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  1. Changes of gut flora and endotoxin in rats with D-galactosamine-induced acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Lan-Juan Li; Zhong-Wen Wu; Dang-Sheng Xiao; Ji-Fang Sheng

    2004-01-01

    AIM: To investigate the changes of gut microflora and endotoxin levels in rats with acute liver failure (ALF) induced by D-galactosamine (GalN).METHODS: Flora and endotoxin levels in the jejunum, ileum and colon in normal rats (group A) and rats with GalNinduced ALF were determined at 24 h (group B) or 48 h (group C) after GalN injection, as well as the endotoxin level in portal venous blood (PVB) and right ventricle blood (RVB) were determined by chromogenic limulus amoebocyte assay.RESULTS: Intestinal (jejunum, ileum, colon)lactobacillus count was statistically reduced in group B compared with those in group A (3.4±0.3 vs4.9±0.3, 6.1±0.4 vs 8.0±0.3,8.1±0.2 vs 9.3±0.2, P<0.001, P<0.001 and P<0.001respectively) and recovered partially in the group C compared with those in the group B, whereas the count of Enterobacteriaceae in the jejunum, ileum and colon in group B was increased markedly compared with those in the group A (5.1±0.3 vs 3.6±0.2, 6.9±0.5 vs 5.3±0.3,8.7±0.2 vs7.6±0.1, P<0.001, P<0.05 and P<0.05 respectively)and restored partially in the group C compared with those in the group B. The endotoxin level in ileum was increased in the group B compared with those in the group A (111.3±22.8 vs 51.5±8.9, P<0.05). In addition, the endotoxin level in PVB was obviously increased in group B compared with that in the group A (76.8±9.1 vs40.6±7.3,P<0.01) and reduced to the baseline at 48 h (group C).CONCLUSIOM: Severely disturbed gut flora in rats with GalN-induced acute liver failure plays an important role in the elevation of endotoxin level in PVB.

  2. Hepatoprotective role of Ricinus communis leaf extract against d-galactosamine induced acute hepatitis in albino rats.

    Science.gov (United States)

    Babu, Pappithi Ramesh; Bhuvaneswar, Cherukupalle; Sandeep, Gandham; Ramaiah, Chintha Venkata; Rajendra, Wudayagiri

    2017-04-01

    Ricinus communis (RC) is a traditional medicinal plant which has been used by Chenchu and Yerukula tribes for treating their liver ailments. The present work is aimed to explore the hepatoprotective efficacy of Ricinus communis against d-galactosamine (D-GalN) induced hepatitis rat model and its therapeutic potential compared with standard drug, silymarin (100mg/kg.bw). In vitro antioxidant activity of Methanolic extract of Ricinus communis leaves (MERCL) was assayed through DPPH and H2O2 free radical scavenging activity. Qualitative and quantitative analysis of MERCL using HPLC, demonstrated that Rutin was found to be predominant bioactive compound in the extract. Hepatitis was induced by treating the rats with D-GalN at a single intraperitoneal dose of 800mg/kg.bw. Serum markers viz, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and Malondialdehyde (MDA) levels were significantly increased and the activity levels of antioxidant enzymes such as Superoxide dismutase (SOD),Catalase (CAT), Glutathione reductase (GR), Glutathione peroxidase (GPx), non-enzymatic antioxidant Glutathione (GSH) levels were decreased in the liver of hepatitis induced rats when compared to controls. Pre and post treatment with MERCL significantly altered the enzyme activities, GSH and MDA to normal levels. Histopathological observations also showed protective and curative effects of MERCL against D-GalN intoxication. These results demonstrated that MERCL significantly protected the liver from d-galactosamine induced hepatitis, improved the curative effect in the liver and hence, MERCL can be used as a potent hepatoprotective drug in future. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

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    Pan, Chen-wei; Pan, Zhen-zhen; Hu, Jian-jian; Chen, Wei-lai; Zhou, Guang-yao; Lin, Wei; Jin, Ling-xiang; Xu, Chang-long

    2016-01-05

    Mangiferin, a glucosylxanthone from Mangifera indica, has been reported to have anti-inflammatory effects. However, the protective effects and mechanisms of mangiferin on liver injury remain unclear. This study aimed to determine the protective effects and mechanisms of mangiferin on lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver injury. Mangiferin was given 1h after LPS and D-GalN treatment. The results showed that mangiferin inhibited the levels of serum ALT, AST, IL-1β, TNF-α, MCP-1, and RANTES, as well as hepatic malondialdehyde (MDA) and ROS levels. Moreover, mangiferin significantly inhibited IL-1β and TNF-α production in LPS-stimulated primary hepatocytes. Mangiferin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. Furthermore, mangiferin inhibited LPS/d-GalN-induced hepatic NLRP3, ASC, caspase-1, IL-1β and TNF-α expression. In conclusion, mangiferin protected against LPS/GalN-induced liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.

  4. Heat shock proteins 27 and 70 contribute to the protection of Schisandrin B against d-galactosamine-induced liver injury in mice.

    Science.gov (United States)

    Gao, Zhiying; Zhang, Jishun; Li, Libo; Shen, Longqing; Li, Qingyi; Zou, Yu; Du, Xiaohui; Zhao, Zhibo

    2016-04-01

    Schisandrin B is a hepatoprotective component isolated from a traditional Chinese herb, Schisandra chinensis (Turcz.) Baill. This study determined the effect of Schisandrin B on d-galactosamine -induced liver injury and the role of heat shock proteins 27 and 70 against liver injury in mice. Acute liver injury was induced by intraperitoneal injection of d-galactosamine to mice, and Schisandrin B was given orally. The protein and gene expression of heat shock proteins 27 and 70 were detected by western blot and real-time quantitative polymerase chain reaction, respectively. Liver tissues were subjected to histological evaluation, and the activities of alanine aminotransferase and aspartate aminotransferase in the serum were measured. Pretreatment of Schisandrin B significantly attenuated d-galactosamine-induced liver injury in mice. This result was evidenced by improved alteration of histopathological hepatic necrosis and reduced alanine aminotransferase and aspartate aminotransferase activities in the serum. The hepatoprotective effect was accompanied with overexpression of heat shock proteins 27 and 70 both at the protein and mRNA levels. However, the aforementioned actions of Schisandrin B were all markedly suppressed by the heat shock protein inhibitor quercetin. Heat shock proteins 27 and 70 were involved in the protective effect of Schisandrin B against d-galactosamine-induced liver injury in mice.

  5. Anti-hepatotoxic potential of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental rodents

    Institute of Scientific and Technical Information of China (English)

    Ramesh Kr Gupta; Rajnish Kr Singh; Sudhansu Ranjan Swain; Talib Hussain; Chandana Venkateswara Rao

    2012-01-01

    Objective: To evaluate hepatoprotective potential of the methanolic extract of Hedyotis corymbosa against D-galactosamine-induced hepatopathy in experimental animals. Methods: In the present study, in- vivo hepatoprotective effect of 50% methanolic extract of Hedyotis corymbosa (HCE, 100 and 200 mg/kg body weight) was evaluated using experimental models D-Galactosamine (D-GalN) (200 mg/kg, body weight i.p.) induced hepatotoxicity in experimental animals. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), γ-glutamyl transferase (γ-GT) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Results: Obtained results demonstrated that the treatment with HCE signi-cantly (P<0.05-P<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, HCE signi-cantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that HCE attenuated the hepatocellular necrosis and led to reduction of in ammatory cells in-ltration. Conclusions: The results of this study strongly indicate the protective effect of HCE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scienti-cally support its traditional use.

  6. [Hepatoprotective effect of Hypecoum erectum extract on experimental D-galactosamine-induced damage of rat liver].

    Science.gov (United States)

    Nikolaev, S M; Fedorov, A V; Toropova, A A; Razuvaeva, Ia G; Sambueva, Z G; Lubsandorzhieva, P B

    2014-01-01

    Hepatoprotective properties of the extract derived from the herbs of Hypecoum erectum L. have been studied on a model of D-galactosamine-induced hepatitis in rats. It is established that Hypecoum erectum extract in a dose of 50 mg/kg diminishes the development of cytolysis and cholestasis syndromes, as manifested by maximum decrease in the following indices after 7 days of the experiment: ALT activity by 26%; AST activity by 44%; alkaline phosphatase activity by 30%; β-lipoproteins by 21%; and bilirubin by 29% (p < 0.05). The Hypecoum erectum extract (i) increases the energy potential of hepatocytes, manifested by increasing the ATP content by 70% (p = 0.001) and normalizing the ratio of lactate and pyruvate in the liver homogenate; (ii) inhibits lipid peroxidation, manifested by decreasing the content of malonic dialdehyde in the liver homogenate and diene conjugates in the blood serum on the average by 30% (p < 0.05); (iii) activates the antioxidant system of the organism, increasing the catalase activity in liver homogenates by 58% (p < 0.05) and 11% and the content of reduced glutathione in the blood by 56% (p < 0.05) and 36% (p < 0.05), respectively, on the 3rd and 7th days of the experiment.

  7. Adiponectin deficiency exacerbates lipopolysaccharide/ D-galactosamine-induced liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Hitoshi Matsumoto; Yuji Matsuzawa; Iichiro Shimomura; Norio Hayashi; Shinji Tamura; Yoshihiro Kamada; Shinichi Kiso; Juichi Fukushima; Akira Wada; Norikazu Maeda; Shinji Kihara; Tohru Funahashi

    2006-01-01

    AIM: To examine the effects of adiponectin on the functions of Kupffer cells, key modulators of lipopolysaccharide (LPS) -induced liver injury.METHODS: D-galactosamine (GaIN) and LPS were injected intraperitoneally into adiponectin-/- mice and wild type mice. Kupffer cells, isolated from Sprague-Dawley rats, were preincubated with or without adiponectin, and then treated with LPS.RESULTS: In knockout mice, GalN/LPS injection significantly lowered the survival rate, significantly raised the plasma levels of alanine transaminase and tumor necrosis factor-α (TNF-α) and significantly reduced IL-10 levels compared with wild type mice. TNF-α gene expression in the liver was which higher and those of IL-10 were lower in knockout mice than in wild type mice. In cultured adiponectin-pre-treated Kupffer cells, LPS significantly lowered TNF-α levels and raised IL-10 levels in the culture media and their respective gene expression levels, compared with Kupffer cells without adiponectinpre-treatment.CONCLUSION: Adiponectin supresses TNF-α production and induces IL-10 production by Kupffer cells in response to LPS stimulation, and a lack of adiponectin enhances LPS-induced liver injury.

  8. Protective effects of vitamin D3 against d-galactosamine-induced liver injury in rats.

    Science.gov (United States)

    Colakoglu, Neriman; Kuloglu, Tuncay; Ozan, Enver; Kocaman, Nevin; Dabak, Durrin Ozlem; Parlak, Gozde

    2016-08-01

    In this study, we examined liver damage induced by d-galactosamine (d-GaIN) and the protective effects of vitamin D3 in relation to d-GaIN toxicity. Twenty Wistar albino rats were used in this study. The rats were divided into four groups. Group I rats were used as the control group. Group II rats were given a single intraperitoneal injection of d-GaIN. Group III rats were given a single intraperitoneal injection of d-GaIN, intramuscular vitamin D3 for five days. Group IV rats were given intramuscular vitamin D3 for five days. All of rats were euthanized by cervical decapitation on the fifth day of experiment. Upon completion of the experiment, a midsaggital incision was performed, and the livers of all rats were removed and fixed. The livers were processed to perform TUNEL technique and histochemical staining. During the microscope examination, we observed inflamatory cell infiltration, sinusoidal dilatation, and apoptotic bodies due to d-GaIN exposure. In addition, glycogen content of the group II hepatocytes was significantly decreased. Vitamin D3 treatment provided better structural apperance of the livers in group III. TUNEL positive cells were extremly pervasive in the group II livers. The study found group III TUNEL positive cells at a reduced rate in relation to group II due to vitamin D3 treatment. This findings indicate that d-GaIN causes inflamation in the liver. This inflamation triggers the apoptotic process gradually. Vitamin D3 has potency to decrease the severity of d-GaIN-caused structural liver damage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Li-Kun Wang; Lu-Wen Wang; Xun Li

    2013-01-01

    BACKGROUND: The  pathogenesis  and  progression  of  acute liver  failure  (ALF)  are  closely  associated  with  intestinal endotoxemia  because  of  the  high  permeability  of  the intestinal  wall.  Treatment  with  ethyl  pyruvate  (EP)  has  been shown  to  protect  liver  failure  effectively.  The  current  study aimed  to  explore  the  relationship  between  proinflammatory cytokines  and  intestinal  permeability,  and  to  investigate whether  EP  administration  might  prevent  the  release  of multiple  proinflammatory  cytokines  and  decrease  intestinal permeability and therefore, protect the liver from injury. METHODS:  The ALF model was induced by D-galactosamine in  rats.  The  rats  were  randomly  divided  into  control  (saline, i.p.),  model  (D-galactosamine,  1.2  g/kg,  i.p.),  prevention  [EP injection  (40  mg/kg)  2  hours  ahead  of  D-galactosamine]  and treatment groups (EP injection 2 hours after D-galactosamine). Samples were obtained at 12 and 24 hours after ALF induction, respectively.  The  histology  of  liver  and  intestinal  tissue  was accessed.  Serum  alanine  aminotransferase,  endotoxin,  D(-)-lactate,  diamine  oxidase  (DAO),  tumor  necrosis  factor-alpha (TNF-α),  interferon-γ  (IFN-γ)  and  high  mobility  group  box-1 (HMGB1) were evaluated. The survival of rats was also recorded. RESULTS: The  rats  in  model  group  showed  severe  damage  to liver  tissue  and  intestinal  mucosa  12  and  24  hours  after  ALF induction. EP significantly improved liver or intestinal injury. In  addition,  serum  endotoxin,  D(-)-lactate,  DAO,  TNF-α, IFN-γ  and  HMGB1  levels  were  significantly  increased  in  the model  group  compared  with  the  control  group.  There  was a  positive  correlation  between  intestinal  permeability  and proinflammatory  cytokines.  EP  significantly  reduced  serum endotoxin, D(-)-lactate, DAO, TNF-α, IFN-γ and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group). CONCLUSIONS: EP has protective and therapeutic effects on intestinal  mucosa.  EP  decreases  intestinal  permeability,  and inhibits the release of multiple proinflammatory cytokines in rats with ALF.

  10. Pharmacological effect of carvacrol on D: -galactosamine-induced mitochondrial enzymes and DNA damage by single-cell gel electrophoresis.

    Science.gov (United States)

    Aristatile, Balakrishnan; Al-Numair, Khalid S; Al-Assaf, Abdullah H; Pugalendi, Kodukkur Viswanathan

    2011-07-01

    The present study aimed at investigating the effect of carvacrol on hepatic mitochondrial enzyme activities and DNA damage in D: -galactosamine (D: -GalN)-induced hepatotoxicity in male albino Wistar rats. The activities of hepatic mitochondrial enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADPH dehydrogenase and cytochrome c oxidase significantly decreased in D: -GalN-hepatotoxic rats, and administration of carvacrol brought these parameters towards normality. In D: -GalN-hepatotoxic rats, the hepatic mitochondrial concentration of thiobarbituric acid reactive substances significantly increased, and administration of carvacrol significantly reduced them towards normality. Furthermore, the activities of enzymatic antioxidants such as superoxide dismutase and glutathione peroxidase and the levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced glutathione decreased significantly in the liver mitochondria. Administration of carvacrol returned the enzymatic and non-enzymatic antioxidants towards normality. D: -GalN-hepatotoxic rats had increased DNA damage, which administration of carvacrol significantly decreased. These results suggest that carvacrol has liver mitochondrial antioxidant properties and possesses a defensive effect against mitochondrial enzymes and DNA damage in D: -GalN-induced rats.

  11. Effect of Piper betle on plasma antioxidant status and lipid profile against D-galactosamine-induced hepatitis in rats.

    Science.gov (United States)

    Pushpavalli, Ganesan; Veeramani, Chinnadurai; Pugalendi, Kodukkur Viswanathan

    2009-01-01

    Betle leaf chewing is an old traditional practice in India and other countries of East Asia. We have investigated the antioxidant and antihyperlipidaemic potential of an alcoholic leaf-extract of Piper betle against D-galactosamine (D-GalN; 400 mg/kg body weight, i.p. single dose) intoxication in male albino Wistar rats. Rats were treated with leaf-extract (200 mg/kg body weight) by intragastric intubations daily for 20 days. The animals were divided randomly into five groups of six animals each as control, control plus extract, D-GalN control, D-GalN-rats on treatment with extract or silymarin, a standard drug. We observed an increase in the plasma levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and a decrease in vitamin C, vitamin E and reduced glutathione concentrations. Very low density lipoprotein cholesterol and low density lipoprotein cholesterol increased significantly while high density lipoprotein cholesterol decreased. Further, increase in the levels of total cholesterol, phospholipids, triglycerides, free fatty acids in the plasma and tissues of liver and kidney were observed in D-GalN-treated rats. Administration of P. betle leaf-extract prevented the increase or decrease of these parameters and brought towards normality. These results suggest that P. betle could afford a significant antioxidant and antihyperlipidaemic effect against D-GalN-intoxication.

  12. Influence of Piper betle on hepatic marker enzymes and tissue antioxidant status in D-galactosamine-induced hepatotoxic rats.

    Science.gov (United States)

    Pushpavalli, Ganesan; Veeramani, Chinnadurai; Pugalendi, Kodukkur Viswanathan

    2008-01-01

    D-galactosamine is a well-established hepatotoxicant that induces a diffuse type of liver injury closely resembling human viral hepatitis. D-galactosamine by its property of generating free radicals causes severe damage to the membrane and affects almost all organs of the human body. The leaves of Piper betle L., a commonly used masticatory in Asian countries, possess several biological properties. Our aim is to investigate the in vivo antioxidant potential of P. betle leaf-extract against oxidative stress induced by D-galactosamine intoxication in male albino Wistar rats. Toxicity was induced by an intraperitoneal injection of D-galactosamine, 400 mg/kg body weight (BW) for 21 days. Rats were treated with P. betle extract (200 mg/kg BW) via intragastric intubations. We assessed the activities of liver marker enzymes (aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transpeptidase) and levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione. The extract significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, and liver marker enzymes when compared with the D-galactosamine treated group, demonstrating its hepatoprotective and antioxidant properties.

  13. Does prostaglandin-E1 modulate d-galactosamine induced cell death in primary culture of human hepatocytes?

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    Sameh S. Tawfik

    2015-12-01

    Full Text Available Background: Cell death pathway can occur under physiological or pathological conditions. In vitro and in vivo studies have shown that d-galactosamine (DGA induces hepatocyte damage. Objective: The present study aims to evaluate the protective effect of prostaglandin E1 (PGE1 on DGA-induced apoptosis, necrosis and oxidative stress in primary culture of human hepatocytes. Methods: Normal human hepatocytes were obtained from the safety margin of liver specimens, removed during hepatectomy operation to liver cancer patients, and isolated using the classical collagenase perfusion method. After culture stabilization, PGE1 (1 μM was added 2 h before DGA (5 mM. Cultures were maintained for 24 h before the parameters for apoptosis, necrosis and oxidative stress were measured. Apoptosis was studied by DNA-fragmentation, neutral (nSMase and acid (aSMase sphingomyelinase and caspase-3 activity. Necrosis was investigated by lactate dehydrogenase (LDH and transaminases (ALT & AST enzymes. The oxidative stress was assessed by malondialdehyde (MDA, glutathione (GSH, oxidized glutathione (GSSH, glutathione S-transferase (GST, glutathione peroxidase (GSPx, catalase (CAT, superoxide dismutase (SOD and nitric oxide (NO. Results: The hepatotoxin DGA induced apoptosis and enhanced all parameters related to necrosis and intracellular oxidative stress. On the other hand, PGE1 reduced the measured values for the parameters indicative for the DAG induced apoptosis, necrosis and oxidative stress. In addition, PGE1 proved also to prevent GSH depletion. The obtained results provided evidences for the biochemical hepatotoxic effects of DGA (5 mM especially through the induction of apoptosis, necrosis and oxidative stress alterations in the cultured human hepatocytes. Conclusion: PGE1 could be a useful protective treatment against DGA-induced hepatocyte cell death.

  14. Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2–NFκB pathways

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    Das, Joydeep; Ghosh, Jyotirmoy; Roy, Anandita; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

    2012-04-01

    Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantly increased the nuclear translocation of NFκB and elevated iNOS protein expression. The same exposure also elevated TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18 and decreased IL-10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GSTα. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NFκB inhibition. Highlights: ►Galactosamine induces hepatocytes death via oxidative and nitrosative stress. ►Mangiferin exerts hepatoprotective effect/antioxidant defense via Nrf2 pathway. ►Mangiferin exerts anti-inflammatory responses by inhibiting NF-κB. ►Mangiferin suppresses galactosamine-induced repression of IL-10 mRNA.

  15. Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2-NFκB pathways.

    Science.gov (United States)

    Das, Joydeep; Ghosh, Jyotirmoy; Roy, Anandita; Sil, Parames C

    2012-04-01

    Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantly increased the nuclear translocation of NFκB and elevated iNOS protein expression. The same exposure also elevated TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18 and decreased IL-10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GSTα. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NFκB inhibition.

  16. Sesamin ameliorates lipopolysaccharide/d-galactosamine-induced fulminant hepatic failure by suppression of Toll-like receptor 4 signaling in mice.

    Science.gov (United States)

    Ma, Li; Gong, Xia; Kuang, Ge; Jiang, Rong; Chen, Rongchun; Wan, Jingyuan

    2015-05-29

    Sesamin has been described to exert anti-oxidant and anti-inflammatory properties. In present study, we investigated the potential effects and mechanisms of sesamin on lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in d-galactosamine (D-GalN)-sensitized mice. Our results showed that pretreatment with sesamin dose-dependently improved LPS/D-GalN-induced mortality and liver injury as indicated by reduced serum levels of aminotransferases and alleviated pathological damage as well as hepatocyte apoptosis in mice. Additionally, sesamin markedly attenuated LPS/D-GalN-induced adhesion molecules expression, and decreased neutrophils recruitment. Furthermore, sesamin inhibited LPS-induced tumor necrosis factor-alpha (TNF-α) production, p38 mitogen-activated protein kinases (MAPK) and NF-κB activation, and Toll like receptor (TLR) 4 expression in mice and in RAW264.7 macrophage cells. In summary, these results demonstrate that sesamin protects mice from LPS-induced FHF and the molecular mechanisms may down-regulate the expression of TLR4, block MAPK and NF-κB activation, decrease the production of TNF-α.

  17. Exploratory Studies of (-)-Epicatechin, a Bioactive Compound of Phyllanthus niruri, on the Antioxidant Enzymes and Oxidative Stress Markers in D-galactosamine-induced Hepatitis in Rats: A Study with Reference to Clinical Prospective.

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    Shanmugam, Bhasha; Shanmugam, Kondeti Ramudu; Ravi, Sahukari; Subbaiah, Ganjikunta Venkata; Ramakrishana, Chilakala; Mallikarjuna, Korivi; Reddy, Kesireddy Sathyavelu

    2017-01-01

    Hepatitis is a health problem affecting millions of people worldwide and it is the major risk factor for liver cirrhosis. In India, many plants are used to treat hepatitis. But little is known about the effects of (-)-epicatechin a bioactive compound of Phyllanthus niruri (PN) in hepatitis rats. The present study was designed to explore the antioxidant property of (-)-epicatechin isolated from PN in D-Galactosamine (D-GalN) induced hepatitis rats. The rats are divided into five groups as per the experimental design. (-)-Epicatchin pretreatment was given to the hepatitis rats for 21 days and biochemical analysis was carried out. The hepatic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA) and serum markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, and bilirubin are estimated. All the antioxidant enzymes activities and albumin levels are depleted in hepatitic rats. Whereas GST, ALP, AST, ALT activities and MDA, and bilirubin levels are elevated in hepatitis rats, (-)-epicatechin pretreatment increased all the antioxidant enzymes and decreased the GST, ALP, AST, ALT, and MDA levels in hepatitis rats. However, histopatholoigic studies also proves that (-)-epicatechin pretreatment decreased the tissue damage in hepatitis condition. This is the first report on the antioxidant enzymes and hepatoprotective effect of (-)-epicatechin in hepatitis rats. From this study, we conclude that (-)-epicatechin treatment decreased the oxidative damage in hepatitis rats. The present study was carried out to know the impact of (-)-epicatechin on antioxidant enzymes activities in hepatitis rats. From this study, we found that the antioxidant enzymes SOD, CAT, GPx, GR, GSH depleted in hepatitis rats and increased with (-)-epicatechin in hepatitis rats.MDA levels

  18. Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating D-Galactosamine induced fulminant hepatic failure in Wistar rats

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    Ganai, Ajaz A., E-mail: ganaikashmir@gmail.com; Khan, Athar A., E-mail: atharbiotech@gmail.com; Malik, Zainul A., E-mail: mzabdin@rediffmail.com; Farooqi, Humaira, E-mail: humbiotech@gmail.com

    2015-03-01

    Genistein is an isoflavanoid abundantly found in soy. It has been found to play an important role in the prevention of various chronic diseases including cancer. In this study, we evaluated potential therapeutic properties of Genistein against D-Galactosamine (D-GalN) induced inflammation and hepatotoxicity in male Wistar rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal injection of D-GalN (700 mg/kgBW). Genistein (5 mg/kgBW/day) was given as pre-treatment for 30 days via intra-gastric route followed by D-GalN (700 mg/kgBW) injection. The hepatoprotective and curative effects of Genistein were evident from a significant decrease in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as well as prevention of histological damage by pre-treatment of Genistein. Genistein pre-treatment significantly inhibited the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly suppressed the production of D-GalN-induced proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. These inhibitory effects were associated with the suppression of nuclear factor-kappa B (NF-ĸB) activation, IKKα/β and Mitogen activated protein kinase (MAPK) phosphorylation by Genistein in D-GalN-treated animals. In conclusion, our results suggest that Genistein may serve as a potential supplement in the prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to maintain the redox potential and strengthens the antioxidant defense system of a cell. - Highlights: • First study to evaluate hepatoprotective effect of Genistein against D-GalN • Genistein prevents oxidative damage induced by D-GalN. • Genistein blunts iNOS, COX-2, NF-ĸB, IKKα/β and MAPK expression. • Genistein prevents D-GalN induced apoptosis and

  19. Protective mechanism of Potentilla anserina polysaccharide on mice with D-galactosamine-induced acute liver injury%蕨麻多糖保护D-氨基半乳糖急性肝损伤小鼠的作用机制

    Institute of Scientific and Technical Information of China (English)

    闵光涛; 王利军; 段钟平; 闵光宁; 贺志云; 王永强

    2016-01-01

    目的 考察蕨麻多糖(PAP)对D-氨基半乳糖(D-GlaN)诱导的急性肝损伤小鼠肝脏的保护作用机制.方法 60只昆明小鼠随机分为正常对照组、模型对照组、联苯双酯组(阳性对照)以及PAP 50、100、200mg/kg各剂量组,每组10只.先分别给予生理盐水、联苯双酯以及不同剂量受试药PAP,然后除正常对照组注射生理盐水外,其余5组均于给药7d后用8% D-GlaN腹腔注射,建立D-GlaN急性肝损伤模型.24 h后处死,测定小鼠肝组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、谷胱甘肽(GSH)等指标.结果 模型对照组小鼠肝组织中的MDA含量升高,SOD和GSH-Px活性降低,GSH含量降低,与正常对照组比较差异有统计学意义(P<0.05,P<0.01);联苯双酯以及50、100、200mg/kg各剂量PAP均可明显降低D-GlaN急性肝损伤小鼠肝组织中的MDA含量,提高SOD和GSH-Px的活性,增加GSH含量,与模型对照组相比差异有统计学意义(P<0.05,P<0.01).结论 PAP对D-GlaN急性肝损伤小鼠肝脏的保护作用可能与其清除自由基、保护细胞膜和抗脂质过氧化有关.

  20. Does prostaglandin-E1 modulate d-galactosamine induced cell ...

    African Journals Online (AJOL)

    Sameh S. Tawfik

    2015-01-05

    Jan 5, 2015 ... removed during hepatectomy operation to liver cancer patients, and isolated using the classical col- lagenase ... energy metabolism of hepatocytes, destroys the enzymes .... Lactate dehydrogenase (LDH) was measured by a colorimetric .... oxygen/nitrogen species.35 Among therapeutics for liver dis-.

  1. Hepatoprotective activity of Sphaeranthus amaranthoides on D-galactosamine induced hepatitis in albino rats

    Institute of Scientific and Technical Information of China (English)

    SwarnalathaL; PNeelakanta Reddy

    2012-01-01

    Objective: The plant sphaeranthus amaranthoides Burm.f is used in the district thriunalveli in the treatment of various liver disorders. Methods: in the present study the ethanol extract from sphaeranthus amaranthoides was studied against the D-galactosamine hepatotoxicity. Results: significant hepatoprotective effect was obtained against liver damage induced by the D-galactosamine as evident from changed antioxidant enzymes like CAT, SOD, GPx, GST, GSH, G6PD and GR and a normal architecture of liver and mitochondria compared to toxin controls. Conclusions: the results indicate that ethanol extract of the sphaeranthus amaranthoides could be useful in preventing D-galatosamine induced liver injury.

  2. Hepatoprotective Activity of Methanolic Extract of Oldenlandia herbacea Against D - Galactosamine Induced Rats

    Directory of Open Access Journals (Sweden)

    S Pandian

    2013-03-01

    Full Text Available Summary: The present study is to evaluate the hepatoprotective activity of methanolic extract of Oldenlandia herbacea against D - Galactosamine/ Lipopolysacharide (D - GalN induced rats. Hepatoprotective activity was performed by using the toxicant D-GalN (200 mg/kg in Wistar rats. Methanolic extract of the whole plant of O. herbacea was administered orally at doses of 100 and 200 mg/kg/day for 8 days. Silymarin (100 mg/kg was used as standard drug. Levels of various biochemical parameters in serum the histopathology of liver were assessed to study the hepatoprotective effect of the extract.  The extract showed significant reduction in the D-GalN induced liver damage and symptoms of liver injury by restoration of the deviated levels of various biochemical parameters of liver which were observed in toxic control group. Histopathology of the liver sections confirmed that the extract prevented hepatic damage induced by D-GalN. The methanolic extract of O. herbacea showed significant hepatoprotective activity. Industrial relevance: The herbal drugs continue to serve as an important source of conventional therapies for diverse disease conditions and reactions. This is a preliminary study and this will support us to isolate the biological active phyto-constituents for treating liver disorders. This study will help in discovering a new or active phytochemicals and thus create a novel hepatoprotective moiety with less adverse effect for the betterment of the human society and more affordable and accessible to the users. Keywords: Oldenlandia herbacea; D-galactosamine; Hepatoprotective activity; Silymarin.

  3. Protective effect of wild ginseng cambial meristematic cells on d-galactosamine-induced hepatotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Seok-Joo Kim

    2015-10-01

    Conclusion: Our findings suggest that wild ginseng CMCs protects liver against GalN-induced inflammation by suppressing proinflammatory mediators and enhancing production of anti-inflammatory mediators.

  4. Does Acute Static Stretching Reduce Muscle Power?

    Directory of Open Access Journals (Sweden)

    Francis M. Kozub

    2012-12-01

    Full Text Available Context: Stretching is commonly used as a technique for injury prevention in the training and clinical setting. Recently, stretching in the warm-up has been shown to decrease several muscular performance variables, but the dose-response of this effect is unknown and moreover these stretching bouts are not representative of athletes during warm up procedures, as they are usually time consuming. Our findings may improve the understanding of the neuromuscular responses to stretching and help sportsmen, coaches, physiotherapist and clinicians make decisions for integrating stretching as a part of warm up or rehabilitation treatment plan.Purpose: The aim of the present study was to examine whether acute static stretching is responsible for losses in isokinetic peak torque production and if it does, than which time of stretching effect muscle peak torque?Design: Randomized, counterbalanced, within-subjects experimental design.Setting: A university human project laboratory.Methods: Twenty (n=20 light to moderate young exercisers, male and female, from University of Limerick community, with an average age of 22.1±3.6 years, height of 175.6±5 cm, and weight of 73.1±9.9 kg, were randomly selected to take part in the study. Prior to the main study, volunteers attended the lab on two occasions to be familiarized with the knee extension protocol on the Con - trex isokinetic system and with the static stretching protocol. All participants than performed five additional static stretching protocols randomly, in non-consecutive training session. The stretching protocols were 0, 60,120, 180 and 180 with alternative pattern.Results: The results of the statistical analysis (P > 0.05 indicated that peak torque remained unchanged following the static stretching for 0-180 sec at 60 & 180° s−1 angular velocities.Conclusion: The findings suggest that an athletic stretching (shorter duration ranging from 0-180 sec does not produce decreases in peak torque. Athletes

  5. Acute encephalopathy with biphasic seizures and late reduced diffusion

    Directory of Open Access Journals (Sweden)

    Saroj S Yadav

    2013-01-01

    Full Text Available Acute encephalopathy with biphasic seizures and reduced diffusion (AESD is a syndrome of encephalopathy characterized by biphasic seizures and altered consciousness in the acute stage followed in the subacute stage by restricted diffusion in the subcortical white matter on magnetic resonance imaging. The etiology of AESD has been attributed to viral infection like influenza A and human herpes virus 6. The exact pathogenesis of AESD is uncertain. Here we report a case of AESD, diagnosed based on clinicoradiological correlation.

  6. Acute stress selectively reduces reward sensitivity

    Directory of Open Access Journals (Sweden)

    Lisa H Berghorst

    2013-04-01

    Full Text Available Stress may promote the onset of psychopathology by disrupting reward processing. However, the extent to which stress impairs reward processing, rather than incentive processing more generally, is unclear. To evaluate the specificity of stress-induced reward processing disruption, 100 psychiatrically healthy females were administered a probabilistic stimulus selection task enabling comparison of sensitivity to reward-driven (Go and punishment-driven (NoGo learning under either ‘no stress’ or ‘stress’ (threat-of-shock conditions. Cortisol samples and self-report measures were collected. Contrary to hypotheses, the groups did not differ significantly in task performance or cortisol reactivity. However, further analyses focusing only on individuals under ‘stress’ who were high responders with regard to both cortisol reactivity and self-reported negative affect revealed reduced reward sensitivity relative to individuals tested in the ‘no stress’ condition; importantly, these deficits were reward-specific. Overall, findings provide preliminary evidence that stress-reactive individuals show diminished sensitivity to reward but not punishment under stress. While such results highlight the possibility that stress-induced anhedonia might be an important mechanism linking stress to affective disorders, future studies are necessary to confirm this conjecture.

  7. 1-methylmalate from camu-camu (Myrciaria dubia) suppressed D-galactosamine-induced liver injury in rats.

    Science.gov (United States)

    Akachi, Toshiyuki; Shiina, Yasuyuki; Kawaguchi, Takumi; Kawagishi, Hirokazu; Morita, Tatsuya; Sugiyama, Kimio

    2010-01-01

    To evaluate the protective effects of fruit juices against D-galactosamine (GalN)-induced liver injury, lyophilized fruit juices (total 12 kinds) were fed to rats for 7 d, and then we evoked liver injury by injecting GalN. The juice of camu-camu (Myrciaria dubia) significantly suppressed GalN-induced liver injury when the magnitude of liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, although some other juices (acerola, dragon fruit, shekwasha, and star fruit) also tended to have suppressive effects. An active compound was isolated from camu-camu juice by solvent fractionation and silica gel column chromatography. The structure was determined to be 1-methylmalate. On the other hand, malate, 1,4-dimethylmalate, citrate, and tartrate had no significant effect on GalN-induced liver injury. It is suggested that 1-methylmalate might be a rather specific compound among organic acids and their derivatives in fruit juices in suppressing GalN-induced liver injury.

  8. Effects of various kinds of edible seaweeds in diets on the development of D-galactosamine-induced hepatopathy in rats.

    Science.gov (United States)

    Kawano, Naoko; Egashira, Yukari; Sanada, Hiroo

    2007-08-01

    In the present study we investigated the effects of 11 kinds of edible seaweeds (6 brown and 5 red algae) which contain characteristic seaweed dietary fibers on the induction of D-GalN (D-galactosamine)-hepatopathy in rats (Exps. 1 and 2). Then, the efficacy of various components prepared from Gelidium sp., which was found to alleviate the hepatopathy in Exps. 1 and 2, was examined (Exp. 3). The rats were fed the diets containing various kinds of seaweeds (Exps. 1 and 2), or several components of Gelidium sp. such as total dietary fiber (TDF), soluble dietary fiber (SDF), insoluble dietary fiber (IDF) and dietary fiber-free components (DFFC) (Exp. 3), for 8 d. The rats in all experiments were injected with D-GalN (800 mg/kg body weight) intraperitoneally at the 7th day to induce liver injury and were sacrificed 24 h after the injection of D-GalN. The serum transaminase activities (ALT and AST) and lactate dehydrogenase (LDH) were determined to evaluate the levels of hepatopathy. In Exp. 3, the total GSH concentration in the liver, plasma and cecal contents and organic acid concentration in cecal contents were also evaluated. In Exps. 1 and 2, repressive effects against D-GalN-hepatopathy were shown by four seaweeds Laminaria sp., Gelidium sp., Sargassum fulvellum and Eisenia bicyclis. In Exp. 3, it was found that protective activity in Gelidium sp. against D-GalN-hepatopathy existed not only in the SDF but also in the DFFC fraction. The results in Exp. 3 also indicated that the total GSH but not organic acid concentration in the cecal contents were significantly correlated with serum AST activity, suggesting that the protective effect of Gelidium sp. on D-GalN-hepatopathy in rats is related to GSH metabolism in the intestine.

  9. Hepatoprotective effects of flavonoids from shekwasha (Citrus depressa) against D-galactosamine-induced liver injury in rats.

    Science.gov (United States)

    Akachi, Toshiyuki; Shiina, Yasuyuki; Ohishi, Yayoi; Kawaguchi, Takumi; Kawagishi, Hirokazu; Morita, Tatsuya; Mori, Makoto; Sugiyama, Kimio

    2010-01-01

    We attempted to isolate the constituent(s) responsible for the suppressive effect of the juice of shekwasha, a citrus produced in Okinawa Prefecture, on D-galactosamine (GalN)-induced liver injury in rats. Liver injury-suppressive activity, as assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, was found only in the fraction that was extracted with n-hexane when three fractions were added to the diet and fed to rats. Of five compounds isolated from the n-hexane-soluble fraction by silica gel column chromatography, three compounds had liver injury-suppressive effects when five compounds were singly force-fed to rats at a level of 300 mg/kg body wt 4 h before the injection with GalN. The structures of the three active compounds were determined as 3',4',5,6,7,8-hexamethoxyflavanone (citromitin), 4',5,6,7,8-pentamethoxyflavone (tangeretin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin), which are known flavonoids mainly existing in citrus. Nobiletin, the most important compound in the n-hexane-soluble fraction, also had suppressive effects on liver injuries induced by carbon tetrachloride, acetaminophen and GalN/lipopolysaccharide (LPS) in addition to liver injury induced GalN. Nobiletin suppressed GalN/LPS-induced increases in plasma tumor necrosis factor (TNF)-alpha and nitric oxide (NO) concentrations and hepatic mRNA levels for inducible NO synthase and DNA fragmentation. These results suggest that nobiletin suppressed GalN/LPS-induced liver injury at least by suppressing the production of both TNF-alpha and NO. The results obtained here indicate that the hepatoprotective effect of shekwasha juice is mainly ascribed to several polymethoxy flavonoids included in the juice.

  10. Protective effect of pinitol against D-galactosamine-induced hepatotoxicity in rats fed on a high-fat diet.

    Science.gov (United States)

    Zhou, Yusi; Park, Chung-Mu; Cho, Chung-Won; Song, Young-Sun

    2008-07-01

    The protective effect of pinitol against D-galactosamine (GalN)-induced liver damage was examined. Forty male Sprague-Dawley rats were divided into normal control, GalN control, and pinitol groups (0.5%, 1%, and 2%). After 8 weeks of feeding, a single dose of GalN (650 mg/kg) was administered 24 h before their sacrifice. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly increased after an injection with GalN (Ppinitol supplementation at the level of 0.5% reversed these changes to normal levels. Significant decreases in serum triglyceride and cholesterol and increases in hepatic cholesterol were observed in GalN-intoxicated rats. However, supplementation with pinitol significantly attenuated these trends. In addition, pinitol elevated the Mn-superoxide dismutase, glutathione reductase, and catalase activities, prevented hepatic lipid peroxidation, and restored the hepatic GSH levels and cytochrome P450 2E1 function. Thus, 0.5% pinitol supplementation protected the rats from the hepatotoxicity induced by GalN, at least part of its effect being attributable to attenuation of the oxidative stress and inflammatory process promoted by GalN.

  11. Effect of dietary fiber in edible seaweeds on the development of D-galactosamine-induced hepatopathy in rats.

    Science.gov (United States)

    Kawano, Naoko; Egashira, Yukari; Sanada, Hiroo

    2007-10-01

    Previous studies in our laboratory demonstrated the repressive effect of seaweeds (Laminaria sp., Sargassum fulvellum, Eisenia bicyclis and Gelidium sp.) against D-galactosamine (D-GalN)-induced hepatopathy. However, the mechanism by which these four seaweeds attenuate the D-GalN-hepatopathy has not been completely clarified. This study was carried out to determine the constituents of these seaweeds that protect rats against the D-GalN-hepatopathy. Male Wistar rats were fed for 8 d diets containing 5% seaweeds with or without the antibiotic neomycin (NEO) in experiment 1, and typical seaweed dietary fibers (laminaran, fucoidan, alginate, agar and kappa-carrageenan) of these seaweeds in experiment 2. On the 7th day, the rats were treated with D-GalN (1,900 mg in experiment 1 and 800 mg/kg in experiment 2) and then sacrificed 24 h after the injection of D-GalN. Their serum transaminase (aspartate and alanine aminotransferases: AST and ALT) activities were then determined. In experiment 1, the serum AST and ALT levels in the rats fed the four kinds of seaweeds without NEO were significantly low in comparison to that of the control group, but those with NEO were not significantly different among the groups. In experiment 2, the serum AST and ALT levels in the rats fed fucoidan were significantly low in comparison to those of the other groups fed the dietary fibers and the control. These results suggest that the protective effect of the three kinds of brown seaweeds Laminaria sp., Sargassum fulvellum and Eisenia bicyclis against D-GalN-hepatopathy was caused at least in part by fucoidan.

  12. Acute psychosocial stress reduces pain modulation capabilities in healthy men.

    Science.gov (United States)

    Geva, Nirit; Pruessner, Jens; Defrin, Ruth

    2014-11-01

    Anecdotes on the ability of individuals to continue to function under stressful conditions despite injuries causing excruciating pain suggest that acute stress may induce analgesia. However, studies exploring the effect of acute experimental stress on pain perception show inconsistent results, possibly due to methodological differences. Our aim was to systematically study the effect of acute stress on pain perception using static and dynamic, state-of-the-art pain measurements. Participants were 29 healthy men who underwent the measurement of heat-pain threshold, heat-pain intolerance, temporal summation of pain, and conditioned pain modulation (CPM). Testing was conducted before and during exposure to the Montreal Imaging Stress Task (MIST), inducing acute psychosocial stress. Stress levels were evaluated using perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol. The MIST induced a significant stress reaction. Although pain threshold and pain intolerance were unaffected by stress, an increase in temporal summation of pain and a decrease in CPM were observed. These changes were significantly more robust among individuals with stronger reaction to stress ("high responders"), with a significant correlation between the perception of stress and the performance in the pain measurements. We conclude that acute psychosocial stress seems not to affect the sensitivity to pain, however, it significantly reduces the ability to modulate pain in a dose-response manner. Considering the diverse effects of stress in this and other studies, it appears that the type of stress and the magnitude of its appraisal determine its interactions with the pain system.

  13. Acute sleep deprivation reduces energy expenditure in healthy men.

    Science.gov (United States)

    Benedict, Christian; Hallschmid, Manfred; Lassen, Arne; Mahnke, Christin; Schultes, Bernd; Schiöth, Helgi Birgir; Born, Jan; Lange, Tanja

    2011-06-01

    Epidemiologic evidence indicates that chronic sleep curtailment increases risk of developing obesity, but the mechanisms behind this relation are largely unknown. We examined the influence of a single night of total sleep deprivation on morning energy expenditures and food intakes in healthy humans. According to a balanced crossover design, we examined 14 normal-weight male subjects on 2 occasions during a regular 24-h sleep-wake cycle (including 8 h of nocturnal sleep) and a 24-h period of continuous wakefulness. On the morning after regular sleep and total sleep deprivation, resting and postprandial energy expenditures were assessed by indirect calorimetry, and the free-choice food intake from an opulent buffet was tested in the late afternoon at the end of the experiment. Circulating concentrations of ghrelin, leptin, norepinephrine, cortisol, thyreotropin, glucose, and insulin were repeatedly measured over the entire 24-h session. In comparison with normal sleep, resting and postprandial energy expenditures assessed on the subsequent morning were significantly reduced after sleep deprivation by ≈5% and 20%, respectively (P sleep conditions were detected. Our findings show that one night of sleep deprivation acutely reduces energy expenditure in healthy men, which suggests that sleep contributes to the acute regulation of daytime energy expenditure in humans.

  14. Reduced myocardial blood flow in acute and chronic digitalization.

    Science.gov (United States)

    Steiness, E; Bille-Brahe, N E; Hansen, J F; Lomholt, N; Ring-Larsen, H

    1978-07-01

    The myocardial blood flow was measured by the 133Xenon disappearance curve from the left ventricular wall following an injection of 133Xenon in the left coronary artery in 8 dogs without digoxin pretreatment and in 8 chronically digitalized dogs. The myocardial blood flow was significantly less (30%) in the digitalized dogs than in the dogs without pretreatment. In the digitalized dogs as well as in those without pretreatment an intravenous injection of digoxin resulted in a further significant decrease of the myocardial blood flow of about 20% and a significant increase of the coronary vascular resistance. The reduced myocardial blood flow both during acute and chronic digitalization is beleived to be of clinical importance.

  15. Melatonin reduces acute lung injury in endotoxemic rats

    Institute of Scientific and Technical Information of China (English)

    SHANG You; XU San-peng; WU Yan; JIANG Yuan-xu; WU Zhou-yang; YUAN Shi-ying; YAO Shang-long

    2009-01-01

    Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia.Methods Thirty-two male Sprague-Dawley rats were randomly assigned to four groups: vehicle + saline group, melatonin + saline group, vehicle + lipopolysaccharide group, melatonin + lipopolysaccharide group. The rats were treated with melatonin (10 mg/kg, intraperitoneal injection (I.p.)) or vehicle (1% ethanol saline), 30 minutes prior to lipopolysaccharide administration (6 mg/kg, intravenous injection). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios (W/D), myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha (TNF-a) and interleukin-10 (IL-10) levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B (NF-KB) p65 was evaluated by Western blotting. Results PaO2 in the vehicle + lipopolysaccharide group decreased compared with that in the vehicle + saline group. This decrease was significantly reduced in the melatonin + lipopolysaccharide group. The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin + lipopolysaccharide group. The W/D ratio increased significantly in the vehicle + lipopolysaccharide group (6.1±0.18) as compared with that in the vehicle + saline group (3.611±0.3) (P <0.01), which was significantly reduced in the melatonin + lipopolysaccharide group (4.8±0.25) (P <0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle + lipopolysaccharide group compared with that in the vehicle + saline group, which

  16. Heart rate variability is reduced during acute uncomplicated diverticulitis

    DEFF Research Database (Denmark)

    Huang, Chenxi; Alamili, Mahdi; Rosenberg, Jacob

    2016-01-01

    BACKGROUND: The aim of the present study was to report the trajectory of heart rate variability (HRV) indices during a low-grade acute inflammation and their associations to biomarkers for infection. METHODS: Twelve patients with uncomplicated acute diverticulitis completed this observational study...

  17. Azithromycin reduces inflammation in a rat model of acute conjunctivitis

    Science.gov (United States)

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

  18. Acute khat use reduces response conflict in habitual users.

    Science.gov (United States)

    Colzato, Lorenza S; Sellaro, Roberta; Ruiz, Manuel J; Sikora, Katarzyna; Hommel, Bernhard

    2013-01-01

    Khat consumption has become a worldwide phenomenon broadening from Eastern Africa and the south west of the Arabian Peninsula to ethnic communities in the rest of the world. So far, the cognitive effects of khat use are poorly understood and no studies have looked into the relation between acute khat use and cognitive control functions, the way we control our thoughts and goal directed behavior. We studied how acute khat use affects the emergence and the resolution of response conflict, a central cognitive control function. Khat users (n = 11) and khat-free controls (n = 18) were matched in terms of education, sex, alcohol, and cannabis consumption. Groups were tested on response conflict, as measured by the Simon task. In one single session, participants worked through two task blocks: the khat group chewed exclusively khat whereas the khat-free group chewed solely a gum. Results showed that in the second block, which reflects the acute impact of khat, the khat group was better than controls in resolving stimulus-induced response conflict as indexed by a smaller Simon effect. These results suggest that the acute intake of khat may improve participants' ability of handling response conflict.

  19. Acute normobaric hypoxia reduces body temperature in humans.

    Science.gov (United States)

    DiPasquale, Dana M; Kolkhorst, Fred W; Buono, Michael J

    2015-03-01

    Anapyrexia is the regulated decrease in body temperature during acute exposure to hypoxia. This study examined resting rectal temperature (Trec) in adult humans during acute normobaric hypoxia (NH). Ten subjects breathed air consisting of 21% (NN), 14% (NH14), and 12% oxygen (NH12) for 30 min each in thermoneutral conditions while Trec and blood oxygen saturation (Spo2) were measured. Linear regression indicated that Spo2 was progressively lower in NH14 (p=0.0001) and NH12 (p=0.0001) compared to NN, and that Spo2 in NH14 was different than NH12 (p=0.00001). Trec was progressively lower during NH14 (p=0.014) and in NH12 (p=0.0001) compared to NN. The difference in Trec between NH14 and NH12 was also significant (p=0.0287). Spo2 was a significant predictor of Trec such that for every 1% decrease in Spo2, Trec decreased by 0.15°C (p=0.0001). The present study confirmed that, similar to many other species, human adults respond to acute hypoxia exposure by lowering rectal temperature.

  20. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    Directory of Open Access Journals (Sweden)

    Rita eDe Gasperi

    2012-12-01

    Full Text Available Blast-induced traumatic brain injury (TBI has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI. The β-amyloid (Aβ peptide associated with the development of Alzheimer’s disease (AD is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, BACE-1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain.

  1. Acute alcohol consumption and motivation to reduce drinking among injured patients in a Swedish emergency department.

    Science.gov (United States)

    Trinks, Anna; Festin, Karin; Bendtsen, Preben; Cherpitel, Cheryl J; Nilsen, Per

    2012-10-01

    Injuries constitute a major public health problem. Millions of people are injured each year, and acute drinking is a well-known risk factor for injuries. Research suggests that acknowledgment of alcohol as a factor in an injury enhances willingness to change drinking behavior, possibly because the patient becomes aware of the negative consequences of their drinking. This study aims to investigate the prevalence of acute alcohol consumption (drinking before the event) among injury patients and to examine the importance of factors potentially associated with motivation to reduce alcohol consumption among these patients. All patients aged 18-69 years were requested to answer alcohol-related questions on a touchscreen computer. Fifteen percent of injured patients were categorized as acute drinkers, and of these, 64% reported that their injury was connected to alcohol. There were significant differences for all sociodemographic and drinking characteristics between acute drinkers and nonacute drinkers. Acute drinkers were categorized as risky drinkers to a much higher extent than nonacute drinkers. Acute drinkers had a considerably higher average weekly alcohol consumption and engaged far more frequently in heavy episodic drinking than nonacute drinkers. Acute drinkers were motivated to reduce their alcohol intake to a greater extent than nonacute drinkers; 51% were in the action, preparation, and contemplation stages, compared with 19% of the nonacute drinkers. Acute drinkers had considerably more detrimental alcohol consumption than nonacute drinkers, and the acute drinkers were more motivated to reduce their drinking than the nonacute drinkers.

  2. Acute hyperhydration reduces athlete biological passport OFF-hr score

    DEFF Research Database (Denmark)

    Bejder Rasmussen, Jacob; Hoffmann, M F; Ashenden, M

    2016-01-01

    Anecdotal evidence suggests that athletes hyperhydrate to mask prohibited substances in urine and potentially counteract suspicious fluctuations in blood parameters in the athlete biological passport (ABP). It is examined if acute hyperhydration changes parameters included in the ABP. Twenty...... subjects received recombinant human erythropoietin (rhEPO) for 3 weeks. After 10 days of rhEPO washout, 10 subjects ingested normal amount of water (∼ 270 mL), whereas the remaining 10 ingested a 1000 mL bolus of water. Blood variables were measured 20, 40, 60, and 80 min after ingestion. Three days later...... with atypical blood profiles (99% specificity level) before drinking 1000 mL of water, whereas 11% (n = 18), 10% and 11% (n = 18) were identified 40, 60, and 80 min, respectively, after ingestion. This was different (P 

  3. Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event.

    Science.gov (United States)

    Rehnqvist, N; Olsson, G; Erhardt, L; Ekman, A M

    1987-06-01

    Fifty three of the 5778 patients included in the MIAMI (Metoprolol in Acute Myocardial Infarction) trial were investigated with long-term ECG recordings in order to evaluate the effect of acute beta-blockade on premature ventricular complexes in and after acute myocardial infarction. Twenty five patients were given placebo and 28 metoprolol in a double-blind randomized fashion for 15 days. After this period the patients were put on open beta-blockade without breaking individual study codes. The mean number of premature ventricular complexes during the inclusion day (day 0) was the same in the two groups. The median numbers were also similar in the two groups: 190 and 154 in the placebo and metoprolol groups, respectively. Metoprolol significantly reduced the median number of premature ventricular complexes in the randomized period. The median numbers on days 1, 2 and 15 were 146, 101, 84 in the placebo group and 73, 59 and 10 in the metoprolol group, respectively (P less than 0.05). Also during the further follow-up, when investigated 1, 3 and 6 months after the infarction, the median number of premature ventricular complexes was lower in the metoprolol group (74, 257, 142 in the placebo group and 7, 5 and 11 in the metoprolol group, P less than 0.05). This indicates that metoprolol treatment in the acute phase of myocardial infarction reduces ventricular arrhythmias both in the early stage and also after the acute event.

  4. Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice.

    Directory of Open Access Journals (Sweden)

    Karl J Kaiyala

    Full Text Available Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1 increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2 exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21 °C to 28 °C rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40 ± 1% and dark cycle energy expenditure (15 ± 3% at normal ambient temperature (21 °C. Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65 ± 7%, thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14 ± 2% at 21 °C; 21 ± 4% at 28 °C, while food intake was reduced during the dark cycle (0.9 ± 0.1 g in mice housed at 28 °C, but during the light cycle (0.3 ± 0.1 g in mice housed at 21 °C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R(2 = 0.51, p<0.01. We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure.

  5. RAGE inhibition reduces acute lung injury in mice.

    Science.gov (United States)

    Blondonnet, Raiko; Audard, Jules; Belville, Corinne; Clairefond, Gael; Lutz, Jean; Bouvier, Damien; Roszyk, Laurence; Gross, Christelle; Lavergne, Marilyne; Fournet, Marianne; Blanchon, Loic; Vachias, Caroline; Damon-Soubeyrand, Christelle; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

    2017-08-03

    The receptor for advanced glycation end-products (RAGE) is involved in inflammatory response during acute respiratory distress syndrome (ARDS). Growing body of evidence support strategies of RAGE inhibition in experimental lung injury, but its modalities and effects remain underinvestigated. Anesthetised C57BL/6JRj mice were divided in four groups; three of them underwent orotracheal instillation of acid and were treated with anti-RAGE monoclonal antibody (mAb) or recombinant soluble RAGE (sRAGE), acting as a decoy receptor. The fourth group served as a control. Lung injury was assessed by the analysis of blood gases, alveolar permeability, histology, AFC, and cytokines. Lung expression and distribution epithelial channels ENaC, Na,K-ATPase, and aquaporin (AQP)-5 were assessed. Treatment with either anti-RAGE mAb or sRAGE improved lung injury, arterial oxygenation and decreased alveolar inflammation in acid-injured animals. Anti-RAGE therapies were associated with restored AFC and increased lung expression of AQP-5 in alveolar cell. Blocking RAGE had potential therapeutic effects in a translational mouse model of ARDS, possibly through a decrease in alveolar type 1 epithelial cell injury as shown by restored AFC and lung AQP-5 expression. Further mechanistic studies are warranted to describe intracellular pathways that may control such effects of RAGE on lung epithelial injury and repair.

  6. Reduced acute nociception and chronic pain in Shank2-/- mice.

    Science.gov (United States)

    Ko, Hyoung-Gon; Oh, Seog-Bae; Zhuo, Min; Kaang, Bong-Kiun

    2016-01-01

    Autism spectrum disorder is a debilitating mental illness and social issue. Autism spectrum disorder patients suffer from social isolation, cognitive deficits, compulsive behavior, and sensory deficits, including hyposensitivity to pain. However, recent studies argued that autism spectrum disorder patients show physiological pain response and, in some cases, even extremely intense pain response to harmless stimulation. Recently, Shank gene family was reported as one of the genetic risk factors of autism spectrum disorder. Thus, in this study, we used Shank2(-) (/) (-) (Shank2 knock-out, KO) mice to investigate the controversial pain sensitivity issue and found that Shank2 KO mice showed reduced tactile perception and analgesia to chronic pain.

