium judiciously for needle tip confirmation. We feel more confident using gadolinium in the lumbar spine and in cervical nerve blocks. Gadolinium should probably not be used as an injectate volume expander. The indications for gadolinium use in cervical needle-guided spine procedures are less clear and use of a blunt-tipped needle should be considered.« less

  10. [Gadolinium-based contrast agents for magnetic resonance imaging].

    PubMed

    Carrasco Muñoz, S; Calles Blanco, C; Marcin, Javier; Fernández Álvarez, C; Lafuente Martínez, J

    2014-06-01

    Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients. Copyright © 2014 SERAM. Published by Elsevier Espana. All rights reserved.

  11. [Signaling mechanisms involved in resolution of inflammation].

    PubMed

    Cervantes-Villagrana, Rodolfo Daniel; Cervantes-Villagrana, Alberto Rafael; Presno-Bernal, José Miguel

    2014-01-01

    Inflammation is a physiological process, which eliminates pathogens and induces repair of damaged tissue. This process is controlled by negative feedback mechanisms, but if the inflammation persists, it generates a deleterious autoimmune process or can to contribute with diseases such as obesity or cancer. The inflammation resolution involves mechanisms such as decrease of proliferation and maturation of immune cells, phagocytosis and apoptosis of immune cells, and decrease of proinflammatory mediators. Therefore, is relevant to study the physiological effects of specific receptors that participate in inflammation resolution and the design of specific agonists as conventional anti-inflammatory therapeutics, without dramatic collateral effects. In this review, we study some mechanisms associated with inflammation inhibition, particularly the transduction of receptors for ligands with anti-inflammatory effects and that are relevant for their potential therapeutic.

  12. Theoretical study of structure and stability of small gadolinium carboxylate complexes in liquid scintillator solvents.

    PubMed

    Huang, Pin-Wen

    2014-09-01

    The structural properties of three small gadolinium carboxylate complexes in three liquid scintillator solvents (pseudocumene, linear alkylbenzene, and phenyl xylylethane) were theoretically investigated using density functional theory (B3LYP/LC-RECP) and polarizable continuum model (PCM). The average interaction energy between gadolinium atom and carboxylate ligand (E(int)) and the energy difference of the highest singly occupied molecular orbital and lowest unoccupied molecular orbital (Δ(SL)) were calculated to evaluate and compare the relative stability of these complexes in solvents. The calculation results show that the larger (with a longer alkyl chain) gadolinium carboxylate complex has greater stability than the smaller one, while these gadolinium carboxylates in linear alkylbenzene were found to have greater stability than those in the other two solvents.

  13. Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy (abstract)

    NASA Astrophysics Data System (ADS)

    Lee, Dongkyu; Maeng, Inhee; Oh, Seung Jae; Kim, Taekhoon; Cho, Byung Kyu; Lee, Kwangyeol; Son, Joo-Hiuk

    2009-04-01

    The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRI technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd2O3) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.

  14. Toxicological and pharmacological effects of gadolinium and samarium chlorides

    PubMed Central

    Haley, T. J.; Raymond, K.; Komesu, N.; Upham, H. C.

    1961-01-01

    A study has been made of the toxicology and pharmacology of gadolinium and samarium chlorides. The symptoms of acute toxicity following intraperitoneal injection are described. The chronic oral ingestion of both chemicals for 12 weeks produced no effects on growth or the blood picture, and only the male rats receiving gadolinium chloride showed liver damage. The pharmacological responses to both chemicals were mainly depressant on all systems studied, and death was associated with cardiovascular collapse coupled with respiratory paralysis. The greatest damage seen was on abraded skin, where non-healing ulcers were produced by both chemicals, whereas irritation of intact skin and ocular tissues was only transient in nature. PMID:13903826

  15. Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents.

    PubMed

    Yan, Guo-Ping; Li, Zhen; Xu, Wei; Zhou, Cheng-Kai; Yang, Lian; Zhang, Qiao; Li, Liang; Liu, Fan; Han, Lin; Ge, Yuan-Xing; Guo, Jun-Fang

    2011-04-04

    Porphyrin-containing polyaspartamide ligands (APTSPP-PHEA-DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP-PHEA-DTPA-Gd). Experimental data of (1)H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP-PHEA-DTPA-Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd-DTPA. Moreover, APTSPP-PHEA-DTPA-Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  16. Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

    PubMed

    Wang, Chun-Hua; Chou, Pai-Chien; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Ho, Shu-Chuan; Lin, Horng-Chyuan; Huang, Chien-Da; Chung, Fu-Tsai; Chung, Kian Fan; Kuo, Han-Pin

    2014-08-30

    Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines. Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group. A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019).

  17. Dendrobium chrysotoxum Lindl. Alleviates Diabetic Retinopathy by Preventing Retinal Inflammation and Tight Junction Protein Decrease

    PubMed Central

    Yu, Zengyang; Gong, Chenyuan; Lu, Bin; Yang, Li; Sheng, Yuchen; Ji, Lili; Wang, Zhengtao

    2015-01-01

    Diabetic retinopathy (DR) is a serious complication of diabetes mellitus. This study aimed to observe the alleviation of the ethanol extract of Dendrobium chrysotoxum Lindl. (DC), a traditional Chinese herbal medicine, on DR and its engaged mechanism. After DC (30 or 300 mg/kg) was orally administrated, the breakdown of blood retinal barrier (BRB) in streptozotocin- (STZ-) induced diabetic rats was attenuated by DC. Decreased retinal mRNA expression of tight junction proteins (including occludin and claudin-1) in diabetic rats was also reversed by DC. Western blot analysis and retinal immunofluorescence staining results further confirmed that DC reversed the decreased expression of occludin and claudin-1 proteins in diabetic rats. DC reduced the increased retinal mRNA expressions of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor α (TNFα), interleukin- (IL-) 6, and IL-1β in diabetic rats. In addition, DC alleviated the increased 1 and phosphorylated p65, IκB, and IκB kinase (IKK) in diabetic rats. DC also reduced the increased serum levels of TNFα, interferon-γ (IFN-γ), IL-6, IL-1β, IL-8, IL-12, IL-2, IL-3, and IL-10 in diabetic rats. Therefore, DC can alleviate DR by inhibiting retinal inflammation and preventing the decrease of tight junction proteins, such as occludin and claudin-1. PMID:25685822

  18. Proton Relaxivity and Magnetic Hyperthermia Evaluation of Gadolinium Doped Nickel Ferrite Nanoparticles as Potential Theranostic Agents.

    PubMed

    Yadavalli, Tejabhiram; Raja, Paradeep; Ramaswamy, Shivaraman; Chandrasekharan, Gopalakrishnan; Chennakesavulu, Ramasamy

    2017-02-01

    This paper outlines the preparation of gadolinium doped nickel ferrite nanoparticles as potential magnetic carriers and longitudinal magnetic resonance imaging contrast agents using hydrothermal method with gadolinium concentration varying from 10% to 40%. A concise effect on the crystal structure was observed at 10% and 20% gadolinium doping, while gadolinium oxide was observed to leach at concentrations exceeding 20%. Further, gadolinium doped nickel ferrites were analyzed for their morphological, magnetic, proton relaxation and magnetic hyperthermia heating properties to understand their potential role as magnetic carrier agents. Low temperature and room temperature magnetic studies conducted on the samples showed comparatively high magnetic saturation with low remanent magnetization. Further, relaxometry studies revealed a high relaxation rate of 6.63 s−1 at a concentration of 0.1 mg/mL. Magnetic hyperthermia studies of the samples at a concentration of 1 mg/mL, assessed that the samples attained a temperature of 68 °C in 240 seconds.

  19. Removal of gadolinium, a neutron poison from the moderator system of nuclear reactors.

    PubMed

    Rufus, A L; Kumar, Padma S; Jeena, K; Velmurugan, S

    2018-01-15

    Gadolinium as gadolinium nitrate is used as neutron poison in the moderator system for regulating and controlling the power generation of Pressurized Heavy Water Reactors (PHWR) and proposed to be used in Advanced Heavy Water Reactors (AHWR) owing to its high neutron absorption cross section. Removal of the added gadolinium nitrate (Gd 3+ and NO 3 - ) from the system after its intended use is done using ion exchange resins. In the present investigation, attempts have been made to optimize the ion exchange process for generation of low radioactive waste and maximize utilization of the ion exchange resins by employing different types of resins and different modes of operation. The investigations revealed that use of mixed bed (MB) resin column consisting of Strong Acid Cation (SAC) resin and Strong Base Anion (SBA) resin followed by SAC resin column is efficient in removing the Gd 3+ and NO 3 - from the system besides maintaining the pH of the moderator system in the desirable regime, where gadolinium does not get precipitated as its hydroxide. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Gadolinium Scandium Gallium Garnet (GSGG) as a Solid-State Laser Host

    DTIC Science & Technology

    1987-07-01

    o*SATI CODSi1.SBEC EM (otne nrvrs fnceayad dniy nb)k ubr ~~~~~~~~ Gadolinium Scandium Gallium Garnet (GSGG)asaSldtteLerHt 17. ABSTRACT 6.SUJCTTEM...certain other garnet materials for replacement. It also addresses the solid-state laser host material Gadolinium Scandium Gal- lium Garnet (GSGG) and its...by neodymium-doped yttrium aluminum garnet (Nd:YAG) or other mate- rials for most applications. In the years after the invention of the ruby laser, in

  1. The effect of inflammation and its reduction on brain plasticity in multiple sclerosis: MRI evidence.

    PubMed

    Tomassini, Valentina; d'Ambrosio, Alessandro; Petsas, Nikolaos; Wise, Richard G; Sbardella, Emilia; Allen, Marek; Tona, Francesca; Fanelli, Fulvia; Foster, Catherine; Carnì, Marco; Gallo, Antonio; Pantano, Patrizia; Pozzilli, Carlo

    2016-07-01

    Brain plasticity is the basis for systems-level functional reorganization that promotes recovery in multiple sclerosis (MS). As inflammation interferes with plasticity, its pharmacological modulation may restore plasticity by promoting desired patterns of functional reorganization. Here, we tested the hypothesis that brain plasticity probed by a visuomotor adaptation task is impaired with MS inflammation and that pharmacological reduction of inflammation facilitates its restoration. MS patients were assessed twice before (sessions 1 and 2) and once after (session 3) the beginning of Interferon beta (IFN beta), using behavioural and structural MRI measures. During each session, 2 functional MRI runs of a visuomotor task, separated by 25-minutes of task practice, were performed. Within-session between-run change in task-related functional signal was our imaging marker of plasticity. During session 1, patients were compared with healthy controls. Comparison of patients' sessions 2 and 3 tested the effect of reduced inflammation on our imaging marker of plasticity. The proportion of patients with gadolinium-enhancing lesions reduced significantly during IFN beta. In session 1, patients demonstrated a greater between-run difference in functional MRI activity of secondary visual areas and cerebellum than controls. This abnormally large practice-induced signal change in visual areas, and in functionally connected posterior parietal and motor cortices, was reduced in patients in session 3 compared with 2. Our results suggest that MS inflammation alters short-term plasticity underlying motor practice. Reduction of inflammation with IFN beta is associated with a restoration of this plasticity, suggesting that modulation of inflammation may enhance recovery-oriented strategies that rely on patients' brain plasticity. Hum Brain Mapp 37:2431-2445, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Gadolinium Brain Deposition after Macrocyclic Gadolinium Administration: A Pediatric Case-Control Study.

    PubMed

    Tibussek, Daniel; Rademacher, Christin; Caspers, Julian; Turowski, Bernd; Schaper, Jörg; Antoch, Gerald; Klee, Dirk

    2017-10-01

    Purpose To determine whether signal intensity (SI) in T1 sequences as a potential indicator of gadolinium deposition increases after repeated administration of the macrocyclic gadolinium-based contrast agents (GBCAs) gadoteridol and gadoterate meglumine in a pediatric cohort. Materials and Methods This retrospective case-control study of children with brain tumors who underwent nine or more contrast material-enhanced brain magnetic resonance (MR) imaging studies from 2008 to 2015 was approved by the local ethics board. Informed consent was obtained for MR imaging. Twenty-four case patients aged 5-18 years and appropriate control patients with nonpathologic MR neuroimaging findings (and no GBCA administration), matched for age and sex, were inculded. SI was measured on unenhanced T1-weighted MR images for the following five regions of interest (ROIs): the dentate nucleus (DN), pons, substantia nigra (SN), pulvinar thalami, and globus pallidus (GP). Paired t tests were used to compare SI and SI ratios (DN to pons, GP to thalamus) between case patients and control patients. Pearson correlations between relative signal changes and the number of GBCA administrations and total GBCA dose were calculated. Results The mean number of GBCA administrations was 14.2. No significant differences in mean SI for any ROI and no group differences were found when DN-to-pons and GP-to-pulvinar ratios were compared (DN-to-pons ratio in case patients: mean, 1.0083 ± 0.0373 [standard deviation]; DN-to-pons ratio in control patients: mean, 1.0183 ± 0.01917; P = .37; GP-to-pulvinar ratio in case patients: mean, 1.1335 ± 0.04528; and GP-to-pulvinar ratio in control patients: mean, 1.1141 ± 0.07058; P = .29). No correlation was found between the number of GBCA administrations or the total amount of GBCA administered and signal change for any ROI. (Number of GBCA applications: DN: r = -0.254, P = .31; pons: r = -0.097, P = .65; SN: r = -0.194, P = .38; GP: r = -0.175, P = .41; pulvinar: r

  3. Gadolinium Endohedral Metallofullerene-Based MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Bolskar, Robert D.

    With the ability to encapsulate and carry the highly paramagnetic Gd3+ ion, gadolinium endohedral metallofullerenes or "gadofullerenes" are being explored as alternatives to the chelate complexes that are currently used for contrast-enhanced magnetic resonance imaging (MRI). Reviewed here are the various water-soluble derivatives of the gadofullerenes Gd@C82, Gd@C60, and Gd3N@C80 that have been investigated as MRI contrast agents. The water proton r1 relaxivities of gadofullerenes can be more than an order of magnitude higher than those of clinically used chelate agents. Gadofullerene relaxivity mechanisms have been studied, and multiple factors are found to contribute to their high relaxivities. In vitro and in vivoT1-weighted MRI tests of gadofullerene derivatives have shown their utility as bright image-enhancing agents. The gadofullerene MRI contrast agents are a promising new and unique style of gadolinium carrier for advanced imaging applications, including cellular and molecular imaging.

  4. miR-122-SOCS1-JAK2 axis regulates allergic inflammation and allergic inflammation-promoted cellular interactions

    PubMed Central

    Kim, Hanearl; Kim, Hyuna; Byun, Jaehwan; Park, Yeongseo; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

    2017-01-01

    The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation. TargetScan analysis predicted the binding of miR-122 to the 3′-UTR of SOCS1. miR-122 inhibitor induced in vitro and in vivo allergic features in SOCS1-dependent manner. SOCS1 was necessary for allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells. SOCS1 and miR-122 regulated cellular interactions involving cancer cells, mast cells and macrophages during allergic inflammation. SOCS1 mimetic peptide, D-T-H-F-R-T-F-R-S-H-S-D-Y-R-R-I, inhibited in vitro and in vivo allergic inflammation, allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells, and cellular interactions during allergic inflammation. Janus kinase 2 (JAK2) exhibited binding to SOCS1 mimetic peptide and mediated allergic inflammation. Transforming growth factor- Δ1 (TGF-Δ1) was decreased during allergic inflammation and showed an anti-allergic effect. SOCS1 and JAK2 regulated the production of anti-allergic TGF-Δ1. Taken together, our results show that miR-122-SOCS1 feedback loop can be employed as a target for the development of anti-allergic and anti-cancer drugs. PMID:28968979

  5. Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

    PubMed

    McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

    2017-11-01

    Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m 2 ) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial

  6. Tumor Xenograft Response to Redox-Active Therapies Assessed by Magnetic Resonance Imaging Using a Thiol-Bearing DOTA Complex of Gadolinium1

    PubMed Central

    Guntle, Gerald P; Jagadish, Bhumasamudram; Mash, Eugene A; Powis, Garth; Dorr, Robert T; Raghunand, Natarajan

    2012-01-01

    Gd-LC6-SH is a thiol-bearing DOTA complex of gadolinium designed to bind plasma albumin at the conserved Cys34 site. The binding of Gd-LC6-SH shows sensitivity to the presence of competing thiols. We hypothesized that Gd-LC6-SH could provide magnetic resonance imaging (MRI) enhancement that is sensitive to tumor redox state and that the prolonged retention of albumin-bound Gd-LC6-SH in vivo can be exploited to identify a saturating dose above which the shortening of MRI longitudinal relaxation time (T1) of tissue is insensitive to the injected gadolinium dose. In the Mia-PaCa-2 pancreatic tumor xenograft model in SCID mice, both the small-molecule Gd-DTPA-BMA and the macromolecule Galbumin MRI contrast agents produced dose-dependent decreases in tumor T1. By contrast, the decreases in tumor T1 provided by Gd-LC6-SH at 0.05 and 0.1 mmol/kg were not significantly different at longer times after injection. SCID mice bearing Mia-PaCa-2 or NCI-N87 tumor xenografts were treated with either the glutathione synthesis inhibitor buthionine sulfoximine or the thiol-oxidizing anticancer drug Imexon, respectively. In both models, there was a significantly greater increase in tumor R1 (=1/T1) 60 minutes after injection of Gd-LC6-SH in drug-treated animals relative to saline-treated controls. In addition, Mercury Orange staining for nonprotein sulfhydryls was significantly decreased by drug treatment relative to controls in both tumor models. In summary, these studies show that thiol-bearing complexes of gadolinium such as Gd-LC6-SH can serve as redox-sensitive MRI contrast agents for detecting differences in tumor redox status and can be used to evaluate the effects of redox-active drugs. PMID:22741038

  7. Gadolinium-based nanoparticles to improve the hadrontherapy performances.

    PubMed

    Porcel, Erika; Tillement, Olivier; Lux, François; Mowat, Pierre; Usami, Noriko; Kobayashi, Katsumi; Furusawa, Yoshiya; Le Sech, Claude; Li, Sha; Lacombe, Sandrine

    2014-11-01

    Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Coagonist of GLP-1 and glucagon decreases liver inflammation and atherosclerosis in dyslipidemic condition.

    PubMed

    Patel, Vishal; Joharapurkar, Amit; Kshirsagar, Samadhan; Sutariya, Brijesh; Patel, Maulik; Pandey, Dheerendra; Patel, Hiren; Ranvir, Ramchandra; Kadam, Shekhar; Patel, Dipam; Bahekar, Rajesh; Jain, Mukul

    2018-02-25

    Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and glucagon are under clinical investigation for the treatment of obesity and diabetes. Earlier, we have observed that coagonist reduced circulating and hepatic lipids, independent of its anorexic effects. Here, we investigated the role of coagonist of GLP-1 and glucagon receptors in complications of diet-induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of GLP-1 and glucagon receptors (75 and 150 μg/kg). Pair-fed control was maintained. Cholesterol fed transgenic mice overexpressing hApoB100 and hCETP with coagonist (300 μg/kg) for 4 weeks. After the completion of treatment, biochemical estimations were done. Coagonist treatment reduced triglycerides in plasma, liver and aorta, plasma cholesterol and hepatic triglyceride secretion rate. Expressions of HMG-CoA reductase and SBREBP-1C were reduced and expressions of LDLR, CYP7A1, ABCA1 and ABCB11 were increased in liver, due to coagonist treatment. Coagonist treatment increased bile flow rate and biliary cholesterol excretion. IL-6 and TNF-α were reduced in plasma and expression of TNF-α, MCP-1, MMP-9 and TIMP-1 decreased in liver. Treatment with coagonist reduced oxidative stress in liver and aorta. Energy expenditure was increased and respiratory quotient was reduced by coagonist treatment. These changes were correlated with reduced hepatic inflammation and lipids in liver and aorta in coagonist treated hamsters. Coagonist treatment also reduced lipids in cholesterol-fed transgenic mice. These changes were independent of glycaemia and anorexia observed after coagonist treatment. Long term treatment with coagonist of GLP-1 and glucagon receptor ameliorated diet-induced dyslipidemia and atherosclerosis by regulating bile homeostasis, liver inflammation and energy expenditure. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis: Retrospective Analysis of an 18-Year Longitudinal Study.

    PubMed

    Forslin, Y; Shams, S; Hashim, F; Aspelin, P; Bergendal, G; Martola, J; Fredrikson, S; Kristoffersen-Wiberg, M; Granberg, T

    2017-07-01

    Gadolinium-based contrast agents have been associated with lasting high T1-weighted signal intensity in the dentate nucleus and globus pallidus, with histopathologically confirmed gadolinium retention. We aimed to longitudinally investigate the relationship of multiple gadolinium-based contrast agent administrations to the Signal Intensity Index in the dentate nucleus and globus pallidus and any associations with cognitive function in multiple sclerosis. The Signal Intensity Index in the dentate nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving multiple gadolinium-based contrast agent administrations and 23 healthy age- and sex-matched controls. Participants also underwent comprehensive neuropsychological testing. Patients with MS had a higher Signal Intensity Index in the dentate nucleus ( P < .001), but not in the globus pallidus ( P = .19), compared with non-gadolinium-based contrast agent-exposed healthy controls by an unpaired t test. Increasing numbers of gadolinium-based contrast agent administrations were associated with an increased Signal Intensity Index in the dentate nucleus (β = 0.45, P < .001) and globus pallidus (β = 0.60, P < .001). This association remained stable with corrections for the age, disease duration, and physical disability for both the dentate nucleus (β = 0.43, P = .001) and globus pallidus (β = 0.58, P < .001). An increased Signal Intensity Index in the dentate nucleus among patients with MS was associated with lower verbal fluency scores, which remained significant after correction for several aspects of disease severity (β = -0.40 P = .013). Our data corroborate previous reports of lasting gadolinium retention in brain tissues. An increased Signal Intensity Index in the dentate nucleus and globus pallidus was associated with lower verbal fluency, which does not prove causality but encourages further studies on cognition

  10. Hypophosphatemia is Associated with the Serial Administration of Triple-Dose Gadolinium to Patients for Brain MRI.

    PubMed

    Wolansky, Leo J; Cadavid, Diego; Punia, Vineet; Kim, Soyeon; Cheriyan, Jojy; Haghighi, Mershad; Cook, Stuart D

    2015-01-01

    The purpose of this study is to report a metabolic abnormality associated with frequent, triple-dose Gadolinium (TdGd) use in MS patients during BECOME trial. Potential clinical adverse events and lab abnormalities were monitored at each monthly MRI visit. Hypophosphatemia was defined as phosphate <2.5 mg/dL. Statistical analysis included McNemar's test for pairwise comparisons across visits and generalized estimating equations (GEE) to fit models over time. Eight hundred seventy seven phosphate values were analyzed from the first 12 months. Compared with 4% of subjects at screening, an average of 15.1% (95% confidence interval (CI): 11.4%-19.7%) of patients had hypophosphatemia at visits from months 1 to 12, during which subjects received serial TdGd. Forty four of seventy five (59%) patients developed hypophosphatemia at least once. We also found a significant increasing trend in hypophosphatemia by visit when treatment groups were evaluated together or separately (p < .001). There was a statistically significant decrease in frequency to 9.8% (95% CI: 4.6-19.8%) by month 24 (p = .005) coinciding with a period of less frequent gadolinium administration. Serial TdGd in MS patients, unrelated to immunomodulatory treatment, was associated with increased frequency of hypophosphatemia that progressed with cumulative triple-dose and markedly decreased in second year, with less frequent triple-dose administration. Copyright © 2015 by the American Society of Neuroimaging.

  11. Myocardial late gadolinium enhancement in specific cardiomyopathies by cardiovascular magnetic resonance: a preliminary experience.

    PubMed

    Silva, Caterina; Moon, James C; Elkington, Andrew G; John, Anna S; Mohiaddin, Raad H; Pennell, Dudley J

    2007-12-01

    Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.

  12. Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

    PubMed

    Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

    2016-12-01

    While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of

  13. The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

    NASA Astrophysics Data System (ADS)

    Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2016-07-01

    We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.

  14. Analytical Interference in Serum Iron Determination Reveals Iron Versus Gadolinium Transmetallation With Linear Gadolinium-Based Contrast Agents

    PubMed Central

    Fretellier, Nathalie; Poteau, Nathalie; Factor, Cécile; Mayer, Jean-François; Medina, Christelle; Port, Marc; Idée, Jean-Marc; Corot, Claire

    2014-01-01

    Objectives The purposes of this study were to evaluate the risk for analytical interference with gadolinium-based contrast agents (GBCAs) for the colorimetric measurement of serum iron (Fe3+) and to investigate the mechanisms involved. Materials and Methods Rat serum was spiked with several concentrations of all molecular categories of GBCAs, ligands, or “free” soluble gadolinium (Gd3+). Serum iron concentration was determined by 2 different colorimetric methods at pH 4.0 (with a Vitros DT60 analyzer or a Cobas Integra 400 analyzer). Secondly, the cause of interference was investigated by (a) adding free soluble Gd3+ or Mn2+ to serum in the presence of gadobenic acid or gadodiamide and (b) electrospray ionization mass spectrometry. Results Spurious decrease in serum Fe3+ concentration was observed with all linear GBCAs (only with the Vitros DT60 technique occurring at pH 4.0) but not with macrocyclic GBCAs or with free soluble Gd3+. Spurious hyposideremia was also observed with the free ligands present in the pharmaceutical solutions of the linear GBCAs gadopentetic acid and gadodiamide (ie, diethylene triamine pentaacetic acid and calcium-diethylene triamine pentaacetic acid bismethylamide, respectively), suggesting the formation of Fe-ligand chelate. Gadobenic acid-induced interference was blocked in a concentration-dependent fashion by adding a free soluble Gd3+ salt. Conversely, Mn2+, which has a lower affinity than Gd3+ and Fe3+ for the ligand of gadobenic acid (ie, benzyloxypropionic diethylenetriamine tetraacetic acid), was less effective (interference was only partially blocked), suggesting an Fe3+ versus Gd3+ transmetallation phenomenon at pH 4.0. Similar results were observed with gadodiamide. Mass spectrometry detected the formation of Fe-ligand with all linear GBCAs tested in the presence of Fe3+ and the disappearance of Fe-ligand after the addition of free soluble Gd3+. No Fe-ligand chelate was found in the case of the macrocyclic GBCA gadoteric

  15. In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

    PubMed

    Mowat, P; Mignot, A; Rima, W; Lux, F; Tillement, O; Roulin, C; Dutreix, M; Bechet, D; Huger, S; Humbert, L; Barberi-Heyob, M; Aloy, M T; Armandy, E; Rodriguez-Lafrasse, C; Le Duc, G; Roux, S; Perriat, P

    2011-09-01

    Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

  16. Aging, not age-associated inflammation, determines blood pressure and endothelial responses to acute inflammation.

    PubMed

    Lane-Cordova, Abbi D; Ranadive, Sushant M; Kappus, Rebecca M; Cook, Marc D; Phillips, Shane A; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Fernhall, Bo

    2016-12-01

    Aging is characterized by a state of chronic, low-grade inflammation that impairs vascular function. Acute inflammation causes additional decrements in vascular function, but these responses are not uniform in older compared with younger adults. We sought to determine if older adults with low levels of baseline inflammation respond to acute inflammation in a manner similar to younger adults. We hypothesized age-related differences in the vascular responses to acute inflammation, but that older adults with low baseline inflammation would respond similarly to younger adults. Inflammation was induced with an influenza vaccine in 96 participants [older = 67 total, 38 with baseline C-reactive protein (CRP) > 1.5 mg/l and 29 with CRP < 1.5 mg/l; younger = 29]; serum inflammatory markers IL-6 and CRP, blood pressure and flow-mediated dilation (FMD) were measured 24 and 48 h later. Younger adults increased IL-6 and CRP more than the collective older adult group and increased pulse pressure, whereas older adults decreased SBP and reduced pulse pressure. The entire cohort decreased FMD from 11.3 ± 0.8 to 8.3 ± 0.7 to 8.7 ± 0.7% in younger and from 5.8 ± 0.3 to 5.0 ± 0.4 to 4.7 ± 0.4% in older adults, P less than 0.05 for main effect. Older adult groups with differing baseline CRP had the same IL-6, blood pressure, and FMD response to acute inflammation, P less than 0.05 for all interactions, but the low-CRP group increased CRP at 24 and 48 h (from 0.5 ± 0.1 to 1.4 ± 0.2 to 1.7 ± 0.3 mg/l), whereas the high-CRP group did not (from 4.8 ± 0.5 to 5.4 ± 0.5 to 5.4 ± 0.6 mg/l), P less than 0.001 for interaction. Aging, not age-related chronic, low-grade inflammation, determines the vascular responses to acute inflammation.

  17. Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

    PubMed Central

    Coughlin, Andrew J.; Ananta, Jeyarama S.; Deng, Nanfu; Larina, Irina V.; Decuzzi, Paolo

    2014-01-01

    Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, we have engineered gadolinium-conjugated gold nanoshells and demonstrated that they enhance contrast for magnetic resonance imaging, X-Ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation. PMID:24115690

  18. A High-Fat Diet Decreases Bone Mass in Growing Mice with Systemic Chronic Inflammation Induced by Low-Dose, Slow-Release Lipopolysaccharide Pellets.

    PubMed

    Cao, Jay J; Gregoire, Brian R; Shen, Chwan-Li

    2017-10-01

    Background: Chronic inflammation is associated with increased bone resorption and is linked to osteopenia, or low bone mass. Obesity is also associated with low-grade chronic upregulation of inflammatory cytokines. Objective: This study investigated the effect of high-fat (HF) diet-induced obesity on bone structure changes in growing mice with existing systemic chronic inflammation induced by low-dose, slow-release lipopolysaccharide (LPS). Methods: Forty-eight 6-wk-old female C57BL/6 mice were randomly assigned to 4 treatment groups ( n = 12/group) in a 2 × 2 factorial design-control (placebo) or LPS treatment (1.5 μ g/d)-and consumed either a normal-fat (NF, 10% of energy as fat) or an HF (45% of energy as fat) diet ad libitum for 13 wk. Bone structure, serum biomarkers of bone turnover, and osteoclast differentiation were measured. Results: No alterations were observed in final body weights, fat mass, or lean mass in response to LPS treatment. LPS treatment increased serum concentration of tartrate-resistant acid phosphatase (TRAP, a bone resorption marker) and bone marrow osteoclast differentiation and decreased femoral and lumbar vertebral bone volume (BV):total volume (TV) by 25% and 24%, respectively, compared with the placebo. Mice fed the HF diet had greater body weight at the end of the study ( P < 0.01) due to increased fat mass ( P < 0.01) than did mice fed the NF diet. The HF diet increased serum TRAP concentration, bone marrow osteoclast differentiation, and expression of tumor necrosis factor α, interleukin 1β and interleukin 6 in adipose tissue. Compared with the NF diet, the HF diet decreased BV:TV by 10% and 8% at femur and lumbar vertebrae, respectively, and the HF diet was detrimental to femoral and lumbar vertebral bone structure with decreased trabecular number and increased trabecular separation and structure model index. Conclusion: Results suggest that HF diets and systemic chronic inflammation have independent negative effects on bone

  19. Effects of iodinated contrast agent, xylocaine and gadolinium concentration on the signal emitted in magnetic resonance arthrography: a samples study*

    PubMed Central

    da Silva, Yvana Lopes Pinheiro; Costa, Rita Zanlorensi Visneck; Pinho, Kátia Elisa Prus; Ferreira, Ricardo Rabello; Schuindt, Sueliton Miyamoto

    2015-01-01

    Objective To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography. PMID:25987746

  20. The Effect of gadolinium on the ESR response of alanine and ammonium tartrate exposed to thermal neutrons.

    PubMed

    Marrale, Maurizio; Brai, Maria; Gennaro, Gaetano; Bartolotta, Antonio; D'Oca, Maria Cristina

    2008-02-01

    Many efforts have been made to develop neutron capture therapy (NCT) for cancer treatment. Among the challenges in using NCT is the characterization of the features of the mixed radiation field and of its components. In this study, we examined the enhancement of the ESR response of pellets of alanine and ammonium tartrate with gadolinium oxide exposed to a thermal neutron beam. In particular, the ESR response of these dosimeters as a function of the gadolinium content inside the dosimeter was analyzed. We found that the addition of gadolinium improves the sensitivity of both alanine and ammonium tartrate. However, the use of gadolinium reduces or abolishes tissue equivalence because of its high atomic number (Z(Gd) = 64). Therefore, it is necessary to find the optimum compromise between the sensitivity to thermal neutrons and the reduction of tissue equivalence. Our analysis showed that a low concentration of gadolinium oxide (of the order of 5% of the total mass of the dosimeter) can enhance the thermal neutron sensitivity more than 13 times with an insignificant reduction of tissue equivalence.

  1. Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice

    NASA Astrophysics Data System (ADS)

    Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B.; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

    2017-09-01

    Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

  2. Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice.

    PubMed

    Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

    2017-09-06

    Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64 Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64 Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18 F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

  3. Gadolinium-loaded Plastic Scintillators for Thermal Neutron Detection using Compensation

    NASA Astrophysics Data System (ADS)

    Dumazert, Jonathan; Coulon, Romain; Hamel, Matthieu; Carrel, Frédérick; Sguerra, Fabien; Normand, Stéphane; Méchin, Laurence; Bertrand, Guillaume H. V.

    2016-06-01

    Plastic scintillator loading with gadolinium-rich organometallic complexes shows a high potential for the deployment of efficient and cost-effective neutron detectors. Due to the low-energy photon and electron signature of thermal neutron capture by Gd-155 and Gd-157, alternative treatment to pulse-shape discrimination has to be proposed in order to display a count rate. This paper discloses the principle of a compensation method applied to a two-scintillator system: a detection scintillator interacts with photon and fast neutron radiation and is loaded with gadolinium organometallic compound to become a thermal neutron absorber, while a not-gadolinium loaded compensation scintillator solely interacts with the fast neutron and photon part of incident radiation. After the nonlinear smoothing of the counting signals, a hypothesis test determines whether the resulting count rate post-background response compensation falls into statistical fluctuations or provides a robust indication of neutron activity. Laboratory samples are tested under both photon and neutron irradiations, allowing the authors to investigate the performance of the overall detection system in terms of sensitivity and detection limits, especially with regards to a similar-active volume He-3 based commercial counter. The study reveals satisfactory figures of merit in terms of sensitivity and directs future investigation toward promising paths.

  4. Tracing gadolinium-based contrast agents from surface water to drinking water by means of speciation analysis.

    PubMed

    Birka, Marvin; Wehe, Christoph A; Hachmöller, Oliver; Sperling, Michael; Karst, Uwe

    2016-04-01

    In recent decades, a significant amount of anthropogenic gadolinium has been released into the environment as a result of the broad application of contrast agents for magnetic resonance imaging (MRI). Since this anthropogenic gadolinium anomaly has also been detected in drinking water, it has become necessary to investigate the possible effect of drinking water purification on these highly polar microcontaminats. Therefore, a novel highly sensitive method for speciation analysis of gadolinium is presented. For that purpose, the hyphenation of hydrophilic interaction liquid chromatography (HILIC) and inductively coupled plasma-mass spectrometry (ICP-MS) was employed. In order to enhance the detection power, sample introduction was carried out by ultrasonic nebulization. In combination with a novel HILIC method using a diol-based stationary phase, it was possible to achieve superior limits of detection for frequently applied gadolinium-based contrast agents below 20pmol/L. With this method, the contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A were determined in concentrations up to 159pmol/L in samples from several waterworks in a densely populated region of Germany alongside the river Ruhr as well as from a waterworks near a catchment lake. Thereby, the direct impact of anthropogenic gadolinium species being present in the surface water on the amount of anthropogenic gadolinium in drinking water was shown. There was no evidence for the degradation of contrast agents, the release of Gd(3+) or the presence of further Gd species. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

    PubMed

    Smith, Cartney E; Shkumatov, Artem; Withers, Sarah G; Yang, Binxia; Glockner, James F; Misra, Sanjay; Roy, Edward J; Wong, Chun-Ho; Zimmerman, Steven C; Kong, Hyunjoon

    2013-11-26

    Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.

  6. A Polymeric Fastener can Easily Functionalize Liposome Surfaces with Gadolinium for Enhanced Magnetic Resonance Imaging

    PubMed Central

    Smith, Cartney E.; Shkumatov, Artem; Withers, Sarah G.; Glockner, James F.; Misra, Sanjay; Roy, Edward J.; Wong, Chun-Ho; Zimmerman, Steven C.; Kong, Hyunjoon

    2013-01-01

    Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization, and therefore has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication. PMID:24083377

  7. Gadolinium-based compounds induce NLRP3-dependent IL-1β production and peritoneal inflammation.

    PubMed

    Schmidt-Lauber, Christian; Bossaller, Lukas; Abujudeh, Hani H; Vladimer, Gregory I; Christ, Anette; Fitzgerald, Katherine A; Latz, Eicke; Gravallese, Ellen M; Marshak-Rothstein, Ann; Kay, Jonathan

    2015-11-01

    Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing disorder that may develop in patients with chronic kidney disease after administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis subsequently develops. However, the precise mechanism by which fibrosis occurs in NSF is incompletely understood. Because other profibrotic agents, such as silica or asbestos, activate the nucleotide-binding oligomerisation domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and initiate interleukin (IL)-1β release with the subsequent development of fibrosis, we evaluated the effects of GBCAs on inflammasome activation. Bone marrow derived macrophages from C57BL/6, Nlrp3(-/-) and Asc(-/-) mice were incubated with three Gd-containing compounds and IL-1β activation and secretion was detected by ELISA and western blot analysis. Inflammasome activation and regulation was investigated in IL-4- and interferon (IFN)γ-polarised macrophages by ELISA, quantitative real time (qRT)-PCR and NanoString nCounter analysis. Furthermore, C57BL/6 and Nlrp3(-/-)mice were intraperitoneally injected with GBCA and recruitment of inflammatory cells to the peritoneum was analysed by fluorescence-activated cell sorting (FACS). Free Gd and GBCAs activate the NLRP3 inflammasome and induce IL-1β secretion in vitro. Gd-diethylenetriaminepentaacetic acid also induces the recruitment of neutrophils and inflammatory monocytes to the peritoneum in vivo. Gd activated IL-4-polarised macrophages more effectively than IFNγ-polarised macrophages, which preferentially expressed genes known to downregulate inflammasome activity. These data suggest that Gd released from GBCAs triggers a NLRP3 inflammasome-dependent inflammatory response that leads to fibrosis in an appropriate clinical setting. The preferential activation of IL-4-differentiated macrophages is consistent with the predominantly fibrotic

  8. Gadolinium deposition disease: Initial description of a disease that has been around for a while.

    PubMed

    Semelka, Richard C; Ramalho, Joana; Vakharia, Ami; AlObaidy, Mamdoh; Burke, Lauren M; Jay, Michael; Ramalho, Miguel

    2016-12-01

    To describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function. Participants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30days of this MRI, and no pre-existent clinical symptoms and/or signs of this type. 42 subjects responded to the survey (age: 28-69, mean 49.1±22.4years). The most common findings were: central pain (n=15), peripheral pain (n=26), headache (n=28), and bone pain (n=26). Only subjects with distal leg and arm distribution described skin thickening (n=22). Clouded mentation and headache were the symptoms described as persistent beyond 3months in 29 subjects. Residual disease was present in all patients. Twenty-eight patients described symptoms following administration of one brand of Gadolinium-Based Contrast Agent (GBCA), 21 after a single GBCA administration and 7 after multiple GBCA administrations, including: gadopentetate dimeglumine, n=9; gadodiamide, n=4; gadoversetamide, n=4; gadobenate dimeglumine, n=4; gadobutrol, n=1; gadoteridol, n=2; and unknown, n=4. Gadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

    PubMed

    Taoka, Toshiaki; Naganawa, Shinji

    2018-04-10

    After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

  10. Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

    PubMed Central

    Taoka, Toshiaki; Naganawa, Shinji

    2018-01-01

    After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

  11. Do we need gadolinium-based contrast medium for brain magnetic resonance imaging in children?

    PubMed

    Dünger, Dennis; Krause, Matthias; Gräfe, Daniel; Merkenschlager, Andreas; Roth, Christian; Sorge, Ina

    2018-06-01

    Brain imaging is the most common examination in pediatric magnetic resonance imaging (MRI), often combined with the use of a gadolinium-based contrast medium. The application of gadolinium-based contrast medium poses some risk. There is limited evidence of the benefits of contrast medium in pediatric brain imaging. To assess the diagnostic gain of contrast-enhanced sequences in brain MRI when the unenhanced sequences are normal. We retrospectively assessed 6,683 brain MR examinations using contrast medium in children younger than 16 years in the pediatric radiology department of the University Hospital Leipzig to determine whether contrast-enhanced sequences delivered additional, clinically relevant information to pre-contrast sequences. All examinations were executed using a 1.5-T or a 3-T system. In 8 of 3,003 (95% confidence interval 0.12-0.52%) unenhanced normal brain examinations, a relevant additional finding was detected when contrast medium was administered. Contrast enhancement led to a change in diagnosis in only one of these cases. Children with a normal pre-contrast brain MRI rarely benefit from contrast medium application. Comparing these results to the risks and disadvantages of a routine gadolinium application, there is substantiated numerical evidence for avoiding routine administration of gadolinium in a pre-contrast normal MRI examination.

  12. Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

    PubMed

    Fujimoto, T; Ichikawa, H; Akisue, T; Fujita, I; Kishimoto, K; Hara, H; Imabori, M; Kawamitsu, H; Sharma, P; Brown, S C; Moudgil, B M; Fujii, M; Yamamoto, T; Kurosaka, M; Fukumori, Y

    2009-07-01

    Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

  13. Inflammation Stimulates the Expression of PCSK9

    PubMed Central

    Feingold, Kenneth R.; Moser, Arthur H.; Shigenaga, Judy K.; Patzek, Sophie M.; Grunfeld, Carl

    2008-01-01

    Inflammation induces marked changes in lipid and lipoprotein metabolism. Proprotein convertase subtilisin kexin 9 (PCSK9) plays an important role in regulating LDL receptor degradation. Here we demonstrate that LPS decreases hepatic LDL receptor protein but at the same time hepatic LDL receptor mRNA levels are not decreased. We therefore explored the effect of LPS on PCSK9 expression. LPS results in a marked increase in hepatic PCSK9 mRNA levels (4 hours-2.5 fold increase; 38 hours-12.5 fold increase). The increase in PCSK9 is a sensitive response with 1 ug LPS inducing a ½ maximal response. LPS also increased PCSK9 expression in the kidney. Finally, zymosan and turpentine, other treatments that induce inflammation, also stimulated hepatic expression of PCSK9. Thus, inflammation stimulates PCSK9 expression leading to increased LDL receptor degradation and decreasing LDL receptors thereby increasing serum LDL, which could have beneficial effects on host defense. PMID:18638454

  14. Menhaden Oil Decreases High-Fat Diet–Induced Markers of Hepatic Damage, Steatosis, Inflammation, and Fibrosis in Obese Ldlr−/− Mice123

    PubMed Central

    Depner, Christopher M.; Torres-Gonzalez, Moises; Tripathy, Sasmita; Milne, Ginger; Jump, Donald B.

    2012-01-01

    The frequency of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with obesity in the United States. NASH is progressive and characterized by hepatic damage, inflammation, fibrosis, and oxidative stress. Because C20–22 (n-3) PUFA are established regulators of lipid metabolism and inflammation, we tested the hypothesis that C20–22 (n-3) PUFA in menhaden oil (MO) prevent high-fat (HF) diet–induced fatty liver disease in mice. Wild-type (WT) and Ldlr−/− C57BL/6J mice were fed the following diets for 12 wk: nonpurified (NP), HF with lard (60% of energy from fat), HF–high-cholesterol with olive oil (HFHC-OO; 54.4% of energy from fat, 0.5% cholesterol), or HFHC-OO supplemented with MO (HFHC-MO). When compared with the NP diet, the HF and HFHC-OO diets induced hepatosteatosis and hepatic damage [elevated plasma alanine aminotransferase (ALT) and aspartate aminotransferases] and elevated hepatic expression of markers of inflammation (monocyte chemoattractant protein-1), fibrosis (procollagen 1α1), and oxidative stress (heme oxygenase-1) (P ≤ 0.05). Hepatic damage (i.e., ALT) correlated (r = 0.74, P < 0.05) with quantitatively higher (>140%, P < 0.05) hepatic cholesterol in Ldlr−/− mice fed the HFHC-OO diet than WT mice fed the HF or HFHC-OO diets. Plasma and hepatic markers of liver damage, steatosis, inflammation, and fibrosis, but not oxidative stress, were lower in WT and Ldlr−/− mice fed the HFHC-MO diet compared with the HFHC-OO diet (P < 0.05). In conclusion, MO [C20–22 (n-3) PUFA at 2% of energy] decreases many, but not all, HF diet–induced markers of fatty liver disease in mice. PMID:22739374

  15. Acute coronary disease Athero-Inflammation: Therapeutic approach

    PubMed Central

    Altman, Raul

    2003-01-01

    Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events. Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease. PMID:12904261

  16. Measurement of gamma-ray production from thermal neutron capture on gadolinium for neutrino experiments

    NASA Astrophysics Data System (ADS)

    Yano, Takatomi; 2012B0025 Collaboration; 2014B0126 Collaboration

    2017-02-01

    Recently, several scientific applications of gadolinium are found in neutrino physics experiments. Gadolinium-157 is the nucleus, which has the largest thermal neutron capture cross-section among all stable nuclei. Gadolinium-155 also has the large cross-section. These neutron capture reactions provide the gamma-ray cascade with the total energy of about 8 MeV. This reaction is applied for several neutrino experiments, e.g. reactor neutrino experiments and Gd doped large water Cherenkov detector experiments, to recognize inverse-beta-decay reaction. A good Gd(n,γ) simulation model is needed to evaluate the detection efficiency of the neutron capture reaction, i.e. the efficiency of IBD detection. In this presentation, we will report the development and study status of a Gd(n,γ) calculation model and comparison with our experimental data taken at ANNRI/MLF beam line, J-PARC.

  17. Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.

    PubMed

    Runge, Val M

    2017-06-01

    For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was

  18. Type-II domains in ferroelectric gadolinium molybdate (in German)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bohm, J.; Kuersten, H.D.

    Etching (001)-faces of gadolinium molybdate (GMO) reveals new kinds of domains. They are created by a translation, that leaves the spontaneous polarization and the transition parameter invariant. The translation vector is a part of a lattice vector, similar to stacking faults. (auth)

  19. Targeting inflammation in diabetes: Newer therapeutic options

    PubMed Central

    Agrawal, Neeraj Kumar; Kant, Saket

    2014-01-01

    Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resistance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflammation.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. Interleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce inflammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabetes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory markers. Retinopathy drugs are used to target vascular endothelial growth factor, angiopoietin-2, various proteinases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapamycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, peroxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory therapies represent a potential approach for the therapy of diabetes and its complications. PMID:25317247

  20. Nanoamplifiers synthesized from gadolinium and gold nanocomposites for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Tian, Xiumei; Shao, Yuanzhi; He, Haoqiang; Liu, Huan; Shen, Yingying; Huang, Wenlin; Li, Li

    2013-03-01

    We have synthesized an efficient and highly sensitive nanoamplifier composed of gadolinium-doped silica nanoparticles and gold nanoparticles (AuNPs). Magnetic resonance imaging (MRI) in vitro and in vivo assays revealed enhancement of signal sensitivity, which may be explained by electron transfer between water and gadolinium-doped nanoparticles, apparent in the presence of gold. In vitro and in vivo evaluation demonstrated nanoamplifier incurred minimal cytotoxicity and immunotoxicity, increased stability, and gradual excretion patterns. Tumor targeted properties were preliminarily determined when the nanoamplifier was injected into mouse models of colon cancer liver metastasis. Furthermore, although AuNPs departed from the nanoamplifiers in specific mice tissues, optical and magnetic resonance imaging was efficient, especially in metastatic tumors. These assays validate our nanoamplifier as an effective MRI signal enhancer with sensitive cancer diagnosis potential.We have synthesized an efficient and highly sensitive nanoamplifier composed of gadolinium-doped silica nanoparticles and gold nanoparticles (AuNPs). Magnetic resonance imaging (MRI) in vitro and in vivo assays revealed enhancement of signal sensitivity, which may be explained by electron transfer between water and gadolinium-doped nanoparticles, apparent in the presence of gold. In vitro and in vivo evaluation demonstrated nanoamplifier incurred minimal cytotoxicity and immunotoxicity, increased stability, and gradual excretion patterns. Tumor targeted properties were preliminarily determined when the nanoamplifier was injected into mouse models of colon cancer liver metastasis. Furthermore, although AuNPs departed from the nanoamplifiers in specific mice tissues, optical and magnetic resonance imaging was efficient, especially in metastatic tumors. These assays validate our nanoamplifier as an effective MRI signal enhancer with sensitive cancer diagnosis potential. Electronic supplementary information

  1. Analysis of Blood Gadolinium in an Isotope Geochemist Following Contrast MRI

    NASA Astrophysics Data System (ADS)

    Wasylenki, L. E.

    2011-12-01

    Normal brain tissue does not have blood flowing throughout it; instead oxygen diffuses across a blood-brain barrier in order to oxygenate brain cells. Brain tumors, however, do grow blood supplies, so an abnormal distribution of blood in the brain is a key indicator of abnormal cell growth. But how is the distribution of blood in inside the brain observed? The lanthanide ion gadolinium(III) has unpaired 5f-shell electrons and is thus paramagnetic. As such, the presence of Gd causes the nuclei of nearby atoms to relax more quickly when excited to high-energy spin states by pulses of radio-frequency energy than they would without Gd nearby. The signal in magnetic resonance imaging correlates with this nuclear spin relaxation time, so gadolinium's presence in certain body tissues makes those tissues appear as bright areas on MRI images. Gadolinium is therefore commonly injected intravenously just prior to MRI imaging, so that the distribution of blood in and around the brain can be mapped. Gadolinium as a free ion is toxic, so it is injected in a relatively inert form, often as gadoversetamide, in which Gd is tightly bound in nine-fold coordination with N, C, and O. This compound is removed from the blood by the kidneys at a rate that is fast compared to the rate of breakdown of this compound in the blood, thus preventing release of toxic Gd in the bloodstream. But how quickly can the kidneys of an isotope geochemist remove Gd from blood? In this experiment, a single isotope geochemist's wristwatch was synchronized with that of the MRI technician and then left in a dressing room with all other magnetically susceptible objects until after the MRI. The time of intravenous injection of gadoversetamide into the isotopist was recorded by the technician and later transmitted verbally to the isotopist. Following the MRI session, blood samples were collected by self-fingerprick, in a Class 100 trace metal clean lab, from 47 to 281 minutes after intravenous injection. For each

  2. Very low-dose fluvastatin-valsartan combination decreases parameters of inflammation and oxidative stress in patients with type 1 diabetes mellitus.

    PubMed

    Lunder, Mojca; Janić, Miodrag; Savić, Vedran; Janež, Andrej; Kanc, Karin; Šabovič, Mišo

    2017-05-01

    Previously we revealed the effectiveness of a new therapeutic approach with a short-term, very-low dose fluvastatin-valsartan combination on the improvement of arterial function in type 1 diabetes mellitus patients (T1DM). In this study we explored whether this approach influences inflammation and oxidative stress and explored any association of these effects with arterial function improvement. This was a supplementary analysis of the two previous double blind randomized studies (included 44 T1DM patients). Treatment group received very-low dose fluvastatin-valsartan, the control group received placebo. Blood samples were collected and inflammation parameters: high-sensitivity CRP (hsCRP), interleukin 6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and oxidative stress parameter total antioxidant status (TAS) were measured. Treatment decreased hsCRP values (by 56.5%, P<0.05) and IL-6 values (by 33.6%, P<0.05) and increased TAS values (by 21.1%; P<0.05) after 30days of treatment. High sensitivity CRP and TAS remained decreased 3months after treatment discontinuation. Importantly, the anti-inflammatory and anti-oxidative action significantly correlated with arterial function improvement. The approach consisting of short-term (30days) treatment with a very low-dose fluvastatin-valsartan combination acts anti-inflammatory and anti-oxidative in T1DM patients. These observations along with the improvement of arterial function support the assumption that this approach could have an important clinical benefit in T1DM patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Chronic Low-Grade Inflammation in Childhood Obesity Is Associated with Decreased IL-10 Expression by Monocyte Subsets.

    PubMed

    Mattos, Rafael T; Medeiros, Nayara I; Menezes, Carlos A; Fares, Rafaelle C G; Franco, Eliza P; Dutra, Walderez O; Rios-Santos, Fabrício; Correa-Oliveira, Rodrigo; Gomes, Juliana A S

    2016-01-01

    Chronic low-grade inflammation is related to the development of comorbidities and poor prognosis in obesity. Monocytes are main sources of cytokines and play a pivotal role in inflammation. We evaluated monocyte frequency, phenotype and cytokine profile of monocyte subsets, to determine their association with the pathogenesis of childhood obesity. Children with obesity were evaluated for biochemical and anthropometric parameters. Monocyte subsets were characterized by flow cytometry, considering cytokine production and activation/recognition molecules. Correlation analysis between clinical parameters and immunological data delineated the monocytes contribution for low-grade inflammation. We observed a higher frequency of non-classical monocytes in the childhood obesity group (CO) than normal-weight group (NW). All subsets displayed higher TLR4 expression in CO, but their recognition and antigen presentation functions seem to be diminished due to lower expression of CD40, CD80/86 and HLA-DR. All subsets showed a lower expression of IL-10 in CO and correlation analyses showed changes in IL-10 expression profile. The lower expression of IL-10 may be decisive for the maintenance of the low-grade inflammation status in CO, especially for alterations in non-classical monocytes profile. These cells may contribute to supporting inflammation and loss of regulation in the immune response of children with obesity.

  4. Chronic Low-Grade Inflammation in Childhood Obesity Is Associated with Decreased IL-10 Expression by Monocyte Subsets

    PubMed Central

    Mattos, Rafael T.; Medeiros, Nayara I.; Menezes, Carlos A.; Fares, Rafaelle C. G.; Franco, Eliza P.; Dutra, Walderez O.; Rios-Santos, Fabrício; Correa-Oliveira, Rodrigo; Gomes, Juliana A. S.

    2016-01-01

    Chronic low-grade inflammation is related to the development of comorbidities and poor prognosis in obesity. Monocytes are main sources of cytokines and play a pivotal role in inflammation. We evaluated monocyte frequency, phenotype and cytokine profile of monocyte subsets, to determine their association with the pathogenesis of childhood obesity. Children with obesity were evaluated for biochemical and anthropometric parameters. Monocyte subsets were characterized by flow cytometry, considering cytokine production and activation/recognition molecules. Correlation analysis between clinical parameters and immunological data delineated the monocytes contribution for low-grade inflammation. We observed a higher frequency of non-classical monocytes in the childhood obesity group (CO) than normal-weight group (NW). All subsets displayed higher TLR4 expression in CO, but their recognition and antigen presentation functions seem to be diminished due to lower expression of CD40, CD80/86 and HLA-DR. All subsets showed a lower expression of IL-10 in CO and correlation analyses showed changes in IL-10 expression profile. The lower expression of IL-10 may be decisive for the maintenance of the low-grade inflammation status in CO, especially for alterations in non-classical monocytes profile. These cells may contribute to supporting inflammation and loss of regulation in the immune response of children with obesity. PMID:27977792

  5. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    PubMed Central

    2010-01-01

    Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd. PMID:21170410

  6. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

    2010-12-01

    Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

  7. Electron magnetic resonance investigation of gadolinium diffusion in zircon powders

    NASA Astrophysics Data System (ADS)

    de Biasi, R. S.; Grillo, M. L. N.

