Science.gov

Sample records for hyperoxic treatment induces

  1. Treatment with Geranylgeranylacetone Induces Heat Shock Protein 70 and Attenuates Neonatal Hyperoxic Lung Injury in a Model of Bronchopulmonary Dysplasia.

    PubMed

    Tokuriki, Shuko; Igarashi, Aiko; Okuno, Takashi; Ohta, Genrei; Naiki, Hironobu; Ohshima, Yusei

    2017-08-01

    Bronchopulmonary dysplasia (BPD) is a respiratory complication characterized by abnormal alveolar development in premature infants. Geranylgeranylacetone (GGA) can induce heat shock protein (HSP) 70, which has cytoprotective effects against various stressors. Here, we investigated whether GGA protected neonatal lungs from hyperoxic stress in a murine BPD model, and measured the serum HSP70 levels in preterm humans treated with oxygen. Newborn mice were exposed to >90% oxygen and administered GGA or vehicle alone orally on days 1, 2, and 3 of life. At 2 days of age, HSP70 expression in the lung was determined by western blotting. At 8 days of age, the lungs were processed for histological analysis. Radial alveolar count (RAC) and mean linear intercept (MLI) were measured as parameters of alveolarization. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and cleaved caspase-3 immunohistochemistry. Serum HSP70 levels in preterm humans treated with oxygen were measured by enzyme-linked immunosorbent assay. GGA administration enhanced the HSP70 expression to two-fold compared with normoxia-exposed and vehicle-treated mice. Hyperoxia reduced HSP70 expression, whereas GGA abrogated the effects. Hyperoxia-exposed mice exhibited more apoptotic cells in lung parenchyma and a more simplified alveolar structure with less RAC and larger MLI than normoxia-exposed mice. GGA suppressed the increase in apoptotic cells and the structural changes of the lungs induced by hyperoxia. Serum HSP70 levels of preterm human infants gradually decreased with age. GGA may attenuate hyperoxic injury in neonatal lungs and thereby may prevent the development of BPD.

  2. Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

    PubMed Central

    Lee, Sang-Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Li, Jin; Latoche, Joseph D.; Peck Palmer, Octavia M.; Stolz, Donna Beer; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.

    2013-01-01

    Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury. PMID:23275622

  3. Enhanced Resolution of Hyperoxic Acute Lung Injury as a result of Aspirin Triggered Resolvin D1 Treatment

    PubMed Central

    Cox, Ruan; Phillips, Oluwakemi; Fukumoto, Jutaro; Fukumoto, Itsuko; Parthasarathy, Prasanna Tamarapu; Arias, Stephen; Cho, Young; Lockey, Richard F.

    2015-01-01

    Acute lung injury (ALI), which presents as acute respiratory failure, is a major clinical problem that requires aggressive care, and patients who require prolonged oxygen exposure are at risk of developing this disease. Although molecular determinants of ALI have been reported, the molecules involved in disease catabasis associated with oxygen toxicity have not been well studied. It has been reported that lung mucosa is rich in omega-3 fatty acid dicosahexanoic acid (DHA), which has antiinflammatory properties. Aspirin-triggered resolvin D1 (AT-RvD1) is a potent proresolution metabolite of DHA that can curb the inflammatory effects in various acute injuries, yet the effect of AT-RvD1 on hyperoxic acute lung injury (HALI) or in the oxygen toxicity setting in general has not been investigated. The effects of AT-RvD1 on HALI were determined for the first time in 8- to 10-week-old C57BL/6 mice that were exposed to hyperoxia (≥95% O2) for 48 hours. Mice were given AT-RvD1 (100 ng) in saline or a saline vehicle for 24 hours in normoxic (≈21% O2) conditions after hyperoxia. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected for analysis associated with proinflammatory signaling and lung inflammation. AT-RvD1 treatment resulted in reduced oxidative stress, increased glutathione production, and significantly decreased tissue inflammation. AT-RvD1 treatment also significantly reduced the lung wet/dry ratio, protein in BAL fluid, and decreased apoptotic and NF-κB signaling. These results show that AT-RvD1 curbs oxygen-induced lung edema, permeability, inflammation, and apoptosis and is thus an effective therapy for prolonged hyperoxia exposure in this murine model. PMID:25647402

  4. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

    PubMed Central

    Kawamura, Tomohiro; Wakabayashi, Nobunao; Shigemura, Norihisa; Huang, Chien-Sheng; Masutani, Kosuke; Tanaka, Yugo; Noda, Kentaro; Peng, Ximei; Takahashi, Toru; Billiar, Timothy R.; Okumura, Meinoshin; Toyoda, Yoshiya; Kensler, Thomas W.

    2013-01-01

    Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen. PMID:23475767

  5. Hyperoxic Acute Lung Injury

    PubMed Central

    Kallet, Richard H; Matthay, Michael A

    2013-01-01

    Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823

  6. Prenatal administration of the cytochrome P4501A inducer, {Beta}-naphthoflavone (BNF), attenuates hyperoxic lung injury in newborn mice: Implications for bronchopulmonary dysplasia (BPD) in premature infants

    SciTech Connect

    Couroucli, Xanthi I.; Liang Yanhong Wei; Jiang Weiwu; Wang Lihua; Barrios, Roberto; Yang Peiying; Moorthy, Bhagavatula

    2011-10-15

    Supplemental oxygen contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this investigation, we tested the hypothesis that prenatal treatment of pregnant mice (C57BL/6J) with the cytochrome P450 (CYP)1A1 inducer, ss-napthoflavone (BNF), will lead to attenuation of lung injury in newborns (delivered from these dams) exposed to hyperoxia by mechanisms entailing transplacental induction of hepatic and pulmonary CYP1A enzymes. Pregnant mice were administered the vehicle corn oil (CO) or BNF (40 mg/kg), i.p., once daily for 3 days on gestational days (17-19), and newborns delivered from the mothers were either maintained in room air or exposed to hyperoxia (> 95% O{sub 2}) for 1-5 days. After 3-5 days of hyperoxia, the lungs of CO-treated mice showed neutrophil infiltration, pulmonary edema, and perivascular inflammation. On the other hand, BNF-pretreated neonatal mice showed decreased susceptibility to hyperoxic lung injury. These mice displayed marked induction of ethoxyresorufin O-deethylase (EROD) (CYP1A1) and methoxyresorufin O-demethylase (MROD) (CYP1A2) activities, and levels of the corresponding apoproteins and mRNA levels until PND 3 in liver, while CYP1A1 expression alone was augmented in the lung. Prenatal BNF did not significantly alter gene expression of pulmonary NAD(P)H quinone reductase (NQO1). Hyperoxia for 24-72 h resulted in increased pulmonary levels of the F{sub 2}-isoprostane 8-iso-PGF{sub 2{alpha}}, whose levels were decreased in mice prenatally exposed to BNF. In conclusion, our results suggest that prenatal BNF protects newborns against hyperoxic lung injury, presumably by detoxification of lipid hydroperoxides by CYP1A enzymes, a phenomenon that has implications for prevention of BPD in infants. - Highlights: > Supplemental oxygen is routinely administered to premature infants. > Hyperoxia causes lung injury in experimental animals. > Prenatal treatment of mice with beta-naphthoflavone attenuates oxygen

  7. Seasonal variation in maintenance of phenylephrine-induced tone in isolated equine digital arteries under hypoxic or hyperoxic conditions in vitro.

    PubMed

    Borer-Weir, K E; Bailey, S R; Harris, P A; Menzies-Gow, N J; Elliott, J

    2013-06-01

    Digital vasoconstriction, ischaemia and hypoxia may predispose to acute laminitis. Laminitis incidence varies seasonally, peaking in spring and summer. Direct seasonal influences on equine digital artery (EDA) contractility have not been investigated. This study assessed seasonal variation in maintenance of phenylephrine (PHE)-induced tone in isolated EDAs under hypoxic (95% nitrogen) and hyperoxic (95% oxygen) conditions. The objective was to measure change in arterial tone over time after constriction to a plateau with PHE. Tone was measured at plateau and over time and percentage change calculated. Hyperoxic EDAs maintained PHE-induced tone over 1 h with no seasonal variation. Hypoxic EDAs relaxed in fall (median [inter-quartile range] 59% [44-77%] decrease from plateau; P=0.008), contracted in spring (65% [20-192%] increase from plateau; P=0.03) and did not significantly change tone in winter (18% [0-28%] decrease; P=0.13). Continued contraction under hypoxic conditions in spring may contribute to digital vasoconstriction.

  8. Investigation of biphasic tumor oxygen dynamics induced by hyperoxic gas intervention: the dynamic phantom approach

    NASA Astrophysics Data System (ADS)

    Kim, Jae G.; Liu, Hanli

    2008-01-01

    We have developed dynamic tumor vascular phantoms and utilized them to investigate the biphasic behavior of increases in light absorption, which is directly associated with oxygenated hemoglobin concentration that was observed in vivo from rat breast tumor experiments during carbogen/oxygen inhalation. The experimental setup for the phantom study included a continuous-wave, multichannel, near-infrared spectroscopy (NIRS) system and syringe pumps to drive the simulated blood through the dynamic vascular phantoms. The results from such phantom experiments clearly show that the two time constants observed in tumor oxygenation dynamics in vivo can result from two different perfusion rates or two different blood flow velocities. We provide experimental support for our previous hypothesis: the biphasic tumor hemodynamic feature stems from a well-perfused and poorly perfused region that could be detected with the two time constants of the NIRS signals. With a multichannel approach, noninvasive NIRS measurements may have useful and prognostic values to quantify the therapeutic effects of cancer treatments.

  9. Adiponectin protects against hyperoxic lung injury and vascular leak

    PubMed Central

    Sliman, Sean M.; Patel, Rishi B.; Cruff, Jason P.; Kotha, Sainath R.; Newland, Christie A.; Schrader, Carrie A.; Sherwani, Shariq I.; Gurney, Travis O.; Magalang, Ulysses J.; Parinandi, Narasimham L.

    2014-01-01

    Adiponectin (Ad), an adipokine exclusively secreted by the adipose tissue, has emerged as a paracrine metabolic regulator as well as a protectant against oxidative stress. Pharmacological approaches of protecting against clinical hyperoxic lung injury during oxygen therapy/treatment are limited. Earlier, we have reported that Ad inhibits the NADPH oxidase-catalyzed formation of superoxide from molecular oxygen in human neutrophils. Having this as the premise, we conducted studies to determine whether (i) exogenous Ad would protect against the hyperoxia-induced barrier dysfunction in the lung endothelial cells (ECs) in vitro and (ii) endogenously synthesized Ad would protect against hyperoxic lung injury in wild type (WT) and Ad-overexpressing transgenic (AdTg) mice in vivo. The results demonstrated that exogenous Ad protected against the hyperoxia-induced oxidative stress, loss of glutathione (GSH), cytoskeletal reorganization, barrier dysfunction, and leak in the lung ECs in vitro. Furthermore, the hyperoxia-induced lung injury, vascular leak, and lipid peroxidation were significantly attenuated in AdTg mice in vivo. Also, AdTg mice exhibited elevated levels of total thiols and GSH in the lungs as compared to WT mice. For the first time, our studies demonstrated that Ad protected against the hyperoxia-induced lung damage apparently through attenuation of oxidative stress and modulation of thiol-redox status. PMID:22183615

  10. Hyperoxic gassing with Tiron enhances bradykinin-induced endothelium-dependent and EDH-type relaxation through generation of hydrogen peroxide.

    PubMed

    Wong, Pui San; Roberts, Richard E; Randall, Michael D

    2015-01-01

    Oxygenation with 95%O2 is routinely used in organ bath studies. However, hyperoxia may affect tissue responses, particularly in studies which involve reactive oxygen species (ROS). Here, the effects of the antioxidant, Tiron, were investigated under different gassing conditions in the porcine isolated coronary artery (PCA). Distal PCAs from male and female pigs were mounted in a wire myograph gassed with either 95%O2/5%CO2 or 95% air/5%CO2 and pre-contracted with U46619. Concentration-response curves to bradykinin were constructed in the presence of Tiron (1mM), a cell permeable superoxide scavenger and catalase (1000Uml(-1)) to breakdown H2O2. The H2O2 level in Krebs'-Henseleit solution was detected using Amplex Red. Bradykinin produced concentration-dependent vasorelaxations in male and female PCAs when gassed with either 95%O2 or air, with no differences in the Rmax or EC50. Tiron increased the potency of bradykinin only when gassed with 95%O2 in PCAs from both sexes. At 95%O2, catalase prevented the leftward shift caused by Tiron in both sexes indicating that catalase prevented the formation of H2O2 by Tiron. In female PCAs, addition of catalase to Tiron significantly reduced the Rmax. In the EDH-type response (using L-NAME and indomethacin), Tiron enhanced the potency of the bradykinin-induced vasorelaxation when gassed with 95%O2 in PCAs from both sexes. Biochemical analysis using Amplex Red demonstrated that H2O2 was generated in Krebs'-Henseleit solution when gassed with 95%O2, but not with air. Therefore, hyperoxic gassing conditions could alter the environment generating superoxide within the Krebs'-Henseleit buffer, which may, in turn, influence the in vitro pharmacological responses.

  11. Adenosine promotes vascular barrier function in hyperoxic lung injury

    PubMed Central

    Davies, Jonathan; Karmouty‐Quintana, Harry; Le, Thuy T.; Chen, Ning‐Yuan; Weng, Tingting; Luo, Fayong; Molina, Jose; Moorthy, Bhagavatula; Blackburn, Michael R.

    2014-01-01

    Abstract Hyperoxic lung injury is characterized by cellular damage from high oxygen concentrations that lead to an inflammatory response in the lung with cellular infiltration and pulmonary edema. Adenosine is a signaling molecule that is generated extracellularly by CD73 in response to injury. Extracellular adenosine signals through cell surface receptors and has been found to be elevated and plays a protective role in acute injury situations. In particular, ADORA2B activation is protective in acute lung injury. However, little is known about the role of adenosine signaling in hyperoxic lung injury. We hypothesized that hyperoxia‐induced lung injury leads to CD73‐mediated increases in extracellular adenosine, which is protective through ADORA2B signaling pathways. To test this hypothesis, we exposed C57BL6, CD73−/−, and Adora2B−/− mice to 95% oxygen or room air and examined markers of pulmonary inflammation, edema, and monitored lung histology. Hyperoxic exposure caused pulmonary inflammation and edema in association with elevations in lung adenosine levels. Loss of CD73‐mediated extracellular adenosine production exacerbated pulmonary edema without affecting inflammatory cell counts. Furthermore, loss of the ADORA2B had similar results with worsening of pulmonary edema following hyperoxia exposure without affecting inflammatory cell infiltration. This loss of barrier function correlated with a decrease in occludin in pulmonary vasculature in CD73−/− and Adora2B−/− mice following hyperoxia exposure. These results demonstrate that exposure to a hyperoxic environment causes lung injury associated with an increase in adenosine concentration, and elevated adenosine levels protect vascular barrier function in hyperoxic lung injury through the ADORA2B‐dependent regulation of occludin. PMID:25263205

  12. Myocardial protection evoked by hyperoxic exposure involves signaling through nitric oxide and mitogen activated protein kinases.

    PubMed

    Ruusalepp, Arno; Czibik, Gabor; Flatebø, Torun; Vaage, Jarle; Valen, Guro

    2007-07-01

    Hyperoxic exposure in vivo (> 95% oxygen) attenuates ischemia-reperfusion injury, but the signaling mechanisms of this cardioprotection are not fully determined. We studied a possible role of nitric oxide (NO) and mitogen activated protein kinases (MAPK) in hyperoxic protection. Mice (n = 7-9 in each group) were kept in normoxic or hyperoxic environments for 15 min prior to harvesting the heart and Langendorff perfusion with global ischemia (45 min) and reperfusion (60 min). Endpoints were cardiac function and infarct size. Additional hearts were collected to evaluate MAPK phosphorylation (immunoblot). The nitric oxide synthase inhibitor L-NAME, the ERK1/2 inhibitor PD98059 and the p38 MAPK inhibitor FR167653 were injected intraperitoneally before hyperoxia or normoxia. Hyperoxia improved postischemic functional recovery and reduced infarct size (p < 0.05). Hyperoxic exposure caused cardiac phosphorylation of the MAPK family members p38 and ERK1/2, but not JNK. L-NAME, PD98059 and FR167653 all reduced the protection afforded by hyperoxic exposure, but did not influence performance or infarction in hearts of normoxic mice. The hyperoxia-induced phosphorylation of ERK1/2 and p38 was reduced by L-NAME and both MAPK inhibitors. Nitric oxide triggers hyperoxic protection, and ERK1/2 and p38 MAPK are involved in signaling of protection against ischemia-reperfusion injury.

  13. Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation

    PubMed Central

    Tyurin, Vladimir A.; Kaynar, A. Murat; Kapralova, Valentyna I.; Wasserloos, Karla; Li, Jin; Mosher, Mackenzie; Wright, Lindsay; Wipf, Peter; Watkins, Simon; Pitt, Bruce R.; Kagan, Valerian E.

    2010-01-01

    Reactive oxygen species have been shown to play a significant role in hyperoxia-induced acute lung injury, in part, by inducing apoptosis of pulmonary endothelium. However, the signaling roles of phospholipid oxidation products in pulmonary endothelial apoptosis have not been studied. Using an oxidative lipidomics approach, we identified individual molecular species of phospholipids involved in the apoptosis-associated peroxidation process in a hyperoxic lung. C57BL/6 mice were killed 72 h after exposure to hyperoxia (100% oxygen). We found that hyperoxia-induced apoptosis (documented by activation of caspase-3 and -7 and histochemical terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of pulmonary endothelium) was accompanied by nonrandom oxidation of pulmonary lipids. Two anionic phospholipids, mitochondria-specific cardiolipin (CL) and extramitochondrial phosphatidylserine (PS), were the two major oxidized phospholipids in hyperoxic lung. Using electrospray ionization mass spectrometry, we identified several oxygenation products in CL and PS. Quantitative assessments revealed a significant decrease of CL and PS molecular species containing C18:2, C20:4, C22:5, and C22:6 fatty acids. Similarly, exposure of mouse pulmonary endothelial cells (MLEC) to hyperoxia (95% oxygen; 72 h) resulted in activation of caspase-3 and -7 and significantly decreased the content of CL molecular species containing C18:2 and C20:4 as well as PS molecular species containing C22:5 and C22:6. Oxygenated molecular species were found in the same two anionic phospholipids, CL and PS, in MLEC exposed to hyperoxia. Treatment of MLEC with a mitochondria-targeted radical scavenger, a conjugate of hemi-gramicidin S with nitroxide, XJB-5-131, resulted in significantly lower oxidation of both CL and PS and a decrease in hyperoxia-induced changes in caspase-3 and -7 activation. We speculate that cytochrome c driven oxidation of CL and PS is associated with the signaling

  14. Transient hyperoxic reoxygenation reduces cytochrome C oxidase activity by increasing superoxide dismutase and nitric oxide.

    PubMed

    Arab, Amina; Wang, Jin; Bausch, Kathrin; von Schmädel, Katharina; Bode, Christoph; Hehrlein, Christoph

    2010-04-09

    Oxygen therapies have been shown to be cytoprotective in a dose-dependent fashion. Previously, we have characterized the protective effects of moderate hyperoxia on cell viability of ischemic human cardiomyocytes and their mitochondrial membrane potential by transient addition of oxygenated perfluorocarbons to the cell medium. Now, we report that the activity and expression of cytochrome c oxidase (COX) after prolonged ischemia depend on the amount of oxygen delivered during reoxygenation. Transient hyperoxia during reoxygenation results in a decrease of COX activity by 62 +/- 15% and COX expression by 67 +/- 5%, when hyperoxic tensions of approximately = 300 mm Hg are reached in the cell medium. This decrease in COX expression is prevented by the inhibition of inducible nitric-oxide synthase (iNOS). Immunoblot analysis of ischemic human cardiomyocytes revealed that hyperoxic reoxygenation causes a 2-fold increase of iNOS, leading to a rise in nitric oxide production by 140 +/- 45%. Hyperoxic reoxygenation is further responsible for a 2-fold activation of hydrogen peroxide production and an increase in cytosolic superoxide dismutase expression by 35 +/- 10%. NADPH availability has no effect on the hyperoxia-induced decrease of superoxide. Overall, these results indicate that transient hyperoxic reoxygenation in optimal concentrations increases the level of nitric oxide by activation of iNOS and superoxide dismutase, thereby inducing respiration arrest in mitochondria of ischemic cardiomyocytes.

  15. Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury.

    PubMed Central

    Barazzone, C; Belin, D; Piguet, P F; Vassalli, J D; Sappino, A P

    1996-01-01

    Hyperoxia-induced lung disease is associated with prominent intraalveolar fibrin deposition. Fibrin turnover is tightly regulated by the concerted action of proteases and antiproteases, and inhibition of plasmin-mediated proteolysis could account for fibrin accumulation in lung alveoli. We show here that lungs of mice exposed to hyperoxia overproduce plasminogen activator inhibitor-1 (PAI-1), and that PAI-1 upregulation impairs fibrinolytic activity in the alveolar compartment. To explore whether increased PAI-1 production is a causal or only a correlative event for impaired intraalveolar fibrinolysis and the development of hyaline membrane disease, we studied mice genetically deficient in PAI-1. We found that these mice fail to develop intraalveolar fibrin deposits in response to hyperoxia and that they are more resistant to the lethal effects of hyperoxic stress. These observations provide clear and novel evidence for the pathogenic contribution of PAI-1 in the development of hyaline membrane disease. They identify PAI-1 as a major deleterious mediator of hyperoxic lung injury. PMID:8981909

  16. Mice Deficient in the Gene for Cytochrome P450 (CYP)1A1 Are More Susceptible Than Wild-Type to Hyperoxic Lung Injury: Evidence for Protective Role of CYP1A1 Against Oxidative Stress

    PubMed Central

    Wang, Lihua; Wang, Gangduo; Couroucli, Xanthi I.; Shivanna, Binoy; Welty, Stephen E.; Barrios, Roberto; Khan,  M. Firoze; Nebert, Daniel W.; Roberts, L. Jackson; Moorthy, Bhagavatula

    2014-01-01

    Hyperoxia contributes to acute lung injury in diseases such as acute respiratory distress syndrome in adults and bronchopulmonary dysplasia in premature infants. Cytochrome P450 (CYP)1A1 has been shown to modulate hyperoxic lung injury. The mechanistic role(s) of CYP1A1 in hyperoxic lung injury in vivo is not known. In this investigation, we hypothesized that Cyp1a1(–/–) mice would be more susceptible to hyperoxic lung injury than wild-type (WT) mice, and that the protective role of CYP1A1 is in part due to CYP1A1-mediated decrease in the levels of reactive oxygen species-mediated lipid hydroperoxides, e.g., F2-isoprostanes/isofurans, leading to attenuation of oxidative damage. Eight- to ten-week-old male WT (C57BL/6J) or Cyp1a1(–/–) mice were exposed to hyperoxia (>95% O2) or room air for 24–72 h. The Cyp1a1(–/–) mice were more susceptible to oxygen-mediated lung damage and inflammation than WT mice, as evidenced by increased lung weight/body weight ratio, lung injury, neutrophil infiltration, and augmented expression of IL-6. Hyperoxia for 24–48 h induced CYP1A expression at the mRNA, protein, and enzyme levels in liver and lung of WT mice. Pulmonary F2-isoprostane and isofuran levels were elevated in WT mice after hyperoxia for 24 h. On the other hand, Cyp1a1(–/–) mice showed higher levels after 48–72 h of hyperoxia exposure compared to WT mice. Our results support the hypothesis that CYP1A1 protects against hyperoxic lung injury by decreasing oxidative stress. Future research could lead to the development of novel strategies for prevention and/or treatment of acute lung injury. PMID:24893714

  17. Nitric oxide and hyperoxic acute lung injury

    PubMed Central

    Liu, Wen-wu; Han, Cui-hong; Zhang, Pei-xi; Zheng, Juan; Liu, Kan; Sun, Xue-jun

    2016-01-01

    Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI. PMID:27867474

  18. Dynamic Response of Breast Tumor Oxygenation to Hyperoxic Respiratory Challenge Monitored with Three Oxygen-Sensitive Parameters

    NASA Astrophysics Data System (ADS)

    Gu, Yueqing; Bourke, Vincent A.; Kim, Jae G.; Constantinescu, Anca; Mason, Ralph P.; Liu, Hanli

    2003-06-01

    The simultaneous measurement of three oxygen-sensitive parameters [arterial hemoglobin oxygen saturation (SaO2 ), tumor vascular-oxygenated hemoglobin concentration ( [HbO2 ), and tumor oxygen tension (pO]2 ) in response to hyperoxic respiratory challenge is demonstrated in rat breast tumors. The effects of two hyperoxic gases ] [oxygen and carbogen (5% CO2 and 95% O2 ) were compared, by use of two groups of Fisher rats with subcutaneous 13762NF breast tumors implanted in pedicles on the foreback. Two different gas-inhalation sequences were compared, i.e., air-carbogen-air-oxygen-air and air-oxygen-air-carbogen-air. The results demonstrate that both of the inhaled, hyperoxic gases significantly improved the tumor oxygen status. All three parameters displayed similar dynamic response to hyperoxic gas interventions, but with different response times: the fastest for arterial SaO]2 , followed by biphasic changes in tumor vascular [HbO2 , and then delayed responses for pO]2 . Both of the gases induced similar changes in vascular oxygenation and regional tissue pO2 in the rat tumors, and changes in [HbO2 and mean pO]2 showed a linear correlation with large standard deviations, which presumably results from global versus local measurements. Indeed, the pO2 data revealed heterogeneous regional response to hyperoxic interventions. Although preliminary near-infrared measurements had been demonstrated previously in this model, the addition of the pO2 optical fiber probes provides a link between the noninvasive relative measurements of vascular phenomena based on endogenous reporter molecules, with the quantitative, albeit, invasive pO2 determinations.

  19. [Increased expression of fatty acid binding protein 4 in lungs of preterm rats after hyperoxic lung injury].

    PubMed

    Wang, Wei; Cui, Zhi-Rui; Cai, Li-Xia; Luo, Xiao-Ping

    2014-11-01

    To study the expression of fatty acid binding protein 4 (FABP4) in lungs and bronchoalveolar lavage fluid (BALF) of preterm rats exposed to 60% O2 and to elucidate the relationship between the changes of FABP4 expression and the pathogenesis of bronchopulmonary dysplasia (BPD). Hyperoxic lung injury was induced by exposing to 60% O2 in Spraque-Dawley rats within 6 hours after birth. Rats exposed to air were used as the control group. The lungs from groups aged postnatal days 3, 7 and 14 were removed and dissected from the main bronchi for analysis. Eight rats of each group were used to assess expression of FABP4 in lungs by immunohistochemistry and ELISA. Lung FABP4 mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction. The levels of FABP4 in BALF were measured using ELISA. FABP4 immunoreactivity was detected in the majority of alveolar macrophages, bronchial epithelial cells and endothelial cells. FABP4 protein levels in lung tissues in the hyperoxic exposure group increased significantly compared with the control group on days 3, 7 and 14 after birth (P<0.05), and FABP4 mRNA levels in lung tissues also increased significantly in the hyperoxic exposure group compared with the control group on days 7 and 14 after birth (P<0.05). The hyperoxic exposure group demonstrated increased FABP4 levels in BALF compared with the control group on days 7 and 14 after birth (P<0.05). FABP4 levels increase in preterm rat lungs after hyperoxic lung injury, which may contribute to the pathogenesis of BPD.

  20. Regulation of cytochrome P4501A1 expression by hyperoxia in human lung cell lines: Implications for hyperoxic lung injury

    SciTech Connect

    Bhakta, Kushal Y. Jiang, Weiwu; Couroucli, Xanthi I.; Fazili, Inayat S.; Muthiah, Kathirvel; Moorthy, Bhagavatula

    2008-12-01

    Supplemental oxygen, used to treat pulmonary insufficiency in newborns, contributes to the development of bronchopulmonary dysplasia (BPD). Cytochrome P4501A enzymes are induced by hyperoxia in animal models, but their role in human systems is unknown. Here we investigated the molecular mechanisms of induction of CYP1A1 by hyperoxia in human lung cell lines. Three human lung cell lines were exposed to hyperoxia (95% O2) for 0-72 h, and CYP1A1 activities, apoprotein contents, and mRNA levels were determined. Hyperoxia significantly induced CYP1A1 activity and protein contents (2-4 fold), and mRNA levels (30-40 fold) over control in each cell line. Transfection of a CYP1A1 promoter/luciferase reporter construct, followed by hyperoxia (4-72 h), showed marked (2-6 fold) induction of luciferase expression. EMSA and siRNA experiments strongly suggest that the Ah receptor (AHR) is involved in the hyperoxic induction of CYP1A1. MTT reduction assays showed attenuation of cell injury with the CYP1A1 inducer beta-naphthoflavone (BNF). Our results strongly suggest that hyperoxia transcriptionally activates CYP1A1 expression in human lung cell lines by AHR-dependent mechanisms, and that CYP1A1 induction is associated with decreased toxicity. This novel finding of induction of CYP1A1 in the absence of exogenous AHR ligands could lead to novel interventions in the treatment of BPD.

  1. Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise.

    PubMed

    Smith, K J; Wildfong, K W; Hoiland, R L; Harper, M; Lewis, N C; Pool, A; Smith, S L; Kuca, T; Foster, G E; Ainslie, P N

    2016-04-15

    Cerebral blood flow (CBF) is temporally related to exercise-induced changes in partial pressure of end-tidal carbon dioxide (PetCO2 ); hyperoxia is known to enhance this relationship. We examined the hypothesis that preventing PetCO2 from rising (isocapnia) during submaximal exercise with and without hyperoxia [end-tidal Po2(PetO2 ) = 300 mmHg] would attenuate the increases in CBF. Additionally, we aimed to identify the magnitude that breathing, per se, influences the CBF response to normoxic and hyperoxic exercise. In 14 participants, CBF (intra- and extracranial) measurements were measured during exercise [20, 40, 60, and 80% of maximum workload (Wmax)] and during rest while ventilation (V̇e) was volitionally increased to mimic volumes achieved during exercise (isocapnic hyperpnea). While V̇ewas uncontrolled during poikilocapnic exercise, during isocapnic exercise and isocapnic hyperpnea, V̇ewas increased to prevent PetCO2 from rising above resting values (∼40 mmHg). Although PetCO2 differed by 2 ± 3 mmHg during normoxic poikilocapnic and isocapnic exercise, except for a greater poikilocapnic compared with isocapnic increase in blood velocity in the posterior cerebral artery at 60% Wmax, the between condition increases in intracranial (∼12-15%) and extracranial (15-20%) blood flow were similar at each workload. The poikilocapnic hyperoxic increases in both intra- and extracranial blood-flow (∼17-29%) were greater compared with poikilocapnic normoxia (∼8-20%) at intensities >40% Wmax(P< 0.01). During both normoxic and hyperoxic conditions, isocapnia normalized both the intracranial and extracranial blood-flow differences. Isocapnic hyperpnea did not alter CBF. Our findings demonstrate a differential effect of PetCO2 on CBF during exercise influenced by the prevailing PetO2.

  2. Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs.

    PubMed

    Audi, Said H; Bongard, Robert D; Krenz, Gary S; Rickaby, David A; Haworth, Steven T; Eisenhauer, Jessica; Roerig, David L; Merker, Marilyn P

    2005-11-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by approximately 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.

  3. Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise

    PubMed Central

    Wildfong, K. W.; Hoiland, R. L.; Harper, M.; Lewis, N. C.; Pool, A.; Smith, S. L.; Kuca, T.; Ainslie, P. N.

    2016-01-01

    Cerebral blood flow (CBF) is temporally related to exercise-induced changes in partial pressure of end-tidal carbon dioxide (PetCO2); hyperoxia is known to enhance this relationship. We examined the hypothesis that preventing PetCO2 from rising (isocapnia) during submaximal exercise with and without hyperoxia [end-tidal Po2 (PetO2) = 300 mmHg] would attenuate the increases in CBF. Additionally, we aimed to identify the magnitude that breathing, per se, influences the CBF response to normoxic and hyperoxic exercise. In 14 participants, CBF (intra- and extracranial) measurements were measured during exercise [20, 40, 60, and 80% of maximum workload (Wmax)] and during rest while ventilation (V̇e) was volitionally increased to mimic volumes achieved during exercise (isocapnic hyperpnea). While V̇e was uncontrolled during poikilocapnic exercise, during isocapnic exercise and isocapnic hyperpnea, V̇e was increased to prevent PetCO2 from rising above resting values (∼40 mmHg). Although PetCO2 differed by 2 ± 3 mmHg during normoxic poikilocapnic and isocapnic exercise, except for a greater poikilocapnic compared with isocapnic increase in blood velocity in the posterior cerebral artery at 60% Wmax, the between condition increases in intracranial (∼12-15%) and extracranial (15–20%) blood flow were similar at each workload. The poikilocapnic hyperoxic increases in both intra- and extracranial blood-flow (∼17–29%) were greater compared with poikilocapnic normoxia (∼8–20%) at intensities >40% Wmax (P < 0.01). During both normoxic and hyperoxic conditions, isocapnia normalized both the intracranial and extracranial blood-flow differences. Isocapnic hyperpnea did not alter CBF. Our findings demonstrate a differential effect of PetCO2 on CBF during exercise influenced by the prevailing PetO2. PMID:26769951

  4. A novel model of retinopathy of prematurity in normobaric hyperoxic conditions

    PubMed Central

    Ozgurtas, Taner; Tekin, Sercan; Yesildal, Fatih; Karaca, Umut; Aydin, Fevzi Nuri; Ugurlu, Muhammed Talha; Ozler, Mehmet; Durukan, Hakan

    2016-01-01

    AIM To examine changes in retinal vasculature after treatment with different oxygen concentrations from common retinopathy of prematurity (ROP) models and to determine a novel and practical ROP model. METHODS A sample of 14 newborn Sprague-Dawley rats was used. The study group (n=7) was exposed to 95% oxygen for 4h per day followed by normoxic laboratory conditions for 20h. This cycle was repeated for 14d. The control group (n=7) was subjected to normobaric normoxic conditions. On postnatal day 14 (P14), the two groups were placed in room air for 7d. On P21, the two groups were examined using indirect ophthalmoscopy. All eyes were enucleated for immunofluorescence (IF) staining of the vasculature of retinas and analysis of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), placental growth factor (PLGF) in vitreous humor, and then the rats were sacrificed by decapitation. All procedures were repeated using another litter of 14 pups. RESULTS In the study group and under normobaric hyperoxic conditions, retinal neovascularization and peripheral avascular retina were determined in 85% of the rats through indirect ophthalmoscopic examination. Also IF staining of retina of the study group showed retarded peripheral vascular growth. The difference between the two groups for VEGF, HIF-1α and PLGF concentrations of vitreous humor was statistically significant (P=0.003, 0.007, 0.027 respectively). CONCLUSION Fluctuating oxygen concentrations are primarily responsible for retinal neovascularization. Our new ROP model is practical and applicable for all retinal neovascularization studies, considering the laboratory procedures. PMID:27672589

  5. Glutathione reductase targeted to type II cells does not protect mice from hyperoxic lung injury.

    PubMed

    Heyob, Kathryn M; Rogers, Lynette K; Welty, Stephen E

    2008-12-01

    Exposure of the lung epithelium to reactive oxygen species without adequate antioxidant defenses leads to airway inflammation, and may contribute to lung injury. Glutathione peroxidase catalyzes the reduction of peroxides by oxidation of glutathione (GSH) to glutathione disulfide (GSSG), which can in turn be reduced by glutathione reductase (GR). Increased levels of GSSG have been shown to correlate negatively with outcome after oxidant exposure, and increased GR activity has been protective against hyperoxia in lung epithelial cells in vitro. We tested the hypothesis that increased GR expression targeted to type II alveolar epithelial cells would improve outcome in hyperoxia-induced lung injury. Human GR with a mitochondrial targeting sequence was targeted to mouse type II cells using the SPC promoter. Two transgenic lines were identified, with Line 2 having higher lung GR activities than Line 1. Both transgenic lines had lower lung GSSG levels and higher GSH/GSSG ratios than wild-type. Six-week-old wild-type and transgenic mice were exposed to greater than 95% O2 or room air (RA) for 84 hours. After exposure, Line 2 mice had higher right lung/body weight ratios and lavage protein concentrations than wild-type mice, and both lines 1 and 2 had lower GSSG levels than wild-type mice. These findings suggest that GSSG accumulation in the lung may not play a significant role in the development of hyperoxic lung injury, or that compensatory responses to unregulated GR expression render animals more susceptible to hyperoxic lung injury.

  6. Normoxic and Hyperoxic Cardiopulmonary Bypass in Congenital Heart Disease

    PubMed Central

    Mokhtari, Amir

    2014-01-01

    Cyanotic congenital heart disease comprises a diverse spectrum of anatomical pathologies. Common to all, however, is chronic hypoxia before these lesions are operated upon when cardiopulmonary bypass is initiated. A range of functional and structural adaptations take place in the chronically hypoxic heart, which, whilst protective in the hypoxic state, are deleterious when the availability of oxygen to the myocardium is suddenly improved. Conventional cardiopulmonary bypass delivers hyperoxic perfusion to the myocardium and is associated with cardiac injury and systemic stress, whilst a normoxic perfusate protects against these insults. PMID:25328889

  7. Manipulation of cortical gray matter oxygenation by hyperoxic respiratory challenge: field dependence of R(2) * and MR signal response.

    PubMed

    Rossi, Cristina; Boss, Andreas; Donati, Olivio F; Luechinger, Roger; Kollias, Spyridon S; Valavanis, Antonios; Hodler, Juerg; Nanz, Daniel

    2012-08-01

    The aim of this study was to quantitatively assess the field strength dependence of the transverse relaxation rate (R(2) *) change in cortical gray matter induced by hyperoxia and hyperoxic hypercapnia versus normoxia in an intra-individual comparison of young healthy volunteers. Medical air (21% O(2) ), pure oxygen and carbogen (95% O(2) , 5% CO(2) ) were alternatively administered in a block-design temporal pattern to induce normoxia, hyperoxia and hyperoxic hypercapnia, respectively. Local R(2) * values were determined from three-dimensional, multiple, radiofrequency-spoiled, fast field echo data acquired at 1.5, 3 and 7 T. Image quality was good at all field strengths. Under normoxia, the mean gray matter R(2) * values were 13.3 ± 2.7 s(-1) (1.5 T), 16.9 ± 0.9 s(-1) (3 T) and 29.0 ± 2.6 s(-1) (7 T). Both hyperoxic gases induced relaxation rate decreases ΔR(2) *, whose magnitudes increased quadratically with the field strength [carbogen: -0.69 ± 0.20 s(-1) (1.5 T), -1.49 ± 0.49 s(-1) (3 T), -5.64 ± 0.67 s(-1) (7 T); oxygen: -0.39 ± 0.20 s(-1) (1.5 T), -0.78 ± 0.48 s(-1) (3 T), -3.86 ± 1.00 s(-1) (7 T)]. Carbogen produced larger R(2) * changes than oxygen at all field strengths. The relative change ΔR(2) */R(2) * also increased with the field strength with a power between 1 and 2 for both carbogen and oxygen. The statistical significance of the R(2) * response improved with increasing B(0) and was higher for carbogen than for oxygen. For a sequence with pure T(2) * weighting of the signal response to respiratory challenge, the results suggested a maximum carbogen-induced signal difference of 19.3% of the baseline signal at 7 T and TE = 38 ms, but a maximum oxygen-induced signal difference of only 3.0% at 1.5 T and TE = 76 ms. For 3 T, maximum signal changes of 4.7% (oxygen) and 8.9% (carbogen) were computed. In conclusion, the R(2) * response to hyperoxic respiratory challenge was stronger for carbogen than for oxygen, and increased quadratically with

  8. A potential early physiological marker for CNS oxygen toxicity: hyperoxic hyperpnea precedes seizure in unanesthetized rats breathing hyperbaric oxygen.

    PubMed

    Pilla, Raffaele; Landon, Carol S; Dean, Jay B

    2013-04-01

    Hyperbaric oxygen (HBO(2)) stimulates presumptive central CO2-chemoreceptor neurons, increases minute ventilation (V(min)), decreases heart rate (HR) and, if breathed sufficiently long, produces central nervous system oxygen toxicity (CNS-OT; i.e., seizures). The risk of seizures when breathing HBO(2) is variable between individuals and its onset is difficult to predict. We have tested the hypothesis that a predictable pattern of cardiorespiration precedes an impending seizure when breathing HBO2. To test this hypothesis, 27 adult male Sprague-Dawley rats were implanted with radiotelemetry transmitters to assess diaphragmatic/abdominal electromyogram, electrocardiogram, and electroencephalogram. Seven days after surgery, each rat was placed in a sealed, continuously ventilated animal chamber inside a hyperbaric chamber. Both chambers were pressurized in parallel using poikilocapnic 100% O(2) (animal chamber) and air (hyperbaric chamber) to 4, 5, or 6 atmospheres absolute (ATA). Breathing 1 ATA O(2) initially decreased V(min) and HR (Phase 1 of the compound hyperoxic ventilatory response). With continued exposure to normobaric hyperoxia, however, V(min) began increasing toward the end of exposure in one-third of the animals tested. Breathing HBO2 induced an early transient increase in V(min) (Phase 2) and HR during the chamber pressurization, followed by a second significant increase of V(min) ≤8 min prior to seizure (Phase 3). HR, which subsequently decreased during sustained hyperoxia, showed no additional changes prior to seizure. We conclude that hyperoxic hyperpnea (Phase 3 of the compound hyperoxic ventilatory response) is a predictor of an impending seizure while breathing poikilocapnic HBO(2) at rest in unanesthetized rats.

  9. Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii

    PubMed Central

    Chavez-Valdez, Raul; Mason, Ariel; Nunes, Ana R.; Northington, Frances J.; Tankersley, Clarke; Ahlawat, Rajni; Johnson, Sheree M.

    2012-01-01

    Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% (P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% (P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% (P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs. PMID:22422797

  10. Dose-Dependent Effects of Glucocorticoids on Pulmonary Vascular Development in a Murine Model of Hyperoxic Lung Injury

    PubMed Central

    Perez, Marta; Wisniewska, Kamila; Lee, Keng Jin; Cardona, Herminio J.; Taylor, Joann M.; Farrow, Kathryn N.

    2015-01-01

    BACKGROUND Exposure of neonatal mice to hyperoxia results in pulmonary vascular remodeling and aberrant phosphodiesterase-5 (PDE5) signaling. Although glucocorticoids are frequently utilized in the NICU, little is known about their effects on the developing pulmonary vasculature and on PDE5. We sought to determine the effects of hydrocortisone (HC) on pulmonary vascular development and on PDE5 in a neonatal mouse model of hyperoxic lung injury. METHODS C57BL/6 mice were placed in 21% O2 or 75% O2 within 24h of birth and received HC (1, 5, or 10 mg/kg subcutaneously every other day) or vehicle. At 14d, right ventricular hypertrophy (RVH), medial wall thickness (MWT), lung morphometry, and pulmonary artery (PA) PDE5 activity were assessed. PDE5 activity was measured in isolated pulmonary artery smooth muscle cells (PASMC) exposed to 21% or 95% O2 ± 100nM HC for 24h. RESULTS Hyperoxia resulted in alveolar simplification, RVH, increased MWT, and increased PA PDE5 activity. HC decreased hyperoxia-induced RVH and attenuated MWT. HC had dose-dependent effects on alveolar simplification. HC decreased hyperoxia-induced PDE5 activity in vivo and in vitro. CONCLUSIONS HC decreases hyperoxia-induced pulmonary vascular remodeling and attenuates PDE5 activity. These findings suggest that HC may protect against hyperoxic injury in the developing pulmonary vasculature. PMID:26756781

  11. Thioredoxin-Related Mechanisms in Hyperoxic Lung Injury in Mice

    PubMed Central

    Tipple, Trent E.; Welty, Stephen E.; Rogers, Lynette K.; Hansen, Thomas N.; Choi, Young-Eun; Kehrer, James P.; Smith, Charles V.

    2007-01-01

    Reduction of glutathione disulfide (GSSG) to glutathione (GSH) by glutathione reductase (GR) enhances the efficiency of GSH-dependent antioxidant activities. However, GR-deficient (a1Neu) mice are less susceptible to acute lung injury from continuous exposure to > 95% O2 (96 h: 6.9 ± 0.1 g right lung/kg body versus room air 3.6 ± 0.3) than are C3H/HeN control mice (10.6 ± 1.3 versus 4.2 ± 0.3, P < 0.001). a1Neu mice have greater hepatic thioredoxin (Trx)1 and Trx2 levels than do C3H/HeN mice, suggesting compensation for the absence of GR. a1Neu mice exposed to hyperoxia for 96 hours showed lower levels of inflammatory infiltrates in lungs than did similarly exposed C3H/HeN mice. Pretreatment with aurothioglucose (ATG), a thioredoxin reductase (TrxR) inhibitor, exacerbated the effects of hyperoxia on lung injury in a1Neu mice (11.6 ± 0.8, P < 0.001), but attenuated hyperoxic lung edema and inflammation in C3H/HeN mice (6.3 ± 0.4, P < 0.001). No consistent alterations were observed in lung GSH contents or liver GSH or GSSG levels after ATG pretreatment. The data suggest that modulation of Trx/TrxR systems might provide therapeutically useful alterations of cellular resistance to oxidant stresses. The protective effects of ATG against hyperoxic lung injury could prove to be particularly useful therapeutically. PMID:17575077

  12. Airway Hyperreactivity is Delayed After Mild Neonatal Hyperoxic Exposure

    PubMed Central

    H, Onugha; PM, MacFarlane; CA, Mayer; A, Abrah; A, Jafri; RJ, Martin

    2015-01-01

    Background Wheezing disorders are prominent in former preterm infants beyond the neonatal period. Objectives We used a neonatal mouse model to investigate the time course of airway hyperreactivity in response to mild (40% O2) or severe (70% O2) neonatal hyperoxia. Methods After hyperoxic exposure during the first week of postnatal life we measured changes in airway reactivity using the in vitro living lung slice preparation at the end of exposure (P8) and 2 weeks later (P21). This was accompanied by measures of ∀ smooth muscle actin, myosin light chain [MLC] and alveolar morphology. Results Neither mild nor severe hyperoxia exposure affected airway reactivity to methacholine at P8 compared to normoxic controls. In contrast, airway reactivity was enhanced at P21, in mice exposed to mild (but not severe) hyperoxia, two weeks after exposure ended. This was associated with increased airway α smooth muscle actin expression at P21 after 40% oxygen exposure without significant increase in MLC. Alveolar morphology via radial alveolar counts was comparably diminished by both 40% and 70% oxygen at both P8 and P21. Conclusions These data demonstrate that early mild hyperoxia exposure causes a delayed augmentation of airway reactivity, suggesting a long-term alteration in the trajectory of airway smooth muscle development and consistent with resultant symptomatology. PMID:26021677

  13. Riboflavin supplementation does not attenuate hyperoxic lung injury in transgenic spc–mthGR mice

    PubMed Central

    Heyob, Kathryn M.; Rogers, Lynette K.; Tipple, Trent E.; Welty, Stephen E.

    2017-01-01

    The aims of this study were to test the hypothesis that mice expressing mitochondrially targeted human glutathione reductase (GR) driven by a surfactant protein C promoter (spc–mthGR) are functionally riboflavin deficient and that this deficiency exacerbates hyperoxic lung injury. The authors further hypothesized that dietary supplementation with riboflavin (FADH) will improve the bioactivity of GR, thus enhancing resistance to hyperoxic lung injury. Transgenic mt–spchGR mice and their nontransgenic littermates were fed control or riboflavin-supplemented diets upon weaning. At 6 weeks of age the mice were exposed to either room air (RA) or >95% O2 for up to 84 hours. GR activities (with and without exogenous FADH) and GR protein levels were measured in lung tissue homogenates. Glutathione (GSH) and glutathione disulfide (GSSG) concentrations were assayed to identify changes in GR activity in vivo. Lung injury was assessed by right lung to body weight ratios and bronchoalveolar lavage protein concentrations. The data showed that enhanced GR activity in the mitochondria of lung type II cells does not protect adult mice from hyperoxic lung injury. Furthermore, the addition of riboflavin to the diets of spc–mthGR mice neither enhances GR activities nor offers protection from hyperoxic lung injury. The results indicated that modulation of mitochondrial GR activity in lung type II cells is not an effective therapy to minimize hyperoxic lung injury. PMID:21128861

  14. Riboflavin supplementation does not attenuate hyperoxic lung injury in transgenic (spc-mt)hGR mice.

    PubMed

    Heyob, Kathryn M; Rogers, Lynette K; Tipple, Trent E; Welty, Stephen E

    2011-04-01

    The aims of this study were to test the hypothesis that mice expressing mitochondrially targeted human glutathione reductase (GR) driven by a surfactant protein C promoter ((spc-mt)hGR) are functionally riboflavin deficient and that this deficiency exacerbates hyperoxic lung injury. The authors further hypothesized that dietary supplementation with riboflavin (FADH) will improve the bioactivity of GR, thus enhancing resistance to hyperoxic lung injury. Transgenic (mt-spc)hGR mice and their nontransgenic littermates were fed control or riboflavin-supplemented diets upon weaning. At 6 weeks of age the mice were exposed to either room air (RA) or >95% O(2) for up to 84 hours. GR activities (with and without exogenous FADH) and GR protein levels were measured in lung tissue homogenates. Glutathione (GSH) and glutathione disulfide (GSSG) concentrations were assayed to identify changes in GR activity in vivo. Lung injury was assessed by right lung to body weight ratios and bronchoalveolar lavage protein concentrations. The data showed that enhanced GR activity in the mitochondria of lung type II cells does not protect adult mice from hyperoxic lung injury. Furthermore, the addition of riboflavin to the diets of (spc-mt)hGR mice neither enhances GR activities nor offers protection from hyperoxic lung injury. The results indicated that modulation of mitochondrial GR activity in lung type II cells is not an effective therapy to minimize hyperoxic lung injury.

  15. [The influence of hyperoxic gas mixture on the respiratory part of the lungs in rats].

    PubMed

    Berezovskiĭ, V A; Ianko, R V; Chaka, E G; Litovka, I G; Levashov, M I; Zamorskaia, T M

    2014-01-01

    The respiratory part of the lungs was investigated in rats of 3 and 12 months of age before and after the influence of normobaric hyperoxic gas mixture (40 % and 90 % oxygen). We found the reduction in middle diameter, depth, cross-sectional area, width of the entrance to alveolus and the total width of respiratory bronchioles, alveolar ducts and sacs after 28 daily hyperoxic sessions (60 mines each). We detected increasing the amount of collagen fibers, the alveolar wall thickness and oxyproline concentration in a lung after breathing the hyperoxic gas mixture. These findings could indicate the connecting tissue growth in the respiratory part of the lungs and worsening of oxygen diffusion through the blood-air barrier. The investigated indexes changed to a greater degree in rats of 3 month of age.

  16. TYLOXAPOL CONFERS DURABLE PROTECTION AGAINST HYPEROXIC LUNG INJURY IN THE RAT

    EPA Science Inventory

    We tested the hypothesis that the non-lipid components of ExosurfR, tyloxapol (TY) and cetyl alcohol (CA), protect against hyperoxic lung injury by either 1) direct radical scavenging activity or 2) induction of the animals? endogenous anti-oxidant defenses. Adult rats were in...

  17. TYLOXAPOL CONFERS DURABLE PROTECTION AGAINST HYPEROXIC LUNG INJURY IN THE RAT

    EPA Science Inventory

    We tested the hypothesis that the non-lipid components of ExosurfR, tyloxapol (TY) and cetyl alcohol (CA), protect against hyperoxic lung injury by either 1) direct radical scavenging activity or 2) induction of the animals? endogenous anti-oxidant defenses. Adult rats were in...

  18. Aryl hydrocarbon Receptor is Necessary to Protect Fetal Human Pulmonary Microvascular Endothelial Cells against Hyperoxic Injury: Mechanistic Roles of Antioxidant Enzymes and RelB

    PubMed Central

    Zhang, Shaojie; Patel, Ananddeep; Chu, Chun; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Activation of the aryl hydrocarbon receptor (AhR) protects adult and newborn mice against hyperoxic lung injury by mediating increases in the expression of phase I (cytochrome P450 (CYP) 1A) and phase II (NADP(H) quinone oxidoreductase (NQO1)) antioxidant enzymes (AOE). AhR positively regulates the expression of RelB, a component of the nuclear factor-kappaB (NF-κB) protein that contributes to anti-inflammatory processes in adult animals. Whether AhR regulates the expression of AOE and RelB, and protects fetal primary human lung cells against hyperoxic injury is unknown. Therefore, we tested the hypothesis that AhR-deficient fetal human pulmonary microvascular endothelial cells (HPMEC) will have decreased RelB activation and AOE, which will in turn predispose them to increased oxidative stress, inflammation, and cell death compared to AhR-sufficient HPMEC upon exposure to hyperoxia. AhR-deficient HPMEC showed increased hyperoxia-induced reactive oxygen species (ROS) generation, cleavage of poly (ADP-ribose) polymerase (PARP), and cell death compared to AhR-sufficient HPMEC. Additionally, AhR-deficient cell culture supernatants displayed increased macrophage inflammatory protein 1α and 1β, indicating a heightened inflammatory state. Interestingly, loss of AhR was associated with a significantly attenuated CYP1A1, NQO1, superoxide dismutase 1(SOD1), and nuclear RelB protein expression. These findings support the hypothesis that decreased RelB activation and AOE in AhR-deficient cells is associated with increased hyperoxic injury compared to AhR-sufficient cells. PMID:25831079

  19. Improved fMRI calibration: precisely controlled hyperoxic versus hypercapnic stimuli.

    PubMed

    Mark, Clarisse I; Fisher, Joseph A; Pike, G Bruce

    2011-01-15

    The calibration of functional magnetic resonance imaging (fMRI) for the estimation of neuronal activation-induced changes in cerebral metabolic rate of oxygen (CMRO(2)) has been achieved through hypercapnic-induced iso-metabolic increases in cerebral blood flow (CBF). Hypercapnia (HC) has been traditionally implemented through alterations in the fixed inspired fractional concentrations of carbon dioxide (F(I)CO(2)) without otherwise controlling end-tidal partial pressures of carbon dioxide (P(ET)CO(2)) or oxygen (P(ET)O(2)). There are several shortcomings to the use of this manual HC method that may be improved by using precise targeting of P(ET)CO(2) while maintaining iso-oxia. Similarly, precise control of blood gases can be used to induce isocapnic hyperoxia (HO) to reduce venous deoxyhaemoglobin (dHb) and thus increase BOLD signals, without appreciably altering CMRO(2) or CBF. The aim of our study was to use precise end-tidal targeting to compare the calibration of BOLD signals under an isocapnic hyperoxic protocol (HOP) (rises in P(ET)O(2) to 140, 240 and 340 mm Hg from baseline) to that of an iso-oxic hypercapnic protocol (HCP) (rises in P(ET)CO(2) of 3, 5, 7 and 9 mm Hg from baseline). Nine healthy volunteers were imaged at 3T while monitoring end-tidal gas concentrations and simultaneously measuring BOLD and CBF signals, via arterial spin labeling (ASL), during graded HCP and HOP, alternating with normocapnic states in a blocked experimental design. The variability of the calibration constant obtained under HOP (M(HOP)) was 0.3-0.5 that of the HCP one (M(HCP)). In addition, M-variances with precise gas targeting (M(HCP) and M(HOP)) were less than those reported in studies using traditional F(I)CO(2) and F(I)O(2) methods (M(HC) and M(HO), respectively). We conclude that precise controlled gas delivery markedly improves BOLD-calibration for fMRI studies of oxygen metabolism with both the HCP and the more precise HOP-alternative.

  20. Protein Expression Profile of Rat Type Two Alveolar Epithelial Cells During Hyperoxic Stress and Recovery

    NASA Astrophysics Data System (ADS)

    Bhargava, Maneesh

    Rationale: In rodent model systems, the sequential changes in lung morphology resulting from hyperoxic injury are well characterized, and are similar to changes in human acute respiratory distress syndrome (ARDS). In the injured lung, alveolar type two (AT2) epithelial cells play a critical role restoring the normal alveolar structure. Thus characterizing the changes in AT2 cells will provide insights into the mechanisms underpinning the recovery from lung injury. Methods: We applied an unbiased systems level proteomics approach to elucidate molecular mechanisms contributing to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from rat lungs at predetermined intervals during hyperoxic injury and recovery. Protein expression profiles were determined by using iTRAQRTM with tandem mass spectrometry. Results: Of 959 distinct proteins identified, 183 significantly changed in abundance during the injury-recovery cycle. Gene Ontology enrichment analysis identified cell cycle, cell differentiation, cell metabolism, ion homeostasis, programmed cell death, ubiquitination, and cell migration to be significantly enriched by these proteins. Gene Set Enrichment Analysis of data acquired during lung repair revealed differential expression of gene sets that control multicellular organismal development, systems development, organ development, and chemical homeostasis. More detailed analysis identified activity in two regulatory pathways, JNK and miR 374. A Short Time-series Expression Miner (STEM) algorithm identified protein clusters with coherent changes during injury and repair. Conclusion: Coherent changes occur in the AT2 cell proteome in response to hyperoxic stress. These findings offer guidance regarding the specific molecular mechanisms governing repair of the injured lung.

  1. Aryl hydrocarbon receptor is necessary to protect fetal human pulmonary microvascular endothelial cells against hyperoxic injury: Mechanistic roles of antioxidant enzymes and RelB

    SciTech Connect

    Zhang, Shaojie; Patel, Ananddeep; Chu, Chun; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-07-15

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Activation of the aryl hydrocarbon receptor (AhR) protects adult and newborn mice against hyperoxic lung injury by mediating increases in the expression of phase I (cytochrome P450 (CYP) 1A) and phase II (NADP(H) quinone oxidoreductase (NQO1)) antioxidant enzymes (AOE). AhR positively regulates the expression of RelB, a component of the nuclear factor-kappaB (NF-κB) protein that contributes to anti-inflammatory processes in adult animals. Whether AhR regulates the expression of AOE and RelB, and protects fetal primary human lung cells against hyperoxic injury is unknown. Therefore, we tested the hypothesis that AhR-deficient fetal human pulmonary microvascular endothelial cells (HPMEC) will have decreased RelB activation and AOE, which will in turn predispose them to increased oxidative stress, inflammation, and cell death compared to AhR-sufficient HPMEC upon exposure to hyperoxia. AhR-deficient HPMEC showed increased hyperoxia-induced reactive oxygen species (ROS) generation, cleavage of poly(ADP-ribose) polymerase (PARP), and cell death compared to AhR-sufficient HPMEC. Additionally, AhR-deficient cell culture supernatants displayed increased macrophage inflammatory protein 1α and 1β, indicating a heightened inflammatory state. Interestingly, loss of AhR was associated with a significantly attenuated CYP1A1, NQO1, superoxide dismutase 1(SOD1), and nuclear RelB protein expression. These findings support the hypothesis that decreased RelB activation and AOE in AhR-deficient cells is associated with increased hyperoxic injury compared to AhR-sufficient cells. - Highlights: • AhR deficiency potentiates oxygen toxicity in human fetal lung cells. • Deficient AhR signaling increases hyperoxia-induced cell death. • AhR deficiency increases hyperoxia-induced ROS generation and inflammation. • Anti-oxidant enzyme levels are attenuated in AhR-deficient lung cells

  2. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  3. A model of hemodynamic responses of rat tumors to hyperoxic gas challenge

    NASA Astrophysics Data System (ADS)

    Xia, Mengna; Mason, Ralph P.; Liu, Hanli

    2005-04-01

    We measured the changes of oxy-hemoglobin (Δ[HbO2]) and deoxy-hemoglobin concentration (Δ[Hb]) in rat breast 13762NF tumors with respect to oxygen or carbogen inhalation using near-infrared spectroscopy (NIRS). The changes in tumor blood flow can be estimated from the NIRS data provided with certain model assumptions. In the theoretical approach, we modified the Windkessel model so as to associate the mathematical model with such physiological parameters of tumor vasculature as total hemoglobin concentration ([HbT]), tumor blood flow (TBF), and tumor metabolic rate of oxygen (TMRO2). The computational results show that hyperoxic gas administration to the rat tumors always gave rise to improvement of tumor Δ[HbO2], while the same hyperoxic gas intervention could result in different responses in tumor [HbT], TBF, and TMRO2. This preliminary study has demonstrated that NIRS, a noninvasive tool to monitor tumor oxygenation, may also be used to estimate tumor perfusion and oxygen consumption rate in response to therapeutic interventions, if a suitable mathematical model is provided.

  4. VEGF‐D promotes pulmonary oedema in hyperoxic acute lung injury

    PubMed Central

    Sato, Teruhiko; Paquet‐Fifield, Sophie; Harris, Nicole C; Roufail, Sally; Turner, Debra J; Yuan, Yinan; Zhang, You‐Fang; Fox, Stephen B; Hibbs, Margaret L; Wilkinson‐Berka, Jennifer L; Williams, Richard A; Stacker, Steven A; Sly, Peter D

    2016-01-01

    Abstract Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF‐D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF‐D in pathological oedema was unknown. To address these issues, we exposed Vegfd‐deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd‐deficient mice was substantially reduced compared to wild‐type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf‐d and its receptor Vegfr‐3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild‐type mice, indicating that components of the Vegf‐d signalling pathway are up‐regulated in hyperoxia. Importantly, VEGF‐D and its receptors were co‐localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF‐D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf‐d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF‐D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:26924464

  5. Efficient treatment of induced dipoles

    PubMed Central

    Simmonett, Andrew C.; Pickard, Frank C.; Shao, Yihan; Cheatham, Thomas E.; Brooks, Bernard R.

    2015-01-01

    Most existing treatments of induced dipoles in polarizable molecular mechanics force field calculations use either the self-consistent variational method, which is solved iteratively, or the “direct” approximation that is non-iterative as a result of neglecting coupling between induced dipoles. The variational method is usually implemented using assumptions that are only strictly valid under tight convergence of the induced dipoles, which can be computationally demanding to enforce. In this work, we discuss the nature of the errors that result from insufficient convergence and suggest a strategy that avoids such problems. Using perturbation theory to reintroduce the mutual coupling into the direct algorithm, we present a computationally efficient method that combines the precision of the direct approach with the accuracy of the variational approach. By analyzing the convergence of this perturbation series, we derive a simple extrapolation formula that delivers a very accurate approximation to the infinite order solution at the cost of only a few iterations. We refer to the new method as extrapolated perturbation theory. Finally, we draw connections to our previously published permanent multipole algorithm to develop an efficient implementation of the electric field and Thole terms and also derive some necessary, but not sufficient, criteria that force field parameters must obey. PMID:26298123

  6. Brca1/p53 deficient mouse breast tumor hemodynamics during hyperoxic respiratory challenge monitored by a novel wide-field functional imaging (WiFI) system

    NASA Astrophysics Data System (ADS)

    Moy, Austin; Kim, Jae G.; Lee, Eva Y. H. P.; Tromberg, Bruce; Cerussi, Albert; Choi, Bernard

    2009-02-01

    Current imaging modalities allow precise visualization of tumors but do not enable quantitative characterization of the tumor metabolic state. Such quantitative information would enhance our understanding of tumor progression and response to treatment, and to our overall understanding of tumor biology. To address this problem, we have developed a wide-field functional imaging (WiFI) instrument which combines two optical imaging modalities, spatially modulated imaging (MI) and laser speckle imaging (LSI). Our current WiFI imaging protocol consists of multispectral imaging in the near infrared (650-980 nm) spectrum, over a wide (7 cm × 5 cm) field of view. Using MI, the spatially-resolved reflectance of sinusoidal patterns projected onto the tissue is assessed, and optical properties of the tissue are estimated using a Monte Carlo model. From the spatial maps of local absorption and reduced scattering coefficients, tissue composition information is extracted in the form of oxy-, deoxy-, and total hemoglobin concentrations, and percentage of lipid and water. Using LSI, the reflectance of a 785 nm laser speckle pattern on the tissue is acquired and analyzed to compute maps of blood perfusion in the tissue. Tissue metabolism state is estimated from the values of blood perfusion, volume and oxygenation state. We currently are employing the WiFI instrument to study tumor development in a BRCA1/p53 deficient mice breast tumor model. The animals are monitored with WiFI during hyperoxic respiratory challenge. At present, four tumors have been measured with WiFI, and preliminary data suggest that tumor metabolic changes during hyperoxic respiratory challenge can be determined.

  7. Sex-specific Differences in Hyperoxic Lung Injury in Mice: Implications for Acute and Chronic Lung Disease in Humans

    PubMed Central

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2014-01-01

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2α) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. CytochromeP450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F>M) and VEGF (M>F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. PMID:23792423

  8. VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury.

    PubMed

    Sato, Teruhiko; Paquet-Fifield, Sophie; Harris, Nicole C; Roufail, Sally; Turner, Debra J; Yuan, Yinan; Zhang, You-Fang; Fox, Stephen B; Hibbs, Margaret L; Wilkinson-Berka, Jennifer L; Williams, Richard A; Stacker, Steven A; Sly, Peter D; Achen, Marc G

    2016-06-01

    Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF-D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF-D in pathological oedema was unknown. To address these issues, we exposed Vegfd-deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd-deficient mice was substantially reduced compared to wild-type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf-d and its receptor Vegfr-3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild-type mice, indicating that components of the Vegf-d signalling pathway are up-regulated in hyperoxia. Importantly, VEGF-D and its receptors were co-localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF-D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf-d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF-D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  9. In vitro effects of hyperoxia on alveolar type II pneumocytes: inhibition of glutathione synthesis increases hyperoxic cell injury.