  7. Acute resistance exercise reduces heart rate complexity and increases QTc interval.

    Science.gov (United States)

    Heffernan, K S; Sosnoff, J J; Jae, S Y; Gates, G J; Fernhall, B

    2008-04-01

    Acute resistance exercise (RE) has been shown to reduce cardiac vagal control. Whether this would in turn affect QTc interval (an index of ventricular depolarization/repolarization) or heart rate complexity is not known. Heart rate variability (HRV), heart rate complexity (SampEn), and QT interval (rate corrected using Bazett, Fridericia, Hodges, and Framingham) were measured before and 5 min after an acute RE bout in twelve healthy young men. Normalized high frequency power of HRV (an index of cardiac parasympathetic modulation; HF (nu)), and SampEn were reduced following RE (p heart rate complexity and increased QTc length. Thus, during recovery from acute RE, there is prolongation of depolarization and repolarization of the ventricles concomitant with reduced cardiac irregularity, and this may be related to a reduction in cardiac vagal control.

  8. Mechanism of reduced myocardial glucose utilization during acute hypertriglyceridemia in rats.

    Science.gov (United States)

    Ménard, Sébastien L; Ci, Xiuli; Frisch, Frédérique; Normand-Lauzière, François; Cadorette, Jules; Ouellet, René; Van Lier, Johannes E; Bénard, François; Bentourkia, M'hamed; Lecomte, Roger; Carpentier, André C

    2009-01-01

    The purpose of the research is to study the effect of acute inhibition of intravascular lipolysis on myocardial substrate selection during hypertriglyceridemia using in vivo radiotracer analysis and positron emission tomography. We induced acute hypertriglyceridemia in vivo using an intravenous infusion of Intralipid 20% (IL) without and with acute inhibition of fatty acid delivery from circulating triglycerides with injection of Triton WR-1339 (TRI) during a euglycemic-hyperinsulinemic clamp in Wistar rats. We determined the effect of TRI on myocardial uptake of circulating triglycerides and free fatty acids using intravenous injection of [(3)H]-triolein and [(14)C]-bromopalmitate, respectively. Myocardial blood flow, oxidative metabolism, and metabolic rate of glucose (MMRG) were determined using micro-positron emission tomography (microPET) with [(13)N]-ammonia, [(11)C]-acetate, and 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG). TRI reduced myocardial incorporation of [(3)H]-triolein but not [(14)C]-bromopalmitate showing that it selectively reduces myocardial fatty acid delivery from circulating triglycerides but not from free fatty acids. IL reduced myocardial blood flow and MMRG by 37% and 56%, respectively, but did not affect myocardial oxidative metabolism. TRI did not abolish the effect of IL on myocardial blood flow and MMRG. Hypertriglyceridemia acutely reduces myocardial blood flow and MMRG in rats, but this effect is not explained by increased myocardial fatty acid delivery through intravascular triglyceride lipolysis.

  9. Reduced Admissions for Acute Myocardial Infarction Associated with a Public Smoking Ban: Matched Controlled Study

    Science.gov (United States)

    Seo, Dong-Chul; Torabi, Mohammad R.

    2007-01-01

    There has been no research linking implementation of a public smoking ban and reduced incidence of acute myocardial infarction (AMI) among nonsmoking patients. An ex post facto matched control group study was conducted to determine whether there was a change in hospital admissions for AMI among nonsmoking patients after a public smoking ban was…

  10. Whole-grain pasta reduces appetite and meal-induced thermogenesis acutely

    DEFF Research Database (Denmark)

    Cioffi, Iolanda; Santarpia, Lidia; Vaccaro, Andrea

    2016-01-01

    In epidemiological studies, the intake of foods rich in dietary fiber is associated with a reduced risk of developing overweight and type 2 diabetes. This work aims to identify acute strategies to regulate appetite and improve glucose control by using different pasta meals. Hence, 4 different iso...

  11. Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury

    NARCIS (Netherlands)

    Li, Shenyang; Nagothu, K.; Ranganathan, G.; Ali, S.M.; Shank, B.; Gokden, N.; Ayyadevara, S.; Megysi, J.; Olivecrona, G.; Chugh, S.S.; Kersten, A.H.; Portilla, D.

    2012-01-01

    Peroxisome proliferator-activated receptor-a (PPARa) activation attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation could also contribute. Here, we investigated the effects of PPARa and CP

  12. Cortisol administration acutely reduces threat-selective spatial attention in healthy young men.

    Science.gov (United States)

    Putman, Peter; Hermans, Erno J; van Honk, Jack

    2010-03-03

    There is mounting evidence that single administrations of glucocorticoids may acutely reduce human fear. We previously reported that administration of cortisol acutely reduced non-spatial selective attention to fearful faces and likewise reduced preferential processing of fearful faces in a spatial working memory task. Here we report the acute effects of 40 mg cortisol (administered in a double-blind, placebo-controlled crossover design) on a different experimental task for measuring threat-selective attention. Twenty healthy young males had to localize a target which was presented in a peripheral location that was either gazed at or not by a preceding dynamic happy or fearful face. This reliable method has been used repeatedly to demonstrate fear-driven selective attention. Present results showed that after placebo, as usual, the fearful gaze cues caused stronger orienting of attention than happy faces. Cortisol abolished this typical anxious response pattern, but only in low anxious participants. These data provide evidence that cortisol acutely influences also spatial threat-selective attention. Possible neuroendocrine mechanisms are discussed. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  13. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Minmin Li

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  14. Acute immobilization stress following contextual fear conditioning reduces fear memory: timing is essential.

    Science.gov (United States)

    Uwaya, Akemi; Lee, Hyunjin; Park, Jonghyuk; Lee, Hosung; Muto, Junko; Nakajima, Sanae; Ohta, Shigeo; Mikami, Toshio

    2016-02-24

    Histone acetylation is regulated in response to stress and plays an important role in learning and memory. Chronic stress is known to deteriorate cognition, whereas acute stress facilitates memory formation. However, whether acute stress facilitates memory formation when it is applied after fear stimulation is not yet known. Therefore, this study aimed to investigate the effect of acute stress applied after fear training on memory formation, mRNA expression of brain-derived neurotrophic factor (BDNF), epigenetic regulation of BDNF expression, and corticosterone level in mice in vivo. Mice were subjected to acute immobilization stress for 30 min at 60 or 90 min after contextual fear conditioning training, and acetylation of histone 3 at lysine 14 (H3K14) and level of corticosterone were measured using western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A freezing behavior test was performed 24 h after training, and mRNA expression of BDNF was measured using real-time polymerase chain reactions. Different groups of mice were used for each test. Freezing behavior significantly decreased with the down-regulation of BDNF mRNA expression caused by acute immobilization stress at 60 min after fear conditioning training owing to the reduction of H3K14 acetylation. However, BDNF mRNA expression and H3K14 acetylation were not reduced in animals subjected to immobilization stress at 90 min after the training. Further, the corticosterone level was significantly high in mice subjected to immobilization stress at 60 min after the training. Acute immobilization stress for 30 min at 60 min after fear conditioning training impaired memory formation and reduced BDNF mRNA expression and H3K14 acetylation in the hippocampus of mice owing to the high level of corticosterone.

  15. Economic evaluation of the benefits of reducing acute cardiorespiratory morbidity associated with air pollution

    Directory of Open Access Journals (Sweden)

    Anis Aslam H

    2002-12-01

    Full Text Available Abstract Background Few assessments of the costs and benefits of reducing acute cardiorespiratory morbidity related to air pollution have employed a comprehensive, explicit approach to capturing the full societal value of reduced morbidity. Methods We used empirical data on the duration and severity of episodes of cardiorespiratory disease as inputs to complementary models of cost of treatment, lost productivity, and willingness to pay to avoid acute cardiorespiratory morbidity outcomes linked to air pollution in epidemiological studies. A Monte Carlo estimation procedure was utilized to propagate uncertainty in key inputs and model parameters. Results Valuation estimates ranged from $13 (1997, Canadian (95% confidence interval, $0–28 for avoidance of an acute respiratory symptom day to $5,200 ($4,000–$6,400 for avoidance of a cardiac hospital admission. Cost of treatment accounted for the majority of the overall value of cardiac and respiratory hospital admissions as well as cardiac emergency department visits, while lost productivity generally represented a small proportion of overall value. Valuation estimates for days of restricted activity, asthma symptoms and acute respiratory symptoms were sensitive to alternative assumptions about level of activity restriction. As an example of the application of these values, we estimated that the observed decrease in particulate sulfate concentrations in Toronto between 1984 and 1999 resulted in annual benefits of $1.4 million (95% confidence interval $0.91–1.8 million in relation to reduced emergency department visits and hospital admissions for cardiorespiratory disease. Conclusion Our approach to estimating the value of avoiding a range of acute morbidity effects of air pollution addresses a number of limitations of the current literature, and is applicable to future assessments of the benefits of improving air quality.

  16. Reduced Tic Symptomatology in Tourette Syndrome After an Acute Bout of Exercise: An Observational Study.

    Science.gov (United States)

    Nixon, Elena; Glazebrook, Cris; Hollis, Chris; Jackson, Georgina M

    2014-03-01

    In light of descriptive accounts of attenuating effects of physical activity on tics, we used an experimental design to assess the impact of an acute bout of aerobic exercise on tic expression in young people (N = 18) with Tourette Syndrome (TS). We compared video-based tic frequency estimates obtained during an exercise session with tic rates obtained during pre-exercise (baseline) and post-exercise interview-based sessions. Results showed significantly reduced tic rates during the exercise session compared with baseline, suggesting that acute exercise has an attenuating effect on tics. Tic rates also remained reduced relative to baseline during the post-exercise session, likely reflecting a sustained effect of exercise on tic reduction. Parallel to the observed tic attenuation, exercise also had a beneficial impact on self-reported anxiety and mood levels. The present findings provide novel empirical evidence for the beneficial effect of exercise on TS symptomatology bearing important research and clinical implications.

  17. Low-dose dopamine reduces inlfammatory factors of acute pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Shun Zhang; Xin-Gang Peng; Chang-Chang Liu; Hong Liu; Yun Lu

    2007-01-01

    BACKGROUND:Acute pancreatitis, especially acute necrotizing pancreatitis (ANP), is a serious disease with a high morbidity because of multiorgan dysfunction. Recent studies have indicated that during the pathogenesis of ANP, changes of the microcirculation play an important role in the worsening of the disease. This study based on a model of acute pancreatitis in Wistar rats was to determine the effect of treatment with low-dose dopamine on acute pancreatitis by the dynamic measurement of serum levels of inlfammatory factors IL-6 and TNF-α. METHODS:Fifty Wistar rats were randomly divided into two groups, and a model of ANP was set up by injecting sodium taurocholate into the pancreatic duct. Rats in the dopamine group (treatment group) were given dopamine by vein and those in the acute pancreatitis group (control group) were given normal saline. To assess the effect of low-dose dopamine (5 μg·kg-1·min-1) on induced acute pancreatitis, the antibody sandwich ELISA method was used to measure the serum levels of IL-6 and TNF-α at different times before and after the induction of ANP. RESULTS:The serum levels of IL-6 and TNF-α in the treatment and control groups before and after ANP induction were signiifcantly different. There was a markedly signiifcant difference in the comparison of the two groups after ANP induction (P0.05). Postoperative pancreatic histopathologic changes in the treatment group were more marked than those in the control group. CONCLUSIONS:Low-dose dopamine is effective in treating ANP by alleviating inlfammatory reactions. This effect may be related to the fact that low-dose dopamine not only can increase the blood lfow of the pancreatic microcirculation but also reduce its permeability.

  18. A strategy to reduce the numbers of fish used in acute ecotoxicity testing of pharmaceuticals.

    Science.gov (United States)

    Hutchinson, Thomas H; Barrett, Sarah; Buzby, Mary; Constable, David; Hartmann, Andreas; Hayes, Eileen; Huggett, Duane; Laenge, Reinhard; Lillicrap, Adam D; Straub, Jürg Oliver; Thompson, Roy S

    2003-12-01

    The pharmaceutical industry gives high priority to animal welfare in the process of drug discovery and safety assessment. In the context of environmental assessments of active pharmaceutical ingredients (APIs), existing U.S. Food and Drug Administration and draft European regulations may require testing of APIs for acute ecotoxicity to algae, daphnids, and fish (base-set ecotoxicity data used to derive the predicted no-effect concentration [PNECwater] from the most sensitive of three species). Subject to regulatory approval, it is proposed that testing can be moved from fish median lethal concentration (LC50) testing (typically using > or = 42 fish/API) to acute threshold tests using fewer fish (typically 10 fish/API). To support this strategy, we have collated base-set ecotoxicity data from regulatory studies of 91 APIs (names coded for commercial reasons). For 73 of the 91 APIs, the algal median effect concentration (EC50) and daphnid EC50 values were lower than or equal to the fish LC50 data. Thus, for approximately 80% of these APIs, algal and daphnid acute EC50 data could have been used in the absence of fish LC50 data to derive PNECwater values. For the other 18 APIs, use of an acute threshold test with a step-down factor of 3.2 is predicted to give comparable PNECwater outcomes. Based on this preliminary scenario of 91 APIs, this approach is predicted to reduce the total number of fish used from 3,822 to 1,025 (approximately 73%). The present study, although preliminary, suggests that the current regulatory requirement for fish LC50 data regarding APIs should be succeeded by fish acute threshold (step-down) test data, thereby achieving significant animal welfare benefits with no loss of data for PNECwater estimates.

  19. Neovestitol, an isoflavonoid isolated from Brazilian red propolis, reduces acute and chronic inflammation: involvement of nitric oxide and IL-6

    OpenAIRE

    Marcelo Franchin; Colón, David F.; da Cunha, Marcos G; Castanheira, Fernanda V. S.; André L. L. Saraiva; Bruno Bueno-Silva; Alencar,Severino M.; Cunha, Thiago M; Rosalen, Pedro L.

    2016-01-01

    Isoflavonoids have been largely studied due to their distinct biological activities identified thus far. Herein, we evaluated the activity of neovestitol, an isoflavonoid isolated from Brazilian red propolis, in acute and chronic inflammation. As for acute inflammation, we found that neovestitol reduced neutrophil migration, leukocyte rolling and adhesion, as well as expression of ICAM-1 in the mesenteric microcirculation during lipopolysaccharide-induced acute peritonitis. No changes were ob...

  20. One size does not fit all: evaluating an intervention to reduce antibiotic prescribing for acute bronchitis

    Science.gov (United States)

    2013-01-01

    Background Overuse of antibiotics for upper respiratory tract infections (URIs) and acute bronchitis is a persistent and vexing problem. In the U.S., more than half of all patients with upper respiratory tract infections and acute bronchitis are treated with antibiotics annually, despite the fact that most cases are viral in etiology and are not responsive to antibiotics. Interventions aiming to reduce unnecessary antibiotic prescribing have had mixed results, and successes have been modest. The objective of this evaluation is to use mixed methods to understand why a multi-level intervention to reduce antibiotic prescribing for acute bronchitis among primary care providers resulted in measurable improvement in only one third of participating clinicians. Methods Clinician perspectives on print-based and electronic intervention strategies, and antibiotic prescribing more generally, were elicited through structured telephone surveys at high and low performing sites after the first year of intervention at the Geisinger Health System in Pennsylvania (n = 29). Results Compared with a survey on antibiotic use conducted 10 years earlier, clinicians demonstrated greater awareness of antibiotic resistance and how it is impacted by individual prescribing decisions—including their own. However, persistent perceived barriers to reducing prescribing included patient expectations, time pressure, and diagnostic uncertainty, and these factors were reported as differentially undermining specific intervention components’ effectiveness. An exam room poster depicting a diagnostic algorithm was the most popular strategy. Conclusions Future efforts to reduce antibiotic prescribing should address multi-level barriers identified by clinicians and tailor strategies to differences at individual clinician and group practice levels, focusing in particular on changing how patients and providers make decisions together about antibiotic use. PMID:24188573

  1. Can a chronic disease management pulmonary rehabilitation program for COPD reduce acute rural hospital utilization?

    Science.gov (United States)

    Rasekaba, T M; Williams, E; Hsu-Hage, B

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) imposes a costly burden on healthcare. Pulmonary rehabilitation (PR) is the best practice to better manage COPD to improve patient outcomes and reduce acute hospital care utilization. To evaluate the impact of a once-weekly, eight-week multidisciplinary PR program as an integral part of the COPD chronic disease management (CDM) Program at Kyabram District Health Services. The study compared two cohorts of COPD patients: CDM-PR Cohort (4-8 weeks) and Opt-out Cohort (0-3 weeks) between February 2006 and March 2007. The CDM-PR Program involved multidisciplinary patient education and group exercise training. Nonparametric statistical tests were used to compare acute hospital care utilization 12 months before and after the introduction of CDM-PR. The number of patients involved in the CDM-PR Cohort was 29 (n = 29), and that in the Opt-out Cohort was 24 (n = 24). The CDM-PR Cohort showed significant reductions in cumulative acute hospital care utilization indicators (95% emergency department presentations, 95% inpatient admissions, 99% length of stay; effect sizes = 0.62-0.66, P indicators were statistically insignificant for the Opt-out Cohort (emergency department presentations decreased by 5%, inpatient admissions decreased by 12%, length of stay increased by 30%; effect size = 0.14-0.40, P > 0.05). Total costs associated with the hospital care utilization decreased from $130,000 to $7,500 for the CDM-PR Cohort and increased from $77,700 to $101,200 for the Opt-out Cohort. Participation in the CDM-PR for COPD patients can significantly reduce acute hospital care utilization and associated costs in a small rural health service.

  2. Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review.

    Science.gov (United States)

    Warren-Gash, Charlotte; Fragaszy, Ellen; Hayward, Andrew C

    2013-09-01

    Hand hygiene may be associated with modest protection against some acute respiratory tract infections, but its specific role in influenza transmission in different settings is unclear. We aimed to review evidence that improving hand hygiene reduces primary and secondary transmission of (i) influenza and (ii) acute respiratory tract infections in community settings. We searched Medline, Embase, Global Health and Cochrane databases up to 13 February 2012 for reports in any language of original research investigating the effect of hand hygiene on influenza or acute respiratory tract infection where aetiology was unspecified in community settings including institutions such as schools, and domestic residences. Data were presented and quality rated across outcomes according to the Grading of Recommendations Assessment, Development and Evaluation system. Sixteen articles met inclusion criteria. There was moderate to low-quality evidence of a reduction in both influenza and respiratory tract infection with hand hygiene interventions in schools, greatest in a lower-middle-income setting. There was high-quality evidence of a small reduction in respiratory infection in childcare settings. There was high-quality evidence for a large reduction in respiratory infection with a hand hygiene intervention in squatter settlements in a low-income setting. There was moderate- to high-quality evidence of no effect on secondary transmission of influenza in households that had already experienced an index case. While hand hygiene interventions have potential to reduce transmission of influenza and acute respiratory tract infections, their effectiveness varies depending on setting, context and compliance. © 2012 John Wiley & Sons Ltd.

  3. Iterative reconstruction technique with reduced volume CT dose index: diagnostic accuracy in pediatric acute appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Didier, Ryne A. [Oregon Health and Science University, Department of Diagnostic Radiology, DC7R, Portland, OR (United States); Vajtai, Petra L. [Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States); Oregon Health and Science University, Department of Diagnostic Radiology, DC7R, Portland, OR (United States); Hopkins, Katharine L. [Oregon Health and Science University, Department of Diagnostic Radiology, DC7R, Portland, OR (United States); Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States)

    2014-07-05

    Iterative reconstruction technique has been proposed as a means of reducing patient radiation dose in pediatric CT. Yet, the effect of such reductions on diagnostic accuracy has not been thoroughly evaluated. This study compares accuracy of diagnosing pediatric acute appendicitis using contrast-enhanced abdominopelvic CT scans performed with traditional pediatric weight-based protocols and filtered back projection reconstruction vs. a filtered back projection/iterative reconstruction technique blend with reduced volume CT dose index (CTDI{sub vol}). Results of pediatric contrast-enhanced abdominopelvic CT scans done for pain and/or suspected appendicitis were reviewed in two groups: A, 192 scans performed with the hospital's established weight-based CT protocols and filtered back projection reconstruction; B, 194 scans performed with iterative reconstruction technique and reduced CTDI{sub vol}. Reduced CTDI{sub vol} was achieved primarily by reductions in effective tube current-time product (mAs{sub eff}) and tube peak kilovoltage (kVp). CT interpretation was correlated with clinical follow-up and/or surgical pathology. CTDI{sub vol}, size-specific dose estimates (SSDE) and performance characteristics of the two CT techniques were then compared. Between groups A and B, mean CTDI{sub vol} was reduced by 45%, and mean SSDE was reduced by 46%. Sensitivity, specificity and diagnostic accuracy were 96%, 97% and 96% in group A vs. 100%, 99% and 99% in group B. Accuracy in diagnosing pediatric acute appendicitis was maintained in contrast-enhanced abdominopelvic CT scans that incorporated iterative reconstruction technique, despite reductions in mean CTDI{sub vol} and SSDE by nearly half as compared to the hospital's traditional weight-based protocols. (orig.)

  4. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Baron, F; Labopin, M; Niederwieser, D;

    2012-01-01

    This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of rela...... of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P...

  5. Thrombolysis significantly reduces transient myocardial ischaemia following first acute myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1992-01-01

    In order to investigate whether thrombolysis affects residual myocardial ischaemia, we prospectively performed a predischarge maximal exercise test and early out-of-hospital ambulatory ST segment monitoring in 123 consecutive men surviving a first acute myocardial infarction (AMI). Seventy...... less than 0.02). Thrombolysis resulted in a non-significant reduction in exercise-induced ST segment depression: prevalence 43% vs 62% in controls. However, during ambulatory monitoring the duration of transient myocardial ischaemia was significantly reduced in thrombolysed patients: 322 min vs 1144...... myocardial ischaemia. This may explain the improvement in myocardial function during physical activities, which was also observed in this study....

  6. Acute upper gastrointestinal bleeding in patients with AIDS: a relatively uncommon condition associated with reduced survival.

    Science.gov (United States)

    Parente, F; Cernuschi, M; Valsecchi, L; Rizzardini, G; Musicco, M; Lazzarin, A; Bianchi Porro, G

    1991-01-01

    To determine the cumulative incidence of acute upper gastrointestinal bleeding and its effect upon survival in patients with AIDS, 453 consecutive AIDS patients diagnosed in our hospital between June 1985 and March 1989 were followed for a median period of six months (maximum 42 months). The cumulative probability of acute gastrointestinal bleeding was 3% at six months and 6% at 14 months. This event was associated with significantly reduced survival. Independent risk factors for bleeding were: severe thrombocytopenia at the time of diagnosis and non-Hodgkin's lymphoma as the first clinical manifestation of AIDS. The potential causes of bleeding were investigated in all cases by emergency endoscopy or by necropsy examination in those patients whose clinical condition precluded the procedure. In nine of 15 patients, bleeding was due to lesions specifically associated with AIDS, but in the remainder the source of bleeding was not a direct consequence of HIV infection. We conclude that acute upper gastrointestinal bleeding rarely complicates the course of AIDS, but its occurrence is associated with decreased survival. As many of the causes are potentially treatable, a complete diagnostic approach is indicated in these patients, except those who are terminally ill. PMID:1916503

  7. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor.

  8. A Cluster-Randomized Trial of Decision Support Strategies for Reducing Antibiotic Use for Acute Bronchitis

    Science.gov (United States)

    Gonzales, Ralph; Anderer, Tammy; McCulloch, Charles E.; Maselli, Judith H.; Bloom, Frederick J; Graf, Thomas R; Stahl, Melissa; Yefko, Michelle; Molecavage, Julie; Metlay, Joshua P

    2013-01-01

    Background National quality indicators show little change in the overuse of antibiotics for uncomplicated acute bronchitis. We compared the impact of two decision support strategies on antibiotic treatment of uncomplicated acute bronchitis. Methods We conducted a three-arm, cluster-randomized trial among 33 primary care practices belonging to an integrated health care system in central Pennsylvania. The printed intervention arm (n=11 practices) received decision support for acute cough illness through a print-based strategy, the computerized intervention group (n=11) received decision support through an electronic medical record-based strategy, and third group of practices (n=11) served as the control arm. Both intervention groups also received provider education and feedback on prescribing practices, and patient education brochures at check-in. Antibiotic prescription rates for uncomplicated acute bronchitis in the winter period (October 2009 – March 2010) following introduction of the intervention were compared with the previous three winter periods in an intent-to-treat analysis. Results Compared with the baseline period, the percentage of adolescents and adults prescribed antibiotics during the intervention period decreased at the printed (from 80.0% to 68.3%) and computerized intervention sites (from 74.0% to 60.7%), but increased slightly at the control sites (from 72.5% to 74.3%). After controlling for patient and provider characteristics, and clustering of observations by provider and practice site, the differences for the intervention groups were statistically significant from control (control vs. printed P=0.003; control vs. computerized P=0.014) but no among themselves (printed vs. computerized P=0.67). Changes in total visits, proportion diagnosed as uncomplicated acute bronchitis and thirty-day return visit rates were similar between study groups. Conclusions Implementation of a decision support strategy for acute bronchitis can help reduce overuse

  9. A cluster randomized trial of decision support strategies for reducing antibiotic use in acute bronchitis.

    Science.gov (United States)

    Gonzales, Ralph; Anderer, Tammy; McCulloch, Charles E; Maselli, Judith H; Bloom, Frederick J; Graf, Thomas R; Stahl, Melissa; Yefko, Michelle; Molecavage, Julie; Metlay, Joshua P

    2013-02-25

    -assisted decision support intervention sites). Changes in total visits, 30-day return visit rates, and proportion diagnosed as having uncomplicated acute bronchitis were similar among the study sites. Implementation of a decision support strategy for acute bronchitis can help reduce the overuse of antibiotics in primary care settings. The effect of printed vs computer-assisted decision support strategies for providing decision support was equivalent. clinicaltrials.gov Identifier: NCT00981994.

  10. Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice.

    Directory of Open Access Journals (Sweden)

    Marina Burgos-Silva

    Full Text Available Acute and chronic kidney injuries (AKI and CKI constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs in an experimental model of nephrotoxicity induced by folic acid (FA in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

  11. Homeopathic Ear Drops as an Adjunct in Reducing Antibiotic Usage in Children With Acute Otitis Media.

    Science.gov (United States)

    Taylor, James A; Jacobs, Jennifer

    2014-01-01

    Objective. To determine if use of a homeopathic ear drop preparation reduces antibiotic use in children diagnosed with acute otitis media (AOM). Methods. Children 6 months to 11 years old, diagnosed with AOM and managed with a delayed antibiotic approach, were randomized to standard therapy alone or standard therapy plus a homeopathic ear drop preparation. The primary outcome was whether or not the antibiotic prescription given at the index visit was filled during a 12- to 15-day follow-up period. Results. Among 210 enrolled children, follow-up antibiotic data were collected on 206. During the 12- to 15-day follow-up period, fewer parents of children randomized to the homeopathic ear drops group filled the antibiotic prescription compared with those of children receiving standard therapy alone (26.9% and 41.2%, respectively, P = .032). Conclusion. Homeopathic ear drops may be effective in reducing the use of antibiotics in children with AOM managed with a delayed antibiotic approach.

  12. Simple In-Hospital Interventions to Reduce Door-to-CT Time in Acute Stroke

    Science.gov (United States)

    Taheraghdam, Aliakbar; Rikhtegar, Reza; Mehrvar, Kaveh; Mehrara, Mehrdad; Hassasi, Rogayyeh; Aliyar, Hannane; Farzi, Mohammadamin; Hasaneh Tamar, Somayyeh

    2016-01-01

    Background. Intravenous tissue plasminogen activator, a time dependent therapy, can reduce the morbidity and mortality of acute ischemic stroke. This study was designed to assess the effect of simple in-hospital interventions on reducing door-to-CT (DTC) time and reaching door-to-needle (DTN) time of less than 60 minutes. Methods. Before any intervention, DTC time was recorded for 213 patients over a one-year period at our center. Five simple quality-improvement interventions were implemented, namely, call notification, prioritizing patients for CT scan, prioritizing patients for lab analysis, specifying a bed for acute stroke patients, and staff education. After intervention, over a course of 44 months, DTC time was recorded for 276 patients with the stroke code. Furthermore DTN time was recorded for 106 patients who were treated with IV thrombolytic therapy. Results. The median DTC time significantly decreased in the postintervention period comparing to the preintervention period [median (IQR); 20 (12–30) versus 75 (52.5–105), P DTC time and resulted in an acceptable DTN time. These interventions are feasible in most hospitals and should be considered. PMID:27478641

  13. Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments.

    Science.gov (United States)

    Kameneva, Marina V; Wu, Zhongjun J; Uraysh, Arkady; Repko, Brandon; Litwak, Kenneth N; Billiar, Timothy R; Fink, Mitchell P; Simmons, Richard L; Griffith, Bartley P; Borovetz, Harvey S

    2004-01-01

    Over the past several decades, blood-soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG-3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG-200), which possesses no drag-reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two-hour survival rate, the latter from 19% (Control) and 14% (PEG-200) to 100% (AVP) and 100% (PEG-3500). Furthermore, the Control and PEG-200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG-3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag-reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.

  14. Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques.

    Science.gov (United States)

    Pandrea, Ivona; Xu, Cuiling; Stock, Jennifer L; Frank, Daniel N; Ma, Dongzhu; Policicchio, Benjamin B; He, Tianyu; Kristoff, Jan; Cornell, Elaine; Haret-Richter, George S; Trichel, Anita; Ribeiro, Ruy M; Tracy, Russell; Wilson, Cara; Landay, Alan L; Apetrei, Cristian

    2016-01-01

    Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

  15. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  16. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

    Directory of Open Access Journals (Sweden)

    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  17. Seizure characteristics of epilepsy in childhood after acute encephalopathy with biphasic seizures and late reduced diffusion.

    Science.gov (United States)

    Ito, Yuji; Natsume, Jun; Kidokoro, Hiroyuki; Ishihara, Naoko; Azuma, Yoshiteru; Tsuji, Takeshi; Okumura, Akihisa; Kubota, Tetsuo; Ando, Naoki; Saitoh, Shinji; Miura, Kiyokuni; Negoro, Tamiko; Watanabe, Kazuyoshi; Kojima, Seiji

    2015-08-01

    The aim of this study was to clarify characteristics of post-encephalopathic epilepsy (PEE) in children after acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), paying particular attention to precise diagnosis of seizure types. Among 262 children with acute encephalopathy/encephalitis registered in a database of the Tokai Pediatric Neurology Society between 2005 and 2012, 44 were diagnosed with AESD according to the clinical course and magnetic resonance imaging (MRI) findings and were included in this study. Medical records were reviewed to investigate clinical data, MRI findings, neurologic outcomes, and presence or absence of PEE. Seizure types of PEE were determined by both clinical observation by pediatric neurologists and ictal video-electroencephalography (EEG) recordings. Of the 44 patients after AESD, 10 (23%) had PEE. The period between the onset of encephalopathy and PEE ranged from 2 to 39 months (median 8.5 months). Cognitive impairment was more severe in patients with PEE than in those without. Biphasic seizures and status epilepticus during the acute phase of encephalopathy did not influence the risk of PEE. The most common seizure type of PEE on clinical observation was focal seizures (n = 5), followed by epileptic spasms (n = 4), myoclonic seizures (n = 3), and tonic seizures (n = 2). In six patients with PEE, seizures were induced by sudden unexpected sounds. Seizure types confirmed by ictal video-EEG recordings were epileptic spasms and focal seizures with frontal onset, and all focal seizures were startle seizures induced by sudden acoustic stimulation. Intractable daily seizures remain in six patients with PEE. We demonstrate seizure characteristics of PEE in children after AESD. Epileptic spasms and startle focal seizures are common seizure types. The specific seizure types may be determined by the pattern of diffuse subcortical white matter injury in AESD and age-dependent reorganization of the brain

  18. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents

    Directory of Open Access Journals (Sweden)

    Zbys Fedorowicz

    Full Text Available BACKGROUND: Vomiting is a common manifestation of acute gastroenteritis in children and adolescents. When untreated, it can be a hindrance to oral rehydration therapy, which is the cornerstone in the management of acute gastroenteritis. Evidence is needed concerning the safety and efficacy of antiemetic use for vomiting in acute gastroenteritis in children. OBJECTIVES: To assess the safety and effectiveness of antiemetics on gastroenteritis induced vomiting in children and adolescents. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conferences. The search was re-run and is up to date as on 20 July 2010. SELECTION CRITERIA: Randomized controlled trials comparing antiemetics with placebo or no treatment, in children and adolescents under the age of 18, for vomiting due to gastroenteritis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: We included seven trials involving 1,020 participants. Mean time to cessation of vomiting in one study was 0.34 days less with dimenhydrinate suppository compared to placebo (P value = 0.036. Pooled data from three studies comparing oral ondansetron with placebo showed: a reduction in the immediate hospital admission rate (RR 0.40, NNT 17, 95% CI 10 to 100 but no difference between the hospitalization rates at 72 hours after discharge from the Emergency Department (ED; a reduction in IV rehydration rates both during the ED stay (RR 0.41, NNT 5, 95% CI 4 to 8, and in follow-up to 72 hours after discharge from the ED stay (worst-best scenario for ondansetron RR 0.57, NNT 6, 95% CI 4 to 13 and an increase in the proportion of patients with cessation of vomiting (RR 1.34, NNT 5, 95% CI 3 to 7. No significant difference was noted in the revisit

  19. Acute digoxin loading reduces ABCA8A mRNA expression in the mouse liver.

    Science.gov (United States)

    Wakaumi, Michi; Ishibashi, Kenichi; Ando, Hitoshi; Kasanuki, Hiroshi; Tsuruoka, Shuichi

    2005-12-01

    Human ABCA8, a new member of the ATP binding cassette (ABC) transporter family, transports certain lipophilic drugs, such as digoxin. To investigate the roles of this transporter, we cloned a mouse homologue of ABCA8, from a mouse heart cDNA library, named ABCA8a. The deduced mouse ABCA8a protein is 66% identical with that of human ABCA8 and possesses features common to the ABC superfamily. It was found that ABCA8a was mainly expressed in the liver and heart, similar to human ABCA8. We further evaluated the effect of acute digoxin (a substrate for ABCA8) intoxication on the mRNA expression of ABCA8 using northern blotting with a 3' non-coding region as a probe to avoid cross-hybridization with other ABCA genes. Following acute digoxin infusion, the mRNA expression of ABCA8 was significantly reduced in the liver 12-24 h after injection (14.7% of vehicle treatment), but not in the heart and kidney. Real-time quantitative polymerase chain reaction analysis confirmed the reduction in ABCA8a mRNA. Similar reductions in ABCA5, ABCA7, ABCA8b and ABCA9 mRNA were also observed. A comparable amount of digitoxin did not affect ABCA8a mRNA expression in the liver. The results suggest that ABCA8 may play a role in digoxin metabolism in the liver.

  20. Disrupted glutamate-glutamine cycle in acute encephalopathy with biphasic seizures and late reduced diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Takanashi, Jun-ichi; Terai, Masaru [Tokyo Women' s Medical University Yachiyo Medical Center, Department of Pediatrics, Yachiyo-shi (Japan); Mizuguchi, Masashi [The University of Tokyo, Department of Developmental Medical Sciences, Graduate School of Medicine, Tokyo (Japan); Barkovich, A.J. [University of California San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2015-11-15

    Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of AESD; excitotoxicity is postulated to be the pathogenesis based on elevated glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx, or whether MR spectroscopy is useful for an early diagnosis. Five Japanese patients with AESD (three boys and two girls, 1 year of age) were enrolled in this study. MR spectroscopy was acquired from the frontal white matter (repetition time (TR) of 5000 ms, echo time (TE) of 30 ms) with a 1.5- or 3.0-T scanner. MR spectroscopy was performed four times for two patients, three times for one patient, and two times for two patients. Quantification of Glu and Gln was performed using LCModel. Glu was elevated in three of four studies on days 1-4 and became normal or low afterward. Gln was normal in three studies on days 1-2, elevated in all seven studies on days 4-12, and became normal or low afterward. These findings suggest that MR spectroscopy may be useful for an early diagnosis. Acute Glu elevation changes to subacute Gln elevation, suggesting that a disrupted Glu-Gln cycle may play an important role. (orig.)

  1. Burden of Recurrent Hospitalizations Following an Admission for Acute Heart Failure: Preserved Versus Reduced Ejection Fraction.

    Science.gov (United States)

    Santas, Enrique; Valero, Ernesto; Mollar, Anna; García-Blas, Sergio; Palau, Patricia; Miñana, Gema; Núñez, Eduardo; Sanchis, Juan; Chorro, Francisco Javier; Núñez, Julio

    2017-04-01

    Heart failure with preserved ejection fraction and reduced ejection fraction share a high mortality risk. However, differences in the rehospitalization burden over time between these 2 entities remains unclear. We prospectively included 2013 consecutive patients discharged for acute heart failure. Of these, 1082 (53.7%) had heart failure with preserved ejection fraction and 931 (46.2%) had heart failure with reduced ejection fraction. Cox and negative binomial regression methods were used to evaluate the risks of death and repeat hospitalizations, respectively. At a median follow-up of 2.36 years (interquartile range: 0.96-4.65), 1018 patients (50.6%) died, and 3804 readmissions were registered in 1406 patients (69.8%). Overall, there were no differences in mortality between heart failure with preserved ejection fraction and heart failure with reduced ejection fraction (16.7 vs 16.1 per 100 person-years, respectively; P=0794), or all-cause repeat hospitalization rates (62.1 vs 62.2 per 100 person-years, respectively; P=.944). After multivariable adjustment, and compared with patients with heart failure with reduced ejection fraction, patients with heart failure with preserved ejection fraction exhibited a similar risk of all-cause readmissions (incidence rate ratio=1.04; 95%CI, 0.93-1.17; P=.461). Regarding specific causes, heart failure with preserved ejection fraction showed similar risks of cardiovascular and heart failure-related rehospitalizations (incidence rate ratio=0.93; 95%CI, 0.82-1.06; P=.304; incidence rate ratio=0.96; 95% confidence interval, 0.83-1.13; P=.677, respectively), but had a higher risk of noncardiovascular readmissions (incidence rate ratio=1.24; 95%CI, 1.04-1.47; P=.012). Following an admission for acute heart failure, patients with heart failure with preserved ejection fraction have a similar rehospitalization burden to those with heart failure with reduced ejection fraction. However, patients with heart failure with preserved ejection

  2. Acute Exposure to Pacific Ciguatoxin Reduces Electroencephalogram Activity and Disrupts Neurotransmitter Metabolic Pathways in Motor Cortex.

    Science.gov (United States)

    Kumar, Gajendra; Au, Ngan Pan Bennett; Lei, Elva Ngai Yu; Mak, Yim Ling; Chan, Leanne Lai Hang; Lam, Michael Hon Wah; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-09-10

    Ciguatera fish poisoning (CFP) is a common human food poisoning caused by consumption of ciguatoxin (CTX)-contaminated fish affecting over 50,000 people worldwide each year. CTXs are classified depending on their origin from the Pacific (P-CTXs), Indian Ocean (I-CTXs), and Caribbean (C-CTXs). P-CTX-1 is the most toxic CTX known and the major source of CFP causing an array of neurological symptoms. Neurological symptoms in some CFP patients last for several months or years; however, the underlying electrophysiological properties of acute exposure to CTXs remain unknown. Here, we used CTX purified from ciguatera fish sourced in the Pacific Ocean (P-CTX-1). Delta and theta electroencephalography (EEG) activity was reduced remarkably in 2 h and returned to normal in 6 h after a single exposure. However, second exposure to P-CTX-1 induced not only a further reduction in EEG activities but also a 2-week delay in returning to baseline EEG values. Ciguatoxicity was detected in the brain hours after the first and second exposure by mouse neuroblastoma assay. The spontaneous firing rate of single motor cortex neuron was reduced significantly measured by single-unit recording with high spatial resolution. Expression profile study of neurotransmitters using targeted profiling approach based on liquid chromatography-tandem mass spectrometry revealed an imbalance between excitatory and inhibitory neurotransmitters in the motor cortex. Our study provides a possible link between the brain oscillations and neurotransmitter release after acute exposure to P-CTX-1. Identification of EEG signatures and major metabolic pathways affected by P-CTX-1 provides new insight into potential biomarker development and therapeutic interventions.

  3. Repeat Effort Performance is Reduced 24 h following Acute Dehydration in Mixed Martial Arts Athletes.

    Science.gov (United States)

    Barley, Oliver R; Iredale, Fiona; Chapman, Dale W; Hopper, Amanda; Abbiss, Chris

    2017-09-11

    This study sought to determine the influence of acute dehydration on physical performance and physiology in Mixed Martial Arts (MMA). MMA athletes (n=14; age: 23±4 years), completed in a randomised counterbalanced order a dehydration protocol, (DHY: 3 h cycling at 60 W in 40°C to induce 5% dehydration) or thermoneutral control (25°C: CONT) exercise, followed by ad libitum fluid/food intake. Performance testing (a repeat sled push test, medicine ball chest throw and vertical jump) was completed 3 and 24 h following the intervention, while urine and blood samples were collected before, 20 min, 3 and 24 h following the intervention. Body mass was reduced (4.8±0.8%) following DHY (p<0.001) and remained lower than CONT at 3 and 24 h post (p=0.003 and p=0.024, respectively). Compared to CONT average sled push times were slower 3 and 24 h following DHY (19±15%; p=0.001; g=1.229 and 14±15%; p=0.012; g=0.671, respectively). When compared to the CONT hand grip was weaker 3 h following DHY (53±8 and 51±8 kg; p=0.044, g=0.243 respectively) and medicine ball chest throw distances were shorter 24 h following DHY (474±52 and 449±44 cm; p=0.016, g=0.253 respectively). No significant differences were observed in vertical jump (p=0.467). Urine specific gravity was higher than CONT 20 min (p=0.035) and 24 h (p=0.035) following DHY. Acute dehydration of 4.8% body mass results in reduced physical performance 3 and 24 h following. There is need for caution when athletes use dehydration for weight loss 24 h prior to competition.

  4. Acute Stressors Reduce Neural and Behavioral Inhibition to Food Cues among Binge Eating Disorder Symptomatic Women

    Directory of Open Access Journals (Sweden)

    Zhenyong Lyu

    2016-10-01

    Full Text Available Stressors can trigger binge-eating but researchers have yet to consider their effects on both neural responses to food cues and food consumption among those at risk. In this experiment, we examined the impact of acute stressors on neural activation to food images and subsequent food consumption within binge-eating disorder (BED and non-eating disordered control groups. Eighteen women meeting DSM-IV BED criteria and 26 women serving as non-eating disordered controls were randomly assigned to unpleasant stressor (painful cold pressor test followed by negative performance feedback or less unpleasant stressor (non-painful sensory discrimination task followed by positive performance feedback conditions. Subsequently, they were scanned with functional magnetic resonance imaging (fMRI while viewing food and neutral images. After the scans, participants completed a self-report battery in an environment conducive to snacking. During exposure to food images, BED-symptomatic women in the unpleasant stressor condition reported more liking of high calorie food images and showed less activation in one inhibitory area, the hippocampus, compared to controls in this condition. BED-symptomatic women exposed to unpleasant stressors also consumed more chocolate than any other group during the post-scan questionnaire completion. Crucially, reduced hippocampal activation to high calorie food images predicted more chocolate consumption following fMRI scans within the entire sample. This experiment provides initial evidence suggesting unpleasant acute stressors contribute to reduced inhibitory region responsiveness in relation to external food cues and later food consumption among BED-symptomatic women.

  5. Educational intervention for parents and healthcare providers leads to reduced antibiotic use in acute otitis media.

    Science.gov (United States)

    Småbrekke, Lars; Berild, Dag; Giaever, Anton; Myrbakk, Torni; Fuskevåg, Airin; Ericson, Johanna U; Flaegstad, Trond; Olsvik, Orjan; Ringertz, Signe H

    2002-01-01

    We used a controlled before-and-after design with the aims of reducing both the total consumption of antibiotics and the use of broad-spectrum antibiotics against acute otitis media (AOM), and to study to what extent prescriptions for antibiotics against AOM were dispensed. Information on evidence-based treatment of uncomplicated AOM was provided to doctors and nurses, and written guidelines were implemented. Pamphlets and oral information concerning symptomatic treatment and the limited effect of antibiotic use in AOM were given to parents. Eligible patients were 819 children aged 1-15 y. The proportion of patients receiving a prescription for antibiotics was reduced from 90% at baseline to 74% during the study period. The proportion of prescriptions for penicillin V increased from 72% at baseline to 85% during the study period. There were no significant changes at the control site. The proportion of dispensed prescriptions was 70% both at baseline and during the study period. Educational efforts reduced the total consumption of antibiotics and the use of broad-spectrum antibiotics for AOM in children aged 1-15 y at an emergency call service. Data on antibiotic use in AOM based only on prescribing overestimates the use of antibiotics.

  6. Simvastatin reduces endotoxin-induced acute lung injury by decreasing neutrophil recruitment and radical formation.

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    Jochen Grommes

    Full Text Available INTRODUCTION: Treatment of acute lung injury (ALI remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. METHODS: C57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. RESULTS: Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. CONCLUSION: Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

  7. Acute psychological stress reduces working memory-related activity in the dorsolateral prefrontal cortex.

    NARCIS (Netherlands)

    Qin, S.; Hermans, E.J.; Marle, H.J.F. van; Luo, J.; Fernandez, G.S.E.

    2009-01-01

    BACKGROUND: Acute psychological stress impairs higher-order cognitive function such as working memory (WM). Similar impairments are seen in various psychiatric disorders that are associated with higher susceptibility to stress and with prefrontal cortical dysfunctions, suggesting that acute stress

  8. Fibrosis Reduces Severity of Acute-on-Chronic Pancreatitis in Humans

    Science.gov (United States)

    Acharya, Chathur; Cline, Rachel A.; Jaligama, Deepthi; Noel, Pawan; Delany, James P.; Bae, Kyongtae; Furlan, Alessandro; Baty, Catherine J.; Karlsson, Jenny M.; Rosario, Bedda L; Patel, Krutika; Mishra, Vivek; Durgampudi, Chandra; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P.

    2013-01-01

    BACKGROUND & AIMS Acute pancreatitis (AP) and chronic pancreatitis (CP) share etiologies, but AP can be more severe and has higher mortality. We investigated features of CP that protect against severity. The amount of intra-pancreatic fat (IPF) is increased in obesity and fibrosis is increased in CP; so we studied whether fibrosis or fat regulate severity of AP attacks in patients with CP. METHODS We reviewed records from the University of Pittsburg Medical Center Autopsy database (1998–2008) for patients with diagnosed AP (n=23), CP (n=35), or both (AP-on-CP; n=15). Pancreatic histology samples from these patients and 50 randomly selected Controls (no pancreatic disease) were analyzed, and IPF data were correlated with computed tomography data. An adipocyte and acinar cell transwell co-culture system, with or without collagen Type-I (collagen-I), was used to study the effects of fibrosis on acinar-adipocyte interactions. We studied the effects of non-esterified fatty acids (NEFA) and adipokines on acinar cells in culture. RESULTS Levels of IPF were significantly higher among non-obese patients with CP than non-obese Controls. In CP or AP-on-CP, areas of IPF were surrounded by significantly more fibrosis than in Controls or patients with AP. Fat necrosis (FN)-associated peri-fat acinar necrosis (PFAN, indicated by NEFA spillage) contributed to most of the necrosis observed in AP samples; however, PFAN and total necrosis were significantly lower in samples from patients with CP and AP-on-CP. Fibrosis appeared to wall off the FN and limit PFAN, reducing acinar necrosis. In vitro, collagen-I limited the lipolytic flux between acinar cells and adipocytes and prevented increases in adipokines in the acinar compartment. This was associated with reduced acinar cell necrosis. However, NEFA, but not adipokines, caused acinar-cell necrosis. CONCLUSIONS Based on analysis of pancreatic samples from patients with CP, AP and AP-on-CP, and in vitro studies, fibrosis reduces the

  9. Front-end specialists reduce time to a treatment plan for patients with acute abdomen

    DEFF Research Database (Denmark)

    Schultz, Helen; Backer Mogensen, Christian; Pedersen, Birthe D

    2013-01-01

    Emergency departments (EDs) are replacing acute specialised wards in Denmark. The aim was to compare time to a treatment plan for patients with acute abdomen at a surgical assessment unit (SAU) and at an ED, respectively.......Emergency departments (EDs) are replacing acute specialised wards in Denmark. The aim was to compare time to a treatment plan for patients with acute abdomen at a surgical assessment unit (SAU) and at an ED, respectively....

  10. Front-end specialists reduce time to a treatment plan for patients with acute abdomen

    DEFF Research Database (Denmark)

    Schultz, Helen; Backer Mogensen, Christian; Pedersen, Birthe D

    2013-01-01

    Emergency departments (EDs) are replacing acute specialised wards in Denmark. The aim was to compare time to a treatment plan for patients with acute abdomen at a surgical assessment unit (SAU) and at an ED, respectively.......Emergency departments (EDs) are replacing acute specialised wards in Denmark. The aim was to compare time to a treatment plan for patients with acute abdomen at a surgical assessment unit (SAU) and at an ED, respectively....

  11. Bryostatin improves survival and reduces ischemic brain injury in aged rats following acute ischemic stroke

    Science.gov (United States)

    Tan, Zhenjun; Turner, Ryan C.; Leon, Rachel L.; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F.; Naser, Zachary J.; Alkon, Daniel L.; Rosen, Charles L.; Huber, Jason D.

    2014-01-01

    Background and Purpose Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer's disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator (tPA) reperfusion in aged rats. Methods Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18-20 month old female Sprague-Dawley rats using an autologous blood clot with tPA-mediated reperfusion. Bryostatin was administered at 6 h post-MCAO then at 3, 6, 9, 12, 15, and 18 d after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 d after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 d post-MCAO. Histological assessment of PKC isozymes was performed at 24 h post-MCAO. Results Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 d. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 d post-MCAO. Changes in PKC alpha expression and PKC epsilon expression in neurons were noted in bryostatin-treated rats at 24 h post-MCAO. Conclusions Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome following MCAO. PMID:24172582

  12. Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

    Science.gov (United States)

    Tan, Zhenjun; Turner, Ryan C; Leon, Rachel L; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F; Naser, Zachary J; Alkon, Daniel L; Rosen, Charles L; Huber, Jason D

    2013-12-01

    Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats. Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18- to 20-month-old female Sprague-Dawley rats using an autologous blood clot with tissue plasminogen activator-mediated reperfusion. Bryostatin was administered at 6 hours post-MCAO, then at 3, 6, 9, 12, 15, and 18 days after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 days after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 days post-MCAO. Histological assessment of PKC isozymes was performed at 24 hours post-MCAO. Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 days. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 days post-MCAO. Changes in αPKC expression and εPKC expression in neurons were noted in bryostatin-treated rats at 24 hours post-MCAO. Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome after MCAO.

  13. Homeopathic Ear Drops as an Adjunct in Reducing Antibiotic Usage in Children With Acute Otitis Media

    Directory of Open Access Journals (Sweden)

    James A. Taylor MD

    2014-11-01

    Full Text Available Objective. To determine if use of a homeopathic ear drop preparation reduces antibiotic use in children diagnosed with acute otitis media (AOM. Methods. Children 6 months to 11 years old, diagnosed with AOM and managed with a delayed antibiotic approach, were randomized to standard therapy alone or standard therapy plus a homeopathic ear drop preparation. The primary outcome was whether or not the antibiotic prescription given at the index visit was filled during a 12- to 15-day follow-up period. Results. Among 210 enrolled children, follow-up antibiotic data were collected on 206. During the 12- to 15-day follow-up period, fewer parents of children randomized to the homeopathic ear drops group filled the antibiotic prescription compared with those of children receiving standard therapy alone (26.9% and 41.2%, respectively, P = .032. Conclusion. Homeopathic ear drops may be effective in reducing the use of antibiotics in children with AOM managed with a delayed antibiotic approach.

  14. Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

    Science.gov (United States)

    Cheng, Shun-Yang; Chou, Yu-Hsiang; Liao, Fang-Ling; Lin, Chi-Chun; Chang, Fan-Chi; Liu, Chia-Hao; Huang, Tao-Min; Lai, Chun-Fu; Lin, Yu-Feng; Wu, Vin-Cent; Chu, Tzong-Shinn; Wu, Ming-Shiou; Lin, Shuei-Liong

    2016-01-01

    Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury. Despite functional recovery, focal tubular atrophy, interstitial cell infiltration and fibrosis, upregulation of genes encoding angiotensinogen and AT1a receptor were shown in kidneys 4 weeks after AKI. Thereafter mice manifested increase of blood pressure, albuminuria and azotemia progressively. Drinking water with or without losartan or hydralazine was administered to mice from 4 weeks after AKI. Increase of mortality, blood pressure, albuminuria, azotemia and kidney fibrosis was noted in mice with vehicle administration during the 5-month experimental period. On the contrary, these parameters in mice with losartan administration were reduced to the levels shown in control group. Hydralazine did not provide similar beneficial effect though blood pressure was controlled. These findings demonstrate that losartan can reduce ensuing CKD and mortality after functional recovery from AKI. PMID:27677327

  15. Whole-grain pasta reduces appetite and meal-induced thermogenesis acutely: a pilot study.

    Science.gov (United States)

    Cioffi, Iolanda; Santarpia, Lidia; Vaccaro, Andrea; Iacone, Roberto; Labruna, Giuseppe; Marra, Maurizio; Contaldo, Franco; Kristensen, Mette; Pasanisi, Fabrizio

    2016-03-01

    In epidemiological studies, the intake of foods rich in dietary fiber is associated with a reduced risk of developing overweight and type 2 diabetes. This work aims to identify acute strategies to regulate appetite and improve glucose control by using different pasta meals. Hence, 4 different isocaloric lunch meals, consisting of (i) refined-grain pasta (RG+T), (ii) whole-grain pasta (WG+T), (iii) lemon juice-supplemented refined-grain pasta (LRG+T), and (iv) refined-grain pasta with legumes (RG+L), were administered to 8 healthy participants in a crossover design. On the test days, participants underwent baseline measurements, including appetite sensation, blood sample, and resting energy expenditure (EE), after which the test lunch was served. Subjective appetite was assessed and a blood sample was taken each hour for 240 min, and postprandial EE was measured for 3 h. In repeated-measures analysis of covariance (ANCOVA), postprandial fullness (p = 0.001) increased and hunger (p = 0.038) decreased. WG+T had a lower EE than did both LGR+T (p = 0.02) and RG+L (p pasta may promote fullness and reduce hunger, lowering postprandial thermogenesis, and adding lemon juice to the pasta or legumes does not appear to affect appetite. However, none of pasta meal alterations improved the postprandial metabolic profile.

  16. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans.

    Science.gov (United States)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke; Lundby, Carsten; Olsen, Niels V; Secher, Niels H; van Lieshout, Johannes J

    2012-03-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic and cerebrovascular variables following acute (30,000 IU/d for 3 d; n=8) and chronic (5000 IU/week for 13 wk; n=8) administration of EPO, while the responsiveness of the vasculature was challenged during cycling exercise, with and without hypoxia. Prolonged administration of EPO increased hematocrit from 42.5 ± 3.7 to 47.6 ± 4.1% (PEPO administration. Yet, the two EPO regimes increased arterial pressure similarly (by 8±4 and 7±3 mmHg, respectively; P=0.01) through reduced vascular conductance (by 7±3 and 5±2%; PEPO regimes widened the arterial-to-jugular O(2) differences at rest as well as during normoxic and hypoxic exercise (PEPO to healthy humans lowers systemic and cerebral conductance independent of its effect on hematocrit.

  17. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Yuepeng Jin

    Full Text Available The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP. AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF. The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP.

  18. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    Science.gov (United States)

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials.

  19. Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization.

    Science.gov (United States)

    Yoo, Sun Hong; Jang, Jeong Won; Kwon, Jung Hyun; Jung, Seung Min; Jang, Bohyun; Choi, Jong Young

    2016-12-01

    Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. Our findings suggest that preemptive antiviral therapy significantly reduces the risk of

  20. Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans.