    2011-11-01

    The electron magnetic resonance (EMR) technique was used to investigate the diffusion of gadolinium in zircon (ZrSiO4) powders. The EMR absorption intensity was measured for several annealing times and three different temperatures of isothermal annealing: 1273, 1323 and 1373 K. The activation energy for diffusion, calculated from the experimental data using a theoretical model based on the Fick equation, was found to be EA=506±5 kJ mol-1. This value is close to the ones for the diffusion of Gd in UO2 and CeO2, but much larger than for the diffusion of gadolinium in a compound with the same crystal structure as zircon, YVO4. This is attributed to a difference in the relative sizes of the ions involved in the diffusion process.

  8. Gadolinium concentration analysis in brain phantom by X-ray fluorescence.

    PubMed

    Almalki, Musaed; Majid, Samir Abdul; Butler, Philip H; Reinisch, Lou

    2010-06-01

    We have measured the X-ray fluorescence from gadolinium as a function of concentration and position in tumors of different sizes and shapes in a head phantom. The gadolinium fluorescence was excited with a 36 GBq Am-241 source. The fluorescence signal was detected with a CdTe detector and a multi-channel analyzer. The fluorescence peak was clearly separated from the scattered X-rays. Concentrations of 5.62-78.63 mg/ml of Gd ion were used in 1, 2, and 3 cm diameter spherical tumors and a 2x4 cm oblate spheroid tumor. The data show trends approaching saturation for the highest concentrations, probably due to reabsorption in the tumor. A comparison of X-ray photographic imaging and densitometer measurements to determine concentration is also presented.

  9. RIP3-dependent necrosis induced inflammation exacerbates atherosclerosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meng, Lingjun, E-mail: menglingjun@nibs.ac.cn; National Institute of Biological Sciences, Beijing 102206; Jin, Wei

    Atherothrombotic vascular disease is already the leading cause of mortality worldwide. Atherosclerosis shares features with diseases caused by chronic inflammation. More attention should concentrates on the innate immunity effect atherosclerosis progress. RIP3 (receptor-interacting protein kinase 3) act through the transcription factor named Nr4a3 (Nuclear orphan receptors) to regulate cytokine production. Deletion RIP3 decreases IL-1α production. Injection of anti-IL-1α antibody protects against the progress of atherosclerosis in ApoE −/− mice. RIP3 as a molecular switch in necrosis, controls macrophage necrotic death caused inflammation. Inhibiting necrosis will certainly reduce atherosclerosis through limit inflammation. Necrotic cell death caused systemic inflammation exacerbated cardiovascular disease. Inhibitionmore » of necrosis may yield novel therapeutic targets for treatment in years to come. - Highlights: • RIP3 regulate the Nr4a3 to control cytokine production. • Deletion RIP3 decreases IL-1a production. • Injection anti-IL-1a antibody protects against the progress of atherosclerosis. • RIP3 controls macrophage necrotic dead caused inflammation.« less

  10. Modulation of channel activity and gadolinium block of MscL by static magnetic fields.

    PubMed

    Petrov, Evgeny; Martinac, Boris

    2007-02-01

    The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of living organisms. Experimental studies of the magnetic sense have, however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by these organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magnetoreception. In this study we have investigated the effect of static magnetic fields (SMFs) of moderate intensity on the activity and gadolinium block of MscL, the bacterial MS channel of large conductance, which has served as a model channel to study the basic physical principles of mechanosensory transduction in living cells. In addition to showing that direct application of the magnetic field decreased the activity of the MscL channel, our study demonstrates for the first time that SMFs can reverse the effect of gadolinium, a well-known blocker of MS channels. The results of our study are consistent with a notion that (1) the effects of SMFs on the MscL channels may result from changes in physical properties of the lipid bilayer due to diamagnetic anisotropy of phospholipid molecules and consequently (2) cooperative superdiamagnetism of phospholipid molecules under influence of SMFs could cause displacement of Gd(3+) ions from the membrane bilayer and thus remove the MscL channel block.

  11. Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance.

    PubMed

    Lopez, Javier E; Yeo, Khung; Caputo, Gary; Buonocore, Michael; Schaefer, Saul

    2009-11-11

    Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies.

  12. Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance

    PubMed Central

    2009-01-01

    Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies. PMID:19906310

  13. High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation[S

    PubMed Central

    McGrath, Kristine C.; Li, Xiao Hong; Whitworth, Phillippa T.; Kasz, Robert; Tan, Joanne T.; McLennan, Susan V.; Celermajer, David S.; Barter, Philip J.; Rye, Kerry-Anne; Heather, Alison K.

    2014-01-01

    Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. PMID:24347528

  14. Acute side effects of three commonly used gadolinium contrast agents in the paediatric population.

    PubMed

    Neeley, Chris; Moritz, Michael; Brown, Jeffrey J; Zhou, Yihua

    2016-07-01

    To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance(®) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist(®) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist(®) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications.

  15. Layered gadolinium hydroxides for low-temperature magnetic cooling.

    PubMed

    Abellán, Gonzalo; Espallargas, Guillermo Mínguez; Lorusso, Giulia; Evangelisti, Marco; Coronado, Eugenio

    2015-09-28

    Layered gadolinium hydroxides have revealed to be excellent candidates for cryogenic magnetic refrigeration. These materials behave as pure 2D magnetic systems with a Heisenberg-Ising critical crossover, induced by dipolar interactions. This 2D character and the possibility offered by these materials to be delaminated open the possibility of rapid heat dissipation upon substrate deposition.

  16. Gadolinium-148 and other spallation production cross section measurements for accelerator target facilities

    NASA Astrophysics Data System (ADS)

    Kelley, Karen Corzine

    At the Los Alamos Neutron Science Center accelerator complex, protons are accelerated to 800 MeV and directed to two tungsten targets, Target 4 at the Weapons Neutron Research facility and the 1L target at the Lujan Center. The Department of Energy requires hazard classification analyses to be performed on these targets and places limits on certain radionuclide inventories in the targets to avoid characterizing the facilities as "nuclear facilities." Gadolinium-148 is a radionuclide created from the spallation of tungsten. Allowed isotopic inventories are particularly low for this isotope because it is an alpha-particle emitter with a 75-year half-life. The activity level of Gadolinium-148 is low, but it encompasses almost two-thirds of the total dose burden for the two tungsten targets based on present yield estimates. From a hazard classification standpoint, this severely limits the lifetime of these tungsten targets. The cross section is not well-established experimentally and this is the motivation for measuring the Gadolinium-148 production cross section from tungsten. In a series of experiments at the Weapons Neutron Research facility, Gadolinium-148 production was measured for 600- and 800-MeV protons on tungsten, tantalum, and gold. These experiments used 3 mum thin tungsten, tantalum, and gold foils and 10 mum thin aluminum activation foils. In addition, spallation yields were determined for many short-lived and long-lived spallation products with these foils using gamma and alpha spectroscopy and compared with predictions of the Los Alamos National Laboratory codes CEM2k+GEM2 and MCNPX. The cumulative Gadolinium-148 production cross section measured from tantalum, tungsten, and gold for incident 600-MeV protons were 15.2 +/- 4.0, 8.31 +/- 0.92, and 0.591 +/- 0.155, respectively. The average production cross sections measured at 800 MeV were 28.6 +/- 3.5, 19.4 +/- 1.8, and 3.69 +/- 0.50 for tantalum, tungsten, and gold, respectively. These cumulative

  17. Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

    PubMed Central

    Felger, Jennifer C; Treadway, Michael T

    2017-01-01

    Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation. PMID:27480574

  18. Solid solutions of gadolinium doped zinc oxide nanorods by combined microwave-ultrasonic irradiation assisted crystallization

    NASA Astrophysics Data System (ADS)

    Kiani, Armin; Dastafkan, Kamran; Obeydavi, Ali; Rahimi, Mohammad

    2017-12-01

    Nanocrystalline solid solutions consisting of un-doped and gadolinium doped zinc oxide nanorods were fabricated by a modified sol-gel process utilizing combined ultrasonic-microwave irradiations. Polyvinylpyrrolidone, diethylene glycol, and triethylenetetramine respectively as capping, structure directing, and complexing agents were used under ultrasound dynamic aging and microwave heating to obtain crystalline nanorods. Crystalline phase monitoring, lattice parameters and variation, morphology and shape, elemental analysis, functional groups, reducibility, and the oxidation state of emerged species were examined by PXRD, FESEM, TEM, EDX, FTIR, micro Raman, H2-TPR, and EPR techniques. Results have verified that irradiation mechanism of gelation and crystallization reduces the reaction time, augments the crystal quality, and formation of hexagonal close pack structure of Wurtzite morphology. Besides, dissolution of gadolinium within host lattice involves lattice deformation, unit cell distortion, and angular position variation. Structure related shape and growth along with compositional purity were observed through microscopic and spectroscopic surveys. Furthermore, TPR and EPR studies elucidated more detailed behavior upon exposure to the exerted irradiations and subsequent air-annealing including the formed oxidation states and electron trapping centers, presence of gadolinium, zinc, and oxygen disarrays and defects, as well as alteration in the host unit cell via gadolinium addition.

  19. Scutellaria barbata attenuates diabetic retinopathy by preventing retinal inflammation and the decreased expression of tight junction protein

    PubMed Central

    Mei, Xi-Yu; Zhou, Ling-Yu; Zhang, Tian-Yu; Lu, Bin; Ji, Li-Li

    2017-01-01

    AIM To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE) against diabetic retinopathy (DR) and its engaged mechanism. METHODS C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg) for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg) for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB) breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. RESULTS SE (100, 200 mg/kg) reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction (TJ) proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-α and IL-1β. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 (ICAM-1). SE reduced the increased phosphorylation of nuclear factor kappa B (NFκB) p65 and its subsequent nuclear translocation in retinas from STZ-induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 (Iba1) demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19. PMID:28730076

  20. The network formers role of gadolinium(III) ions in some zinc-borate glass ceramics

    NASA Astrophysics Data System (ADS)

    Bosca, Maria; Pop, Lidia; Pascuta, Petru

    2017-12-01

    EPR and magnetic susceptibility measurements were performed on glass ceramics from the (Gd2O3)x.(B2O3)(60-x).(ZnO)40 system, with 0 ≤ x ≤ 15 mol%, in order to determine the role of gadolinium ions on structural and magnetic properties. At low Gd2O3 contents (x ≤ 1 mol%) the EPR spectra show four resonance lines with effective g-values of ˜ 6, 4.8, 2.8 and 2, typical for Gd3+ ions uniformly distributed in the glass and glass ceramic samples. For higher contents of gadolinium ions (x ≥ 3 mol%) the EPR spectra are dominated by a single broad line centered at g ˜ 2, which can be due to the magnetic clusters containing Gd3+ ions. The magnetic susceptibility data show that the gadolinium ions are involved in superexchange interactions in all the investigated glass ceramics, being antiferromagnetically coupled.

  1. Sensitive and transportable gadolinium-core plastic scintillator sphere for neutron detection and counting

    NASA Astrophysics Data System (ADS)

    Dumazert, Jonathan; Coulon, Romain; Carrel, Frédérick; Corre, Gwenolé; Normand, Stéphane; Méchin, Laurence; Hamel, Matthieu

    2016-08-01

    Neutron detection forms a critical branch of nuclear-related issues, currently driven by the search for competitive alternative technologies to neutron counters based on the helium-3 isotope. The deployment of plastic scintillators shows a high potential for efficient detectors, safer and more reliable than liquids, more easily scalable and cost-effective than inorganic. In the meantime, natural gadolinium, through its 155 and mostly 157 isotopes, presents an exceptionally high interaction probability with thermal neutrons. This paper introduces a dual system including a metal gadolinium core inserted at the center of a high-scale plastic scintillator sphere. Incident fast neutrons are thermalized by the scintillator shell and then may be captured with a significant probability by gadolinium 155 and 157 nuclei in the core. The deposition of a sufficient fraction of the capture high-energy prompt gamma signature inside the scintillator shell will then allow discrimination from background radiations by energy threshold, and therefore neutron detection. The scaling of the system with the Monte Carlo MCNPX2.7 code was carried out according to a tradeoff between the moderation of incident fast neutrons and the probability of slow neutron capture by a moderate-cost metal gadolinium core. Based on the parameters extracted from simulation, a first laboratory prototype for the assessment of the detection method principle has been synthetized. The robustness and sensitivity of the neutron detection principle are then assessed by counting measurement experiments. Experimental results confirm the potential for a stable, highly sensitive, transportable and cost-efficient neutron detector and orientate future investigation toward promising axes.

  2. Novel PPARα agonist MHY553 alleviates hepatic steatosis by increasing fatty acid oxidation and decreasing inflammation during aging.

    PubMed

    Kim, Seong Min; Lee, Bonggi; An, Hye Jin; Kim, Dae Hyun; Park, Kyung Chul; Noh, Sang-Gyun; Chung, Ki Wung; Lee, Eun Kyeong; Kim, Kyung Mok; Kim, Do Hyun; Kim, Su Jeong; Chun, Pusoon; Lee, Ho Jeong; Moon, Hyung Ryong; Chung, Hae Young

    2017-07-11

    Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.

  3. Doxycycline attenuates breast cancer related inflammation by decreasing plasma lysophosphatidate concentrations and inhibiting NF-κB activation.

    PubMed

    Tang, Xiaoyun; Wang, Xianyan; Zhao, Yuan Y; Curtis, Jonathan M; Brindley, David N

    2017-02-08

    We previously discovered that tetracyclines increase the expression of lipid phosphate phosphatases at the surface of cells. These enzymes degrade circulating lysophosphatidate and therefore doxycycline increases the turnover of plasma lysophosphatidate and decreases its concentration. Extracellular lysophosphatidate signals through six G protein-coupled receptors and it is a potent promoter of tumor growth, metastasis and chemo-resistance. These effects depend partly on the stimulation of inflammation that lysophosphatidate produces. In this work, we used a syngeneic orthotopic mouse model of breast cancer to determine the impact of doxycycline on circulating lysophosphatidate concentrations and tumor growth. Cytokine/chemokine concentrations in tumor tissue and plasma were measured by multiplexing laser bead technology. Leukocyte infiltration in tumors was analyzed by immunohistochemistry. The expression of IL-6 in breast cancer cell lines was determined by RT-PCR. Cell growth was measured in Matrigel™ 3D culture. The effects of doxycycline on NF-κB-dependent signaling were analyzed by Western blotting. Doxycycline decreased plasma lysophosphatidate concentrations, delayed tumor growth and decreased the concentrations of several cytokines/chemokines (IL-1β, IL-6, IL-9, CCL2, CCL11, CXCL1, CXCL2, CXCL9, G-CSF, LIF, VEGF) in the tumor. These results were compatible with the effects of doxycycline in decreasing the numbers of F4/80 + macrophages and CD31 + blood vessel endothelial cells in the tumor. Doxycycline also decreased the lysophosphatidate-induced growth of breast cancer cells in three-dimensional culture. Lysophosphatidate-induced Ki-67 expression was inhibited by doxycycline. NF-κB activity in HEK293 cells transiently expressing a NF-κB-luciferase reporter vectors was also inhibited by doxycycline. Treatment of breast cancer cells with doxycycline also decreased the translocation of NF-κB to the nucleus and the mRNA levels for IL-6 in the presence

  4. Prostate Angiogenesis in Development and Inflammation

    PubMed Central

    Wong, Letitia; Gipp, Jerry; Carr, Jason; Loftus, Christopher; Benck, Molly; Lee, Sanghee; Mehta, Vatsal; Vezina, Chad; Bushman, Wade

    2014-01-01

    BACKGROUND Prostatic inflammation is an important factor in development and progression of BPH/LUTS. This study was performed to characterize the normal development and vascular anatomy of the mouse prostate and then examine, for the first time, the effects of prostatic inflammation on the prostate vasculature. METHODS Adult mice were perfused with India ink to visualize the prostatic vascular anatomy. Immunostaining was performed on the E16.5 UGS and the P5, P20 and adult prostate to characterize vascular development. Uropathogenic E. coli 1677 was instilled transurethrally into adult male mice to induce prostate inflammation. RT-PCR and BrdU labeling was performed to assay anigogenic factor expression and endothelial proliferation, respectively. RESULTS An artery on the ventral surface of the bladder trifurcates near the bladder neck to supply the prostate lobes and seminal vesicle. Development of the prostatic vascular system is associated with endothelial proliferation and robust expression of pro-angiogenic factors Pecam1, Tie1, Tek, Angpt1, Angpt2, Fgf2, Vegfa, Vegfc, Figf. Bacterial-induced prostatic inflammation induced endothelial cell proliferation and increased vascular density but surprisingly decreased pro-angiogenic factor expression. CONCLUSIONS The striking decrease in pro-angiogenic factor mRNA expression associated with endothelial proliferation and increased vascular density during inflammation suggests that endothelial response to injury is not a recapitulation of normal development and may be initiated and regulated by different regulatory mechanisms. PMID:24293357

  5. T1 relaxivity of core-encapsulated gadolinium liposomal contrast agents--effect of liposome size and internal gadolinium concentration.

    PubMed

    Ghaghada, Ketan; Hawley, Catherine; Kawaji, Keigo; Annapragada, Ananth; Mukundan, Srinivasan

    2008-10-01

    Long circulating core-encapsulated gadolinium (CE-Gd) liposomal nanoparticles that have surface conjugated polyethylene glycol are a promising platform technology for use as blood pool T1-based magnetic resonance (MR) contrast agents. The objective of this study was to investigate the effect of liposome size and internal (core) Gd concentration on the T1 relaxivity of CE-Gd liposomes. Twelve different liposomal formulations were synthesized and characterized, resulting in a size (50, 100, 200, and 400 nm) and core Gd-concentration (200, 350, and 500 mM) "matrix" of test samples. Subsequently, CE-Gd liposomes were diluted in deionized water (four diluted samples) and molar T1 relaxivity (r1) measurements were performed at 2- and 7-T MR field strengths. The r1 of CE-Gd liposomes was inversely related to the liposome size. The largest change in r1 was observed between liposomes that were extruded through 50- and 100-nm filter membranes. At both field strengths, the variation in internal gadolinium concentration did not show any significant correlation (alpha < or = 0.05) with r1. The size of CE-Gd liposomal nanoparticles significantly affects the T1 relaxivity. An inverse relation was observed between liposome size and T1 relaxivity. The T1 relaxivity did not change significantly with core Gd concentration over the measured concentration range.

  6. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    PubMed

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  7. Magnetization reversal and inverted magnetoresistance of exchange-biased spin valves with a gadolinium layer

    NASA Astrophysics Data System (ADS)

    Milyaev, M.; Naumova, L.; Chernyshova, T.; Proglyado, V.; Kamensky, I.; Krinitsina, T.; Ryabukhina, M.; Ustinov, V.

    2017-03-01

    FeMn-based spin valves with a gadolinium layer have been fabricated by magnetron sputtering. The magnetoresistive properties of the spin valves have been investigated at temperatures of 80-293 K. Temperature-induced switching between low- and high-resistance magnetic states has been revealed. Realization of the low- or high-resistance states depends on which magnetic moment dominates in the exchange-coupled Gd/CoFe, of Gd or CoFe. It has been shown that the switching temperature depends on the thickness of the gadolinium layer.

  8. Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

    2014-06-01

    We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

  9. Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection.

    PubMed

    Kim, Hyemin; Jang, Mirim; Kim, Yejin; Choi, Jiyea; Jeon, Jane; Kim, Jihoon; Hwang, Young-Il; Kang, Jae Seung; Lee, Wang Jae

    2016-03-01

    Because red ginseng and vitamin C have immunomodulatory function and anti-viral effect, we investigated whether red ginseng and vitamin C synergistically regulate immune cell function and suppress viral infection. Red ginseng and vitamin C were treated to human peripheral blood mononuclear cells (PBMCs) or sarcoma-associated herpesvirus (KSHV)-infected BCBL-1, and administrated to Gulo(-/-) mice, which are incapable of synthesizing vitamin C, with or without influenza A virus/H1N1 infection. Red ginseng and vitamin C increased the expression of CD25 and CD69 of PBMCs and natural killer (NK) cells. Co-treatment of them decreased cell viability and lytic gene expression in BCBL-1. In Gulo(-/-) mice, red ginseng and vitamin C increased the expression of NKp46, a natural cytotoxic receptor of NK cells and interferon (IFN)-γ production. Influenza infection decreased the survival rate, and increased inflammation and viral plaque accumulation in the lungs of vitamin C-depleted Gulo(-/-) mice, which were remarkably reduced by red ginseng and vitamin C supplementation. Administration of red ginseng and vitamin C enhanced the activation of immune cells like T and NK cells, and repressed the progress of viral lytic cycle. It also reduced lung inflammation caused by viral infection, which consequently increased the survival rate. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  10. Characterization of the reaction products and precipitates at the interface of carbon fiber reinforced magnesium–gadolinium composite

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Yaping; Jiang, Longtao, E-mail: longtaojiang@163.com; Chen, Guoqin

    2016-03-15

    In the present work, carbon fiber reinforced magnesium-gadolinium composite was fabricated by pressure infiltration method. The phase composition, micro-morphology, and crystal structure of reaction products and precipitates at the interface of the composite were investigated. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed the segregation of gadolinium element at the interface between carbon fiber and matrix alloy. It was shown that block-shaped Gd4C5, GdC2 and nano-sized Gd2O3 were formed at the interface during the fabrication process due to the interfacial reaction. Furthermore, magnesium-gadolinium precipitates including needle-like Mg5Gd (or Mg24Gd5) and thin plate-shaped long period stacking-ordered phase, were also observedmore » at the interface and in the matrix near the interface. The interfacial microstructure and bonding mode were influenced by these interfacial products, which were beneficial for the improvement of the interfacial bonding strength. - Highlights: • Gadolinium element segregated on the surface of carbon fibers. • Block-shaped Gd{sub 4}C{sub 5} and GdC{sub 2} were formed at the interface via chemical reaction. • Gadolinium and oxygen reacted at the interface and formed nano-scaled Gd{sub 2}O{sub 3}. • The precipitates formed in the interface were identified to be Mg{sub 5}Gd (or Mg{sub 24}Gd{sub 5}) and plate-shaped long period stacking-ordered phase.« less

  11. Hypothalamic inflammation and gliosis in obesity

    PubMed Central

    Dorfman, Mauricio D.; Thaler, Joshua P.

    2015-01-01

    Structured Abstract Purpose of review Hypothalamic inflammation and gliosis are recently discovered mechanisms that may contribute to obesity pathogenesis. Current research in this area suggests that investigation of these CNS responses may provide opportunities to develop new weight loss treatments. Recent findings In rodents, hypothalamic inflammation and gliosis occur rapidly with high-fat diet consumption prior to significant weight gain. In addition, sensitivity or resistance to diet-induced obesity in rodents generally correlates with the presence or absence of hypothalamic inflammation and reactive gliosis (brain response to injury). Moreover, functional interventions that increase or decrease inflammation in neurons and glia correspondingly alter diet-associated weight gain. However, some conflicting data have recently emerged that question the contribution of hypothalamic inflammation to obesity pathogenesis. However, several studies have detected gliosis and disrupted connectivity in obese humans, highlighting the potential translational importance of this mechanism. Summary There is growing evidence that obesity is associated with brain inflammation in humans, particularly in the hypothalamus where its presence may disrupt body weight control and glucose homeostasis. More work is needed to determine whether this response is common in human obesity and to what extent it can be manipulated for therapeutic benefit. PMID:26192704

  12. Inflammation, aging, and adiposity: implications for physical therapists.

    PubMed

    Addison, Odessa; LaStayo, Paul C; Dibble, Leland E; Marcus, Robin L

    2012-01-01

    Physical therapists treat older individuals, characterized as both a needy and expanding population. Frailty, a predisability condition with links to chronic inflammatory conditions, is estimated to affect 7% of individuals older than 60 years and 40% of people older than 80 years. Chronic inflammation is one of the most important physiologic correlates of the frailty syndrome and high levels of proinflammatory cytokines, related to both aging and increasing adiposity in older individuals are related to an increased risk of mortality, sarcopenia, reduced muscle strength and decreased mobility. The purpose of this narrative review is to inform the physical therapist of the effects of aging and increasing adiposity on chronic inflammation and the association of inflammation with muscle loss, strength, and mobility impairments in older adults; and to review the current evidence to provide clinical recommendations on physical activity and exercise regimes that may mitigate chronic inflammation in older adults. As physical therapists help manage and treat an increasingly older population, understanding how the inflammatory milieu changes with aging and increasing adiposity and how these changes can be impacted by physical therapists via exercise and physical activity is critical. Exercise is a potent preventive intervention strategy and countermeasure for chronic inflammation and adiposity. Exercise can also benefit the frail older individual by combating the negative effects of chronic inflammation and optimally balancing the production of pro and anti-inflammatory cytokines. In addition to providing an anti-inflammatory environment within muscle to mitigate the effects of chronic inflammation, exercise has the added benefit of improving muscle mass and function and decreasing adiposity in older adults.

  13. Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents

    PubMed Central

    Marckmann, Peter; Logager, Vibeke B.

    2007-01-01

    Abstract Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination. PMID:17905680

  14. Measurement of gadolinium retention: current status and review from an applied radiation physics perspective.

    PubMed

    Gräfe, James L; McNeill, Fiona E

    2018-06-28

    This article briefly reviews the main measurement techniques for the non-invasive detection of residual gadolinium (Gd) in those exposed to gadolinium-based contrast agents (GBCAs). Approach and Main results: The current status of in vivo Gd measurement is discussed and is put into the context of concerns within the radiology community. The main techniques are based on applied atomic/nuclear medicine utilizing the characteristic atomic and nuclear spectroscopic signature of Gd. The main emission energies are in the 40-200 keV region and require spectroscopic detectors with good energy resolution. The two main techniques, prompt gamma neutron activation analysis and x-ray fluorescence, provide adequate detection limits for in vivo measurement, whilst delivering a low effective radiation dose on the order of a few µSv. Gadolinium is being detected in measureable quantities in people with healthy renal function who have received FDA approved GBCAs. The applied atomic/nuclear medicine techniques discussed in this review will be useful in determining the significance of this retention, and will help on advising future administration protocols.

  15. Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents: Differences in Long-Term Biodistribution and Excretion.

    PubMed

    Lancelot, Eric

    2016-11-01

    Gadolinium-based contrast agents (GBCAs) have been used for years for magnetic resonance imaging examinations. Because of their rapid blood clearance, they were considered as very safe products until some of them were shown to induce nephrogenic systemic fibrosis in patients with renal failure and hypersignals on T1-weighted unenhanced brain scans of patients with normal renal function. To date, these adverse effects have been related almost exclusively to the use of low-stability linear agents, which are more prone to release free gadolinium. The aim of the present meta-analysis was to ascertain the existence of a deep compartment for gadolinium storage in the body and to assess whether all the GBCAs present the same toxicokinetic profile. Applying a systematic literature search methodology, all clinical and preclinical studies reporting time-dependent plasma concentrations and renal excretion data of gadolinium were identified and analyzed. Since the individual data were not available, the analysis focused on the average values per groups of subjects or animals, which had received a given GBCA at a given dose. The rate constants of the distribution phase (α), rapid elimination phase (β), and residual excretion phase (γ) of gadolinium were determined in each group from the plasma concentration (Cp) time curves and the relative urinary excretion rate (rER) time curves, taking the 2-hour time point as a reference. Moreover, as bone may represent a reservoir for long-term gadolinium accumulation and slow release into the blood stream, the time curves of the relative concentration in the bone (rCB) of Gd-labeled GBCAs in mice or rats were analyzed taking day 1 concentrations as a reference. The ratio of gadolinium concentrations in the bone marrow (CBM) as compared with the bone (CB) was also calculated. The relative urinary excretion rate (rER) plots revealed a prolonged residual excretion phase of gadolinium in healthy volunteers, consistent with the existence of

  16. Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging.

    PubMed

    Nitta, Yoshikazu; Tahara, Nobuhiro; Tahara, Atsuko; Honda, Akihiro; Kodama, Norihiro; Mizoguchi, Minori; Kaida, Hayato; Ishibashi, Masatoshi; Hayabuchi, Naofumi; Ikeda, Hisao; Yamagishi, Sho-ichi; Imaizumi, Tsutomu

    2013-11-01

    The aim of this study was to compare the effect of pioglitazone with glimepiride on coronary arterial inflammation with serial (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) angiography. Recent studies have shown that FDG-PET combined with CT is a reliable tool to visualize and quantify vascular inflammation. Although pioglitazone significantly prevented the progression of coronary atherosclerosis and reduced the recurrence of myocardial infarction in patients with type 2 diabetes mellitus (DM), it remains unclear whether pioglitazone could attenuate coronary artery inflammation. Fifty atherosclerotic patients with impaired glucose tolerance or type 2 DM underwent determination of blood chemistries, anthropometric and inflammatory variables, and FDG-PET/CT angiography, and then were randomized to receive either pioglitazone or glimepiride for 16 weeks. Effects of the treatments on vascular inflammation of the left main trunk were evaluated by FDG-PET/CT angiography at baseline and end of the study. Vascular inflammation of the left main trunk was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. Three patients dropped out of the study during the assessment or treatment. Finally, 25 pioglitazone-treated patients and 22 glimepiride-treated patients (37 men; mean age: 68.1 ± 8.3 years; glycosylated hemoglobin: 6.72 ± 0.70%) completed the study. After 16-week treatments, fasting plasma glucose and glycosylated hemoglobin values were comparably reduced in both groups. Changes in target-to-background ratio values from baseline were significantly greater in the pioglitazone group than in the glimepiride group (-0.12 ± 0.06 vs. 0.09 ± 0.07, p = 0.032), as well as changes in high-sensitivity C-reactive protein (pioglitazone vs. glimepiride group: median: -0.24 [interquartile range (IQR): -1.58 to -0.04] mg/l vs. 0.08 [IQR: -0.07 to 0.79] mg/l, p = 0.031). Our study

  17. Osthole Alleviates Bleomycin-Induced Pulmonary Fibrosis via Modulating Angiotensin-Converting Enzyme 2/Angiotensin-(1-7) Axis and Decreasing Inflammation Responses in Rats.

    PubMed

    Hao, Yuewen; Liu, Yan

    2016-01-01

    Studies have shown that angiotensin-converting enzyme 2 (ACE2) plays modulating roles in lung pathophysiology, including pulmonary fibrosis (PF) and acute lung injury. Pulmonary fibrosis is a common complication in these interstitial lung diseases, and PF always has a poor prognosis and short survival. To date, there are few promising methods for treating PF, and they are invariably accompanied by severe side effects. Recent studies have showed that the traditional Chinese herbal extract, osthole, had beneficial effects on lipopolysaccharide (LPS) induced acute lung injury (ALI) via an ACE2 pathway. Here we further investigated the protective effects of osthole on bleomycin induced pulmonary fibrosis and attempted to determine the underlying mechanism. PF mode rats were induced by bleomycin (BLM) and then subsequently administered osthole. Histopathological analyses were employed to identify PF changes. The results showed that BLM resulted in severe PF and diffuse lung inflammation, together with significant elevation of inflammatory factors and a marked increase in expression of angiotensin II (ANG II) and transforming growth factor-beta 1 (TGF-β1). ACE2 and angiotensin-(1-7) [ANG-(1-7)] were both greatly reduced after BLM administration. Meanwhile, osthole treatment attenuated BLM induced PF and inflammation, decreased the expression of these inflammatory mediators, ANG II, and TGF-β1, and reversed ACE2 and ANG-(1-7) production in rat lungs. We conclude that osthole may exert beneficial effects on BLM induced PF in rats, perhaps via modulating the ACE2/ANG-(1-7) axis and inhibiting lung inflammation pathways.

  18. Gadolinium prevents high airway pressure-induced permeability increases in isolated rat lungs.

    PubMed

    Parker, J C; Ivey, C L; Tucker, J A

    1998-04-01

    To determine the initial signaling event in the vascular permeability increase after high airway pressure injury, we compared groups of lungs ventilated at different peak inflation pressures (PIPs) with (gadolinium group) and without (control group) infusion of 20 microM gadolinium chloride, an inhibitor of endothelial stretch-activated cation channels. Microvascular permeability was assessed by using the capillary filtration coefficient (Kfc), a measure of capillary hydraulic conductivity. Kfc was measured after ventilation for 30-min periods with 7, 20, and 30 cmH2O PIP with 3 cmH2O positive end-expiratory pressure and with 35 cmH2O PIP with 8 cmH2O positive end-expiratory pressure. In control lungs, Kfc increased significantly to 1.8 and 3.7 times baseline after 30 and 35 cmH2O PIP, respectively. In the gadolinium group, Kfc was unchanged from baseline (0.060 +/- 0.010 ml . min-1 . cmH2O-1 . 100 g-1) after any PIP ventilation period. Pulmonary vascular resistance increased significantly from baseline in both groups before the last Kfc measurement but was not different between groups. These results suggest that microvascular permeability is actively modulated by a cellular response to mechanical injury and that stretch-activated cation channels may initiate this response through increases in intracellular calcium concentration.

  19. Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration

    PubMed Central

    Adin, M.E.; Kleinberg, L.; Vaidya, D.; Zan, E.; Mirbagheri, S.; Yousem, D.M.

    2016-01-01

    BACKGROUND AND PURPOSE A hyperintense appearance of the dentate nucleus on T1-weighted MR images has been related to various clinical conditions, but the etiology remains indeterminate. We aimed to investigate the possible associations between a hyperintense appearance of the dentate nucleus on T1-weighted MR images in patients exposed to radiation and factors including, but not limited to, the cumulative number of contrast-enhanced MR images, amount of gadolinium administration, dosage of ionizing radiation, and patient demographics. MATERIALS AND METHODS The medical records of 706 consecutive patients who were treated with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and 2010 were blindly reviewed by 2 readers. RESULTS One hundred eighty-four subjects were included for dentate nuclei analysis. Among the 184 subjects who cumulatively underwent 2677 MR imaging studies following intravenous gadolinium administration, 103 patients had hyperintense dentate nuclei on precontrast T1-weighted MR images. The average number of gadolinium-enhanced MR imaging studies performed in the group with normal dentate nuclei was significantly lower than that of the group with hyperintense dentate nuclei. The average follow-up time was 62.5 months. No significant difference was observed between hyperintense and normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine and calcium/phosphate levels, patient demographics, history of chemotherapy, and strength of the scanner. No dentate nuclei abnormalities were found on the corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS Repeat performance of gadolinium-enhanced studies likely contributes to a long-standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR images. PMID:26294649

  20. Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

    DOE PAGES

    Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.; ...

    2018-01-11

    Gadolinium silicide (Gd 5Si 4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd 5Si 4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd 5Si 4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd 5Si 3 impurity. Here as the particle sizes decrease, the volumemore » fraction of Gd 5Si 3 phase increases at the expense of the Gd 5Si 4 phase, and the ferromagnetic transition temperature of Gd 5Si 4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.« less

  1. Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.; Gupta, Shalabh; Pecharsky, Vitalij K.; Hadimani, Ravi L.

    2018-05-01

    Gadolinium silicide (Gd5Si4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd5Si4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd5Si4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd5Si3 impurity. As the particle sizes decrease, the volume fraction of Gd5Si3 phase increases at the expense of the Gd5Si4 phase, and the ferromagnetic transition temperature of Gd5Si4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.

  2. Investigating phase transition temperatures of size separated gadolinium silicide magnetic nanoparticles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hunagund, Shivakumar G.; Harstad, Shane M.; El-Gendy, Ahmed A.

    Gadolinium silicide (Gd 5Si 4) nanoparticles (NPs) exhibit different properties compared to their parent bulk materials due to finite size, shape, and surface effects. NPs were prepared by high energy ball-milling of the as-cast Gd 5Si 4 ingot and size separated into eight fractions using time sensitive sedimentation in an applied dc magnetic field with average particle sizes ranging from 700 nm to 82 nm. The largest Gd 5Si 4 NPs order ferromagnetically at 316 K. A second anomaly observed at 110 K can be ascribed to a Gd 5Si 3 impurity. Here as the particle sizes decrease, the volumemore » fraction of Gd 5Si 3 phase increases at the expense of the Gd 5Si 4 phase, and the ferromagnetic transition temperature of Gd 5Si 4 is reduced from 316 K to 310 K, while the ordering of the minor phase is independent of the particle size, remaining at 110 K.« less

  3. Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

    PubMed Central

    Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

    2012-01-01

    Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

  4. The evolution of gadolinium based contrast agents: from single-modality to multi-modality

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Liu, Ruiqing; Peng, Hui; Li, Penghui; Xu, Zushun; Whittaker, Andrew K.

    2016-05-01

    Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications.

  5. Assessment of blood flow with (68)Ga-DOTA PET in experimental inflammation: a validation study using (15)O-water.

    PubMed

    Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

    2014-01-01

    Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog ((68)Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 (15)O) and 30-min (68)Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 (15)O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of (68)Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the (68)Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 (15)O-based blood flow and (68)Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that (68)Ga-DOTA PET imaging is useful for the quantification of

  6. A smart T(1)-weighted MRI contrast agent for uranyl cations based on a DNAzyme-gadolinium conjugate.

    PubMed

    Xu, Weichen; Xing, Hang; Lu, Yi

    2013-11-07

    Rational design of smart MRI contrast agents with high specificity for metal ions remains a challenge. Here, we report a general strategy for the design of smart MRI contrast agents for detecting metal ions based on conjugation of a DNAzyme with a gadolinium complex. The 39E DNAzyme, which has high selectivity for UO2(2+), was conjugated to Gd(III)-DOTA and streptavidin. The binding of UO2(2+) to its 39E DNAzyme resulted in the dissociation of Gd(III)-DOTA from the large streptavidin, leading to a decrease of the T1 correlation time, and a change in the MRI signal.

  7. Light deflection in gadolinium molybdate ferroelastic crystals

    NASA Astrophysics Data System (ADS)

    Staniorowski, Piotr; Bornarel, Jean

    2000-02-01

    The deflection of a He-Ne light beam by polydomain gadolinium molybdate (GMO) crystals has been studied with respect to incidence angle icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> i on the sample at room temperature. The A and B deflected beams do not cross each other during the icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> i variation, in contrast to results and calculations previously published. The model using the Fresnel equation confirms this result. The model presented is more accurate for numerical calculation than that using the Huygens construction.

  8. Rice Hull Extract Suppresses Benign Prostate Hyperplasia by Decreasing Inflammation and Regulating Cell Proliferation in Rats.

    PubMed

    Kim, Chae-Yun; Chung, Kyung-Sook; Cheon, Se-Yun; Lee, Jong-Hyun; Park, Youn-Bum; An, Hyo-Jin

    2016-08-01

    Even though rice hull has various physiological functions with high antioxidant potential, the molecular mechanism(s) underlying the effects of rice hull on benign prostatic hyperplasia (BPH) have not been evaluated. The aim of this study was to determine the protective effect of rice hull water extract (RHE) against BPH, which is a common disorder in elderly men and involves inflammation that induces an imbalance between cell proliferation and cell death. In this study, RHE-treated mice exhibited lower prostate weights and ratios of prostate weight to body weight compared to those for the BPH-induced group. In addition, RHE-treated mice had lower serum levels of dihydrotestosterone, mRNA expression of 5α-reductase2, and protein expressions of proliferating cell nuclear antigen (PCNA). Furthermore, RHE treatment significantly decreased cell proliferation by regulating the expression levels of inflammatory-related proteins (iNOS and COX-2) and apoptosis-associated proteins (Fas, FADD, procaspase-8, -3, and Bcl-2 family proteins). These results suggest that RHE could protect against the development of BPH through its anti-inflammatory and apoptotic properties and has good potential as a treatment for BPH.

  9. The Role of Dopamine in Inflammation-Associated Depression: Mechanisms and Therapeutic Implications.

    PubMed

    Felger, Jennifer C

    Studies investigating the impact of a variety of inflammatory stimuli on the brain and behavior have consistently reported evidence that inflammatory cytokines affect the basal ganglia and dopamine to mediate depressive symptoms related to motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal responses to hedonic reward, decreased dopamine and dopamine metabolites in cerebrospinal fluid, and decreased availability of striatal dopamine, all of which correlate with symptoms of anhedonia, fatigue, and psychomotor retardation. Similar relationships between alterations in dopamine-relevant corticostriatal reward circuitry and symptoms of anhedonia and psychomotor slowing have also been observed in patients with major depression who exhibit increased peripheral cytokines and other inflammatory markers, such as C-reactive protein. Of note, these inflammation-associated depressive symptoms are often difficult to treat in patients with medical illnesses or major depression. Furthermore, a wealth of literature suggests that inflammation can decrease dopamine synthesis, packaging, and release, thus sabotaging or circumventing the efficacy of standard antidepressant treatments. Herein, the mechanisms by which inflammation and cytokines affect dopamine neurotransmission are discussed, which may provide novel insights into treatment of inflammation-related behavioral symptoms that contribute to an inflammatory malaise.

  10. Suppression of Rabbit VX‐2 Subcutaneous Tumor Growth by Gadolinium Neutron Capture Therapy

    PubMed Central

    Tokita, Nobuhiko; Tokuuye, Koichi; Satoh, Michinao; Churei, Hisahiko; Pechoux, Cécile Le; Kobayashi, Tooru; Kanda, Keiji

    1993-01-01

    VX‐2 tumors growing in hind legs of New Zealand White rabbits (n=4) were exposed to thermal neutrons for 40 min (2.1 × 1012 neutrons cm−2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5–6 fold higher than that in the contralateral tumor. Growth of gadolinium‐infused tumors was significantly inhibited compared to that of control tumors (P<0.05) between the 16th and 23rd days after treatment. PMID:8407547

  11. Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model.

    PubMed

    Speidl, Walter S; Cimmino, Giovanni; Ibanez, Borja; Elmariah, Sammy; Hutter, Randolph; Garcia, Mario J; Fuster, Valentin; Goldman, Martin E; Badimon, Juan J

    2010-08-01

    Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.

  12. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation

    PubMed Central

    Demidowich, Andrew P.; Davis, Angela I.; Dedhia, Nicket; Yanovski, Jack A.

    2016-01-01

    Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. PMID:27241260

  13. Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary?

    PubMed

    Klenk, Christopher; Gawande, Rakhee; Tran, Vy Thao; Leung, Jennifer Trinh; Chi, Kevin; Owen, Daniel; Luna-Fineman, Sandra; Sakamoto, Kathleen M; McMillan, Alex; Quon, Andy; Daldrup-Link, Heike E

    2016-01-01

    With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images. First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging. There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors. Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. In vitro comparison of intracranial stent visibility using various concentrations of gadolinium contrast agent under 1.5 T and 3 T MR angiography.

    PubMed

    Chiang, Chen-Hua; Tseng, Ying-Chi; Chen, Ai-Chi; Huang, Yen-Lin; Chen, David Yen-Ting; Chen, Chi-Jen; Lin, Yen-Kuang; Hsu, Hui-Ling

    2017-04-01

    MR angiography (MRA) is an increasingly used evaluation method following intracranial stenting. However, the various artifacts created by the stent limit this technique. The purpose of this study was to investigate the effects of various concentrations of gadolinium contrast agent on the visibility and signal characteristics of two stents using the a contrast enhanced MRA technique. Two intracranial stents (Enterprise and Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mmol/L dimeglumine gadopentetate, respectively) and imaged using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis. The Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed mean RIS values much less than those for the Helistent for all different doses of gadolinium solution. Increased gadolinium concentration resulted in a gradual reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise group showed no or little change with various gadolinium doses. The Enterprise stent demonstrated good luminal visibility regardless of gadolinium concentration. The relative in-stent signals were more predictable in the Enterprise stent with various doses of gadolinium. Therefore, the Enterprise stent has been shown to provide better in-stent visibility compared with the Helistent using various gadolinium doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. [Orbital inflammation].

    PubMed

    Mouriaux, F; Coffin-Pichonnet, S; Robert, P-Y; Abad, S; Martin-Silva, N

    2014-12-01

    Orbital inflammation is a generic term encompassing inflammatory pathologies affecting all structures within the orbit : anterior (involvement up to the posterior aspect of the globe), diffuse (involvement of intra- and/or extraconal fat), apical (involvement of the posterior orbit), myositis (involvement of only the extraocular muscles), dacryoadenitis (involvement of the lacrimal gland). We distinguish between specific inflammation and non-specific inflammation, commonly referred to as idiopathic inflammation. Specific orbital inflammation corresponds to a secondary localization of a "generalized" disease (systemic or auto-immune). Idiopathic orbital inflammation corresponds to uniquely orbital inflammation without generalized disease, and thus an unknown etiology. At the top of the differential diagnosis for specific or idiopathic orbital inflammation are malignant tumors, represented most commonly in the adult by lympho-proliferative syndromes and metastases. Treatment of specific orbital inflammation begins with treatment of the underlying disease. For idiopathic orbital inflammation, treatment (most often corticosteroids) is indicated above all in cases of visual loss due to optic neuropathy, in the presence of pain or oculomotor palsy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Study of the Photon Strength Functions for Gadolinium Isotopes with the DANCE Array

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.

    2009-03-10

    The gadolinium isotopes are interesting for reactor applications as well as for medicine and astrophysics. The gadolinium isotopes have some of the largest neutron capture cross sections. As a consequence they are used in the control rod in reactor fuel assembly. From the basic science point of view, there are seven stable isotopes of gadolinium with varying degrees of deformation. Therefore they provide a good testing ground for the study of deformation dependent structure such as the scissors mode. Decay gamma rays following neutron capture on Gd isotopes are detected by the DANCE array, which is located at flight pathmore » 14 at the Lujan Neutron Scattering Center at Los Alamos National Laboratory. The high segmentation and close packing of the detector array enable gamma-ray multiplicity measurements. The calorimetric properties of the DANCE array coupled with the neutron time-of-flight technique enables one to gate on a specific resonance of a specific isotope in the time-of-flight spectrum and obtain the summed energy spectrum for that isotope. The singles gamma-ray spectrum for each multiplicity can be separated by their DANCE cluster multiplicity. Various photon strength function models are used for comparison with experimentally measured DANCE data and provide insight for understanding the statistical decay properties of deformed nuclei.« less

  17. High longitudinal relaxivity of ultra-small gadolinium oxide prepared by microsecond laser ablation in diethylene glycol

    NASA Astrophysics Data System (ADS)

    Luo, Ningqi; Tian, Xiumei; Xiao, Jun; Hu, Wenyong; Yang, Chuan; Li, Li; Chen, Dihu

    2013-04-01

    Ultra-small gadolinium oxide (Gd2O3) can be used as T1-weighted Magnetic Resonance Imaging (MRI) contrast agent own to its high longitudinal relaxivity (r1) and has attracted intensive attention in these years. In this paper, ultra-small Gd2O3 nanoparticles of 3.8 nm in diameter have been successfully synthesized by a microsecond laser ablating a gadolinium (Gd) target in diethylene glycol (DEG). The growth inhibition effect induced by the large viscosity of DEG makes it possible to synthesize ultra-small Gd2O3 by laser ablation in DEG. The r1 value and T1-weighted MR images are measured by a 3.0 T MRI spectroscope. The results show these nanoparticles with a high r1 value of 9.76 s-1 mM-1 to be good MRI contrast agents. We propose an explanation for the high r1 value of ultra-small Gd2O3 by considering the decreasing factor (surface to volume ratio of the nanoparticles, S/V) and the increasing factor (water hydration number of the Gd3+ on Gd2O3 surface, q), which offer a new look into the relaxivity studies of MRI contrast agents. Our research provides a new approach to preparing ultra-small Gd2O3 of high r1 value by laser ablation in DEG and develops the understanding of high relaxivity of ultra-small Gd2O3 MRI contrast agents.

  18. Kinetic characteristics of the luminescence decay for industrial yttrium-gadolinium-aluminium garnet based phosphors

    NASA Astrophysics Data System (ADS)

    Lisitsyn, V. M.; Stepanov, S. A.; Valiev, D. T.; Vishnyakova, E. A.; Abdullin, H. A.; Marhabaeva, A. A.; Tulegenova, A. T.

    2016-02-01

    The spectral and decay kinetic characteristics of pulse cathodoluminescence and photoluminescence of phosphors based on yttrium-gadolinium-aluminum garnet were investigated using pulsed optical time resolved spectroscopy.

  19. Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T1 contrast ability

    NASA Astrophysics Data System (ADS)

    Ni, Kaiyuan; Zhao, Zhenghuan; Zhang, Zongjun; Zhou, Zijian; Yang, Li; Wang, Lirong; Ai, Hua; Gao, Jinhao

    2016-02-01

    High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy

  20. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation.

    PubMed

    Demidowich, Andrew P; Davis, Angela I; Dedhia, Nicket; Yanovski, Jack A

    2016-07-01

    Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. Published by Elsevier Ltd.

  1. Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance with Gadolinium Enhancement and Added Value to [18F]FDG PET.

    PubMed

    Sun, Hongzan; Xin, Jun; Zhou, Jinyuan; Lu, Zaiming; Guo, Qiyong

    2018-06-01

    The purpose of this study is to evaluate the diagnostic concordance and metric correlations of amide proton transfer (APT) imaging with gadolinium-enhanced magnetic resonance imaging (MRI) and 2-deoxy-2-[ 18 F-]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET), using hybrid brain PET/MRI. Twenty-one subjects underwent brain gadolinium-enhanced [ 18 F]FDG PET/MRI prospectively. Imaging accuracy was compared between unenhanced MRI, MRI with enhancement, APT-weighted (APTW) images, and PET based on six diagnostic criteria. Among tumors, the McNemar test was further used for concordance assessment between gadolinium-enhanced imaging, APT imaging, and [ 18 F]FDG PET. As well, the relation of metrics between APT imaging and PET was analyzed by the Pearson correlation analysis. APT imaging and gadolinium-enhanced MRI showed superior and similar diagnostic accuracy. APTW signal intensity and gadolinium enhancement were concordant in 19 tumors (100 %), while high [ 18 F]FDG avidity was shown in only 12 (63.2 %). For the metrics from APT imaging and PET, there was significant correlation for 13 hypermetabolic tumors (P < 0.05) and no correlation for the remaining six [ 18 F]FDG-avid tumors. APT imaging can be used to increase diagnostic accuracy with no need to administer gadolinium chelates. APT imaging may provide an added value to [ 18 F]FDG PET in the evaluation of tumor metabolic activity during brain PET/MR studies.

  2. Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

    PubMed

    Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

    2013-08-01

    To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

  3. Gadolinium sulfate modified by formate to obtain optimized magneto-caloric effect.

    PubMed

    Xu, Long-Yang; Zhao, Jiong-Peng; Liu, Ting; Liu, Fu-Chen

    2015-06-01

    Three new Gd(III) based coordination polymers [Gd2(C2H6SO)(SO4)3(H2O)2]n (1), {[Gd4(HCOO)2(SO4)5(H2O)6]·H2O}n (2), and [Gd(HCOO)(SO4)(H2O)]n (3) were obtained by modifying gadolinium sulfate. With the gradual increase of the volume ratio of HCOOH and DMSO in synthesis, the formate anions begin to coordinate with metal centers; this results in the coordination numbers of sulfate anion increasing and the contents of water and DMSO molecules decreasing in target complexes. Accordingly, spin densities both per mass and per volume were enhanced step by step, which are beneficial for the magneto-caloric effect (MCE). Magnetic studies reveal that with the more formate anions present, the larger the negative value of magnetic entropy change (-ΔSm) is. Complex 3 exhibits the largest -ΔSm = 49.91 J kg(-1) K(-1) (189.51 mJ cm(-3) K(-1)) for T = 2 K and ΔH = 7 T among three new complexes.

  4. Short communication: initiation of an abacavir-containing regimen in HIV-infected adults is associated with a smaller decrease in inflammation and endothelial activation markers compared to non-abacavir-containing regimens.

    PubMed

    Hileman, Corrilynn O; Wohl, David A; Tisch, Daniel J; Debanne, Sara M; McComsey, Grace A

    2012-12-01

    Abacavir has been associated with myocardial infarction in several studies. This may be related to inflammation and endothelial cell activation. We compared changes in inflammation and endothelial activation markers between antiretroviral-naive adults initiating zidovudine, lamivudine, abacavir, and nonnucleoside reverse transcriptase inhibitor (NNRTI) or this regimen without abacavir. Changes in soluble tumor necrosis factor receptors-I, -II (sTNFR-I, -II), high sensitivity C-reactive protein, and soluble vascular cell adhesion molecule-1 (sVCAM-1) from baseline (pre-ART) to a second time point about 24 weeks after initiating antiretroviral therapy (ART) were compared between groups using multivariable linear regression. A total of 37 met eligibility criteria; 12 received abacavir. The median (interquartile range) age was 37 years (27-45). Most were men (32/37), African-American (15/37), or white (15/37). The median nadir CD4(+) and baseline HIV-1 RNA were 230 cells/mm(3) (180-301) and 82,642 copies/ml (34,400-204,703). In all, 15/30 smoked, 7/37 had hypertension, 1/37 had diabetes, and 1/37 had hyperlipidemia. None had coronary or renal disease. Changes in CD4(+) and HIV-1 RNA level and timing of stored samples with regard to ART initiation were not different between groups. In univariable analysis, log transformed percent change in sTNFR-I (p=0.05) and -II (p=0.04) showed significant between-group differences and trended toward significance for sVCAM-1 (p=0.08). These markers decreased less in the abacavir group. After adjustment for confounders, significantly less decrease for sTNFR-II and sVCAM-1 was seen for those receiving the abacavir-containing regimen. When taken with an NNRTI, abacavir induced a smaller decrease in inflammation biomarkers in this cohort, suggesting a possible proinflammatory effect of this nucleoside analogue.

  5. Polythermal investigation of viscosity of solution of metal carboxylates in VIK-grade mixed carboxylic acids: Yttrium and gadolinium carboxylates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mezhov, E.A.; Samatov, A.V.; Troyanovskii, L.V.

    Kinematic viscosities have been measured for solutions of yttrium and gadolinium carboxylates in grade VIK mixed carboxylic acids (MCA). It has been established that the optimal fluidity of these metal carboxylate solutions for application to articles is reached at 333 K. A regression model has been developed to describe the concentration and temperature dependences of the viscosity of yttrium- and gadolinium-containing MCA solutions. 2 refs., 3 tabs.

  6. The performance of hafnium and gadolinium self powered neutron detectors in the TREAT reactor

    NASA Astrophysics Data System (ADS)

    Imel, G. R.; Hart, P. R.

    1996-05-01

    The use of gadolinium and hafnium self powered neutron detectors in a transient reactor is described in this paper. The detectors were calibrated to the fission rate of U-235 using calibrated fission chambers; the calibration factors were tested in two reactors in steady state and found to be consistent. Calibration of the detectors in transient reactor conditions was done by using uranium wires that were analyzed by radiochemistry techniques to determine total fissions during the transient. This was correlated to the time-integrated current of the detectors during the transient. A temperature correction factor was derived to account for self-shielding effects in the hafnium and gadolinium detectors. The dynamic response of the detectors under transient conditions was studied, and found to be excellent.