    PubMed

    Aerts, C; Wallaert, B; Voisin, C

    1992-01-01

    An in vitro model of alveolar epithelial oxidant injury was developed based on exposure to hyperoxia of cultured guinea pig type II pneumocytes using a biphasic cell culture system in aerobiosis. The present study investigates the roles of intracellular antioxidant enzymes and of glutathione in providing protection against hyperoxia. A 2-day type II cell culture in normoxia was associated with a significant decrease in protein, catalase, and Cu-Zn SOD cell content, whereas ATP cell content, Mn-SOD, and glutathione peroxidase (GPx) activities did not change and glutathione cell content significantly increased. Exposure of type II cells to hyperoxia did not induce significant changes in cell content in protein, SOD, catalase, GPx, or glutathione cell content when compared to control cells (exposed to normoxia). With ATP cell content expressed as a cell injury index (CII), type II cell injury was found to increase with increasing O2 concentrations. Indeed, a 2-day 50% O2 and 95% O2 exposure resulted in a CII of -7.5 +/- 6.2% and 17.9 +/- 5.9%, respectively, LDH release by type II cells was not significantly increased after hypoxic exposure. Cell injury effects of hyperoxia did not correlate with the endogenous antioxidant enzyme activities (SOD, Mn-SOD, catalase). In marked contrast, there was a significant correlation between the CII and total glutathione content of type II cells (p < .01). This correlation was largely due to the close relationship between CII and reduced glutathione. Hyperoxic induced cell injury (as demonstrated by CII > 0) was clearly associated with significantly lower intracellular glutathione level when compared to experiments without hyperoxia induced cell injury (CII < 0). In addition, in the presence of buthionine sulfoximine (BSO), the ability of type II cells to synthetize new glutathione was severely impaired, whereas ATP cell content and cell antioxidant enzyme activities did not change. As a consequence, the reduction of intracellular

  10. Detoxification of Mitochondrial Oxidants and Apoptotic Signaling Are Facilitated by Thioredoxin-2 and Peroxiredoxin-3 during Hyperoxic Injury

    PubMed Central

    Forred, Benjamin J.; Daugaard, Darwin R.; Titus, Brianna K.; Wood, Ryan R.; Floen, Miranda J.; Booze, Michelle L.

    2017-01-01

    Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2). The goal of this study was to understand the role of the mitochondrial thioredoxin system and mitochondrial injuries during hyperoxic exposure. Flow analysis of the redox-sensitive, mitochondrial-specific fluorophore, MitoSOX, indicated increased levels of mitochondrial oxidant formation in human adenocarcinoma cells cultured in 95% oxygen. Increased expression of Trx2 and TrxR2 in response to hyperoxia were not attributable to changes in mitochondrial mass, suggesting that hyperoxic upregulation of mitochondrial thioredoxins prevents accumulation of oxidized Prx3. Mitochondrial oxidoreductase activities were modulated through pharmacological inhibition of TrxR2 with auranofin and genetically through shRNA knockdown of Trx2 and Prx3. Diminished Trx2 and Prx3 expression was associated with accumulation of mitochondrial superoxide; however, only shRNA knockdown of Trx2 increased susceptibility to hyperoxic cell death and increased phosphorylation of apoptosis signal-regulating kinase-1 (ASK1). In conclusion, the mitochondrial thioredoxin system regulates hyperoxic-mediated death of pulmonary epithelial cells through detoxification of oxidants and regulation of redox-dependent apoptotic signaling. PMID:28045936

  11. Perinatal hyperoxic exposure reconfigures the central respiratory network contributing to intolerance to anoxia in newborn rat pups

    PubMed Central

    Bierman, Alexis M.; Tankersley, Clarke G.; Wilson, Christopher G.; Chavez-Valdez, Raul

    2013-01-01

    Perinatal exposure to hyperoxia (30–60% O2) alters the respiratory control system via modulation of peripheral arterial chemoreceptor development and function. Furthermore, hyperoxic exposure during the first two postnatal weeks of life can alternatively modulate the different phases of the hypoxic ventilatory response. Given the effects of perinatal hyperoxia, the aims of our study were 1) to determine the effect on survival time in response to lethal anoxic stimuli in rat pups and 2) to characterize the output of the isolated central respiratory network in response to acute hypoxic stimuli. We hypothesized that perinatal hyperoxic exposure would modify the neonatal rat ventilatory response to anoxia by affecting a central component of the respiratory network in addition to the maturation of the carotid body chemoreceptors. We found that animals continuously exposed to 60% oxygen up to age 5 days after parturition (P5) have reduced breathing frequency at baseline and within the first 10 min of a fatal anoxic challenge. Hyperoxic rat pups also have a shortened time to last gasp in response to anoxia that is not associated with lung injury or inflammation. This study is the first to demonstrate that these in vivo findings correlate with reduced phrenic burst frequency from the isolated brainstem ex vivo. Thus hyperoxic exposure reduced the phrenic burst frequency at baseline and in response to ex vivo anoxia. Importantly, our data suggest that perinatal hyperoxia alters ventilation and the response to anoxia at P5 in part by altering the frequency of phrenic bursts generated by the central respiratory network. PMID:24157524

  12. Hyperoxic sheep pulmonary microvascular endothelial cells generate free radicals via mitochondrial electron transport.

    PubMed Central

    Sanders, S P; Zweier, J L; Kuppusamy, P; Harrison, S J; Bassett, D J; Gabrielson, E W; Sylvester, J T

    1993-01-01

    Free radical generation by hyperoxic endothelial cells was studied using electron paramagnetic resonance (EPR) spectroscopy and the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Studies were performed to determine the radical species produced, whether mitochondrial electron transport was involved, and the effect of the radical generation on cell mortality. Sheep pulmonary microvascular endothelial cell suspensions exposed to 100% O2 for 30 min exhibited prominent DMPO-OH and, occasionally, additional smaller DMPO-R signals thought to arise from the trapping of superoxide anion (O2-.), hydroxyl (.OH), and alkyl (.R) radicals. Superoxide dismutase (SOD) quenched both signals suggesting that the observed radicals were derived from O2-.. Studies with deferoxamine suggested that the generation of .R occurred secondary to the formation of .OH from O2-. via an iron-mediated Fenton reaction. Blocking mitochondrial electron transport with rotenone (20 microM) markedly decreased radical generation. Cell mortality increased slightly in oxygen-exposed cells. This increase was not significantly altered by SOD or deferoxamine, nor was it different from the mortality observed in air-exposed cells. These results suggest that endothelial cells exposed to hyperoxia for 30 min produce free radicals via mitochondrial electron transport, but under the conditions of these experiments, this radical generation did not appear cause cell death. PMID:8380815

  13. Treatment of Radiation-Induced Urethral Strictures.

    PubMed

    Hofer, Matthias D; Liu, Joceline S; Morey, Allen F

    2017-02-01

    Radiation therapy may result in urethral strictures from vascular damage. Most radiation-induced urethral strictures occur in the bulbomembranous junction, and urinary incontinence may result as a consequence of treatment. Radiation therapy may compromise reconstruction due to poor tissue healing and radionecrosis. Excision and primary anastomosis is the preferred urethroplasty technique for radiation-induced urethral stricture. Principles of posterior urethroplasty for trauma may be applied to the treatment of radiation-induced urethral strictures. Chronic management with suprapubic tube is an option based on patient comorbidities and preference.

  14. Disruption of Cytochrome P4501A2 in mice leads to increased susceptibility to hyperoxic lung injury

    PubMed Central

    Wang, Lihua; Lingappan, Krithika; Jiang, Weiwu; Couroucli, Xanthi I.; Welty, Stephen E.; Shivanna, Binoy; Barrios, Roberto; Wang, Gangduo; Khan, M. Firoze; Gonzalez, Frank J.; Roberts, L Jackson; Moorthy, Bhagavatula

    2015-01-01

    Hyperoxia contributes to acute lung injury (ALI) in diseases such as acute respiratory distress syndrome (ARDS). Cytochrome P450 (CYP)1A enzymes have been implicated in hyperoxic lung injury, but the mechanistic role(s) of CYP1A2 in pulmonary injury is not known. We hypothesized that mice lacking the gene for Cyp1a2 (which is predominantly expressed in the liver) will be more sensitive to lung injury and inflammation mediated by hyperoxia, and that CYP1A2 will play a protective role by attenuating lipid peroxidation and oxidative stress in the lung. Eight to ten week old WT (C57BL/6) or Cyp1a2(−/−) mice were exposed to hyperoxia (>95% O2) or maintained in room air for 24–72 h. Lung injury was assessed by determining the ratios of lung weight/body weight (LW/BW), and by histology. Extent of inflammation was determined by measuring the number of neutrophils in the lung as well as cytokine expression. The Cyp1a2(−/−) mice under hyperoxic conditions showed increased LW/BW ratios, lung injury, neutrophil infiltration, IL-6 and TNF-α levels, and augmented lipid peroxidation, as evidenced by increased formation of malondialdehyde (MDA)- and 4-hydroxynonenal (4-HNE)-protein adducts, and pulmonary isofurans compared to those of WT mice. In vitro experiments showed that the F2-isoprostane PGF2-α is metabolized by CYP1A2 to a dinor metabolite, providing evidence for a catalytic role for CYP1A2 in the metabolism of F2-isoprostanes. In summary, our results support the hypothesis that hepatic CYP1A2 plays a critical role in the attenuation against hyperoxic lung injury by decreasing lipid peroxidation and oxidative stress in vivo. PMID:25680282

  15. Measurement of oxygen extraction fraction (OEF): An optimized BOLD signal model for use with hypercapnic and hyperoxic calibration.

    PubMed

    Merola, Alberto; Murphy, Kevin; Stone, Alan J; Germuska, Michael A; Griffeth, Valerie E M; Blockley, Nicholas P; Buxton, Richard B; Wise, Richard G

    2016-04-01

    Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic respiratory challenges. More recently, methods based on respiratory challenges that include both hypercapnia and hyperoxia have been developed to assess absolute CMRO2, an important parameter for understanding brain energetics. In this paper, we empirically optimize a previously presented "original calibration model" relating BOLD and blood flow signals specifically for the estimation of oxygen extraction fraction (OEF) and absolute CMRO2. To do so, we have created a set of synthetic BOLD signals using a detailed BOLD signal model to reproduce experiments incorporating hypercapnic and hyperoxic respiratory challenges at 3T. A wide range of physiological conditions was simulated by varying input parameter values (baseline cerebral blood volume (CBV0), baseline cerebral blood flow (CBF0), baseline oxygen extraction fraction (OEF0) and hematocrit (Hct)). From the optimization of the calibration model for estimation of OEF and practical considerations of hypercapnic and hyperoxic respiratory challenges, a new "simplified calibration model" is established which reduces the complexity of the original calibration model by substituting the standard parameters α and β with a single parameter θ. The optimal value of θ is determined (θ=0.06) across a range of experimental respiratory challenges. The simplified calibration model gives estimates of OEF0 and absolute CMRO2 closer to the true values used to simulate the experimental data compared to those estimated using the original model incorporating literature values of α and β. Finally, an error propagation analysis demonstrates the susceptibility of the original and simplified calibration models to measurement errors and potential violations in the underlying assumptions of isometabolism

  16. Effects of hyperoxic training on performance and cardiorespiratory response to exercise.

    PubMed

    Perry, Christopher G R; Reid, Julie; Perry, Wendy; Wilson, Brian A

    2005-07-01

    To determine whether training in a hyperoxic environment would result in greater increases in VO2max and performance at 90% VO2max as compared with training in normoxia. In a single blind design nine athletes trained for 6 wk on a cycle ergometer 3 d.wk(-1), 1 h.d(-1) (10 x 4-min intervals, with 2 min of rest between intervals) at 90% HR(max). Training HR range was maintained by adjusting the power output. Subjects were randomly assigned to H (60% O2) or N (21% O2) breathing conditions for training. After 12 wk of detraining, a second 6-wk training protocol was completed with the breathing conditions reversed. VO2max, performance time at 90% VO2max and cardiorespiratory response to a steady-state exercise at 80% VO2max were measured pre- and posttraining. All pre- and posttraining tests were conducted under normoxic conditions. There were no significant differences between pretraining results for any of the parameters. Power output was 8.1% higher while training in H compared with N, to maintain training HR. Both H and N training resulted in increased performance time, with H being greater than N. Although there was a trend for a greater increase in VO2max after H versus N training, this difference was not significant. HR(max) did not change for H or N. HR VE at 80% VO2max decreased posttraining with no differences between H and N. The data showed that a higher power output was required to maintain HR during H training. This increased training intensity during H resulted in improved exercise performance whereas cycling at 90% VO2max in room air and may be due to peripheral factors because cardiorespiratory responses were similar.

  17. Evaluation of MR derived cerebral oxygen metabolic index in experimental hyperoxic hypercapnia, hypoxia and ischemia

    PubMed Central

    An, Hongyu; Liu, Qingwei; Chen, Yasheng; Lin, Weili

    2009-01-01

    Background and Purpose A non-invasive MRI method to measure cerebral oxygen metabolism has the potential to assess tissue viability during cerebral ischemia. The purposes of this study were 1) to validate MR oxygenation measurements across a wide range of global cerebral oxygenation; and 2) to examine the spatiotemporal evolution of oxygen metabolism during focal middle cerebral artery occlusion (MCAO) in rats. Methods A group of rats (n=28) under normal, hyperoxic hypercapnia and hypoxia were studied to compare MR measured cerebral oxygen saturation (O2SatMRv) with blood gas oximetry measurements in the jugular vein (O2SatJV) and superior sagittal sinus (O2SatSSS). In a separate group of rats (n=31), MR measured cerebral oxygen metabolic index (MR_COMI) was acquired at multiple time-points during MCAO. Histogram analysis was performed on the normalized MR_COMI (rMR_COMI) to examine evolution of oxygen metabolism during acute ischemia. Results Highly linear relationships were obtained between O2SatMRv and O2SatJV/O2SatSSS in rats under global cerebral oxygenation alterations. In the focal ischemia study, rMR_COMI values were significantly lower within the areas of eventual infarction than other regions. Moreover, the rMR_COMI values within the ischemic territory decreased with time, concomitant with an increase in the number of voxels with severely impaired oxygen metabolism. Conclusion Accurate estimates of O2SatMRv can be obtained across a broad and physiologically relevant range of cerebral oxygenation. Furthermore, this method demonstrates a dynamic alteration of cerebral oxygen metabolism during acute ischemia in rats. PMID:19359642

  18. The Lung Alveolar Lipofibroblast: An Evolutionary Strategy Against Neonatal Hyperoxic Lung Injury

    PubMed Central

    Torday, John S.

    2014-01-01

    Abstract Significance: Oxygen, the main mode of support for premature infants with immature lungs, can cause toxicity by producing reactive oxygen species (ROS) that disrupt homeostasis; yet, these same molecules were entrained to promote vertebrate lung phylogeny. By providing a deeper understanding of this paradox, we propose physiologically rational strategies to prevent chronic lung disease (CLD) of prematurity. Recent Advances: To prevent neonatal hyperoxic lung damage biologically, we have exploited the alveolar defense mechanism(s) that evolutionarily evolved to combat increased atmospheric oxygen during the vertebrate water to land transition. Critical Issues: Over the course of vertebrate lung evolution, ROS promoted the formation of lipofibroblasts, specialized adepithelial cells, which protect the alveoli against oxidant injury; peroxisome proliferator-activated receptor gamma (PPARγ), the master switch for lipofibroblast differentiation, prevents such oxidant lung injury, both by directly promoting mesodermal differentiation and its antioxidant defenses, and indirectly by stimulating the developmental epithelial–mesenchymal paracrine interactions that have physiologically determined lung surfactant production in accord with the lung's phylogenetic adaptation to atmospheric oxygen, preventing Respiratory Distress Syndrome at birth. Future Directions: The molecular strategy (PPARγ agonists) to prevent CLD of prematurity, proposed by us, although seems to be robust, effective, and safe under experimental conditions, it awaits detailed pharmacokinetic and pharmacodynamic studies for its safe and effective clinical translation to human infants. Antioxid. Redox Signal. 21, 1893–1904. “I have procured air [oxygen]…between five and six times as good as the best common air that I have ever met with.” —Joseph Priestley, 1775 PMID:24386954

  19. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    PubMed Central

    SEPEHR, REYHANEH; AUDI, SAID H.; MALEKI, SEPIDEH; STANISZEWSKI, KEVIN; EIS, ANNIE L.; KONDURI, GIRIJA G.; RANJI, MAHSA

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure. PMID:24672581

  20. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS.

    PubMed

    Sepehr, Reyhaneh; Audi, Said H; Maleki, Sepideh; Staniszewski, Kevin; Eis, Annie L; Konduri, Girija G; Ranji, Mahsa

    2013-07-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  1. Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation.

    PubMed Central

    Waxman, A B; Einarsson, O; Seres, T; Knickelbein, R G; Warshaw, J B; Johnston, R; Homer, R J; Elias, J A

    1998-01-01

    Acute lung injury is a frequent and treatment-limiting consequence of therapy with hyperoxic gas mixtures. To determine if IL-11 is protective in oxygen toxicity, we compared the effects of 100% O2 on transgenic mice that overexpress IL-11 in the lung and transgene (-) controls. IL-11 markedly enhanced survival in 100% O2 with 100% of transgene (-) animals dying within 72-96 h and > 90% of transgene (+) animals surviving for more than 10 d. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, lipid peroxidation, and pulmonary neutrophil recruitment. Significant differences in copper zinc superoxide dismutase and catalase activities were not noted and the levels of total, reduced and oxidized glutathione were similar in transgene (+) and (-) animals. Glutathione reductase, glutathione peroxidase, and manganese superoxide dismutase activities were slightly higher in transgene (+) as versus (-) mice after 100% O2 exposure, and IL-11 diminished hyperoxia-induced expression of IL-1 and TNF. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals and IL-11 markedly diminished this cell death response. These studies demonstrate that IL-11 markedly diminishes hyperoxic lung injury. They also demonstrate this protection is associated with small changes in lung antioxidants, diminished hyperoxia-induced IL-1 and TNF production, and markedly suppressed hyperoxia-induced DNA fragmentation. PMID:9576762

  2. Effect of hyperoxic and hyperbaric conditions on the adenosinergic pathway and CD26 expression in rat.

    PubMed

    Bruzzese, Laurie; Rostain, Jean-Claude; Née, Laëtitia; Condo, Jocelyne; Mottola, Giovanna; Adjriou, Nabil; Mercier, Laurence; Berge-Lefranc, Jean-Louis; Fromonot, Julien; Kipson, Nathalie; Lucciano, Michel; Durand-Gorde, Josée-Martine; Jammes, Yves; Guieu, Régis; Ruf, Jean; Fenouillet, Emmanuel

    2015-07-15

    The nucleoside adenosine acts on the nervous and cardiovascular systems via the A2A receptor (A2AR). In response to oxygen level in tissues, adenosine plasma concentration is regulated in particular via its synthesis by CD73 and via its degradation by adenosine deaminase (ADA). The cell-surface endopeptidase CD26 controls the concentration of vasoactive and antioxidant peptides and hence regulates the oxygen supply to tissues and oxidative stress response. Although overexpression of adenosine, CD73, ADA, A2AR, and CD26 in response to hypoxia is well documented, the effects of hyperoxic and hyperbaric conditions on these elements deserve further consideration. Rats and a murine Chem-3 cell line that expresses A2AR were exposed to 0.21 bar O2, 0.79 bar N2 (terrestrial conditions; normoxia); 1 bar O2 (hyperoxia); 2 bar O2 (hyperbaric hyperoxia); 0.21 bar O2, 1.79 bar N2 (hyperbaria). Adenosine plasma concentration, CD73, ADA, A2AR expression, and CD26 activity were addressed in vivo, and cAMP production was addressed in cellulo. For in vivo conditions, 1) hyperoxia decreased adenosine plasma level and T cell surface CD26 activity, whereas it increased CD73 expression and ADA level; 2) hyperbaric hyperoxia tended to amplify the trend; and 3) hyperbaria alone lacked significant influence on these parameters. In the brain and in cellulo, 1) hyperoxia decreased A2AR expression; 2) hyperbaric hyperoxia amplified the trend; and 3) hyperbaria alone exhibited the strongest effect. We found a similar pattern regarding both A2AR mRNA synthesis in the brain and cAMP production in Chem-3 cells. Thus a high oxygen level tended to downregulate the adenosinergic pathway and CD26 activity. Hyperbaria alone affected only A2AR expression and cAMP production. We discuss how such mechanisms triggered by hyperoxygenation can limit, through vasoconstriction, the oxygen supply to tissues and the production of reactive oxygen species.

  3. Treatment of chemotherapy-induced alopecia.

    PubMed

    Yeager, Caroline E; Olsen, Elise A

    2011-01-01

    Chemotherapy-induced alopecia has been well documented as a cause of distress to patients undergoing cancer treatment. Despite the importance of hair loss to patients, however, patients often receive little more counseling than the advice to purchase a wig or other head covering for the duration of their treatment. Research into non-camouflage (wigs, turbans, and head scarves) treatment methods has been complicated both by a lack of a standardized methodology for evaluating hair loss and hair regrowth and by a lack of human trials. Nevertheless, scalp cooling as a method of preventing hair loss during chemotherapy and 2% topical minoxidil as a therapy for accelerating regrowth after chemotherapy are both effective non-camouflage options for treatment. Other proposed treatments for prevention of hair loss during chemotherapy have demonstrated promise in early trials, but these findings will need validation from rigorous further studies. The increasing number of reports of permanent alopecia not just with pre-bone marrow transplant, high-dose busulfan, and cyclophosphamide regimens but also with standard breast cancer chemotherapy regimens illustrates the importance of further research into treatment methods for chemotherapy-induced alopecia. © 2011 Wiley Periodicals, Inc.

  4. Interstitial Lung Disease Induced by Pazopanib Treatment

    PubMed Central

    Ide, Shotaro; Sakamoto, Noriho; Hara, Shintaro; Hara, Atsuko; Kakugawa, Tomoyuki; Nakamura, Yoichi; Futsuki, Yoji; Izumikawa, Koichi; Ishimatsu, Yuji; Yanagihara, Katsunori; Mukae, Hiroshi

    2017-01-01

    Although pneumothorax has been reported to be a major pulmonary adverse event in patients treated with pazopanib, a multikinase inhibitor, drug-induced interstitial lung disease (DILD) has not been reported. A 74-year-old Japanese man who received pazopanib for the treatment of femoral leiomyosarcoma and lung metastasis presented with dyspnea and fatigue. He had mild interstitial pneumonia when pazopanib treatment was initiated. Chest computed tomography revealed progressive bilateral ground-glass opacity (GGO) and traction bronchiectasis. We diagnosed DILD due to pazopanib. The patient's pazopanib treatment was interrupted and a steroid was administered. The symptoms and GGO were improved with treatment. Physicians should be aware of DILD due to pazopanib in patients with pre-existing interstitial lung disease. PMID:28050004

  5. Hyperbaric oxygen treatment induces antioxidant gene expression.

    PubMed

    Godman, Cassandra A; Joshi, Rashmi; Giardina, Charles; Perdrizet, George; Hightower, Lawrence E

    2010-06-01

    Although the underlying molecular causes of aging are not entirely clear, hormetic agents like exercise, heat, and calorie restriction may generate a mild pro-oxidant stress that induces cell protective responses to promote healthy aging. As an individual ages, many cellular and physiological processes decline, including wound healing and reparative angiogenesis. This is particularly critical in patients with chronic non-healing wounds who tend to be older. We are interested in the potential beneficial effects of hyperbaric oxygen as a mild hormetic stress on human microvascular endothelial cells. We analyzed global gene expression changes in human endothelial cells following a hyperbaric exposure comparable to a clinical treatment. Our analysis revealed an upregulation of antioxidant, cytoprotective, and immediate early genes. This increase coincided with an increased resistance to a lethal oxidative stress. Our data indicate that hyperbaric oxygen can induce protection against oxidative insults in endothelial cells and may provide an easily administered hormetic treatment to help promote healthy aging.

  6. Induced vasodilation as treatment for Raynaud's disease.

    PubMed

    Jobe, J B; Sampson, J B; Roberts, D E; Beetham, W P

    1982-11-01

    We examined the efficacy of induced vasodilation as a treatment of idiopathic Raynaud's disease. Eight persons with Raynaud's disease and seven normal persons each received 27 simultaneous pairings of hand immersion in warm water (43 degrees C) for 10 minutes with exposure of the whole body to cold (0 degrees C). A second group of seven normal persons and nine persons with Raynaud's disease received no treatments. All subjects had cold test exposures (0 degrees C) at the start and end of the study. Subjects with Raynaud's disease who received treatments showed significant increases in digital temperatures (2.2 degrees C) during the cold test compared with the values of untreated subjects with Raynaud's disease (p less than 0.05); normal subjects who had received treatments showed no difference from those who had not. Digital temperatures of subjects with Raynaud's disease after treatment increased to levels approaching those of normal subjects, although they showed lower digital temperatures during initial exposure to cold (p less than 0.01). This therapy offers a practical alternative to traditional treatments.

  7. Perindopril treatment in streptozotocin induced diabetic nephropaty.

    PubMed

    Trojacanec, J; Zafirov, D; Labacevski, N; Jakjovski, K; Zdravkovski, P; Trojacanec, P; Petrusevska, G

    2013-01-01

    Diabetic nephropathy (DN) is one of the most common causes of terminal stadium damage to the kidneys. The angiotensin-converting enzyme (ACE) represents a significant risk factor for the progression of DN. ACE inhibitors are medications of particular interest knowing the role of angiotensin II in the development of DN. This study aimed to examine the effects of ACE inhibitor treatment perindopril (PER), administered to rats with streptozotocin (STZ) induced DN, that developed albuminuria, renal hypertrophy and mild glomerulussclerosis. DN was induced by a STZ (60 mg/kg ip) single injection to normotensive Wistar rats. The administration of STZ caused diabetes mellitus (DM) with symptoms and signs of DN including poor general condition, body-weight loss, kidney weight increase as well as increased values of BUN and serum creatinine, accompanied by increased diuresis as well as distinct albuminuria. The majority of these symptoms were manifested 4 weeks after, and even more distinctly 8 and 12 weeks after administering STZ. The perindopril treatment (6 mg/kg BW), starting 4 weeks after administering STZ, resulted in a significant improvement of all symptoms and signs of DN, significantly lowering the values of BUN and serum creatinine, albuminuria and diuresis. The histopathological examination of the renal samples at 8 and 12 weeks after the beginning of the study have shown that perindopril significantly lowers the progression of glomerulopathy, and significantly improves the glomerulosclerotic index, as well as the progression of renal histological abnormalities induced with STZ. Thus perindopril treatment ameliorates STZ-induced nephropathic changes in DM rats.

  8. Sex-specific differences in hyperoxic lung injury in mice: role of Cytochrome P450 (CYP)1A

    PubMed Central

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Moorthy, Bhagavatula

    2015-01-01

    Sex-specific differences in pulmonary morbidity in adults and preterm infants are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. Cytochrome P450 (CYP)1A enzymes have been shown to play a mechanistic role in hyperoxic lung injury (HLI) in animal models. Whether CYP1A enzymes contribute to gender-specific differences in relation to HLI is unknown. In this investigation, we tested the hypothesis that mice will display gender-specific differences in HLI, and that this phenomenon will be altered in mice lacking the genes for Cyp1a1 or 1a2. Eight week-old male and female wild type (WT) (C57BL/6J) mice, Cyp1a1−/−, and Cyp1a2−/− mice were exposed to 72 hours of hyperoxia (FiO2>0.95). Lung injury and inflammation were assessed and pulmonary and hepatic CYP1A1 and CYP1A2 levels were quantified at the enzyme activity, protein and mRNA level. Upon exposure to hyperoxia, liver and lung microsomal proteins showed higher pulmonary CYP1A1 (apoprotein level and activity) in WT females compared to WT males and a greater induction in hepatic CYP1A2 mRNA levels and activity in WT females after hyperoxia exposure. The gender based female advantage was lost or reversed in Cyp1a1−/− and Cyp1a2−/− mice. These findings suggest an important role for CYP1A enzymes in the gender-specific modulation of hyperoxic lung injury. PMID:25703676

  9. Influence of Hypoxic Interval Training and Hyperoxic Recovery on Muscle Activation and Oxygenation in Connection with Double-Poling Exercise

    PubMed Central

    Zinner, Christoph; Hauser, Anna; Born, Dennis-Peter; Wehrlin, Jon P.; Holmberg, Hans-Christer; Sperlich, Billy

    2015-01-01

    Here, we evaluated the influence of breathing oxygen at different partial pressures during recovery from exercise on performance at sea-level and a simulated altitude of 1800 m, as reflected in activation of different upper body muscles, and oxygenation of the m. triceps brachii. Ten well-trained, male endurance athletes (25.3±4.1 yrs; 179.2±4.5 cm; 74.2±3.4 kg) performed four test trials, each involving three 3-min sessions on a double-poling ergometer with 3-min intervals of recovery. One trial was conducted entirely under normoxic (No) and another under hypoxic conditions (Ho; FiO2 = 0.165). In the third and fourth trials, the exercise was performed in normoxia and hypoxia, respectively, with hyperoxic recovery (HOX; FiO2 = 1.00) in both cases. Arterial hemoglobin saturation was higher under the two HOX conditions than without HOX (p<0.05). Integrated muscle electrical activity was not influenced by the oxygen content (best d = 0.51). Furthermore, the only difference in tissue saturation index measured via near-infrared spectroscopy observed was between the recovery periods during the NoNo and HoHOX interventions (P<0.05, d = 0.93). In the case of HoHo the athletes’ Pmean declined from the first to the third interval (P < 0.05), whereas Pmean was unaltered under the HoHOX, NoHOX and NoNo conditions. We conclude that the less pronounced decline in Pmean during 3 x 3-min double-poling sprints in normoxia and hypoxia with hyperoxic recovery is not related to changes in muscle activity or oxygenation. Moreover, we conclude that hyperoxia (FiO2 = 1.00) used in conjunction with hypoxic or normoxic work intervals may serve as an effective aid when inhaled during the subsequent recovery intervals. PMID:26468885

  10. Treatment of drug-induced seizures.

    PubMed

    Chen, Hsien-Yi; Albertson, Timothy E; Olson, Kent R

    2016-03-01

    Seizures are a common complication of drug intoxication, and up to 9% of status epilepticus cases are caused by a drug or poison. While the specific drugs associated with drug-induced seizures may vary by geography and change over time, common reported causes include antidepressants, stimulants and antihistamines. Seizures occur generally as a result of inadequate inhibitory influences (e.g., gamma aminobutyric acid, GABA) or excessive excitatory stimulation (e.g. glutamate) although many other neurotransmitters play a role. Most drug-induced seizures are self-limited. However, status epilepticus occurs in up to 10% of cases. Prolonged or recurrent seizures can lead to serious complications and require vigorous supportive care and anticonvulsant drugs. Benzodiazepines are generally accepted as the first line anticonvulsant therapy for drug-induced seizures. If benzodiazepines fail to halt seizures promptly, second line drugs include barbiturates and propofol. If isoniazid poisoning is a possibility, pyridoxine is given. Continuous infusion of one or more anticonvulsants may be required in refractory status epilepticus. There is no role for phenytoin in the treatment of drug-induced seizures. The potential role of ketamine and levetiracetam is promising but not established.

  11. Induced radioisotopes in a linac treatment hall.

    PubMed

    Vega-Carrillo, Héctor René; de Leon-Martinez, Héctor Asael; Rivera-Perez, Esteban; Luis Benites-Rengifo, Jorge; Gallego, Eduardo; Lorente, Alfredo

    2015-08-01

    When linacs operate above 8MV an undesirable neutron field is produced whose spectrum has three main components: the direct spectrum due to those neutrons leaking out from the linac head, the scattered spectrum due to neutrons produced in the head that collides with the nuclei in the head losing energy and the third spectrum due to room-return effect. The third category of spectrum has mainly epithermal and thermal neutrons being constant at any location in the treatment hall. These neutrons induce activation in the linac components, the concrete walls and in the patient body. Here the induced radioisotopes have been identified in concrete samples located in the hall and in one of the wedges. The identification has been carried out using a gamma-ray spectrometer.

  12. Bioactivity of NANOZR Induced by Alkali Treatment.

    PubMed

    Nishizaki, Mariko; Komasa, Satoshi; Taguchi, Yoichiro; Nishizaki, Hiroshi; Okazaki, Joji

    2017-04-06

    In recent years, zirconia has been a recognized implant material in clinical dentistry. In the present study, we investigated the performance of an alkali-modified ceria-stabilized tetragonal ZrO₂ polycrystalline ceramic-based nanostructured zirconia/alumina composite (NANOZR) implant by assessing surface morphology and composition, wettability, bovine serum albumin adsorption rate, rat bone marrow (RBM) cell attachment, and capacity for inducing bone differentiation. NANOZR surfaces without and with alkali treatment served as the control and test groups, respectively. RBM cells were seeded in a microplate with the implant and cultured in osteogenic differentiation medium, and their differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, osteocalcin (OCN) production, calcium deposition, and osteogenic gene expression. The alkali-treated NANOZR surface increased ALP activity, OCN production, calcium deposition, and osteogenesis-related gene expression in attached RBM cells. These data suggest that alkali treatment enhances the osteogenesis-inducing capacity of NANOZR implants and may therefore improve their biointegration into alveolar bone.

  13. Transcriptome Analysis of the Preterm Rabbit Lung after Seven Days of Hyperoxic Exposure

    PubMed Central

    Brady, Paul; Jimenez, Julio; Nagatomo, Taro; Deprest, Jan; Toelen, Jaan

    2015-01-01

    The neonatal management of preterm born infants often results in damage to the developing lung and subsequent morbidity, referred to as bronchopulmonary dysplasia (BPD). Animal models may help in understanding the molecular processes involved in this condition and define therapeutic targets. Our goal was to identify molecular pathways using the earlier described preterm rabbit model of hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31 days) and kept in hyperoxia (95% O2) for 7 days. Controls were preterm pups kept in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity Pathway Analysis (IPA), in order to identify the central molecules responsible for the observed transcriptional changes. We detected 2217 significantly dysregulated transcripts following hyperoxia, of which 90% could be identified. Major pathophysiological dysregulations were found in inflammation, lung development, vascular development and reactive oxygen species (ROS) metabolism. To conclude, amongst the many dysregulated transcripts, major changes were found in the inflammatory, oxidative stress and lung developmental pathways. This information may be used for the generation of new treatment hypotheses for hyperoxia-induced lung injury and BPD. PMID:26317699

  14. Niaspan Treatment Induces Neuroprotection After Stroke

    PubMed Central

    Shehadah, Amjad; Chen, Jieli; Zacharek, Alex; Cui, Yisheng; Ion, Madalina; Roberts, Cynthia; Kapke, Alissa; Chopp, Michael

    2010-01-01

    Outcome Was Positively Correlated With P-PI3K (R=0.7, P<0.05). Conclusions Treatment Of Stroke With Niaspan At 2 Hours After Mcao Reduces Infarct Volume And Improves Neurological Outcome And Provides Neuroprotection. The Neuroprotective Effects Of Niaspan Were Associated With Reduction Of Apoptosis And Attenuation Of TNF-Alpha Expression. VEGF And The PI3K/Akt Pathway May Contribute To The Niaspan-Induced Neuroprotection After Stroke. PMID:20554037

  15. Hyperoxia Induces Inflammation and Cytotoxicity in Human Adult Cardiac Myocytes.

    PubMed

    Hafner, Christina; Wu, Jing; Tiboldi, Akos; Hess, Moritz; Mitulovic, Goran; Kaun, Christoph; Krychtiuk, Konstantin Alexander; Wojta, Johann; Ullrich, Roman; Tretter, Eva Verena; Markstaller, Klaus; Klein, Klaus Ulrich

    2017-04-01

    Supplemental oxygen (O2) is used as adjunct therapy in anesthesia, emergency, and intensive care medicine. We hypothesized that excessive O2 levels (hyperoxia) can directly injure human adult cardiac myocytes (HACMs). HACMs obtained from the explanted hearts of transplantation patients were exposed to constant hyperoxia (95% O2), intermittent hyperoxia (alternating 10 min exposures to 5% and 95% O2), constant normoxia (21% O2), or constant mild hypoxia (5% O2) using a bioreactor. Changes in cell morphology, viability as assessed by lactate dehydrogenase (LDH) release and trypan blue (TB) staining, and secretion of vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), and various pro-inflammatory cytokines (interleukin, IL; chemokine C-X-C motif ligand, CXC; granulocyte-colony stimulating factor, G-CSF; intercellular adhesion molecule, ICAM; chemokine C-C motif ligand, CCL) were compared among treatment groups at baseline (0 h) and after 8, 24, and 72 h of treatment. Changes in HACM protein expression were determined by quantitative proteomic analysis after 48 h of exposure. Compared with constant normoxia and mild hypoxia, constant hyperoxia resulted in a higher TB-positive cell count, greater release of LDH, and elevated secretion of VEGF, MIF, IL-1β, IL-6, IL-8, CXCL-1, CXCL-10, G-CSF, ICAM-1, CCL-3, and CCL-5. Cellular inflammation and cytotoxicity gradually increased and was highest after 72 h of constant and intermittent hyperoxia. Quantitative proteomic analysis revealed that hypoxic and hyperoxic O2 exposure differently altered the expression levels of proteins involved in cell-cycle regulation, energy metabolism, and cell signaling. In conclusion, constant and intermittent hyperoxia induced inflammation and cytotoxicity in HACMs. Cell injury occurred earliest and was greatest after constant hyperoxia, but even relatively brief repeating hyperoxic episodes induced a substantial inflammatory response.

  16. Treatment of cytokine-induced depression.

    PubMed

    Capuron, Lucile; Hauser, Peter; Hinze-Selch, Dunja; Miller, Andrew H; Neveu, Pierre J

    2002-10-01

    A high proportion of cancer and hepatitis C patients who receive cytokine immunotherapy develop symptoms of depression that are indistinguishable from those found in major depressive disorders. These symptoms are alleviated by anti-depressant treatment. Moreover, preventive treatment with anti-depressants, in particular selective serotonin reuptake inhibitors (SSRIs) attenuates IFN-alpha-associated symptoms of depression, anxiety, and neurotoxicity. The intermediate mechanisms of these effects are still unclear. Studies suggest that the state of depression is associated with an increase in plasma levels of various cytokines and soluble cytokine receptors. Furthermore, anti-depressants have been shown to shift the cytokine network towards a decreased production of pro-inflammatory cytokines and an increased production of anti-inflammatory cytokines. Other studies suggest that anti-depressants can also modify immune reactivity by acting on neural structures involved in neuroimmunomodulation. It is possible that anti-depressants could help to normalize the serotoninergic neurotransmission that is likely disrupted during immunotherapy due to the potent effects of cytokines on the metabolism of the amino acid precursor tryptophan. Further work is needed to optimize strategies for preventing neuropsychiatric side effects of cytokine immunotherapy, to clarify the mechanisms involved in the alleviating effects of anti-depressants on cytokine-induced depression, as well as to assess the possible consequences of anti-depressant therapy on the efficacy of immunotherapy on the disease process.

  17. Indication of BOLD-specific venous flow-volume changes from precisely controlled hyperoxic vs. hypercapnic calibration.

    PubMed

    Mark, Clarisse I; Pike, G Bruce

    2012-04-01

    Deriving cerebral metabolic rate of oxygen consumption (CMRO(2)) from blood oxygenation level-dependent (BOLD) signals involves a flow-volume parameter (α), reflecting total cerebral blood volume changes, and a calibration constant (M). Traditionally, the former is assumed a fixed value and the latter is measured under alterations in fixed inspired fractional concentrations of carbon dioxide. We recently reported on reductions in M-variability via precise control of end-tidal pressures of both hypercapnic (HC) and hyperoxic (HO) gases. In light of these findings, our aim was to apply the improved calibration alternatives to neuronal activation, making use of their distinct vasoactive natures to evaluate the α-value. Nine healthy volunteers were imaged at 3 T while simultaneously measuring BOLD and arterial spin-labeling signals during controlled, graded, HC, and HO, followed by visual (VC) and sensorimotor cortices (SMC) activation. On the basis of low M- and CMRO(2)-variability, the comparison of these calibration alternatives accurately highlighted a reduced venous flow-volume relationship (α=0.16±0.02, with α(VC)=0.12±0.04, and α(SMC)=0.20±0.02), as appropriate for BOLD modeling.

  18. Prevention and Treatment of Noise-Induced Tinnitus

    DTIC Science & Technology

    2014-09-01

    of exposed rats. There is increasing evidence that noise induced loss of connections between sensory cells and the auditory nerve can induce tinnitus...explanation. 1b: Determine if the appearance of the noise-induced tinnitus correlates with the extent of loss of sensory cells (hair cells ) – will...noise compared to groups of noise exposed animals without treatment. The next set of studies targeted the auditory brain stem and treatment rather

  19. Exploration of Prostate Cancer Treatment Induced Neurotoxicity with Neuroimaging

    DTIC Science & Technology

    2008-05-01

    AD_________________ Award Number: W81XWH-06-1-0033 TITLE: Exploration of Prostate Cancer Treatment Induced...Prostate Cancer Treatment Induced Neurotoxicity with Neuroimaging 5b. GRANT NUMBER W81XWH-06-1-0033 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jeri...consequences on brain health of prostate cancer treatments in men despite data suggesting that ADT may cause memory or other cognitive impairments. Our study

  20. Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene

    PubMed Central

    Thakur, Vijay S.; Liang, Yanhong W.; Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Barrios, Roberto; Zhou, Guodong; Guntupalli, Bharath; Shivanna, Binoy; Maturu, Paramahamsa; Welty, Stephen E.; Moorthy, Bhagavatula; Couroucli, Xanthi I.

    2014-01-01

    Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25 mg/Kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days. Hyperoxic newborn rats prenatally exposed to the vehicle CO showed lung injury and alveolar simplification, and inflammation, and these effects were potentiated in rats that were prenatally exposed to BP. Prenatal exposure to BP, followed by hyperoxia, also resulted in significant modulation of hepatic and pulmonary cytochrome P450 (CYP)1A and 1B1 enzymes at PND 7-14. These rats displayed significant oxidative stress in lungs at postnatal day (PND) 14, as evidenced by increased levels of the F2-isoprostane 8-iso-PGF2α. Furthermore, these animals showed BP-derived DNA adducts and oxidative DNA adducts in the lung. In conclusion, our results show increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification following maternal exposure to BP, and our results suggest that modulation of CYP1A/1B1 enzymes, increases in oxidative stress, and BP-DNA adducts contributed to this phenomenon. PMID:24657529

  1. Chemotherapy induced nausea and vomiting--prevention and treatment.

    PubMed

    Feeney, Kynan; Cain, Michael; Nowak, Anna K

    2007-09-01

    Chemotherapy induced nausea and vomiting are among the most feared consequences of cancer treatment. Recent developments in drug treatment make the goal of no nausea or vomiting during chemotherapy realistic. In this article we review the pathogenesis and management of chemotherapy induced nausea and vomiting. Regimens to prevent chemotherapy induced nausea and vomiting are guided by the emetogenic potential of the chemotherapeutic agents used. Combined prophylactic therapy targets different pathways, improving the efficacy of prevention and treatment of chemotherapy induced nausea and vomiting. General practitioners have an important role in patients undergoing chemotherapy by reinforcing the importance of prophylactic treatment and administering rescue treatment for patients with breakthrough or prolonged nausea and vomiting postchemotherapy.

  2. The common antitussive agent dextromethorphan protects against hyperoxia-induced cell death in established in vivo and in vitro models of neonatal brain injury.

    PubMed

    Posod, A; Pinzer, K; Urbanek, M; Wegleiter, K; Keller, M; Kiechl-Kohlendorfer, U; Griesmaier, E

    2014-08-22

    Preterm infants are prematurely subjected to relatively high oxygen concentrations, even when supplemental oxygen is not administered. There is increasing evidence to show that an excess of oxygen is toxic to the developing brain. Dextromethorphan (DM), a frequently used antitussive agent with pleiotropic mechanisms of action, has been shown to be neuroprotective in various models of central nervous system pathology. Due to its numerous beneficial properties, it might also be able to counteract detrimental effects of a neonatal oxygen insult. The aim of the current study was to evaluate its therapeutic potential in established cell culture and rodent models of hyperoxia-induced neonatal brain injury. For in vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of DM. For in vivo studies 6-day-old Wistar rat pups received a single intraperitoneal injection of DM in two different dosages prior to being exposed to hyperoxia for 24h. Cell viability and caspase-3 activation were assessed as outcome parameters at the end of exposure. DM significantly increased cell viability in immature oligodendroglial cells subjected to hyperoxia. In pre-oligodendroglial cells cell viability was not significantly affected by DM treatment. In vivo caspase-3 activation induced by hyperoxic exposure was significantly lower after administration of DM in gray and white matter areas. In control animals kept under normoxic conditions DM did not significantly influence caspase-3-dependent apoptosis. The present results indicate that DM is a promising and safe treatment strategy for neonatal hyperoxia-induced brain injury that merits further investigation. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Cancer Treatment-Induced Neurotoxicity: A Focus on Newer Treatments

    PubMed Central

    Stone, Jacqueline B.; DeAngelis, Lisa M.

    2016-01-01

    Neurotoxicity from traditional chemotherapy and radiotherapy is widely recognized. The adverse effects of newer therapeutics such as biological and immunotherapeutic agents are less familiar and they are also associated with significant neurotoxicity in the central and peripheral nervous systems. This review addresses the main toxicities of cancer treatment by symptom with a focus on the newer therapeutics. Recognition of these patterns of toxicity is important as drug discontinuation or dose adjustment may prevent further neurologic injury. Also, knowledge of these toxicities helps to differentiate treatment-related symptoms from progression of cancer or its involvement of the nervous system. PMID:26391778

  4. [Medical prevention and treatment of radiation-induced pulmonary complications].

    PubMed

    Vallard, A; Rancoule, C; Le Floch, H; Guy, J-B; Espenel, S; Le Péchoux, C; Deutsch, É; Magné, N; Chargari, C

    2017-08-01

    Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  5. Breast cancer treatment-induced cardiotoxicity.

    PubMed

    Martel, Samuel; Maurer, Christian; Lambertini, Matteo; Pondé, Noam; De Azambuja, Evandro

    2017-09-01

    Breast cancer is the most frequent cancer affecting women worldwide. In every setting, the majority of women are treated with an evergrowing arsenal of therapeutic agents that have greatly improved their outcomes. However, these therapies can also be associated with significant adverse events. Areas covered: This review aims to thoroughly describe the current state of the evidence regarding the potential cardiotoxicity of agents commonly used in the treatment of breast cancer. These include chemotherapeutic agents, anti-HER2 therapies and CDK4/6 and mTOR inhibitors. Furthermore, issues related to the risk stratification and monitoring tools are explored. Expert opinion: Anthracycline- and trastuzumab-related cardiac toxicities have been extensively studied. Substantial evidence is now available concerning additional anti-HER2 agents such as pertuzumab, T-DM1 and tyrosine kinase inhibitors; overall, the cardiotoxicity profile is reassuring. Cardiac events due to endocrine therapy are mostly ischemic and, in the context of prolonged therapy, need specific attention. Novel agents implicated in the treatment of hormone receptor-positive disease are potentially arrhythmogenic and the exact risk will need to be further refined. As for today, assessment of baseline risk factors prior to treatment initiation and cardiac imaging before and during treatment remains the optimal way to prevent cardiac dysfunction. Cardioprotective therapy in primary prevention is still a matter of debate.

  6. Inflammatory and epithelial responses in mouse strains that differ in sensitivity to hyperoxic injury.

    PubMed

    Johnston, C J; Stripp, B R; Piedbeouf, B; Wright, T W; Mango, G W; Reed, C K; Finkelstein, J N

    1998-01-01

    The pulmonary response to various toxicants including bleomycin, ozone, ionizing radiation, and hyperoxia is highly variable among mouse strains. The current study tests the hypothesis that at a similar stage of injury, regardless of strain, expression of inflammatory cytokine and epithelial marker genes would be similar, indicating a common pathway of injury progression. Three strains of mice, C57B1/6J, 129/J, and C3H/HeJ, ranging from sensitive to resistant, were exposed to > 95% O2 for varying times. Ribonuclease protection was used to quantify changes in cytokine mRNA. Despite differences in the kinetics, each strain demonstrated similar hyperoxia-induced changes in the abundance of interleukin (IL)-6, IL-1 beta, IL-3, and tumor neucrosis factor (TNF)-alpha. For each strain, death was accompanied by similar increases in cytokine mRNAs above steady-state control levels. Other inflammatory cytokines, including IL-1 alpha, IL-4, and interferon (IFN)-gamma, were unaltered in all strains at all times. In situ hybridization analysis of the epithelial markers, surfactant protein B (SPB), and clara cell secretory protein (CCSP) at the time of proinflammatory induction showed a similar pattern of expression in all strains. Increased SPB was detected in bronchiolar epithelium, while the number of type II cells expressing this message declined. Both the number of cells expressing CCSP as well as abundance per cell declined. These results suggest that although differences in acute sensitivity to hyperoxia exist between mouse strains, once initiated, acute epithelial cell injury and associated inflammatory changes follow the same pattern in all strains.

  7. Delayed hyperoxic ventilation attenuates oxygen-induced free radical accumulation during early reperfusion after global brain ischemia.

    PubMed

    Wang, Yan; Yuan, Li; Liu, Ping; Zhao, Min

    2015-02-11

    To compare the effect of immediate and delayed administration of oxygen on the accumulation of free radicals in ischemia-reperfusion animal models. Thirty-two adult male Mongolian gerbils with microdialysis probes implanted in the right hippocampal CA1 were divided randomly into four groups (eight each). One group was sham-operated (Sham group) whereas the other three groups were subjected to 10 min bilateral carotid artery occlusion (BCAO). BCAO-treated animals were then subjected to the following: (a) immediate 30% O2 (near normoxia, NO group), (b) immediate 100% O2 (hyperoxia, HO group), and (c) 30% O2 for 60 min, followed by 100% O2 for 60 min (delayed hyperoxia, DHO group). Hippocampal accumulation of hydroxyl radicals (•OH) during reperfusion was estimated by measuring 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA in microdialysis perfusate. Hippocampi were removed 2 h after perfusion to measure malondialdehyde, pyruvate dehydrogenase activity, indices of lipid peroxidation, and cellular respiration. At 24 h after BCAO, the histology of hippocampi was analyzed to rate the injury. Immediately after the onset of reperfusion, all groups showed markedly elevated DHBA, which returned to baseline over 1-2 h. Compared with the NO group, the HO group showed significantly higher peak DHBA and slower recovery. In contrast, the DHO group was not significantly different from the NO group in terms of the DHBA level. DHO animals also showed significantly lower hippocampal malondialdehyde accumulation and higher pyruvate dehydrogenase activity at 2 h after reperfusion versus the HO group. Histology analysis also showed animals in the DHO group with ameliorated injury compared with the HO group. Hydroxyl radical accumulation was more sensitive to O2 during early reperfusion. Delayed hyperoxia may re-establish oxidative metabolism while minimizing oxidative stress after CA.

  8. Treatment of neurolept-induced tardive dyskinesia

    PubMed Central

    Jankelowitz, Stacey K

    2013-01-01

    Tardive dyskinesia (TDK) includes orobuccolingual movements and “piano-playing” movements of the limbs. It is a movement disorder of delayed onset that can occur in the setting of neuroleptic treatment as well as in other diseases and following treatment with other drugs. The specific pathophysiology resulting in TDK is still not completely understood but possible mechanisms include postsynaptic dopamine receptor hypersensitivity, abnormalities of striatal gamma-aminobutyric acid (GABA) neurons, and degeneration of striatal cholinergic interneurons. More recently, the theory of synaptic plasticity has been proposed. Considering these proposed mechanisms of disease, therapeutic interventions have attempted to manipulate dopamine, GABA, acetylcholine, norepinephrine and serotonin pathways and receptors. The data for the effectiveness of each class of drugs and the side effects were considered in turn. PMID:24072972

  9. Treatment of neurolept-induced tardive dyskinesia.

    PubMed

    Jankelowitz, Stacey K

    2013-01-01

    Tardive dyskinesia (TDK) includes orobuccolingual movements and "piano-playing" movements of the limbs. It is a movement disorder of delayed onset that can occur in the setting of neuroleptic treatment as well as in other diseases and following treatment with other drugs. The specific pathophysiology resulting in TDK is still not completely understood but possible mechanisms include postsynaptic dopamine receptor hypersensitivity, abnormalities of striatal gamma-aminobutyric acid (GABA) neurons, and degeneration of striatal cholinergic interneurons. More recently, the theory of synaptic plasticity has been proposed. Considering these proposed mechanisms of disease, therapeutic interventions have attempted to manipulate dopamine, GABA, acetylcholine, norepinephrine and serotonin pathways and receptors. The data for the effectiveness of each class of drugs and the side effects were considered in turn.

  10. Metabolic syndrome induced by anticancer treatment in childhood cancer survivors.

    PubMed

    Chueh, Hee Won; Yoo, Jae Ho

    2017-06-01

    The number of childhood cancer survivors is increasing as survival rates improve. However, complications after treatment have not received much attention, particularly metabolic syndrome. Metabolic syndrome comprises central obesity, dyslipidemia, hypertension, and insulin resistance, and cancer survivors have higher risks of cardiovascular events compared with the general population. The mechanism by which cancer treatment induces metabolic syndrome is unclear. However, its pathophysiology can be categorized based on the cancer treatment type administered. Brain surgery or radiotherapy may induce metabolic syndrome by damaging the hypothalamic-pituitary axis, which may induce pituitary hormone deficiencies. Local therapy administered to particular endocrine organs directly damages the organs and causes hormone deficiencies, which induce obesity and dyslipidemia leading to metabolic syndrome. Chemotherapeutic agents interfere with cell generation and growth, damage the vascular endothelial cells, and increase the cardiovascular risk. Moreover, chemotherapeutic agents induce oxidative stress, which also induces metabolic syndrome. Physical inactivity caused by cancer treatment or the cancer itself, dietary restrictions, and the frequent use of antibiotics may also be risk factors for metabolic syndrome. Since childhood cancer survivors with metabolic syndrome have higher risks of cardiovascular events at an earlier age, early interventions should be considered. The optimal timing of interventions and drug use has not been established, but lifestyle modifications and exercise interventions that begin during cancer treatment might be beneficial and tailored education and interventions that account for individual patients' circumstances are needed. This review evaluates the recent literature that describes metabolic syndrome in cancer survivors, with a focus on its pathophysiology.

  11. Metabolic syndrome induced by anticancer treatment in childhood cancer survivors

    PubMed Central

    Chueh, Hee Won

    2017-01-01

    The number of childhood cancer survivors is increasing as survival rates improve. However, complications after treatment have not received much attention, particularly metabolic syndrome. Metabolic syndrome comprises central obesity, dyslipidemia, hypertension, and insulin resistance, and cancer survivors have higher risks of cardiovascular events compared with the general population. The mechanism by which cancer treatment induces metabolic syndrome is unclear. However, its pathophysiology can be categorized based on the cancer treatment type administered. Brain surgery or radiotherapy may induce metabolic syndrome by damaging the hypothalamic-pituitary axis, which may induce pituitary hormone deficiencies. Local therapy administered to particular endocrine organs directly damages the organs and causes hormone deficiencies, which induce obesity and dyslipidemia leading to metabolic syndrome. Chemotherapeutic agents interfere with cell generation and growth, damage the vascular endothelial cells, and increase the cardiovascular risk. Moreover, chemotherapeutic agents induce oxidative stress, which also induces metabolic syndrome. Physical inactivity caused by cancer treatment or the cancer itself, dietary restrictions, and the frequent use of antibiotics may also be risk factors for metabolic syndrome. Since childhood cancer survivors with metabolic syndrome have higher risks of cardiovascular events at an earlier age, early interventions should be considered. The optimal timing of interventions and drug use has not been established, but lifestyle modifications and exercise interventions that begin during cancer treatment might be beneficial and tailored education and interventions that account for individual patients' circumstances are needed. This review evaluates the recent literature that describes metabolic syndrome in cancer survivors, with a focus on its pathophysiology. PMID:28690985

  12. [Treatment of anovulatory cycle induced sterility].

    PubMed

    Botella Llusia, J

    1983-03-01

    Of all the clinical aspects of human sterility, the anovulatory cycle is undoubtedly 1 that has produced the widest range of therapuetic successes. While in other fields progress has been very slow (male sterility or tubal obstruction), ovarian pharmacoendocrinology has shown several advances over recent years. This progress is due partly to new chemicals such as urinary menopausal gonadotropins, LH-RH, and their analogues Clomiphene and Bromocriptine. Contributing further to these good results is a greater knowledge of the etiology of anovulation and a more accurate selection of cases for treatment.

  13. Mechanisms of suppression of alveolar epithelial cell GM-CSF expression in the setting of hyperoxic stress

    PubMed Central

    Sturrock, Anne; Vollbrecht, Timothy; Mir-Kasimov, Mustafa; McManus, Michael; Wilcoxen, Steven E.

    2010-01-01

    Pulmonary expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) is critically important for normal functional maturation of alveolar macrophages. We found previously that lung GM-CSF is dramatically suppressed in mice exposed to hyperoxia. Alveolar epithelial cells (AEC) are a major source of GM-CSF in the peripheral lung, and in vivo hyperoxia resulted in greatly reduced expression of GM-CSF protein by AEC ex vivo. We now explore the mechanisms responsible for this effect, using primary cultures of murine AEC exposed to hyperoxia in vitro. Exposure of AEC to 80% oxygen/5% CO2 for 48 h did not induce overt toxicity, but resulted in significantly decreased GM-CSF protein and mRNA expression compared with cells in normoxia. Similar effects were seen when AEC were stressed with serum deprivation, an alternative inducer of oxidative stress. The effects in AEC were opposite those in a murine lung epithelial cell line (MLE-12 cells), in which hyperoxia induced GM-CSF expression. Both hyperoxia and serum deprivation resulted in increased intracellular reactive oxygen species (ROS) in AEC. Hyperoxia and serum deprivation induced significantly accelerated turnover of GM-CSF mRNA. Treatment of AEC with catalase during oxidative stress preserved GM-CSF protein and mRNA and was associated with stabilization of GM-CSF mRNA. We conclude that hyperoxia-induced suppression of AEC GM-CSF expression is a function of ROS-induced destabilization of GM-CSF mRNA. We speculate that AEC oxidative stress results in significantly impaired pulmonary innate immune defense due to effects on local GM-CSF expression in the lung. PMID:20034963

  14. Pulsed dye laser in treatment of steroid-induced atrophy.

    PubMed

    Mansouri, Parvin; Ranjbar, Maryam; Abolhasani, Ehsan; Chalangari, Reza; Martits-Chalangari, Katalin; Hejazi, Somayeh

    2015-12-01

    One of the important and distressing cutaneous side effects of steroid therapy is skin atrophy, which has no definite and effective treatment. To the best of our knowledge, laser therapy for steroid-induced atrophic scars has not been investigated to date. The aim of this study was to evaluate the efficacy and safety of pulsed dye laser in the treatment of steroid-induced atrophic scars. In this pilot study, 15 patients with at least one atrophic patch were treated with the 585-nm pulsed dye laser at 4-week interval sessions until achieving complete improvement or until patient were lost to follow-up. Clinical outcome was assessed via standard photographic method before each treatment session and after the final visit. An independent dermatologist evaluated the photographs. All of the patients (13 females and two males) with 25-59 years of age experienced some degree of improvement, except one patient who withdrew from the treatment after three sessions. The treatment was well tolerated. The results of our study indicated that pulsed dye laser therapy could be employed as a new method in the treatment of steroid-induced atrophic scars. Pulsed dye laser might affect the lesions through inducing collagen deposition and production of more superficial dermal elastin as well as less unidirectional collagen in clusters. © 2015 Wiley Periodicals, Inc.

  15. Mechanisms and Treatment of Blast Induced Hearing Loss

    PubMed Central

    2012-01-01

    The main objective of this study is to provide an overview of the basic mechanisms of blast induced hearing loss and review pharmacological treatments or interventions that can reduce or inhibit blast induced hearing loss. The mechanisms of blast induced hearing loss have been studied in experimental animal models mimicking features of damage or injury seen in human. Blast induced hearing loss is characterized by perforation and rupture of the tympanic membrane, ossicular damage, basilar membrane damage, inner and outer hair cell loss, rupture of round window, changes in chemical components of cochlear fluid, vasospasm, ischemia, oxidative stress, excitotoxicity, hematoma, and hemorrhage in both animals and humans. These histopathological consequences of blast exposure can induce hearing loss, tinnitus, dizziness, and headache. The pharmacological approaches to block or inhibit some of the auditory pathological consequences caused by blast exposure have been developed with antioxidant drugs such as 2,4-disulfonyl α-phenyl tertiary butyl nitrone (HXY-059, now called HPN-07) and N-acetylcysteine (NAC). A combination of antioxidant drugs (HPN-07 and NAC) was administered to reduce blast induced cochlear damage and hearing loss. The combination of the antioxidant drugs can prevent or treat blast induced hearing loss by reducing damage to the mechanical and neural component of the auditory system. Although information of the underlying mechanisms and treatment of blast induced hearing loss are provided, further and deep research should be achieved due to the limited and controversial knowledge. PMID:24653882

  16. Drug-induced methaemoglobinaemia. Treatment issues.

    PubMed

    Coleman, M D; Coleman, N A

    1996-06-01

    -mediated acute methaemoglobinaemia among physicians should lead to prompt diagnosis and treatment of this potentially life-threatening condition.

  17. Omalizumab in the Treatment of Chronic Inducible Urticaria.

    PubMed

    Chicharro, P; Rodríguez, P; de Argila, D

    2017-06-01

    Omalizumab is a recombinant humanized monoclonal antibody that inhibits immunoglobulin E. It has been approved for the treatment of severe asthma and chronic spontaneous urticaria refractory to other treatments. Its use in the management of chronic inducible urticaria (a type triggered by certain stimuli) is still considered off-label, although this use has been discussed in some consensus papers. This review brings together case reports and case series describing the use of omalizumab to treat chronic inducible urticaria. We analyze the most important aspects of the cases and the outcomes reported. The results seem to position omalizumab as a potentially effective, safe treatment alternative in some cases of chronic inducible urticaria. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Prevention and Treatment of Noise-Induced Tinnitus

    DTIC Science & Technology

    2012-07-01

    Tinnitus PRINCIPAL INVESTIGATOR: Dr. Richard A. Altschuler CONTRACTING ORGANIZATION: The University of Michigan...DATE 01-07-2012 2. REPORT TYPE ANNUAL 3. DATES COVERED 4. TITLE AND SUBTITLE Prevention and Treatment of Noise-Induced Tinnitus 5a. CONTRACT...Results indicate that a small arms fire – like noise will induce tinnitus in Results from the first year of studies indicate that a 2 ½ minute

  19. Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse

    DTIC Science & Technology

    2017-07-01

    AWARD NUMBER: W81XWH-14-1-0087 TITLE: Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse PRINCIPAL INVESTIGATOR: Dr. Masoud...SUBTITLE 5a. CONTRACT NUMBER Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse 5b. GRANT NUMBER W81XWH-14-1-0087 5c. PROGRAM...expedited tumor relapse. The purpose of the study  was to determine if transient blockade of autophagy by CQ was  associated  with anti‐inflammatory function

  20. Abnormal uterine bleeding induced by glucocorticoid treatment for pemphigus

    PubMed Central

    Luo, Xiaobo; Feng, Hui; Jiang, Lu; Chen, Qianming

    2016-01-01

    Glucocorticoids are the first-line treatment option for pemphigus. Moreover, abnormal uterine bleeding (AUB) is a rarely reported side effect of glucocorticoid treatment that usually manifests as abnormal and excessive endometrial bleeding; in fact, AUB can be induced by the systemic or topical application of glucocorticoids. In the present report, we describe the cases of 3 patients with pemphigus who developed AUB following glucocorticoid administration. It is important to note that the administration mode of glucocorticoids, and the onset time and duration of AUB differed among these patients. Thus, we propose the following treatment algorithm for AUB following glucocorticoid administration: 1. perform a gynecological and physical examination to exclude organic diseases. 2. continue glucocorticoid treatment. 3. if AUB persists, change the mode of administration of glucocorticoids. 4. if AUB still persists, despite these measures, completely withdraw treatment with glucocorticoids and use non-glucocorticoid treatments. PMID:27570861

  1. The effects of head-up and head-down tilt on central respiratory chemoreflex loop gain tested by hyperoxic rebreathing.

    PubMed

    Skow, Rachel J; Tymko, Michael M; MacKay, Christina M; Steinback, Craig D; Day, Trevor A

    2014-01-01

    Central respiratory chemosensitivity is mediated via chemoreceptor neurons located throughout brain stem tissue. These receptors detect proximal CO2/[H(+)] (i.e., controller gain) and modulate breathing in a classic negative feedback loop. Loop gain (responsiveness) is the theoretical product of controller (chemoreceptors), mixing/feedback (cardiovascular and cerebrovascular systems), and plant (pulmonary system) gains. The level of chemoreceptor stimulation is determined by interactions between mixing and plant gains. The extent to which steady-state changes in body position may affect central chemoreflex loop gain in response to CO2 is unclear. Because of the potential effects of tilt on pulmonary mechanics, we hypothesized that plant gain would be altered by head-up and head-down tilt (HUT, HDT) during hyperoxic rebreathing, which theoretically isolates plant gain by eliminating systemic arterial-tissue gradients. Sixteen subjects (eight females) underwent hyperoxic rebreathing tests on a tilt table to quantify central chemoreflex loop gain in five steady-state positions: 90° HUT, 45° HUT, supine, 45° HDT, and 90° HDT. Respiratory responses (tidal volume, VT; frequency, fR; minute ventilation, VE) were quantified during steady-state and increases in CO2 during rebreathing by linear regression above the ventilatory recruitment threshold (VRT). Using one-factor analysis of variance, we found that there were no differences in the respiratory responses between the five positions (VRT, P=0.711; VT, P=0.290; fR, P=0.748; VE, P=0.325). Our findings suggest that during steady-state orthostatic stress, the ability of subjects to mount a normal ventilatory response to increased CO2 was unaffected, despite any potential changes in pulmonary mechanics associated with positional challenges.