    Science.gov (United States)

    Palmer, Nicholette D; Lehtinen, Allison B; Langefeld, Carl D; Campbell, Joel K; Haffner, Steven M; Norris, Jill M; Bergman, Richard N; Goodarzi, Mark O; Rotter, Jerome I; Bowden, Donald W

    2008-01-01

    Genetic variation at the transcription factor 7-like 2 locus has been linked to type 2 diabetes in predominantly European-derived populations. The biological basis of these associations remains to be determined. The objective of this study was to evaluate previously associated variants for association with measures of glucose homeostasis in Hispanic-Americans and African-Americans and determine the biological mechanism(s) through which these variants exert their effect. This study was the Insulin Resistance Atherosclerosis Family Study (IRAS-FS). The IRAS-FS is a community-based study of Hispanic-Americans (San Antonio, TX, and San Luis Valley, CO) and African-Americans (Los Angeles, CA). A total of 1040 Hispanic-American and 500 African-American individuals from the IRAS-FS formed the basis of this study. MAIN OUTCOMES MEASURES(S): The primary glucose homeostasis phenotypes of interest in this study were derived from the frequently sampled iv glucose tolerance test and include insulin sensitivity, acute insulin response, and disposition index. In Hispanic-Americans, significant evidence of association was observed between single-nucleotide polymorphisms rs7903146 and rs112255372 with reduced insulin secretion as measured by acute insulin response and adjusted for the degree of insulin sensitivity (P = 0.032 and 0.036, respectively). Other quantitative measures, e.g. insulin sensitivity or disposition index, were not associated with the single nucleotide polymorphisms examined. In African-Americans there was no evidence of association observed. These results suggest that transcription factor 7-like 2 variants could play a role in the pathogenesis of type 2 diabetes in the Hispanic-American population through a mechanism involving insulin secretion.

  1. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

    Science.gov (United States)

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis. PMID:26218284

  2. Ghrelin reduces liver impairment in a model of concanavalin A-induced acute hepatitis in mice

    Directory of Open Access Journals (Sweden)

    Mao YQ

    2015-09-01

    Full Text Available Yuqing Mao,1 Jianbo Wang,2 Fujun Yu,1 Jian Cheng,1 Huanqing Li,1 Chuanyong Guo,3 Xiaoming Fan11Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai, 2Department of Gastroenterology and Hepatology, The Central Hospital of Lishui City, Wenzhou Medical University, Zhejiang, 3Department of Gastroenterology and Hepatology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of ChinaBackground and aims: Ghrelin is a 28-amino-acid gut hormone that was first discovered as a potent growth hormone secretagogue. Recently, it has been shown to exert a strong anti-inflammatory effect. The purpose of the study reported here was to explore the effect and mechanism of ghrelin on concanavalin (Con A-induced acute hepatitis.Methods: Balb/C mice were divided into four groups: normal control (NC (mice injected with vehicle [saline]; Con A (25 mg/kg; Con A + 10 µg/kg ghrelin; and Con A + 50 µg/kg ghrelin (1 hour before Con A injection. Pro-inflammatory cytokine levels were detected. Protein levels of phosphoinositide 3-kinase (PI3K; phosphorylated Akt (p-Akt; caspase 3, 8, and 9; and microtubule-associated protein 1 light chain 3 (LC3 were also detected. Perifosine (25 mM (an Akt inhibitor was used to investigate whether the protective effect of ghrelin was interrupted by an Akt inhibitor. Protein levels of p-AKT; Bcl-2; Bax; and caspase 3, 8, and 9 were also detected.Results: Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by ghrelin pretreatment in Con A-induced hepatitis. Inflammatory cytokines were significantly reduced by ghrelin pretreatment. Bcl-2; Bax; and caspase 3, 8, and 9 expression were also clearly affected by ghrelin pretreatment, compared with the Con A-treated group. However, the Akt kinase inhibitor reversed the decrease of Bax and caspase 3, 8, 9, and reduced the protein level of p-Akt and Bcl-2. Ghrelin

  3. Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents.

    Science.gov (United States)

    Parrish, Jennifer B; Teske, Jennifer A

    2017-01-01

    Chronic partial sleep deprivation (SD) by environmental noise exposure increases weight gain and feeding in rodents, which contrasts weight loss after acute SD by physical methods. This study tested whether acute environmental noise exposure reduced sleep and its effect on weight gain, food intake, physical activity, and energy expenditure (EE). It was hypothesized that acute exposure would (1) increase weight gain and feeding and (2) reduce sleep, physical activity, and EE (total and individual components); and (3) behavioral changes would persist throughout recovery from SD. Three-month old male Sprague-Dawley rats slept ad libitum, were noise exposed (12-h light cycle), and allowed to recover (36 h). Weight gain, food intake, sleep/wake, physical activity, and EE were measured. Acute environmental noise exposure had no effect on feeding, increased weight gain (P sleep (P sleep, rest, and physical activity reduce total EE and contribute to weight gain during acute SD and recovery from SD. These data emphasize the importance of increasing physical activity after SD to prevent obesity. © 2016 The Obesity Society.

  4. Pargyline reduces/prevents neuroleptic-induced acute dystonia in monkeys.

    Science.gov (United States)

    Heintz, R; Casey, D E

    1987-01-01

    The neuropharmacologic mechanisms underlying neuroleptic-induced extrapyramidal syndromes (EPS) were studied using a nonhuman primate model. Twenty-six Cebus albifrons monkeys were given weekly challenges of haloperidol (0.025 mg/kg IM), and half of the animals received the monoamine oxidase (MAO) inhibitor pargyline (5 mg/kg PO) daily for 17 consecutive days during the protocol. Pargyline caused no changes in baseline behaviors, but significantly reduced haloperidol-induced acute dystonia (AD) (-67%, P less than 0.002) and parkinsonism (-56%, P less than 0.005). The majority (8 of 13) of the experimental group had complete prevention of neuroleptic-induced EPS during cotreatment with pargyline. Behavioral scores returned to baseline levels after stopping pargyline, and did not show the further sensitization to haloperidol-induced AD that occurred in the control group. The possible mechanisms by which an MAO inhibitor might influence neuroleptic-induced AD were considered. The most likely explanation would appear to involve facilitation of striatal dopamine (DA) neurotransmission by inhibition of intra- and extraneuronal MAO, thus supporting the hypothesis that AD is due to decreased striatal DA function with secondary cholinergic hyperfunction.

  5. Successful treatment of acute myelogenous leukemia with favorable cytogenetics by reduced-intensity stem cell transplantation.

    Science.gov (United States)

    Kondo, Takeshi; Yasumoto, Atsushi; Arita, Kotaro; Sugita, Jun-Ichi; Shigematsu, Akio; Okada, Kohei; Takahata, Mutsumi; Onozawa, Masahiro; Kahata, Kaoru; Takeda, Yukari; Obara, Masato; Yamamoto, Satoshi; Endo, Tomoyuki; Nishio, Mitsufumi; Sato, Norihiro; Tanaka, Junji; Hashino, Satoshi; Koike, Takao; Asaka, Masahiro; Imamura, Masahiro

    2010-03-01

    Acute myelogenous leukemia (AML) with favorable cytogenetics responds well to chemotherapy. If the leukemia relapses, allogenic hematopoietic stem transplantation (allo-HSCT) is considered as a treatment option. Since the efficacy of reduced-intensity stem cell transplantation (RIST) for AML with favorable cytogenetics has not been established, we retrospectively analyzed the outcomes of allo-HSCT in AML patients according to cytogenetic risks. The outcome of allo-HSCT for AML patients with favorable cytogenetics seemed to be superior to that for AML patients with intermediate cytogenetics. In AML patients with favorable cytogenetics, the 3-year overall survival (OS) and relapse-free survival (RFS) rates were 88 and 76%, respectively, in the RIST group. Both the 3-year OS and RFS rates were 81% in the conventional stem cell transplantation (CST) group. The outcome of RIST for AML patients with favorable cytogenetics was comparable to that for patients who received CST despite the more advanced age and greater organ dysfunction in RIST group than in CST group. None of the patients died within 90 days after RIST. Moreover, there was no relapse in patients with favorable cytogenetics who were in hematological remission prior to RIST. Thus, RIST for AML patients with favorable cytogenetics in remission is safe and effective.

  6. Effectiveness of a multifactorial handwashing program to reduce school absenteeism due to acute gastroenteritis.

    Science.gov (United States)

    Azor-Martínez, Ernestina; Cobos-Carrascosa, Elena; Gimenez-Sanchez, Francisco; Martínez-López, Jose Miguel; Garrido-Fernández, Pablo; Santisteban-Martínez, Joaquin; Seijas-Vazquez, Maria Luisa; Campos-Fernandez, Maria Amparo; Bonillo-Perales, Antonio

    2014-02-01

    Acute gastroenteritis (AGE) is one of the most common diseases among children and an important cause of school absenteeism. The aim of this study was to assess the effectiveness of a handwashing program using hand sanitizers for the prevention of school absenteeism due to AGE. A randomized, controlled and open study of a sample of 1341 children between 4 and 12 years of age, attending 5 state schools in Almería (Spain), with an 8-month follow up (academic year). The experimental group (EG) washed their hands with soap and water, complementing this with the use of a hand sanitizer, and the control group (CG) followed the usual handwashing procedure. Absenteeism rates due GI were compared between the 2 groups through the multivariate Poisson regression analysis. Percent days absent in both groups were compared with a Z-test. 446 cases of school absenteeism due to AGE were registered. The school children from the EG had a 36% lower risk of absenteeism due to AGE (IRR: 0.64, 95% confidence interval: 0.52-0.78) and a decrease in absenteeism of 0.13 episodes/child/academic year (0.27 of EG vs 0.40 CG/episodes/child/academic year, P soap is an efficient measure to reduce absent days and the number of school absenteeism cases due to AGE.

  7. Acute appendicitis: Is removal of a normal appendix still existing and can we reduce its rate?

    Directory of Open Access Journals (Sweden)

    Khairy Gamal

    2009-01-01

    Full Text Available Background/Aim: To determine the incidence of negative appendectomies and to identify factors that may reduce the risk of having the normal appendices removed surgically. Design: Cross-sectional study. Setting: College of Medicine and King Khalid University Hospital, Riyadh, Saudi Arabia. Materials and Methods: The surgical and histological data of 852 patients who underwent appendicectomy were reviewed. All incidental or interval appendicectomies were excluded. Only patients who were admitted and whose appendices were removed and subjected to histology were included (585 patients. The data on patients who had a normal appendix on histology further analyzed to include demographics, specific investigations, operative findings of the appendix and additional operative findings that need other surgical procedures. Results: A normal appendix was removed in 54 (9.2% of the patients. Only 5.5% of those patients had a computed tomography (CT scan preoperatively and 3.7% had diagnostic laparoscopy. In 21 patients, additional operative and histological findings were obtained that might have caused the right lower abdominal pain. Conclusion: In spite of the advances in the diagnostic and imaging techniques, the rates of negative findings on appendicectomy have not decreased much. Clinical judgment is still the most important factor in the management of patients with suspected acute appendicitis. The routine use of CT scan or diagnostic laparoscopy for all patients who are suspected to have appendicitis is neither cost-effective nor safe.

  8. Consumption of an acute dose of caffeine reduces acquisition but not memory in the honey bee.

    Science.gov (United States)

    Mustard, Julie A; Dews, Lauren; Brugato, Arlana; Dey, Kevin; Wright, Geraldine A

    2012-06-15

    Caffeine affects several molecules that are also involved in the processes underlying learning and memory such as cAMP and calcium. However, studies of caffeine's influence on learning and memory in mammals are often contradictory. Invertebrate model systems have provided valuable insight into the actions of many neuroactive compounds including ethanol and cocaine. We use the honey bee (Apis mellifera) to investigate how the ingestion of acute doses of caffeine before, during, and after conditioning influences performance in an appetitive olfactory learning and memory task. Consumption of caffeine doses of 0.01 M or greater during or prior to conditioning causes a significant reduction in response levels during acquisition. Although bees find the taste of caffeine to be aversive at high concentrations, the bitter taste does not explain the reduction in acquisition observed for bees fed caffeine before conditioning. While high doses of caffeine reduced performance during acquisition, the response levels of bees given caffeine were the same as those of the sucrose only control group in a recall test 24h after conditioning. In addition, caffeine administered after conditioning had no affect on recall. These results suggest that caffeine specifically affects performance during acquisition and not the processes involved in the formation of early long term memory.

  9. Nanoparticles of Zinc Oxide Reduces Acute Somatic Pain in Adult Female Wistar Rats

    Directory of Open Access Journals (Sweden)

    Mahnaz Kesmati

    2014-06-01

    Full Text Available Background: With appearance of nano particles as an important component in modern medicine, and considering to new properties of these components, study of their effects on human health is essential. Since zinc components influences mechanisms of nociception, the aim of this study was to evaluate the effect of nano zinc oxide as a new source of zinc and important components in pharmaceutical and hygienic cosmetic production on nociception in adult female rats. Materials and Methods: Female rats were divided into groups: control (receiving saline 0.9% and receiving nano ZnO (0.5, 1, and 5 mg/kg. Hot plate and tail flick tests as models of somatic acute pain were used for evaluation of the pain. The mean of latency time in paw licking and tail withdrawal respectively recorded as nociception indexes in each test for every animal. The animal numbers in each group was seven. Results: In tail flick test, nano ZnO (0.5, 1 mg/kg and in the hot plate test in dose of 0.5 mg/kg, induces significant analgesia (p<0.05 and with increasing of dose reduced its analgesic effect. Conclusion: It seems nano ZnO inhibit the nociception mechanisms and these analgesic properties are more efficient in the low doses. Probably by increasing dose of nano particles aggregation phenomenon prevent of anti-nociception effects of nano ZnO.

  10. Generalization of the Right Acute Stroke Prevention Strategies in Reducing in-Hospital Delays.

    Directory of Open Access Journals (Sweden)

    Qiang Huang

    Full Text Available The aim of this study was to reduce the door-to-needle (DTN time of intravenous thrombolysis (IVT in acute ischemic stroke (AIS through a comprehensive, hospital-based implementation strategy. The intervention involved a systemic literature review, identifying barriers to rapid IVT treatment at our hospital, setting target DTN time intervals, and building an evolving model for IVT candidate selection. The rate of non-in-hospital delay (DTN time ≤ 60 min was set as the primary endpoint. A total of 348 IVT cases were enrolled in the study (202 and 146 in the pre- and post-intervention group, respectively. The median age was 61 years in both groups; 25.2% and 26.7% of patients in the pre- and post-intervention groups, respectively, were female. The post-intervention group had higher rates of dyslipidemia and minor stroke [defined as National Institutes of Health Stroke Scale (NIHSS ≤ 3]; less frequent atrial fibrillation; higher numbers of current smokers, heavy drinkers, referrals, and multi-model head imaging cases; and lower NIHSS scores and blood sugar level (all P 0.05. These findings indicate that it is possible to achieve a DTN time ≤ 60 min for up to 60% of hospitals in the current Chinese system, and that this logistical change can yield a notable improvement in the outcome of IVT patients.

  11. Point-of-care procalcitonin test to reduce antibiotic exposure in patients hospitalized with acute exacerbation of COPD

    DEFF Research Database (Denmark)

    Corti, Caspar; Fally, Markus; Fabricius-Bjerre, Andreas

    2016-01-01

    BACKGROUND: This study was conducted to investigate whether point-of-care (POC) procalcitonin (PCT) measurement can reduce redundant antibiotic treatment in patients hospitalized with acute exacerbation of COPD (AECOPD). METHODS: One-hundred and twenty adult patients admitted with AECOPD were enr...

  12. Oral glutamate intake reduces acute and chronic effects of ethanol in ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights ... Oral treatment with 2.5 g/kg of glutamate reversed the acute motor effects of .... error of means (SEM). For the acute .... a clinical review.

  13. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    Science.gov (United States)

    Scott, Bart L; Pasquini, Marcelo C; Logan, Brent R; Wu, Juan; Devine, Steven M; Porter, David L; Maziarz, Richard T; Warlick, Erica D; Fernandez, Hugo F; Alyea, Edwin P; Hamadani, Mehdi; Bashey, Asad; Giralt, Sergio; Geller, Nancy L; Leifer, Eric; Le-Rademacher, Jennifer; Mendizabal, Adam M; Horowitz, Mary M; Deeg, H Joachim; Horwitz, Mitchell E

    2017-04-10

    Purpose The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) is unknown. We hypothesized that lower treatment-related mortality (TRM) with reduced-intensity conditioning (RIC) would result in improved overall survival (OS) compared with myeloablative conditioning (MAC). To test this hypothesis, we performed a phase III randomized trial comparing MAC with RIC in patients with acute myeloid leukemia or myelodysplastic syndromes. Patients and Methods Patients age 18 to 65 years with HCT comorbidity index ≤ 4 and < 5% marrow myeloblasts pre-HCT were randomly assigned to receive MAC (n = 135) or RIC (n = 137) followed by HCT from HLA-matched related or unrelated donors. The primary end point was OS 18 months post-random assignment based on an intent-to-treat analysis. Secondary end points included relapse-free survival (RFS) and TRM. Results Planned enrollment was 356 patients; accrual ceased at 272 because of high relapse incidence with RIC versus MAC (48.3%; 95% CI, 39.6% to 56.4% and 13.5%; 95% CI, 8.3% to 19.8%, respectively; P < .001). At 18 months, OS for patients in the RIC arm was 67.7% (95% CI, 59.1% to 74.9%) versus 77.5% (95% CI, 69.4% to 83.7%) for those in the MAC arm (difference, 9.8%; 95% CI, -0.8% to 20.3%; P = .07). TRM with RIC was 4.4% (95% CI, 1.8% to 8.9%) versus 15.8% (95% CI, 10.2% to 22.5%) with MAC ( P = .002). RFS with RIC was 47.3% (95% CI, 38.7% to 55.4%) versus 67.8% (95% CI, 59.1% to 75%) with MAC ( P < .01). Conclusion OS was higher with MAC, but this was not statistically significant. RIC resulted in lower TRM but higher relapse rates compared with MAC, with a statistically significant advantage in RFS with MAC. These data support the use of MAC as the standard of care for fit patients with acute myeloid leukemia or myelodysplastic syndromes.

  14. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction

    DEFF Research Database (Denmark)

    Pedersen, O D; Bagger, H; Køber, Lars Valeur;

    1999-01-01

    BACKGROUND: Studies have suggested that ACE inhibitors have an antiarrhythmic effect on ventricular arrhythmias. Whether they have an effect on atrial fibrillation is unknown. METHODS AND RESULTS: We investigated the effect of ACE inhibition with trandolapril on the incidence of atrial fibrillation...... of atrial fibrillation in patients with left ventricular dysfunction after acute myocardial infarction....... in patients with reduced left ventricular function secondary to acute myocardial infarction. The patients in this study were those who qualified for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study, a randomized double-blind placebo-controlled study and who had sinus rhythm on the ECG obtained...

  15. Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment.

    Science.gov (United States)

    Garibaldi, Brian T; D'Alessio, Franco R; Mock, Jason R; Files, D Clark; Chau, Eric; Eto, Yoshiki; Drummond, M Bradley; Aggarwal, Neil R; Sidhaye, Venkataramana; King, Landon S

    2013-01-01

    Acute lung injury (ALI) causes significant morbidity and mortality. Fibroproliferation in ALI results in worse outcomes, but the mechanisms governing fibroproliferation remain poorly understood. Regulatory T cells (Tregs) are important in lung injury resolution. Their role in fibroproliferation is unknown. We sought to identify the role of Tregs in ALI fibroproliferation, using a murine model of lung injury. Wild-type (WT) and lymphocyte-deficient Rag-1(-/-) mice received intratracheal LPS. Fibroproliferation was characterized by histology and the measurement of lung collagen. Lung fibrocytes were measured by flow cytometry. To dissect the role of Tregs in fibroproliferation, Rag-1(-/-) mice received CD4(+)CD25(+) (Tregs) or CD4(+)CD25(-) Tcells (non-Tregs) at the time of LPS injury. To define the role of the chemokine (C-X-C motif) ligand 12 (CXCL12)-CXCR4 pathway in ALI fibroproliferation, Rag-1(-/-) mice were treated with the CXCR4 antagonist AMD3100 to block fibrocyte recruitment. WT and Rag-1(-/-) mice demonstrated significant collagen deposition on Day 3 after LPS. WT mice exhibited the clearance of collagen, but Rag-1(-/-) mice developed persistent fibrosis. This fibrosis was mediated by the sustained epithelial expression of CXCL12 (or stromal cell-derived factor 1 [SDF-1]) that led to increased fibrocyte recruitment. The adoptive transfer of Tregs resolved fibroproliferation by decreasing CXCL12 expression and subsequent fibrocyte recruitment. Blockade of the CXCL12-CXCR4 axis with AMD3100 also decreased lung fibrocytes and fibroproliferation. These results indicate a central role for Tregs in the resolution of ALI fibroproliferation by reducing fibrocyte recruitment along the CXCL12-CXCR4 axis. A dissection of the role of Tregs in ALI fibroproliferation may inform the design of new therapeutic tools for patients with ALI.

  16. New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure.

    Directory of Open Access Journals (Sweden)

    Nélson R Carvalho

    Full Text Available The acute liver failure (ALF induced by acetaminophen (APAP is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe2], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe2 to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe2 to the N-acetylcysteine (NAC during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg, (PhSe2 (15.6 mg/kg, NAC (1200 mg/kg, APAP+(PhSe2 or APAP+NAC, where the (PhSe2 or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe2. The effectiveness of (PhSe2 was similar at a lower dose than NAC. In summary, (PhSe2 provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.

  17. Coffee reduces the risk of death after acute myocardial infarction: a meta-analysis.

    Science.gov (United States)

    Brown, Oliver I; Allgar, Victoria; Wong, Kenneth Y-K

    2016-11-01

    Habitual coffee consumption is protective against coronary heart disease in women; however, it is not clear whether such cardioprotection is conferred on those who have already experienced an acute myocardial infarction (AMI). Our aim was to investigate whether coffee consumption affected mortality after AMI. We carried out a dose-response meta-analysis of prospective studies that examined the relationship between coffee intake and mortality after an AMI. Using a defined-search strategy, electronic databases (MEDLINE and Embase) were searched for papers published between 1946 and 2015. Two eligible studies investigating post-AMI mortality risk against coffee consumption were identified and assessed using set criteria. Combined, these studies recruited a total of 3271 patients and 604 died. The hazard ratios for the following experimental groups were defined: light coffee drinkers (1-2 cups/day) versus noncoffee drinkers, heavy coffee drinkers (>2 cups/day) versus noncoffee drinkers and heavy coffee drinkers versus light coffee drinkers. A statistically significant inverse correlation was observed between coffee drinking and mortality; all three groups showed a significant reduction in risk ratio. Light coffee drinkers versus noncoffee drinkers were associated with a risk ratio of 0.79 [95% confidence interval (CI): 0.66-0.94, P=0.008]; heavy coffee drinkers versus noncoffee drinkers were associated with a risk ratio of 0.54 (95% CI: 0.45-0.65, Pcoffee drinkers versus light coffee drinkers were associated with a risk ratio of 0.69 (95% CI: 0.58-0.83, Pcoffee habitually following AMI was associated with a reduced risk of mortality.

  18. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia

    NARCIS (Netherlands)

    Meijers, JCM; Oudijk, EJD; Mosnier, LO; Nieuwenhuis, HK; Fijnheer, R; Bouma, Bonno N.; Bos, R

    Acute promyelocytic leukaemia (APL) is a disease that is distinguished from other leukaemias by the high potential for early haemorrhagic death. Several processes are involved, such as disseminated intravascular coagulation and hyperfibrinolysis. Recently, TAFI (thrombin-activatable fibrinolysis

  19. Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response

    NARCIS (Netherlands)

    van den Goor, J.; Nieuwland, R.; van den Brink, A.; van Oeveren, W.; Rutten, 27818; Tijssen, J.; Eijsman, L.; Rutten, P

    2004-01-01

    Objective: In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated-

  20. Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media.

    Science.gov (United States)

    Hoberman, Alejandro; Paradise, Jack L; Rockette, Howard E; Jeong, Jong-Hyeon; Kearney, Diana H; Bhatnagar, Sonika; Shope, Timothy R; Muñiz, Gysella; Martin, Judith M; Kurs-Lasky, Marcia; Haralam, MaryAnn; Pope, Marcia A; Nagg, Jennifer P; Zhao, Wenchen; Miah, Mohammad Kowser; Beumer, Jan; Venkataramanan, Raman; Shaikh, Nader

    2017-07-01

    Amoxicillin-clavulanate (A/C) is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but the standard dosage of 90 mg amoxicillin/6.4 mg clavulanate/kg of body weight/day commonly causes diarrhea. We examined whether an A/C formulation containing lower concentrations of clavulanate would result in less diarrhea while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to achieve clinical success. We conducted an open-label study in children with AOM who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced-clavulanate A/C formulation providing 90 mg amoxicillin/3.2 mg clavulanate/kg/day for 10 days. In phase 2, we treated 72 children with the same formulation at a dosage of 80 mg amoxicillin/2.85 mg clavulanate/kg/day for 10 days. We compared the rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical response in these children with rates we had reported in children who received the standard A/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving phase 2 and standard regimens were 17% and 26%, respectively (P = 0.10). The corresponding rates of diaper dermatitis were 21% and 33% (P = 0.04) and of AOM treatment failure were 12% and 16% (P = 0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit β-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side effects without reducing clinical efficacy. (This study has been registered at ClinicalTrials.gov under registration no. NCT02630992.). Copyright © 2017 American Society for Microbiology.

  1. Reducing Inappropriate Antibiotic Prescribing for Adults With Acute Bronchitis in an Urgent Care Setting: A Quality Improvement Initiative.

    Science.gov (United States)

    Link, Tamara L; Townsend, Mary L; Leung, Eugene; Kommu, Sekhar; Vega, Rhonda Y; Hendrix, Cristina C

    Acute bronchitis is a predominantly viral illness and, according to clinical practice guidelines, should not be treated with antibiotics. Despite clear guidelines, acute bronchitis continues to be the most common acute respiratory illness for which antibiotics are incorrectly prescribed. Although the national benchmark for antibiotic prescribing for adults with acute bronchitis is 0%, a preliminary record review before implementing the intervention at the project setting showed that 96% (N = 30) of adults with acute bronchitis in this setting were prescribed an antibiotic. This quality improvement project utilized a single-group, pre-post design. The setting for this project was a large urgent care network with numerous locations in central North Carolina. The purpose was to determine whether nurse practitioners and physician assistants, after participating in a multifaceted provider education session, would reduce inappropriate antibiotic prescribing for healthy adults with acute uncomplicated bronchitis. Twenty providers attended 1 of 4 training sessions offered in October and November 2015. The face-to-face interactive training sessions focused on factors associated with inappropriate antibiotic prescribing, current clinical practice guidelines, and patient communication skills. Retrospective medical record review of 217 pretraining and 335 posttraining encounters for acute bronchitis by 19 eligible participating providers demonstrated a 61.9% reduction in immediate antibiotic prescribing from 91.7% to 29.8%. Delayed prescribing, which accounted for a small percentage of the total prescriptions given, had a small but significant increase of 9.3% after training. Overall, this multifaceted, interactive provider training resulted in significant reductions in inappropriate prescriptions.

  2. Urgent ERCP for acute cholangitis reduces mortality and hospital stay in elderly and very elderly patients

    Institute of Scientific and Technical Information of China (English)

    Chan Sun Park; Hee Seok Jeong; Ki Bae Kim; Joung-Ho Han; Hee Bok Chae; Sei Jin Youn; Seon Mee Park

    2016-01-01

    BACKGROUND: Acute cholangitis in old people is a cause of mortality and prolonged hospital stay. We evaluated the effects of methods and timing of biliary drainage on the outcomes of acute cholangitis in elderly and very elderly patients. METHODS: We analyzed 331 patients who were older than 75 years and were diagnosed with acute calculous cholangitis. They were admitted to our hospital from 2009 to 2014. Pa-tients’ demographics, severity grading, methods and timing of biliary drainage, mortality, and hospital stay were retrospec-tively obtained from medical records. Clinical parameters and outcomes were compared between elderly (75-80 years,n=156) and very elderly (≥81 years,n=175) patients. We analyzed the effects of methods [none, endoscopic retrograde cholangio-pancreatography (ERCP), percutaneous transhepatic biliary drainage, or failure] and timing (urgent or early) of biliary drainage on mortality and hospital stay in these patients. RESULTS: Acute cholangitis in older patients manifested as atypical symptoms characterized as infrequent Charcot’s triad (4.2%) and comorbidity in one-third of the patients. Patients were graded as mild, moderate, and severe cholangitis in 104 (31.4%), 175 (52.9%), and 52 (15.7%), respectively. Urgent bili-ary drainage (≤24 hours) was performed for 80.5% (247/307) of patients. Very elderly patients tended to have more severe grades and were treated with sequential procedures of tran-sient biliary drainage and stone removal at different sessions. Hospital stay was related to methods and timing of biliary drainage. Mortality was very low (1.5%) and not related to patient age but rather to the success or failure of biliary drainage and severity grading of the acute cholangitis. CONCLUSIONS: The methods and timing used for biliary drainage and severity of cholangitis are the major determi-nants of mortality and hospital stay in elderly and very elderly patients with acute cholangitis. Urgent successful ERCP is mandatory for

  3. Experience based co-design reduces formal complaints on an acute mental health ward.

    Science.gov (United States)

    Springham, Neil; Robert, Glenn

    2015-01-01

    An acute mental health triage ward at Oxleas NHS Foundation Trust was attracting high levels of formal service user and family complaints. The Trust used experience based co-design to examine the issues and redesign procedures. This resulted in an immediate eradication of formal complaints for a period of 23 months. This paper describes two outcomes: firstly, the successful adaptations made to the experience based co-design methodology from its origins in physical care, in order to ensure it was safe and effective in an acute mental health setting; and, secondly, the changes made to the ward as a result of this quality improvement intervention.

  4. Neovestitol, an isoflavonoid isolated from Brazilian red propolis, reduces acute and chronic inflammation: involvement of nitric oxide and IL-6

    Science.gov (United States)

    Franchin, Marcelo; Colón, David F.; da Cunha, Marcos G.; Castanheira, Fernanda V. S.; Saraiva, André L. L.; Bueno-Silva, Bruno; Alencar, Severino M.; Cunha, Thiago M.; Rosalen, Pedro L.

    2016-01-01

    Isoflavonoids have been largely studied due to their distinct biological activities identified thus far. Herein, we evaluated the activity of neovestitol, an isoflavonoid isolated from Brazilian red propolis, in acute and chronic inflammation. As for acute inflammation, we found that neovestitol reduced neutrophil migration, leukocyte rolling and adhesion, as well as expression of ICAM-1 in the mesenteric microcirculation during lipopolysaccharide-induced acute peritonitis. No changes were observed in the levels of TNF-α, CXCL1/KC and CXCL2/MIP-2 upon pretreatment with neovestitol. The administration of an inducible nitric oxide synthase (iNOS) inhibitor abolished the inhibitory effects of neovestitol in neutrophil migration and ICAM-1 expression. Nitrite levels increased upon treatment with neovestitol. No effects of neovestitol were observed on the chemotaxis of neutrophils in vitro. As for chronic inflammation, neovestitol also reduced the clinical score and joint damage in a collagen-induced arthritis model. There was no change in the frequency of IL-17-producing TCD4+ cells. In addition, pretreatment with neovestitol reduced the levels of IL-6. These results demonstrate a potential anti-inflammatory activity of neovestitol, which may be useful for therapeutic purposes and/or as a nutraceutical. PMID:27819273

  5. Neovestitol, an isoflavonoid isolated from Brazilian red propolis, reduces acute and chronic inflammation: involvement of nitric oxide and IL-6.

    Science.gov (United States)

    Franchin, Marcelo; Colón, David F; da Cunha, Marcos G; Castanheira, Fernanda V S; Saraiva, André L L; Bueno-Silva, Bruno; Alencar, Severino M; Cunha, Thiago M; Rosalen, Pedro L

    2016-11-07

    Isoflavonoids have been largely studied due to their distinct biological activities identified thus far. Herein, we evaluated the activity of neovestitol, an isoflavonoid isolated from Brazilian red propolis, in acute and chronic inflammation. As for acute inflammation, we found that neovestitol reduced neutrophil migration, leukocyte rolling and adhesion, as well as expression of ICAM-1 in the mesenteric microcirculation during lipopolysaccharide-induced acute peritonitis. No changes were observed in the levels of TNF-α, CXCL1/KC and CXCL2/MIP-2 upon pretreatment with neovestitol. The administration of an inducible nitric oxide synthase (iNOS) inhibitor abolished the inhibitory effects of neovestitol in neutrophil migration and ICAM-1 expression. Nitrite levels increased upon treatment with neovestitol. No effects of neovestitol were observed on the chemotaxis of neutrophils in vitro. As for chronic inflammation, neovestitol also reduced the clinical score and joint damage in a collagen-induced arthritis model. There was no change in the frequency of IL-17-producing TCD4+ cells. In addition, pretreatment with neovestitol reduced the levels of IL-6. These results demonstrate a potential anti-inflammatory activity of neovestitol, which may be useful for therapeutic purposes and/or as a nutraceutical.

  6. New standardized nursing cooperation workflow to reduce stroke thrombolysis delays in patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Zhou Y

    2017-05-01

    Full Text Available Yan Zhou,1 Zhuojun Xu,2 Jiali Liao,1 Fangming Feng,1 Lai Men,3 Li Xu,2 Yanan He,2 Gang Li2 1Nursing Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 2Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Paddington Dental Practice, London, UK Objective: We assessed the effectiveness of a new standardized nursing cooperation workflow in patients with acute ischemic stroke (AIS to reduce stroke thrombolysis delays.Patients and methods: AIS patients receiving conventional thrombolysis treatment from March to September 2015 were included in the control group, referred to as T0. The intervention group, referred to as T1 group, consisted of AIS patients receiving a new standardized nursing cooperation workflow for intravenous thrombolysis (IVT at the emergency department of Shanghai East Hospital (Shanghai, People’s Republic of China from October 2015 to March 2016. Information was collected on the following therapeutic techniques used: application or not of thrombolysis, computed tomography (CT time, and door-to-needle (DTN time. A nursing coordinator who helped patients fulfill the medical examinations and diagnosis was appointed to T1 group. In addition, a nurse was sent immediately from the stroke unit to the emergency department to aid the thrombolysis treatment.Results: The average value of the door-to-CT initiation time was 38.67±5.21 min in the T0 group, whereas it was 14.39±4.35 min in the T1 group; the average values of CT completion-to-needle time were 55.06±4.82 and 30.26±3.66 min; the average values of DTN time were 100.43±6.05 and 55.68±3.62 min, respectively; thrombolysis time was improved from 12.8% (88/689 in the T0 group to 32.5% (231/712 in the T1 group (all P<0.01. In addition, the new standardized nursing cooperation workflow decreased the National Institutes of Health Stroke Scale (NIHSS scores at 24 h (P<0

  7. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the red

  8. Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation

    NARCIS (Netherlands)

    Oliveira, M.C.; Silveira, A.L.; Tavares, L.P.; Rodrigues, D.F.; Loo, F.A.J. van de; Sousa, L.P.; Teixeira, M.M.; Amaral, F.A.; Ferreira, A.V.

    2017-01-01

    OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known a

  9. Reduced occurrence of atrial fibrillation in acute myocardial infarction treated with streptokinase

    DEFF Research Database (Denmark)

    Nielsen, F E; Sørensen, H T; Christensen, J H

    1991-01-01

    In a historical follow-up study of 152 hospital patients with acute myocardial infarction, the frequency of life-threatening arrhythmias (ventricular fibrillation, sustained ventricular tachycardia, 3rd degree AV-block, 2nd degree AV-block (Mobitz type II), and asystole) and atrial fibrillation...

  10. Cortisol acutely reduces selective attention for erotic words in healthy young men.

    Science.gov (United States)

    Putman, Peter; Berling, Sylvia

    2011-10-01

    Psychological stress prompts activity of the hypothalamic-pituitary-adrenal (HPA) axis resulting in increased release of cortisol. Long-term HPA aberrations have been observed for stress-related affective disorders but research into acute effects of cortisol on affect-regulation has only recently begun. Previous studies reported that exogenous cortisol acutely attenuated automatic attentional processing of task-irrelevant threatening information. This has been taken to suggest that cortisol may have acute anxiolytic properties, possibly through facilitating inhibition of threatening information. However, the role of cortisol in attentional inhibition of non-threatening arousing stimuli remained unclear. Therefore acute effects of 40 mg cortisol on performance of a masked and unmasked emotional Stroop task (EST) were assessed. Results for only the unmasked task demonstrated EST interference (interpreted as increased automatic attention) for erotic stimuli which was abolished by cortisol administration. This implies that effects of cortisol may not be restricted to attenuation of specifically anxiogenic information processing, as previously suggested. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Treatment with intravenous thrombolysis in acute ischemic stroke is associated with reduced bed day use

    DEFF Research Database (Denmark)

    Terkelsen, Thorkild; Schmitz, Marie Louise; Simonsen, Claus Z.

    2015-01-01

    Introduction: Several studies have demonstrated the beneficial effects of intravenous tissue-type plasminogen activator (IV-tPA) on neurological outcome in acute ischemic stroke. It is uncertain whether the improved neurological outcome also translates into less morbidity and lower need for hospi...

  12. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L.; Wehner, Peder S.

    2017-01-01

    with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C...

  13. Reduced plasma noradrenaline during angiotensin II-induced acute hypertension in man

    DEFF Research Database (Denmark)

    Henriksen, J H; Kastrup, J; Christensen, N J

    1985-01-01

    .005) and similarly to the decrease obtained with ANG II infusion. 4. The results indicate that a decrease in sympathoadrenal activity occurs during ANG II-induced acute hypertension in man. This may be elicited by the arterial baroreflex, which seems to dominate any direct sympathoadrenergic facilitating effect...

  14. Acute reduction of lipolysis reduces adiponectin and IL-18:evidence from an intervention study with acipimox and nsulin

    DEFF Research Database (Denmark)

    Lindegaard, B.; Ditlevsen, Susanne; Plomgaard, P.;

    2013-01-01

    and plasma IL-18 were reduced during both situations where lipolysis was inhibited (p TNF-α did not change during low NEFA concentrations...... assessed whether (1) overnight administration of a low dose of acipimox and/or (2) insulin-induced suppression of NEFA flux altered circulating plasma levels of adiponectin, IL-18, TNF-α and IL-6 in the basal condition and in a two-stage euglycaemic–hyperinsulinaemic clamp combined with stable isotopes....... Conclusions/interpretation Using two different tools to manipulate lipolysis, the present study found that acute inhibition of lipolysis reduces levels of adiponectin and IL-18 in patients with HIV-associated lipodystrophy....

  15. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo.

    Science.gov (United States)

    Chan, Michael C W; Kuok, Denise I T; Leung, Connie Y H; Hui, Kenrie P Y; Valkenburg, Sophie A; Lau, Eric H Y; Nicholls, John M; Fang, Xiaohui; Guan, Yi; Lee, Jae W; Chan, Renee W Y; Webster, Robert G; Matthay, Michael A; Peiris, J S Malik

    2016-03-29

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

  16. Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs.

    Science.gov (United States)

    Uemura, Kazunori; Inagaki, Masashi; Zheng, Can; Kawada, Toru; Li, Meihua; Fukumitsu, Masafumi; Sugimachi, Masaru

    2017-04-01

    Ivabradine, a bradycardic agent, has been shown to stably reduce patient's heart rate (HR) in the setting of acute cardiac care. However, an association between atrial fibrillation (AF) risk and acute ivabradine treatment remains a controversial clinical issue, and has not been thoroughly investigated. Bradycardia and abnormal atrial refractoriness induced by ivabradine treatment may enhance vulnerability to AF induction, especially when vagal nerve is concurrently activated. We aimed to experimentally investigate the effects of acute ivabradine treatment with/without concurrent vagal activation on AF inducibility. In 16 anesthetized dogs, cervical vagal nerves were prepared for electrical stimulation (VS). AF induction rate (AFIR) was determined by atrial burst pacing. HR, atrial action potential duration (APD), atrial effective refractory period (ERP), and AFIR were obtained consecutively at baseline, during delivery of VS (VS alone), after intravenous injection of ivabradine 0.5 mg/kg (n = 8, ivabradine group) or saline (n = 8, saline group), and again during VS delivery (drug+VS). In the ivabradine group, ivabradine alone significantly lowered HR compared to baseline, while ivabradine+VS significantly lowered HR compared to VS alone. Contrary to expectations, there were no significant differences in trends of APD, temporal dispersion of APD, ERP, and AFIR between ivabradine and saline groups. Irrespective of whether ivabradine or saline was injected, VS significantly shortened APD and ERP, and increased AFIR. Interestingly, although bradycardia in response to ivabradine injection was more intense than that to VS alone, AFIR was significantly lower after ivabradine injection than during VS alone. We conclude that, despite its intense bradycardic effect, acute ivabradine treatment does not increase AF inducibility irrespective of underlying vagal activity. This study may constitute support for the safety of using ivabradine in the setting of acute cardiac

  17. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

    Institute of Scientific and Technical Information of China (English)

    Mohammad Shahandeh; Valiollah Dabidi Roshan; Somayeh Hosseinzadeh; Soleiman Mahjoub; Vaginak Sarkisian

    2013-01-01

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15–22 m/min, 25–64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P < 0.001), and significantly decreased plasma level of malondialdehyde (P < 0.001). Acute exercise only decreased the hippocampal malondialdehyde level (P = 0.09) and increased brain-derived neurotrophic factor level in the hippocampus (P = 0.66). Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly (P = 0.99). These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

  18. Cardiology Consultation in the Emergency Department Reduces Re-hospitalizations for Low-Socioeconomic Patients with Acute Decompensated Heart Failure.

    Science.gov (United States)

    Tabit, Corey E; Coplan, Mitchell J; Spencer, Kirk T; Alcain, Charina F; Spiegel, Thomas; Vohra, Adam S; Adelman, Daniel; Liao, James K; Sanghani, Rupa Mehta

    2017-09-01

    Re-hospitalization after discharge for acute decompensated heart failure is a common problem. Low-socioeconomic urban patients suffer high rates of re-hospitalization and often over-utilize the emergency department (ED) for their care. We hypothesized that early consultation with a cardiologist in the ED can reduce re-hospitalization and health care costs for low-socioeconomic urban patients with acute decompensated heart failure. There were 392 patients treated at our center for acute decompensated heart failure who received standardized education and follow-up. Patients who returned to the ED received early consultation with a cardiologist; 392 patients who received usual care served as controls. Thirty- and 90-day re-hospitalization, ED re-visits, heart failure symptoms, mortality, and health care costs were recorded. Despite guideline-based education and follow-up, the rate of ED re-visits was not different between the groups. However, the rate of re-hospitalization was significantly lower in patients receiving the intervention compared with controls (odds ratio 0.592), driven by a reduction in the risk of readmission from the ED (0.56 vs 0.79, respectively). Patients receiving the intervention accumulated 14% fewer re-hospitalized days than controls and 57% lower 30-day total health care cost. Despite the reduction in health care resource consumption, mortality was unchanged. After accounting for the total cost of intervention delivery, the health care cost savings was substantially greater than the cost of intervention delivery. Early consultation with a cardiologist in the ED as an adjunct to guideline-based follow-up is associated with reduced re-hospitalization and health care cost for low-socioeconomic urban patients with acute decompensated heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. CELECOXIB - Chemoradiation therapy for reducing mucositis and other acute side effects in advance head and neck carcinoma

    Directory of Open Access Journals (Sweden)

    Izadi Sh

    2009-02-01

    Full Text Available "nBackground: Chemo-radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay or interruption of treatment plan, cyclo-oxygenase 2 (COX2 is an inducible enzyme primarily expressed in inflamed and tumoral tissues. COX-2 inhibitors have shown promise to reduce chemoradiation induce toxicities. We conducted a phase III, randomized double blind clinical trial to evaluate the toxicity and efficacy of celecoxib, a selective COX2 inhibitor, administered concurrently with chemoradiation for locally advanced head and neck cancer. Here in we report the first report about the role of COX-2 inhibitor in acute toxicicities. "nMethods: Patients with stage III/IV (locally advance head and neck carcinoma who referred to department of radiation-oncology were eligible. Patients were treated with chemotherapy with cisplatin concurrently with radiation (60-70Gy. Celecoxib (100mg qid was started at the first day of radiotherapy and was given for a total of 8 weeks. Acute toxicities were evaluated every week by WHO scale. "nResults: One hundred twenty two patients were enrolled into the study, (61 patients for each group. In repeated mesurment analysis of variance there is a significant difference in the time of onset of grade II acute toxicities between the two groups; The mucositis, dysphagia, epidermitis and oral pain score changed significantly over the typical five weeks in two groups but these changes were more sever in placebo group (p=0.0001. In the analysis of the overall changes in the following laboratory parame-ters: WBC, hemoglobin and platelet showed that these parameters decreased over time in both groups without a significant difference between groups. "nConclusion: The results of these study showed that the use of a COX-2 inhibitor (celecoxib that is a safe and inexpensive drug may reduce acute toxicities of chemoradiation specially

  20. Smoking Is Associated with Acute and Chronic Prostatic Inflammation: Results from the REDUCE Study.

    Science.gov (United States)

    Moreira, Daniel M; Nickel, J Curtis; Gerber, Leah; Muller, Roberto L; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2015-04-01

    Both anti- and proinflammatory effects of cigarette smoking have been described. As prostate inflammation is common, we hypothesized smoking could contribute to prostate inflammation. Thus, we evaluated the association of smoking status with acute and chronic inflammation within the prostate of men undergoing prostate biopsy. We retrospectively analyzed 8,190 men ages 50 to 75 years with PSA levels between 2.5 and 10 ng/mL enrolled in the Reduction by Dutasteride of Prostate Cancer Events study. Smoking status was self-defined as never, former, or current. Prostate inflammation was assessed by systematic central review blinded to smoking status. The association of smoking with inflammation in the baseline, 2-year, and 4-year biopsies was evaluated with univariable and multivariable logistic regressions. At study enrollment, 1,233 (15%), 3,203 (39%), and 3,754 (46%) men were current, former, and never smokers, respectively. Current smokers were significantly younger and had smaller prostates than former and never smokers (all P chronic prostate inflammations were identified in 1,261 (15%) and 6,352 (78%) baseline biopsies, respectively. In univariable analysis, current smokers were more likely to have acute inflammation than former (OR, 1.35; P, 0.001) and never smokers (OR, 1.36; P, 0.001). The results were unchanged at 2- and 4-year biopsies. In contrast, current smoking was linked with chronic inflammation in the baseline biopsy, but not at 2- and 4-year biopsies. In conclusion, among men undergoing prostate biopsy, current smoking was independently associated with acute and possibly chronic prostate inflammations.

  1. Reduced thrombin activatable fibrinolysis inhibitor and enhanced proinflammatory cytokines in acute coronary syndrome.

    Science.gov (United States)

    Pang, H; Zhang, C; Liu, F; Gong, X; Jin, X; Su, C

    2016-12-27

    A study was made of the changes in the serum levels of thrombin activatable fibrinolysis inhibitor (TAFI), proinflammatory cytokines and acute phase proteins in the acute stage of acute coronary syndrome (ACS), in order to explore the possibility of using TAFI as a biomarker for ACS risk assessment. A total of 211 patients with ACS were enrolled, and healthy subjects were used as controls. Blood samples were taken within 24h after admission. Serum TAFI levels were determined by immunoturbidimetry. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Procalcitonin (PCT) and C-reactive protein (CRP) levels were measured by gold-immunochromatographic assay. Serum TAFI levels in ACS patients were significantly decreased versus the controls. The IL-1β, IL-6, TNF-α, PCT and CRP levels were markedly higher in the ACS patients than in the controls. Correlation analysis revealed a strong negative correlation between TAFI concentration and the IL-1β, IL-6, TNF-а, PCT and CRP levels in ACS patients and in controls. Multivariate logistic regression analysis suggested decreased serum TAFI to be an independent risk factor for ACS (OR 9.459; 95% CI 2.306-38.793; P=0.002). The area under the receiver operating characteristic (ROC) curve for TAFI was 0.872 (95% CI 0.787-0.909; P<0.001). The optimum TAFI cutoff point for the prediction of ACS was 24μg/ml, with a sensitivity of 75.83% and a specificity of 72.57%. These findings suggest that TAFI can be useful as a potential biomarker for ACS risk assessment. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  2. Preoperative dexamethasone reduces acute but not sustained pain after lumbar disk surgery

    DEFF Research Database (Denmark)

    Nielsen, Rikke V; Siegel, Hanna; Fomsgaard, Jonna S

    2015-01-01

    with morphine. Primary outcome was pain during mobilization (visual analog scale) 2 to 24 hours postoperatively. Secondary outcomes were acute pain at rest, morphine consumption, nausea, vomiting, ondansetron consumption, sedation, and quality of sleep. Patients were followed up by written questionnaire 3...... in the dexamethasone group (17 episodes) vs placebo (51 episodes) P = 0.036. No other differences were observed. However, 6.5% (95% CI 2-15) in the dexamethasone group vs placebo 0% had an antibiotically treated wound infection (P = 0.13). Sixteen percent (95% CI 7-26) vs 8% (95% CI 0-17) reported new weakness/paralysis...

  3. Does Prone Positioning Improve Oxygenation and Reduce Mortality in Patients with Acute Respiratory Distress Syndrome?

    Directory of Open Access Journals (Sweden)

    William R Henderson

    2014-01-01

    Full Text Available The emergence of computed tomography imaging more than 25 years ago led to characterization of acute respiratory distress syndrome (ARDS as areas of relatively normal lung parenchyma juxtaposed with areas of dense consolidation and atelectasis. Given that this heterogeneity is often dorsally distributed, investigators questioned whether care for ARDS patients in the prone position would lead to improved mortality outcomes. This clinical review discusses the physiological rationale and clinical evidence supporting prone positioning in treating ARDS, in addition to its complications and contraindications.

  4. Comparison of zinc-probiotic combination theraphy to zinc theraphy alone in reducing the severity of acute diarrhea

    Directory of Open Access Journals (Sweden)

    Muhammad Hatta

    2011-01-01

    Full Text Available Background Although the incidence of diarrhea in Indonesia has declined in the last five years, the mortality rate in children under five years old is still high. Therefore, appropriate and comprehensive management of diarrhea is essential. There have been many studies on the role of zinc therapy and probiotic therapy in reducing the severity of acute diarrhea, but not many studies have compared the use of a combination of the two therapies to zinc therapy alone. Objective To compare the efficacy of zinc-probiotic combination therapy to zinc alone in reducing the severity of acute diarrhea. Methods We conducted a randomized, open-label, controlled trial from July 2009 to January 2010 in Adam Malik Hospital and Pirngadi Hospital , Medan. Children aged between 1 month and 5 years who met the criteria were divided into two groups. Group I recieved zinc sulphate (aged 6 months: 20mg/day combined with heat-killed Lactobacillus acidophilus (3x1010 CFU/day for 10 days. zinc sulphate at the same dosage as group I. Measurement of disease severity was based on the frequency of diarrhea (times/day and the duration of diarrhea (hours after initial drug consumption. Results Eighty subjects were enrolled, randomised, and divided equally into two groups. 40 children received zinc-probiotic in combination (group I and the remainder (group II received zinc alone. We observed significant differences in frequency of diarrhea (2.1 vs 3.1 times/day, P= 0.001, 95%CI-1.62 to -0.49, and duration of diarrhea (52.1 vs 72.6 hours, P=0.001, 95%CI-30.91 to -10.18 in the two groups. Conclusion Combination of zinc-probiotic therapy was more effective in reducing the severity of acute diarrhea than zinc therapy alone in children under five years of age. [Paediatr Indones. 2011;51:1-6].

  5. Rapid eye movement-sleep is reduced in patients with acute uncomplicated diverticulitis—an observational study

    Directory of Open Access Journals (Sweden)

    Chenxi Huang

    2015-08-01

    Full Text Available Introduction. Sleep disturbances are commonly found in patients in the postoperative period. Sleep disturbances may give rise to several complications including cardiopulmonary instability, transient cognitive dysfunction and prolonged convalescence. Many factors including host inflammatory responses are believed to cause postoperative sleep disturbances, as inflammatory responses can alter sleep architecture through cytokine-brain interactions. Our aim was to investigate alteration of sleep architecture during acute infection and its relationships to inflammation and clinical symptoms.Materials & Methods. In this observational study, we included patients with acute uncomplicated diverticulitis as a model to investigate the isolated effects of inflammatory responses on sleep. Eleven patients completed the study. Patients were admitted and treated with antibiotics for two nights, during which study endpoints were measured by polysomnography recordings, self-reported discomfort scores and blood samples of cytokines. One month later, the patients, who now were in complete remission, were readmitted and the endpoints were re-measured (the baseline values.Results. Total sleep time was reduced 4% and 7% the first (p = 0.006 and second (p = 0.014 nights of diverticulitis, compared to baseline, respectively. The rapid eye movement sleep was reduced 33% the first night (p = 0.016, compared to baseline. Moreover, plasma IL-6 levels were correlated to non-rapid eye movement sleep, rapid eye movement sleep and fatigue.Conclusion. Total sleep time and rapid eye movement sleep were reduced during nights with active diverticulitis and correlated with markers of inflammation.

  6. Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats.

    Science.gov (United States)

    Kiss, Krisztina; Csonka, Csaba; Pálóczi, János; Pipis, Judit; Görbe, Anikó; Kocsis, Gabriella F; Murlasits, Zsolt; Sárközy, Márta; Szűcs, Gergő; Holmes, Christopher P; Pan, Yijun; Bhandari, Ashok; Csont, Tamás; Shamloo, Mehrdad; Woodburn, Kathryn W; Ferdinandy, Péter; Bencsik, Péter

    2016-11-01

    Erythropoietin (EPO) has been shown to protect the heart against acute myocardial infarction in pre-clinical studies, however, EPO failed to reduce infarct size in clinical trials and showed significant safety problems. Here, we investigated cardioprotective effects of two selective non-erythropoietic EPO receptor ligand dimeric peptides (AF41676 and AF43136) lacking erythropoietic activity, EPO, and the prolonged half-life EPO analogue, darbepoetin in acute myocardial infarction (AMI) in rats. In a pilot study, EPO at 100U/mL significantly decreased cell death compared to vehicle (33.8±2.3% vs. 40.3±1.5%, pEPO reduced infarct size significantly compared to vehicle (45.3±4.8% vs. 59.8±4.5%, pEPO receptor ligand dimeric peptides AF41676 and AF43136 administered before reperfusion are able to reduce infarct size in a rat model of AMI. Therefore, non-erythropoietic EPO receptor peptide ligands may be promising cardioprotective agents.

  7. Apocynin reduced doxycycline-induced acute liver injury in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Satoru Mitazaki

    2016-01-01

    Full Text Available To determine the physiological role of estrogen in the development of liver injury, we examined the sensitivities of sham and ovariectomy (ovx mice against doxycycline (DOXY-induced acute liver injury. Ovx or sham operation was performed in C57BL/6J wild-type female mice of eight weeks of age. Sham mice and ovx mice were treated with DOXY (240 mg/kg ip 8 weeks after the operation, 30 min after apocynin (5 mg/kg or saline administration. Blood and liver samples were obtained at 3 and 6 h after DOXY administration. Liver dysfunction occurred soon after DOXY administration and became more severe in ovx mice than in sham mice. At early phase after DOXY injection, TNF-α and iNOS inductions upregulated almost the same levels in sham and ovx mice. On the other hand, expression levels of IL-6, IL-10, c-fos, cox-2 and HO-1, downstream genes of TNF-α, were significantly increased in ovx mice compared to those in sham mice, correlated with liver dysfunction. In addition, apocynin, a NADPH oxidase (Nox inhibitor, totally improved DOXY-induced liver injury in both sham and ovx mice, indicating that reactive oxygen species generated through Nox activation by DOXY are responsible for development of acute liver injury.

  8. Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway

    Directory of Open Access Journals (Sweden)

    Gulbrandsen Pål

    2005-08-01

    Full Text Available Abstract Background Acute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+ to the hospitalised infants with non-RSV bronchiolitis (RS- according to the same endpoints. Methods 57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit. Results The children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups. Conclusion Children hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by

  9. Impact of postremission consolidation chemotherapy on outcome after reduced-intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission

    DEFF Research Database (Denmark)

    Yeshurun, Moshe; Labopin, Myriam; Blaise, Didier;

    2014-01-01

    The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1).......The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1)....

  10. Can improvised somatic dance reduce acute pain for young people in hospital?

    Science.gov (United States)

    Dowler, Lisa

    2016-11-08

    Aim This study explores the effects of improvised somatic dance (ISD) on children and young people experiencing acute pain following orthopaedic or cardiac surgery, or post-acquired brain injury. Methods The study involved 25 children and young people and adopted a mixed methods approach. This included a descriptive qualitative approach to help the participants and witnesses verbalise their experience of ISD, and pain scores were assessed before and after ISD using validated pain assessment tools. Data were analysed using descriptive statistical analysis. Findings A total of 92% of participants experienced a reduction in pain, with 80% experiencing a >50% reduction. There was an improved sense of well-being for all. Conclusion Although not a replacement for pharmacological treatments, a multidimensional, child-centred and inclusive approach with ISD can be a useful complementary, non-pharmacological method of pain management in children and young people.

  11. Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

    Directory of Open Access Journals (Sweden)

    Zeng Dong-Feng

    2012-10-01

    Full Text Available Hypoxia inducible factor-1α (HIF-1α is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenviroment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF and stromal cell-derived factor-1α (SDF-1α were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1 secreted by stromal cells were decreased. When HIF-1α was blocked, the co-cultured Jurkat cell’s adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.