  7. FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation.

    PubMed

    Ge, Xiao Na; Bastan, Idil; Dileepan, Mythili; Greenberg, Yana; Ha, Sung Gil; Steen, Kaylee A; Bernlohr, David A; Rao, Savita P; Sriramarao, P

    2018-04-26

    Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a pro-inflammatory role for FABP4 in allergic asthma, although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, was not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation. CRA exposure led to airway recruitment of FABP4-expressing inflammatory cells, specifically eosinophils, in wild type (WT) mice. FABP4 expression in eosinophils was induced by TNF-α as well as IL-4 and IL-13. FABP4-deficient eosinophils exhibited markedly decreased cell spreading/formation of leading edges on vascular cell adhesion molecule-1 and significantly decreased adhesion to intercellular adhesion molecule-1 associated with reduced β2 integrin expression relative to WT cells. Further, FABP4-deficient eosinophils exhibited decreased migration, F-actin polymerization, calcium flux and ERK (1/2) phosphorylation in response to eotaxin-1. In vivo, CRA-challenged FABP4-deficient mice exhibited attenuated eosinophilia and significantly reduced airway inflammation (improved airway reactivity, lower IL-5, IL-13, TNFα and LTC4 levels, decreased airway structural changes) compared to WT mice. In conclusion, expression of FABP4 in eosinophils is induced during conditions of inflammation and plays a pro-inflammatory role in the development of allergic asthma by promoting eosinophil adhesion and migration and contributing to the development of various aspects of airway inflammation.

  8. Assessment of blood flow with 68Ga-DOTA PET in experimental inflammation: a validation study using 15O-water

    PubMed Central

    Autio, Anu; Saraste, Antti; Kudomi, Nobuyuki; Saanijoki, Tiina; Johansson, Jarkko; Liljenbäck, Heidi; Tarkia, Miikka; Oikonen, Vesa; Sipilä, Hannu T; Roivainen, Anne

    2014-01-01

    Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N‘,N‘‘,N‘‘‘-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog (68Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 15O) and 30-min 68Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 15O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of 68Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the 68Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 15O-based blood flow and 68Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that 68Ga-DOTA PET imaging is useful for the quantification of increased

  9. Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol.

    PubMed

    Jingu, Akiko; Fukuda, Junya; Taketomi-Takahashi, Ayako; Tsushima, Yoshito

    2014-10-06

    Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR).The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. The protocol was applied to a total of 252 examinations (153 patients, ages 15-87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma.

  10. Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

    PubMed Central

    2014-01-01

    Background Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. Methods All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. Results The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Conclusion Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma. PMID:25287952

  11. Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs

    PubMed Central

    Tivers, Michael S.; Handel, Ian; Gow, Adam G.; Lipscomb, Victoria J.; Jalan, Rajiv; Mellanby, Richard J.

    2015-01-01

    Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that

  12. Inhibition of Tumor Necrosis Factor Improves Sleep Continuity in Patients with Treatment Resistant Depression and High Inflammation

    PubMed Central

    Weinberger, Jeremy F.; Raison, Charles L.; Rye, David B.; Montague, Amy R.; Woolwine, Bobbi J.; Felger, Jennifer C.; Haroon, Ebrahim; Miller, Andrew H.

    2014-01-01

    Blockade of the inflammatory cytokine tumor necrosis factor (TNF) in depressed patients with increased inflammation has been associated with decreased depressive symptoms. Nevertheless, the impact of TNF blockade on sleep in depressed patients has not been examined. Accordingly, sleep parameters were measured using polysomnography in 36 patients with treatment resistant major depression at baseline and 2 weeks after 3 infusions (week 8) of either the TNF antagonist infliximab (n=19) or placebo (n=17). Markers of inflammation including c-reactive protein (CRP) and TNF and its soluble receptors were assessed along with depression measured by the 17-item Hamilton Depression Rating Scale. No differences in sleep parameters were found as a function of infliximab treatment over time. Nevertheless, Wake After Sleep Onset (WASO), the spontaneous arousal index and sleep period time significantly decreased, and sleep efficiency significantly increased, from baseline to week 8 in infliximab-treated patients with high (CRP>5mg/L)(n=9) versus low inflammation (CRP≤5mg/L)(n=10), controlling for changes in scores of depression. Stage 2 sleep also significantly decreased in infliximab-treated patients with high versus low inflammation. Decreases in soluble TNF receptor 1 significantly correlated with decreases in WASO and increases in sleep efficiency in infliximab-treated subjects with high inflammation. Placebo-treated subjects exhibited no sleep changes as a function of inflammation, and no correlations between inflammatory markers and sleep parameters in placebo-treated patients were found. These data suggest that inhibition of inflammation may be a viable strategy to improve sleep alterations in patients with depression and other disorders associated with increased inflammation. PMID:25529904

  13. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of cadaveric shoulders: comparison of contrast dynamics in hyaline and fibrous cartilage after intraarticular gadolinium injection.

    PubMed

    Wiener, E; Hodler, J; Pfirrmann, C W A

    2009-01-01

    Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a novel method to investigate cartilaginous and fibrocartilaginous structures. To investigate the contrast dynamics in hyaline and fibrous cartilage of the glenohumeral joint after intraarticular injection of gadopentetate dimeglumine. Transverse T(1) maps were acquired on a 1.5T scanner before and after intraarticular injection of 2.0 mmol/l gadopentetate dimeglumine in five cadaveric shoulders using a dual flip angle three-dimensional gradient echo (3D-GRE) sequence. The acquisition time for the T(1) maps was 5 min 5 s for the whole shoulder. Measurements were repeated every 15 min over 2.5 hours. Regions of interest (ROIs) covering the glenoid cartilage and the labrum were drawn to assess the temporal evolution of the relaxation parameters. T(1) of unenhanced hyaline cartilage of the glenoid was 568+/-34 ms. T(1) of unenhanced fibrous cartilage of the labrum was 552+/-38 ms. Significant differences (P=0.002 and 0.03) in the relaxation parameters were already measurable after 15 min. After 2 to 2.5 hours, hyaline and fibrous cartilage still demonstrated decreasing relaxation parameters, with a larger range of the T(1)(Gd) values in fibrous cartilage. T(1) and triangle Delta R(1) values of hyaline and fibrous cartilage after 2.5 hours were 351+/-16 ms and 1.1+/-0.09 s(-1), and 332+/-31 ms and 1.2+/-0.1 s(-1), respectively. A significant decrease in T(1)(Gd) was found 15 min after intraarticular contrast injection. Contrast accumulation was faster in hyaline than in fibrous cartilage. After 2.5 hours, contrast accumulation showed a higher rate of decrease in hyaline cartilage, but neither hyaline nor fibrous cartilage had reached equilibrium.

  14. Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

    PubMed Central

    Curtet, C; Tellier, C; Bohy, J; Conti, M L; Saccavini, J C; Thedrez, P; Douillard, J Y; Chatal, J F; Koprowski, H

    1986-01-01

    Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors. Images PMID:3459174

  15. Influence of gamma-irradiation on the non-isothermal decomposition of calcium-gadolinium oxalate

    NASA Astrophysics Data System (ADS)

    Moharana, S. C.; Praharaj, J.; Bhatta, D.

    Thermal decomposition of co-precipitated unirradiated and irradiated Ca-Gd oxalate has been studied by adopting differential thermal analysis (DTA) and thermogravimetric (TG) techniques. The reaction occurs through two stages corresponding to the decomposition of gadolinium oxalate (Gd-Ox) followed by that of calcium oxalate (Ca-Ox). The kinetic parameters for both the stages are calculated by using solid state reaction models and Coats-Redfern's equation. The co-precipitation as well as irradiation alter the DTA peak temperatures and the kinetic parameters of Ca-Ox. The decomposition of Gd-Ox follows the two dimensional Contracting area (R-2) mechanism, while that of Ca-Ox follows the Avrami-Erofeev (A(2)) mechanism (n =2), which are also exhibited by the co-precipitated and irradiated samples. Co-precipitation decreases the energy of activation and the pre-exponential factor of the individual components but the reverse phenomenon takes place upon irradiation of the co-precipitate. The mechanisms underlying the phenomena are explored.

  16. Application of an oscillation-type linear cadmium telluride detector to enhanced gadolinium K-edge computed tomography

    NASA Astrophysics Data System (ADS)

    Matsukiyo, Hiroshi; Sato, Eiichi; Hagiwara, Osahiko; Abudurexiti, Abulajiang; Osawa, Akihiro; Enomoto, Toshiyuki; Watanabe, Manabu; Nagao, Jiro; Sato, Shigehiro; Ogawa, Akira; Onagawa, Jun

    2011-03-01

    A linear cadmium telluride (CdTe) detector is useful for carrying out energy-discrimination X-ray imaging, including computed tomography (CT). To perform enhanced gadolinium K-edge CT, we used an oscillation-type linear CdTe detector with an energy resolution of 1.2 keV. CT is performed by repeating the linear scan and the rotation of an object. Penetrating X-ray photons from the object are detected by the CdTe detector, and event signals of X-ray photons are produced using charge-sensitive and shaping amplifiers. Both the photon energy and the energy width are selected using a multichannel analyzer, and the number of photons is counted by a counter card. In energy-discrimination CT, tube voltage and current were 80 kV and 20 μA, respectively, and X-ray intensity was 1.55 μGy/s at 1.0 m from the source at a tube voltage of 80 kV. Demonstration of enhanced gadolinium K-edge X-ray CT was carried out by selecting photons with energies just beyond gadolinium K-edge energy of 50.3 keV.

  17. Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

    PubMed

    Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg

    2018-02-13

    There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P < 0.001) improvements over the low-dose images (>5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly

  18. Nephrogenic systemic fibrosis and class labeling of gadolinium-based contrast agents by the Food and Drug Administration.

    PubMed

    Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine

    2012-10-01

    In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. © RSNA, 2012.

  19. Curcuma and Scutellaria plant extracts protect chickens against inflammation and Salmonella Enteritidis infection.

    PubMed

    Varmuzova, Karolina; Matulova, Marta Elsheimer; Gerzova, Lenka; Cejkova, Darina; Gardan-Salmon, Delphine; Panhéleux, Marina; Robert, Fabrice; Sisak, Frantisek; Havlickova, Hana; Rychlik, Ivan

    2015-09-01

    After a ban on the use of antibiotics as growth promoters in farm animals in the European Union in 2006, an interest in alternative products with antibacterial or anti-inflammatory properties has increased. In this study, we therefore tested the effects of extracts from Curcuma longa and Scutellaria baicalensis used as feed additives against cecal inflammation induced by heat stress or Salmonella Enteritidis (S. Enteritidis) infection in chickens. Curcuma extract alone was not enough to decrease gut inflammation induced by heat stress. However, a mixture of Curcuma and Scutellaria extracts used as feed additives decreased gut inflammation induced by heat or S. Enteritidis, decreased S. Enteritidis counts in the cecum but was of no negative effect on BW or humoral immune response. Using next-generation sequencing of 16S rRNA we found out that supplementation of feed with the 2 plant extracts had no effect on microbiota diversity. However, if the plant extract supplementation was provided to the chickens infected with S. Enteritidis, Faecalibacterium, and Lactobacillus, both bacterial genera with known positive effects on gut health were positively selected. The supplementation of chicken feed with extracts from Curcuma and Scutelleria thus may be used in poultry production to effectively decrease gut inflammation and increase chicken performance. © 2015 Poultry Science Association Inc.

  20. Kondo effect and enhanced magnetic properties in gadolinium functionalized carbon nanotube supramolecular complex.

    PubMed

    Ncube, S; Coleman, C; Strydom, A; Flahaut, E; de Sousa, A; Bhattacharyya, S

    2018-05-23

    We report on the enhancement of magnetic properties of multiwalled carbon nanotubes (MWNTs) functionalized with a gadolinium based supramolecular complex. By employing a newly developed synthesis technique we find that the functionalization method of the nanocomposite enhances the strength of magnetic interaction leading to a large effective moment of 15.79 µ B and non-superparamagnetic behaviour unlike what has been previously reported. Saturating resistance at low temperatures is fitted with the numerical renormalization group formula verifying the Kondo effect for magnetic impurities on a metallic electron system. Magnetoresistance shows devices fabricated from aligned gadolinium functionalized MWNTs (Gd-Fctn-MWNTs) exhibit spin-valve switching behaviour of up to 8%. This study highlights the possibility of enhancing magnetic interactions in carbon systems through chemical modification, moreover we demonstrate the rich physics that might be useful for developing spin based quantum computing elements based on one-dimensional (1D) channels.

  1. Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus nonionic contrast agent.

    PubMed

    Menezes, Nina M; Olear, Elizabeth A; Li, Xiaoming; Connolly, Susan A; Zurakowski, David; Foley, Mary; Shapiro, Frederic; Jaramillo, Diego

    2006-05-01

    To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). The results suggest different roles for the two gadolinium-based contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for

  2. Imaging of cauda equina edema in lumbar canal stenosis by using gadolinium-enhanced MR imaging: experimental constriction injury.

    PubMed

    Kobayashi, S; Uchida, K; Takeno, K; Baba, H; Suzuki, Y; Hayakawa, K; Yoshizawa, H

    2006-02-01

    It has been reported that disturbance of blood flow arising from circumferential compression of the cauda equina by surrounding tissue plays a major role in the appearance of neurogenic intermittent claudication (NIC) associated with lumbar spinal canal stenosis (LSCS). We created a model of LSCS to clarify the mechanism of enhancement within the cauda equina on gadolinium-enhanced MR images from patients with LSCS. In 20 dogs, a lumbar laminectomy was performed by applying circumferential constriction to the cauda equina by using a silicon tube, to produce 30% stenosis of the circumferential diameter of the dural tube. After 1 and 3 weeks, gadolinium and Evans blue albumin were injected intravenously at the same time. The sections were used to investigate the status of the blood-nerve barrier function under a fluorescence microscope and we compared gadolinium-enhanced MR images with Evans blue albumin distribution in the nerve. The other sections were used for light and transmission electron microscopic study. In this model, histologic examination showed congestion and dilation in many of the intraradicular veins, as well as inflammatory cell infiltration. The intraradicular edema caused by venous congestion and Wallerian degeneration can also occur at sites that are not subject to mechanical compression. Enhanced MR imaging showed enhancement of the cauda equina at the stenosed region, demonstrating the presence of edema. Gadolinium-enhanced MR imaging may be a useful tool for the diagnosis of microcirculatory disorders of the cauda equina associated with LSCS.

  3. Clinical, biological, and skin histopathologic effects of ionic macrocyclic and nonionic linear gadolinium chelates in a rat model of nephrogenic systemic fibrosis.

    PubMed

    Fretellier, Nathalie; Idée, Jean-Marc; Guerret, Sylviane; Hollenbeck, Claire; Hartmann, Daniel; González, Walter; Robic, Caroline; Port, Marc; Corot, Claire

    2011-02-01

    the purpose of this study was to compare the clinical, pathologic, and biochemical effects of repeated administrations of ionic macrocyclic or nonionic linear gadolinium chelates (GC) in rats with impaired renal function. rats submitted to subtotal nephrectomy were allocated to single injections of 2.5 mmol/kg of gadodiamide (nonionic linear chelate), nonformulated gadodiamide (ie, without the free ligand caldiamide), gadoterate (ionic macrocyclic chelate), or saline for 5 consecutive days. Blinded semi-quantitative histopathologic and immunohistochemical examinations of the skin were performed, as well as clinical, hematological, and biochemical follow-up. Rats were killed at day 11. Long-term (up to day 32) follow-up of rats was also performed in an auxiliary study. epidermal lesions (ulcerations and scabs) were found in 4 of the 10 rats treated with nonformulated gadodiamide. Two rats survived the study period. Inflammatory signs were observed in this group. No clinical, hematological, or biochemical signs were observed in the saline and gadoterate- or gadodiamide-treated groups. Plasma fibroblast growth factor-23 levels were significantly higher in the gadodiamide group than in the gadoterate group (day 11). Decreased plasma transferrin-bound iron levels were measured in the nonformulated gadodiamide group. Histologic lesions were in the range: nonformulated gadodiamide (superficial epidermal lesions, inflammation, necrosis, and increased cellularity in papillary dermis) > gadodiamide (small superficial epidermal lesions and signs of degradation of collagen fibers in the dermis) > gadoterate (very few pathologic lesions, similar to control rats). repeated administration of the nonionic linear GC gadodiamide to renally impaired rats is associated with more severe histologic lesions and higher FGF-23 plasma levels than the macrocyclic GC gadoterate.

  4. In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging.

    PubMed

    Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

    2015-01-01

    Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.

  5. In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

    PubMed Central

    Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

    2015-01-01

    Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N′-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. PMID:26316749

  6. Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model.

    PubMed

    Kartamihardja, A Adhipatria P; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

    2016-10-01

    The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

  7. Placental inflammation and fetal hemodynamics in a rat model of chorioamnionitis.

    PubMed

    Abdulkadir, Adegboyega A; Kimimasa, Tobita; Bell, Michael J; Macpherson, Trevor A; Keller, Bradley B; Yanowitz, Toby D

    2010-12-01

    The relative contributions of inflammation and ischemia to the pathogenesis of periventricular leukomalacia (PVL) have not been elucidated. We hypothesized that fetal cardiovascular function and cerebral blood flow velocity (BFV) would be decreased in a rat model of chorioamnionitis. We also tested whether placental inflammation was related to proximity to the cervix in our model of chorioamnionitis [intracervical lipopolysaccharide (LPS) or vehicle (PBS) injection]. On embryonic d 15, Sprague-Dawley rats underwent baseline maternal and fetal echocardiography, followed by LPS or PBS injection, then serial echocardiographic evaluations until embryonic day (ED) 21. One hour after birth, pups had middle cerebral artery (MCA) BFV measured. Placentas of LPS-exposed pups exhibited uniform, higher inflammation grades (p < 0.001). All fetal BFVs increased with advancing GA (p < 0.001) whereas resistance index (RI) decreased (p < 0.001). There was no difference in fetal BFV between the groups other than a reduced gestation-related increase in descending aorta BFV in LPS-exposed rats (p < 0.05). Newborn pups exposed to LPS had lower heart rate (p = 0.006) and MCA BFV (p = 0.024) and higher RI (p = 0.003) and pulsatility index (PI; p = 0.004). In conclusion, intracervical LPS injection produces an inflammation independent of placental position, a blunted increase in gestation-related aortic BFV, and a decrease in MCA BFV in newborn pups.

  8. Pulmonary exposure to diesel exhaust particles enhances coagulatory disturbance with endothelial damage and systemic inflammation related to lung inflammation.

    PubMed

    Inoue, Ken-Ichiro; Takano, Hirohisa; Sakurai, Miho; Oda, Toshio; Tamura, Hiroshi; Yanagisawa, Rie; Shimada, Akinori; Yoshikawa, Toshikazu

    2006-11-01

    Pulmonary exposure to diesel exhaust particles (DEP) enhances lung inflammation related to bacterial endotoxin (lipopolysaccharide [LPS]) in mice. Severe lung inflammation can reportedly induce coagulatory abnormalities and systemic inflammation. This study examined the effects of components of DEP on lung inflammation, pulmonary permeability, coagulatory changes, systemic inflammatory response, and lung-to-systemic translocation of LPS in a murine model of lung inflammation. ICR mice were divided into six experimental groups that intratracheally received vehicle, LPS (2.5 mg/kg), organic chemicals in DEP (DEP-OC; 4 mg/kg) extracted with dicloromethane), residual carbonaceous nuclei of DEP (washed DEP: 4 mg/kg), DEP-OC + LPS, or washed DEP + LPS. Both DEP components exacerbated lung inflammation, vascular permeability, and the increased fibrinogen and E-selectin levels induced by LPS. With overall trends, the exacerbation was more prominent with washed DEP than with DEP-OC. Washed DEP + LPS significantly decreased activated protein C and antithrombin-III and elevated circulatory levels of interleukin (IL)-6, keratinocyte chemoattractant (KC), and LPS as compared with LPS alone, whereas DEP-OC + LPS elevated IL-6, KC, and LPS without significance. These results show that DEP components, especially washed DEP, amplify the effects if LPS on the respiratory system and suggest that they contribute to the adverse health effects of particulate air pollution on the sensitive populations with predisposing vascular and/or pulmonary diseases, including ischemic vascular diseases and respiratory infection.

  9. Low grade inflammation inhibits VEGF induced HUVECs migration in p53 dependent manner

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Panta, Sushil; Yamakuchi, Munekazu; Kagoshima University Hospital, Kagoshima

    In the course of studying crosstalk between inflammation and angiogenesis, high doses of pro-inflammatory factors have been reported to induce apoptosis in cells. Under normal circumstances also the pro-inflammatory cytokines are being released in low doses and are actively involved in cell signaling pathways. We studied the effects of low grade inflammation in growth factor induced angiogenesis using tumor necrosis factor alfa (TNFα) and vascular endothelial growth factor A (VEGF) respectively. We found that low dose of TNFα can inhibit VEGF induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Low dose of TNFα induces mild upregulation and moreover nuclearmore » localization of tumor suppressor protein 53 (P53) which causes decrease in inhibitor of DNA binding-1 (Id1) expression and shuttling to the cytoplasm. In absence of Id1, HUVECs fail to upregulate β{sub 3}-integrin and cell migration is decreased. Connecting low dose of TNFα induced p53 to β{sub 3}-integrin through Id1, we present additional link in cross talk between inflammation and angiogenesis. - Highlights: • Low grade inflammation (low dose of TNF alfa) inhibits VEGF induced endothelial cells migration. • The low grade inflammation with VEGF treatment upregulates P53 to a nonlethal level. • P53 activation inhibits Id1 shuttling to the cytoplasm in endothelial cells. • Inhibition of Id1 resulted in downregulation of β{sub 3}-integrin which cause decrease in cell migration. • Inflammation and angiogenesis might cross-talk by P53 – Id1 – β{sub 3}-integrin pathway in endothelial cells.« less

  10. Dietary Quercetin Attenuates Adipose Tissue Expansion and Inflammation and Alters Adipocyte Morphology in a Tissue-Specific Manner

    PubMed Central

    Forney, Laura A.; Lenard, Natalie R.; Stewart, Laura K.

    2018-01-01

    Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation. Here, we determined the effects of quercetin and red onion extract (ROE) containing quercetin on subcutaneous (inguinal, IWAT) vs. visceral (epididymal, EWAT) white adipose tissue morphology and inflammation in mice fed low fat, high fat, high fat plus 50 μg/day quercetin or high fat plus ROE containing 50 μg/day quercetin equivalents for 9 weeks. Quercetin and ROE similarly ameliorated HFD-induced increases in adipocyte size and decreases in adipocyte number in IWAT and EWAT. Furthermore, quercetin and ROE induced alterations in adipocyte morphology in IWAT. Quercetin and ROE similarly decreased HFD-induced IWAT inflammation. However, quercetin and red onion differentially affected HFD-induced EWAT inflammation, with quercetin decreasing and REO increasing inflammatory marker gene expression. Quercetin and REO also differentially regulated circulating adipokine levels. These results show that quercetin or botanical extracts containing quercetin induce white adipose tissue remodeling which may occur through inflammatory-related mechanisms. PMID:29562620

  11. Inflammation-induced effects on iron-related proteins in splenic macrophages and the liver in mice.

    PubMed

    Sukumaran, Abitha; Venkatraman, Aparna; Jacob, Molly

    2012-06-15

    Anemia of inflammation is characterized by disturbances in systemic iron homeostasis. In order to better understand the events involved, we carried out a time-course study on the effects of acute and chronic inflammation on iron-related proteins in mouse splenic macrophages and the liver. Mice were sacrificed at various time points ranging from 0 h up to 4 weeks after induction of inflammation with turpentine oil. Expression levels of iron-related proteins in the splenic macrophages and liver were determined. Iron levels in the serum, spleen and liver were also measured. Hepatic hepcidin was found to be induced in response to inflammation. In the macrophages, expression levels of ferroportin and TfR1 were decreased at some of the time points. The expression of hepatic TfR1 and ferritin was significantly higher at the early time points. Ferritin levels in the liver decreased progressively thereafter; this was associated with significantly higher ferroportin expression in the liver, despite high levels of hepcidin, suggesting that hepcidin may not regulate ferroportin levels in the liver, unlike in the macrophages. The effects of hepcidin, thus, appeared to be tissue-specific. Serum iron levels were decreased initially; these then rose and were associated with decreasing iron levels in the liver and spleen. Thus, inflammation affected the expression levels of many proteins involved in iron homeostasis in splenic macrophages and the liver, with differences seen in the effects at these 2 sites. These effects are likely to contribute to the development of anemia of inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Montgomery, J. M.; Samudrala, G. K.; Vohra, Y. K.

    A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high-pressure area on the order of a few tens of seconds. This device is then used to scan the phasemore » diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in this experiment, the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp → αSm transition proceeds in discontinuous steps at points along the expected phase boundary. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0–10 GPa and 300–650 K.« less

  13. High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

    NASA Astrophysics Data System (ADS)

    Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.; Vohra, Y. K.

    2016-04-01

    A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high-pressure area on the order of a few tens of seconds. This device is then used to scan the phase diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in this experiment, the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp → αSm transition proceeds in discontinuous steps at points along the expected phase boundary. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0-10 GPa and 300-650 K.

  14. Disparate ultrafast dynamics of itinerant and localized magnetic moments in gadolinium metal

    PubMed Central

    Frietsch, B.; Bowlan, J.; Carley, R.; Teichmann, M.; Wienholdt, S.; Hinzke, D.; Nowak, U.; Carva, K.; Oppeneer, P. M.; Weinelt, M.

    2015-01-01

    The Heisenberg–Dirac intra-atomic exchange coupling is responsible for the formation of the atomic spin moment and thus the strongest interaction in magnetism. Therefore, it is generally assumed that intra-atomic exchange leads to a quasi-instantaneous aligning process in the magnetic moment dynamics of spins in separate, on-site atomic orbitals. Following ultrashort optical excitation of gadolinium metal, we concurrently record in photoemission the 4f magnetic linear dichroism and 5d exchange splitting. Their dynamics differ by one order of magnitude, with decay constants of 14 versus 0.8 ps, respectively. Spin dynamics simulations based on an orbital-resolved Heisenberg Hamiltonian combined with first-principles calculations explain the particular dynamics of 5d and 4f spin moments well, and corroborate that the 5d exchange splitting traces closely the 5d spin-moment dynamics. Thus gadolinium shows disparate dynamics of the localized 4f and the itinerant 5d spin moments, demonstrating a breakdown of their intra-atomic exchange alignment on a picosecond timescale. PMID:26355196

  15. K3 Li3 Gd7 (BO3 )9 : A New Gadolinium-Rich Orthoborate for Cryogenic Magnetic Cooling.

    PubMed

    Xia, Mingjun; Shen, Shipeng; Lu, Jun; Sun, Young; Li, Rukang

    2018-03-02

    Magnetic cooling technology based on magnetocaloric effect (MCE) has attracted great interest in obtaining extremely low temperatures, for example, for space exploration. Here, we grew a new gadolinium-rich orthoborate K 3 Li 3 Gd 7 (BO 3 ) 9 (1) as a promising cryogenic magnetic coolant. It exhibits a complicated three dimensional framework constructed from BO 3 groups and gadolinium-oxygen chains. The Gd-O chain consists of two types of clusters of Gd 3 O 20 and Gd 3 O 19 interconnection by Gd(4)O 8 polyhydron. Due to its high gadolinium concentration, a large -ΔS m of 56.6 J kg -1  K -1 for 1 was obtained at 2 K and ΔH=7 T, much larger than that of the commercial benchmark Gd 3 Ga 5 O 12 (GGG) crystal (38.4 J kg -1  K -1 ), suggesting it to be an excellent MCE material. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Transient arterial phase respiratory motion-related artifact in MR imaging of the liver: an analysis of four different gadolinium-based contrast agents.

    PubMed

    Shah, Mansi R; Flusberg, Milana; Paroder, Viktoriya; Rozenblit, Alla M; Chernyak, Victoria

    The purpose was to compare hepatic arterial phase (HAP) respiratory motion artifact (RMA) between gadoxetate, gadobutrol, gadopentetate, and gadobenate. Two hundred cases of each gadolinium agent were included. RMA was assigned using 5-point Likert scale (1=no motion, 5=extreme motion) on precontrast and HAP. RMA increase (increase ≥1 on HAP from precontrast) was the outcome in logistic regression. Odds of RMA increase for gadoxetate were 5.5 (P<.001), 3.6 (P=.034), and 9.5 (P<.001) times higher than gadobutrol, gadopentetate, and gadobenate, respectively. Gadolinium volume and dose were not independent predictors of RMA increase. Gadoxetate has increased odds of RMA compared with other gadolinium agents; tight contrast bolus is not a contributor. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Gadolinium-enhanced inner ear magnetic resonance imaging for evaluation of delayed endolymphatic hydrops, including a bilateral case.

    PubMed

    Fukushima, Munehisa; Oya, Ryohei; Akazawa, Hitoshi; Tsuruta, Yukinori; Inohara, Hidenori

    2016-01-01

    The data suggests that gadolinium-enhanced inner ear MR imaging is useful for diagnosis of delayed endolymphatic hydrops (DEH) because it is independent of inner ear function, and the size of the affected endolymphatic space is clearly enlarged. This study was performed to semi-quantitatively evaluate the endolymphatic space in patients with all types of DEH using gadolinium-enhanced inner ear magnetic resonance (MR) imaging. Seven patients (age range = 21-77 years; five female, two male) with ipsilateral DEH (n = 5), contralateral DEH (n = 1), and bilateral DEH (n = 1). All patients underwent 3T MR imaging 4 h after intravenous injection of gadolinium. Software was used to determine the size of the endolymphatic space. Pure tone audiometry and caloric testing using an electronystagmogram were carried out. One side of the endolymphatic space was dominantly extended in patients with ipsilateral DEH, and both sides of the space were extended in patients with contralateral and bilateral DEH. In patients with ipsilateral DEH, the volume ratio of endolymph to vestibule was 2.5-4.3-times that in the unaffected ear. The volume ratio of endolymph to vestibule was nearly equal in patients with contralateral and bilateral DEH.

  18. Chronic skin-specific inflammation promotes vascular inflammation and thrombosis.

    PubMed

    Wang, Yunmei; Gao, Huiyun; Loyd, Candace M; Fu, Wen; Diaconu, Doina; Liu, Shijian; Cooper, Kevin D; McCormick, Thomas S; Simon, Daniel I; Ward, Nicole L

    2012-08-01

    Patients with psoriasis have systemic and vascular inflammation and are at increased risk for myocardial infarction, stroke, and cardiovascular death. However, the underlying mechanism(s) mediating the link between psoriasis and vascular disease is incompletely defined. This study sought to determine whether chronic skin-specific inflammation has the capacity to promote vascular inflammation and thrombosis. Using the KC-Tie2 doxycycline-repressible (Dox-off) murine model of psoriasiform skin disease, spontaneous aortic root inflammation was observed in 33% of KC-Tie2 compared with 0% of control mice by 12 months of age (P=0.04) and was characterized by the accumulation of macrophages, T lymphocytes, and B lymphocytes, as well as by reduced collagen content and increased elastin breaks. Importantly, aortic inflammation was preceded by increases in serum tumor necrosis factor-α, IL-17A, vascular endothelial growth factor, IL-12, monocyte chemotactic protein-1, and S100A8/A9, as well as splenic and circulating CD11b(+)Ly-6C(hi) pro-inflammatory monocytes. Doxycycline treatment of old mice with severe skin disease eliminated skin inflammation and the presence of aortic root lesion in 1-year-old KC-Tie2 animals. Given the bidirectional link between inflammation and thrombosis, arterial thrombosis was assessed in KC-Tie2 and control mice; mean time to occlusive thrombus formation was shortened by 64% (P=0.002) in KC-Tie2 animals; and doxycycline treatment returned thrombosis clotting times to that of control mice (P=0.69). These findings demonstrate that sustained skin-specific inflammation promotes aortic root inflammation and thrombosis and suggest that aggressive treatment of skin inflammation may attenuate pro-inflammatory and pro-thrombotic pathways that produce cardiovascular disease in psoriasis patients.

  19. Monte Carlo simulation of energy absorbed in phenolic ESR dosimeters added with gadolinium exposed to thermal, epithermal and fast neutrons

    NASA Astrophysics Data System (ADS)

    Longo, A.; Collura, G.; Gallo, S.; Bartolotta, A.; Marrale, M.

    2017-11-01

    In this work analyses of the energy released per unit mass in phenolic compound exposed to neutron beams were performed with the aim of predicting the increase in dose achievable by addition of gadolinium (Gd) inside the pellets. In particular, Monte Carlo (MC) simulations were carried out for IRGANOX® 1076 phenolic compound irradiated with neutron beams with different energy spectra at various depths inside a water phantom. The addition of gadolinium increases sensitivity of phenolic ESR (electron spin resonance) dosimeters to neutrons thanks to the high gadolinium cross section for neutron capture and to the large number of secondary particles (mainly Auger and internal conversion electrons) which are able to release energy inside the sensitive material layers. For small depths in water phantom and low energy neutron spectra the increase in dose due to gadolinium is large (more than a factor 50). The enhancement is smaller in case of epithermal neutron beam, whereas the increase in dose for fast neutrons is less than 50%. In order to have a comparison with other ESR dosimeters the energy released per unit mass in phenolic compound was compared with that calculated in alanine pellets. For thermal neutron beams the energy released in phenolic compound with gadolinium is comparable to that released in alanine for small depths in phantom, whereas it is larger than in alanine for large depths. In case of epithermal and fast neutron beams the energy released in phenolic compound is larger than in alanine samples because the elastic scattering with hydrogen nuclei is more probable for high neutron energies and this phenolic compound is characterized by an higher number of 1H nuclei than alanine. All results here found suggest that these phenolic pellets could be fruitfully used for dosimetric applications in Neutron Capture Therapy.

  20. CD39 improves survival in microbial sepsis by attenuating systemic inflammation

    PubMed Central

    Csóka, Balázs; Németh, Zoltán H.; Törő, Gábor; Koscsó, Balázs; Kókai, Endre; Robson, Simon C.; Enjyoji, Keiichi; Rolandelli, Rolando H.; Erdélyi, Katalin; Pacher, Pál; Haskó, György

    2015-01-01

    Sepsis remains the leading cause of morbidity and mortality in critically ill patients. Excessive inflammation is a major cause of organ failure and mortality in sepsis. Ectonucleoside triphosphate diphosphohydrolase 1, ENTPDase1 (CD39) is a cell surface nucleotide-metabolizing enzyme, which degrades the extracellular purines ATP and ADP, thereby regulating purinergic receptor signaling. Although the role of purinergic receptor signaling in regulating inflammation and sepsis has been addressed previously, the role of CD39 in regulating the host’s response to sepsis is unknown. We found that the CD39 mimic apyrase (250 U/kg) decreased and knockout or pharmacologic blockade with sodium polyoxotungstate (5 mg/kg; IC50 ≈ 10 μM) of CD39 increased mortality of mice with polymicrobial sepsis induced by cecal ligation and puncture. CD39 decreased inflammation, organ damage, immune cell apoptosis, and bacterial load. Use of bone marrow chimeric mice revealed that CD39 expression on myeloid cells decreases inflammation in septic mice. CD39 expression is upregulated during sepsis in mice, as well as in both murine and human macrophages stimulated with Escherichia coli. Moreover, E. coli increases CD39 promoter activity in macrophages. Altogether, these data indicate CD39 as an evolutionarily conserved inducible protective pathway during sepsis. We propose CD39 as a novel therapeutic target in the management of sepsis.—Csóka, B., Németh, Z. H., Törő, G., Koscsó, B., Kókai, E., Robson, S. C., Enjyoji, K., Rolandelli, R. H., Erdélyi, K., Pacher, P., Haskó, G. CD39 improves survival in microbial sepsis by attenuating systemic inflammation. PMID:25318479

  1. Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

    PubMed

    Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

    2014-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

  2. Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yamazaki, Etsuo; Fukuda, Hozumi; Shibuya, Hitoshi

    The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. The increase in frequency of SCE seen after the addition of Gd-DTPA wasmore » decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related. 14 refs., 6 tabs.« less

  3. Gadolinium chelate coated gold nanoparticles as contrast agents for both X-ray computed tomography and magnetic resonance imaging.

    PubMed

    Alric, Christophe; Taleb, Jacqueline; Le Duc, Géraldine; Mandon, Céline; Billotey, Claire; Le Meur-Herland, Alice; Brochard, Thierry; Vocanson, Francis; Janier, Marc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2008-05-07

    Functionalized gold nanoparticles were applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. These particles were obtained by encapsulating gold cores within a multilayered organic shell which is composed of gadolinium chelates bound to each other through disulfide bonds. The contrast enhancement in MRI stems from the presence of gadolinium ions which are entrapped in the organic shell, whereas the gold core provides a strong X-ray absorption. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in the lungs, spleen, and liver.

  4. Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications

    NASA Astrophysics Data System (ADS)

    Erogbogbo, Folarin; Chang, Ching-Wen; May, Jasmine L.; Liu, Liwei; Kumar, Rajiv; Law, Wing-Cheung; Ding, Hong; Yong, Ken Tye; Roy, Indrajit; Sheshadri, Mukund; Swihart, Mark T.; Prasad, Paras N.

    2012-08-01

    Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000 mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they

  5. Aqueous stability of gadolinium in surface waters receiving sewage treatment plant effluent, Boulder Creek, Colorado.

    PubMed

    Verplanck, Philip L; Taylor, Howard E; Nordstrom, D Kirk; Barber, Larry B

    2005-09-15

    In many surface waters, sewage treatment plant (STP) effluent is a substantial source of both regulated and unregulated contaminants, including a suite of complex organic compounds derived from household chemicals, pharmaceuticals, and industrial and medical byproducts. In addition, STP effluents in some urban areas have also been shown to have a positive gadolinium (Gd) anomaly in the rare earth element (REE) pattern, with the Gd derived from its use in medical facilities. REE concentrations are relatively easy to measure compared to many organic wastewater compounds and may provide a more widely utilized tracer of STP effluents. To evaluate whether sewage treatment plant-associated Gd is a useful tracer of treatment plant effluent, an investigation of the occurrence, fate, and transport of rare earth elements was undertaken. The rare earth element patterns of four of five STP effluents sampled display positive Gd anomalies. The one site that did not have a Gd anomaly serves a small community, population 1200, with no medical facilities. Biosolids from a large metropolitan STP are not enriched in Gd even though the effluent is, suggesting that a substantial fraction of Gd remains in the aqueous phase through routine treatment plant operation. To evaluate whether STP-derived Gd persists in the fluvial environment, a 14-km study reach downstream of an STP was sampled. Gadolinium anomalies were present at all five downstream sites, but the magnitude of the anomaly decreased. Effluent from STPs is a complex mixture of organic and inorganic constituents, and to better understand the chemical interactions and their effect on REEs, the aqueous speciation was modeled using comprehensive chemical analyses of water samples collected downstream of STP input. These calculations suggest that the REEs will likely remain dissolved because phosphate and carbonate complexes dominate over free REE ions. This study supports the application of Gd anomalies as a useful tracer of urban

  6. Aqueous stability of gadolinium in surface waters receiving sewage treatment plant effluent Boulder Creek, Colorado

    USGS Publications Warehouse

    Verplanck, P.L.; Taylor, Howard E.; Nordstrom, D. Kirk; Barber, L.B.

    2005-01-01

    In many surface waters, sewage treatment plant (STP) effluent is a substantial source of both regulated and unregulated contaminants, including a suite of complex organic compounds derived from household chemicals, pharmaceutical, and industrial and medical byproducts. In addition, STP effluents in some urban areas have also been shown to have a positive gadolinium (Gd) anomaly in the rare earth element (REE) pattern, with the Gd derived from its use in medical facilities. REE concentrations are relatively easy to measure compared to many organic wastewater compounds and may provide a more widely utilized tracer of STP effluents. To evaluate whether sewage treatment plant-associated Gd is a useful tracer of treatment plant effluent, an investigation of the occurrence, fate, and transport of rare earth elements was undertaken. The rare earth element patterns of four of five STP effluents sampled display positive Gd anomalies. The one site that did not have a Gd anomaly serves a small community, population 1200, with no medical facilities. Biosolids from a large metropolitan STP are not enriched in Gd even though the effluent is, suggesting that a substantial fraction of Gd remains in the aqueous phase through routine treatment plant operation. To evaluate whether STP-derived Gd persists in the fluvial environment, a 14-km study reach downstream of an STP was sampled. Gadolinium anomalies were present at all five downstream sites, but the magnitude of the anomaly decreased. Effluent from STPs is a complex mixture of organic and inorganic constituents, and to better understand the chemical interactions and their effect on REEs, the aqueous speciation was modeled using comprehensive chemical analyses of water samples collected downstream of STP input. These calculations suggest that the REEs will likely remain dissolved because phosphate and carbonate complexes dominate over free REE ions. This study supports the application of Gd anomalies as a useful tracer of urban

  7. Removal of gadolinium nitrate from heavy water

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilde, E.W.

    2000-03-22

    Work was conducted to develop a cost-effective process to purify 181 55-gallon drums containing spent heavy water moderator (D2O) contaminated with high concentrations of gadolinium nitrate, a chemical used as a neutron poison during former nuclear reactor operations at the Savannah River Site (SRS). These drums also contain low level radioactive contamination, including tritium, which complicates treatment options. Presently, the drums of degraded moderator are being stored on site. It was suggested that a process utilizing biological mechanisms could potentially lower the total cost of heavy water purification by allowing the use of smaller equipment with less product loss andmore » a reduction in the quantity of secondary waste materials produced by the current baseline process (ion exchange).« less

  8. Studies of MRI relaxivities of gadolinium-labeled dendrons

    NASA Astrophysics Data System (ADS)

    Pan, Hongmu; Daniel, Marie-Christine

    2011-05-01

    In cancer detection, imaging techniques have a great importance in early diagnosis. The more sensitive the imaging technique and the earlier the tumor can be detected. Contrast agents have the capability to increase the sensitivity in imaging techniques such as magnetic resonance imaging (MRI). Until now, gadolinium-based contrast agents are mainly used for MRI, and show good enhancement. But improvement is needed for detection of smaller tumors at the earliest stage possible. The dendrons complexed with Gd(DOTA) were synthesized and evaluated as a new MRI contrast agent. The longitudinal and transverse relaxation effects were tested and compared with commercial drug Magnevist, Gd(DTPA).

  9. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

    PubMed Central

    Pacurari, Maricica; Kafoury, Ramzi; Tchounwou, Paul B.; Ndebele, Kenneth

    2014-01-01

    The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS's role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors. PMID:24804145

  10. Insights into the use of gadolinium and gadolinium/boron-based agents in imaging-guided neutron capture therapy applications.

    PubMed

    Deagostino, Annamaria; Protti, Nicoletta; Alberti, Diego; Boggio, Paolo; Bortolussi, Silva; Altieri, Saverio; Crich, Simonetta Geninatti

    2016-05-01

    Gadolinium neutron capture therapy (Gd-NCT) is currently under development as an alternative approach for cancer therapy. All of the clinical experience to date with NCT is done with (10)B, known as boron neutron capture therapy (BNCT), a binary treatment combining neutron irradiation with the delivery of boron-containing compounds to tumors. Currently, the use of Gd for NCT has been getting more attention because of its highest neutron cross-section. Although Gd-NCT was first proposed many years ago, its development has suffered due to lack of appropriate tumor-selective Gd agents. This review aims to highlight the recent advances for the design, synthesis and biological testing of new Gd- and B-Gd-containing compounds with the task of finding the best systems able to improve the NCT clinical outcome.

  11. Impact of Cocoa Consumption on Inflammation Processes—A Critical Review of Randomized Controlled Trials

    PubMed Central

    Ellinger, Sabine; Stehle, Peter

    2016-01-01

    Background: Cocoa flavanols have strong anti-inflammatory properties in vitro. If these also occur in vivo, cocoa consumption may contribute to the prevention or treatment of diseases mediated by chronic inflammation. This critical review judged the evidence for such effects occurring after cocoa consumption. Methods: A literature search in Medline was performed for randomized controlled trials (RCTs) that investigated the effects of cocoa consumption on inflammatory biomarkers. Results: Thirty-three RCTs were included, along with 9 bolus and 24 regular consumption studies. Acute cocoa consumption decreased adhesion molecules and 4-series leukotrienes in serum, nuclear factor κB activation in leukocytes, and the expression of CD62P and CD11b on monocytes and neutrophils. In healthy subjects and in patients with cardiovascular diseases, most regular consumption trials did not find any changes except for a decreased number of endothelial microparticles, but several cellular and humoral inflammation markers decreased in patients suffering from type 2 diabetes and impaired fasting glucose. Conclusions: Little evidence exists that consumption of cocoa-rich food may reduce inflammation, probably by lowering the activation of monocytes and neutrophils. The efficacy seems to depend on the extent of the basal inflammatory burden. Further well-designed RCTs with inflammation as the primary outcome are needed, focusing on specific markers of leukocyte activation and considering endothelial microparticles as marker of vascular inflammation. PMID:27240397

  12. Impact of Cocoa Consumption on Inflammation Processes-A Critical Review of Randomized Controlled Trials.

    PubMed

    Ellinger, Sabine; Stehle, Peter

    2016-05-26

    Cocoa flavanols have strong anti-inflammatory properties in vitro. If these also occur in vivo, cocoa consumption may contribute to the prevention or treatment of diseases mediated by chronic inflammation. This critical review judged the evidence for such effects occurring after cocoa consumption. A literature search in Medline was performed for randomized controlled trials (RCTs) that investigated the effects of cocoa consumption on inflammatory biomarkers. Thirty-three RCTs were included, along with 9 bolus and 24 regular consumption studies. Acute cocoa consumption decreased adhesion molecules and 4-series leukotrienes in serum, nuclear factor κB activation in leukocytes, and the expression of CD62P and CD11b on monocytes and neutrophils. In healthy subjects and in patients with cardiovascular diseases, most regular consumption trials did not find any changes except for a decreased number of endothelial microparticles, but several cellular and humoral inflammation markers decreased in patients suffering from type 2 diabetes and impaired fasting glucose. Little evidence exists that consumption of cocoa-rich food may reduce inflammation, probably by lowering the activation of monocytes and neutrophils. The efficacy seems to depend on the extent of the basal inflammatory burden. Further well-designed RCTs with inflammation as the primary outcome are needed, focusing on specific markers of leukocyte activation and considering endothelial microparticles as marker of vascular inflammation.

  13. FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis

    PubMed Central

    Verbeke, Len; Mannaerts, Inge; Schierwagen, Robert; Govaere, Olivier; Klein, Sabine; Vander Elst, Ingrid; Windmolders, Petra; Farre, Ricard; Wenes, Mathias; Mazzone, Massimiliano; Nevens, Frederik; van Grunsven, Leo A.; Trebicka, Jonel; Laleman, Wim

    2016-01-01

    Hepatic inflammation drives hepatic stellate cells (HSC), resulting in liver fibrosis. The Farnesoid-X receptor (FXR) antagonizes inflammation through NF-κB inhibition. We investigated preventive and therapeutic effects of FXR agonist obeticholic acid (OCA) on hepatic inflammation and fibrosis in toxic cirrhotic rats. Cirrhosis was induced by thioacetamide (TAA) intoxication. OCA was given during or after intoxication with vehicle-treated rats as controls. At sacrifice, fibrosis, hemodynamic and biochemical parameters were assessed. HSC activation, cell turn-over, hepatic NF-κB activation, pro-inflammatory and pro-fibrotic cytokines were determined. The effect of OCA was further evaluated in isolated HSC, Kupffer cells, hepatocytes and liver sinusoidal endothelial cells (LSEC). OCA decreased hepatic inflammation and fibrogenesis during TAA-administration and reversed fibrosis in established cirrhosis. Portal pressure decreased through reduced intrahepatic vascular resistance. This was paralleled by decreased expression of pro-fibrotic cytokines (transforming growth-factor β, connective tissue growth factor, platelet-derived growth factor β-receptor) as well as markers of hepatic cell turn-over, by blunting effects of pro-inflammatory cytokines (e.g. monocyte chemo-attractant protein-1). In vitro, OCA inhibited both LSEC and Kupffer cell activation; while HSC remained unaffected. This related to NF-κB inhibition via up-regulated IκBα. In conclusion, OCA inhibits hepatic inflammation in toxic cirrhotic rats resulting in decreased HSC activation and fibrosis. PMID:27634375

  14. A combination of lactic acid bacteria regulates Escherichia coli infection and inflammation of the bovine endometrium.

    PubMed

    Genís, Sandra; Sánchez-Chardi, Alejandro; Bach, Àlex; Fàbregas, Francesc; Arís, Anna

    2017-01-01

    Uterine function in cattle is compromised by bacterial contamination and inflammation after calving. The objective of this study was to select a combination of lactic acid bacteria (LAB) to decrease endometrium inflammation and Escherichia coli infection. Primary endometrial epithelial cells were cultured in vitro to select the most favorable LAB combination modulating basal tissue inflammation and E. coli infection. Supernatants were obtained to determine expression of pro-inflammatory cytokines, and E. coli infection was evaluated after harvesting the tissue and plate counting. The selected LAB combination was tested in uterus explants to assess its capacity to modulate basal and acute inflammation (associated with E. coli infection). The combination of Lactobacillus rhamnosus, Pediococcus acidilactici, and Lactobacillus reuteri at a ratio of 25:25:2, respectively, reduced E. coli infection in vitro with (89.77%) or without basal tissue inflammation (95.10%) compared with single LAB strains. Lactic acid bacteria treatment reduced CXCL8 and IL1B expression 4.7- and 2.2-fold, respectively, under acute inflammation. Ex vivo, the tested LAB combination reduced acute inflammation under E. coli infection, decreasing IL-8, IL-1β, and IL-6 up to 2.2-, 2.5-, and 2.2-fold, respectively. In the total inflammation model, the LAB combination decreased IL-8 1.6-fold and IL-6 1.2-fold. Ultrastructural evaluation of the tissue suggested no direct interaction between the LAB and E. coli, although pathological effects of E. coli in endometrial cells were greatly diminished or even reversed by the LAB combination. This study shows the promising potential of LAB probiotics for therapeutic use against endometrial inflammation and infection. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.

    A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially-grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high pressure area on the order of a few tens of seconds. This device is then used to scanmore » the phase diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in the experiment the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp→αSm transition proceeds in discontinuous steps at points along the expected phase boundary. Additionally, the unit cell volumes of each phase deviate from the expected thermal expansion behavior just before each transition is observed from the diffraction data. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0 - 10 GPa and 300 - 650 K.« less

  16. Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

    PubMed Central

    Gaffney, K.; Cookson, J.; Blades, S.; Coumbe, A.; Blake, D.

    1998-01-01

    OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

 Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity PMID:9640130

  17. High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

    DOE PAGES

    Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.; ...

    2016-04-07

    A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially-grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high pressure area on the order of a few tens of seconds. This device is then used to scanmore » the phase diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in the experiment the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp→αSm transition proceeds in discontinuous steps at points along the expected phase boundary. Additionally, the unit cell volumes of each phase deviate from the expected thermal expansion behavior just before each transition is observed from the diffraction data. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0 - 10 GPa and 300 - 650 K.« less

  18. Engineered gadolinium-doped carbon dots for magnetic resonance imaging-guided radiotherapy of tumors.

    PubMed

    Du, Fengyi; Zhang, Lirong; Zhang, Li; Zhang, Miaomiao; Gong, Aihua; Tan, Youwen; Miao, Jiawen; Gong, Yuhua; Sun, Mingzhong; Ju, Huixiang; Wu, Chaoyang; Zou, Shenqiang

    2017-03-01

    The effectiveness of radiotherapy can decrease due to inaccurate positioning of machinery and inherent radioresistance of tumors. To address this issue, we present a novel theranostic nanoplatform based on gadolinium-doped carbon dots (Gd-doped CDs) designed specifically for magnetic resonance imaging (MRI)-guided radiotherapy of tumors. The Gd-doped CDs (∼18 nm) with dispersibility in water and stable photoluminescence were synthesized via a one-step hydrothermal approach. After tail vein injection of the Gd-doped CDs, they exhibited a relatively long circulation time (∼6 h), enabled efficient passive tumor targeting. Gd-doped CDs accumulate in the kidney and could be cleared out of the body from bladder. Importantly, they exhibited favorable biocompatibility with excellent performance in longitudinal relaxivity rate (r 1 ) of 6.45 mM -1 S -1 and radiosensitization enhancements. These results show that Gd-doped CDs are excellent T 1 contrast agents and radiosensitizers, possessing great promise for MRI-guided radiotherapy of tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy.

    PubMed

    Mi, Peng; Dewi, Novriana; Yanagie, Hironobu; Kokuryo, Daisuke; Suzuki, Minoru; Sakurai, Yoshinori; Li, Yanmin; Aoki, Ichio; Ono, Koji; Takahashi, Hiroyuki; Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2015-06-23

    Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.

  20. Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

    PubMed

    De Stasio, Gelsomina; Rajesh, Deepika; Casalbore, Patrizia; Daniels, Matthew J; Erhardt, Robert J; Frazer, Bradley H; Wiese, Lisa M; Richter, Katherine L; Sonderegger, Brandon R; Gilbert, Benjamin; Schaub, Sebastien; Cannara, Rachel J; Crawford, John F; Gilles, Mary K; Tyliszczak, Tolek; Fowler, John F; Larocca, Luigi M; Howard, Steven P; Mercanti, Delio; Mehta, Minesh P; Pallini, Roberto

    2005-06-01

    Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents. Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA. In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA. Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

  1. Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

    PubMed Central

    Ranga, Anju; Agarwal, Yatish; Garg, Kanika J

    2017-01-01

    Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs) appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles. PMID:28744073

  2. Reaction of gadolinium chelates with ozone and hydroxyl radicals.

    PubMed

    Cyris, Maike; Knolle, Wolfgang; Richard, Jessica; Dopp, Elke; von Sonntag, Clemens; Schmidt, Torsten C

    2013-09-03

    Gadolinium chelates are used in increasing amounts as contrast agents in magnetic resonance imaging, and their fate in wastewater treatment has recently become the focus of research. Oxidative processes, in particular the application of ozone, are currently discussed or even implemented for advanced wastewater treatment. However, reactions of the gadolinium chelates with ozone are not yet characterized. In this study, therefore, rate constants with ozone were determined for the three commonly used chelates Gd-DTPA, Gd-DTPA-BMA, and Gd-BT-DO3A, which were found to be 4.8 ± 0.88, 46 ± 2.5, and 24 ± 1.5 M(-1) s(-1), respectively. These low rate constants indicate that a direct reaction with ozone in wastewater is negligible. However, application of ozone in wastewater leads to substantial yields of (•)OH. Different methods have been applied and compared for determination of k((•)OH+Gd chelate). From rate constants determined by pulse radiolysis experiments (k((•)OH+Gd-DTPA) = 2.6 ± 0.2 × 10(9) M(-1) s(-1), k((•)OH+Gd-DTPA-BMA) = 1.9 ± 0.7 × 10(9) M(-1) s(-1), k((•)OH+Gd-BT-DO3A) = 4.3 ± 0.2 × 10(9) M(-1) s(-1)), it is concluded that a reaction in wastewater via (•)OH radicals is feasible. Toxicity has been tested for educt and product mixtures of both reactions. Cytotoxicity (MTT test) and genotoxicity (micronuclei assay) were not detectable.