  2. Hydraulic Fracturing Treatment Controls on Induced Microseismicity Attributes

    NASA Astrophysics Data System (ADS)

    Reyes-Montes, J. M.; Kelly, C.; Huang, J.; Zhao, X.; Young, R. P.

    2014-12-01

    Hydraulic fracturing imposes stress changes in the treated rock through the injection of a mix of fluid and proppant at variable rates and can result in stimulated microseismicity (induced or triggered) with a wide range of magnitudes associated to the opening of new cracks or the mobilisation of pre-existing fractures. Optimizing the treatment is vital for the economic and sustainable development of hydrocarbon reservoir and for the minimization of potential environmental impacts. The analysis of the induced seismicity and of event parameters provide an estimate of the effect of the treatment and the extent of the changes in the rock reservoir properties affecting fluid conductivity. This gives critical feedback for the optimization of the treatment, especially during real-time monitoring. In this study, we correlate microseismic attributes such as the fracture dimensions, event distribution and b-values with the fluid treatment parameters such as the pumping pressure and the slurry rate across different reservoir treatments. Although the microseismic attributes are influenced by many different factors such as the reservoir elastic properties, the stress regime and in-situ fracturing, we consistently observed positive correlations between the slurry rate, plateau treatment pressure and the fracture dimensions. In addition, the variation and systematic deviation of b-value from the natural average of 1.0 gives an insight into the geomechanical behavior of the reservoir. Similar to b-value, another fractal dimension, D-value, indicates the fracture spatial propagation from linear advancement (D=1.0) to planar distribution (D=2.0) to full space occurrence (D=3.0). By merging microseismic events from multiple treatment stages, we statistically analyzed magnitude distribution and spatial and temporal structure of the microseismic cloud induced during the stimulation of a range of different reservoirs with a total population of ~20,000 MS events. Analysis on multiple

  3. Neuroprotective Treatment of Laser-Induced Retinal Injuries

    DTIC Science & Technology

    2001-10-01

    to evaluate the neuroprotective effect of dextromethorphan , memantine and brimonidine in our rat model of laser- induced retinal-lesions Methods: Argon... dextromethorphan , memantine or brimonidine. The control groups (18 rats for each compound) received the solvent at the same volume and schedule as...size and the magnitude of photoreceptor nuclei loss within the lesions. Conclusions: Systemic treatments with dextromethorphan , memantine or brimonidine

  4. Treatment modalities for drug-induced gingival enlargement.

    PubMed

    Moffitt, Michelle; Bencivenni, Davide; Cohen, Robert

    2012-01-01

    This paper identifies 3 specific classifications of commonly prescribed medications that are known to cause gingival enlargement and describes surgical and non-surgical treatment therapies. Primary risks associated with drug-induced gingival enlargement, including increased dental decay and periodontal disease are also discussed. The precise bacterial etiology in gingival enlargement remains unclear, although sufficient evidence exists to support the role of good oral hygiene in decreasing the incidence and severity of gingival enlargement and improving overall gingival health. Etiology, treatment planning and coordination of care between physician, dentist or dental hygienist when indicated are important factors determining whether a surgical or non-surgical course of treatment should be considered.

  5. [Chemotherapy-induced peripheral neuropathy: characteristics, diagnosis and treatment].

    PubMed

    Istenes, Ildikó; Nagy, Zsolt; Demeter, Judit

    2016-06-06

    Longer remissions and better overall survival rates can be achieved with the introduction of new, effective treatments and targeted therapies in the past 1-2 decades, however, the incidence of side effects is also increasing parallelly. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially debilitating side effect due to peripheral somatic or autonomic nerve dysfunction. CIPN becomes increasingly important, as it affects patients' quality of life, and it is very often a dose limiting factor with the potential for reduced treatment efficacy. The pathomechanism, diagnosis, prevention and treatment possibilities are described in this review with special attention to the different groups of drugs.

  6. Treatment of hypertriglyceridemia-induced acute pancreatitis with insulin

    PubMed Central

    Erkan, Nazif; Yakan, Savas; Yildirim, Mehmet; Carti, Erdem; Ucar, Deniz; Oymaci, Erkan

    2015-01-01

    Introduction Hypertriglyceridaemia (HT)-induced pancreatitis rarely occurs unless triglyceride levels exceed 1000 mg/dl. Hypertriglyceridaemia over 1,000 mg/dl can provoke acute pancreatitis (AP) and its persistence can worsen the clinical outcome. In contrast, a rapid decrease in triglyceride level is beneficial. Insulin-stimulated lipoprotein lipase is known to decrease serum triglyceride levels. However, their efficacy in HT-induced AP is not well documented. Aim To present 12 cases of AP successfully treated by insulin administration. Material and methods Three hundred and forty-three cases of AP were diagnosed at our clinic between 2005 and 2012. Twelve (3.5%) of these cases were HT-induced AP. Twelve patients who suffered HT-induced AP are reported. Initial blood triglyceride levels were above 1000 mg/dl. Besides the usual treatment of AP, insulin was administered intravenously in continuous infusion. The patients’ medical records were retrospectively evaluated in this study. Results Serum triglyceride levels decreased to < 500 mg/dl within 2–3 days. No complications of treatment were seen and good clinical outcome was observed. Conclusions Our results are compatible with the literature. Insulin may be used safely and effectively in HT-induced AP therapy. Administration of insulin is efficient when used to reduce triglyceride levels in patients with HT-induced AP. PMID:25960810

  7. Enamel structural changes induced by hydrochloric and phosphoric acid treatment.

    PubMed

    Bertacci, Angelica; Lucchese, Alessandra; Taddei, Paola; Gherlone, Enrico F; Chersoni, Stefano

    2014-12-30

    The aim of this study was to evaluate enamel acid-induced structural changes after 2 different treatments, by means of Raman and infrared (IR) spectroscopy analyses, and to correlate these findings with permeability measured as fluid discharge from outer enamel. Two different treatments were investigated: 10 enamel slices were etched with 15% hydrochloric acid (HCl) for 120 seconds and 10 slices with 37% phosphoric acid gel (H3PO4) for 30 seconds, rinsed for 30 seconds and then air-dried for 20 seconds. Powders of enamel treated as previously described were produced. Replicas of enamel subjected to the same treatments were obtained to evaluate the presence of fluid droplets on enamel surface. Raman and IR spectroscopy showed that the treatment with both hydrochloric and phosphoric acids induced a decrease in the carbonate content of the enamel apatite. At the same time, both acids induced the formation of HPO42- ions. After H3PO4 treatment, the bands due to the organic component of enamel decreased in intensity, while they increased after HCl treatment. Replicas of H3PO4 treated enamel showed a strongly reduced permeability. Replicas of HCl 15% treated samples showed a maintained permeability. A decrease of the enamel organic component, as resulted after H3PO4 treatment, involves a decrease in enamel permeability, while the increase of the organic matter (achieved by HCl treatment) still maintains enamel permeability.The results suggested a correlation between organic matter and enamel permeability. Permeability was affected by etching technique and could be involved in marginal seal, gap and discoloration at the enamel interface, still causes of restoration failure.

  8. Furosemide in the treatment of phosgene induced acute lung injury.

    PubMed

    Grainge, C; Smith, A J; Jugg, B J; Fairhall, S J; Mann, T; Perrott, R; Jenner, J; Millar, T; Rice, P

    2010-12-01

    Using previously validated methods, 16 anaesthetised large white pigs were exposed to phosgene (target inhaled dose 0.3 mg kg(-1)), established on mechanical ventilation and randomised to treatment with either nebulised furosemide (4 ml of 10 mg x ml(-1) solution) or saline control. Treatments were given at 1, 3, 5, 7, 9, 12, 16 and 20 hours post phosgene exposure; the animals were monitored to 24 hours following phosgene exposure. Furosemide treatment had no effect on survival, and had a deleterious effect on PaO2: FiO2 ratio between 19 and 24 hours. All other measures investigated were unaffected by treatment. Nebulised furosemide treatment following phosgene induced acute lung injury does not improve survival and worsens PaO2: FiO2 ratio. Nebulised furosemide should be avoided following phosgene exposure.

  9. Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment.

    PubMed

    Guchelaar, H J; Vermes, A; Meerwaldt, J H

    1997-07-01

    Xerostomia, or oral dryness, is one of the most common complaints experienced by patients who have had radiotherapy of the oral cavity and neck region. The hallmarks of radiation-induced damage are acinar atrophy and chronic inflammation of the salivary glands. The early response, resulting in atrophy of the secretory cells without inflammation might be due to radiation-induced apoptosis. In contrast, the late response with inflammation could be a result of radiation-induced necrosis. The subjective complaint of a dry mouth appears to be poorly correlated with objective findings of salivary gland dysfunction. Xerostomia, with secondary symptoms of increased dental caries, difficulty in chewing, swallowing and speaking, and an increased incidence of oral candidiasis, can have a significant effect on the quality of life. At present there is no causal treatment for radiation-induced xerostomia. Temporary symptomatic relief can be offered by moistening agents and saliva substitutes, and is the only option for patients without residual salivary function. In patients with residual salivary function, oral administration of pilocarpine 5-10 mg three times a day is effective in increasing salivary flow and improving the symptoms of xerostomia, and this therapy should be considered as the treatment of choice. Effectiveness of sialogogue treatment requires residual salivary function, which emphasizes the potential benefit from sparing normal tissue during irradiation. The hypothesis concerning the existence of early apoptotic and late necrotic effects of irradiation on the salivary glands theoretically offers a way of achieving this goal.

  10. Ragweed-induced allergic rhinoconjunctivitis: current and emerging treatment options

    PubMed Central

    Ihler, Friedrich; Canis, Martin

    2015-01-01

    Ragweed (Ambrosia spp.) is an annually flowering plant whose pollen bears high allergenic potential. Ragweed-induced allergic rhinoconjunctivitis has long been seen as a major immunologic condition in Northern America with high exposure and sensitization rates in the general population. The invasive occurrence of ragweed (A. artemisiifolia) poses an increasing challenge to public health in Europe and Asia as well. Possible explanations for its worldwide spread are climate change and urbanization, as well as pollen transport over long distances by globalized traffic and winds. Due to the increasing disease burden worldwide, and to the lack of a current and comprehensive overview, this study aims to review the current and emerging treatment options for ragweed-induced rhinoconjunctivitis. Sound clinical evidence is present for the symptomatic treatment of ragweed-induced allergic rhinoconjunctivitis with oral third-generation H1-antihistamines and leukotriene antagonists. The topical application of glucocorticoids has also been efficient in randomized controlled clinical trials. Combined approaches employing multiple agents are common. The mainstay of causal treatment to date, especially in Northern America, is subcutaneous immunotherapy with the focus on the major allergen, Amb a 1. Beyond this, growing evidence from several geographical regions documents the benefit of sublingual immunotherapy. Future treatment options promise more specific symptomatic treatment and fewer side effects during causal therapy. Novel antihistamines for symptomatic treatment are aimed at the histamine H3-receptor. New adjuvants with toll-like receptor 4 activity or the application of the monoclonal anti-immunoglobulin E antibody, omalizumab, are supposed to enhance conventional immunotherapy. An approach targeting toll-like receptor 9 by synthetic cytosine phosphate–guanosine oligodeoxynucleotides promises a new treatment paradigm that aims to modulate the immune response, but it has

  11. Effects of metformin treatment on glioma-induced brain edema

    PubMed Central

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5’-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo. PMID:27648126

  12. Effects of metformin treatment on glioma-induced brain edema.

    PubMed

    Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

    2016-01-01

    Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

  13. The Triaging and Treatment of Cold-Induced Injuries.

    PubMed

    Sachs, Christoph; Lehnhardt, Marcus; Daigeler, Adrien; Goertz, Ole

    2015-10-30

    In Central Europe, cold-induced injuries are much less common than burns. In a burn center in western Germany, the mean ratio of these two types of injury over the past 10 years was 1 to 35. Because cold-induced injuries are so rare, physicians often do not know how to deal with them. This article is based on a review of publications (up to December 2014) retrieved by a selective search in PubMed using the terms "freezing," "frostbite injury," "non-freezing cold injury," and "frostbite review," as well as on the authors' clinical experience. Freezing and cold-induced trauma are part of the treatment spectrum in burn centers. The treatment of cold-induced injuries is not standardized and is based largely on case reports and observations of use. distinction is drawn between non-freezing injuries, in which there is a slow temperature drop in tissue without freezing, and freezing injuries in which ice crystals form in tissue. In all cases of cold-induced injury, the patient should be slowly warmed to 22°-27°C to prevent reperfusion injury. Freezing injuries are treated with warming of the body's core temperature and with the bathing of the affected body parts in warm water with added antiseptic agents. Any large or open vesicles that are already apparent should be debrided. To inhibit prostaglandin-mediated thrombosis, ibuprofen is given (12 mg/kg body weight b.i.d.). The treatment of cold-induced injuries is based on their type, severity, and timing. The recommendations above are grade C recommendations. The current approach to reperfusion has yielded promising initial results and should be further investigated in prospective studies.

  14. Supplier-induced demand for newborn treatment: evidence from Japan.

    PubMed

    Shigeoka, Hitoshi; Fushimi, Kiyohide

    2014-05-01

    We estimate the degree of supplier-induced demand for newborn treatment by exploiting changes in reimbursement arising from the introduction of the partial prospective payment system (PPS) in Japan. Under the partial PPS, neonatal intensive care unit (NICU) utilization became relatively more profitable than other procedures, since it was excluded from prospective payments. We find that hospitals have responded to PPS adoption by increasing NICU utilization and by more frequently manipulating infants' reported birth weights which in large part determine their maximum allowable stay in the NICU. This induced demand substantially increases the reimbursements received by hospitals.

  15. [Symptoms, diagnosis and treatment of radiation-induced enteritis].

    PubMed

    Sinkó, Dániel; Baranyai, Zsolt; Nemeskéri, Csaba; Teknos, Dániel; Jósa, Valéria; Hegedus, László; Mayer, Arpád

    2010-09-05

    The number of radiotherapy in the treatment of malignant diseases is increasing worldwide. During the radiotherapy of tumors in the minor pelvis and abdomen intestinal inflammation of different degree may occur even if special attention is paid. Irradiation to the minor pelvis causes in half of the cases radiation induced acute enteritis, whereas in 25% chronic enteritis and colitis will develop. Chronic enteritis following radiotherapy raises a number of diagnostic and therapeutic problems that can be solved only with cooperation of different specialties. Authors present a short review regarding therapeutical options of radiation induced enteritis.

  16. Keratoconus Progression Induced by In Vitro Fertilization Treatment.

    PubMed

    Yuksel, Erdem; Yalinbas, Duygu; Aydin, Bahri; Bilgihan, Kamil

    2016-01-01

    To evaluate patients with keratoconus who manifested progression after in vitro fertilization (IVF) treatment. Patients with keratoconus who received IVF treatment were included in this study. None of the patients became pregnant as a result of the IVF treatment. Progression of keratoconus was determined by changes in corrected distance visual acuity and/or topographic changes and subjective assessments. Three patients with keratoconus received IVF treatment and keratoconus progression was detected in all 6 eyes of the patients. The mean age of the patients was 32.3 ± 3.6 years (range: 28 to 36 years) and the mean follow-up duration was 15.6 ± 3.2 months (range: 12 to 18 months). The mean and the maximum keratometry values increased and corrected distance visual acuity decreased after 2.3 IVF treatments. Drugs used in IVF treatment increase estrogen levels, which may affect corneal biomechanics and induce progression of keratoconus. Corneal cross-linking treatment could be offered to minimize the risk of keratoconus progression before IVF treatment. Copyright 2016, SLACK Incorporated.

  17. Cancer treatment induced metabolic syndrome: Improving outcome with lifestyle.

    PubMed

    Westerink, N L; Nuver, J; Lefrandt, J D; Vrieling, A H; Gietema, J A; Walenkamp, A M E

    2016-12-01

    Increasing numbers of long-term cancer survivors face important treatment related adverse effects. Cancer treatment induced metabolic syndrome (CTIMetS) is an especially prevalent and harmful condition. The aetiology of CTIMetS likely differs from metabolic syndrome in the general population, but effective treatment and prevention methods are probably similar. In this review, we summarize the potential mechanisms leading to the development of CTIMetS after various types of cancer treatment. Furthermore, we propose a safe and accessible method to treat or prevent CTIMetS through lifestyle change. In particular, we suggest that a lifestyle intervention and optimization of energy balance can prevent or mitigate the development of CTIMetS, which may contribute to optimal survivorship care.

  18. Neutron distribution and induced activity inside a Linac treatment room.

    PubMed

    Juste, B; Miró, R; Verdú, G; Díez, S; Campayo, J M

    2015-01-01

    Induced radioactivity and photoneutron contamination inside a radiation therapy bunker of a medical linear accelerator (Linac) is investigated in this work. The Linac studied is an Elekta Precise electron accelerator which maximum treatment photon energy is 15 MeV. This energy exceeds the photonuclear reaction threshold (around 7 MeV for high atomic number metals). The Monte Carlo code MCNP6 has been used for quantifying the neutron contamination inside the treatment room for different gantry rotation configuration. Walls activation processes have also been simulated. The approach described in this paper is useful to prevent the overexposure of patients and medical staff.

  19. Treatment of chemotherapy-induced nausea and vomiting.

    PubMed

    Inrhaoun, Hanane; Kullmann, Tamás; Elghissassi, Ibrahim; Mrabti, Hind; Errihani, Hassan

    2012-12-01

    Recent improvements in medical oncology include both development of anticancer and supportive therapy. Serotonin receptor antagonists were introduced in clinical practice 20 years ago. Since then, the prevention and treatment of chemotherapy-induced nausea and vomiting allows continuing efficacious chemotherapy that earlier had to be stopped sometimes for intolerance. This anniversary review summarises the current antiemetic arsenal focussing on the most potent antiemetic drugs such as serotonin and substance P receptor antagonists. Antiemetic treatment improves quality of life under chemotherapy and contributes to the survival benefit as well. In spite of the use of these new drugs, a significant number of patients still experience nausea and vomiting. Special complications like delayed emesis can be alleviated by combination therapies. Prevention and optimal management of chemotherapy-induced nausea and vomiting should be a goal for most patients receiving emetogenic chemotherapy.

  20. Pre-Treatment with Tyrosine Reverses Hypothermia Induced Behavioral Depression

    DTIC Science & Technology

    1989-09-01

    Treatn,-iL with Tv-rosine Reverses Hypothermia Induced Behavioral Depression 12 PERSONAL AUTHOR(S) T. Michael Rau- .. and Harris R. Lieberman 13a... depression on the open field test. Two experimeaits were performed on adult male rats. First, it was determined whether systematic lowering of core...body temperature produce,! behavioral depression in the swim test. Second, treatment with the ,A precursor tvrosine was employed in an attempt to prevent

  1. Rifampicin-induced disseminated intravascular coagulation in pulmonary tuberculosis treatment

    PubMed Central

    Chen, Guo; He, Jian-Qing

    2017-01-01

    Abstract Rationale: Disseminated intravascular coagulation (DIC) induced by daily rifampicin therapy is rare, especially the patient is absent of malignancy, severe infection, and prior exposure to rifampicin. Patient concerns: We report a case of DIC induced by daily rifampicin treatment for pulmonary tuberculosis. A 22-year-old, previously healthy man received an anti-tuberculosis therapy consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide on the daily dose recommended by the World Health Organization tuberculosis guidelines after a diagnosis of pulmonary tuberculosis. Two weeks later, he was transferred to the West China Hospital with nasal hemorrhage for 1 week, hematochezia, hematuria, and petechiae for 5 days. Diagnoses: Laboratory data and symptoms on admission indicated DIC. Interventions: The anti-tuberculosis drugs were discontinued after admission and he was initiated with targeted treatment for DIC, omeprazole and polyene hosphatidylcholine infusion, as well as nutrition supportive treatment. Five days after admission, ethambutol, moxifloxacin, and amikacin were added to the patient without further active hemorrhage. Eight days after admission, the platelet count had risen gradually. Isoniazid was administered on 24 days after admission, while his liver function tests and platelet counts returned to normal. No recurrence of DIC occurred. The diagnosis of rifampicin-induced DIC was confirmed. Outcomes: The patient recovered and left hospital with isoniazid, ethambutol, levofloxacin, and streptomycin after 4 weeks of hospitalization. There was no recurrence of DIC or hemorrhage during the 8 months of follow-up. The literature review revealed that there were 10 other cases of rifampicin-induced DIC. Only 4 cases received rifampicin on a daily basis for pulmonary tuberculosis treatment and the others were on intermittent dosing schedule for pulmonary tuberculosis or leprosy treatment. Lessons: As a rare adverse effect, DIC induced by

  2. Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments.

    PubMed

    Herradón, Esperanza; González, Cristina; Uranga, José A; Abalo, Raquel; Martín, Ma I; López-Miranda, Visitacion

    2017-01-01

    In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.

  3. Characterization of Cardiovascular Alterations Induced by Different Chronic Cisplatin Treatments

    PubMed Central

    Herradón, Esperanza; González, Cristina; Uranga, José A.; Abalo, Raquel; Martín, Ma I.; López-Miranda, Visitacion

    2017-01-01

    In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries) and vascular (aortic and mesenteric) functions were evaluated in chronic (5 weeks) saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week). Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations. PMID:28533750

  4. Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations.

    PubMed

    Arout, Caroline A; Edens, Ellen; Petrakis, Ismene L; Sofuoglu, Mehmet

    2015-06-01

    Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

  5. Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment.

    PubMed

    Yogasundaram, Haran; Putko, Brendan N; Tien, Julia; Paterson, D Ian; Cujec, Bibiana; Ringrose, Jennifer; Oudit, Gavin Y

    2014-12-01

    Drug-induced heart and vascular disease remains an important health burden. Hydroxychloroquine and its predecessor chloroquine are medications commonly used in the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders. Hydroxychloroquine interferes with malarial metabolites, confers immunomodulatory effects, and also affects lysosomal function. Clinical monitoring and early recognition of toxicity is an important management strategy in patients who undergo long-term treatment with hydroxychloroquine. Retinal toxicity, neuromyopathy, and cardiac disease are recognized adverse effects of hydroxychloroquine. Immediate withdrawal of hydroxychloroquine is essential if toxicity is suspected because of the early reversibility of cardiomyopathy. In addition to recommended ophthalmological screening, regular screening with 12-lead electrocardiogram and transthoracic echocardiography to detect conduction system disease and/or biventricular morphological or functional changes should be considered in hydroxychloroquine-treated patients. Cardiac magnetic resonance imaging and endomyocardial biopsy are valuable tools to provide prognostic insights and confirm the diagnosis of hydroxychloroquine-induced cardiomyopathy. In conclusion, chronic use of hydroxychloroquine can result in an acquired lysosomal storage disorder, leading to a drug-induced cardiomyopathy characterized by concentric hypertrophy and conduction abnormalities associated with increased adverse clinical outcomes and mortality.

  6. Telmisartan treatment attenuates arsenic-induced hepatotoxicity in mice.

    PubMed

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2012-10-28

    The protective effect of telmisartan, the angiotensin II-receptor antagonist, against liver toxicity induced by sodium arsenite (5 mg/kg/day, p.o., for 30 days) was investigated in mice. Telmisartan treatment (10 mg/kg/day, p.o.) was applied for 30 days, starting on the same day of arsenic administration. Telmisartan significantly reduced serum alanine aminotransferase level which was increased by sodium arsenite. Telmisartan significantly suppressed lipid peroxidation, and prevented the reduced glutathione depletion and nitric oxide elevation in the liver tissue resulted from arsenic administration. Also, the increase of arsenic ion, and the reductions of selenium and zinc ions in liver tissue were attenuated by telmisartan. Histopathological examination showed that liver tissue injury mediated by arsenic was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan significantly decreased the arsenic-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in liver tissue. It was concluded that telmisartan may represent a potential option to protect the liver tissue from the detrimental effects of arsenic toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Epigenetic changes in the rat livers induced by pyrazinamide treatment

    SciTech Connect

    Kovalenko, V.M.; Bagnyukova, T.V.; Sergienko, O.V.; Bondarenko, L.B.; Shayakhmetova, G.M.; Matvienko, A.V.; Pogribny, I.P.

    2007-12-15

    Drug-induced liver injury, including drug-induced hepatotoxicity during the treatment of tuberculosis infection, is a major health problem with increasingly significant challenges to modern hepatology. Therefore, the assessment and monitoring of the hepatotoxicity of antituberculosis drugs for prevention of liver injury are great concerns during disease treatment. The recently emerged data showing the ability of toxicants, including pharmaceutical agents, to alter cellular epigenetic status, open a unique opportunity for early detection of drug hepatotoxicity. Here we report that treatment of male Wistar rats with antituberculosis drug pyrazinamide at doses of 250, 500 or 1000 mg/kg/day body weight for 45 days leads to an early and sustained decrease in cytosine DNA methylation, progressive hypomethylation of long interspersed nucleotide elements (LINE-1), and aberrant promoter hypermethylation of placental form glutathione-S-transferase (GSTP) and p16{sup INK4A} genes in livers of pyrazinamide-treated rats, while serum levels of bilirubin and activity of aminotransferases changed modestly. The early occurrence of these epigenetic alterations and their association with progression of liver injury specific pathological changes indicate that alterations in DNA methylation may be useful predictive markers for the assessment of drug hepatotoxicity.

  8. New approaches to the treatment of opioid-induced constipation

    PubMed Central

    Holzer, Peter

    2015-01-01

    Opiates are indispensable for the treatment of moderate to severe pain. The gastrointestinal tract is one of the major victims of the undesired effects of opiates, because the enteric nervous system expresses all major subtypes of opioid receptors. As a result, propulsive motility and secretory processes in the gut are inhibited by opioid analgesics, and the ensuing constipation is one of the most frequent and troublesome adverse reactions. Many treatments involving laxatives, prokinetic drugs and opioid-sparing regimens have been explored to circumvent opioid-induced bowel dysfunction, but the outcome has in general been unsatisfactory. Specific antagonism of peripheral opioid receptors offers a more rational approach to the management of the adverse actions of opioid analgesics in the gut. This goal is currently addressed by the use of opioid receptor antagonists with limited absorption such as oral naloxone and by the development of peripherally restricted opioid receptor antagonists such as methylnaltrexone and alvimopan. These investigational drugs hold considerable promise in preventing constipation due to opiate treatment, whereas the analgesic action of opiates remains unabated. Postoperative ileus associated with opioid-induced postsurgical pain control is likewise ameliorated by the compounds. With this proof of concept, several phase III studies are under way to define optimal dosage, dosing regimen as well as long-term efficacy and safety of methylnaltrexone and alvimopan. In addition, there is preliminary evidence that these peripherally restricted opioid receptor antagonists may act as prokinetic drugs in their own right. PMID:18924451

  9. PHARMACOLOGIC TREATMENT OF HYPERALGESIA EXPERIMENTALLY INDUCED BY NUCLEUS PULPOSUS

    PubMed Central

    de Souza Grava, André Luiz; Ferrari, Luiz Fernando; Parada, Carlos Amílcar; Defino, Helton Luiz Aparecido

    2015-01-01

    Objective: To evaluate the effect of anti-inflammatory drugs (dexamethasone, indomethacin, atenolol and indomethacin plus atenolol) and analgesic drugs (morphine) on hyperalgesia experimentally induced by the nucleus pulposus (NP) in contact with the L5 dorsal root ganglion (DRG). Methods: Thirty male Wistar rats of weights ranging from 220 to 250 g were used in the study. Hyperalgesia was induced by means of a fragment of NP removed from the sacrococcygeal region that was placed in contact with the L5 dorsal root ganglion. The 30 animals were divided into experimental groups according to the drug used. The drugs were administered for two weeks after the surgical procedure to induce hyperalgesia. Mechanical and thermal hyperalgesia was evaluated using the paw pressure test, von Frey electronic test and Hargreaves test, over a seven-week period. Results: The greatest reduction of hyperalgesia was observed in the group of animals treated with morphine, followed by dexamethasone, indomethacin and atenolol. Reductions in hyperalgesia were observed after drug administration ceased, except for the group of animals treated with morphine, in which there was an increase in hyperalgesia after discontinuation of the treatment. Conclusion: Hyperalgesia induced by NP contact with the DRG can be reduced through administration of anti-inflammatory and analgesic drugs, but a greater reduction was observed with the administration of dexamethasone. PMID:27026966

  10. Emerging treatments in chemotherapy-induced nausea and vomiting.

    PubMed

    Grunberg, Steven M; Slusher, Barbara; Rugo, Hope S

    2013-02-01

    Chemotherapy-induced nausea and vomiting (CINV) is a concern for many cancer patients. It can have an enormous impact on quality of life. CINV occurring in the first 24 hours after treatment is considered acute, and CINV occurring on days 2 through 5 after treatment is considered delayed. Anticipatory nausea and depression can also occur when patients are reminded of their chemotherapy treatment. CINV can lead to weight changes, fatigue, and the need for additional medications. Even mild to moderate CINV can increase health care utilization and costs, as well as delay treatment. Nausea and vomiting are separate events, although their mechanisms are entwined. Drugs that stop vomiting do not necessarily treat nausea. Control of CINV allows patients to complete treatment and to minimize use of health care resources and additional medications. Current antiemesis agents, such as 5-hydroxytryptamine-3 (5-HT3) antagonists and neurokinin-1 (NK-1) antagonists, have markedly decreased hospitalization for chemotherapy and have nearly eliminated acute emesis. The second-generation 5-HT3 receptor palonosetron has a unique pharmacology that makes it especially effective at preventing delayed emesis.

  11. Pharmacological treatment of combat-induced PTSD: a literature review.

    PubMed

    Bastien, Debra Lynn

    Historically, soldiers have returned from war changed men. Over the years there has been an increase in awareness of post-traumatic stress disorder (PTSD) and the impact of diagnosis. Treatment of PTSD presents a challenge on every level. This literature review provides some insight into the risks and benefits of three groups of drugs commonly prescribed for combat-induced PTSD: beta-blockers, selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines (BZDs). When prescribed in conjunction with other non-pharmacological treatments, these drugs help to minimize, and in some cases eliminate, the signs and symptoms of PTSD. Combination therapy would ideally result in better compliance and eventual completion of treatment programmes provided for PTSD sufferers. Healthcare professionals strive to provide patients with holistic care. Patients present with unique mental and physical intricacies, and nurses and health professionals must peel away the layers to uncover the nature of the PTSD. While there are many aspects to PTSD treatment, this literature review focuses on pharmacological treatment, specifically beta-blockers, SSRIs and BZDs.

  12. Pulse mode of laser photodynamic treatment induced cell apoptosis.

    PubMed

    Klimenko, Vladimir V; Knyazev, Nickolay A; Moiseenko, Fedor V; Rusanov, Anatoliy A; Bogdanov, Alexey A; Dubina, Michael V

    2016-03-01

    One of the factors limiting photodynamic therapy (PDT) is hypoxia in tumor cells during photodynamic action. PDT with pulse mode irradiation and appropriate irradiation parameters could be more effective in the singlet oxygen generation and tissue re-oxygenation than continuous wave (CW) mode. We theoretically demonstrate differences between the cumulative singlet oxygen concentration in PDT using pulse mode and CW mode of laser irradiation. In vitro experimental results show that photodynamic treatment with pulse mode irradiation has similar cytotoxicity to CW mode and induces mainly cell apoptosis, whereas CW mode induces necrotic cell death. We assume that the cumulative singlet oxygen concentration and the temporal distribution of singlet oxygen are important in photodynamic cytotoxicity and apoptosis initiation. We expect our research may improve irradiation protocols and photodynamic therapy efficiency.

  13. [Nonsurgical treatment of chronic radiation-induced hemorrhagic proctitis].

    PubMed

    de Parades, Vincent; Bauer, Pierre; Marteau, Philippe; Chauveinc, Laurent; Bouillet, Thierry; Atienza, Patrick

    2008-01-01

    The incidence of radiation-induced chronic hemorrhagic proctitis is less than 10 to 20%. The onset of this proctitis is delayed relative to the radiation therapy and generally develops from 6 to 24 months later. There are numerous predisposing factors, the most important of which is the radiation therapy dose: risk increases exponentially above 40-45 Gy. Its pathophysiology involves progressive obliterating endarteritis and transmural interstitial fibrosis, which induce chronic ischemia that is irreversible and progressive during the years after radiation therapy. Its diagnosis depends most often on the combination of clinical history and typical endoscopic appearance (congestive mucosa and/or telangiectases). Topical administrative of sucralfate or corticosteroids as well as argon plasma coagulation, with formalin treatment if necessary, provides relief for most patients.

  14. Ultrastructural analysis of contractile cell development in lung microvessels in hyperoxic pulmonary hypertension. Fibroblasts and intermediate cells selectively reorganize nonmuscular segments.

    PubMed Central

    Jones, R.

    1992-01-01

    The current study traces the development of contractile cells in the nonmuscular segments of rat lung microvessels in hyperoxic pulmonary hypertension. New intimal cells first develop into a well-defined layer beneath the endothelium and internal to an elastic lamina. Ultrastructurally, these cells are found to be 1) fibroblasts recruited to the vessel wall from the interstitium and 2) intermediate cells, a population of preexisting vascular cells (structurally between a smooth muscle cell and a pericyte). Early in hyperoxia (days 3 through 7), interstitial fibroblasts migrate and align around the smallest vessels in which an elastic lamina is either absent or fragmentary. These cells then are incorporated into the vessel wall by tropoelastin secretion and the formation of an elastic lamina along their abluminal margin. After day 7, the new mural fibroblasts acquire the features of contractile cells, namely a basal lamina, extensive microfilaments, and dense bodies. In other vessels, as early as day 3 of hyperoxia, intermediate cells within the vessel intima begin to acquire the additional filaments and dense bodies of contractile cells. As hyperoxia continues, each cell pathway gives rise to vessels with distinct intimal or medial layers of contractile cells. In this way, thick-walled 'newly muscularized' vessel segments form adjacent to the capillary bed. Images Figure 1 Figure 5 Figure 6 Figure 7 p1500-a Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:1466406

  15. Measurement of the retinal arteriolar response to a hyperoxic provocation in nonsmokers and smokers, using a high-resolution confocal scanning laser ophthalmoscope

    NASA Astrophysics Data System (ADS)

    O' Halloran, Margaret; O'Donoghue, Eamonn; Dainty, Chris

    2014-07-01

    We used a high-resolution confocal scanning laser ophthalmoscope to measure the magnitude of change in retinal arteriolar diameters in response to oxygen breathing in young, healthy nonsmokers and smokers. Image sequences were obtained before and during oxygen breathing. Image sequences were desinusoided, registered, and averaged, before vessel diameters were measured using a sliding linear regression filter. Arteriole diameters were observed to constrict during the first 5 min. of oxygen breathing, plateau, and remain stable while hyperoxia was maintained, returning to baseline at the end of the hyperoxic period. Blood flow to the temporal retina was found to be higher than to the nasal retina (p=0.008). The percentage constriction of vessels did not vary across retinal quadrants (p=0.372, analysis of variance) and did not depend on vessel size (p=0.538). Baseline diameters were unaffected by acute cigarette smoking. The magnitude of vasoconstriction was diminished in smokers compared to nonsmokers (p=0.017), while acute smoking did not influence the percentage constriction attained by the vessels (p=0.621). Using a high-resolution imaging technique allowed us to measure reactivity to a high degree of accuracy and to assess it in vessels of smaller caliber than were previously studied.

  16. Contractile responses of isolated equine digital arteries under hypoxic or hyperoxic conditions in vitro: role of reactive oxygen species and Rho kinase.

    PubMed

    Borer, K E; Bailey, S R; Harris, P A; Elliott, J

    2013-06-01

    The underlying pathophysiological triggers for equine acute laminitis are unknown, although digital vasoconstriction, ischaemia, hypoxia and reperfusion injury may be involved. The contractile responses of isolated equine digital arteries (EDAs), harvested from the hindlimbs of normal horses postmortem at an abattoir, were studied acutely (up to 3 h) under hyperoxic (95% oxygen, 5% CO2 ) and hypoxic (95% nitrogen, 5% CO2 ) conditions in organ baths. Phenylephrine (PHE; 10(-6) m), 5-hydroxytryptamine (5-HT; 10(-7) m) and high potassium (K(+) ; 118 mm) caused contraction in EDAs which was significantly (P<0.0001) enhanced under hypoxic conditions. In contrast, contraction stimulated by 9,11-dideoxy-9α,11α-epoxymethanoprostaglandin F2α (U44069; 3 × 10(-8) m) was not significantly enhanced by hypoxia (P=0.75). Hypoxia-enhanced contraction in response to K(+) was greater (P<0.03) in vessels with a functional endothelium than in vessels in which the endothelium was removed by rubbing. Fasudil (10(-6) to 10(-5) m), a Rho kinase inhibitor, and apocynin (10(-3) to 3 × 10(-3) m), an NADPH oxidase inhibitor, significantly (P ≤ 0.05) inhibited hypoxia-enhanced contraction in response to PHE and 5-HT. In conclusion, hypoxia-enhanced contraction occurred in EDAs. This appears to be partially mediated by reactive oxygen species produced by NAPDH oxidase, which activate Rho kinase to increase calcium sensitisation and enhance smooth muscle contraction.

  17. Treatment of radiation- and chemotherapy-induced stomatitis

    SciTech Connect

    Carnel, S.B.; Blakeslee, D.B.; Oswald, S.G.; Barnes, M. )

    1990-04-01

    Severe stomatitis is a common problem encountered during either radiation therapy or chemotherapy. Most therapeutic regimens are empirical, with no scientific basis. The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiation- or chemotherapy-induced stomatitis. Eighteen patients were entered into a prospective double-blinded study to test several topical solutions: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride 1.0% (Dyclone); (3) kaolin-pectin solution, diphenhydramine plus saline (KBS); and (4) a placebo solution. Degree of pain relief, duration of relief, side effects, and palatability were evaluated. The results showed that Dyclone provided the most pain relief. Dyclone and viscous lidocaine with 1% cocaine provided the longest pain relief, which averaged 50 minutes This study provides objective data and defines useful guidelines for treatment of stomatitis.

  18. Granulomatous tattoo reaction induced by intense pulse light treatment.

    PubMed

    Tourlaki, Athanasia; Boneschi, Vinicio; Tosi, Diego; Pigatto, Paolo; Brambilla, Lucia

    2010-10-01

    Cosmetic tattooing involves implantation of pigments into the dermis in order to create a permanent makeup. Here, we report a case of sarcoidal granulomatous reaction to old cosmetic tattoos after an intense pulsed light (IPL) treatment for facial skin rejuvenation. We consider this case as a peculiar example of photo-induced reaction to tattoo. In addition, we hypothesize that an underlying immune dysfunction was present, and acted as a predisposing factor for this unusual response, as the patient had suffered from an episode of acute pulmonary sarcoidosis 15 years before. Overall, our observation suggests that IPL treatment should be used cautiously in patients with tattoos, especially when a history of autoimmune disease is present. © 2010 John Wiley & Sons A/S.

  19. Analgesic treatment of ciguatoxin-induced cold allodynia.

    PubMed

    Zimmermann, Katharina; Deuis, Jennifer R; Inserra, Marco C; Collins, Lindon S; Namer, Barbara; Cabot, Peter J; Reeh, Peter W; Lewis, Richard J; Vetter, Irina

    2013-10-01

    Ciguatera, the most common form of nonbacterial ichthyosarcotoxism, is caused by consumption of fish that have bioaccumulated the polyether sodium channel activator ciguatoxin. The neurological symptoms of ciguatera include distressing, often persistent sensory disturbances such as paraesthesias and the pathognomonic symptom of cold allodynia. We show that intracutaneous administration of ciguatoxin in humans elicits a pronounced axon-reflex flare and replicates cold allodynia. To identify compounds able to inhibit ciguatoxin-induced Nav responses, we developed a novel in vitro ciguatoxin assay using the human neuroblastoma cell line SH-SY5Y. Pharmacological characterisation of this assay demonstrated a major contribution of Nav1.2 and Nav1.3, but not Nav1.7, to ciguatoxin-induced Ca2+ responses. Clinically available Nav inhibitors, as well as the Kv7 agonist flupirtine, inhibited tetrodotoxin-sensitive ciguatoxin-evoked responses. To establish their in vivo efficacy, we used a novel animal model of ciguatoxin-induced cold allodynia. However, differences in the efficacy of these compounds to reverse ciguatoxin-induced cold allodynia did not correlate with their potency to inhibit ciguatoxin-induced responses in SH-SY5Y cells or at heterologously expressed Nav1.3, Nav1.6, Nav1.7, or Nav1.8, indicating cold allodynia might be more complex than simple activation of Nav channels. These findings highlight the need for suitable animal models to guide the empiric choice of analgesics, and suggest that lamotrigine and flupirtine could be potentially useful for the treatment of ciguatera. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  20. Adjunctive treatment with aripiprazole for risperidone-induced hyperprolactinemia

    PubMed Central

    Ranjbar, Fatemeh; Sadeghi-Bazargani, Homayoun; Niari Khams, Parisa; Arfaie, Asghar; Salari, Azim; Farahbakhsh, Mostafa

    2015-01-01

    Background Antipsychotics have been used for more than 50 years in the treatment of schizophrenia and many other psychiatric disorders. Prolactin levels usually increase in patients treated with risperidone. Aripiprazole, which has a unique effect as an antipsychotic, is a D2 receptor partial agonist. It is an atypical antipsychotic with limited extrapyramidal symptoms. Since it acts as an antagonist in hyperdopaminergic conditions and as an agonist in hypodopaminergic conditions, it does not have adverse effects on serum prolactin levels. The present study aimed to investigate the effect of aripiprazole on risperidone-induced hyperprolactinemia. Methods This before-and-after clinical trial was performed in 30 patients. Baseline prolactin levels were measured in all patients who were candidates for treatment with risperidone. In subjects with elevated serum prolactin, aripiprazole was added to their treatment. Serum prolactin levels were measured during the first week, second week, and monthly thereafter for at least 3 months or until prolactin levels became normal. The data were analyzed using Stata version 11 software. Survival analysis and McNemar’s test were also performed. Results The mean age of the participants was 30.8 years. Prolactin levels normalized in 23 (77%) participants during the study, and menstrual disturbances normalized in 25 (83.3%). Prolactin levels normalized in most patients between days 50 and 110. The median time to recovery based on normalization of prolactin was 84 days. Psychotic symptoms were present in 26 subjects at baseline, but in only two by the end of the study. Conclusion The results of this study confirm the effects of aripiprazole in reducing risperidone-induced hyperprolactinemia and its sequelae. Aripiprazole also led to significant improvements in psychotic symptoms when compared with those present prior to treatment with aripiprazole. PMID:25784810

  1. Interferon-induced thyroiditis during treatment of chronic hepatitis C.

    PubMed

    Kozielewicz, Dorota; Halota, Waldemar

    2012-01-01

    Thyroid function disorders affect between 5% and 15% of patients treated with IFNα and RBV for chronic hepatitis C. Women and patients with thyroid peroxidase antibodies (TPOAb) found before the treatment are at risk of developing the disorders (46.1% vs. 5.4%). The spectrum of IFNα-induced thyroiditis (IIT) includes two groups. Disorders with an autoimmune background are: presence of thyroid autoantibodies without clinical disease, Hashimoto's disease and Graves' disease. The second group comprises diseases caused by the direct toxic effect of IFNα on the thyroid gland, i.e. destructive thyroiditis and non-autoimmune hypothyroidism. Thyroid diseases are not an absolute contraindication for IFNα and RBV therapy. In patients diagnosed with thyroid dysfunction, before the antiviral therapy it is necessary to achieve euthyreosis. Thyroid function disorders may occur at any moment of the therapy. The earliest have been observed in the 4th week of treatment, and the latest 12 months after its termination. During the therapy, in order to diagnose IIT early, it is recommended to determine TSH level every 2-3 months depending on the presence of TPOAb before the treatment. The diagnosis and treatment of thyroid function disorders should be conducted in co-operation with an endocrinologist.

  2. Frovatriptan as preemptive treatment for fasting-induced migraine.

    PubMed

    Latsko, Meryl; Silberstein, Stephen; Rosen, Noah

    2011-03-01

    To examine frovatriptan's efficacy as preemptive treatment for fasting-induced migraine. Fasting is a common migraine trigger that cannot always be avoided. The development of a short-term preemptive approach would be of benefit. Because of its longer half-life, frovatriptan has been effectively used for short-term daily use to prevent menstrually related migraines and might prove useful in the prevention of fasting-induced migraine. This was a double-blind, placebo-controlled, randomized, parallel-group trial. With a history of fasting-induced episodic migraine were randomly assigned to receive either frovatriptan (5.0 mg) or placebo (ratio 1:1). Took a single dose of study medication at the start of their 20-hour fast. Information about headache intensity, associated symptoms, and use of rescue medication was captured at defined time points from the start of the fast through 20 hours post-fast. Of the 75 subjects screened, 74 subjects were randomized and 71 subjects completed the study. Demographic characteristics of the placebo and frovatriptan treatment groups were not statistically different. Thirty-three subjects received active drug. Twelve (36.4%) developed a headache between 6 and 20 hours after the start of the fast (1/33 mild, 11/33 moderate or severe). In the placebo group, 18/34 (52.9%) developed a headache (4/34 mild, 14/34 moderate or severe). The difference between the 2 treatment groups did not achieve statistical significance; Pearson chi-square, P = .172. Kaplan-Meier survival analysis showed no difference between the 2 treatment groups with respect to the time of onset of headache of any intensity (log rank, P = .264) and for the time of onset of a moderate or severe intensity (log rank, P = .634). More subjects on placebo developed a headache than those on frovatriptan. Perhaps because of the small number of subjects involved, the differences in headache incidences observed did not achieve statistical significance. © 2011

  3. Sepsis-induced immunoparalysis: mechanisms, markers, and treatment options.

    PubMed

    Hamers, L; Kox, M; Pickkers, P

    2015-04-01

    Sepsis remains the leading cause of death in the ICU. Considering the key role of the immune system in sepsis, immunomodulation represents an attractive target for adjunctive therapy. Until recently, clinical trials focused on suppression of the immune system, but this approach failed to improve sepsis outcome. Recent advances in the understanding of sepsis have led to the view that not the initial hyperinflammatory state, but rather a profoundly suppressed state of the immune system, called sepsis-induced immunoparalysis, accounts for the majority of sepsis-related deaths. Immunoparalysis results in ineffective clearance of septic foci, and renders the septic patient more vulnerable to secondary infections, as well as reactivation of latent infections. Several mechanisms behind immunoparalysis have been recognised. Furthermore, due to recognition of the importance of immunoparalysis, immunostimulatory treatment is emerging as a possible adjunctive treatment for sepsis. As such, identification of patients suffering from immunoparalysis using biomarkers is of utmost importance to guide immunostimulatory treatment. In this review, an short overview of the concept of immunoparalysis is presented, while the main focus is on potential biological markers of immunoparalysis and promising immunostimulatory therapeutic agents. The challenging heterogeneity of septic patients in respect to immunomodulatory advances will be discussed, and recommendations for future research are provided.

  4. Experimental treatment of antipsychotic-induced movement disorders

    PubMed Central

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  5. Current treatment and future prospects of dopa-induced dyskinesias.

    PubMed

    Mazzucchi, S; Frosini, D; Bonuccelli, U; Ceravolo, R

    2015-05-01

    Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes difficult, so preventive strategies should be first evaluated. Although levodopa (LD) treatment has recently been related as risk factor for LID, the main strategy to delay LID is to start PD treatment with dopamine agonists, adding LD at low doses. After LID onset, approaches include reducing single LD doses, reducing or discontinuing monoamine oxidase type B/catechol O-methyltransferase (MAO-B/COMT) inhibitors and extended-release (ER) LD. Amantadine represents the best antidyskinetic tool, and ER amantadine is the most promising upcoming antidyskinetic drug. New LD formulations such as IPX-066 (able to provide continuous dopaminergic stimulation) also represent promising new approaches. The involvement of a nondopaminergic system in the pathogenesis of LID suggests that the modulation of glutamate, serotonin and adenosine could have potential as new upcoming drug targets, but the role of such drugs will still need to be confirmed in randomized controlled trials.

  6. Cerium oxide nanoparticle treatment ameliorates peritonitis-induced diaphragm dysfunction.

    PubMed

    Asano, Shinichi; Arvapalli, Ravikumar; Manne, Nandini D P K; Maheshwari, Mani; Ma, Bing; Rice, Kevin M; Selvaraj, Vellaisamy; Blough, Eric R

    2015-01-01

    The severe inflammation observed during sepsis is thought to cause diaphragm dysfunction, which is associated with poor patient prognosis. Cerium oxide (CeO2) nanoparticles have been posited to exhibit anti-inflammatory and antioxidative activities suggesting that these particles may be of potential use for the treatment of inflammatory disorders. To investigate this possibility, Sprague Dawley rats were randomly assigned to the following groups: sham control, CeO2 nanoparticle treatment only (0.5 mg/kg iv), sepsis, and sepsis+CeO2 nanoparticles. Sepsis was induced by the introduction of cecal material (600 mg/kg) directly into the peritoneal cavity. Nanoparticle treatment decreased sepsis-associated impairments in diaphragmatic contractile (P(o)) function (sham: 25.6±1.6 N/cm(2) vs CeO2: 23.4±0.8 N/cm(2) vs Sep: 15.9±1.0 N/cm(2) vs Sep+CeO2: 20.0±1.0 N/cm(2), P<0.05). These improvements in diaphragm contractile function were accompanied by a normalization of protein translation signaling (Akt, FOXO-1, and 4EBP1), diminished proteolysis (caspase 8 and ubiquitin levels), and decreased inflammatory signaling (Stat3 and iNOS). Histological analysis suggested that nanoparticle treatment was associated with diminished sarcolemma damage and diminished inflammatory cell infiltration. These data indicate CeO2 nanoparticles may improve diaphragmatic function in the septic laboratory rat.

  7. Pesticide-induced scleroderma and early intensive immunosuppressive treatment.

    PubMed

    Sozeri, Betul; Gulez, Nesrin; Aksu, Guzide; Kutukculer, Necil; Akalın, Taner; Kandiloglu, Gulsen

    2012-01-01

    The authors report 2 children with generalized cutaneous sclerosis exposed to pesticides containing malathion and diniconazole. Treatment with immunosuppressives resulted in partial improvement in the cutaneous signs, particularly over the face, trunk, and proximal limbs. The considerable exposure to chemicals related with the initiation of symptoms and absence of organ involvement suggested a diagnosis of chemically induced scleroderma-like disorder. Although autoantibodies were negative, previously reported relevant associations of anti-kinetochore and anti-topoisomerase function of active ingredients-diniconazole and phosphorodithioate-and solvents of these pesticides are also discussed. Careful follow-up for systemic involvement is warranted, since these agents may have triggered systemic scleroderma in these patients. Elimination of chemical exposure of children is stressed.

  8. Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

    PubMed Central

    Coriat, Romain; Alexandre, Jérôme; Nicco, Carole; Quinquis, Laurent; Benoit, Evelyne; Chéreau, Christiane; Lemaréchal, Hervé; Mir, Olivier; Borderie, Didier; Tréluyer, Jean-Marc; Weill, Bernard; Coste, Joel; Goldwasser, François; Batteux, Frédéric

    2013-01-01

    Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer. Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Results. Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation. In mice, serum AOPPs decreased after 4 weeks of mangafodipir treatment. In 77% of patients treated with oxaliplatin and mangafodipir, neuropathy improved or stabilized after 4 cycles. After 8 cycles, neurotoxicity was downgraded to grade ≥2 in 6 of 7 patients. Prior to enrollment, patients received an average of 880 ± 239 mg/m2 oxaliplatin. Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy. Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin. Serum AOPPs were lower in responders compared with those in nonresponders. Conclusion. Our study suggests that mangafodipir can prevent and/or relieve oxaliplatin-induced neuropathy in cancer patients. Trial registration. Clinicaltrials.gov NCT00727922. Funding. Université Paris Descartes, Ministère de la Recherche et de l’Enseignement Supérieur, and Assistance Publique-Hôpitaux de Paris. PMID:24355920

  9. Emerging treatments for noise-induced hearing loss

    PubMed Central

    Oishi, Naoki; Schacht, Jochen

    2011-01-01

    Introduction Approximately 5% of the population worldwide suffer from industrial, military, or recreational noise-induced hearing loss (NIHL) at great economic cost and detriment to the quality of life of affected individuals. This review discusses pharmacological strategies to attenuate NIHL that have been developed in animal models and that are now beginning to be tested in field trials. Areas covered The review describes the epidemiology, pathology and pathophysiology of NIHL in experimental animals and human. The underlying molecular mechanisms of damage are then discussed as a basis for therapeutic approaches to ameliorate the loss of auditory function. Finally, studies in military, industrial, and recreational settings are evaluated. Literature was searched employing the terms “noise-induced hearing loss” and “noise trauma”. Expert opinion NIHL, in principle, can be prevented. With the current pace of development, oral drugs to protect against NIHL should be available within the next 5 to 10 years. Positive results from ongoing trials combined with additional laboratory tests might accelerate the time from the bench to clinical treatment. PMID:21247358

  10. Exercise-Induced Anaphylaxis: An Update on Diagnosis and Treatment

    PubMed Central

    Barg, Wojciech; Medrala, Wojciech

    2010-01-01

    Exercise-induced anaphylaxis (EIA) and food-dependent, exercise-induced anaphylaxis (FDEIA) are rare but potentially life-threatening clinical syndromes in which association with exercise is crucial. The range of triggering physical activities is broad, including as mild an effort as a stroll. EIA is not fully repeatable (ie, the same exercise may not always result in anaphylaxis in a given patient). In FDEIA, the combined ingestion of sensitizing food and exercise is necessary to precipitate symptoms. Clinical features and management do not differ significantly from other types of anaphylaxis. The pathophysiology of EIA and FDEIA is not fully understood. Different hypotheses concerning the possible influence of exercise on the development of anaphylactic symptoms are taken into consideration. These include increased gastrointestinal permeability, blood flow redistribution, and most likely increased osmolality. This article also describes current diagnostic and therapeutic possibilities, including changes in lifestyle and preventive properties of antiallergic drugs as well as acute treatment of these dangerous syndromes. PMID:20922508

  11. Therapeutic treatments of phosgene-induced lung injury.

    PubMed

    Sciuto, Alfred M; Hurt, Holcombe H

    2004-07-01

    A series of studies was performed to address treatment against the former chemical warfare edemagenic gas phosgene. Both in situ and in vivo models were used to assess the efficacy of postexposure treatment of phosgene-induced lung injury using clinically existing drugs. The degree of efficacy was judged by examining treatment effects on pulmonary edema formation (PEF) as measured by wet/dry weight (WW/DW) ratios, real-time (in situ) lung weight gain (LWG), survival rates (SR), odds ratios, and glutathione (GSH) redox states. Drugs included N-acetylcysteine (NAC), ibuprofen (IBU), aminophylline (AMIN), and isoproterenol (ISO). Using the in situ isolated perfused rabbit lung model (IPRLM), intratracheal (IT) NAC (40 mg/kg bolus) delivered 45-60 min after phosgene exposure (650 mg/m(3)) for10 min lowered pulmonary artery pressure, LWG, leukotrienes (LT) C(4)/D(4)/E(4), lipid peroxidation, and oxidized GSH. We concluded that NAC protected against phosgene-induced lung injury by acting as an antioxidant by maintaining protective levels of GSH, reducing both lipid peroxidation and production of arachidonic acid metabolites. Also in IPRLM, administration of AMIN (30 mg/kg) 80-90 min after phosgene exposure significantly reduced lipid peroxidation and perfusate LTC(4)/D(4)/E(4), reduced LWG, and prevented phosgene-induced decreases in lung tissue cAMP. These data suggest that protective mechanisms observed with AMIN involve decreased LTC(4)/D(4)/E(4) mediated pulmonary capillary permeability and attenuated lipid peroxidation. Direct antipermeability effects of AMIN-induced upregulation of cAMP on cellular contraction may also be important in protection against phosgene-induced lung injury. Posttreatment with ISO in the IPRLM by either combined intravascular (iv; infused into pulmonary artery at 24 microg/min infused) + IT (24 microg bolus) or IT route alone 50-60 min after phosgene exposure significantly lowered pulmonary artery pressure, tracheal pressure, and LWG. ISO

  12. Platinum-induced hearing loss after treatment for childhood cancer.

    PubMed

    van As, Jorrit W; van den Berg, Henk; van Dalen, Elvira C

    2016-08-03

    Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. Unfortunately, one of the most important adverse effects is the occurrence of hearing loss or ototoxicity. There is a wide variation in the reported prevalence of platinum-induced ototoxicity and the associated risk factors. More insight into the prevalence of and risk factors for platinum-induced hearing loss is essential in order to develop less ototoxic treatment protocols for the future treatment of children with cancer and to develop adequate follow-up protocols for childhood cancer survivors treated with platinum-based therapy. To evaluate the existing evidence on the association between childhood cancer treatment including platinum analogues and the occurrence of hearing loss. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 8), MEDLINE (PubMed) (1945 to 23 September 2015) and EMBASE (Ovid) (1980 to 23 September 2015). In addition, we searched reference lists of relevant articles and the conference proceedings of the International Society for Paediatric Oncology (2008 to 2014), the American Society of Pediatric Hematology/Oncology (2008 to 2015) and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (2010 to 2015). Experts in the field provided information on additional studies. All study designs, except case reports, case series (i.e. a description of non-consecutive participants) and studies including fewer than 100 participants treated with platinum-based therapy who had an ototoxicity assessment, examining the association between childhood cancer treatment including platinum analogues and the occurrence of hearing loss. Two review authors independently performed the study selection. One review author performed data extraction and risk of bias assessment, which was checked by another review author. We identified

  13. Molecular Mechanisms and Treatment of Radiation-Induced Lung Fibrosis

    PubMed Central

    Ding, Nian-Hua; Li, Jian Jian; Sun, Lun-Quan

    2014-01-01

    Radiation-induced lung fibrosis (RILF) is a severe side effect of radiotherapy in lung cancer patients that presents as a progressive pulmonary injury combined with chronic inflammation and exaggerated organ repair. RILF is a major barrier to improving the cure rate and well-being of lung cancer patients because it limits the radiation dose that is required to effectively kill tumor cells and diminishes normal lung function. Although the exact mechanism is unclear, accumulating evidence suggests that various cells, cytokines and regulatory molecules are involved in the tissue reorganization and immune response modulation that occur in RILF. In this review, we will summarize the general symptoms, diagnostics, and current understanding of the cells and molecular factors that are linked to the signaling networks implicated in RILF. Potential approaches for the treatment of RILF will also be discussed. Elucidating the key molecular mediators that initiate and control the extent of RILF in response to therapeutic radiation may reveal additional targets for RILF treatment to significantly improve the efficacy of radiotherapy for lung cancer patients. PMID:23909719

  14. Gonadectomy and progesterone treatment induce protection in murine cysticercosis.

    PubMed

    Vargas-Villavicencio, J A; Larralde, C; Morales-Montor, J

    2006-12-01

    The effects of progesterone on castrated mice of both sexes infected with Taenia crassiceps cysticerci were studied. Gonadectomy and treatment with progesterone before infection decreased parasite loads by 100% compared with intact uninfected mice. mRNA levels of IFN-gamma and IL-2 (typically associated to Th1-like profiles) were markedly decreased in infected gonadectomized (Gx) mice, whereas progesterone treatment of infected Gx mice did not affected its expression. mRNA levels of IL-4, and IL-10 (typically associated with Th2-like profiles) were reduced by gonadectomy, whereas restitution with progesterone did not affected this pattern in infected Gx progesterone-treated mice. Infection markedly induced expression of progesterone receptor isoform A in splenocytes of Gx mice (5-fold), whereas isoform B had no changes. Progesterone metabolism to dehydroepiandrosterone (DHEA) in Gx animals was increased 3-fold only in infected progesterone-treated uninfecteds of both sexes, but was not detectable in infected Gx progesterone-treated mice. Conversely, DHEA levels increased 100-fold in infected Gx progesterone-treated mice. However, androgen receptor expression in splenocytes of male mice showed a reduction by gonadectomy, and by infection, whereas in females AR expression showed no changes in the different mouse groups. These results suggest that progesterone, through its metabolism to DHEA, negatively affects the establishment, growth, and reproduction of Taenia crassiceps, by a mechanism that does not implicate a classic genomic pathway involving a nuclear androgen receptor.

  15. Induced pluripotent stem cells and Parkinson's disease: modelling and treatment.

    PubMed

    Xu, Xiaoyun; Huang, Jinsha; Li, Jie; Liu, Ling; Han, Chao; Shen, Yan; Zhang, Guoxin; Jiang, Haiyang; Lin, Zhicheng; Xiong, Nian; Wang, Tao

    2016-02-01

    Many neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSCs, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD, using hiPSCs, as well as the potential value of hiPSCs in modelling for PD, have been summarized for application of iPSCs technology to clinical translation for PD treatment. © 2016 John Wiley & Sons Ltd.

  16. Phenytoin-induced gingival overgrowth management with periodontal treatment.

    PubMed

    Gurgel, Bruno César de Vasconcelos; de Morais, Carlos Roberto Batista; da Rocha-Neto, Pedro Carlos; Dantas, Euler Maciel; Pinto, Leão Pereira; Costa, Antonio de Lisboa Lopes

    2015-01-01

    Phenytoin-induced gingival overgrowth (PIGO) is a common complication of the continuous use of medications. This paper presents a case of PIGO hindering oral function and compromising oral hygiene and aesthetics, which was treated with a combination of nonsurgical and surgical periodontal therapies. A 39-year-old male patient was referred for dental treatment with several complaints, especially upper and lower gingival overgrowth that hindered speech and swallowing. Generalized deep probing pockets and bone loss were detected. Diagnosis of gingival overgrowth associated with phenytoin and chronic periodontitis was established. The treatment plan consisted of conservative therapy with education on oral health, motivation and meticulous oral hygiene instruction in combination with scaling and root planing. During the revaluation period, a marked reduction in the clinical parameters was noted, particularly probing pocket depth reduction. Surgical therapy for removal of gingival overgrowth was also performed to achieve pocket reduction. Supportive periodontal therapy was proposed and the patient is currently under follow-up for 4 years. Management of PIGO may be obtained by the use of periodontal procedures combined with good oral hygiene and periodontal supportive care.

  17. Apoptosis in vascular cells induced by cold atmospheric plasma treatment

    NASA Astrophysics Data System (ADS)

    Sladek, Raymond; Stoffels, Eva

    2006-10-01

    Apoptosis is a natural mechanism of cellular self-destruction. It can be triggered by moderate, yet irreversible damage. Apoptosis plays a major role in tissue renewal. Artificial apoptosis induction will become a novel therapy that meets all requirements for tissue-saving surgery. Diseased tissues can disappear without inflammation and scarring. This is particularly important in treatment of blockages in body tracts (e.g. cardiovascular diseases). Artificial induction of apoptosis can be achieved by means of cold plasma treatment. In this work an atmospheric micro-plasma operated in helium/air has been used to induce apoptosis in vascular cells. Parametric studies of apoptosis induction have been conducted; the efficiency is almost 100%. The apoptotic factors are ROS/RNS (reactive oxygen and nitrogen species). Their densities in the plasma have been measured by mass spectrometry. For apoptosis induction, RNS seem to be more important than ROS, because of their relative abundance. Moreover, addition of a ROS scavenger (ascorbic acid) to the cell culture medium does not reduce the occurrence of apoptosis. Cold plasma is a very efficient tool for fundamental studies of apoptosis, and later, for controlled tissue removal in vivo.

  18. Cancer treatment-induced diarrhea: interventions to minimize the roller coaster ride.

    PubMed

    2004-01-01

    This program used a case-study approach to discuss interventions that nurses can implement in their daily clinical environment to minimize cancer treatment-induced diarrhea. Manifestations of cancer treatment-induced diarrhea, medical treatment options, and nutritional interventions were covered.

  19. Antituberculosis Drug-Induced Liver Injury with Autoimmune Features: Facing Diagnostic and Treatment Challenges

    PubMed Central

    Pinto Pais, Isabel; Duarte, Raquel; Carvalho, Isabel

    2017-01-01

    The authors present a case report of antituberculosis drug-induced liver injury that offered diagnostic challenges (namely, the possibility of drug-induced autoimmune hepatitis) and treatment difficulties. PMID:28116201

  20. Antituberculosis Drug-Induced Liver Injury with Autoimmune Features: Facing Diagnostic and Treatment Challenges.

    PubMed

    Rangel, Maria Adriana; Pinto Pais, Isabel; Duarte, Raquel; Carvalho, Isabel

    2017-01-01

    The authors present a case report of antituberculosis drug-induced liver injury that offered diagnostic challenges (namely, the possibility of drug-induced autoimmune hepatitis) and treatment difficulties.