  12. Proton Beam Craniospinal Irradiation Reduces Acute Toxicity for Adults With Medulloblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Aaron P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Barney, Christian L. [Baylor College of Medicine, Houston, Texas (United States); Grosshans, David R.; McAleer, Mary Frances [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Groot, John F. de; Puduvalli, Vinay K. [Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crawford, Cody N.; Khan, Meena [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Khatua, Soumen [Department of Pediatric Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gilbert, Mark R. [Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brown, Paul D. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita, E-mail: amahajan@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-06-01

    Purpose: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma. Methods and Materials: Forty adult medulloblastoma patients treated with x-CSI (n=21) or p-CSI (n=19) at the University of Texas MD Anderson Cancer Center from 2003 to 2011 were retrospectively reviewed. Median CSI and total doses were 30.6 and 54 Gy, respectively. The median follow-up was 57 months (range 4-103) for x-CSI patients and 26 months (range 11-63) for p-CSI. Results: p-CSI patients lost less weight than x-CSI patients (1.2% vs 5.8%; P=.004), and less p-CSI patients had >5% weight loss compared with x-CSI (16% vs 64%; P=.004). p-CSI patients experienced less grade 2 nausea and vomiting compared with x-CSI (26% vs 71%; P=.004). Patients treated with x-CSI were more likely to have medical management of esophagitis than p-CSI patients (57% vs 5%, P<.001). p-CSI patients had a smaller reduction in peripheral white blood cells, hemoglobin, and platelets compared with x-CSI (white blood cells 46% vs 55%, P=.04; hemoglobin 88% vs 97%, P=.009; platelets 48% vs 65%, P=.05). Mean vertebral doses were significantly associated with reductions in blood counts. Conclusions: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. Patients treated with p-CSI experienced less treatment-related morbidity including fewer acute gastrointestinal and hematologic toxicities.

  13. Silencing HIF-1α reduces the adhesion and secretion functions of acute leukemia hBMSCs

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Dong-Feng [Department of Hematology, XinQiao Hospital, Third Military Medical University, ChongQing (China); Liu, Ting [Department of Ophthalmology, DaPing Hospital, Third Military Medical University, ChongQing (China); Chang, Cheng; Zhang, Xi; Liang, Xue; Chen, Xing-Hua; Kong, Pei-Yan [Department of Hematology, XinQiao Hospital, Third Military Medical University, ChongQing (China)

    2012-06-29

    Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenvironment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1α secreted by stromal cells was decreased. When HIF-1α was blocked, the co-cultured Jurkat cell's adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.

  14. How to reduce avoidable admissions due to acute diabetes complications?: Interrelation between primary and specialized attention in a diabetes unit

    Directory of Open Access Journals (Sweden)

    N. V. García-Talavera Espín

    2012-12-01

    Full Text Available Introduction: Type 2 Diabetes Mellitus is a serious health problem. In the year 2030 it will affect 366 million people around the world. Objective: Evaluate the effectiveness of a mixed intervention and reducing the amount and seriousness of acute complications in diabetics from our Health Area. Materials and method: Protocols of action as well as information documents were produced. Diabetes Unit coordinated educational activities in the different support levels of the Area VII of Murcia. Information talks were provided for the people in charge of the Diabetes Unit in every Care Center and Service of the Health Area. Personalized training was provided for patients treated in the differet Care levels. The study comprised three stages. Information leaflets were spread and talks offered to the patient regarding in house handling of hypo and hyper glycemia. Results: A reduction of 39% of the emergencies due to acute non complicated diabetes was achieved, as well as a reduction of 47.6% of hospital admissions. There was a reduction of 67.8% of the amount of total hospital stays for the group of patients under 35 years who were admitted into the hospital due to type 1 or 2 diabetes mellitus that didn't show any complications (GRD295. Conclusions: There was a reduction of more than thirty percent in the emergencies due to acute decompensations in the disease and a significant reduction in the avoidable hospital stays in the young adult, thus improving the patients' life quality and reducing the social cost of the diabetic patient.

  15. C-peptide attenuates acute lung inflammation in a murine model of hemorrhagic shock and resuscitation by reducing gut injury.

    Science.gov (United States)

    Kao, Raymond L C; Xu, Xuemei; Xenocostas, Anargyros; Parry, Neil; Mele, Tina; Martin, Claudio M; Rui, Tao

    2017-08-01

    The study aims to evaluate whether C-peptide can reduce gut injury during hemorrhagic shock (HS) and resuscitation (R) therefore attenuate shock-induced inflammation and subsequent acute lung injury. Twelve-week-old male mice (C57/BL6) were hemorrhaged (mean arterial blood pressure maintained at 35 mm Hg for 60 minutes) and then resuscitated with Ringer's lactate, followed by red blood cell transfusion with (HS/R) or without C-peptide (HS/R + C-peptide). Mouse gut permeability, bacterial translocation into the circulatory system and intestinal pathology, circulating HMGB1, and acute lung injury were assessed at different times after R. The mice in the control group underwent sham procedures without HS. Compared to the sham group, the mice in the HS/R group showed increased gut permeability (6.07 ± 3.41 μg of FD4/mL) and bacterial translocation into the circulatory system (10.05 ± 4.92, lipopolysaccharide [LPS] of pg/mL), and increased gut damage; conversely, mice in the HS/R + C-peptide group showed significantly reduced gut permeability (1.59 ± 1.39 μg of FD4/mL; p C-peptide group showed decreased HMGB1 (7.27 ± 1.93 ng/mL; p C-peptide exerts beneficial effects to attenuate gut injury and dysfunction, therefore diminishing lung inflammation and subsequent injury in mice with HS and R.

  16. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    Science.gov (United States)

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  17. Both acute and prolonged administration of EPO reduce cerebral and systemic vascular conductance in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Kim, Yu-Sok; Krogh-Madsen, Rikke

    2012-01-01

    Administration of erythropoietin (EPO) has been linked to cerebrovascular events. EPO reduces vascular conductance, possibly because of the increase in hematocrit. Whether EPO in itself affects the vasculature remains unknown; here it was evaluated in healthy males by determining systemic...

  18. Root Cause Analyses of Transfers of Skilled Nursing Facility Patients to Acute Hospitals: Lessons Learned for Reducing Unnecessary Hospitalizations.

    Science.gov (United States)

    Ouslander, Joseph G; Naharci, Ilkin; Engstrom, Gabriella; Shutes, Jill; Wolf, David G; Alpert, Graig; Rojido, Carolina; Tappen, Ruth; Newman, David

    2016-03-01

    Performing root cause analyses (RCA) on transfers of skilled nursing facility (SNF) patients to acute hospitals can help identify opportunities for care process improvements and education that may help prevent unnecessary emergency department (ED) visits, hospitalizations, and hospital readmissions. To describe the results of structured, retrospective RCAs performed by SNF staff on hospital transfers to identify lessons learned for reducing these transfers. SNFs enrolled in a randomized, controlled implementation trial of the INTERACT (Interventions to Reduce Acute Care Transfers) quality improvement program submitted RCAs on hospital transfers during a 12-month implementation period. SNFs from across the United States that volunteered and met the enrollment criteria for the implementation trial. Sixty-four of 88 SNFs randomized to the intervention group performed and submitted retrospective RCAs on hospital transfers. SNFs received education and technical assistance in INTERACT implementation. Data were summarized from the INTERACT Quality Improvement (QI) tool, a structured, retrospective RCA on hospital transfers. A total of 4856 QI tools were submitted during the 12-month implementation period. Most transfers were precipitated by multiple symptoms and signs, many of them nonspecific. Patient and/or family preference or insistence was noted to have played a role in 16% of the transfers. Hospital transfers were relatively equally distributed among days of the week, and 29% occurred on the night or evening shift. Approximately 1 in 5 transfers occurred within 6 days of SNF admission from a hospital, and 1 in 10 occurred within 2 days of SNF admission. After completing the RCA, SNF staff identified 1044 (23%) of the transfers as potentially preventable. Common reasons for these ratings included recognition that the condition could have been detected earlier and/or could have been managed safely in the SNF, and that earlier advance care planning and discussions with

  19. The approach taken to reducing the risk of transfusion related acute lung injury in Canada

    Directory of Open Access Journals (Sweden)

    Growe G

    2008-01-01

    Full Text Available Transfusion related acute lung injury (TRALI has become a major reported cause of severe transfusion reactions and mortality. Over the past four years significant changes have been taken in Canada in order both to improve the recognition of the risk and to decrease its incidence. An international meeting was held in April of 2004 entitled "Towards an Understanding of TRALI". As a result of the analysis and recommendations from this meeting, the Canadian Blood Services established an ongoing review committee and established a laboratory diagnostic facility to identify at risk donors and recipients. A system has been developed to identify implicated donors and exclude them from the blood donor pool. Other steps have been taken to exclude potentially high risk donors, such as previously pregnant females, from the plasma and platelet donor pool. A considerable amount of education also has been offered to clinical services in the country. This paper summarizes the definitions, categorizations of implicated donors, and the ongoing precautionary activities related to plasma products. Noted within the article are the methods used for locating and selecting data. These were primarily based on the international TRALI conference in 2004, and from ongoing discussions and information provided by the Canadian Blood Services TRALI Review Committee. No ethics referral or approval was requested, and a summary is included in the article.

  20. Acute stress reduces blood flow in the orofacial area, in conscious rabbits.

    Science.gov (United States)

    Roatta, Silvestro; Mohammed, Mazher; Passatore, Magda

    2009-04-01

    In the complex neurovascular control of the orofacial area, the only vasoconstrictor action is mediated by the sympathetic nervous system; however, its functional role is still unclear as little evidence exists of vasoconstrictor responses to physiological stimuli in both animal and human models. Aim of the present study was to investigate, orofacial vascular responses to acute stress in conscious rabbits. Twenty rabbits, implanted with chronic perivascular flow probes on the facial artery and with a telemetric probe for arterial blood pressure, were subjected to different alerting/stress stimuli, i.e., noise, taps on the rabbit's box, air jet, noxious cutaneous stimuli. Smaller groups of animal also underwent electromyographic (EMG) activity recording from the masseter muscle, unilateral section of the cervical sympathetic nerve (n=8), and alpha-adrenergic blockade with phentolamine (n=6). On average, all stressors evoked a pressor response accompanied by variable changes in heart rate and induced a marked, short-latency reduction in facial artery blood flow, corresponding to a decrease of 37-50% in vascular conductance of the facial artery. Local sympathetic denervation abolished the short-latency (15s) phase of the long-lasting response to the air jet. All vasoconstrictor effects were blocked by phentolamine. Increases in blood flow were observed only in concomitance with masseter EMG activity either during masticatory activity or in the form of brief occasional spontaneous contractions. This study provides evidence of an effective vasoconstrictor control by the sympathetic system in the orofacial area under stress conditions.

  1. Reduced cardiorespiratory fitness in adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Tonorezos, Emily S; Snell, Peter G; Moskowitz, Chaya S; Eshelman-Kent, Debra A; Liu, Jennifer E; Chou, Joanne F; Smith, Stephanie M; Dunn, Andrea L; Church, Timothy S; Oeffinger, Kevin C

    2013-08-01

    Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited. To assess cardiorespiratory fitness, maximal oxygen uptake (VO2 max) was measured in 115 ALL survivors (median age, 23.5 years; range 18-37). We compared VO2 max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003-2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest. Compared to NHANES participants, ALL survivors had a substantially lower VO2 max (mean 30.7 vs. 39.9 ml/kg/min; adjusted P VO2 max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2 max compared with NHANES participants (all comparisons, P VO2 max. Among females, CRT was associated with low VO2 max (P = 0.02), but anthracycline exposure was not (P = 0.58). In contrast, among males, anthracycline exposure ≥ 100 mg/m(2) was associated with low VO2 max (P = 0.03), but CRT was not (P = 0.54). Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population. Copyright © 2013 Wiley Periodicals, Inc.

  2. Cycling efficiency and time to exhaustion are reduced after acute passive stretching administration.

    Science.gov (United States)

    Esposito, F; Cè, E; Limonta, E

    2012-12-01

    The aim of this study was to assess the effects of acute passive stretching on cycling efficiency during an exercise of heavy intensity. After maximum aerobic power (VO(2max)) assessment, nine active males (24 ± 5 years; stature 1.71 ± 0.09 m; body mass 69 ± 7 kg; mean ± standard deviation) performed tests at 85% of VO(2max) (W(85)) until exhaustion, with and without pre-exercise stretching. During the tests, we determined the gas exchange, metabolic and cardiorespiratory parameters. With stretching, no differences in VO(2max) occurred (3.64 ± 0.14 vs 3.66 ± 0.07 L/min for stretching and control, respectively). During W(85), pre-exercise stretching (i) decreased time to exhaustion (t(lim)) by 26% (Pstretching and control, respectively; Pstretching and control, respectively; Pstretching did not have an effect on VO(2max), t(lim) and e(net) during heavy constant load exercise were significantly affected. These results are suggestive of an impairment in cycling efficiency due to changes in muscle neural activation and viscoelastic characteristics induced by stretching.

  3. Reduced consumption of analgesics in patients with diabetes mellitus admitted to hospital for acute myocardial infarction

    DEFF Research Database (Denmark)

    Nielsen, F E; Gram-Hansen, P; Christensen, J H;

    1991-01-01

    .05). There was no statistically significant trend for the duration of pain to be shorter in the diabetes group. There was no difference between the two groups with respect to number of patients with Q-wave infarct, initial heart rate-blood pressure product or body weight, all of which are possible confounders. We conclude......In a case-control study, the consumption of analgesics was analysed in 39 patients with diabetes, admitted with acute myocardial infarction (MI). The control group comprised of non-diabetics with MI was computer-matched to the diabetic group with respect to age and sex as well as enzyme......-estimated size of the infarction. The median number of injections of opioid analgesics in the diabetes and non-diabetes groups was 2 and 5, respectively (0.01 less than P less than 0.05), and the median consumption of morphine was 20 mg and 35 mg, respectively (0.01 less than P less than 0...

  4. Acute leptin exposure reduces megalin expression and upregulates TGFβ1 in cultured renal proximal tubule cells.

    Science.gov (United States)

    Briffa, Jessica F; Grinfeld, Esther; Mathai, Michael L; Poronnik, Phillip; McAinch, Andrew J; Hryciw, Deanne H

    2015-02-05

    Increased leptin concentrations observed in obesity can lead to proteinuria, suggesting that leptin may play a role in obesity-related kidney disease. Obesity reduces activation of AMP-activated protein kinase (AMPK) and increases transforming growth factor-β1 (TGF-β1) expression in the kidney, leading to albuminuria. Thus we investigated if elevated leptin altered AMPK and TGF-β1 signaling in proximal tubule cells (PTCs). In opossum kidney (OK) PTCs Western blot analysis demonstrated that leptin upregulates TGF-β1 secretion (0.50 µg/ml) and phosphorylated AMPKα (at 0.25, and 0.50 µg/ml), and downregulates megalin expression at all concentrations (0.05-0.50 µg/ml). Using the AMPK inhibitor, Compound C, leptin exposure regulated TGF-β1 expression and secretion in PTCs via an AMPK mediated pathway. In addition, elevated leptin exposure (0.50 µg/ml) reduced albumin handling in OK cells independently of megalin expression. This study demonstrates that leptin upregulates TGF-β1, reduces megalin, and reduces albumin handling in PTCs by an AMPK mediated pathway.

  5. Acute stress reduces wound-induced activation of microbicidal potential of ex vivo isolated human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Ulrike Kuebler

    Full Text Available BACKGROUND: Psychological stress delays wound healing but the precise underlying mechanisms are unclear. Macrophages play an important role in wound healing, in particular by killing microbes. We hypothesized that (a acute psychological stress reduces wound-induced activation of microbicidal potential of human monocyte-derived macrophages (HMDM, and (b that these reductions are modulated by stress hormone release. METHODS: Fourty-one healthy men (mean age 35 ± 13 years were randomly assigned to either a stress or stress-control group. While the stress group underwent a standardized short-term psychological stress task after catheter-induced wound infliction, stress-controls did not. Catheter insertion was controlled. Assessing the microbicidal potential, we investigated PMA-activated superoxide anion production by HMDM immediately before and 1, 10 and 60 min after stress/rest. Moreover, plasma norepinephrine and epinephrine and salivary cortisol were repeatedly measured. In subsequent in vitro studies, whole blood was incubated with norepinephrine in the presence or absence of phentolamine (norepinephrine blocker before assessing HMDM microbicidal potential. RESULTS: Compared with stress-controls, HMDM of the stressed subjects displayed decreased superoxide anion-responses after stress (p's <.05. Higher plasma norepinephrine levels statistically mediated lower amounts of superoxide anion-responses (indirect effect 95% CI: 4.14-44.72. Norepinephrine-treated HMDM showed reduced superoxide anion-production (p<.001. This effect was blocked by prior incubation with phentolamine. CONCLUSIONS: Our results suggest that acute psychological stress reduces wound-induced activation of microbicidal potential of HMDM and that this reduction is mediated by norepinephrine. This might have implications for stress-induced impairment in wound healing.

  6. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

    Science.gov (United States)

    Mohty, Mohamad; Malard, Florent; Blaise, Didier; Milpied, Noel; Socié, Gérard; Huynh, Anne; Reman, Oumédaly; Yakoub-Agha, Ibrahim; Furst, Sabine; Guillaume, Thierry; Tabrizi, Resa; Vigouroux, Stéphane; Peterlin, Pierre; El-Cheikh, Jean; Moreau, Philippe; Labopin, Myriam; Chevallier, Patrice

    2017-01-01

    The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients’ outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33–71) at 1 year and 38% (95% CI: 18–46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26–64) at 1 year and 29% (95% CI: 13–48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1–24) at 1 year and 12% (95% CI: 3–19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174. PMID:27561720

  7. Reduce mortality risk above all else: a discrete-choice experiment in acute coronary syndrome patients.

    Science.gov (United States)

    Mühlbacher, Axel C; Bethge, Susanne

    2015-01-01

    Cardiovascular disease is the main cause of death in Germany and other industrialized countries. However, until now, little has been known about how people with acute coronary syndrome (ACS) value aspects of their medical treatment. The objective of this study was to evaluate patients' preferences regarding different antiplatelet medication options following an ACS. After identification of patient-relevant treatment attributes (a literature review and qualitative interviews), a discrete-choice experiment (DCE) including five patient-relevant attributes was conducted. The DCE used a forced-choice approach in which no "opt out" was present, as no treatment is not an option after ACS. The attribute and level combinations were created using a fractional-factorial NGene design with priors. Data analysis was performed using a random-effects logit model. An additional generalized linear latent and mixed models (GLLAMM) analysis was performed to evaluate subgroup differences. ACS patients (N = 683) participated in computer-assisted personal interviews. Preference analysis showed a clear dominance of the attribute "mortality risk" (coefficient: 0.803). Ranked second was "side effect: dyspnea" (coefficient: 0.550) followed by "risk of a new myocardial infarction" (coefficient: 0.464) and "side effect: bleeding" (coefficient: 0.400). "Frequency of intake" was less important (coefficient: 0.025). Within the 3-class GLLAMM, the variables "marital status" (p = 0.008), "highest level of education" (p = 0.003), and "body-mass index" (according to World Health Organization cluster; p = 0.014) showed a significant impact on the estimated class probabilities. Our study found "mortality risk" to be of the highest value for patients. Patient-centered care and decision making requires consideration of patient preferences; moreover, the information on preferences can be used to develop effective therapies after an ACS. The data generated will enable healthcare decision makers and

  8. Reduced subjective response to acute ethanol administration among young men with a broad bipolar phenotype.

    Science.gov (United States)

    Yip, Sarah W; Doherty, Joanne; Wakeley, Judi; Saunders, Kate; Tzagarakis, Charidimos; de Wit, Harriet; Goodwin, Guy M; Rogers, Robert D

    2012-07-01

    Elevated lifetime prevalence rates of alcohol use disorders (AUDs) are a feature of bipolar disorder (BD). Individuals at-risk for AUDs exhibit blunted subjective responses to alcohol (low levels of response), which may represent a biomarker for AUDs. Thus, individuals at-risk for BD may exhibit low responses to alcohol. Participants were 20 unmedicated adult males who reported high rates of hypomanic experiences (bipolar phenotype participants; BPPs), aged 18 to 21 years, and 20 healthy controls matched on age, gender, IQ, BMI, and weekly alcohol intake. Subjective and pharmacokinetic responses to acute alcohol (0.8 g/kg) vs placebo administration were collected in a randomized, double-blind, cross-over, placebo-controlled, within-subjects design. BPP participants reported significantly lower subjective intoxication effects ('feel high': F=14.2, p=0.001; 'feel effects': F=8.1, p=0.008) across time, but did not differ in their pharmacokinetic, stimulant, or sedative responses. Paradoxically, however, the BPP participants reported significantly higher expectations of the positive effects of alcohol than controls. Our results suggest that unmedicated young males with previous hypomanic experiences exhibit diminished subjective responses to alcohol. These blunted alcohol responses are not attributable to differences in weekly alcohol intake, pharmacokinetic effects (eg, absorption rates), or familial risk of AUDs. These observations suggest that the dampened intoxication may contribute to the increased rates of alcohol misuse in young people at-risk for BD, and suggest possible shared etiological factors in the development of AUDs and BD.

  9. Sabiporide improves cardiovascular function, decreases the inflammatory response and reduces mortality in acute metabolic acidosis in pigs.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available INTRODUCTION: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na(+/H(+ exchanger (NHE1 could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid. METHODS AND RESULTS: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP and pulmonary vascular resistance (PVR. Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group, and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-α (by 33%, IL-6 (by 63%, troponin-I (by 54%, ALT (by 34%, AST (by 35%, and urea (by 40%. CONCLUSION: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man.

  10. Acute pulmonary edema in patients with reduced left ventricular ejection fraction is associated with concentric left ventricular geometry.

    Science.gov (United States)

    Imanishi, Junichi; Kaihotsu, Kenji; Yoshikawa, Sachiko; Nishimori, Makoto; Sone, Naohiko; Honjo, Tomoyuki; Iwahashi, Masanori

    2017-08-02

    Although acute pulmonary edema (APE) is common in patients with heart failure (HF) with preserved ejection fraction (EF), its pathogenesis in patients with HF with reduced EF (HFrEF) is not completely understood. The purpose of our study was to explore the contributions of left ventricular (LV) geometry to understand the difference between HFrEF patients with or without APE. We studied 122 consecutive acute decompensated HF patients with HFrEF (≤40%). APE was defined as acute-onset dyspnea and radiographic alveolar edema requiring immediate airway intervention. LV geometry was determined from a combination of the LV mass index and relative wall thickness (RWT). Long-term unfavorable outcome events were tracked during a follow-up of a median of 21 months (interquartile range, 10-28 months), during which APE was observed in 29 patients (24%). Compared to those without APE, hospitalized patients with APE had a higher systolic blood pressure, RWT, and LVEF and lower end-diastolic dimension. Among echocardiographic variables, a multivariate logistic regression analysis identified RWT as the only independent determinant of APE (hazard ratio: 2.46, p geometry (n = 25; RWT > 0.42) had a higher incidence of APE relative to those with non-concentric geometry. Furthermore, among patients with APE, mortality was significantly higher among those with concentric geometry (log-rank, p = 0.008). Compared with non-concentric geometry, concentric geometry (increased RWT, not LV mass) was strongly associated with APE onset and a poorer outcome among APE patients. An easily obtained echocardiographic RWT index may facilitate the risk stratification of patients.

  11. Eugenol reduces acute pain in mice by modulating the glutamatergic and tumor necrosis factor alpha (TNF-α) pathways.

    Science.gov (United States)

    Dal Bó, Wladmir; Luiz, Ana Paula; Martins, Daniel F; Mazzardo-Martins, Leidiane; Santos, Adair R S

    2013-10-01

    Eugenol is utilized together with zinc oxide in odontological clinical for the cementation of temporary prostheses and the temporary restoration of teeth and cavities. This work explored the antinociceptive effects of the eugenol in different models of acute pain in mice and investigated its possible modulation of the inhibitory (opioid) and excitatory (glutamatergic and pro-inflammatory cytokines) pathways of nociceptive signaling. The administration of eugenol (3-300 mg/kg, p.o., 60 min or i.p., 30 min) inhibited 82 ± 10% and 90 ± 6% of the acetic acid-induced nociception, with ID₅₀ values of 51.3 and 50.2 mg/kg, respectively. In the glutamate test, eugenol (0.3-100 mg/kg, i.p.) reduced the response behavior by 62 ± 5% with an ID₅₀ of 5.6 mg/kg. In addition, the antinociceptive effect of eugenol (10 mg/kg, i.p.) in the glutamate test was prevented by the i.p. treatment for mice with naloxone. The pretreatment of mice with eugenol (10 mg/kg, i.p.) was able to inhibit the nociception induced by the intrathecal (i.t.) injection of glutamate (37 ± 9%), kainic (acid kainite) (41 ± 12%), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (55 ± 5%), and substance P (SP) (39 ± 8%). Furthermore, eugenol (10 mg/kg, i.p.) also inhibited biting induced by tumor necrosis factor alpha (TNF-α, 65 ± 8%). These results extend our current knowledge of eugenol and confirm that it promotes significant antinociception against different mouse models of acute pain. The mechanism of action appears to involve the modulation of the opioid system and glutamatergic receptors (i.e., kainate and AMPA), and the inhibition of TNF-α. Thus, eugenol could represent an important compound in the treatment for acute pain.

  12. Comparison of zinc-probiotic combination therapy to zinc therapy alone in reducing the severity of acute diarrhea

    Directory of Open Access Journals (Sweden)

    Muhammad Hatta

    2011-02-01

    Full Text Available Background Although the incidence of diarrhea in Indonesia has declined in the last five years, the mortality rate in children under five years old is still high. Therefore, appropriate and comprehensive management of diarrhea is essential. There have been many studies on the role of zinc therapy and probiotic therapy in reducing the severity of acute diarrhea, but not many studies have compared the use of a combination of the two therapies to zinc therapy alone. Objective To compare the efficacy of zinc-probiotic combination therapy to zinc alone in reducing the severity of acute diarrhea. Methods We conducted a randomized, open-label, controlled trial from July 2009 to January 2010 in Adam Malik Hospital and Pirngadi Hospital, Medan. Children aged between 1 month and 5 years who met the criteria were divided into two groups. Group I received zinc sulphate (aged <6 months: 10 mg/day; aged 2:6 months: 20 mg/day combined with heat-killed Lactobacillus acidophilus (3x101O CFU/day for 10 days. Group II received only zinc sulphate at the same dosage as group I. Measurement of disease severity was based on the frequency of diarrhea (times/day and the duration of diarrhea (hours after initial drug consumption. Results Eighty subjects were enrolled, randomised, and divided equally into two groups. 40 children received zinc-probiotic in combination (group I and the remainder (group II received zinc alone. We observed significant differences in frequency of diarrhea (2.1 vs 3.1 times/day, P=0.001, 95%CI -1.62 to -0.49, and duration of diarrhea (52.1 vs. 72.6 hours, P=0.00l, 95%CI -30.91 to -10.18 in the two groups. Conclusion Combination of zinc-probiotic therapy was more effective in reducing the severity of acute diarrhea than zinc therapy alone in children under five years of age.

  13. Reducing acute poisoning in developing countries--options for restricting the availability of pesticides

    DEFF Research Database (Denmark)

    Konradsen, Flemming; van der Hoek, Wim; Cole, Donald C

    2003-01-01

    Hundreds of thousands of people are dying around the world each year from the effects of the use, or misuse, of pesticides. This paper reviews the different options to reduce availability of the most hazardous chemicals, focusing on issues in developing countries. Emphasis is placed on the fatal......, alcohol or drug addiction, emotional distress, depression, physical illness, social isolation or financial hardship. These should be addressed through preventive health programmes and community development efforts....

  14. Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

    DEFF Research Database (Denmark)

    Bengtson, Stefan; Knudsen, KB; Kyjovska, ZO

    2017-01-01

    the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90...... without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.......We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we...

  15. Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

    Science.gov (United States)

    Hamaki, T; Kami, M; Kanda, Y; Yuji, K; Inamoto, Y; Kishi, Y; Nakai, K; Nakayama, I; Murashige, N; Abe, Y; Ueda, Y; Hino, M; Inoue, T; Ago, H; Hidaka, M; Hayashi, T; Yamane, T; Uoshima, N; Miyakoshi, S; Taniguchi, S

    2005-03-01

    Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

  16. Prediction of acute encephalopathy with biphasic seizures and late reduced diffusion in patients with febrile status epilepticus.

    Science.gov (United States)

    Yokochi, Takaoki; Takeuchi, Takahito; Mukai, Jumpei; Akita, Yukihiro; Nagai, Kojiro; Obu, Keizo; Kakuma, Tatsuyuki; Matsuishi, Toyojiro

    2016-02-01

    Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of acute encephalopathy among children in Japan. The pathogenesis of AESD is mostly delayed cerebral edema caused by excitotoxic injury. It is difficult to discriminate AESD and complex febrile seizure in the early phase. Many cases have neurologic sequelae because early intervention is difficult. To establish an early diagnostic method, we assessed 213 hospitalized cases of febrile status epilepticus (FSE) between January 2004 and August 2014. We categorized FSE cases into an AESD group and a non-AESD group and compared their clinical courses, laboratory data and cranial computed tomography (CT) findings. Of 213 hospitalized FSE cases, 19 (9%) were AESD. Univariate analysis showed that the AESD group took a significantly longer time to wake after FSE, had a higher degree of respiratory acidemia, and higher levels of serum AST, ALT, LD, hyperglycemia and hyperammonemia than the non-AESD group. We developed a scoring model that predicts AESD based on multivariate analysis. Using cut-off points of 4 and more with this scoring model, we could identify the AESD cases with 93% sensitivity and 91% specificity. These scores also had a positive correlation with prognosis. Our scoring model enables early diagnosis of AESD. Patients with high scores should be observed carefully and early intervention should be considered. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. Long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) study

    DEFF Research Database (Denmark)

    Bloch Thomsen, Poul Erik; Jons, Christian; Raatikainen, M J Pekka

    2010-01-01

    Knowledge about the incidence of cardiac arrhythmias after acute myocardial infarction has been limited by the lack of traditional ECG recording systems to document and confirm asymptomatic and symptomatic arrhythmias. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction (C...... (CARISMA) trial was designed to study the incidence and prognostic significance of arrhythmias documented by an implantable cardiac monitor among patients with acute myocardial infarction and reduced left ventricular ejection fraction.......Knowledge about the incidence of cardiac arrhythmias after acute myocardial infarction has been limited by the lack of traditional ECG recording systems to document and confirm asymptomatic and symptomatic arrhythmias. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction...

  18. Septic Encephalopathy Characterized by Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion and Early Nonconvulsive Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Hiroshi Yamaguchi

    2016-01-01

    Full Text Available Infection, whether viral or bacterial, can result in various forms of brain dysfunction (encephalopathy. Septic encephalopathy (SE is caused by an excessive immune reaction to infection, with clinical features including disturbed consciousness and seizures. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD is usually accompanied by viral infection in children and is characterized by biphasic seizures and impaired consciousness. The initial neurologic symptom of AESD is typically a febrile seizure that frequently lasts longer than 30 minutes. However, the possible forms this seizure takes are unclear. For example, it is unknown if nonconvulsive status epilepticus (NCSE could be an early seizure symptomatic of AESD. In addition, thus far no cases of combined SE and AESD have been reported. Here, we describe the first reported case of SE with AESD that notably demonstrated NCSE as an early seizure.

  19. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

    Science.gov (United States)

    Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

    2015-07-01

    Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties.

  20. Use of a total quality management model to reduce pressure ulcer prevalence in the acute care setting.

    Science.gov (United States)

    Sacharok, C; Drew, J

    1998-03-01

    As the population ages and becomes more frail, pressure ulcer prevalence and incidence within specific care settings are being evaluated through outcomes review. This article summarizes the process and outcomes of an ongoing prevalence study at a 300-bed acute care community hospital. All patients on the adult medical, surgical, and critical care units were examined regularly by the "Rear Admirals," a team comprising a skin care resource person and a nursing unit representative. The Total Quality Management model, characterized by the phrase "Plan-Do-Check-Act," was used to address barriers to quality care. Findings during that time prompted changes in policies, products, protocols, work assignments, and documentation tools. The outcomes achieved demonstrated the effectiveness of those strategies. After implementation of the Total Quality Management model at our Institution, the prevalence of patients with nosocomial pressure ulcers was reduced by 83%.

  1. PS-022 Complex automated medication systems reduce medication administration error rates in an acute medical ward

    DEFF Research Database (Denmark)

    Risør, Bettina Wulff; Lisby, Marianne; Sørensen, Jan

    2017-01-01

    Background Medication errors have received extensive attention in recent decades and are of significant concern to healthcare organisations globally. Medication errors occur frequently, and adverse events associated with medications are one of the largest causes of harm to hospitalised patients....... Reviews have suggested that up to 50% of the adverse events in the medication process may be preventable. Thus the medication process is an important means to improve safety. Purpose The objective of this study was to evaluate the effectiveness of two automated medication systems in reducing...... the medication administration error rate in comparison with current practice. Material and methods This was a controlled before and after study with follow-up after 7 and 14 months. The study was conducted in two acute medical hospital wards. Two automated medication systems were tested: (1) automated dispensing...

  2. Reducing the inappropriate use of parenteral nutrition in an acute care teaching hospital.

    Science.gov (United States)

    Maurer, J; Weinbaum, F; Turner, J; Brady, T; Pistone, B; D'Addario, V; Lun, W; Ghazali, B

    1996-01-01

    Parenteral nutrition (PN) is a form of nutrition that can be life-saving, but its use has inherent risks and it is expensive. Nutrition support teams have been shown to reduce both the rate of complications and excessive use of PN. Criteria were established to evaluate the appropriateness of PN use in a 487-bed community teaching hospital. A prospective study of 50 consecutive patients, who received either central or peripheral PN, was conducted. The 50 patients received 469 days of PN. We found that 233 (49.7%) of the 469 days of PN were avoidable. This resulted in the creation of a formal approval process that required prior approval by a physician-directed multidisciplinary advisory committee before PN could be instituted. The amount of PN subsequently decreased from 500 patient days of PN per month to less than 100. This study supports the idea that inappropriate use of PN can be reduced by physician education plus the continuing oversight of a physician-directed multidisciplinary advisory group.

  3. Aged Residential Care Health Utilisation Study (ARCHUS: a randomised controlled trial to reduce acute hospitalisations from residential aged care

    Directory of Open Access Journals (Sweden)

    Foster Susan J

    2012-09-01

    Full Text Available Abstract Background For residents of long term care, hospitalisations can cause distress and disruption, and often result in further medical complications. Multi-disciplinary team interventions have been shown to improve the health of Residential Aged Care (RAC residents, decreasing the need for acute hospitalisation, yet there are few randomised controlled trials of these complex interventions. This paper describes a randomised controlled trial of a structured multi-disciplinary team and gerontology nurse specialist (GNS intervention aiming to reduce residents’ avoidable hospitalisations. Methods/Design This Aged Residential Care Healthcare Utilisation Study (ARCHUS is a cluster- randomised controlled trial (n = 1700 residents of a complex multi-disciplinary team intervention in long-term care facilities. Eligible facilities certified for residential care were selected from those identified as at moderate or higher risk of resident potentially avoidable hospitalisations by statistical modelling. The facilities were all located in the Auckland region, New Zealand and were stratified by District Health Board (DHB. Intervention The intervention provided a structured GNS intervention including a baseline facility needs assessment, quality indicator benchmarking, a staff education programme and care coordination. Alongside this, three multi-disciplinary team (MDT meetings were held involving a geriatrician, facility GP, pharmacist, GNS and senior nursing staff. Outcomes Hospitalisations are recorded from routinely-collected acute admissions during the 9-month intervention period followed by a 5-month follow-up period. ICD diagnosis codes are used in a pre-specified definition of potentially reducible admissions. Discussion This randomised-controlled trial will evaluate a complex intervention to increase early identification and intervention to improve the health of residents of long term care. The results of this trial are expected in early

  4. Acute Stressors Reduce Neural Inhibition to Food Cues and Increase Eating Among Binge Eating Disorder Symptomatic Women

    Science.gov (United States)

    Lyu, Zhenyong; Jackson, Todd

    2016-01-01

    Stressors can trigger binge-eating but researchers have yet to consider their effects on both neural responses to food cues and food consumption among those at risk. In this experiment, we examined the impact of acute stressors on neural activation to food images and subsequent food consumption within binge-eating disorder (BED) and non-eating disordered control groups. Eighteen women meeting DSM-IV BED criteria and 26 women serving as non-eating disordered controls were randomly assigned to unpleasant stressor (painful cold pressor test (CPT) followed by negative performance feedback) or less unpleasant stressor (non-painful sensory discrimination task followed by positive performance feedback) conditions. Subsequently, they were scanned with functional magnetic resonance imaging (fMRI) while viewing food and neutral images. After the scans, participants completed a self-report battery in an environment conducive to snacking. During exposure to food images, BED-symptomatic women in the unpleasant stressor condition reported more liking of high calorie food images and showed less activation in one inhibitory area, the hippocampus, compared to controls in this condition. BED-symptomatic women exposed to unpleasant stressors also consumed more chocolate than any other group during the post-scan questionnaire completion. Crucially, reduced hippocampal activation to high calorie food images predicted more chocolate consumption following fMRI scans within the entire sample. This experiment provides initial evidence suggesting unpleasant acute stressors contribute to reduced inhibitory region responsiveness in relation to external food cues and later food consumption among BED-symptomatic women. PMID:27790097

  5. Acute Stressors Reduce Neural Inhibition to Food Cues and Increase Eating Among Binge Eating Disorder Symptomatic Women.

    Science.gov (United States)

    Lyu, Zhenyong; Jackson, Todd

    2016-01-01

    Stressors can trigger binge-eating but researchers have yet to consider their effects on both neural responses to food cues and food consumption among those at risk. In this experiment, we examined the impact of acute stressors on neural activation to food images and subsequent food consumption within binge-eating disorder (BED) and non-eating disordered control groups. Eighteen women meeting DSM-IV BED criteria and 26 women serving as non-eating disordered controls were randomly assigned to unpleasant stressor (painful cold pressor test (CPT) followed by negative performance feedback) or less unpleasant stressor (non-painful sensory discrimination task followed by positive performance feedback) conditions. Subsequently, they were scanned with functional magnetic resonance imaging (fMRI) while viewing food and neutral images. After the scans, participants completed a self-report battery in an environment conducive to snacking. During exposure to food images, BED-symptomatic women in the unpleasant stressor condition reported more liking of high calorie food images and showed less activation in one inhibitory area, the hippocampus, compared to controls in this condition. BED-symptomatic women exposed to unpleasant stressors also consumed more chocolate than any other group during the post-scan questionnaire completion. Crucially, reduced hippocampal activation to high calorie food images predicted more chocolate consumption following fMRI scans within the entire sample. This experiment provides initial evidence suggesting unpleasant acute stressors contribute to reduced inhibitory region responsiveness in relation to external food cues and later food consumption among BED-symptomatic women.

  6. Did clinical trials in which erythropoietin failed to reduce acute myocardial infarct size miss a narrow therapeutic window?

    Directory of Open Access Journals (Sweden)

    Mark I Talan

    Full Text Available BACKGROUND: To test a hypothesis that in negative clinical trials of erythropoietin in patients with acute myocardial infarction (MI the erythropoietin (rhEPO could be administered outside narrow therapeutic window. Despite overwhelming evidence of cardioprotective properties of rhEPO in animal studies, the outcomes of recently concluded phase II clinical trials have failed to demonstrate the efficacy of rhEPO in patients with acute MI. However, the time between symptoms onset and rhEPO administration in negative clinical trials was much longer that in successful animal experiments. METHODOLOGY/PRINCIPAL FINDINGS: MI was induced in rats either by a permanent ligation of a descending coronary artery or by a 2-hr occlusion followed by a reperfusion. rhEPO, 3000 IU/kg, was administered intraperitoneally at the time of reperfusion, 4 hrs after beginning of reperfusion, or 6 hrs after permanent occlusion. MI size was measured histologically 24 hrs after coronary occlusion. The area of myocardium at risk was similar among groups. The MI size in untreated rats averaged ~42% of area at risk, or ~24% of left ventricle, and was reduced by more than 50% (p<0.001 in rats treated with rhEPO at the time of reperfusion. The MI size was not affected by treatment administered 4 hrs after reperfusion or 6 hrs after permanent coronary occlusion. Therefore, our study in a rat experimental model of MI demonstrates that rhEPO administered within 2 hrs of a coronary occlusion effectively reduces MI size, but when rhEPO was administered following a delay similar to that encountered in clinical trials, it had no effect on MI size. CONCLUSIONS/SIGNIFICANCE: The clinical trials that failed to demonstrate rhEPO efficacy in patients with MI may have missed a narrow therapeutic window defined in animal experiments.

  7. Acute oral administration of lauric acid reduces energy intake in healthy male

    DEFF Research Database (Denmark)

    Feltrin, K. L.; Brennan, I.M.; Rades, Thomas

    2014-01-01

    12 would result in a dose-related suppression of appetite and subsequent energy intake at breakfast and lunch. Methods 14 healthy men were studied on four separate occasions in double-blind, randomised fashion. Following ingestion of C12 (2 g (77 kJ), 4 g (153 kJ), or 6 g (230 kJ)) or control, energy...... intake at breakfast (30 min after C12 ingestion), perceptions of appetite, nausea and bloating (for 180 min following breakfast), and energy intake at lunch (180 min after breakfast), were measured. Results C12 ingestion did not induce nausea or bloating. While there was no effect of C12 on energy intake...... at breakfast, energy intake at lunch was reduced significantly after ingestion of both C12(2 g) (by 13.7%, P

  8. Reduced acute nociception and chronic pain in Shank2−/− mice

    Science.gov (United States)

    Ko, Hyoung-Gon; Oh, Seog-Bae; Zhuo, Min

    2016-01-01

    Autism spectrum disorder is a debilitating mental illness and social issue. Autism spectrum disorder patients suffer from social isolation, cognitive deficits, compulsive behavior, and sensory deficits, including hyposensitivity to pain. However, recent studies argued that autism spectrum disorder patients show physiological pain response and, in some cases, even extremely intense pain response to harmless stimulation. Recently, Shank gene family was reported as one of the genetic risk factors of autism spectrum disorder. Thus, in this study, we used Shank2−/− (Shank2 knock-out, KO) mice to investigate the controversial pain sensitivity issue and found that Shank2 KO mice showed reduced tactile perception and analgesia to chronic pain. PMID:27145803

  9. Ukrain (NSC 631570) ameliorates intestinal ischemia-reperfusion-induced acute lung injury by reducing oxidative stress

    Science.gov (United States)

    Kocak, Cengiz; Kocak, Fatma Emel; Akcilar, Raziye; Akcilar, Aydin; Savran, Bircan; Zeren, Sezgin; Bayhan, Zulfu; Bayat, Zeynep

    2016-01-01

    Intestinal ischemia-reperfusion (I/R) causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570) is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L.) plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS), total antioxidant status (TAS) were measured and oxidative stress indices (OSI) were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05). TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05). Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05). Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects. PMID:26773189

  10. Ukrain (NSC 631570 ameliorates intestinal ischemia-reperfusion-induced acute lung injury by reducing oxidative stress

    Directory of Open Access Journals (Sweden)

    Cengiz Kocak

    2016-01-01

    Full Text Available Intestinal ischemia-reperfusion (I/R causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570 is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L. plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS, total antioxidant status (TAS were measured and oxidative stress indices (OSI were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05. TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05. Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed  in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05. Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects. 

  11. Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy.

    Science.gov (United States)

    Brouwers, Bas; Pruniau, Vincent P E G; Cauwelier, Elisa J G; Schuit, Frans; Lerut, Evelyne; Ectors, Nadine; Declercq, Jeroen; Creemers, John W M

    2013-09-20

    Streptozotocin (STZ) is widely used as diabetogenic agent in animal models for diabetic nephropathy (DN). However, it is also directly cytotoxic to kidneys, making it difficult to distinguish between DN-related and STZ-induced nephropathy. Therefore, an improved protocol to generate mice for DN studies, with a quick and robust achievement of the diabetic state, without direct kidney toxicity is required. To investigate the mechanism leading to STZ-induced nephropathy, kidney damage was induced with a high dose of STZ. This resulted in delayed gastric emptying, at least partially caused by impaired desacyl ghrelin clearance. STZ uptake in the kidneys is to a large extent mediated by the sodium/glucose cotransporters (Sglts) because the Sglt inhibitor phlorizin could reduce STZ uptake in the kidneys. Consequently, the direct toxic effects in the kidney and the gastric dilatation were resolved without interfering with the β-cell toxicity. Furthermore, pancreatic STZ uptake was increased, hereby decreasing the threshold for β-cell toxicity, allowing for single low non-nephrotoxic STZ doses (70 mg/kg). In conclusion, this study provides novel insights into the mechanism of STZ toxicity in kidneys and suggests a more efficient regime to induce DN with little or no toxic side effects.

  12. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

    Directory of Open Access Journals (Sweden)

    Roberto Furlanetto Jr

    2017-02-01

    Full Text Available Objective: We studied the effect of resistance exercise (RE on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF. Material and methods : Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams were randomly allocated into five groups: control group (CT-Sham; n = 6; group with rheumatoid arthritis (RA; n = 6; group with rheumatoid arthritis subjected to RE (RAEX; n = 6; ovariectomy group with rheumatoid arthritis (RAOV; n = 6; and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6. After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results : The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV, but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions : LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1. However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF.

  13. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

    Science.gov (United States)

    Furlanetto, Roberto; de Paula Souza, Aletéia; de Oliveira, Anselmo Alves; Nunes, Paulo Ricardo Prado; Michelin, Márcia Antoniazi; Chica, Javier Emilio Lazo; Murta, Eddie Fernando Candido

    2017-01-01

    Objective We studied the effect of resistance exercise (RE) on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF). Material and methods Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams) were randomly allocated into five groups: control group (CT-Sham; n = 6); group with rheumatoid arthritis (RA; n = 6); group with rheumatoid arthritis subjected to RE (RAEX; n = 6); ovariectomy group with rheumatoid arthritis (RAOV; n = 6); and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6). After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA) of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV), but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1). However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF. PMID:28250722

  14. Comprehensive geriatric care reduces acute perioperative delirium in elderly patients with hip fractures: A meta-analysis.

    Science.gov (United States)

    Wang, Yiyang; Tang, Jun; Zhou, Feiya; Yang, Lei; Wu, Jianbin

    2017-06-01

    The aim of the current meta-analysis was to assess the treatment effect of comprehensive geriatric care in reducing acute perioperative delirium in older patients with hip fractures, compared with the effect of a routine orthopedic treatment protocol. We conducted a search of multiple databases to identify randomized controlled trials (RCTs) and quasi-RCTs comparing comprehensive geriatric care and routine orthopedic treatment regarding the following outcomes: incidence of delirium, assessment of cognitive status, and duration of delirium. Odds ratios (ORs) and mean differences (MDs) were pooled using either a fixed-effects or a random-effects model, depending on the heterogeneity of the trials included in the analysis. Six RCTs and 1 quasi-RCT provided data from 1840 patients. These data revealed that comprehensive geriatric care may reduce the incidence of perioperative delirium (OR = 0.71; 95% confidence interval [CI], 0.57-0.89; P = .003) and that it was associated with higher cognitive status during hospitalization or at 1 month postoperatively (MD = 1.03; 95% CI, 0.93-1.13; P ≤ .00001). There was no significant difference in duration of perioperative delirium between the 2 treatment groups (MD = -2.48; 95% CI, -7.36 to 2.40; P = .32). Based on the quality of evidence provided, comprehensive geriatric care may reduce the incidence of perioperative delirium. To obtain evidence regarding the merits of comprehensive geriatric care in reducing severity of delirium and shortening the duration of delirium, there is a need for multicenter RCTs with high methodological quality.

  15. Fish oil-supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

    Science.gov (United States)

    Li, Xiaolong; Zhang, Xianxiang; Yang, Enqin; Zhang, Nanyang; Cao, Shougen; Zhou, Yanbing

    2015-09-01

    The objectives were to confirm that intravenous fish oil (FO) emulsions could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis and to explore the mechanisms of these effects. Thirty-six adult male Sprague-Dawley rats were divided into 4 groups randomly. Two days after central venous catheterization, rats were subjected to cecal ligation and puncture to produce abdominal sepsis. Rats were assigned to receive normal saline or total parenteral nutrition (TPN) containing standard soybean oil emulsions or FO-supplemented TPN at the onset of sepsis for 5 days. A sham operation and control treatment were performed in control group rats. Acute lung injury scores, peripheral blood lymphocyte subsets, plasma cytokines, and Foxp3 expression in the spleen were determined. Compared with the normal saline and TPN without FO, FO-supplemented TPN beneficially altered the distributions of the T-lymphocyte subsets and downregulated the acute lung injury scores, plasma cytokines, and expression of Foxp3 due to sepsis. Fish oil-supplemented TPN can decrease acute lung injury scores, alleviate histopathology, reduce the bacterial load in the peritoneal lavage fluid, modulate the lymphocyte subpopulation in the peripheral blood, downregulate Foxp3 expression in the spleen, and reduce plasma cytokines, which means that FO-supplemented TPN can alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

  16. Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain – a randomized, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Blahova Z

    2016-12-01

    Full Text Available Zuzana Blahova,1 Janina Claudia Holm,1 Thomas Weiser,2 Erika Richter,2 Matthias Trampisch,2 Elena Akarachkova3 1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany; 3I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background/objective: Low back pain affects many patients and has a high socioeconomic impact. Topical capsaicinoids have been used for decades to treat musculoskeletal pain. This study investigated the effects of the fixed dose combination (FDC of nonivamide (a capsaicinoid and nicoboxil (a nicotinic acid ester cream in the treatment of acute nonspecific low back pain.Materials and methods: This phase III randomized, double-blind, placebo-controlled, multinational, multi-center trial investigated efficacy, safety, and tolerability of topical nicoboxil 1.08%/nonivamide 0.17% (Finalgon® cream in treatment of acute nonspecific low back pain with the endpoints: pain intensity (PI difference between pre-dose baseline and 8 hours after first application and the end of treatment, mobility score, and efficacy score.Results: Patients (n=138, 21–65 years of age, were treated for up to 4 days with FDC or placebo cream. Mean baseline PI was 6.8 on a 0–10 point numerical rating scale. After 8 hours, pain was more reduced with the FDC than with placebo (adjusted means: 2.824 vs. 0.975 points; p<0.0001. On the last treatment day, mean pain reduction by the FDC was stronger than with placebo (adjusted means: 5.132 vs. 2.174 points; p<0.0001. Mobility on Day 1 was in favor of the FDC when compared to placebo (odds ratio [95% confidence interval {CI}]: 7.200 [3.609, 14.363], p<0.0001. At the end of treatment, patients treated with the FDC rated efficacy significantly higher than placebo (odds ratio [95% CI]: 11.370 [5.342, 24.199], p<0.0001. Both treatments were tolerated well. No serious adverse events were reported.Conclusion: Nicoboxil

  17. Acute caffeine ingestion enhances strength performance and reduces perceived exertion and muscle pain perception during resistance exercise.

    Science.gov (United States)

    Duncan, Michael J; Stanley, Michelle; Parkhouse, Natalie; Cook, Kathryn; Smith, Mike

    2013-01-01

    . With caffeine, pain perception was significantly higher in the deadlift and back squat compared to the bench press. However, with placebo, pain perception was significantly higher for the deadlift and back squat compared to the prone row only. Therefore, acute caffeine ingestion not only enhances resistance exercise performance to failure but also reduces perception of exertion and muscle pain.

  18. FTY720 ameliorates acute ischemic stroke in mice by reducing thrombo-inflammation but not by direct neuroprotection.

    Science.gov (United States)

    Kraft, Peter; Göb, Eva; Schuhmann, Michael K; Göbel, Kerstin; Deppermann, Carsten; Thielmann, Ina; Herrmann, Alexander M; Lorenz, Kristina; Brede, Marc; Stoll, Guido; Meuth, Sven G; Nieswandt, Bernhard; Pfeilschifter, Waltraud; Kleinschnitz, Christoph

    2013-11-01

    Lymphocytes are important players in the pathophysiology of acute ischemic stroke. The interaction of lymphocytes with endothelial cells and platelets, termed thrombo-inflammation, fosters microvascular dysfunction and secondary infarct growth. FTY720, a sphingosine-1-phosphate receptor modulator, blocks the egress of lymphocytes from lymphoid organs and has been shown to reduce ischemic neurodegeneration; however, the underlying mechanisms are unclear. We investigated the mode of FTY720 action in models of cerebral ischemia. Transient middle cerebral artery occlusion (tMCAO) was induced in wild-type and lymphocyte-deficient Rag1(-/-) mice treated with FTY720 (1 mg/kg) or vehicle immediately before reperfusion. Stroke outcome was assessed 24 hours later. Immune cells in the blood and brain were counted by flow cytometry. The integrity of the blood-brain barrier was analyzed using Evans Blue dye. Thrombus formation was determined by immunohistochemistry and Western blot, and was correlated with cerebral perfusion. FTY720 significantly reduced stroke size and improved functional outcome in wild-type mice on day 1 and day 3 after transient middle cerebral artery occlusion. This protective effect was lost in lymphocyte-deficient Rag1(-/-) mice and in cultured neurons subjected to hypoxia. Less lymphocytes were present in the cerebral vasculature of FTY720-treated wild-type mice, which in turn reduced thrombosis and increased cerebral perfusion. In contrast, FTY720 was unable to prevent blood-brain barrier breakdown and transendothelial immune cell trafficking after transient middle cerebral artery occlusion. Induction of lymphocytopenia and concomitant reduction of microvascular thrombosis are key modes of FTY720 action in stroke. In contrast, our findings in Rag1(-/-) mice and cultured neurons argue against direct neuroprotective effects of FTY720.

  19. Clinical and Economic Impact of a Multisciplinary Intervention to Reduce Bleeding Risk in Patients With Acute Coronary Syndrome.

    Science.gov (United States)

    de Lorenzo-Pinto, Ana; Herranz-Alonso, Ana; Cuéllar-Basterrechea, Begoña; Bellón-Cano, José María; Sanjurjo-Sáez, María; Bueno, Héctor

    2017-04-11

    To evaluate the clinical and economic impact of a multidisciplinary program to reduce bleeding events in patients with acute coronary syndrome through optimization of antithrombotic therapy. We designed a preintervention (PRE) and postintervention (POST) quasi-experimental study using a retrospective analysis of 2 cohorts. The first cohort was analyzed to detect correctable measures contributing to bleeding (PRE). Afterward, a quality improvement intervention with a bundle of recommendations was implemented. Finally, a second cohort of patients was evaluated to investigate the impact of the measures on bleeding reduction (POST). The impact on health outcomes was evaluated through comparison of the percentage of in-hospital bleeding events and 30-day readmissions between the 2 cohorts. The economic analysis took into account the costs associated with the implementation of the program and the cost-savings associated with the prevention of bleeding events and 30-day readmissions. A total of 677 patients were included (377 in PRE and 300 in POST). The total bleeding rate was reduced after the implementation of the bundled intervention by 29.2% (31.6% in POST vs 22.3% in PRE; OR, 0.62; 95%CI, 0.44-0.88) while 30-day readmission rates were 7.7% in PRE and 5% in POST (P=.20). The estimated avoided cost was €95 113.6 per year, meaning that €10.1 would be obtained in return for each euro invested during the first year and €36.3 during the following years. This multidisciplinary program has proven to be effective in reducing bleeding events and is economically attractive. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia.

    Science.gov (United States)

    Asmussen, Sven; Ito, Hiroshi; Traber, Daniel L; Lee, Jae W; Cox, Robert A; Hawkins, Hal K; McAuley, Daniel F; McKenna, David H; Traber, Lillian D; Zhuo, Hanjing; Wilson, Jennifer; Herndon, David N; Prough, Donald S; Liu, Kathleen D; Matthay, Michael A; Enkhbaatar, Perenlei

    2014-09-01

    Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS. Adult sheep (30-40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10(11) CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10(6) hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10(6) hMSCs/kg, n=4. By 24 h, the PaO2/FiO2 ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO2/FiO2 of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9-5.8] vs control: 6.7 g wet/g dry [IQR 6.4-7.5] (p=0.01)). The hMSCs had no adverse effects. Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS. NCT01775774 for Phase 1. NCT02097641 for Phase 2. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. [Successful treatment with reduced-intensity cord blood transplantation for acute myeloid leukemia with complete tetraploidy (92, XXXX)].

    Science.gov (United States)

    Iwasaki, Junko; Onozawa, Masahiro; Takahashi, Shojiro; Okada, Kohei; Takahata, Mutsumi; Shigematsu, Akio; Kahata, Kaoru; Kondo, Takeshi; Hashino, Satoshi; Imamura, Masahiro; Asaka, Masahiro

    2011-03-01

    A 56-year-old female was diagnosed with acute myeloid leukemia (FAB: AML-M1). G-banding karyotype of her bone marrow showed complete tetraploidy (92, XXXX [24/24]). Although she achieved complete remission (CR) after induction therapy and maintained CR during consolidation therapy, relapse occurred only 2 months after discharge. When the relapse occurred, bone marrow karyotypic analysis showed complete tetraploidy again. The patient received reduced-intensity cord blood transplantation (RI-CBT), which induced CR for the second time. The patient is currently alive 24 months after transplantation and there have not been any signs of recurrence to date. There have been a few reports of AML with near-tetraploidy, but cases of AML with complete tetraploidy are extremely rare. Tetraploid AML has been reported to have a poor prognosis and there have been very few cases maintaining CR over the long term after chemotherapy alone. This is the first case of complete tetraploid AML successfully treated by RI-CBT. The clinical course of this case suggests that hematopoietic stem cell transplantation during the first CR phase should be considered a treatment option for tetraploid AML.