  3. Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging.

    PubMed

    Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Kobeiter, Hicham; Breil, Stephane; Rahmouni, Alain

    2003-12-01

    To determine the patterns of dynamic enhancement of normal spinal bone marrow in adults at gadolinium-enhanced magnetic resonance (MR) imaging and the changes that occur with aging. Dynamic contrast material-enhanced MR imaging of the thoracolumbar spine was performed in 71 patients. The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from bone marrow enhancement time curves (ETCs). The bone marrow signal intensity on T1-weighted spin-echo MR images was qualitatively classified into three grade categories. Quantitative ETC values were correlated with patient age and bone marrow fat content grade. Statistical analysis included mean t test comparison, analysis of variance, and regression analysis of the correlations between age and quantitative MR parameters. Emax, slope, and washout varied widely among the patients. Emax values were obtained within 1 minute after contrast material injection and ranged from 0% to 430%. Emax values were significantly higher in patients younger than 40 years than in those aged 40 years or older (P <.001). These values decreased with increasing age in a logarithmic relationship (r = 0.71). Emax values decreased as fat content increased, but some overlap among the fat content grades was noted. Analysis of variance revealed that Emax was significantly related to age (younger than 40 years vs 40 years or older) (P <.001) and fat content grade (P <.001) but not significantly related to sex. Dynamic contrast-enhanced MR imaging patterns of normal spinal bone marrow are dependent mainly on patient age and fat content.

  4. Polycystic ovary syndrome and chronic inflammation: pharmacotherapeutic implications.

    PubMed

    Sirmans, Susan Maureen; Weidman-Evans, Emily; Everton, Victoria; Thompson, Daniel

    2012-03-01

    To examine the relationship between polycystic ovary syndrome (PCOS), cardiovascular risk factors, cardiovascular disease (CVD), and chronic inflammation and analyze data regarding pharmacologic therapies that are recommended to reduce CVD risk in PCOS and the impact of those therapies on chronic inflammation. A search of MEDLINE (1950-October 2011) was conducted to identify clinical studies pertaining to the identification and treatment of CVD and chronic low-grade inflammation in PCOS. Search terms included polycystic ovary syndrome, cardiovascular disease, inflammation, metformin, thiazolidinedione, and statin. Bibliographies of these studies and review articles were also examined. English-language clinical studies evaluating the effect of metformin, thiazolidinediones, and statins on inflammatory markers, endothelial function, adhesion molecules, fibrinolysis, cytokines, and adipokines in PCOS were included. Women with PCOS have an increased prevalence of many cardiovascular risk factors including obesity, android fat distribution, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, hypertension, and metabolic syndrome. Markers of chronic low-grade inflammation, which are associated with an increased risk of CVD, are also elevated in PCOS. Clinical guidelines recommend the use of insulin sensitizers and statins to prevent CVD in some patients with PCOS. Current literature indicates that each of these medication classes has beneficial effects on inflammation, as well. Although there are currently no studies to determine whether these treatments decrease CVD in PCOS, it can be hypothesized that drugs impacting chronic inflammation may reduce cardiovascular risk. Some studies show that metformin, thiazolidinediones, and statins have beneficial effects on inflammatory markers in PCOS; however, the data are inconsistent. There is insufficient information to recommend any pharmacologic therapies for their antiinflammatory effects in PCOS in the

  5. Periodontal treatment reduces chronic systemic inflammation in peritoneal dialysis patients.

    PubMed

    Siribamrungwong, Monchai; Yothasamutr, Kasemsuk; Puangpanngam, Kutchaporn

    2014-06-01

    Chronic systemic inflammation, a non traditional risk factor of cardiovascular diseases, is associated with increasing mortality in chronic kidney disease, especially peritoneal dialysis patients. Periodontitis is a potential treatable source of systemic inflammation in peritoneal dialysis patients. Clinical periodontal status was evaluated in 32 stable chronic peritoneal dialysis patients by plaque index and periodontal disease index. Hematologic, blood chemical, nutritional, and dialysis-related data as well as highly sensitive C-reactive protein were analyzed before and after periodontal treatment. At baseline, high sensitive C-reactive protein positively correlated with the clinical periodontal status (plaque index; r = 0.57, P < 0.01, periodontal disease index; r = 0.56, P < 0.01). After completion of periodontal therapy, clinical periodontal indexes were significantly lower and high sensitivity C-reactive protein significantly decreased from 2.93 to 2.21 mg/L. Moreover, blood urea nitrogen increased from 47.33 to 51.8 mg/dL, reflecting nutritional status improvement. Erythropoietin dosage requirement decreased from 8000 to 6000 units/week while hemoglobin level was stable. Periodontitis is an important source of chronic systemic inflammation in peritoneal dialysis patients. Treatment of periodontal diseases can improve systemic inflammation, nutritional status and erythropoietin responsiveness in peritoneal dialysis patients. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

  6. Dramatic impact of the giant local magnetic fields on spin-dependent recombination processes in gadolinium based garnets

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Romanov, N. G., E-mail: nikolai.romanov@mail.ioffe.ru; Tolmachev, D. O.; Gurin, A. S.

    2015-06-29

    A giant magnetic field effect on spin-dependent recombination of the radiation-induced defects has been found in cerium doped gadolinium based garnet crystals and ceramics, promising materials for scintillator applications. A sharp and strong increase in the afterglow intensity stimulated by external magnetic field and an evidence of the magnetic field memory have been discovered. The effect was ascribed to huge Gd-induced internal magnetic fields, which suppress the recombination, and cross-relaxation with Gd{sup 3+} ions leading to reorientation of the spins of the electron and hole centers. Thus, the spin system of radiation-induced defects in gadolinium garnet based scintillator materials wasmore » shown to accumulate significant energy which can be released in external magnetic fields.« less

  7. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation.

    PubMed

    Hermouet, Sylvie; Bigot-Corbel, Edith; Gardie, Betty

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation.

  8. Pathogenesis of Myeloproliferative Neoplasms: Role and Mechanisms of Chronic Inflammation

    PubMed Central

    Bigot-Corbel, Edith; Gardie, Betty

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are a heterogeneous group of clonal diseases characterized by the excessive and chronic production of mature cells from one or several of the myeloid lineages. Recent advances in the biology of MPNs have greatly facilitated their molecular diagnosis since most patients present with mutation(s) in the JAK2, MPL, or CALR genes. Yet the roles played by these mutations in the pathogenesis and main complications of the different subtypes of MPNs are not fully elucidated. Importantly, chronic inflammation has long been associated with MPN disease and some of the symptoms and complications can be linked to inflammation. Moreover, the JAK inhibitor clinical trials showed that the reduction of symptoms linked to inflammation was beneficial to patients even in the absence of significant decrease in the JAK2-V617F mutant load. These observations suggested that part of the inflammation observed in patients with JAK2-mutated MPNs may not be the consequence of JAK2 mutation. The aim of this paper is to review the different aspects of inflammation in MPNs, the molecular mechanisms involved, the role of specific genetic defects, and the evidence that increased production of certain cytokines depends or not on MPN-associated mutations, and to discuss possible nongenetic causes of inflammation. PMID:26538820

  9. Gadolinium enhanced cardiovascular magnetic resonance in Anderson-Fabry disease. Evidence for a disease specific abnormality of the myocardial interstitium.

    PubMed

    Moon, James C C; Sachdev, Bhavesh; Elkington, Andrew G; McKenna, William J; Mehta, Atul; Pennell, Dudley J; Leed, Philip J; Elliott, Perry M

    2003-12-01

    Anderson-Fabry Disease (AFD), an X-linked disorder of sphingolipid metabolism, is a cause of idiopathic left ventricular hypertrophy but the mechanism of hypertrophy is poorly understood. Gadolinium enhanced cardiovascular magnetic resonance can detect focal myocardial fibrosis. We hypothesised that hyperenhancement would be present in AFD. Eighteen males (mean 43+/-14 years) and eight female heterozygotes (mean 48+/-12 years) with AFD underwent cine and late gadolinium cardiovascular magnetic resonance. Nine male (50%) had myocardial hyperenhancement ranging from 3.4% to 20.6% (mean 7.7+/-5.7%) of total myocardium; in males, percentage hyperenhancement related to LV mass index (r=0.78, P=0.0002) but not to ejection fraction or left ventricular volumes. Lesser hyperenhancement was also found in four (50%) heterozygous females (mean 4.6%). In 12 (92%) patients with abnormal gadolinium uptake, hyperenhancement occurred in the basal infero-lateral wall where, unlike myocardial infarction, it was not sub-endocardial. In two male patients with severe LVH (left ventricular hypertrophy) and systolic impairment there was additional hyperenhancement in other myocardial segments. These observations suggests that myocardial fibrosis occurs in AFD and may contribute to the hypertrophy and the natural history of the disease.

  10. FDP-E induces adipocyte inflammation and suppresses insulin-stimulated glucose disposal: effect of inflammation and obesity on fibrinogen Bβ mRNA.

    PubMed

    Kang, Minsung; Vaughan, Roger A; Paton, Chad M

    2015-12-01

    Obesity is associated with increased fibrinogen production and fibrin formation, which produces fibrin degradation products (FDP-E and FDP-D). Fibrin and FDPs both contribute to inflammation, which would be expected to suppress glucose uptake and insulin signaling in adipose tissue, yet the effect of FDP-E and FDP-D on adipocyte function and glucose disposal is completely unknown. We tested the effects of FDPs on inflammation in 3T3-L1 adipocytes and primary macrophages and adipocyte glucose uptake in vitro. High-fat-fed mice increased hepatic fibrinogen mRNA expression ninefold over chow-fed mice, with concomitant increases in plasma fibrinogen protein levels. Obese mice also displayed increased fibrinogen content of epididymal fat pads. We treated cultured 3T3-L1 adipocytes and primary macrophages with FDP-E, FDP-D, or fibrinogen degradation products (FgnDP-E). FDP-D and FgnDP-E had no effect on inflammation or glucose uptake. Cytokine mRNA expression in RAW264.7 macrophage-like cells and 3T3-L1 adipocytes treated with FDP-E induced inflammation with maximal effects at 100 nM and 6 h. Insulin-stimulated 2-deoxy-d-[(3)H]glucose uptake was reduced by 71% in adipocytes treated with FDP-E. FDP-E, but not FDP-D or FgnDP-E, induces inflammation in macrophages and adipocytes and decreases glucose uptake in vitro. FDP-E may contribute toward obesity-associated acute inflammation and glucose intolerance, although its chronic role in obesity remains to be elucidated. Copyright © 2015 the American Physiological Society.

  11. Electrical and Structural Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance Imaging.

    PubMed

    Andrews, Christopher M; Srinivasan, Neil T; Rosmini, Stefania; Bulluck, Heerajnarain; Orini, Michele; Jenkins, Sharon; Pantazis, Antonis; McKenna, William J; Moon, James C; Lambiase, Pier D; Rudy, Yoram

    2017-07-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a significant cause of sudden cardiac death in the young. Improved noninvasive assessment of ARVC and better understanding of the disease substrate are important for improving patient outcomes. We studied 20 genotyped ARVC patients with a broad spectrum of disease using electrocardiographic imaging (a method for noninvasive cardiac electrophysiology mapping) and advanced late gadolinium enhancement cardiac magnetic resonance scar imaging. Compared with 20 healthy controls, ARVC patients had longer ventricular activation duration (median, 52 versus 42 ms; P =0.007) and prolonged mean epicardial activation-recovery intervals (a surrogate for local action potential duration; median, 275 versus 241 ms; P =0.014). In these patients, we observed abnormal and varied epicardial activation breakthrough locations and regions of nonuniform conduction and fractionated electrograms. Nonuniform conduction and fractionated electrograms were present in the early concealed phase of ARVC. Electrophysiological abnormalities colocalized with late gadolinium enhancement scar, indicating a relationship with structural disease. Premature ventricular contractions were common in ARVC patients with variable initiation sites in both ventricles. Premature ventricular contraction rate increased with exercise, and within anatomic segments, it correlated with prolonged repolarization, electric markers of scar, and late gadolinium enhancement (all P <0.001). Electrocardiographic imaging reveals electrophysiological substrate properties that differ in ARVC patients compared with healthy controls. A novel mechanistic finding is the presence of repolarization abnormalities in regions where ventricular ectopy originates. The results suggest a potential role for electrocardiographic imaging and late gadolinium enhancement in early diagnosis and noninvasive follow-up of ARVC patients. © 2017 American Heart Association, Inc.

  12. Resveratrol Increases Osteoblast Differentiation In Vitro Independently of Inflammation.

    PubMed

    Ornstrup, Marie Juul; Harsløf, Torben; Sørensen, Lotte; Stenkjær, Liselotte; Langdahl, Bente Lomholt; Pedersen, Steen Bønløkke

    2016-08-01

    Low-grade inflammation negatively affects bone. Resveratrol is a natural compound proven to possess both anti-inflammatory and bone protective properties. However, it is uncertain if the bone effects are mediated though anti-inflammatory effects. Firstly, we investigated if resveratrol affects proliferation and differentiation of human bone marrow-derived mesenchymal stem cells. Secondly, we investigated if inflammation negatively affects proliferation and differentiation, and if resveratrol counteracts this through anti-inflammatory effects. Mesenchymal stem cells were obtained from bone marrow aspiration in 13 healthy individuals and cultured towards the osteoblast cell lineage. The cells were stimulated with resveratrol, lipopolysaccharide (LPS), LPS + resveratrol, or vehicle (control) for 21 days. Compared to control, resveratrol decreased cell number by 35 % (p < 0.05) and induced differentiation (a 3-fold increase in alkaline phosphatase (p < 0.002), while P1NP and OPG showed similar trends). LPS induced inflammation with a 44-fold increase in interleukin-6 (p < 0.05) and an extremely prominent increase in interleukin-8 production (p < 0.05) relative to control. In addition, LPS increased cell count (p < 0.05) and decreased differentiation (a reduction in P1NP production (p < 0.02)). Co-stimulation with LPS + resveratrol did not reduce interleukin-6 or interleukin-8, but nonetheless, cell count was reduced (p < 0.05) and alkaline phosphatase, P1NP, and OPG increased (p < 0.05 for all). Thus, resveratrol stimulates osteoblast differentiation independently of inflammation.

  13. Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation

    PubMed Central

    Gyires, Klára; Zádori, Zoltán S.

    2016-01-01

    Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids representing potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation. Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gastric acid secretion and gastric motor activity, and decreases the formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central mechanisms. Similarly, indirect activation of cannabinoid receptors through elevation of endocannabinoid levels by globally acting or peripherally restricted inhibitors of their metabolizing enzymes (FAAH, MAGL) or by inhibitors of their cellular uptake reduces the gastric mucosal lesions induced by NSAIDs in a CB1 receptor-dependent fashion. Dual inhibition of FAAH and cyclooxygenase enzymes induces protection against both NSAID-induced gastrointestinal damage and intestinal inflammation. Moreover, in intestinal inflammation direct or indirect activation of CB1 and CB2 receptors exerts also multiple beneficial effects. Namely, activation of both CB receptors was shown to ameliorate intestinal inflammation in various murine colitis models, to decrease visceral hypersensitivity and abdominal pain, as well as to reduce colitis-associated hypermotility and diarrhea. In addition, CB1 receptors suppress secretory processes and also modulate intestinal epithelial barrier functions. Thus, experimental data suggest that the endocannabinoid system represents a promising target in the treatment of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies. PMID:26935536

  14. Switching of the polarization of ferroelectric-ferroelastic gadolinium molybdate in a magnetic field

    NASA Astrophysics Data System (ADS)

    Yakushkin, E. D.

    2017-10-01

    A change in the character of the electric switching of polydomain ferroelectric-ferroelastic gadolinium molybdate in an external magnetic field has been detected. This change has been attributed to a magnetically stimulated increase in the pinning of domain walls. Under certain conditions, the loop of switchable polarization is degenerated into an ellipse characteristic of a linear insulator with leakage current.

  15. Transgenic up-regulation of Claudin-6 decreases fine diesel particulate matter (DPM)-induced pulmonary inflammation.

    PubMed

    Lewis, Joshua B; Bodine, Jared S; Gassman, Jason R; Muñoz, Samuel Arce; Milner, Dallin C; Dunaway, Todd M; Egbert, Kaleb M; Monson, Troy D; Broberg, Dallin S; Arroyo, Juan A; Reynolds, Paul R

    2018-04-25

    Claudin-6 (Cldn6) is a tetraspanin transmembrane protein that contributes to tight junctional complexes and has been implicated in the maintenance of lung epithelial barriers. In the present study, we tested the hypothesis that genetic up-regulation of Cldn-6 influences inflammation in mice exposed to short-term environmental diesel particulate matter (DPM). Mice were subjected to ten exposures of nebulized DPM (PM2.5) over a period of 20 days via a nose-only inhalation system (Scireq, Montreal, Canada). Using real-time RT-PCR, we discovered that the Cldn6 gene was up-regulated in control mice exposed to DPM and in lung-specific transgenic mice that up-regulate Cldn-6 (Cldn-6 TG). Interestingly, DPM did not further enhance Cldn-6 expression in Cldn-6 TG mice. DPM caused increased cell diapedesis into bronchoalveolar lavage fluid (BALF) from control mice; however, Cldn-6 TG mice had less total cells and PMNs in BALF following DPM exposure. Because Cldn-6 TG mice had diminished cell diapedesis, other inflammatory intermediates were screened to characterize the impact of increased Cldn-6 on inflammatory signaling. Cytokines that mediate inflammatory responses including TNF-α and IL-1β were differentially regulated in Cldn6 TG mice and controls following DPM exposure. These results demonstrate that epithelial barriers organized by Cldn-6 mediate, at least in part, diesel-induced inflammation. Further work may show that Cldn-6 is a key target in understanding pulmonary epithelial gateways exacerbated by environmental pollution.

  16. Neurosarcoidosis--demonstration of meningeal disease by gadolinium enhanced magnetic resonance imaging.

    PubMed Central

    Khaw, K T; Manji, H; Britton, J; Schon, F

    1991-01-01

    Arriving at a firm diagnosis of neurosarcoidosis continues to pose serious problems, particularly when evidence of granulomatous disease outside the nervous system is lacking. The commonest mode of presentation of neurosarcoidosis is with cranial nerve palsies. Two cases of presumed neurosarcoidosis with cranial nerve palsies showed clear evidence of focal meningeal disease on gadolinium-DTPA enhanced MRI brain scans. Although not specific for sarcoidosis, this technique may be very useful in aiding the diagnosis in suspected cases. Images PMID:1880510

  17. Gadolinium-modulated 19F signals from Perfluorocarbon Nanoparticles as a New Strategy for Molecular Imaging

    PubMed Central

    Neubauer, Anne M.; Myerson, Jacob; Caruthers, Shelton D.; Hockett, Franklin D.; Winter, Patrick M.; Chen, Junjie; Gaffney, Patrick J.; Robertson, J. David; Lanza, Gregory M.; Wickline, Samuel A.

    2008-01-01

    Recent advances in the design of fluorinated nanoparticles for magnetic resonance molecular imaging have enabled specific detection of 19F nuclei, providing unique and quantifiable spectral signatures. However, a pressing need for signal enhancement exists because the total 19F in imaging voxels is often limited. By directly incorporating a relaxation agent (gadolinium) into the lipid monolayer that surrounds the perfluorocarbon, a marked augmentation of the 19F signal from 200nm nanoparticles was achieved. This design increases the magnetic relaxation rate of the 19F nuclei 4-fold at 1.5 T and effects a 125% increase in signal, an effect which is maintained when they are targeted to human plasma clots. By varying the surface concentration of gadolinium, the relaxation effect can be quantitatively modulated to tailor particle properties. This novel strategy dramatically improves the sensitivity and range of 19F MRI/MRS and forms the basis for designing contrast agents capable of sensing their surface chemistry. PMID:18956457

  18. Effect of high-dose intravenous vitamin C on inflammation in cancer patients.

    PubMed

    Mikirova, Nina; Casciari, Joseph; Rogers, Andrea; Taylor, Paul

    2012-09-11

    An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer.Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels.Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods.CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment.There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein.Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that

  19. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    PubMed Central

    2012-01-01

    Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels. In

  20. Right ventricular stress-induced perfusion defects and late gadolinium enhancement in coronary artery disease.

    PubMed

    Milks, Michael Wesley; Upadhya, Bharathi; Hall, Michael E; Vasu, Sujethra; Hundley, William Gregory; Stacey, Richard Brandon

    2015-01-01

    The assessment of right ventricular (RV) perfusion defects has remained challenging during vasodilator stress perfusion with cardiovascular magnetic resonance (CMR). The significance of RV signal abnormalities during vasodilator stress perfusion and late gadolinium-enhanced CMR is yet uncertain. Among 61 individuals who underwent adenosine CMR stress testing before cardiac catheterization, we assessed the severity of coronary artery stenoses, mortality, the presence of stress and rest perfusion defects, as well as the presence of late gadolinium enhancement (LGE). Right ventricular stress-induced perfusion defects were positively associated with left anterior descending artery and proximal right coronary artery stenoses but were negatively associated with left circumflex artery stenoses. The presence of RVLGE was associated with mortality, but 77% of those with RVLGE also had left ventricular LGE. Proximal right coronary artery and left anterior descending artery stenoses are positively associated, whereas left circumflex artery stenoses are negatively associated with RV stress-induced perfusion defects. Right ventricular LGE was associated with mortality, but further study is needed to determine whether this is independent of left ventricular LGE.

  1. Effect of solid-phase amorphization on the spectral characteristics of europium-doped gadolinium molybdate

    NASA Astrophysics Data System (ADS)

    Shmurak, S. Z.; Kiselev, A. P.; Kurmasheva, D. M.; Red'Kin, B. S.; Sinitsyn, V. V.

    2010-05-01

    A method is proposed for detecting spectral characteristics of optically inactive molybdates of rare-earth elements by their doping with rare-earth ions whose luminescence lies in the transparency region of all structural modifications of the sample. Gadolinium molybdate is chosen as the object of investigations, while europium ions are used as an optically active and structurally sensitive admixture. It is shown that after the action of a high pressure under which gadolinium molybdate passes to the amorphous state, the spectral characteristics of Gd1.99Eu0.01(MoO4)3 (GMO:Eu) change radically; namely, considerable line broadening is observed in the luminescence spectra and the luminescence excitation spectra, while the long-wave threshold of optical absorption is shifted considerably (by approximately 1.1 eV) towards lower energies. It is found that by changing the structural state of GMO:Eu by solid-state amorphization followed by annealing, the spectral characteristics of the sample can be purposefully changed. This is extremely important for solving the urgent problem of designing high-efficiency light-emitting diodes producing “white” light.

  2. Cytochrome P4502E1 inhibitor, chlormethiazole, decreases lipopolysaccharide-induced inflammation in rat Kupffer cells with ethanol treatment

    USDA-ARS?s Scientific Manuscript database

    To investigate the role of Cytochrome P4502E1 in sensitizing Kupffer cells to lipopolysaccharide (LPS)-mediated inflammation after ethanol induction. Sprague-Dawley rats were fed a liquid ethanol diet, control diet or ethanol diet supplemented with CYP2E1 inhibitor, chlormethiazole (CMZ), for 4'week...

  3. hMSCs suppress neutrophil-dominant airway inflammation in a murine model of asthma

    PubMed Central

    Hong, Gyong Hwa; Kwon, Hyouk-Soo; Lee, Kyoung Young; Ha, Eun Hee; Moon, Keun-Ai; Kim, Seong Who; Oh, Wonil; Kim, Tae-Bum; Moon, Hee-Bom; Cho, You Sook

    2017-01-01

    Although chronic eosinophilic inflammation is a common feature in patients with asthma, some patients have neutrophil-dominant inflammation, which is known to be associated with severe asthma.Human mesenchymal stem cells (hMSCs) have shown promise in treating various refractory immunological diseases. Thus, hMSCs may represent an alternative therapeutic option for asthma patients with neutrophil-dominant inflammation, in whom current treatments are ineffective. BALB/c mice exposed to ovalbumin and polyinosinic:polycytidylic acid (Poly I:C) to induce neutrophilic airway inflammation were systemically treated with hMSCs to examine whether the hMSCs can modulate neutrophilic airway inflammation. In addition, cytokine production was evaluated in co-cultures of hMSCs with either anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asthmatic patients or cells of the human bronchial epithelial cell line BEAS-2B to assess the response to hMSC treatment. The total number of immune cells in bronchoalveolar lavage fluid (BALF) showed a dramatic decrease in hMSC-treated asthmatic mice, and, in particular, neutrophilic infiltration was significantly attenuated. This phenomenon was accompanied by reduced CXCL15 production in the BALF. BEAS-2B cells co-cultured with hMSCs showed reduced secretion of IL-8. Moreover, decreased secretion of IL-4, IL-13 and IFN-γ was observed when human PBMCs were cultured with hMSCs, whereas IL-10 production was greatly enhanced. Our data imply that hMSCs may have a role in reducing neutrophilic airway inflammation by downregulating neutrophil chemokine production and modulating T-cell responses. PMID:28127050

  4. Graphene oxide-gadolinium (III) oxide nanoparticle composite: a novel MR contrast agent with high longitudinal and transverse relaxivity

    NASA Astrophysics Data System (ADS)

    Venkatesha, N.; Poojar, Pavan; Geethanath, Sairam; Srivastava, Chandan

    2014-12-01

    Production of bio-compatible contrast agent materials to enhance the sensitivity of the magnetic resonance imaging (MRI) technique is a highly active area in MRI related research. This work illustrates the potential of a new material: graphene oxide-gadolinium (III) oxide nanoparticle (GO-Gd2O3) composite in yielding both transverse (16.3 mM-1 s-1) and longitudinal relaxivity (40 mM-1 s-1) values which are significantly higher than the proton relaxivity values achieved using the gadolinium based contrast agents currently used in MRI. Such high proton relaxivity values can facilitate low dosage of GO-Gd2O3 composite for obtaining both T1 and T2 weighted high signal-to-noise ratio images in MRI.

  5. A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part II: gadolinium neutron capture therapy models and therapeutic effects.

    PubMed

    Wangerin, K; Culbertson, C N; Jevremovic, T

    2005-08-01

    The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for gadolinium neutron capture therapy (GdNCT) related modeling. The validity of COG NCT model has been established for this model, and here the calculation was extended to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating brain cancers. The computational results were compared with the widely used MCNP code. The differences between the COG and MCNP predictions were generally small and suggest that the COG code can be applied to similar research problems in NCT. Results for this study also showed that a concentration of 100 ppm gadolinium in the tumor was most beneficial when using an epithermal neutron beam.

  6. Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

    Treesearch

    Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

    2009-01-01

    Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

  7. High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

    PubMed Central

    Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

    2017-01-01

    Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging. PMID:28091590

  8. High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

    NASA Astrophysics Data System (ADS)

    Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

    2017-01-01

    Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging.

  9. Use of gadolinium chloride as a contrast agent for imaging spruce knots by magnetic resonance

    Treesearch

    Thomas L. Eberhardt; Chi-Leung So; Amy H. Herlihy; Po-Wah So

    2006-01-01

    Treatments of knot-containing spruce wood blocks with a paramagnetic salt, gadolinium (III) chloride, in combination with solvent pretreatments, were evaluated as strategies to enhance the visualization of wood features by magnetic resonance imaging (MRI). Initial experiments with clear wood and excised knot samples showed differences in moisture uptake after...

  10. Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults

    PubMed Central

    Mave, Vidya; Erlandson, Kristine M.; Gupte, Nikhil; Balagopal, Ashwin; Asmuth, David M.; Campbell, Thomas B.; Smeaton, Laura; Kumarasamy, Nagalingeswaran; Hakim, James; Santos, Breno; Riviere, Cynthia; Hosseinipour, Mina C.; Sugandhavesa, Patcharaphan; Infante, Rosa; Pillay, Sandy; Cardoso, Sandra W.; Tripathy, Srikanth; Mwelase, Noluthando; Berendes, Sima; Andrade, Bruno B.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

    2016-01-01

    Background. Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation during human immunodeficiency virus infection is unknown. Methods. Among a random virologically suppressed participants of the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings trial, inflammatory markers were measured at weeks 0, 24, and 48 after antiretroviral therapy (ART) initiation. Associations between both baseline and change in body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and changes in inflammation markers were assessed using random effects models. Results. Of 246 participants, 27% were overweight/obese (BMI, ≥ 25), and 8% were underweight (BMI < 18.5) at baseline. After 48 weeks, 37% were overweight/obese, and 3% were underweight. While level of many inflammatory markers decreased 48 weeks after ART initiation in the overall group, the decrease in C-reactive protein (CRP) level was smaller in overweight/obese participants (P = .01), and the decreases in both CRP (P = .01) and interleukin 18 (P = .02) levels were smaller in underweight participants. Each 1-unit gain in BMI among overweight/obese participants was associated with a 0.02-log10 increase in soluble CD14 level (P = .05), while each 1-unit BMI gain among underweight participants was associated with a 9.32-mg/L decrease in CRP level (P = .001). Conclusions. Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation. PMID:26962236

  11. Effects of blueberries on inflammation, motor performance and cognitive function

    USDA-ARS?s Scientific Manuscript database

    Motor and cognitive function decrease with age, to include deficits in balance, coordination, gait, processing speed, executive function, memory, and spatial learning. These functional declines may be caused by long term increases in and susceptibility to oxidative stress and inflammation. Research ...

  12. Regulation of diet-induced adipose tissue and systemic inflammation by salicylates and pioglitazone.

    PubMed

    Kim, Myung-Sunny; Yamamoto, Yasuhiko; Kim, Kyungjin; Kamei, Nozomu; Shimada, Takeshi; Liu, Libin; Moore, Kristin; Woo, Ju Rang; Shoelson, Steven E; Lee, Jongsoon

    2013-01-01

    It is increasingly accepted that chronic inflammation participates in obesity-induced insulin resistance and type 2 diabetes (T2D). Salicylates and thiazolidinediones (TZDs) both have anti-inflammatory and anti-hyperglycemic properties. The present study compared the effects of these drugs on obesity-induced inflammation in adipose tissue (AT) and AT macrophages (ATMs), as well as the metabolic and immunological phenotypes of the animal models. Both drugs improved high fat diet (HFD)-induced insulin resistance. However, salicylates did not affect AT and ATM inflammation, whereas Pioglitazone improved these parameters. Interestingly, HFD and the drug treatments all modulated systemic inflammation as assessed by changes in circulating immune cell numbers and activation states. HFD increased the numbers of circulating white blood cells, neutrophils, and a pro-inflammatory monocyte subpopulation (Ly6C(hi)), whereas salicylates and Pioglitazone normalized these cell numbers. The drug treatments also decreased circulating lymphocyte numbers. These data suggest that obesity induces systemic inflammation by regulating circulating immune cell phenotypes and that anti-diabetic interventions suppress systemic inflammation by normalizing circulating immune phenotypes.

  13. Nur77 deficiency leads to systemic inflammation in elderly mice.

    PubMed

    Li, Xiu-Ming; Lu, Xing-Xing; Xu, Qian; Wang, Jing-Ru; Zhang, Shen; Guo, Peng-Da; Li, Jian-Ming; Wu, Hua

    2015-01-01

    Nur77, an orphan member of the nuclear receptor superfamily, has been implicated in the regulation of inflammation. However, the in vivo function of Nur77 remains largely unexplored. In the current study, we investigated the role of Nur77 in inflammation and immunity in mice. We found that elderly 8-month-old Nur77-deficient mice (Nur77(-/-)) developed systemic inflammation. Compared to wild-type (WT) mice (Nur77(+/+)), Nur77(-/-) mice showed splenomegaly, severe infiltration of inflammatory cells in several organs including liver, lung, spleen and kidney, increased hyperplasia of fibrous tissue in the lung and enlargement of kidney glomeruli. Additionally, Nur77(-/-) mice had increased production of pro-inflammatory cytokines and immunoglobulin, and elicited pro-inflammatory M1-like polarization in macrophages as revealed by increased expression of CXCL11 and INDO, and decreased expression of MRC1. These in vivo observations provide evidence for a pivotal role for Nur77 in the regulation of systemic inflammation and emphasize the pathogenic significance of Nur77 in vivo.

  14. Strategies for the preparation of bifunctional gadolinium(III) chelators

    PubMed Central

    Frullano, Luca; Caravan, Peter

    2012-01-01

    The development of gadolinium chelators that can be easily and readily linked to various substrates is of primary importance for the development high relaxation efficiency and/or targeted magnetic resonance imaging (MRI) contrast agents. Over the last 25 years a large number of bifunctional chelators have been prepared. For the most part, these compounds are based on ligands that are already used in clinically approved contrast agents. More recently, new bifunctional chelators have been reported based on complexes that show a more potent relaxation effect, faster complexation kinetics and in some cases simpler synthetic procedures. This review provides an overview of the synthetic strategies used for the preparation of bifunctional chelators for MRI applications. PMID:22375102

  15. SWI enhances vein detection using gadolinium in multiple sclerosis

    PubMed Central

    Mazzoni, Lorenzo N; Moretti, Marco; Grammatico, Matteo; Chiti, Stefano; Massacesi, Luca

    2015-01-01

    Susceptibility weighted imaging (SWI) combined with the FLAIR sequence provides the ability to depict in vivo the perivenous location of inflammatory demyelinating lesions – one of the most specific pathologic features of multiple sclerosis (MS). In addition, in MS white matter (WM) lesions, gadolinium-based contrast media (CM) can increase vein signal loss on SWI. This report focuses on two cases of WM inflammatory lesions enhancing on SWI images after CM injection. In these lesions in fact the CM increased the contrast between the parenchyma and the central vein allowing as well, in one of the two cases, the detection of a vein not visible on the same SWI sequence acquired before CM injection. PMID:25815209

  16. The structural response of gadolinium phosphate to pressure

    DOE PAGES

    Heffernan, Karina M.; Ross, Nancy L.; Spencer, Elinor C.; ...

    2016-06-16

    In this study, accurate elastic constants for gadolinium phosphate (GdPO 4) have been measured by single-crystal high-pressure diffraction methods. The bulk modulus of GdPO 4 determined under hydrostatic conditions, 128.1(8) GPa (K'=5.8(2)), is markedly different from that obtained with GdPO 4 under non-hydrostatic conditions (160(2) GPa), which indicates the importance of shear stresses on the elastic response of this phosphate. Finally, high pressure Raman and diffraction analysis indicate that the PO 4 tetrahedra behave as rigid units in response to pressure and that contraction of the GdPO 4 structure is facilitated by bending/twisting of the Gd–O–P links that result inmore » increased distortion in the GdO 9 polyhedra.« less

  17. Interleukin-33/ST2 system attenuates aldosterone-induced adipogenesis and inflammation.

    PubMed

    Martínez-Martínez, Ernesto; Cachofeiro, Victoria; Rousseau, Elodie; Álvarez, Virginia; Calvier, Laurent; Fernández-Celis, Amaya; Leroy, Céline; Miana, María; Jurado-López, Raquel; Briones, Ana M; Jaisser, Frederic; Zannad, Faiez; Rossignol, Patrick; López-Andrés, Natalia

    2015-08-15

    Interleukin-33 (IL-33) but not soluble ST2 (sST2) exerts anti-inflammatory and protective effects in several tissues. Aldosterone, a proinflammatory mediator which promotes adipogenesis, is elevated in obese patients. The aim of this study was to investigate the interactions between IL-33/ST2 system and Aldosterone in adipose tissue. Rats fed a high fat diet presented increased sST2 expression, diminished IL-33/sST2 ratio and enhanced levels of differentiation and inflammation in adipose tissue as compared to controls. A similar pattern was observed in adipose tissue from C57BL/6 Aldosterone-treated mice. In both animal models, Aldosterone was correlated with sST2. Treatment of 3T3-L1 adipocytes with IL-33 delayed adipocyte differentiation diminished lipid accumulation and decreased inflammation. Aldosterone decreased IL-33 and increased sST2 expressions in differentiated adipocytes. Aldosterone-induced adipocyte differentiation and inflammation were blocked by IL-33 treatment, but sST2 did not exert any effects. The crosstalk between IL-33/ST2 and Aldosterone could be relevant in the metabolic consequences of obesity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

    USDA-ARS?s Scientific Manuscript database

    Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptos...

  19. HDL cholesterol transport during inflammation.

    PubMed

    van der Westhuyzen, Deneys R; de Beer, Frederick C; Webb, Nancy R

    2007-04-01

    The aim of this article is to review recent advances made towards understanding how inflammation and acute phase proteins, particularly serum amyloid A and group IIa secretory phospholipase A2, may alter reverse cholesterol transport by HDL during inflammation and the acute phase response. Findings suggest that the decreased apoA-I content and markedly increased serum amyloid A content in HDL during the acute phase response result from reciprocal and coordinate transcriptional regulation of these proteins as well as HDL remodeling by group IIa secretory phospholipase A2. Serum amyloid A functions efficiently in a lipid-free or lipid-poor form to promote cholesterol efflux by ATP binding cassette protein ABCA1, evidently by functioning directly as an acceptor for cholesterol efflux as well as by increasing the availability of cellular free cholesterol. Serum amyloid A increases the ability of acute phase HDL to serve as an acceptor for SR-BI-dependent cellular cholesterol efflux. Altered remodeling of HDL by group IIa secretory phospholipase A2 in concert with cholesterol ester transfer protein may contribute to the generation of lipid-poor apoA-I and serum amyloid A acceptors for cholesterol efflux. Current data support a model for the acute phase response in which serum amyloid A and sPLA2-IIa, present at sites of inflammation and tissue damage, play a protective role by enhancing cellular cholesterol efflux, thereby promoting the removal of excess cholesterol from macrophages.

  20. Non-invasive monitoring of skin inflammation using an oxygen-sensing paint-on bandage

    PubMed Central

    Li, Zongxi; Navarro-Alvarez, Nalu; Keeley, Emily J.; Nowell, Nicholas H.; Goncalves, Beatriz M. M.; Huang, Christene A.; Evans, Conor L.

    2017-01-01

    Inflammation involves a cascade of cellular and molecular mediators that ultimately lead to the infiltration of immune cells into the affected area. This inflammatory process in skin is common to many diseases including acne, infection, and psoriasis, with the presence or absence of immune cells a potential diagnostic marker. Here we show that skin inflammation can be non-invasively measured and mapped using a paint-on oxygen sensing bandage in an in vivo porcine inflammation model. After injection of a known inflammatory agent, the bandage could track the increase, plateau, and decrease in oxygen consumption at the injury site over 7 weeks, as well as discern inflammation resultant from injection at various depths beneath the surface of the skin. Both the initial rate of pO2 change and the change in bandage pO2 at equilibration (CBP20) were found to be directly related to the metabolic oxygen consumption rate of the tissue in contact. Healthy skin demonstrated an initial pO2 decrease rate of 6.5 mmHg⋅min−1, and CBP20 of 84 mmHg. Inflamed skin had a significantly higher initial consumption rate of 55 mmHg⋅min−1, and a larger CBP20 of 140 mmHg. The change in the bandage pO2 before and after equilibration with tissue was found to correlate well with histological evidence of skin inflammation in the animals. PMID:29082091

  1. Preparation of 152Gd targets from a small quantity of gadolinium oxide in a pyrochemical reaction

    NASA Astrophysics Data System (ADS)

    Lipski, A. R.

    1995-02-01

    A simple method utilizing small amounts (< 5 mg) of isotopically enriched material for the production of gadolinium targets is discussed. An electrostatically focused e-gun is used in the procedure in which 152Gd 2O 3 powder undergoes reduction-distillation and deposition onto an Fe foil.

  2. Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

    PubMed Central

    Michopoulos, Vasiliki; Powers, Abigail; Gillespie, Charles F; Ressler, Kerry J; Jovanovic, Tanja

    2017-01-01

    The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear- and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear- and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions. PMID:27510423

  3. Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond.

    PubMed

    Michopoulos, Vasiliki; Powers, Abigail; Gillespie, Charles F; Ressler, Kerry J; Jovanovic, Tanja

    2017-01-01

    The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear- and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear- and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.

  4. High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates: Nano-sized MRI Contrast Agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meux, Susan C.; Datta, Ankona; Hooker, Jacob M.

    2007-08-29

    High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd{sup 3+} ion) of 41.6 mM{sup -1}s{sup -1} at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (1) theremore » is facile diffusion of water to the interior of capsids and (2) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal ({tau}{sub RI} = 440 ps) and external ({tau}{sub RI} = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.« less

  5. Autophagy and kidney inflammation.

    PubMed

    Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

    2017-06-03

    Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases.

  6. Corrosion resistance of 0Kh18N10T steel in gadolinium nitrate solutions in the liquid regulation of the reactivity of nuclear reactors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ganzha, V.D.; Konoplev, K.A.; Mashchetov, V.P.

    1986-03-01

    This study was carried out in connection with the preparation of the design for the PIK research reactor. The corrosion resistance of 0Kh18N10T steel in gadolinium nitrate solutions was tested in laboratory, ampule, and loop corrosion tests. At all stages of the tests, the authors investigated the effect produced on the corrosion processes by factors related to the technology of preparation of the equipment (mechanical working of the surfaces, welding, sensitizing, annealing, stressed state of the material, cracks, etc.). Ampule tests were conducted in order to determine the effect produced by reactor radiation and shutdown regimes on the corrosion resistancemore » of the steel. Special ampules made of 0Kh18N10T steel were filled with gadolinium nitrate solutions of various concentrations, sealed, and irradiated for a long period in the core of the VVR-M reactor at a temperature of 20-50 degrees C. The results of the tests are shown. The investigations showed that the corrosion of 0Kh18N10T steel in solutions of gadolinium nitrate is uniform, regardless of the state of the surface, the concentration of gadolinium nitrate, the duration of the tests, the action of the reactor radiation under static and dynamic conditions, and the presence of mechanical stresses.« less

  7. Age-related inflammation and insulin resistance: a review of their intricate interdependency.

    PubMed

    Park, Min Hi; Kim, Dae Hyun; Lee, Eun Kyeong; Kim, Nam Deuk; Im, Dong Soon; Lee, Jaewon; Yu, Byung Pal; Chung, Hae Young

    2014-12-01

    Chronic inflammation is a major risk factor underlying aging and the associated diseases of aging; of particular interest is insulin resistance during aging. Chronic inflammation impairs normal lipid accumulation, adipose tissue function, mitochondrial function, and causes endoplasmic reticulum (ER) stress, which lead to insulin resistance. However, some studies show that insulin resistance itself amplifies chronic inflammation. The activity of the insulin-dependent Akt signaling pathway is highlighted because of its decrease in insulin-sensitive organs, like liver and muscle, which may underlie insulin resistance and hyperinsulinemia, and its increased levels in non-metabolic organs, such as kidney and aorta. In that the prevalence of obesity has increased substantially for all age groups in recent years, our review summarizes the data showing the involvement of chronic inflammation in obesity-induced insulin resistance, which perpetuates reciprocal interactions between the chronic inflammatory process and increased adiposity, thereby accelerating the aging process.

  8. A novel cryogenic magnetic refrigerant metal-organic framework based on 1D gadolinium(III) chain

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tang, Qun; Li, Peng-Fei; Zou, Zhi-Ming, E-mail: 2014005@glut.edu.cn

    2017-02-15

    A metal-organic framework (MOF) based on gadolinium ion (Gd{sup 3+}) and tricarboxylate ligand, [Gd(BTPCA)(H{sub 2}O)]·2DMF·3H{sub 2}O (Gd-BTPCA) (H{sub 3}BTPCA =1,1′,1′-(benzene-1,3,5-triyl)tripiperidine-4-carboxylic acid; DMF=dimethylformamide), was synthesized and structurally characterized. The adjacent Gd{sup 3+} ions are intraconnected by the carboxylate groups of the BTPCA{sup 3-} ligands to form a 1D Gd{sup 3+} ion chain. The 1D Gd{sup 3+} ion chains are interconnected by the BTPCA{sup 3-} ligands, giving rise to a 3D framework with 1D open channel. The magnetic studies indicate that Gd-BTPCA exhibits weak ferromagnetic interactions, and acts as a cryogenic magnetic refrigerant having the magnetic entropy change (−ΔS{sub m}) of 20.40more » J kg{sup −1} K{sup −1} for ΔH =7 T at 3 K. - Graphical abstract: A 1D gadolinium(III) chains-based metal-organic framework performed ferromagnetic coupling on the magnetic property. Magnetic investigation reveals that Gd-BTPCA exhibits the entropy change (−ΔS{sub m}) of 20.40 J kg{sup −1} K{sup −1} for ΔH =7 T at 3 K. - Highlights: • The MOF based on gadolinium ion and tricarboxylate ligand was synthesized. • This MOF is connected with 1D Gd{sup 3+} ions chain and the carboxylate groups of BTPCA{sup 3-} ligands. • The magnetic studies indicate that the MOF exhibits the weak ferromagnetic interactions. • Magnetic investigation reveals that the MOF exhibits the high entropy change.« less

  9. Influence of acquired obesity on coronary vessel wall late gadolinium enhancement in discordant monozygote twins.

    PubMed

    Makowski, Marcus R; Jansen, Christian H P; Ebersberger, Ullrich; Schaeffter, Tobias; Razavi, Reza; Mangino, Massimo; Spector, Tim D; Botnar, Rene M; Greil, Gerald F

    2017-11-01

    The aim of this study was to investigate the impact of BMI on late gadolinium enhancement (LGE) of the coronary artery wall in identical monozygous twins discordant for BMI. Coronary LGE represents a useful parameter for the detection and quantification of atherosclerotic coronary vessel wall disease. Thirteen monozygote female twin pairs (n = 26) with significantly different BMIs (>1.6 kg/m2) were recruited out of >10,000 twin pairs (TwinsUK Registry). A coronary 3D-T2prep-TFE MR angiogram and 3D-IR-TFE vessel wall scan were performed prior to and following the administration of 0.2 mmol/kg of Gd-DTPA on a 1.5 T MR scanner. The number of enhancing coronary segments and contrast to noise ratios (CNRs) of the coronary wall were quantified. An increase in BMI was associated with an increased number of enhancing coronary segments (5.3 ± 1.5 vs. 3.5 ± 1.6, p < 0.0001) and increased coronary wall enhancement (6.1 ± 1.1 vs. 4.8 ± 0.9, p = 0.0027) compared to matched twins with lower BMI. This study in monozygous twins indicates that acquired factors predisposing to obesity, including lifestyle and environmental factors, result in increased LGE of the coronary arteries, potentially reflecting an increase in coronary atherosclerosis in this female study population. • BMI-discordant twins allow the investigation of the influence of lifestyle factors independent from genetic confounders. • Only thirteen obesity-discordant twins were identified underlining the strong genetic component of BMI. • In female twins, a BMI increase is associated with increased coronary late gadolinium enhancement. • Increased late gadolinium enhancement in the coronary vessel wall potentially reflects increased atherosclerosis.

  10. Intra-amniotic Ureaplasma parvum-Induced Maternal and Fetal Inflammation and Immune Responses in Rhesus Macaques.

    PubMed

    Senthamaraikannan, Paranthaman; Presicce, Pietro; Rueda, Cesar M; Maneenil, Gunlawadee; Schmidt, Augusto F; Miller, Lisa A; Waites, Ken B; Jobe, Alan H; Kallapur, Suhas G; Chougnet, Claire A

    2016-11-15

     Although Ureaplasma species are the most common organisms associated with prematurity, their effects on the maternal and fetal immune system remain poorly characterized.  Rhesus macaque dams at approximately 80% gestation were injected intra-amniotically with 10 7 colony-forming units of Ureaplasma parvum or saline (control). Fetuses were delivered surgically 3 or 7 days later. We performed comprehensive assessments of inflammation and immune effects in multiple fetal and maternal tissues.  Although U. parvum grew well in amniotic fluid, there was minimal chorioamnionitis. U. parvum colonized the fetal lung, but fetal systemic microbial invasion was limited. Fetal lung inflammation was mild, with elevations in CXCL8, tumor necrosis factor (TNF) α, and CCL2 levels in alveolar washes at day 7. Inflammation was not detected in the fetal brain. Significantly, U. parvum decreased regulatory T cells (Tregs) and activated interferon γ production in these Tregs in the fetus. It was detected in uterine tissue by day 7 and induced mild inflammation and increased expression of connexin 43, a gap junction protein involved with labor.  U. parvum colonized the amniotic fluid and caused uterine inflammation, but without overt chorioamnionitis. It caused mild fetal lung inflammation but had a more profound effect on the fetal immune system, decreasing Tregs and polarizing them toward a T-helper 1 phenotype. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  11. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

    PubMed

    Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

    2009-12-01

    Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

  12. Synthesis of samarium doped gadolinium oxide nanorods, its spectroscopic and physical properties

    NASA Astrophysics Data System (ADS)

    Boopathi, G.; Gokul Raj, S.; Ramesh Kumar, G.; Mohan, R.; Mohan, S.

    2018-06-01

    One-dimensional samarium doped gadolinium oxide [Sm:Gd2O3] nanorods have been synthesized successfully through co-precipitation technique in aqueous solution. The as-synthesized and calcined products were characterized by using powder X-ray diffraction pattern, Fourier transform Raman spectroscopy, thermogravimetric/differential thermal analysis, scanning electron microscopy with energy-dispersive X-ray analysis, transmission electron microscopy, Fourier transform infrared spectroscopy, Ultraviolet-Visible spectrometry, photoluminescence spectrophotometer and X-ray photoelectron spectroscopy techniques. The obtained results are discussed in detailed manner.

  13. Update on inflammation in chronic kidney disease.

    PubMed

    Akchurin, Oleh M; Kaskel, Frederick

    2015-01-01

    Despite recent advances in chronic kidney disease (CKD) and end-stage renal disease (ESRD) management, morbidity and mortality in this population remain exceptionally high. Persistent, low-grade inflammation has been recognized as an important component of CKD, playing a unique role in its pathophysiology and being accountable in part for cardiovascular and all-cause mortality, as well as contributing to the development of protein-energy wasting. The variety of factors contribute to chronic inflammatory status in CKD, including increased production and decreased clearance of pro-inflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, including those related to dialysis access, altered metabolism of adipose tissue, and intestinal dysbiosis. Inflammation directly correlates with the glomerular filtration rate (GFR) in CKD and culminates in dialysis patients, where extracorporeal factors, such as impurities in dialysis water, microbiological quality of the dialysate, and bioincompatible factors in the dialysis circuit play an additional role. Genetic and epigenetic influences contributing to inflammatory activation in CKD are currently being intensively investigated. A number of interventions have been proposed to target inflammation in CKD, including lifestyle modifications, pharmacological agents, and optimization of dialysis. Importantly, some of these therapies have been recently tested in randomized controlled trials. Chronic inflammation should be regarded as a common comorbid condition in CKD and especially in dialysis patients. A number of interventions have been proven to be safe and effective in well-designed clinical studies. This includes such inexpensive approaches as modification of physical activity and dietary supplementation. Further investigations are needed to evaluate the effects of these interventions on hard outcomes, as well as to better understand the role of inflammation in selected CKD populations (e.g., in

  14. Impact of agglomeration on the relaxometric properties of paramagnetic ultra-small gadolinium oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Faucher, Luc; Gossuin, Yves; Hocq, Aline; Fortin, Marc-André

    2011-07-01

    Ultra-small gadolinium oxide nanoparticles (US-Gd2O3) are used to provide 'positive' contrast effects in magnetic resonance imaging (MRI), and are being considered for molecular and cellular imaging applications. However, these nanoparticles can aggregate over time in aqueous medium, as well as when internalized into cells. This study is aimed at measuring in vitro, in aqueous medium, the impact of aggregation on the relaxometric properties of paramagnetic US-Gd2O3 particles. First, the nanoparticle core size as well as aggregation behaviour was assessed by HRTEM. DLS (hydrodynamic diameter) was used to measure the hydrodynamic diameter of nanoparticles and nanoaggregates. The relaxometric properties were measured by NMRD profiling, as well as with 1H NMR relaxometers. Then, the positive contrast enhancement effect was assessed by using magnetic resonance scanners (at 1.5 and 7 T). At every magnetic field, the longitudinal relaxivity (r1) decreased upon agglomeration, while remaining high enough to provide positive contrast. On the other hand, the transverse relaxivity (r2) slightly decreased at 0.47 and 1.41 T, but it was enhanced at higher fields (7 and 11.7 T) upon agglomeration. All NMRD profiles revealed a characteristic relaxivity peak in the range 60-100 MHz, suggesting the possibility to use US-Gd2O3 as an efficient 'positive-T1' contrast agent at clinical magnetic fields (1-3 T), in spite of aggregation.

  15. Investigation of suspected Guillain-Barre syndrome in childhood: what is the role for gadolinium enhanced magnetic resonance imaging of the spine?

    PubMed

    Smith, Nicholas; Pereira, John; Grattan-Smith, Padraic

    2014-10-01

    To review the role of gadolinium-enhanced magnetic resonance imaging of the spine in the diagnosis of paediatric Guillain-Barre syndrome and compare it with nerve conduction studies and cerebrospinal fluid analysis. A retrospective review of investigations undertaken in children admitted to our institution with acute Guillain-Barre syndrome over a 10-year period was performed. Seven of eight children (88%) displayed post-gadolinium nerve root enhancement consistent with Guillain-Barre syndrome. This compared with supportive nerve conduction studies in 21/24 children (88%) and cerebrospinal fluid protein analysis consistent with the diagnosis in 16/20 children (80%). Nerve conduction studies are the recognised 'gold standard' technique for confirming a clinical diagnosis of Guillain-Barre syndrome. In this study, a high positive rate was demonstrated. While more experience is necessary, this study and the literature support gadolinium enhanced magnetic resonance imaging of the spine as a valuable, although not necessarily superior, investigation in the diagnosis of Guillain-Barre syndrome. It may be of particular benefit when specialist neurophysiology expertise is unavailable. © 2010 The Authors. Journal compilation © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  16. Gadolinium Enhancement in Intracranial Atherosclerotic Plaque and Ischemic Stroke: A Systematic Review and Meta-Analysis.

    PubMed

    Gupta, Ajay; Baradaran, Hediyeh; Al-Dasuqi, Khalid; Knight-Greenfield, Ashley; Giambrone, Ashley E; Delgado, Diana; Wright, Drew; Teng, Zhongzhao; Min, James K; Navi, Babak B; Iadecola, Costantino; Kamel, Hooman

    2016-08-15

    Gadolinium enhancement on high-resolution magnetic resonance imaging (MRI) has been proposed as a marker of inflammation and instability in intracranial atherosclerotic plaque. We performed a systematic review and meta-analysis to summarize the association between intracranial atherosclerotic plaque enhancement and acute ischemic stroke. We searched the medical literature to identify studies of patients undergoing intracranial vessel wall MRI for evaluation of intracranial atherosclerotic plaque. We recorded study data and assessed study quality, with disagreements in data extraction resolved by a third reader. A random-effects odds ratio was used to assess whether, in any given patient, cerebral infarction was more likely in the vascular territory supplied by an artery with MRI-detected plaque enhancement as compared to territory supplied by an artery without enhancement. We calculated between-study heterogeneity using the Cochrane Q test and publication bias using the Begg-Mazumdar test. Eight articles published between 2011 and 2015 met inclusion criteria. These studies provided information about plaque enhancement characteristics from 295 arteries in 330 patients. We found a significant positive relationship between MRI enhancement and cerebral infarction in the same vascular territory, with a random effects odds ratio of 10.8 (95% CI 4.1-28.1, P<0.001). No significant heterogeneity (Q=11.08, P=0.14) or publication bias (P=0.80) was present. Intracranial plaque enhancement on high-resolution vessel wall MRI is strongly associated with ischemic stroke. Evaluation for plaque enhancement on MRI may be a useful test to improve diagnostic yield in patients with ischemic strokes of undetermined etiology. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. Autophagy and kidney inflammation

    PubMed Central

    Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

    2017-01-01

    ABSTRACT Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases. PMID:28441075

  18. Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults.