  1. Treatment with Dimethyl Fumarate attenuates calcineurin inhibitor-induced Nephrotoxicity

    PubMed Central

    Takasu, Chie; Vaziri, Nosratola D.; Li, Shiri; Robles, Lourdes; Vo, Kelly; Takasu, Mizuki; Pham, Christine; Liu, Shuman; Farzaneh, Seyed H.; Foster, Clarence E; Stamos, Michael J; Ichii, Hirohito

    2014-01-01

    Background Cyclosporine A (CsA) is an immunosuppressive drug which has been widely used to prevent rejection following organ transplantation. However, its therapeutic use is limited by nephrotoxicity, in part mediated by oxidative stress. The present study aims to investigate the protective effects of Dimethyl Fumarate (DMF) on CsA-induced nephrotoxicity by enhancing the antioxidant defense system. Methods Male Sprague-Dawley rats were treated with CsA (n=8, 20 mg/kg/day i.p.) orCsA + DMF (n=7, 50 mg/kg/day p.o.) for 28 days. Renal function, histopathology, malondialdehyde (MDA), myeloperoxidase (MPO) levels and anti-oxidant enzyme expression were determined. Results DMF co-treatment ameliorated CsA-induced renal dysfunction as evidenced by significant decrease in serum creatinine (CsA 0.79 ± 0.02 mg/dl vs. CsA + DMF 0.62 ± 0.04 mg/dl, P=0.001) and urea (CsA 66.9 ± 0.4 mg/dl vs. CsA + DMF 53.3 ± 2.6 mg/dl, P<0.0001) levels, as well as improvement of creatinine clearance. DMF also significantly decreased serum MDA and renal tissue MDA and MPO contents. The protein expression of NQO-1, a major cellular anti-oxidant and detoxifying enzyme was significantly enhanced by DMF administration in kidney. Conclusions Administration of DMF has a protective potential against CsA nephrotoxicity. The protection afforded by DMF is mediated in part through inhibiting oxidative stress and inflammation and enhancing the antioxidant capacity. PMID:25710612

  2. Relationship of Neurocognitive Function to Breast Cancer Treatment and Induced Menopause

    DTIC Science & Technology

    2005-05-01

    AD Award Number: W81XWH-04-1-0528 TITLE: Relationship of Neurocognitive Function to Breast Cancer Treatment and Induced Menopause PRINCIPAL...Neurocognitive Function (NCF) to Breast Cancer Treatment and Induced Menopause. The grant has a training component and a research component. The training...April 8, 2005. * Relationship of Neurocognitive Function to Breast Cancer Treatment and Induced Menopause, University of Connecticut Health Center

  3. Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.

    PubMed

    Zeitler, Heike; Balta, Zeynep; Klein, Burkhard; Strassburg, Christian P

    2015-08-01

    Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia-induced pancreatitis (HTGP). The rationale behind this approach is the depletion of triglycerides and the reduction of inflammatory cytokines. The time span between onset of clinical symptoms and start of plasmapheresis might have an important impact on mortality. Hyperviscosity of patients' plasma represents another special challenge for the applied separation technology. The procedures can be performed either by centrifugal device (CFD) or membrane based (MBS) units. The present study reports the outcome of 10 patients suffering from HTG. The expected mortality of the collective was 25%. Plasmapheresis was started after an average 16.3 h (SD ± 6.7 h) after onset of symptoms. No mortality occurred. Apheresis was statistically equally effective with both devices. A median of 3 sessions reduced the TG level to normal and correlated with patients' improvement. During follow up, three patients developed a pancreatic pseudocyst requiring surgical intervention without further complication.

  4. Sample treatment and preparation for laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Jantzi, Sarah C.; Motto-Ros, Vincent; Trichard, Florian; Markushin, Yuri; Melikechi, Noureddine; De Giacomo, Alessandro

    2016-01-01

    One of the most widely cited advantages of laser-induced breakdown spectroscopy (LIBS) is that it does not require sample preparation, but this may also be the biggest factor holding it back from becoming a mature analytical technique like LA-ICP-MS, ICP-OES, or XRF. While there are certain specimen types that have enjoyed excellent LIBS results without any sample treatment (mostly homogeneous solids such as metals, glass, and polymers), the possible applications of LIBS have been greatly expanded through the use of sample preparation techniques that have resulted in analytical performance (i.e., limits of detection, accuracy, and repeatability) on par with XRF, ICP-OES, and often ICP-MS. This review highlights the work of many LIBS researchers who have developed, adapted, and improved upon sample preparation techniques for various specimen types in order to improve the quality of the analytical data that LIBS can produce in a large number of research domains. Strategies, not only for solids, but also liquids, gases, and aerosols are discussed, including newly developed nanoparticle enhancement and biological imaging and tagging techniques.

  5. Treatment and Prevention of Heparin-Induced Thrombocytopenia

    PubMed Central

    Dans, Antonio L.; Moores, Lisa K.; Bona, Robert; Davidson, Bruce L.; Schulman, Sam; Crowther, Mark

    2012-01-01

    Background: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Methods: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Conclusions: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed. PMID:22315270

  6. Treatment induced diabetic neuropathy– a reversible painful autonomic neuropathy

    PubMed Central

    Gibbons, Christopher H; Freeman, Roy

    2011-01-01

    Objective To describe the natural history, clinical, neurophysiological and histological features and outcomes of diabetic patients presenting with acute painful neuropathy associated with glycemic control, also referred to as ‘insulin neuritis’. Methods Sixteen subjects, presenting with acute painful neuropathy had neurological and retinal examinations, laboratory studies, autonomic testing and pain assessments over 18 months. Eight subjects had skin biopsies for evaluation of intra-epidermal nerve fiber density. Results All subjects developed severe pain within 8 weeks of intensive glucose control. There was a high prevalence of autonomic cardiovascular, gastrointestinal, genitourinary, and sudomotor symptoms in all subjects. Orthostatic hypotension and parasympathetic dysfunction were seen in 69% of subjects. Retinopathy worsened in all subjects. Reduced intra-epidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results and IENFD. Greater improvements were seen after 18 months in type 1 vs. type 2 diabetic subjects in autonomic symptoms (cardiovascular p<0.01; gastrointestinal p<0.01; genitourinary p<0.01) and autonomic function tests (p<0.01, sympathetic and parasympathetic function tests). Interpretation Treatment induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration and autonomic dysfunction after intensive glycemic control. The neuropathy occurred in parallel with worsening diabetic retinopathy suggesting a common underlying pathophysiological mechanism. Clinical features and objective measures of small myelinated and unmyelinated nerve fibers can improve in these diabetic patients despite a prolonged history of poor glucose control, with greater improvement seen in patients with type 1 diabetes. PMID:20437589

  7. Novel antioxidant capability of titanium induced by UV light treatment.

    PubMed

    Ueno, Takeshi; Ikeda, Takayuki; Tsukimura, Naoki; Ishijima, Manabu; Minamikawa, Hajime; Sugita, Yoshihiko; Yamada, Masahiro; Wakabayashi, Noriyuki; Ogawa, Takahiro

    2016-11-01

    The intracellular production of reactive oxygen species (ROS) is a representative form of cellular oxidative stress and plays an important role in triggering adverse cellular events, such as the inflammatory reaction and delayed or compromised differentiation. Osteoblastic reaction to titanium with particular focus on ROS production remains unknown. Ultraviolet (UV) light treatment improves the physicochemical properties of titanium, specifically the induction of super hydrophilicity and removal of hydrocarbon, and eventually enhances its osteoconductivity. We hypothesized that there is a favorable regulatory change of ROS production within osteoblasts in contact with UV-treated titanium. Osteoblasts were cultured on titanium disks with or without UV-pretreatment. The intracellular production of ROS was higher on acid-etch-created rough titanium surfaces than on machine-prepared smooth ones. The ROS production was reduced by 40-50% by UV pretreatment of titanium regardless of the surface roughness. Oxidative DNA damage, as detected by 8-OHdG expression, was alleviated by 50% on UV-treated titanium surfaces. The expression of inflammatory cytokines was consistently lower in osteoblasts cultured on UV-treated titanium. ROS scavenger, glutathione, remained more without being depleted in osteoblasts on UV-treated titanium. Bio-burden test further showed that culturing osteoblasts on UV-treated titanium can significantly reduce the ROS production even with the presence of hydrogen peroxide, an oxidative stress inducer. These data suggest that the intracellular production of ROS and relevant inflammatory reaction, which unavoidably occurs in osteoblasts in contact with titanium, can be significantly reduced by UV pretreatment of titanium, implying a novel antioxidant capability of the particular titanium.

  8. Effective treatment of rat adjuvant-induced arthritis by celastrol

    PubMed Central

    Cascão, R.; Vidal, B.; Raquel, H.; Neves-Costa, A.; Figueiredo, N.; Gupta, V.; Fonseca, J.E.; Moita, L.F.

    2012-01-01

    We have previously reported an increase in interleukin (IL)-1β and IL-17 levels, and a continuous activation of caspase-1 in early rheumatoid arthritis (RA) patients. These results suggest that drugs targeting IL-1β regulatory pathways, in addition to tumor necrosis factor (TNF), may constitute promising therapeutic agents in early RA. We have recently used a THP-1 macrophage-like cell line to screen 2320 compounds for those that down-regulate both IL-1β and TNF secretion. Celastrol was one of the most promising therapeutic candidates identified in that study. Our main goal in the present work was to investigate whether administration of celastrol is able to attenuate inflammation in a rat model of adjuvant-induced arthritis (AIA). Moreover, since IL-1β is known to play a role in the polarization of Th17 cells, we also investigate whether administration of digoxin, a specific inhibitor of Th17 cells polarization, is able to attenuate inflammation in the same rat model. We found that celastrol administration significantly suppressed joint inflammation. The histological and immunohistochemical evaluation revealed that celastrol-treated rats had a normal joint structure with complete abrogation of the inflammatory infiltrate and cellular proliferation. In contrast, we observed that digoxin administration significantly ameliorated inflammation but only if administrated in the early phase of disease course (after 4 days of disease induction), and it was not efficient at inhibiting the infiltration of immune cells within the joint and in preventing damage. Thus, our results suggest that celastrol has significant anti-inflammatory and anti-proliferative properties and can constitute a potential anti-inflammatory drug with therapeutic efficacy in the treatment of immune-mediated inflammatory diseases such as RA. Furthermore, we find that early inhibition of Th17 cells polarization ameliorates arthritis but it is not as effective as celastrol. PMID:22415021

  9. Pharmacological preconditioning with hyperbaric oxygen: can this therapy attenuate myocardial ischemic reperfusion injury and induce myocardial protection via nitric oxide?

    PubMed

    Yogaratnam, Jeysen Zivan; Laden, Gerard; Guvendik, Lavent; Cowen, Mike; Cale, Alex; Griffin, Steve

    2008-09-01

    Ischemic reperfusion injury (IRI) is an inevitable part cardiac surgery such as coronary artery bypass graft (CABG). While ischemic hypoxia and the ensuing normoxic or hyperoxic reperfusion are critical to the initiation and propagation of IRI, conditioning myocardial cells to an oxidative stress prior to IRI may limit the consequences of this injury. Hyperbaric oxygen (HBO2) is a modality of treatment that is known to generate an oxidative stress. Studies have shown that treatment with HBO2 postischemia and reperfusion is useful in ameliorating myocardial IRI. Moreover, preconditioning the myocardium with HBO2 before reperfusion has demonstrated a myocardial protective effect by limiting the infarct size post ischemia and reperfusion. Current evidence suggests that HBO2 preconditioning may partly attenuate IRI by stimulating the endogenous production of nitric oxide (NO). As NO has the capacity to reduce neutrophil sequestration, adhesion and associated injury, and improve vascular flow, HBO2 preconditioning induced NO may play a role in providing myocardial protection during interventions that involve an inevitable episode of IRI. This current opinion review article attempts to suggest that HBO2 may be used to pharmacologically precondition and protect the myocardium from the effects of IRI that is known to occur during cardiac surgery.

  10. Oxygen-induced changes in mitochondrial DNA and DNA repair enzymes in aging rat lens.

    PubMed

    Zhang, Yi; Ouyang, Shan; Zhang, Lan; Tang, Xianling; Song, Zhen; Liu, Ping

    2010-01-01

    The treatment of patients with hyperbaric oxygen (HBO), vitrectomy and loss of vitreous gel during aging is associated with a high risk of subsequent development of nuclear cataract. Many studies proved that oxidation is the key reason of nuclear cataract. Reactive oxygen species (ROS) are formed in mitochondria as a by-product of normal metabolism and as a consequence of exposure to environmental compounds. Therefore, mitochondrial DNA (mtDNA) is at particularly high risk of ROS-induced damage. Oxidative damage to mtDNA has been implicated as a causative factor in a wide variety of degenerative diseases and aging. However, the effect of mtDNA damage to the lens has not been studied. The goals of the study were to identify if there was increased mtDNA damage in lens when the eye were exposed to hyperoxic or hypoxic conditions and also to evaluate the changes in gene expression of mtDNA base excision repair (mtBER) enzymes. Our data have shown that the damage of mtDNA, the expression of mtBER enzymes and the level of 8-OHdG in lens increased after inspired hyperoxia, which is likely associated with oxidative stress. However, there was no effect to mtDNA and mtBER enzymes in lens after inspired hypoxia. Nuclear cataract appeared rapidly at 14 month old rats in hyperoxia group, and lens kept transparency in other groups.

  11. Medication-induced osteoporosis: screening and treatment strategies

    PubMed Central

    Panday, Keshav; Gona, Amitha

    2014-01-01

    Drug-induced osteoporosis is a significant health problem and many physicians are unaware that many commonly prescribed medications contribute to significant bone loss and fractures. In addition to glucocorticoids, proton pump inhibitors, selective serotonin receptor inhibitors, thiazolidinediones, anticonvulsants, medroxyprogesterone acetate, aromatase inhibitors, androgen deprivation therapy, heparin, calcineurin inhibitors, and some chemotherapies have deleterious effects on bone health. Furthermore, many patients are treated with combinations of these medications, possibly compounding the harmful effects of these drugs. Increasing physician awareness of these side effects will allow for monitoring of bone health and therapeutic interventions to prevent or treat drug-induced osteoporosis. PMID:25342997

  12. NLRP3 protein deficiency exacerbates hyperoxia-induced lethality through Stat3 protein signaling independent of interleukin-1β.

    PubMed

    Mizushina, Yoshiko; Shirasuna, Koumei; Usui, Fumitake; Karasawa, Tadayoshi; Kawashima, Akira; Kimura, Hiroaki; Kobayashi, Motoi; Komada, Takanori; Inoue, Yoshiyuki; Mato, Naoko; Yamasawa, Hideaki; Latz, Eicke; Iwakura, Yoichiro; Kasahara, Tadashi; Bando, Masashi; Sugiyama, Yukihiko; Takahashi, Masafumi

    2015-02-20

    Supplemental oxygen inhalation is frequently used to treat severe respiratory failure; however, prolonged exposure to hyperoxia causes hyperoxic acute lung injury (HALI), which induces acute respiratory distress syndrome and leads to high mortality rates. Recent investigations suggest the possible role of NLRP3 inflammasomes, which regulate IL-1β production and lead to inflammatory responses, in the pathophysiology of HALI; however, their role is not fully understood. In this study, we investigated the role of NLRP3 inflammasomes in mice with HALI. Under hyperoxic conditions, NLRP3(-/-) mice died at a higher rate compared with wild-type and IL-1β(-/-) mice, and there was no difference in IL-1β production in their lungs. Under hyperoxic conditions, the lungs of NLRP3(-/-) mice exhibited reduced inflammatory responses, such as inflammatory cell infiltration and cytokine expression, as well as increased and decreased expression of MMP-9 and Bcl-2, respectively. NLRP3(-/-) mice exhibited diminished expression and activation of Stat3, which regulates MMP-9 and Bcl-2, in addition to increased numbers of apoptotic alveolar epithelial cells. In vitro experiments revealed that alveolar macrophages and neutrophils promoted Stat3 activation in alveolar epithelial cells. Furthermore, NLRP3 deficiency impaired the migration of neutrophils and chemokine expression by macrophages. These findings demonstrate that NLRP3 regulates Stat3 signaling in alveolar epithelial cells by affecting macrophage and neutrophil function independent of IL-1β production and contributes to the pathophysiology of HALI. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Electrically Induced Redox Barriers for Treatment of Groundwater

    DTIC Science & Technology

    2008-12-01

    2  Methods and Materials...9  Methods and Materials...electrodes that provide equivalent or better performance in terms of electrode longevity and/or treatment efficacy. Methods and Materials Primary

  14. Treatment-Induced Autophagy Associated with Tumor Dormancy and Relapse

    DTIC Science & Technology

    2015-07-01

    called ICON (402– 404)) can treat pathological angiogenesis- dependent diseases, including cancer and many non -cancerous diseases. Under physiological...we determine the relationship(s) between immunogenic versus non -immunogenic tumor dormancy and autophagy. Major accomplishments: ADR...experiments demonstrate distinct differences in the nature of autophagy induced by ADR ( non -protective or cytotoxic) and radiation (protective) in

  15. New Treatment Strategies for Alcohol-Induced Heart Damage

    PubMed Central

    Fernández-Solà, Joaquim; Planavila Porta, Ana

    2016-01-01

    High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use. PMID:27690014

  16. Ultrasonically Induced Enhancement in Treatment of Livestock Waste Sludge

    NASA Astrophysics Data System (ADS)

    Park, Jiho; Kim, Young Uk; Lee, Jong-Sub; Wang, Mian Chen

    2009-07-01

    The effects of ultrasound on the total mass, dewaterability, turbidity, and coliform counts of livestock waste sludge were investigated. The study involved laboratory tests and a pilot plant experiment under various test conditions including treatment time, ultrasonic energy level, and sludge volume. Laboratory test results showed that ultrasound caused the decreases in sludge particle size, capillary suction time, and coliform counts. The results of the pilot plant experiment proved that ultrasonic treatment significantly enhances the dewaterability, volume, mass, and water content of sludge.

  17. Treatment of clozapine- and molindone-induced agranulocytosis with granulocyte colony-stimulating factor.

    PubMed

    Geibig, C B; Marks, L W

    1993-10-01

    To report a case of clozapine- and molindone-induced agranulocytosis and to discuss treatment using filgrastim, a granulocyte colony-stimulating factor. A 64-year-old woman who had been on long-term clozapine therapy for schizophrenia was hospitalized with presumed drug-induced agranulocytosis. She had also been on short-term molindone therapy. A bone marrow biopsy and the initial white blood cell (WBC) count were consistent with drug-induced agranulocytosis. Following seven days of treatment with subcutaneous filgrastim 300 micrograms/d, her absolute neutrophil count was above 500 x 10(6)/L. Reports in the literature discussing antipsychotic drug-induced agranulocytosis are reviewed. A relationship between treatment with filgrastim and WBC response is postulated. Filgrastim may be useful in ameliorating the effects of clozapine- and molindone-induced agranulocytosis.

  18. Effective treatment of d-penicillamine induced elastosis perforans serpiginosa with ALA-PDT.

    PubMed

    Wang, Duoqin; Liang, Jun; Xu, Jinhua; Chen, Lianjun

    2015-03-01

    A case of D-penicillamine(DPA) induced elastosis perforans serpiginosa(EPS) in a 32-year-old Chinese man was reported. The presentation lasted two years and was refractory to traditional medical treatment. He was then commenced on 7.6% 5-aminolevulinic acid (ALA) induced photodynamic therapy(PDT) by a LED light of 633 nm at dose levels of 130J/ cm2 for each session with total 3 sessions at one week interval. The patient was tolerated and responded well to this new approach for DPA-induced EPS without any adverse events. The etiology, pathophysiology, natural history, and treatment options for DPA-induced EPS are reviewed, and the authors suggest this method of treatment to be effective and safe for patients of DPA-induced EPS refractory to conventional therapy.

  19. Antipsychotic induced metabolic changes & treatment response: a prospective study.

    PubMed

    Sharma, Eesha; Venkatasubramanian, Ganesan; Varambally, Shivarama; Sivakumar, Palanimuthu T; Subbakrishna, Doddaballapur K; Gangadhar, Bangalore N

    2014-10-01

    Metabolic side effects of antipsychotics contribute to morbidity and non-compliance in treatment of psychosis. Multiple studies suggest that metabolic side effects correlate with response to antipsychotic treatment. However, few studies have systematically looked at this. We conducted an exploratory, naturalistic, prospective, trans-diagnostic study to examine this association. 100 patients with psychosis, initiated on antipsychotic treatment alone, were assessed on Brief Psychiatric Rating Scale (BPRS), visual analog scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and fasting serum lipid and glucose profiles at baseline, 2-4 weeks (n=71) and 8-12 weeks (n=39). Subjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2-4 weeks) increase in appetite and triglyceride levels (R(2)=0.257; p=0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2-4 weeks) increase in triglyceride levels (R(2)=0.169; p=0.009). Early appetite and triglyceride changes predicted antipsychotic treatment response. Involvement of dopaminergic, serotonergic and histaminergic neural pathways could explain the association between appetite and treatment response. Insulin signaling pathways have been implicated in lipid changes with antipsychotics. Study findings suggest metabolic side effects may be early predictors of antipsychotic response. These findings warrant further examination to elucidate the interaction between metabolic pathways and psychotic illnesses, and possibly mechanism of action of antipsychotics beyond dopamine blockade. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Neuroprotective Strategies for the Treatment of Blast-Induced Optic Neuropathy

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0559 TITLE: Neuroprotective Strategies for the Treatment of Blast-Induced Optic Neuropathy PRINCIPAL INVESTIGATOR...potential, and optical coherence tomography. Finally, a pre-application to the DoD for a clinical study was invited for a full submission. 15...Prescribed by ANSI Std. Z39.18 Neuroprotective Strategies for the Treatment of Blast-Induced Optic Neuropathy None provided. Table of Contents

  1. Evaluation of ADD392124 for the Delayed Treatment of Nerve Agent-Induced Status Epilepticus Seizures

    DTIC Science & Technology

    2011-09-01

    Induced Status Epilepticus Seizures John H. McDonough Kerry E. Van Shura Megan E. Lyman Claire G. Eisner Amelia Mazza Robert K. Kan Tsung...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Evaluation of ADD392124 for the delayed treatment of nerve agent-induced status epilepticus seizures 5b... status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a

  2. Research in Prevention and Treatment of Noise-Induced Hearing Loss (NIHL)

    DTIC Science & Technology

    2013-04-01

    Noise-Induced Hearing Loss ( NIHL ) PRINCIPAL INVESTIGATOR: Dr. Kathleen Campbell...Prevention and Treatment of Noise-Induced Hearing Loss ( NIHL ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0031 5c. PROGRAM ELEMENT NUMBER...methionine Dose Response Curves for Prevention of Noise Induced Hearing Loss ( NIHL ) for Steady State and Impulse Noise Target required for clinical

  3. Valproic-acid-induced thrombocytopenia and hepatotoxicity: discontinuation of treatment?

    PubMed

    Lackmann, Gerd-Michael

    2004-02-01

    We report the case of a 4-year-old boy with long-term sodium valproate (valproic acid; VPA) therapy who suddenly developed clinically relevant thrombocytopenia and signs of hepatotoxicity. Reduction of the VPA dosage led to clinical and laboratory parameter improvement, while discontinuation of therapy was not necessary. The current practice of the management of VPA-induced side effects is discussed in view of the current recommendations from the literature. Copyright 2004 S. Karger AG, Basel

  4. Electrically Induced Redox Barriers for Treatment of Groundwater

    DTIC Science & Technology

    2005-03-01

    Chloride Calcium Nitrate Potassium Nitrite Magnesium Phosphate Sodium Fluoride Iron Sulfate Manganese Carbonate Chromium Bicarbonate Cadmium...mediated under field conditions. To assess changes in the microbial populations induced by the operation of the e-barrier, and to obtain a first-level...analysis and (b) total soil microbial DNA measurements. Produced Gases – At an electrical potential of 6.5 volts, gases were collected from the surface

  5. Movement disorders induced in monkeys by chronic haloperidol treatment.

    PubMed

    Weiss, B; Santelli, S; Lusink, G

    1977-08-16

    After several months of treatment, Cebus apella, Cebus albifrons, and Saimiri sciurea monkeys maintained on haloperidol, in doses of 0.5 or 1.0 mg/kg orally 5 days per week, began to display severe movement disorders, typically 1-6 h post-drug. Cebus monkeys exhibited violent, uncontrolled movements that flung the animals about the cage. Such episodes usually lasted only a few minutes, recurring several times during the period following drug ingestion. Writhing and bizarre postures dominated the response in S. sciurea. Cessation of drug treatment produced no distinctive after-effects. When tested as long as 508 days after the last administration, however, Cebus monkeys responded to haloperidol with several episodes of hyperkinesis, even at challenge doses considerably lower than those in the original treatment.

  6. Corneal toxicity induced by vesicating agents and effective treatment options

    PubMed Central

    Goswami, Dinesh G.; Tewari-Singh, Neera; Agarwal, Rajesh

    2016-01-01

    The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial (HCE) cells and rabbit corneal organ culture models with the SM analog nitrogen mustard (NM), which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries. PMID:27327041

  7. Carnitine in the treatment of valproic acid-induced toxicity.

    PubMed

    Lheureux, Philippe E R; Hantson, Philippe

    2009-02-01

    Valproic acid (VPA) is a broad-spectrum antiepileptic drug that is now used commonly for several other neurological and psychiatric indications. VPA is usually well tolerated, but serious complications, including hepatotoxicity and hyperammonemic encephalopathy, may occur. These complications may also arise following acute VPA overdose, the incidence of which is increasing. Intoxication usually only results in mild central nervous system depression, but serious toxicity and death have been reported. As a branched chain carboxylic acid, VPA is extensively metabolized by the liver via glucuronic acid conjugation, mitochondrial beta- and cytosolic omega-oxidation to produce multiple metabolites, some of which may be involved in its toxicity. Carnitine is an amino acid derivative that is an essential cofactor in the beta-oxidation of fatty acids. It is synthesized endogenously from the essential amino acids, methionine and lysine. VPA inhibits the biosynthesis of carnitine by decreasing the concentration of alpha-ketoglutarate and may contribute to carnitine deficiency. It is postulated that carnitine supplementation may increase the beta-oxidation of VPA, thereby limiting cytosolic omega-oxidation and the production of toxic metabolites that are involved in liver toxicity and ammonia accumulation. VPA-induced hepatotoxicity and hyperammonemic encephalopathy may be promoted either by a pre-existing carnitine deficiency or by deficiency induced by VPA per se. Some experimental and clinical data suggest that early intravenous supplementation with l-carnitine could improve survival in severe VPA-induced hepatotoxicity. Carnitine administration has been shown to speed the decrease of ammonemia in patients with VPA-induced encephalopathy although a correlation between ammonia concentrations and the clinical condition was not always observed. As it does not appear to be harmful, l-carnitine is commonly recommended in severe VPA poisoning, especially in children, although the

  8. [Medical treatment of chemotherapy-induced nausea and vomiting].

    PubMed

    Herrstedt, Jørn

    2007-02-26

    Patients consider nausea and vomiting among the worst side effects of chemotherapy. This paper reviews the development of antiemetics during the past 12 years, focusing on the neurokinin (NK)1-receptor antagonist, aprepitant, and the new 5-HT3-receptor antagonist palonosetron. Evidence-based recommendations for prophylaxis of chemotherapy-induced nausea and vomiting are given. Antiemetics are effective in prevention of vomiting, but less effective against nausea. Therefore studies with potential new antiemetics, such as olanzapine and ghrelin are awaited with suspense.

  9. Successful treatment of hydromorphone-induced neurotoxicity and hyperalgesia.

    PubMed

    Chung, Keun Sam; Carson, Shawn; Glassman, David; Vadivelu, Nalini

    2004-10-01

    There has been an increase in opioid consumption world wide in the last decade. There has also been a disturbing increase in the number of reports of neuroexcitatory opioid-related side effects observed in patients receiving large doses of systemically administered morphine and its structural analogue, hydromorphone. It is now becoming clearer that patients receiving long-term opioid therapy can develop unexpected pain. We describe an interesting case of successful management of hydromorphone-induced neurotoxicity and hyperalgesia produced by short-term therapy with rapidly escalating doses of systemic hydromorphone.

  10. Botulinum toxin in the treatment of lingual dystonia induced by speaking.

    PubMed

    Budak, F; Aydın, E; Koçkaya, A; Ilbay, G

    2013-01-01

    Primary lingual dystonia is a rare condition, especially when it is only induced by speaking. Trihexyphenidyl failed to improve the symptoms. Several case series have demonstrated the effectiveness of botulinum toxin injection for the management of focal lingual movement disorders. Only 1 case of botulinum toxin injection for primary lingual dystonia induced by speaking has been reported, but this treatment has limited effectiveness. Our patient was treated with botulinum toxin using a superficial approach for injection into the tongue with continuing excellent results. Lingual botulinum toxin injection is a fairly simple, safe and viable treatment option for lingual dystonia induced by speaking.

  11. Systemic Treatment in HPV-Induced Recurrent or Metastatic HNSCC.

    PubMed

    Rieke, Damian T; Keilholz, Ulrich

    Recurrent or metastatic head and neck cancer describes tumor deposits that arise locally, regionally, or at distant sites after treatment or distant metastases at the time of primary diagnosis. Prognosis for R/M squamous cell carcinomas of the head and neck (HNSCC) is poor and treatment options are limited in this situation. Human papillomavirus (HPV) is an important risk factor for HNSCC. About 40 % of all HNSCC have been attributed to HPV in Europe. HPV positivity at initial diagnosis is the single best prognostic factor for survival. However, data for the prognostic and predictive value of HPV in the R/M situation are still scarce. Due to the rising incidence of HPV-associated cancers, the number of R/M HPV+ carcinomas is also expected to rise. This chapter therefore aims to give an overview of the current knowledge concerning the role of HPV as a prognostic and predictive marker in recurrent or metastatic HNSCC.

  12. Herbal Medicine as Inducers of Apoptosis in Cancer Treatment

    PubMed Central

    Safarzadeh, Elham; Sandoghchian Shotorbani, Siamak; Baradaran, Behzad

    2014-01-01

    Cancer is uncontrolled growth of abnormal cells in the body. Nowadays, cancer is considered as a human tragedy and one of the most prevalent diseases in the wide, and its mortality resulting from cancer is being increased. It seems necessary to identify new strategies to prevent and treat such a deadly disease. Control survival and death of cancerous cell are important strategies in the management and therapy of cancer. Anticancer agents should kill the cancerous cell with the minimal side effect on normal cells that is possible through the induction of apoptosis. Apoptosis is known as programmed cell death in both normal and damaged tissues. This process includes some morphologically changes in cells such as rapid condensation and budding of the cell, formation of membrane-enclosed apoptotic bodies with well-preserved organelles. Induction of apoptosis is one of the most important markers of cytotoxic antitumor agents. Some natural compounds including plants induce apoptotic pathways that are blocked in cancer cells through various mechanisms in cancer cells. Multiple surveys reported that people with cancer commonly use herbs or herbal products. Vinca Alkaloids, Texans, podo phyllotoxin, Camptothecins have been clinically used as Plant derived anticancer agents. The present review summarizes the literature published so far regarding herbal medicine used as inducers of apoptosis in cancer. PMID:25364657

  13. Lead induced spermatoxicity in mouse and MPG treatment.

    PubMed

    Gautam, A K; Agarwal, K; Shah, B A; Kumar, S; Saiyed, H N

    2001-10-01

    Protective efficacy of MPG (2-mercaptopropionyl glycine) was studied against the toxic effects of lead acetate in Swiss albino mice. The animals were treated with single dose of lead acetate @ 180, 200 and 250 mg/kg b.wt. in presence and absence of MPG. The results indicated that the body weight was slightly higher in MPG treated groups on day 10 as compared to only respective lead treated groups in all the three dose level. However, significantly lower body weight was observed in both lead treated and lead along with MPG treated groups as compared to control. Patten of mortality is similar in both lead treated and lead plus MPG treated groups. Conspicuous degenerative changes in testicular tissues and elevation in sperm head shape abnormality were observed in both lead treated and lead along with MPG treated groups but the sperm head shape abnormality and damage were more in lead treated groups as compared to lead plus MPG treated groups. But this difference was non-significant between the two groups. These observations suggest that MPG may not be significantly effective against lead induced damage in testicular tissues at cellular level. However, MPG is able to maintain slightly lower level of sperm abnormality in all the three dose level as compared to their respective lead treated groups. Further, studies are needed to find out the optimum dose of MPG for protection against the lower doses of lead induced lethality as MPG is not significantly effective against the higher doses of lead.

  14. Volume changes of human endothelial cells induced by photodynamic treatment

    NASA Astrophysics Data System (ADS)

    Leunig, Andreas; Staub, Frank; Plesnila, Nick; Peters, Jurgen; Feyh, Jens; Gutmann, Ralph; Goetz, Alwin E.

    1996-01-01

    Photodynamic therapy (PDT) has shown promising results in treatment of malignant tumors. However, the mechanisms leading to tumor destruction during PDT are still not completely understood. In addition to effects on the microcirculation, damage to cellular structures has been observed following exposure of cells to PDT. A phenomenon preceding these events might possibly be cell swelling. We therefore studied the influence of treatment with Photofrin (PF) and laser light on volume changes and cell viability of endothelial cells. Endothelial cells were obtained from human umbilical cord veins (HUVEC) by an adaption of the method of Maruyama (1963). After subcultivation the cells were harvested and transferred as a cell suspension into a specially designed incubation chamber. Cells received either PF in concentrations of 1.5 or 3.0 (mu) g/ml and laser illumination (630 nm; 40 mW/cm2, 4 Joule), PF alone, or laser treatment only. Following start of PF incubation and after phototreatment cell samples were taken for volume measurements using flow cytometry and for studies of cellular morphology using scanning electron microscopy. Simultaneously, cell viability was monitored by the trypan blue exclusion test and colorimetric MTT assay. (abstract truncated)

  15. Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast.

    PubMed

    Cai, Wen-Wen; Zhang, Ming-Hua; Yu, Yong-Sheng; Cai, Jin-Hua

    2013-01-01

    Tumor necrosis factor-alpha (TNFα) plays a crucial role in inflammatory diseases such as rheumatoid arthritis and postmenopausal osteoporosis. Recently, it has been demonstrated that hydrogen gas, known as a novel antioxidant, can exert therapeutic anti-inflammatory effect in many diseases. In this study, we investigated the effect of treatment with hydrogen molecule (H(2)) on TNFα-induced cell injury in osteoblast. The osteoblasts isolated from neonatal rat calvariae were cultured. It was found that TNFα suppressed cell viability, induced cell apoptosis, suppressed Runx2 mRNA expression, and inhibited alkaline phosphatase activity, which was reversed by co-incubation with H(2). Incubation with TNFα-enhanced intracellular reactive oxygen species (ROS) formation and malondialdehyde production increased NADPH oxidase activity, impaired mitochondrial function marked by increased mitochondrial ROS formation and decreased mitochondrial membrane potential and ATP synthesis, and suppressed activities of antioxidant enzymes including SOD and catalase, which were restored by co-incubation with H(2). Treatment with H(2) inhibited TNFα-induced activation of NFκB pathway. In addition, treatment with H(2) inhibited TNFα-induced nitric oxide (NO) formation through inhibiting iNOS activity. Treatment with H(2) inhibited TNFα-induced IL-6 and ICAM-1 mRNA expression. In conclusion, treatment with H(2) alleviates TNFα-induced cell injury in osteoblast through abating oxidative stress, preserving mitochondrial function, suppressing inflammation, and enhancing NO bioavailability.

  16. Clinical Features, Pathophysiology, and Treatment of Levodopa-Induced Dyskinesias in Parkinson's Disease

    PubMed Central

    Guridi, J.; González-Redondo, R.; Obeso, J. A.

    2012-01-01

    Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood. PMID:23125942

  17. Radiographic assessment of photodynamic therapy as an adjunctive treatment on induced periodontitis in immunosuppressed rats

    PubMed Central

    FERNANDES, Leandro Araújo; MARTINS, Thiago Marchi; de ALMEIDA, Juliano Milanezi; THEODORO, Letícia Helena; GARCIA, Valdir Gouveia

    2010-01-01

    Objective The aim of this study was to assess radiographically the effect of photodynamic therapy (PDT) as an adjunctive treatment to scaling and root planing (SRP) on induced periodontitis in dexamethasone-induced immunosuppressed rats. Material and Methods The animals were divided into 2 groups: ND group (n=60): saline treatment; D group (n=60): dexamethasone treatment. In both ND and D groups, periodontal disease was induced by the placement of a ligature in the left first mandibular molar. After 7 days, ligature was removed and all animals received SRP, being divided according to the following treatments: SRP: saline and PDT: phenothiazinium dye (TBO) plus laser irradiation. Ten animals per treatment were killed at 7, 15 and 30 days. The distance between the cementoenamel junction and the height of the alveolar bone crest in the mesial surface of the mandibular left first molars was determined in millimeters in each radiograph. The radiographic values were analyzed statistically by ANOVA and Tukey's test at a p value <0.05. Results Intragroup radiographic assessment (ND and D groups) showed that there was statistically significant less bone loss in the animals treated with PDT in all experimental periods compared to those submitted to SRP. Intergroup radiographic analysis (ND and D groups) demonstrated that there was greater bone loss in the ND group treated with SRP compared to the D group treated with PDT at 7 and 30 days. Conclusion PDT was an effective adjunctive treatment to SRP on induced periodontitis in dexamethasone-induced immunosuppressed rats. PMID:20857000

  18. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis.

    PubMed

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-16

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection.

  19. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis

    PubMed Central

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-01

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection. PMID:25596288

  20. A Novel Combination of Thermal Ablation and Heat-Inducible Gene Therapy for Breast Cancer Treatment

    DTIC Science & Technology

    2007-04-01

    and Heat-Inducible Gene Therapy for Breast Cancer Treatment PRINCIPAL INVESTIGATOR: Yunbo Liu...Breast Cancer Treatment 5b. GRANT NUMBER W81XWH-06-1-0461 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Yunbo Liu Pei Zhong...therapy (via the control of hsp70B-heat shock promoter) to improve the overall efficiency of breast cancer treatment . In the first year of the project

  1. Ceramic surface modifications induced by pulsed laser treatment

    NASA Astrophysics Data System (ADS)

    Cappelli, E.; Orlando, S.; Sciti, D.; Montozzi, M.; Pandolfi, L.

    2000-02-01

    Technical polycrystalline sintered Al 2O 3 (90%) substrates have been irradiated, in a vacuum chamber, at grazing incident angles (˜30°), with pulsed ArF ( λ=193 nm, hν=6.4 eV) excimer laser, at different fluences and numbers of pulses, to modify the structure and morphology of the surface. Vacuum, inert gas and oxygen atmospheres, at different substrate temperatures, ˜25°C and ˜700°C, have been used to study surface chemistry and morphology modifications induced by laser energy. Surface chemistry has been analysed by XPS spectroscopy. Morphological modifications have been studied by SEM/EDS microscopy. Changes in surface roughness have been quantified by a standard profilometer.

  2. Surface modification of ceramic matrix composites induced by laser treatment

    NASA Astrophysics Data System (ADS)

    Costil, S.; Lukat, S.; Langlade, C.; Coddet, C.

    2008-12-01

    Ceramics or ceramic composites present many advantages (hardness, chemical resistance, low density, etc.) which induce some more and more important applications particularly from the industrial point of view. The evolution of technology can also be beneficial to enlarge their global application areas. This is particularly the aim of this work which consists in applying a laser beam on the ceramic in order to clean its surface. A Nd:YAG laser has been used to study the basic mechanism roughening the surface of silicon carbide composite (ceramic matrix composite (CMC)). Investigations on different surfaces (two chemical compositions) show a strong influence of the nature of the material on the development of a characteristic conic structure. Microscopic studies (SEM) and elementary analyses (EDS and RMS) demonstrated the formation of a regular cone-like structure with a kinetic and a chemical modification specific to each material.

  3. Late onset radioiodine-induced hypothyroidism presenting with psychosis 14 years after treatment: a rare case

    PubMed Central

    Er, Chaozer; Sule, Ashish Anil

    2016-01-01

    Radioiodine treatment-induced hypothyroid psychosis is uncommon. Our literature search shows only three cases of hypothyroid psychosis developed within 3 months after the radioiodine treatment. Our case represents the first case of radioiodine-induced hypothyroidism presenting as psychosis much later (14 years) after the radioiodine treatment. A 60-year-old Chinese lady, with long-standing primary hypothyroidism due to the radioiodine treatment performed 14 years ago, presented with a 1-week history of hallucination, delusion and agitation. She was not on thyroid replacement. Thyroid function test done 14 years ago and again upon her admission to our facility was consistent with primary hypothyroidism. General blood tests and brain imaging were unremarkable. Her psychotic features resolved within 1 week with thyroid replacement and 9 days of antipsychotics. No further relapse of psychosis was noted. This emphasizes that radioiodine-induced hypothyroidism can go unnoticed for many years and present much later solely as psychosis. PMID:27099771

  4. New treatments for levodopa-induced motor complications.

    PubMed

    Rascol, Olivier; Perez-Lloret, Santiago; Ferreira, Joaquim J

    2015-09-15

    Levodopa (l-dopa)-induced motor complications, including motor fluctuations and dyskinesia, affect almost all patients with Parkinson's disease (PD) at some point during the disease course, with relevant implications in global health status. Various dopaminergic and nondopaminergic pharmacological approaches as well as more invasive strategies including devices and functional surgery are available to manage such complications. In spite of undisputable improvements during the last decades, many patients remain significantly disabled, and a fully satisfying management of l-dopa-induced motor complications is still an important unmet need of PD therapy. This article reviews the recent trial results published from 2013 to April 2015 about pharmacological and nonpharmacological interventions to treat motor complications. Randomized controlled trials conducted in patients suffering from already established complications showed that new levodopa (l-dopa) formulations such as intrajejunal l-dopa-carbidopa infusion and bilayered extended-release l-dopa-carbidopa (IPX066) can improve motor fluctuations. Positive results were also obtained with a new monoamine oxidase B (MAO-B) inhibitor (safinamide) and a catechol-O-methyltransferase COMT inhibitor (opicapone). Pilot data suggest that new formulations of dopamine agonists (inhaled apomorphine) are also of potential interest. The development of novel nondopaminergic adenosine A2A antagonists (istradefylline, preladenant, and tozadenant) to treat motor fluctuations showed conflicting results in phase 2 and phase 3 trials. For dyskinesia, trials with new amantadine extended-release formulations confirmed the interest of the glutamatergic N-methyl-d-aspartate (NMDA) antagonist approach. Positive pilot antidyskinetic effects were also recently reported using serotonin agents such as eltoprazine and glutamate mGluR5 modulators such as mavoglurant. However, the translation to clinical practice of such innovative concepts remains

  5. Improved methodology to induce hyperoxaluria without treatment using hydroxyproline.

    PubMed

    Wiessner, John H; Garrett, Michael R; Hung, Linda Y; Wille, David F; Mandel, Neil S

    2011-10-01

    The use of hydroxyproline (HP) to generate hyperoxaluria in the rat is a problem because it is impossible to separate the effect of oxalate on renal injury from the effects of HP and the large array of metabolic intermediates formed when HP is converted to oxalate. Previously, the Dahl salt-sensitive (SS) and Brown Norway (BN) rat strains were studied to determine genetic control of resistance or susceptibility to HP-induced renal injury and crystal deposition. To develop a better model to induce hyperoxaluria without causing injury from HP metabolites, animals were fed a diet containing various levels of added oxalate (0, 1, 2, 3, or 5%). After 5 weeks rats were killed and the kidneys were removed for microscopic evaluation of tubule changes and crystal deposition. The 3 and 5% oxalate-fed groups had a substantial increase in urine oxalate, about 50 and 140 μmol/g body weight over controls, respectively. Both the SS and BN 3% oxalate-fed animals showed only slightly elevated tubule area and no crystal deposition. However, BN animals fed 5% oxalate had a dramatic increase in their percent tubule areas compared to control BN rats and treated SS rats. Crystal deposition in the kidneys was only observed in the 5% oxalate-fed groups. The BN kidneys demonstrated a threefold higher crystal deposition compared to oxalate-fed SS rats. We conclude that oxalate-supplemented food is a better method of producing hyperoxaluria in the rat than using HP which may introduce metabolic intermediates injurious to the kidney.

  6. Spinal cord injury-induced pain: mechanisms and treatments.

    PubMed

    Siddall, Philip J; Middleton, James W

    2015-01-01

    Pain is a common consequence of a spinal cord injury (SCI) and has a major impact on quality of life through its impact on physical function, mood and participation in work, recreational and social activities. Several types of pain typically present following SCI with central neuropathic pain being a frequent and difficult to manage occurrence. Despite advances in our understanding of the mechanisms contributing to this type of pain and an increasing number of trials examining treatment efficacy, our ability to relieve neuropathic SCI pain is still very limited. Optimal management relies upon an integrated approach that uses a combination of pharmacological and nonpharmacological options.

  7. Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

    NASA Astrophysics Data System (ADS)

    Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

    2004-03-01

    Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

  8. Early Dexamethasone Treatment Induces Placental Apoptosis in Sheep

    PubMed Central

    Meng, Wenbin; Shang, Hongkai; Li, Shaofu; Sloboda, Deborah M.; Ehrlich, Loreen; Lange, Karolin; Xu, Huaisheng; Henrich, Wolfgang; Dudenhausen, Joachim W.; Plagemann, Andreas; Newnham, John P.; Challis, John R. G.

    2015-01-01

    Glucocorticoid treatment given in late pregnancy in sheep resulted in altered placental development and function. An imbalance of placental survival and apoptotic factors resulting in an increased rate of apoptosis may be involved. We have now investigated the effects of dexamethasone (DEX) in early pregnancy on binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 49, intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at 40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and 140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax, p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC numbers and apoptotic markers were restored to normal. In males, ovine placental lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG significantly decreased compared to controls. In contrast to females, these changes were independent of altered BNC numbers or apoptotic markers. Early DEX was associated with sex-specific, transient alterations in BNC numbers, which may contribute to changes in placental and fetal development. Furthermore, in females, altered placental apoptosis markers may be involved. PMID:25063551

  9. Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease

    PubMed Central

    Pětrošová, Helena; Eshghi, Azad; Anjum, Zoha; Zlotnikov, Nataliya; Cameron, Caroline E.; Moriarty, Tara J.

    2017-01-01

    Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatment of bacterial infections in the context of obesity are scarce. To address this research gap, we assessed efficacy of antibiotic treatment in diet-induced obese mice infected with the Lyme disease pathogen, Borrelia burgdorferi. Diet-induced obese C3H/HeN mice and normal-weight controls were infected with B. burgdorferi, and treated during the acute phase of infection with two doses of tigecycline, adjusted to the weights of diet-induced obese and normal-weight mice. Antibiotic treatment efficacy was assessed 1 month after the treatment by cultivating bacteria from tissues, measuring severity of Lyme carditis, and quantifying bacterial DNA clearance in ten tissues. In addition, B. burgdorferi-specific IgG production was monitored throughout the experiment. Tigecycline treatment was ineffective in reducing B. burgdorferi DNA copies in brain. However, diet-induced obesity did not affect antibiotic-dependent bacterial DNA clearance in any tissues, regardless of the tigecycline dose used for treatment. Production of B. burgdorferi-specific IgGs was delayed and attenuated in mock-treated diet-induced obese mice compared to mock-treated normal-weight animals, but did not differ among experimental groups following antibiotic treatment. No carditis or cultivatable B. burgdorferi were detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses to B. burgdorferi, but did not affect efficacy of antibiotic treatment. PMID:28286500

  10. Advances in the treatment of virus-induced asthma.

    PubMed

    Tay, Hock; Wark, Peter A B; Bartlett, Nathan W

    2016-06-01

    Viral exacerbations continue to represent the major burden in terms of morbidity, mortality and health care costs associated with asthma. Those at greatest risk for acute asthma are those with more severe airways disease and poor asthma control. It is this group with established asthma in whom acute exacerbations triggered by virus infections remain a serious cause of increased morbidity. A range of novel therapies are emerging to treat asthma and in particular target this group with poor disease control, and in most cases their efficacy is now being judged by their ability to reduce the frequency of acute exacerbations. Critical for the development of new treatment approaches is an improved understanding of virus-host interaction in the context of the asthmatic airway. This requires research into the virology of the disease in physiological models in conjunction with detailed phenotypic characterisation of asthma patients to identify targets amenable to therapeutic intervention.

  11. An empirical extrapolation scheme for efficient treatment of induced dipoles

    NASA Astrophysics Data System (ADS)

    Simmonett, Andrew C.; Pickard, Frank C.; Ponder, Jay W.; Brooks, Bernard R.

    2016-10-01

    Many cutting edge force fields include polarization, to enhance their accuracy and range of applicability. In this work, we develop efficient strategies for the induced dipole polarization method. By fitting various orders of perturbation theory (PT) dipoles to a diverse training set, we arrive at a family of fully analytic methods — whose nth order is referred to OPTn — that span the full spectrum of polarization methods from the fast zeroth-order approach that neglects mutual dipole coupling, approaching the fully variational approach at high order. Our training set contains many difficult cases where the PT series diverges, and we demonstrate that our OPTn methods still deliver excellent results in these cases. Our tests show that the OPTn methods exhibit rapid convergence towards the exact answer with each increasing PT order. The fourth order OPT4 method, whose costs are commensurate with three iterations of the leading conjugate gradient method, is a particularly promising candidate to be used as a drop-in replacement for existing solvers without further parameterization.

  12. Penicillin-induced liver injury during treatment for ocular neurosyphilis.

    PubMed

    Wilkinson, Janelle; Zainal, Abir; Naqvi, Syed Yaseen

    2016-07-07

    A 51-year-old man, homosexual, recently diagnosed with ocular neurosyphilis, presented to the emergency room with a 1-day history of fevers and chills. His vital signs were significant for a temperature of 102.8°F and tachycardia of 125 bpm. The patient had experienced blurred vision in his left eye and was diagnosed with ocular neurosyphilis 10 days prior to the current presentation. He was treated with a 14-day course of high-dose intravenous penicillin and oral prednisone. His laboratory studies were significant for transaminitis, with an aspartate aminotransferase of 1826 U/L, alanine aminotransferase of 1743 U/L, total bilirubin of 1.2 mg/dL and alkaline phosphatase of 68 U/L. After ruling out viral aetiologies and toxin-induced hepatic injury, penicillin was discontinued on the day following admission and transaminases promptly improved with resolution of symptoms. The patient's vision returned to normal within 2 weeks after discharge from hospital.

  13. Repeated cocaine treatments induce distinct locomotor effects in crayfish.

    PubMed

    Nathaniel, Thomas I; Huber, Robert; Panksepp, Jaak

    2012-02-10

    A repeated injection of cocaine regime is known to induce complex locomotion alterations in both vertebrate and invertebrate models of drug addiction. However, the specific effect of cocaine on behaviorally distinct locomotion and non locomotion parameters is not well known. The present experiments determined whether cocaine has distinct effect on multifarious locomotor activity of crayfish (Orconectes rusticus). Following repeated injections of 2.5 μg/g or 10.0 μg/g dose of cocaine for three days, videotaped recordings of locomotion were analyzed to determine whether repeated injections of cocaine produced distinct effect on multifarious locomotor activity of crayfish. Cocaine decreased immobility in day 1 when compared with saline. Thereafter, cocaine increased immobility in days 2 and 3. Repeated injections of cocaine increased distance traveled, average speed, mobility and decreased lingering episodes. These findings indicate that cocaine has distinct action on movement and non-movement behavioral activities, suggesting that locomotion as a unitary phenomenon comprised of assemblage of multifarious components, which can be manipulated and separated by cocaine in crayfish. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Prevention and treatment of ulcers induced by nonsteroidal anti-inflammatory drugs: an update.

    PubMed

    Dajani, E Z; Agrawal, N M

    1995-03-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are most frequently used for the treatment of rheumatic disease due to their anti-inflammatory and analgesic properties. All NSAIDs have the potential to cause damage to the gastrointestinal (GI) tract and have been associated with the induction of peptic ulcers and massive life-threatening bleeding. The therapeutic approaches for the treatment and prevention of NSAID-induced ulcers is critically reviewed using data derived from carefully controlled, world-wide clinical studies with anti-ulcer drugs. Histamine (H2) antagonists, omeprazole, sucralfate and E-prostaglandin (PGE) analogs are effective for the treatment of NSAID-induced gastric and duodenal ulcers, if NSAIDs are discontinued. However, if NSAIDs are continued while GI damage is present, the PGE analogs misoprostol, arbaprostil and enprostil have shown efficacy in healing NSAID-induced ulcers. Furthermore, one limited clinical study demonstrated that omeprazole has efficacy in healing NSAID-associated ulcers. Neither H2 antagonists, sucralfate and sulglycotide (a cytoprotective drug) have shown efficacy in preventing NSAID-induced gastric ulcers. However H2 antagonists have shown efficacy in preventing NSAID-induced duodenal ulcers. In contrast, only misoprostol prevents the development of NSAID-induced gastric and duodenal ulcers. Such pharmacological observations suggest that the pathophysiologic mechanisms for the induction of NSAID-induced gastric ulcer are distinctly different from those of NSAID-induced duodenal ulcers. Mild diarrhea and GI intolerance were the predominant adverse reactions experienced by patients receiving synthetic PGEs, particularly enprostil and arbaprostil. From the published data, we conclude that misoprostol is the only anti-ulcer drug proven to be well tolerated and effective for the treatment and prevention of NSAID-induced gastric and duodenal ulcers in patients receiving chronic NSAIDs therapy.

  15. Time course of the attenuation effect of repeated antipsychotic treatment on prepulse inhibition disruption induced by repeated phencyclidine treatment

    PubMed Central

    Li, Ming; He, Erik; Volf, Nick

    2011-01-01

    Antagonism of prepulse inhibition (PPI) deficits produced by psychotomimetic drugs has been widely used as an effective tool for the study of the mechanisms of antipsychotic action and identifying potential antipsychotic drugs. Many studies have relied on the acute effect of a single administration of antipsychotics, whereas patients with schizophrenia are treated chronically with antipsychotic drugs. The clinical relevance of acute antipsychotic effect in this model is still an open question. In this study, we investigated the time course of repeated antipsychotic treatment on persistent PPI deficit induced by repeated phencyclidine (PCP) treatment. After a baseline test with saline, male Sprague-Dawley rats were repeatedly injected with either vehicle, haloperidol (0.05 mg/kg), clozapine (5.0 or 10.0 mg/kg), olanzapine (2.0 mg/kg), risperidone (1.0 mg/kg) or quetiapine (10 mg/kg), followed by PCP (1.5 mg/kg, sc) and tested for PPI once daily for 6 consecutive days. A single injection of PCP disrupted PPI and this effect was maintained with repeated PCP injections throughout the testing period. Acute clozapine, but not other antipsychotic drugs, attenuated acute PCP-induced PPI disruption at both tested doses. With repeated treatment, clozapine and quetiapine maintained their attenuation, while risperidone enhanced its effect with a significant reduction of PCP-induced disruption toward the end of treatment period. In contrast, repeated haloperidol and olanzapine treatments were ineffective. The PPI effects of these drugs were more conspicuous at a higher prepulse level (e.g. 82 dB) and were dissociable from their effects on startle response and general activity. Overall, the repeated PCP-PPI model appears to be a useful model for the study of the time-dependent antipsychotic effect, and may help identify potential treatments that have a quicker onset of action than current antipsychotics. PMID:21402097

  16. Assault induced stab injuries: epidemiology and actual treatment strategy.

    PubMed

    El-Abdellati, E; Messaoudi, N; Van Hee, R

    2011-01-01

    To investigate and analyse epidemiology, demographics and patterns of presentation of assault induced stab injuries in a main Belgian trauma centre. To evaluate surgical management, complications and postoperative follow-up of the stab wound victims. One hundred and seventy assaulted patients, hospitalised because of stab injuries from January 2000 to June 2007 are studied retrospectively. Ninety-five percent of the assaults occurred on men and the mean age of the patients was 31.1 +/- 9.7 years. Ethnic minorities represent 77% of the patients hospitalised for assaults and 26.5% of all patients proved to be under toxic influence, predominantly from alcohol (21.8%). A decline of admissions of patients with stab injuries during the period 2002-2004 is recorded. However, the incidence doubled in the next two-year period. A weekend peak and circadian rhythm is apparent with more than 20% of the patients admitted between 4 and 6 am. The trunk is most frequently stabbed (54.5%) resulting in a laparotomy rate of 51%. One third of the patients who underwent thoraco-abdominal surgery revealed diaphragmatic injuries. Seventy-five percent of the patients left the hospital in a good condition while 2.4% had neuromuscular lesions. Two patients had serious vascular complications during follow-up. During the study period, no mortality was recorded. Stab wounds were recorded mainly in young and middle-aged men from ethnic minorities, whereas almost 27% were under the influence of drugs. A conservative approach was generally used resulting in a low laparotomy and thoracotomy rate without affecting mortality. Neuromuscular lesions are important long-term complications of stab injuries.

  17. Intermittent hypoxia during recovery from neonatal hyperoxic lung injury causes long-term impairment of alveolar development: A new rat model of BPD.

    PubMed

    Mankouski, Anastasiya; Kantores, Crystal; Wong, Mathew J; Ivanovska, Julijana; Jain, Amish; Benner, Eric J; Mason, Stanley N; Tanswell, A Keith; Auten, Richard L; Jankov, Robert P

    2017-02-01

    Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O2 until day 14 were recovered in air with or without IH (FIO2 = 0.10 for 10 min every 6 h) until day 28 Animals exposed to 60% O2 and recovered in air had no evidence of abnormal lung morphology on day 28 or at 10-12 wk. In contrast, 60% O2-exposed animals recovered in IH had persistently increased mean chord length, more dysmorphic septal crests, and fewer peripheral arteries. Recovery in IH also increased pulmonary vascular resistance, Fulton index, and arterial wall thickness. IH-mediated abnormalities in lung structure (but not pulmonary hypertension) persisted when reexamined at 10-12 wk, accompanied by increased pulmonary vascular reactivity and decreased exercise tolerance. Increased mean chord length secondary to IH was prevented by treatment with a peroxynitrite decomposition catalyst [5,10,15,20-Tetrakis(4-sulfonatophenyl)-21H,23H-porphyrin iron (III) chloride, 30 mg/kg/day, days 14-28], an effect accompanied by fewer inflammatory cells. We conclude that IH during recovery from hyperoxia-induced injury prevents recovery of alveologenesis and leads to changes in lung and pulmonary vascular function lasting into adulthood, thus more closely mimicking contemporary BPD.

  18. Translational approaches to treatment-induced symptoms in cancer patients

    PubMed Central

    Dantzer, Robert; Meagher, Mary W.; Cleeland, Charles S.

    2012-01-01

    Cancer therapy makes patients sick. The therapies that are available to clinicians allow them to successfully control nausea, emesis, and pain. However, this is not the case for a number of other symptoms that include fatigue, distractibility, poor memory, and diminished interest in previously pleasurable activities. These symptoms cluster during the course of cancer therapy and impair patient quality of life, limit therapy options, and do not always resolve at the cessation of treatment. It is possible to describe the intensity and temporal features of symptoms and assess their relationship with the inflammatory response that is associated with cancer and cancer therapy. At the preclinical level, sophisticated animal models still need to be deployed to study the causal role of inflammation in specific components of cancer-related symptoms. Various approaches can be optimally combined in a translational symptom research pathway to provide a framework for assessing in a systematic manner the neurobehavioral toxicity of existing and newly developed cancer therapies. Ultimately this knowledge will allow derivation of mechanism-based interventions to prevent or alleviate cancer-related symptoms. PMID:22641361

  19. Changes in some physical properties induced by vacuum heat treatment

    NASA Technical Reports Server (NTRS)

    Hultquist, A. E.

    1972-01-01

    A method is proposed for reducing or eliminating outgassing of materials by heat treating them in vacuum prior to use. This may be performed on the raw material prior to manufacturing and installation or after fabrication of parts. Processing of a fabricated part can be performed only on relatively small parts and on assemblies containing no components which are affected by the required temperatures and pressures. Processing conditions of temperature and time are dependent on the particular application and the materials involved. Silicone-coated fiber glass cloth was vacuum-heat treated for 100 hrs at 400 + or - 25 F at pressures of 0.001 torr or less. The materials were tested in terms of tensile strength and tear properties in both the smooth and several creased configurations. Data obtained on one side silicone coated fiber glass showed large reductions in these properties as a result of the vacuum-heat treatment. The problem was alleviated by coating both sides of the fiber glass.

  20. Antiresorptive Treatment for Spaceflight Induced Bone Atrophy - Preliminary Results

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian; Matsumoto, toshio; Jones, Jeff; Shapiro, Jay; Lang, Thomas; Shackelford, Linda C.; Smith, Scott M.; Evans, Harlan J.; Spector, Elisabeth R.; Ploutz-Snyder, Robert; Sibonga, Jean; Nakamura, Toshitaka; Kohri, Kenjiro; Ohshima, Hiroshi

    2011-01-01

    Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from critical skeletal sub-regions. The most important BMD losses are from the femoral hip, averaging about -1.6%/mo integral to -2.3%/mo trabecular. Importantly these studies have documented the wide range in individual BMD loss from -0.5 to -5%/mo. Associated elevated urinary Ca increases the risk of renal stone formation during flight, a serious impact to mission success. To date, countermeasures have not been satisfactory. The purpose of this study is to determine if the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss (mass and strength) and reducing renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the spine, femur neck and total hip were significantly improved from -0.8 +/- 0.5%/mo to 1.0 +/- 1.1%/mo, -1.1 +/- 0.5%/mo to -0.2 +/- 0.3%/mo, -1.1 +/- 0.5%/mo to 0.04 +/- 0.3%/mo respectively. QCT-determined trabecular BMD of the femur neck, trochanter and total hip were significantly improved from -2.7 +/- 1.9%/mo to -0.2 +/- 0.8%/mo, -2.2 +/- 0.9%/mo to -0.3 +/- 1.9%/mo and -2.3 +/- 1.0%/mo to -0.2 +/- 1.8%/mo respectively. Significance was calculated from a one-tailed t test. Resorption markers were unchanged, in contrast to measurements from previous ISS crewmembers that showed typical increases of 50-100% above baseline. Urinary Ca showed no increase compared to baseline levels, also distinct from the elevated levels of 50% or greater in previous crews. While these results are encouraging, the current n (4) is small, and the large SDs indicate that, while the means are improved, there

  1. Cannabinoids As Potential Treatment for Chemotherapy-Induced Nausea and Vomiting

    PubMed Central

    Rock, Erin M.; Parker, Linda A.

    2016-01-01

    Despite the advent of classic anti-emetics, chemotherapy-induced nausea is still problematic, with vomiting being somewhat better managed in the clinic. If post-treatment nausea and vomiting are not properly controlled, anticipatory nausea—a conditioned response to the contextual cues associated with illness-inducing chemotherapy—can develop. Once it develops, anticipatory nausea is refractive to current anti-emetics, highlighting the need for alternative treatment options. One of the first documented medicinal uses of Δ9-tetrahydrocannabinol (Δ9-THC) was for the treatment of chemotherapy-induced nausea and vomiting (CINV), and recent evidence is accumulating to suggest a role for the endocannabinoid system in modulating CINV. Here, we review studies assessing the therapeutic potential of cannabinoids and manipulations of the endocannabinoid system in human patients and pre-clinical animal models of nausea and vomiting. PMID:27507945

  2. Usefulness of duloxetine for Paclitaxel-induced peripheral neuropathy treatment in gynecological cancer patients.

    PubMed

    Otake, Akiko; Yoshino, Kiyoshi; Ueda, Yutaka; Sawada, Kenjiro; Mabuchi, Seiji; Kimura, Toshihiro; Kobayashi, Eiji; Isobe, Aki; Egawa-Takata, Tomomi; Matsuzaki, Shinya; Fujita, Masami; Kimura, Tadashi

    2015-01-01

    The present study aimed at evaluating the usefulness and adverse effects of duloxetine treatment for paclitaxel-induced peripheral neuropathy in gynecological cancer patients. Medical records of gynecological cancer patients treated with duloxetine were retrospectively studied to evaluate the drug's efficacy for paclitaxel-induced peripheral neuropathy. RESULTS from 25 patients showed that an improved response was observed in 14 (56%). By univariate and multivariate analysis, the patient's age, tumor origin, regimen of chemotherapy, accumulated doses of paclitaxel or carboplatin, previous medication, maintenance dosage and timing of treatment with duloxetine were found not to be associated with the effectiveness of duloxetine treatment. Adverse effects with duloxetine were mild and well-tolerated. As an option, duloxetine can be effectively used for paclitaxel-induced peripheral neuropathy in patients with gynecological cancers, irrespective of patients' age, origin of the tumor, regimen of chemotherapy, or previous medication. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. [Randomized controlled trials for the prevention and treatment of glucocorticoid-induced osteoporosis].

    PubMed

    Suzuki, Yasuo

    2006-11-01

    The effectiveness of drug therapy for the prevention or treatment of glucocorticoid-induced osteoporosis has been reported. Especially, the beneficial effects of bisphosphonates (etidoronate, alendronate, and risedronate) to prevent bone loss and fractures have been confirmed by the large-scale, multicenter, double-blind, randomized controlled trials in terms of both primary and secondary prevention. This article reviews the results of recent randomized prospective trials using bisphosphonates in glucocorticoid-induced osteoporosis.

  4. The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

    NASA Astrophysics Data System (ADS)

    Vishnevskia-Dai, Victoria; Belokopytov, Mark; Dubinsky, Galina; Nachum, Gal; Avni, Isaac; Belkin, Michael; Rosner, Mordechai

    2005-04-01

    Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (P<0.01). The shorter HBO treatment was less effective, showing an increase only in nuclei density at the central area of lesion (P< 0.01). Hyperbaric oxygen seems to exert a neuroprotective effect on laser-induced retinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.

  5. Synergism Between Anticholinergic and Oxime Treatments Against Sarin-Induced Ocular Insult in Rats.

    PubMed

    Gore, A; Brandeis, R; Egoz, I; Turetz, J; Nili, U; Grauer, E; Bloch-Shilderman, E

    2015-08-01

    Eye exposure to the extremely toxic organophosphorus sarin results in long-term miosis and visual impairment. As current treatment using atropine or homatropine eye drops may lead to considerable visual side effects, alternative combined treatments of intramuscular (im) oximes (16.8 µmol/kg, im) with atropine (0.5 mg/kg, im) or with the short acting antimuscarinic tropicamide (0.5%; w/v) eye drops were thus evaluated. The combined treatments efficacy following topical exposure to sarin (1 µg) was assessed by measuring pupil width and light reflex using an infra-red based digital photographic system. Results showed that the combined treatment of various oximes with atropine or with topical tropicamide eye drops rapidly reversed the sarin-induced miosis and presented a long-term improvement of 67-98% (oxime+tropicamide) or 84-109% (oxime+atropine) in pupil widening as early as 10-min following treatment. This recovery was shown to persist for at least 8-h following exposure. All combined treatments facilitated the ability of the iris to contract following sarin insult as tested by a light reflex response.Our findings emphasize the high efficacy of im oxime treatment combined with either atropine im or tropicamide eye drops in counteracting sarin-induced ocular insult. Therefore, in a mass casualty scenario the systemic combined treatment may be sufficient to ameliorate sarin-induced ocular insult with no need for additional, topical anticholinergic treatment at least in the initial stage of intoxication. For very mild casualties, who are unlikely to receive im treatment, the combined oxime (im) with topical tropicamide treatment may be sufficient in ameliorating the ocular insult.