  2. Does breastfeeding reduce acute procedural pain in preterm infants in the neonatal intensive care unit? A randomized clinical trial.

    Science.gov (United States)

    Holsti, Liisa; Oberlander, Timothy F; Brant, Rollin

    2011-11-01

    Managing acute procedural pain effectively in preterm infants in the neonatal intensive care unit remains a significant problem. The objectives of this study were to evaluate the efficacy of breastfeeding for reducing pain and to determine if breastfeeding skills were altered after this treatment. Fifty-seven infants born at 30-36 weeks gestational age were randomized to be breastfed (BF) or to be given a soother during blood collection. Changes in the Behavioral Indicators of Infant Pain (BIIP) and in mean heart rate (HR) across 3 phases of blood collection were measured. In the BF group, the Premature Infant Breastfeeding Behaviors (PIBBS) scale was scored before and 24 hours after blood collection. Longitudinal regression analysis was used to compare changes in Lance/squeeze and Recovery phases of blood collection between groups, with gestational age at birth, baseline BIIP scores, and mean HR included as covariates. Differences in PIBBS scores were assessed using a paired t-test. Relationships between PIBBS scores, BIIP scores, and HR were evaluated with Pearson correlations. No differences between treatment groups were found: BIIP (P=0.44, confidence interval [CI] -1.60-0.69); HR (P=0.73, CI -7.0-10.0). Infants in the BF group showed improved PIBBS scores after the treatment (Ppain indices or interfere with the acquisition of breastfeeding skills. Exploratory analyses indicate there may be benefit for infants with mature breastfeeding abilities.

  3. Mometasone Furoate Cream Reduces Acute Radiation Dermatitis in Patients Receiving Breast Radiation Therapy: Results of a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hindley, Andrew, E-mail: andrew.hindley@lthtr.nhs.uk [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom); Zain, Zakiyah [College of Arts and Sciences, Universiti Utara Malaysia, Kedah (Malaysia); Wood, Lisa [Department of Social Sciences, Lancaster Medical School, Lancaster (United Kingdom); Whitehead, Anne [Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster (United Kingdom); Sanneh, Alison; Barber, David; Hornsby, Ruth [Rosemere Cancer Centre, Royal Preston Hospital, Preston (United Kingdom)

    2014-11-15

    Purpose: We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Boström et al, Radiother Oncol 2001;59:257-265). Methods and Materials: The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results: Mean RTOG scores were significantly less for MF than for D (P=.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D (P=.018 and P=.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions: MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

  4. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

    Science.gov (United States)

    Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

    2016-01-01

    The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

  5. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

    Science.gov (United States)

    Shih, Juey-Ming; Shih, Yao-Ming; Pai, Man-Hui; Hou, Yu-Chen; Yeh, Chiu-Li; Yeh, Sung-Ling

    2016-03-15

    Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  6. Does amifostine reduce metabolic rate? Effect of the drug on gas exchange and acute ventilatory hypoxic response in humans.

    Science.gov (United States)

    Pandit, Jaideep J; Allen, Caroline; Little, Evelyn; Formenti, Federico; Harris, Adrian L; Robbins, Peter A

    2015-04-16

    Amifostine is added to chemoradiation regimens in the treatment of many cancers on the basis that, by reducing the metabolic rate, it protects normal cells from toxic effects of therapy. We tested this hypothesis by measuring the metabolic rate (by gas exchange) over 255 min in 6 healthy subjects, at two doses (500 mg and 1000 mg) of amifostine infused over 15 min at the start of the protocol. We also assessed the ventilatory response to six 1 min exposures to isocapnic hypoxia mid-protocol. There was no change in metabolic rate with amifostine as measured by oxygen uptake (p = 0.113). However in carbon dioxide output and respiratory quotient, we detected a small decline over time in control and drug protocols, consistent with a gradual change from carbohydrate to fat metabolism over the course of the relatively long study protocol. A novel result was that amifostine (1000 mg) increased the mean ± SD acute hypoxic ventilatory response from 12.4 ± 5.1 L/min to 20.3 ± 11.9 L/min (p = 0.045). In conclusion, any cellular protective effects of amifostine are unlikely due to metabolic effects. The stimulatory effect on hypoxic ventilatory responses may be due to increased levels of hypoxia inducible factor, either peripherally in the carotid body, or centrally in the brain.

  7. The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3,4-methylenedioxymethamphetamine ('Ecstasy') in healthy volunteers.

    Science.gov (United States)

    Liechti, M E; Vollenweider, F X

    2000-01-01

    MDMA (3,4-methylenedioxymethamphetamine) or 'Ecstasy' is a widely used recreational drug that produces a state of heightened mood but also cardiovascular and vegetative side-effects. In animals, MDMA releases serotonin and, to a lesser extent, dopamine and norepinephrine. The release of serotonin can be blocked by serotonin uptake inhibitors such as citalopram. It is unknown to what extent this mechanism is also responsible for the physiological side-effects of MDMA seen in humans. We investigated the effect of citalopram pretreatment (40 mg i.v.) on vegetative and cardiovascular effects of MDMA (1.5 mg/kg p.o.) in a double-blind placebo-controlled study in 16 healthy volunteers. MDMA moderately increased blood pressure and heart rate, slightly elevated body temperature and produced a broad range of acute and short-term side-effects. Citalopram reduced all these MDMA-induced physiological changes except for body temperature. These findings suggest that physiological effects of MDMA in humans are partially due to an interaction of MDMA with the serotonin carrier and a subsequent release of serotonin.

  8. Does Amifostine Reduce Metabolic Rate? Effect of the Drug on Gas Exchange and Acute Ventilatory Hypoxic Response in Humans

    Directory of Open Access Journals (Sweden)

    Jaideep J. Pandit

    2015-04-01

    Full Text Available Amifostine is added to chemoradiation regimens in the treatment of many cancers on the basis that, by reducing the metabolic rate, it protects normal cells from toxic effects of therapy. We tested this hypothesis by measuring the metabolic rate (by gas exchange over 255 min in 6 healthy subjects, at two doses (500 mg and 1000 mg of amifostine infused over 15 min at the start of the protocol. We also assessed the ventilatory response to six 1 min exposures to isocapnic hypoxia mid-protocol. There was no change in metabolic rate with amifostine as measured by oxygen uptake (p = 0.113. However in carbon dioxide output and respiratory quotient, we detected a small decline over time in control and drug protocols, consistent with a gradual change from carbohydrate to fat metabolism over the course of the relatively long study protocol. A novel result was that amifostine (1000 mg increased the mean ± SD acute hypoxic ventilatory response from 12.4 ± 5.1 L/min to 20.3 ± 11.9 L/min (p = 0.045. In conclusion, any cellular protective effects of amifostine are unlikely due to metabolic effects. The stimulatory effect on hypoxic ventilatory responses may be due to increased levels of hypoxia inducible factor, either peripherally in the carotid body, or centrally in the brain.

  9. Natural antioxidant ice cream acutely reduces oxidative stress and improves vascular function and physical performance in healthy individuals.

    Science.gov (United States)

    Sanguigni, Valerio; Manco, Melania; Sorge, Roberto; Gnessi, Lucio; Francomano, Davide

    2017-01-01

    The formation of reactive oxygen species (ROS) contributes to the pathogenesis and progression of several diseases. Polyphenols have been shown to be beneficial against ROS. The aim of this study was to evaluate the effects of a natural antioxidant ice cream on oxidative stress, vascular function, and physical performance. In this controlled, single-blind, crossover study, 14 healthy individuals were randomized to consume 100 g of either antioxidant ice cream containing dark cocoa powder and hazelnut and green tea extracts or milk chocolate ice cream (control ice cream). Participants were studied at baseline and 2 h after ingesting ice cream. Serum polyphenols, antioxidant status (ferric-reducing ability of plasma [FRAP]), nitric oxide (NOx) bioavailability, markers of oxidative stress (determination of reactive oxygen metabolites [d-ROMs] and hydrogen peroxide [H2O2]), endothelium function (flow-mediated dilation [FMD] and reactive hyperemia index [RHI]), and exercise tolerance (stress test) were assessed, and the double product was measured. Serum polyphenols (P ice cream ingestion. No changes were found after control ice cream ingestion. To our knowledge, this is the first study to demonstrate that a natural ice cream rich in polyphenols acutely improved vascular function and physical performance in healthy individuals through a reduction in oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Statins Therapy Can Reduce the Risk of Atrial Fibrillation in Patients with Acute Coronary Syndrome: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xue Zhou, Jian-lin Du, Jia Yuan, Yun-qing Chen

    2013-01-01

    Full Text Available Background: It is a controversy whether statins therapy could be beneficial for the occurrence of atrial fibrillation (AF in acute coronary syndrome (ACS. To clarify this problem, we performed a meta-analysis with the currently published literatures.Methods: The electronic databases were searched to obtain relevant trials which met the inclusion criteria through October 2011. Two authors independently read the trials and extracted the related information from the included studies. Either fixed-effects models or random-effects models were assumed to calculate the overall combined risk estimates according to I2 statistic. Sensitivity analysis was conducted by omitting one study in each turn, and publication bias was evaluated using Begg's and Egger's test.Results: Six studies were eligible to inclusion criteria, of the six studies, 161305 patients were included in this meta-analysis, 77920 (48.31% patients had taken the statins therapy, 83385 (51.69% patients had taken non-statins therapy. Four studies had investigated the effect of statins therapy on occurrence of new-onset AF in ACS patients, another two had described the association between statins therapy and occurrence of AF in ACS patients with AF in baseline. The occurrence of AF was reduced 35% in statins therapy group compared to that in non-statins group (95% confident interval: 0.55-0.77, P<0.0001, and the effect of statins therapy seemed more beneficial for new-onset AF (RR=0.59, 95%CI: 0.48-0.73, p=0.096 than secondary prevention of AF (RR=0.70, 95%CI: 0.43-1.14, p=0.085. There was no publication bias according to the Begg's and Egger's test (Begg, p=0.71; Egger, p=0.73.Conclusion: Statins therapy could reduce the risk of atrial fibrillation in patients with ACS.

  11. Reduced defense of central blood volume during acute lower body negative pressure-induced hypovolemic circulatory stress in aging women.

    Science.gov (United States)

    Lindenberger, Marcus; Länne, Toste

    2012-06-01

    Elderly humans are more vulnerable to trauma and hemorrhage than young and elderly men and respond with decreased defense of central blood volume during acute experimental hypovolemia induced by lower body negative pressure (LBNP). However, these defense mechanisms have not been evaluated in elderly women. The aim of this study was to determine the effectiveness of compensatory responses to defend central blood volume during experimental hypovolemia in elderly and young women. Cardiovascular responses in 34 women, 12 elderly (66 ± 1 years) and 22 young women (23 ± 0.4 years), were studied during experimental hypovolemia induced by LBNP of 11 to 44 mmHg. Air plethysmography was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as net capillary fluid transfer from tissue to blood in the arm. Lower body negative pressure seemed to create comparable hypovolemia measured as total calf volume increase in elderly and young women. Heart rate increased less in elderly women (LBNP of 44 mmHg: 20 ± 2 vs. 37 ± 4%; P < 0.01) but with similar (%) increase in forearm vascular resistance. Mobilization of capacitance blood from the peripheral circulation was both slower and decreased by ∼60% in elderly women (P < 0.001), and net capillary fluid absorption from surrounding tissues was reduced by ∼40% (P < 0.01, LBNP of 44 mmHg). Elderly women responded with less increase in heart rate but with equal forearm vascular resistance (%) response during LBNP. Furthermore, the compensatory capacitance response was both slower and substantially decreased, and net capillary fluid absorption considerably reduced, collectively indicating less efficiency to defend central blood volume in elderly than in young women.

  12. Acute aerobic exercise reduces 24-h ambulatory blood pressure levels in long-term-treated hypertensive patients

    Directory of Open Access Journals (Sweden)

    Emmanuel G. Ciolac

    2008-01-01

    Full Text Available BACKGROUND: Even with anti-hypertensive therapy, it is difficult to maintain optimal systemic blood pressure values in hypertensive patients. Exercise may reduce blood pressure in untreated hypertensive, but its effect when combined with long-term anti-hypertensive therapy remains unclear. Our purpose was to evaluate the acute effects of a single session of aerobic exercise on the blood pressure of long-term-treated hypertensive patients. METHODS: Fifty treated hypertensive patients (18/32 male/female; 46.5±8.2 years; Body mass index: 27.8±4.7 kg/m² were monitored for 24 h with respect to ambulatory (A blood pressure after an aerobic exercise session (post-exercise and a control period (control in random order. Aerobic exercise consisted of 40 minutes on a cycle-ergometer, with the mean exercise intensity at 60% of the patient's reserve heart rate. RESULTS: Post-exercise ambulatory blood pressure was reduced for 24 h systolic (126±8.6 vs. 123.1±8.7 mmHg, p=0.004 and diastolic blood pressure (81.9±8 vs. 79.8±8.5 mmHg, p=0.004, daytime diastolic blood pressure (85.5±8.5 vs. 83.9±8.8 mmHg, p=0.04, and nighttime S (116.8±9.9 vs. 112.5±9.2 mmHg, p<0.001 and diastolic blood pressure (73.5±8.8 vs. 70.1±8.4 mmHg, p<0.001. Post-exercise daytime systolic blood pressure also tended to be reduced (129.8±9.3 vs. 127.8±9.4 mmHg, p=0.06. These post-exercise decreases in ambulatory blood pressure increased the percentage of patients displaying normal 24h systolic blood pressure (58% vs. 76%, p=0.007, daytime systolic blood pressure (68% vs. 82%, p=0.02, and nighttime diastolic blood pressure (56% vs. 72%, p=0.02. Nighttime systolic blood pressure also tended to increase (58% vs. 80%, p=0.058. CONCLUSION: A single bout of aerobic exercise reduced 24h ambulatory blood pressure levels in long-term-treated hypertensive patients and increased the percentage of patients reaching normal ambulatory blood pressure values. These effects suggest that

  13. Large-scale field application of RNAi technology reducing Israeli Acute Paralysis Virus Disease in honey bees (Apis mellifera, Hymenoptera; Apidae)

    Science.gov (United States)

    We present the first successful use of RNAi under a large-scale real-world application for disease control. Israeli acute paralysis virus, IAPV, has been linked as a contributing factor in coolly collapse, CCD, of honey bees. IAPV specific homologous dsRNA were designed to reduce impacts from IAPV i...

  14. Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

    Institute of Scientific and Technical Information of China (English)

    Shafi Mojadadi; Abbas Jamali; Behzad Khansarinejad; Hoorieh Soleimanjahi; Taravat Bamdad

    2009-01-01

    Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-1. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation. Cellular & Molecular Immunology.

  15. Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

    Energy Technology Data Exchange (ETDEWEB)

    Albino, C.C., E-mail: ccalbino@uol.com.b [Instituto de Diabetes e Endocrinologia de Maringa, PR (Brazil); Graf, H.; Paz-Filho, G. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital das Clinicas. Servico de Endocrinologia e Metabologia; Diehl, L.A. [Universidade Estadual de Londrina (UEL), PR (Brazil); Olandoski, M.; Sabbag, A. [Pontificia Univ. Catolica do Parana (PUCPR), Curitiba, PR (Brazil). Nucleo de Bioestatistica; Buchpiguel, C. [Universidade de Sao Paulo (USP), SP (Brazil). Dept. de Radiologia

    2006-03-15

    Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of {sup 131}I for treating MNG. Euthyroid patients with MNG (69.3 +- 62.0 mL, 20 females, 2 males, 64 +- 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq {sup 131}I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 +- 17.6%) and II (21.6 +- 17.8%), but not in group III (2.7 +- 15.3%). After 12 months, TV decreased significantly in groups I (36.7 +- 18.1%) and II (37.4 +- 27.1%), but not in group III (19.0 +- 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed {sup 131}I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus {sup 131}I (author)

  16. H2S Attenuates LPS-Induced Acute Lung Injury by Reducing Oxidative/Nitrative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Hong-Xia Zhang

    2016-12-01

    Full Text Available Background: Hydrogen sulfide (H2S, known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI induced by endotoxemia. Methods: Male ICR mice were divided in six groups: (1 Control group; (2 GYY4137treatment group; (3 L-NAME treatment group; (4 lipopolysaccharide (LPS treatment group; (5 LPS with GYY4137 treatment group; and (6 LPS with L-NAME treatment group. The lungs were analysed by histology, NO production in the mouse lungs determined by modified Griess (Sigma-Aldrich reaction, cytokine levels utilizing commercialkits, and protein abundance by Western blotting. Results: GYY4137, a slowly-releasing H2S donor, improved the histopathological changes in the lungs of endotoxemic mice. Treatment with NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase (NOS inhibitor, increased anti-oxidant biomarkers such as thetotal antioxidant capacity (T-AOC and theactivities of catalase (CAT and superoxide dismutase (SOD but decreased a marker of peroxynitrite (ONOO- action and 3-nitrotyrosine (3-NT in endotoxemic lung. L-NAME administration also suppressed inflammation in endotoxemic lung, as evidenced by the decreased pulmonary levels of interleukin (IL-6, IL-8, and myeloperoxidase (MPO and the increased level of anti-inflammatory cytokine IL-10. GYY4137 treatment reversed endotoxin-induced oxidative/nitrative stress, as evidenced by a decrease in malondialdehyde (MDA, hydrogenperoxide (H2O2 and 3-NT and an increase in the antioxidant biomarker ratio of reduced/oxidized glutathione(GSH/GSSG ratio and T-AOC, CAT and SOD activity. GYY4137 also attenuated endotoxin-induced lung inflammation. Moreover, treatment with GYY4137 inhibited inducible NOS (iNOS expression and nitric oxide (NO production in the

  17. Combined intra-arterial thrombolysis and neuprotectant agents reduce cerebral infarction in rabbits with experimental acute cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pei Shi

    2006-01-01

    BACKGROUND:The intra-arterial thrombolytic therapy is one of main methods for more patients to obtain bene-fits.The percentage of arterial recanalization treated with intre-arterial therapy is higher than with intra-venous therapy.next,the dose of thrombolytic medicines is lower and the therapeutic time window may be possibly longer.Related researches are focus on intra-artedal thrombolysis combining with neuprotectant agents to treat acute ischemic stroke.The results show that combination of them can further prolong the therapeutic time window.improve the percentage of arterial recanalization and reduce cerebral infarction volume.OBJECTIVE:To observe the effect of single thmmbolitic therapy combined with neuroprotectant agents in the treatment of acute ischemic stroke.DESIGN:Randomized block design.SETTING:Xinhua Hospital of Xixiang City.Henan Province.MATERIALS:Thirty-six adult male white rabbits.weighing 1.5-2.0 kg.dean grade.were provided by Expedmental Animal Center of Xinxiang Medical College.All rabbits were randomly divided into three groups:intra-arterial thrombolysis control group.corenalin control group and combination group with 12 in each group.Urekinase was provided by Beijing Saisheng Pharmaceutical Co.,Ltd.(batch number:020923);corenalin by Sanjing Pharmaceutical Co.,Ltd.of Harbin Pharmacautical Group(batch number:021106):nimodipine by Shandong Xihua Pharmaceutical Co.,Ltd.(batch number:020611):contrast medium IOPAMlR0300 by Bracco s.P.a.Milano italian (batch number:0584);2,3,5-triphenyltetrazolium chloride(TTC)by Beijing Mashi Fine ChemicaL Product Co.,Ltd.(batch number:020926).METHODS: The experiment was camed out in the Department of Intervention. Second People's Hospital of Xinxiang from September 2002 to May 2003.①According to techniques of Benes et al and Zhu et al,animal models with acute ischemia were established.Two hours later.the therapy began.Intra-artedal thrombolysis control group:5 000 U/kg urokinase was dripped in Ieft common

  18. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice

    Directory of Open Access Journals (Sweden)

    Juey-Ming Shih

    2016-03-01

    Full Text Available Acute kidney injury (AKI is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP. The antibiotic was injected intraperitoneally (IP after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO, while the other two groups were given either a mixed oil emulsion (MO or saline (SC. The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th1/Th-2/Th-17 and Treg cells (p < 0.05. Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05. Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p < 0.05, at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  19. Protective ventilation of preterm lambs exposed to acute chorioamnionitis does not reduce ventilation-induced lung or brain injury.

    Directory of Open Access Journals (Sweden)

    Samantha K Barton

    Full Text Available The onset of mechanical ventilation is a critical time for the initiation of cerebral white matter (WM injury in preterm neonates, particularly if they are inadvertently exposed to high tidal volumes (VT in the delivery room. Protective ventilation strategies at birth reduce ventilation-induced lung and brain inflammation and injury, however its efficacy in a compromised newborn is not known. Chorioamnionitis is a common antecedent of preterm birth, and increases the risk and severity of WM injury. We investigated the effects of high VT ventilation, after chorioamnionitis, on preterm lung and WM inflammation and injury, and whether a protective ventilation strategy could mitigate the response.Pregnant ewes (n = 18 received intra-amniotic lipopolysaccharide (LPS 2 days before delivery, instrumentation and ventilation at 127±1 days gestation. Lambs were either immediately euthanased and used as unventilated controls (LPSUVC; n = 6, or were ventilated using an injurious high VT strategy (LPSINJ; n = 5 or a protective ventilation strategy (LPSPROT; n = 7 for a total of 90 min. Mean arterial pressure, heart rate and cerebral haemodynamics and oxygenation were measured continuously. Lungs and brains underwent molecular and histological assessment of inflammation and injury.LPSINJ lambs had poorer oxygenation than LPSPROT lambs. Ventilation requirements and cardiopulmonary and systemic haemodynamics were not different between ventilation strategies. Compared to unventilated lambs, LPSINJ and LPSPROT lambs had increases in pro-inflammatory cytokine expression within the lungs and brain, and increased astrogliosis (p<0.02 and cell death (p<0.05 in the WM, which were equivalent in magnitude between groups.Ventilation after acute chorioamnionitis, irrespective of strategy used, increases haemodynamic instability and lung and cerebral inflammation and injury. Mechanical ventilation is a potential contributor to WM injury in infants exposed

  20. The effect of antiemetics and reduced radiation fields on acute gastrointestinal morbidity of adjuvant radiotherapy in Stage I seminoma of the testis: a randomized pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Khoo, V.S.; Rainford, K.; Horwich, A.; Dearnaley, D.P. [Royal Marsden NHS Trust, Sutton (United Kingdom)

    1997-12-31

    The purpose of this pilot study was to evaluate the acute gastrointestinal morbidity of adjuvant radiotherapy (RT) for Stage I seminoma of the testis. Ten Stage I patients receiving para-aortic and ipsilateral pelvic nodal (dog-leg) RT provided a toxicity baseline (group A). Twenty Stage I patients randomized to dog-let RT or para-aortic RT (10 per group) were further randomized to received prophylactic ondansetron or expectant therapy with metoclopramide (group B). Daily patient-completed questionnaires evaluated acute toxicity. Dog-leg RT for Stage I seminomas is associated with readily demonstrable gastrointestinal tract (GIT) toxicity. The number of patients in this study is too small to produce definitive results, but there appears to be reduced GIT toxicity with prophylactic antiemetics. The effect of reduced RT fields has been assessed further in the MRC randomized tiral of field sizes (TE10). (Author).

  1. Wheat germ agglutinin anchored chitosan microspheres of reduced brominated derivative of noscapine ameliorated acute inflammation in experimental colitis.

    Science.gov (United States)

    Kaur, Kamalpreet; Sodhi, Rupinder Kaur; Katyal, Anju; Aneja, Ritu; Jain, Upendra Kumar; Katare, Om Prakash; Madan, Jitender

    2015-08-01

    Reduced brominated derivative of noscapine (Red-Br-Nos, EM012), has potent anti-inflammatory property. However, physicochemical limitations of Red-Br-Nos like low aqueous solubility (0.43×10(-3) g/mL), high lipophilicity (logP∼2.94) and ionization at acidic pH greatly encumber the scale-up of oral drug delivery systems for the management of colitis. Therefore, in present investigation, chitosan microspheres bearing Red-Br-Nos (CTS-MS-Red-Br-Nos) were prepared by emulsion polymerization method and later coated with wheat germ agglutinin (WGA-CTS-MS-Red-Br-Nos) to boost the bioadhesive property. The mean particle size and zeta-potential of CTS-MS-Red-Br-Nos were measured to be 10.5±5.4 μm and 8.1±2.2 mV, significantly (P<0.05) lesser than, 30.2±3.2 μm and 19.2±2.3 mV of WGA-CTS-MS-Red-Br-Nos. Furthermore, various spectral techniques like SEM, FT-IR, DSC and PXRD substantiated that Red-Br-Nos was molecularly dispersed in tailored microspheres in amorphous state. Surface bioadhesive property of WGA-CTS-MS-Red-Br-Nos promoted the affinity toward colon mucin cells in simulated colonic fluid (SCF, pH∼7.2). In vitro release studies carried out on WGA-CTS-MS-Red-Br-Nos and CTS-MS-Red-Br-Nos indicated that SCF with colitis milieu (pH∼4.7) favored the controlled release of Red-Br-Nos, owing to solubilization at acidic pH. Consistently, in vivo investigation also demonstrated the utility of WGA-CTS-MS-Red-Br-Nos, which remarkably attenuated the DSS encouraged neutrophil infiltration, myeloperoxidase activity, and pro-inflammatory cytokine production in C57BL6J mice, as compared to CTS-MS-Red-Br-Nos and Red-Br-Nos suspension. The noteworthy anti-inflammatory activity of WGA-CTS-MS-Red-Br-Nos against acute colitis may be attributed to enhanced drug delivery, affinity and utmost drug exposure at inflamed mucosal layers of colon. In conclusion, WGA-CTS-MS-Red-Br-Nos warrants further in-depth in vitro and in vivo investigations to scale-up the technology for clinical

  2. Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults

    Institute of Scientific and Technical Information of China (English)

    Wei-xing CHEN; Chuan-qin XU; Shao-hua CHEN; Gen-yun XU; Huai-zhuang YE

    2012-01-01

    .05),while there were no significant differences between the latter two treatments.The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption.It may also affect some blood biochemical indicators,but the specific mechanisms need further research.

  3. Reduced triglyceride secretion in response to an acute dietary fat challenge in obese compared to lean mice.

    Directory of Open Access Journals (Sweden)

    Aki eUchida

    2012-02-01

    Full Text Available Obesity results in abnormally high levels of triglyceride (TG storage in tissues such as liver, heart and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO and leptin-deficient (ob/ob mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after fasting. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice.

  4. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

    OpenAIRE

    Chan, Michael C W; Kuok, Denise I. T.; Leung, Connie Y. H.; Hui, Kenrie P Y; Valkenburg, Sophie A.; Lau, Eric H. Y.; Nicholls, John M; Fang, Xiaohui; Guan, Yi; Lee, Jae W; Chan, Renee W. Y.; Webster, Robert G; Matthay, Michael A.; Peiris, J. S. Malik

    2016-01-01

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstr...

  5. Reducing the Incidence of Acute Pesticide Poisoning by Educating Farmers on Integrated Pest Management in South India

    NARCIS (Netherlands)

    Mancini, F.; Jiggins, J.L.S.; O'Malley, M.

    2009-01-01

    Sixty-five farmers reported on pesticide use and the signs and symptoms of acute pesticide poisoning when using two different plant protection strategies: in 2003 using chemical controls and in 2004 using an approach to Integrated Pest Management (IPM) based on an ecological analysis of the field

  6. Reducing the Incidence of Acute Pesticide Poisoning by Educating Farmers on Integrated Pest Management in South India

    NARCIS (Netherlands)

    Mancini, F.; Jiggins, J.L.S.; O'Malley, M.

    2009-01-01

    Sixty-five farmers reported on pesticide use and the signs and symptoms of acute pesticide poisoning when using two different plant protection strategies: in 2003 using chemical controls and in 2004 using an approach to Integrated Pest Management (IPM) based on an ecological analysis of the field co

  7. Effect of acute and chronic graft-versus-host disease on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

    Science.gov (United States)

    Ringdén, Olle; Shrestha, Smriti; da Silva, Gisela Tunes; Zhang, Mei-Jie; Dispenzieri, Angela; Remberger, Mats; Kamble, Rammurti; Freytes, Cesar O.; Gale, Robert Peter; Gibson, John; Gupta, Vikas; Holmberg, Leona; Lazarus, Hillard; McCarthy, Philip; Meehan, Kenneth; Schouten, Harry; Milone, Gustavo A.; Lonial, Sagar; Hari, Parameswaran N

    2011-01-01

    We evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on relapse and survival after allogeneic haematopoietic stem cell transplantation (HSCT) for multiple myeloma (MM) using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005 following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (grades I–IV) was 42% (95% confidence interval (CI) 35 – 49%) and of chronic GVHD at five years was 59% (95% CI 49 – 69%), with 70% developing extensive chronic GVHD. In multivariate analysis, acute GVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42; p=0.016), whereas limited chronic GVHD significantly decreased the risk of myeloma relapse (RR=0.35, p=0.035) and was associated with superior event-free survival (RR=0.40, p=0.027). Acute GVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52; p=0.001). The reduction in relapse risk associated with chronic GVHD is consistent with a beneficial graft-versus-myeloma effect, but this did not translate into a survival advantage. PMID:21946381

  8. Acute appendicitis: prospective evaluation of a diagnostic algorithm integrating ultrasound and low-dose CT to reduce the need of standard CT

    Energy Technology Data Exchange (ETDEWEB)

    Poletti, Pierre-Alexandre; Platon, Alexandra [University Hospital of Geneva, Department of Radiology, Geneva (Switzerland); University Hospital of Geneva, Emergency Center, Geneva (Switzerland); Perrot, Thomas de; Becker, Christoph D. [University Hospital of Geneva, Department of Radiology, Geneva (Switzerland); Sarasin, Francois; Rutschmann, Olivier [University Hospital of Geneva, Emergency Center, Geneva (Switzerland); Andereggen, Elisabeth [University Hospital of Geneva, Emergency Center, Geneva (Switzerland); University Hospital of Geneva, Department of Surgery, Geneva (Switzerland); Dupuis-Lozeron, Elise; Perneger, Thomas [University Hospital of Geneva, Division of Clinical Epidemiology, Geneva (Switzerland); Gervaz, Pascal [University Hospital of Geneva, Department of Surgery, Geneva (Switzerland)

    2011-12-15

    To evaluate an algorithm integrating ultrasound and low-dose unenhanced CT with oral contrast medium (LDCT) in the assessment of acute appendicitis, to reduce the need of conventional CT. Ultrasound was performed upon admission in 183 consecutive adult patients (111 women, 72 men, mean age 32) with suspicion of acute appendicitis and a BMI between 18.5 and 30 (step 1). No further examination was recommended when ultrasound was positive for appendicitis, negative with low clinical suspicion, or demonstrated an alternative diagnosis. All other patients underwent LDCT (30 mAs) (step 2). Standard intravenously enhanced CT (180 mAs) was performed after indeterminate LDCT (step 3). No further imaging was recommended after ultrasound in 84 (46%) patients; LDCT was obtained in 99 (54%). LDCT was positive or negative for appendicitis in 81 (82%) of these 99 patients, indeterminate in 18 (18%) who underwent standard CT. Eighty-six (47%) of the 183 patients had a surgically proven appendicitis. The sensitivity and specificity of the algorithm were 98.8% and 96.9%. The proposed algorithm achieved high sensitivity and specificity for detection of acute appendicitis, while reducing the need for standard CT and thus limiting exposition to radiation and to intravenous contrast media. (orig.)

  9. Acute appendicitis: prospective evaluation of a diagnostic algorithm integrating ultrasound and low-dose CT to reduce the need of standard CT.

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Platon, Alexandra; De Perrot, Thomas; Sarasin, Francois; Andereggen, Elisabeth; Rutschmann, Olivier; Dupuis-Lozeron, Elise; Perneger, Thomas; Gervaz, Pascal; Becker, Christoph D

    2011-12-01

    To evaluate an algorithm integrating ultrasound and low-dose unenhanced CT with oral contrast medium (LDCT) in the assessment of acute appendicitis, to reduce the need of conventional CT. Ultrasound was performed upon admission in 183 consecutive adult patients (111 women, 72 men, mean age 32) with suspicion of acute appendicitis and a BMI between 18.5 and 30 (step 1). No further examination was recommended when ultrasound was positive for appendicitis, negative with low clinical suspicion, or demonstrated an alternative diagnosis. All other patients underwent LDCT (30 mAs) (step 2). Standard intravenously enhanced CT (180 mAs) was performed after indeterminate LDCT (step 3). No further imaging was recommended after ultrasound in 84 (46%) patients; LDCT was obtained in 99 (54%). LDCT was positive or negative for appendicitis in 81 (82%) of these 99 patients, indeterminate in 18 (18%) who underwent standard CT. Eighty-six (47%) of the 183 patients had a surgically proven appendicitis. The sensitivity and specificity of the algorithm were 98.8% and 96.9%. The proposed algorithm achieved high sensitivity and specificity for detection of acute appendicitis, while reducing the need for standard CT and thus limiting exposition to radiation and to intravenous contrast media.

  10. Immunization Str.pneumonia vaccine reduces the incidence orphanage children’s acute otitis media (preliminary results

    Directory of Open Access Journals (Sweden)

    A. A. Dzhumagaziev

    2012-01-01

    Full Text Available In order to assess the impact of pneumococcal vaccine on the incidence of ear infections in children in the first four years of life, the comparative analysis of monthly incidence of the disease in 18 months in previously vaccinated children, and for the first six months after the catch-up immunization of 7- (PCV7 or 23 – valent (PPV23 pneumococcal vaccine . Traced threefold reduction in the incidence of hospitalization 114 children being raised in orphanages for acute otitis after a single use of pneumococcal vaccine. Early immunization of 101 children against pneumococcus contributes monthly prevent 1 case of hospitalization for acute otitis media.

  11. Rapid eye movement-sleep is reduced in patients with acute uncomplicated diverticulitis—an observational study

    DEFF Research Database (Denmark)

    Huang, Chenxi; Alamili, Mahdi; Nielsen, Claus Henrik

    2015-01-01

    responses are believed to cause postoperative sleep disturbances, as inflammatory responses can alter sleep architecture through cytokine-brain interactions. Our aim was to investigate alteration of sleep architecture during acute infection and its relationships to inflammation and clinical symptoms......Introduction. Sleep disturbances are commonly found in patients in the postoperative period. Sleep disturbances may give rise to several complications including cardiopulmonary instability, transient cognitive dysfunction and prolonged convalescence. Many factors including host inflammatory....... Materials & Methods. In this observational study, we included patients with acute uncomplicated diverticulitis as a model to investigate the isolated effects of inflammatory responses on sleep. Eleven patients completed the study. Patients were admitted and treated with antibiotics for two nights, during...

  12. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

    DEFF Research Database (Denmark)

    Castellano, J M; Bentsen, A H; Romero, M;

    2010-01-01

    of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin......-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake...... and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center...

  13. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Nishihori Taiga

    2010-10-01

    Full Text Available Abstract Optimal conditioning therapy for hematopoietic cell transplantation (HCT in acute myelogenous leukemia (AML remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days and cyclophosphamide (60 mg/kg IV × 2 days - (Bu/Cy with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC

  14. Effectiveness of acute in-hospital physiotherapy with knee-extension strength training in reducing strength deficits in patients with a hip fracture

    DEFF Research Database (Denmark)

    Kronborg, Lise; Bandholm, Thomas; Palm, Henrik

    2017-01-01

    QUESTION: Is acute in-hospital physiotherapy with additional progressive knee-extension strength training (ST) of the fractured limb more effective in reducing knee-extension strength deficit at follow-up compared to physiotherapy without strength training in patients with a hip fracture? DESIGN......: Assessor blinded, randomised controlled trial with intention-to-treat analysis. PARTICIPANTS: 90 patients with a hip fracture admitted to an acute orthopaedic Hip Fracture Unit at a university hospital between October 2013 and May 2015. INTERVENTION: Daily physiotherapy with or without progressive knee...... strength training from baseline to follow-up. In the per-protocol analysis of non-missing data, significant between-group improvements by 10.5% (95% CI 0.3; 20.7) were found in favour of additional ST. No significant between-group differences were found in any secondary outcome. CONCLUSION: Physiotherapy...

  15. Acute exercise reduces hepatic glucose production through inhibition of the Foxo1/HNF-4alpha pathway in insulin resistant mice.

    Science.gov (United States)

    De Souza, Cláudio T; Frederico, Marisa J S; da Luz, Gabrielle; Cintra, Dennys E; Ropelle, Eduardo R; Pauli, José R; Velloso, Lício A

    2010-06-15

    Protein hepatocyte nuclear factor 4alpha (HNF-4alpha) is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. HNF-4alpha and Foxo1 can physically interact with each other and represent an important signal transduction pathway that regulates the synthesis of glucose in the liver. Foxo1 and HNF-4alpha interact with their own binding sites in the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) promoters, and this binding is required for their effects on those promoters. However, the effect of physical activity on the HNF-4alpha/Foxo1 pathway is currently unknown. Here, we investigate the protein levels of HNF-4alpha and the HNF-4alpha/Foxo1 pathway in the liver of leptin-deficient (ob/ob) and diet-induced obese Swiss (DIO) mice after acute exercise. The ob/ob and DIO mice swam for four 30 min periods, with 5 min rest intervals for a total swimming time of 2h. Eight hours after the acute exercise protocol, the mice were submitted to an insulin tolerance test (ITT) and determination of biochemical and molecular parameters. Acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions. These phenomena were accompanied by a reduction in the expression of gluconeogenesis genes, such as PEPCK and G6Pase. Importantly, the PI3K inhibitor LY292004 reversed the acute effect of exercise on fasting hyperglycaemia, confirming the involvement of the PI3K pathway. The present study shows that exercise acutely improves the action of insulin in the liver of animal models of obesity and diabetes, resulting in increased phosphorylation and nuclear exclusion of Foxo1, and a reduction in the Foxo1/HNF-4alpha pathway. Since nuclear localization and the association of these proteins is involved in the activation of PEPCK and G6Pase, we believe that the regulation of Foxo1

  16. Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17.

    Science.gov (United States)

    Sun, Yan; Lin, Lian-Jie; Lin, Yan; Sang, Li-Xuan; Jiang, Min; Zheng, Chang-Qing

    2015-01-01

    This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).

  17. Acute nierschade

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; van Heurn, L.W.E.; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  18. Mass media interventions to reduce help-seeking delay in people with symptoms of acute myocardial infarction: time for a new approach?

    Science.gov (United States)

    Caldwell, Mary A; Miaskowski, Christine

    2002-01-01

    Minimizing patient delay in seeking care for acute myocardial infarction (AMI) is important in the reduction of morbidity and mortality. However, mass media interventions to reduce these delays have had limited success. This paper critiques delay reducing intervention studies and draws on other public health campaigns to identify new directions. A Medline search for the years 1985 through 2000 yielded eight intervention studies meeting inclusion criteria. Three of eight studies reported successful interventions although two of three were only marginally successful. Most studies used similar messages. Campaign lengths, type of media, and sample sizes varied. High risk populations and those with confirmed MI responded more quickly. To reduce patient delay, media messages need to do more than create awareness. Future interventions should target high risk audiences, promote dialogue between previous AMI patients and high risk patients, address problems of denial, provide gender specific education, and emphasize symptom evaluation, problem solving, and decision-making skills.

  19. The contribution made by an armchair with integral pressure-reducing cushion in the prevention of pressure sore incidence in the elderly, acutely ill patient.

    Science.gov (United States)

    Collins, F

    1999-10-01

    The paper describes a clinical controlled trial of an armchair with integral pressure-reducing cushion, which took place on two elderly acute medical wards in a district general hospital. The aim of the study was to evaluate whether the armchair would have an impact on reducing the occurrence of pressure sores. All patients were provided with a mattress or overlay in accordance with the hospital policy on mattress provision following a Waterlow risk assessment. Patients on ward A were provided with an armchair with integral pressure-reducing cushion, whilst patients on ward B continued to use their existing bedside armchair. Nominal data were collected on all pressure sores in patients who were not bedridden. Ward A had a significantly lower incidence of hospital-acquired pressure sores compared to ward B, and non-hospital-acquired pressure sores on this ward showed more improvement than those on ward B.

  20. Evaluation of some in vitro tests to reduce and replace the sub-acute animal toxicity studies.

    Science.gov (United States)

    Chhabra, Rajendra S; Ress, Nancy B; Harbell, John W; Curren, Rodger D

    2004-06-01

    The toxicologic and carcinogenic potential of chemicals is usually determined through a sequence of acute, sub-acute (14-day), sub-chronic (90-day) and chronic (two-year) studies in rats and mice of both sexes. The US National Toxicology Program (NTP) does not conduct acute toxicity studies. Dose levels for 14-day toxicity studies are typically estimated from information in the literature, if available. The toxicology information obtained from 14-day studies is used in the selection of doses for 90-day studies. The protocol for 14-day studies consists of five doses and control groups and five animals per group of each sex and species, resulting in the use of 120 animals per study. At present, in addition to refining the current testing protocols, the NTP is evaluating the potential for in vitro test methods to partially or completely avoid the need for 14-day toxicity studies, especially for chemicals where the dermal route of exposure is used. The in vitro assays used were the EpiDerm bioassay to estimate dermal irritation, the neutral red uptake (NRU) bioassay to estimate systemic toxicity and the primary rat hepatocyte cytotoxicity (PRHC) assay to estimate hepatotoxicity. The purpose of using these assays was to assess their potential for predicting relative in vivo toxicity and to support dose selection decisions for 90-day studies. In general, based on these limited number of studies, the EpiDerm and NRU tests were predictive of the responses observed in in vivo studies. However, a larger comparative database is needed to derive definitive conclusions regarding the value of in vitro tests in the prediction of in vivo effects.

  1. Acute stress alters transcript expression pattern and reduces processing of proBDNF to mature BDNF in Dicentrarchus labrax

    Directory of Open Access Journals (Sweden)

    Saroglia Marco

    2010-01-01

    Full Text Available Abstract Background Stress involves alterations of brain functioning that may precipitate to mood disorders. The neurotrophin Brain Derived Neurotrophic Factor (BDNF has recently been involved in stress-induced adaptation. BDNF is a key regulator of neuronal plasticity and adaptive processes. Regulation of BDNF is complex and may reflect not only stress-specific mechanisms but also hormonal and emotional responses. For this reason we used, as an animal model of stress, a fish whose brain organization is very similar to that of higher vertebrates, but is generally considered free of emotional reactions. Results We provide a comprehensive characterization of BDNF gene in the Dicentrarchus labrax and its transcriptional, translational and post-translational regulation following acute stress. While total BDNF mRNA levels are unchanged, BDNF transcripts 1c and 1d resulted down regulated after acute stress. Acute stress induces also a significant increase in proBDNF levels and reduction in mature BDNF suggesting altered regulation of proBDNF proteolytic processing. Notably, we provide here the first evidence that fishes possess a simplified proteolytic regulation of BDNF since the pro28Kda form, generated by the SKI-1 protease in mammals, is absent in fishes because the cleavage site has first emerged in reptilians. Finally, we show that the proBDNF/totBDNF ratio is a highly predictive novel quantitative biomarker to detect stress in fishes with sensitivity = 100%, specificity = 87%, and Negative Predictive Value = 100%. Conclusion The high predictivity of proBDNF/totBDNF ratio for stress in lower vertebrates indicates that processing of BDNF is a central mechanism in adaptation to stress and predicts that a similar regulation of pro/mature BDNF has likely been conserved throughout evolution of vertebrates from fish to man.

  2. Acute exercise reduces insulin resistance-induced TRB3 expression and amelioration of the hepatic production of glucose in the liver of diabetic mice.

    Science.gov (United States)

    Lima, Athos F; Ropelle, Eduardo R; Pauli, José R; Cintra, Dennys E; Frederico, Marisa J S; Pinho, Ricardo A; Velloso, Lício A; De Souza, Cláudio T

    2009-10-01

    TRB3 (a mammalian homolog of Drosophila) is emerging as an important player in the regulation of insulin signaling. TRB3 can directly bind to Ser/Thr protein kinase Akt, the major downstream kinase of insulin signaling. Conversely, physical exercise has been linked to improved glucose homeostasis and enhanced insulin sensitivity; however, the molecular mechanisms by which exercise improves glucose homeostasis, particularly in the hepatic tissue, are only partially known. Here, we demonstrate that acute exercise reduces fasting glucose in two models diabetic mice. Western blot analysis showed that 8 h after a swimming protocol, TRB3 expression was reduced in the hepatic tissue from diet-induced obesity (Swiss) and leptin-deficient (ob/ob) mice, when compared with respective control groups at rest. In parallel, there was an increase in insulin responsiveness in the canonical insulin-signaling pathway in hepatic tissue from DIO and ob/ob mice after exercise. In addition, the PEPCK expression was reduced in the liver after the exercise protocol, suggesting that acute exercise diminished hepatic glucose production through insulin-signaling restoration. Thus, these results provide new insights into the mechanism by which physical activity improves glucose homeostasis in type 2 diabetes.

  3. Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli-Induced Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Curley, Gerard F; Jerkic, Mirjana; Dixon, Steve; Hogan, Grace; Masterson, Claire; O'Toole, Daniel; Devaney, James; Laffey, John G

    2017-02-01

    Although mesenchymal stem/stromal cells represent a promising therapeutic strategy for acute respiratory distress syndrome, clinical translation faces challenges, including scarcity of bone marrow donors, and reliance on bovine serum during mesenchymal stem/stromal cell proliferation. We wished to compare mesenchymal stem/stromal cells from human umbilical cord, grown in xeno-free conditions, with mesenchymal stem/stromal cells from human bone marrow, in a rat model of Escherichia coli pneumonia. In addition, we wished to determine the potential for umbilical cord-mesenchymal stem/stromal cells to reduce E. coli-induced oxidant injury. Randomized animal study. University research laboratory. Male Sprague-Dawley rats. Acute respiratory distress syndrome was induced in rats by intratracheal instillation of E. coli (1.5-2 × 10 CFU/kg). "Series 1" compared the effects of freshly thawed cryopreserved umbilical cord-mesenchymal stem/stromal cells with bone marrow-mesenchymal stem/stromal cells on physiologic indices of lung injury, cellular infiltration, and E. coli colony counts in bronchoalveolar lavage. "Series 2" examined the effects of cryopreserved umbilical cord-mesenchymal stem/stromal cells on survival, as well as measures of injury, inflammation and oxidant stress, including production of reactive oxidative species, reactive oxidative species scavenging by superoxide dismutase-1 and superoxide dismutase-2. In "Series 1," animals subjected to E. coli pneumonia who received umbilical cord-mesenchymal stem/stromal cells had improvements in oxygenation, respiratory static compliance, and wet-to-dry ratios comparable to bone marrow-mesenchymal stem/stromal cell treatment. E. coli colony-forming units in bronchoalveolar lavage were reduced in both cell therapy groups, despite a reduction in bronchoalveolar lavage neutrophils. In series 2, umbilical cord-mesenchymal stem/stromal cells enhanced animal survival and decreased alveolar protein and proinflammatory

  4. An enriched environment reduces the stress level and locomotor activity induced by acute morphine treatment and by saline after chronic morphine treatment in mice.

    Science.gov (United States)

    Xu, Jia; Sun, Jinling; Xue, Zhaoxia; Li, Xinwang

    2014-06-18

    This study investigated the relationships among an enriched environment, stress levels, and drug addiction. Mice were divided randomly into four treatment groups (n=12 each): enriched environment without restraint stress (EN), standard environment without restraint stress (SN), enriched environment with restraint stress (ES), and standard environment with restraint stress (SS). Mice were reared in the respective environment for 45 days. Then, the ES and SS groups were subjected to restraint stress daily (2 h/day) for 14 days, whereas the EN and SN groups were not subjected to restraint stress during this stage. The stress levels of all mice were tested in the elevated plus maze immediately after exposure to restraint stress. After the 2-week stress testing period, mice were administered acute or chronic morphine (5 mg/kg) treatment for 7 days. Then, after a 7-day withdrawal period, the mice were injected with saline (1 ml/kg) or morphine (5 mg/kg) daily for 2 days to observe locomotor activity. The results indicated that the enriched environment reduced the stress and locomotor activity induced by acute morphine administration or saline after chronic morphine treatment. However, the enriched environment did not significantly inhibit locomotor activity induced by morphine challenge. In addition, the stress level did not mediate the effect of the enriched environment on drug-induced locomotor activity after acute or chronic morphine treatment.

  5. Acute Superoxide Radical Scavenging Reduces Blood Pressure but Does Not Influence Kidney Function in Hypertensive Rats with Postischemic Kidney Injury

    Directory of Open Access Journals (Sweden)

    Zoran Miloradović

    2014-01-01

    Full Text Available Acute kidney injury (AKI is associated with significant morbidity and mortality in hypertensive surroundings. We investigated superoxide radical molecules influence on systemic haemodynamic and kidney function in spontaneously hypertensive rats (SHR with induced postischemic AKI. Experiment was performed in anesthetized adult male SHR. The right kidney was removed, and left renal artery was subjected to ischemia by clamping for 40 minutes. The treated group received synthetic superoxide dismutase mimetic TEMPOL in the femoral vein 5 minutes before, during, and 175 minutes after the period of reperfusion, while the control AKI group received the vehicle via the same route. All parameters were measured 24 h after renal reperfusion. TEMPOL treatment significantly decreased mean arterial pressure and total peripheral resistance P<0.05 compared to AKI control. It also increased cardiac output and catalase activity P<0.05. Lipid peroxidation and renal vascular resistance were decreased in TEMPOL P<0.05. Plasma creatinine and kidney morphological parameters were unchanged among TEMPOL treated and control groups. Our study shows that superoxide radicals participate in haemodynamic control, but acute superoxide scavenging is ineffective in glomerular and tubular improvement, probably due to hypertension-induced strong endothelial dysfunction which neutralizes beneficial effects of O2− scavenging.

  6. Tele-Interpersonal Psychotherapy Acutely Reduces Depressive Symptoms in Depressed HIV-Infected Rural Persons: A Randomized Clinical Trial.

    Science.gov (United States)

    Heckman, Timothy G; Heckman, Bernadette D; Anderson, Timothy; Lovejoy, Travis I; Markowitz, John C; Shen, Ye; Sutton, Mark

    2016-04-26

    Human immunodeficiency virus (HIV)-positive rural individuals carry a 1.3-times greater risk of a depressive diagnosis than their urban counterparts. This randomized clinical trial tested whether telephone-administered interpersonal psychotherapy (tele-IPT) acutely relieved depressive symptoms in 132 HIV-infected rural persons from 28 states diagnosed with Diagnostic and Statistical Manual of Mental Disorders-IV major depressive disorder (MDD), partially remitted MDD, or dysthymic disorder. Patients were randomized to either 9 sessions of one-on-one tele-IPT (n = 70) or standard care (SC; n = 62). A series of intent-to-treat (ITT), therapy completer, and sensitivity analyses assessed changes in depressive symptoms, interpersonal problems, and social support from pre- to postintervention. Across all analyses, tele-IPT patients reported significantly lower depressive symptoms and interpersonal problems than SC controls; 22% of tele-IPT patients were categorized as a priori "responders" who reported 50% or higher reductions in depressive symptoms compared to only 4% of SC controls in ITT analyses. Brief tele-IPT acutely decreased depressive symptoms and interpersonal problems in depressed rural people living with HIV.

  7. Fish oil diet associated with acute reperfusion related haemorrhage, and with reduced stroke-related sickness behaviours and motor impairment

    Directory of Open Access Journals (Sweden)

    Michaela Celeste Pascoe

    2014-02-01

    Full Text Available Ischemic stroke is associated with motor impairment and increased incidence of affective disorders such as anxiety/clinical depression. In non-stroke populations, successful management of such disorders and symptoms has been reported following diet supplementation with long chain omega-3-polyunsaturated-fatty-acids (PUFA. However, the potential protective effects of PUFA supplementation on affective behaviours after experimentally induced stroke and sham surgery have not been examined previously. This study investigated the behavioural effects of PUFA supplementation over a six-week period following either middle cerebral artery occlusion or sham surgery in the hooded-Wistar rat. The PUFA diet supplied during the acclimation period prior to surgery was found to be associated with an increased risk of acute haemorrhage following the reperfusion component of the surgery. In surviving animals, PUFA supplementation did not influence infarct size as determined six weeks after surgery, but did decrease omega-6-fatty-acid levels, moderate sickness behaviours, acute motor impairment and longer-term locomotor hyperactivity and depression/anxiety-like behaviour.

  8. Acute and Chronic Administrations of Rheum palmatum Reduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

    Directory of Open Access Journals (Sweden)

    Ying-Chang Chi

    2012-01-01

    Full Text Available The rhizome of Rheum palmatum (RP is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat. Rats were orally administered with PHT (200 mg/kg with and without RP decoction (single dose and seven doses of 2 g/kg in a crossover design. The serum concentrations of PHT, PHT glucuronide (PHT-G, 4-hydroxyphenytoin (HPPH, and HPPH glucuronide (HPPH-G were determined by HPLC method. Cell line models were used to identify the underlying mechanisms. The results showed that coadministration of single dose or multiple doses of RP significantly decreased the Cmax and AUC0-t as well as the K10 of PHT, PHT-G, HPPH, and HPPH-G. Cell line studies revealed that RP significantly induced the P-gp-mediated efflux of PHT and inhibited the MRP-2-medicated transport of PHT and HPPH. In conclusion, acute and chronic coadministrations of RP markedly decreased the oral bioavailability of PHT via activation of P-gp, although the MRP-2-mediated excretion of PHT was inhibited. It is recommended that caution should be exercised during concurrent use of RP and PHT.

  9. Acute and Chronic Administrations of Rheum palmatum Reduced the Bioavailability of Phenytoin in Rats: A New Herb-Drug Interaction

    Science.gov (United States)

    Chi, Ying-Chang; Juang, Shin-Hun; Chui, Wai Keung; Hou, Yu-Chi; Chao, Pei-Dawn Lee

    2012-01-01

    The rhizome of Rheum palmatum (RP) is a commonly used herb in clinical Chinese medicine. Phenytoin (PHT) is an antiepileptic with narrow therapeutic window. This study investigated the acute and chronic effects of RP on the pharmacokinetics of PHT in rat. Rats were orally administered with PHT (200 mg/kg) with and without RP decoction (single dose and seven doses of 2 g/kg) in a crossover design. The serum concentrations of PHT, PHT glucuronide (PHT-G), 4-hydroxyphenytoin (HPPH), and HPPH glucuronide (HPPH-G) were determined by HPLC method. Cell line models were used to identify the underlying mechanisms. The results showed that coadministration of single dose or multiple doses of RP significantly decreased the Cmax and AUC0-t as well as the K10 of PHT, PHT-G, HPPH, and HPPH-G. Cell line studies revealed that RP significantly induced the P-gp-mediated efflux of PHT and inhibited the MRP-2-medicated transport of PHT and HPPH. In conclusion, acute and chronic coadministrations of RP markedly decreased the oral bioavailability of PHT via activation of P-gp, although the MRP-2-mediated excretion of PHT was inhibited. It is recommended that caution should be exercised during concurrent use of RP and PHT. PMID:22829856

  10. Low central venous pressure versus acute normovolemic hemodilution versus conventional fluid management for reducing blood loss in radical retropubic prostatectomy: a randomized controlled trial.