    PubMed

    Mave, Vidya; Erlandson, Kristine M; Gupte, Nikhil; Balagopal, Ashwin; Asmuth, David M; Campbell, Thomas B; Smeaton, Laura; Kumarasamy, Nagalingeswaran; Hakim, James; Santos, Breno; Riviere, Cynthia; Hosseinipour, Mina C; Sugandhavesa, Patcharaphan; Infante, Rosa; Pillay, Sandy; Cardoso, Sandra W; Tripathy, Srikanth; Mwelase, Noluthando; Berendes, Sima; Andrade, Bruno B; Thomas, David L; Bollinger, Robert C; Gupta, Amita

    2016-07-01

    Both wasting and obesity are associated with inflammation, but the extent to which body weight changes influence inflammation during human immunodeficiency virus infection is unknown. Among a random virologically suppressed participants of the Prospective Evaluation of Antiretrovirals in Resource-Limited Settings trial, inflammatory markers were measured at weeks 0, 24, and 48 after antiretroviral therapy (ART) initiation. Associations between both baseline and change in body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) and changes in inflammation markers were assessed using random effects models. Of 246 participants, 27% were overweight/obese (BMI, ≥ 25), and 8% were underweight (BMI < 18.5) at baseline. After 48 weeks, 37% were overweight/obese, and 3% were underweight. While level of many inflammatory markers decreased 48 weeks after ART initiation in the overall group, the decrease in C-reactive protein (CRP) level was smaller in overweight/obese participants (P = .01), and the decreases in both CRP (P = .01) and interleukin 18 (P = .02) levels were smaller in underweight participants. Each 1-unit gain in BMI among overweight/obese participants was associated with a 0.02-log10 increase in soluble CD14 level (P = .05), while each 1-unit BMI gain among underweight participants was associated with a 9.32-mg/L decrease in CRP level (P = .001). Being either overweight or underweight at ART initiation was associated with heightened systemic inflammation. While weight gain among overweight/obese persons predicted increased inflammation, weight gain among underweight persons predicted reduced inflammation. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  19. MAG-EPA resolves lung inflammation in an allergic model of asthma.

    PubMed

    Morin, C; Fortin, S; Cantin, A M; Rousseau, É

    2013-09-01

    Asthma is a chronic disease characterized by airways hyperresponsiveness, inflammation and airways remodelling involving reversible bronchial obstruction. Omega-3 fatty acids and their derivatives are known to reduce inflammation in several tissues including lung. The effects of eicosapentaenoic acid monoacylglyceride (MAG-EPA), a newly synthesized EPA derivative, were determined on the resolution of lung inflammation and airway hyperresponsiveness in an in vivo model of allergic asthma. Ovalbumin (OVA)-sensitized guinea-pigs were treated or not with MAG-EPA administered per os. Isometric tension measurements, histological analyses, homogenate preparation for Western blot experiments or total RNA extraction for RT-PCR were performed to assess the effect of MAG-EPA treatments. Mechanical tension measurements revealed that oral MAG-EPA treatments reduced methacholine (MCh)-induced bronchial hyperresponsiveness in OVA-sensitized guinea-pigs. Moreover, MAG-EPA treatments also decreased Ca(2+) hypersensitivity of bronchial smooth muscle. Histological analyses and leucocyte counts in bronchoalveolar lavages revealed that oral MAG-EPA treatments led to less inflammatory cell recruitment in the lung of OVA-sensitized guinea-pigs when compared with lungs from control animals. Results also revealed a reduction in mucin production and MUC5AC expression level in OVA-sensitized animals treated with MAG-EPA. Following MAG-EPA treatments, the transcript levels of pro-inflammatory markers such as IL-5, eotaxin, IL-13 and IL-4 were markedly reduced. Moreover, per os MAG-EPA administrations reduced COX2 over-expression in OVA-sensitized animals. We demonstrate that MAG-EPA reduces airway hyperresponsiveness and lung inflammation in OVA-sensitized animals, a finding consistent with a decrease in IL-4, IL-5, IL-13, COX-2 and MUC5AC expression levels in the lung. The present data suggest that MAG-EPA represents a new potential therapeutic strategy for resolving inflammation in allergic

  20. Vitamin D supplementation, bone turnover, and inflammation in HIV-infected patients.

    PubMed

    Benguella, L; Arbault, A; Fillion, A; Blot, M; Piroth, C; Denimal, D; Duvillard, L; Ornetti, P; Chavanet, P; Maillefert, J-F; Piroth, L

    2018-04-13

    To assess whether vitamin D supplementation could be associated with a modification of inflammatory markers and bone turnover in HIV-1-infected patients. Patients who participated in an initial survey in 2010 and who were followed in the same department were included in a new study in 2012. Between 2010 and 2012, vitamin D supplementation was offered to patients presenting with hypovitaminosis D as per appropriate guidelines. Clinical examinations were performed, and fasting blood samples were taken for inflammation and bone marker evaluations. Of the 263 patients who participated in the 2010 study, 198 were included in the 2012 study. Hypovitaminosis D was observed in 47% (36/77) of participants supplemented as per appropriate guidelines, in 78% (75/97) of transiently or incompletely supplemented participants, and in 71% (17/24) of non-supplemented participants (mainly because vitamin D levels in 2010 were normal). No significant correlation between vitamin D supplementation and the 2-year inflammation outcome (IL-6 and hsCRP) or C-terminal telopeptide levels was observed. However, a decrease in IL6 levels over the 2 years significantly correlated with reaching a normal vitamin D level (OR=0.89 per+1pg/mL IL6 increase, 95% CI=0.81-0.97, P=0.015). Vitamin D supplementation decreases the risk of hypovitaminosis D but does not decrease the risk of inflammation nor bone turnover, unless normal 25-OH vitamin D levels are reached. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  1. Effects of local nasal immunotherapy in allergic airway inflammation: Using urea denatured Dermatophagoides pteronyssinus

    PubMed Central

    Yu, Sheng-Jie; Liao, En-Chih; Tsai, Jaw-Ji

    2015-01-01

    Despite improvements in anti-allergy medication, the prevalence of allergic airway inflammation remains high, affecting up to 40% of the population worldwide. Allergen immunotherapy is effective for inducing tolerance but has the adverse effect of severe allergic reaction. This can be avoided by denaturing with urea. In this study, we demonstrated that the serum level of allergen-specific IgE in mice sensitized with native Dermatophagoides pteronyssinus (Der p) crude extract after receiving local nasal immunotherapy (LNIT) with urea-denatured Der p crude extract (DN-Dp) significantly decreased compared to that in the normal saline (NS) treatment group. Expressions of IL-4 were significantly reduced in lung tissues after treatment. Inflammation around the bronchial epithelium improved and airway hypersensitivity was down-regulated. LNIT with DN-Dp can down-regulate IL-1b, IL-6 and TNF-a expression and then decrease Der p-induced allergic airway inflammation. This therapeutic modality may be used as an alternative treatment for airway allergic diseases. PMID:25933184

  2. Differential Effects of Sepsis and Chronic Inflammation on Diaphragm Muscle Fiber Type, Thyroid Hormone Metabolism, and Mitochondrial Function.

    PubMed

    Bloise, Flavia F; van der Spek, Anne H; Surovtseva, Olga V; Ortiga-Carvalho, Tania Maria; Fliers, Eric; Boelen, Anita

    2016-04-01

    The diaphragm is the main respiratory muscle, and its function is compromised during severe illness. Altered local thyroid hormone (TH) metabolism may be a determinant of impaired muscle function during illness. This study investigates the effects of bacterial sepsis and chronic inflammation on muscle fiber type, local TH metabolism, and mitochondrial function in the diaphragm. Two mouse models were used: sepsis induced by S. pneumoniae infection or chronic inflammation induced by subcutaneous turpentine injection. In vitro, the effect of bacterial endotoxin (LPS) on mitochondrial function in C2C12 myotubes was studied. Sepsis induced a transient increase in the fiber type I profile and increased Dio3 expression while decreasing Dio2, Thra1, and Slc16a2 expression. Triiodothyronine positively regulated genes Tnni2 and Myog were decreased, indicating reduced TH signaling in the diaphragm. In contrast, chronic inflammation increased the fiber type II profile in the diaphragm as well as Thra1, Thrb1, and Myog expression while decreasing Dio3 expression, suggesting increased TH responsiveness during chronic inflammation. LPS-stimulated C2C12 myotubes showed decreased Dio2 expression and reduced basal oxygen consumption as well as non-mitochondrial respiration. The same respiratory profile was induced by Dio2 knockdown in myotubes. The in vivo results show differential effects of sepsis and chronic inflammation on diaphragm muscle fiber type, TH metabolism, and mitochondrial function, while the in vitro results point to a causal role for altered TH metabolism in functional muscle impairment. These findings may be relevant for the pathogenesis of impaired respiratory function in critical illness.

  3. Clinical application of a gadolinium-based capsule as an MRI contrast agent in slow transit constipation diagnostics.

    PubMed

    Zhi, M; Zhou, Z; Chen, H; Xiong, F; Huang, J; He, H; Zhang, M; Su, M; Gao, X; Hu, P

    2017-06-01

    As a traditional method for the assessment of colon dynamics, radio-opaque markers (ROMs) are limited in clinical use because of their ionizing radiation. We compared the accuracy and applicability of gadolinium-based capsules with ROMs in the measurement of colon dynamics in healthy controls and slow transit constipation (STC) patients. Seven patients with STC and nine healthy controls under a normal diet orally consumed ROMs and gadolinium-based capsules simultaneously. All subjects underwent X-ray and magnetic resonance imaging (MRI). Healthy control images were acquired at 12, 24, and 48 h, and STC patient images were acquired at 24, 48, and 72 h. The scores based on the position of the labeling capsules and ROMs in the colon and the colon transit times (CTTs) in the two groups were compared. The CTTs obtained via the ROMs were 34.7±17.4 and 67.3±6.5 h in the healthy controls and STC patients, respectively (P<.05). The CTTs obtained via MRI were 30.9±15.9 and 74.1±7.2 h in the healthy controls and STC patients, respectively (P<.05). The CTTs of the STC patients were significantly longer than the healthy controls. The correlation (r s ) between the scores based on the position of the labeling capsule and ROMs in the healthy group and the STC patients was .880 (P<.05) and .889 (P<.05), respectively. As a MRI contrast label, gadolinium-based capsules exhibit results comparable to ROMs in colon motility measurements. © 2017 John Wiley & Sons Ltd.

  4. Inflammation on the Cervical Papanicolaou Smear: Evidence for Infection in Asymptomatic Women?

    PubMed Central

    Tsirmpa, Ioanna; Chasiakou, Anthia; Tsouma, Iliana; Politi, Ekaterina; Gennimata, Vassiliki; Kouskouni, Evangelia

    2013-01-01

    Background. The significance of the possible presence of infection on the Pap smear of asymptomatic women based on cytological criteria is practically unknown. Materials and Methods. A total of 1117 asymptomatic nonpregnant women had Pap smear tests and vaginal as well as cervical cultures completed (622 with and 495 without inflammation on the Pap smear). Results. Out of the 622 women with inflammation on Pap test, 251 (40.4%) had negative cultures (normal flora present), while 371 (59.6%) women had positive cultures with different pathogens. In contrast, the group of women without inflammation on Pap test displayed significantly increased percentage of negative cultures (67.1%, P < 0.001) and decreased percentage of positive cultures (32.9%, P < 0.001). Bacterial vaginosis was diagnosed more frequently in both groups and significantly more in the group with inflammation on Pap smear compared to the group without inflammation (P < 0.02). Conclusions. A report of inflammatory changes on the cervical Pap smear cannot be used to reliably predict the presence of a genital tract infection, especially in asymptomatic women. Nevertheless, the isolation of different pathogens in about 60% of the women with inflammation on the Pap smear cannot be overlooked and must be regarded with concern. PMID:24204103

  5. Relaxivity enhancement of aquated Tris(β-diketonate)gadolinium(III) chelates by confinement within ultrashort single-walled carbon nanotubes.

    PubMed

    Law, Justin J; Guven, Adem; Wilson, Lon J

    2014-01-01

    Ultrashort single-walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T1 -weighted relaxivities (>100 mm(-1) s(-1) ). To further examine the effect of nanoconfinement on the relaxivity of gadolinium-based contrast agents for magnetic resonance imaging, a series of ultrashort single-walled carbon nanotube (US-tube) materials internally loaded with gadolinium chelates have been prepared and studied. US-tubes were loaded with Gd(acac)3  · 2H2 O, Gd(hfac)3  · 2H2 O, and Gd(thd)3 (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm(-1) s(-1) for Gd(acac)3  · 2H2 O@US-tubes, 105 mm(-1) s(-1) for Gd(hfac)3  · 2H2 O@US-tubes and 26 mm(-1) s(-1) for Gd(thd)3 @US-tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm(-1) s(-1) ) as well as accounting for the T1 reduction observed for the empty US-tubes, the boost in relaxivity for chelate-loaded US-tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Triple dose of gadolinium-DTPA and delayed MRI in patients with benign multiple sclerosis.

    PubMed Central

    Filippi, M; Capra, R; Campi, A; Colombo, B; Prandini, F; Marcianò, N; Gasparotti, R; Comi, G

    1996-01-01

    OBJECTIVES--To evaluate whether a triple dose of gadolinium-DTPA (Gd-DTPA) or delayed MRI increase the number, size, and conspicuousness of enhancing lesions in patients with benign multiple sclerosis. METHODS--T1 weighted brain MRI was carried out on 20 patients with benign multiple sclerosis (expanded disability status scale < 3 with a disease duration > 10 years) in two sessions. In the first session, one scan was obtained before and two scans five to seven minutes and 20-30 minutes after the injection of 0.1 mmol/kg Gd-DTPA (standard dose). In the second session, six to 24 hours later, the same procedure was repeated with 0.3 mmol/kg Gd-DTPA (triple dose). RESULTS--Nine enhancing lesions were found in seven patients (35%) using the standard dose of Gd-DTPA. The numbers of enhancing lesions increased to 13 (P = 0.03) and the number of patients with such lesions to eight (40%) on the delayed standard dose scans. On the early triple dose scans, we found 19 enhancing lesions in 10 patients (50%). The number of enhancing lesions was significantly higher (P = 0.01) than that obtained with the early standard dose. The number of enhancing lesions was 18 and the number of "active" patients 11 (55%) on the delayed triple dose scans. The enhancing areas increased progressively from the early standard dose scans to the delayed triple dose scans. The contrast ratios of the lesions detected in early standard dose scans was lower than those of lesions present in the early (P = 0.01) and delayed (P = 0.04) triple dose scans. CONCLUSIONS--More enhancing lesions were detected in patients with benign multiple sclerosis with both delay of MRI and the use of triple dose of Gd-DTPA suggesting that the amount of inflammation in the lesions of such patients is mild and heterogeneous. Images PMID:8778257

  7. Thermophysical Property Measurements of Liquid Gadolinium by Containerless Methods

    NASA Astrophysics Data System (ADS)

    Ishikawa, T.; Okada, J. T.; Paradis, P.-F.; Watanabe, Y.

    2010-02-01

    Thermophysical properties of liquid gadolinium were measured using non-contact diagnostic techniques with an electrostatic levitator. Over the 1585 K to 1920 K temperature range, the density can be expressed as ρ( T) = 7.41 × 103 - 0.46 ( T - T m) (kg · m-3) where T m = 1585 K, yielding a volume expansion coefficient of 6.2 × 10-5 K-1. In addition, the surface tension data can be fitted as γ( T) = 8.22 × 102 - 0.097( T - T m)(10-3 N · m-1) over the 1613 K to 1803 K span and the viscosity as η( T) = 1.7exp[1.4 × 104/( RT)](10-3 Pa · s) over the same temperature range.

  8. Complex imaging features of accidental cerebral intraventricular gadolinium administration.

    PubMed

    Nayak, Nita B; Huang, Jimmy C; Hathout, Gasser M; Shaba, Wisam; El-Saden, Suzie M

    2013-05-01

    Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) is a contrast agent commonly used for enhancing MRI. In this paper, the authors report on 2 cases of postoperative inadvertent administration of Gd-DTPA directly into a ventriculostomy tubing side port that was mistaken for intravenous tubing. Both cases demonstrated a low signal on MRI throughout the ventricular system and dependent portions of the subarachnoid spaces, which was originally believed to be CSF with areas of T1 shortening in the nondependent portions of the subarachnoid spaces, and misinterpreted as basal leptomeningeal enhancement and meningitis. The authors propose that the appearance of profound T1 hypointensity within the ventricles and diffuse susceptibility artifact along the ependyma is pathognomonic of intraventricular Gd-DTPA and should be recognized.

  9. Psoriatic inflammation enhances allergic airway inflammation through IL-23/STAT3 signaling in a murine model.

    PubMed

    Nadeem, Ahmed; Al-Harbi, Naif O; Ansari, Mushtaq A; Al-Harbi, Mohammed M; El-Sherbeeny, Ahmed M; Zoheir, Khairy M A; Attia, Sabry M; Hafez, Mohamed M; Al-Shabanah, Othman A; Ahmad, Sheikh F

    2017-01-15

    Psoriasis is an autoimmune inflammatory skin disease characterized by activated IL-23/STAT3/Th17 axis. Recently psoriatic inflammation has been shown to be associated with asthma. However, no study has previously explored how psoriatic inflammation affects airway inflammation. Therefore, this study investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on cockroach extract (CE)-induced airway inflammation in murine models. Mice were subjected to topical and intranasal administration of IMQ and CE to develop psoriatic and airway inflammation respectively. Various analyses in lung/spleen related to inflammation, Th17/Th2/Th1 cell immune responses, and their signature cytokines/transcription factors were carried out. Psoriatic inflammation in allergic mice was associated with increased airway inflammation with concurrent increase in Th2/Th17 cells/signature cytokines/transcription factors. Splenic CD4+ T and CD11c+ dendritic cells in psoriatic mice had increased STAT3/RORC and IL-23 mRNA expression respectively. This led us to explore the effect of systemic IL-23/STAT3 signaling on airway inflammation. Topical application of STA-21, a small molecule STAT3 inhibitor significantly reduced airway inflammation in allergic mice having psoriatic inflammation. On the other hand, adoptive transfer of IL-23-treated splenic CD4+ T cells from allergic mice into naive recipient mice produced mixed neutrophilic/eosinophilic airway inflammation similar to allergic mice with psoriatic inflammation. Our data suggest that systemic IL-23/STAT3 axis is responsible for enhanced airway inflammation during psoriasis. The current study also suggests that only anti-asthma therapy may not be sufficient to alleviate airway inflammatory burden in asthmatics with psoriasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Magnetic resonance imaging with gadolinium arthrography to assess acetabular cartilage delamination.

    PubMed

    Zaragoza, Edward; Lattanzio, Pierre-Jean; Beaule, Paul E

    2009-01-01

    Recent reports have demonstrated magnetic resonance imaging (MRI) as a promising technique in detecting articular cartilage lesions of the hip joint. The purpose of our study was to evaluate the diagnostic performance of MRI with gadolinium arthrography in detecting acetabular cartilage delamination in patients with pre-arthritic hip pain. 46 patients (48 hips) underwent surgical dislocation of the hip. Mean age was 38.8 (range 17-56). There were 26 males and 20 females. All patients had Magnetic Resonance Imaging with gadolinium arthrography (MRA) before undergoing open hip surgery where the acetabular cartilage was inspected. Acetabular cartilage delamination on MRA was seen on sagittal images as a linear intra-articular filling defect of low signal intensity >1mm in thickness on T1 weighted images and surrounded by contrast. On MRA all hips had a labral tear confirmed at surgery. At surgery 30 hips had evidence of acetabular cartilage delamination, 4 hips had ulceration and 14 had no articular cartilage damage. The majority of labral tears and cartilage damage were located in the antero-superior quadrant. The sensitivity and specificity of MRA detection of cartilage delamination confirmed at surgery were 97% and 84%, respectively. The positive and negative predictive values of the MRA finding were 90% and 94%, respectively. The presence of the acetabular cartilage delamination represents an early stage of articular cartilage degeneration. When evaluating a young adult with hip pain, labral tears in association with cartilage delamination should be considered. MRA represents an effective diagnostic tool.

  11. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    NASA Astrophysics Data System (ADS)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  12. Attenuated Low-Grade Inflammation Following Long-Term Dietary Intervention in Postmenopausal Women with Obesity.

    PubMed

    Blomquist, Caroline; Alvehus, Malin; Burén, Jonas; Ryberg, Mats; Larsson, Christel; Lindahl, Bernt; Mellberg, Caroline; Söderström, Ingegerd; Chorell, Elin; Olsson, Tommy

    2017-05-01

    Abdominal fat accumulation after menopause is associated with low-grade inflammation and increased risk of metabolic disorders. Effective long-term lifestyle treatment is therefore needed. Seventy healthy postmenopausal women (age 60 ± 5.6 years) with BMI 32.5 ± 5.5 were randomized to a Paleolithic-type diet (PD) or a prudent control diet (CD) for 24 months. Blood samples and fat biopsies were collected at baseline, 6 months, and 24 months to analyze inflammation-related parameters. Android fat decreased significantly more in the PD group (P = 0.009) during the first 6 months with weight maintenance at 24 months in both groups. Long-term significant effects (P < 0.001) on adipose gene expression were found for toll-like receptor 4 (decreased at 24 months) and macrophage migration inhibitory factor (increased at 24 months) in both groups. Serum interleukin 6 (IL-6) and tumor necrosis factor α levels were decreased at 24 months in both groups (P < 0.001) with a significant diet-by-time interaction for serum IL-6 (P = 0.022). High-sensitivity C-reactive protein was decreased in the PD group at 24 months (P = 0.001). A reduction of abdominal obesity in postmenopausal women is linked to specific changes in inflammation-related adipose gene expression. © 2017 The Obesity Society.

  13. Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress.

    PubMed

    Veličković, Nataša; Teofilović, Ana; Ilić, Dragana; Djordjevic, Ana; Vojnović Milutinović, Danijela; Petrović, Snježana; Preitner, Frederic; Tappy, Luc; Matić, Gordana

    2018-05-29

    High-fructose consumption and chronic stress are both associated with metabolic inflammation and insulin resistance. Recently, disturbed activity of energy sensor AMP-activated protein kinase (AMPK) was recognized as mediator between nutrient-induced stress and inflammation. Thus, we analyzed the effects of high-fructose diet, alone or in combination with chronic stress, on glucose homeostasis, inflammation and expression of energy sensing proteins in the rat liver. In male Wistar rats exposed to 9-week 20% fructose diet and/or 4-week chronic unpredictable stress we measured plasma and hepatic corticosterone level, indicators of glucose homeostasis and lipid metabolism, hepatic inflammation (pro- and anti-inflammatory cytokine levels, Toll-like receptor 4, NLRP3, activation of NFκB, JNK and ERK pathways) and levels of energy-sensing proteins AMPK, SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). High-fructose diet led to glucose intolerance, activation of NFκB and JNK pathways and increased intrahepatic IL-1β, TNFα and inhibitory phosphorylation of insulin receptor substrate 1 on Ser 307 . It also decreased phospho-AMPK/AMPK ratio and increased SIRT1 expression. Stress alone increased plasma and hepatic corticosterone but did not influence glucose tolerance, nor hepatic inflammatory or energy-sensing proteins. After the combined treatment, hepatic corticosterone was increased, glucose tolerance remained preserved, while hepatic inflammation was partially prevented despite decreased AMPK activity. High-fructose diet resulted in glucose intolerance, hepatic inflammation, decreased AMPK activity and reduced insulin sensitivity. Chronic stress alone did not exert such effects, but when applied together with high-fructose diet it could partially prevent fructose-induced inflammation, presumably due to increased hepatic glucocorticoids.

  14. Radiation, Inflammation, and Immune Responses in Cancer

    PubMed Central

    Multhoff, Gabriele; Radons, Jürgen

    2012-01-01

    Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR. PMID:22675673

  15. Liver acquisition with acceleration volume acquisition gadolinium-enhanced magnetic resonance combined with T2 sequences in the diagnosis of local recurrence of rectal cancer.

    PubMed

    Cao, Wuteng; Li, Fangqian; Gong, Jiaying; Liu, Dechao; Deng, Yanhong; Kang, Liang; Zhou, Zhiyang

    2016-11-22

    To investigate the efficacy of liver acquisition with acceleration volume acquisition (LAVA) gadolinium-enhanced magnetic resonance (MR) sequences and to assess its added accuracy in diagnosing local recurrence (LR) of rectal cancer with conventional T2-weighted fast spin echo (FSE) sequences. Pelvic MRI, including T2-weighted FSE sequences, gadolinium-enhanced sequences of LAVA and T1-weighted FSE with fat suppression, was performed on 225 patients with postoperative rectal cancer. Two readers evaluated the presence of LR according to "T2" (T2 sequences only), "T2 + LAVA-Gad" (LAVA and T2 imaging), and "T2 + T1-fs-Gad" (T1 fat suppression-enhanced sequence with T2 images). To evaluate diagnostic efficiency, imaging quality with LAVA and T1-fs-Gad by subjective scores and the signal intensity (SI) ratio. In the result, the SI ratio of LAVA was significantly higher than that of T1-fs-Gad (p = 0.0001). The diagnostic efficiency of "T2 + LAVA-Gad" was better than that of "T2 + T1-fs-Gad" (p = 0.0016 for Reader 1, p = 0.0001 for Reader 2) and T2 imaging only (p = 0.0001 for Reader 1; p = 0.0001 for Reader 2). Therefore, LAVA gadolinium-enhanced MR increases the accuracy of diagnosis of LR from rectal cancer and could replace conventional T1 gadolinium-enhanced sequences in the postoperative pelvic follow-up of rectal cancer.

  16. Complex interactions between hypoxia-ischemia and inflammation in preterm brain injury.

    PubMed

    Galinsky, Robert; Lear, Christopher A; Dean, Justin M; Wassink, Guido; Dhillon, Simerdeep K; Fraser, Mhoyra; Davidson, Joanne O; Bennet, Laura; Gunn, Alistair J

    2018-02-01

    Children surviving preterm birth have a high risk of disability, particularly cognitive and learning problems. There is extensive clinical and experimental evidence that disability is now primarily related to dysmaturation of white and gray matter, defined by failure of oligodendrocyte maturation and neuronal dendritic arborization, rather than cell death alone. The etiology of this dysmaturation is multifactorial, with contributions from hypoxia-ischemia, infection/inflammation and barotrauma. Intriguingly, these factors can interact to both increase and decrease damage. In this review we summarize preclinical and clinical evidence that all of these factors trigger secondary or chronic inflammation and gliosis. Thus, we hypothesize that these shared pathological features play a key role in a final common pathway that leads to the impaired neural maturation and connectivity and cognitive/motor impairments that are commonly observed in infants born preterm. This raises the possibility that secondary or chronic inflammation may be a viable therapeutic target for delayed interventions to improve neurodevelopmental outcomes after preterm birth. Hypoxia-ischemia, infection/inflammation, and barotrauma/volutrauma all contribute to preterm brain injury. Multiple different triggers of preterm brain injury are associated with central nervous system dysmaturation. Secondary brain inflammation may be a viable target to improve neurodevelopment after preterm birth. © 2017 Mac Keith Press.

  17. Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla.

    PubMed

    Kelle, Sebastian; Schlendorf, Kelly; Hirsch, Glenn A; Gerstenblith, Gary; Fleck, Eckart; Weiss, Robert G; Stuber, Matthias

    2010-10-11

    Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30-45 minutes after administration of the contrast agent.

  18. Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue

    PubMed Central

    Leroyer, Stéphanie; Vatier, Camille; Kadiri, Sarah; Quette, Joëlle; Chapron, Charles; Capeau, Jacqueline; Antoine, Bénédicte

    2011-01-01

    Glyceroneogenesis, a metabolic pathway that participates during lipolysis in the recycling of free fatty acids to triglycerides into adipocytes, contributes to the lipid-buffering function of adipose tissue. We investigated whether glyceroneogenesis could be affected by human immunodeficiency virus (HIV) protease inhibitors (PIs) responsible or not for dyslipidemia in HIV-infected patients. We treated explants obtained from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depots from lean individuals. We observed that the dyslipidemic PIs nelfinavir, lopinavir and ritonavir, but not the lipid-neutral PI atazanavir, increased lipolysis and decreased glyceroneogenesis, leading to an increased release of fatty acids from SAT but not from VAT. At the same time, dyslipidemic PIs decreased the amount of perilipin and increased interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secretion in SAT but not in VAT. Parthenolide, an inhibitor of the NFκB pathway, counteracted PI-induced increased inflammation and decreased glyceroneogenesis. IL-6 (100 ng) inhibited the activity of phosphoenolpyruvate carboxykinase, the key enzyme of glyceroneogenesis, in SAT but not in VAT. Our data show that dyslipidemic but not lipid-neutral PIs decreased glyceroneogenesis as a consequence of PI-induced increased inflammation in SAT that could have an affect on adipocytes and/or macrophages. These results add a new link between fat inflammation and increased fatty acids release and suggest a greater sensitivity of SAT than VAT to PI-induced inflammation. PMID:21068005

  19. Effects of gadolinium-based MRI contrast agents on liver tissue.

    PubMed

    Mercantepe, Tolga; Tümkaya, Levent; Çeliker, Fatma Beyazal; Topal Suzan, Zehra; Çinar, Seda; Akyildiz, Kerimali; Mercantepe, Filiz; Yilmaz, Adnan

    2018-04-01

    MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models. To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation. Institutional Review Board (IRB)-approved controlled longitudinal study. In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4). Not applicable. Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained. Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test. An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P < 0.05). In contrast, we determined no change in TOS (P = 0.568 and P = 0.094, respectively), TAS (P = 0.151 and P = 0.055, respectively), or OSI (P = 0.949 and P = 0.494, respectively) values. These data suggest that gadodiamide and gadoteric acid trigger hepatocellular necrosis and apoptosis by causing damage in hepatocytes, although no change occurs in total antioxidant and antioxidant capacity. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

  20. Inflammation during obesity is not all bad: evidence from animal and human studies

    PubMed Central

    McGuinness, Owen P.

    2013-01-01

    Chronic inflammation is a characteristic of obesity and is associated with accompanying insulin resistance, a hallmark of type 2 diabetes mellitus (T2DM). Although proinflammatory cytokines are known for their detrimental effects on adipose tissue function and insulin sensitivity, their beneficial effects in the regulation of metabolism have not drawn sufficient attention. In obesity, inflammation is initiated by a local hypoxia to augment angiogenesis and improve adipose tissue blood supply. A growing body of evidence suggests that macrophages and proinflammatory cytokines are essential for adipose remodeling and adipocyte differentiation. Phenotypes of multiple lines of transgenic mice consistently suggest that proinflammatory cytokines increase energy expenditure and act to prevent obesity. Removal of proinflammatory cytokines by gene knockout decreases energy expenditure and induces adult-onset obesity. In contrast, elevation of proinflammatory cytokines augments energy expenditure and decreases the risk for obesity. Anti-inflammatory therapies have been tested in more than a dozen clinical trials to improve insulin sensitivity and glucose homeostasis in patients with T2DM, and the results are not encouraging. One possible explanation is that anti-inflammatory therapies also attenuate the beneficial effects of inflammation in stimulating energy expenditure, which may have limited the efficacy of the treatment by promoting energy accumulation. Thus, the positive effects of proinflammatory events should be considered in evaluating the impact of inflammation in obesity and type 2 diabetes. PMID:23269411

  1. Blockade of IL-23 ameliorates allergic lung inflammation via decreasing the infiltration of Tc17 cells.

    PubMed

    Cheng, Sheng; Chen, Huilong; Wang, Aili; Bunjhoo, Hansvin; Cao, Yong; Xie, Jungang; Xu, Yongjian; Xiong, Weining

    2016-12-01

    Tc17 cells are interleukin (IL)-17-producing CD8 + T cells and have been found to participate in the development of allergic asthma. Interleukin-23 is a cytokine that may be involved in modulating the IL-17 response via Th17 cells. This study aimed to investigate whether IL-23 also has immunomodulatory effects on Tc17 cells. An allergic asthmatic mouse model was induced by sensitizing and challenging with ovalbumin (OVA). Anti-IL-23 antibody was administered intratracheally before challenge to the OVA-induced asthmatic mouse model. Airway hyperresponsiveness, lung inflammation, Tc17 cell percentages and IL-17 level in the lung tissue homogenate were measured. Anti-IL-23 treatment reduced airway hyperresponsiveness (Rn 2.471 ±0.5077 vs. 4.051 ±0.2334, p < 0.05), inflammatory cell infiltration in bronchoalveolar lavage fluid (eosinophils 140.0 ±9.869 vs. 222.4 ±31.55, p < 0.05, neutrophils 75.93 ±6.745 vs. 127.4 ±19.73, p < 0.05), airway inflammation and mucus secretion. Treatment with anti-IL-23 antibody also markedly reduced IL-17 level (398.1 ±28.74 vs. 590.6 ±36.13, p < 0.01) and percentage of Th17 and Tc17 cells in lung tissue homogenate (4.200 ±0.1581 vs. 9.314 ±1.027, p < 0.01 and 2.852 ±0.2566 vs. 5.588 ±0.3631, p < 0.01, Th17 and Tc17 cells respectively). Our data suggest that the IL-23/Tc17 cell axis may be involved in the pathogenesis of asthma as the complement of IL-23/Th17 cells.

  2. Bi-atrial fibrosis detected using three-dimensional late gadolinium enhancement magnetic resonance imaging in a patient with cardiac sarcoidosis.

    PubMed

    Spence, Stewart; Pena, Elena; Thornhill, Rebecca E; Nery, Pablo B; Birnie, David H

    2018-05-01

    Presented is the case of a 62-year old male with a history of sarcoidosis and sinus node dysfunction, who underwent late gadolinium enhancement magnetic resonance imaging, which demonstrated left ventricular hyperenhancement and bi-atrial fibrosis.

  3. Synthesis of Tumor-avid Photosensitizer-Gd(III)DTPA conjugates: impact of the number of gadolinium units in T1/T2 relaxivity, intracellular localization, and photosensitizing efficacy.

    PubMed

    Goswami, Lalit N; White, William H; Spernyak, Joseph A; Ethirajan, Manivannan; Chen, Yihui; Missert, Joseph R; Morgan, Janet; Mazurchuk, Richard; Pandey, Ravindra K

    2010-05-19

    To develop novel bifunctional agents for tumor imaging (MR) and photodynamic therapy (PDT), certain tumor-avid photosensitizers derived from chlorophyll-a were conjugated with variable number of Gd(III)aminobenzyl DTPA moieties. All the conjugates containing three or six gadolinium units showed significant T(1) and T(2) relaxivities. However, as a bifunctional agent, the 3-(1'-hexyloxyethyl)pyropheophorbide-a (HPPH) containing 3Gd(III) aminophenyl DTPA was most promising with possible applications in tumor-imaging and PDT. Compared to HPPH, the corresponding 3- and 6Gd(III)aminobenzyl DTPA conjugates exhibited similar electronic absorption characteristics with a slightly decreased intensity of the absorption band at 660 nm. However, compared to HPPH, the excitation of the broad "Soret" band (near 400 nm) of the corresponding 3Gd(III)aminobenzyl-DTPA analogues showed a significant decrease in the fluorescence intensity at 667 nm.

  4. [The relationship between corneal lymphangiogenesis and inflammation index after corneal alkali injury].

    PubMed

    Ling, Shi-qi; Li, Wei-hua; Xu, Jian-gang; Kuang, Wen-hui; Li, Chao-yang

    2010-11-01

    To discuss the relationship between corneal lymphangiogenesis and inflammation index (IF) in alkali burned corneas. Experimental research. Rat corneal hemangiogenesis and lymphangiogenesis were examined by 5'-nase-alkaline phosphatase (5'-NA-ALP) double enzyme-histochemistry and whole mount immunofluorescence at 1 day, 3 days, and 1, 2, 3, 4, 5, 6, 7, 8 weeks after alkaline burns, and the blood vessel counting (BVC) and the lymphatic vessel counting (LVC) were recorded. The state of corneal inflammation was observed under the slit lamp and evaluated by inflammation index (IF) grading at the same time. Then, the association of LVC with IF was examined. In addition, eleven human alkali burned corneas were obtained from 11 patients undergoing corneal transplantation in Zhongshan Ophthalmic Center from January 2005 to June 2008. Corneal lymphangiogenesis was examined by lymphatic vessel endothelial receptor (LYVE-1) immunohistochemistry. The significance of the differences in IF, inflammatory cells counting, burn history, and age between two groups was analyzed by using paired student's t-test. New lymphatic vessels were present in rat alkali burned corneas. Corneal lymphangiogenesis developed 3 days after alkaline burns, reached the top 2 weeks after the injury, then decreased gradually, and disappeared at the end of the 5th week. Corneal lymphatics occurred behind corneal inflammation, but disappeared before corneal inflammation and hemangiogenesis. LVC was strongly and positively correlated with IF (r = 0.572, P < 0.01) after corneal alkaline burns. Among eleven human alkali burned corneas, corneal lymphatic vessels were present in 3 corneas. Compared with the other 8 cases without corneal lymphangiogenesis, the scores of IF was significantly higher (t = 3.28, P < 0.05), the inflammatory cells counting dramatically increased (t = 2.42, P < 0.05), but the age decreased significantly (t = 2.62, P < 0.05). However, the difference in burn history between two groups was

  5. Inflammation-induced preterm lung maturation: lessons from animal experimentation.

    PubMed

    Moss, Timothy J M; Westover, Alana J

    2017-06-01

    Intrauterine inflammation, or chorioamnionitis, is a major contributor to preterm birth. Prematurity per se is associated with considerable morbidity and mortality resulting from lung immaturity but exposure to chorioamnionitis reduces the risk of neonatal respiratory distress syndrome (RDS) in preterm infants. Animal experiments have identified that an increase in pulmonary surfactant production by the preterm lungs likely underlies this decreased risk of RDS in infants exposed to chorioamnionitis. Further animal experimentation has shown that infectious or inflammatory agents in amniotic fluid exert their effects on lung development by direct effects within the developing respiratory tract, and probably not by systemic pathways. Differences in the effects of intrauterine inflammation and glucocorticoids demonstrate that canonical glucocorticoid-mediated lung maturation is not responsible for inflammation-induced changes in lung development. Animal experimentation is identifying alternative lung maturational pathways, and transgenic animals and cell culture techniques will allow identification of novel mechanisms of lung maturation that may lead to new treatments for the prevention of RDS. Copyright © 2016. Published by Elsevier Ltd.

  6. Cannabinoids mediate opposing effects on inflammation-induced intestinal permeability

    PubMed Central

    Alhamoruni, A; Wright, KL; Larvin, M; O'Sullivan, SE

    2012-01-01

    BACKGROUND AND PURPOSE Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion and intestinal motility. The ability to modulate intestinal permeability in inflammation may be important in therapy aimed at maintaining epithelial barrier integrity. The aim of the present study was to determine whether cannabinoids modulate the increased permeability associated with inflammation in vitro. EXPERIMENTAL APPROACH Confluent Caco-2 cell monolayers were treated for 24 h with IFNγ and TNFα (10 ng·mL−1). Monolayer permeability was measured using transepithelial electrical resistance and flux measurements. Cannabinoids were applied either apically or basolaterally after inflammation was established. Potential mechanisms of action were investigated using antagonists for CB1, CB2, TRPV1, PPARγ and PPARα. A role for the endocannabinoid system was established using inhibitors of the synthesis and degradation of endocannabinoids. KEY RESULTS Δ9-Tetrahydrocannabinol (THC) and cannabidiol accelerated the recovery from cytokine-induced increased permeability; an effect sensitive to CB1 receptor antagonism. Anandamide and 2-arachidonylglycerol further increased permeability in the presence of cytokines; this effect was also sensitive to CB1 antagonism. No role for the CB2 receptor was identified in these studies. Co-application of THC, cannabidiol or a CB1 antagonist with the cytokines ameliorated their effect on permeability. Inhibiting the breakdown of endocannabinoids worsened, whereas inhibiting the synthesis of endocannabinoids attenuated, the increased permeability associated with inflammation. CONCLUSIONS AND IMPLICATIONS These findings suggest that locally produced endocannabinoids, acting via CB1 receptors play a role in mediating changes in permeability with inflammation, and that phytocannabinoids have therapeutic potential for reversing the disordered intestinal permeability associated with inflammation. LINKED ARTICLES This

  7. Hypoxia and Mucosal Inflammation

    PubMed Central

    Colgan, Sean P.; Campbell, Eric L.; Kominsky, Douglas J.

    2016-01-01

    Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called “inflammatory hypoxia,” which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2-consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity. PMID:27193451

  8. Burns, inflammation, and intestinal injury: protective effects of an anti-inflammatory resuscitation strategy.

    PubMed

    Costantini, Todd W; Peterson, Carrie Y; Kroll, Lauren; Loomis, William H; Putnam, James G; Wolf, Paul; Eliceiri, Brian P; Baird, Andrew; Bansal, Vishal; Coimbra, Raul

    2009-12-01

    Intestinal barrier breakdown after severe burn can lead to intestinal inflammation, which may act as the source of the systemic inflammatory response. In vitro intestinal cell studies have shown that mitogen-activated protein kinase (MAPK) signaling is an important modulator of intestinal inflammation. We have previously observed that pentoxifylline (PTX) attenuates burn-induced intestinal permeability and tight junction breakdown. We hypothesized that PTX would limit intestinal barrier breakdown and attenuate inflammatory signaling via the MAPK pathway. Male balb/c mice underwent 30% total body surface area full-thickness steam burn. Immediately after burn, animals received an intraperitoneal injection of PTX (12.5 mg/kg) in normal saline or normal saline alone. In vivo intestinal permeability to 4 kDa fluorescein isothiocyanate-dextran was measured. Intestinal extracts were obtained to measure interleukin-6 by enzyme-linked immunosorbent assay, and phosphorylated p38 MAPK, p38 MAPK, phosphorylated extracellular signal-related kinase (1/2) (ERK (1/2)), and ERK (1/2) by immunoblotting. Acute lung injury was assessed by histology at 24 hours after burn. Administration of PTX immediately after injury attenuated burn-induced intestinal permeability. PTX also decreased the burn-induced phosphorylation of p38 MAPK and decreased phosphorylation of ERK (1/2) at 2 hours and 24 hours after injury. Animals given PTX had decreased intestinal interleukin-6 levels. A single dose of PTX also decreased histologic lung injury at 24 hours after burn. PTX attenuates burn-induced intestinal permeability and subsequent intestinal inflammation. Use of PTX after burn was also associated with decreased acute lung injury. Because of its compelling anti-inflammatory effects, PTX may be an ideal candidate for use as an immunomodulatory adjunct to resuscitation fluid.

  9. Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

    DOE PAGES

    Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.; ...

    2018-03-13

    Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

  10. Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.

    Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

  11. [Combined use of contrast media containing iodine and gadolinium for imaging and intervention : A hitherto widely ignored topic in radiological practice].

    PubMed

    Golder, W

    2012-02-01

    The synchronous use of chemically different contrast media in the same body compartment is a challenge for the radiologist, whether it is scheduled or unexpected. However, to inject contrast media containing iodine and gadolinium at the same time can be a prerequisite for the examination of several organs or organ systems. Unlike other topics of contrast-enhanced imaging procedures, the difficulties encountered with double contrast injections have been widely ignored in the literature. In the absence of reliable data from experimental and clinical studies the radiologist is dependent on case reports, information provided by the contrast media manufacturers, personal communications, mostly scanty personal experiences and a skilful time management, in order to overcome the situation. Only the combination of X-ray, computed tomography and magnetic resonance arthrography can be performed without another thought. However, the more or less synchronous vascular application of contrast media containing iodine and gadolinium requires vigilance. The more seriously ill the patient is, the more caution is advised even if the decision on the combined administration has to be reached urgently. The following overview gives a description of the properties of contrast media containing iodine and gadolinium as far as interactions following simultaneous administration are concerned. Subsequently, the clinically relevant situations and constellations are outlined and analyzed.

  12. Rapid colorimetric sensing of gadolinium by EGCG-derived AgNPs: the development of a nanohybrid bioimaging probe.

    PubMed

    Singh, Rohit Kumar; Mishra, Sourav; Jena, Satyapriya; Panigrahi, Bijayananda; Das, Bhaskar; Jayabalan, Rasu; Parhi, Pankaj Kumar; Mandal, Dindyal

    2018-04-17

    Polyphenol functionalized silver nanoparticles (AgNPs) have been developed and demonstrated as colorimetric sensors for the selective detection of gadolinium. The newly obtained AgNP-Gd3+ conjugates exhibit high aqueous dispersibility and excitation dependent fluorescence emission. The conjugates offer multicolor bioimaging potential owing to their excellent luminescence properties.

  13. FABP4 inhibitor BMS309403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation.

    PubMed

    Bosquet, Alba; Girona, Josefa; Guaita-Esteruelas, Sandra; Heras, Mercedes; Saavedra-García, Paula; Martínez-Micaelo, Neus; Masana, Lluís; Rodríguez-Calvo, Ricardo

    2018-06-01

    Fatty acid binding protein 4 (FABP4) inhibitors have been proposed as potential therapeutic approaches against insulin resistance-related inflammation and type 2 diabetes mellitus. However, the underlying molecular mechanisms by which these molecules drive these effects in skeletal muscle remain unknown. Here, we assessed whether the FABP4 inhibitor BMS309403 prevented lipid-induced endoplasmic reticulum (ER) stress-associated inflammation in skeletal muscle. The BMS309403 treatment was assessed both in the skeletal muscle of high-fat diet (HFD)-fed mice and in palmitate-stimulated C2C12 myotubes. HFD feeding promoted insulin resistance, which is characterized by increased plasma levels of glucose, insulin, non-esterified fatty acids, triglycerides, resistin, and leptin and reduced plasma levels of adiponectin compared with control mice fed a standard diet. Additionally, insulin-resistant animals showed increased FABP4 plasma levels. In line with this evidence, recombinant FABP4 attenuated the insulin-induced AKT phosphorylation in C2C12 myotubes. Treatment with BMS309403 reduced lipid-induced ER stress and inflammation in both mouse skeletal muscle and C2C12 myotubes. The effects of the FABP4 inhibitor reducing lipid-induced ER stress-associated inflammation were related to the reduction of fatty acid-induced intramyocellular lipid deposits, ROS and nuclear factor-kappaB (NF-κB) nuclear translocation. Accordingly, BMS309403 reduced lipid-induced p38 MAPK phosphorylation, which is upstream of NF-κB activation. Overall, these findings indicate that BMS309403 reduces fatty acid-induced ER stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Chronic inflammation potentiates kidney aging.

    PubMed

    Mei, Changlin; Zheng, Feng

    2009-11-01

    Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-alpha, interleukin-6, C-reactive protein, and plasminogen activator inhibitor-1, and the presence of inflammatory-related diseases, are seen commonly in aging. Both the dysregulation of immune cells and phenotypic changes in parenchymal cells may contribute to chronic inflammation in aging. Moreover, senescent cells are an important source of inflammatory factors. Oxidative stress, via activation of p38 and c-Jun N-terminal kinase and induction of cell senescence, is likely to play a critical role in inflammation. Endoplasmic reticulum stress also may be present in aging and be involved in inflammation. Advanced glycation end products also are important contributors to inflammation in aging. Because the kidney is a major site for the excretion, and perhaps the degradation, of advanced glycation end products and small inflammatory molecules, reduced renal function in aging may promote oxidative stress and inflammation. Chronic inflammation in turn may potentiate the initiation and progression of lesions in the aging kidney.

  15. Insulin Sensitivity and Inflammation Mediate the Impact of Fitness on Cerebrovascular Health in Adolescents.

    PubMed

    Yau, Po Lai; Ross, Naima; Tirsi, Andrew; Arif, Arslan; Ozinci, Zeynep; Convit, Antonio

    2017-06-01

    To investigate in adolescents the relationships between retinal vessel diameter, physical fitness, insulin sensitivity, and systemic inflammation. We evaluated 157 adolescents, 112 with excessive weight and 45 lean, all without type 2 diabetes mellitus. All received detailed evaluations, including measurements of retinal vessel diameter, insulin sensitivity, levels of inflammation, and physical fitness. Overweight/obese adolescents had significantly narrower retinal arteriolar and wider venular diameters, significantly lower insulin sensitivity, and physical fitness. They also had decreased levels of anti-inflammatory and increased levels of proinflammatory markers as well as an overall higher inflammation balance score. Fitness was associated with larger retinal arteriolar and narrower venular diameters and these relationships were mediated by insulin sensitivity. We demonstrate that inflammation also mediates the relationship between fitness and retinal venular, but not arterial diameter; insulin sensitivity and inflammation balance score jointly mediate this relationship with little overlap in their effects. Increasing fitness and insulin sensitivity and reducing inflammation among adolescents carrying excess weight may improve microvascular integrity. Interventions to improve physical fitness and insulin function and reduce inflammation in adolescents, a group likely to benefit from such interventions, may reduce not only cardiovascular disease in middle age, but also improve cerebrovascular function later in life.

  16. α-Galacto-oligosaccharides Dose-Dependently Reduce Appetite and Decrease Inflammation in Overweight Adults.

    PubMed

    Morel, Fanny B; Dai, Qiuping; Ni, Jiayi; Thomas, Doneal; Parnet, Patricia; Fança-Berthon, Pascale

    2015-09-01

    Dietary fibers have been associated with a reduction in appetite and energy intake. Although a few studies suggest that nonviscous fibers can exert such effects, likely through colonic fermentation, limited data are available. The objective of this study was to determine whether α-galacto-oligosaccharides (α-GOSs), fermentable soluble fibers extracted from legumes, could reduce appetite, food intake, and inflammation in overweight subjects. In 2 single-center, double-blind, randomized, placebo-controlled trials, 88 overweight adults [50% men and 50% women; 18-60 y old; body mass index (in kg/m(2)): 25-28] were supplemented for 14 d with tea that contained α-GOSs with different α-GOS dosages (6, 12, or 18 g α-GOSs/d), formulas (12 g α-GOSs/d with >80% of molecules with a degree of polymerization of 2, 3, or 4), or a control substance (glucose syrup). Appetite scores (5 appetite dimensions were assessed on visual analog scales during a preload test meal), food intake (test meal and 24-h food recall), and inflammatory markers [plasma lipopolysaccharide (LPS) and C-reactive protein (CRP)] were evaluated at day 0 (baseline) and day 15. Changes in appetite scores from day 0 to day 15 were significantly higher after α-GOS intake, with areas under the curve for the satiety score of +121 ± 108, +218 ± 218, and +306 ± 205 score · min for 6, 12, and 18 g α-GOSs/d, respectively, and -5 ± 64 score · min for the control group. We observed dose-dependent effects that did not vary by α-GOS composition. The administration of 6, 12, or 18 g α-GOSs/d significantly and dose-dependently increased the change in energy intake from day 0 to day 15 during a test meal (-13 ± 19, -26 ± 22, and -32 ± 22 kcal, respectively; +6 ± 21 kcal for the control group). Reductions in energy intake during lunch and dinner were also higher in the α-GOS groups in the dose-effect study. At day 15, LPS was dose-dependently reduced without an association with α-GOS composition (0.16 ± 0

  17. A first principles kinetic Monte Carlo investigation of the adsorption and mobility of gadolinium on the (100) surface of tungsten

    NASA Astrophysics Data System (ADS)

    Samin, Adib J.; Zhang, Jinsuo

    2017-05-01

    An accurate characterization of lanthanide adsorption and mobility on tungsten surfaces is important for pyroprocessing. In the present study, the adsorption and diffusion of gadolinium on the (100) surface of tungsten was investigated. It was found that the hollow sites were the most energetically favorable for the adsorption. It was further observed that a magnetic moment was induced following the adsorption of gadolinium on the tungsten surface and that the system with adsorbed hollow sites had the largest magnetization. A pathway for the surface diffusion of gadolinium was determined to occur by hopping between the nearest neighbor hollow sites via the bridge site and the activation energy for the hop was calculated to be 0.75 eV. The surface diffusion process was further assessed using two distinct kinetic Monte Carlo models; one that accounted for lateral adsorbate interactions up to the second nearest neighbor and one that did not account for such interatomic interactions in the adlayer. When the lateral interactions were included in the simulations, the diffusivity was observed to have a strong dependence on coverage (for the coverage values being studied). The effects of lateral interactions were further observed in a one-dimensional simulation of the diffusion equation where the asymmetry in the surface coverage profile upon its approach to a steady state distribution was clear in comparison with the simulations which did not account for those interactions.

  18. G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production.

    PubMed

    Queto, Túlio; Vasconcelos, Zilton F M; Luz, Ricardo Alves; Anselmo, Carina; Guiné, Ana Amélia A; e Silva, Patricia Machado R; Farache, Júlia; Cunha, José Marcos T; Bonomo, Adriana C; Gaspar-Elsas, Maria Ignez C; Xavier-Elsas, Pedro

    2011-05-09

    Granulocyte Colony-Stimulating Factor (G-CSF), which mobilizes hemopoietic stem cells (HSC), is believed to protect HSC graft recipients from graft-versus-host disease by enhancing Th2 cytokine secretion. Accordingly, G-CSF should aggravate Th2-dependent allergic pulmonary inflammation and the associated eosinophilia. We evaluated the effects of G-CSF in a model of allergic pulmonary inflammation. Allergic pulmonary inflammation was induced by repeated aerosol allergen challenge in ovalbumin-sensitized C57BL/6J mice. The effects of allergen challenge and of G-CSF pretreatment were evaluated by monitoring: a) eosinophilia and cytokine/chemokine content of bronchoalveolar lavage fluid, pulmonary interstitium, and blood; b) changes in airway resistance; and c) changes in bone-marrow eosinophil production. Contrary to expectations, G-CSF pretreatment neither induced nor enhanced allergic pulmonary inflammation. Instead, G-CSF: a) suppressed accumulation of infiltrating eosinophils in bronchoalveolar, peribronchial and perivascular spaces of challenged lungs; and b) prevented ovalbumin challenge-induced rises in airway resistance. G-CSF had multiple regulatory effects on cytokine and chemokine production: in bronchoalveolar lavage fluid, levels of IL-1 and IL-12 (p40), eotaxin and MIP-1a were decreased; in plasma, KC, a neutrophil chemoattractant, was increased, while IL-5 was decreased and eotaxin was unaffected. In bone-marrow, G-CSF: a) prevented the increase in bone-marrow eosinophil production induced by ovalbumin challenge of sensitized mice; and b) selectively stimulated neutrophil colony formation. These observations challenge the view that G-CSF deviates cytokine production towards a Th2 profile in vivo, and suggest that this neutrophil-selective hemopoietin affects eosinophilic inflammation by a combination of effects on lung cytokine production and bone-marrow hemopoiesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Glucocorticosteroids associated with a decreased risk of psychosis.