  6. NAD(+) treatment prevents rotenone-induced apoptosis and necrosis of differentiated PC12 cells.

    PubMed

    Hong, Yunyi; Nie, Hui; Wu, Danhong; Wei, Xunbin; Ding, Xianting; Ying, Weihai

    2014-02-07

    Nicotinamide adenine dinucleotide (NAD(+)) plays critical roles in not only energy metabolism and mitochondrial functions, but also calcium homeostasis and immunological functions. It has been reported that NAD(+) administration can reduce ischemic brain damage. However, the mechanisms underlying the protective effects remain unclear. Because mitochondrial impairments play a key role in the cell death in cerebral ischemia, in this study we tested our hypothesis that NAD(+) can decrease mitochondrial damage-induced cell death using differentiated PC12 cells as a cellular model. We found that NAD(+) can decrease both early-stage and late-stage apoptosis, as well as necrosis of rotenone-treated PC12 cells, as assessed by FACS-based Annexin V/AAD assay. We also found that NAD(+) treatment can restore the intracellular NAD(+) levels of the rotenone-treated cells. Moreover, NAD(+) treatment can prevent rotenone-induced mitochondria depolarization. In summary, our study has provided first direct evidence that NAD(+) treatment can prevent rotenone-induced apoptosis and necrosis. Our study has also indicated that NAD(+) treatment can prevent mitochondrial damage-induced cell death, which may at least partially result from its protective effects on rotenone-induced mitochondrial depolarization. Because both mitochondrial damage and apoptosis play key roles in multiple neurological disorders, our study has highlighted the therapeutic potential of NAD(+) for brain ischemia and other neurological diseases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism.

    PubMed

    Tyler, Christina R; Solomon, Benjamin R; Ulibarri, Adam L; Allan, Andrea M

    2014-09-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism.

  8. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

    PubMed Central

    Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

    2014-01-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

  9. Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats.

    PubMed

    Devenny, James J; Godonis, Helen E; Harvey, Susan J; Rooney, Suzanne; Cullen, Mary J; Pelleymounter, Mary Ann

    2012-08-01

    Dapagliflozin is a potent and selective sodium glucose cotransporter-2 (SGLT2) inhibitor which promotes urinary glucose excretion and induces weight loss. Since metabolic compensation can offset a negative energy balance, we explored the potential for a compensatory physiological response to the weight loss induced by dapagliflozin. Dapagliflozin was administered (0.5-5 mpk; p.o.) to diet-induced obese (DIO) rats with or without ad libitum access to food for 38 days. Along with inducing urinary glucose excretion, chronic administration of dapagliflozin dose-dependently increased food and water intake relative to vehicle-treated controls. Despite this, it reduced body weight by 4% (relative to controls) at the highest dose. The degree of weight loss was increased by an additional 9% if hyperphagia was prevented by restricting food intake to that of vehicle controls. Neither oxygen consumption (vO2) or the respiratory exchange ratio (RER) were altered by dapagliflozin treatment alone. Animals treated with dapagliflozin and pair-fed to vehicle controls (5 mpk PF-V) showed a reduction in RER and an elevation in nonfasting β-hydroxybutyrate (BHBA) relative to ad libitum-fed 5 mpk counterparts. Fasting BHBA was elevated in the 1 mpk, 5 mpk, and 5 mpk PF-V groups. Serum glucose was reduced in the fasted, but not the unfasted state. Insulin was reduced in the non-fasted state. These data suggest that in rodents, the persistent urinary glucose excretion induced by dapagliflozin was accompanied by compensatory hyperphagia, which attenuated the weight loss induced by SGLT2 inhibition. Therefore, it is possible that dapagliflozin-induced weight loss could be enhanced with dietary intervention.

  10. Localized linear IgA dermatosis induced by UV light-treatment for herpes zoster.

    PubMed

    He, Chundi; Xu, Honghui; Xiao, Ting; Geng, Long; Chen, Hong-Duo

    2007-05-01

    We report a case of localized linear IgA dermatosis (LID). The patient suffered from herpes zoster on the right waist and received three localized ultraviolet (UV) light treatments. One month later he presented with bullae on the same site. Direct immunofluorescence showed deposition of linear IgA and weak C3 along the basement membrane zone. Indirect immunofluorescence on the salt-split human skin demonstrated that IgA antibodies were bound to the epidermal side. To our knowledge, this is the first case of localized LID induced by UV light treatment for herpes zoster. It is also the third case of LID induced by UV light.

  11. Treatment of permanent chemotherapy-induced alopecia with low dose oral minoxidil.

    PubMed

    Yang, Xinyi; Thai, Keng-Ee

    2015-05-13

    Chemotherapy-induced alopecia is a well-established cause of major distress to patients. Permanent chemotherapy-induced alopecia (PCIA) is the absence of or incomplete hair regrowth lasting longer than 6 months after the cessation of chemotherapy and it does not respond to standard treatments of scalp cooling or topical minoxidil. The increasing numbers of reports of PCIA highlight the need for research into an effective treatment. We report a case of a 39 year-old woman with cosmetically significant regrowth after continuous therapy with oral minoxidil.

  12. Comparison of lens oxidative damage induced by vitrectomy and/or hyperoxia in rabbits

    PubMed Central

    Yan, Hong; Wang, Dan; Ding, Tian-Bing; Zhou, Hai-Yan; Yan, Wei-Jia; Wang, Xin-Chuan

    2017-01-01

    AIM To compare of lens oxidative damage induced by vitrectomy and/or hyperoxia in rabbit. METHODS Sixteen New Zealand rabbits (2.4-2.5 kg) were randomly divided into two groups (Group A, n=12; Group B, n=4). In Group A, the right eyes were treated with vitrectomy and systemic hyperoxia (oxygen concentration: 80%-85%, 1 ATA, 4h/d) (Group A-right), and the left eyes were treated with hyperoxia without vitrectomy surgery (Group A-left). Four rabbits in group B (eight eyes) were untreated as the controls. Lens transparency was monitored with a slit lamp and recorded before and after vitrectomy. After hyperoxic treatment for 6mo, the eyeballs were removed and the lens cortices (containing the capsules) and nuclei were separated for further morphological and biochemical evaluation. RESULTS Six months after treatments, there were no significant morphological changes in the lenses in any experimental group when observed with a slit lamp. However, the levels of water-soluble proteins and ascorbate, and the activities of catalase and Na+-K+-ATPase were significantly reduced, whereas the levels of malondialdehyde and transforming growth factor β2 (TGF-β2) were significantly elevated, in both the cortices and nuclei of eyes treated with vitrectomy and hyperoxia. The increase in protein-glutathione mixed disulfides and the reduction in water-soluble proteins were more obvious in the lens nuclei. The levels of ascorbate in the vitreous fluid were also reduced after vitrectomy, whereas TGF-β2 increased after vitrectomy and hyperoxia. Systemic hyperoxia exposure increased these effects. CONCLUSION Removal of the intact vitreous gel with vitrectomy and exposing the lens to increased oxygen from the retina induce lens oxidation and aggregation. Thus, an intact vitreous gel structure may protect the lens from oxidative insult and maintain lens transparency. PMID:28149770

  13. Magnitude, Impact, and Management of Respiration-induced Target Motion in Radiotherapy Treatment: A Comprehensive Review

    PubMed Central

    Yoganathan, S. A.; Maria Das, K. J.; Agarwal, Arpita; Kumar, Shaleen

    2017-01-01

    Tumors in thoracic and upper abdomen regions such as lungs, liver, pancreas, esophagus, and breast move due to respiration. Respiration-induced motion introduces uncertainties in radiotherapy treatments of these sites and is regarded as a significant bottleneck in achieving highly conformal dose distributions. Recent developments in radiation therapy have resulted in (i) motion-encompassing, (ii) respiratory gating, and (iii) tracking methods for adapting the radiation beam aperture to account for the respiration-induced target motion. The purpose of this review is to discuss the magnitude, impact, and management of respiration-induced tumor motion. PMID:28974854

  14. Hyperbaric oxygen in the treatment of radiation-induced optic neuropathy

    SciTech Connect

    Guy, J.; Schatz, N.J.

    1986-08-01

    Four patients with radiation-induced optic neuropathies were treated with hyperbaric oxygen. They had received radiation therapy for treatment of pituitary tumors, reticulum cell sarcoma, and meningioma. Two presented with amaurosis fugax before the onset of unilateral visual loss and began hyperbaria within 72 hours after development of unilateral optic neuropathy. Both had return of visual function to baseline levels. The others initiated treatment two to six weeks after visual loss occurred in the second eye and had no significant improvement of vision. Treatment consisted of daily administration of 100% oxygen under 2.8 atmospheres of pressure for 14-28 days. There were no medical complications of hyperbaria. While hyperbaric oxygen is effective in the treatment of radiation-induced optic neuropathy, it must be instituted within several days of deterioration in vision for restoration of baseline function.

  15. Resolution of adalimumab-induced psoriasis after vitamin D deficiency treatment.

    PubMed

    Werner de Castro, Gláucio Ricardo; Neves, Fabrício Souza; Pereira, Ivanio Alves; Fialho, Sonia Cristina Magalhaes Souza; Ribeiro, Giovana; Zimmermann, Adriana Fontes

    2012-05-01

    Tumoral necrosis factor alpha blockers are very efficient in the treatment of many inflammatory systemic diseases, including rheumatoid arthritis and psoriasis. However, a paradoxical arouse of psoriasiform lesions may occur in a few patients taking anti-TNFα. The etiology of this rare side effect is still a mystery, and its treatment may be difficult. The authors report the resolution of adalimumab-induced psoriasis in a woman with rheumatoid arthritis after the use of high vitamin D(3) doses for the treatment of vitamin D deficiency. This is the first report of resolution of anti-TNFα-induced psoriasiform lesions by high doses of vitamin D(3) in a patient with rheumatoid arthritis and vitamin D deficiency. This case raises interesting questions on the role of vitamin D deficiency in the pathogenesis of this side effect and on the possible usefulness of high-dose vitamin D(3) in its treatment.

  16. Gamma knife surgery-induced ependymoma after the treatment of meningioma - a case report.

    PubMed

    Wang, Ke; Pan, Li; Che, Xiaoming; Lou, Meiqing

    2012-01-01

    Gamma knife surgery is widely used for a number of neurological disorders. However, little is known about its long-term complications such as carcinogenic risks. Here, we present a case of a radiosurgery-induced ependymoma by gamma knife surgery for the treatment of a spinal meningioma in a 7-year-old patient. In light of reviewing the previous reports, we advocate high caution in making young patients receive this treatment.

  17. Hyperoxia, but not thoracic X-irradiation, potentiates bleomycin- and cyclophosphamide-induced lung damage in mice

    SciTech Connect

    Hakkinen, P.J.; Whiteley, J.W.; Witschi, H.R.

    1982-08-01

    The intraperitoneal administration of cyclophosphamide or bleomycin to BALB/c mice resulted in lung cell damage followed by cellular proliferation, which was quantitated by measuring the increase in thymidine incorporation into pulmonary DNA. We have previously shown that administration of the antioxidant butylated hydroxytoluene produces lung damage that can be potentiated by both hyperoxia and thoracic X-irradiation. In the present study we show that hyperoxic exposure also potentiates bleomycin- and cyclophosphamide-induced acute lung damage. However, thoracic X-irradiation does not potentiate bleomycin- and cyclophosphamide-induced lung toxicity.

  18. Fluctuations induced extinction and stochastic resonance effect in a model of tumor growth with periodic treatment

    NASA Astrophysics Data System (ADS)

    Li, Dongxi; Xu, Wei; Guo, Yongfeng; Xu, Yong

    2011-01-01

    We investigate a stochastic model of tumor growth derived from the catalytic Michaelis-Menten reaction with positional and environmental fluctuations under subthreshold periodic treatment. Firstly, the influences of environmental fluctuations on the treatable stage are analyzed numerically. Applying the standard theory of stochastic resonance derived from the two-state approach, we derive the signal-to-noise ratio (SNR) analytically, which is used to measure the stochastic resonance phenomenon. It is found that the weak environmental fluctuations could induce the extinction of tumor cells in the subthreshold periodic treatment. The positional stability is better in favor of the treatment of the tumor cells. Besides, the appropriate and feasible treatment intensity and the treatment cycle should be highlighted considered in the treatment of tumor cells.

  19. Mode of treatment governs curcumin response on doxorubicin-induced toxicity in cardiomyoblasts.

    PubMed

    Jain, Aditi; Rani, Vibha

    2017-09-19

    Doxorubicin (Dox) is an effective anti-cancer drug with severe reported cardiotoxicity. Cardiovascular risks associated with present cancer therapeutics demand urgent attention. There has been a growing interest in naturally occurring compounds to improve the therapeutic index as well as prevent non-tumour tissues from sustaining chemotherapy-induced damages. In the present study, the effects of curcumin, a polyphenol isolated from Curcuma longa and well known for its anti-oxidative, anti-cancerous and anti-inflammatory properties, was studied in relation to the Dox-induced cardiotoxicity. As literature suggests conflicting role of curcumin in Dox-induced cardiotoxicity, concentration- and time-dependent studies were conducted to study the different curcumin effects. H9C2 cardiomyoblasts were used in the study and cell viability assays were done to study Dox-induced cellular death. Drug uptake assay for Dox was performed followed by cellular growth inhibition analysis by FACS Calibur. Morphological alterations, intracellular ROS levels and mitochondrial integrity were observed by fluorescent-based microscopic studies. Catalases and superoxide dismutase-inbuilt anti-oxidant enzyme activities were studied, and it was observed that Dox-dependent cardiotoxicity occurs through ROS overproduction by exaggerating the inbuilt anti-oxidant mechanism. Expression analysis for cell death and ROS markers-BCl2, Bax, SOD, catalase-was investigated by semi-quantitative RT-PCR, and the Dox-induced stress on cardiac cells was confirmed. Initiator and effector caspases activity analysis also confirmed these findings. Our study proposes that curcumin exerts time-dependent responses on Dox-induced cardiotoxicity, where parallel treatment potentiates and pre-treatment suppresses the Dox-induced toxicity in H9C2 cardiomyoblasts. In conclusion, pre-treatment of curcumin suppresses the Dox-induced cardiotoxicity and holds a great potential as future cardio-oncological therapeutics.

  20. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    SciTech Connect

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J.; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  1. Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice.

    PubMed

    Thelen, Connor; Sens, Jonathon; Mauch, Joseph; Pandit, Radhika; Pitychoutis, Pothitos M

    2016-10-01

    One of the most striking discoveries in the treatment of major depression was the finding that infusion of a single sub-anesthetic dose of ketamine induces rapid and sustained antidepressant effects in treatment-resistant depressed patients. However, ketamine's antidepressant-like actions are transient and can only be sustained by repeated drug treatment. Despite the fact that women experience major depression at roughly twice the rate of men, research regarding the neurobiological antidepressant-relevant effects of ketamine has focused almost exclusively on the male sex. Importantly, knowledge regarding the sex-differentiated effects, the frequency and the dose on which repeated ketamine administration stops being beneficial, is limited. In the current study, we investigated the behavioral, neurochemical and synaptic molecular effects of repeated ketamine treatment (10mg/kg; 21days) in male and female C57BL/6J mice. We report that ketamine induced beneficial antidepressant-like effects in male mice, but induced both anxiety-like (i.e., decreased time spent in the center of the open field arena) and depressive-like effects (i.e., enhanced immobility duration in the forced swim test; FST) in their female counterparts. Moreover, repeated ketamine treatment induced sustained sex-differentiated neurochemical and molecular effects, as it enhanced hippocampal synapsin protein levels and serotonin turnover in males, but attenuated glutamate and aspartate levels in female mice. Taken together, our findings indicate that repeated ketamine treatment induces opposite behavioral effects in male and female mice, and thus, present data have far-reaching implications for the sex-oriented use of ketamine in both experimental and clinical research settings.

  2. In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease.

    PubMed

    Wang, Yan; Lin, Bo

    2013-07-01

    No anabolic drugs are currently approved to treat multiple myeloma (MM)-induced bone disease and the anti-MM agent bortezomib exhibits the anabolic effects in the clinic. In this study, we focus on investigating potential anabolic treatments of MM-induced bone disease using our previously proposed MM-bone model, with the goal for clarifying the underlying molecular/cellular mechanisms. Firstly, a variety of virtual drug treatments are explored by the parametric study to clarify the anabolic-related molecular/cellular mechanisms. The real drug (i.e., bortezomib) treatments are further examined by developing an integrated model with bortezomib to validate the clarified anabolic-related molecular/cellular mechanisms. The simulated responses to the bortezomib treatments that are validated by the clinical data are consistent with the simulated responses to the virtual drug treatments. Our study clarifies that the anabolic effects in the treatment of MM-induced bone disease are associated with promoting the differentiation of bone marrow stromal cells (BMSC) and inhibiting the apoptosis of active osteoblasts, while promoting the differentiation of osteoblast precursors is instead suggested to be associated with the anti-catabolic effects. Compared with the individual anabolic therapies, the anabolic therapies that promote the differentiation of BMSC in combination with the anti-MM/anti-catabolic therapies are found to induce a greater increase in the bone volume, while the anabolic therapies that inhibit the apoptosis of active osteoblasts in combination with the anti-MM/anti-catabolic therapies induce a lower increase in the bone volume. The simulations also suggest that the direct inhibition of bortezomib on the osteoclast activity is probably a redundant mechanism. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. METHAMPHETAMINE TREATMENT CAUSES DELAYED DECREASE IN NOVELTY-INDUCED LOCOMOTOR ACTIVITY IN MICE

    PubMed Central

    Krasnova, Irina N.; Hodges, Amber B.; Ladenheim, Bruce; Rhoades, Raina; Phillip, Crystal G.; Ceseňa, Angela; Ivanova, Ekaterina; Hohmann, Christine F.; Cadet, Jean Lud

    2009-01-01

    Methamphetamine (METH) is a psychostimulant that causes damage to dopamine (DA) axons and to non-monoaminergic neurons in the brain. The aim of the present study was to investigate short- and long-term effects of neurotoxic METH treatment on novelty-induced locomotor activity in mice. Male BALB/c mice, 12–14 weeks old, were injected with saline or METH (i.p., 7.5 mg/kg × 4 times, every 2 hours). Behavior and neurotoxic effects were assessed at 10 days, 3 and 5 months following drug treatment. METH administration caused marked decreases in DA levels in the mouse striatum and cortex at 10 days post-drug. However, METH did not induce any changes in novelty-induced locomotor activity. At 3 and 5 months after treatment METH-exposed mice showed significant recovery of DA levels in the striatum and cortex. In contrast, these animals demonstrated significant decreases in locomotor activity at 5 months in comparison to aged-matched control mice. Further assessment of METH toxicity using TUNEL staining showed that the drug induced increased cell death in the striatum and cortex at 3 days after administration. Taken together, these data suggest that delayed deficits in novelty-induced locomotor activity observed in METH exposed animals are not due to neurodegeneration of DA terminals but to combined effects of METH and age-dependent dysfunction of non-DA intrinsic striatal and/or corticostriatal neurons. PMID:19559060

  4. Olopatadine hydrochloride suppresses hot flashes induced by topical treatment with tacrolimus ointment in rats.

    PubMed

    Satake, Kyosuke; Ikeda, Junichi; Tamura, Tadafumi; Amano, Toru; Kobayashi, Katsuya

    2015-10-15

    Tacrolimus ointment is prescribed for patients with atopic dermatitis, although it is known to cause transient burning sensations and hot flashes in the applied skin. The aim of this study was to evaluate the effects of olopatadine hydrochloride (olopatadine), an antiallergic agent with a histamine H1 receptor (H1R) antagonistic activity, on the incidence of hot flashes induced by topical treatment with tacrolimus ointment in rats. Consequently, the skin temperature was increased by the topical application of tacrolimus ointment in rats, and the rise in skin temperature was inhibited by pretreatment with olopatadine in a dose-dependent manner. Inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation was significantly more potent than that of cetirizine hydrochloride, other antiallergic agent with H1R antagonistic activity, at doses in which both agents exhibit comparable H1R antagonistic activity in rats. These results suggest that H1R antagonistic activity-independent mechanism contribute to the inhibitory effect of olopatadine on tacrolimus-induced skin temperature elevation. Olopatadine also significantly inhibited increases in vascular permeability and nerve growth factor production in the skin induced by topical tacrolimus treatment. Thus, the onset of hot flashes in rats is quantitatively determined by measuring the skin temperature and olopatadine attenuates hot flashes induced by topical tacrolimus ointment in rats, suggesting that the combination application with olopatadine and tacrolimus ointment is useful for improving medication adherence with tacrolimus ointment treatment in patients with atopic dermatitis. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Treatment of early pregnancy failure: does induced abortion training affect later practices?

    PubMed

    Dalton, Vanessa K; Harris, Lisa H; Bell, Jason D; Schulkin, Jay; Steinauer, Jodi; Zochowski, Melissa; Fendrick, A Mark

    2011-06-01

    The objective of the study was to examine the relationship between induced abortion training and views toward, and use of, office uterine evacuation and misoprostol in early pregnancy failure (EPF) care. We surveyed 308 obstetrician-gynecologists on their knowledge and attitudes toward treatment options for EPF and previous training in office-based uterine evacuation. Sixty-seven percent of respondents reported training in office uterine evacuation, and 20.3% reported induced abortion training. Induced abortion training was associated with strongly positive views toward both office-based uterine evacuation and misoprostol as treatment for EPF compared with those with office uterine evacuation training in other settings (odds ratio [OR], 2.64; P < .004 and OR, 3.22; P < .003, respectively). Furthermore, induced abortion training was associated with the use of office uterine evacuation for EPF treatment compared with those with office evacuation training in other settings (OR, 2.90; P = .004). Training experiences, especially induced abortion training, are associated with the use of office uterine evacuation for EPF. Copyright © 2011 Mosby, Inc. All rights reserved.

  6. Measuring Therapy-Induced Peripheral Neuropathy: Preliminary Development and Validation of the Treatment-Induced Neuropathy Assessment Scale.

    PubMed

    Mendoza, Tito R; Wang, Xin Shelley; Williams, Loretta A; Shi, Qiuling; Vichaya, Elisabeth G; Dougherty, Patrick M; Thomas, Sheeba K; Yucel, Emre; Bastida, Christel C; Woodruff, Jeanie F; Cleeland, Charles S

    2015-10-01

    Various sensory and motor effects are associated with cancer treatment-induced peripheral neuropathy. The current method for capturing the multifaceted nature of neuropathy includes a combination of objective tests, clinician evaluation, and subjective patient report, an approach that is often not logistically feasible, especially for multisite trials. We report the performance of a brief yet comprehensive, easily administered measure, the Treatment-Induced Neuropathy Assessment Scale (TNAS), for assessing the severity and course of neuropathy across various cancer treatments. Data were derived from 4 longitudinal or cross-sectional patient cohorts (N = 573). Patients with multiple myeloma treated primarily with bortezomib and patients with colorectal cancer receiving oxaliplatin evaluated candidate items. Cognitive debriefing showed that all items were easy to understand, and this preliminary TNAS demonstrated reliability, validity, and sensitivity. Numbness/tingling was the most severe item, regardless of therapeutic agent. Although numbness and general pain were moderately correlated, patients perceived them as distinct. Most TNAS items were more severe at follow-up, demonstrating the sensitivity of the instrument to accumulating dose. The TNAS will be refined with further patient input, with final psychometric evaluation conducted in a new patient sample receiving treatments known to be associated with peripheral neuropathy. The nonpainful component of neuropathy may be more disabling than the pain component. Our data suggest that the nonpainful components of neuropathy may be more disabling than the pain component during cancer treatment. Here we report data on sensory and motor symptoms reported by patients receiving neurotoxic cancer therapy, and we detail the development of a neuropathy assessment scale that follows regulatory guidance for patient-reported outcomes. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  7. Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats.

    PubMed

    González, Ricardo; Borrego, Aluet; Zamora, Zullyt; Romay, Cheyla; Hernández, Frank; Menéndez, Silvia; Montero, Teresita; Rojas, Enis

    2004-12-01

    Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species To analyze the effect of ozone administration after cisplatin-induced acute nephrotoxicity. Male Sprague-Dawley rats were treated with five intra-rectal applications of ozone/oxygen mixture at 0.36, 1.1 and 1.8 mg/kg after cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were taken off 5 days after cisplatin treatment. Creatinine was measured in the serum and the activities of antioxidant enzymes and thiobarbituric acid reactive substances and glutathione content were analyzed in renal homogenate. Ozone treatment diminished the increase in serum creatinine levels, the glutathione depletion and also reversed the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric reactive substances was decreased by ozone/oxygen mixture applied after cisplatin. Intrarectal applications of ozone reversed the renal pro-oxidant unbalance induced by cisplatin treatment by the way of stimulation to some constituents of antioxidant system in the kidney, and thereby it decreased the renal damage.

  8. Reversion by ozone treatment of acute nephrotoxicity induced by cisplatin in rats.

    PubMed Central

    González, Ricardo; Borrego, Aluet; Zamora, Zullyt; Romay, Cheyla; Hernández, Frank; Menéndez, Silvia; Montero, Teresita; Rojas, Enis

    2004-01-01

    BACKGROUND: Ozone therapy has become a useful treatment for pathological processes, in which the damage mediated by reactive oxygen species is involved. Several lines of evidence suggest that cisplatin-induced acute nephrotoxicity is partially mediated by reactive oxygen species AIMS: To analyze the effect of ozone administration after cisplatin-induced acute nephrotoxicity. METHODS: Male Sprague-Dawley rats were treated with five intra-rectal applications of ozone/oxygen mixture at 0.36, 1.1 and 1.8 mg/kg after cisplatin intraperitoneal injection (6 mg/kg). Serum and kidneys were taken off 5 days after cisplatin treatment. Creatinine was measured in the serum and the activities of antioxidant enzymes and thiobarbituric acid reactive substances and glutathione content were analyzed in renal homogenate. RESULTS: Ozone treatment diminished the increase in serum creatinine levels, the glutathione depletion and also reversed the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. Also, the renal content of thiobarbituric reactive substances was decreased by ozone/oxygen mixture applied after cisplatin. CONCLUSION: Intrarectal applications of ozone reversed the renal pro-oxidant unbalance induced by cisplatin treatment by the way of stimulation to some constituents of antioxidant system in the kidney, and thereby it decreased the renal damage. PMID:15770045

  9. Pediatric Susceptibility to Nerve Agent-Induced Seizures and Effectiveness of Anticonvulsant Treatments

    DTIC Science & Technology

    2014-12-01

    poisoning can result in status epilepticus (SE), which can become pharmacoresistant if treatment is delayed. Virtually no data exist on OP-induced...5 Introduction Organophosphate (OP) exposure can lead to continuous, repetitive seizures (i.e., status epilepticus, SE), which are...monitoring involved a novel miniature telemetry device, which has allowed us to study freely- moving rats, thus leading to unrestricted behavior

  10. Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation.

    PubMed

    McKallip, Robert J; Ban, Hao; Uchakina, Olga N

    2015-01-01

    Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation. Culturing LPS-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production, and an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from LPS-induced lung injury. Specifically, 4-MU treatment led to a reduction in LPS-induced hyaluronic acid synthase (HAS) messenger RNA (mRNA) levels, reduction in lung permeability, and reduction in proinflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target HA production may be an effective treatment for the inflammatory response following exposure to LPS.

  11. Acute nicotine treatment prevents REM sleep deprivation-induced learning and memory impairment in rat.

    PubMed

    Aleisa, A M; Helal, G; Alhaider, I A; Alzoubi, K H; Srivareerat, M; Tran, T T; Al-Rejaie, S S; Alkadhi, K A

    2011-08-01

    Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning and memory and hippocampal long-term potentiation (LTP). An increase in nicotine consumption among habitual smokers and initiation of tobacco use by nonsmokers was observed during SD. Although nicotine treatment was reported to attenuate the impairment of learning and memory and LTP associated with several mental disorders, the effect of nicotine on SD-induced learning and memory impairment has not been studied. Modified multiple platform paradigm was used to induce SD for 24 or 48 h during which rats were injected with saline or nicotine (1 mg kg(-1) s.c.) twice a day. In the radial arm water maze (RAWM) task, 24- or 48-h SD significantly impaired learning and short-term memory. In addition, extracellular recordings from CA1 and dentate gyrus (DG) regions of the hippocampus in urethane anesthetized rats showed a significant impairment of LTP after 24- and 48-h SD. Treatment of normal rats with nicotine for 24 or 48 h did not enhance spatial learning and memory or affect magnitude of LTP in the CA1 and DG regions. However, concurrent, acute treatment of rats with nicotine significantly attenuated SD-induced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity.

  12. Effect of vitamin E in the treatment of bovine-albumin-induced uveitis in rabbits.

    PubMed

    Yücel, I; Paksoy, N; Yücel, G; Aksu, G; Aksu, T A

    1992-01-01

    In order to assess the role of vitamin E, an antioxidant, in the treatment of uveitis, a controlled experimental study was carried out on 20 New Zealand albino rabbits with bovine-albumin-induced uveitis. In all vitamin-E-treated animals, clinical and histopathological study of the retina and uvea revealed no significant changes in comparison with those in untreated rabbits.

  13. Treatment with the hyaluronic acid synthesis inhibitor 4-methylumbelliferone suppresses SEB-induced lung inflammation.

    PubMed

    McKallip, Robert J; Hagele, Harriet F; Uchakina, Olga N

    2013-10-17

    Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB.

  14. Treatment with the Hyaluronic Acid Synthesis Inhibitor 4-Methylumbelliferone Suppresses SEB-Induced Lung Inflammation

    PubMed Central

    McKallip, Robert J.; Hagele, Harriet F.; Uchakina, Olga N.

    2013-01-01

    Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation. Culturing SEB-activated immune cells with 4-MU led to reduced proliferation, reduced cytokine production as well as an increase in apoptosis when compared to untreated cells. Treatment of mice with 4-MU led to protection from SEB-induced lung injury. Specifically, 4-MU treatment led to a reduction in SEB-induced HA levels, reduction in lung permeability, and reduced pro-inflammatory cytokine production. Taken together, these results suggest that use of 4-MU to target hyaluronic acid production may be an effective treatment for the inflammatory response following exposure to SEB. PMID:24141285

  15. A case of enoxaparin-induced thrombocytopaenia during treatment of acute myocardial infarction.

    PubMed

    Lim, Snag Yup; Lee, Se Ryeon; Kim, Yong Hyun; Kim, Jin Seok; Kim, Seong Hwan; Ahn, Jeong Chun; Song, Woo Hyuk

    Heparin-induced thrombocytopaenia is a life-threatening complication, affecting the morbidity and mortality of the patient if not properly treated. We report a case of a 75-year-old female patient who experienced enoxaparininduced thrombocytopaenia during medical treatment of acute ST-segment elevation myocardial infarction due to thrombotic total occlusion in the large right coronary artery.

  16. Hyperleucocytosis following G-CSF treatment for sulfasalazine-induced agranulocytosis

    PubMed Central

    Chan, Kenneth; Farooq, Redwan

    2015-01-01

    Agranulocytosis is a rare but serious adverse effect of sulfasalazine treatment. We present a case of a 51-year-old woman receiving sulfasalazine for inflammatory arthritis presenting with sore throat, fever, lethargy and leucopenia (white cell count 0.9×109/L). After 9 days of treatment with filgrastim (granulocyte-colony stimulating factor, G-CSF), her white cell count increased to 77.4×109/L. This case highlights the importance of recognising sulfasalazine-induced agranulocytosis and the management of hyperleucocytosis following G-CSF treatment, to prevent harmful sequelae. PMID:26178004

  17. Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies

    PubMed Central

    Oh, Gi-Su; Kim, Hyung-Jin; Shen, AiHua; Lee, Su Bin; Khadka, Dipendra; Pandit, Arpana

    2014-01-01

    Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity. PMID:25606044

  18. Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes

    PubMed Central

    Freeman, Roy

    2015-01-01

    Treatment-induced neuropathy in diabetes (also referred to as insulin neuritis) is considered a rare iatrogenic small fibre neuropathy caused by an abrupt improvement in glycaemic control in the setting of chronic hyperglycaemia. The prevalence and risk factors of this disorder are not known. In a retrospective review of all individuals referred to a tertiary care diabetic neuropathy clinic over 5 years, we define the proportion of individuals that present with and the risk factors for development of treatment-induced neuropathy in diabetes. Nine hundred and fifty-four individuals were evaluated for a possible diabetic neuropathy. Treatment-induced neuropathy in diabetes was defined as the acute onset of neuropathic pain and/or autonomic dysfunction within 8 weeks of a large improvement in glycaemic control—specified as a decrease in glycosylated haemoglobin A1C (HbA1c) of ≥2% points over 3 months. Detailed structured neurologic examinations, glucose control logs, pain scores, autonomic symptoms and other microvascular complications were measured every 3–6 months for the duration of follow-up. Of 954 patients evaluated for diabetic neuropathy, 104/954 subjects (10.9%) met criteria for treatment-induced neuropathy in diabetes with an acute increase in neuropathic or autonomic symptoms or signs coinciding with a substantial decrease in HbA1c. Individuals with a decrease in HbA1c had a much greater risk of developing a painful or autonomic neuropathy than those individuals with no change in HbA1c (P < 0.001), but also had a higher risk of developing retinopathy (P < 0.001) and microalbuminuria (P < 0.001). There was a strong correlation between the magnitude of decrease in HbA1c, the severity of neuropathic pain (R = 0.84, P < 0.001), the degree of parasympathetic dysfunction (R = −0.52, P < 0.01) and impairment of sympathetic adrenergic function as measured by fall in blood pressure on tilt-table testing (R = −0.63, P < 0.001). With a decrease in HbA1c of 2

  19. Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes.

    PubMed

    Gibbons, Christopher H; Freeman, Roy

    2015-01-01

    Treatment-induced neuropathy in diabetes (also referred to as insulin neuritis) is considered a rare iatrogenic small fibre neuropathy caused by an abrupt improvement in glycaemic control in the setting of chronic hyperglycaemia. The prevalence and risk factors of this disorder are not known. In a retrospective review of all individuals referred to a tertiary care diabetic neuropathy clinic over 5 years, we define the proportion of individuals that present with and the risk factors for development of treatment-induced neuropathy in diabetes. Nine hundred and fifty-four individuals were evaluated for a possible diabetic neuropathy. Treatment-induced neuropathy in diabetes was defined as the acute onset of neuropathic pain and/or autonomic dysfunction within 8 weeks of a large improvement in glycaemic control-specified as a decrease in glycosylated haemoglobin A1C (HbA1c) of ≥2% points over 3 months. Detailed structured neurologic examinations, glucose control logs, pain scores, autonomic symptoms and other microvascular complications were measured every 3-6 months for the duration of follow-up. Of 954 patients evaluated for diabetic neuropathy, 104/954 subjects (10.9%) met criteria for treatment-induced neuropathy in diabetes with an acute increase in neuropathic or autonomic symptoms or signs coinciding with a substantial decrease in HbA1c. Individuals with a decrease in HbA1c had a much greater risk of developing a painful or autonomic neuropathy than those individuals with no change in HbA1c (P < 0.001), but also had a higher risk of developing retinopathy (P < 0.001) and microalbuminuria (P < 0.001). There was a strong correlation between the magnitude of decrease in HbA1c, the severity of neuropathic pain (R = 0.84, P < 0.001), the degree of parasympathetic dysfunction (R = -0.52, P < 0.01) and impairment of sympathetic adrenergic function as measured by fall in blood pressure on tilt-table testing (R = -0.63, P < 0.001). With a decrease in HbA1c of 2

  20. A Review of Differences in Clinical Characteristics between Tardive Syndrome Induced or Improved by Aripiprazole Treatment.

    PubMed

    Chen, Yen-Wen; Tseng, Ping-Tao

    2016-09-15

    Tardive syndrome is a troublesome complication secondary to the long-term usage of antipsychotic medication. At present, there is a lack of effective treatment for tardive syndrome. Aripiprazole has been used in the treatment of tardive syndrome, with some reports of a good response. However, other reports have suggested that tardive syndrome can actually be induced by aripiprazole. The aim of current study was to investigate whether aripiprazole is beneficial or harmful for the treatment of tardive syndrome in specific patients. We performed a thorough literature search via PubMed. We included all of the studies discussing the relationship between tardive syndrome and aripiprazole, either with regards to "inducing" or "improving" the disease. None of the included studies were well-designed clinical trials, and all were case reports or case series. A total of 26 articles were included in which aripiprazole induced tardive syndrome, and another 24 in which tardive syndrome was improved by aripiprazole treatment. In the "improved" group, there were significantly more cases of schizophrenia than in the "induced" group (p=0.002). However, there were significantly more cases with other miscellaneous diagnoses in the "induced" group than in the "improved" group (p=0.003). In addition, the cases in the "induced" group had a significantly longer duration of aripiprazole usage than those in the "improved" group (p=0.001). Current study is important for clinicians to pay attention to the risk of tardive syndrome when prescribing aripiprazole in patients with a diagnosis other than a psychiatric illness or in the long-term administration of aripiprazole.

  1. The impact of modern treatment principles may have eliminated lithium-induced renal failure.

    PubMed

    Aiff, Harald; Attman, Per-Ola; Aurell, Mattias; Bendz, Hans; Schön, Staffan; Svedlund, Jan

    2014-02-01

    We have previously shown that lithium can cause end-stage renal disease (ESRD): however, this serious side-effect of lithium in prophylactic treatment of mood disorders may reflect the treatment regime of the 1960s and 1970s. Today's modern treatment routines, intended to reduce or eliminate lithium-induced ESRD (Li-ESRD), were introduced in Sweden in the early 1980s. The aim of the present study was to test the hypothesis that these routines have eliminated the risk of Li-ESRD. We used the Swedish Renal Registry to identify patients on renal replacement therapy (RRT), treated with dialysis or renal transplantation, with suspected Li-ESRD in two regions of Sweden with altogether about three million inhabitants. We reviewed their medical records to verify the exposure to lithium treatment, the diagnosis of Li-ESRD and the date of starting the lithium treatment. We found 32 RRT patients in whom lithium treatment was the sole or main contributing cause of ESRD. The starting year of their lithium treatment was between 1965-1980 in all patients. No patient started lithium treatment later than 1980. Modern lithium treatment may have eliminated the risk of Li-ESRD. Our findings support the continued use of lithium as a safe drug for the long-term treatment of mood disorders.

  2. Effect of Bauhinia holophylla treatment in Streptozotocin-induced diabetic rats.

    PubMed

    Pinheiro, Marcelo S; Rodrigues, Luhara S; S, Leila; Moraes-Souza, Rafaianne Q; Soares, Thaigra S; Américo, Madileine F; Campos, Kleber E; Damasceno, Débora C; Volpato, Gustavo T

    2017-02-16

    Bauhinia holophylla, commonly known as "cow's hoof", is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400 mg/kg during 21 days. On day 17 of treatment, the Oral Glucose Tolerance Test was performed to determine the area under the curve. At the end of the treatment, the animals were anesthetized and blood was collected for serum biochemical parameters analysis. After treatment with Bauhinia holophylla extract, non-diabetic and diabetic rats presented no glycemic changes. On the other hand, the plant treatment decreased body weight and increased ALT and AST activities. In conclusion, the treatment with aqueous extract of B. holophylla leaves given to diabetic rats presented no hypoglycemic effect in nondiabetic animals and no antidiabetic effect in diabetic animals with the doses studied. In addition, the diabetic animals treated with the B. holophylla extract showed inconvenient effects and its indiscriminate consumption requires particular carefulness.

  3. Tiagabine treatment in kainic acid induced cerebellar lesion of dystonia rat model

    PubMed Central

    Wang, Tsui-chin; Ngampramuan, Sukonthar; Kotchabhakdi, Naiphinich

    2016-01-01

    Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements. The exaggerated movements have been studied and have implicated basal ganglia as the point of origin. In more recent studies, the cerebellum has also been identified as the possible target of dystonia, in the search for alternative treatments. Tiagabine is a selective GABA transporter inhibitor, which blocks the reuptake and recycling of GABA. The study of GABAergic drugs as an alternative treatment for cerebellar induced dystonia has not been reported. In our study, tiagabine was i.p. injected into kainic acid induced, cerebellar dystonic adult rats, and the effects were compared with non-tiagabine injected and sham-operated groups. Beam walking apparatus, telemetric electromyography (EMG) recording, and histological verification were performed to confirm dystonic symptoms in the rats on post-surgery treatment. Involuntary dystonic spasm was observed with repetitive rigidity, and twisting movements in the rats were also confirmed by a high score on the dystonic scoring and a high amplitude on the EMG data. The rats with tiagabine treatment were scored based on motor amelioration assessed via beam walking. The result of this study suggests and confirms that low dose of kainic acid microinjection is sufficient to induce dystonia from the cerebellar vermis. In addition, from the results of the EMG recording and the behavioral assessment through beam walking, tiagabine is demonstrated as being effective in reducing dystonic spasm and may be a possible alternative therapeutic drug in the treatment of dystonia. PMID:28337103

  4. Repeated, intermittent treatment with amphetamine induces neurite outgrowth in rat pheochromocytoma cells (PC12 cells).

    PubMed

    Park, Yang Hae; Kantor, Lana; Wang, Kevin K W; Gnegy, Margaret E

    2002-09-27

    Repeated, intermittent treatment with amphetamine (AMPH) leads to long-term neurobiological adaptations in rat brain including an increased number and branching of dendritic spines. This effect depends upon several different cell types in the intact brain. Here we demonstrate that repeated, intermittent AMPH treatment induces neurite outgrowth in cultured PC12 cells without the requirement for integrated synaptic pathways. PC12 cells were treated with 1 micro M AMPH for 5 min a day, for 5 days. After 10 days of withdrawal, there was an increase in the percentage of cells with neurites ( approximately 30%) and the length of neurites as well as an increase in the level of GAP-43 and neurofilament-M. Neurite outgrowth was enhanced as withdrawal time was increased. Neurite outgrowth was much greater following repeated, intermittent treatment with AMPH compared to continuous or single treatment with AMPH. Pretreatment with cocaine, a monoamine transporter blocker, inhibited the AMPH-mediated increase in neurite outgrowth. Neither NGF antibody nor DA receptor antagonists blocked AMPH-induced neurite outgrowth, demonstrating that AMPH-induced neurite outgrowth is not dependent on endogenous NGF release or DA receptors. Thus we have demonstrated that repeated, intermittent treatment with AMPH has a neurotrophic effect in PC12 cells. The effect requires the action of AMPH on the norepinephrine transporter, and shares characteristics in its development with other forms of sensitization but does not require an intact neuroanatomy.

  5. Cerenkov radiation-induced phototherapy for depth-independent cancer treatment (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Akers, Walter J.; Achilefu, Samuel; Kotagiri, Nalinikanth

    2017-02-01

    Light emitted as the result of high-energy particle transport through biological tissues (Cerenkov radiation) can be exploited for noninvasive diagnostic imaging using high sensitivity scientific cameras. We have investigated the energy transfer potential of Cerenkov radiation, discovering a new phototherapeutic technique for treatment of localized and disseminated cancers. This technique, Cerenkov radiation-induced phototherapy (CRIT), like photodynamic therapy, requires the presence of both light and photosensitive agent together to induce cytotoxicity and effective cancer treatment. But unlike conventional phototherapy strategies in which tissue ablation or activation of photoactive molecules is limited to superficial structures, radiation-induced phototherapy enables phototherapy delivery to the tumor sites throughout the body. Titanium oxide nanoparticles, which produce cytotoxic reactive oxygen species upon irradiation with UV light, were targeted to tumor tissue by surface decoration with transferrin. Subsequent administration of tumor-avid radiotracer, 18-fluorodeoxyglucose (18FDG) provided localized UV light source via Cerenkov radiation. Treatment of tumor-bearing mice with the combination of Titanium nanoparticles and 18FDG resulted in effective reduction in tumor growth, while individual agents were not therapeutic. This new strategy in cancer therapy extends the reach of phototherapy beyond what was previously possible, with potential for treatment of cancer metastases and rescue from treatment resistance.

  6. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice.

    PubMed

    Yabuki, Y; Ohizumi, Y; Yokosuka, A; Mimaki, Y; Fukunaga, K

    2014-02-14

    Nobiletin, a polymethoxylated flavonoid found in citrus fruit peel, reportedly improves memory impairment in rodent models. Here we report its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor and cognitive deficits. Nobiletin administration (50mg/kg i.p.) for 2 consecutive weeks improved motor deficits seen in MPTP-induced Parkinson model mice by 2weeks, an effect that continued until 2weeks after drug withdrawal. Drug treatment promoted similar rescue of MPTP-induced cognitive impairment at equivalent time points. Nonetheless, nobiletin treatment did not block loss of dopaminergic neurons seen in the MPTP-treated mouse midbrain, nor did it rescue decreased tyrosine hydroxylase (TH) protein levels seen in the striatum or hippocampal CA1 region of these mice. Interestingly, nobiletin administration (50mg/kg i.p.) rescued reduced levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation at Thr-34 of dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) in striatum and hippocampal CA1 to levels seen in sham-operated mice. Likewise, CaMKII- and cAMP kinase-dependent TH phosphorylation was significantly restored by nobiletin treatment. MPTP-induced reduction of dopamine contents in the striatum and hippocampal CA1 region was improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal administration of nobiletin also enhanced dopamine release in striatum and hippocampal CA1, an effect partially inhibited by treatment with nifedipine (a L-type Ca(2+) channel inhibitor) or NNC 55-0396 (a T-type Ca(2+) channel inhibitor) and completely abolished by combined treatment with both. Overall, our study describes a novel nobiletin activity in brain and suggests that nobiletin rescues motor and cognitive dysfunction in MPTP-induced Parkinson model mice, in part by enhancing dopamine release.

  7. Opioid-induced Hallucinations: A Review of the Literature, Pathophysiology, Diagnosis, and Treatment.

    PubMed

    Sivanesan, Eellan; Gitlin, Melvin C; Candiotti, Keith A

    2016-10-01

    Despite their association with multiple adverse effects, opioid prescription continues to increase. Opioid-induced hallucination is an uncommon yet significant adverse effect of opioid treatment. The practitioner may encounter patient reluctance to volunteer the occurrence of this phenomenon because of fears of being judged mentally unsound. The majority of the literature concerning opioid-induced hallucinations arises from treatment during end-of-life care and cancer pain. Because the rate of opioid prescriptions continues to increase in the population, the rate of opioid-associated hallucinations may also conceivably increase. With a forecasted increase in the patient-to-physician ratio, opioid therapy is predicted to be provided by practitioners of varying backgrounds and medical specialties. Hence, knowledge of the pharmacology and potential adverse effects of these agents is required. This review seeks to increase awareness of this potential complication through a discussion of the literature, potential mechanisms of action, diagnosis, and treatment strategies.

  8. Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the Treatment of Trigeminal Neuralgia

    PubMed Central

    Ono, Yuko; Shirafuji, Yoshinori; Hamada, Toshihisa; Masui, Masanori; Obata, Kyoichi; Yao, Mayumi; Kishimoto, Koji; Sasaki, Akira

    2016-01-01

    An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient developed a skin rash accompanied by fever. He was admitted to hospital and diagnosed with drug-induced hypersensitivity syndrome (DIHS) caused by carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed acute liver and acute renal failure. Drug-induced lymphocyte stimulation test (DLST) for carbamazepine, human herpes virus-6 (HHV-6) IgG, and CMV-HRP were negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6 IgG antibodies was then detected (640 times). Following treatment, liver and renal function improved and the erythema disappeared. PMID:27885344

  9. Donepezil in the treatment of opioid-induced sedation: report of six cases.

    PubMed

    Slatkin, N E; Rhiner, M; Bolton, T M

    2001-05-01

    Donepezil, an oral acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, was given to 6 cancer pain patients having sedation related to the analgesic use of opioids. Each patient was taking more than 200 mg of oral morphine equivalents per day, and several were receiving complex analgesic regimens consisting of multiple adjuvant medications. Sedation improved at least moderately in 5 of the patients and mildly in 1 after they began taking donepezil. Patients reported a decrease in episodes of spontaneous sleeping during the day, fewer myoclonic twitches, improved daily function and greater social interaction. Several also reported improved sleep at night. Analgesia was not compromised by the use of donepezil, and in some cases it appeared improved. Donepezil may be a valuable alternative to psychostimulants in the treatment of opioid-induced sedation. A prospective controlled trial comparing the treatment effects of psychostimulants and donepezil on patients having opioid-induced sedation is underway.

  10. Optical spectroscopy by 5-aminolevulinic acid hexylester induced photodynamic treatment in rat bladder cancer

    NASA Astrophysics Data System (ADS)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Arum, Carl-Jørgen; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2006-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as 5-aminolevulinic acid hexylester (hALA) may increase the efficiency of PDT. Monitoring of the tissue response provides important information for optimizing factors such as drug and light dose for this treatment modality. Optical spectroscopy may be suited for this task. To test the efficacy of hALA induced PDT, a study on rats with a superficial bladder cancer model, in which a bladder cancer cell line (AY-27) is instilled, will be performed. Preliminary studies have included a PDT feasibility study on rats, fluorescence spectroscopy on AY-27 cell suspensions, and optical reflection and fluorescence spectroscopy in rat bladders in vivo. The results from the preliminary studies are promising, and the study on hALA induced PDT treatment of bladder cancer will be continued.

  11. Changes at cholecystokinin receptors induced by long-term treatment with diazepam and haloperidol.

    PubMed

    Vasar, E; Soosaar, A; Harro, J; Lang, A

    1992-12-01

    Fourteen days administration of haloperidol (1 mg/kg daily) prevented the motor depressant effect of caerulein (an agonist at cholecystokinin receptors, 15 micrograms/kg) and the antagonistic effect of caerulein (100 micrograms/kg) against (+)-amphetamine (5 mg/kg) induced hyperlocomotion in mice. The antiaggressive effect of caerulein (40 micrograms/kg) in saline-treated mice was replaced by increased aggressiveness after long-term haloperidol and diazepam (5 mg/kg daily) treatment. The anticonvulsant effect of caerulein (125 micrograms/kg) against picrotoxin (10 mg/kg) induced seizures was abolished after 14 days diazepam, but not after haloperidol, treatment. The above described changes in the mouse behaviour are probably related to the development of subsensitivity at CCKA receptors, whereas the CCKB receptor subtype becomes more sensitized to the action of caerulein after long-term haloperidol and diazepam treatment.

  12. Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation.

    PubMed

    Fotopoulos, Vasileios Ch; Mouzopoulos, George; Floros, Themistoklis; Tzurbakis, Matthaios

    2015-09-01

    Osteonecrosis of the femoral head is a devastating complication of steroid administration and has rarely been observed in the treatment of immune thrombocytopenia. The treatment of osteochondral defects in advanced stages of avascular necrosis (AVN), characterized by collapse of the subchondral bone, remains an unsolved burden in orthopedic surgery. In this report, we present a case of a 19-year-old female that was admitted in the Emergency Department with walking disability and painful hip joint movement due to steroid-induced femoral head osteonecrosis. Two years before she was diagnosed with immune thrombocytopenia, for which she received pulse steroid therapy with high dose of dexamethasone and underwent a splenectomy. This case report is the first to describe the use of osteochondral autograft transplantation as a treatment of steroid-induced AVN of the femoral head due to immune thrombocytopenia at the age of 19 years with very good clinical and radiological results 3 years postoperatively.

  13. TRPA1 contributed to the neuropathic pain induced by docetaxel treatment.

    PubMed

    Huang, Kun; Bian, Donglin; Jiang, Bin; Zhai, Qixi; Gao, Ningning; Wang, Ruiying

    2017-04-01

    Peripheral mechanical neuropathic pain is a serious side effect of docetaxel chemotherapy for cancer. However, the underlying mechanism for this side effect is unknown. In the present study, we found that docetaxel treatment induced mechanical allodynia in rats. We further revealed that the transient receptor potential ankyrin subtype 1 protein (TRPA1) protein level is upregulated and the TRPA1 activator allyl isothiocyanate induced larger ion currents in the dorsal root ganglion neurons from the docetaxel treated rats. In addition, application the TRPA1 blocker Ap18 reversed the docetaxel-induced mechanical hypersensitivity. We suggest that the docetaxel-induced mechanical allodynia is mediated by upregulation of TRPA1 in dorsal root ganglion neurons. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Risk-reduction and treatment of chemotherapy-induced peripheral neuropathy.

    PubMed

    Bakogeorgos, Marios; Georgoulias, Vassilis

    2017-09-11

    Chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of several chemotherapeutic agents, has a significant impact on quality of life and may even compromise treatment efficacy, requiring chemotherapy dose reduction or discontinuation. CIPN is predominantly related with sensory rather than motor symptoms and the most common related cytotoxic agents are platinum compounds, taxanes and vinca alkaloids. CIPN symptoms may resolve after treatment cessation, but they can also be permanent and continue for years. Areas covered: We present an overview of CIPN pathophysiology, clinical assessment, prevention and treatment identified through a Pubmed search. Expert commentary: No substantial progress has been made in the last few years within the field of prevention and/or treatment of CIPN, in spite of remarkable efforts. Continuous research could expand our knowledge about chemotherapeutic-specific neuropathic pathways and eventually lead to the conception of innovative and targeted agents for the prevention and/or treatment of this debilitating chemotherapy adverse effect.

  15. Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers.

    PubMed

    Takayama, Masaki; Matsui, Shigenaga; Kawasaki, Masanori; Asakuma, Yutaka; Sakurai, Toshiharu; Kashida, Hiroshi; Kudo, Masatoshi

    2013-09-14

    To prospectively compare the healing rates of endoscopic submucosal dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI) or rebamipide. We examined 90 patients with early gastric cancer who had undergone ESD. All patients were administered an intravenous infusion of the PPI lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45; PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were compared. No significant differences were noted in patient age, underlying disease, tumor location, Helicobacter pylori infection rate, or ESD-induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%; rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer bleeding or complications due to the drugs were observed in either treatment group. The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.

  16. Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

    PubMed Central

    Takayama, Masaki; Matsui, Shigenaga; Kawasaki, Masanori; Asakuma, Yutaka; Sakurai, Toshiharu; Kashida, Hiroshi; Kudo, Masatoshi

    2013-01-01

    AIM: To prospectively compare the healing rates of endoscopic submucosal dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI) or rebamipide. METHODS: We examined 90 patients with early gastric cancer who had undergone ESD. All patients were administered an intravenous infusion of the PPI lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45; PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were compared. RESULTS: No significant differences were noted in patient age, underlying disease, tumor location, Helicobacter pylori infection rate, or ESD-induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%; rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer bleeding or complications due to the drugs were observed in either treatment group. CONCLUSION: The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing. PMID:24039365

  17. Treatment with hydrogen molecule attenuates cardiac dysfunction in streptozotocin-induced diabetic mice.

    PubMed

    Wu, Feng; Qiu, Yihua; Ye, Guangming; Luo, Hede; Jiang, Junsong; Yu, Feng; Zhou, Wei; Zhang, Shuai; Feng, Jinzhong

    2015-01-01

    Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. The aim of present study was to investigate the therapeutic effect of hydrogen molecule on streptozotocin-induced diabetic cardiomyopathy in mice. Diabetes was induced in adult male mice by consecutive peritoneal injection of streptozotocin (50 mg/kg/day) for 5 days. Then, they were treated with hydrogen water (1.3±0.2 mg/l) for 8 weeks (four groups, n=83-88 in each group). Although treatment of diabetic mice with hydrogen water did not significantly affect blood glucose level, it significantly attenuated cardiac hypertrophy and reduced expression of atrial natriuretic factor and β-myosin heavy chain; it alleviated cardiac fibrosis and reduced expression of collagen I and III, transforming growth factor beta, alpha-smooth muscle actin, and osteopontin; it reduced cardiac caspase-3 activity and ratio of bax/bcl-2. Importantly, hydrogen water treatment improved cardiac function in streptozotocin-diabetic mice. Furthermore, it was found that hydrogen water treatment abated oxidative stress, suppressed inflammation, and attenuated endoplasmic reticulum stress in the hearts of streptozotocin-diabetic mice. In addition, hydrogen water treatment suppressed activation of Jun NH2-terminal kinase and p38 mitogen activated protein kinase signaling and nuclear factor κB signaling in the hearts of streptozotocin-diabetic mice. Treatment with hydrogen molecule attenuated cardiac dysfunction in streptozotocin-induced diabetic mice, which was independent of glycemic control. Treatment with hydrogen molecule attenuated cardiac dysfunction in streptozotocin-induced type 1 diabetic mice. Molecular hydrogen could thus be envisaged as a nutritional countermeasure for diabetic cardiomyopathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Chloral Hydrate Treatment Induced Apoptosis of Macrophages via Fas Signaling Pathway

    PubMed Central

    Cai, Jun; Peng, Yanxia; Chen, Ting; Liao, Huanjin; Zhang, Lifang; Chen, Qiuhua; He, Yiming; Wu, Ping; Xie, Tong; Pan, Qingjun

    2016-01-01

    Background There are recent reports on several anesthetics that have anti-inflammatory and anti-infective effects apart from their uses for pain relief and muscle relaxation. Chloral hydrate is a clinical anesthetic drug and sedative that has also been reported to attenuate inflammatory response, but the mechanisms are not clearly understood. Material/Methods This study investigated the effect of chloral hydrate treatment on the apoptosis of macrophages and explored the underlying mechanisms. RAW264.7 macrophages were treated with various concentrations of chloral hydrate for various lengths of time. Morphological changes were observed under a light microscope and apoptosis was detected with annexin-V-FITC/PI double-staining assay, Hochest 33258 and DNA ladder assay, the expression of Fas/FasL was detected with a flow cytometer, and the Fas signaling pathway was assessed by Western blotting. Results The results showed that chloral hydrate treatment induced the morphology of RAW264.7 macrophages to change shape from typical fusiform to round in a concentration- and time-dependent manner, and was finally suspended in the supernatant. For the induction of apoptosis, chloral hydrate treatment induced the apoptosis of RAW264.7 macrophages from early-to-late stage apoptosis in a concentration- and time-dependent manner. For the mechanism, chloral hydrate treatment induced higher expression of Fas on RAW264.7 macrophages, and was also associated with changes in the expression of proteins involved in Fas signaling pathways. Conclusions Chloral hydrate treatment can induce the apoptosis of RAW264.7 macrophages through the Fas signaling pathway, which may provide new options for adjunctive treatment of acute inflammation. PMID:27941708

  19. Chloral Hydrate Treatment Induced Apoptosis of Macrophages via Fas Signaling Pathway.

    PubMed

    Cai, Jun; Peng, Yanxia; Chen, Ting; Liao, Huanjin; Zhang, Lifang; Chen, Qiuhua; He, Yiming; Wu, Ping; Xie, Tong; Pan, Qingjun

    2016-12-10

    BACKGROUND There are recent reports on several anesthetics that have anti-inflammatory and anti-infective effects apart from their uses for pain relief and muscle relaxation. Chloral hydrate is a clinical anesthetic drug and sedative that has also been reported to attenuate inflammatory response, but the mechanisms are not clearly understood. MATERIAL AND METHODS This study investigated the effect of chloral hydrate treatment on the apoptosis of macrophages and explored the underlying mechanisms. RAW264.7 macrophages were treated with various concentrations of chloral hydrate for various lengths of time. Morphological changes were observed under a light microscope and apoptosis was detected with annexin-V-FITC/PI double-staining assay, Hochest 33258 and DNA ladder assay, the expression of Fas/FasL was detected with a flow cytometer, and the Fas signaling pathway was assessed by Western blotting. RESULTS The results showed that chloral hydrate treatment induced the morphology of RAW264.7 macrophages to change shape from typical fusiform to round in a concentration- and time-dependent manner, and was finally suspended in the supernatant. For the induction of apoptosis, chloral hydrate treatment induced the apoptosis of RAW264.7 macrophages from early-to-late stage apoptosis in a concentration- and time-dependent manner. For the mechanism, chloral hydrate treatment induced higher expression of Fas on RAW264.7 macrophages, and was also associated with changes in the expression of proteins involved in Fas signaling pathways. CONCLUSIONS Chloral hydrate treatment can induce the apoptosis of RAW264.7 macrophages through the Fas signaling pathway, which may provide new options for adjunctive treatment of acute inflammation.

  20. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells.

    PubMed

    Luo, Yi; Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients.

  1. Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges

    PubMed Central

    Payne, Heather; Adamson, Andrew; Bahl, Amit; Borwell, Jonathan; Dodds, David; Heath, Catherine; Huddart, Robert; McMenemin, Rhona; Patel, Prashant; Peters, John L; Thompson, Andrew

    2013-01-01

    To review the published data on predisposing risk factors for cancer treatment-induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition. Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. A systematic literature review was undertaken to evaluate the evidence for preventative measures and treatment options in the management of cancer treatment-induced HC. There is a wide range of reported incidence due to several factors including variability in study design and quality, the type of causal agent, the grading of bleeding, and discrepancies in definition criteria. The most frequently reported causal factors are radiotherapy to the pelvic area, where HC has been reported in up to 20% of patients, and treatment with cyclophosphamide and bacillus Calmette-Guérin, where the incidence has been reported as up to 30%. Mesna (2-mercaptoethane sodium sulphonate), hyperhydration and bladder irrigation have been the most frequently used prophylactic measures to prevent treatment-related cystitis, but are not always effective. Cranberry juice is widely cited as a preventative measure and sodium pentosanpolysulphate as a treatment, although the evidence for both is very limited. The best evidence exists for intravesical hyaluronic acid as an effective preventative and active treatment, and for hyperbaric oxygen as an equally effective treatment option. The lack of robust data and variability in treatment strategies used highlights the need for further research, as well as best practice guidance and consensus on the management of HC. PMID:24000900

  2. Constraint-induced aphasia therapy versus intensive semantic treatment in fluent aphasia.

    PubMed

    Wilssens, Ineke; Vandenborre, Dorien; van Dun, Kim; Verhoeven, Jo; Visch-Brink, Evy; Mariën, Peter

    2015-05-01

    The authors compared the effectiveness of 2 intensive therapy methods: Constraint-Induced Aphasia Therapy (CIAT; Pulvermüller et al., 2001) and semantic therapy (BOX; Visch-Brink & Bajema, 2001). Nine patients with chronic fluent aphasia participated in a therapy program to establish behavioral treatment outcomes. Participants were randomly assigned to one of two groups (CIAT or BOX). Intensive therapy significantly improved verbal communication. However, BOX treatment showed a more pronounced improvement on two communication-namely, a standardized assessment for verbal communication, the Amsterdam Nijmegen Everyday Language Test (Blomert, Koster, & Kean, 1995), and a subjective rating scale, the Communicative Effectiveness Index (Lomas et al., 1989). All participants significantly improved on one (or more) subtests of the Aachen Aphasia Test (Graetz, de Bleser, & Willmes, 1992), an impairment-focused assessment. There was a treatment-specific effect. BOX treatment had a significant effect on language comprehension and semantics, whereas CIAT treatment affected language production and phonology. The findings indicate that in patients with fluent aphasia, (a) intensive treatment has a significant effect on language and verbal communication, (b) intensive therapy results in selective treatment effects, and (c) an intensive semantic treatment shows a more striking mean improvement on verbal communication in comparison with communication-based CIAT treatment.

  3. PGRMC1-dependent autophagy by hyperoside induces apoptosis and sensitizes ovarian cancer cells to cisplatin treatment.

    PubMed

    Zhu, Xiaofei; Ji, Mingde; Han, Yue; Guo, Yuanyuan; Zhu, Wenqiang; Gao, Feng; Yang, Xuewen; Zhang, Chunbing

    2017-03-01

    Cisplatin treatment some times leads to chemoresistance, which is now acknowledged partially due to the inductive expression of progesterone receptor membrane component (PGRMC)1 in ovarian cancer cells. PGRMC1 enhances autophagy, activates cytochrome p450, and inveigles signaling pathways to promote cell survival and reduce the effect of drug treatments. In this study, we give first line evidence that hyperoside inhibits cell viability, triggers autophagy and apoptosis in ovarian cancer cell lines. Mechanistically, PGRMC1-dependent autophagy was utilized by hyperoside to induce apoptotic cell death. Hyperoside induced the conversion of LC3B-I to LC3B-II and the formation of autophagosomes in ovarian cancer cells. Notably, PGRMC1 colocolized with LC3B‑II, and PGRMC1 overexpression enhanced hyperoside-induced autophagy and apoptosis, while PGRMC1 knockdown abrogated the action. Additionally, AKT signaling and Bcl-2 family were also involved in the hyperoside-induced autophagy and apoptosis. Importantly, in cisplatin-resistant ovarian cancer cells where PGRMC1 was overexpressed, hyperoside sensitized the cells to cisplatin treatment. Together these findings indicate hyperoside functions as a complementary therapy for ovarian cancer patients receiving platinum-based therapy.

  4. Memantine prevents "bipolar-like" behavior induced by chronic treatment with imipramine in rats.

    PubMed

    Demontis, Francesca; Falconi, Marcella; Canu, Desirèe; Serra, Gino

    2015-04-05

    A great deal of evidence suggests that virtually all antidepressant treatments induce a dopaminergic behavioral supersensitivity. We have suggested that this effect may play a key role not only in the antidepressant effect of these treatments, but also in their ability to induce a switch from depression to mania. In 2003-4 we found that the sensitization of dopamine receptors induced by imipramine is followed, after imipramine withdrawal, by a desensitization of these receptors associated with a depressive-like behavior assessed in the forced swimming test. The dopamine receptor sensitization can be prevented by MK-801, an NMDA receptor antagonist, but not by currently used mood stabilizers (lithium, carbamazepine, valproate). These observations led us to suggest - and later confirm - with preliminary clinical observations that memantine may have an acute antimanic and a long-lasting mood-stabilizing effect in treatment-resistant bipolar disorder patients. Here we present data showing that memantine prevents not only the dopamine receptor sensitization induced by imipramine, as observed with MK-801, but also the ensuing desensitization and the associated depressive-like behaviorq observed after antidepressant withdrawal.