    Science.gov (United States)

    Habib, Ashraf S; Moul, Judd W; Polascik, Thomas J; Robertson, Cary N; Roche, Anthony M; White, William D; Hill, Stephen E; Nosnick, Israel; Gan, Tong J

    2014-05-01

    To compare acute normovolemic hemodilution versus low central venous pressure strategy versus conventional fluid management in reducing intraoperative estimated blood loss, hematocrit drop and need for blood transfusion in patients undergoing radical retropubic prostatectomy under general anesthesia. Patients undergoing radical retropubic prostatectomy under general anesthesia were randomized to conventional fluid management, acute normovolemic hemodilution or low central venous pressure (≤5 mmHg). Treatment effects on estimated blood loss and hematocrit change were tested in multivariable regression models accounting for surgeon, prostate size, and all two-way interactions. Ninety-two patients completed the study. Estimated blood loss (mean ± SD) was significantly lower with low central venous pressure (706 ± 362 ml) compared to acute normovolemic hemodilution (1103 ± 635 ml) and conventional (1051 ± 714 ml) groups (p = 0.0134). There was no difference between the groups in need for blood transfusion, or hematocrit drop from preoperative values. The multivariate model predicting estimated blood loss showed a significant effect of treatment (p = 0.0028) and prostate size (p = 0.0323), accounting for surgeon (p = 0.0013). In the model predicting hematocrit change, accounting for surgeon difference (p = 0.0037), the treatment effect depended on prostate size (p = 0.0007) with the slope of low central venous pressure differing from the other two groups. Hematocrit was predicted to drop more with increased prostate size in acute normovolemic hemodilution and conventional groups but not with low central venous pressure. Limitations include the inability to blind providers to group assignment, possible variability between providers in estimation of blood loss, and the relatively small sample size that was not powered to detect differences between the groups in need for blood transfusion. Maintaining low central venous

  11. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Mikell, John L., E-mail: jmikell@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waller, Edmund K. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hall, William A. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Langston, Amelia A. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khoury, H. Jean [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  12. Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant

    Institute of Scientific and Technical Information of China (English)

    Yan Chenhua; Xu Lanping; Liu Daihong; Chen Huan; Wang Yu; Liu Kaiyan; Huang Xiaojun

    2014-01-01

    Background In haploidentical hematopoietic stem cell transplantation (HSCT),the duration of graft-versus-host disease (GVHD) prophylaxis after modified donor lymphocyte infusion (DLI) was the only risk factor of DLI-associated grades 3-4 acute GVHD.However,the successful application of modified DLI depended not only on the reduction of severe GVHD,but also on the preservation of graft-versus-leukemia (GVL) effect.Therefore,this study was performed to compare the impact of prophylaxis for 6-8 weeks and prophylaxis for <6 weeks on GVL effect after modified DLI in haploidentical HSCT.Methods A total of 103 consecutive patients developing hematological relapse or minimal residual disease (MRD)-positive status after haploidentical HSCT and receiving modified DLI were investigated retrospectively.Fifty-two patients received prophylaxis for 6-8 weeks after modified DLI; the remaining 51 patients received prophylaxis for <6 weeks.Results First,compared with prophylaxis for <6 weeks,prophylaxis for 6-8 weeks reduced incidence of relapse in total patients (26.6% vs.69.0%,P <0.001).Besides,prophylaxis for 6-8 weeks also reduced incidence of relapse in 54 patients developing hematological relapse post-transplant (P=0.018) and in 49 patients developing MRD-positive status post-transplant (P <0.001).Second,prophylaxis for 6-8 weeks reduced incidence of acute GVHD (P <0.05),reduced the therapeutic application of immunosuppressive agents (P=0.019),but increased the incidence of chronic GVHD (P<0.05).Third,prophylaxis for 6-8 weeks improved overall survival and disease-free survival in total patients,as well as in patients developing hematological relapse post-transplant and in patients developing MRD-positive status post-transplant (P <0.05).Conclusions In haploidentical HSCT,prophylaxis for 6-8 weeks after modified DLI does not reduce GVL effect,but reduces the incidence of DLI-associated acute GVHD compared with prophylaxis for <6 weeks.This strategy will

  13. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

    DEFF Research Database (Denmark)

    Castellano, J M; Bentsen, A H; Romero, M;

    2010-01-01

    Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function...... of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin...... for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation....

  14. Modified Da-Cheng-Qi Decoction reduces intra-abdominal hypertension in severe acute pancreatitis: a pilot study

    Institute of Scientific and Technical Information of China (English)

    WAN Mei-hua; LI Juan; HUANG Wei; Rajarshi Mukherjee; GONG Han-lin; XIA Qing; ZHU Lin; CHENG Gui-lan; TANG Wen-fu

    2012-01-01

    Background Intra-abdominal hypertension (IAH) is a recognized prognostic marker for severity of severe acute pancreatitis (SAP) and has a strong impact on the clinical course of SAP.Previous studies indicate that a Da-Cheng-Qi Decoction (DCQD) is beneficial in the treatment of SAP.The purpose of this study was to evaluate the effect of modified DCQD on IAH in patients with SAP.Methods Between January 2008 and December 2008,42 patients from the West China Hospital were randomized into either the DCQD or control group (n=21 in each group).Mortality,intra-abdominal pressure (lAP),Acute Physiology and Chronic Health Evaluation II (APACHE II) score,C-reactive protein (CRP),oxygenation index,Balthazar CT score,rate of renal failure,decompression rate,intensive care unit (ICU) transfer rate,and length of hospital stay (LOS) were compared between the two groups.Results Compared to the control group,the modified DCQD treatment significantly decreased lAP (P <0.05) and APACHE Ⅱ (P <0.05) scores on days 4-8,CRP on day 8 (P <0.01 ),renal failure rate (P <0.05),and LOS (P <0.05).The oxygenation index was significantly improved in the DCQD group compared with the control group (P <0.05).No significant differences in the Balthazar CT score,shock rate,ICU transfer rate,or mortality occurred between the two groups.Conclusions The modified DCQD can effectively relieve IAH and decrease LOS for patients with SAP.Larger clinical trials are needed to confirm these findings.

  15. Dietary long-chain unsaturated fatty acids acutely and differently reduce the activities of lipogenic enzymes and of citrate carrier in rat liver.

    Science.gov (United States)

    Gnoni, Antonio; Giudetti, Anna M

    2016-09-01

    The activities of lipogenic enzymes appear to fluctuate with changes in the level and type of dietary fats. Polyunsaturated fatty acids (PUFAs) are known to induce on hepatic de novo lipogenesis (DNL) the highest inhibitory effect, which occurs through a long-term adaptation. Data on the acute effects of dietary fatty acids on DNL are lacking. In this study with rats, the acute 1-day effect of high-fat (15 % w/w) diets (HFDs) enriched in saturated fatty acids (SFAs) or unsaturated fatty acids (UFAs), i.e., monounsaturated (MUFA) and PUFA, of the ω-6 and ω-3 series on DNL and plasma lipid level was investigated; a comparison with a longer time feeding (21 days) was routinely carried out. After 1-day HFD administration UFA, when compared to SFA, reduced plasma triacylglycerol (TAG) level and the activities of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), a decreased activity of the citrate carrier (CIC), a mitochondrial protein linked to lipogenesis, was also detected. In this respect, ω-3 PUFA was the most effective. On the other hand, PUFA maintained the effects at longer times, and the acute inhibition induced by MUFA feeding on DNL enzyme and CIC activities was almost nullified at 21 days. Mitochondrial fatty acid composition was slightly but significantly changed both at short- and long-term treatment, whereas the early changes in mitochondrial phospholipid composition vanished in long-term experiments. Our results suggest that in the early phase of administration, UFA coordinately reduced both the activities of de novo lipogenic enzymes and of CIC. ω-3 PUFA showed the greatest effect.

  16. The role of reduced glutathione during the course of acute haemolysis in glucose-6-phosphate dehydrogenase deficient patients: clinical and pharmacodynamic aspects.

    Science.gov (United States)

    Corbucci, G G

    1990-01-01

    Tissue hypoperfusion leads to cellular oxidative and peroxidative damage due to biochemical disorders in the oxygen and substrate metabolism. The metabolic turnover of glutathione (GSH) represents one the main cytoprotective systems against the peroxide attack and the depletion or defect in resynthesis of this compound is accompanied by pathological consequences. In the present study the clinical effects of glutathione depletion were investigated in conditions of acute tissue hypoxia due to marked haemolysis in glucose-6-phosphate dehydrogenase deficient patients (favism syndrome). In these subjects a significant marker of the tissue oxidative damage was represented by the uric acid blood levels, presumably linked to xanthine-hypoxanthine altered metabolism. To antagonize the effects of oxyradical pathology, reduced glutathione was administered to a group of patients and the results confirmed the cytoprotective role played by the GSH supplementation. The GSH action was evident on the tissue metabolism and this supports the opinion that reduced glutathione could represent a new and interesting therapeutic approach in marked and acute hypoxic conditions.

  17. PPAR-Alpha Agonist Used at the Acute Phase of Experimental Ischemic Stroke Reduces Occurrence of Thrombolysis-Induced Hemorrhage in Rats

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    Sophie Gautier

    2015-01-01

    Full Text Available The impact of fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-α agonist, on the risk of thrombolysis-induced hemorrhage during the acute phase of stroke in a rat model of stroke was studied. One-hour middle cerebral artery occlusion followed by thrombolysis with tissue plasminogen activator was made in rats receiving either fenofibrate or vehicle for 72 h after stroke. Evaluation of infarct, hemorrhage, middle cerebral artery vasoreactivity, and immunochemistry (CD11b for microglial activation, myeloperoxidase, and ICAM-1 for neutrophil infiltration was performed. The PPAR-alpha agonist significantly reduced the risk of hemorrhage after thrombolysis in parallel with a decrease in the infarct volume and in the stroke-induced vascular endothelial dysfunction. These effects are concomitant with a reduction in microglial activation and neutrophil infiltration in infarct area. Our results strengthen the idea that using drugs such as fenofibrate, with pleiotropic properties due to PPAR-alpha agonism, may be of value to reduce thrombolysis-induced hemorrhage during acute stroke.

  18. Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis

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    Laura R. R. Ribeiro

    2015-01-01

    Full Text Available Cysteinyl leukotrienes (CysLTs and lipoxins (LXs are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J and susceptible (B10.A mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.

  19. Nebulized Hypertonic Saline Treatment Reduces Both Rate and Duration of Hospitalization for Acute Bronchiolitis in Infants: An Updated Meta-analysis

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    Yen-Ju Chen

    2014-12-01

    Full Text Available Nebulized hypertonic saline (HS treatment reduced the length of hospitalization in infants with acute bronchiolitis in a previous meta-analysis. However, there was no reduction in the admission rate. We hypothesized that nebulized HS treatment might significantly decrease both the duration and the rate of hospitalization if more randomized controlled trials (RCTs were included. We searched MEDLINE, PubMed, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL without a language restriction. A meta-analysis was performed based on the efficacy of nebulized HS treatment in infants with acute bronchiolitis. We used weighted mean difference (WMD and risk ratio as effect size metrics. Eleven studies were identified that enrolled 1070 infants. Nebulized HS treatment significantly decreased the duration and rate of hospitalization compared with nebulized normal saline (NS [duration of hospitalization: WMD = −0.96, 95% confidence interval (CI = −1.38 to −0.54, p < 0.001; rate of hospitalization: risk ratio = 0.59, 95% CI = 0.37–0.93, p = 0.02]. Furthermore, nebulized HS treatment had a beneficial effect in reducing the clinical severity (CS score of acute bronchiolitis infants post-treatment (Day 1: WMD = −0.77, 95% CI = −1.30 to −0.24, p = 0.005; Day 2: WMD = −0.85, 95% CI = −1.30 to −0.39, p < 0.001; Day 3: WMD = −1.14, 95% CI = −1.69 to −0.58, p < 0.001. There was no decrease in the rate of readmission (risk ratio = 1.08, 95% CI = 0.68–1.73, p = 0.74. Nebulized HS treatment significantly decreased both the rate and the duration of hospitalization. Due to the efficacy and cost-effectiveness, HS should be considered for the treatment of acute bronchiolitis in infants.

  20. North American ginseng protects against muscle damage and reduces neutrophil infiltration after an acute bout of downhill running in rats.

    Science.gov (United States)

    Estaki, Mehrbod; Noble, Earl G

    2015-02-01

    Eccentric muscle contractions such as those experienced during downhill running are associated with inflammation, delayed-onset of muscle soreness, myofiber damage, and various functional deficits. North American ginseng (Panax quinquefolius L.) has been reported to possess anti-inflammatory properties and thus may offset some of this exercise-induced damage. Hence, we tested the hypothesis that intervention with North American ginseng would reduce eccentric exercise-induced muscle damage and inflammation. Male Wistar rats were fed (300 mg/(kg·day)(-1)) of either an alcohol (AL) or aqueous (AQ) extract of North American ginseng for 14 days before a single bout of downhill running and were compared with matching nonexercised (C) groups. Plasma creatine kinase levels were significantly reduced in both ginseng treated groups compared with the C group that received a water placebo (p damage (hemotoxylin and eosin) as well as reduced levels of infiltrating neutrophils (HIS48) in the soleus muscle (p muscle damage and inflammation.

  1. Sarcandra glabra combined with lycopene protect rats from lipopolysaccharide induced acute lung injury via reducing inflammatory response.

    Science.gov (United States)

    Liu, Tian-Yin; Chen, Shi-Biao

    2016-12-01

    Sarcandra glabra (Chinese name, Zhongjiefeng) is an important herb widely used in traditional Chinese medicine. Lycopene has been shown to be a powerful antioxidant. This study aims to test the hypothesis that Sarcandra glabra combined with lycopene protect rats from lipopolysaccharide (LPS) induced acute lung injury (ALI). Metabolomics approach combined with pathological inspection, serum biochemistry examination, enzyme-linked immunosorbent assay and western blotting were used to explore the protective effects of Sarcandra glabra and lycopene on LPS-induced ALI, and to elucidate the underlying mechanisms. Results showed that Sarcandra glabra and lycopene could significantly ameliorate LPS-induced histopathological injuries, improve the anti-oxidative activities of rats, decrease the levels of TNF-α and IL-6, suppress the activations of MAPK and transcription factor NF-κB and reverse the disturbed metabolism towards the normal status. Taken together, this integrated study revealed that Sarcandra glabra combined with lycopene had great potential in protecting rats from LPS-induced ALI, which would be helpful to guide the clinical medication.

  2. Do alcohol-based hand rubs reduce the incidence of acute diarrhea during military deployments? A prospective randomized trial.

    Science.gov (United States)

    Succo, Tiphanie; De Laval, Franck; Sicard, Sébastien; Belleoud, Didier; Marimoutou, Catherine; Mayet, Aurélie; Sagaon-Teyssier, Luis; Michel, Rémy

    Acute diarrhea remains a public health concern in armed forces deployed in tropical areas where access to water and soap is limited. This study aims to assess the effectiveness of alcohol-based hand rubs (ABHR) on incidence of diarrhea in poor hygiene conditions. A prospective randomized trial was conducted between November 2014 and January 2015 among French military troops deployed in Africa to compare a group of soldiers receiving usual hand hygiene recommendations (control group), to a group of soldiers who received ABHR in addition to usual hand hygiene recommendations (intervention group). Data on diarrhea and hygiene behaviors were collected using self-questionnaires. The incidence rate of diarrhea episodes in groups was compared. Participation rate was 59% (236/400). The proportion of individuals who used ABHR was 97% in the intervention group and 62% in the control group. The overall incidence rate of diarrheal episodes was observed to be in the region of 60 per 100 persons-month without any significant difference between groups after adjustment on confounding factors (p = 0.93). Handwashing with soap was used on average 4 times a day in the control group and twice a day in the intervention group (p = 0.93). It was the only significant protective factor for diarrhea (p soap and good quality water should be a priority on the field. Copyright © 2016. Published by Elsevier Ltd.

  3. Reducing unnecessary prescriptions of antibiotics for acute cough: Adaptation of a leaflet aimed at Turkish immigrants in Germany

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    Fuchs Angela

    2008-10-01

    Full Text Available Abstract Background The reduction in the number of unnecessary prescriptions of antibiotics has become one of the most important objectives for primary health care. German GPs report that they are under "pressure to prescribe" antibiotics particularly in consultations with Turkish immigrants. And so a qualitative approach was used to learn more about the socio-medical context of Turkish patients in regard to acute coughs. A German leaflet designed to improve the doctor-patient communication has been positively tested and then adapted for Turkish patients. Methods The original leaflet was first translated into Turkish. Then 57 patients belonging to 8 different GPs were interviewed about the leaflet using a semi-standardised script. The material was audio recorded, fully transcribed, and analysed by three independent researchers. As a first step a comprehensive content analysis was performed. Secondly, elements crucial to any Turkish version of the leaflet were identified. Results The interviews showed that the leaflets' messages were clearly understood by all patients irrespective of age, gender, and educational background. We identified no major problems in the perception of the translated leaflet but identified several minor points which could be improved. We found that patients were starting to reconsider their attitudes after reading the leaflet. Conclusion The leaflet successfully imparted relevant and new information to the target patients. A qualitative approach is a feasible way to prove general acceptance and provides additional information for its adaptation to medico-cultural factors.

  4. Flow cytometric minimal residual disease monitoring in children with acute lymphoblastic leukemia treated by regimens with reduced intensity

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    A. M. Popov

    2015-01-01

    Full Text Available 191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188, 36 (n = 191, and 85 (n = 187 of remission induction. Minimal residual disease (MRD was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001: 35.64 % patients with MRD < 0.1 % represented 5-year event-free survival (EFS of 100 %; 48.40 % cases with 0.1 % ≤ MRD< 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 % belonged to group with poor outcome (EFS 56.7 ± 9.0 %. At the end of remission induction (day 36 36 children (18.85 % with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001. From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor.

  5. The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party

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    Marie T. Rubio

    2016-08-01

    Full Text Available Abstract Background Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD allogeneic hematopoietic stem cell transplant (allo-SCT following reduced intensity conditioning regimens for acute myeloid leukemia are limited. Methods We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567, 9/10 (n = 723, or 8/10 (n = 108 mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results HLA matching had no impact on engraftment (p = 0.31. In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II–IV acute graft-versus-host disease (GVHD (p = 0.0002, similar rates of chronic GVHD (p = 0.138 but increased incidence of its extensive form (p = 0.047. Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1 with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS (p = 0.005 and overall survivals (OS (56.7, 46.1, and 50.2 %, respectively, p = 0.005, while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001, similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001, and OS (HR 1.27, p = 0.0001. There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. Conclusions Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other

  6. Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

    Science.gov (United States)

    Towers, Albert E; Oelschlager, Maci L; Patel, Jay; Gainey, Stephen J; McCusker, Robert H; Freund, Gregory G

    2017-06-01

    Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Aged red garlic extract reduces lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages and acute pulmonary inflammation through haeme oxygenase-1 induction.

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    Park, H-J; Jeon, B T; Kim, H C; Roh, G S; Shin, J-H; Sung, N-J; Han, J; Kang, D

    2012-05-01

    It is known that garlic has antioxidative and anti-inflammatory properties. Aged red garlic (ARG), a novel aged garlic formulation, has higher antioxidant effects than fresh raw garlic. This study was performed to examine the anti-inflammatory effects of ARG extract (ARGE). The anti-inflammatory effects of ARGE were evaluated in the lipopolysaccharide (LPS)-treated Raw 264.7 macrophages and acute lung inflammatory mice. NO production was determined by the Griess method, and iNOS, HO-1 and COX-2 expressions were measured using Western blot analysis. Histology and inflammation extent of lung were analysed using haematoxylin-eosin staining and immunohistochemistry. ARGE treatment markedly reduced LPS-induced nitrite production in RAW 264.7 macrophages and reduced inducible nitric oxide synthase (iNOS) expression. Treatment of cells with ARGE led to a significant increase in haeme oxygenase-1 (HO-1) protein expression, which was mediated by stimulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). Treatment with zinc protoporphyrin, a selective inhibitor of HO-1, significantly reversed the ARGE-mediated inhibition of nitrite production (P < 0.05). In LPS-induced inflammatory mice, ARGE treatment down-regulated iNOS and COX-2 expressions, while it up-regulated HO-1 expression. These results show that ARGE reduces LPS-induced nitric oxide production in RAW 264.7 macrophages through HO-1 induction and suggest that ARGE may have potential effects on prevention and treatment of acute inflammatory lung injury. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  8. Sodium modelling to reduce intradialytic hypotension during haemodialysis for acute kidney injury in the intensive care unit.

    Science.gov (United States)

    Lynch, Katherine E; Ghassemi, Fatimah; Flythe, Jennifer E; Feng, Mengling; Ghassemi, Marzyeh; Celi, Leo Anthony; Brunelli, Steven M

    2016-10-01

    Intradialytic hypotension often complicates haemodialysis for patients with acute kidney injury (AKI) and may impact renal recovery. Sodium modelling is sometimes used as prophylaxis against intradialytic hypotension in the chronic haemodialysis population, but there is little evidence for its use among critically ill patients with AKI. A retrospective cohort with AKI requiring intermittent haemodialysis in the intensive care unit from 2001 to 2008 was used to study the association of prophylactic sodium modelling and multiple outcomes. Outcomes included a composite of in-hospital death or dialysis dependence at hospital discharge, as well as intradialytic hypotension, ultrafiltration goal achievement and net ultrafiltration volume. Associations were estimated using logistic regression, mixed linear models and generalized estimating equations adjusting for demographic and clinical characteristics. One hundred and ninety-one individuals who underwent 892 sessions were identified; sodium modelling was prescribed in 27.1% of the sessions. In adjusted analyses, sodium modelling was not significantly associated with intradialytic hypotension (P = 0.67) or with the ultrafiltration goal achievement (P = 0.06). Sodium modelling during the first dialysis session was numerically associated with lower risk for the composite of in-hospital death or dialysis dependence: adjusted odds ratio (95% confidence interval) 0.39 (0.15-1.02; P = 0.06); however, this association did not reach statistical significance. We did not observe statistically significant associations between sodium modelling and improved outcomes among AKI patients receiving intermittent dialysis in the intensive care unit. However, suggestive findings warrant further study. © 2015 Asian Pacific Society of Nephrology.

  9. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD.

    Science.gov (United States)

    Carapito, Raphael; Jung, Nicolas; Kwemou, Marius; Untrau, Meiggie; Michel, Sandra; Pichot, Angélique; Giacometti, Gaëlle; Macquin, Cécile; Ilias, Wassila; Morlon, Aurore; Kotova, Irina; Apostolova, Petya; Schmitt-Graeff, Annette; Cesbron, Anne; Gagne, Katia; Oudshoorn, Machteld; van der Holt, Bronno; Labalette, Myriam; Spierings, Eric; Picard, Christophe; Loiseau, Pascale; Tamouza, Ryad; Toubert, Antoine; Parissiadis, Anne; Dubois, Valérie; Lafarge, Xavier; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Vago, Luca; Ciceri, Fabio; Paillard, Catherine; Querol, Sergi; Sierra, Jorge; Fleischhauer, Katharina; Nagler, Arnon; Labopin, Myriam; Inoko, Hidetoshi; von dem Borne, Peter A; Kuball, Jürgen; Ota, Masao; Katsuyama, Yoshihiko; Michallet, Mauricette; Lioure, Bruno; Peffault de Latour, Régis; Blaise, Didier; Cornelissen, Jan J; Yakoub-Agha, Ibrahim; Claas, Frans; Moreau, Philippe; Milpied, Noël; Charron, Dominique; Mohty, Mohamad; Zeiser, Robert; Socié, Gérard; Bahram, Seiamak

    2016-10-13

    Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.

  10. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

    Science.gov (United States)

    Carapito, Raphael; Jung, Nicolas; Kwemou, Marius; Untrau, Meiggie; Michel, Sandra; Pichot, Angélique; Giacometti, Gaëlle; Macquin, Cécile; Ilias, Wassila; Morlon, Aurore; Kotova, Irina; Apostolova, Petya; Schmitt-Graeff, Annette; Cesbron, Anne; Gagne, Katia; Oudshoorn, Machteld; van der Holt, Bronno; Labalette, Myriam; Spierings, Eric; Picard, Christophe; Loiseau, Pascale; Tamouza, Ryad; Toubert, Antoine; Parissiadis, Anne; Dubois, Valérie; Lafarge, Xavier; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Vago, Luca; Ciceri, Fabio; Paillard, Catherine; Querol, Sergi; Sierra, Jorge; Fleischhauer, Katharina; Nagler, Arnon; Labopin, Myriam; Inoko, Hidetoshi; von dem Borne, Peter A.; Kuball, Jürgen; Ota, Masao; Katsuyama, Yoshihiko; Michallet, Mauricette; Lioure, Bruno; Peffault de Latour, Régis; Blaise, Didier; Cornelissen, Jan J.; Yakoub-Agha, Ibrahim; Claas, Frans; Moreau, Philippe; Milpied, Noël; Charron, Dominique; Mohty, Mohamad; Zeiser, Robert; Socié, Gérard

    2016-01-01

    Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain–related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B. Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice. PMID:27549307

  11. Characterization of acute graft-versus-host disease following reduced-intensity stem-cell transplantation from an HLA-identical related donor.

    Science.gov (United States)

    Murashige, Naoko; Kami, Masahiro; Mori, Shin-ichiro; Katayama, Yuta; Kobayashi, Kazuhiko; Onishi, Yasushi; Hori, Akiko; Kishi, Yukiko; Hamaki, Tamae; Tajima, Kinuko; Kanda, Yoshinobu; Tanosaki, Ryuji; Takaue, Yoichi

    2008-08-01

    To investigate clinical features of acute graft-versus-host disease (GVHD) following reduced intensity stem-cell transplantation (RIST), we retrospectively investigated medical records of 65 patients with hematologic malignancies who underwent RIST from a matched related donor. Preparative regimen comprised fludarabine 30 mg/m(2) (n = 53) or cladribine 0.11 mg/kg (n = 12) for 6 days plus busulfan 4 mg/kg for 2 days. Twelve patients received rabbit antithymocyte globulin 2.5 mg/kg/day for 2-4 consecutive days. Grade II to IV acute GVHD was diagnosed in 36 patients (55%). Its median onset was day 58 (range, 17-109), while it was bimodal, peaking day 15-29 (early-onset GVHD, n = 18) and day 75-89 days (late-onset GVHD, n = 18). Variables that were more common in early-onset GVHD than late-onset GVHD included skin rash (89% vs. 61%) and noninfectious fevers (33% vs. 11%). Desaturation, pulmonary infiltrates and hyperbilirubinemia (>2.0 mg/dL) were more common in late-onset GVHD (6% vs. 22%, 0% vs. 17%, and 6% vs. 33%, respectively). All of the patients with early-onset GVHD given corticosteroid responded to it, while 5 of the 18 patients with late-onset GVHD failed to respond it. Patients with either early-onset or late-onset GVHD tended to have better progression-free survival (PFS) than those without it; however, there was no significant difference in PFS between patients with early-onset GVHD and those with late-onset GVHD. This study suggests that several etiologies might have contributed to the development of acute GVHD following RIST.

  12. Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

    Science.gov (United States)

    Kobayashi, Kazuhiko; Kami, Masahiro; Murashige, Naoko; Kusumi, Eiji; Kishi, Yukiko; Hamaki, Tamae; Hori, Akiko; Matsumura, Tomoko; Yuji, Koichiro; Masuo, Shigeru; Mori, Shinichiro; Miyakoshi, Shigesaburo; Tanosaki, Ryuji; Mitamura, Tadayuki; Takaue, Yoichi; Taniguchi, Shuichi

    2005-06-01

    The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

  13. TNF-α mediated increase of HIF-1α inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI).

    Science.gov (United States)

    Tang, Mengjie; Tian, Yihao; Li, Doulin; Lv, Jiawei; Li, Qun; Kuang, Changchun; Hu, Pengchao; Wang, Ying; Wang, Jing; Su, Ke; Wei, Lei

    2014-01-01

    Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function and increased pulmonary vascular permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated with all types of modulations of cytoskeleton rearrangement-dependent cellular morphology and function, such as adhesion, shrinkage, and permeability. The present studies were conducted to investigate the effects and mechanisms by which tumor necrosis factor-alpha (TNF-α) increases the tight junction permeability in lung tissue associated with acute lung inflammation. After incubating A549 cells for 24 hours with different concentrations (0-100 ng/mL) of TNF-α, 0.1 to 8 ng/mL TNF-α exhibited no significant effect on cell viability compared with the 0 ng/mL TNF-α group (control group). However, 10 ng/mL and 100 ng/mL TNF-α dramatically inhibited the viability of A549 cells compared with the control group (*pTNF-α for 24 hours displayed significantly increased cell permeability (*pinhibition of VASP expression increased the cell permeability (*pTNF-α in lung tissues and serum significantly increased at one hour, and the value reached a peak at four hours. Moreover, the Evans Blue absorption value of the mouse lung tissues reached a peak at four hours. The HIF-1α protein expression level in mouse lung tissues increased significantly at four hours and eight hours (**pTNF-α to inhibit VASP expression and to modulate the acute pulmonary inflammation process, and these molecules play an important role in the impairment of the alveolar-capillary barrier.

  14. Impact of iterative reconstruction on the diagnosis of acute pulmonary embolism (PE) on reduced-dose chest CT angiograms

    Energy Technology Data Exchange (ETDEWEB)

    Pontana, Francois; Henry, Simon; Faivre, Jean-Baptiste; Tacelli, Nunzia; Pagniez, Julien; Remy, Jacques; Remy-Jardin, Martine [CHRU et Universite de Lille 2 Nord de France, Department of Thoracic Imaging, Hospital Calmette (EA 2694), Lille (France); Duhamel, Alain [CHRU et Universite de Lille 2 Nord de France, Department of Biostatistics (EA 2694), Lille (France)

    2015-04-01

    To evaluate the impact of iterative reconstruction on the detectability of clots. Fifty-three patients were enrolled in a study comparing reduced-dose and full-dose images, available from the same dual-source data set. From each acquisition, three series of images were generated: (1) full-dose images (from both tubes), reconstructed with filtered back projection (FBP) (group 1; standard of reference), (2) reduced-dose images (from tube A only; 60 % dose reduction) reconstructed with FBP (group 2) and iterative reconstruction (SAFIRE) (group 3). In group 1 (mean DLP: 264.6 mGy.cm), (1) PE was diagnosed in 8 patients (15 %) with 82 clots in the central (n = 5), segmental (n = 39) and subsegmental (n = 38) arteries and (2) mean level of noise was 30.56 ± 5.07. In group 2 (mean DLP: 105.8 mGy.cm), a significant increase in noise (44.56 ± 6.24; p < 0.0001) (1) hampered detection of PE in one patient and (2) altered detection of peripheral clots (12 false-negative and 2 false-positive results). In group 3, image noise was not significantly different from that in group 1 (p = 0.1525; effect size: 0.2683), with a similar detection of PE compared to group 1 (p = 1). Reconstruction of reduced-dose images (60 % dose reduction) with SAFIRE provided image quality and diagnostic value comparable to those of full-dose FBP images. (orig.)

  15. Initial fluconazole prophylaxis may not be required in adults with acute leukemia or myelodysplastic/myeloproliferative disorders after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.

    Science.gov (United States)

    Brissot, Eolia; Cahu, Xavier; Guillaume, Thierry; Delaunay, Jacques; Ayari, Sameh; Peterlin, Pierre; Le Bourgeois, Amandine; Harousseau, Jean-Luc; Milpied, Noel; Bene, Marie-Christine; Moreau, Philippe; Mohty, Mohamad; Chevallier, Patrice

    2015-04-01

    In the myeloablative transplant setting, the early use of fluconazole prophylaxis provides a benefit in overall survival. Recent changes in transplantation practices, including the use of peripheral blood stem cells (PBSC) and/or reduced intensity conditioning (RIC) regimen may have favorably impacted the epidemiology of invasive fungal infections (IFI) after allogeneic stem cell transplantation (allo-SCT). Yet, the impact of removing fluconazole prophylaxis after RIC PBSC allotransplant is ill known. Here, a retrospective analysis was performed comparing patients who received fluconazole as antifungal prophylaxis (n = 53) or not (n = 56) after allo-SCT for acute leukemia or myelodysplastic/myeloproliferative syndrome. Sixteen IFI were documented (14 %) at a median time of 103 days after transplantation, including eight before day +100, at a similar rate, whether the patients received fluconazole prophylaxis (13 %) or not (16 %). IFI were due mainly to Aspergillus species (87 %), and only two Candida-related IFI (13 %) were documented in the non-fluconazole group before day +100. The incidences of IFI (overall, before or after day +100) as well as 3-year overall and disease-free survival, non-relapse mortality, or acute and chronic graft-versus-host disease (GVHD) were similar between both groups. In conclusion, this study suggests that fluconazole may not be required at the initial phase of RIC allo-SCT using PBSC. This result has to be confirmed prospectively while Aspergillus prophylaxis should be discussed in this particular setting.

  16. The abnormal cannabidiol analogue O-1602 reduces nociception in a rat model of acute arthritis via the putative cannabinoid receptor GPR55.

    Science.gov (United States)

    Schuelert, Niklas; McDougall, Jason J

    2011-08-01

    Cannabinoids classically act via CB₁ and CB₂ receptors to modulate nociception; however, recent findings suggest that some cannabinoids bind to atypical receptors. One such receptor is GPR55 which is activated by the abnormal cannabidiol analogue O-1602. This study investigated whether the synthetic GPR55 agonist O-1602 can alter joint nociception in a rat model of acute joint inflammation. Acute (24 h) inflammatory joint pain was induced in male Wistar rats by intra-articular injection of 2% kaolin and 2% carrageenan. Single unit extracellular recordings were made from arthritic joint afferents in response to mechanical rotation of the knee. Peripheral administration of O-1602 significantly reduced movement-evoked firing of nociceptive C fibres and this effect was blocked by the GPR55 receptor antagonist O-1918. Co-administration of the CB₁ and CB₂ antagonists (AM281 and AM630 respectively) had no effect on O-1602 responses. This study clearly shows that atypical cannabinoid receptors are involved in joint nociception and these novel targets may be advantageous for the treatment of inflammatory pain.

  17. Nebulized hypertonic saline treatment reduces both rate and duration of hospitalization for acute bronchiolitis in infants: an updated meta-analysis.

    Science.gov (United States)

    Chen, Yen-Ju; Lee, Wen-Li; Wang, Chuang-Ming; Chou, Hsin-Hsu

    2014-12-01

    Nebulized hypertonic saline (HS) treatment reduced the length of hospitalization in infants with acute bronchiolitis in a previous meta-analysis. However, there was no reduction in the admission rate. We hypothesized that nebulized HS treatment might significantly decrease both the duration and the rate of hospitalization if more randomized controlled trials (RCTs) were included. We searched MEDLINE, PubMed, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) without a language restriction. A meta-analysis was performed based on the efficacy of nebulized HS treatment in infants with acute bronchiolitis. We used weighted mean difference (WMD) and risk ratio as effect size metrics. Eleven studies were identified that enrolled 1070 infants. Nebulized HS treatment significantly decreased the duration and rate of hospitalization compared with nebulized normal saline (NS) [duration of hospitalization: WMD = -0.96, 95% confidence interval (CI) = -1.38 to -0.54, p bronchiolitis infants post-treatment (Day 1: WMD = -0.77, 95% CI = -1.30 to -0.24, p = 0.005; Day 2: WMD = -0.85, 95% CI = -1.30 to -0.39, p bronchiolitis in infants.

  18. Methotrexate Reduces the Incidence of Severe Acute Graft-versus-Host Disease without Increasing the Risk of Relapse after Reduced-Intensity Allogeneic Stem Cell Transplantation from Unrelated Donors.

    Science.gov (United States)

    Vigouroux, Stéphane; Tabrizi, Reza; Melot, Cyril; Coiffard, Joelle; Lafarge, Xavier; Marit, Gérald; Bouabdallah, Krimo; Pigneux, Arnaud; Leguay, Thibaut; Dilhuydy, Marie-Sarah; Schmitt, Anna; Boiron, Jean-Michel; Milpied, Noël

    2011-01-01

    Optimized prophylaxis against graft-versus-host disease (GVHD) after unrelated reduced-intensity allogeneic transplantation when preceded by a conditioning regimen utilizing antithymocyte globulin (ATG) is poorly defined. To investigate the effects of methotrexate (MTX) in this treatment setting, we conducted a retrospective analysis. Sixty-three patients were selected based on the administration of a total dose of 5 mg/kg of ATG in the conditioning regimen and then separated into either group M+ (n = 39), which received MTX or group M- (n = 24), which did not. All patients received cyclosporine. In the M- and M+ groups, cumulative incidences (CI) of grade III-IV acute GVHD (aGVHD) were 43% and 10%, respectively (P = .002). Multivariate analysis indicated that grade III-IV aGVHD was favored by both the absence of MTX and the provision of a female donor for a male recipient. At 2 years, the M+ and M- groups exhibited, respectively: overall survival of 69% and 40% (P = .06), disease-free survival of 57% and 43% (P = .2), nonrelapse mortality of 20% and 44% (P = .1), and incidence of relapse of 27% and 35% (P = .6). These data suggest that MTX reduces the incidence of severe aGVHD without increasing the risk of relapse but with an accompanying trend toward improved survival after unrelated reduced-intensity transplantation with ATG in the conditioning regimen.

  19. Amniotic-fluid-derived mesenchymal stem cells overexpressing interleukin-1 receptor antagonist improve fulminant hepatic failure.

    Directory of Open Access Journals (Sweden)

    Yu-Bao Zheng

    Full Text Available Uncontrolled hepatic immunoactivation is regarded as the primary pathological mechanism of fulminant hepatic failure (FHF. The major acute-phase mediators associated with FHF, including IL-1β, IL-6, and TNF-α, impair the regeneration of liver cells and stem cell grafts. Amniotic-fluid-derived mesenchymal stem cells (AF-MSCs have the capacity, under specific conditions, to differentiate into hepatocytes. Interleukin-1-receptor antagonist (IL-1Ra plays an anti-inflammatory and anti-apoptotic role in acute and chronic inflammation, and has been used in many experimental and clinical applications. In the present study, we implanted IL-1Ra-expressing AF-MSCs into injured liver via the portal vein, using D-galactosamine-induced FHF in a rat model. IL-1Ra expression, hepatic injury, liver regeneration, cytokines (IL-1β, IL-6, and animal survival were assessed after cell transplantation. Our results showed that AF-MSCs over-expressing IL-1Ra prevented liver failure and reduced mortality in rats with FHF. These animals also exhibited improved liver function and increased survival rates after injection with these cells. Using green fluorescent protein as a marker, we demonstrated that the engrafted cells and their progeny were incorporated into injured livers and produced albumin. This study suggests that AF-MSCs genetically modified to over-express IL-1Ra can be implanted into the injured liver to provide a novel therapeutic approach to the treatment of FHF.

  20. Associations of Anemia and Renal Dysfunction with Outcomes among Patients Hospitalized for Acute Decompensated Heart Failure with Preserved or Reduced Ejection Fraction

    Science.gov (United States)

    Sato, Naoki; Keida, Takehiko; Sakata, Yasushi; Takano, Teruo

    2014-01-01

    Background and objectives The relationship among anemia, renal dysfunction, left ventricular ejection fraction, and outcomes of patients hospitalized for acute decompensated heart failure is unclear. The aim of this study was to evaluate the association between cardiorenal anemia syndrome and postdischarge outcomes in patients hospitalized for heart failure with a preserved or reduced ejection fraction. Design, setting, participants, & measurements Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes Registry between April 1, 2007 and December 31, 2011, 4393 patients were evaluated to investigate the association among anemia, renal dysfunction, preserved or reduced ejection fraction, and the primary end point (mortality and readmission for heart failure since discharge). The patients were divided into four groups on the basis of eGFR and hemoglobin at discharge. The median follow-up period after discharge was 432 (range=253–659) days. Results The primary end point was reached in 37.6% and 34.8% of the preserved and reduced ejection fraction groups, respectively. After adjustment for multiple comorbidities, there was no significant association of either renal dysfunction or anemia alone with the primary end point in patients with preserved ejection fraction, but the combination of renal dysfunction and anemia was associated with a significantly higher risk than that without either condition (hazard ratio, 1.54; 95% confidence interval, 1.12 to 2.12; P<0.01). In patients with reduced ejection fraction, adjusted analysis showed that a significantly higher risk of the primary end point was associated with renal dysfunction alone (hazard ratio, 1.65; 95% confidence interval, 1.21 to 2.25; P=0.002) and also, renal dysfunction plus anemia relative to the risk without either condition (hazard ratio, 2.19; 95% confidence interval, 1.62 to 2.96; P<0.001). Conclusions The findings show that renal dysfunction combined with anemia is associated with an

  1. Antivirals reduce the formation of key Alzheimer's disease molecules in cell cultures acutely infected with herpes simplex virus type 1.

    Directory of Open Access Journals (Sweden)

    Matthew A Wozniak

    Full Text Available Alzheimer's disease (AD afflicts around 20 million people worldwide and so there is an urgent need for effective treatment. Our research showing that herpes simplex virus type 1 (HSV1 is a risk factor for AD for the brains of people who possess a specific genetic factor and that the virus causes accumulation of key AD proteins (β-amyloid (Aβ and abnormally phosphorylated tau (P-tau, suggests that anti-HSV1 antiviral agents might slow AD progression. However, currently available antiviral agents target HSV1 DNA replication and so might be successful in AD only if Aβ and P-tau accumulation depend on viral DNA replication. Therefore, we investigated firstly the stage(s of the virus replication cycle required for Aβ and P-tau accumulation, and secondly whether antiviral agents prevent these changes using recombinant strains of HSV1 that progress only partly through the replication cycle and antiviral agents that inhibit HSV1 DNA replication. By quantitative immunocytochemistry we demonstrated that entry, fusion and uncoating of HSV1, are insufficient to induce Aβ and P-tau production. We showed also that none of the "immediate early" viral proteins is directly responsible, and that Aβ and P-tau are produced at a subsequent stage of the HSV1 replication cycle. Importantly, the anti-HSV1 antiviral agents acyclovir, penciclovir and foscarnet reduced Aβ and P-tau accumulation, as well as HSV1, with foscarnet being less effective in each case. P-tau accumulation was found to depend on HSV1 DNA replication, whereas Aβ accumulation was not. The antiviral-induced decrease in Aβ is attributable to the reduced number of new viruses, and hence the reduction in viral spread. Since antiviral agents reduce greatly Aβ and P-tau accumulation in HSV1-infected cells, they would be suitable for treating AD with great advantage unlike current AD therapies, only the virus, not the host cell, would be targeted.

  2. High Prestroke Physical Activity Is Associated with Reduced Infarct Growth in Acute Ischemic Stroke Patients Treated with Intravenous tPA and Randomized to Remote Ischemic Perconditioning

    DEFF Research Database (Denmark)

    Blauenfeldt, Rolf Ankerlund; Hougaard, Kristina D; Mouridsen, Kim

    2017-01-01

    infarct growth in a cohort of acute ischemic stroke patients treated with intravenous tPA and randomized to remote ischemic perconditioning. METHODS: In this predefined subanalysis, data from a randomized clinical trial investigating the effect of remote ischemic perconditioning (RIPerC) on AIS was used......-on to intravenous thrombolysis, the level of PA the week before the stroke was associated with decreased 24-h infarct growth and final infarct size. These results are highly encouraging and stress the need for further exploration of the potentially protective effects of both PA and remote ischemic conditioning.......BACKGROUND: A high prestroke physical activity (PA) level is associated with reduced stroke rate, stroke mortality, better functional outcome, and possible neuroprotective abilities. The aim of the present study was to examine the possible neuroprotective effect of prestroke PA on 24-h cerebral...

  3. T helper type 2-polarized invariant natural killer T cells reduce disease severity in acute intra-abdominal sepsis.

    Science.gov (United States)

    Anantha, R V; Mazzuca, D M; Xu, S X; Porcelli, S A; Fraser, D D; Martin, C M; Welch, I; Mele, T; Haeryfar, S M M; McCormick, J K

    2014-11-01

    Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNK T) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNK T cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNK T cells in a mouse model of intra-abdominal sepsis (IAS). Our data show that iNK T cells are pathogenic in IAS, and that T helper type 2 (Th2) polarization of iNK T cells using the synthetic glycolipid OCH significantly reduces mortality from IAS. This reduction in mortality is associated with the systemic elevation of the anti-inflammatory cytokine interleukin (IL)-13 and reduction of several proinflammatory cytokines within the spleen, notably interleukin (IL)-17. Finally, we show that treatment of sepsis with OCH in mice is accompanied by significantly reduced apoptosis of splenic T and B lymphocytes and macrophages, but not natural killer cells. We propose that modulation of iNK T cell responses towards a Th2 phenotype may be an effective therapeutic strategy in early sepsis.

  4. Thrombosis is reduced by inhibition of COX-1, but unaffected by inhibition of COX-2, in an acute model of platelet activation in the mouse.

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    Paul C Armstrong

    Full Text Available BACKGROUND: Clinical use of selective inhibitors of cyclooxygenase (COX-2 appears associated with increased risk of thrombotic events. This is often hypothesised to reflect reduction in anti-thrombotic prostanoids, notably PGI(2, formed by COX-2 present within endothelial cells. However, whether COX-2 is actually expressed to any significant extent within endothelial cells is controversial. Here we have tested the effects of acute inhibition of COX on platelet reactivity using a functional in vivo approach in mice. METHODOLOGY/PRINCIPAL FINDINGS: A non-lethal model of platelet-driven thromboembolism in the mouse was used to assess the effects of aspirin (7 days orally as control diclofenac (1 mg.kg(-1, i.v. and parecoxib (0.5 mg.kg(-1, i.v. on thrombus formation induced by collagen or the thromboxane (TX A(2-mimetic, U46619. The COX inhibitory profiles of the drugs were confirmed in mouse tissues ex vivo. Collagen and U46619 caused in vivo thrombus formation with the former, but not latter, sensitive to oral dosing with aspirin. Diclofenac inhibited COX-1 and COX-2 ex vivo and reduced thrombus formation in response to collagen, but not U46619. Parecoxib inhibited only COX-2 and had no effect upon thrombus formation caused by either agonist. CONCLUSIONS/SIGNIFICANCE: Inhibition of COX-1 by diclofenac or aspirin reduced thrombus formation induced by collagen, which is partly dependent upon platelet-derived TXA(2, but not that induced by U46619, which is independent of platelet TXA(2. These results are consistent with the model demonstrating the effects of COX-1 inhibition in platelets, but provide no support for the hypothesis that acute inhibition of COX-2 in the circulation increases thrombosis.

  5. Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats.

    Directory of Open Access Journals (Sweden)

    Agnieszka A Pozdzik

    Full Text Available The platelet-derived growth factor receptor β (PDGFRβ+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target.In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ inhibition in a rat model of AAN.Neutralizing anti-TGFβ antibody (1D11 and its control isotype (13C4 were administered (5 mg/kg, i.p. at Days -1, 0, 2 and 4; AA (15 mg/kg, sc was injected daily.At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro.The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation.

  6. Reduced acute neuroinflammation and improved functional recovery after traumatic brain injury by α-linolenic acid supplementation in mice.

    Science.gov (United States)

    Desai, Abhishek; Park, Taeyeop; Barnes, Jaquel; Kevala, Karl; Chen, Huazhen; Kim, Hee-Yong

    2016-09-23

    Adequate consumption of polyunsaturated fatty acids (PUFA) is vital for normal development and functioning of the central nervous system. The long-chain n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid are anti-inflammatory and neuroprotective in the models of central nervous system injury including traumatic brain injury (TBI). In the present study, we tested whether a higher brain DHA status in a mouse model on an adequate dietary α-linolenic acid (ALA) leads to reduced neuroinflammation and improved spontaneous recovery after TBI in comparison to a moderately lowered brain DHA status that can occur in humans. Mice reared on diets with differing ALA content were injured by a single cortical contusion impact. Change in the expression of inflammatory cytokines was measured, and cellular changes occurring after injury were analyzed by immunostaining for macrophage/microglia and astrocytes. Behavioral studies included rotarod and beam walk tests and contextual fear conditioning. Marginal supply (0.04 %) of ALA as the sole dietary source of n-3 PUFA from early gestation produced reduction of brain DHA by 35 % in adult offspring mice in comparison to the mice on adequate ALA diet (3.1 %). The DHA-depleted group showed significantly increased TBI-induced expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the brain as well as slower functional recovery from motor deficits compared to the adequate ALA group. Despite the reduction of pro-inflammatory cytokine expression, adequate ALA diet did not significantly alter either microglia/macrophage density around the contusion site or the relative M1/M2 phenotype. However, the glial fibrillary acidic protein immunoreactivity was reduced in the injured cerebral cortex of the mice on adequate ALA diet, indicating that astrocyte activation may have contributed to the observed differences in cellular and behavioral responses to TBI. Increasing the brain DHA level even from a moderately DHA

  7. Experimentally induced pain perception is acutely reduced by aerobic exercise in people with chronic low back pain.

    Science.gov (United States)

    Hoffman, Martin D; Shepanski, Melissa A; Mackenzie, Sean P; Clifford, Philip S

    2005-01-01

    This study examined whether subjects with chronic low back pain demonstrate exercise-induced analgesia to experimentally induced pressure pain. We employed a repeated measures design to study eight subjects with chronic low back pain (mean +/- standard deviation age = 40 +/- 10, duration of pain = 7 +/- 4 years). Pain ratings were measured immediately before and 2 minutes and 32 minutes after 25 minutes of cycle ergometry (5 minutes at 50% peak oxygen uptake, then 20 minutes at 70% peak oxygen uptake). We based the pain ratings on subject input on a visual analog scale at 10-second intervals during the 2-minute pressure pain stimulus to the nondominant index finger. Compared with preexercise values, pain ratings were significantly (p exercise at both 2 and 32 minutes postexercise. We conclude that pressure pain perception can be reduced for more than 30 minutes following aerobic exercise from leg cycling among people with chronic low back pain.

  8. Reducing Door to- Balloon- Time for Acute ST Elevation Myocardial Infarction In Primary Percutaneous Intervention: Transformation using Robust Performance Improvement.

    Science.gov (United States)

    Ellahham Md, Samer; Aljabbari, Samir; Harold Mananghaya, Tristan; J Raji, Salama; Al Zubaidi, Abdulmajeed

    2015-01-01

    Cardiovascular diseases (CVDs) are the leading causes of death in the UAE. Prompt reperfusion access is essential for patients who have Myocardial Infarction (MI) with ST-segment elevation as they are at a relatively high risk of death.This risk may be reduced by primary percutaneous coronary intervention (PCI), but only if it is performed in a timely manner. Guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation (door-to-balloon (D2B) time) during primary PCI should be 90 minutes or less. The earlier therapy is initiated, the better the outcome. Our aim was to decrease the door-to-balloon time for patients with ST segment elevation myocardial infarction (STEMI) who come through the emergency department (ED) in Sheikh Khalifa Medical City,a tertiary hospital in UAE, to meet the standard of less than 90 minutes. A multidisciplinary team was formed including interventional cardiologists, catheterization laboratory personnel, emergency department caregivers and quality staff. The project utilized the Lean Six Sigma Methodology which provided a powerful approach to quality improvement. The process minimized waste and variation, and a decreased median door-to-balloon time from 75.9 minutes to 60.1 minutes was noted. The percentage of patients who underwent PCI within 90 minutes increased from 73% to 96%. In conclusion, implementing the Lean Six Sigma methodology resulted in having processes that are leaner, more efficient and minimally variable. While recent publication failed to provide evidence of better outcome, the lessons learned were extrapolated to other primary percutaneous coronary intervention centers in our system.This would have marked impact on patient safety, quality of care and patient experience.

  9. Reducing Door to- Balloon- Time for Acute ST Elevation Myocardial Infarction In Primary Percutaneous Intervention: Transformation using Robust Performance Improvement

    Science.gov (United States)

    Ellahham, MD, Samer; Aljabbari, Samir; Harold Mananghaya, Tristan; J. Raji, Salama; Al Zubaidi, Abdulmajeed

    2015-01-01

    Cardiovascular diseases (CVDs) are the leading causes of death in the UAE. Prompt reperfusion access is essential for patients who have Myocardial Infarction (MI) with ST-segment elevation as they are at a relatively high risk of death.This risk may be reduced by primary percutaneous coronary intervention (PCI), but only if it is performed in a timely manner. Guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation (door-to-balloon (D2B) time) during primary PCI should be 90 minutes or less. The earlier therapy is initiated, the better the outcome. Our aim was to decrease the door-to-balloon time for patients with ST segment elevation myocardial infarction (STEMI) who come through the emergency department (ED) in Sheikh Khalifa Medical City,a tertiary hospital in UAE, to meet the standard of less than 90 minutes. A multidisciplinary team was formed including interventional cardiologists, catheterization laboratory personnel, emergency department caregivers and quality staff. The project utilized the Lean Six Sigma Methodology which provided a powerful approach to quality improvement. The process minimized waste and variation, and a decreased median door-to-balloon time from 75.9 minutes to 60.1 minutes was noted. The percentage of patients who underwent PCI within 90 minutes increased from 73% to 96%. In conclusion, implementing the Lean Six Sigma methodology resulted in having processes that are leaner, more efficient and minimally variable. While recent publication failed to provide evidence of better outcome, the lessons learned were extrapolated to other primary percutaneous coronary intervention centers in our system.This would have marked impact on patient safety, quality of care and patient experience. PMID:26734321

  10. Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

    Science.gov (United States)

    Liu, Xiaoli; Simpson, Jeremy A; Brunt, Keith R; Ward, Christopher A; Hall, Sean R R; Kinobe, Robert T; Barrette, Valerie; Tse, M Yat; Pang, Stephen C; Pachori, Alok S; Dzau, Victor J; Ogunyankin, Kofo O; Melo, Luis G

    2007-07-01

    We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

  11. Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome.

    Science.gov (United States)

    Törlén, Johan; Ringdén, Olle; Le Rademacher, Jennifer; Batiwalla, Minoo; Chen, Junfang; Erkers, Tom; Ho, Vincent; Kebriaei, Partow; Keever-Taylor, Carolyn; Kindwall-Keller, Tamila; Lazarus, Hillard M; Laughlin, Mary J; Lill, Michael; O'Brien, Tracey; Perales, Miguel-Angel; Rocha, Vanderson; Savani, Bipin N; Szwajcer, David; Valcarcel, David; Eapen, Mary

    2014-09-01

    Reduced-intensity conditioning/nonmyeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34(+) dose to be important for transplantation outcome using myeloablative conditioning. The role of CD34(+) dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced-intensity conditioning/nonmyeloablative HCT. We studied 1054 patients, ages 45 to 75 years, with acute myeloid leukemia or myelodysplastic syndrome who underwent transplantation between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing after myeloablative HCT, CD34(+) dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34(+) doses >4 × 10(6) CD34(+)/kg and >6 × 10(6) CD34(+)/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.

  12. Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok

    Science.gov (United States)

    Kroon, Eugène D.M.B.; Phanuphak, Nittaya; Shattock, Andrew J.; Fletcher, James L.K.; Pinyakorn, Suteeraporn; Chomchey, Nitiya; Akapirat, Siriwat; de Souza, Mark S.; Robb, Merlin L.; Kim, Jerome H.; van Griensven, Frits; Ananworanich, Jintanat; Wilson, David P.

    2017-01-01

    Abstract Introduction: Antiretroviral treatment (ART) reduces HIV transmission. Despite increased ART coverage, incidence remains high among men who have sex with men (MSM) in many places. Acute HIV infection (AHI) is characterized by high viral replication and increased infectiousness. We estimated the feasible reduction in transmission by targeting MSM with AHI for early ART. Methods: We recruited a cohort of 88 MSM with AHI in Bangkok, Thailand, who initiated ART immediately. A risk calculator based on viral load and reported behaviour, calibrated to Thai epidemiological data, was applied to estimate the number of onwards transmissions. This was compared with the expected number without early interventions. Results: Forty of the MSM were in 4th-generation AHI stages 1 and 2 (4thG stage 1, HIV nucleic acid testing (NAT)+/4thG immunoassay (IA)-/3rdG IA–; 4thG stage 2, NAT+/4thG IA+/3rdG IA–) while 48 tested positive on third-generation IA but had negative or indeterminate western blot (4thG stage 3). Mean plasma HIV RNA was 5.62 log10 copies/ml. Any condomless sex in the four months preceding the study was reported by 83.7%, but decreased to 21.2% by 24 weeks on ART. After ART, 48/88 (54.6%) attained HIV RNA HIV transmission occurs during AHI. Diagnosis of AHI with early ART initiation can substantially reduce onwards transmission. PMID:28691441

  13. Electroacupuncture Reduces the Effects of Acute Noxious Stimulation on the Electrical Activity of Pain-Related Neurons in the Hippocampus of Control and Neuropathic Pain Rats

    Directory of Open Access Journals (Sweden)

    Jun-Ying Wang

    2016-01-01

    Full Text Available To study the effects of acupuncture analgesia on the hippocampus, we observed the effects of electroacupuncture (EA and mitogen-activated protein kinase (MEK inhibitor on pain-excited neurons (PENs and pain-inhibited neurons (PINs in the hippocampal area CA1 of sham or chronic constrictive injury (CCI rats. The animals were randomly divided into a control, a CCI, and a U0126 (MEK1/2 inhibitor group. In all experiments, we briefly (10-second duration stimulated the sciatic nerve electrically and recorded the firing rates of PENs and PINs. The results showed that in both sham and CCI rats brief sciatic nerve stimulation significantly increased the electrical activity of PENs and markedly decreased the electrical activity of PINs. These effects were significantly greater in CCI rats compared to sham rats. EA treatment reduced the effects of the noxious stimulus on PENs and PINs in both sham and CCI rats. The effects of EA treatment could be inhibited by U0126 in sham-operated rats. The results suggest that EA reduces effects of acute sciatic nerve stimulation on PENs and PINs in the CA1 region of the hippocampus of both sham and CCI rats and that the ERK (extracellular regulated kinase signaling pathway is involved in the modulation of EA analgesia.

  14. Efficacy of synbiotics to reduce acute radiation proctitis symptoms and improve quality of life: a randomized, double-blind, placebo-controlled pilot trial.