    PubMed

    Laan, Wijnand; Smeets, Hugo; de Wit, Niek J; Kahn, René S; Grobbee, Diederick E; Burger, Huibert

    2009-06-01

    The hypothesis that chronic inflammation may play a role in psychosis receives increasing attention. In this study, we aim to investigate whether the use of steroidal anti-inflammatory drugs is associated with a decreased risk of psychosis.A longitudinal nested case-control study was performed investigating the association of glucocorticosteroid (GCS) consumption with a new diagnosis of a psychotic disorder. Significantly reduced odds ratios of 0.52 (95% confidence interval, 0.36-0.75) were found for GCS in men only (odds ratio in women, 0.84 [95% confidence interval, 0.590-1.20]). Similar risk reductions were present for the inhaled and systemic GCSs. A dose-response relationship was present. Our finding of an inverse relation between GCS consumption and new psychotic episodes may promote further research into inflammation in schizophrenia.

  20. Exercise protects against high-fat diet-induced hypothalamic inflammation.

    PubMed

    Yi, Chun-Xia; Al-Massadi, Omar; Donelan, Elizabeth; Lehti, Maarit; Weber, Jon; Ress, Chandler; Trivedi, Chitrang; Müller, Timo D; Woods, Stephen C; Hofmann, Susanna M

    2012-06-25

    Hypothalamic inflammation is a potentially important process in the pathogenesis of high-fat diet-induced metabolic disorders that has recently received significant attention. Microglia are macrophage-like cells of the central nervous system which are activated by pro-inflammatory signals causing local production of specific interleukins and cytokines, and these in turn may further promote systemic metabolic disease. Whether or how this microglial activation can be averted or reversed is unknown. Since running exercise improves systemic metabolic health and has been found to promote neuronal survival as well as the recovery of brain functions after injury, we hypothesized that regular treadmill running may blunt the effect of western diet on hypothalamic inflammation. Using low-density lipoprotein receptor deficient (l dlr-/-) mice to better reflect human lipid metabolism, we first confirmed that microglial activation in the hypothalamus is severely increased upon exposure to a high-fat, or "western", diet. Moderate, but regular, treadmill running exercise markedly decreased hypothalamic inflammation in these mice. Furthermore, the observed decline in microglial activation was associated with an improvement of glucose tolerance. Our findings support the hypothesis that hypothalamic inflammation can be reversed by exercise and suggest that interventions to avert or reverse neuronal damage may offer relevant potential in obesity treatment and prevention. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Immunotoxicity and environment: immunodysregulation and systemic inflammation in children.

    PubMed

    Calderón-Garcidueñas, Lilian; Macías-Parra, Mercedes; Hoffmann, Hans J; Valencia-Salazar, Gildardo; Henríquez-Roldán, Carlos; Osnaya, Norma; Monte, Ofelia Camacho-Del; Barragán-Mejía, Gerardo; Villarreal-Calderon, Rodolfo; Romero, Lina; Granada-Macías, Margarita; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Maronpot, Robert R

    2009-02-01

    Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis that exposure to severe air pollution plays a role in the immune responses of asymptomatic, apparently healthy children. Blood measurements for markers of immune function, inflammatory mediators, and molecules interacting with the lipopolysaccharide recognition complex were obtained from two cohorts of matched children (aged 9.7 +/- 1.2 years) from southwest Mexico City (SWMC) (n = 66) and from a control city (n = 93) with criteria pollutant levels below current standards. MC children exhibited significant decreases in the numbers of natural killer cells (p = .003) and increased numbers of mCD14+ monocytes (p < .001) and CD8+ cells (p = .02). Lower concentrations of interferon gamma (p = .009) and granulocyte-macrophage colony-stimulating factor (p < .001), an endotoxin tolerance-like state, systemic inflammation, and an anti-inflammatory response were also present in the highly exposed children. C-reactive protein and the prostaglandin E metabolite levels were positively correlated with twenty-four- and forty-eight-hour cumulative concentrations of PM(2.5). Exposure to urban air pollution is associated with immunodysregulation and systemic inflammation in children and is a major health threat.

  2. The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

    PubMed Central

    Sancey, L; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

    2014-01-01

    A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

  3. Osthole attenuates the development of carrageenan-induced lung inflammation in rats.

    PubMed

    Li, Zhipeng; Ji, Haijie; Song, Xiuyun; Hu, Jinfeng; Han, Ning; Chen, Naihong

    2014-05-01

    Osthole has been reported to possess a variety of pharmacological activities, such as antiinflammatory effect. In the present study, we have investigated the effect of osthole on lung inflammation associated with carrageenan-induced pleurisy in rats. The result showed that osthole could inhibit significantly pleural exudates formation and PMNs infiltration. Histological examination revealed osthole could reduce lung inflammation in rats treated with carrageenan. The myeloperoxidase (MPO) level was examined in pleural exudates. The result showed that osthole could attenuate MPO level in pleural exudates. Further studies showed osthole could decrease tumor necrosis factor alpha (TNF-α) and interleukin 1beta (IL-1β) levels in the lungs. Taken together, the present results suggested that osthole could inhibit lung inflammation on carrageenan-induced pleurisy in rats and that could be related to a reduction of PMNs infiltration and release of inflammatory factors. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Systemic inflammation, heart rate variability and air pollution in a cohort of senior adults

    PubMed Central

    Luttmann-Gibson, Heike; Suh, Helen H; Coull, Brent A; Dockery, Douglas W; Sarnat, Stefanie Ebelt; Schwartz, Joel; Stone, Peter H; Gold, Diane R

    2015-01-01

    Objectives Short-term elevation of ambient particulate air pollution has been associated with autonomic dysfunction and increased systemic inflammation, but the interconnections between these pathways are not well understood. We examined the association between inflammation and autonomic dysfunction and effect modification of inflammation on the association between air pollution and heart rate variability (HRV) in elderly subjects. Methods 25 elderly subjects in Steubenville, Ohio, were followed up to 24 times with repeated 30-min ECG Holter monitoring (545 observations). C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble inter-cellular adhesion molecule 1 (sICAM-1), and white blood cell and platelet counts were measured in peripheral blood samples collected in the first month of the study. Increased systemic inflammation was defined for subjects within the upper 20% of the distribution for each marker. A central ambient monitoring station provided daily fine particle (PM2.5) and sulphate (SO42−) data. Linear mixed models were used to identify associations between inflammatory markers and HRV and to assess effect modification of the association between air pollution and HRV due to inflammatory status. Results A 5.8 mg/l elevation in CRP was associated with decreases of between −8% and −33% for time and frequency domain HRV outcomes. A 5.1 μg/m3 increase in SO42− on the day before the health assessment was associated with a decrease of −6.7% in the SD of normal RR intervals (SDNN) (95% CI −11.8% to −1.3%) in subjects with elevated CRP, but not in subjects with lower CRP (p value interaction=0.04), with similar findings for PM2.5. Conclusions Increased systemic inflammation is associated with autonomic dysfunction in the elderly. Air pollution effects on reduced SDNN are stronger in subjects with elevated systemic inflammation. PMID:20519749

  5. Systemic inflammation, heart rate variability and air pollution in a cohort of senior adults.

    PubMed

    Luttmann-Gibson, Heike; Suh, Helen H; Coull, Brent A; Dockery, Douglas W; Sarnat, Stefanie Ebelt; Schwartz, Joel; Stone, Peter H; Gold, Diane R

    2010-09-01

    Short-term elevation of ambient particulate air pollution has been associated with autonomic dysfunction and increased systemic inflammation, but the interconnections between these pathways are not well understood. We examined the association between inflammation and autonomic dysfunction and effect modification of inflammation on the association between air pollution and heart rate variability (HRV) in elderly subjects. 25 elderly subjects in Steubenville, Ohio, were followed up to 24 times with repeated 30-min ECG Holter monitoring (545 observations). C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble inter-cellular adhesion molecule 1 (sICAM-1), and white blood cell and platelet counts were measured in peripheral blood samples collected in the first month of the study. Increased systemic inflammation was defined for subjects within the upper 20% of the distribution for each marker. A central ambient monitoring station provided daily fine particle (PM(2.5)) and sulphate (SO(4)(2-)) data. Linear mixed models were used to identify associations between inflammatory markers and HRV and to assess effect modification of the association between air pollution and HRV due to inflammatory status. A 5.8 mg/l elevation in CRP was associated with decreases of between -8% and -33% for time and frequency domain HRV outcomes. A 5.1 microg/m(3) increase in SO(4)(2-) on the day before the health assessment was associated with a decrease of -6.7% in the SD of normal RR intervals (SDNN) (95% CI -11.8% to -1.3%) in subjects with elevated CRP, but not in subjects with lower CRP (p value interaction=0.04), with similar findings for PM(2.5). Increased systemic inflammation is associated with autonomic dysfunction in the elderly. Air pollution effects on reduced SDNN are stronger in subjects with elevated systemic inflammation.

  6. Role of inflammation in the aging bones.

    PubMed

    Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F

    2015-02-15

    Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

    PubMed

    Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

    2017-07-01

    Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

  8. Semaphorin 4C Protects against Allergic Inflammation: Requirement of Regulatory CD138+ Plasma Cells.

    PubMed

    Xue, Di; Kaufman, Gabriel N; Dembele, Marieme; Beland, Marianne; Massoud, Amir H; Mindt, Barbara C; Fiter, Ryan; Fixman, Elizabeth D; Martin, James G; Friedel, Roland H; Divangahi, Maziar; Fritz, Jörg H; Mazer, Bruce D

    2017-01-01

    The regulatory properties of B cells have been studied in autoimmune diseases; however, their role in allergic diseases is poorly understood. We demonstrate that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial role in B cell regulatory function. Mice deficient in Sema4C exhibited increased airway inflammation after allergen exposure, with massive eosinophilic lung infiltrates and increased Th2 cytokines. This phenotype was reproduced by mixed bone marrow chimeric mice with Sema4C deficient only in B cells, indicating that B lymphocytes were the key cells affected by the absence of Sema4C expression in allergic inflammation. We determined that Sema4C-deficient CD19 + CD138 + cells exhibited decreased IL-10 and increased IL-4 expression in vivo and in vitro. Adoptive transfer of Sema4c -/- CD19 + CD138 + cells induced marked pulmonary inflammation, eosinophilia, and increased bronchoalveolar lavage fluid IL-4 and IL-5, whereas adoptive transfer of wild-type CD19 + CD138 + IL-10 + cells dramatically decreased allergic airway inflammation in wild-type and Sema4c -/- mice. This study identifies a novel pathway by which Th2-mediated immune responses are regulated. It highlights the importance of plasma cells as regulatory cells in allergic inflammation and suggests that CD138 + B cells contribute to cytokine balance and are important for maintenance of immune homeostasis in allergic airways disease. Furthermore, we demonstrate that Sema4C is critical for optimal regulatory cytokine production in CD138 + B cells. Copyright © 2016 by The American Association of Immunologists, Inc.

  9. Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice.

    PubMed

    Yamada, Tomomi; Obata, Atsushi; Kashiwagi, Yuto; Rokugawa, Takemi; Matsushima, Shuuichi; Hamada, Tadateru; Watabe, Hiroshi; Abe, Kohji

    2016-07-01

    The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Twenty male C57/BL6 mice aged 8weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (Tmax) and half-life of elimination RE (T1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6weeks, but significant fibrosis was observed only in mice fed MCD for 6weeks. Gd-EOB-DTPA-enhanced MRI showed that Tmax was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0±0.7min; MCD 6w, 12.1±1.6min), although there was no alteration in the 2- and 4-week groups. T1/2 was significantly prolonged in mice fed MCD for 4 and 6weeks compared to the control group (control, 19.9±2.0min; MCD 4w, 46.7±8.7min; MCD 6w, 65.4±8.8min). The parameters of Gd-EOB-DTPA kinetics (Tmax and T1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs Tmax, rho=0.69, P=0.0007; inflammation vs Tmax, rho=0.66, P=0.00155; steatosis vs T1/2, rho=0.77, P<0.0001; inflammation vs T1/2, rho=0.73, P=0.0003). The liver kinetics of Gd-EOB-DTPA correlated well with the inflammation score in the mouse model of NASH, suggesting the possibility of

  10. Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoyong; Zhou, Zijian; Wang, Zhiyong; Xue, Yunxin; Zeng, Yun; Gao, Jinhao; Zhu, Lei; Zhang, Xianzhong; Liu, Gang; Chen, Xiaoyuan

    2013-08-01

    This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability.This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02797j

  11. Identification of a selective glucocorticoid receptor modulator that prevents both diet-induced obesity and inflammation.

    PubMed

    van den Heuvel, José K; Boon, Mariëtte R; van Hengel, Ingmar; Peschier-van der Put, Emma; van Beek, Lianne; van Harmelen, Vanessa; van Dijk, Ko Willems; Pereira, Alberto M; Hunt, Hazel; Belanoff, Joseph K; Rensen, Patrick C N; Meijer, Onno C

    2016-06-01

    High-fat diet consumption results in obesity and chronic low-grade inflammation in adipose tissue. Whereas glucocorticoid receptor (GR) antagonism reduces diet-induced obesity, GR agonism reduces inflammation, the combination of which would be desired in a strategy to combat the metabolic syndrome. The purpose of this study was to assess the beneficial effects of the selective GR modulator C108297 on both diet-induced weight gain and inflammation in mice and to elucidate underlying mechanisms. Ten-week-old C57Bl/6 J mice were fed a high-fat diet for 4 weeks while being treated with the selective GR modulator C108297, a full GR antagonist (RU486/mifepristone) or vehicle. C108297 and, to a lesser extent, mifepristone reduced body weight gain and fat mass. C108297 decreased food and fructose intake and increased lipolysis in white adipose tissue (WAT) and free fatty acid levels in plasma, resulting in decreased fat cell size and increased fatty acid oxidation. Furthermore, C108297 reduced macrophage infiltration and pro-inflammatory cytokine expression in WAT, as well as in vitro LPS-stimulated TNF-α secretion in macrophage RAW 264.7 cells. However, mifepristone also increased energy expenditure, as measured by fully automatic metabolic cages, and enhanced expression of thermogenic markers in energy-combusting brown adipose tissue (BAT) but did not affect inflammation. C108297 attenuates obesity by reducing caloric intake and increasing lipolysis and fat oxidation, and in addition attenuates inflammation. These data suggest that selective GR modulation may be a viable strategy for the reduction of diet-induced obesity and inflammation. © 2016 The British Pharmacological Society.

  12. Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation.

    PubMed

    Han, Claudia Z; Juncadella, Ignacio J; Kinchen, Jason M; Buckley, Monica W; Klibanov, Alexander L; Dryden, Kelly; Onengut-Gumuscu, Suna; Erdbrügger, Uta; Turner, Stephen D; Shim, Yun M; Tung, Kenneth S; Ravichandran, Kodi S

    2016-11-24

    Professional phagocytes (such as macrophages) and non-professional phagocytes (such as epithelial cells) clear billions of apoptotic cells and particles on a daily basis. Although professional and non-professional macrophages reside in proximity in most tissues, whether they communicate with each other during cell clearance, and how this might affect inflammation, is not known. Here we show that macrophages, through the release of a soluble growth factor and microvesicles, alter the type of particles engulfed by non-professional phagocytes and influence their inflammatory response. During phagocytosis of apoptotic cells or in response to inflammation-associated cytokines, macrophages released insulin-like growth factor 1 (IGF-1). The binding of IGF-1 to its receptor on non-professional phagocytes redirected their phagocytosis, such that uptake of larger apoptotic cells was reduced whereas engulfment of microvesicles was increased. IGF-1 did not alter engulfment by macrophages. Macrophages also released microvesicles, whose uptake by epithelial cells was enhanced by IGF-1 and led to decreased inflammatory responses by epithelial cells. Consistent with these observations, deletion of IGF-1 receptor in airway epithelial cells led to exacerbated lung inflammation after allergen exposure. These genetic and functional studies reveal that IGF-1- and microvesicle-dependent communication between macrophages and epithelial cells can critically influence the magnitude of tissue inflammation in vivo.

  13. Effects of Zanthoxylum piperitum ethanol extract on osteoarthritis inflammation and pain.

    PubMed

    Hwang, Kyung-A; Kwon, Jeong Eun; Noh, YooHun; Park, BongKyun; Jeong, Yong Joon; Lee, Sun-Mee; Kim, Se-Young; Kim, InHye; Kang, Se Chan

    2018-06-05

    Degenerative arthritis, also known as osteoarthritis (OA), is the most common type of arthritis, which is caused by degenerative damage of the cartilage, which primarily protects the joints, leading to inflammation and pain. The objective of this study was to investigate the in vivo and in vitro effects of treatment with ZPE-LR (90% EtOH extract of Zanthoxylum piperitum) on pain severity and inflammation. When using an in vivo OA model MIA (monosodiumidoacetate-induced arthritis) rats, ZPE-LR (100 mg/kg) oral-administratio significantly inhibited MIA-induced change in loaded weight ratio on the left foot, and articular cartilage thickness. To confirm the positive effects on pain relief, acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. Pain related KCNJ6 mRNA expression as well as K + current was increased after ZPE-LR treatment in BV-2 cells. To confirm the positive effects on inflammation, TPA (12-O-tetradecanoylphorbol-13-acetate) induced inflammation measured by mouse ear thickness and biopsy punch weight and TPA-induced iNOS, COX-2 mRNA and protein expression were remarkably suppressed by 50 and 100 mg/kg ZPE-LR oral-administration. In addition, TPA-induced iNOS, COX-2 mRNA level and protein expression were reduced. Acetic acid, heat and formalin-induced pain were remarkably decreased by 50 and 100 mg/kg ZPE-LR oral-administration. We examined in vitro ZPE-LR effects in LPS-induced RAW 264.7 cells. LPS-induced p65 translocation to the nucleus was prohibited by ZPE-LR 100 μg/ml oral administration. Moreover, ROS generation by LPS was significantly inhibited by ZPE-LR 50 and 100 μg/ml treatment. To investigate new ZPE-LR activating mechanisms, the gene fishing method (not a typical term, should probably use PCR based genetic screening) was used. LPS-induced HPRT1 (hypoxanthine phosphoribosyltransferase 1) was decreased by ZPE-LR. However, RPL8 (Ribosomal protein L8) which

  14. The effect of boron and gadolinium burnable poisons on the hot-to-cold reactivity swing of a pressurized water reactor assembly

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Galperin, A.; Segev, M.; Radkowsky, A.

    1986-11-01

    Control requirements for advanced pressurized water reactor designs must be met with heavy loadings of burnable poison rods, the required reactivity hold-down typically amounting to 30% or more in a poisoned subassembly. Two apparent choices for poisons are natural boron rods and natural gadolinium rods. Studied and analyzed is the effect of these two poisons on the hot-to-cold reactivity upswing. Compared with an upswing of 2.9% in a nonpoisoned assembly, the upswing in the gadolinium-poisoned assembly is 3.0%, and the upswing in the boron-poisoned assembly is 8.8%. Thus the hot-to-cold control penalty is almost nil for the choice of gadoliniummore » and is considerable for the choice of boron.« less

  15. Protective effects of platinum nanoparticles against UV-light-induced epidermal inflammation.

    PubMed

    Yoshihisa, Yoko; Honda, Ayumi; Zhao, Qing-Li; Makino, Teruhiko; Abe, Riichiro; Matsui, Kotaro; Shimizu, Hiroshi; Miyamoto, Yusei; Kondo, Takashi; Shimizu, Tadamichi

    2010-11-01

    Intracellular reactive oxygen species (ROS) and apoptosis play important roles in the ultraviolet (UV)-induced inflammatory responses in the skin. Metal nanoparticles have been developed to increase the catalytic activity of metals, which is because of the large surface area of smaller particles. Platinum nanoparticles (nano-Pt) protected by poly acrylic acid were manufactured by reduction with ethanol. A marked increase in ROS production was observed in UV-treated HaCaT keratinocytes cell lines, while a decrease in ROS production was observed in nano-Pt-treated cells. Pretreatment of the cells with nano-Pt also caused a significant inhibition of UVB- and UVC-induced apoptosis. Furthermore, we found that mice treated with nano-Pt gel prior to UV irradiation showed significant inhibition of UVB-induced inflammation and UVA-induced photoallergy compared to UV-irradiated control mice. These results suggest that nano-Pt effectively protects against UV-induced inflammation by decreasing ROS production and inhibiting apoptosis in keratinocytes. © 2010 John Wiley & Sons A/S.

  16. Microbiota Promotes Chronic Pulmonary Inflammation by Enhancing IL-17A and Autoantibodies.

    PubMed

    Yadava, Koshika; Pattaroni, Céline; Sichelstiel, Anke K; Trompette, Aurélien; Gollwitzer, Eva S; Salami, Olawale; von Garnier, Christophe; Nicod, Laurent P; Marsland, Benjamin J

    2016-05-01

    Changes in the pulmonary microbiota are associated with progressive respiratory diseases including chronic obstructive pulmonary disease (COPD). Whether there is a causal relationship between these changes and disease progression remains unknown. To investigate the link between an altered microbiota and disease, we used a murine model of chronic lung inflammation that is characterized by key pathological features found in COPD and compared responses in specific pathogen-free (SPF) mice and mice depleted of microbiota by antibiotic treatment or devoid of a microbiota (axenic). Mice were challenged with LPS/elastase intranasally over 4 weeks, resulting in a chronically inflamed and damaged lung. The ensuing cellular infiltration, histological damage, and decline in lung function were quantified. Similar to human disease, the composition of the pulmonary microbiota was altered in diseased animals. We found that the microbiota richness and diversity were decreased in LPS/elastase-treated mice, with an increased representation of the genera Pseudomonas and Lactobacillus and a reduction in Prevotella. Moreover, the microbiota was implicated in disease development as mice depleted, or devoid, of microbiota exhibited an improvement in lung function, reduced inflammation, and lymphoid neogenesis. The absence of microbial cues markedly decreased the production of IL-17A, whereas intranasal transfer of fluid enriched with the pulmonary microbiota isolated from diseased mice enhanced IL-17A production in the lungs of antibiotic-treated or axenic recipients. Finally, in mice harboring a microbiota, neutralizing IL-17A dampened inflammation and restored lung function. Collectively, our data indicate that host-microbial cross-talk promotes inflammation and could underlie the chronicity of inflammatory lung diseases.

  17. Obesity-related inflammation & cardiovascular disease: efficacy of a yoga-based lifestyle intervention.

    PubMed

    Sarvottam, Kumar; Yadav, Raj Kumar

    2014-06-01

    Obesity is a global health burden and its prevalence is increasing substantially due to changing lifestyle. Chronic adiposity is associated with metabolic imbalance leading to dyslipidaemia, diabetes, hypertension and cardiovascular diseases (CVD). Adipose tissue acts as an endocrine organ releasing several adipocytokines, and is associated with increased levels of tissue and circulating inflammatory biomolecules causing vascular inflammation and atherogenesis. Further, inflammation is also associated independently with obesity as well as CVD. Keeping this in view, it is possible that a reduction in weight may lead to a decrease in inflammation, resulting in CVD risk reduction, and better management of patients with CVD. Lifestyle intervention has been endorsed by several health authorities in prevention and management of chronic diseases. A yoga-based lifestyle intervention appears to be a promising option in reducing the risk for CVD as well as management of patients with CVD as it is simple to follow and cost-effective with high compliance. The efficacy of such lifestyle intervention programmes is multifaceted, and is achieved via reduction in weight, obesity-related inflammation and stress, thereby culminating into risk reduction towards several chronic diseases including CVD. In this review, the association between obesity-related inflammation and CVD, and the role of yoga-based lifestyle intervention in prevention and management of CVD are discussed.

  18. Inflammation by Breast Implants and Adenocarcinoma: Not Always a Bad Company.

    PubMed

    Orciani, Monia; Sorgentoni, Giulia; Olivieri, Fabiola; Mattioli-Belmonte, Monica; Di Benedetto, Giovanni; Di Primio, Roberto

    2017-07-01

    Inflammation and tumor are now an inseparable binomial. Inflammation may also derive by the use of breast implants followed by the formation of a periprosthetic capsule. It is known that tumor cells, in an inflamed microenvironment, can profit by the paracrine effect exerted also by mesenchymal stem cells (MSCs). Here we evaluated the role of inflammation on the immunobiology of MSCs before and after cocultures with cells derived from breast adenocarcinoma. MSCs derived from both inflamed (I-MSCs) and control (C-MSCs) tissues were isolated and cocultured with MCF7 cells derived from breast adenocarcinoma. Before and after cocultures, the proliferation rate of MCF7 cells and the expression/secretion of cytokines related to inflammation were tested. Before cocultures, higher levels of cytokine related to chronic inflammation were detected in I-MSCs than in C-MSCs. After cocultures with MCF7, C- and I-MSCs show a variation in cytokine production. In detail, IL-2, IL-4, IL-5, IL-10, IL-13, TGF-β and G-CSF were decreased, whereas IL-6, IL-12, IFN-γ, and IL-17 were oversecreted. Proliferation of MCF7 was significantly increased after cocultures with I-MSCs. Inflammation at the site of origin of MSCs affects their immunobiology. Even if tumor cells increased their proliferation rate after cocultures with I-MSCs, the analysis of the cytokines, known to play a role in the interference of tumor cells with the host immune system, absolves completely the breast implants from the insult to enforce the risk of adenocarcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Age-related ventricular-vascular coupling during acute inflammation in humans: Effect of physical activity.

    PubMed

    Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Ranadive, Sushant M; Yan, Huimin; Phillips, Shane; Baynard, Tracy; Woods, Jeffrey A; Motl, Robert; Fernhall, Bo

    2015-07-01

    Aging is commonly accompanied by increased arterial and ventricular stiffness (determined by arterial elastance (Ea) and ventricular elastance (Elv)), augmented ventricular-vascular coupling ratios (Ea/Elv) and systemic inflammation. Acute inflammation may impact ventricular-vascular coupling and predispose older adults to cardiovascular events. However, physically active older adults have more compliant large arteries and left ventricles and lower inflammation than sedentary older adults. We hypothesized that acute inflammation would alter Ea, Elv, and Ea/Elv more in older versus younger adults but that higher levels of physical activity would attenuate inflammation-induced changes. End-systolic and central blood pressures were obtained using applanation tonometry before and at 24 and 48 h post-influenza vaccination in 24 older and 38 younger adults. Ultrasonography was used to measure ventricular volumes and other indices of cardiac performance. Physical activity was measured with accelerometry. Ea and Ea/Elv were maintained (p > 0.05), but Elv was reduced (p < 0.05) 24 h post-inflammation. Other indices of systolic performance were reduced in older but not younger adults; diastolic performance was attenuated in both groups 24 h post-inflammation (p < 0.05 for all). Older, but not younger, adults decreased central pressure during inflammation (p < 0.05). When controlled for age, physical activity was not related to the inflammation-induced changes in elastance (p > 0.05) except in the most active group of seniors (p < 0.05). Aging did not affect the elastance responses but did affect central blood pressure and other ventricular systolic responses to acute inflammation. Aging, not physical activity, appears to modulate cardiovascular responses to acute inflammation, except in the most active older adults. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  20. MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells*

    PubMed Central

    Kwon, Yoojung; Kim, Youngmi; Eom, Sangkyung; Kim, Misun; Park, Deokbum; Kim, Hyuna; Noh, Kyeonga; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

    2015-01-01

    Cyclooxgenase-2 (COX-2) knock-out mouse experiments showed that COX-2 was necessary for in vivo allergic inflammation, such as passive cutaneous anaphylaxis, passive systemic anaphylaxis, and triphasic cutaneous allergic reaction. TargetScan analysis predicted COX-2 as a target of miR-26a and miR-26b. miR-26a/-26b decreased luciferase activity associated with COX-2–3′-UTR. miR-26a/-26b exerted negative effects on the features of in vitro and in vivo allergic inflammation by targeting COX-2. ChIP assays showed the binding of HDAC3 and SNAIL, but not COX-2, to the promoter sequences of miR-26a and miR-26b. Cytokine array analysis showed that the induction of chemokines, such as MIP-2, in the mouse passive systemic anaphylaxis model occurred in a COX-2-dependent manner. ChIP assays showed the binding of HDAC3 and COX-2 to the promoter sequences of MIP-2. In vitro and in vivo allergic inflammation was accompanied by the increased expression of MIP-2. miR-26a/-26b negatively regulated the expression of MIP-2. Allergic inflammation enhanced the tumorigenic and metastatic potential of cancer cells and induced positive feedback involving cancer cells and stromal cells, such as mast cells, macrophages, and endothelial cells. miR-26a mimic and miR-26b mimic negatively regulated the positive feedback between cancer cells and stromal cells and the positive feedback among stromal cells. miR-26a/-26b negatively regulated the enhanced tumorigenic potential by allergic inflammation. COX-2 was necessary for the enhanced metastatic potential of cancer cells by allergic inflammation. Taken together, our results indicate that the miR26a/-26b-COX-2-MIP-2 loop regulates allergic inflammation and the feedback relationship between allergic inflammation and the enhanced tumorigenic and metastatic potential. PMID:25907560

  1. Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus.

    PubMed

    Lee, Yoo Jin; Hussain, Zahid; Huh, Cheal Wung; Lee, Young Ju; Park, Hyojin

    2018-01-30

    Postoperative ileus (POI) is characterized by impaired propulsive function of the gastrointestinal tract after surgery. Although inflammation is considered to be an important pathogenesis of POI, significant data are lacking. We aim to correlate the recovery time of postoperative dysmotility with that of inflammation and mucosal permeability. An experimental POI model of guinea pig was used. Contractile activity of the circular muscle of the stomach, jejunum, ileum, and proximal colon was measured through a tissue bath study. Inflammatory cells were counted, and the expression of calprotectin and tryptase were analyzed. The expression of protease-activated receptor 2 (PAR-2), claudin-1, and claudin-2 were analyzed with immunofluorescence. The small bowel and colon showed decreased contractile amplitude in the POI groups compared to control. In contrast to the colon, the contractile amplitude of the small bowel significantly recovered in the POI group at 6 hours after the operation compared to the control group. Inflammation was highly significant in the POI groups compared to the control and sham groups, especially in the colon. Immunofluorescence showed increased PAR-2 expression in the POI groups compared to sham. The decreased claudin-1 expression and increased claudin-2 expression may suggest increased mucosal permeability of the small bowel and colon in the POI groups. Increased inflammation and mucosal permeability may play an important role in the differential recovery stages in POI. These data may provide further insights into the pathophysiology and potential new therapeutic prospects of POI.

  2. Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy.

    PubMed

    Li, Lele; Tong, Rong; Li, Mengyuan; Kohane, Daniel S

    2016-03-01

    Nanoparticles with combined diagnostic and therapeutic functions are promising tools for cancer diagnosis and treatment. Here, we demonstrate a theranostic nanoparticle that integrates an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile supramolecular self-assembly synthesis, where the anti-cancer drug gemcitabine-5'-monophosphate (a phosphorylated active metabolite of the anti-cancer drug gemcitabine) was used to coordinate with Gd(III) to self-assemble into theranostic nanoparticles. The formulation exhibits a strong T1 contrast signal for magnetic resonance imaging of tumors in vivo, with enhanced retention time. Furthermore, the nanoparticles did not require other inert nanocarriers or excipients and thus had an exceptionally high drug loading (55 wt%), resulting in the inhibition of MDA-MB-231 tumor growth in mice. Recent advances in nanoparticle-based drug delivery systems have spurred the development of "theranostic" multifunctional nanoparticles, which combine therapeutic and diagnostic functionalities in a single formulation. Developing simple and efficient synthetic strategies for the construction of nanotheranostics with high drug loading remains a challenge. Here, we demonstrate a theranostic nanoparticle that integrates high loadings of an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile synthesis. The nanoparticles were better T1 contrast agents than currently used Gd-DTPA and had prolonged retention in tumor. Moreover they exhibited enhanced in vivo antitumor activity compared to free drug in a breast cancer xenograft mouse model. The strategy provides a scalable way to fabricate nanoparticles that enables enhancement of both therapeutic and diagnostic capabilities. Published by Elsevier Ltd.

  3. The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy

    PubMed Central

    Whitfield-Cargile, Canaan M.; Cohen, Noah D.; Chapkin, Robert S.; Weeks, Brad R.; Davidson, Laurie A.; Goldsby, Jennifer S.; Hunt, Carrie L.; Steinmeyer, Shelby H.; Menon, Rani; Suchodolski, Jan S.; Jayaraman, Arul; Alaniz, Robert C.

    2016-01-01

    ABSTRACT Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co-administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota. PMID:27007819

  4. Lactate produced during labor modulates uterine inflammation via GPR81 (HCA1).

    PubMed

    Madaan, Ankush; Nadeau-Vallée, Mathieu; Rivera, Jose Carlos; Obari, Dima; Hou, Xin; Sierra, Estefania Marin; Girard, Sylvie; Olson, David M; Chemtob, Sylvain

    2017-01-01

    Uterine inflammatory processes trigger prolabor pathways and orchestrate on-time labor onset. Although essential for successful labor, inflammation needs to be regulated to avoid uncontrolled amplification and resolve postpartum. During labor, myometrial smooth muscle cells generate ATP mainly via anaerobic glycolysis, resulting in accumulation of lactate. Aside from its metabolic function, lactate has been shown to activate a G protein-coupled receptor, GPR81, reported to regulate inflammation. We therefore hypothesize that lactate produced during labor may act via GPR81 in the uterus to exert in a feedback manner antiinflammatory effects, to resolve or mitigate inflammation. We sought to investigate the role of lactate produced during labor and its receptor, GPR81, in regulating inflammation in the uterus. We investigated the expression of GPR81 in the uterus and the pharmacological role of lactate acting via GPR81 during labor, using shRNA-GPR81 and GPR81 -/- mice. (1) Uterine lactate levels increased substantially from 2 to 9 mmol/L during labor. (2) Immunohistological analysis revealed expression of GPR81 in the uterus with high expression in myometrium. (3) GPR81 expression increased during gestation, and peaked near labor. (4) In primary myometrial smooth muscle cell and ex vivo uteri from wild-type mice, lactate decreased interleukin-1β-induced transcription of key proinflammatory Il1b, Il6, Ccl2, and Pghs2; suppressive effects of lactate were not observed in cells and tissues from GPR81 -/- mice. (5) Conversely, proinflammatory gene expression was augmented in the uterus at term in GPR81 -/- mice and wild-type mice treated intrauterine with lentiviral-encoded shRNA-GPR81; GPR81 silencing also induced proinflammatory gene transcription in the uterus when labor was induced by endotoxin (lipopolysaccharide). (6) Importantly, administration to pregnant mice of a metabolically stable specific GPR81 agonist, 3,5-dihydroxybenzoic acid, decreased endotoxin

  5. Usefulness of the advanced neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state images for gamma knife radiosurgery and planning microsurgical procedures for skull base tumors.

    PubMed

    Hayashi, Motohiro; Chernov, Mikhail F; Tamura, Noriko; Yomo, Shoji; Tamura, Manabu; Horiba, Ayako; Izawa, Masahiro; Muragaki, Yoshihiro; Iseki, Hiroshi; Okada, Yoshikazu; Ivanov, Pavel; Régis, Jean; Takakura, Kintomo

    2013-01-01

    Gamma Knife radiosurgery (GKS) is currently performed with 0.1 mm preciseness, which can be designated microradiosurgery. It requires advanced methods for visualizing the target, which can be effectively attained by a neuroimaging protocol based on plain and gadolinium-enhanced constructive interference in steady state (CISS) images. Since 2003, the following thin-sliced images are routinely obtained before GKS of skull base lesions in our practice: axial CISS, gadolinium-enhanced axial CISS, gadolinium-enhanced axial modified time-of-flight (TOF), and axial computed tomography (CT). Fusion of "bone window" CT and magnetic resonance imaging (MRI), and detailed three-dimensional (3D) delineation of the anatomical structures are performed with the Leksell GammaPlan (Elekta Instruments AB). Recently, a similar technique has been also applied to evaluate neuroanatomy before open microsurgical procedures. Plain CISS images permit clear visualization of the cranial nerves in the subarachnoid space. Gadolinium-enhanced CISS images make the tumor "lucid" but do not affect the signal intensity of the cranial nerves, so they can be clearly delineated in the vicinity to the lesion. Gadolinium-enhanced TOF images are useful for 3D evaluation of the interrelations between the neoplasm and adjacent vessels. Fusion of "bone window" CT and MRI scans permits simultaneous assessment of both soft tissue and bone structures and allows 3D estimation and correction of MRI distortion artifacts. Detailed understanding of the neuroanatomy based on application of the advanced neuroimaging protocol permits performance of highly conformal and selective radiosurgical treatment. It also allows precise planning of the microsurgical procedures for skull base tumors.

  6. Investigation of Plutonium and Uranium Precipitation Behavior with Gadolinium as a Neutron Poison

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Visser, A.E.

    2003-10-17

    The caustic precipitation of plutonium (Pu)-containing solutions has been investigated to determine whether the presence of 3:1 uranium (U):Pu in solutions stored in the H-Canyon Facility at the U.S. Department of Energy's (DOE) Savannah River Site (SRS) would adversely impact the use of gadolinium nitrate (Gd(NO3)3) as a neutron poison. In the past, this disposition strategy has been successfully used to discard solutions containing approximately 100 kg of Pu to the SRS high level waste (HLW) system. In the current experiments, gadolinium (as Gd(NO3)3) was added to samples of a 3:1 U:Pu solution, a surrogate 3 g/L U solution, andmore » a surrogate 3 g/L U with 1 g/L Pu solution. A series of experiments was then performed to observe and characterize the precipitate at selected pH values. Solids formed at pH 4.5 and were found to contain at least 50 percent of the U and 94 percent of the Pu, but only 6 percent of the Gd. As the pH of the solution increased (e.g., pH greater than 14 with 1.2 or 3.6 M sodium hydroxide (NaOH) excess), the precipitate contained greater than 99 percent of the Pu, U, and Gd. After the pH greater than 14 systems were undisturbed for one week, no significant changes were found in the composition of the solid or supernate for each sample. The solids were characterized by X-ray diffraction (XRD) which found sodium diuranate (Na2U2O7) and gadolinium hydroxide (Gd(OH)3) at pH 14. Thermal gravimetric analysis (TGA) indicated sufficient water molecules were present in the solids to thermalize the neutrons, a requirement for the use of Gd as a neutron poison. Scanning electron microscopy (SEM) was also performed and the accompanying back-scattering electron analysis (BSE) found Pu, U, and Gd compounds in all pH greater than 14 precipitate samples. The rheological properties of the slurries at pH greater than 14 were also investigated by performing precipitate settling rate studies and measuring the viscosity and density of the materials. Based

  7. Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression

    PubMed Central

    Rielland, Maïté; Cantor, David J.; Graveline, Richard; Hajdu, Cristina; Mara, Lisa; de Diego Diaz, Beatriz; Miller, George; David, Gregory

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We previously demonstrated that the histone deacetylase–associated protein SIN3B is essential for oncogene-induced senescence in cultured cells. Here, using a mouse model of pancreatic cancer, we have demonstrated that SIN3B is required for activated KRAS-induced senescence in vivo. Surprisingly, impaired senescence as the result of genetic inactivation of Sin3B was associated with delayed PDAC progression and correlated with an impaired inflammatory response. In murine and human pancreatic cells and tissues, levels of SIN3B correlated with KRAS-induced production of IL-1α. Furthermore, evaluation of human pancreatic tissue and cancer cells revealed that Sin3B was decreased in control and PDAC samples, compared with samples from patients with pancreatic inflammation. These results indicate that senescence-associated inflammation positively correlates with PDAC progression and suggest that SIN3B has potential as a therapeutic target for inhibiting inflammation-driven tumorigenesis. PMID:24691445

  8. Comparative theoretical study of the structures and stabilities of four typical gadolinium carboxylates in different scintillator solvents.

    PubMed

    Huang, Pin-Wen

    2016-03-01

    The structural properties and stabilities of four typical gadolinium carboxylates (Gd-CBX) in toluene, linear alkyl benzene (LAB), and phenyl xylyl ethane (PXE) solvents were theoretically studied using density functional theory (DFT/B3LYP with the basis sets 6-311G(d) and MWB54) and the polarizable continuum model (PCM). The average Gd-ligand interaction energies (E int, corrected for dispersion) and the values of the energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (ΔHL) for the gadolinium complexes were calculated to compare the relative stabilities of the four Gd-CBX molecules in the three liquid scintillator solvents. According to the calculations, the values of E int and ΔHL for Gd-CBX in LAB are larger than the corresponding values in PXE and toluene. Gd-CBX may therefore be more compatible with LAB than with PXE and toluene. It was also found that, in the three scintillator solvents, the stabilities of the four Gd-CBX molecules increase in the order Gd-2EHA < Gd-2MVA < Gd-pivalate < Gd-TMHA.

  9. Rebamipide ameliorates atherosclerosis by controlling lipid metabolism and inflammation.

    PubMed

    Jhun, JooYeon; Kwon, Jeong-Eun; Kim, Se-Young; Jeong, Jeong-Hee; Na, Hyun Sik; Kim, Eun-Kyung; Lee, Seung Hoon; Jung, KyungAh; Min, Jun-Ki; Cho, Mi-La

    2017-01-01

    The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases.

  10. Docosahexaenoic Acid Attenuates Hepatic Inflammation, Oxidative Stress, and Fibrosis without Decreasing Hepatosteatosis in a Ldlr−/− Mouse Model of Western Diet-Induced Nonalcoholic Steatohepatitis123

    PubMed Central

    Depner, Christopher M.; Philbrick, Kenneth A.; Jump, Donald B.

    2013-01-01

    The incidence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has increased in parallel with the incidence of obesity. While both NAFLD and NASH are characterized by hepatosteatosis, NASH is characterized by hepatic damage, inflammation, oxidative stress, and fibrosis. We previously reported that feeding Ldlr−/− mice a high-fat, high-cholesterol diet containing menhaden oil attenuated several markers of NASH, including hepatosteatosis, inflammation, and fibrosis. Herein, we test the hypothesis that DHA [22:6 (n-3)] is more effective than EPA [20:5 (n-3)] at preventing Western diet (WD)-induced NASH in Ldlr−/− mice. Mice were fed the WD supplemented with either olive oil (OO), EPA, DHA, or EPA + DHA for 16 wk. WD + OO feeding induced a severe NASH phenotype, characterized by robust hepatosteatosis, inflammation, oxidative stress, and fibrosis. Whereas none of the C20–22 (n-3) fatty acid treatments prevented WD-induced hepatosteatosis, all 3 (n-3) PUFA-containing diets significantly attenuated WD-induced inflammation, fibrosis, and hepatic damage. The capacity of dietary DHA to suppress hepatic markers of inflammation (Clec4F, F4/80, Trl4, Trl9, CD14, Myd88), fibrosis (Procol1α1, Tgfβ1), and oxidative stress (NADPH oxidase subunits Nox2, p22phox, p40phox, p47phox, p67phox) was significantly greater than dietary EPA. The effects of DHA on these markers paralleled DHA-mediated suppression of hepatic Fads1 mRNA abundance and hepatic arachidonic acid content. Because DHA suppression of NASH markers does not require a reduction in hepatosteatosis, dietary DHA may be useful in combating NASH in obese humans. PMID:23303872

  11. Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

    PubMed Central

    Batumalaie, Kalaivani; Amin, Muhammad Arif; Murugan, Dharmani Devi; Sattar, Munavvar Zubaid Abdul; Abdullah, Nor Azizan

    2016-01-01

    Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings. PMID:27250532

  12. Low-grade inflammation disrupts structural plasticity in the human brain.

    PubMed

    Szabó, C; Kelemen, O; Kéri, S

    2014-09-05

    Increased low-grade inflammation is thought to be associated with several neuropsychiatric disorders characterized by decreased neuronal plasticity. The purpose of the present study was to investigate the relationship between structural changes in the human brain during cognitive training and the intensity of low-grade peripheral inflammation in healthy individuals (n=56). A two-month training (30 min/day) with a platformer video game resulted in a significantly increased volume of the right hippocampal formation. The number of stressful life events experienced during the past year was associated with less pronounced enlargement of the hippocampus. However, the main predictor of hippocampal volume expansion was the relative peripheral expression of Nuclear Factor-κB (NF-κB), a transcription factor playing a central role in the effect of pro-inflammatory cytokines. Interleukin-6 (IL-6) and C-reactive protein levels were not related to hippocampal plasticity when NF-κB was taken into consideration. These results suggest that more intensive peripheral inflammation is associated with weaker neuronal plasticity during cognitive training. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Structural, kinetic, and thermodynamic characterization of the interconverting isomers of MS-325, a gadolinium(III)-based magnetic resonance angiography contrast agent.

    PubMed

    Tyeklar, Zoltan; Dunham, Stephen U; Midelfort, Katarina; Scott, Daniel M; Sajiki, Hirano; Ong, Karen; Lauffer, Randall B; Caravan, Peter; McMurry, Thomas J

    2007-08-06

    The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 comprises a GdDTPA core with an appended phosphodiester moiety linked to a diphenylcyclohexyl group to facilitate noncovalent binding to serum albumin and extension of the plasma half-life in vivo. The chiral DTPA ligand (R) was derived from L-serine, and upon complexation with gadolinium, forms two interconvertible diastereomers, denoted herein as isomers A and B. X-ray crystallography of the tris(ethylenediamine)cobalt(III) salt derivative of isomer A revealed a structure in the polar acentric space group P32. The structure consisted of three independent molecules of the gadolinium complex in the asymmetric unit along with three Delta-[Co(en)3]3+ cations, and it represents an unusual example of spontaneous Pasteur resolution of the cobalt cation. The geometry of the coordination core was best described as a distorted trigonal prism, and the final R factor was 5.6%. The configuration of the chiral central nitrogen of the DTPA core was S. The Gd-water (2.47-2.48 A), the Gd-acetate oxygens (2.34-2.42 A), and the Gd-N bond distances (central N, 2.59-2.63 A; terminal N, 2.74-2.80 A) were similar to other reported GdDTPA structures. The structurally characterized single crystal was one of two interconvertable diastereomers (isomers A and B) that equilibrated to a ratio of 1.81 to 1 at pH 7.4 and were separable at elevated pH by ion-exchange chromatography. The rate of isomerization was highly pH dependent: k1 = (1.45 +/- 0.08) x 102[H+] + (4.16 +/- 0.30) x 105[H+]2; k-1 = (2.57 +/- 0.17) x 102[H+] + (7.54 +/- 0.60) x 105[H+]2.

  14. Affective reactivity to daily stressors is associated with elevated inflammation.

    PubMed

    Sin, Nancy L; Graham-Engeland, Jennifer E; Ong, Anthony D; Almeida, David M

    2015-12-01

    Inflammation increases the risk of chronic diseases, but the links between emotional responses to daily events and inflammation are unknown. We examined individual differences in affective reactivity to daily stressors (i.e., changes in positive and negative affect in response to stressors) as predictors of inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP). A cross-sectional sample of 872 adults from the National Study of Daily Experiences (substudy of Midlife in the United States II) reported daily stressors and affect during telephone interviews for 8 days. Blood samples were obtained at a separate clinic visit and assayed for inflammatory markers. Multilevel models estimated trait affective reactivity slopes for each participant, which were inputted into regression models to predict inflammation. People who experienced greater decreases in positive affect on days when stressors occurred (i.e., positive affect reactivity) had elevated log IL-6, independent of demographic, physical, psychological, and behavioral factors (B = 1.12, SE = 0.45, p = .01). Heightened negative affect reactivity was associated with higher log CRP among women (p = .03) but not men (p = .57); health behaviors accounted for this association in women. Adults who fail to maintain positive affect when faced with minor stressors in everyday life appear to have elevated levels of IL-6, a marker of inflammation. Women who experience increased negative affect when faced with minor stressors may be at particular risk of elevated inflammation. These findings add to growing evidence regarding the health implications of affective reactivity to daily stressors. (c) 2015 APA, all rights reserved).

  15. Affective reactivity to daily stressors is associated with elevated inflammation

    PubMed Central

    Sin, Nancy L.; Graham-Engeland, Jennifer E.; Ong, Anthony D.; Almeida, David M.

    2015-01-01

    Objective Inflammation increases the risk of chronic diseases, but the links between emotional responses to daily events and inflammation are unknown. We examined individual differences in affective reactivity to daily stressors (i.e., changes in positive and negative affect in response to stressors) as predictors of inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP). Methods A cross-sectional sample of 872 adults from the National Study of Daily Experiences (sub-study of Midlife in the United States II) reported daily stressors and affect during telephone interviews for 8 days. Blood samples were obtained at a separate clinic visit and assayed for inflammatory markers. Multilevel models estimated trait affective reactivity slopes for each participant, which were inputted into regression models to predict inflammation. Results People who experienced greater decreases in positive affect on days when stressors occurred (i.e, positive affect reactivity) had elevated log IL-6, independent of demographic, physical, psychological, and behavioral factors (B = 1.12, SE = 0.45, p = 0.01). Heightened negative affect reactivity was associated with higher log CRP among women (p = 0.03) but not men (p = 0.57); health behaviors accounted for this association in women. Conclusions Adults who fail to maintain positive affect when faced with minor stressors in everyday life appear to have elevated levels of IL-6, a marker of inflammation. Women who experience increased negative affect when faced with minor stressors may be at particular risk of elevated inflammation. These findings add to growing evidence regarding the health implications of affective reactivity to daily stressors. PMID:26030309

  16. Microstructural Anisotropy of Magnetocaloric Gadolinium Cylinders: Effect on the Mechanical Properties of the Material

    PubMed Central

    Petrovič, Darja Steiner; Šturm, Roman; Naglič, Iztok; Markoli, Boštjan; Pepelnjak, Tomaž

    2016-01-01

    The development of advanced materials and technologies based on magnetocaloric Gd and its compounds requires an understanding of the dependency of mechanical properties on their underlying microstructure. Therefore, the aim of the study was to characterize microstructural inhomogeneities in the gadolinium that can be used in magnetocaloric refrigeration systems. Microstructures of magnetocaloric gadolinium cylinders were investigated by light microscopy and FE-SEM (Field Emission Scanning Electron Microscopy), EDS (Energy-dispersive X-ray Spectroscopy), and BSE (Back-scattered Electrons) in both the extrusion and the extrusion-transversal directions. XRD (X-ray Diffraction) analyses were performed to reveal the presence of calcium- and fluorine-based compounds. Metallographic characterization showed an oxidized and inhomogeneous microstructure of the cross-sections. The edges and the outer parts of the cylinders were oxidized more intensively on the surfaces directly exposed to the processing tools. Moreover, a significant morphological anisotropy of the non-metallic inclusions was observed. CaF inclusions act as active nucleation sites for internal oxidation. The non-metallic, Ca- and F-containing inclusions can be classified as complex calciumoxyfluorides. The solubility of Er and Yb in the CaF was negligible compared to the Gd matrix and/or the oxide phase. Lower mechanical properties of the material are a consequence of the lower structural integrity due to selective oxidation of surfaces and interfaces. PMID:28773502

  17. Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

    PubMed

    Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

    2017-06-15

    Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

  18. Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?

    PubMed Central

    da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, João Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio

    2013-01-01

    An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315

  19. Gadolinium(III)-sensitized fluorescence of europium in its mixed-metal compounds with trifluroacetate

    NASA Astrophysics Data System (ADS)

    Kalinovskaya, I. V.; Zadorozhnaya, A. N.

    2017-04-01

    The fluorescence properties of mixed-metal compounds of Eu(III) and Gd(III) with trifluoroacetic acid, Eu1-хGdx(С2F3O2)3·yD·zH2O, where D - 1,10-phenanthroline, 2,2-dipyridil, diphenylguanidine, x = 0, 0.25, 0.5, or 0.7, were studied. Luminescence spectroscopic evidence and the examination of excitation spectra indicate the occurrence of efficient energy transfer from the gadolinium to the europium ion. The greatest promotion of Eu3+ photoluminescence at 615 nm is observed when Eu:Gd = 1:1.

  20. Gadolinium for neutron detection in current nuclear instrumentation research: A review

    NASA Astrophysics Data System (ADS)

    Dumazert, J.; Coulon, R.; Lecomte, Q.; Bertrand, G. H. V.; Hamel, M.

    2018-02-01

    Natural gadolinium displays a number of remarkable physical properties: it is a rare earth element, composed of seven stable or quasi-stable isotopes, with an exceptionally high magnetization and a Curie point near room temperature. Its use in the field of nuclear instrumentation historically relates to its efficiency as a neutron poison in power reactors. Gadolinium is indeed the naturally occurring element with the highest interaction probability with neutrons at thermal energy, shared between Gd-157 (15.65%, 254000 b cross section) and Gd-155 (14.8%, 60900 b) isotopes. Considering that neutron capture results in an isotopic change, followed by a radiative rearrangement of nuclear and atomic structures, Gd may be embodied not merely as a neutron poison but as a neutron converter into a prompt photon and an electron source term. Depending on the nature and energy of the reaction products (from a few-keV Auger electrons up to 8 MeV gamma rays) that the detector aims at isolating as an indirect neutron signature, a variety of sensor media and counting methods have been introduced during the last decades. This review first draws a theoretical description of the radiative cascade following Gd(n , γ) capture. The cascade may be subdivided into regions of interest, each corresponding to dedicated detection designs and optimizations whose current status is detailed. This inventory has allowed the authors to extract and benchmark key figures of merit for the definition of a detection scheme: neutron attenuation, neutron sensitivity (cps/nv), gamma rejection, neutron detection limit in a mixed field, intrinsic or extrinsic moderation, and transportability. On this basis, the authors have identified promising paths for Gd-based neutron detection in contemporary instrumentation.

  1. Impaired Resolution of Inflammation in Alzheimer's Disease: A Review.

    PubMed

    Whittington, Robert A; Planel, Emmanuel; Terrando, Niccolò

    2017-01-01

    Alzheimer's disease (AD) remains the leading cause of dementia worldwide, and over the last several decades, the role of inflammation in the pathogenesis of this neurodegenerative disorder has been increasingly elucidated. The initiation of the acute inflammatory response is counterbalanced by an active process termed resolution. This process is designed to restore homeostasis and promote tissue healing by the activation of neutrophilic apoptosis, promotion of neutrophil clearance by macrophages, and increasing anti-inflammatory cytokine levels, while concurrently leading to a diminution in pro-inflammatory mediators. The switch from the initiation to the resolution phase of inflammation is initially characterized by increased production of arachidonic acid-derived pro-resolving lipoxins and decreases in pro-inflammatory prostaglandin and leukotriene levels, subsequently followed by increases in specialized pro-resolving lipid mediators derived from omega-3 fatty acids (ω-3 FAs). There is mounting evidence that in AD, the resolution of inflammation is impaired, resulting in chronic inflammation and the exacerbation of the AD-related pathology. In this review, we examine preclinical and clinical evidence supporting the hypothesis that AD is a neurodegenerative disorder where the impairment or failure of resolution contributes to the disease process. Moreover, we review the literature supporting the potential therapeutic role of ω-3 FAs and specialized pro-resolving lipid mediators in the management of the disease. Lastly, we highlight areas that could strengthen the association of failed resolution to AD and should, therefore, be the focus of future scientific investigations in this research field.