  5. Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model

    PubMed Central

    Iraporda, Carolina; Romanin, David E.; Bengoa, Ana A.; Errea, Agustina J.; Cayet, Delphine; Foligné, Benoit; Sirard, Jean-Claude; Garrote, Graciela L.; Abraham, Analía G.; Rumbo, Martín

    2016-01-01

    Lactate has long been considered as a metabolic by-product of cells. Recently, this view has been changed by the observation that lactate can act as a signaling molecule and regulates critical functions of the immune system. We previously identified lactate as the component responsible for the modulation of innate immune epithelial response of fermented milk supernatants in vitro. We have also shown that lactate downregulates proinflammatory responses of macrophages and dendritic cells. So far, in vivo effects of lactate on intestinal inflammation have not been reported. We evaluated the effect of intrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The increase in lactate concentration in colon promoted protective effects against TNBS-induced colitis preventing histopathological damage, as well as bacterial translocation and rise of IL-6 levels in serum. Using intestinal epithelial reporter cells, we found that flagellin treatment induced reporter gene expression, which was abrogated by lactate treatment as well as by glycolysis inhibitors. Furthermore, lactate treatment modulated glucose uptake, indicating that high levels of extracellular lactate can impair metabolic reprograming induced by proinflammatory activation. These results suggest that lactate could be a potential beneficial microbiota metabolite and may constitute an overlooked effector with modulatory properties. PMID:28082985

  6. Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model.

    PubMed

    Iraporda, Carolina; Romanin, David E; Bengoa, Ana A; Errea, Agustina J; Cayet, Delphine; Foligné, Benoit; Sirard, Jean-Claude; Garrote, Graciela L; Abraham, Analía G; Rumbo, Martín

    2016-01-01

    Lactate has long been considered as a metabolic by-product of cells. Recently, this view has been changed by the observation that lactate can act as a signaling molecule and regulates critical functions of the immune system. We previously identified lactate as the component responsible for the modulation of innate immune epithelial response of fermented milk supernatants in vitro. We have also shown that lactate downregulates proinflammatory responses of macrophages and dendritic cells. So far, in vivo effects of lactate on intestinal inflammation have not been reported. We evaluated the effect of intrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The increase in lactate concentration in colon promoted protective effects against TNBS-induced colitis preventing histopathological damage, as well as bacterial translocation and rise of IL-6 levels in serum. Using intestinal epithelial reporter cells, we found that flagellin treatment induced reporter gene expression, which was abrogated by lactate treatment as well as by glycolysis inhibitors. Furthermore, lactate treatment modulated glucose uptake, indicating that high levels of extracellular lactate can impair metabolic reprograming induced by proinflammatory activation. These results suggest that lactate could be a potential beneficial microbiota metabolite and may constitute an overlooked effector with modulatory properties.

  7. Effectiveness and safety of topical emollients in the treatment of PUVA-induced pruritus.

    PubMed

    Turan, Enver; Gurel, Mehmet Salih; Erdemir, Asli Turgut; Usta, Murat; Kutlu, Nurdan Seda; Yurt, Nurdan

    2013-01-01

    In this study we tried to assess the efficacy of topical emollients in the treatment of patients with PUVA-induced pruritus. 41 patients over 18 years of age, who received PUVA treatment in the phototherapy unit, were included in the study. Patients were randomly divided into two groups; Group I was administered with a 4% urea lotion and Group II was administered with liquid petrolatum. The follow-up period was minimum 4 weeks. During the first 2 weeks, patients were administered topical emollients and received PUVA treatment together. The next 2 weeks, they continued PUVA treatment without any medication. When time-dependent changes in the visual analogue scale scores for pruritus of both groups were considered, both treatment methods were found to be remarkably successful (p < 0.0001). In addition, an insignificant group-time interaction was identified (p = 0.753). Topical emollients were found to be effective in the treatment of PUVA-induced pruritus. Both forms of medication can be successfully administered and increase the patient's compliance with medication.

  8. A Survey of Chinese Medicinal Herbal Treatment for Chemotherapy-Induced Oral Mucositis

    PubMed Central

    Meyer-Hamme, Gesa; Beckmann, Kathrin; Radtke, Janine; Efferth, Thomas; Greten, Henry Johannes; Rostock, Matthias; Schröder, Sven

    2013-01-01

    Oral mucositis is one of the common side effects of chemotherapy treatment with potentially severe implications. Despite several treatment approaches by conventional and complementary western medicine, the therapeutic outcome is often not satisfactory. Traditional Chinese Medicine (TCM) offers empirical herbal formulas for the treatment of oral ulceration which are used in adaptation to chemotherapy-induced mucositis. While standard concepts for TCM treatment do not exist and acceptance by conventional oncologists is still low, we conducted a review to examine the evidence of Chinese herbal treatment in oral mucositis. Eighteen relevant studies on 4 single herbs, 2 combinations of 2 herbs, and 11 multiherbal prescriptions involving 3 or more compounds were included. Corresponding molecular mechanisms were investigated. The knowledge about detailed herbal mechanisms, especially in multi-herbal prescriptions is still limited. The quality of clinical trials needs further improvement. Meta-analysis on the existent database is not possible but molecular findings on Chinese medicinal herbs indicate that further research is still promising for the treatment of chemotherapy-induced oral mucositis. PMID:24285975

  9. Xylanase Treatment Suppresses Light- and Heat-Induced Yellowing of Pulp

    PubMed Central

    Zhang, Daolei; Li, Xuezhi; Wang, Meimei; Ye, Yanxin; Du, Jian; Lu, Xianqin; Zhao, Jian

    2016-01-01

    Xylanase is commonly applied in pulp and paper industries to ease cost-related and environmental pressures. The effect of xylanase treatment on pulp bleaching is well-established, however, few studies were conducted on the effects of xylanase treatment in pulp yellowing, especially the mechanism of pulp yellowing inhibition by xylanase treatment. In this study, pure xylanase (EC 3.2.1.8) was applied to treat wheat straw chemical pulp (CP) and poplar chemi-thermo-mechanical pulp (CTMP) to determine their effects on pulp brightness and on light- and heat-induced yellowing. The xylanase treatment decreased the post-color number of the pulps during light- and heat-induced yellowing. However, differences were observed in the yellowing inhibition between the wheat straw CP and poplar CTMP. The changes in chemical components of pulps after the xylanase treatment, for example, lignin, hemicellulose, and HexA contents, and analysis of UV–vis absorption spectra and Fourier transform infrared-attenuated total reflectance spectrum were used to explore the pulp yellowing inhibition causes by the xylanase treatment. PMID:27917912

  10. Repeated Treatments with Ingenol Mebutate Prevents Progression of UV-Induced Photodamage in Hairless Mice

    PubMed Central

    Thaysen-Petersen, Daniel; Bay, Christiane; Hald, Andreas; Skak, Kresten; Zibert, John Robert; Paasch, Uwe; Wulf, Hans Christian; Haedersdal, Merete

    2016-01-01

    Background and Aim Ingenol mebutate (IngMeb) is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local skin responses (LSR). Methods Hairless mice (n = 60; 3 groups of 20 mice) were irradiated with solar simulated ultraviolet radiation (UVR) throughout the study. Five single treatments with IngMeb were given at 4-week intervals (Days 21, 49, 77, 105, and 133). Clobetasol propionate (CP) was applied once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 (Days 28, 84, and 140), biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale (0–12). LSR (0–24) were assessed once daily (Days 1–7) after each IngMeb treatment. Results IngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 (UVR 10.25 vs. UVR+IngMeb 6.00, p = 0.002) compared to UVR alone. IngMeb induced LSR, including erythema, flaking, crusting, bleeding, vesiculation, and ulceration. Concurrent CP increased LSR (max LSR Tx 1–5: UVR+IngMeb+CP 3.6–5.5 vs. UVR+IngMeb 2.6–4.3) and provided better prevention of photodamage compared to IngMeb alone (Day 140: UVR+IngMeb 6.00 vs. UVR+IngMeb+CP 3.00 p < 0.001). Conclusion Repeated field-directed treatments with IngMeb prevent progression of cutaneous photodamage in hairless mice, while CP cannot be used to alleviate IngMeb-induced LSR. The findings suggest that IngMeb may potentially serve as a prophylactic treatment for UV-induced tumors. PMID:27636884

  11. Treatment with Sildenafil and Donepezil Improves Angiogenesis in Experimentally Induced Critical Limb Ischemia

    PubMed Central

    Constantinescu, Ioana M.; Bolfa, Pompei; Mironiuc, Aurel I.

    2017-01-01

    Objectives. In this study, we aimed to demonstrate the role of sildenafil (an antagonist of phosphodiesterase type 5 (PDE-5)) and donepezil (a specific and reversible inhibitor of acetylcholinesterase (Ach)) in increasing ischemia-induced angiogenesis. Method. Critical limb ischemia was induced by ligation of the common femoral artery followed by ligation of the common iliac artery. The operated animals were divided into 3 groups: receiving sildenafil, receiving donepezil, and surgery alone; the contralateral lower limb was used as a negative control. The results were controlled based on clinical score and Doppler ultrasound. Gastrocnemius muscle samples were taken from all animals, both from the ischemic and nonischemic limb and were used for histopathological and immunohistochemical examination for the evaluation of the number of nuclei/field, endothelial cells (CD31), dividing cells (Ki-67), and vascular endothelial growth factor (VEGFR-3). Results. An increasing tendency of the number of nuclei/field with time was observed both in the case of sildenafil and donepezil treatment. The formation of new capillaries (the angiogenesis process) was more strongly influenced by donepezil treatment compared to sildenafil or no treatment. This treatment significantly influenced the capillary/fiber ratio, which was increased compared to untreated ligated animals. Sildenafil treatment led to a gradual increase in the number of dividing cells, which was significantly compared to the negative control group and compared to the ligation control group. The same effect (increase in the number of Ki-67 positive cells) was more obvious in the case of donepezil treatment. Conclusion. Donepezil treatment has a better effect in ligation-induced ischemia compared to sildenafil, promoting angiogenesis in the first place, and also arteriogenesis. PMID:28243607

  12. Responses to hexyl 5-aminolevulinate-induced photodynamic treatment in rat bladder cancer model

    NASA Astrophysics Data System (ADS)

    Arum, Carl-Jørgen; Gederas, Odrun; Larsen, Eivind; Randeberg, Lise; Zhao, Chun-Mei

    2010-02-01

    OBJECTIVES: In this study, we evaluated histologically the effects of hexyl 5-aminolevulinateinduced photodynamic treatment in the AY-27 tumor cell induced rat bladder cancer model. MATERIAL & METHODS: The animals (fischer-344 female rats) were divided into 2 groups, half of which were orthotopically implanted with 400,000 syngeniec AY-27 urothelia1 rat bladder cancer cells and half sham implanted. 14 days post implantation 6 rats from each group were treated with hexyl 5-aminolevulinate-induced photodynamic treatment (8mM HAL and light fluence of 20 J/cm2). Additional groups of animals were only given HAL instillation, only light treatment, or no treatment. All animals were sacrificed 7 days after the PDT/only HAL/only light or no treatment. Each bladder was removed, embedded in paraffin and stained with hematoxylin, eosin, and saferin for histological evaluation at high magnification for features of tissue damage by a pathologist blinded to the sample source. RESULTS: In all animals that were AY-27 implanted and not given complete PDT treatment, viable tumors were found in the bladder mucosa and wall. In the animals treated with complete HAL-PDT only 3 of 6 animals had viable tumor. In the 3 animals with viable tumor it was significantly reduced in volume compared to the untreated animals. It was also noted that in the PDT treated animals there was a significantly increased inflammatory response (lymphocytic and mononuclear cell infiltration) in the peri-tumor area compared to implanted animals without complete HAL-PDT. CONCLUSION: Our results suggest that hexyl 5-aminolevulinate-induced photodynamic treatment in a rat bladder cancer model involves both direct effects on cell death (necrosis and apoptosis) and indirect effects to evoke the host immune-response, together contributing to tumor eradication.

  13. Management of late radiation-induced rectal injury after treatment of carcinoma of the uterus

    SciTech Connect

    Allen-Mersh, T.G.; Wilson, E.J.; Hope-Stone, H.F.; Mann, C.V.

    1987-06-01

    Sixty-one of 1418 (4.3 per cent) patients treated with radiation for carcinoma of the uterus from 1963 to 1983 had significant radiation-induced complications of the intestine develop which required a surgical opinion considering further management. Ninety-three per cent of these complications involved the rectum. Florid proctitis resolved within two years of onset in 33 per cent of the patients who were managed conservatively while 22 per cent of the patients died of disseminated disease within the same time period. Surgical treatment was eventually necessary in 39 per cent of the patients who were initially treated conservatively for radiation induced proctitis. Rectal excision with coloanal sleeve anastomosis produced a satisfactory result in eight of 11 patients with severe radiation injury involving the rectum. The incidence of radiation-induced and malignant rectovaginal fistula were similar (1 per cent), but disease-induced symptoms tended to occur earlier after primary treatment (a median of eight months) compared with radiation-induced symptoms (a median of 16 months).

  14. Effects of Pretreatment With Single-Dose or Intermittent Oxygen on Cisplatin-Induced Nephrotoxicity in Rats

    PubMed Central

    Rasoulian, Bahram; Kaeidi, Ayat; Pourkhodadad, Soheila; Dezfoulian, Omid; Rezaei, Maryam; Wahhabaghai, Hannaneh; Alirezaei, Masoud

    2014-01-01

    Background: Renal injury is the main side effect of cisplatin (CP), an anticancer drug. It has been shown that pretreatment with single-dose oxygen (0.5 to six hours) could reduce CP-induced renal toxicity in rats. Objectives: The present study aimed to compare the effects of pretreatment with single-dose and intermittent O2 on CP-induced nephrotoxicity. Materials and Methods: Adult male rats were allocated to seven groups (eight rats in each group). The rats were kept in normal air or hyperoxic environment (O2, 80%) for either a single six-hour period or intermittent six hours per day for seven days and then were subjected to intraperitoneal injection of saline or CP (5 mg/kg) at 48 hours, 72 hours, or seven days after exposure to O2. Three days after CP (or Saline) injection, renal function tests, renal tissue injury scores, and cleaved Caspase-3 and Bax/Bcl-2 genes expression (as markers of renal cell apoptosis) were assessed. Results: Treatment with the 6-hour single-dose O2 reduced renal injury significantly when CP was administrated 48 hours after O2 pretreatment. Pretreatment with intermittent seven days of six hours per day had no protective effects and even relatively worsened renal injury when CP was injected 48 hours or 72 hours after the last session of O2 pretreatment. The beneficial effects of pretreatment with O2 on renal structure and function were seen if CP was administrates seven days after pretreatment with intermittent O2. Conclusions: The pattern of pretreatment with O2 could change this potential and highly protective strategy against CP-induced nephropathy to an ineffective or even mildly deteriorating one. Therefore, O2 administration before CP injection to patients with cancer, for therapeutic purposes or as a preconditioning approach, should be performed and investigated with caution until exact effects of different protocols has been determined in human. PMID:25695032

  15. Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats?

    PubMed Central

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Mayir, Burhan; Akyüz, Cebrail; Polat, Cemal; Baştürk, Ahmet; Soyer, Vural; Koç, Süleyman; Şehirli, Ahmet Özer

    2015-01-01

    Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue. PMID:26550330

  16. Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats?

    PubMed

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Mayir, Burhan; Akyüz, Cebrail; Polat, Cemal; Baştürk, Ahmet; Soyer, Vural; Koç, Süleyman; Şehirli, Ahmet Özer

    2015-01-01

    Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue.

  17. Positive interaction between prebiotics and thiazolidinedione treatment on adiposity in diet-induced obese mice.

    PubMed

    Alligier, Maud; Dewulf, Evelyne M; Salazar, Nuria; Mairal, Aline; Neyrinck, Audrey M; Cani, Patrice D; Langin, Dominique; Delzenne, Nathalie M

    2014-07-01

    To investigate whether inulin-type fructan (ITF) prebiotics could counteract the thiazolidinedione (TZD, PPARγ activator) induced-fat mass gain, without affecting its beneficial effect on glucose homeostasis, in high-fat (HF) diet fed mice. Male C57bl6/J mice were fed a HF diet alone or supplemented with ITF prebiotics (0.2 g/day × mouse) or TZD (30 mg pioglitazone (PIO)/kg body weight × day) or both during 4 weeks. An insulin tolerance test was performed after 3 weeks of treatment. As expected, PIO improved glucose homeostasis and increased adiponectinaemia. Furthermore, it induced an over-expression of several PPARγ target genes in white adipose tissues. ITF prebiotics modulated the PIO-induced PPARγ activation in a tissue-dependent manner. The co-treatment with ITF prebiotics and PIO maintained the beneficial impact of TZD on glucose homeostasis and adiponectinaemia. Moreover, the combination of both treatments reduced fat mass accumulation, circulating lipids and hepatic triglyceride content, suggesting an overall improvement of metabolism. Finally, the co-treatment favored induction of white-to-brown fat conversion in subcutaneous adipose tissue, thereby leading to the development of brite adipocytes that could increase the oxidative capacity of the tissue. ITF prebiotics decrease adiposity and improve the metabolic response in HF fed mice treated with TZD. © 2014 The Obesity Society.

  18. Pharmacological agents used for treatment and prevention in noise-induced hearing loss.

    PubMed

    Sakat, Muhammed Sedat; Kilic, Korhan; Bercin, Sami

    2016-12-01

    Noise is a stress factor that causes auditory, psychological and physiological effects. The realization that sudden loud noises or chronic exposure to noise in social and working environments can cause hearing loss has led to increased interest in noise-induced hearing loss (NIHL). The best means of preventing primary damage is protection against noise. Since this protection is not always possible for various reasons, the use of pharmacological agents to prevent or treat NIHL should also be considered. The purpose of this study is to discuss current pharmacological protection and treatment options in the light of the literature, since no such extensive reviews have been performed to date, including agents used for protection against and treatment of NIHL. We reviewed both animal and clinical studies, and these are discussed separately for ease of comprehension. For each agent, first animal studies, then clinical studies, if available, are discussed. We also performed a two-step search of the literature. In the first step, we searched the terms "noise induced hearing loss", "treatment" and "protection" in Pubmed. Based on the results obtained, we identified the agents used for the treatment of and protection against NIHL. In the second step, we searched the names of the agents identified in the first step, together with the term "noise induced hearing loss," and reviewed the results.

  19. A successful treatment strategy for clozapine-induced parotid swelling: a clinical case and systematic review.

    PubMed

    Immadisetty, Vyasa; Agrawal, Pradeep

    2012-12-01

    Parotid gland swelling is a less frequently reported side effect of clozapine and has no licensed treatment. A 58-year-old man treated with clozapine for treatment-resistant schizophrenia developed bilateral painful parotid swellings and hypersalivation. Initial trials of dose alteration and antihypersalivatory medication had limited success. A combination of benzatropine and terazosin was successful in treating the parotid hyperplasia. Clozapine was the probable cause of parotid swelling in our case, as established using the Naranjo adverse drug reaction probability scale and World Health Organization causality categories. Literature for treatments of clozapine-induced parotid gland swellings was reviewed. None of the published articles suggested a treatment regimen for clozapine-induced parotid hyperplasia. Most reports only highlighted the occurrence of salivary gland swelling with clozapine. Others mentioned management strategies, which included spontaneous resolution, or resolution on discontinuing clozapine. One report, a trial with benzatropine and ipratropium, had variable success. In this case the re-emergence of parotid swelling when terazosin and benzatropine doses were missed followed by a quick resolution upon recompliance, goes some way in proving that this combination is indeed effective. The combination of terazosin and benzatropine appears to have a role in treating parotid gland swellings induced by clozapine.

  20. Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis.

    PubMed

    Borab, Zachary; Mirmanesh, Michael D; Gantz, Madeleine; Cusano, Alessandro; Pu, Lee L Q

    2017-04-01

    Every year, 1.2 million cancer patients receive radiation therapy in the United States. Late radiation tissue injury occurs in an estimated 5-15% of these patients. Tissue injury can include skin necrosis, which can lead to chronic nonhealing wounds. Despite many treatments available to help heal skin necrosis such as hyperbaric oxygen therapy, no clinical guidelines exist and evidence is lacking. The purpose of this review is to identify and comprehensively summarize studies published to date to evaluate the effectiveness of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Adhering to PRISMA guidelines, a systematic review of currently published articles was performed, evaluating the use of hyperbaric oxygen to treat skin necrosis. Eight articles were identified, including one observational cohort, five case series, and two case reports. The articles describe changes in symptoms and alteration in wound healing of radiation-induced skin necrosis after treatment with hyperbaric oxygen therapy. Hyperbaric oxygen therapy is a safe intervention with promising outcomes; however, additional evidence is needed to endorse its application as a relevant therapy in the treatment of radiation-induced skin necrosis.

  1. Cyclosporine A and palmitic acid treatment synergistically induce cytotoxicity in HepG2 cells

    SciTech Connect

    Luo, Yi Rana, Payal; Will, Yvonne

    2012-06-01

    Immunosuppressant cyclosporine A (CsA) treatment can cause severe side effects. Patients taking immunosuppressant after organ transplantation often display hyperlipidemia and obesity. Elevated levels of free fatty acids have been linked to the etiology of metabolic syndromes, nonalcoholic fatty liver and steatohepatitis. The contribution of free fatty acids to CsA-induced toxicity is not known. In this study we explored the effect of palmitic acid on CsA-induced toxicity in HepG2 cells. CsA by itself at therapeutic exposure levels did not induce detectible cytotoxicity in HepG2 cells. Co-treatment of palmitic acid and CsA resulted in a dose dependent increase in cytotoxicity, suggesting that fatty acid could sensitize cells to CsA-induced cytotoxicity at the therapeutic doses of CsA. A synergized induction of caspase-3/7 activity was also observed, indicating that apoptosis may contribute to the cytotoxicity. We demonstrated that CsA reduced cellular oxygen consumption which was further exacerbated by palmitic acid, implicating that impaired mitochondrial respiration might be an underlying mechanism for the enhanced toxicity. Inhibition of c-Jun N-terminal kinase (JNK) attenuated palmitic acid and CsA induced toxicity, suggesting that JNK activation plays an important role in mediating the enhanced palmitic acid/CsA-induced toxicity. Our data suggest that elevated FFA levels, especially saturated FFA such as palmitic acid, may be predisposing factors for CsA toxicity, and patients with underlying diseases that would elevate free fatty acids may be susceptible to CsA-induced toxicity. Furthermore, hyperlipidemia/obesity resulting from immunosuppressive therapy may aggravate CsA-induced toxicity and worsen the outcome in transplant patients. -- Highlights: ► Palmitic acid and cyclosporine (CsA) synergistically increased cytotoxicity. ► The impairment of mitochondrial functions may contribute to the enhanced toxicity. ► Inhibition of JNK activity attenuated

  2. Dabigatran in the Treatment of Warfarin-Induced Skin Necrosis: A New Hope

    PubMed Central

    Bakoyiannis, Christos; Karaolanis, Georgios; Patelis, Nikolaos; Maskanakis, Anastasios; Tsaples, Georgios; Klonaris, Christos; Georgopoulos, Sotirios; Liakakos, Theodoros

    2016-01-01

    Warfarin-induced skin necrosis is an infrequent and well-recognized complication of warfarin treatment. The incidence was estimated between 0.01% and 0.1% whereas a paradoxal prothrombotic state that arises from warfarin therapy seems to be responsible for this life-threatening disease. To the best of our knowledge we present the first case of an old woman diagnosed with warfarin-induced skin necrosis, in whom novel oral anticoagulants and extensive surgical debridement were combined safely with excellent results. PMID:27110410

  3. Hot Air Treatment Induces Disease Resistance through Activating the Phenylpropanoid Metabolism in Cherry Tomato Fruit.

    PubMed

    Wei, Yingying; Zhou, Dandan; Peng, Jing; Pan, Leiqing; Tu, Kang

    2017-09-13

    To explore the effects of hot air (HA, 38 °C for 12 h) treatment on the phenylpropanoid metabolism in cherry tomatoes, phenylpropanoid metabolite levels and the activities and expression of key enzymes were analyzed in HA-treated fruit. HA treatment enhanced phenylpropanoid metabolism, as evidenced by elevated levels of phenolics and flavonoids, higher activities of phenylalanine ammonia-lyase and cinnamate-4-hydroxylase, and upregulated expression of LeCHS, LeCHI, LeF3H, and LeFLS. Levels of several phenylpropanoid metabolites were higher after HA treatment, including p-coumaric acid, caffeic acid, chlorogenic acid, isoquercitrin, quercetin, and rutin. These metabolic changes may be related to the reduced disease incidence and smaller lesion diameters observed in HA-treated fruit inoculated with Alternaria alternata (black mold) or Botrytis cinerea (gray mold). The results suggest that HA treatment induces disease resistance by activating the phenylpropanoid pathway in cherry tomato fruit.

  4. Clinical utility of naloxegol in the treatment of opioid-induced constipation.

    PubMed

    Bruner, Heather C; Atayee, Rabia S; Edmonds, Kyle P; Buckholz, Gary T

    2015-01-01

    Opioids are a class of medications frequently used for the treatment of acute and chronic pain, exerting their desired effects at central opioid receptors. Agonism at peripherally located opioid receptors, however, leads to opioid-induced constipation (OIC), one of the most frequent and debilitating side effects of prolonged opioid use. Insufficient relief of OIC with lifestyle modification and traditional laxative treatments may lead to decreased compliance with opioid regimens and undertreated pain. Peripherally acting mu-opioid receptor antagonists (PAMORAs) offer the reversal of OIC without loss of central pain relief. Until recently, PAMORAs were restricted to subcutaneous route or to narrow patient populations. Naloxegol is the first orally dosed PAMORA indicated for the treatment of OIC in noncancer patients. Studies have suggested its efficacy in patients failing traditional constipation treatments; however, insufficient evidence exists to establish its role in primary prevention of OIC at this time.

  5. Clinical utility of naloxegol in the treatment of opioid-induced constipation

    PubMed Central

    Bruner, Heather C; Atayee, Rabia S; Edmonds, Kyle P; Buckholz, Gary T

    2015-01-01

    Opioids are a class of medications frequently used for the treatment of acute and chronic pain, exerting their desired effects at central opioid receptors. Agonism at peripherally located opioid receptors, however, leads to opioid-induced constipation (OIC), one of the most frequent and debilitating side effects of prolonged opioid use. Insufficient relief of OIC with lifestyle modification and traditional laxative treatments may lead to decreased compliance with opioid regimens and undertreated pain. Peripherally acting mu-opioid receptor antagonists (PAMORAs) offer the reversal of OIC without loss of central pain relief. Until recently, PAMORAs were restricted to subcutaneous route or to narrow patient populations. Naloxegol is the first orally dosed PAMORA indicated for the treatment of OIC in noncancer patients. Studies have suggested its efficacy in patients failing traditional constipation treatments; however, insufficient evidence exists to establish its role in primary prevention of OIC at this time. PMID:26109876

  6. Treatment of antigen-induced arthritis in rabbits with dysprosium-165-ferric hydroxide macroaggregates

    SciTech Connect

    Zuckerman, J.D.; Sledge, C.B.; Shortkroff, S.; Venkatesan, P.

    1989-01-01

    Dysprosium-165-ferric hydroxide macroaggregates (/sup 165/Dy-FHMA) was used as an agent of radiation synovectomy in an antigen-induced arthritis model in New Zealand white rabbits. Animals were killed up to 6 months after treatment. /sup 165/Dy-FHMA was found to have a potent but temporary antiinflammatory effect on synovium for up to 3 months after treatment. Treated knees also showed significant preservation of articular cartilage architecture and proteoglycan content compared with untreated controls, but only during the first 3 months after treatment. In animals killed 3 and 6 months after treatment there were only minimal differences between the treated and untreated knees, indicating that the antiinflammatory effects on synovial tissue and articular cartilage preservation were not sustained.

  7. Combination antibiotics for the treatment of Chlamydia-induced reactive arthritis: is a cure in sight?

    PubMed Central

    Carter, John D; Gérard, Hervé C; Whittum-Hudson, Judith A; Hudson, Alan P

    2011-01-01

    The inflammatory arthritis that develops in some patients subsequent to urogenital infection by the obligate intracellular bacterial pathogen Chlamydia trachomatis, and that induced subsequent to pulmonary infection with C. pneumoniae, both have proved difficult to treat in either their acute or chronic forms. Over the last two decades, molecular genetic and other studies of these pathogens have provided a good deal of information regarding their metabolic and genetic structures, as well as the detailed means by which they interact with their host cells. In turn, these insights have provided for the first time a window into the bases for treatment failures for the inflammatory arthritis. In this article we discuss the biological bases for those treatment failures, provide suggestions as to research directions that should allow improvement in treatment modalities, and speculate on how treatment regimens that currently show promise might be significantly improved over the near future using nanotechological means. PMID:21853013

  8. Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers

    PubMed Central

    Culbertson, Christopher S.; Bramen, Jennifer; Cohen, Mark S.; London, Edythe D.; Olmstead, Richard E.; Gan, Joanna J.; Costello, Matthew R.; Shulenberger, Stephanie; Mandelkern, Mark A.; Brody, Arthur L.

    2011-01-01

    Context Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design Randomized, double-blind, before-after controlled trial. Setting Academic brain imaging center. Participants Thirty nicotine-dependent smokers (paid volunteers). Interventions Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions. PMID:21199957

  9. Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials.

    PubMed

    Wu, R-R; Zhang, F-Y; Gao, K-M; Ou, J-J; Shao, P; Jin, H; Guo, W-B; Chan, P K; Zhao, J-P

    2016-11-01

    Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day(-1) metformin (n=103) or placebo (n=98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l(-1) at baseline to -0.86 mmol l(-1) at the end of week 24, decreased by 1.02 mmol l(-1) (P<0.0001); and 25.3% of patients in the metformin group had LDL-C ≥3.37 mmol l(-1), which is significantly <64.8% in the placebo group (P<0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia.

  10. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission

    PubMed Central

    Rooks, Michelle G; Veiga, Patrick; Wardwell-Scott, Leslie H; Tickle, Timothy; Segata, Nicola; Michaud, Monia; Gallini, Carey Ann; Beal, Chloé; van Hylckama-Vlieg, Johan ET; Ballal, Sonia A; Morgan, Xochitl C; Glickman, Jonathan N; Gevers, Dirk; Huttenhower, Curtis; Garrett, Wendy S

    2014-01-01

    Dysregulated immune responses to gut microbes are central to inflammatory bowel disease (IBD), and gut microbial activity can fuel chronic inflammation. Examining how IBD-directed therapies influence gut microbiomes may identify microbial community features integral to mitigating disease and maintaining health. However, IBD patients often receive multiple treatments during disease flares, confounding such analyses. Preclinical models of IBD with well-defined disease courses and opportunities for controlled treatment exposures provide a valuable solution. Here, we surveyed the gut microbiome of the T-bet−/− Rag2−/− mouse model of colitis during active disease and treatment-induced remission. Microbial features modified among these conditions included altered potential for carbohydrate and energy metabolism and bacterial pathogenesis, specifically cell motility and signal transduction pathways. We also observed an increased capacity for xenobiotics metabolism, including benzoate degradation, a pathway linking host adrenergic stress with enhanced bacterial virulence, and found decreased levels of fecal dopamine in active colitis. When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. Thus, our study provides insight into specific microbial clades and pathways associated with health, active disease and treatment interventions in a mouse model of colitis. PMID:24500617

  11. Chemotherapy of East Coast fever: parvaquone treatment of clinical disease induced by isolates of Theileria parva.

    PubMed

    Dolan, T T; Young, A S; Leitch, B L; Stagg, D A

    1984-08-01

    Two experiments were carried out in which parvaquone was used to treat experimentally-induced acute clinical East Coast fever infections. In the first experiment, infections with Theileria parva parva (Kiambu 5) were induced by applying infected Rhipicephalus appendiculatus ticks or by inoculation of triturated infected-tick stabilate. The character of the disease was similar with both methods of infection and following a single treatment with parvaquone at 20 mg kg-1, 5 of 7 cattle in each group recovered. All untreated control cattle died. In the second experiment, 5 stabilate isolates from different locations within East Africa, and representative of the challenge likely to be met in the field, were used. Treatment was administered in 2 X 10 mg kg-1 doses 48 h apart. The isolates used were T. p. parva (Mbita), T. p. parva (Pugu), T. p. parva (Entebbe), T. p. lawrencei (Mara) and T. p. lawrencei/(Manyara); following treatment 3/7, 6/6, 6/7, 5/7 and 6/7 animals recovered, respectively. All untreated control cattle died. There was evidence of a difference in susceptibility of isolates to treatment, and some animals showed prolonged disease episodes. The nature of the response to treatment and the problems in treating a lympho-destructive disease are discussed.

  12. Radiation-Induced Leiomyosarcoma after Breast Cancer Treatment and TRAM Flap Reconstruction

    PubMed Central

    Olcina, M.; Merck, B.; Giménez-Climent, M. J.; Almenar, S.; Sancho-Merle, M. F.; Llopis, F.; Vázquez-Albadalejo, C.

    2008-01-01

    The development of a radiation-induced sarcoma (RIS) in the post mastectomy thoracic treatment volume is an infrequent, but recognized, event. Its frequency is rising in relation with increasing survival of breast cancer patients treated with adjuvant radiation therapy, and is associated with poor prognosis despite treatment. We present a case of leiomyosarcoma in a patient who underwent mastectomy followed by radiotherapy for invasive ductal carcinoma. A delayed TRAM flap reconstruction was performed 10 years after and a rapid growing mass under the reconstructed flap appeared, on routine follow-up, twenty years later. This report analyzes the diagnostic and therapeutic approach of patients with RIS. PMID:18464918

  13. Optimizing treatment outcomes in patients at risk for chemotherapy-induced nausea and vomiting.

    PubMed

    Thompson, Nancy

    2012-06-01

    Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial in maximizing patients' quality of life and optimizing outcomes of cancer therapy, and can be done more effectively than ever before. Appropriate antiemetic therapy combined with targeted patient education, clear communication, and management of patient expectations results in optimal emetogenic control. Oncology nurses play a critical role in the prevention and management of CINV. This column reviews the history and pathophysiology of treatments for CINV, as well as patient- and chemotherapy-specific risk factors that should be considered to optimize treatment outcomes in patients with CINV.

  14. [Research progress of induced pluripotent stem cells in treatment of muscle atrophy].

    PubMed

    Yao, Zhongkai; Yang, Chensong; Sun, Guixin

    2016-03-01

    Muscle atrophy caused by nerve injury is a common and difficult clinical problem. The development of stem cell researches has opened up a new way for the treatment of nerve injury-induced muscle atrophy. The induced pluripotent stem cells(iPSCs)can differentiate into various types of cells and have more advantages than embryonic stem cells (ESCs). After being transplanted into the damaged area, iPSCs are guided by neurogenic signals to the lesion sites, to repair the damaged nerve, promote generation of axon myelination, rebuild neural circuits and restore physiological function. Meanwhile, iPSCs can also differentiate into muscle cells and promote muscle tissue regeneration. Therefore, it would be possible to attenuate muscle atrophy caused by nerve injury with iPSCs treatment.

  15. Radiation recall dermatitis induced by tamoxifen during adjuvant breast cancer treatment

    PubMed Central

    Rhee, Jiyoung; Kim, Gwi Eon; Lee, Chang Hyun; Kwon, Jung-Mi; Han, Sang-Hoon; Kim, Young Suk

    2014-01-01

    Tamoxifen and radiotherapy are used in breast cancer treatment worldwide. Radiation recall dermatitis (RRD), induced by tamoxifen, has been rarely reported. Herein, we report a RRD case induced by tamoxifen. A 47-year-old woman had a right quadrantectomy and an axillary lymph node dissection due to breast cancer. The tumor was staged pT2N0; it was hormone receptor positive, and human epidermal growth factor receptor 2 negative. The patient received adjuvant chemotherapy followed by tamoxifen and radiotherapy. After 22 months of tamoxifen, the patient developed a localized heating sensation, tenderness, edema, and redness at the irradiated area of the right breast. The symptoms improved within 1 week without treatment. Three weeks later, however, the patient developed similar symptoms in the same area of the breast. She continued tamoxifen before and during dermatitis, and symptoms resolved within 1 week. PMID:25568855

  16. Locally Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment.

    PubMed

    Zhang, Yuqi; Liu, Qiongming; Yu, Jicheng; Yu, Shuangjiang; Wang, Jinqiang; Qiang, Li; Gu, Zhen

    2017-09-26

    Obesity is one of the most serious public health problems in the 21st century that may lead to many comorbidities such as type-2 diabetes, cardiovascular diseases, and cancer. Current treatments toward obesity including diet, physical exercise, pharmacological therapy, as well as surgeries are always associated with low effectiveness or undesired systematical side effects. In order to enhance treatment efficiency with minimized side effects, we developed a transcutaneous browning agent patch to locally induce adipose tissue transformation. This microneedle-based patch can effectively deliver browning agents to the subcutaneous adipocytes in a sustained manner and switch on the "browning" at the targeted region. It is demonstrated that this patch reduces treated fat pad size, increases whole body energy expenditure, and improves type-2 diabetes in vivo in a diet-induced obesity mouse model.

  17. Pathophysiology of visual disorders induced by phosphodiesterase inhibitors in the treatment of erectile dysfunction.

    PubMed

    Moschos, Marilita M; Nitoda, Eirini

    2016-01-01

    The aim of this review was to summarize the ocular action of the most common phosphodiesterase (PDE) inhibitors used for the treatment of erectile dysfunction and the subsequent visual disorders. This is a literature review of several important articles focusing on the pathophysiology of visual disorders induced by PDE inhibitors. PDE inhibitors have been associated with ocular side effects, including changes in color vision and light perception, blurred vision, transient alterations in electroretinogram (ERG), conjunctival hyperemia, ocular pain, and photophobia. Sildenafil and tadalafil may induce reversible increase in intraocular pressure and be involved in the development of non-arteritic ischemic optic neuropathy. Reversible idiopathic serous macular detachment, central serous chorioretinopathy, and ERG disturbances have been related to the significant impact of sildenafil and tadalafil on retinal perfusion. So far, PDE inhibitors do not seem to cause permanent toxic effects on chorioretinal tissue and photoreceptors. However, physicians should write down any visual symptom observed during PDE treatment and refer the patients to ophthalmologists.

  18. The effects of combinatorial treatments with stress inducing molecules on growth of E. coli colonies.

    PubMed

    Middler, Steven L; Gomez, Salvador; Parker, Christapher D; Palenchar, Peter M

    2011-12-01

    Stress inducing molecules affect both the mean behavior of bacterial growth and also variations in the growth. While the mechanisms that cause changes in the mean behavior are well understood, little is known about changes in the variation of the population. A true understanding of how organisms respond to stress must include an understanding of the mechanisms and purposes of changes in variation and the distribution not directly related to changes in the mean of the population. We have explored the results of combinatorial treatments using EDTA, copper sulfate, hydrogen peroxide, and hydrochloric acid as stress inducing molecules on bacterial colony formation and area on LB-agar plates. Three different combinations of X-gal and IPTG were used to create different background conditions. Some treatments alter the variation and/or the distribution of the area without having a significant effect on the mean, others affect the mean without altering the distribution, and yet others affect distribution and the mean.

  19. Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection.

    PubMed

    Cortjens, Bart; de Jong, Rineke; Bonsing, Judith G; van Woensel, Job B M; Antonis, Adriaan F G; Bem, Reinout A

    2017-08-05

    Respiratory syncytial virus (RSV) infection is characterised by airway obstruction with mucus plugs, containing DNA networks in the form of neutrophil extracellular traps (NETs). We investigated the effect of dornase alfa on histopathological NETs-induced airway obstruction and viral load in an age-relevant calf model of severe bovine RSV disease. As compared with the control animals, dornase alfa treatment resulted in a strong reduction of NETs-induced airway obstruction. Viral load in the lower respiratory tract was not different between the two groups. We conclude that NETs form a relevant target for treatment of airway obstruction in severe RSV disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis.

    PubMed

    Wang, X; Luo, F; Huang, K; Xie, Z

    2016-03-01

    Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft. The patients were followed for 27.5 months (24 to 32). Radiographic bone union occurred at six months for 26 cases (81%) and clinical healing occurred in 29 cases (90%) at ten months. A total of six cases had a second debridement before bone grafting because of recurrence of infection and one patient required a third debridement. No cases of osteomyelitis had recurred at the time of the last follow-up visit. The induced membrane technique for the treatment of post-traumatic osteomyelitis is a simple, reliable method, with good early results. However, there are many challenges in determining the scope of the debridement, type of limb fixation and source of bone graft to be used.Cite this article: Dr Z. Xie. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint Res 2016;5:101-105. DOI: 10.1302/2046-3758.53.2000487. © 2016 Xie et al.

  1. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin.

    PubMed

    Al-Harbi, Naif O; Imam, Faisal; Nadeem, Ahmed; Al-Harbi, Mohammed M; Iqbal, Muzaffar; Ahmad, Sheikh Fayaz

    2014-08-01

    Liver is a vital organ for the detoxification of toxic substances present in the body and hepatic injury is associated with excessive exposure to toxicants. The present study was designed to evaluate the possible hepatoprotective effects of riboflavin against carbon tetrachloride (CCl4) induced hepatic injury in rats. Rats were divided into six groups. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl4 in experimental rats. Riboflavin was administered at 30 and 100mg/kg by oral gavage to test its protective effect on hepatic injury biochemically and histopathologically in the blood/liver and liver respectively. The administration of CCl4 resulted in marked alteration in serum hepatic enzymes (like AST, ALT and ALP), oxidant parameters (like GSH and MDA) and pro-inflammatory cytokine TNF-α release from blood leukocytes indicative of hepatic injury. Changes in serum hepatic enzymes, oxidant parameters and TNF-α production induced by CCl4 were reversed by riboflavin treatment in a dose dependent manner. Treatment with standard drug, silymarin also reversed CCl4 induced changes in biomarkers of liver function, oxidant parameters and inflammation. The biochemical observations were paralleled by histopathological findings in rat liver both in the case of CCl4 and treatment groups. In conclusion, riboflavin produced a protective effect against CCl4-induced liver damage. Our study suggests that riboflavin may be used as a hepato-protective agent against toxic effects caused by CCl4 and other chemical agents in the liver. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis

    PubMed Central

    Wang, X.; Luo, F.; Huang, K.

    2016-01-01

    Objectives Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. Methods A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft. Results The patients were followed for 27.5 months (24 to 32). Radiographic bone union occurred at six months for 26 cases (81%) and clinical healing occurred in 29 cases (90%) at ten months. A total of six cases had a second debridement before bone grafting because of recurrence of infection and one patient required a third debridement. No cases of osteomyelitis had recurred at the time of the last follow-up visit. Conclusion The induced membrane technique for the treatment of post-traumatic osteomyelitis is a simple, reliable method, with good early results. However, there are many challenges in determining the scope of the debridement, type of limb fixation and source of bone graft to be used. Cite this article: Dr Z. Xie. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint Res 2016;5:101–105. DOI: 10.1302/2046-3758.53.2000487. PMID:27033845

  3. Drug-induced systemic lupus erythematosus in a child after 3 years of treatment with carbamazepine.

    PubMed

    Molina-Ruiz, Ana María; Lasanta, Begoña; Barcia, Ana; Pérez-Vega, Elisa; Requena, Luis

    2017-02-01

    Drug-induced lupus erythematosus (DILE) is a less severe variant of systemic lupus erythematosus (SLE) that generally resolves within weeks or months after the withdrawal of the implicated drug. DILE is unusual during childhood, with the most frequent age of presentation being at 50-70 years of age. Among different drugs, most commonly procainamide and hydralazine have been implicated as a cause of DILE. However carbamazepine (CBZ) is considered a low-risk drug and very few cases have been reported in children. We describe the case of CBZ-induced SLE in a 9-year-old girl following 3 years of CBZ therapy. This case report shows that drug-induced SLE is an important side-effect to be considered, even after long-term treatment with CBZ, and also during childhood.

  4. Treatment of radiation-induced hemorrhagic gastritis with prednisolone: A case report

    PubMed Central

    Zhang, Lan; Xie, Xiao-Ying; Wang, Yan; Wang, Yan-Hong; Chen, Yi; Ren, Zheng-Gang

    2012-01-01

    Radiation-induced gastritis is an infrequent cause of gastrointestinal bleeding. It is a serious complication arising from radiation therapy, and the standard treatment method has not been established. The initial injury is characteristically acute inflammation of gastric mucosa. We presented a 46-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for metastatic retroperitoneal lymph node of hepatocellular carcinoma. The endoscopic examination showed diffuse edematous hyperemicmucosa with telangiectasias in the whole muscosa of the stomach and duodenal bulb. Multiple hemorrhagic patches with active oozing were found over the antrum. Anti-secretary therapy was initiated for hemostasis, but melena still occurred off and on. Finally, he was successfully treated by prednisolone therapy. We therefore strongly argue in favor of perdnisolone therapy to effectively treat patients with radiation-induced hemorrhagic gastritis. PMID:23326152

  5. Epoetin beta for the treatment of chemotherapy-induced anemia: an update

    PubMed Central

    Galli, Luca; Ricci, Clara; Egan, Colin Gerard

    2015-01-01

    Epoetin beta belongs to the class of erythropoiesis-stimulating agents (ESAs) that are currently available to treat anemic patients receiving chemotherapy. Chemotherapy-induced anemia affects a high percentage of cancer patients and, due to its negative effects on disease outcome and the patient’s quality of life, should be treated when first diagnosed. Initial trials with ESAs have shown efficacy in improving quality of life and reducing the need for blood transfusions in patients with chemotherapy-induced anemia. However, recent meta-analyses have provided conflicting data on the impact of ESAs on survival and tumor progression. Here we provide an overview of these recent data and review the role of epoetin beta in the treatment of chemotherapy-induced anemia over the past 20 years. PMID:25784818

  6. [Deafness, induced by sodium ethacrynate in guinea pigs, alleviated by microwave treatment].

    PubMed

    Chen, X M; Din, D L; Luo, D F; Huangfu, M S; Jin, X M

    1992-01-01

    Microwave is used to treat temporal hearing loss caused by intravenous injection of the ethacrynic acid in guinea pigs. The recovery of hearing is much faster in the treated groups than in the control group. The article proposes possible mechanism of the effects against the ethacrynic acid induced deafness and assume that the result of this research can provide an experimental basis for treatment of some perceptive deafness due to ischemia of stria vascularis of the cochlea.

  7. Successful treatment of laser induced hypopigmentation with narrowband ultraviolet B targeted phototherapy.

    PubMed

    Mysore, Venkataram; Anitha, B; Hosthota, Abhineetha

    2013-04-01

    Q-switched 1064 nm neodymium-doped yttrium aluminium garnet (Qs 1064 nm Nd: YAG) laser plays an important role in the treatment of pigmentary skin disorders, including tattoos. Although it has high efficacy and safety, adverse effect like hypopigmentation may occur causing anxiety to patients. We present a case report of Qs 1064 nm Nd: YAG laser induced hypopigmentation which was successfully treated with ultraviolet B targeted phototherapy, with rapid and satisfactory re-pigmentation.

  8. Successful Treatment of Laser Induced Hypopigmentation with Narrowband Ultraviolet B Targeted Phototherapy

    PubMed Central

    Mysore, Venkataram; Anitha, B; Hosthota, Abhineetha

    2013-01-01

    Q-switched 1064 nm neodymium-doped yttrium aluminium garnet (Qs 1064 nm Nd: YAG) laser plays an important role in the treatment of pigmentary skin disorders, including tattoos. Although it has high efficacy and safety, adverse effect like hypopigmentation may occur causing anxiety to patients. We present a case report of Qs 1064 nm Nd: YAG laser induced hypopigmentation which was successfully treated with ultraviolet B targeted phototherapy, with rapid and satisfactory re-pigmentation. PMID:24023438

  9. Changes induced in spice paprika powder by treatment with ionizing radiation and saturated steam

    NASA Astrophysics Data System (ADS)

    Kispéter, J.; Bajúsz-Kabók, K.; Fekete, M.; Szabó, G.; Fodor, E.; Páli, T.

    2003-12-01

    The changes in spice paprika powder induced by ionizing radiation, saturated steam (SS) and their combination were studied as a function of the absorbed radiation dose and the storage time. The SS treatment lead to a decrease in color content (lightening) after 12 weeks of storage, together with the persistence of free radicals and viscosity changes for a longer period. The results suggest that ionizing radiation is a more advantageous method as concerns preservation of the quality of spice paprika.

  10. Vasoactive Intestinal Polypeptide and Muscarinic Receptors: Supersensitivity Induced by Long-Term Atropine Treatment

    NASA Astrophysics Data System (ADS)

    Hedlund, Britta; Abens, Janis; Bartfai, Tamas

    1983-04-01

    Long-term treatment of rats with atropine induced large increases in the numbers of muscarinic receptors and receptors for vasoactive intestinal polypeptide in the salivary glands. Since receptors for vasoactive intestinal polypeptide coexist with muscarinic receptors on the same neurons in this preparation, the results suggest that a drug that alters the sensitivity of one receptor may also affect the sensitivity of the receptor for a costored transmitter and in this way contribute to the therapeutic or side effects of the drug.

  11. Restoration of MPTP-induced deficits by exercise and Milmed® co-treatment

    PubMed Central

    Archer, Trevor; Fredriksson, Anders

    2014-01-01

    1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces permanent neurochemical and functional deficits. Following the administration of either two or four injections of the dopamine neurotoxin, MPTP, at a dose of 40 mg/kg, C57/BL6 mice were given access to running-wheels (30-min sessions, four times/week, Monday–Thursday) and treatment with the treated yeast, Milmed® (four times/week, Monday–Thursday), or simply running-wheel exercise by itself, over ten weeks. It was observed that the combination of physical exercise and Milmed® treatment, the MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed® (MC)], restored spontaneous motor activity markedly by test day 10, restored completely subthreshold L-Dopa-induced activity, and dopamine concentration to 76% of control values, in the condition wherein two administrations of MPTP (2 × 40 mg/kg) were given prior to initiation of exercise and/or Milmed® treatment. Physical exercise by itself, MPTP + Exercise (MC) group, attenuated these deficits only partially. Administration of MPTP four times (i.e., 40 mg/kg, s.c., once weekly over four weeks for a total of 160 mg/kg, MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed® (SC)] and MPTP + Exercise (SC), induced a lesioning effect that was far too severe for either exercise alone or the exercise + Milmed® combination to ameliorate. Nevertheless, these findings indicate a powerful effect of physical exercise reinforced by Milmed® treatment in restoring MPTP-induced deficits of motor function and dopamine neurochemistry in mice. PMID:25210657

  12. Penicillin-induced hemolytic anemia and acute hepatic failure following treatment of tetanus in a horse.

    PubMed

    Step, D L; Blue, J T; Dill, S G

    1991-01-01

    Acute, severe hemolytic anemia occurred in a horse being treated for tetanus with intravenous penicillin and tetanus antitoxin. During treatment, the horse developed a positive direct antiglobulin test and a high titer (maximum 1:1024) of IgG anti-penicillin antibody. The horse recovered from the tetanus and penicillin induced hemolytic anemia, but later developed acute hepatic failure, probably resulting from the administration of equine origin tetanus antitoxin.

  13. [Successful treatment of enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome and acute encephalopathy].

    PubMed

    Mizuno, Hideki; Minouchi, Keiji; Aoyama, Shou; Hinoue, Yoshinobu

    2015-07-01

    We report a case of a woman in her twenties with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome who developed acute encephalopathy on day 5 of admission. She recovered after treatment with steroid pulse therapy, plasmapheresis, and recombinant thrombomodulin, without any adverse sequelae. We report this interesting case and provide a summary of the recent outbreak of enterohemorrhagic Escherichia coli O111.

  14. Eurycoma longifolia in Radix for the treatment of ethanol-induced gastric lesion in rats.

    PubMed

    Qodriyah, H M S; Asmadi, A Y

    2013-12-01

    The effect of treatment with Radix on ethanol-induced gastric lesions was investigated. The main ingredient of Radix is Eurycoma longifolia. Twenty-four rats of the Sprague-Dawley species were randomly divided into four groups. Three groups were given 0.5 mL 100% ethanol orally. Another group was used as a control and was given only distilled water orally (control). After 6 h all the rats were fed with normal diet. One group that was administered with ethanol was only given distilled water orally (no treatment). Another two groups that were administered with ethanol were treated with oral Radix 0.128 mg g(-1) b.wt. (Radix) and oral ranitidine 21.4 mg kg(-1) b.wt. (Ranitidine), respectively. After one week, all the rats were fasted overnight and sacrificed. The stomach was isolated and examined for the presence and severity of gastric lesions. Measurements for malondialdehyde content and gastric acid concentration were also done. It is found that the ulcer index was lower in the Radix and ranitidine group compared to the no treatment group whereas in the control group there was no lesion. There was no difference in ulcer index between the Radix and ranitidine group. The gastric MDA content was significantly higher in all the groups that were induced with ethanol compared to the control group but no difference between all the ethanol-induced groups. There was no difference in the gastric acid concentration in all groups. Hence it is concluded that Eurycoma longifolia in Radix is as effective as ranitidine in the treatment of ethanol-induced gastric lesions in rats.

  15. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin.

    PubMed

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants.

  16. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    PubMed Central

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2015-01-01

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51% reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. PMID:25791923

  17. Treatment with Piribedil and Memantine Reduces Noise-Induced Loss of Inner Hair Cell Synaptic Ribbons

    PubMed Central

    Altschuler, Richard A.; Wys, Noel; Prieskorn, Diane; Martin, Cathy; DeRemer, Susan; Bledsoe, Sanford; Miller, Josef M.

    2016-01-01

    Noise overstimulation can induce loss of synaptic ribbons associated with loss of Inner Hair Cell – Auditory Nerve synaptic connections. This study examined if systemic administration of Piribedil, a dopamine agonist that reduces the sound evoked auditory nerve compound action potential and/or Memantine, an NMDA receptor open channel blocker, would reduce noise-induced loss of Inner Hair Cell ribbons. Rats received systemic Memantine and/or Piribedil for 3 days before and 3 days after a 3 hour 4 kHz octave band noise at 117 dB (SPL). At 21 days following the noise there was a 26% and 38% loss of synaptic ribbons in regions 5.5 and 6.5 mm from apex, respectively, elevations in 4-, 8- and 20 kHz tonal ABR thresholds and reduced dynamic output at higher intensities of stimulation. Combined treatment with Piribedil and Memantine produced a significant reduction in the noise-induced loss of ribbons in both regions and changes in ABR sensitivity and dynamic responsiveness. Piribedil alone gave significant reduction in only the 5.5 mm region and Memantine alone did not reach significance in either region. Results identify treatments that could prevent the hearing loss and hearing disorders that result from noise-induced loss of Inner Hair Cell – Auditory Nerve synaptic connections. PMID:27686418

  18. Increased Impulsivity and Disrupted Attention Induced by Repeated Phencyclidine are not Attenuated by Chronic Quetiapine Treatment

    PubMed Central

    Amitai, Nurith; Markou, Athina

    2009-01-01

    Atypical antipsychotic medications differ in how effectively they attenuate cognitive and other deficits in schizophrenia. The present study aimed to explore whether quetiapine, an atypical antipsychotic medication, would reverse disruptions of performance in the 5-choice serial reaction time task (5-CSRTT), a test of attention and impulsivity, induced by repeated administration of the psychotomimetic phencyclidine (PCP). In confirmation of previous findings, repeated PCP administration (2 mg/kg, s.c., 30 min before behavioral testing, for two consecutive days, followed by a 2-week PCP-free period and then five consecutive days of PCP treatment) increased premature responding (impulsivity), decreased accuracy (attention), and increased response latencies (processing speed) and timeout responding (impulsivity/cognitive inflexibility). Chronic quetiapine (5 or 10 mg/kg/day, s.c.) did not attenuate these PCP-induced disruptions in performance, while at the highest dose used, quetiapine disrupted 5-CSRTT performance in the absence of PCP treatment and tended to exacerbate the PCP-induced increase in premature responding. Considering that clozapine, another atypical antipsychotic, was shown previously to reverse PCP-induced deficits in the same task (Amitai et al. 2007), the present findings demonstrate differences between clozapine and quetiapine in their effectiveness on schizophrenia-like cognitive deficits and impulsivity that may be attributable to their different receptor affinity profiles. PMID:18809428

  19. The protective effect of intraperitoneal medical ozone preconditioning and treatment on hepatotoxicity induced by methotrexate

    PubMed Central

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Akyüz, Cebrail; Baştürk, Ahmet; Polat, Cemal; Gündüz, Umut; Mayir, Burhan; Şehirli, Ahmet Özer

    2015-01-01

    The aim of this study is to determine the effects of medical ozone preconditioning and treatment on the methotrexate acute induced hepatotoxicity in rats that has not reports elsewhere. Eighteen rats were randomly assigned into three equal groups; control, Mtx and Mtx with ozone. Hepatotoxicity was performed with a single dose of 20 mg/kg Mtx to group 2 and group 3 at the fifteenth day. The medical ozone preconditioning was administered intraperitonealy in group 3 for fifteen days and more five days after inducing Mtx. The other rats of the group 1 and 2 received saline injection. At the twentyfirst day the blood and the liver tissue samples were obtained to measure the levels of liver enzymes ALT and AST, proinflamatory cytokines TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. And the histolopatological examination was evaluated for injury score. In our study Mtx administration caused a significant increase on the liver enzymes ALT and AST, the tissue MDA and MPO activity and significant decrease in the tissue GSH. Moreover the both pro-inflammatory cytokines were significantly increased in the Mtx group. Medical ozone preconditioning and treatment reversed all these biochemical parameters and histopathological changes of the hepatotoxicity induced by Mtx. We conclude that medical ozone ameliorates Mtx induced hepatotoxicity in rats. PMID:26550257

  20. The protective effect of intraperitoneal medical ozone preconditioning and treatment on hepatotoxicity induced by methotrexate.

    PubMed

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Akyüz, Cebrail; Baştürk, Ahmet; Polat, Cemal; Gündüz, Umut; Mayir, Burhan; Şehirli, Ahmet Özer

    2015-01-01

    The aim of this study is to determine the effects of medical ozone preconditioning and treatment on the methotrexate acute induced hepatotoxicity in rats that has not reports elsewhere. Eighteen rats were randomly assigned into three equal groups; control, Mtx and Mtx with ozone. Hepatotoxicity was performed with a single dose of 20 mg/kg Mtx to group 2 and group 3 at the fifteenth day. The medical ozone preconditioning was administered intraperitonealy in group 3 for fifteen days and more five days after inducing Mtx. The other rats of the group 1 and 2 received saline injection. At the twentyfirst day the blood and the liver tissue samples were obtained to measure the levels of liver enzymes ALT and AST, proinflamatory cytokines TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. And the histolopatological examination was evaluated for injury score. In our study Mtx administration caused a significant increase on the liver enzymes ALT and AST, the tissue MDA and MPO activity and significant decrease in the tissue GSH. Moreover the both pro-inflammatory cytokines were significantly increased in the Mtx group. Medical ozone preconditioning and treatment reversed all these biochemical parameters and histopathological changes of the hepatotoxicity induced by Mtx. We conclude that medical ozone ameliorates Mtx induced hepatotoxicity in rats.

  1. Modelling biofilm-induced formation damage and biocide treatment in subsurface geosystems

    PubMed Central

    Ezeuko, C C; Sen, A; Gates, I D

    2013-01-01

    Biofilm growth in subsurface porous media, and its treatment with biocides (antimicrobial agents), involves a complex interaction of biogeochemical processes which provide non-trivial mathematical modelling challenges. Although there are literature reports of mathematical models to evaluate biofilm tolerance to biocides, none of these models have investigated biocide treatment of biofilms growing in interconnected porous media with flow. In this paper, we present a numerical investigation using a pore network model of biofilm growth, formation damage and biocide treatment. The model includes three phases (aqueous, adsorbed biofilm, and solid matrix), a single growth-limiting nutrient and a single biocide dissolved in the water. Biofilm is assumed to contain a single species of microbe, in which each cell can be a viable persister, a viable non-persister, or non-viable (dead). Persisters describe small subpopulation of cells which are tolerant to biocide treatment. Biofilm tolerance to biocide treatment is regulated by persister cells and includes ‘innate’ and ‘biocide-induced’ factors. Simulations demonstrate that biofilm tolerance to biocides can increase with biofilm maturity, and that biocide treatment alone does not reverse biofilm-induced formation damage. Also, a successful application of biological permeability conformance treatment involving geologic layers with flow communication is more complicated than simply engineering the attachment of biofilm-forming cells at desired sites. PMID:23164434

  2. Multiple Treatments of Pediatric Constraint-Induced Movement Therapy (pCIMT): A Clinical Cohort Study

    PubMed Central

    Ramey, Sharon Landesman; Trucks, Mary Rebekah; Wallace, Dorian Ainsworth

    2015-01-01

    Pediatric constraint-induced movement therapy (pCIMT) is one of the most efficacious treatments for children with cerebral palsy (CP). Distinctive components of pCIMT include constraint of the less impaired upper extremity (UE), high-intensity therapy for the more impaired UE (≥3 hr/day, many days per week, for multiple weeks), use of shaping techniques combined with repetitive task practice, and bimanual transfer. A critical issue is whether multiple treatments of pCIMT produce additional benefit. In a clinical cohort (mean age = 31 mo) of 28 children with asymmetrical CP whose parents sought multiple pCIMT treatments, the children gained a mean of 13.2 (standard deviation [SD] = 4.2) new functional skills after Treatment 1; Treatment 2 produced a mean of 7.3 (SD = 4.7) new skills; and Treatment 3, 6.5 (SD = 4.2). These findings support the conclusion that multiple pCIMT treatments can produce clinically important functional gains for children with hemiparetic CP. PMID:26565094

  3. Luteolin supplementation adjacent to aspirin treatment reduced dimethylhydrazine-induced experimental colon carcinogenesis in rats.

    PubMed

    Osman, Neamt H A; Said, Usama Z; El-Waseef, Ahmed M; Ahmed, Esraa S A

    2015-02-01

    Previous studies have shown that aspirin is used in colon cancer treatment. However, long-term of Aspirin usage is limited to gastric and renal toxicity. Luteolin (LUT) has cancer prevention and anti-inflammatory effects. The present study was designed to investigate the effect of LUT supplementation and Aspirin treatment in dimethylhydrazine (DMH)-induced carcinogenesis in rats. DMH (20 mg/kg BW/week) treated rats received gavages with Aspirin (50 mg/kg BW/week) and LUT (0.2 mg/kg BW/day) for 15 weeks. DMH injections induce colon polyps and renal bleeding, significantly increasing carcinoembryonic antigen (CEA), cyclooxygenase-2 (COX-2), oxidative stress, and kidney function tests and reducing antioxidant markers. Either Aspirin or LUT gavages alone or combined produce a significant decrease in colon polyp number and size, significantly decreasing CEA, COX-2, and oxidative stress and increasing antioxidant markers. In conclusion, the supplementations of LUT adjacent to Aspirin in the treatment of DMH-induced carcinogenesis in rats reflect a better effect than the use of Aspirin alone.

  4. Evaluation of N-acetylcysteine treatment in acute pancreatitis-induced lung injury.

    PubMed

    Yubero, Sara; Ramudo, Laura; Manso, Manuel A; Collía, Francisco; De Dios, Isabel

    2012-07-01

    Pulmonary complications are frequent during acute pancreatitis (AP). We investigate the effects of N-acetylcysteine (NAC) on lung injury in mild and severe AP. ANIMALS AND TREATMENT: Mild and severe AP was induced in rats by bile-pancreatic duct obstruction (BPDO) and infusion of 3.5 % sodium taurocholate (NaTc) into the bile-pancreatic duct, respectively. NAC (50 mg/kg) was given 1 h before and 1 h after AP. Amylase activity was measured in plasma. Lungs were harvested for mRNA expression analysis of monocyte chemoattractant protein-1 (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity and histological examination. Hyperamylasemia was reduced by NAC in both AP models. NAC down-regulated MCP-1, CINC and P-selectin in BPDO- but not in NaTc-induced AP. Pulmonary insults did not vary in mild AP and were exacerbated in severe AP by NAC treatment. NAC reduced lung MPO activity in mild but not in severe AP. Although NAC treatment down-regulated inflammatory mediators in lungs during AP it did not prevent leukocyte infiltration, which could be responsible for maintaining the lung injury. As a result, NAC aggravated the lung damage in severe AP and failed to exert beneficial effects in the mild disease model.