    Science.gov (United States)

    Nascimento, Mariana; Aguilar-Nascimento, José Eduardo; Caporossi, Cervantes; Castro-Barcellos, Heloisa Michelon; Motta, Rodrigo Teixeira

    2014-10-01

    To evaluate whether the daily intake of synbiotics interferes in radiation-induced acute proctitis symptoms and in quality of life in patients with prostate cancer. Twenty patients who underwent 3-dimensional conformal radiation therapy for prostate cancer were randomized to intake either a synbiotic powder containing Lactobacillus reuteri 10(8) colony-forming units and 4.3 g of soluble fiber (Nestlé) or placebo. The questionnaire EORTC QLQ-PRT23 was applied before the beginning of radiation therapy and in every week for the first 4 weeks of treatment. The sum of both the complete (proctitis symptoms plus quality of life) and partial (proctitis symptoms) scores of the EORTC QLQ-PRT23 (European Organization for Research and Treatment of Cancer Quality of Life Module for Proctitis-23 items) questionnaire were the main endpoints. This pilot study showed that the complete questionnaire score (median [range]) was higher in the second (23 [21-30] vs 26.5 [22-34], P<.05) and third (23 [21-32] vs 27.5 [24-33], P<.01) weeks in the placebo group. Proctitis symptoms were highest scored in the placebo group in both the second (19.5 [16-25]) and third (19 [17-24]) weeks than in the synbiotic group (week 2: 16.5 [15-20], P<.05; week 3: 17 [15-23], P<.01). In both scores the placebo group had a significantly higher result (P<.01) than the synbiotic group (repeated-measures analysis of variance). Synbiotics reduce proctitis symptoms and improve quality of life in radiation-induced acute proctitis during radiation therapy for prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Efficacy of Synbiotics to Reduce Acute Radiation Proctitis Symptoms and Improve Quality of Life: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Mariana, E-mail: mari1980hemato@yahoo.com.br [Department of Medicine, University Center of Varzea Grande (UNIVAG), Varzea Grande, Mato Grosso (Brazil); Aguilar-Nascimento, José Eduardo [Department of Medicine, University Center of Varzea Grande (UNIVAG), Varzea Grande, Mato Grosso (Brazil); Caporossi, Cervantes; Castro-Barcellos, Heloisa Michelon; Motta, Rodrigo Teixeira [Department of Medicine, Federal University of Mato Grosso (UFMT), Cuiabá, Mato Grosso (Brazil)

    2014-10-01

    Purpose: To evaluate whether the daily intake of synbiotics interferes in radiation-induced acute proctitis symptoms and in quality of life in patients with prostate cancer. Methods and Materials: Twenty patients who underwent 3-dimensional conformal radiation therapy for prostate cancer were randomized to intake either a synbiotic powder containing Lactobacillus reuteri 10{sup 8} colony-forming units and 4.3 g of soluble fiber (Nestlé) or placebo. The questionnaire EORTC QLQ-PRT23 was applied before the beginning of radiation therapy and in every week for the first 4 weeks of treatment. The sum of both the complete (proctitis symptoms plus quality of life) and partial (proctitis symptoms) scores of the EORTC QLQ-PRT23 (European Organization for Research and Treatment of Cancer Quality of Life Module for Proctitis–23 items) questionnaire were the main endpoints. Results: This pilot study showed that the complete questionnaire score (median [range]) was higher in the second (23 [21-30] vs 26.5 [22-34], P<.05) and third (23 [21-32] vs 27.5 [24-33], P<.01) weeks in the placebo group. Proctitis symptoms were highest scored in the placebo group in both the second (19.5 [16-25]) and third (19 [17-24]) weeks than in the synbiotic group (week 2: 16.5 [15-20], P<.05; week 3: 17 [15-23], P<.01). In both scores the placebo group had a significantly higher result (P<.01) than the synbiotic group (repeated-measures analysis of variance). Conclusions: Synbiotics reduce proctitis symptoms and improve quality of life in radiation-induced acute proctitis during radiation therapy for prostate cancer.

  16. Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2 trial: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    McAuley Daniel F

    2012-09-01

    Full Text Available Abstract Background Acute lung injury (ALI is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2 trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI. Methods/Design Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1:1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms

  17. Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice.

    Science.gov (United States)

    Soranno, Danielle E; Rodell, Christopher B; Altmann, Christopher; Duplantis, Jane; Andres-Hernando, Ana; Burdick, Jason A; Faubel, Sarah

    2016-08-01

    Injectable hydrogels can be used to deliver drugs in situ over a sustained period of time. We hypothesized that sustained delivery of interleukin-10 (IL-10) following acute kidney injury (AKI) would mitigate the local and systemic proinflammatory cascade induced by AKI and reduce subsequent fibrosis. Wild-type C57BL/6 mice underwent ischemia-reperfusion AKI with avertin anesthesia. Three days later, mice were treated with either hyaluronic acid injectable hydrogel with or without IL-10, or IL-10 suspended in saline, injected under the capsule of the left kidney, or hydrogel with IL-10 injected subcutaneously. Untreated AKI served as controls. Serial in vivo optical imaging tracked the location and degradation of the hydrogel over time. Kidney function was assessed serially. Animals were killed 28 days following AKI and the following were evaluated: serum IL-6, lung inflammation, urine neutrophil gelatinase-associated lipocalin, and renal histology for fibroblast activity, collagen type III deposition and fibrosis via Picrosirius Red staining and second harmonic imaging. Our model shows persistent systemic inflammation, and renal inflammation and fibrosis 28 days following AKI. The hydrogels are biocompatible and reduced serum IL-6 and renal collagen type III 28 days following AKI even when delivered without IL-10. Treatment with IL-10 reduced renal and systemic inflammation, regardless of whether the IL-10 was delivered in a sustained manner via the injectable hydrogel under the left kidney capsule, as a bolus injection via saline under the left kidney capsule, or via the injectable hydrogel subcutaneously. Injectable hydrogels are suitable for local drug delivery following renal injury, are biocompatible, and help mitigate local and systemic inflammation. Copyright © 2016 the American Physiological Society.

  18. Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

    LENUS (Irish Health Repository)

    O'Seaghdha, C M

    2011-04-06

    We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng\\/mL (n = 122, range 2-13.5 ng\\/mL), Group 2: median 17 ng\\/mL (n = 123, range 14-20 ng\\/mL), Group 3: median 24 ng\\/mL (n = 108, range 20.5-27 ng\\/mL) and Group 4: median 33.5 ng\\/mL (n = 116, range 27.5-77.5 ng\\/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

  19. Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Zhang, Xiaohui; Zhou, Yi; Xu, Lanping; Han, Wei; Chen, Huan; Chen, Yuhong; Fu, Haixia; Zhou, Shiyuan; Zhao, Jingzhong; Wang, Qianming; Feng, Feier; Zhu, Xiaolu; Liu, Kaiyan; Huang, Xiaojun

    2015-05-01

    Acute graft-versus-host disease (aGVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that suppresses the immune response. This prospective study explored IL-35 plasma levels in 65 patients after HSCT. The results revealed that the peripheral blood of patients with grades III-IV aGVHD (23.46 ng/ml) had reduced IL-35 compared to transplanted patients with grades I-II aGVHD (40.26 ng/ml, p IL-35 levels with respect to aGVHD. The patients who received lower levels of IL-35 cells in the GBM (28.0 ng/ml, p = 0.551) or lower levels of IL-35 in PBPC (53.46 ng/ml, p = 0.03) exhibited a higher incidence of aGVHD. Patients with aGVHD have increased platelet aggregation. IL-35 was added to patient blood in vitro, and platelet aggregation was inhibited by IL-35 in a dose-dependent manner. The markers of platelet activation (CD62P/PAC-1) can also be inhibited by IL-35. The results indicate that IL-35 may affect the development of aGVHD by inhibiting platelet activation and aggregation. Our data suggests that IL-35 represents a potentially effective therapeutic agent against aGVHD after allo-HSCT.

  20. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats

    Directory of Open Access Journals (Sweden)

    Xiaofan Lu

    2016-01-01

    Full Text Available Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD risk window (RW have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS, moxifloxacin + salbutamol/NS (MXF+STL/NS, TSG/Bufei Yishen Granule (BYG, MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA and C-reactive protein (CRP, pulmonary histomorphology and myeloperoxidase (MPO, polymorphonuclear (PMN elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF- α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14–18 days. All biomarkers were improved in treated groups with shorter recovery times of 4–10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines.

  1. Angiotensin II AT1 receptor blockade by telmisartan reduces impairment of spatial maze performance induced by both acute and chronic stress.

    Science.gov (United States)

    Wincewicz, Dominik; Braszko, Jan J

    2015-09-01

    Despite recognition of stress as a causation of severe neuropsychological dysfunctions, no casual and clinically effective anti-stress therapeutic strategy has yet been found. We have previously shown that blockade of initial stress response by angiotensin receptor blockers alleviates the negative effect of prolonged stress on cognitive non-spatial functions of rats. Here we aimed to find whether telmisartan reduces stress-related memory decline in spatial hippocampal-dependent learning tasks conditioned upon differences in level of stress induced by aversive nature of memory tests. Male Wistar rats were exposed to chronic restraint stress for three weeks and daily treated with either vehicle or telmisartan (1 mg/kg). Afterwards rats were tested in three spatial learning and memory paradigms: Morris water maze (MWM), radial arm maze (RAM), and Barnes maze (BM). Stressed animals demonstrated significantly impaired performance in all the tests, which was normalized in the animals stressed and treated with telmisartan. Interestingly, despite the fact that MWM and RAM are more stressful, which affects animal behavior, therefore considered less sensitive than BM, more significant effect of telmisartan was found in MWM and RAM than BM. AT1 angiotensin receptor blockade attenuates negative effect of both acute and chronic stress on spatial memory. © The Author(s) 2014.

  2. Higher levels of mucosal antibody to pneumococcal vaccine candidate proteins are associated with reduced acute otitis media caused by Streptococcus pneumoniae in young children.

    Science.gov (United States)

    Xu, Q; Casey, J R; Pichichero, M E

    2015-09-01

    Mucosal immunity has a crucial role in controlling human respiratory tract infections. This study characterizes the naturally acquired mucosal antibody levels to three Streptococcus pneumoniae (Spn) protein antigens, pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and pneumolysin (Ply), and assesses the association of the mucosal antibody levels with occurrence of acute otitis media (AOM) caused by Spn. Both nasopharyngeal (NP) immunoglobulin G (IgG) and IgA levels to all three proteins slightly decreased in children from 6 to 9 months of age and then gradually increased through 24 months of age. Spn NP colonization was associated with higher mucosal antibody levels to all three proteins. However, children with Spn AOM had 5-8-fold lower IgG and 3-6-fold lower IgA levels to the three proteins than children without AOM but asymptomatically colonized with Spn. Antigen-specific antibody levels in the middle ear fluid (MEF) were correlated with antibody levels in the NP. Children with AOM caused by Spn had lower antibody levels in both the MEF and NP than children with AOM caused by other pathogens. These results indicate that higher naturally acquired mucosal antibody levels to PhtD, PcpA and Ply are associated with reduced AOM caused by Spn.

  3. The clinical utility of repetitive transcranial magnetic stimulation in reducing the risks of transitioning from acute to chronic pain in traumatically injured patients.

    Science.gov (United States)

    Jodoin, Marianne; Rouleau, Dominique; Larson-Dupuis, Camille; Gosselin, Nadia; De Beaumont, Louis

    2017-07-08

    Pain is a multifaceted condition and a major ongoing challenge for healthcare professionals having to treat patients in whom pain put them at risk of developing other conditions. Significant efforts have been invested in both clinical and research settings in an attempt to demystify the mechanisms at stake and develop optimal treatments as well as to reduce individual and societal costs. It is now universally accepted that neuroinflammation and central sensitization are two key underlying factors causing pain chronification as they result from maladaptive central nervous system plasticity. Recent research has shown that the mechanisms of action of repetitive transcranial magnetic stimulation (rTMS) make it a particularly promising avenue in treating various pain conditions. This review will first discuss the contribution of neuroinflammation and central sensitization in the transition from acute to chronic pain in traumatically injured patients. A detailed discussion on how rTMS may allow the restoration from maladaptive plasticity in addition to breaking down the chain of events leading to pain chronification will follow. Lastly, this review will provide a theoretical framework of what might constitute optimal rTMS modalities in dealing with pain symptoms in traumatically injured patients based on an integrated perspective of the physiopathological mechanisms underlying pain. Copyright © 2017. Published by Elsevier Inc.

  4. Consuming polydextrose in a mid-morning snack increases acute satiety measurements and reduces subsequent energy intake at lunch in healthy human subjects.

    Science.gov (United States)

    Hull, Sarah; Re, Roberta; Tiihonen, Kirsti; Viscione, Luisa; Wickham, Martin

    2012-12-01

    Polydextrose (Litesse®, DuPont) is a polysaccharide that is partially fermented in the colon. Evidence suggests that polydextrose increases satiety when consumed over several weeks; however studies assessing its acute effects on satiety are lacking. This study therefore aimed to assess the impact of different doses of polydextrose on satiety and energy intake at subsequent meals during a test day. Three yogurt-based drinks containing different amounts of polydextrose (0, 6.25 and 12.5g) were tested using a randomised, single-blinded, placebo controlled, cross-over design. Thirty-four healthy male and female volunteers were provided with a standard breakfast, then consumed the test product mid-morning, 90min before an ad libitum lunch, which was followed by an ad libitum dinner. Visual analogue scales were used to measure subjective ratings of appetite, liking and discomfort. Consuming 6.25 and 12.5g polydextrose increased satiety and decreased appetite compared to control immediately after consumption. A reduction in energy intake (218.8kJ) at lunchtime was observed for 12.5g polydextrose. This reduction in energy intake was not compensated for at dinner. This study suggests that polydextrose may aid in increasing satiety feelings post consumption and also reduce energy intake as a result.

  5. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl phthalate in male Long Evans rats.

    Directory of Open Access Journals (Sweden)

    Catherine A Smith

    Full Text Available Early developmental exposure to di(2-ethylhexyl phthalate (DEHP has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  6. Reduced hippocampal dendritic spine density and BDNF expression following acute postnatal exposure to di(2-ethylhexyl) phthalate in male Long Evans rats.

    Science.gov (United States)

    Smith, Catherine A; Holahan, Matthew R

    2014-01-01

    Early developmental exposure to di(2-ethylhexyl) phthalate (DEHP) has been linked to a variety of neurodevelopmental changes, particularly in rodents. The primary goal of this work was to establish whether acute postnatal exposure to a low dose of DEHP would alter hippocampal dendritic morphology and BDNF and caspase-3 mRNA expression in male and female Long Evans rats. Treatment with DEHP in male rats led to a reduction in spine density on basal and apical dendrites of neurons in the CA3 dorsal hippocampal region compared to vehicle-treated male controls. Dorsal hippocampal BDNF mRNA expression was also down-regulated in male rats exposed to DEHP. No differences in hippocampal spine density or BDNF mRNA expression were observed in female rats treated with DEHP compared to controls. DEHP treatment did not affect hippocampal caspase-3 mRNA expression in male or female rats. These results suggest a gender-specific vulnerability to early developmental DEHP exposure in male rats whereby postnatal DEHP exposure may interfere with normal synaptogenesis and connectivity in the hippocampus. Decreased expression of BDNF mRNA may represent a molecular mechanism underlying the reduction in dendritic spine density observed in hippocampal CA3 neurons. These findings provide initial evidence for a link between developmental exposure to DEHP, reduced levels of BDNF and hippocampal atrophy in male rats.

  7. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats

    Science.gov (United States)

    Lu, Xiaofan; Li, Ya; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang

    2016-01-01

    Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14–18 days. All biomarkers were improved in treated groups with shorter recovery times of 4–10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333

  8. Mutated Ptpn11 alters leukemic stem cell frequency and reduces the sensitivity of acute myeloid leukemia cells to Mcl1 inhibition.

    Science.gov (United States)

    Chen, L; Chen, W; Mysliwski, M; Serio, J; Ropa, J; Abulwerdi, F A; Chan, R J; Patel, J P; Tallman, M S; Paietta, E; Melnick, A; Levine, R L; Abdel-Wahab, O; Nikolovska-Coleska, Z; Muntean, A G

    2015-06-01

    PTPN11 encodes the Shp2 non-receptor protein-tyrosine phosphatase implicated in several signaling pathways. Activating mutations in Shp2 are commonly associated with juvenile myelomonocytic leukemia but are not as well defined in other neoplasms. Here we report that Shp2 mutations occur in human acute myeloid leukemia (AML) at a rate of 6.6% (6/91) in the ECOG E1900 data set. We examined the role of mutated Shp2 in leukemias harboring MLL translocations, which co-occur in human AML. The hyperactive Shp2E76K mutant, commonly observed in leukemia patients, significantly accelerated MLL-AF9-mediated leukemogenesis in vivo. Shp2E76K increased leukemic stem cell frequency and affords MLL-AF9 leukemic cells IL3 cytokine hypersensitivity. As Shp2 is reported to regulate anti-apoptotic genes, we investigated Bcl2, Bcl-xL and Mcl1 expression in MLL-AF9 leukemic cells with and without Shp2E76K. Although the Bcl2 family of genes was upregulated in Shp2E76K cells, Mcl1 showed the highest upregulation in MLL-AF9 cells in response to Shp2E76K. Indeed, expression of Mcl1 in MLL-AF9 cells phenocopies expression of Shp2E76K, suggesting Shp2 mutations cooperate through activation of anti-apoptotic genes. Finally, we show Shp2E76K mutations reduce sensitivity of AML cells to small-molecule-mediated Mcl1 inhibition, suggesting reduced efficacy of drugs targeting MCL1 in patients with hyperactive Shp2.

  9. Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.

    Science.gov (United States)

    Parikh, Amay; Rizzo, John A; Canetta, Pietro; Forster, Catherine; Sise, Meghan; Maarouf, Omar; Singer, Eugenia; Elger, Antje; Elitok, Saban; Schmidt-Ott, Kai; Barasch, Jonathon; Nickolas, Thomas L

    2017-01-01

    Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone. A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated. For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs. Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.

  10. Utility of population models to reduce uncertainty and increase value relevance in ecological risk assessments of pesticides: an example based on acute mortality data for daphnids.

    Science.gov (United States)

    Hanson, Niklas; Stark, John D

    2012-04-01

    Traditionally, ecological risk assessments (ERA) of pesticides have been based on risk ratios, where the predicted concentration of the chemical is compared to the concentration that causes biological effects. The concentration that causes biological effect is mostly determined from laboratory experiments using endpoints on the level of the individual (e.g., mortality and reproduction). However, the protection goals are mostly defined at the population level. To deal with the uncertainty in the necessary extrapolations, safety factors are used. Major disadvantages with this simplified approach is that it is difficult to relate a risk ratio to the environmental protection goals, and that the use of fixed safety factors can result in over- as well as underprotective assessments. To reduce uncertainty and increase value relevance in ERA, it has been argued that population models should be used more frequently. In the present study, we have used matrix population models for 3 daphnid species (Ceriodaphnia dubia, Daphnia magna, and D. pulex) to reduce uncertainty and increase value relevance in the ERA of a pesticide (spinosad). The survival rates in the models were reduced in accordance with data from traditional acute mortality tests. As no data on reproductive effects were available, the conservative assumption that no reproduction occurred during the exposure period was made. The models were used to calculate the minimum population size and the time to recovery. These endpoints can be related to the European Union (EU) protection goals for aquatic ecosystems in the vicinity of agricultural fields, which state that reversible population level effects are acceptable if there is recovery within an acceptable (undefined) time frame. The results of the population models were compared to the acceptable (according to EU documents) toxicity exposure ratio (TER) that was based on the same data. At the acceptable TER, which was based on the most sensitive species (C. dubia

  11. Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro.

    Science.gov (United States)

    Chen, Lili; Gui, Chunshan; Luo, Xiaomin; Yang, Qingang; Günther, Stephan; Scandella, Elke; Drosten, Christian; Bai, Donglu; He, Xichang; Ludewig, Burkhard; Chen, Jing; Luo, Haibin; Yang, Yiming; Yang, Yifu; Zou, Jianping; Thiel, Volker; Chen, Kaixian; Shen, Jianhua; Shen, Xu; Jiang, Hualiang

    2005-06-01

    The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CLpro. As a target for screening, both a homology model and the crystallographic structure of the binding pocket of the enzyme were used. Cinanserin (SQ 10,643), a well-characterized serotonin antagonist that has undergone preliminary clinical testing in humans in the 1960s, showed a high score in the screening and was chosen for further experimental evaluation. Binding of both cinanserin and its hydrochloride to bacterially expressed 3CLpro of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology. The catalytic activity of both enzymes was inhibited with 50% inhibitory concentration (IC50) values of 5 microM, as tested with a fluorogenic substrate. The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E. All assays revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations. The level of virus RNA and infectious particles was reduced by up to 4 log units, with IC50 values ranging from 19 to 34 microM. These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase.

  12. Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model.

    Science.gov (United States)

    Ma, Qing; Wang, Changqing; Jones, Dan; Quintanilla, Kathryn E; Li, Dan; Wang, Yang; Wieder, Eric D; Clise-Dwyer, Karen; Alatrash, Gheath; Mj, You; Munsell, Mark F; Lu, Sijie; Qazilbash, Muzaffar H; Molldrem, Jeffrey J

    2010-12-01

    Tumor antigen-specific cytotoxic T lymphocytes (CTL) have been used in the treatment of human cancer, including leukemia. Several studies have established PR1 peptide, an HLA-A2.1-restricted peptide derived from proteinase 3 (P3), as a human leukemia-associated antigen. PR1-specific CTL elicited in vitro from healthy donors have been shown to lyse P3-expressing AML cells from patients. We investigated whether PR1-CTL can be adoptively transferred into NOD/SCID mice to eliminate human leukemia cells. PR1-CTL were generated in bulk culture from peripheral blood mononuclear cells (PBMC) stimulated with autologous dendritic cells. Human acute myeloid leukemia (AML) patient samples were injected and engrafted in murine bone marrow at 2 weeks post-transfer. Following adoptive transfer, bone marrow aspirate from mice that received AML alone had 72-88% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 3-18% blasts in a hypocellular marrow. The PR1-CTL persisted in the bone marrow and liver and maintained a CD45RA⁻CD28+ effector phenotype. We found that adoptive transfer of PR1-CTL generated in vitro is associated with reduced AML cells in NOD/SCID mice. PR1-CTL can migrate to the sites of disease and maintain their capacity to kill the AML cells. The surface phenotype of PR1-CTL was consistent with their trafficking pattern in both vascular and end-organ tissues.

  13. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in swine hearts: a novel therapeutic approach for acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Hisaaki eIshiguro

    2011-06-01

    Full Text Available Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigate the cardioprotective effect of midkine (MK in swine subjected to ischemia/reperfusion (I/R. I/R was created in swine by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion (midkine injected group; MKT. Saline was injected in controls (CONT. Survival rate 24h after I/R was significantly higher in MKT than in CONT, whereas infarct size/area at risk was almost 5 times smaller. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher % fractional shortening and a lower E/e’ compared with CONT. LV catheterization in MKT showed a lower LVEDP, and a higher dP/dtmax compared with CONT. TUNEL-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we showed that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and mortality and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  14. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome.

    Science.gov (United States)

    Ishiguro, Hisaaki; Horiba, Mitsuru; Takenaka, Hiroharu; Sumida, Arihiro; Opthof, Tobias; Ishiguro, Yuko S; Kadomatsu, Kenji; Murohara, Toyoaki; Kodama, Itsuo

    2011-01-01

    Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigated the cardioprotective effect of midkine (MK) in swine subjected to ischemia/reperfusion (I/R). I/R was created by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion [MK-treated (MKT) group]. Saline was injected in controls (CONT). Infarct size/area at risk (24 h after I/R) in MKT was almost five times smaller than in CONT. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher left ventricular (LV) fractional shortening, and a lower E/e(') (ratio of transmitral to annular flow) compared with CONT. LV catheterization in MKT showed a lower LV end-diastolic pressure, and a higher dP/dt(max) compared with CONT. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we demonstrate that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  15. Impact of Cyclosporine Levels on the Development of Acute Graft versus Host Disease after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Irene García Cadenas

    2014-01-01

    Full Text Available We analyze the impact of cyclosporine (CsA levels in the development of acute graft-versus-host disease (aGVHD after reduced intensity conditioning allogeneic hematopoietic transplantation (allo-RIC. We retrospectively evaluated 156 consecutive patients who underwent HLA-identical sibling allo-RIC at our institution. CsA median blood levels in the 1st, 2nd, 3rd and 4th weeks after allo-RIC were 134 (range: 10–444, 219 (54–656, 253 (53–910 and 224 (30–699 ng/mL; 60%, 16%, 11% and 17% of the patients had median CsA blood levels below 150 ng/mL during these weeks. 53 patients developed grade 2–4 aGVHD for a cumulative incidence of 45% (95% CI 34–50% at a median of 42 days. Low CsA levels on the 3rd week and sex-mismatch were associated with the development of GVHD. Risk factors for 1-year NRM and OS were advanced disease status (HR: 2.2, P=0.02 and development of grade 2–4 aGVHD (HR: 2.5, P<0.01, while there was a trend for higher NRM in patients with a low median CsA concentration on the 3rd week (P=0.06. These results emphasize the relevance of sustaining adequate levels of blood CsA by close monitoring and dose adjustments, particularly when engraftment becomes evident. CsA adequate management will impact on long-term outcomes in the allo-RIC setting.

  16. Higher education is associated with reduced risk of heart failure among patients with acute myocardial infarction: A nationwide analysis using data from the CVDNOR project.

    Science.gov (United States)

    Sulo, Gerhard; Nygård, Ottar; Vollset, Stein Emil; Igland, Jannicke; Ebbing, Marta; Sulo, Enxhela; Egeland, Grace M; Tell, Grethe S

    2016-11-01

    Coronary heart disease (CHD) outcomes are characterised by socioeconomic gradients. Although heart failure (HF) is a severe complication of CHD, sparse evidence exists on the association between socioeconomic status and HF among coronary patients. This study aimed to explore potential educational differences in the risk of HF among acute myocardial infarction (AMI) patients in Norway during 2001-2009. A total of 70,506 patients hospitalised for an incident (first) AMI and without history of HF were included in the analyses. Information on education was obtained from the Norwegian Education Database and categorised into primary, secondary or tertiary. In 12,487 (17.7%) patients, HF was present at admission or developed during the AMI hospitalisation (early-onset HF). Compared to patients with primary education, patients with secondary or tertiary education had 9% [incidence rate ratio (IRR) = 0.91; 95% confidence interval (CI): 0.87-0.94] and 20% (IRR = 0.80; 95% CI: 0.75-0.86) lower risks of early-onset HF, respectively. Of the 54,095 AMI patients discharged alive without concurrent HF, 6375 (11.8%) were subsequently hospitalised with or died from late-onset HF during a median follow-up period of 3.4 years. Compared to patients with primary education, those with secondary or tertiary education had 14% [hazard ratio (HR = 0.86; 95% CI: 0.82-0.91] and 27% (HR = 0.73; 95% CI: 0.66-0.80) lower risks of HF, respectively. Educational differences in the risk of HF were not influenced by gender. We observed an inverse association between educational level and risk of HF. More efforts in preventing this severe complication of AMI among less educated patients may help to reduce the socioeconomic gap in survival following coronary events. © The European Society of Cardiology 2016.

  17. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions

    Institute of Scientific and Technical Information of China (English)

    Li Zhu; Zhong Cheng Yang; Ao Li; De Chang Cheng

    2000-01-01

    AIM To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS A rat model with 30% TBSA fullthickness burn injury was employed and the gastric acid production, together with gastric mucosal blood flow (GMBF) and energy charge ( EC ) were measured serially within 48h postburn.RESULTS The gastric acid production in the acute shock period was markedly inhibited after severe burn injury. At the 3rd h postburn, the gastric juice volume, total acidity and acid output were already significantly decreased (P<0.01), and reached the lowest point,0.63mL/L ± 0.20mL/L, 10.81mmol/L ±2.58mmol/L and 2.23 mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24 h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore,taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment.

  18. An intervention with access to C-reactive protein rapid test reduces antibiotic overprescribing in acute exacerbations of chronic bronchitis and COPD

    DEFF Research Database (Denmark)

    F. Strykowski, David; Nielsen, Anni Brit Sternhagen; Llor, Carles

    2015-01-01

    Background. In acute exacerbation of chronic obstructive pulmonary disease (AECOPD) antibiotic overprescribing leads to antimicrobial resistance and underprescribing may cause poor patient outcomes. Objective. This study aimed to evaluate changes in over- and underprescribing of antibiotics after...

  19. Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration

    DEFF Research Database (Denmark)

    Hebebrand, J; Blum, W F; Barth, N;

    1997-01-01

    Circulating leptin concentrations are known to be low in acute anorexia nervosa (AN), which is characterized by low weight, amenorrhea and specific psychopathological features. In this study plasma leptin concentrations were determined during inpatient treatment of 23 adolescent females...

  20. Large-scale field application of RNAi technology reducing Israeli acute paralysis virus disease in honey bees (Apis mellifera, Hymenoptera: Apidae)

    National Research Council Canada - National Science Library

    Hunter, Wayne; Ellis, James; Vanengelsdorp, Dennis; Hayes, Jerry; Westervelt, Dave; Glick, Eitan; Williams, Michael; Sela, Ilan; Maori, Eyal; Pettis, Jeffery; Cox-Foster, Diana; Paldi, Nitzan

    2010-01-01

    ...), which is a disease syndrome that is likely caused by several factors. Data from an initial study in which investigators compared pathogens in honey bees affected by CCD suggested a putative role for Israeli Acute Paralysis Virus, IAPV...

  1. Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome.

    Science.gov (United States)

    Mawad, Raya; Gooley, Ted A; Rajendran, Joseph G; Fisher, Darrell R; Gopal, Ajay K; Shields, Andrew T; Sandmaier, Brenda M; Sorror, Mohamed L; Deeg, Hans Joachim; Storb, Rainer; Green, Damian J; Maloney, David G; Appelbaum, Frederick R; Press, Oliver W; Pagel, John M

    2014-09-01

    We treated patients under age 50 years with iodine-131 ((131)I)-anti-CD45 antibody combined with fludarabine and 2 Gy total body irradiation to create an improved hematopoietic cell transplantation (HCT) strategy for advanced acute myeloid leukemia or high-risk myelodysplastic syndrome patients. Fifteen patients received 332 to 1561 mCi of (131)I, delivering an average of 27 Gy to bone marrow, 84 Gy to spleen, and 21 Gy to liver. Although a maximum dose of 28 Gy was delivered to the liver, no dose-limiting toxicity was observed. Marrow doses were arbitrarily capped at 43 Gy to avoid radiation-induced stromal damage; however, no graft failure or evidence of stromal damage was observed. Twelve patients (80%) developed grade II graft-versus-host disease (GVHD), 1 patient developed grade III GVHD, and no patients developed grade IV GVHD during the first 100 days after HCT. Of the 12 patients with chronic GVHD data, 10 developed chronic GVHD, generally involving the skin and mouth. Six patients (40%) are surviving after a median of 5.0 years (range, 4.2 to 8.3 years). The estimated survival at 1 year was 73% among the 15 treated patients. Eight patients relapsed, 7 of whom subsequently died. The median time to relapse among these 8 patients was 54 days (range, 26 to 1364 days). No cases of nonrelapse mortality were observed in the first year after transplantation. However, 2 patients died in remission from complications of chronic GVHD and cardiomyopathy, at 18 months and 14 months after transplantation, respectively. This study suggests that patients may tolerate myeloablative doses >28 Gy delivered to the liver using (131)I-anti-CD45 antibody in addition to standard reduced-intensity conditioning. Moreover, the arbitrary limit of 43 Gy to the marrow may be unnecessarily conservative, and continued escalation of targeted radioimmunotherapy doses may be feasible to further reduce relapse.

  2. Modelling sewer sediment deposition, erosion, and transport processes to predict acute influent and reduce combined sewer overflows and CO(2) emissions.

    Science.gov (United States)

    Mouri, Goro; Oki, Taikan

    2010-01-01

    Understanding of solids deposition, erosion, and transport processes in sewer systems has improved considerably in the past decade. This has provided guidance for controlling sewer solids and associated acute pollutants to protect the environment and improve the operation of wastewater systems. Although measures to decrease combined sewer overflow (CSO) events have reduced the amount of discharged pollution, overflows continue to occur during rainy weather in combined sewer systems. The solution lies in the amount of water allotted to various processes in an effluent treatment system, in impact evaluation of water quality and prediction technology, and in stressing the importance of developing a control technology. Extremely contaminated inflow has been a serious research subject, especially in connection with the influence of rainy weather on nitrogen and organic matter removal efficiency in wastewater treatment plants (WWTP). An intensive investigation of an extremely polluted inflow load to WWTP during rainy weather was conducted in the city of Matsuyama, the region used for the present research on total suspended solid (TSS) concentration. Since the inflow during rainy weather can be as much as 400 times that in dry weather, almost all sewers are unsettled and overflowing when a rain event is more than moderate. Another concern is the energy consumed by wastewater treatment; this problem has become important from the viewpoint of reducing CO(2) emissions and overall costs. Therefore, while establishing a prediction technology for the inflow water quality characteristics of a sewage disposal plant is an important priority, the development of a management/control method for an effluent treatment system that minimises energy consumption and CO(2) emissions due to water disposal is also a pressing research topic with regards to the quality of treated water. The procedure to improve water quality must make use of not only water quality and biotic criteria, but also

  3. Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration

    DEFF Research Database (Denmark)

    Hebebrand, J; Blum, W F; Barth, N

    1997-01-01

    Circulating leptin concentrations are known to be low in acute anorexia nervosa (AN), which is characterized by low weight, amenorrhea and specific psychopathological features. In this study plasma leptin concentrations were determined during inpatient treatment of 23 adolescent females with AN u......Circulating leptin concentrations are known to be low in acute anorexia nervosa (AN), which is characterized by low weight, amenorrhea and specific psychopathological features. In this study plasma leptin concentrations were determined during inpatient treatment of 23 adolescent females...

  4. Curcumin reduces expression of Bcl-2, leading to apoptosis in daunorubicin-insensitive CD34+ acute myeloid leukemia cell lines and primary sorted CD34+ acute myeloid leukemia cells

    Science.gov (United States)

    2011-01-01

    Background Acute myeloid leukemia (AML) is an immunophenotypically heterogenous malignant disease, in which CD34 positivity is associated with poor prognosis. CD34+ AML cells are 10-15-fold more resistant to daunorubicin (DNR) than CD34- AML cells. Curcumin is a major component of turmeric that has shown cytotoxic activity in multiple cancers; however, its anti-cancer activity has not been well studied in DNR-insensitive CD34+ AML cells. The aim of this study was to therefore to explore curcumin-induced cytotoxicity in DNR-insensitive CD34+ AML cell lines (KG1a, Kasumi-1), DNR-sensitive U937 AML cells, and primary CD34+ AML bone-marrow-derived cells. Methods Primary human CD34+ cells were isolated from peripheral blood mononuclear cells or bone marrow mononuclear cells using a CD34 MicroBead kit. The growth inhibitory effects of curcumin were evaluated by MTT and colony-formation assays. Cell cycle distribution was examined by propidium iodide (PI) assay. Apoptosis was analyzed by Wright-Giemsa, Hoechst 33342 and Annexin-V/PI staining assays. The change in mitochondrial membrane potential (MMP) was examined by JC-1 staining and flow cytometry. Expression of apoptosis-related proteins was determined by reverse transcription-polymerase chain reaction and Western blotting. Short interfering RNA (siRNA) against Bcl-2 was used in CD34+ KG1a and Kasumi-1 cells incubated with/without DNR. Results Curcumin inhibited proliferation and induced apoptosis and G1/S arrest in both DNR-insensitive KG1a, Kasumi-1 and DNR-sensitive U937 cells. Curcumin-induced apoptosis was associated with reduced expression of both Bcl-2 mRNA and protein, subsequent loss of MMP, and activation of caspase-3 followed by PARP degradation. Curcumin synergistically enhanced the cytotoxic effect of DNR in DNR-insensitive KG1a and Kasumi-1 cells, consistent with decreased Bcl-2 expression. Accordingly, siRNA against Bcl-2 increased the susceptibility of KG1a and Kasumi-1 cells to DNR-induced apoptosis

  5. Curcumin reduces expression of Bcl-2, leading to apoptosis in daunorubicin-insensitive CD34+ acute myeloid leukemia cell lines and primary sorted CD34+ acute myeloid leukemia cells

    Directory of Open Access Journals (Sweden)

    Huang Sheng-Shan

    2011-05-01

    Full Text Available Abstract Background Acute myeloid leukemia (AML is an immunophenotypically heterogenous malignant disease, in which CD34 positivity is associated with poor prognosis. CD34+ AML cells are 10-15-fold more resistant to daunorubicin (DNR than CD34- AML cells. Curcumin is a major component of turmeric that has shown cytotoxic activity in multiple cancers; however, its anti-cancer activity has not been well studied in DNR-insensitive CD34+ AML cells. The aim of this study was to therefore to explore curcumin-induced cytotoxicity in DNR-insensitive CD34+ AML cell lines (KG1a, Kasumi-1, DNR-sensitive U937 AML cells, and primary CD34+ AML bone-marrow-derived cells. Methods Primary human CD34+ cells were isolated from peripheral blood mononuclear cells or bone marrow mononuclear cells using a CD34 MicroBead kit. The growth inhibitory effects of curcumin were evaluated by MTT and colony-formation assays. Cell cycle distribution was examined by propidium iodide (PI assay. Apoptosis was analyzed by Wright-Giemsa, Hoechst 33342 and Annexin-V/PI staining assays. The change in mitochondrial membrane potential (MMP was examined by JC-1 staining and flow cytometry. Expression of apoptosis-related proteins was determined by reverse transcription-polymerase chain reaction and Western blotting. Short interfering RNA (siRNA against Bcl-2 was used in CD34+ KG1a and Kasumi-1 cells incubated with/without DNR. Results Curcumin inhibited proliferation and induced apoptosis and G1/S arrest in both DNR-insensitive KG1a, Kasumi-1 and DNR-sensitive U937 cells. Curcumin-induced apoptosis was associated with reduced expression of both Bcl-2 mRNA and protein, subsequent loss of MMP, and activation of caspase-3 followed by PARP degradation. Curcumin synergistically enhanced the cytotoxic effect of DNR in DNR-insensitive KG1a and Kasumi-1 cells, consistent with decreased Bcl-2 expression. Accordingly, siRNA against Bcl-2 increased the susceptibility of KG1a and Kasumi-1 cells to

  6. Hydrostatin-SN1, a Sea Snake-Derived Bioactive Peptide, Reduces Inflammation in a Mouse Model of Acute Lung Injury.

    Science.gov (United States)

    Wu, Guosheng; Wang, Junjie; Luo, Pengfei; Li, An; Tian, Song; Jiang, Hailong; Zheng, Yongjun; Zhu, Feng; Lu, Yiming; Xia, Zhaofan

    2017-01-01

    Snake venom has been used for centuries as a traditional Chinese medicine. Hydrostatin-SN1 (H-SN1), a bioactive peptide extracted from the Hydrophis cyanocinctus venom gland T7 phage display library, was reported to have the ability to reduce inflammation in a dextran sulfate sodium-induced murine colitis model. In this study, we sought to investigate the inhibitory potential of H-SN1 on inflammation in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI), and elucidate the anti-inflammatory mechanism in LPS-stimulated RAW 264.7 cells. In vivo, C57BL/6 male mice were intratracheally instilled with LPS or physiological saline with concurrent intraperitoneal injection of H-SN1 or saline alone. Lung histopathologic changes, lung wet-to-dry weight ratio, and myeloperoxidase activity in lung tissues were assessed. Total cell number, the protein concentration, and cytokine levels were determined in the bronchial alveolar lavage fluid. In vitro, RAW 264.7 cells were treated with various concentrations of H-SN1 for 2 h followed by incubation with or without 1 μg/ml LPS for 0.5 or 24 h. The mRNA expression of inflammatory cytokines was determined via RT-PCR and protein levels in the supernatants were measured via ELISA. Extracellular-signal related kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) pathways were analyzed via western blot. H-SN1 improved pulmonary edema status, decreased vascular permeability, suppressed pro-inflammatory cytokine production, and lessened lung morphological injury. H-SN1 also dose-dependently inhibited the mRNA expression and release of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW 264.7 cells. Moreover, H-SN1 inhibited the LPS-induced phosphorylation of ERK1/2 and the nuclear translocation of NF-κB. Our results suggest that H-SN1 could attenuate LPS-induced ALI in mice, which is associated with the anti-inflammatory effect of H-SN1. The mechanism might involve inhibiting the production of inflammatory cytokines by

  7. Hydrostatin-SN1, a Sea Snake-Derived Bioactive Peptide, Reduces Inflammation in a Mouse Model of Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Guosheng Wu

    2017-05-01

    Full Text Available Snake venom has been used for centuries as a traditional Chinese medicine. Hydrostatin-SN1 (H-SN1, a bioactive peptide extracted from the Hydrophis cyanocinctus venom gland T7 phage display library, was reported to have the ability to reduce inflammation in a dextran sulfate sodium-induced murine colitis model. In this study, we sought to investigate the inhibitory potential of H-SN1 on inflammation in a murine model of lipopolysaccharide (LPS-induced acute lung injury (ALI, and elucidate the anti-inflammatory mechanism in LPS-stimulated RAW 264.7 cells. In vivo, C57BL/6 male mice were intratracheally instilled with LPS or physiological saline with concurrent intraperitoneal injection of H-SN1 or saline alone. Lung histopathologic changes, lung wet-to-dry weight ratio, and myeloperoxidase activity in lung tissues were assessed. Total cell number, the protein concentration, and cytokine levels were determined in the bronchial alveolar lavage fluid. In vitro, RAW 264.7 cells were treated with various concentrations of H-SN1 for 2 h followed by incubation with or without 1 μg/ml LPS for 0.5 or 24 h. The mRNA expression of inflammatory cytokines was determined via RT-PCR and protein levels in the supernatants were measured via ELISA. Extracellular-signal related kinase 1/2 (ERK1/2 and nuclear factor-κB (NF-κB pathways were analyzed via western blot. H-SN1 improved pulmonary edema status, decreased vascular permeability, suppressed pro-inflammatory cytokine production, and lessened lung morphological injury. H-SN1 also dose-dependently inhibited the mRNA expression and release of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW 264.7 cells. Moreover, H-SN1 inhibited the LPS-induced phosphorylation of ERK1/2 and the nuclear translocation of NF-κB. Our results suggest that H-SN1 could attenuate LPS-induced ALI in mice, which is associated with the anti-inflammatory effect of H-SN1. The mechanism might involve inhibiting the production of inflammatory

  8. Acute cor pulmonale.

    Science.gov (United States)

    Jardin, François; Vieillard-Baron, Antoine

    2009-02-01

    Acute cor pulmonale is a form of acute right heart failure produced by a sudden increase in resistance to blood flow in the pulmonary circulation, which is now rapidly recognized by bedside echocardiography. In the clinical setting, acute cor pulmonale is mainly observed as a complication of massive pulmonary embolism or acute respiratory distress syndrome. In acute respiratory distress syndrome, the worsening effect of mechanical ventilation has been recently emphasized. As a general rule, the treatment consists in rapidly reducing resistance to blood flow in the pulmonary circulation, obtained by a specific strategy according to etiology.

  9. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Mookerjee, Rajeshwar P; Pavesi, Marco; Thomsen, Karen Louise

    2016-01-01

    BACKGROUND AND AIMS: Non-selective beta-blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute on chronic liver failure (ACLF...

  10. Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis

    NARCIS (Netherlands)

    Minnen, van L.P.; Timmerman, H.M.; Lutgendorff, F.; Verheem, A.; Harmsen, W.; Konstantinov, S.R.; Smidt, H.; Visser, M.R.; Rijkers, G.T.; Gooszen, H.G.; Akkermans, L.M.

    2007-01-01

    Infection of pancreatic necrosis by gut bacteria is a major cause of morbidity and mortality in patients with severe acute pancreatitis. Use of prophylactic antibiotics remains controversial. The aim of this experiment was assess if modification of intestinal flora with specifically designed multisp

  11. Global left ventricular longitudinal strain is closely associated with increased neurohormonal activation after acute myocardial infarction in patients with both reduced and preserved ejection fraction

    DEFF Research Database (Denmark)

    Ersbøll, Mads; Valeur, Nana; Mogensen, Ulrik Madvig;

    2012-01-01

    N-terminal pro brain natriuretic peptide (NT-proBNP) is released in response to increased myocardial wall stress and is associated with adverse outcome in acute myocardial infarction. However, little is known about the relationship between longitudinal deformation indices and NT-proBNP....

  12. The calcineurin inhibitor cyclosporin A cyclophilin A complex reduces desensitization of GABA(A)-mediated responses in acutely dissociated rat hippocampal neurons

    NARCIS (Netherlands)

    Martina, M; Mozrzymas, JW; Boddeke, HWGM; Cherubini, E

    1996-01-01

    The effects of the selective inhibitor of calcineurin, cyclosporin A-cyclophilin A (CC) complex on the desensitization kinetics of GABA(A) receptors was studied in acutely dissociated hippocampal neurons, using the patch clamp technique in the whole cell configuration. In control conditions, the dec

  13. Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis

    NARCIS (Netherlands)

    Minnen, van L.P.; Timmerman, H.M.; Lutgendorff, F.; Verheem, A.; Harmsen, W.; Konstantinov, S.R.; Smidt, H.; Visser, M.R.; Rijkers, G.T.; Gooszen, H.G.; Akkermans, L.M.

    2007-01-01

    Infection of pancreatic necrosis by gut bacteria is a major cause of morbidity and mortality in patients with severe acute pancreatitis. Use of prophylactic antibiotics remains controversial. The aim of this experiment was assess if modification of intestinal flora with specifically designed

  14. [Acute kidney injury

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; Heurn, L.W. van; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  15. Leukocytosis in acute stroke

    DEFF Research Database (Denmark)

    Kammersgaard, L P; Jørgensen, H S; Nakayama, H

    1999-01-01

    Leukocytosis is a common finding in the acute phase of stroke. A detrimental effect of leukocytosis on stroke outcome has been suggested, and trials aiming at reducing the leukocyte response in acute stroke are currently being conducted. However, the influence of leukocytosis on stroke outcome has...

  16. [Acute kidney injury

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; Heurn, L.W. van; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  17. Activation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    2010-01-01

    Acute liver failure and acute pancreatitis are accompanied by substantial changes in the hemostatic system. In acute liver failure, defective synthesis of coagulation factors and intravascular activation of coagulation results in thrombocytopenia and reduced levels of proteins involved in coagulatio

  18. Activation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    Acute liver failure and acute pancreatitis are accompanied by substantial changes in the hemostatic system. In acute liver failure, defective synthesis of coagulation factors and intravascular activation of coagulation results in thrombocytopenia and reduced levels of proteins involved in

  19. High N-terminal pro-B-type natriuretic peptide levels are associated with reduced heart rate variability in acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Luc Lorgis

    Full Text Available AIM: We investigated the relationships between the autonomic nervous system, as assessed by heart rate variability (HRV and levels of N-terminal Pro-B-type Natriuretic Peptide (Nt-proBNP in patients with acute myocardial infarction (MI. METHODS AND RESULTS: The mean of standard deviation of RR intervals (SDNN, the percentage of RR intervals with >50 ms variation (pNN50, square root of mean squared differences of successive RR intervals (rMSSD, and frequency domain parameters (total power (TP, high frequency and low frequency power ratio (LF/HF were assessed by 24 h Holter ECG monitoring. 1018 consecutive patients admitted <24 h for an acute MI were included. Plasma Nt-proBNP (Elecsys, Roche was measured from blood samples taken on admission. The median (IQR Nt-proBNP level was 681(159-2432 pmol/L. Patients with the highest quartile of Nt-proBNP were older, with higher rate of risk factors and lower ejection fraction. The highest Nt-proBNP quartile group had the lowest SDNN, LF/HF and total power but similar pNN50 and rMSSD levels. Nt-proBNP levels correlated negatively with SDNN (r = -0.19, p<0.001, LF/HF (r = -0.37, p<0.001, and LF (r = -0.29, p<0.001 but not HF (r = -0.043, p = 0.172. Multiple regression analysis showed that plasma propeptide levels remained predictive of LF/HF (B(SE = -0.065(0.015, p<0.001, even after adjustment for confounders. CONCLUSIONS: In conclusion, our population-based study highlights the importance of Nt-proBNP levels to predict decreased HRV after acute MI.

  20. Role of minimal residual disease and chimerism after reduced-intensity and myeloablative allo-transplantation in acute myeloid leukemia and high-risk myelodysplastic syndrome.

    Science.gov (United States)

    Bernal, Teresa; Diez-Campelo, María; Godoy, Vicky; Rojas, Silvia; Colado, Enrique; Alcoceba, Miguel; González, Marcos; Vidriales, Belén; Sánchez-Guijo, Fermín M; López-Corral, Lucía; Luño, Elisa; del Cañizo, Consuelo

    2014-05-01

    We evaluated the impact of detection of minimal residual disease by flow cytometry (FCMRD) and CD3 chimerism in relapse in a cohort of 87 patients with acute myeloid leukemia or myelodysplastic syndrome undergoing stem cell transplantation. Patients with a positive FCMRD at day +100 after transplantation showed higher relapse rates and worse overall survival. In multivariate analysis, a positive FCMRD after transplantation was a significant predictor of relapse. Mixed chimerism showed a trend to statistical signification. We conclude that FCMRD at day 100 after SCT is the best predictor of relapse after SCT in patients with aggressive myeloid malignancies.

  1. Case of Acute Graft Failure during Suspected Humoral Rejection with Preserved Ejection Fraction, but Severely Reduced Longitudinal Deformation Detected by 2D-Speckle Tracking

    Directory of Open Access Journals (Sweden)

    Tor Skibsted Clemmensen

    2014-01-01

    Full Text Available This case displays limited utility of left ventricular ejection fraction to detect acute graft failure due to microvascular vasculopathy and suspected humoral rejection. Despite severe and progressive graft failure, clinically and by right heart catheterizations, left ventricular ejection fraction remained unchanged, indicating need of more reliable noninvasive methods for graft function surveillance. Global longitudinal strain relates to clinical heart failure, filling pressure, and cardiac index during suspected humoral rejection and microvascular dysfunction in this HTX patient. We suggest routine monitoring of graft function by global longitudinal strain as supplement to routine left ventricular ejection fraction and diastolic Doppler measurements.

  2. Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Labopin, Myriam; Shimoni, Avichai;

    2012-01-01

    to compare the outcome of mobilized peripheral blood stem cells (PBSC) (n = 1430) vs. bone marrow (BM) (n = 107) for acute myelogenous leukemia (AML) patients with complete remission that underwent RIC-alloSCT from compatible sibling donors. The leukemia features, the disease status, and the time from......, relapse, and NRM when comparing PBSC to BM grafts from sibling donors following RIC conditioning. This is the first study comparing PBSC to BM grafts in the RIC setting, analyzing a homogeneous population of patients with AML in remission. Whether PBSC should be preferred for advanced phases...

  3. Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

    Science.gov (United States)

    Schneider, Sebastian; Strumpf, Annette; Schetelig, Johannes; Wunderlich, Gerd; Ehninger, Gerhard; Kotzerke, Jörg; Bornhäuser, Martin

    2015-10-01

    The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome.

  4. Supplementation of folic acid and vitamin B₁₂ reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke.

    Science.gov (United States)

    Xia, Xiao-Shuang; Li, Xin; Wang, Lin; Wang, Ji-Zuo; Ma, Jin-Ping; Wu, Cun-Jin

    2014-09-01

    Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3 days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500 μg twice daily) for 12 weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12 weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (psupplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12 weeks (psupplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke.

  5. Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

    Science.gov (United States)

    Guberina, Hana; Rebmann, Vera; Wagner, Bettina; da Silva Nardi, Fabiola; Dziallas, Phillip; Dolff, Sebastian; Bienholz, Anja; Wohlschlaeger, Jeremias; Bankfalvi, Agnes; Heinemann, Falko M; Witzke, Oliver; Zoet, Yvonne M; Claas, Frans H J; Horn, Peter A; Kribben, Andreas; Doxiadis, Ilias I N

    2017-03-01

    Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (pE-mediated immune activation. Moreover, HLA-E expression correlated with deterioration in renal allograft function (pE along with high numbers of mismatched HLA-class I leader peptides might represent additional targets for immune-activating responses.

  6. Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Sakellari, Ioanna; Mallouri, Despina; Gavriilaki, Eleni; Batsis, Ioannis; Kaliou, Maria; Constantinou, Varnavas; Papalexandri, Apostolia; Lalayanni, Chrysavgi; Vadikolia, Chrysanthi; Athanasiadou, Anastasia; Yannaki, Evangelia; Sotiropoulos, Damianos; Smias, Christos; Anagnostopoulos, Achilles

    2017-03-01

    Treosulfan has been incorporated in conditioning regimens for sustained remission without substantial toxicity and treatment-related mortality (TRM). We aimed to analyze the safety and efficacy of a fludarabine 150 mg/m(2) and treosulfan 42 g/m(2) (FluTreo) conditioning regimen in medically infirm patients. Outcomes were compared with those of a similar historical group treated with fludarabine 150 mg/m(2) to 180 mg/m(2), busulfan 6.4 mg/kg, and antithymocyte globulin (ATG) 5 mg/kg to 7.5 mg/kg (FluBuATG). Thirty-one consecutive patients with acute myeloid leukemia (AML; n = 21), myelodysplastic syndrome (MDS; n = 6), or treatment-related AML (n = 4) received FluTreo conditioning. The historical group consisted of 26 consecutive patients treated with FluBuATG. In the FluTreo group, engraftment was prompt in all patients and 74% achieved >99% donor chimerism by day +30. No grades III or IV organ toxicities were noted. One-year cumulative incidences (CI) of acute and chronic graft-versus-host disease (GVHD) were 19.4% and 58.4%. The groups were similar for age, disease risk, lines of treatment, hematopoietic cell transplantation-specific comorbidity index, and acute or chronic GVHD incidence, except that there were more matched unrelated donor recipients in the FluTreo group (P < .001). With 20 (range, 2 to 36) months follow-up for FluTreo and 14 (range, 2 to 136) for FluBuATG, the 1-year cumulative overall survival (OS) probability was 76% versus 57%, respectively (P = .026); 1-year disease-free survival (DFS) was 79% versus 38% (P < .001). In multivariate analysis, the only significantly favorable factor for OS and DFS was FluTreo (P = .010 and P = .012). The CI of relapse mortality was markedly decreased in FluTreo versus FluBuATG (7.4% versus 42.3%, P < .001). In conclusion, the treosulfan-based regimen resulted in favorable OS and DFS with acceptable toxicity and low relapse rates compared with busulfan-based conditioning.

  7. Acute mountain sickness

    Science.gov (United States)

    High altitude cerebral edema; Altitude anoxia; Altitude sickness; Mountain sickness; High altitude pulmonary edema ... Acute mountain sickness is caused by reduced air pressure and lower oxygen levels at high altitudes. The faster you ...

  8. Acute heart failure syndrome

    African Journals Online (AJOL)

    tandfonline.com/ ... When heart failure develops gradually, there is time for the compensatory ... of this can be seen in acute brain injury, some forms of takotsubo syndrome or .... reduce blood pressure in cases presenting with elevated blood pressure.

  9. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  10. Cystitis - acute

    Science.gov (United States)

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  11. Reduced transcapillary escape of albumin during acute blood pressure-lowering in type 1 (insulin-dependent) diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Kastrup, J; Smidt, U M

    1985-01-01

    The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance...... induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p less than 0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p less than 0.01), albuminuria diminished from 1434 to 815 micrograms/min (p less than 0.......01), and plasma volume raised slightly from 2916 to 2995 ml (p less than 0.05). Our findings demonstrate that the enhanced albumin passage through the wall of the microvasculature characteristically found in long-term Type 1 diabetic patients with clinical microangiopathy is pressure-dependent to a large extent...

  12. Measures to reduce infarct size in treatment of acute myocardial infarction%急性心肌梗死治疗中缩小梗死范围的措施

    Institute of Scientific and Technical Information of China (English)

    蒋运发

    2015-01-01

    Objective:To analyze and summarize the measures to reduce infarct size in treatment of acute myocardial infarction. Methods:120 patients with acute myocardial infarction were selected from 2011 to 2014.They were randomly divided into the control group and the observation group with 60 cases in each group.The control group was treated with routine method,and the observation group was treated by metoprolol on the basis of the control group,before discharge,QRS scoring system was used to calculate the last 1 ECG score.We compared infarct size and hospital mortality of two groups of patients,and summarized the measures to reduce the infarct size in acute myocardial infarction treatment.Results:After 4 weeks of treatment,in the observation group,the infarct size was significantly lower than that of control group.In the control group,the mortality rate was 23.33%,the observation group was 3.33%,the mortality rate of the observation group was significantly lower than the control group.Conclusion:On the basis of conventional therapy,plus beta blockers for the treatment of acute myocardial infarction can reduce infarct area, reduce the mortality rate;after acute myocardial infarction.We should strengthen the nursing,increase myocardial oxygen supply and myocardial energy supply,reduce myocardial oxygen consumption,protect ischemic myocardium,and we also can use external counterpulsation surgery or thrombolytic therapy for the treatment,in order to reduce infarct range.%目的:分析并总结急性心肌梗死治疗中缩小梗死范围的措施。方法:2011-2014年收治急性心肌梗死患者120例,随机分为对照组和观察组,各60例。对照组采用常规方法治疗,观察组在此基础上加用美托洛尔治疗,于出院前使用QRS计分系统计算最后1次心电图记分,比较两组患者的梗死范围及住院期间病死率,并总结急性心肌梗死治疗中缩小梗死范围的措施。结果:经4周治疗后,观察组的梗

  13. Garlic compounds selectively kill childhood pre-B acute lymphoblastic leukemia cells in vitro without reducing T-cell function: Potential therapeutic use in the treatment of ALL

    Directory of Open Access Journals (Sweden)

    Greg Hodge

    2008-03-01

    Full Text Available Greg Hodge1, Stephen Davis2, Michael Rice1, Heather Tapp1, Ben Saxon1, Tamas Revesz11Haematology/Oncology Department, Women’s and Children’s Hospital, North Adelaide, Australia; 2Department of Mycology, Women’s and Children’s Hospital, North Adelaide, AustraliaAbstract: Drugs used for remission induction therapy for childhood precursor-B acute lymphoblastic leukemia (ALL are nonselective for malignant cells. Several garlic compounds have been shown to induce apoptosis of cancer cells and to alter lymphocyte function. To investigate the effect of garlic on the apoptosis of ALL cells and lymphocyte immune function, cells from newly diagnosed childhood ALL patients were cultured with several commonly used chemotherapeutic agents and several garlic compounds. Apoptosis, lymphocyte proliferation and T-cell cytokine production were determined using multiparameter flow cytometry. At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferonγ, interleukin-2 or tumor necrosis factor-α intracellular cytokine production. In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production. In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.Keywords: childhood precursor-B acute lymphoblastic leukemia, garlic, apoptosis, immune function, intracellular cytokines

  14. REFINE (REducing Falls in In-patieNt Elderly) using bed and bedside chair pressure sensors linked to radio-pagers in acute hospital care: a randomised controlled trial.