  2. Susceptibility to chronic inflammation: an update.

    PubMed

    Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R

    2017-03-01

    Chronic inflammation is defined by the persistence of inflammatory processes beyond their physiological function, resulting in tissue destruction. Chronic inflammation is implicated in the progression of many chronic diseases and plays a central role in chronic inflammatory and autoimmune disease. As such, this review aims to collate some of the latest research in relation to genetic and environmental susceptibilities to chronic inflammation. In the genetic section, we discuss some of the updates in cytokine research and current treatments that are being developed. We also discuss newly identified canonical and non-canonical genes associated with chronic inflammation. In the environmental section, we highlight some of the latest updates and evidence in relation to the role that infection, diet and stress play in promoting inflammation. The aim of this review is to provide an overview of the latest research to build on our current understanding of chronic inflammation. It highlights the complexity associated with chronic inflammation, as well as provides insights into potential new targets for therapies that could be used to treat chronic inflammation and consequently prevent disease progression.

  3. The effect of dietary resistant starch type 2 on the microbiota and markers of gut inflammation in rural Malawi children

    USDA-ARS?s Scientific Manuscript database

    Resistant starch (RS) decreases intestinal inflammation in some settings. We tested the hypothesis that gut inflammation will be reduced with dietary supplementation with RS in rural Malawian children. Eighteen stunted 3-5-year-old children were supplemented with 8.5 g/day of RS type 2 for 4 weeks. ...

  4. The use of innovative gadolinium-based contrast agent for MR-diagnosis of cancer in the experiment

    NASA Astrophysics Data System (ADS)

    Chernov, V.; Medvedeva, A.; Sinilkin, I.; Zelchan, R.; Grigorev, E.; Frolova, I.; Nam, I.

    2016-02-01

    The present study of the functional suitability and specific activity of the contrast agent gadolinium-based for magnetic resonance imaging demonstrated that the investigated contrast agent intensively accumulates in organs and anatomical structures of the experimental animals. In the model of tumor lesions in animals, study have shown that investigational contrast agent accumulates in the tumor tissue and retained there in for a long enough time.

  5. Activation of AMPK improves inflammation and insulin resistance in adipose tissue and skeletal muscle from pregnant women.

    PubMed

    Liong, Stella; Lappas, Martha

    2015-12-01

    Gestational diabetes mellitus (GDM) is characterised by maternal peripheral insulin resistance and inflammation. Sterile inflammation and bacterial infection are key mediators of this enhanced inflammatory response. Adenosine monophosphate (AMP)-activated kinase (AMPK), which is decreased in insulin resistant states, possesses potent pro-inflammatory actions. There are, however, no studies on the role of AMPK in pregnancies complicated by GDM. Thus, the aims of this study were (i) to compare the expression of AMPK in adipose tissue and skeletal muscle from women with GDM and normal glucose-tolerant (NGT) pregnant women; and (ii) to investigate the effect of AMPK activation on inflammation and insulin resistance induced by the bacterial endotoxin lipopolysaccharide (LPS) and the pro-inflammatory cytokine IL-1β. When compared to NGT pregnant women, AMPKα activity was significantly lower in women with GDM as evidenced by a decrease in threonine phosphorylation of AMPKα. Activation of AMPK, using two pharmacologically distinct compounds, AICAR or phenformin, significantly suppressed LPS- or IL-1β-induced gene expression and secretion of pro-inflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, and COX-2 and subsequent prostaglandin release from adipose tissue and skeletal muscle. In addition, activators of AMPK decreased skeletal muscle insulin resistance induced by LPS or IL-1β as evidenced by increased insulin-stimulated phosphorylation of IRS-1, GLUT-4 expression and glucose uptake. These findings suggest that AMPK may play an important role in inflammation and insulin resistance.

  6. Effect of Ergothioneine on Acute Lung Injury and Inflammation in Cytokine Insufflated Rats

    PubMed Central

    Repine, John E.; Elkins, Nancy D.

    2012-01-01

    Objective The Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), is a highly-fatal, diffuse non-cardiogenic edematous lung disorder. The pathogenesis of ARDS is unknown but lung inflammation and lung oxidative stress are likely contributing factors. Since no specific pharmacologic intervention exists for ARDS, our objective was to determine the effect of treatment with ergothioneine---a safe agent with multiple anti-inflammatory and antioxidant properties on the development of lung injury and inflammation in rats insufflated with cytokines found in lung lavages of ARDS patients. Method Sprague-Dawley rats (3-10/group) were given 15 mg/kg or 150 mg/kg L-ergothioneine intravenously 1 hour before or 18 hours after cytokine (IL-1 and IFNγ) insufflation. Lung injury (lavage LDH levels) and lung inflammation (lavage neutrophil numbers) were measured 24 hours after cytokine insufflation. Results Ergothioneine pre- and post- treatment generally decreased lung injury and lung inflammation in cytokine insufflated rats. Conclusion Ergothioneine should be considered for additional testing as a potential therapy for treating and preventing ARDS. PMID:22197759

  7. Inhalation of environmental stressors & chronic inflammation: autoimmunity and neurodegeneration.

    PubMed

    Gomez-Mejiba, Sandra E; Zhai, Zili; Akram, Hammad; Pye, Quentin N; Hensley, Kenneth; Kurien, Biji T; Scofield, R Hal; Ramirez, Dario C

    2009-03-31

    Human life expectancy and welfare has decreased because of the increase in environmental stressors in the air. An environmental stressor is a natural or human-made component present in our environment that upon reaching an organic system produces a coordinated response. This response usually involves a modification of the metabolism and physiology of the system. Inhaled environmental stressors damage the airways and lung parenchyma, producing irritation, recruitment of inflammatory cells, and oxidative modification of biomolecules. Oxidatively modified biomolecules, their degradation products, and adducts with other biomolecules can reach the systemic circulation, and when found in higher concentrations than normal they are considered to be biomarkers of systemic oxidative stress and inflammation. We classify them as metabolic stressors because they are not inert compounds; indeed, they amplify the inflammatory response by inducing inflammation in the lung and other organs. Thus the lung is not only the target for environmental stressors, but it is also the source of a number of metabolic stressors that can induce and worsen pre-existing chronic inflammation. Metabolic stressors produced in the lung have a number of effects in tissues other than the lung, such as the brain, and they can also abrogate the mechanisms of immunotolerance. In this review, we discuss recent published evidence that suggests that inflammation in the lung is an important connection between air pollution and chronic inflammatory diseases such as autoimmunity and neurodegeneration, and we highlight the critical role of metabolic stressors produced in the lung. The understanding of this relationship between inhaled environmental pollutants and systemic inflammation will help us to: (1) understand the molecular mechanism of environment-associated diseases, and (2) find new biomarkers that will help us prevent the exposure of susceptible individuals and/or design novel therapies.

  8. Eupafolin nanoparticles protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress

    PubMed Central

    Lin, Zih-Chan; Lee, Chiang-Wen; Tsai, Ming-Horng; Ko, Horng-Huey; Fang, Jia-You; Chiang, Yao-Chang; Liang, Chan-Jung; Hsu, Lee-Fen; Hu, Stephen Chu-Sung; Yen, Feng-Lin

    2016-01-01

    Exposure to particulate matter (PM), a major form of air pollution, can induce oxidative stress and inflammation and may lead to many diseases in various organ systems including the skin. Eupafolin, a flavonoid compound derived from Phyla nodiflora, has been previously shown to exhibit various pharmacological activities, including antioxidant and anti-inflammatory effects. Unfortunately, eupafolin is characterized by poor water solubility and skin penetration, which limits its clinical applications. To address these issues, we successfully synthesized a eupafolin nanoparticle delivery system (ENDS). Our findings showed that ENDS could overcome the physicochemical drawbacks of raw eupafolin with respect to water solubility and skin penetration, through reduction of particle size and formation of an amorphous state with hydrogen bonding. Moreover, ENDS was superior to raw eupafolin in attenuating PM-induced oxidative stress and inflammation in HaCaT keratinocytes, by mediating the antioxidant pathway (decreased reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) and anti-inflammation pathway (decreased cyclooxygenase-2 expression and prostaglandin E2 production through downregulation of mitogen-activated protein kinase and nuclear factor-κB signaling). In summary, ENDS shows better antioxidant and anti-inflammatory activities than raw eupafolin through improvement of water solubility and skin penetration. Therefore, ENDS may potentially be used as a medicinal drug and/or cosmeceutical product to prevent PM-induced skin inflammation. PMID:27570454

  9. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle

    PubMed Central

    Dagdeviren, Sezin; Jung, Dae Young; Friedline, Randall H.; Noh, Hye Lim; Kim, Jong Hun; Patel, Payal R.; Tsitsilianos, Nicholas; Inashima, Kunikazu; Tran, Duy A.; Hu, Xiaodi; Loubato, Marilia M.; Craige, Siobhan M.; Kwon, Jung Yeon; Lee, Ki Won; Kim, Jason K.

    2017-01-01

    Altered energy balance and insulin resistance are important characteristics of aging. Skeletal muscle is a major site of glucose disposal, and the role of aging-associated inflammation in skeletal muscle insulin resistance remains unclear. To investigate, we examined glucose metabolism in 18-mo-old transgenic mice with muscle-specific overexpression of IL-10 (MIL10) and in wild-type mice during hyperinsulinemic–euglycemic clamping. Despite similar fat mass and energy balance, MIL10 mice were protected from aging-associated insulin resistance with significant increases in glucose infusion rates, whole-body glucose turnover, and skeletal muscle glucose uptake (∼60%; P < 0.05), as compared to age-matched WT mice. This protective effect was associated with decreased muscle inflammation, but no changes in adipose tissue inflammation in aging MIL10 mice. These results demonstrate the importance of skeletal muscle inflammation in aging-mediated insulin resistance, and our findings further implicate a potential therapeutic role of anti-inflammatory cytokine in the treatment of aging-mediated insulin resistance.—Dagdeviren, S., Jung, D. Y., Friedline, R. H., Noh, H. L., Kim, J. H., Patel, P. R., Tsitsilianos, N., Inashima, K., Tran, D. A., Hu, X., Loubato, M. M., Craige, S. M., Kwon, J. Y., Lee, K. W., Kim, J. K. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle. PMID:27811060

  10. Malondialdehyde epitopes are sterile mediators of hepatic inflammation in hypercholesterolemic mice

    PubMed Central

    Weismann, David; Jäckel, Sven; Walenbergh, Sofie M. A.; Rendeiro, André F.; Weißer, Juliane; Puhm, Florian; Hladik, Anastasiya; Göderle, Laura; Papac-Milicevic, Nikolina; Haas, Gerald; Millischer, Vincent; Subramaniam, Saravanan; Knapp, Sylvia; Bennett, Keiryn L.; Bock, Christoph; Reinhardt, Christoph; Shiri-Sverdlov, Ronit; Binder, Christoph J.

    2018-01-01

    Background and Rationale Diet-related health issues such as non-alcoholic fatty liver disease and cardiovascular disorders are known to have a major inflammatory component. However, the exact pathways linking diet-induced changes e.g. hyperlipidemia, and the ensuing inflammation have remained elusive so far. Main Results We identified biological processes related to innate immunity and oxidative stress as prime response pathways in livers of Ldlr-/- mice on Western-type diet using RNA sequencing and in silico functional analyses of transcriptome data. The observed changes were independent of the presence of microbiota and thus indicative of a role for sterile triggers. We further show that MDA epitopes, products of lipid peroxidation and markers for enhanced oxidative stress, are detectable in hepatic inflammation predominantly on dying cells and stimulate cytokine secretion as well as leukocyte recruitment in vitro and in vivo. MDA-induced cytokine secretion in vitro was dependent on the presence of scavenger receptors CD36 and MSR1. Moreover, in vivo neutralization of endogenously generated MDA epitopes by intravenous injection of a specific MDA antibody results in decreased hepatic inflammation in Ldlr-/- mice on Western-type diet. Conclusions Accumulation of MDA epitopes plays a major role during diet-induced hepatic inflammation and can be ameliorated by administration of an anti-MDA antibody. PMID:27981604

  11. Geometry of electromechanically active structures in Gadolinium - doped Cerium oxides

    DOE PAGES

    Li, Yuanyuan; Kraynis, Olga; Kas, Joshua; ...

    2016-05-20

    Local distortions from average structure are important in many functional materials, such as electrostrictors or piezoelectrics, and contain clues about their mechanism of work. However, the geometric attributes of these distortions are exceedingly difficult to measure, leading to a gap in knowledge regarding their roles in electromechanical response. This task is particularly challenging in the case of recently reported non-classical electrostriction in Cerium-Gadolinium oxides (CGO), where only a small population of Ce-O bonds that are located near oxygen ion vacancies responds to external electric field. In this study, we used high-energy resolution fluorescence detection (HERFD) technique to collect X-ray absorptionmore » spectra in CGO in situ, with and without an external electric field, coupled with theoretical modeling to characterize three-dimensional geometry of electromechanically active units.« less

  12. Geometry of electromechanically active structures in Gadolinium - doped Cerium oxides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Yuanyuan; Zacharowicz, Renee; Frenkel, Anatoly I., E-mail: igor.lubomirsky@weizmann.ac.il, E-mail: anatoly.frenkel@yu.edu

    2016-05-15

    Local distortions from average structure are important in many functional materials, such as electrostrictors or piezoelectrics, and contain clues about their mechanism of work. However, the geometric attributes of these distortions are exceedingly difficult to measure, leading to a gap in knowledge regarding their roles in electromechanical response. This task is particularly challenging in the case of recently reported non-classical electrostriction in Cerium-Gadolinium oxides (CGO), where only a small population of Ce-O bonds that are located near oxygen ion vacancies responds to external electric field. We used high-energy resolution fluorescence detection (HERFD) technique to collect X-ray absorption spectra in CGOmore » in situ, with and without an external electric field, coupled with theoretical modeling to characterize three-dimensional geometry of electromechanically active units.« less

  13. Adsorption Studies of Gadolinium ion on Graphitic Carbon Nitride

    NASA Astrophysics Data System (ADS)

    Kuila, S. K.; Kundu, T. K.

    2018-03-01

    Bulk graphitic carbon nitride (g-C3N4) is synthesized by thermal decomposition of urea and used as an adsorbent for gadolinium ion (Gd3+) from aqueous solution. Adsorption capacity of g-C3N4 is found to be influenced by initial Gd3+ concentration, solution pH and contact time. Adsorbed Gd3+is separated from g-C3N4 by ultracentrifuge. Initial and Gd ion accumulated g-C3N4 adsorbent are characterized by X-ray diffraction technique (XRD) for phase identification, UV-visible and Fourier transform infrared (FTIR) spectroscopy for adsorption characteristics and optical property, scanning electron microscopy (SEM) for morphological behaviour along with energy dispersive X-ray spectroscopy (EDS) for elemental study. HNO3(0.1M), NaOH (0.1M) and de-ionized water are used for desorption and around 97% quantitative recovery of Gd ion is observed.

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

    PubMed

    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.

  15. Inflammation, Impaired Motility, and Permeability in a Guinea Pig Model of Postoperative Ileus

    PubMed Central

    Lee, Yoo Jin; Hussain, Zahid; Huh, Cheal Wung; Lee, Young Ju; Park, Hyojin

    2018-01-01

    Background/Aims Postoperative ileus (POI) is characterized by impaired propulsive function of the gastrointestinal tract after surgery. Although inflammation is considered to be an important pathogenesis of POI, significant data are lacking. We aim to correlate the recovery time of postoperative dysmotility with that of inflammation and mucosal permeability. Methods An experimental POI model of guinea pig was used. Contractile activity of the circular muscle of the stomach, jejunum, ileum, and proximal colon was measured through a tissue bath study. Inflammatory cells were counted, and the expression of calprotectin and tryptase were analyzed. The expression of protease-activated receptor 2 (PAR-2), claudin-1, and claudin-2 were analyzed with immunofluorescence. Results The small bowel and colon showed decreased contractile amplitude in the POI groups compared to control. In contrast to the colon, the contractile amplitude of the small bowel significantly recovered in the POI group at 6 hours after the operation compared to the control group. Inflammation was highly significant in the POI groups compared to the control and sham groups, especially in the colon. Immunofluorescence showed increased PAR-2 expression in the POI groups compared to sham. The decreased claudin-1 expression and increased claudin-2 expression may suggest increased mucosal permeability of the small bowel and colon in the POI groups. Conclusions Increased inflammation and mucosal permeability may play an important role in the differential recovery stages in POI. These data may provide further insights into the pathophysiology and potential new therapeutic prospects of POI. PMID:29291615

  16. Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery

    PubMed Central

    Lee, John Y-K.; Thawani, Jayesh P.; Pierce, John; Zeh, Ryan; Martinez-Lage, Maria; Chanin, Michelle; Venegas, Ollin; Nims, Sarah; Learned, Kim; Keating, Jane; Singhal, Sunil

    2016-01-01

    Background Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. Objective To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Methods Fifteen patients were identified and administered an FDA-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) prior to surgical resection. An NIR camera was utilized to localize the tumor prior to resection and to visualize surgical margins following resection. Neuropathology and MR imaging data were used to assess the accuracy and precision of NIR-fluorescence in identifying tumor tissue. Results NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12/15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with SBR (P = .03). Non-enhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). Conclusion Using Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. PMID:27741220

  17. Modulation of Roquin function in myeloid cells reduces Mycobacterium tuberculosis induced inflammation

    PubMed Central

    Nagalingam, Gayathri; Vinuesa, Carola G.; Britton, Warwick J; Saunders, Bernadette M.

    2017-01-01

    Damaging inflammation is a hallmark of Mycobacterium tuberculosis infection, and understanding how this is regulated is important for the development of new therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is involved in immune regulation, however its role in immunity to M. tuberculosis is unknown. To address this we infected mice with a point mutation in Roquin1/Rc3h1 (sanroque). Aerosol-infected sanroque mice showed enhanced control of M. tuberculosis infection associated with delayed bacterial dissemination and upregulated TNF production in the lung after 2 weeks. However, this early control of infection was not maintained, and by 8 weeks post-infection sanroque mice demonstrated increased bacterial burden and dysregulated inflammation in the lung. As the inflammation in the lung of the sanroque mice could have been influenced by emerging autoimmune conditions that are characteristic of aging sanroque mice, the function of Roquin was examined in immune cell subsets in the absence of autoimmune complications. Mycobacterium bovis BCG-primed sanroque T cells transferred into Rag1-/- mice provided equivalent protection in the spleen and liver. Interestingly, the transfer of mycobacteria-specific (P25 CD4+ TCR transgenic) wild-type spleen cells into sanroque.Rag1-/- mice actually led to enhanced protection with reduced bacterial load, decreased chemokine expression and reduced inflammation in the lung compared with transfers into Rag1-/- mice expressing intact Roquin. These studies suggest that modulation of Roquin in myeloid cells may reduce both inflammation and bacterial growth during the chronic phase of M. tuberculosis infection. PMID:28747346

  18. Intestinal inflammation induces genotoxicity to extraintestinal tissues and cell types in mice

    PubMed Central

    Westbrook, Aya M.; Wei, Bo; Braun, Jonathan; Schiestl, Robert H.

    2011-01-01

    Chronic intestinal inflammation leads to increased risk of colorectal and small intestinal cancers, and is also associated with extraintestinal manifestations such as lymphomas, other solid cancers, and autoimmune disorders. We have previously found that acute and chronic intestinal inflammation causes DNA damage to circulating peripheral leukocytes, manifesting a systemic effect in genetic and chemically-induced models of intestinal inflammation. This study addresses the scope of tissue targets and genotoxic damage induced by inflammation-associated genotoxicity. Using several experimental models of intestinal inflammation, we analyzed various types of DNA damage in leukocyte subpopulations of the blood, spleen, mesenteric and peripheral lymph nodes; and, in intestinal epithelial cells, hepatocytes, and the brain. Genotoxicity in the form of DNA single and double stranded breaks accompanied by oxidative base damage was found in leukocyte subpopulations of the blood, diverse lymphoid organs, intestinal epithelial cells, and hepatocytes. The brain did not demonstrate significant levels of DNA double strand breaks as measured by γ-H2AX immunostaining. CD4+ and CD8+ T-cells were most sensitive to DNA damage versus other cell types in the peripheral blood. In vivo measurements and in vitro modeling suggested that genotoxicity was induced by increased levels of systemically circulating proinflammatory cytokines. Moreover, genotoxicity involved increased damage rather than reduced repair, since it not associated with decreased expression of the DNA double-strand break recognition and repair protein, ataxia telangiectasia mutated (ATM). These findings suggest that levels of intestinal inflammation contribute to the remote tissue burden of genotoxicity, with potential effects on non-intestinal diseases and cancer. PMID:21520038

  19. Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti-Inflammatory Agents

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-2-0153 TITLE: Decreasing Skin Graft Contraction through Topical Wound Bed Preparation with Anti - Inflammatory Agents...Sep 2015 4. TITLE AND SUBTITLE Decreasing Skin Graft Contraction Through Topical Wound Bed Preparation with Anti - Inflammatory Agents 5a. CONTRACT...applied anti - inflammatory drugs that will reduce recipient site inflammation and skin graft contraction. 15. SUBJECT TERMS Graft contraction, anti

  20. Topical Minocycline Effectively Decontaminates and Reduces Inflammation in Infected Porcine Wounds.

    PubMed

    Daly, Lauren Tracy; Tsai, David M; Singh, Mansher; Nuutila, Kristo; Minasian, Raquel A; Lee, Cameron C Y; Kiwanuka, Elizabeth; Hackl, Florian; Onderdonk, Andrew B; Junker, Johan P E; Eriksson, Elof; Caterson, Edward J

    2016-11-01

    Wound infection can impair postoperative healing. Topical antibiotics have potential to treat wound infection and inflammation and minimize the adverse effects associated with systemic antibiotics. Full-thickness porcine wounds were infected with Staphylococcus aureus. Using polyurethane wound enclosure devices, wounds were treated with topical 100 μg/ml minocycline, topical 1000 μg/ml minocycline, topical saline control, or 4 mg/kg intravenous minocycline. Bacteria were quantified in wound tissue and fluid obtained over 9 hours. Immunosorbent assays were used to analyze inflammatory marker concentrations. Minocycline's effect on in vitro migration and proliferation of human keratinocytes and fibroblasts was tested using scratch assays and metabolic assays, respectively. After 6 hours, 100 and 1000 μg/ml topical minocycline decreased bacteria in wound tissue to 3.5 ± 0.87 and 2.9 ± 2.3 log colony-forming units/g respectively, compared to 8.3 ± 0.9 log colony-forming units/g in control wounds (p < 0.001) and 6.9 ± 0.2 log colony-forming units/g in wounds treated with 4 mg/kg intravenous minocycline (p < 0.01). After 2 hours, topical minocycline reduced concentrations of the inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α (p < 0.01), and inflammatory cell counts in wound tissue (p < 0.05). In noninfected wounds, topical minocycline significantly reduced interleukin-1β, interleukin-6, and inflammatory cell counts after 4 hours (p < 0.01). Matrix metalloproteinase-9 concentrations decreased after 1-hour treatment (p < 0.05). Keratinocyte and fibroblast in vitro functions were not adversely affected by 10 μg/ml minocycline or less. Topical minocycline significantly reduces bacterial burden and inflammation in infected wounds compared with wounds treated with intravenous minocycline or control wounds. Minocycline also decreases local inflammation independently of its antimicrobial effect.

  1. Inflammation, atrophy, and gastric cancer

    PubMed Central

    Fox, James G.; Wang, Timothy C.

    2006-01-01

    The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment. PMID:17200707

  2. Influence of fitness and age on the endothelial response to acute inflammation.

    PubMed

    Schroeder, Elizabeth C; Lane-Cordova, Abbi D; Ranadive, Sushant M; Baynard, Tracy; Fernhall, Bo

    2018-06-01

    What is the central question of the study? What are the effects of age and fitness on the vascular response to acute inflammation in younger and older adults? What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function after acute inflammation. Compared with older adults with low fitness, older, moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications in support of the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24 h after vaccination. Peak oxygen uptake was measured via a treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age- and sex-determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P < 0.05). The YA (low fit, from 11.5 ± 1.8 to 9.2 ± 1.3%; moderately fit, from 11.9 ± 0.8 to 9.0 ± 0.8%) and moderately fit OA (from 7.5 ± 1.0 to 3.9 ± 0.8%) had similar reductions in FMD at 24 h (P < 0.05). Low-fit OA did not reduce FMD at 24 h (from 5.5 ± 0.4 to 5.2 ± 0.5%, P > 0.05). The reduction in FMD in YA was similar between fitness groups (P > 0.05). All groups had similar reductions in mean

  3. Reverse microemulsion synthesis of layered gadolinium hydroxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Xu, Yadong; Suthar, Jugal; Egbu, Raphael; Weston, Andrew J.; Fogg, Andrew M.; Williams, Gareth R.

    2018-02-01

    A reverse microemulsion approach has been explored for the synthesis of layered gadolinium hydroxide (LGdH) nanoparticles in this work. This method uses oleylamine as a multifunctional agent, acting as surfactant, oil phase and base. 1-butanol is additionally used as a co-surfactant. A systematic study of the key reaction parameters was undertaken, including the volume ratio of surfactant (oleylamine) to water, the reaction time, synthesis temperature, and the amount of co-surfactant (1-butanol) added. It proved possible to obtain pristine LGdH materials at temperatures of 120 °C or below with an oleylamine: water ratio of 1:4. Using larger amounts of surfactant or higher temperatures caused the formation of Gd(OH)3, either as the sole product or as a major impurity phase. The LGdH particles produced have sizes of ca. 200 nm, with this size being largely independent of temperature or reaction time. Adjusting the amount of 1-butanol co-surfactant added permits the size to be varied between 200 and 300 nm.

  4. Gadolinium-Based Contrast Agents for MR Cancer Imaging

    PubMed Central

    Zhou, Zhuxian; Lu, Zheng-Rong

    2013-01-01

    Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

  5. Heparanase-driven inflammation from the AGEs-stimulated macrophages changes the functions of glomerular endothelial cells.

    PubMed

    Xu, Guang; Qin, Qiaojing; Yang, Min; Qiao, Zhongdong; Gu, Yong; Niu, Jianying

    2017-02-01

    Amounts of macrophages were infiltrated in glomeruli in diabetic nephropathy. Heparanase has been thought to be closely related to proteinuria. Our aims were to determine the effect of heparanase on the inflammation in AGEs-stimulated macrophages and its role on the functions of glomerular endothelial cells (GEnCs). The expression of inflammation cytokines in macrophages were assayed by q-RT PCR, western, and ELISA. Then western was used to measure the expression of RAGE and key proteins in NF-κB pathway in macrophages. The expression of the adherence molecules and tight junction proteins in GEnCs were assessed by western. The adherence of mononuclear cells to GEnCs were observed by HE staining and transendothelial FITC-BSA were tested for the permeability of GEnCs. HPA siRNA and heparanase inhibitor sulodexide could attenuate the increasing inflammatory factors (TNF-α and IL-1β) in AGEs-stimulated macrophages. NF-κB inhibitor PDTC could also decrease the augmented inflammation cytokines through inhibiting the activation of the NF-κB pathway induced by AGEs. The phosphorylation of NF-κB signaling pathway could be also attenuated by HPA siRNA and sulodexide, the same to the receptor of AGEs RAGE. When the macrophage-conditioned culture medium were added to the glomerular endothelial cells, we found HPA siRNA and sulodexide groups could decrease the increasing adherence and permeability of GEnCs induced by AGEs. Heparanase increases the inflammation in AGEs-stimulated macrophages through activating the RAGE-NF-κB pathway. Heparanase driven inflammation from AGEs-stimulated macrophages increases the adherence of GEnCs and augments the permeability of GEnCs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Where Does Inflammation Fit?

    PubMed

    Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

    2017-09-01

    This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

  7. Cranberry extract attenuates hepatic inflammation in high fat-fed obese mice

    PubMed Central

    Glisan, Shannon L.; Ryan, Caroline; Neilson, Andrew P.; Lambert, Joshua D.

    2016-01-01

    Cranberry (Vaccinium macrocarpon) consumption has been associated with health beneficial effects. Non-alcoholic fatty liver disease (NAFLD) is a co-morbidity of obesity. In the present study, we investigated the effect of a polyphenol-rich cranberry extract (CBE) on hepatic inflammation in high fat-fed obese C57BL/6J mice. Following dietary treatment with 0.8% CBE for 10 weeks, we observed no change in body weight or visceral fat mass in CBE supplemented mice compared to high fat-fed control mice. We did observe a significant decrease in plasma alanine aminotransferase (31%) and histological severity of NAFLD (33% decrease in area of involvement, 29% decrease in lipid droplet size) compared to high fat-fed controls. Hepatic protein levels of tumor necrosis factor alpha and C-C chemokine ligand 2 were reduced by 28% and 19%, respectively, following CBE supplementation. CBE significantly decreased hepatic mRNA levels of toll-like receptor 4 (TLR4, 63%) and nuclear factorκ B (NFκB, 24%), as well as a number of genes related to the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome. In conclusion, CBE reduced NAFLD and hepatic inflammation in high fat-fed obese C57BL/6J mice. These effects appear to be related to mitigation of TLR4-NFκB related signaling, however further studies into the underlying mechanisms of these hepatoprotective effects are needed. PMID:27619543

  8. Cranberry extract attenuates hepatic inflammation in high-fat-fed obese mice.

    PubMed

    Glisan, Shannon L; Ryan, Caroline; Neilson, Andrew P; Lambert, Joshua D

    2016-11-01

    Cranberry (Vaccinium macrocarpon) consumption has been associated with health beneficial effects. Nonalcoholic fatty liver disease (NAFLD) is a comorbidity of obesity. In the present study, we investigated the effect of a polyphenol-rich cranberry extract (CBE) on hepatic inflammation in high fat (HF)-fed obese C57BL/6J mice. Following dietary treatment with 0.8% CBE for 10 weeks, we observed no change in body weight or visceral fat mass in CBE-supplemented mice compared to HF-fed control mice. We did observe a significant decrease in plasma alanine aminotransferase (31%) and histological severity of NAFLD (33% decrease in area of involvement, 29% decrease in lipid droplet size) compared to HF-fed controls. Hepatic protein levels of tumor necrosis factor α and C-C chemokine ligand 2 were reduced by 28% and 19%, respectively, following CBE supplementation. CBE significantly decreased hepatic mRNA levels of toll-like receptor 4 (TLR4, 63%) and nuclear factor κB (NFκB, 24%), as well as a number of genes related to the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 inflammasome. In conclusion, CBE reduced NAFLD and hepatic inflammation in HF-fed obese C57BL/6J mice. These effects appear to be related to mitigation of TLR4-NFκB related signaling; however, further studies into the underlying mechanisms of these hepatoprotective effects are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.

    PubMed

    Lewis, James D; Chen, Eric Z; Baldassano, Robert N; Otley, Anthony R; Griffiths, Anne M; Lee, Dale; Bittinger, Kyle; Bailey, Aubrey; Friedman, Elliot S; Hoffmann, Christian; Albenberg, Lindsey; Sinha, Rohini; Compher, Charlene; Gilroy, Erin; Nessel, Lisa; Grant, Amy; Chehoud, Christel; Li, Hongzhe; Wu, Gary D; Bushman, Frederic D

    2015-10-14

    Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Inflammation in aging part 1: physiology and immunological mechanisms.

    PubMed

    Hunt, Katherine J; Walsh, Bronagh M; Voegeli, David; Roberts, Helen C

    2010-01-01

    During the aging process, remodeling of several body systems occurs, and these changes can have a startling effect upon the immune system. The reduction in sex steroids and growth hormones and declines in vitamin D concentration that accompany the aging process are associated with increases in the baseline levels of inflammatory proteins. At the same time, inflammation arising from atherosclerosis and other chronic diseases further contributes to the inflammatory milieu and effects a state of chronic inflammation. This chronic inflammation, or ''inflammaging'' as it has been termed, seems to be associated with a host of adverse effects contributing to many of the health problems that increase morbidity and decrease both quality of life and the ability to maintain independence in old age. For nurses to be truly informed when caring for older people and to ensure that they have a detailed understanding of the complexities of older people's health needs, they must have a knowledge of the physiological and immunological changes with age. This is the first of a two-part article on inflammatory processes in aging. These age-related changes are presented here, including an examination of the impact of genetic and lifestyle factors. The effect of these changes on the health of the individual and implications for practice are described in Part 2.

  11. Bioactive Egg Components and Inflammation

    PubMed Central

    Andersen, Catherine J.

    2015-01-01

    Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk. PMID:26389951

  12. Pancreatic Cancer, Inflammation and Microbiome

    PubMed Central

    Zambirinis, Constantinos P.; Pushalkar, Smruti; Saxena, Deepak; Miller, George

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist and available treatment modalities do not effectively treat the disease. Inflammatory conditions such as pancreatitis represent a well-known risk for pancreatic cancer development. Yet only in the past two decades has pancreatic cancer been recognized as an inflammation-driven cancer, and the precise mechanisms underlying the pathogenic role of inflammation are beginning to be explored in detail. A substantial amount of preclinical and clinical evidence suggests that bacteria are likely to influence this process by activating immune receptors and perpetuating cancer-associated inflammation. The recent explosion of investigations into the human microbiome have highlighted how perturbations of commensal bacterial populations can promote inflammation and promote disease processes, including carcinogenesis. The elucidation of the interplay between inflammation and microbiome in the context of pancreatic carcinogenesis will provide novel targets for intervention in order to both prevent and treat pancreatic cancer more efficiently. Further studies towards this direction are urgently needed. PMID:24855007

  13. Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy

    PubMed Central

    Villalta, S. Armando; Rosenthal, Wendy; Martinez, Leonel; Kaur, Amanjot; Sparwasser, Tim; Tidball, James G.; Margeta, Marta; Spencer, Melissa J.; Bluestone, Jeffrey A.

    2016-01-01

    We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs were largely absent in the muscle of wildtype mice and normal human muscle, they were present in necrotic lesions, displayed an activated phenotype and showed increased expression of interleukin (IL)-10 in dystrophic muscle from mdx mice. Depletion of Tregs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-gamma (IFNγ) response and activation of M1 macrophages. To test the therapeutic value of targeting Tregs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes (IL-2c), and found that Tregs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooygenase-2 and decreased myofiber injury. These findings suggest that Tregs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of Treg-modulating agents as therapeutics for DMD. PMID:25320234

  14. Plumbagin protects liver against fulminant hepatic failure and chronic liver fibrosis via inhibiting inflammation and collagen production

    PubMed Central

    Cheng, Xixi; Yang, Fengrui; Zhang, Qi; Xue, Zhenyi; Li, Yan; Zhang, Lijuan; Yang, Luhong; Miao, Guolin; Li, Daiqing; Guan, Zhiyu; Da, Yurong; Yao, Zhi; Gao, Fei; Qiao, Liang; Kong, Li; Zhang, Rongxin

    2016-01-01

    Plumbagin is a quinonoid constituent extracted from Plumbago genus, and it exhibits diverse pharmacological effects. This study thoroughly investigated the effects of plumbagin on thioacetamide-induced acute and chronic liver injury. Results shown that plumbagin increased survival rate, reduced liver congestion and inflammation, and decreased macrophages and neutrophils in the fulminant hepatic failure model, and remarkably diminished liver fibrosis and inflammation in the chronic liver injury model. Furthermore, plumbagin significantly suppress the HSCs/myofibroblasts activation by reduced expression of markers α-SMA and COL-1/3, and reduced macrophage in liver. In the in vitro study, plumbagin induced apoptosis and suppressed the proliferation of LX-2 cells (human HSCs). Plumbagin treatment increased AMPK phosphorylation and attenuated NF-κB, STAT3, and Akt/mTOR signals in LX-2 cells, while SMAD2 phosphorylation was not changed. Noticeably, plumbagin promoted AMPK binding to p300 which is a cofactor of SMAD complex, this may further competitively decreases the p300/SMAD complex initiated transcription of COL-1/3 and α-SMA. Additionally, plumbagin hampered inflammation related NF-κB signal in RAW 264.7 cells. In conclusion, these findings indicate that plumbagin may be a powerful drug candidate to protect the liver from acute and chronic damage by inhibiting inflammation and collagen production. PMID:27756878

  15. Ferromagnetic coupling in the three-dimensional malonato-bridged gadoliniumIII complex [Gd2(mal)3(H2O)6] (H2mal = malonic acid).

    PubMed

    Hernández-Molina, María; Ruiz-Pérez, Catalina; López, Trinidad; Lloret, Francesc; Julve, Miguel

    2003-09-08

    The novel gadolinium(III) complex of formula [Gd(2)(mal)(3)(H(2)O)(6)] (1) (H(2)mal = 1,3-propanedioic acid) has been prepared and characterized by X-ray diffraction analysis. Crystal data for 1: monoclinic, space group I2/a, a = 11.1064(10) A, b = 12.2524(10) A, c =13.6098(2) A, beta = 92.925(10) degrees, U = 1849.5(3) A(3), Z = 4. Compound 1 is a three-dimensional network made up of malonate-bridged gadolinium(III) ions where the malonate exhibits two bridging modes, eta(5)-bidentate + unidentate and eta(3):eta(3) + bis(unidentate). The gadolinium atom is nine-coordinate with three water molecules and six malonate oxygen atoms from three malonate ligands forming a distorted monocapped square antiprism. The shortest metal-metal separations are 4.2763(3) A [through the oxo-carboxylate bridge] and 6.541(3) A [through the carboxylate in the anti-syn coordination mode]. The value of the angle at the oxo-carboxylate atom is 116.8(2) degrees. Variable-temperature magnetic susceptibility measurements reveal the occurrence of a significant ferromagnetic interaction through the oxo-carboxylate pathway (J = +0.048(1) cm(-1), H = -JS(Gd(1)) x S(Gd(1a))).

  16. Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice.

    PubMed

    Kawai, Junya; Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

    2014-01-01

    Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10  μ g/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3-1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection.

  17. Pleurotus eryngii Ameliorates Lipopolysaccharide-Induced Lung Inflammation in Mice

    PubMed Central

    Andoh, Tsugunobu; Ouchi, Kenji; Inatomi, Satoshi

    2014-01-01

    Pleurotus eryngii (P. eryngii) is consumed as a fresh cultivated mushroom worldwide and demonstrated to have multiple beneficial effects. We investigated the anti-inflammatory effect of P. eryngii in mice with acute lung injury (ALI). Intranasal instillation of lipopolysaccharide (LPS) (10 μg/site/mouse) induced marked lung inflammation (increase in the number of inflammatory cells, protein leakage, and production of nitric oxide in bronchoalveolar lavage fluid) as well as histopathological damage in the lung, 6 h after treatment. Mice administered heat-treated P. eryngii (0.3–1 g/kg, p.o. (HTPE)) 1 h before LPS challenge showed decreased pulmonary inflammation and ameliorated histopathological damage. These results suggest that HTPE has anti-inflammatory effects against ALI. Thus, P. eryngii itself may also have anti-inflammatory effects and could be a beneficial food for the prevention of ALI induced by bacterial infection. PMID:24799939

  18. Validation of the analytical methods in the LWR code BOXER for gadolinium-loaded fuel pins

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paratte, J.M.; Arkuszewski, J.J.; Kamboj, B.K.

    1990-01-01

    Due to the very high absorption occurring in gadolinium-loaded fuel pins, calculations of lattices with such pins present are a demanding test of the analysis methods in light water reactor (LWR) cell and assembly codes. Considerable effort has, therefore, been devoted to the validation of code methods for gadolinia fuel. The goal of the work reported in this paper is to check the analysis methods in the LWR cell/assembly code BOXER and its associated cross-section processing code ETOBOX, by comparison of BOXER results with those from a very accurate Monte Carlo calculation for a gadolinium benchmark problem. Initial results ofmore » such a comparison have been previously reported. However, the Monte Carlo calculations, done with the MCNP code, were performed at Los Alamos National Laboratory using ENDF/B-V data, while the BOXER calculations were performed at the Paul Scherrer Institute using JEF-1 nuclear data. This difference in the basic nuclear data used for the two calculations, caused by the restricted nature of these evaluated data files, led to associated uncertainties in a comparison of the results for methods validation. In the joint investigations at the Georgia Institute of Technology and PSI, such uncertainty in this comparison was eliminated by using ENDF/B-V data for BOXER calculations at Georgia Tech.« less

  19. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

    PubMed

    Patel, Vaibhav B; Mori, Jun; McLean, Brent A; Basu, Ratnadeep; Das, Subhash K; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M; Grant, Maria B; Lopaschuk, Gary D; Oudit, Gavin Y

    2016-01-01

    Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

    PubMed

    Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

    2015-02-01

    We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

  1. Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females.

    PubMed

    Lennard, Katie; Dabee, Smritee; Barnabas, Shaun L; Havyarimana, Enock; Blakney, Anna; Jaumdally, Shameem Z; Botha, Gerrit; Mkhize, Nonhlanhla N; Bekker, Linda-Gail; Lewis, David A; Gray, Glenda; Mulder, Nicola; Passmore, Jo-Ann S; Jaspan, Heather B

    2018-01-01

    Young African females are at an increased risk of HIV acquisition, and genital inflammation or the vaginal microbiome may contribute to this risk. We studied these factors in 168 HIV-negative South African adolescent females aged 16 to 22 years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters (subtypes), one of which was strongly associated with genital inflammation. In a multivariate model, the microbiome compositional subtype and hormonal contraception were significantly associated with genital inflammation. We identified 40 taxa significantly associated with inflammation, including those reported previously ( Prevotella , Sneathia , Aerococcus , Fusobacterium , and Gemella ) as well as several novel taxa (including increased frequencies of bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3, Prevotella amnii , Prevotella pallens , Parvimonas micra , Megasphaera , Gardnerella vaginalis , and Atopobium vaginae and decreased frequencies of Lactobacillus reuteri , Lactobacillus crispatus , Lactobacillus jensenii , and Lactobacillus iners ). Women with inflammation-associated microbiomes had significantly higher body mass indices and lower levels of endogenous estradiol and luteinizing hormone. Community functional profiling revealed three distinct vaginal microbiome subtypes, one of which was characterized by extreme genital inflammation and persistent bacterial vaginosis (BV); this subtype could be predicted with high specificity and sensitivity based on the Nugent score (≥9) or BVAB1 abundance. We propose that women with this BVAB1-dominated subtype may have chronic genital inflammation due to persistent BV, which may place them at a particularly high risk for HIV infection. Copyright © 2017 American Society for Microbiology.

  2. Microbial Composition Predicts Genital Tract Inflammation and Persistent Bacterial Vaginosis in South African Adolescent Females

    PubMed Central

    Lennard, Katie; Dabee, Smritee; Barnabas, Shaun L.; Havyarimana, Enock; Blakney, Anna; Jaumdally, Shameem Z.; Botha, Gerrit; Mkhize, Nonhlanhla N.; Bekker, Linda-Gail; Lewis, David A.; Gray, Glenda; Mulder, Nicola; Passmore, Jo-Ann S.

    2017-01-01

    ABSTRACT Young African females are at an increased risk of HIV acquisition, and genital inflammation or the vaginal microbiome may contribute to this risk. We studied these factors in 168 HIV-negative South African adolescent females aged 16 to 22 years. Unsupervised clustering of 16S rRNA gene sequences revealed three clusters (subtypes), one of which was strongly associated with genital inflammation. In a multivariate model, the microbiome compositional subtype and hormonal contraception were significantly associated with genital inflammation. We identified 40 taxa significantly associated with inflammation, including those reported previously (Prevotella, Sneathia, Aerococcus, Fusobacterium, and Gemella) as well as several novel taxa (including increased frequencies of bacterial vaginosis-associated bacterium 1 [BVAB1], BVAB2, BVAB3, Prevotella amnii, Prevotella pallens, Parvimonas micra, Megasphaera, Gardnerella vaginalis, and Atopobium vaginae and decreased frequencies of Lactobacillus reuteri, Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners). Women with inflammation-associated microbiomes had significantly higher body mass indices and lower levels of endogenous estradiol and luteinizing hormone. Community functional profiling revealed three distinct vaginal microbiome subtypes, one of which was characterized by extreme genital inflammation and persistent bacterial vaginosis (BV); this subtype could be predicted with high specificity and sensitivity based on the Nugent score (≥9) or BVAB1 abundance. We propose that women with this BVAB1-dominated subtype may have chronic genital inflammation due to persistent BV, which may place them at a particularly high risk for HIV infection. PMID:29038128

  3. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis.

    PubMed

    Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A; Banypersad, Sanjay M; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J; Herrey, Anna S; Lachmann, Helen J; Wechalekar, Ashutosh D; Manisty, Charlotte H; Schelbert, Eric B; Kellman, Peter; Gillmore, Julian D; Hawkins, Philip N; Moon, James C

    2015-10-20

    The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1-13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E', and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3-13.1; P<0.05). There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after adjustment for known prognostic factors. © 2015 The Authors.

  4. The ubiquitin ligase Siah2 regulates obesity-induced adipose tissue inflammation.

    PubMed

    Kilroy, Gail; Carter, Lauren E; Newman, Susan; Burk, David H; Manuel, Justin; Möller, Andreas; Bowtell, David D; Mynatt, Randall L; Ghosh, Sujoy; Floyd, Z Elizabeth

    2015-11-01

    Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases regulate inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored. Herein, the effect of the ubiquitin ligase Siah2 on obesity-related adipose tissue inflammation was examined. Wild-type and Siah2KO mice were fed a low- or high-fat diet for 16 weeks. Indirect calorimetry, body composition, and glucose and insulin tolerance were assayed along with glucose and insulin levels. Gene and protein expression, immunohistochemistry, adipocyte size distribution, and lipolysis were also analyzed. Enlarged adipocytes in obese Siah2KO mice were not associated with obesity-induced insulin resistance. Proinflammatory gene expression, stress kinase signaling, fibrosis, and crown-like structures were reduced in the Siah2KO adipose tissue, and Siah2KO adipocytes were more responsive to insulin-dependent inhibition of lipolysis. Loss of Siah2 increased expression of PPARγ target genes involved in lipid metabolism and decreased expression of proinflammatory adipokines regulated by PPARγ. Siah2 links adipocyte hypertrophy with adipocyte dysfunction and recruitment of proinflammatory immune cells to adipose tissue. Selective regulation of PPARγ activity is a Siah2-mediated mechanism contributing to obesity-induced adipose tissue inflammation. © 2015 The Obesity Society.

  5. A high-fat diet decreases bone mass in growing mice with systemic chronic inflammation induced by low-dose, slow-release lipopolysaccharide pellets

    USDA-ARS?s Scientific Manuscript database

    Chronic inflammation is linked to osteopenia or low bone mass, observed in a variety of physiological conditions such as aging and post-menopause with estrogen deficiency. Evidence suggests that obesity is also associated with low-grade chronic up-regulation of inflammatory cytokines. This study inv...

  6. Effect of advanced glycation end product intake on inflammation and aging: a systematic review.

    PubMed

    Van Puyvelde, Katrien; Mets, Tony; Njemini, Rose; Beyer, Ingo; Bautmans, Ivan

    2014-10-01

    Aging is associated with a chronic low-grade inflammatory status that contributes to chronic diseases such as age-related muscle wasting, kidney disease, and diabetes mellitus. Since advanced glycation end products (AGEs) are known to be proinflammatory, this systematic review examined the relation between the dietary intake of AGEs and inflammatory processes. The PubMed and Web of Science databases were screened systematically. Seventeen relevant studies in humans or animals were included. The intervention studies in humans showed mainly a decrease in inflammation in subjects on a low-AGE diet, while an increase in inflammation in subjects on a high-AGE diet was less apparent. About half of the observational studies found a relationship between inflammatory processes and AGEs in food. When the results are considered together, the dietary intake of AGEs appears to be related to inflammatory status and the level of circulating AGEs. Moreover, limiting AGE intake may lead to a decrease in inflammation and chronic diseases related to inflammatory status. Most of the trials were conducted in patients with chronic kidney disease or diabetes, and thus additional studies in healthy individuals are needed. Further investigation is needed to elucidate the effects of lifetime exposure of dietary AGEs on aging and health. © 2014 International Life Sciences Institute.

  7. Inflammation Fuels Tumor Progress and Metastasis

    PubMed Central

    Liu, Jingyi; Lin, Pengnian Charles; Zhou, Binhua P.

    2017-01-01

    Inflammation is a beneficial response that can remove pathogens, repair injured tissue and restore homeostasis to damaged tissues and organs. However, increasing evidence indicate that chronic inflammation plays a pivotal role in tumor development, as well as progression, metastasis, and resistance to chemotherapy. We will review the current knowledge regarding the contribution of inflammation to epithelial mesenchymal transition. We will also provide some perspectives on the relationship between ER-stress signals and metabolism, and the role of these processes in the development of inflammation. PMID:26004407

  8. Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia.

    PubMed

    Tsunekawa, Taku; Banno, Ryoichi; Mizoguchi, Akira; Sugiyama, Mariko; Tominaga, Takashi; Onoue, Takeshi; Hagiwara, Daisuke; Ito, Yoshihiro; Iwama, Shintaro; Goto, Motomitsu; Suga, Hidetaka; Sugimura, Yoshihisa; Arima, Hiroshi

    2017-02-01

    Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT). In hypothalamic organotypic cultures, incubation with TNFα led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice.

    PubMed

    Zare, Ahad; Farzaneh, Parvaneh; Pourpak, Zahra; Zahedi, Fatemeh; Moin, Mostafa; Shahabi, Shahram; Hassan, Zuhair M

    2008-09-01

    Garlic is known as a potent spice and a medicinal herb with broad therapeutic properties ranging from antibacterial to anticancer and anticoagulant. Our previous studies have shown some immunoregulatory effects for aged garlic extract, suggesting a key role for 14-kD glycoprotein of garlic in shifting the cytokine pattern to T helper-1. In present study, we investigated the effect of 1, 2, and 3 times intraperitoneal injections of aged garlic extract on an established allergic airway inflammation in murine model (BALB/c mice). The garlic extract, isolated by biochemical method, includes proteins precipitation by ammonium sulfate. After injection of the aged garlic extract, IFN-, anti allergen specific IgE and IgG1 were measured in lavage and serum by ELISA and histological assessment was performed on the lung tissues. The results indicated that three-time intra peritoneal injections of the aged garlic extract caused a significant decrease in the hallmark criteria of allergic airway inflammation levels which included eosinophil percentage in lavage, peribronchial lung eosinophils, IgG1 level in lavage and serum, mucous producing goblet cells grade and peribronchial and perivascular inflammation. Our findings in the present research suggested that aged garlic extract has the potential of attenuation of inflammatory features of allergic airway inflammation in murine model.

  10. Inflammation-initiating illnesses, inflammation-related proteins, and cognitive impairment in extremely preterm infants.

    PubMed

    O'Shea, T Michael; Shah, Bhavesh; Allred, Elizabeth N; Fichorova, Raina N; Kuban, Karl C K; Dammann, Olaf; Leviton, Alan

    2013-03-01

    Neonatal inflammation is associated with perinatal brain damage. We evaluated to what extent elevated blood levels of inflammation-related proteins supplement information about the risk of impaired early cognitive function provided by inflammation-related illnesses. From 800 infants born before the 28th week of gestation, we collected blood spots on days 1, 7 and 14, for analysis of 25 inflammation-related proteins, and data about culture-positive bacteremia, necrotizing enterocolitis (Bell stage IIIb), and isolated perforation of the intestine, during the first two weeks, and whether they were ventilated on postnatal day 14. We considered a protein to be persistently or recurrently elevated if its concentration was in the top quartile (for gestational age and day blood was collected) on two separate days one week apart. We assessed the children at 2 years of age with the Bayley Mental Development Index (MDI). The combinations of NEC and ventilation on day 14, and of bacteremia and ventilation on day 14 consistently provided information about elevated risk of MDI <55, regardless of whether or not a variable for an elevated protein concentration was included in the model. A variable for a persistently or recurrently elevated concentration of each of the following proteins provided additional information about an increased risk of MDI <55: CRP, SAA, IL-6, TNF-alpha, IL-8, MIP-1beta, ICAM-1, E-SEL, and IGFBP-1. We conclude that elevated blood concentrations of inflammation-related proteins provide information about the risk of impaired cognitive function at age 2 years that supplements information provided by inflammation-associated illnesses. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats.

    PubMed

    Giraud, O; Seince, P F; Rolland, C; Leçon-Malas, V; Desmonts, J M; Aubier, M; Dehoux, M

    2000-12-01

    Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific

  12. Ethanol intoxication prolongs post-burn pulmonary inflammation: role of alveolar macrophages

    PubMed Central

    Shults, Jill A.; Curtis, Brenda J.; Boe, Devin M.; Ramirez, Luis; Kovacs, Elizabeth J.

    2016-01-01

    In this study, the role and fate of AMs were examined in pulmonary inflammation after intoxication and injury. Clinical evidence has revealed that half of all burn patients brought to the emergency department are intoxicated at the time of injury. This combined insult results in amplified neutrophil accumulation and pulmonary edema, with an increased risk of lung failure and mortality, relative to either insult alone. We believe that this excessive pulmonary inflammation, which also parallels decreased lung function, is mediated in part by AMs. Restoration of lung tissue homeostasis is dependent on the eradication of neutrophils and removal of apoptotic cells, both major functions of AMs. Thirty minutes after binge ethanol intoxication, mice were anesthetized and given a 15% total body surface area dorsal scald injury. At 24 h, we found a 50% decrease in the total number of AMs (P < 0.05) and observed a proinflammatory phenotype on the remaining lung AMs. Loss of AMs paralleled a 6-fold increase in the number of TUNEL+ lung apoptotic cells (P < 0.05) and a 3.5-fold increase in the percentage of annexin V+ apoptotic cells in BAL (P < 0.05), after intoxication and injury, relative to controls. In contrast to the reduction in the number of cells, AMs from intoxicated and injured mice had a 4-fold increase in efferocytosis (P < 0.05). In summary, these data suggest that loss of AMs may delay resolution of inflammation, resulting in the pulmonary complications and elevated mortality rates observed in intoxicated and burn-injured patients. PMID:27531926

  13. Gadolinium-free MR in coarctation-can contrast-enhanced MR angiography be replaced?

    PubMed

    Kalmar, Peter I; Koestenberger, Martin; Marterer, Robert; Tschauner, Sebastian; Sorantin, Erich

    2016-01-01

    To determine the difference in vessel measurements, signal-to-noise ratio (SNR), and voxel size between contrast-enhanced and noncontrast magnetic resonance techniques in patients with coarctation of the aorta (CoA). In 39 patients, vessel size, SNR, and voxel size were compared in cine magnetic resonance imaging (MRI), gadolinium-free magnetic resonance angiography (Gd-free MRA), and contrast-enhanced MRA (ce-MRA). There was no significant difference in measurement and SNR, but there was a significant difference in voxel size (P<.001). Our results show that, in CoA patients, monitoring of vessel size using cine MRI and Gd-free MRA is equivalent to ce-MRA while being less invasive. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Electronic transport in gadolinium atomic-size contacts

    NASA Astrophysics Data System (ADS)

    Olivera, B.; Salgado, C.; Lado, J. L.; Karimi, A.; Henkel, V.; Scheer, E.; Fernández-Rossier, J.; Palacios, J. J.; Untiedt, C.