  5. Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells

    PubMed Central

    Lai, Liang-Chuan; Chuang, Eric Y.; Tsai, Mong-Hsun

    2016-01-01

    Since 1984, mitomycin C (MMC) has been applied in the treatment of non-small-cell lung cancer (NSCLC). MMC-based chemotherapeutic regimens are still under consideration owing to the efficacy and low cost as compared with other second-line regimens in patients with advanced NSCLC. Hence, it is important to investigate whether MMC induces potential negative effects in NSCLC. Here, we found that the malignant lung cancer cells, CL1-2 and CL1-5, were more resistant to MMC than were the parental CL1-0 cells and pre-malignant CL1-1 cells. CL1-2 and CL1-5 cells consistently showed lower sub-G1 fractions post MMC treatment. DNA repair-related proteins were not induced more in CL1-5 than in CL1-0 cells, but the levels of endogenous and MMC-induced phosphorylated Akt (p-Akt) were higher in CL1-5 cells. Administering a p-Akt inhibitor reduced the MMC resistance, demonstrating that p-Akt is important in the MMC resistance of CL1-5 cells. Furthermore, we revealed that cell migration was enhanced by MMC but lowered by a p-Akt inhibitor in CL1-5 cells. This study suggests that in CL1-5 cells, the activity of p-Akt, rather than DNA repair mechanisms, may underlie the resistance to MMC and enhance the cells' migration abilities after MMC treatment. PMID:27833080

  6. Evidence-Based Systematic Review: Effects of Intensity of Treatment and Constraint-Induced Language Therapy for Individuals with Stroke-Induced Aphasia

    ERIC Educational Resources Information Center

    Cherney, Leora R.; Patterson, Janet P.; Raymer, Anastasia; Frymark, Tobi; Schooling, Tracy

    2008-01-01

    Purpose: This systematic review summarizes evidence for intensity of treatment and constraint-induced language therapy (CILT) on measures of language impairment and communication activity/participation in individuals with stroke-induced aphasia. Method: A systematic search of the aphasia literature using 15 electronic databases (e.g., PubMed,…

  7. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

    PubMed

    Buckley, Lenore; Guyatt, Gordon; Fink, Howard A; Cannon, Michael; Grossman, Jennifer; Hansen, Karen E; Humphrey, Mary Beth; Lane, Nancy E; Magrey, Marina; Miller, Marc; Morrison, Lake; Rao, Madhumathi; Robinson, Angela Byun; Saha, Sumona; Wolver, Susan; Bannuru, Raveendhara R; Vaysbrot, Elizaveta; Osani, Mikala; Turgunbaev, Marat; Miller, Amy S; McAlindon, Timothy

    2017-08-01

    To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users. Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made. This guideline provides direction for clinicians and patients making treatment decisions. Clinicians

  8. Syzygium jambolanum treatment improves survival in lethal sepsis induced in mice

    PubMed Central

    Maciel, Márcia CG; Farias, Jardel C; Maluf, Michele J; Gomes, Eliane A; Pereira, Paulo VS; Aragão-Filho, Walmir C; Frazão, Josias B; Costa, Graciomar C; Sousa, Sanara M; Silva, Lucilene A; Amaral, Flávia MM; Russo, Momtchilo; Guerra, Rosane NM; Nascimento, Flávia RF

    2008-01-01

    Background The leaves and the fruits from Syzygium jambolanum DC.(Myrtaceae), a plant known in Brazil as sweet olive or 'jambolão', have been used by native people to treat infectious diseases, diabetes, and stomachache. Since the bactericidal activity of S. jambolanum has been confirmed in vitro, the aim of this work was to evaluate the effect of the prophylactic treatment with S. jambolanum on the in vivo polymicrobial infection induced by cecal ligation and puncture (CLP) in mice. Methods C57Bl/6 mice were treated by the subcutaneous route with a hydroalcoholic extract from fresh leaves of S. jambolanum (HCE). After 6 h, a bacterial infection was induced in the peritoneum using the lethal CLP model. The mice were killed 12 h after the CLP induction to evaluate the cellular influx and local and systemic inflammatory mediators' production. Some animals were maintained alive to evaluate the survival rate. Results The prophylactic HCE treatment increased the mice survival, the neutrophil migration to infectious site, the spreading ability and the hydrogen peroxide release, but decreased the serum TNF and nitrite. Despite the increased migration and activation of peritoneal cells the HCE treatment did not decrease the number of CFU. The HCE treatment induced a significant decrease on the bone marrow cells number but did not alter the cell number of the spleen and lymph node. Conclusion We conclude that the treatment with S. jambolanum has a potent prophylactic anti-septic effect that is not associated to a direct microbicidal effect but it is associated to a recruitment of activated neutrophils to the infectious site and to a diminished systemic inflammatory response. PMID:18851742

  9. Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: a case series

    PubMed Central

    Balak, Deepak M.W.; Bouwes Bavinck, Jan Nico; de Vries, Aiko P.J.; Hartman, Jenny; Neumann, Hendrik A. Martino; Zietse, Robert; Thio, Hok Bing

    2016-01-01

    Background Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fanconi syndrome. Methods Descriptive case series with two cases of Fanconi syndrome associated with FAE treatment diagnosed at two Dutch university nephrology departments, three cases reported at the Dutch and German national pharmacovigilance databases and six previously reported cases. Results All 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years [interquartile range (IQR) 37–46]. Patients received long-term FAEs treatment with a median treatment duration of 60 months (IQR 28–111). Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria. Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation. Conclusions FAEs treatment can cause drug-induced Fanconi syndrome, but the association has been reported infrequently. Female patients with psoriasis treated long term with FAEs seem to be particularly at risk. Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome. Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome. PMID:26798466

  10. Chronic Caffeine Treatment Prevents Sleep Deprivation-Induced Impairment of Cognitive Function and Synaptic Plasticity

    PubMed Central

    Alhaider, Ibrahim A.; Aleisa, Abdulaziz M.; Tran, Trinh T.; Alzoubi, Karem H.; Alkadhi, Karim A.

    2010-01-01

    Study Objectives: This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. Experimental Design: We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. Measurement and Results: The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, short-term memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. Conclusions: The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats. Citation: Alhaider IA; Aleisa AM; Tran TT; Alzoubi KH; Alkadhi KA. Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity. SLEEP 2010;33(4):437-444. PMID:20394312

  11. Chronic corticosterone treatment enhances extinction-induced depression in aged rats.

    PubMed

    Huston, Joseph P; Komorowski, Mara; de Souza Silva, Maria A; Lamounier-Zepter, Valéria; Nikolaus, Susanne; Mattern, Claudia; Müller, Christian P; Topic, Bianca

    2016-11-01

    Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID). This is particularly relevant for the aged organism subjected to pronounced loss of former rewards. Avoidance of the former site of reward and increased withdrawal into a distant compartment accompany extinction of food-rewarded behavior in rodent models. During extinction, behavioral markers for re-learning dissociate from indicators of extinction-induced depression. Here we examined the effect of a chronic treatment with corticosterone (CORT), a well-known inducer of depression-related behavior, on EID in adult and aged rats. Adult (3-4months) and aged (18months) male rats were treated with CORT via drinking water for 3weeks prior to extinction of a cued food-reward task. CORT treatment increased the distance from the site of reward and decreased goal tracking behavior during extinction, especially in the aged rats. Plasma hormone levels measured before and after restraint stress showed a decline in basal ACTH- and CORT-levels after chronic CORT treatment in aged animals. The treatment significantly impaired the HPA-axis activation after acute stress in both, adult and aged animals, alike. Altogether, these findings show an enhancement of EID after chronic CORT treatment in the aged organism, which may be mediated by an impaired HPA-axis sensitivity. These findings may have special relevance for the investigation of human geriatric depression. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Treatment of GABA from Fermented Rice Germ Ameliorates Caffeine-Induced Sleep Disturbance in Mice.

    PubMed

    Mabunga, Darine Froy N; Gonzales, Edson Luck T; Kim, Hee Jin; Choung, Se Young

    2015-05-01

    γ-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is involved in sleep physiology. Caffeine is widely used psychoactive substance known to induce wakefulness and insomnia to its consumers. This study was performed to examine whether GABA extracts from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice, without affecting spontaneous locomotor activity and motor coordination. Indeed, caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice. Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg, p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not significantly reduced the caffeine-induced increase in locomotor activity without affecting motor coordination. Additionally, rice germ ferment extracts-GABA per se did not affect the spontaneous locomotor activity and motor coordination of mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter the sleep disturbance induced by caffeine, without affecting the general locomotor activities of mice.

  13. Short-term Outcomes of Induced Membrane Technique in Treatment of Long Bone Defects in Iran

    PubMed Central

    Yeganeh, Ali; Mahmodi, Mani; Farahini, Hosein; Moghtadaei, Mehdi

    2016-01-01

    Introduction: Severe defects in long bones can be caused by several factors such as trauma that lead to open wound and secondary infections after surgery. Induced membrane technique is one of the therapeutic strategies that can be used for these patients. Due to importance of this method and lack of information about this technique in Iran. Aim: this study was performed to investigate technical strengths and weakness of induced membrane technique. Material and Methods: This case series study conducted on 21 patients with bone defects in the femur and tibia and metatarsal bones referred to orthopedic clinic of Rasoul Akram Hospital, Tehran, Iran, for induced membrane surgery in 2012-2015. Demographic and clinical data were obtained using history, clinical examinations and observations for each patient. Union achievement was the main outcome of this study, which was confirmed by radiographic findings and physical examination. Obtained data was analyzed by SPSS ver. 16. Results: All patients were male except one and their mean age was 30.52 years old. Bone defects were in tibia, femur and metatarsus in 9, 9 and 3 patients, respectively. Three patients received soft tissue reconstruction with flap before induced membrane surgery. Age, defects size, cigarette addiction and drug use and delay to start the treatment had no significant effect on union status. In total, 90% of patients had successful surgery. Conclusion: using induced membrane technique in patients with defects in their long bone such as tibia, femur and metatarsus would lead to high success for reconstruction. PMID:27703290

  14. Treatment of GABA from Fermented Rice Germ Ameliorates Caffeine-Induced Sleep Disturbance in Mice

    PubMed Central

    Mabunga, Darine Froy N.; Gonzales, Edson Luck T.; Kim, Hee Jin; Choung, Se Young

    2015-01-01

    γ-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is involved in sleep physiology. Caffeine is widely used psychoactive substance known to induce wakefulness and insomnia to its consumers. This study was performed to examine whether GABA extracts from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice, without affecting spontaneous locomotor activity and motor coordination. Indeed, caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice. Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg, p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not significantly reduced the caffeine-induced increase in locomotor activity without affecting motor coordination. Additionally, rice germ ferment extracts-GABA per se did not affect the spontaneous locomotor activity and motor coordination of mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter the sleep disturbance induced by caffeine, without affecting the general locomotor activities of mice. PMID:25995826

  15. Melatonin inhibits snake venom and antivenom induced oxidative stress and augments treatment efficacy.

    PubMed

    Sharma, Rachana D; Katkar, Gajanan D; Sundaram, Mahalingam S; Swethakumar, Basavarajaiah; Girish, Kesturu S; Kemparaju, Kempaiah

    2017-05-01

    Snakebite is a neglected health hazard. Its patho-physiology has largely been focused on systemic and local toxicities; whereas, venom and antivenom induced oxidative stress has long been ignored. Antivenom therapy although neutralizes venom lethality and saves many lives, remains ineffective against oxidative stress. This prompted us to complement antivenom with an antioxidant molecule melatonin that would protect against oxidative stress and increase the efficacy of the existing snakebite therapy. Here we show that D. russelli and E. carinatus venoms induce strong oxidative stress that persists even after antivenom administration in mice model. Additionally, antivenoms also induce oxidative stress. Polyvalent antivenom induce more oxidative stress than monovalent antivenom. Strikingly, antivenom and melatonin together not only inhibit venom and antivenom induced oxidative stress but also significantly reduce the neutralizing antivenom dose. This study provides a therapeutic potential for enhancing the existing snakebite therapy. The combined treatment of antivenom+melatonin would prevent the upsurge of oxidative stress as well as minimize the antivenom load. Thus the investigation offers immense scope for physicians and toxinologists to reinvestigate, design new strategies and think beyond the conventional mode of antivenom therapy.

  16. Chitosan and blueberry treatment induces arginase activity and inhibits nitric oxide production during acetaminophen-induced hepatotoxicity

    PubMed Central

    Ozcelik, Eda; Uslu, Sema; Burukoglu, Dilek; Musmul, Ahmet

    2014-01-01

    Background: Liver diseases have become a major problem of the worldwide. More than 50% of all cases of liver failure can be attributed to drugs. Among these, acetaminophen is the most common cause. Objective: The aim of this study was to investigate the the hepatoprotective effects of blueberry and chitosan on tissue arginase activity, ornithine and nitric oxide levels during the acetaminophen-induced hepatotoxicity. Materials and Methods: Acetaminophen (250 mg/kg body weight per day), blueberry (60 mg/kg body weight per day) and, chitosan (200 mg/kg body weight per day) were administered to the rats by oral gavage during the experimental period. Results: Blueberry and chitosan significantly decreased liver arginase activity and ornithine levelsand and increased nitric oxide levels. Glutathione levels were remarkably increased by chitosan and blueberry treatments. Conclusion: The results of the present study indicate that blueberry and chitosan effectively protected against the acetaminophen-induced hepatotoxicity. The hepatoprotective effect afforded by blueberry and chitosan can be attributed to its antioxidant and anti-inflammatory activities. PMID:24991095

  17. Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments

    PubMed Central

    McQuade, Rachel M.; Stojanovska, Vanesa; Abalo, Raquel; Bornstein, Joel C.; Nurgali, Kulmira

    2016-01-01

    Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers. PMID:27857691

  18. Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment

    NASA Technical Reports Server (NTRS)

    Durante, M.; George, K.; Wu, H. L.; Yang, T. C.

    1998-01-01

    It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

  19. Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation.

    PubMed

    Ignácio, Zuleide M; Réus, Gislaine Z; Abelaira, Helena M; Maciel, Amanda L; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Gava, Fernanda F; Valvassori, Samira S; Carvalho, André F; Quevedo, João

    2017-03-01

    Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus. Maternally deprived rats had a depressive-like behavior in the forced swimming test and an increase in the HDAC and DNMT activities in the hippocampus and NAc. Treatment with quetiapine reversed depressive-like behavior and reduced the DNMT activity in the hippocampus. This is the first study to show the antidepressant-like effect of quetiapine in animals subjected to MD and a protective effect by quetiapine in reducing epigenetic changes induced by stress in early life. These results reinforce an important role of quetiapine as therapy for MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Chemotherapy-Induced Constipation and Diarrhea: Pathophysiology, Current and Emerging Treatments.

    PubMed

    McQuade, Rachel M; Stojanovska, Vanesa; Abalo, Raquel; Bornstein, Joel C; Nurgali, Kulmira

    2016-01-01

    Gastrointestinal (GI) side-effects of chemotherapy are a debilitating and often overlooked clinical hurdle in cancer management. Chemotherapy-induced constipation (CIC) and Diarrhea (CID) present a constant challenge in the efficient and tolerable treatment of cancer and are amongst the primary contributors to dose reductions, delays and cessation of treatment. Although prevalence of CIC is hard to estimate, it is believed to affect approximately 16% of cancer patients, whilst incidence of CID has been estimated to be as high as 80%. Despite this, the underlying mechanisms of both CID and CIC remain unclear, but are believed to result from a combination of intersecting mechanisms including inflammation, secretory dysfunctions, GI dysmotility and alterations in GI innervation. Current treatments for CIC and CID aim to reduce the severity of symptoms rather than combating the pathophysiological mechanisms of dysfunction, and often result in worsening of already chronic GI symptoms or trigger the onset of a plethora of other side-effects including respiratory depression, uneven heartbeat, seizures, and neurotoxicity. Emerging treatments including those targeting the enteric nervous system present promising avenues to alleviate CID and CIC. Identification of potential targets for novel therapies to alleviate chemotherapy-induced toxicity is essential to improve clinical outcomes and quality of life amongst cancer sufferers.

  1. Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment

    NASA Technical Reports Server (NTRS)

    Durante, M.; George, K.; Wu, H. L.; Yang, T. C.

    1998-01-01

    It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

  2. Transient acid treatment cannot induce neonatal somatic cells to become pluripotent stem cells.

    PubMed

    Tang, Mei Kuen; Lo, Lok Man; Shi, Wen Ting; Yao, Yao; Lee, Henry Siu Sum; Lee, Kenneth Ka Ho

    2014-01-01

    Currently, there are genetic- and chemical-based methods for producing pluripotent stem cells from somatic cells, but all of them are extremely inefficient.  However, a simple and efficient technique has recently been reported by Obokata et al (2014a, b) that creates pluripotent stem cells through acid-based treatment of somatic cells.  These cells were named stimulus-triggered acquisition of pluripotency (STAP) stem cells. This would be a major game changer in regenerative medicine if the results could be independently replicated. Hence, we isolated CD45 (+) splenocytes from five-day-old Oct4-GFP mice and treated the cells with acidified (pH 5.7) Hank's Balanced Salt Solution (HBSS) for 25 min, using the methods described by Obokata et al 2014c. However, we found that this method did not induce the splenocytes to express the stem cell marker Oct4-GFP when observed under a confocal microscope three to six days after acid treatment. qPCR analysis also confirmed that acid treatment did not induce the splenocytes to express the stemness markers Oct4, Sox2 and Nanog.  In addition, we obtained similar results from acid-treated Oct4-GFP lung fibroblasts. In summary, we have not been able to produce STAP stem cells from neonatal splenocytes or lung fibroblasts using the acid-based treatment reported by Obokata et al (2014a, b, c).

  3. Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement

    PubMed Central

    Tanaka, Yugo; Shigemura, Norihisa; Kawamura, Tomohiro; Noda, Kentaro; Isse, Kumiko; Stolz, Donna Beer; Billiar, Timothy R.; Toyoda, Yoshiya; Bermudez, Christian A.; Lyons-Weiler, James; Nakao, Atsunori

    2014-01-01

    Background We previously demonstrated that donor treatment with inhaled hydrogen protects lung grafts from cold ischemia/reperfusion (I/R) injury during lung transplantation. To elucidate the mechanisms underlying hydrogen’s protective effects, we conducted a gene array analysis to identify changes in gene expression associated with hydrogen treatment. Methods Donor rats were exposed to mechanical ventilation with 98% oxygen and 2% nitrogen or 2% hydrogen for 3 h before harvest; lung grafts were stored for 4 h in cold Perfadex. Affymetrix gene array analysis of mRNA transcripts was performed on the lung tissue prior to implantation. Results Pretreatment of donor lungs with hydrogen altered the expression of 229 genes represented on the array (182 upregulated; 47 downregulated). Hydrogen treatment induced several lung surfactant-related genes, ATP synthase genes and stress-response genes. The intracellular surfactant pool, tissue adenosine triphosphate (ATP) levels and heat shock protein 70 (HSP70) expression increased in the hydrogen-treated grafts. Hydrogen treatment also induced the transcription factors C/EBPα and C/EBPβ, which are known regulators of surfactant-related genes. Conclusion Donor ventilation with hydrogen significantly increases expression of surfactant-related molecules, ATP synthases and stress-response molecules in lung grafts. The induction of these molecules may underlie hydrogen’s protective effects against I/R injury during transplantation. PMID:22902635

  4. Does Oxidative Stress Induced by Alcohol Consumption Affect Orthodontic Treatment Outcome?

    PubMed Central

    Barcia, Jorge M.; Portolés, Sandra; Portolés, Laura; Urdaneta, Alba C.; Ausina, Verónica; Pérez-Pastor, Gema M. A.; Romero, Francisco J.; Villar, Vincent M.

    2017-01-01

    HIGHLIGHTS Ethanol, Periodontal ligament, Extracellular matrix, Orthodontic movement. Alcohol is a legal drug present in several drinks commonly used worldwide (chemically known as ethyl alcohol or ethanol). Alcohol consumption is associated with several disease conditions, ranging from mental disorders to organic alterations. One of the most deleterious effects of ethanol metabolism is related to oxidative stress. This promotes cellular alterations associated with inflammatory processes that eventually lead to cell death or cell cycle arrest, among others. Alcohol intake leads to bone destruction and modifies the expression of interleukins, metalloproteinases and other pro-inflammatory signals involving GSKβ, Rho, and ERK pathways. Orthodontic treatment implicates mechanical forces on teeth. Interestingly, the extra- and intra-cellular responses of periodontal cells to mechanical movement show a suggestive similarity with the effects induced by ethanol metabolism on bone and other cell types. Several clinical traits such as age, presence of systemic diseases or pharmacological treatments, are taken into account when planning orthodontic treatments. However, little is known about the potential role of the oxidative conditions induced by ethanol intake as a possible setback for orthodontic treatment in adults. PMID:28179886

  5. Impaired oocyte quality induced by dehydroepiandrosterone is partially rescued by metformin treatment.

    PubMed

    Huang, Ying; Yu, Yang; Gao, Jiangman; Li, Rong; Zhang, Chunmei; Zhao, Hongcui; Zhao, Yue; Qiao, Jie

    2015-01-01

    The present study evaluated the influence of hyperandrogenism on oocyte quality using a murine PCOS model induced by dehydroepiandrosterone (DHEA) and further explored the effect of metformin treatment. Female BALB/c mice were treated with a vehicle control or DHEA (6 mg /100 g body weight) or DHEA plus metformin (50 mg /100 g body weight) for 20 consecutive days. DHEA-induced mice resembled some characters of human PCOS, such as irregular sexual cycles and polycystic ovaries. After the model validation was completed, metaphase II (MII) oocytes were retrieved and subsequent analyses of oocyte quality were performed. DHEA-treated mice yielded fewer MII oocytes, which displayed decreased mtDNA copy number, ATP content, inner mitochondrial membrane potential, excessive oxidative stress and impaired embryo development competence compared with those in control mice. Metformin treatment partially attenuated those damages, as evidenced by the increased fertilization and blastocyst rate, ATP content, GSH concentration and GSH/GSSG ratio, and decreased reactive oxygen species levels. No significant difference in normal spindle assembly was observed among the three groups. During in vitro maturation (IVM), the periods of germinal vesicle breakdown (GVBD) and the first polar body (PB1) extrusion were extended and the maturation rate of GVBD oocytes was decreased in DHEA mice compared with controls. Metformin treatment decreased the time elapsed of GVBD while had no effect on PB1 extrusion. These results indicated that excessive androgen is detrimental to oocyte quality while metformin treatment is, directly or indirectly, beneficial for oocyte quality improvement.

  6. The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

    PubMed

    Tastekin, Didem; Tambas, Makbule; Kilic, Kemal; Erturk, Kayhan; Arslan, Deniz

    2014-12-01

    This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.

  7. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation

    PubMed Central

    CAMILLERI, M.; DROSSMAN, D. A.; BECKER, G.; WEBSTER, L. R.; DAVIES, A. N.; MAWE, G. M.

    2015-01-01

    Background Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral μ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. Purpose At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: ‘A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency’. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group’s discussion and consensus recommendations for patient care and research are presented in this article. PMID:25164154

  8. Antiresorptive therapy in the management of cancer treatment-induced bone loss.

    PubMed

    Garg, Ashwani; Leitzel, Kim; Ali, Suhail; Lipton, Allan

    2015-04-01

    Cancer treatment-induced bone loss treatment has an important role to prevent bone loss-related events like fracture, significant morbidity, mortality, disfigurement and loss of self-esteem, and health-care expenditure. Numerous factors, including treatment regimens and bone metastasis, increase the risk of osteoporosis or local bone destruction in most breast and prostate cancer patients. Cytotoxic chemotherapies, radiation, and hormonal therapies can lead to premature menopause and decrease bone mineral density. Over 60 % of breast cancer patients within 1 year of beginning postoperative adjuvant chemotherapy experience ovarian failure. Also, ovarian ablation and aromatase inhibitors used to treat breast cancer and orchiectomy and androgen deprivation therapy (ADT; to treat prostate cancer) cause substantial bone loss. In this article, we will focus mainly on antiresorptive therapy in the management of cancer treatment-induced bone loss (CTIBL). An understanding of CTIBL is critical for determining how to assess the risk and identify which patients may benefit from preventive therapy.

  9. Effects of non-equilibrium plasma in the treatment of ligature-induced peri-implantitis.

    PubMed

    Shi, Qi; Song, Ke; Zhou, Xincai; Xiong, Zilan; Du, Tianfeng; Lu, Xinpei; Cao, Yingguang

    2015-05-01

    To evaluate the effects of non-equilibrium plasma in the treatment of ligature-induced peri-implantitis in beagle dogs. Six beagles received 12 implants installed in the position of the fourth mandibular premolars. Ligature-induced peri-implantitis was initiated at 3 months post-implantation. When approximately 40% of the supporting bone was lost, the ligatures were removed. The implants were subjected to the muco-periosteal scaling and chlorhexidine irrigation with or without plasma irrigation. Three months later, clinical, radiographic and microbiological analyses were performed. Block biopsies were prepared for micro-CT and histomorphometric analysis. The primary outcome was the difference in bone healing of peri-implant sites, and the secondary outcomes included changes in clinical parameters (SBI, PD) and bacterial detection. At baseline, no significant differences were observed between the two groups. At 3 months post-treatment, the plasma group showed a significantly higher bone level than the control group (p < 0.05), a significantly decreased detection of bacteria (Porphyromonas gingivalis and Tannerella forsythia) (p < 0.05), and a significant improvement in clinical examination (p < 0.05). Within the limits of this study, non-equilibrium plasma treatment as an adjunct to the conventional therapy is a feasible approach for the treatment of peri-implantitis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity.

    PubMed

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alzoubi, Karem H; Alkadhi, Karim A

    2010-04-01

    This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, shortterm memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.

  11. Analysis of physiological responses associated with emotional changes induced by viewing video images of dental treatments.

    PubMed

    Sekiya, Taki; Miwa, Zenzo; Tsuchihashi, Natsumi; Uehara, Naoko; Sugimoto, Kumiko

    2015-03-30

    Since the understanding of emotional changes induced by dental treatments is important for dentists to provide a safe and comfortable dental treatment, we analyzed physiological responses during watching video images of dental treatments to search for the appropriate objective indices reflecting emotional changes. Fifteen healthy young adult subjects voluntarily participated in the present study. Electrocardiogram (ECG), electroencephalogram (EEG) and corrugator muscle electromyogram (EMG) were recorded and changes of them by viewing videos of dental treatments were analyzed. The subjective discomfort level was acquired by Visual Analog Scale method. Analyses of autonomic nervous activities from ECG and four emotional factors (anger/stress, joy/satisfaction, sadness/depression and relaxation) from EEG demonstrated that increases in sympathetic nervous activity reflecting stress increase and decreases in relaxation level were induced by the videos of infiltration anesthesia and cavity excavation, but not intraoral examination. The corrugator muscle activity was increased by all three images regardless of video contents. The subjective discomfort during watching infiltration anesthesia and cavity excavation was higher than intraoral examination, showing that sympathetic activities and relaxation factor of emotion changed in a manner consistent with subjective emotional changes. These results suggest that measurement of autonomic nervous activities estimated from ECG and emotional factors analyzed from EEG is useful for objective evaluation of subjective emotion.

  12. Impaired Oocyte Quality Induced by Dehydroepiandrosterone Is Partially Rescued by Metformin Treatment

    PubMed Central

    Huang, Ying; Yu, Yang; Gao, Jiangman; Li, Rong; Zhang, Chunmei; Zhao, Hongcui; Zhao, Yue; Qiao, Jie

    2015-01-01

    The present study evaluated the influence of hyperandrogenism on oocyte quality using a murine PCOS model induced by dehydroepiandrosterone (DHEA) and further explored the effect of metformin treatment. Female BALB/c mice were treated with a vehicle control or DHEA (6 mg /100 g body weight) or DHEA plus metformin (50 mg /100 g body weight) for 20 consecutive days. DHEA-induced mice resembled some characters of human PCOS, such as irregular sexual cycles and polycystic ovaries. After the model validation was completed, metaphase II (MII) oocytes were retrieved and subsequent analyses of oocyte quality were performed. DHEA-treated mice yielded fewer MII oocytes, which displayed decreased mtDNA copy number, ATP content, inner mitochondrial membrane potential, excessive oxidative stress and impaired embryo development competence compared with those in control mice. Metformin treatment partially attenuated those damages, as evidenced by the increased fertilization and blastocyst rate, ATP content, GSH concentration and GSH/GSSG ratio, and decreased reactive oxygen species levels. No significant difference in normal spindle assembly was observed among the three groups. During in vitro maturation (IVM), the periods of germinal vesicle breakdown (GVBD) and the first polar body (PB1) extrusion were extended and the maturation rate of GVBD oocytes was decreased in DHEA mice compared with controls. Metformin treatment decreased the time elapsed of GVBD while had no effect on PB1 extrusion. These results indicated that excessive androgen is detrimental to oocyte quality while metformin treatment is, directly or indirectly, beneficial for oocyte quality improvement. PMID:25811995

  13. Lithothamnion muelleri Treatment Ameliorates Inflammatory and Hypernociceptive Responses in Antigen-Induced Arthritis in Mice

    PubMed Central

    Costa, Vivian V.; Amaral, Flavio A.; Coelho, Fernanda M.; Queiroz-Junior, Celso M.; Malagoli, Bruna G.; Gomes, Jose Hugo S.; Lopes, Fernando; Silveira, Kátia D.; Sachs, Daniela; Fagundes, Caio T.; Tavares, Lívia D.; Pinho, Vanessa; Silva, Tarcilia A.; Teixeira, Mauro M.; Braga, Fernão C.; Souza, Danielle G.

    2015-01-01

    Rheumatoid Arthritis (RA) is a chronic disease characterized by persistent inflammation and pain. Alternative therapies to reduce these symptoms are needed. Marine algae are valuable sources of diverse bioactive compounds. Lithothamnion muelleri (Hapalidiaceae) is a marine algae with anti-inflammatory, antitumor, and immunomodulatory properties. Here, we investigated the potential anti-inflammatory and analgesic activities of L. muelleri in a murine model of antigen-induced arthritis (AIA) in mice. Our results demonstrate that treatment with L. muelleri prevented inflammation and hypernociception in arthritic mice. Mechanistically, the crude extract and the polysaccharide-rich fractions of L. muelleri may act impairing the production of the chemokines CXCL1 and CXCL2, and consequently inhibit neutrophil influx to the knee joint by dampening the adhesion step of leukocyte recruitment in the knee microvessels. Altogether our results suggest that treatment with L.muelleri has a potential therapeutic application in arthritis treatment. PMID:25793994

  14. Lithothamnion muelleri treatment ameliorates inflammatory and hypernociceptive responses in antigen-induced arthritis in mice.

    PubMed

    Costa, Vivian V; Amaral, Flavio A; Coelho, Fernanda M; Queiroz-Junior, Celso M; Malagoli, Bruna G; Gomes, Jose Hugo S; Lopes, Fernando; Silveira, Kátia D; Sachs, Daniela; Fagundes, Caio T; Tavares, Lívia D; Pinho, Vanessa; Silva, Tarcilia A; Teixeira, Mauro M; Braga, Fernão C; Souza, Danielle G

    2015-01-01

    Rheumatoid Arthritis (RA) is a chronic disease characterized by persistent inflammation and pain. Alternative therapies to reduce these symptoms are needed. Marine algae are valuable sources of diverse bioactive compounds. Lithothamnion muelleri (Hapalidiaceae) is a marine algae with anti-inflammatory, antitumor, and immunomodulatory properties. Here, we investigated the potential anti-inflammatory and analgesic activities of L. muelleri in a murine model of antigen-induced arthritis (AIA) in mice. Our results demonstrate that treatment with L. muelleri prevented inflammation and hypernociception in arthritic mice. Mechanistically, the crude extract and the polysaccharide-rich fractions of L. muelleri may act impairing the production of the chemokines CXCL1 and CXCL2, and consequently inhibit neutrophil influx to the knee joint by dampening the adhesion step of leukocyte recruitment in the knee microvessels. Altogether our results suggest that treatment with L.muelleri has a potential therapeutic application in arthritis treatment.

  15. Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy

    PubMed Central

    Hallett, Robin M.; Huang, Cheng; Motazedian, Ali; Auf der Mauer, Stefanie; Pond, Gregory R.; Hassell, John A.; Nordon, Robert E.; Draper, Jonathan S.

    2015-01-01

    Chemotherapy fails to provide durable cure for the majority of cancer patients. To identify mechanisms associated with chemotherapy resistance, we identified genes differentially expressed before and after chemotherapeutic treatment of breast cancer patients. Treatment response resulted in either increased or decreased cell cycle gene expression. Tumors in which cell cycle gene expression was increased by chemotherapy were likely to be chemotherapy sensitive, whereas tumors in which cell cycle gene transcripts were decreased by chemotherapy were resistant to these agents. A gene expression signature that predicted these changes proved to be a robust and novel index that predicted the response of patients with breast, ovarian, and colon tumors to chemotherapy. Investigations in tumor cell lines supported these findings, and linked treatment induced cell cycle changes with p53 signaling and G1/G0 arrest. Hence, chemotherapy resistance, which can be predicted based on dynamics in cell cycle gene expression, is associated with TP53 integrity. PMID:25749523

  16. Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

    PubMed

    Ma, Yifang; Zheng, Chutian; Feng, Yiping; Xu, Qingsheng

    2017-09-01

    Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

  17. Antiretroviral Treatment Interruptions Induced by the Kenyan Postelection Crisis Are Associated With Virological Failure

    PubMed Central

    Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W.; Sidle, John; Buziba, Nathan; Kantor, Rami

    2014-01-01

    Background Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. Methods We determined effects of unplanned TIs after the 2007–2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Results Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Conclusions Unplanned conflict-related TIs are associated with increased likelihood of virological failure. PMID:24047971

  18. Efficacy of Baptisia tinctoria in the treatment of typhoid: its possible role in inducing antibody formation.

    PubMed

    Banerji, Pratip; Banerji, Prasanta; Das, Gobinda Chandra; Islam, Aminul; Mishra, Shailendra Kumar; Mukhopadhyay, Susmita

    2012-07-02

    Typhoid is one of the most serious infectious bacterial diseases in third world countries. It is usually treated by traditional antibiotics but due to the appearance of antibiotic resistant strains physicians opt for phyto products and other alternative medicines for the treatment of typhoid. Baptisia, an extract from indigo plant root, has been proved to be highly effective ultradilute medicine for the treatment of typhoid; however, the mode of action of the ultradilute extract is uncertain. Due to the antigenic variations of Salmonella it seems to induce immuno system by activating both T and B cells by the formation of antibodies. This principle seems to be highly effective for the development of typhoid vaccine. The present studies found that Baptisia administration possibly caused a salmonella-like reaction in the body as this extract produces an endogenous antibody similar to salmonella reaction. Thus, this study suggests that Baptisia tinctoria extract can be used for the prevention and treatment of typhoid.

  19. Ketamine-induced affective switch in a patient with treatment-resistant depression

    PubMed Central

    Banwari, Girish; Desai, Prutha; Patidar, Prahlad

    2015-01-01

    There is growing evidence to support the rapid, albeit short-lived antidepressant effect of subanesthetic dose of ketamine, a noncompetitive glutamate N-methyl-D-aspartate receptor antagonist in treatment-resistant unipolar and bipolar depression. Ketamine is known to cause transient mood elevation or euphoria, psychotomimetic effects, and dissociative symptoms, but its use in unipolar or bipolar depression has not been reported to induce an affective switch amounting to persistent or prolonged hypomania/mania or manic-like syndrome. We report the case of a 52-year-old male with first episode, continuous, nonpsychotic, treatment-resistant, unipolar major depression of 10 years duration, who manifested a switch from depression to mania while being treated with subanesthetic dose of ketamine, given intramuscularly. This case suggests that polarity switch should be considered as a potential side effect while using ketamine for treatment-resistant depression. PMID:26288483

  20. Blonanserin treatment in patients with methamphetamine-induced psychosis comorbid with intellectual disabilities.

    PubMed

    Okazaki, Kosuke; Makinodan, Manabu; Yamamuro, Kazuhiko; Takata, Tomoyo; Kishimoto, Toshifumi

    2016-01-01

    Methamphetamine (MA) use has recently been associated with high levels of psychiatric hospitalization and serious social dysfunction. MA use causes frequent psychotic symptoms, which can be treated with antipsychotics. However, people with intellectual disabilities (ID) are vulnerable to adverse effects resulting from treatment with antipsychotic medications. We report two cases of MA-induced psychosis (MAP) in patients with ID who were treated with the antipsychotic blonanserin. In both the cases presented, symptoms of psychosis were improved by switching medications from other antipsychotic drugs to blonanserin. Despite the presence of ID in these patients, no significant adverse effects, such as sedation, were detected after treatment with blonanserin. Blonanserin may be an effective and well-tolerated pharmacotherapeutical treatment for patients with MAP comorbid with ID. However, further work is necessary to validate this claim.

  1. Blonanserin treatment in patients with methamphetamine-induced psychosis comorbid with intellectual disabilities

    PubMed Central

    Okazaki, Kosuke; Makinodan, Manabu; Yamamuro, Kazuhiko; Takata, Tomoyo; Kishimoto, Toshifumi

    2016-01-01

    Objective Methamphetamine (MA) use has recently been associated with high levels of psychiatric hospitalization and serious social dysfunction. MA use causes frequent psychotic symptoms, which can be treated with antipsychotics. However, people with intellectual disabilities (ID) are vulnerable to adverse effects resulting from treatment with antipsychotic medications. Method We report two cases of MA-induced psychosis (MAP) in patients with ID who were treated with the antipsychotic blonanserin. Results In both the cases presented, symptoms of psychosis were improved by switching medications from other antipsychotic drugs to blonanserin. Despite the presence of ID in these patients, no significant adverse effects, such as sedation, were detected after treatment with blonanserin. Conclusion Blonanserin may be an effective and well-tolerated pharmacotherapeutical treatment for patients with MAP comorbid with ID. However, further work is necessary to validate this claim. PMID:28008256

  2. Prophylaxis versus treatment: Is there a better way to manage radiotherapy-induced nausea and vomiting?

    SciTech Connect

    Horiot, Jean-Claude . E-mail: horiotjc@dijon.fnclcc.fr

    2004-11-15

    Nausea and vomiting are two of the most distressing side effects of radiotherapy and cytotoxic drugs, which currently are often combined to treat moderately advanced and advanced solid tumors. Inadequate control of these symptoms may result in significant patient suffering and decrease in the patient's quality of life, which has been shown to decrease patients' compliance to treatment, with potential impact on disease outcome. It is, therefore, important that radiation oncologists recognize the need for adequate prophylactic treatment of radiation-induced nausea and vomiting (RINV) to avoid the detrimental effects on patients' quality of life, and optimize chances for cure. The 5-hydroxytryptamine type 3 (5-HT{sub 3})-receptor antagonists have been proved to provide effective antiemetic therapy in patients undergoing highly emetogenic radiotherapy. Nevertheless, several large surveys have shown that optimal treatments are not always used. Hence, a risk exists that waiting for RINV symptoms rather than prescribing prophylactic antiemetic treatment may lead to increased patient suffering, poorer disease control, and less cost-effective therapy options. Prophylactic management with an effective 5-HT{sub 3}-receptor antagonist should offer a better treatment option for patients at high to moderate risk of RINV. Adequate control of RINV should contribute to patient compliance to treatment, improved therapy outcomes, and decreased burdens on nursing and health care resources.

  3. MicroRNA-126 contributes to Niaspan treatment induced vascular restoration after diabetic retinopathy

    PubMed Central

    Wang, Yang; Yan, Hua

    2016-01-01

    Diabetic retinopathy (DR) is a serious microvascular complication of diabetes and a major cause of blindness in the developing world. Early diabetic retinopathy is characterized by a loss of pericytes and vascular endothelial cells, a breakdown of the blood–retinal barrier, vascular dysfunction and vascular-neuroinflammation. However, optimal treatment options and related mechanisms are still unclear. MicroRNA-126 (miR-126) plays a potential role in the pathogenesis in DR, which may regulate VEGF, Ang-1 and VCAM-1 expressions. This study investigated the therapeutic effects and mechanisms of Niaspan treatment of DR in diabetes (DM) rats. DM rats exhibits significantly decreased miR-126 and tight junction Claudin-5/Occludin/ZO-1 genes expression, and increased Blood retinal-barrier (BRB) breakdown, retinal apoptosis and VEGF/VEGFR, as well as VCAM-1/CD45 expressions in the retina compared to normal control group. Niaspan treatment significantly improved clinical and histopathological outcomes; decreased the expressions of VEGF/VEGFR, VCAM-1/CD45, apoptosis and BRB breakdown, significantly increased tight junction proteins and Ang-1/Tie-2 expressions, as well as increased retinal miR-126 expression compared to non-treatment diabetic rats. These data are the first to show that Niaspan treatment ameliorates DR through its repair vascular and inhibits inflammatory effects, and also suggest that the miR-126 pathway may contribute to Niaspan treatment induced benefit effects. PMID:27225425

  4. Red blood cell coagulation induced by low-temperature plasma treatment.

    PubMed

    Miyamoto, Kenji; Ikehara, Sanae; Takei, Hikaru; Akimoto, Yoshihiro; Sakakita, Hajime; Ishikawa, Kenji; Ueda, Masashi; Ikeda, Jun-Ichiro; Yamagishi, Masahiro; Kim, Jaeho; Yamaguchi, Takashi; Nakanishi, Hayao; Shimizu, Tetsuji; Shimizu, Nobuyuki; Hori, Masaru; Ikehara, Yuzuru

    2016-09-01

    Low-temperature plasma (LTP) treatment promotes blood clot formation by stimulation of the both platelet aggregation and coagulation factors. However, the appearance of a membrane-like structure in clots after the treatment is controversial. Based on our previous report that demonstrated characteristics of the form of coagulation of serum proteins induced by LTP treatment, we sought to determine whether treatment with two plasma instruments, namely BPC-HP1 and PN-110/120TPG, formed clots only from red blood cells (RBCs). LTP treatment with each device formed clots from whole blood, whereas LTP treatment with BPC-HP1 formed clots in phosphate-buffered saline (PBS) containing 2 × 10(9)/mL RBCs. Light microscopic analysis results showed that hemolysis formed clots consisting of materials with membrane-like structures from both whole blood and PBS-suspended RBCs. Moreover, electron microscopic analysis results showed a monotonous material with high electron density in the formed clots, presenting a membrane-like structure. Hemolysis disappeared with the decrease in the current through the targets contacting with the plasma flare and clot formation ceased. Taken together, our results and those of earlier studies present two types of blood clot formation, namely presence or absence of hemolysis capability depending on the current through the targets. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Treatment and posttreatment effects induced by the Forsus appliance: A controlled clinical study.

    PubMed

    Cacciatore, Giorgio; Ghislanzoni, Luis Tomas Huanca; Alvetro, Lisa; Giuntini, Veronica; Franchi, Lorenzo

    2014-11-01

    To evaluate treatment and posttreatment dentoskeletal effects induced by the Forsus device (FRD) in growing patients with Class II malocclusion in a retrospective controlled clinical study. Thirty-six Class II patients (mean [SD] age 12.3 [1.2] years) were treated consecutively with the FRD protocol and compared with a sample of 20 subjects with untreated Class II malocclusion (mean [SD] age 12.2 [0.9] years). Lateral cephalograms were taken at the beginning of treatment, at the end of comprehensive treatment (after 2.3 ± 0.4 years), and at a postretention period (after 2.3 ± 1.1 years from the end of comprehensive treatment). Statistical comparisons were carried out with the unpaired t-test and Benjamini-Hochberg correction (P < .05). After comprehensive treatment, the FRD sample showed a significant restriction of the sagittal maxillary growth together with a significant correction in overjet, overbite, and molar relationship. During the overall observation interval, the FRD group exhibited no significant sagittal or vertical skeletal changes, while significant improvements were recorded in overjet (-3.8 mm), overbite (-1.5 mm), and molar relationship (+3.7 mm). The FRD protocol was effective in correcting Class II malocclusion mainly at the dentoalveolar level when evaluated 2 years after the end of comprehensive treatment.

  6. Anti-nerve growth factor antibody attenuates chronic morphine treatment-induced tolerance in the rat.

    PubMed

    Cheppudira, Bopaiah P; Trevino, Alex V; Petz, Lawrence N; Christy, Robert J; Clifford, John L

    2016-09-05

    Nerve growth factor (NGF) is known to induce inflammation and pain; however its role in opioid-induced tolerance has not been studied. This study investigated the effects of an anti-NGF neutralizing antibody on the development of tolerance following chronic morphine treatment in naïve rats. Four groups of rats were used in this study; one treated with saline alone, one with 10 mg/kg of morphine, one with 10 μg of anti-NGF and the other with 10 mg/kg of morphine + 10 μg of anti-NGF, twice per day for 5 days. The route of treatment was subcutaneous (S.C.) for morphine and saline, and intraperitoneal (i.p.) for anti-NGF. Response to a noxious thermal stimulus during the course of drug treatment was assessed (Hargreaves' test). Further, the change in the NGF levels in the lumbar spinal cord was measured by ELISA. Our results showed that repeated administration of morphine produced an apparent tolerance which was significantly attenuated by co-administration of anti-NGF (P < 0.001). Additionally, the area under the curve (AUC) of the analgesic effect produced by the combination of morphine and anti-NGF was significantly (P < 0.001) greater than for saline controls and chronic morphine treated rats. Moreover, the level of NGF in the spinal cord of chronic morphine treated rats was significantly higher (P < 0.05) than in both the saline control group and the group receiving simultaneous administration of anti-NGF with morphine. These results indicate that anti-NGF has the potential to attenuate morphine-induced tolerance behavior by attenuating the effects of NGF at the spinal level. Taken together, our study strongly suggests that the NGF signaling system is a potential novel target for treating opioid-induced tolerance.

  7. Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.

    PubMed

    Antunes, Michelle S; Ruff, Jossana Rodrigues; de Oliveira Espinosa, Dieniffer; Piegas, Manuela Bastos; de Brito, Maicon Lenon Otenio; Rocha, Kellen Athaíde; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Donato, Franciele; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/μl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.

  8. Hyperbaric Oxygen Treatment Induces a Two-Phase Antinociceptive Response of Unusually Long Duration in Mice

    PubMed Central

    Chung, Eunhee; Zelinski, Lisa M.; Ohgami, Yusuke; Shirachi, Donald Y.; Quock, Raymond M.

    2009-01-01

    Hyperbaric oxygen (HBO2) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO2. Research conducted in our laboratory demonstrates that four daily 60-min HBO2 treatments at 3.5 ATA induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least six hours after the HBO2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to three weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the four HBO2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment two weeks after HBO2 treatment. These experimental results implicate a novel mechanism that is activated by HBO2, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain. Perspective Hyperbaric oxygen treatment of mice can induce a two-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems. PMID:20418186

  9. Targeting renal purinergic signalling for the treatment of lithium-induced nephrogenic diabetes insipidus.

    PubMed

    Kishore, B K; Carlson, N G; Ecelbarger, C M; Kohan, D E; Müller, C E; Nelson, R D; Peti-Peterdi, J; Zhang, Y

    2015-06-01

    Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development of nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulphate (Plavix(®)) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unravelled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  10. Targeting Renal Purinergic Signalling for the Treatment of Lithium-induced Nephrogenic Diabetes Insipidus

    PubMed Central

    Kishore, B. K.; Carlson, N. G.; Ecelbarger, C. M.; Kohan, D. E.; Müller, C. E.; Nelson, R. D.; Peti-Peterdi, J.; Zhang, Y.

    2015-01-01

    Lithium still retains its critical position in the treatment of bipolar disorder by virtue of its ability to prevent suicidal tendencies. However, chronic use of lithium is often limited by the development nephrogenic diabetes insipidus (NDI), a debilitating condition. Lithium-induced NDI is due to resistance of the kidney to arginine vasopressin (AVP), leading to polyuria, natriuresis and kaliuresis. Purinergic signalling mediated by extracellular nucleotides (ATP/UTP), acting via P2Y receptors, opposes the action of AVP on renal collecting duct (CD) by decreasing the cellular cAMP and thus AQP2 protein levels. Taking a cue from this phenomenon, we discovered the potential involvement of ATP/UTP-activated P2Y2 receptor in lithium-induced NDI in rats, and showed that P2Y2 receptor knockout mice are significantly resistant to Li-induced polyuria, natriuresis and kaliuresis. Extension of these studies revealed that ADP-activated P2Y12 receptor is expressed in the kidney, and its irreversible blockade by the administration of clopidogrel bisulfate (Plavix®) ameliorates Li-induced NDI in rodents. Parallel in vitro studies showed that P2Y12 receptor blockade by the reversible antagonist PSB-0739 sensitizes CD to the action of AVP. Thus, our studies unraveled the potential beneficial effects of targeting P2Y2 or P2Y12 receptors to counter AVP resistance in lithium-induced NDI. If established in further studies, our findings may pave the way for the development of better and safer methods for the treatment of NDI by bringing a paradigm shift in the approach from the current therapies that predominantly counter the anti-AVP effects to those that enhance the sensitivity of the kidney to AVP action. PMID:25877068

  11. Evolving paradigms in the treatment of opioid-induced bowel dysfunction

    PubMed Central

    Poulsen, Jakob Lykke; Brock, Christina; Olesen, Anne Estrup; Nilsson, Matias; Drewes, Asbjørn Mohr

    2015-01-01

    In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research. PMID:26557892

  12. Protective effects of Artemisia arborescens essential oil on oestroprogestative treatment induced hepatotoxicity

    PubMed Central

    Ettaya, Amani; Elfeki, Abdelfettah; Hfaiedh, Najla

    2015-01-01

    BACKGROUND Currently, natural products have been shown to exhibit interesting biological and pharmacological activities and are used as chemotherapeutic agents. The purpose of this study, conducted on Wistar rats, was to evaluate the beneficial effects of Artemisia arborescens oil on oestroprogestative treatment induced damage on liver. MATERIALS/METHODS A total of 36 Wistar rats were divided into 4 groups; a control group (n = 9), a group of rats who received oestroprogestative treatment by intraperitoneal injection (n = 9), a group pre-treated with Artemisia arborescens then injected with oestroprogestative treatment (n = 9), and a group pre-treated with Artemisia arborescens (n = 9). To minimize the handling stress, animals from each group were sacrificed rapidly by decapitation. Blood serum was obtained by centrifugation and the livers were removed, cleaned of fat, and stored at -80℃ until use. RESULTS In the current study, oestroprogestative poisoning resulted in oxidative stress, which was demonstrated by 1) a significant increase of lipid peroxidation level in hepatic tissue 2) increased levels of serum transaminases (aspartate amino transferase and serum alanine amino transferase), alkaline phosphatase, glycemia and triglycerides and a decrease in the level of cholesterol 3) alteration of hepatic architecture. Pre-administration of Artemisia arborescens oil was found to alleviate oestroprogestative treatment induced damage by lowering lipid peroxidation level and by increasing activity of catalase, superoxide-dismutase, and glutathione-peroxidase in liver and by reducing disruption of biochemical parameters. CONCLUSION Therefore, the results obtained in this study confirmed that Artemisia essential oil protects against oestroprogestative administration induced hepatotoxicity by restoration of liver activities. PMID:26425275

  13. Supraspinal-selective TRPV1 desensitization induced by intracerebroventricular treatment with resiniferatoxin.

    PubMed

    Fukushima, Akihiro; Mamada, Kizuku; Iimura, Aki; Ono, Hideki

    2017-09-29

    The transient receptor potential vanilloid type 1 (TRPV1) is a thermosensitive cation channel that triggers heat pain in the periphery. Long-term desensitization of TRPV1, which can be induced by excess amounts of agonists, has been a method for investigating the physiological relevance of TRPV1-containing neuronal circuits, and desensitization induced by various routes of administration, including systemic, intrathecal and intraganglionic, has been demonstrated in rodents. In the present study, we examined the effect of intracerebroventricular (i.c.v.) treatment with an ultrapotent TRPV1 agonist, resiniferatoxin (RTX), on nociception and the analgesic effect of acetaminophen, which is known to mediate the activation of central TRPV1. I.c.v. administration of RTX a week before the test did not affect the licking/biting response to intraplantar injection of RTX (RTX test), suggesting that such i.c.v. treatment spares the function of TRPV1 at the hindpaw. Mice that had been i.c.v.-administered RTX also exhibited normal nociceptive responses in the formalin test and the tail pressure test, but acetaminophen failed to induce analgesia in those mice in any of the tests. These results suggest that i.c.v. administration of RTX leads to brain-selective TRPV1 desensitization in mice.

  14. [DRUG-INDUCED LUPUS CAUSED BY LONG TERM MINOCYCLINE TREATMENT FOR ACNE VULGARIS].

    PubMed

    Hanai, Shunichiro; Sato, Takeo; Takeda, Koichi; Nagatani, Katsuya; Iwamoto, Masahiro; Minota, Seiji

    2015-09-01

    An 18-year-old Japanese girl had received oral minocycline 200mg daily for treatment of acne vulgaris since 16 years old. She had a fever three months before admission, followed by joint pains in her knees, elbows and several proximal interphalangeal joints one month before admission. She was referred to our hospital because of a high serum level of anti-DNA antibody. She had already discontinued oral minocycline five weeks before admission, because she missed her medication refilled. On admission, the arthralgia and fever spontaneously resolved, and there were no laboratory evidence of hypocomplementemia and cytopenia. She had neither erythema nor internal organ involvements. Because her symptoms subsided spontaneously after the cessation of minocycline, she was considered to have drug-induced lupus. Both the arthralgia and fever did not relapse, and anti-ds DNA antibody returned to normal during a follow-up period without treatment. There are few reports of drug-induced lupus caused by minocycline in Japan. This case highlights the importance of considering minocycline-induced lupus.

  15. Atomized paclitaxel liposome inhalation treatment of bleomycin-induced pulmonary fibrosis in rats.

    PubMed

    Zhou, Y; Zhu, W P; Cai, X J; Chen, M

    2016-04-07

    We sought to determine the efficacy of atomized paclitaxel liposome inhalation treatment of pulmonary fibrosis in a bleomycin-induced rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: healthy control, pulmonary fibrosis without treatment, paclitaxel liposome inhalation-treated, and intravenous paclitaxel liposome-treated. Fibrosis was induced by bleomycin injection. A total of 20 mg/kg paclitaxel liposome was administered by inhalation every other day for a total of 10 doses. The intravenous group received 5 mg/kg paclitaxel liposome on days 1, 7, 14, and 21. We observed the general condition, weight change, survival index, and pathological changes in the lung tissue of the rats. Quantitative analysis of collagen types I and III and transforming growth factor (TGF)-β1 expression in the lungs was also performed. The paclitaxel liposome inhalation and intravenous delivery methods improved survival index and pulmonary fibrosis Ashcroft score, and decreased the thickness of the alveolar interval. No obvious difference was found between the two groups. Compared with the untreated group, paclitaxel liposome inhalation and intravenous injection significantly reduced the levels of collagen types I and III and TGF-β1 expression equally. In conclusion, atomized paclitaxel liposome inhalation protects against severe pulmonary fibrosis in a bleomycin-induced rat model. This delivery method has less systemic side effects and increased safety over intravenous injection.

  16. Protective effects of glycyrrhizic acid by rectal treatment on a TNBS-induced rat colitis model.

    PubMed

    Liu, Ying; Xiang, Jin; Liu, Min; Wang, Shi; Lee, Robert J; Ding, Hong

    2011-03-01

    The research compared rectal and oral treatments with glycyrrhizic acid for trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Wistar rats were randomly divided into seven groups: one normal and six with colitis, including TNBS, glycyrrhizic acid (2, 10 and 50 mg/kg, rectally treated and 10 mg/kg, orally treated) and sulfasalazine (positive control, 225 mg/kg rectally treated) groups. Colitis was induced by colonic administration of TNBS in 30% ethanol. There were significant pathological changes in colon in TNBS-treated groups, and rectal glycyrrhizic acid significantly attenuated colitis. Myeloperoxidase, tumour necrosis factor-α and interleukin-1β of colon tissue or serum in the rectal glycyrrhizic acid groups were markedly reduced when compared with the TNBS group, and lower than in the orally treated glycyrrhizic acid group. It was further noted that, in vitro, glycyrrhizic acid (up to 100 µg/ml) inhibited interleukin-6 and elevated interleukin-10 production in lipopolysaccharide-activated macrophages, and significantly inhibited proliferation of spleen lymphocytes, suggesting the immunoregulatory function of glycyrrhizic acid. Rectally administered glycyrrhizic acid has significant protective effects against TNBS-induced colitis in rats, and the rectal route may be a complementary treatment for inflammatory bowel disease. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  17. Biochemical and histopathological changes induced by different time intervals of methomyl treatment in mice liver.

    PubMed

    El-Demerdash, Fatma; Attia, Azza A; Elmazoudy, Reda H

    2012-01-01

    The present study was designed to evaluate the toxic effects induced by different time intervals of methomyl exposure on liver antioxidant defense system, oxidative stress, liver function biomarkers and histopathology in CD-1 mice. Ten male mice per group were assigned to one of four treatment groups. Group one served as control while group 2, 3 and 4 were orally treated with one mg methomyl/kg BW for 10, 20 and 30 days, respectively. Results obtained showed that methomyl significantly induced TBARS and decreased the activity of antioxidant enzymes, glutathione S-transferase, superoxide dismutase and catalase and the levels of reduced glutathione in mice liver. Aminotransferases and alkaline phosphatase activities were significantly decreased in liver due to methomyl administration, while the activities of these enzymes were significantly increased in serum. In addition, liver lactate dehydrogenase activity was significantly increased. On the contrary, methomyl treatment caused a significant decrease in liver acid phosphatase. The histology of mice liver treated with methomyl for 10, 20 and 30 days of duration showed dilation of central vein, sinusoids between hypertrophied hepatocytes and nuclear degeneration with mononuclear cell infiltration. In conclusion, exposure to methomyl induced toxicity and oxidative stress in mice liver via free radicals mechanism. Also, methomyl might have affected cell metabolism, cell membrane permeability and the detoxification system in liver.

  18. Chronic rhein treatment improves recognition memory in high-fat diet-induced obese male mice.

    PubMed

    Wang, Sen; Huang, Xu-Feng; Zhang, Peng; Wang, Hongqin; Zhang, Qingsheng; Yu, Shijia; Yu, Yinghua

    2016-10-01

    High-fat (HF) diet modulates gut microbiota and increases plasma concentration of lipopolysaccharide (LPS) which is associated with obesity and its related low-grade inflammation and cognitive decline. Rhein is the main ingredient of the rhubarb plant which has been used as an anti-inflammatory agent for several millennia. However, the potential effects of rhein against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, C57BL/6J male mice were fed an HF diet for 8 weeks to induce obesity, and then treated with oral rhein (120 mg/kg body weight/day in HF diet) for a further 6 weeks. Chronic rhein treatment prevented the HF diet-induced recognition memory impairment assessed by the novel object recognition test, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits in the perirhinal cortex. Furthermore, rhein inhibited the HF diet-induced increased plasma LPS level and the proinflammatory macrophage accumulation in the colon and alteration of microbiota, including decreasing Bacteroides-Prevotella spp. and Desulfovibrios spp. DNA and increasing Bifidobacterium spp. and Lactobacillus spp. DNA. Moreover, rhein also reduced body weight and improved glucose tolerance in HF diet-induced obese mice. In conclusion, rhein improved recognition memory and prevented obesity in mice on a chronic HF diet. These beneficial effects occur via the modulation of microbiota, hypoendotoxinemia, inhibition of macrophage accumulation, anti-neuroinflammation and the improvement of BDNF expression. Therefore, supplementation with rhein-enriched food or herbal medicine could be beneficial as a preventive strategy for chronic HF diet-induced cognitive decline, microbiota alteration and neuroinflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity.

    PubMed

    Schmidt, André; Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A; Riecher-Rössler, Anita; Lang, Undine E; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  20. Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

    PubMed

    Clements, C John; Coghlan, Ben; Creati, Mick; Locarnini, Stephen; Tedder, Richard S; Torresi, Joseph

    2010-01-01

    Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes.

  1. Use of Liposomal Gentamicin for Treatment of 5 Foals with Experimentally Induced Rhodococcus equi Pneumonia.

    PubMed

    Cohen, N D; Giguère, S; Burton, A J; Rocha, J N; Berghaus, L J; Brake, C N; Bordin, A I; Coleman, M C

    2016-01-01

    Adverse effects of, and bacterial resistance to, macrolides used to treat Rhodococcus equi infections have prompted search for clinically effective alternative antimicrobials. Liposomal gentamicin (LG) is effective against R. equi in vitro and decreases tissue concentrations of R. equi in experimentally infected mice. Effectiveness of LG treatment of foals with R. equi pneumonia, however, has not been described. Liposomal gentamicin is safe and effective for treating foals with R. equi pneumonia. Ten foals with experimentally induced R. equi pneumonia. Pilot treatment trial. Foals with pneumonia induced by intrabronchial instillation of R. equi were randomly allocated to receive either clarithromycin combined with rifampin (CLR + RIF) PO or LG IV, and followed by daily physical examinations and weekly thoracic ultrasonography and serum creatinine concentration determinations until the resolution of clinical signs. Treatment success was defined as the resolution of clinical signs and ultrasonographically identified pulmonary abscesses. All 10 foals were successfully treated. Two of 5 foals treated with LG developed azotemia within 1 week; LG was discontinued and treatment switched to CLR + RIF for these foals. None of the CLR + RIF treated foals developed azotemia. Liposomal gentamicin IV can be effective for treatment of R. equi pneumonia, but nephrotoxicity indicates that an alternative dosing interval or route (such as nebulization) will be needed before LG is adequately safe for clinical use. Larger comparative trials will be needed to evaluate the relative efficacy of a safer LG dosage regimen. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  2. Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity

    PubMed Central

    Walter, Marc; Gerber, Hana; Seifritz, Erich; Brenneisen, Rudolf; Wiesbeck, Gerhard A.; Riecher-Rössler, Anita; Lang, Undine E.; Borgwardt, Stefan

    2015-01-01

    Recent evidence has shown that a single maintenance dose of heroin attenuates psychophysiological stress responses in heroin-dependent patients, probably reflecting the effectiveness of heroin-assisted therapies for the treatment of severe heroin addiction. However, the underlying neural circuitry of these effects has not yet been investigated. Using a cross-over, double-blind, vehicle-controlled design, 22 heroin-dependent and heroin-maintained outpatients from the Centre of Substance Use Disorders at the University Hospital of Psychiatry in Basel were studied after heroin and placebo administration, while 17 healthy controls from the general population were included for placebo administration only. Functional magnetic resonance imaging was used to detect brain responses to fearful faces and dynamic causal modelling was applied to compute fear-induced modulation of connectivity within the emotional face network. Stress responses were assessed by hormone releases and subjective ratings. Relative to placebo, heroin acutely reduced the fear-induced modulation of connectivity from the left fusiform gyrus to the left amygdala and from the right amygdala to the right orbitofrontal cortex in dependent patients. Both of these amygdala-related connectivity strengths were significantly increased in patients after placebo treatment (acute withdrawal) compared to healthy controls, whose connectivity estimates did not differ from those of patients after heroin injection. Moreover, we found positive correlations between the left fusiform gyrus to amygdala connectivity and different stress responses, as well as between the right amygdala to orbitofrontal cortex connectivity and levels of craving. Our findings indicate that the increased amygdala-related connectivity during fearful face processing after the placebo treatment in heroin-dependent patients transiently normalizes after acute heroin maintenance treatment. Furthermore, this study suggests that the assessment of

  3. Long-term insulin treatment restores cardioprotection induced by sufentanil postconditioning in diabetic rat heart.

    PubMed

    Zhang, Yuwen; Zhang, Lei; Gu, Erwei; Zhu, Bingqing; Zhao, Xianya; Chen, Jingjing

    2016-03-01

    Sufentanil, a commonly used opioid analgesic, could mimic ischemia postconditioning to attenuate ischemia reperfusion injury, but this effect might be hindered in diabetic animals by inhibition of glycogen synthase kinase-3β phosphorylation. Also, diabetes can abrogate the cardioprotection of sevoflurane (an inhaled anesthetic) against ischemia reperfusion injury, and short-term insulin treatment does not restore protection by sevoflurane postconditioning. We hypothesized that long-term insulin treatment might restore the cardioprotective effect of sufentanil postconditioning in diabetic rats via phosphorylation of glycogen synthase kinase-3β. Streptozotocin (55 mg/kg)-induced diabetic rats received insulin (Novolin N, 6-8 u/d) for two days or two weeks, then were exposed to 30-min ischemia and 120-min reperfusion. Sufentanil postconditioning was performed 5 min before the onset of reperfusion. Controls included non-diabetic rats, sham surgery for ischemia/reperfusion, and sufentanil vehicle. Infarct size, cardiac troponin I, and phosphorylated glycogen synthase kinase-3β were examined. Sufentanil postconditioning reduced infarct size by 46% in non-diabetic rats (P < 0.001), but diabetes prevented this protective effect. Two-day insulin treatment was not effective, but two-week treatment reduced infarct size by 45% (P < 0.001), reduced cardiac troponin I by 33% (P < 0.001), and increased phosphorylated glycogen synthase kinase-3β levels (P < 0.001) in the diabetic sufentanil postconditioning group. In conclusion, sufentanil-induced cardioprotection was restored by long-term insulin treatment. The underlying mechanism may be increased phosphorylation of glycogen synthase kinase-3β.

  4. Effects of Debaryomyces hansenii treatment on intestinal microorganisms in mice with antibiotics-induced diarrhea.

    PubMed

    He, Lu; Long, Chengxing; Liu, Youjia; Guo, Yanfang; Xiao, Nenqun; Tan, Zhoujin

    2017-10-01

    To investigate the influence of Debaryomyces hansenii treatment on intestinal microorganisms in mice with antibiotics-induced diarrhea, mouse model of antibiotics-induced diarrhea was created by gavaging mice with mixed antibiotics (23.33 mL/kg/days) composed of gentamycin sulfate and cefradine for 5 days. Mice with the symptom of diarrhea were then treated with D. hansenii by intragastric administration. The control group mice were given with sterile water. After 4 day treatment, total DNA of intestinal microflora of treated and control mice was extracted, and their quantities were measured by sequencing the V4 region of 16S rDNA. The results showed that when compared to the control (sterile water), treatment with D. hansenii increased the operational taxonomic units (OTUs) of intestinal bacteria. The Chao index in diarrhea treated group was higher than diarrhea control group and was similar to healthy control group, while all differences had no significance (P > 0.05). D. hansenii treatment increased the Shannon index but not significantly (P > 0.05). Moreover, there was not significant impact on density and diversity of intestinal bacterial population at phylum and genus levels (P > 0.05). Interestingly, D. hansenii treatment recovered the population density of certain bacterium species, such as Bacteroidaceae (in family level) (P < 0.05). Our results indicate that D. hansenii has potency of adjusting the density and diversity of intestinal bacteria and recovering the population density of Bacteroidaceae in family level.