    2017-02-01

    We report on the fabrication, transport measurements, and density functional theory (DFT) calculations of atomic-size contacts made of gadolinium (Gd). Gd is known to have local moments mainly associated with f electrons. These coexist with itinerant s and d bands that account for its metallic character. Here we explore whether and how the local moments influence electronic transport properties at the atomic scale. Using both scanning tunneling microscope and lithographic mechanically controllable break junction techniques under cryogenic conditions, we study the conductance of Gd when only few atoms form the junction between bulk electrodes made of the very same material. Thousands of measurements show that Gd has an average lowest conductance, attributed to single-atom contact, below 2/e2 h . Our DFT calculations for monostrand chains anticipate that the f bands are fully spin polarized and insulating and that the conduction may be dominated by s , p , and d bands. We also analyze the electronic transport for model nanocontacts using the nonequilibrium Green's function formalism in combination with DFT. We obtain an overall good agreement with the experimental results for zero bias and show that the contribution to the electronic transport from the f channels is negligible and that from the d channels is marginal.

  15. Metabolic Effects of Inflammation on Vitamin A and Carotenoids in Humans and Animal Models.

    PubMed

    Rubin, Lewis P; Ross, A Catharine; Stephensen, Charles B; Bohn, Torsten; Tanumihardjo, Sherry A

    2017-03-01

    The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency. On the other hand, inflammation causes impaired VA absorption and urinary losses that can precipitate VA deficiency in at-risk groups of children. Many epidemiologic studies have suggested that high dietary carotenoid intake and elevated plasma concentrations are correlated with a decreased risk of several chronic diseases; however, large-scale carotenoid supplementation trials have been unable to confirm the health benefits and in some cases resulted in controversial results. However, it has been documented that dietary carotenoids and retinoids play important roles in innate and acquired immunity and in the body's response to inflammation. Although animal models have been useful in investigating retinoid effects on developmental immunity, it is more challenging to tease out the effects of carotenoids because of differences in the absorption, kinetics, and metabolism between humans and animal models. The current understanding of the relations between inflammation and retinoid and carotenoid metabolism and status are the topics of this review. © 2017 American Society for Nutrition.

  16. Clearance of Aspergillus fumigatus is impaired in the airway in allergic inflammation.

    PubMed

    Fukahori, Susumu; Matsuse, Hiroto; Tsuchida, Tomoko; Kawano, Tetsuya; Nishino, Tomoya; Fukushima, Chizu; Kohno, Shigeru

    2014-08-01

    Aspergillus fumigatus (Af) sometimes colonizes and persists within the respiratory tree in some patients with asthma. To date, the precise reasons why the clearance of Af is impaired in patients with asthma remain unknown. To characterize the effects of allergic airway inflammation on clearance of Af. Control and Dermatophagoides farinae (Df) allergen-sensitized BALB/c mice were intranasally infected with Af. After 2 and 9 days of infection, the pathology, fungal burden, and cytokine profile in lung tissue were compared. In a different set of experiments, the phagocytotic activity of alveolar macrophages and the expression of their pathogen recognition receptors also were determined. The Af conidia and neutrophilic airway inflammation disappeared by day 9 after infection in control mice. In Df-sensitized mice, Af conidia and neutrophilic and eosinophilic airway inflammation persisted at day 9 after infection. Compared with control mice, Df allergen-sensitized mice showed significant increases in interleukin (IL)-5 and decreases in IL-12 and interferon-γ in lung tissues at day 2 after infection. Most importantly, compared with Af-infected non-Df-sensitized mice, IL-17 in lung tissues was significantly decreased in Df allergen-sensitized Af-infected mice at day 2 after infection but was significantly increased at day 9. Alveolar macrophages isolated from Df allergen-sensitized mice exhibited significant decreases in phagocytotic activity and expression of Toll-like receptor-4 and dectin-1 compared with those from control mice. In the airway of patients with allergy, T-helper cell type 2-dominant immunity potentially affects the expression of pathogen recognition receptors and attenuates cellular defense against Af. Prolonged IL-17 production also could play an important role. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Inhibitory Effects of 4'-Demethylnobiletin, a Metabolite of Nobiletin, on 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Inflammation in Mouse Ears.

    PubMed

    Wu, Xian; Song, Mingyue; Rakariyatham, Kanyasiri; Zheng, Jinkai; Wang, Minqi; Xu, Fei; Gao, Zili; Xiao, Hang

    2015-12-30

    Nobiletin (NOB) is major citrus flavonoid with many health-promoting benefits. We reported previously that 4'-demethylnobiletin (4DN), a major metabolite of NOB, significantly inhibited lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 macrophages. In this study, we further studied the anti-inflammatory effects of 4DN in TPA-induced skin inflammation in mice. We demonstrated that topical application of 4DN decreased TPA-induced ear edema by >88 ± 4.77% in mice. This inhibitory effect was associated with inhibition on TPA-induced up-regulation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Immunoblotting results showed that 4DN resulted in profound effects on multiple proteins related with inflammation and carcinogenesis. 4DN significantly decreased the expression levels of iNOS, COX-2, and MMP-9, suppressed phosphorylation of PI3K/Akt and ERK, and increased the levels of HO-1 and NQO1 in TPA-treated mice. Overall, the results demonstrated that 4DN had strong anti-inflammatory effects in vivo, which provided a scientific basis for using NOB to inhibit inflammation-driven diseases.

  18. Arctigenin improves vascular tone and decreases inflammation in human saphenous vein.

    PubMed

    Daci, Armond; Neziri, Burim; Krasniqi, Shaip; Cavolli, Raif; Alaj, Rame; Norata, Giuseppe Danilo; Beretta, Giangiacomo

    2017-09-05

    The goal of this study was to test the effects of bioactive phenylpropanoid dibenzylbutyrolactone lignan arctigenin (ATG) in vascular tone. Human bypass graft vessel, from a saphenous vein (SV), were set up in organ bath system and contracted with potassium chloride (KCl, 40mM). Two concentration-response curves of noradrenaline (NE) (10nM-100μM) separated with an incubation period of 30min without (Control) or with ATG (3-100μM) were established. Inhibitors of nitric oxide, prostaglandins, K + related channels or calcium influx were used to delineate the molecular mechanisms beyond ATG effects. To investigate anti-inflammatory actions, SV were treated with 10μM or 100μM ATG and incubated for 18h in the absence or presence of both interleukin-1beta (IL-1β) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators İnterleukine-1 beta (IL-1β), Monocyte Chemoattractant Proteine-1 (MCP-1), Tumor Necrosis Factor- α (TNF-α), İnterleukine-6 (IL-6), Prostaglandin E 2 (PGE 2 ) and İnterleukine-8 (IL-8) in the supernatant were measured. ATG significantly decreased vascular contractile response to NE. Moreover, it reduced contractions induced by KCl and cumulative addition of CaCl 2. The mediators were significantly increased in inflammatory conditions compared to normal conditions, an effect which was inhibited by ATG (10 and 100µM). ATG reduces contractions in SV and decreases the production of proinflammatory-proatherogenic mediators, setting the stage for further evaluating the effect of ATG in cardiovascular diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. H₂S and substance P in inflammation.

    PubMed

    Bhatia, Madhav

    2015-01-01

    Hydrogen sulfide (H2S) and substance P play a key role in inflammation. Using animal models of inflammation of different etiologies such as acute pancreatitis, sepsis, burns, and joint inflammation, studies have recently shown an important role of the proinflammatory action of H2S and substance P. Also, H2S contributes to inflammation in different conditions via substance P. This chapter reviews methods and key data that have led to our current understanding of the role of H2S and substance P in inflammation. © 2015 Elsevier Inc. All rights reserved.

  20. Fecal markers of inflammation, protein loss, and microbial changes in dogs with the acute hemorrhagic diarrhea syndrome (AHDS).

    PubMed

    Heilmann, Romy M; Guard, Melissa M; Steiner, Jörg M; Suchodolski, Jan S; Unterer, Stefan

    2017-09-01

    Idiopathic acute hemorrhagic diarrhea syndrome (AHDS) is characterized by acute onset of bloody diarrhea, severe dehydration, and increased vascular and intestinal mucosal permeability. Markers of gastrointestinal inflammation, protein loss, and changes in the intestinal microbiota have not been studied extensively in dogs with AHDS. For 3 consecutive days, feces were collected from dogs with AHDS, and assayed for calprotectin and S100A12 (both markers of inflammation), α 1 -proteinase inhibitor (a marker of gastrointestinal protein loss), and the presence of selected species of bacteria. Concentrations of all assayed markers were significantly greater than the institutional reference intervals at the time of presentation, and all decreased significantly by Day 3 of treatment. Abundances of selected bacterial groups (Ruminococcaceae, Faecalibacterium spp., Bifidobacterium spp., and Proteobacteria) at the time of diagnosis were consistent with an intestinal bacterial dysbiosis. No differences in the abundance of bacterial groups over time was seen, except for a mild but significant decrease in Ruminococcaceae at Day 3. These results suggest that canine AHDS is associated with a significant but transient gastrointestinal loss of protein and intestinal inflammation. The intestinal bacterial dysbiosis appears to outlast the protein loss and inflammation. © Veterinary Emergency and Critical Care Society 2017.

  1. Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation.

    PubMed

    Lee, Da-In; Park, Mi-Kyung; Kang, Shin Ae; Choi, Jun-Ho; Kang, Seok-Jung; Lee, Jeong-Yeol; Yu, Hak Sun

    2016-01-01

    Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.

  2. Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

    PubMed

    Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

    2016-11-01

    Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Source of Chronic Inflammation in Aging.

    PubMed

    Sanada, Fumihiro; Taniyama, Yoshiaki; Muratsu, Jun; Otsu, Rei; Shimizu, Hideo; Rakugi, Hiromi; Morishita, Ryuichi

    2018-01-01

    Aging is a complex process that results from a combination of environmental, genetic, and epigenetic factors. A chronic pro-inflammatory status is a pervasive feature of aging. This chronic low-grade inflammation occurring in the absence of overt infection has been defined as "inflammaging" and represents a significant risk factor for morbidity and mortality in the elderly. The low-grade inflammation persists even after reversing pro-inflammatory stimuli such as LDL cholesterol and the renin-angiotensin system (RAS). Recently, several possible sources of chronic low-grade inflammation observed during aging and age-related diseases have been proposed. Cell senescence and dysregulation of innate immunity is one such mechanism by which persistent prolonged inflammation occurs even after the initial stimulus has been removed. Additionally, the coagulation factor that activates inflammatory signaling beyond its role in the coagulation system has been identified. This signal could be a new source of chronic inflammation and cell senescence. Here, we summarized the factors and cellular pathways/processes that are known to regulate low-grade persistent inflammation in aging and age-related disease.

  4. Design and development of a Gadolinium-doped water Cherenkov detector

    NASA Astrophysics Data System (ADS)

    Poudyal, Nabin

    This thesis describes a research and development project for neutron capture and detection in Gadolinium doped water. The Sanford Underground Research Facility (SURF) is exploring rare event physics, such as neutrinoless double beta decay (MAJORANA Project) and dark-matter detection (LUX experiment). The success of these experiments requires a careful study and understanding of background radiation, including flux and energy spectrum. The background radiation from surface contamination, radioactive decays of U-238, Th-232, Rn-222 in the surrounding rocks and muon induced neutrons have a large impact on the success of rare-event physics. The main objective of this R&D project is to measure the neutron flux contributing to ongoing experiments at SURF and suppress it by identification and capture method. For this purpose, we first modeled and designed a detector with Geant4 software. The approximate dimension of the detector is determined. The neutron capture percentage of the detector is estimated using Monte Carlo. The energy response of the detector is simulated. Next, we constructed the experimental detector, an acrylic rectangular tank (60cm x 30cm x 30cm), filled with Gadolinium-doped deionized water. The tank is coated with high efficient reflector and then taped with black electrical tape to make it opaque. The voltage dividers attached to PMTs are covered with mu-metal. Two 5-inch Hamamatsu Photomultiplier tubes were attached on both sides facing the tank to collect the Cherenkov light produced in the water. The detector utilizes the principle of Cherenkov light emission by a charged particle moving through a water at a speed higher than the speed of light in the water, hence it has an inherent energy threshold of Cherenkov photon production. This property reduces the lower energy backgrounds. Event data are obtained using the Data Acquisition hardware, Flash Analog to digital converter, along with Multi Instance Data Acquisition software. Post

  5. Anomalous Hall effect in calcium-doped lanthanum cobaltite and gadolinium

    NASA Astrophysics Data System (ADS)

    Baily, Scott Alan

    The physical origin of the anomalous (proportional to magnetization) Hall effect is not very well understood. While many theories account for a Hall effect proportional to the magnetization of a material, these theories often predict effects significantly smaller than those found in ferromagnetic materials. An even more significant deficiency of the conventional theories is that they predict an anomalous Hall resistivity that is proportional to a power of the resistivity, and in the absence of a metal insulator transition cannot account for the anomalous Hall effect that peaks near TC. Recent models based on a geometric, or Berry, phase have had a great deal of success describing the anomalous Hall effect in double-exchange systems (e.g., lanthanum manganite and chromium dioxide). In gadolinium, as in double-exchange magnets, the exchange interaction is mediated by the conduction electrons and the anomalous Hall effect may therefore resemble that of CrO2 and other metallic double-exchange ferromagnets. Lanthanum cobaltite is similar to manganite in many ways, but a strong double-exchange interaction is not present. Calcium-doped lanthanum cobaltite films were found to have the largest anomalous Hall effect of any ferromagnetic metal. The primary purpose of this study is to gain insight into the origin of the anomalous Hall effect with the hope that these theories can be extended to account for the effect in other materials. The Hall resistivity, magnetoresistance, and magnetization of a Gadolinium single crystal were measured in fields up to 30 T. Cobaltite films were grown via laser ablation and characterized by a variety of techniques. Hall resistivity, magnetoresistance, magnetization, and magnetothermopower of L 1-xCaxCoO3 samples with 0.15 < x < 0.4 were measured in fields up to 7 T. The Gd results suggest that Berry's phase contributes partially to the Hall effect near TC. Berry's phase theories hold promise for explaining the large anomalous Hall effect in

  6. Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice

    PubMed Central

    Oh, Ah-Reum; Bae, Jin-Sik; Lee, Junghoon; Shin, Eunji; Oh, Byung-Chul; Park, Sang-Chul; Cha, Ji-Young

    2016-01-01

    Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli. [BMB Reports 2016; 49(2): 105-110] PMID:26350747

  7. Inflammation, cancer, and targets of ginseng.

    PubMed

    Hofseth, Lorne J; Wargovich, Michael J

    2007-01-01

    Chronic inflammation is associated with a high cancer risk. At the molecular level, free radicals and aldehydes, produced during chronic inflammation, can induce deleterious gene mutation and posttranslational modifications of key cancer-related proteins. Other products of inflammation, including cytokines, growth factors, and transcription factors such as nuclear factor kappaB, control the expression of cancer genes (e.g., suppressor genes and oncogenes) and key inflammatory enzymes such as inducible nitric oxide synthase and cyclooxygenase-2. These enzymes in turn directly influence reactive oxygen species and eicosanoid levels. The procancerous outcome of chronic inflammation is increased DNA damage, increased DNA synthesis, cellular proliferation, disruption of DNA repair pathways and cellular milieu, inhibition of apoptosis, and promotion of angiogenesis and invasion. Chronic inflammation is also associated with immunosuppression, which is a risk factor for cancer. Current treatment strategies for reactive species overload diseases are frequently aimed at treating or preventing the cause of inflammation. Although these strategies have led to some progress in combating reactive species overload diseases and associated cancers, exposure often occurs again after eradication, treatment to eradicate the cause fails, or the treatment has long-term side effects. Therefore, the identification of molecules and pathways involved in chronic inflammation and cancer is critical to the design of agents that may help in preventing the progression of reactive species overload disease and cancer associated with disease progression. Here, we use ginseng as an example of an antiinflammatory molecule that targets many of the key players in the inflammation-to-cancer sequence.

  8. Gadolinium oxide nanoplates with high longitudinal relaxivity for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Cho, Minjung; Sethi, Richa; Ananta Narayanan, Jeyarama Subramanian; Lee, Seung Soo; Benoit, Denise N.; Taheri, Nasim; Decuzzi, Paolo; Colvin, Vicki L.

    2014-10-01

    Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values moderately reduce as the size of the Gd2O3 nanoplates increases, and are always larger for the PAA-OA coating. Cytotoxicity studies on human dermal fibroblast cells documented no significant toxicity, with 100% cell viability preserved up to 250 μM for the PAA-OA coated Gd2O3 nanoplates. Given the 10 times increase in longitudinal relaxivity over the commercially available Gd-based molecular agents and the favorable toxicity profile, the 2 nm PAA-OA coated Gd2O3 nanoplates could represent a new class of highly effective T1 MRI contrast agents.Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values

  9. Investigation of terbium in the ferroelectric crystal, gadolinium molybdate, as a potential laser

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crouch, J.E.

    A preliminary non-stimulated study of the laser host combination Gd(2 - x)Tb(x)(MoO4)3 is made. The host material, gadolinium molybdate (GMO), is a ferroelectric/ferroelastic crystal. An investigation of temperature and external electric field affects on the absorption and fluorescence of the crystal did not produce any unusual results. The terbium ion, Tb(3+), peak cross section in GMO for the 5D sub 4 to 7F sub 5 transition is 10 x 10 to the minus twenty first power sq. cm. at 300K. The wavelength of this four level laser transition is 543 nm. (GRA)

  10. Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation.

    PubMed

    Behrends, D A; Hui, D; Gao, C; Awlia, A; Al-Saran, Y; Li, A; Henderson, J E; Martineau, P A

    2017-03-01

    Bone repair is initiated with a local inflammatory response to injury. The presence of systemic inflammation impairs bone healing and often leads to malunion, although the underlying mechanisms remain poorly defined. Our research objective was to use a mouse model of cortical bone repair to determine the effect of systemic inflammation on cells in the bone healing microenvironment. QUESTION/PURPOSES: (1) Does systemic inflammation, induced by lipopolysaccharide (LPS) administration affect the quantity and quality of regenerating bone in primary bone healing? (2) Does systemic inflammation alter vascularization and the number or activity of inflammatory cells, osteoblasts, and osteoclasts in the bone healing microenvironment? Cortical defects were drilled in the femoral diaphysis of female and male C57BL/6 mice aged 5 to 9 months that were treated with daily systemic injections of LPS or physiologic saline as control for 7 days. Mice were euthanized at 1 week (Control, n = 7; LPS, n = 8), 2 weeks (Control, n = 7; LPS, n = 8), and 6 weeks (Control, n = 9; LPS, n = 8) after surgery. The quantity (bone volume per tissue volume [BV/TV]) and microarchitecture (trabecular separation and thickness, porosity) of bone in the defect were quantified with time using microCT. The presence or activity of vascular endothelial cells (CD34), macrophages (F4/80), osteoblasts (alkaline phosphatase [ALP]), and osteoclasts (tartrate-resistant acid phosphatase [TRAP]) were evaluated using histochemical analyses. Only one of eight defects was bridged completely 6 weeks after surgery in LPS-injected mouse bones compared with seven of nine defects in the control mouse bones (odds ratio [OR], 0.04; 95% CI, 0.003-0.560; p = 0.007). The decrease in cortical bone in LPS-treated mice was reflected in reduced BV/TV (21% ± 4% vs 39% ± 10%; p < 0.01), increased trabecular separation (240 ± 36 μm vs 171 ± 29 μm; p < 0.01), decreased trabecular thickness (81 ± 18 μm vs 110 ± 22 μm; p = 0

  11. Optimisation of dynamic nuclear polarisation of [1-13C] pyruvate by addition of gadolinium-based contrast agents

    NASA Astrophysics Data System (ADS)

    Friesen-Waldner, Lanette; Chen, Albert; Mander, Will; Scholl, Timothy J.; McKenzie, Charles A.

    2012-10-01

    Dynamic nuclear polarisation (DNP) of carbon-13 (13C) enriched endogenous compounds provides a novel means for magnetic resonance imaging and spectroscopy of biological processes. Adding small amounts of gadolinium-based contrast agents (GBCAs) to the 13C-enriched substrate matrix increases the amount of hyperpolarisation that can be achieved, but also may decrease the longitudinal relaxation time (T1) of the 13C nucleus in solution. This study examined the effects of five different GBCA at concentrations of 0.5, 1, 2, and 3 mM on [1-13C]-enriched pyruvic acid. It was found that contrast agents with an open chain structure (Gadobenate dimeglumine, Gadopentetate dimeglumine, Gadodiamide) caused the largest enhancement (up to 82%) in solid state polarisation relative to solutions without GBCA. In the liquid state, T1 of pyruvate decreased by as much as 62% and polarisation was much lower (70%) relative to solutions without GBCA added. Conversely, for GBCA with macrocyclic structures (Gadoterate meglumine, Gadoteridol), the solid state polarisation enhancement was only slightly less than the open chain GBCA, but enhanced polarisation was retained much better in the liquid state with minimal decrease in T1 (25% at the highest GBCA concentrations). Near maximum polarisation in the solid state was obtained at a GBCA concentration of 2 mM, with a higher concentration of 3 mM producing minimal improvement. These results indicate that the macrocyclic contrast agents provide the best combination of high solid state and liquid state polarisations with minimal loss of T1 in experiments with hyperpolarised 13C-enriched pyruvate. This suggests that macrocyclic contrast agents should be the GBCA of choice for maximising signal in experiments with hyperpolarised 13C-enriched pyruvate, particularly for in vivo measurements where shortened substrate T1 is especially problematic.

  12. Behavioral and monoamine perturbations in adult male mice with chronic inflammation induced by repeated peripheral lipopolysaccharide administration.

    PubMed

    Krishna, Saritha; Dodd, Celia A; Filipov, Nikolay M

    2016-04-01

    Considering the limited information on the ability of chronic peripheral inflammation to induce behavioral alterations, including on their persistence after inflammatory stimuli termination and on associated neurochemical perturbations, this study assessed the effects of chronic (0.25 mg/kg; i.p.; twice weekly) lipopolysaccharide (LPS) treatment on selected behavioral, neurochemical and molecular measures at different time points in adult male C57BL/6 mice. Behaviorally, LPS-treated mice were hypoactive after 6 weeks, whereas significant hyperactivity was observed after 12 weeks of LPS and 11 weeks after 13 week LPS treatment termination. Similar biphasic responses, i.e., early decrease followed by a delayed increase were observed in the open field test center time, suggestive of, respectively, increased and decreased anxiety. In a forced swim test, mice exhibited increased immobility (depressive behavior) at all times they were tested. Chronic LPS also produced persistent increase in splenic serotonin (5-HT) and time-dependent, brain region-specific alterations in striatal and prefrontocortical dopamine and 5-HT homeostasis. Microglia, but not astrocytes, were activated by LPS early and late, but their activation did not persist after LPS treatment termination. Above findings demonstrate that chronic peripheral inflammation initially causes hypoactivity and increased anxiety, followed by persistent hyperactivity and decreased anxiety. Notably, chronic LPS-induced depressive behavior appears early, persists long after LPS termination, and is associated with increased splenic 5-HT. Collectively, our data highlight the need for a greater focus on the peripheral/central monoamine alterations and lasting behavioral deficits induced by chronic peripheral inflammation as there are many pathological conditions where inflammation of a chronic nature is a hallmark feature. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. TNF-α blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis

    PubMed Central

    Mahanty, Siddhartha; Adrianzen, M. Paz; Arroyo, Gianfranco; Calcina, Juan; Gonzalez, Armando E.; García, Héctor H.; Nash, Theodore E.

    2017-01-01

    )1, angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX pretreated pigs compared to PZQ alone, and only for TNF-α, IL-6, IFN-γ, TGF-β and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The degree of inflammation, assessed by semi-quantitative inflammatory scores, was modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated pigs whereas cyst damage scores were moderately decreased only in cysts from DEX pretreated pigs. However, the proportion of cysts with EB extravasation was not significantly changed in ETN and DEX pretreated groups. Conclusions/Significance Overall, TNF-α blockade using ETN treatment modulated expression of a large variety of genes that play a role in induction and control of inflammation and structural changes. In contrast the number of inflammatory cells was only moderately decreased suggesting weaker effects on cell migration into the inflammatory capsules surrounding cysts than on release of modulatory molecules. Taken together, these data suggest that TNF-α blockade may provide a viable strategy to manage post-treatment pericystic inflammation that follows antiparasitic therapy for neurocysticercosis. PMID:29190292

  14. Diesel exhaust particle promotes tumor lung metastasis via the induction of BLT1-mediated neutrophilic lung inflammation.

    PubMed

    Li, Wenjing; Liu, Ting; Xiong, Yingluo; Lv, Jiaoyan; Cui, Xinyi; He, Rui

    2018-06-05

    BLT1, the primary functional receptor of Leukotriene B4 (LTB4), is involved in tissue inflammation by mediating leukocyte recruitment, and recently LTB4-dependent inflammation was reported to promote lung tumor growth. Exposure to diesel exhaust particle (DEP), the major component of particulate matter 2.5 (PM 2.5 ), can elicit lung inflammation, which may increase the risk of lung cancer. However, it remains unknown about the critical factors mediating DEP-induced lung inflammation and the subsequent effect on tumor metastasis. In this study, we found that DEP exposure led to acute lung inflammation, characterized by abundant infiltration of neutrophils and elevated lung levels in LTB4, as well as several pro-inflammatory cytokines and chemokines, including IL-1β, IL-6, TNF-α, CXCL1/2. Furthermore, DEP exposure promoted lung metastasis of 3LL and 4T1 cells. BLT1 blockade by its specific antagonist U75302 significantly inhibited neutrophilic lung inflammation following DEP exposure. Importantly, BLT1 blockade before the onset of inflammation significantly reduced DEP-enhanced lung metastasis, which was associated with greatly decreased infiltrating neutrophils in lungs. Interestingly, BLT1 blockade after the occurrence of lung metastases had no effect on the magnitude of lung metastasis, suggesting that inhibition of BLT1-mediated lung inflammation was insufficient to suppress established metastatic tumor. Administration of BLT2 inhibitor LY255283 fails to inhibit DEP-induced lung inflammation and tumor metastasis. Collectively, our results demonstrate that DEP exposure causes BLT1-mediated lung neutrophilic inflammation, which is critical for tumor lung metastasis, and suggest that interruption of the LTB4-BLT1 axis could be useful for preventing PM 2.5 -induced inflammation and subsequent susceptible to lung metastasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

    PubMed

    Tobin, W Oliver; Guo, Yong; Krecke, Karl N; Parisi, Joseph E; Lucchinetti, Claudia F; Pittock, Sean J; Mandrekar, Jay; Dubey, Divyanshu; Debruyne, Jan; Keegan, B Mark

    2017-09-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory syndrome predominantly affecting the brainstem, cerebellum, and spinal cord. Following its initial description, the salient features of CLIPPERS have been confirmed and expanded upon, but the lack of formalized diagnostic criteria has led to reports of patients with dissimilar features purported to have CLIPPERS. We evaluated clinical, radiological and pathological features of patients referred for suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from non-CLIPPERS aetiologies. Thirty-five patients were evaluated for suspected CLIPPERS. Clinical and neuroimaging data were reviewed by three neurologists to confirm CLIPPERS by consensus agreement. Neuroimaging and neuropathology were reviewed by experienced neuroradiologists and neuropathologists, respectively, both of whom were blinded to the clinical data. CLIPPERS was diagnosed in 23 patients (18 male and five female) and 12 patients had a non-CLIPPERS diagnosis. CLIPPERS patients' median age of onset was 58 years (interquartile range, 24-72) and were followed a median of 44 months (interquartile range 38-63). Non-CLIPPERS patients' median age of onset was 52 years (interquartile range, 39-59) and were followed a median of 27 months (interquartile range, 14-47). Clinical symptoms of gait ataxia, diplopia, cognitive impairment, and facial paraesthesia did not discriminate CLIPPERS from non-CLIPPERS. Marked clinical and radiological corticosteroid responsiveness was observed in CLIPPERS (23/23), and clinical worsening occurred in all 12 CLIPPERS cases when corticosteroids were discontinued. Corticosteroid responsiveness was common but not universal in non-CLIPPERS [clinical improvement (8/12); radiological improvement (2/12); clinical worsening on discontinuation (3/8)]. CLIPPERS patients had brainstem predominant perivascular gadolinium enhancing

  16. Electronic structure, charge transfer, and intrinsic luminescence of gadolinium oxide nanoparticles: Experiment and theory

    NASA Astrophysics Data System (ADS)

    Zatsepin, D. A.; Boukhvalov, D. W.; Zatsepin, A. F.; Kuznetsova, Yu. A.; Mashkovtsev, M. A.; Rychkov, V. N.; Shur, V. Ya.; Esin, A. A.; Kurmaev, E. Z.

    2018-04-01

    The cubic (c) and monoclinic (m) polymorphs of Gd2O3 were studied using the combined analysis of several materials science techniques - X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and photoluminescence (PL) spectroscopy. Density functional theory (DFT) based calculations for the samples under study were performed as well. The cubic phase of gadolinium oxide (c-Gd2O3) synthesized using a precipitation method exhibits spheroidal-like nanoclusters with well-defined edges assembled from primary nanoparticles with an average size of 50 nm, whereas the monoclinic phase of gadolinium oxide (m-Gd2O3) deposited using explosive pyrolysis has a denser structure compared with natural gadolinia. This phase also has a structure composed of three-dimensional complex agglomerates without clear-edged boundaries that are ∼21 nm in size plus a cubic phase admixture of only 2 at.% composed of primary edge-boundary nanoparticles ∼15 nm in size. These atomic features appear in the electronic structure as different defects ([Gd…Osbnd OH] and [Gd…Osbnd O]) and have dissimilar contributions to the charge-transfer processes among the appropriate electronic states with ambiguous contributions in the Gd 5р - O 2s core-like levels in the valence band structures. The origin of [Gd…Osbnd OH] defects found by XPS was well-supported by PL analysis. The electronic and atomic structures of the synthesized gadolinias calculated using DFT were compared and discussed on the basis of the well-known joint OKT-van der Laan model, and good agreement was established.

  17. Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production

    PubMed Central

    Uchino, Yuichi; Kawakita, Tetsuya; Miyazawa, Masaki; Ishii, Takamasa; Onouchi, Hiromi; Yasuda, Kayo; Ogawa, Yoko; Shimmura, Shigeto; Ishii, Naoaki; Tsubota, Kazuo

    2012-01-01

    Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1) using a modified tetracycline system (Tet-On/Off system). This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC) in humans). The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease. PMID:23071526

  18. Control of Paneth Cell Fate, Intestinal Inflammation, and Tumorigenesis by PKCλ/ι.

    PubMed

    Nakanishi, Yuki; Reina-Campos, Miguel; Nakanishi, Naoko; Llado, Victoria; Elmen, Lisa; Peterson, Scott; Campos, Alex; De, Surya K; Leitges, Michael; Ikeuchi, Hiroki; Pellecchia, Maurizio; Blumberg, Richard S; Diaz-Meco, Maria T; Moscat, Jorge

    2016-09-20

    Paneth cells are a highly specialized population of intestinal epithelial cells located in the crypt adjacent to Lgr5(+) stem cells, from which they differentiate through a process that requires downregulation of the Notch pathway. Their ability to store and release antimicrobial peptides protects the host from intestinal pathogens and controls intestinal inflammation. Here, we show that PKCλ/ι is required for Paneth cell differentiation at the level of Atoh1 and Gfi1, through the control of EZH2 stability by direct phosphorylation. The selective inactivation of PKCλ/ι in epithelial cells results in the loss of mature Paneth cells, increased apoptosis and inflammation, and enhanced tumorigenesis. Importantly, PKCλ/ι expression in human Paneth cells decreases with progression of Crohn's disease. Kaplan-Meier survival analysis of colorectal cancer (CRC) patients revealed that low PRKCI levels correlated with significantly worse patient survival rates. Therefore, PKCλ/ι is a negative regulator of intestinal inflammation and cancer through its role in Paneth cell homeostasis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation

    PubMed Central

    Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

    2015-01-01

    Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD. PMID:26619957

  20. Bee Venom Decreases LPS-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells.

    PubMed

    Jeong, Chang Hee; Cheng, Wei Nee; Bae, Hyojin; Lee, Kyung Woo; Han, Sang Mi; Petriello, Michael C; Lee, Hong Gu; Seo, Han Geuk; Han, Sung Gu

    2017-10-28

    The world dairy industry has long been challenged by bovine mastitis, an inflammatory disease, which causes economic loss due to decreased milk production and quality. Attempts have been made to prevent or treat this disease with multiple approaches, primarily through increased abuse of antibiotics, but effective natural solutions remain elusive. Bee venom (BV) contains a variety of peptides ( e.g. , melittin) and shows multiple bioactivities, including prevention of inflammation. Thus, in the current study, it was hypothesized that BV can reduce inflammation in bovine mammary epithelial cells (MAC-T). To examine the hypothesis, cells were treated with LPS (1 μg/ml) to induce an inflammatory response and the anti-inflammatory effects of BV (2.5 and 5 μg/ml) were investigated. The cellular mechanisms of BV against LPS-induced inflammation were also investigated. Results showed that BV can attenuate expression of an inflammatory protein, COX2, and pro-inflammatory cytokines such as IL-6 and TNF-α. Activation of NF-κB, an inflammatory transcription factor, was significantly downregulated by BV in cells treated with LPS, through dephosphorylation of ERK1/2. Moreover, pretreatment of cells with BV attenuated LPS-induced production of intracellular reactive oxygen species ( e.g. , superoxide anion). These results support our hypothesis that BV can decrease LPS-induced inflammatory responses in bovine mammary epithelial cells through inhibition of oxidative stress, NF-κB, ERK1/2, and COX-2 signaling.

  1. Impaired Resolution of Inflammation in Alzheimer’s Disease: A Review

    PubMed Central

    Whittington, Robert A.; Planel, Emmanuel; Terrando, Niccolò

    2017-01-01

    Alzheimer’s disease (AD) remains the leading cause of dementia worldwide, and over the last several decades, the role of inflammation in the pathogenesis of this neurodegenerative disorder has been increasingly elucidated. The initiation of the acute inflammatory response is counterbalanced by an active process termed resolution. This process is designed to restore homeostasis and promote tissue healing by the activation of neutrophilic apoptosis, promotion of neutrophil clearance by macrophages, and increasing anti-inflammatory cytokine levels, while concurrently leading to a diminution in pro-inflammatory mediators. The switch from the initiation to the resolution phase of inflammation is initially characterized by increased production of arachidonic acid-derived pro-resolving lipoxins and decreases in pro-inflammatory prostaglandin and leukotriene levels, subsequently followed by increases in specialized pro-resolving lipid mediators derived from omega-3 fatty acids (ω-3 FAs). There is mounting evidence that in AD, the resolution of inflammation is impaired, resulting in chronic inflammation and the exacerbation of the AD-related pathology. In this review, we examine preclinical and clinical evidence supporting the hypothesis that AD is a neurodegenerative disorder where the impairment or failure of resolution contributes to the disease process. Moreover, we review the literature supporting the potential therapeutic role of ω-3 FAs and specialized pro-resolving lipid mediators in the management of the disease. Lastly, we highlight areas that could strengthen the association of failed resolution to AD and should, therefore, be the focus of future scientific investigations in this research field. PMID:29163531

  2. Peripheral inflammation and cognitive aging.

    PubMed

    Lim, Alvin; Krajina, Katarina; Marsland, Anna L

    2013-01-01

    Evidence suggests that inflammation, an innate immune response facilitating recovery from injury and pathogenic invasion, is positively associated with age-related cognitive decline and may play a role in risk for dementia. Physiological pathways linking the peripheral immune and central nervous systems are outlined, and studies linking inflammation with neurocognitive function are overviewed. We also present recent studies from our laboratory showing that midlife inflammation is related to cognitive function and brain morphology. Finally, potential implications for treatment, future directions, and limitations are discussed. Copyright © 2013 S. Karger AG, Basel.

  3. Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy.

    PubMed

    Villalta, S Armando; Rosenthal, Wendy; Martinez, Leonel; Kaur, Amanjot; Sparwasser, Tim; Tidball, James G; Margeta, Marta; Spencer, Melissa J; Bluestone, Jeffrey A

    2014-10-15

    We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs were largely absent in the muscle of wild-type mice and normal human muscle, they were present in necrotic lesions, displayed an activated phenotype, and showed increased expression of interleukin-10 (IL-10) in dystrophic muscle from mdx mice. Depletion of Tregs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-γ (IFN-γ) response and activation of M1 macrophages. To test the therapeutic value of targeting Tregs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes and found that Tregs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooxygenase-2 and decreased myofiber injury. These findings suggest that Tregs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of Treg-modulating agents as therapeutics for DMD. Copyright © 2014, American Association for the Advancement of Science.

  4. Magnetic and magnetothermal studies of pure and doped gadolinium silicide nanoparticles for self-controlled hyperthermia applications

    NASA Astrophysics Data System (ADS)

    Alnasir, M. Hisham; Awan, M. S.; Manzoor, Sadia

    2018-03-01

    We report on magnetic and magnetothermal properties of undoped and doped gadolinium silicide (Gd5Si4) nanoparticles with the objective of simultaneously attaining high specific absorption rate (SAR) and low Curie temperature (TC) suitable for self-controlled hyperthermia applications for which TC ∼ 315-320 K. Pellets of doped gadolinium silicide Gd5(Si1-xGex)4 and (Gd1-xRx)5Si4 with R = Ho, Nd and Er and 0 ≤ x ≤ 0.35 were made by arc melting and reduced to nanoparticulate form by surfactant assisted ball milling. Structural and morphological studies were done using X-ray diffraction and scanning electron microscopy respectively. All samples show soft magnetic properties. At low fields there is a ferromagnetic to paramagnetic transition that reduces remanance and coercivity to zero making these materials very attractive for biomedical applications. Zero-field-cooled thermal demagnetization measurements showed that TC of these nanoparticles can be lowered to lie within the limits required for self-controlled hyperthermia by varying the dopant concentration. Specific absorption rates (SAR's) were obtained from magnetothermia measurements made in an ac magnetic field of amplitude 10 Oe and frequency 300 kHz. We have identified samples that have SAR values larger or comparable to those of magnetite and several ferrite nanoparticles, while having Curie temperatures that are low enough for self controlled hyperthermia applications.

  5. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis

    PubMed Central

    Brown, Nancy J.

    2014-01-01

    The steroid hormone aldosterone regulates sodium and potassium homeostasis. Aldosterone and activation of the mineralocorticoid receptor also causes inflammation and fibrosis of the heart, fibrosis and remodelling of blood vessels and tubulointerstitial fibrosis and glomerular injury in the kidney. Aldosterone and mineralocorticoid-receptor activation initiate an inflammatory response by increasing the generation of reactive oxygen species by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria. High salt intake potentiates these effects, in part by activating the Rho family member Rac1, a regulatory subunit of reduced NADPH oxidase that activates the mineralocorticoid receptor. Studies in mice in which the mineralocorticoid receptor has been deleted from specific cell types suggest a key role for macrophages in promoting inflammation and fibrosis. Aldosterone can exert mineralocorticoid-receptor-independent effects via the angiotensin II receptor and via G-protein-coupled receptor 30. Mineralocorticoid-receptor antagonists are associated with decreased mortality in patients with heart disease and show promise in patients with kidney injury, but can elevate serum potassium concentration. Studies in rodents genetically deficient in aldosterone synthase or treated with a pharmacological aldosterone-synthase inhibitor are providing insight into the relative contribution of aldosterone compared with the contribution of mineralocorticoid-receptor activation in inflammation, fibrosis, and injury. Aldosterone-synthase inhibitors are under development in humans. PMID:23774812

  6. Active extravasation of gadolinium-based contrast agent into the subdural space following lumbar puncture.

    PubMed

    Kothari, Pranay D; Hanser, Evelyn M; Wang, Harrison; Farid, Nikdokht

    2016-01-01

    A 38year-old male presented with cauda equina syndrome following multiple lumbar puncture attempts. Lumbar spine magnetic resonance imaging (MRI) showed a subdural hematoma and an area of apparent contrast enhancement in the spinal canal on sagittal post-contrast images. Axial post-contrast images obtained seven minutes later demonstrated an increase in size and change in shape of the region of apparent contrast enhancement, indicating active extravasation of the contrast agent. This is the first reported case of active extravasation of gadolinium-based contrast agent in the spine. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Rutin suppresses palmitic acids-triggered inflammation in macrophages and blocks high fat diet-induced obesity and fatty liver in mice.

    PubMed

    Gao, Mingming; Ma, Yongjie; Liu, Dexi

    2013-11-01

    To elucidate the mechanism of rutin in blocking macrophage-mediated inflammation and high fat diet-induced obesity and fatty liver. Both in vitro and in vivo approaches were taken in evaluating the effects of rutin on palmitic acids-triggered inflammation in cultured macrophages, and on weight gain and development of fatty liver of mice fed a high fat diet. Palmitic acids increase mRNA levels of pro-inflammatory cytokines, and elevate the production of TNFα in cultured macrophages. Pre-exposure of rutin to cells greatly suppressed these elevations. The suppressed inflammation by rutin was correlated with a decrease in transcription of genes responsible for ER stress and production of reactive oxygen species. In vivo, rutin protects mice from high fat diet-induced obesity, fatty liver and insulin resistance. The protective effects were associated with lack of hypertrophy and crown-like structures in the white adipose tissue, decreased mRNA levels of marker genes for macrophages including F4/80, Cd11c and Cd68, and repressed transcription of genes involved in chronic inflammation such as Mcp1 and Tnfα in white adipose tissue. In addition, rutin increases the expression of genes responsible for energy expenditure in brown adipose tissue including Pgc1α and Dio2. Furthermore, rutin suppresses transcription of Srebp1c and Cd36 in the liver, leading to a blockade of fatty liver development. These results suggest that supplementation of rutin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications.

  8. Retention of gadolinium compounds used in magnetic resonance imaging: a critical review and the recommendations of regulatory agencies.

    PubMed

    Martí-Bonmatí, L; Martí-Bonmatí, E

    The Spanish Agency for Drugs and Healthcare Products (AEMPS), based on the recommendations of the European Committee for Risk Assessment in Pharmacovigilance, established on 13 March 2017 that linear gadolinium-based MR contrast media, such as MultiHance, Omniscan, Magnevist (currently not marketed) and Optimark (no longer marketed in Spain), the clinical benefits do not outweigh the potential risks derived from their use. AEMPS recommends to suspend its marketing for general use based on the retention of these compounds in the brain. On the other hand, the AEMPS justifies the maintenance of Primovist and MultiHance for liver studies, and Magnevist of intra-articular administration (not commercialized in Spain), and justified the almost exclusive use of macrocyclic structure contrasts (Gadovist, ProHance and Dotarem). However, this retention is known to be different for each of the contrast media. All existing gadolinium contrasts agents have a distribution phase with tissue retention, due to a very slow exchange, in the interstitium of bone, skin, kidney, brain and other organs. The existence of histological effects or clinical symptoms associated with the accumulation of these trace amounts of gadolinium has not been demonstrated. The major toxicological concern with these contrast agents is related to nephrogenic systemic fibrosis (NSF). Since the safety profiles are mainly related to the interstitial retention space in the tissues, it does not seem justified to actually exclude contrast media that do not have cases related to the NSF. Based on all of this, we disagree with the latest AEMPS recommendation suggesting the marketing stoppage of linear agents without considering the individual retention profiles. This recommendation is not based neither on the data nor existing knowledge about the retention, relaxivity and clinical efficiency of the Gd compounds. It is therefore necessary to carry out prospective studies on the histological and clinical relevance of

  9. Effect of intraarticular tramadol administration in the rat model of knee joint inflammation.

    PubMed

    Garlicki, Jarosław; Dorazil-Dudzik, Magdalena; Wordliczek, Jerzy; Przewłocka, Barbara

    2006-01-01

    Local administration of exogenous opioids may cause effective analgesia without adverse symptoms from the central nervous system. Experiments show that peripheral antinociceptive effect of opioids is observed especially in inflammatory pain. The aim of the research was to estimate the effect of tramadol on nociceptive process at the level of peripheral nervous system, after its local administration in the model of knee joint inflammation. Tramadol was administered intraarticulary into the rat knee joint, before the inflammation as a preemptive analgesia and, for comparison, after the intraarticular injection of carrageenan. The research determined the influence of tramadol injection on pain threshold for thermal stimuli, development of inflammatory processes using the measurement of joint edema and motor function following the induction of knee joint inflammation in the rat. Functional assessment of knee joint with inflammation, in terms of rats' mobility and body position as well as joint loading and mobility were studied. The results of the experiments show that local administration of tramadol induces antinociceptive effect. The effect of tramadol, which elicits also a decrease in inflammatory edema, appears not only after its administration after carrageenan when inflammation was already present, but also in the case of its injection prior to carrageenan in the scheme of preemptive analgesia. The results of the described research show that not only morphine but also another opioid, tramadol, widely used in clinical practice, inhibits nociception, edema and functional impairment of the paw after its local application directly to the inflamed knee joint.

  10. The progress of inflammation and oxidative stress in patients with chronic kidney disease.

    PubMed

    Xu, Gaosi; Luo, Kaiping; Liu, Huixin; Huang, Tianlun; Fang, Xiangdong; Tu, Weiping

    2015-02-01

    The variations and their correlation of inflammation and oxidative stress in chronic kidney disease (CKD) have not been thoroughly understood. Biomarkers of inflammation and oxidative stress were measured in a cohort of 176 patients with CKD ranging from stage 1 to 5 and 67 healthy controls. Correlation analysis in levels between inflammation and oxidative stress was also performed with estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. Concentrations of serum creatinine (Scr), hs-CRP (hypersensitive C reactive protein) and MDA (malondialdehyde) of these participants were measured again after 12 month follow-up. In the present study, with the development of CKD, serum levels of hs-CRP, interleukin-6 (IL-6) and MDA were significantly increased, and the serum levels of SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase) were significantly decreased in these participants. eGFR was inversely associated with MDA and positively with SOD and GSH-PX when adjusting for age and hypertension therapy. IL-6 and hs-CRP were positively correlated with MDA, and negatively associated with SOD and GSH-PX. Notably, after 12-month follow-up, the increase in Scr was positively associated with the increase in hs-CRP (p < 0.01) and MDA (p < 0.05), respectively. Inflammation and oxidative stress interacted with each other and played pivotal roles in the development of CKD. Variation in eGFR was parallel with the changes of oxidative stress and inflammation when CKD developing.

  11. Cryoglobulin-induced inflammation.

    PubMed

    Denko, C W

    1985-10-01

    Inflammation of the rat footpad followed injection of cryoglobulin in crystalline form (Type I) and injection of cryoglobulin in solution (Type II). Rats deficient in essential fatty acids responded with diminished swelling which corrected to normal levels by addition of prostaglandin E1 suggesting that this reaction is prostaglandin mediated. Addition of bradykinin produced no effect. Aggregated cryoglobulin proved more inflammogenic than non-aggregated cryoglobulin. Pre-treatment with choline salicylate and colchicine reduced swelling while pre-treatment with dipyridamole increased edema following cryoglobulin inoculation. Cryoglobulin is considered to be an acute phase reactant in inflammation.

  12. Obesity, Inflammation, and Cancer.

    PubMed

    Deng, Tuo; Lyon, Christopher J; Bergin, Stephen; Caligiuri, Michael A; Hsueh, Willa A

    2016-05-23

    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity.

  13. Ion channels in inflammation.

    PubMed

    Eisenhut, Michael; Wallace, Helen

    2011-04-01

    Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.

  14. Basophils and allergic inflammation

    PubMed Central

    Siracusa, Mark C.; Kim, Brian S.; Spergel, Jonathan M.; Artis, David

    2013-01-01

    Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in humans and murine systems have shown that basophils perform non-redundant effector functions and significantly contribute to the development and progression of TH2 cytokine-mediated inflammation. Although the potential functions of murine and human basophils have provoked some controversy, recent genetic approaches indicate that basophils can migrate into lymphoid tissues and, in some circumstances, cooperate with other immune cells to promote optimal TH2 cytokine responses in vivo. This article provides a brief historical perspective on basophil-related research and discusses recent studies that have identified previously unappreciated molecules and pathways that regulate basophil development, activation and function in the context of allergic inflammation. Further, we highlight the unique effector functions of basophils and discuss their contributions to the development and pathogenesis of allergic inflammation in human disease. Finally, we discuss the therapeutic potential of targeting basophils in preventing or alleviating the development and progression of allergic inflammation. PMID:24075190

  15. Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice

    PubMed Central

    Jung, Sun Hee; Kwon, Jang-Mi; Shim, Jae Won; Kim, Deok Soo; Jung, Hye Lim; Park, Moon Soo; Park, Soo-Hee; Lee, Jinmi; Lee, Won-Young

    2013-01-01

    Purpose Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity. Materials and Methods We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid. Results Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge. Conclusion Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma. PMID:24142648

  16. Chronic Inflammation: Accelerator of Biological Aging.

    PubMed

    Fougère, Bertrand; Boulanger, Eric; Nourhashémi, Fati; Guyonnet, Sophie; Cesari, Matteo

    2017-09-01

    Biological aging is characterized by a chronic low-grade inflammation level. This chronic phenomenon has been named "inflamm-aging" and is a highly significant risk factor for morbidity and mortality in the older persons. The most common theories of inflamm-aging include redox stress, mitochondrial dysfunction, glycation, deregulation of the immune system, hormonal changes, epigenetic modifications, and dysfunction telomere attrition. Inflamm-aging plays a role in the initiation and progression of age-related diseases such as type II diabetes, Alzheimer's disease, cardiovascular disease, frailty, sarcopenia, osteoporosis, and cancer. This review will cover the identification of pathways that control age-related inflammation across multiple systems and its potential causal role in contributing to adverse health outcomes. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Dietary flavonoids from modified apple reduce inflammation markers and modulate gut microbiota in mice.

    PubMed

    Espley, Richard V; Butts, Christine A; Laing, William A; Martell, Sheridan; Smith, Hannah; McGhie, Tony K; Zhang, Jingli; Paturi, Gunaranjan; Hedderley, Duncan; Bovy, Arnaud; Schouten, Henk J; Putterill, Joanna; Allan, Andrew C; Hellens, Roger P

    2014-02-01

    Apples are rich in polyphenols, which provide antioxidant properties, mediation of cellular processes such as inflammation, and modulation of gut microbiota. In this study we compared genetically engineered apples with increased flavonoids [myeloblastis transcription factor 10 (MYB10)] with nontransformed apples from the same genotype, "Royal Gala" (RG), and a control diet with no apple. Compared with the RG diet, the MYB10 diet contained elevated concentrations of the flavonoid subclasses anthocyanins, flavanol monomers (epicatechin) and oligomers (procyanidin B2), and flavonols (quercetin glycosides), but other plant secondary metabolites were largely unaltered. We used these apples to investigate the effects of dietary flavonoids on inflammation and gut microbiota in 2 mouse feeding trials. In trial 1, male mice were fed a control diet or diets supplemented with 20% MYB10 apple flesh and peel (MYB-FP) or RG apple flesh and peel (RG-FP) for 7 d. In trial 2, male mice were fed MYB-FP or RG-FP diets or diets supplemented with 20% MYB10 apple flesh or RG apple flesh for 7 or 21 d. In trial 1, the transcription levels of inflammation-linked genes in mice showed decreases of >2-fold for interleukin-2 receptor (Il2rb), chemokine receptor 2 (Ccr2), chemokine ligand 10 (Cxcl10), and chemokine receptor 10 (Ccr10) at 7 d for the MYB-FP diet compared with the RG-FP diet (P < 0.05). In trial 2, the inflammation marker prostaglandin E(2) (PGE(2)) in the plasma of mice fed the MYB-FP diet at 21 d was reduced by 10-fold (P < 0.01) compared with the RG-FP diet. In colonic microbiota, the number of total bacteria for mice fed the MYB-FP diet was 6% higher than for mice fed the control diet at 21 d (P = 0.01). In summary, high-flavonoid apple was associated with decreases in some inflammation markers and changes in gut microbiota when fed to healthy mice.

  18. Does psychological stress in patients with clinically suspect arthralgia associate with subclinical inflammation and progression to inflammatory arthritis?

    PubMed

    Boer, Aleid C; Ten Brinck, Robin M; Evers, Andrea W M; van der Helm-van Mil, Annette H M

    2018-05-03

    Within established rheumatoid arthritis (RA), stress can have pro-inflammatory effects by activating the immune system via the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. It is unknown if stress levels also promote inflammation during RA development. We studied whether the psychological stress response was increased in clinically suspect arthralgia (CSA) and if this associated with inflammation at presentation with arthralgia and with progression to clinical arthritis. In 241 CSA patients, psychological stress was measured by the Mental Health Inventory (MHI-5) and the Perceived Stress Scale (PSS-10) at first presentation and during follow-up. Systemic inflammation was measured by C-reactive protein (CRP) and joint inflammation by 1.5 T-MRI of wrist, MCP, and MTP joints. At baseline, 12% (24/197) of CSA patients had a high psychological stress response according to the MHI-5. This was not different for patients presenting with or without an elevated CRP, with or without subclinical MRI-detected inflammation and for patients who did or did not develop arthritis. Similar findings were obtained with the PSS-10. When developing clinical arthritis, the percentage of patients with 'high psychological stress' increased to 31% (p = 0.025); during the first year of treatment this decreased to 8% (p = 0.020). 'High psychological stress' in non-progressors remained infrequent over time (range 7-13%). Stress was associated with fatigue (p = 0.003) and wellbeing (p < 0.001). Psychological stress was not increased in the phase of arthralgia, raised at the time of diagnoses and decreased thereafter. The lack of an association with inflammation in arthralgia and this temporal relationship, argue against psychological stress having a significant contribution to progression from CSA to inflammatory arthritis.

  19. [Connective tissue and inflammation].

    PubMed

    Jakab, Lajos

    2014-03-23

    The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

  20. Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.

    PubMed

    Kostyuk, Vladimir A; Potapovich, Alla I; Suhan, Tatyana O; de Luca, Chiara; Korkina, Liudmila G

    2011-05-11

    Oxidized low-density lipoproteins (oxLDL) play a critical role in the initiation of atherosclerosis through activation of inflammatory signaling. In the present work we investigated the role of antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Significant decrease in intracellular NO level and superoxide overproduction was found in human umbilical vein endothelial cells (HUVEC) treated with oxLDL, but not with LDL. The redox imbalance was prevented by the addition of quercetin or resveratrol. Expression analysis of 14 genes associated with oxidative stress and inflammation revealed oxLDL-mediated up-regulation of genes specifically involved in leukocyte recruitment and adhesion. This up-regulation could be partially avoided by the addition of verbascoside or resveratrol, while treatment with quercetin resulted in a further increase in the expression of these genes. Lipopolysaccharide (LPS)-treated HUVEC were also used for the evaluation of anti-inflammatory potency of plant polyphenols. Significant differences between HUVEC treaded with oxLDL and LPS were found in both the expression pattern of inflammation-related genes and the effects of plant polyphenols on cellular responses. The present data indicate that plant polyphenols may affect vascular inflammation not only as antioxidants but also as modulators of inflammatory redox signaling pathways. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.