  5. Risk of contrast-induced nephropathy in patients undergoing endovascular treatment of acute ischemic stroke.

    PubMed

    Sharma, Jitendra; Nanda, Ashish; Jung, Richard S; Mehta, Sonal; Pooria, Javad; Hsu, Daniel P

    2013-11-01

    We report the incidence and risk factors for contrast-induced nephropathy after the use of iodinated contrast for endovascular treatment of acute ischemic stroke. A retrospective chart review was performed in 194 consecutive patients who underwent endovascular treatment for acute ischemic stroke between January 2006 and January 2011. No patients were excluded from treatment for elevated creatinine (Cr). Each patient received approximately 150 ml intra-arterial non-ionic low-osmolar contrast agent (Optiray 320) during the endovascular procedure. Contrast-induced nephropathy (CIN) was defined according to the Acute Kidney Injury Network criteria as a relative increase of serum Cr 50% above the baseline or an absolute increase of 0.3 mg/dl at 48 h following the endovascular procedure. Of 194 patients (mean age 65 ± 14 years), 52% were women (n=100) and 25% (n=48) were diabetic. Baseline Cr levels for 191 patients ranged between 0.4 and 2.7 mg/dl. Three patients on chronic hemodialysis had baseline Cr levels ranging between 5.3 and 6.1 mg/dl. Cr was ≤ 1.5 mg/dl in 163 patients (84%) and ≥ 1.5 mg/dl in 31 (16%). Three of the 191 patients (1.5%) developed CIN as noted from Cr measurements between baseline and within 48 h. One patient who developed an elevated Cr level had a known history of chronic renal insufficiency (Cr > 1.5 mg/dl) and two had baseline Cr levels within the normal range. An additional CT angiogram was obtained in 44 patients, none of which developed CIN. Female gender and diabetes were not associated with a higher risk of developing CIN. The risk of developing CIN is low among patients with acute stroke who undergo emergency endovascular treatment. Treatment of acute stroke should be performed irrespective of Cr levels.

  6. Osimertinib-induced interstitial lung disease after treatment with anti-PD1 antibody.

    PubMed

    Mamesaya, Nobuaki; Kenmotsu, Hirotsugu; Katsumata, Mineo; Nakajima, Takashi; Endo, Masahiro; Takahashi, Toshiaki

    2017-02-01

    We report a case of a 38-year-old woman who was diagnosed with stage IV lung adenocarcinoma, harboring an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790 M mutation on exon 20. The patient was treated with osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) following treatment with nivolumab, an anti-Programmed Cell Death 1 (anti-PD1) antibody. After initiating osimertinib treatment, the patient began to complain of low-grade fever and shortness of breath without hypoxemia, and her chest radiograph and a CT scan revealed a remarkable antitumor response, although faint infiltrations were observed in the bilateral lung field. Bronchoalveolar lavage fluid mainly contained lymphocytes (CD4+/CD8+ ratio of 0.3), and a transbronchial lung biopsy specimen showed lymphocytic alveolitis with partial organization in several alveolar spaces. Therefore we diagnosed the patient with osimertinib-induced interstitial lung disease (ILD) after treatment with anti-PD1 antibody. We considered anti-PD1 therapies may be the risk factor of EGFR-TKI-induced ILD.

  7. Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method

    PubMed Central

    Lu, Chao; You, Jian-Xin; Liu, Hu-Chen; Li, Ping

    2016-01-01

    Health-care waste (HCW) management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM) issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi-granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS) for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS) can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively. PMID:27271652

  8. Preventive effects of vitamin D treatment on bleomycin-induced pulmonary fibrosis

    PubMed Central

    Zhang, Zongmei; Yu, Xiaoting; Fang, Xia; Liang, Aibin; Yu, Zhang; Gu, Pan; Zeng, Yu; He, Jian; Zhu, Hailong; Li, Shuai; Fan, Desheng; Han, Fei; Zhang, Lanjing; Yi, Xianghua

    2015-01-01

    Patients with pulmonary fibrosis often have low vitamin D levels, the effects of which are largely unknown. We here report that early vitamin D supplementation significantly reduced the severity of pulmonary fibrosis and inflammatory cell accumulationin in the bleomycin-induced pulmonary fibrosis mouse model on supplementary days 14, 21 and 28 (P < 0.001). Vitamin D supplementation also prevented some ultrastructural changes in response to bleomycin administration, including basement membrane thickening, interstitial fibrin deposition and microvilli flattening or disappearance on days 14, 21 and 28, and lamellar body swelling or vacuolation on days 21 and 28. The bleomycin group had rising hydroxyproline level on days 14, 21 and 28, whereas the vitamin D treatment group showed consistently lower hydroxyproline level but still higher than that of the control group (P < 0.001). Our immunohistochemistry and densitometry analyses showed less staining for α-smooth muscle actin, a myofibroblast marker, in the vitamin D group compared to the bleomycin group (P < 0.001). Thus, vitamin D treatment could prevent bleomycin-induced pulmonary fibrosis by delaying or suppressing ultrastructural changes, as well as attenuating hydroxyproline accumulation and inhibiting myofibroblastic proliferation. These data further our understanding of the roles of vitamin D in pulmonary fibrogenesis and in the treatment of pulmonary fibrosis. PMID:26627341

  9. Pregnancy-induced hypertension caused by all-trans retinoic acid treatment in acute promyelocytic leukemia

    PubMed Central

    SONG, KUI; LI, MIN

    2015-01-01

    A 23-year-old pregnant female presented with fever and diarrhea during the sixth month of gestation. The patient was diagnosed with acute promyelocytic leukemia (APL) at 26 weeks gestation and was treated with all-trans retinoic acid (ATRA) at an initial dose of 45 mg/m2/day, which was reduced to 25 mg/m2/day 14 days later. The patient experienced chest distress, polypnea, hypertension, general dropsy and dysfunction of the kidneys and heart on day 3 of the treatment, which suggested pregnancy-induced hypertension. Intrauterine fetal demise was apparent on day 8. A cesarean delivery was performed, however, intrauterine fetal mortality had occurred. A favorable outcome was achieved for the patient following treatment, although hematological complete remission was slow. To the best of our knowledge, the present study is the first to describe an APL patient with pregnancy-induced hypertension following treatment with ATRA, and thus ATRA remains a suitable for therapy for APL during pregnancy. PMID:26171031

  10. Aminophylline treatment in meconium-induced acute lung injury in a rabbit model.

    PubMed

    Mokra, D; Mokry, J; Tatarkova, Z; Redfors, B; Petraskova, M; Calkovska, A

    2007-11-01

    Administration of methylxanthines may diminish meconium-induced acute lung injury. Meconium-instilled rabbits intravenously received aminophylline (2.0 mg/kg) at two doses 0.5 h and 2.5 h after meconium instillation or were left without treatment, and were oxygen-ventilated for additional 5 h. At the end of experiment, lungs and trachea were excised. Within 5 h after the first dose of treatment, aminophylline significantly improved gas exchange and decreased right-to-left pulmonary shunts, central venous pressure, and ventilatory pressures. Moreover, aminophylline reduced meconium-induced lung edema formation, airway hyperreactivity to histamine, count of neutrophils in bronchoalveolar lavage fluid associated with higher total white blood cells and neutrophils in the blood, and diminished oxidative modifications of proteins and lipids in lung tissue compared with the non-treated meconium-instilled group. In a rabbit model of the meconium aspiration syndrome, aminophylline treatment enhanced pulmonary functions and alleviated oxidative injury and changes in airway reactivity related to lung inflammation.

  11. Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method.

    PubMed

    Lu, Chao; You, Jian-Xin; Liu, Hu-Chen; Li, Ping

    2016-06-04

    Health-care waste (HCW) management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM) issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi-granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS) for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS) can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively.

  12. Sunitinib treatment does not improve blood supply but induces hypoxia in human melanoma xenografts

    PubMed Central

    2012-01-01

    Background Antiangiogenic agents that disrupt the vascular endothelial growth factor pathway have been demonstrated to normalize tumor vasculature and improve tumor oxygenation in some studies and to induce hypoxia in others. The aim of this preclinical study was to investigate the effect of sunitinib treatment on the morphology and function of tumor vasculature and on tumor oxygenation. Methods A-07-GFP and R-18-GFP human melanoma xenografts grown in dorsal window chambers were used as preclinical tumor models. Morphologic parameters of tumor vascular networks were assessed from high-resolution transillumination images, and tumor blood supply time was assessed from first-pass imaging movies recorded after a bolus of 155 kDa tetramethylrhodamine isothiocyanate-labeled dextran had been administered intravenously. Tumor hypoxia was assessed from immunohistochemical preparations of the imaged tissue by use of pimonidazole as a hypoxia marker. Results Sunitinib treatment reduced vessel densities, increased vessel segment lengths, did not affect blood supply times, and increased hypoxic area fractions. Conclusion Sunitinib treatment did not improve vascular function but induced hypoxia in A-07-GFP and R-18-GFP tumors. PMID:22947392

  13. Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress.

    PubMed

    Comelli, Francesca; Bettoni, Isabella; Colleoni, Mariapia; Giagnoni, Gabriella; Costa, Barbara

    2009-12-01

    Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)-induced diabetic rats without affecting hyperglycemia. In addition, the results showed that eCBD increased the reduced glutathione (GSH) content in the liver leading to a restoration of the defence mechanism and significantly decreased the liver lipid peroxidation suggesting that eCBD provides protection against oxidative damage in STZ-induced diabetes that also strongly contributes to the development of neuropathy. Finally, the nerve growth factor content in the sciatic nerve of diabetic rats was restored to normal following the repeated treatment with eCBD, suggesting that the extract was able to prevent the nerve damage caused by the reduced support of this neurotrophin. These findings highlighted the beneficial effects of cannabis extract treatment in attenuating diabetic neuropathic pain, possibly through a strong antioxidant activity and a specific action upon nerve growth factor. Copyright (c) 2009 John Wiley & Sons, Ltd.

  14. Medical treatment for a fish bone-induced ileal micro-perforation: a case report.

    PubMed

    Kuo, Chein-Chung; Jen, Tsu-Kang; Wen, Cheng-Hsin; Liu, Chih-Ping; Hsiao, Hai-Sung; Liu, Yao-Chi; Chen, Kuan-Ho

    2012-11-07

    Ingested fish bone induced intestinal perforations are seldom diagnosed preoperatively due to incomplete patient history taking and difficulties in image evidence identification. Most literature suggests early surgical intervention to prevent sepsis and complications resulting from fish bone migrations. We report the case of a 44-year-old man suffered from acute abdomen induced by a fish bone micro-perforation. The diagnosis was supported by computed tomography (CT) imaging of fish bone lodged in distal ileum and a history of fish ingestion recalled by the patient. Medical treatment was elected to manage the patient's condition instead of surgical intervention. The treatment resulted in a complete resolution of abdominal pain on hospital day number 4 without complication. Factors affecting clinical treatment decisions include the nature of micro-perforation, the patient's good overall health condition, and the early diagnosis before sepsis signs develop. Micro-perforation means the puncture of intestine wall without CT evidence of free air, purulent peritoneum or abscess. We subsequently reviewed the literature to support our decision to pursue medical instead of surgical intervention.

  15. Deep Friction Massage in Treatment of Radiation-induced Fibrosis: Rehabilitative Care for Breast Cancer Survivors

    PubMed Central

    Warpenburg, Mary J.

    2014-01-01

    Treatment for invasive breast cancer usually involves some combination of surgery, radiation therapy, chemotherapy, hormone therapy, and/or targeted therapy. For approximately 50% of patients, radiation therapy is a component of the therapies used. As a result, radiation-induced fibrosis is becoming a common and crippling side effect, leading to muscle imbalance with a lessened range of motion as well as pain and dysfunction of the vascular and lymphatic systems. No good estimates are available for how many patients experience complications from radiation. Radiation-induced fibrosis can affect the underlying fascia, muscles, organs, and bones within the primary target field and the larger secondary field that is caused by the scatter effect of radioactive elements. For breast cancer patients, the total radiation field may include the neck, shoulder, axillary, and thoracic muscles and the ribs for both the ipsilateral (cancer-affected) and contralateral sides. This case study indicates that therapy using deep friction massage can affect radiation-induced fibrosis beneficially, particularly in the thoracic muscles and the intercostals (ie, the muscles between the ribs). When delivered in intensive sessions using deep friction techniques, massage has the potential to break down fibrotic tissues, releasing the inflammation and free radicals that are caused by radiation therapy. In the course of the massage, painful and debilitating spasms resulting from fibrosis can be relieved and the progressive nature of the radiation-induced fibrosis interrupted. PMID:26770116

  16. Deep Friction Massage in Treatment of Radiation-induced Fibrosis: Rehabilitative Care for Breast Cancer Survivors.

    PubMed

    Warpenburg, Mary J

    2014-10-01

    Treatment for invasive breast cancer usually involves some combination of surgery, radiation therapy, chemotherapy, hormone therapy, and/or targeted therapy. For approximately 50% of patients, radiation therapy is a component of the therapies used. As a result, radiation-induced fibrosis is becoming a common and crippling side effect, leading to muscle imbalance with a lessened range of motion as well as pain and dysfunction of the vascular and lymphatic systems. No good estimates are available for how many patients experience complications from radiation. Radiation-induced fibrosis can affect the underlying fascia, muscles, organs, and bones within the primary target field and the larger secondary field that is caused by the scatter effect of radioactive elements. For breast cancer patients, the total radiation field may include the neck, shoulder, axillary, and thoracic muscles and the ribs for both the ipsilateral (cancer-affected) and contralateral sides. This case study indicates that therapy using deep friction massage can affect radiation-induced fibrosis beneficially, particularly in the thoracic muscles and the intercostals (ie, the muscles between the ribs). When delivered in intensive sessions using deep friction techniques, massage has the potential to break down fibrotic tissues, releasing the inflammation and free radicals that are caused by radiation therapy. In the course of the massage, painful and debilitating spasms resulting from fibrosis can be relieved and the progressive nature of the radiation-induced fibrosis interrupted.

  17. Treatment of capecitabine-induced hand-foot syndrome using a topical retinoid: A case report

    PubMed Central

    INOKUCHI, MASAFUMI; ISHIKAWA, SATOKO; FURUKAWA, HIROYUKI; TAKAMURA, HIROYUKI; NINOMIYA, ITASU; KITAGAWA, HIROHISA; FUSHIDA, SACHIO; FUJIMURA, TAKASHI; OHTA, TETSUO

    2014-01-01

    Capecitabine is a chemotherapeutic drug used in patients with breast, colon and gastric cancer. Hand-foot syndrome (HFS) is a type of dermatitis that frequently occurs as a reaction to capecitabine. To date, no effective strategies have been found to prevent or reverse HFS. Furthermore, chemotherapy induces an elevation in the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), and this activation represents a critical mechanism for the induction of chemotherapeutic resistance. Adapalene is a third-generation synthetic retinoid. Topical retinoids are important therapeutic anti-aging agents for managing photodamaged skin, and are known to increase HB-EGF levels, which is important for skin wound healing. Accordingly, the current report focused on the topical retinoids that increase HB-EGF expression in the skin, and we hypothesized that these topical retinoids induce local chemotherapeutic resistance in the skin of patients receiving chemotherapy and consequently, decrease the cutaneous side-effects of chemotherapy. This report presents a case of the successful treatment of refractory HFS induced by capecitabine using the topical application of adapalene. Topical adapalene was applied for 3 months and significantly reduced inflammation and pain following chemotherapy. Topical retinoids may have the potential to effectively treat capecitabine-induced HFS by increasing HB-EGF expression and decreasing cutaneous side-effects. Further studies are required to establish the therapeutic efficacy of topical retinoids on HFS. PMID:24396465

  18. Antenatal Glucocorticoid Treatment Induces Adaptations in Adult Midbrain Dopamine Neurons, which Underpin Sexually Dimorphic Behavioral Resilience

    PubMed Central

    Virdee, Kanwar; McArthur, Simon; Brischoux, Frédéric; Caprioli, Daniele; Ungless, Mark A; Robbins, Trevor W; Dalley, Jeffrey W; Gillies, Glenda E

    2014-01-01

    We demonstrated previously that antenatal glucocorticoid treatment (AGT, gestational days 16–19) altered the size and organization of the adult rat midbrain dopaminergic (DA) populations. Here we investigated the consequences of these AGT-induced cytoarchitectural disturbances on indices of DA function in adult rats. We show that in adulthood, enrichment of striatal DA fiber density paralleled AGT-induced increases in the numbers of midbrain DA neurons, which retained normal basal electrophysiological properties. This was co-incident with changes in (i) striatal D2-type receptor levels (increased, both sexes); (ii) D1-type receptor levels (males decreased; females increased); (iii) DA transporter levels (males increased; females decreased) in striatal regions; and (iv) amphetamine-induced mesolimbic DA release (males increased; females decreased). However, despite these profound, sexually dimorphic changes in markers of DA neurotransmission, in-utero glucocorticoid overexposure had a modest or no effect on a range of conditioned and unconditioned appetitive behaviors known to depend on mesolimbic DA activity. These findings provide empirical evidence for enduring AGT-induced adaptive mechanisms within the midbrain DA circuitry, which preserve some, but not all, functions, thereby casting further light on the vulnerability of these systems to environmental perturbations. Furthermore, they demonstrate these effects are achieved by different, often opponent, adaptive mechanisms in males and females, with translational implications for sex biases commonly found in midbrain DA-associated disorders. PMID:23929547

  19. Ivabradine, a novel treatment for clozapine-induced sinus tachycardia: a case series

    PubMed Central

    Brook, Jennifer; Dixon, Thomas; Gaughran, Fiona; Shergill, Sukhi; Melikian, Narbeh; MacCabe, James H.

    2014-01-01

    Objectives: Clozapine is the most efficacious treatment for treatment-resistant schizophrenia; however its use can be limited by intolerability. Sinus tachycardia is a common adverse event associated with clozapine use, which may lead to the premature discontinuation of clozapine. Traditionally, β blockers are used to treat clozapine-associated tachycardia, though problems with intolerability and ineffectiveness can limit their utility. Methods: In this article, we present two cases of patients with treatment-resistant schizophrenia who developed symptomatic tachycardia associated with clozapine therapy. Results: We demonstrate that the novel heart rate controlling agent ivabradine can be effectively and safely used to control the heart rate and to allow for continued treatment with clozapine. Conclusion: This is the first report in the literature demonstrating that ivabradine appears to be a well tolerated agent, which should be considered as a symptomatic treatment of clozapine-induced tachycardia if the use of a β blocker fails due to a lack of response or intolerability. PMID:25057344

  20. Partial alleviation of oxidative stress induced by gamma irradiation in Vigna radiata by polyamine treatment.

    PubMed

    Sengupta, Mandar; Raychaudhuri, Sarmistha Sen

    2017-08-01

    Environmental changes generate free radicals and reactive oxygen species (ROS) resulting in abiotic stress in plants. This causes alterations in germination, morphology, growth and development ultimately leading to yield loss. Gamma irradiation was used to experimentally induce oxidative damage in an important pulse crop Vigna radiata (L.) Wilczek or mung bean. Our research was aimed towards augmentation of oxidative stress tolerance through treatment with a group of aliphatic amines known as polyamines. We used sub-lethal doses of gamma irradiation to generate oxidative damage which was evaluated using Nitro blue tetrazolium (NBT) staining, total antioxidant activity, 1, 1-Diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assay, proline content and lipid peroxidation. Changes in internal free polyamines and messenger ribonucleic acid (mRNA) expression of key rate-limiting S-adenosylmethionine decarboxylase (SAMDC) enzyme in polyamine biosynthetic pathway was studied using real-time polymerase chain reaction (PCR). We observed increased oxidative damage with higher irradiation dose which was partially alleviated by putrescine treatment. Internal levels of putrescine and spermidine increased with 1 mM (50 and 100 Gy) and 2 mM putrescine treatment. Expression of SAMDC also increased with putrescine treatment. This study shows that treatment with putrescine can partially alleviate oxidative damage caused by gamma rays.

  1. Antioxidative treatment diminishes ethanol-induced congenital malformations in the rat.

    PubMed

    Wentzel, Parri; Rydberg, Ulf; Eriksson, Ulf J

    2006-10-01

    Intrauterine exposure to ethanol causes embryonic and fetal growth retardation and maldevelopment. Oxidative stress in mother and offspring has been suggested to be part of the teratogenic mechanism, and supplementation of antioxidative agents to the pregnant women may therefore be of value in future prophylactic treatment regimen. There is a need for in vivo experimental work in this field, and in the present study, our aim was to investigate whether chronic ethanol consumption induced congenital malformations in rats and, if so, whether dietary supplementation of vitamin E (alpha-tocopherol) diminished such maldevelopment. Female Sprague-Dawley rats were given drinking water containing 20% ethanol and half of these received food containing 5% vitamin E. Non-ethanol-exposed female rats, with or without vitamin E treatment, served as controls. The pregnancy was interrupted on gestational day 20 when the offspring was evaluated morphologically and fetal hepatic 8-iso-PGF(2alpha) levels were measured to assess the degree of fetal oxidative stress. Exposure to 20% ethanol increased maternal blood ethanol to 1.5 promille and increased resorption and malformation rates in the offspring. Maternal vitamin E treatment did not affect blood ethanol levels, but normalized fetal development. The fetal hepatic levels of 8-iso-PGF(2alpha) were increased in the ethanol-exposed group and normalized by vitamin E treatment of the mother. Ethanol exposure disturbs embryogenesis partly by enhanced oxidative stress, and the adverse effects can be ameliorated by antioxidative treatment.

  2. Transnasal butorphanol for the treatment of opioid-induced pruritus unresponsive to antihistamines.

    PubMed

    Dunteman, E; Karanikolas, M; Filos, K S

    1996-10-01

    Pruritus is a common opioid side effect and can be so severe that opioid therapy must be modified or abandoned. Antihistamines, opioid antagonists, and propofol have been proposed as treatment options, but none is universally effective. The use of intranasal butorphanol, an opioid agonist-antagonist, for pruritus has not been described previously. Six patients complaining of severe opioid-induced pruritus unresponsive to diphenhydramine received 2 mg intranasal butorphanol every 4-6 hr. Scores for pruritus, pain, and sedation were recorded on separate visual analogue scales (VAS). All patients reported significant relief from pruritus 60 min after butorphanol administration (P < 0.001); five patients noted an improvement within 15 min (P < 0.08). Sedation and pain VAS scores were not significantly different from baseline at all time points. These preliminary data demonstrate a substantial effect of intranasal butorphanol on opioid-induced pruritus that has not responded to antihistamines. Prospective controlled studies are needed to validate these findings.

  3. Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation.

    PubMed

    Hoyle, Gary W; Chen, Jing; Schlueter, Connie F; Mo, Yiqun; Humphrey, David M; Rawson, Greg; Niño, Joe A; Carson, Kenneth H

    2016-05-01

    Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation.

  4. Development and Assessment of Countermeasure Formulations for Treatment of Lung Injury Induced by Chlorine Inhalation

    PubMed Central

    Hoyle, Gary W.; Chen, Jing; Schlueter, Connie F.; Mo, Yiqun; Humphrey, David M.; Rawson, Greg; Niño, Joe A.; Carson, Kenneth H.

    2016-01-01

    Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation. PMID:26952014

  5. Melanonychia induced by topical treatment of periungual warts with 5-fluorouracil.

    PubMed

    De Anda, Mariana Catalina; Domínguez, Judith Guadalupe

    2013-03-15

    Periungal and subungual warts are benign epidermal neoplasms caused by human papillomaviruses. They represent a challenge for management because of resistance to treatment. 5-flourouracil is an antimetabolite that interferes with DNA synthesis and inhibits RNA formation. We present a 32-year-old female with subungual and periungual warts of the fingers of both hands and first right toe. She was treated with 5-fluorouracil twice daily under occlusion plus 20 percent urea. After a month she presented with grayish transverse melanonychia along and parallel to the lunula with some maceration of the periungal folds. Nail pigmentation may be a consequence of dermal deposition by systemic drugs and less frequently by topical drugs. In this case melanonychia was induced by the topical application of 5-fluorouracil. The brown-grayish pigmentation, with parallel involvement of the lunula of all the nails treated, presented like that induced by systemically administered cytotoxic drugs.

  6. Long-Term Treatment of Native LDL Induces Senescence of Cultured Human Endothelial Cells

    PubMed Central

    Oh, Sung-Tack; Park, Hoon; Yoon, Hyun Joong

    2017-01-01

    The study aimed to evaluate whether the treatment of primary cultured human endothelial cells with native low-density lipoprotein (nLDL) could induce their senescence and to uncover some of the putative mechanisms involved. For this purpose, human umbilical vein endothelial cells (HUVECs) were subcultured and/or continuously cultured with nLDL (0, 2, 5, and 10 μg protein/mL), for up to 9 days. The results indicated that nLDL inhibited the proliferation of HUVECs by arresting the cell cycle at G1 phase. The G1-arrested cells showed increase in cytosolic senescence-associated-β-galactosidase (SA-β-Gal) activity, a biomarker of cellular senescence. The causative factor of the cellular senescence was nLDL itself and not oxidized LDL (oxLDL), since blocking LDL receptor (LDLR) with the anti-LDLR antibody opposed the nLDL-induced increase of SA-β-Gal activity and decrease of cellular proliferation. In addition, nLDL-induced cellular senescence by inhibiting the phosphorylation of pRb (G1 arrest) via p53 as well as p16 signal transduction pathways. G1 phase arrest of the senescent cells was not overcome by nLDL removal from the culture medium. Moreover, the nLDL-treated cells produced reactive oxygen species (ROS) dose- and time-dependently. These results suggested, for the first time, that long-term treatment of nLDL could induce the premature senescence of endothelial cells. PMID:28197300

  7. Combination of Foot Stimulation and Tramadol Treatment Reverses Irritation Induced Bladder Overactivity in Cats

    PubMed Central

    Mally, Abhijith D.; Zhang, Fan; Matsuta, Yosuke; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.; Tai, Changfeng

    2013-01-01

    Purpose We determined whether transcutaneous electrical foot stimulation combined with a low dose of tramadol (Sigma-Aldrich®) could completely suppress bladder overactivity. Materials and Methods Repeat cystometrograms were performed in 18 α-chloralose anesthetized cats by infusing the bladder with saline or 0.25% acetic acid. Transcutaneous electrical stimulation (5 Hz) of the cat hind foot at 2 to 4 times the threshold intensity needed to induce observable toe movement was applied to suppress acetic acid induced bladder overactivity. Tramadol (1 to 3 mg/kg intravenously) was administered to enhance foot inhibition. Results Acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to a mean ± SE of 26% ± 5% of saline control capacity (p <0.01). Without tramadol, foot stimulation at 2 and 4 threshold intensity applied during acetic acid cystometrograms significantly increased bladder capacity to a mean of 47% ± 5% and 62% ± 6% of saline control capacity, respectively (p <0.05). Without foot stimulation, tramadol (1 mg/kg) only slightly changed bladder capacity to a mean of 39% ± 2% of saline control capacity (p >0.05), while 3 mg/kg significantly increased capacity to 85% ± 14% that of control (p <0.05). However, 1 mg/kg tramadol combined with foot stimulation increased bladder capacity to a mean of 71% ± 18% (2 threshold intensity) and 84% ± 14% (4 threshold intensity), respectively, which did not significantly differ from saline control capacity. In addition, long lasting (greater than 1.5 to 2 hours) post-stimulation inhibition was induced by foot stimulation combined with 3 mg/kg tramadol treatment. Conclusions This study suggests a new treatment strategy for overactive bladder by combining foot stimulation with a low dose of tramadol, which is noninvasive and has potentially high efficacy and fewer adverse effects. PMID:23088991

  8. Antiparasitic Treatment Induces an Improved CD8(+) T Cell Response in Chronic Chagasic Patients.

    PubMed

    Mateus, Jose; Pérez-Antón, Elena; Lasso, Paola; Egui, Adriana; Roa, Nubia; Carrilero, Bartolomé; González, John M; Thomas, M Carmen; Puerta, Concepción J; López, Manuel C; Cuéllar, Adriana

    2017-04-15

    Chagas disease is a chronic infection caused by Trypanosoma cruzi, an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8(+) T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease. There is a lack of biological markers to evaluate the effectiveness of antiparasitic treatment, and little is known about the effect of the treatment on CD8(+) T cells. Thus, the aim of the current study was to analyze the early effects of antiparasitic treatment on CD8(+) T cells from CCPs with asymptomatic clinical forms of disease. To evaluate the CD8(+) T cell subsets, expression of inhibitory receptors, and functionality of T cells in CCPs, PBMCs were isolated. The results showed that treatment of CCPs with the asymptomatic form of the disease induces an increase in the frequency of CD8(+) central memory T cells and terminal effector T cells, a decrease in the coexpression of inhibitory receptors, an improved Ag-specific CD8(+) T cell response exhibited by the individual production of IFN-γ or IL-2, and a multifunctional CD8(+) T cell profile of up to four functions (IFN-γ(+)IL-2(+)Perforin(+)Granzyme B(+)). These findings suggest that, in CCPs, antiparasitic treatment improved the quality of Ag-specific CD8(+) T cell responses associated with a decrease in inhibitory receptor coexpression, which could serve as biomarkers for monitoring the effectiveness of antiparasitic treatment.

  9. Therapeutic treatment with a novel hypoxia-inducible factor hydroxylase inhibitor (TRC160334) ameliorates murine colitis

    PubMed Central

    Gupta, Ram; Chaudhary, Anita R; Shah, Binita N; Jadhav, Avinash V; Zambad, Shitalkumar P; Gupta, Ramesh Chandra; Deshpande, Shailesh; Chauthaiwale, Vijay; Dutt, Chaitanya

    2014-01-01

    Background and aim Mucosal healing in inflammatory bowel disease (IBD) can be achieved by improvement of intestinal barrier protection. Activation of hypoxia-inducible factor (HIF) has been identified as a critical factor for barrier protection during mucosal insult and is linked with improvement in symptoms of colitis. Although prophylactic efficacy of HIF hydroxylase inhibitors in murine colitis have been established, its therapeutic efficacy in clinically relevant therapeutic settings have not been established. In the present study we aim to establish therapeutic efficacy of TRC160334, a novel HIF hydroxylase inhibitor, in animal models of colitis. Methods The efficacy of TRC160334 was evaluated in two different mouse models of colitis by oral route. A prophylactic efficacy study was performed in a 2,4,6-trinitrobenzene sulfonic acid-induced mouse model of colitis representing human Crohn’s disease pathology. Additionally, a therapeutic efficacy study was performed in a dextran sulfate sodium-induced mouse model of colitis, a model simulating human ulcerative colitis. Results TRC160334 treatment resulted in significant improvement in disease end points in both models of colitis. TRC160334 treatment resulted into cytoprotective heatshock protein 70 induction in inflamed colon. TRC160334 successfully attenuated the rate of fall in body weight, disease activity index, and macroscopic and microscopic scores of colonic damage leading to overall improvement in study outcome. Conclusion Our findings are the first to demonstrate that therapeutic intervention with a HIF hydroxylase inhibitor ameliorates IBD in disease models. These findings highlight the potential of TRC160334 for its clinical application in the treatment of IBD. PMID:24493931

  10. Dysregulation of DNA Methylation Induced by Past Arsenic Treatment Causes Persistent Genomic Instability in Mammalian Cells

    PubMed Central

    Mauro, Maurizio; Caradonna, Fabio; Klein, Catherine B.

    2016-01-01

    The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. To investigate potential epigenetic mechanisms, in this study we evaluated global DNA methylation levels in V79 cells and human HaCaT keratinocytes at several time points during expanded growth of cell cultures following removal of arsenite exposures. We have found altered genomic methylation patterns that persisted up to 40 cell generations in HaCaT cells after the treatments were withdrawn. Moreover, mRNA expression levels were evaluated by RT-PCR for DNMT1, DNMT3A, DNMT3B, HMLH1, and HMSH2 genes, demonstrating that the down regulation of DNMT3A and DNMT3B genes, but not DNMT1, occurred in an arsenic dose-dependent manner, and persisted for many cell generations following removal of the arsenite, offering a plausible mechanism of persistently genotoxic arsenic action. Analyses of promoter methylation status of the DNA mismatch repair genes HMLH1 and HMSH2 show that HMSH2, but not HMLH1, was epigenetically regulated by promoter hypermethylation changes following arsenic treatment. The results reported here demonstrate that arsenic exposure promptly induces genome-wide global DNA hypomethylation, and some specific gene promoter methylation changes, that persist for many cell generations following withdrawal of arsenite, supporting the hypothesis that the cells undergo epigenetic reprogramming at both the gene and genome level that is durable over many cell generations in the absence of further arsenic treatment. These DNA methylation changes, in concert with other known epigenome alterations, are likely contributing to long-lasting arsenic-induced genomic instability that manifests in several ways, including aberrant chromosomal effects. PMID:26581878

  11. Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide

    PubMed Central

    Schimpf, Rainer; Veltmann, Christian; Papavassiliu, Theano; Rudic, Boris; Göksu, Turgay; Kuschyk, Jürgen; Wolpert, Christian; Antzelevitch, Charles; Ebner, Alois; Borggrefe, Martin; Brandt, Christian

    2012-01-01

    BACKGROUND The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. OBJECTIVE Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. METHODS Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and Tpeak-Tend intervals were analyzed before and during rufinamide treatment. RESULTS The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). Tpeak-Tend intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. CONCLUSION QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations nothwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings. PMID:22245794

  12. Drug-induced QT-interval shortening following antiepileptic treatment with oral rufinamide.

    PubMed

    Schimpf, Rainer; Veltmann, Christian; Papavassiliu, Theano; Rudic, Boris; Göksu, Turgay; Kuschyk, Jürgen; Wolpert, Christian; Antzelevitch, Charles; Ebner, Alois; Borggrefe, Martin; Brandt, Christian

    2012-05-01

    The arrhythmogenic potential of short QT intervals has recently been highlighted in patients with a short QT syndrome. Drug-induced QT-interval prolongation is a known risk factor for ventricular tachyarrhythmias. However, reports on drug-induced QT-interval shortening are rare and proarrhythmic effects remain unclear. Recently, rufinamide, a new antiepileptic drug for the add-on treatment of Lennox-Gastaut syndrome, was approved in the European Union and the United States. Initial trials showed drug-induced QT-interval shortening. The aim of our study was to evaluate the effects of rufinamide on QT intervals in patients with difficult-to-treat epilepsies. Nineteen consecutive patients with Lennox-Gastaut syndrome and other epilepsy syndromes were included (n = 12 men; mean age 41 ± 12 years). QRS, QT, and T(peak)-T(end) intervals were analyzed before and during rufinamide treatment. The mean QT interval shortened significantly following rufinamide administration (QT interval 349 ± 23 ms vs 327 ± 17 ms; corrected QT interval 402 ± 22 ms vs 382 ± 16 ms; P = .002). T(peak)-T(end) intervals were 79 ± 17 ms before and 70 ± 20 ms on treatment (P = .07). The mean reduction of the corrected QT interval was 20 ± 18 ms. During follow-up (3.04 ± 1.09 years), no adverse events including symptomatic cardiac arrhythmias or sudden cardiac deaths were observed. QTc-interval shortening following oral rufinamide administration in a small patient group was not associated with significant clinical adverse effects. These observations notwithstanding, the ability of rufinamide to significantly shorten the QT interval portends a potential arrhythmogenic risk that may best be guarded against by periodic electrocardiographic recordings. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  13. Dysregulation of DNA methylation induced by past arsenic treatment causes persistent genomic instability in mammalian cells.

    PubMed

    Mauro, Maurizio; Caradonna, Fabio; Klein, Catherine B

    2016-03-01

    The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. To investigate potential epigenetic mechanisms, in this study we evaluated global DNA methylation levels in V79 cells and human HaCaT keratinocytes at several time points during expanded growth of cell cultures following removal of arsenite exposures. We have found altered genomic methylation patterns that persisted up to 40 cell generations in HaCaT cells after the treatments were withdrawn. Moreover, mRNA expression levels were evaluated by RT-PCR for DNMT1, DNMT3A, DNMT3B, HMLH1, and HMSH2 genes, demonstrating that the down regulation of DNMT3A and DNMT3B genes, but not DNMT1, occurred in an arsenic dose-dependent manner, and persisted for many cell generations following removal of the arsenite, offering a plausible mechanism of persistently genotoxic arsenic action. Analyses of promoter methylation status of the DNA mismatch repair genes HMLH1 and HMSH2 show that HMSH2, but not HMLH1, was epigenetically regulated by promoter hypermethylation changes following arsenic treatment. The results reported here demonstrate that arsenic exposure promptly induces genome-wide global DNA hypomethylation, and some specific gene promoter methylation changes, that persist for many cell generations following withdrawal of arsenite, supporting the hypothesis that the cells undergo epigenetic reprogramming at both the gene and genome level that is durable over many cell generations in the absence of further arsenic treatment. These DNA methylation changes, in concert with other known epigenome alterations, are likely contributing to long-lasting arsenic-induced genomic instability that manifests in several ways, including aberrant chromosomal effects.

  14. Statins induce biochemical changes in the Achilles tendon after chronic treatment.

    PubMed

    de Oliveira, Letícia Prado; Vieira, Cristiano Pedrozo; Da Ré Guerra, Flávia; de Almeida, Marcos dos Santos; Pimentel, Edson Rosa

    2013-09-15

    Statins have been widely prescribed as lipid-lowering drugs and are associated with tendon rupture. Therefore, this study aimed to evaluate the possible biochemical changes in the Achilles tendon of rats after chronic treatment with statins. Dosages of statins were calculated using allometric scaling with reference to the 80mg/day and 20mg/day, doses recommended for humans. The rats were divided into the following groups: treated with simvastatin (S-20 and S-80), treated with atorvastatin (A-20 and A-80), and the control group that received no treatment (C). Measurements of low-density lipoprotein (LDL) in the plasma were performed. The levels of non-collagenous proteins, glycosaminoglycans (GAGs) and hydroxyproline were quantified. Western blotting for collagen I was performed, and the presence of metalloproteinases (MMPs)-2 and -9 was investigated through zymography. The concentration of non-collagenous proteins in S-20 was less than the C group. There was a significant increase in pro-MMP-2 activity in A-80 group and in active MMP-2 in S-20 group compared to the C group. A significant increase in latent MMP-9 activity was observed in both the A-80 and S-20 groups when compared to C group. In the A-20 group, there was a lower amount of collagen I in relation to C group. In addition, a higher concentration of hydroxyproline was found in the S-20 group than the C group. The analysis of GAGs showed a significant increase in the A-20 group when compared to C group. The treatment induced remarkable alterations in the Achilles tendon and the response of the tissue seems to depend of the used statin dosage. The presence of MMP-2 and MMP-9 is evidence of the degradation and remodeling processes in the extracellular matrix of the tendons. Our results show that statins induce imbalance of extracellular matrix components and possibly induce microdamage in tendons.

  15. Diffuse interstitial pulmonary fibrosis: pulmonary fibrosis in mice induced by treatment with butylated hydroxytoluene and oxygen

    SciTech Connect

    Haschek, W.M.; Brody, A.R.; Klein-Szanto, A.J.P.; Witschi, H.

    1981-12-01

    It is proposed that the pulmonary fibrosis induced in mice by treatment with BHT and oxygen is a good experimental model for human pulmonary fibrosis. The mechanism of synergistic and additive effects of various agents on pulmonary injury and the epithelial mesenchymal interactions occurring during the early and late phases of lung repair could be studied. This model could be used for study of the effects of various concentrations of oxygen on diffusely damaged lung and assessment of the efficacy of drugs in preventing or resolving excessive collagen accumulation in lung. In addition, the relationship between pulmonary fibrosis and emphysema could be studied.

  16. Levocabastine versus cromolyn sodium in the treatment of pollen-induced conjunctivitis.

    PubMed

    Ciprandi, G; Cerqueti, P M; Sacca, S; Cilli, P; Canonica, G W

    1990-08-01

    Thirty patients with allergic conjunctivitis, caused by Parietaria or grass pollens, participated in a double-blind parallel study comparing levocabastine to cromolyn sodium, both given as eye drops. Symptom and sign scores were recorded during a 4-week period. The patients received only these drugs during the time of observation. The evaluation of the clinical signs and symptoms by the clinicians and by the patients revealed a significant improvement of conjunctivitis in all patients. The intergroup comparison was equal in the two groups treated respectively with levocabastine and cromolyn. Therefore, levocabastine and cromolyn are effective in the treatment of pollen-induced allergic conjunctivitis.

  17. Treatment of refractory ischemic pain from chemotherapy-induced Raynaud's syndrome with spinal cord stimulation.

    PubMed

    Ting, Joseph C; Fukshansky, Mikhail; Burton, Allen W

    2007-06-01

    We report the successful treatment of refractory ischemic pain from cisplatin-induced Raynaud's syndrome with spinal cord stimulation after failed pharmacologic management and surgical sympathectomy. A 48-year-old man developed ischemic pain of the hands while undergoing cisplatin and gemcitabine chemotherapy for metastatic pancreatic carcinoma. After extensive pharmacologic management and surgical sympathectomy failed to provide adequate analgesia, the patient underwent a percutaneous spinal cord stimulation trial followed by permanent implantation and received significant pain relief prior to succumbing to his illness. Spinal cord stimulation provided effective therapy for refractory ischemic pain, even after failed sympathectomy.

  18. Severe duodenal hemorrhage induced by Lugol's solution administered for thyroid crisis treatment.

    PubMed

    Kinoshita, Hiroyuki; Yasuda, Mutsuko; Furumoto, Youhei; Watanabe, Naoko; Horiuchi, Takao; Murayama, Minekazu; Kitamura, Mari; Kaneko, Shingo; Inoshita, Seiji; Maruyama, Yasuki; Suenaga, Matsuhiko; Fujita, Hiroshi; Fujiki, Kazuhiko; Yakushiji, Fumiatsu

    2010-01-01

    Lugol's solution is an iodinated agent used for treating thyroid crisis. It is primarily used in diagnostic tests for esophageal diseases. However, Lugol's solution can cause local mucosal injury and hemorrhage. We report, for the first time, a case of 34-year-old man who exhibited severe duodenal hemorrhage induced by Lugol's solution that was used to treat thyroid crisis. The quantity of Lugol's solution used for treating thyroid crisis is much higher than that used for mucosal disease investigation. Clinical practitioners should be aware of gastrointestinal hemorrhage when using Lugol's solution for the treatment of thyroid crisis.

  19. Pre-hospital treatment of bee and wasp induced anaphylactic reactions: a retrospective study.

    PubMed

    Ruiz Oropeza, Athamaica; Mikkelsen, Søren; Bindslev-Jensen, Carsten; Mortz, Charlotte G

    2017-01-14

    Bee and wasp stings are among the most common triggers of anaphylaxis in adults representing around 20% of fatal anaphylaxis from any cause. Data of pre-hospital treatment of bee and wasp induced anaphylactic reactions are sparse. This study aimed to estimate the incidence of bee and wasp induced anaphylactic reactions, the severity of the reactions and to correlate the pre-hospital treatment with the severity of the anaphylactic reaction. Retrospective and descriptive study based on data from the Mobile Emergency Care Units (MECUs) in the Region of Southern Denmark (2008 only for Odense and 2009-2014 for the whole region). Discharge summaries with diagnosis related to anaphylaxis according to the International Classification of Diseases 10 (ICD-10) were reviewed to identify bee and wasp induced anaphylactic reactions. The severity of the anaphylactic reaction was assessed according to Sampson's severity score and Mueller's severity score. Treatment was evaluated in relation to administration of adrenaline, glucocorticoids and antihistamine. We identified 273 cases (Odense 2008 n = 14 and Region of Southern Denmark 2009-2014 n = 259) of bee and wasp induced anaphylaxis. The Incidence Rate was estimated to 35.8 cases per 1,000,000 person year (95% CI 25.9-48.2) in the Region of Southern Denmark during 2009-2014. According to Sampson's severity score, 65% (n = 177) of the cases were graded as moderate to severe anaphylaxis (grade 3-5). Almost one third of cases could not be graded according to Mueller's severity score. Adrenaline was administrated in 54% (96/177) of cases with moderate to severe anaphylaxis according to Sampson's severity score, compared to 88% receiving intravenous glucocorticoids (p < 0.001) and 91% receiving intravenous antihistamines (p < 0.001). Even in severe anaphylaxis (grade 5) adrenaline was administered in only 80% of the cases. Treatment with adrenaline is not administered in accordance with international guidelines

  20. Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats.

    PubMed

    Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

    2015-12-14

    To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15(th) day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. The DAI was lower in the kefir-colitis group than in the colitis group (on the 3(rd) and 5(th) days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6(th) day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment

  1. Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats

    PubMed Central

    Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

    2015-01-01

    AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15th day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3rd and 5th days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0

  2. Clot-Inducing Minerals Versus Plasma Protein Dressing for Topical Treatment of External Bleeding in the Presence of Coagulopathy

    DTIC Science & Technology

    2010-11-01

    ORIGINAL ARTICLE Clot-Inducing Minerals Versus Plasma Protein Dressing for Topical Treatment of External Bleeding in the Presence of Coagulopathy...N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Clot-inducing minerals versus plasma protein dressing for topical treatment of external bleeding...known sealant properties of smectite clay that form when the dry minerals are mixed with water or blood suggested a possible hemostatic advantage of

  3. Surface treatment analyses of car bearings by using laser-induced breakdown spectroscopy.

    PubMed

    Alvira, F C; Orzi, D J O; Bilmes, G M

    2009-02-01

    Determination of surface coating composition is a problem of great importance for industry and production related to the quality control of products and processes. One of the most outstanding aspects of laser-induced breakdown spectroscopy (LIBS) is its unique ability to carry out real-time depth profile analysis. This allows, for instance, the identification of layered coatings composition. In this work we performed depth profile analysis using LIBS to determine the composition of layered surface treatments of car bearings. Laser ablation thresholds for each coating layer were determined by acoustic measurements. Transitions between the different coating layers were also identified by an acoustic method. We developed faster and simpler semi-quantitative procedures to determine the relative composition of alloy surface coatings of car bearings as well as the possibility to characterize in real time these treatments.

  4. Inducible pluripotent stem cells for the treatment of ischemic stroke: current status and problems.

    PubMed

    Zhu, Yu; Wan, Shu; Zhan, Ren-ya

    2012-01-01

    Despite dramatic advancements in medical and surgical care, effective clinical therapies for ischemic stroke are limited. Stem-cell transplantation has emerged as a potential therapeutic approach for cell replacement in ischemic brain injuries. Inducible pluripotent stem cells (iPSCs) have become an alternative cell source for transplantation. They possess efficient capacities for neural differentiation without ethical and immune-rejection concerns. Substantial function of iPSCs in pre-clinical models of ischemic brain injury has been observed. However, several problems remain regarding the treatment of ischemic stroke with iPSCs: tumorigenicity, poor iPSC derivation methods, and undefined delivery variables. With the development of iPSC research, safer and more effective strategies will be achieved for highly effective and tumor-free cell treatment of ischemic stroke.

  5. [Perspectives in the treatment of subarachnoid-hemorrhage-induced cerebral vasospasm].

    PubMed

    Fandino, J; Fathi, A R; Graupner, T; Jacob, S; Landolt, H

    2007-02-01

    Cerebral vasospasm is still the most important cause of death and disability after rupture of intracranial aneurysms. The therapeutic strategies in the treatment of subarachnoid hemorrhage induced vasospasm vasospasm include four groups: 1) prevention of vasospasm; 2) reversion of vasospasm; 3) improvement of cerebral perfusion; and 4) neuroprotection and rescue therapies. Recent experimental studies allowed the design of phase II clinical studies which demonstrated positive results with medications and compounds such as statins (simvastatin and pravastatin) and endothelin-1 receptor antagonists (clasozentan). Moreover, experimental and clinical evidences showed the advantages of early cerebrospinal fluid drainage, intrathecal administration of NO-donors, effects of Ca2+ protein kinase inhibitor (Fasudil) and catecholamines on the cerebral vessels. This review article summarizes the stage of investigation of these medications and therapeutic strategies which will be relevant in the treatment of cerebral vasospasm.

  6. Exercise-induced cardioprotection is impaired by anabolic steroid treatment through a redox-dependent mechanism.

    PubMed

    Chaves, Elen A; Fortunato, Rodrigo S; Carvalho, Denise P; Nascimento, José Hamilton M; Oliveira, Marcus F

    2013-11-01

    High doses of anabolic androgenic steroids (AAS) impair the cardioprotective effects of exercise against ischemia/reperfusion (I/R) insult, possibly through cellular redox imbalance. Here, the effect of nandrolone decanoate (DECA) treatment on heart redox metabolism was investigated during I/R in sedentary and exercised rats. DECA treatment significantly reduced superoxide dismutase and glutathione reductase activities in exercised rats after heart reperfusion. Catalase and glutathione peroxidase activities were not affected by DECA in both sedentary and trained rats, regardless the I/R period. DECA also induced myocardial oxidative stress, as evidenced by the reduced levels of total reduced thiols after heart reperfusion in exercised rats treated with the anabolic steroid. These results indicate that cardiotoxic effects of supraphysiological doses of AAS involve reduced heart antioxidant capacity.

  7. Processing of Ultrafine-Grained Twinning-Induced Plasticity Steel Using Martensite Treatment

    NASA Astrophysics Data System (ADS)

    Dini, Ghasem; Zamani, Davood

    2017-07-01

    For the first time, martensite treatment was used to fabricate an ultrafine-grained (UFG) twinning-induced plasticity (TWIP) steel. The effects of cold rolling with 70 pct reduction at the liquid nitrogen temperature and subsequently annealing at 973 K (700 °C) for 5 to 20 minutes on the microstructure and mechanical properties of Fe-22Mn-0.4C-1.5Al-1Si TWIP steel were investigated. The results showed that a fully recrystallized UFG TWIP steel with a mean grain size of about 400 to 600 nm can be produced by the designed martensite treatment. The UFG TWIP steel exhibited high yield and tensile strengths and relatively high ductility.

  8. Controlling silicon crystallization in aluminum-induced crystallization via substrate plasma treatment

    NASA Astrophysics Data System (ADS)

    Hainey, Mel F.; Innocent-Dolor, Jon-L.; Choudhury, Tanushree H.; Redwing, Joan M.

    2017-03-01

    The effect of reactive ion etching using chlorine or fluorine-based plasmas on aluminum-induced crystallization (AIC) of silicon on fused silica glass substrates was investigated with the goal of chemically modifying the substrate surface and thereby influencing the crystallization behavior. Chlorine etching of the glass prior to AIC resulted in six times faster silicon crystallization times and smaller grain sizes than films formed on untreated substrates while fluorine etching resulted in crystallization times double than those on untreated surfaces. The differences in crystallization behavior were attributed to changes in surface chemistry and surface energy of the glass as a result of the plasma treatment as supported by X-ray photoelectron spectroscopy and contact angle measurements. The different surface treatments were then combined with optical lithography to control the location of crystallization on the substrate surface to realize the production of patterned polycrystalline silicon films from initially continuous aluminum and silicon.

  9. Efficacy and safety of zoledronic acid in the treatment of glucocorticoid-induced osteoporosis

    PubMed Central

    Serefoglu, Ege Can; Tandogdu, Zafer

    2010-01-01

    Glucocorticoids are essential in treating many disorders and they are widely used in spite of their negative impact on the skeletal system. As bisphosphonates reduce bone resorption through their action on osteoclasts, they play an important role in management of glucocorticoid-induced osteoporosis. Unlike other bisphosphonates, zoledronic acid is given by intravenous infusion and it has a potential advantage of increasing the compliance and adherence of patients when it is given 5 mg once a year. However, this treatment modality seems to be associated with more adverse events than oral administrations, and further studies with longer follow-up periods must be conducted to determine the safety and cost-effectiveness of long-term treatment with zoledronic acid. PMID:20526439

  10. Oralair(®): a causal treatment for grass pollen-induced allergic rhinoconjunctivitis.

    PubMed

    Köberlein, Juliane; Mösges, Ralph

    2013-01-01

    Grass pollen-induced allergic rhinoconjunctivitis is a common disease, comprising more than just the classic symptoms of nasal obstruction, sneezing, rhinorrhea and itchy, watery eyes. Sufferers deal with severe impairments in daily life. Allergic rhinoconjunctivitis is also considered an important risk factor in the development of asthma. Allergen avoidance, medication for symptomatic treatment and allergen-specific immunotherapy are cornerstones in therapeutic management, but immunotherapy is the only available treatment that is able to affect the natural course of allergy. In recent decades, clinical trials have investigated the efficacy and safety of subcutaneous immunotherapy. To date, efforts have been made to develop more convenient routes of administration. Substantial improvement may be achieved through the application of sublingual tablets. This article discusses the development process of immunotherapy and the clinical background of the Oralair(®) (Stallergènes, Hauts-de-Seine, France) five-grass pollen tablet. Furthermore, it outlines this tablet's efficacy and safety properties.

  11. Successful treatment by adding duloxetine to pregabalin for peripheral neuropathy induced by paclitaxel.

    PubMed

    Takenaka, Motoyasu; Iida, Hiroki; Matsumoto, Shigemi; Yamaguchi, Shinobu; Yoshimura, Noritaka; Miyamoto, Maki

    2013-11-01

    Although paclitaxel is a commonly used anticancer drug, peripheral neuropathy may develop as a side effect. Worsening of the symptoms with time may cause patients who receive paclitaxel to give up their chemotherapy. Duloxetine, a serotonin- and norepinephrine-reuptake inhibitor, has been used to treat peripheral neuropathic pain. We report the case of a 68-year-old man with gastric cancer, who underwent gastrectomy and then received 8 cycles of chemotherapy involving weekly administrations of paclitaxel. Under this paclitaxel treatment, he complained of severe peripheral neuropathy, leading to a diminished quality of life. Following treatment with a combination of duloxetine and pregabalin, a remission of his symptoms was achieved. Duloxetine plus pregabalin therapy may be useful for the peripheral neuropathy induced by paclitaxel.

  12. Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1.

    PubMed

    Bai, Qingyun; Yan, Hongyu; Sheng, Yuchen; Jin, Yao; Shi, Liang; Ji, Lili; Wang, Zhengtao

    2017-05-01

    Acetaminophen (APAP)-induced acute liver injury has already been well studied. However, whether long-term administration of APAP will cause liver fibrosis is still not very clear. This study aims to investigate the liver fibrosis in mice induced by long-term APAP treatment and the involvement of early growth response 1 (Egr-1). C57BL/6 mice were orally given with APAP (200, 300mg/kg) for 2, 6 or 10 weeks, respectively. Liver hydroxyproline content, collagen deposition and inflammatory cells infiltration were increased in mice treated with APAP (200, 300mg/kg) for 6 or 10 weeks. Liver mRNA expression of collagen (COL)1a1, Col3a1, transforming growth factor-β (TGF-β) and serum contents of COL1, COL3, TGF-β were all increased in APAP-treated mice. Liver expression of α-smooth muscle actin (α-SMA) and phosphorylated ERK1/2 and Smad2/3 were all increased in APAP-treated mice. Furthermore, increased liver mRNA expression of Egr-1 and its subsequent nuclear translocation were found in APAP-treated mice. Egr-1 knock-out mice were further applied. APAP-induced liver fibrosis was found to be more serious in Egr-1 knock-out mice. N-acetyl-p-benzoquinoneimine (NAPQI), the APAP hepatotoxic metabolite, increased cellular mRNA expression of α-SMA, Col1a1, Col3a1, TGF-β, induced ERK1/2 and Smad2/3 phosphorylation and Egr-1 nuclear translocation in hepatic stellate LX2 cells. In conclusion, long-term administration of APAP induced liver fibrosis in mice, and Egr-1 was critically involved in this process. This study points out a warning and reference for patients with long-term APAP ingestion in clinic. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. [Clinical efficacy and safety of mifepristone in the treatment of abortive remnants of induced abortion].

    PubMed

    Zhuge, Ting; Li, Bin; Huang, Zi-rong

    2012-01-03

    To evaluate the efficacy and safety of treating abortive remnants of induced abortion with different doses of mifepristone. A total of 101 women undergoing post-abortion treatment at our family planning clinic from October 2009 to February 2011 were recruited and divided randomly into 4 groups. They were diagnosed as abortive remnants by ultrasound and blood level of β-HCG (human chorionic gonadotrophin). Three test groups received different doses of mifepristone and one group as control. The efficacy and safety of four groups were evaluated by clinical observations, ultrasonic examinations and blood level of β-HCG. The effective rates of mifepristone test and control groups were 61.60% and 21.40% respectively. And there were statistical significances between two groups (P < 0.01). After a 2-week treatment, the changes of blood level of β-HCG and reduction of residual size tested by ultrasound were better than those of the control group. And there were significant statistical differences (P < 0.01). The group with high dose in short term achieved the best outcomes. After four weeks of treatment, blood level of β-HCG of test groups had no statistical significance (P > 0.05). There was statistical significance in pairwise comparison on reduction of residual size tested by ultrasound among test groups (P < 0.05). The high-dose group with achieved the largest short-term reduction. Statistical significances existed in the hemostatic time of vaginal hemorrhage and menstrual recovery between three test groups and the control group (P < 0.05). No statistical significance was found in healing time and the occurrence of adverse events among these 3 test groups (both P > 0.05). Mifepristone is effective in the treatment of induced incomplete abortion. And a short-term large dose offers a better efficacy.

  14. Arsenite treatment induces oxidative stress, upregulates antioxidant system, and causes phytochelatin synthesis in rice seedlings.

    PubMed

    Mishra, Shruti; Jha, A B; Dubey, R S

    2011-07-01

    The effects of arsenite treatment on generation of reactive oxygen species, induction of oxidative stress, response of antioxidative system, and synthesis of phytochelatins were investigated in two indica rice (Oryza sativa L.) cvs. Malviya-36 and Pant-12 grown in sand cultures for a period of 5-20 days. Arsenite (As(2)O(3); 25 and 50 μM) treatment resulted in increased formation of superoxide anion (O (2) (.-) ), elevated levels of H(2)O(2) and thiobarbituric acid reactive substances, showing enhanced lipid peroxidation. An enhanced level of ascorbate (AA) and glutathione (GSH) was observed irrespective of the variation in the level of dehydroascorbate (DHA) and oxidized glutathione (GSSG) which in turn influenced redox ratios AA/DHA and GSH/GSSG. With progressive arsenite treatment, synthesis of total acid soluble thiols and phytochelatins (PC) increased in the seedlings. Among antioxidative enzymes, the activities of superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), total ascorbate peroxidase (APX, EC 1.11.1.11), chloroplastic ascorbate peroxidase, guaiacol peroxidase (EC 1.11.1.7), monodehydroascorbate reductase (EC 1.6.5.4), and glutathione reductase (EC 1.6.4.2) increased in arsenite treated seedlings, while dehyroascorbate reductase (EC 1.8.5.1) activity declined initially during 5-10 days and increased thereafter. Results suggest that arsenite treatment causes oxidative stress in rice seedlings, increases the levels of many enzymatic and non-enzymatic antioxidants, and induces synthesis of thiols and PCs, which may serve as important components in mitigating arsenite-induced oxidative damage.

  15. Subchronic apocynin treatment attenuates methamphetamine-induced dopamine release and hyperactivity in rats.

    PubMed

    Miller, Dennis K; Oelrichs, Clark E; Sun, Grace Y; Simonyi, Agnes

    2014-03-07

    The effects of methamphetamine are linked to stimulation of dopaminergic neurons, which can be accompanied by production of reactive oxygen species (ROS). Apocynin (4-hydroxy-3-methoxy-acetophenone) is a nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase (NOX) inhibitor shown to mitigate oxidative stress in a number of models. The present study aimed at testing whether apocynin suppresses the dopamine-releasing and locomotor-activating properties of methamphetamine. (1) Apocynin (0.01-100μM) was applied to rat striatal slices preloaded with [(3)H]dopamine and its efficacy to evoke [(3)H]overflow and to alter methamphetamine (3μM)-evoked [(3)H]overflow was measured. (2) Groups of rats received apocynin (15 or 50mg/kg/day) or vehicle injection for seven consecutive days, and the efficacy and potency of methamphetamine to evoke [(3)H]overflow were determined. (3) Groups of apocynin-treated rats were administered methamphetamine (0.5 or 1mg/kg) or saline to determine the effect of apocynin on stimulant-induced hyperactivity. (1) Apocynin applied to striatal slices did not evoke [(3)H]overflow or alter methamphetamine-evoked [(3)H]overflow. (2) However, subchronic apocynin treatment significantly and dose-dependently decreased methamphetamine's potency and efficacy to evoke [(3)H]overflow. (3) Subchronic apocynin treatment also decreased the locomotor activity evoked by methamphetamine. Subchronic apocynin treatment diminished methamphetamine induced dopamine-release and its locomotor-activating properties. The pattern of results indicates that apocynin is more effective after repeated, rather than after acute, treatment. The findings also suggest that NOX inhibitors or agents suppressing oxidative stress may constitute a new area for research to understand how methamphetamine produces its deleterious and neurotoxic outcomes in the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Expression of DNA damage-inducible genes of Escherichia coli upon treatment with methylating, ethylating and propylating agents.

    PubMed

    Volkert, M R; Gately, F H; Hajec, L I

    1989-03-01

    Several alkylation-inducible genes have been identified by construction of Mu-d1 (Apr lac) fusions to genes whose expression is increased in response to alkylation treatment, but not UV treatment. We have examined the induction of 4 different alkylation-inducible genes by treatment with a variety of methylating and ethylating agents, and a propylating agent. We have compared the induction of the alkylation-inducible genes with the induction of the sulA gene, which is a component of the SOS response to DNA damage. We find that the Ada-regulated adaptive response genes (ada-alkB, alkA and aidB) are induced primarily in response to methylation treatment. The ada-independent aidC gene is induced upon treatment with agents that alkylate predominantly by SN1 nucleophilic attack. aidC induction occurs only when cells are not aerated during treatment. The SOS response, as indicated by sulA induction, is strongly induced by all types of alkylating agents used.

  17. Iron dextran treatment does not induce serum protein carbonyls in the newborn pig.

    PubMed

    Caperna, T J; Shannon, A E; Blomberg, L A; Garrett, W M; Ramsay, T G

    2012-01-01

    Oxidation of serum proteins can lead to carbonyl formation that alters their function and is often associated with stress-related diseases. As it is recommended that all pigs reared in modern production facilities be given supplemental iron at birth to prevent anemia, and metals can catalyze the carbonylation of proteins, the primary objective of this study was to determine whether standard iron dextran treatment was associated with enhanced serum protein oxidation in newborn piglets. Piglets were treated with 100 mg of iron dextran intramuscularly either on the day of birth, or on the third day after birth. Blood samples were collected from piglets 48 or 96 h after treatment and serum was harvested. For quantification, serum protein carbonyls were converted to hydrazones with dinitrophenyl hydrazine and analyzed spectrophotometrically. To identify and determine relative distribution of carbonylated proteins, serum protein carbonyls were derivatized with biotin hydrazide, separated by two-dimensional polyacrylamide gel electrophoresis, stained with avidin-fluorescein and identified by mass spectrometry. The standard iron dextran treatment was associated with no increase in total oxidized proteins if given either on the first or third day of life. In addition, with a few noted exceptions, the overall distribution and identification of oxidized proteins were similar between control and iron dextran-treated pigs. These results indicate that while iron dextran treatment is associated with a marked increase in circulating iron, it does not appear to specifically induce the oxidation of serum proteins.

  18. [Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

    PubMed

    Yokoyama, Yuka; Asaoka, Katsuyuki; Sugiyama, Taku; Uchida, Kazuki; Shimbo, Daisuke; Kobayashi, Satoshi; Itamoto, Koji

    2015-10-01

    Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

  19. Improving primary treatment of urban wastewater with lime-induced coagulation.

    PubMed

    Marani, Dario; Ramadori, Roberto; Braguglia, Camilla Maria

    2004-01-01

    The enhancement of primary treatment efficiency through the coagulation process may yield several advantages, including lower aeration energy in the subsequent biological unit and higher recovery of biogas from sludge digestion. In this work sewage coagulation with lime was studied at pilot plant level, using degritted sewage from the city of Rome. The work aimed at optimising the operating conditions (coagulant dosage or treatment pH, and mixing conditions in the coagulation and flocculation tanks), in order to maximise the efficiency of suspended Chemical Oxygen Demand (COD) removal and to minimise sludge production. Lime dosage optimisation resulted in an optimal treatment pH of 9. Lime addition up to pH 9 may increase COD removal rate in the primary treatment from typical 30-35% of plain sedimentation up to 55-70%. Within the velocity gradients experimented in this work (314-795 s(-1) for the coagulation tank and 13-46 s(-1) for the flocculation tank), mixing conditions did not significantly affect the lime-enhanced process, which seems to be controlled by slow lime dissolution. Sludge produced in the lime-enhanced process settled and compacted easily, inducing an average 36% decrease in sludge volume with respect to plain settling. However excess sludge was produced, which was not accounted for by the amount of suspended solids removed. This is probably due to incomplete dissolution of lime, which may be partially incorporated in the sludge.

  20. Mitochondrial biogenesis and degradation are induced by CCCP treatment of porcine oocytes.

    PubMed

    Itami, N; Shiratsuki, S; Shirasuna, K; Kuwayama, T; Iwata, H

    2015-08-01

    In this study, we investigated the mitochondrial quality control system in porcine oocytes during meiotic maturation. Cumulus cell oocyte complexes (COCs) collected from gilt ovaries were treated with 10  μM carbonyl cyanide-m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler) for 2  h. The CCCP treatment was found to significantly reduce ATP content, increase the amount of phosphorylated AMP-activated protein kinase and elevate reactive oxygen species levels in oocytes. When the CCCP-treated COCs were cultured further for 44  h in maturation medium, the ATP levels were restored and the parthenogenetic developmental rate of oocytes to the blastocyst stage was comparable with that of untreated COCs. To examine the effects of CCCP treatment of oocytes on the kinetics of mitochondrial DNA copy number (Mt number), COCs treated with 0 or 10  μM CCCP were cultured for 44