    Science.gov (United States)

    Sahota, Opinder; Drummond, Avril; Kendrick, Denise; Grainge, Matthew J; Vass, Catherine; Sach, Tracey; Gladman, John; Avis, Mark

    2014-03-01

    falls in hospitals are a major problem and contribute to substantial healthcare burden. Advances in sensor technology afford innovative approaches to reducing falls in acute hospital care. However, whether these are clinically effective and cost effective in the UK setting has not been evaluated. pragmatic, parallel-arm, individual randomised controlled trial of bed and bedside chair pressure sensors using radio-pagers (intervention group) compared with standard care (control group) in elderly patients admitted to acute, general medical wards, in a large UK teaching hospital. Primary outcome measure number of in-patient bedside falls per 1,000 bed days. 1,839 participants were randomised (918 to the intervention group and 921 to the control group). There were 85 bedside falls (65 fallers) in the intervention group, falls rate 8.71 per 1,000 bed days compared with 83 bedside falls (64 fallers) in the control group, falls rate 9.84 per 1,000 bed days (adjusted incidence rate ratio, 0.90; 95% confidence interval [CI], 0.66-1.22; P = 0.51). There was no significant difference between the two groups with respect to time to first bedside fall (adjusted hazard ratio (HR), 0.95; 95% CI: 0.67-1.34; P= 0.12). The mean cost per patient in the intervention group was £7199 compared with £6400 in the control group, mean difference in QALYs per patient, 0.0001 (95% CI: -0.0006-0.0004, P= 0.67). bed and bedside chair pressure sensors as a single intervention strategy do not reduce in-patient bedside falls, time to first bedside fall and are not cost-effective in elderly patients in acute, general medical wards in the UK. isrctn.org identifier: ISRCTN44972300.

  15. Using a Cloud Computing System to Reduce Door-to-Balloon Time in Acute ST-Elevation Myocardial Infarction Patients Transferred for Percutaneous Coronary Intervention.

    Science.gov (United States)

    Ho, Chi-Kung; Chen, Fu-Cheng; Chen, Yung-Lung; Wang, Hui-Ting; Lee, Chien-Ho; Chung, Wen-Jung; Lin, Cheng-Jui; Hsueh, Shu-Kai; Hung, Shin-Chiang; Wu, Kuan-Han; Liu, Chu-Feng; Kung, Chia-Te; Cheng, Cheng-I

    2017-01-01

    This study evaluated the impact on clinical outcomes using a cloud computing system to reduce percutaneous coronary intervention hospital door-to-balloon (DTB) time for ST segment elevation myocardial infarction (STEMI). A total of 369 patients before and after implementation of the transfer protocol were enrolled. Of these patients, 262 were transferred through protocol while the other 107 patients were transferred through the traditional referral process. There were no significant differences in DTB time, pain to door of STEMI receiving center arrival time, and pain to balloon time between the two groups. Pain to electrocardiography time in patients with Killip I/II and catheterization laboratory to balloon time in patients with Killip III/IV were significantly reduced in transferred through protocol group compared to in traditional referral process group (both p cloud computing system in our present protocol did not reduce DTB time.

  16. Acute myocardial infarction does not affect functional characteristics of adipose-derived stem cells in rats, but reduces the number of stem cells in adipose tissue.

    Science.gov (United States)

    Naaijkens, B A; Krijnen, P A J; Meinster, E; ter Horst, E N; Vo, K; Musters, R J P; Kamp, O; Niessen, H W M; Juffermans, L J M; van Dijk, A

    2015-12-01

    In most pre-clinical animal studies investigating stem cell therapy in acute myocardial infarction (AMI), the administered stem cells are isolated from healthy donors. In clinical practice, however, patients who suffer from AMI will receive autologous cells, for example using adipose-derived stem cells (ASC). During AMI, inflammation is induced and we hypothesized that this might affect characteristics of ASC. To investigate this, ASC were isolated from rat adipose tissue 1 day (1D group, n = 5) or 7 days (7D group, n = 6) post-AMI, and were compared with ASC from healthy control rats (Control group, n = 6) and sham-operated rats (Sham 1D group, n = 5). We found that significantly fewer ASC were present 1 day post-AMI in the stromal vascular fraction (SVF), determined by a colony-forming-unit assay (p cells in SVF of the 1D group. When cultured, no differences were found in proliferation rate and cell size between the groups in the first three passages. Also, no difference in the differentiation capacity of ASC was found. In conclusion, it was shown that significantly fewer stem cells were present in the SVF 1 day post-AMI; however, the stem cells that were present showed no functional differences.

  17. Large-scale field application of RNAi technology reducing Israeli acute paralysis virus disease in honey bees (Apis mellifera, Hymenoptera: Apidae.

    Directory of Open Access Journals (Sweden)

    Wayne Hunter

    Full Text Available The importance of honey bees to the world economy far surpasses their contribution in terms of honey production; they are responsible for up to 30% of the world's food production through pollination of crops. Since fall 2006, honey bees in the U.S. have faced a serious population decline, due in part to a phenomenon called Colony Collapse Disorder (CCD, which is a disease syndrome that is likely caused by several factors. Data from an initial study in which investigators compared pathogens in honey bees affected by CCD suggested a putative role for Israeli Acute Paralysis Virus, IAPV. This is a single stranded RNA virus with no DNA stage placed taxonomically within the family Dicistroviridae. Although subsequent studies have failed to find IAPV in all CCD diagnosed colonies, IAPV has been shown to cause honey bee mortality. RNA interference technology (RNAi has been used successfully to silence endogenous insect (including honey bee genes both by injection and feeding. Moreover, RNAi was shown to prevent bees from succumbing to infection from IAPV under laboratory conditions. In the current study IAPV specific homologous dsRNA was used in the field, under natural beekeeping conditions in order to prevent mortality and improve the overall health of bees infected with IAPV. This controlled study included a total of 160 honey bee hives in two discrete climates, seasons and geographical locations (Florida and Pennsylvania. To our knowledge, this is the first successful large-scale real world use of RNAi for disease control.

  18. Large-scale field application of RNAi technology reducing Israeli acute paralysis virus disease in honey bees (Apis mellifera, Hymenoptera: Apidae).

    Science.gov (United States)

    Hunter, Wayne; Ellis, James; Vanengelsdorp, Dennis; Hayes, Jerry; Westervelt, Dave; Glick, Eitan; Williams, Michael; Sela, Ilan; Maori, Eyal; Pettis, Jeffery; Cox-Foster, Diana; Paldi, Nitzan

    2010-12-23

    The importance of honey bees to the world economy far surpasses their contribution in terms of honey production; they are responsible for up to 30% of the world's food production through pollination of crops. Since fall 2006, honey bees in the U.S. have faced a serious population decline, due in part to a phenomenon called Colony Collapse Disorder (CCD), which is a disease syndrome that is likely caused by several factors. Data from an initial study in which investigators compared pathogens in honey bees affected by CCD suggested a putative role for Israeli Acute Paralysis Virus, IAPV. This is a single stranded RNA virus with no DNA stage placed taxonomically within the family Dicistroviridae. Although subsequent studies have failed to find IAPV in all CCD diagnosed colonies, IAPV has been shown to cause honey bee mortality. RNA interference technology (RNAi) has been used successfully to silence endogenous insect (including honey bee) genes both by injection and feeding. Moreover, RNAi was shown to prevent bees from succumbing to infection from IAPV under laboratory conditions. In the current study IAPV specific homologous dsRNA was used in the field, under natural beekeeping conditions in order to prevent mortality and improve the overall health of bees infected with IAPV. This controlled study included a total of 160 honey bee hives in two discrete climates, seasons and geographical locations (Florida and Pennsylvania). To our knowledge, this is the first successful large-scale real world use of RNAi for disease control.

  19. Large-Scale Field Application of RNAi Technology Reducing Israeli Acute Paralysis Virus Disease in Honey Bees (Apis mellifera, Hymenoptera: Apidae)

    Science.gov (United States)

    Hunter, Wayne; Ellis, James; vanEngelsdorp, Dennis; Hayes, Jerry; Westervelt, Dave; Glick, Eitan; Williams, Michael; Sela, Ilan; Maori, Eyal; Pettis, Jeffery; Cox-Foster, Diana; Paldi, Nitzan

    2010-01-01

    The importance of honey bees to the world economy far surpasses their contribution in terms of honey production; they are responsible for up to 30% of the world's food production through pollination of crops. Since fall 2006, honey bees in the U.S. have faced a serious population decline, due in part to a phenomenon called Colony Collapse Disorder (CCD), which is a disease syndrome that is likely caused by several factors. Data from an initial study in which investigators compared pathogens in honey bees affected by CCD suggested a putative role for Israeli Acute Paralysis Virus, IAPV. This is a single stranded RNA virus with no DNA stage placed taxonomically within the family Dicistroviridae. Although subsequent studies have failed to find IAPV in all CCD diagnosed colonies, IAPV has been shown to cause honey bee mortality. RNA interference technology (RNAi) has been used successfully to silence endogenous insect (including honey bee) genes both by injection and feeding. Moreover, RNAi was shown to prevent bees from succumbing to infection from IAPV under laboratory conditions. In the current study IAPV specific homologous dsRNA was used in the field, under natural beekeeping conditions in order to prevent mortality and improve the overall health of bees infected with IAPV. This controlled study included a total of 160 honey bee hives in two discrete climates, seasons and geographical locations (Florida and Pennsylvania). To our knowledge, this is the first successful large-scale real world use of RNAi for disease control. PMID:21203478

  20. Deletion of Galgt2 (B4Galnt2) Reduces Muscle Growth in Response to Acute Injury and Increases Muscle Inflammation and Pathology in Dystrophin-Deficient Mice

    Science.gov (United States)

    Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A.; Janssen, Paulus M.L.; Martin, Paul T.

    2016-01-01

    Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2−/−mdx). Galgt2−/− mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice. PMID:26435413

  1. Acute Bronchitis

    Science.gov (United States)

    ... Smoking also slows down the healing process. Acute bronchitis treatment Most cases of acute bronchitis can be treated at home.Drink fluids, but ... bronchial tree. Your doctor will decide if this treatment is right for you. Living with acute bronchitis Most cases of acute bronchitis go away on ...

  2. The impact of center experience on results of reduced intensity : allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

    NARCIS (Netherlands)

    Giebel, S.; Labopin, M.; Mohty, M.; Mufti, G. J.; Niederwieser, D.; Cornelissen, J. J.; Janssen, J. J. W. M.; Milpied, N.; Vindelov, L.; Petersen, E.; Arnold, R.; Bacigalupo, A.; Blaise, D.; Craddock, C.; Nagler, A.; Frassoni, F.; Sadus-Wojciechowska, M.; Rocha, V.

    2013-01-01

    Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related or

  3. The impact of center experience on results of reduced intensity:allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

    DEFF Research Database (Denmark)

    Giebel, S; Labopin, M; Mohty, M

    2013-01-01

    Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related...

  4. Can a Single Session of a Community-Based Group Exercise Program Combining Step Aerobics and Bodyweight Resistance Exercise Acutely Reduce Blood Pressure?

    Directory of Open Access Journals (Sweden)

    Mendes Romeu

    2014-12-01

    Full Text Available This study aimed to analyze the acute effects of a single session of a community-based group exercise program combining step aerobics and bodyweight resistance exercise on blood pressure in healthy young adult women. Twentythree healthy young adult women (aged 31.57 ± 7.87 years participated in two experimental sessions (exercise and control in a crossover study design. Blood pressure was monitored before, immediately after and at 10, 20 and 30 min of recovery. The exercise session consisted of four phases: 1 a warm-up (5 min of dance aerobics; 2 aerobic exercise training (30 min of step aerobics; 3 resistance exercise training (six sets of 12 repetitions of three bodyweight exercises in a circuit mode, 10 min; and 4 a cool-down (5 min of breathing and flexibility exercises; totaling 50 min of duration. Systolic blood pressure after exercise was significantly lower compared to control at the 10th min (-10.83 ± 2.13 vs. -2.6 ± 2.13 mmHg; p = 0.009, 20th min (-11.26 ± 2.13 vs. -3.04 ± 2.13 mmHg; p = 0.009 and 30th min of recovery (-10.87 ± 2.39 vs. -0.48 ± 2.39 mmHg; p = 0.004. A single session of a community-based group exercise program combining step aerobics and bodyweight resistance exercise was effective in inducing significant post-exercise hypotension in healthy young adult women. This type of low-cost exercise interventions may have an important role in the prevention of cardiovascular diseases and in community health promotion.

  5. Reducing TNF receptor 2+ regulatory T cells via the combined action of azacitidine and the HDAC inhibitor, panobinostat for clinical benefit in acute myeloid leukemia patients.

    Science.gov (United States)

    Govindaraj, Chindu; Tan, Peter; Walker, Patricia; Wei, Andrew; Spencer, Andrew; Plebanski, Magdalena

    2014-02-01

    Acute myeloid leukemia (AML) provides an environment that enables immune suppression, resulting in functionally defective effector T cells; regulatory T cells (Treg) are significant contributors to the impaired antitumor immune response. As TNF is present at high levels in AML and TNF receptor-2 (TNFR2)-expressing Tregs identify highly functional Tregs, we examine the hypothesis that TNFR2(+) Tregs are a relevant Treg subset in this cancer. We also determine the effect of the novel combinatorial therapy of the demethylating agent, azacitidine with the histone deacetylase inhibitor, panobinostat on Tregs, particularly TNFR2(+) Tregs. Thirty healthy donors and 14 patients with AML were enrolled in this study. Patients were treated with azacitidine and panobinostat for 28-day cycles. The frequency and functional relevance of TNFR2(+) Tregs were analyzed subsequently. We report that TNFR2(+) Tregs are increased in AML and have a high migration potential toward the bone marrow. Furthermore, we demonstrate that the level of TNFR2(+) Tregs in the peripheral blood and the bone marrow of patients are decreased in vivo after exposure to panobinostat and azacitidine. Reductions in TNFR2(+) Tregs were associated with increases in Interferon (IFN)-γ and interleukin (IL)-2 production by effector T cells within the bone marrow and beneficial clinical responses. In vitro mechanistic studies indicated panobinostat as the primary driver for the reduction of Tregs. Our study provides for the first time, in vivo validation of the ability of panobinostat in combination with azacitidine to suppress prevalent TNFR2(+) Tregs, resulting in clinical benefits within patients with AML. ©2013 AACR.

  6. Field triage reduces treatment delay and improves long-term clinical outcome in patients with acute ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Pedersen, Sune H; Galatius, Soren; Hansen, Peter R

    2009-01-01

    OBJECTIVES: We evaluated the independent impact of field triage on treatment delay and long-term clinical outcome in a large contemporary, consecutive population of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND......: Reduction of treatment delay is crucial for patients with STEMI. METHODS: From January 2005 to July 2008, 1,437 STEMI patients were treated with pPCI at a single high-volume invasive center. We present the 1-year outcome in this observational registry study. RESULTS: A total of 616 patients were admitted...... triage had a reduced risk of reaching the combined end point of all-cause mortality or nonfatal myocardial infarction (hazard ratio: 0.67; 95% confidence interval: 0.46 to 0.97; p=0.035). CONCLUSIONS: This study shows that field triage of STEMI patients to pPCI significantly reduces treatment delay...

  7. Interleukin-17 (IL-17 Expression Is Reduced during Acute Myocardial Infarction: Role on Chemokine Receptor Expression in Monocytes and Their in Vitro Chemotaxis towards Chemokines

    Directory of Open Access Journals (Sweden)

    Guro Valen

    2012-11-01

    Full Text Available The roles of immune cells and their soluble products during myocardial infarction (MI are not completely understood. Here, we observed that the percentages of IL-17, but not IL-22, producing cells are reduced in mice splenocytes after developing MI. To correlate this finding with the functional activity of IL-17, we sought to determine its effect on monocytes. In particular, we presumed that this cytokine might affect the chemotaxis of monocytes important for cardiac inflammation and remodeling. We observed that IL-17 tends to reduce the expression of two major chemokine receptors involved in monocyte chemotaxis, namely CCR2 and CXCR4. Further analysis showed that monocytes pretreated with IL-17 have reduced in vitro chemotaxis towards the ligand for CCR2, i.e., MCP-1/CCL2, and the ligand for CXCR4, i.e., SDF-1α/CXCL12. Our results support the possibility that IL-17 may be beneficial in MI, and this could be due to its ability to inhibit the migration of monocytes.

  8. A potent steroid cream is superior to emollients in reducing acute radiation dermatitis in breast cancer patients treated with adjuvant radiotherapy. A randomised study of betamethasone versus two moisturizing creams.

    Science.gov (United States)

    Ulff, Eva; Maroti, Marianne; Serup, Jörgen; Falkmer, Ursula

    2013-08-01

    The aim was to investigate whether treatment with potent local steroids can reduce signs and symptoms of acute radiation dermatitis in breast cancer patients undergoing adjuvant radiotherapy (RT) compared to emollient creams. The study was randomised and double-blinded. Patients with breast cancer who had undergone mastectomy or breast-conserving surgery were included when they started adjuvant 3-D planned RT. In all, 104 patients were randomised 2:1:1 to three treatment groups, i.e. betamethasone+Essex® cream, Essex® cream or Canoderm® cream. The patients themselves treated the irradiated area during the radiation period (5 weeks) and two weeks after cessation of RT. Signs of RT dermatitis were measured qualitatively with RTOG clinical scoring and quantitatively by colorimeter. In addition, the patients' symptoms were recorded as well as the Fitzpatrick skin type. There was a statistically significant difference (p=0.05) in skin reactions when assessed with RTOG in favour of the group treated with the potent steroid. Patient-related symptoms did not differ between the treatment groups. The effect of the steroid was prominent in three subgroups, i.e. (i) patients treated with ablation of the breast, (ii) patients receiving RT to the armpit and the supraclavicular fossa, and (iii) patients with Fitzpatrick skin type 1. Treatment with betamethasone cream is more efficient than moisturizers for the control of acute RT dermatitis in patients treated with adjuvant RT for breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Nonpharmacological Interventions Targeted at Delirium Risk Factors, Delivered by Trained Volunteers (Medical and Psychology Students), Reduced Need for Antipsychotic Medications and the Length of Hospital Stay in Aged Patients Admitted to an Acute Internal Medicine Ward: Pilot Study

    Science.gov (United States)

    Piotrowicz, Karolina; Rewiuk, Krzysztof; Halicka, Monika; Kalwak, Weronika; Rybak, Paulina

    2017-01-01

    Purpose. Effectiveness of nonpharmacological multicomponent prevention delivered by trained volunteers (medical and psychology students), targeted at delirium risk factors in geriatric inpatients, was assessed at an internal medicine ward in Poland. Patients and Methods. Participants were recruited to intervention and control groups at the internal medicine ward (inclusion criteria: age ≥ 75, acute medical condition, basic orientation, and logical contact on admission; exclusion criteria: life expectancy delirium episodes, and antipsychotic prescriptions were assessed retrospectively from medical documentation. Results. 130 patients (38.4% males) participated in the study, with 65 in the intervention group. Antipsychotic medications were initiated less frequently in the intervention group compared to the control group. There was a trend towards a shorter hospitalization time and a not statistically significant decrease in deaths in the intervention group. Conclusion. Nonpharmacological multicomponent intervention targeted at delirium risk factors effectively reduced length of hospitalization and need for initiating antipsychotic treatment in elderly patients at the internal medicine ward. PMID:28164113

  10. Acute Appendicitis

    DEFF Research Database (Denmark)

    Tind, Sofie; Qvist, Niels

    2017-01-01

    BACKGROUND: The classification of acute appendicitis (AA) into various grades is not consistent, partly because it is not clear whether the perioperative or the histological findings should be the foundation of the classification. When comparing results from the literature on the frequency...... patients were included. In 116 (89 %) of these cases, appendicitis was confirmed histological. There was low concordance between the perioperative and histological diagnoses, varying from 16 to 76 % depending on grade of AA. Only 44 % of the patients receiving antibiotics postoperatively had a positive...... peritoneal fluid cultivation. CONCLUSION: There was a low concordance in clinical and histopathological diagnoses of the different grades of appendicitis. Perioperative cultivation of the peritoneal fluid as a standard should be further examined. The potential could be a reduced postoperative antibiotic use...

  11. Hepatocyte-specific ablation of spermine/spermidine-N1-acetyltransferase gene reduces the severity of CCl4-induced acute liver injury

    Science.gov (United States)

    Barone, Sharon L.; Xu, Jie; Steinbergs, Nora; Schuster, Rebecca; Lentsch, Alex B.; Amlal, Hassane; Wang, Jiang; Casero, Robert A.; Soleimani, Manoocher

    2012-01-01

    Activation of spermine/spermidine-N1-acetyltransferase (SSAT) leads to DNA damage and growth arrest in mammalian cells, and its ablation reduces the severity of ischemic and endotoxic injuries. Here we have examined the role of SSAT in the pathogenesis of toxic liver injury caused by carbon tetrachloride (CCl4). The expression and activity of SSAT increase in the liver subsequent to CCl4 administration. Furthermore, the early liver injury after CCl4 treatment was significantly attenuated in hepatocyte-specific SSAT knockout mice (Hep-SSAT-Cko) compared with wild-type (WT) mice as determined by the reduced serum alanine aminotransferase levels, decreased hepatic lipid peroxidation, and less severe liver damage. Cytochrome P450 2e1 levels remained comparable in both genotypes, suggesting that SSAT deficiency does not affect the metabolism of CCl4. Hepatocyte-specific deficiency of SSAT also modulated the induction of cytokines involved in inflammation and repair as well as leukocyte infiltration. In addition, Noxa and activated caspase 3 levels were elevated in the livers of WT compared with Hep-SSAT-Cko mice. Interestingly, the onset of cell proliferation was significantly more robust in the WT compared with Hep-SSAT Cko mice. The inhibition of polyamine oxidases protected the animals against CCl4-induced liver injury. Our studies suggest that while the abrogation of polyamine back conversion or inhibition of polyamine oxidation attenuate the early injury, they may delay the onset of hepatic regeneration. PMID:22723264

  12. Upregulation of CD19⁺CD24(hi)CD38(hi) regulatory B cells is associated with a reduced risk of acute lung injury in elderly pneumonia patients.

    Science.gov (United States)

    Song, Haihan; Xi, Jianjun; Li, Guang-Gang; Xu, Shumin; Wang, Chunmei; Cheng, Tingting; Li, Hongqiang; Zhang, Ying; Liu, Xiandong; Bai, Jianwen

    2016-04-01

    Acute lung injury (ALI) is a common complication in elderly pneumonia patients who have a rapid progression, and is accompanied by a high mortality rate. Because the treatment options of ALI are limited to supportive care, identifying pneumonia patients who are at higher risk of ALI development is the emphasis of many studies. Here, we approach this problem from an immunological perspective by examining CD19(+)CD24(hi)CD38(hi) B cells, an important participant in acute and chronic inflammation. We find that elderly pneumonia patients have elevated CD19(+)CD24(hi)CD38(hi) B cell frequency compared to healthy individuals. This B cell population may express a higher level of IL-10, which has been was shown to suppress CD4(+) T cell-mediated proinflammatory cytokine interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) production, through an IL-10-dependent mechanism. We also observe that the frequency of CD19(+)CD24(hi)CD38(hi) B cell is positively correlated with the frequency of CD4(+)CD25(+)Foxp3(+)Tregs in peripheral blood. Moreover, consistent with CD19(+)CD24(hi)CD38(hi) B cell's anti-inflammatory role, we find that pneumonia patients who later developed ALI have reduced level of CD19(+)CD24(hi)CD38(hi) B cells. Together, our results demonstrated that CD19(+)CD24(hi)CD38(hi) B cells in pneumonia patients possess regulatory function in vivo, and are associated with a reduced ALI risk.

  13. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model

    Science.gov (United States)

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-ichiro; Egashira, Kensuke

    2016-01-01

    Background There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Methods and Results Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. Conclusions NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic

  14. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation

    DEFF Research Database (Denmark)

    Torp-Pedersen, C; Køber, L

    1999-01-01

    be in terms of an increase in life expectancy, but this approach has not previously been possible because of limited data on long-term outcome. We aimed to calculate the effect of trandolapril on life expectancy with follow-up data from the Trandolapril Cardiac Evaluation (TRACE) Study. METHODS: The TRACE...... they had been followed up for a minimum of 6 years. We estimated life expectancy as median lifetime, which was the time for 50% of the patients to have died. Change in life expectancy is expressed as change in median lifetime. Analysis was by intention to treat. FINDINGS: The life expectancy of patients......-blind treatment; continued use of trandolapril was recommended at study closure. INTERPRETATION: In patients with severely reduced left-ventricular function, long-term treatment with an ACE inhibitor during the critical period after myocardial infarction is associated with a substantial increase in life...

  15. Reducing antibiotic prescriptions for acute cough by motivating GPs to change their attitudes to communication and empowering patients: a cluster-randomized intervention study.

    Science.gov (United States)

    Altiner, Attila; Brockmann, Silke; Sielk, Martin; Wilm, Stefan; Wegscheider, Karl; Abholz, Heinz-Harald

    2007-09-01

    Assessing the efficacy of an educational intervention that aimed to reduce unnecessary antibiotic prescriptions in primary care by motivating GPs to change their attitudes to communication and by empowering patients. One hundred and four GPs in North-Rhine/Westphalia-Lippe, Germany were cluster-randomized into intervention and control. GPs randomized to receive the intervention were visited by peers. The intervention strategy was focused on the communication within the encounter, not on sharing knowledge about antibiotic prescribing. Leaflets and posters were provided that aimed at patient empowerment, thus enabling patients to raise the topic of antibiotic prescriptions themselves. Eighty-six GPs (83%) remained in the study at 6 weeks and 61 GPs (59%) at 12 months. Antibiotic prescription rates within the control group were 54.7% at baseline and 36.4% within the intervention group at baseline. Generalized estimating equation models were applied. Baseline imbalances and confounding variables were controlled by adjustment. After the intervention, the ORs for the prescription of an antibiotic dropped to 0.58 [95% CI: (0.43;0.78), P < 0.001] after 6 weeks and were 0.72 [95% CI: (0.54;0.97), P = 0.028] after 12 months in the intervention group. In the control group, the ORs rose to 1.52 [95% CI: (1.19;1.95), P = 0.001] after 6 weeks and were 1.31 [95% CI: (1.01;1.71), P = 0.044] after 12 months; these ORs correspond to an approximately 60% relative reduction in antibiotic prescription rates at 6 weeks and a persistent 40% relative reduction at 12 months. An interventional strategy that focused on doctor-patient communication and patient empowerment is an effective concept to reduce antibiotic prescriptions in primary care.

  16. Acute Bronchitis

    Science.gov (United States)

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  17. Bronchitis - acute

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001087.htm Bronchitis - acute To use the sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflamed tissue in the main ...

  18. 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity

    Directory of Open Access Journals (Sweden)

    Kan Chen

    2014-01-01

    Full Text Available Objective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA- induced autoimmune hepatitis in mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 μg or 25 μg was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγ activity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 μM 1 h before the stimulation with ConA (30 μg/mL. The NF-κB and PPARγ activity were determined 30 min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARγ, blocked the degradation of IκBα, and inhibited the translocation of NF-κB into the nucleus. Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARγ and the reduction in NF-κB activity.

  19. Direct ambulance transport to catheterization laboratory reduces door-to-balloon time in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: the DIRECT-STEMI study

    Institute of Scientific and Technical Information of China (English)

    QIU Jian-ping; ZHANG Qi; LU Ji-de; WANG Hai-rong; LIN Jie; GE Zhi-ru; ZHANG Rui-yan; SHEN Wei-feng

    2011-01-01

    Background Primary percutaneous coronary intervention (PCI) has been clearly identified as the first therapeutic option for patients with acute ST-segment elevation myocardial infarction (STEMI). The importance of reducing door-to-balloon (D2B) time has gained increased recognition. This study aimed to assess the feasibility, safety and efficacy of the strategy of direct ambulance transportation of patients with acute STEMI to catheterization lab to receive primary PCI.Methods The study population included 141 consecutive patients with chest pain and ST-segment elevation who were admitted to the catheterization laboratory directly by the ambulance and underwent primary PCI (DIRECT group).Another 145 patients with STEMI randomly selected from the PCI database, were served as control group (conventional group); they were transported to catheterization laboratory from emergency room (ER). The primary endpoint of D2B time,and secondary endpoint of in-hospital and 30-day major adverse cardiac events (MACE, including death, non-fatal reinfarction, and target vessel revascularization) were compared.Results Baseline and procedural characteristics between the two groups were comparable, except more patients in the DIRECT group presented TIMI 0-1 flow in culprit vessel at initial angiogram (80.1% and 73.8%, P=0.04). Comparing to conventional group, the primary endpoint of D2B time was reduced ((54±18) minutes and (112±55) minutes, P <0.0001)and the percentage of patients with D2B <90 minutes was increased in the DIRECT group (96.9% and 27.0%, P<0.0001).The success rate of primary PCI with stent implantation with final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was significantly higher in the DIRECT group (93.8% and 85.2%, P=0.03). Although no significant difference was found at 30-day MACE free survival rate between the two groups (95.0% and 89.0%, P=0.06), a trend in improving survival status in the DIRECT group was demonstrated by Kaplan-Meier analysis

  20. Celastrol inhibits lung infiltration in differential syndrome animal models by reducing TNF-α and ICAM-1 levels while preserving differentiation in ATRA-induced acute promyelocytic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Li-min Xu

    Full Text Available All-trans retinoic acid (ATRA is a revolutionary agent for acute promyelocytic leukemia (APL treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1 expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF-α and IL-1β secretion, though treatment showed no effects on IL-8 and MCP-1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy.

  1. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  2. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  3. Acute cholecystitis

    OpenAIRE

    Halpin, Valerie

    2014-01-01

    Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae. About 95% of people with acute cholecystitis have gallstones.It is thought that blockage of the cystic duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.

  4. Does Acute Static Stretching Reduce Muscle Power?

    OpenAIRE

    Francis M. Kozub; Sameer A. Gohir; Alan Donnelly

    2012-01-01

    Context: Stretching is commonly used as a technique for injury prevention in the training and clinical setting. Recently, stretching in the warm-up has been shown to decrease several muscular performance variables, but the dose-response of this effect is unknown and moreover these stretching bouts are not representative of athletes during warm up procedures, as they are usually time consuming. Our findings may improve the understanding of the neuromuscular responses to stretching and help spo...

  5. Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome.

    Science.gov (United States)

    Buchholz, Stefanie; Dammann, Elke; Stadler, Michael; Krauter, Juergen; Beutel, Gernot; Trummer, Arne; Eder, Matthias; Ganser, Arnold

    2012-01-01

    The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

  6. Long-term brain structural magnetic resonance imaging and cognitive functioning in children treated for acute lymphoblastic leukemia with high-dose methotrexate chemotherapy alone or combined with CNS radiotherapy at reduced total dose to 12 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Zajac-Spychala, Olga; Pilarczyk, Jakub; Derwich, Katarzyna; Wachowiak, Jacek [Poznan University of Medical Sciences, Department of Pediatric Oncology, Hematology and Transplantology, Poznan (Poland); Pawlak, Mikolaj A. [Poznan University of Medical Sciences, Department of Neurology and Cerebrovascular Disorders, Poznan (Poland); Karmelita-Katulska, Katarzyna [Poznan University of Medical Sciences, Department of Neuroradiology, Poznan (Poland)

    2017-02-15

    The aim of this study was to assess the long-term side effects of central nervous system prophylaxis (high-dose chemotherapy alone vs chemotherapy and CNS radiotherapy) according to the ALL IC-BFM 2002. Thirty-tree children aged 6.7-19.9 years have been studied. The control group consisted of 12 children newly diagnosed with acute lymphoblastic leukemia. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between two therapeutic schemes and patients prior to treatment. Patients treated with chemotherapy and CNS radiotherapy had smaller hippocampi than two other subgroups and lower IQ score than patients treated with chemotherapy alone. Both treated groups, whether with chemotherapy only or in combination with CNS radiotherapy, had significantly lower volumes of caudate nucleus and performed significantly worse on measures of verbal fluency in comparison with patients prior to treatment. There were no differences in the mean volumes of total white matter, total gray matter, thalamus, putamen, and amygdala between the studied groups. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment was observed, especially in children who received chemotherapy in combination with reduced dose CNS radiotherapy. In all children treated according to the ALL IC-BFM 2002 with high-dose chemotherapy, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who received chemotherapy in combination with CNS radiotherapy. (orig.)

  7. Nonpharmacological Interventions Targeted at Delirium Risk Factors, Delivered by Trained Volunteers (Medical and Psychology Students, Reduced Need for Antipsychotic Medications and the Length of Hospital Stay in Aged Patients Admitted to an Acute Internal Medicine Ward: Pilot Study

    Directory of Open Access Journals (Sweden)

    Stanislaw Gorski

    2017-01-01

    Full Text Available Purpose. Effectiveness of nonpharmacological multicomponent prevention delivered by trained volunteers (medical and psychology students, targeted at delirium risk factors in geriatric inpatients, was assessed at an internal medicine ward in Poland. Patients and Methods. Participants were recruited to intervention and control groups at the internal medicine ward (inclusion criteria: age ≥ 75, acute medical condition, basic orientation, and logical contact on admission; exclusion criteria: life expectancy < 24 hours, surgical hospitalization, isolation due to infectious disease, and discharge to other medical wards. Every day trained volunteers delivered a multicomponent standardized intervention targeted at risk factors of in-hospital complications to the intervention group. The control group, selected using a retrospective individual matching strategy (1 : 1 ratio, regarding age, gender, and time of hospitalization, received standard care. Outcome Measures. Hospitalization time, deaths, falls, delirium episodes, and antipsychotic prescriptions were assessed retrospectively from medical documentation. Results. 130 patients (38.4% males participated in the study, with 65 in the intervention group. Antipsychotic medications were initiated less frequently in the intervention group compared to the control group. There was a trend towards a shorter hospitalization time and a not statistically significant decrease in deaths in the intervention group. Conclusion. Nonpharmacological multicomponent intervention targeted at delirium risk factors effectively reduced length of hospitalization and need for initiating antipsychotic treatment in elderly patients at the internal medicine ward.

  8. A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells.

    Science.gov (United States)

    Kotani, Ai; Ha, Daon; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2010-03-15

    MLL-AF4 acute lymphocytic leukemia has a poor prognosis, and the mechanisms by which these leukemias develop are not understood despite intensive research based on well-known concepts and methods. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate expression of target mRNA transcripts. We recently reported that ectopic expression of miR-128b together with miR-221, two of the miRNAs downregulated in MLL-AF4 ALL, restores glucocorticoid resistance through downregulation of the MLL-AF4 chimeric fusion proteins MLL-AF4 and AF4-MLL that are generated by chromosomal translocation t(4;11). Here we report the identification of new mutations in miR-128b in RS4;11 cells, derived from MLL-AF4 ALL patient. One novel mutation significantly reduces the processing of miR-128b. Finally, this base change occurs in a primary MLL-AF4 ALL sample as an acquired mutation. These results demonstrate that the novel mutation in miR-128b in MLL-AF4 ALL alters the processing of miR-128b and that the resultant downregulation of mature miR-128b contributes to glucocorticoid resistance through the failure to downregulate the fusion oncogenes.

  9. Analgesia for acute pain

    African Journals Online (AJOL)

    ailment known to man, and acute pain is an experience familiar to all. Pain is defined as ... standard drug or cocktail and a satisfactory patient response is based on .... it was found in a systematic review that music therapy reduces anxiety and ...

  10. Thrombolysis in Acute Cerebrovascular Disease

    Institute of Scientific and Technical Information of China (English)

    刘泽霖

    2003-01-01

    @@ Large-scale trials have shown that thrombolytic therapy reduces mortality and preserves left ventricular function in patients with acute myocardial infarction (AMI). That's a rationale for the use of thrombolytic agents in the management of ischemic stroke.

  11. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  12. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  13. Acute Kidney Failure

    Science.gov (United States)

    ... out of balance. Acute kidney failure — also called acute renal failure or acute kidney injury — develops rapidly over ... 2015. Palevsky PM. Definition of acute kidney injury (acute renal failure). http://www.uptodate.com/home. Accessed April ...

  14. Third-party tolerogenic dendritic cells reduce allo-reactivity in vitro and ameliorate the severity of acute graft-versus-host disease in allo-bone marrow transplantation.

    Science.gov (United States)

    Yang, J; Li, R; Ren, Y; Yang, Y; Xie, R; Fan, H

    2013-12-01

    Tolerogenic dendritic cells (tDCs) potently induce and maintain tolerance based on their distinct characteristics compared with conventional DCs. Recent reports show that donor or host tDCs promote allograft survival in mice. In this study, the efficacy of third-party tDCs in the prevention of acute graft-versus-host disease (aGVHD) was evaluated. In vitro, tDCs derived from the bone marrow (BM) of D1 mice were induced by GM-CSF, IL-10 and TGF-β1. The phenotypes, expression of cytokines and suppression of tDCs were analysed. In vivo, the effects of adoptive transfer of third-party-tDCs were evaluated in an MHC-mismatched aGVHD mouse model. Survival, body weight, GVHD scoring, histopathological specimens and serum cytokines were analysed in tDC-treated mice and untreated controls. Tolerogenic DCs had low expression of MHC and co-stimulatory molecules, expressed high levels of 'immunosuppressive' cytokines and suppressed allo-CD4(+) T cell proliferation. In the B6→D2 mouse model, all aGVHD mice died within 18 days. Fortunately, third-party tDCs transferred at low doses (10(4)) effectively prolonged survival after allo-BMT. Furthermore, in the mice treated with 10(4) tDCs, serum levels of IL-10/TGF-β were significantly higher and the percentage of Foxp3(+) cells continually increased compared with the mice treated with other doses of tDCs. Third-party tDCs play a crucial role in reducing the severity of aGVHD by modulating the secretion of various cytokines and expanding Foxp3(+) regulatory T cells, which suggests the possibility of using third-party tDCs for therapeutic applications. Furthermore, special attention should be paid to the optimal range of tDCs for preventing allograft rejection.

  15. ICAM-1 and Acute Pancreatitis Complicated by Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    XiPing Zhang

    2009-01-01

    Full Text Available One of the most common complications of acute pancreatitis is acute lung injury, during which intercellular adhesion molecule-1 (ICAM-1 plays an important role by participating in leukocyte adhesion and activation as well as by inducing the “cascade effect” of inflammatory mediators, pulmonary microcirculation dysfunction and even acute respiratory distress syndrome, multiple organ failure or death. Although it is generally believed that the modulatory mechanism of ICAM-1 during this process is associated with the activation of nuclear transcription factor kappa B which is mediated by IL-1, IL-6, IL-18 and oxygen free radical, etc., further studies are still required to clarify it. Since the upregulation of ICAM-1 expression in the lung during acute lung injury is one of main pathogeneses, the early detection of the ICAM-1 expression level may contribute to the prevention and treatment of acute lung injury. Moreover, reducing pulmonary ICAM-1 expression levels through treatment with anti-ICAM-1 monoclonal antibody (aICAM-1 and antagonists of the neurokinin 1 receptor, etc., should have a positive effect on protecting the lungs during acute pancreatitis. This review aims to further clarify the relationship between ICAM-1 and acute pancreatitis complicated by acute lung injury, and therefore provides a theoretical basis for the formulation of corresponding therapeutic measures in clinical practice for acute pancreatitis.

  16. IMC-EB10, an anti-FLT3 monoclonal antibody, prolongs survival and reduces nonobese diabetic/severe combined immunodeficient engraftment of some acute lymphoblastic leukemia cell lines and primary leukemic samples.

    Science.gov (United States)

    Piloto, Obdulio; Nguyen, Bao; Huso, David; Kim, Kyu-Tae; Li, Yiwen; Witte, Larry; Hicklin, Daniel J; Brown, Patrick; Small, Donald

    2006-05-01

    The class III receptor tyrosine kinase FLT3 is expressed on the blasts of >90% of patients with B-lineage acute lymphoblastic leukemias (ALL). In addition, it is expressed at extremely high levels in ALL patients with mixed lineage leukemia rearrangements or hyperdiploidy and is sometimes mutated in these same patients. In this report, we investigate the effects of treating ALL cell lines and primary samples with human anti-FLT3 monoclonal antibodies (mAb) capable of preventing binding of FLT3 ligand. In vitro studies, examining the ability of two anti-FLT3 mAbs (IMC-EB10 and IMC-NC7) to affect FLT3 activation and downstream signaling in ALL cell lines and primary blasts, yielded variable results. FLT3 phosphorylation was consistently inhibited by IMC-NC7 treatment, but in some cell lines, IMC-EB10 actually stimulated FLT3 activation, possibly as a result of antibody-mediated receptor dimerization. Through antibody-dependent, cell-mediated cytotoxicity, such an antibody could still prove efficacious against leukemia cells in vivo. In fact, IMC-EB10 treatment significantly prolonged survival and/or reduced engraftment of several ALL cell lines and primary ALL samples in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This occurred even when IMC-EB10 treatment resulted in FLT3 activation in vitro. Moreover, fluorescence-activated cell sorting and PCR analysis of IMC-EB10-treated NOD/SCID mice surviving 150 days post-leukemic cell injection revealed that FLT3 immunotherapy reduced leukemic engraftment below the level of detection in these assays (IMC-EB10 treatment did not select for resistant cells, because cells surviving IMC-EB10 treatment remain sensitive to IMC-EB10 cytotoxicity upon retransplantation. In vivo studies involving either partial depletion or activation of natural killer (NK) cells show that most of the cytotoxic effect of IMC-EB10 is mediated through NK cells. Therefore, such an antibody, either naked or conjugated to radioactive

  17. 还原型谷胱甘肽联合注射用丹参对急性胰腺炎治疗效果的影响%Influence of reduced glutathione combined with Danshen powder injection on acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    华占楼; 孙继妹

    2014-01-01

    Objective To study the diagnostic value of reduced glutathione combined with Danshen powder injection on acute pancreatitis.Methods A total of 180 cases with acute pancreatitis were allocated into three groups:treatment group,control group 1 and control group 2 by random digits table method with 60 cases each.The relief time of abdominal pain,the duration of serum/urine amylase recovery,the duration of liver function damage recovery and the hospital stay time was compared.Results After the treatment,patients in treatment group showed better improvement in clinical symptom.The relief time of abdominal pain,the duration of serum/urine amylase recovery,the duration of liver function damage recovery and the hospital stay time in treatment group was shorter than that in control group 1 and control group 2[(2.9 ± 1.3) d vs.(4.1 ± 1.9),(4.5 ±2.3) d; (3.4± 1.2) dvs.(4.0±2.7),(3.9±2.1) d;(4.9± 2.1) d vs.(5.8±2.5),(6.1 ± 1.3)d; (6.7 ± 2.2)d vs.(8.6 ± 4.1),(9.5 ± 2.8)d; (8.1 ± 2.8)d vs.(9.8 ± 2.7),(10.3 ± 3.6) d],and there was significant difference (P <0.05).The total effective rate in treatment group was 96.7% (58/60),which was higher than that in control group 1 and control group 2 [86.7 %(52/60),83.3 % (50/60)],and there was significant difference (P < 0.05).Conclusion Reduced glutathione combined with Danshen powder injection for acute pancreatitis can greatly decrease the serum inflammatory factors and improve the clinical efficacy.%目的 探讨还原型谷胱甘肽联合注射用丹参对急性胰腺炎的治疗价值.方法 180例急性胰腺炎患者按随机数字表法分为治疗组、对照1组和对照2组,每组60例,对患者治疗后腹痛缓解时间、血尿淀粉酶恢复正常时间、肝功能损害恢复正常时间及住院时间等进行分析比较.结果 治疗后治疗组患者临床症状得到明显改善,治疗组腹痛缓解时间、血尿淀粉酶恢复正常时间、肝功能损害恢复正常时间及住

  18. Acute tonsillitis.

    Science.gov (United States)

    Sidell, Doug; Shapiro, Nina L

    2012-08-01

    Acute tonsillitis is an inflammatory process of the tonsillar tissues and is usually infectious in nature. Acute infections of the palatine tonsils predominantly occur in school-aged children, but patients of any age may be affected. Tonsillitis of viral origin is usually treated with supportive care. Bacterial tonsillitis is most commonly caused by Streptococcus pyogenes. Polymicrobial infections and viral pathogens are also important sources of infection. Penicillins remain the treatment of choice for S. pyogenes tonsillitis, and augmented aminopenicillins have gained utility in concert with the increasing incidence of beta-lactamase producing bacteria. We describe the anatomic features and the immunologic function of the palatine tonsils, including a detailed discussion of history and physical examination findings, treatment recommendations, and possible complications of acute tonsillitis. Establishing an accurate diagnosis and initiating appropriate treatment are key components of managing this common pathologic process.

  19. Acute Pain Management/Regional Anesthesia.

    Science.gov (United States)

    Tedore, Tiffany; Weinberg, Roniel; Witkin, Lisa; Giambrone, Gregory P; Faggiani, Susan L; Fleischut, Peter M

    2015-12-01

    Effective and efficient acute pain management strategies have the potential to improve medical outcomes, enhance patient satisfaction, and reduce costs. Pain management records are having an increasing influence on patient choice of health care providers and will affect future financial reimbursement. Dedicated acute pain and regional anesthesia services are invaluable in improving acute pain management. In addition, nonpharmacologic and alternative therapies, as well as information technology, should be viewed as complimentary to traditional pharmacologic treatments commonly used in the management of acute pain. The use of innovative technologies to improve acute pain management may be worthwhile for health care institutions. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Early management of acute pancreatitis.

    Science.gov (United States)

    Schepers, Nicolien J; Besselink, Marc G H; van Santvoort, Hjalmar C; Bakker, Olaf J; Bruno, Marco J

    2013-10-01

    Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.

  1. Effects of ischemia postconditioning in reducing ischemia reperfusion injury in acute limp ischemia%缺血后适应减轻急性下肢缺血再灌注损伤的实验研究

    Institute of Scientific and Technical Information of China (English)

    李韶南; 黄慧芳; 李广镰; 刘震; 陈平安

    2012-01-01

    目的 观察缺血后适应(IPC)减轻急性下肢缺血(AU)再灌注损伤的疗效并探讨其机制.方法 将45只新西兰大白兔采用高脂饮食与动脉内膜球囊损伤结合的方式建立下肢动脉粥样硬化狭窄动物模型,随机分为对照组、缺血再灌注组(IR组)、缺血后适应组(IPC组),每组各15只.检测三组大白兔阻断股动脉前、持续再灌注2h后血液中肌酸激酶(CK)、丙二醛(MDA)、超氧化物岐化酶(SOD)水平,观察再灌注后下肢骨骼肌组织学改变,并采用原位末端标记法(TUNEL)分析三组大白兔下肢再灌注后骨骼肌细胞凋亡情况.结果 与IR组比较,IPC组兔血浆CK、MDA明显降低[(7.49±0.84) U/L与(8.19±1.06) U/L,P<0.05],[(3.67±0.36) nmol/L与(4.06±0.55) nmol/L,P<0.05],而SOD则显著升高[(420.40±30.94)μmol/L与(384.73±44.12) μmol/L,P<0.05],骨骼肌细胞凋亡指数降低[(12.27±2.11)%与(16.62±1.44)%,P<0.01],差异有统计学意义,并且组织形态学观察IPC组兔骨骼肌损伤、坏死程度较IR组减轻.结论 急性下肢缺血应用IPC能显著减轻下肢缺血再灌注损伤,其机制与减少自由基生成、增强抗氧化及减轻缺血再灌注诱导的骨骼肌细胞凋亡有关.%Objective To study the effects of ischemia postconditioning(IPC) in reducing ischemia-reperfusion injury(IRI) in acute limp ischemia(ALI) and investigate the mechanism.Methods 45 New Zealand rabbits were treated with the method that combined high lipid diets and femoral intima injury by balloon inflation to build up limp atherosclerotic stenosis model,then they were randomly divided into three groups( each group 15 rabbits):control group;IR group and IPC group.Serum creatine phosphate kinase(CK),malondialehyde(MDA),superoxide dismutase (SOD) in three groups were measured before occlusion and 2 hours after sustaining reperfusion.The histological changes of limp skeletal muscle of experimental rabbits were analyzed and TUNEL method was used to

  2. Antibiotic Duration After Laparoscopic Appendectomy for Acute Complicated Appendicitis

    NARCIS (Netherlands)

    Rossem, C.C. van; Schreinemacher, M.H.; Geloven, A.A. van; Bemelman, W.A.; Goor, H. van; Knaapen, L.

    2016-01-01

    IMPORTANCE: Optimal duration of antibiotic treatment to reduce infectious complications after an appendectomy for acute complicated appendicitis remains unclear. OBJECTIVE: To investigate the effect of antibiotic duration on infectious complications after laparoscopic appendectomy for acute complica

  3. Nonpharmacological Interventions Targeted at Delirium Risk Factors, Delivered by Trained Volunteers (Medical and Psychology Students), Reduced Need for Antipsychotic Medications and the Length of Hospital Stay in Aged Patients Admitted to an Acute Internal Medicine Ward: Pilot Study.

    Science.gov (United States)

    Gorski, Stanislaw; Piotrowicz, Karolina; Rewiuk, Krzysztof; Halicka, Monika; Kalwak, Weronika; Rybak, Paulina; Grodzicki, Tomasz

    2017-01-01

    Purpose. Effectiveness of nonpharmacological multicomponent prevention delivered by trained volunteers (medical and psychology students), targeted at delirium risk factors in geriatric inpatients, was assessed at an internal medicine ward in Poland. Patients and Methods. Participants were recruited to intervention and control groups at the internal medicine ward (inclusion criteria: age ≥ 75, acute medical condition, basic orientation, and logical contact on admission; exclusion criteria: life expectancy internal medicine ward.

  4. Acute abdomen

    Directory of Open Access Journals (Sweden)

    Wig J

    1978-01-01

    Full Text Available 550 cases of acute abdomen have been analysed in detail includ-ing their clinical presentation and operative findings. Males are more frequently affected than females in a ratio of 3: 1. More than 45% of patients presented after 48 hours of onset of symptoms. Intestinal obstruction was the commonest cause of acute abdomen (47.6%. External hernia was responsible for 26% of cases of intestinal obstruction. Perforated peptic ulcer was the commonest cause of peritonitis in the present series (31.7% while incidence of biliary peritonitis was only 2.4%.. The clinical accuracy rate was 87%. The mortality in operated cases was high (10% while the over-all mortality rate was 7.5%.

  5. Sinusitis (acute)

    Science.gov (United States)

    2008-01-01

    Introduction Acute sinusitis is defined pathologically, by transient inflammation of the mucosal lining of the paranasal sinuses lasting less than 4 weeks. Clinically, it is characterised by nasal congestion, rhinorrhoea, facial pain, hyposmia, sneezing, and, if more severe, additional malaise and fever. It affects 1−5% of the adult population each year in Europe. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with clinically diagnosed acute sinusitis, and with radiologically or bacteriologically confirmed acute sinusitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides, different doses [amoxicillin, co-amoxiclav, doxycycline, cephalosporins, macrolides], long-course regimens), antihistamines, cephalosporins or macrolides, decongestants (xylometazoline, phenylephrine, pseudoephedrine), doxycycline, saline nasal washes, steam inhalation, and topical corticosteroids (intra-nasal). PMID:19450327

  6. Prevention of acute malnutrition

    DEFF Research Database (Denmark)

    de Pee, Saskia; Grais, Rebecca; Fenn, Bridget;

    2015-01-01

    Acute malnutrition is associated with increased morbidity and mortality risk. When episodes are prolonged or frequent, acute malnutrition is also associated with poor growth and development, which contributes to stunting Nutrition-specific and nutrition-sensitive strategies to prevent...... undernutrition during the first 1,000 days from conception to 24 months of age can reduce the risks of wasting, stunting, and micronutrient deficiencies. Under circumstances that exacerbate the underlying causes of undernutrition and increase the incidence of wasting, such as food insecurity related to lean...... seasons or emergencies, or increased incidence of illness, such as diarrhea or measles, additional efforts are required to prevent and treat wasting. Special nutritious foods directly meet the increased nutrient requirements of children at risk for wasting; assistance to vulnerable households, in the form...

  7. Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning: a report on behalf of the acute leukemia working party of European group for blood and marrow transplantation

    Directory of Open Access Journals (Sweden)

    Avichai Shimoni

    2016-11-01

    Full Text Available Abstract Background Myeloablative (MAC and reduced-intensity conditioning (RIC are established approaches for allogeneic stem cell transplantation (SCT in acute myeloid leukemia (AML. Most deaths after MAC occur within the first 2 years after SCT, while patients surviving leukemia-free for 2 years can expect a favorable long-term outcome. However, there is paucity of data on the long-term outcome (beyond 10 years and the pattern of late events following RIC due to the relative recent introduction of this approach. Methods We analyzed long-term outcomes in a cohort of 1423 AML patients, age ≥50 years, after SCT from HLA-matched siblings, during the years 1997–2005, median follow-up 8.3 years (0.1–17. Results The 10-year leukemia-free survival (LFS was 31 % (95CI, 27–35 and 32 % (28–35 after MAC and RIC, respectively (P = 0.57. The 10-year GVHD/ relapse-free survival (GRFS, a surrogate for quality of life was 22 % (18–25 and 21 % (18–24, respectively (P = 0.79. The 10-year non-relapse mortality (NRM was higher and relapse rate was lower after MAC, throughout the early and late post-transplant course. The 10-year LFS among 584 patients surviving leukemia-free 2 years after SCT was 71 % (65–76 and 73 % (67–78 after MAC and RIC, respectively (P = 0.76. Advanced leukemia at SCT was the major predictor of LFS subsequent to the 2-year landmark. Relapse was the major cause of late death after both regimens; however, NRM and in particular chronic graft-versus-host disease and second cancers were more common causes of late death after MAC. Conclusions Long-term LFS and GRFS are similar after RIC and MAC. Most events after RIC or MAC occur within the first 2 years after SCT. Patients who are leukemia-free 2 years after SCT can expect similar good subsequent outcome after both approaches.

  8. Acute Pancreatitis Concomitant Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Okay Abacı

    2013-03-01

    Full Text Available Acute pancreatitis is an inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction. As in our case rarely, acute pancreatitis can be presented with the coexistance of acute coronary syndrome. To prevent a misdiagnosis of acute situation presented with chest or abdominal pain, physicians must be aware for coexisting pathophysiologies and take into account the differential diagnosis of all life-threatening causes such as cardiac ischemia or acute abdominal situations.

  9. Acute pancreatitis: Etiology and common pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Guo-Jun Wang; Chun-Fang Gao; Dong Wei; Cun Wang; Si-Qin Ding

    2009-01-01

    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux. Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.

  10. [Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

    Science.gov (United States)

    Sánchez Marteles, Marta; Urrutia, Agustín

    2014-03-01

    Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

  11. The REFANI-S study protocol: a non-randomised cluster controlled trial to assess the role of an unconditional cash transfer, a non-food item kit, and free piped water in reducing the risk of acute malnutrition among children aged 6-59 months living in camps for internally displaced persons in the Afgooye corridor, Somalia.

    Science.gov (United States)

    Jelle, Mohamed; Grijalva-Eternod, Carlos S; Haghparast-Bidgoli, Hassan; King, Sarah; Cox, Cassy L; Skordis-Worrall, Jolene; Morrison, Joanna; Colbourn, Timothy; Fottrell, Edward; Seal, Andrew J

    2017-07-06

    The prevalence of acute malnutrition is often high in emergency-affected populations and is associated with elevated mortality risk and long-term health consequences. Increasingly, cash transfer programmes (CTP) are used instead of direct food aid as a nutritional intervention, but there is sparse evidence on their nutritional impact. We aim to understand whether CTP reduces acute malnutrition and its known risk factors. A non-randomised, cluster-controlled trial will assess the impact of an unconditional cash transfer of US$84 per month for 5 months, a single non-food items kit, and free piped water on the risk of acute malnutrition in children, aged 6-59 months. The study will take place in camps for internally displaced persons (IDP) in peri-urban Mogadishu, Somalia. A cluster will consist of one IDP camp and 10 camps will be allocated to receive the intervention based on vulnerability targeting criteria. The control camps will then be selected from the same geographical area. Needs assessment data indicates small differences in vulnerability between camps. In each trial arm, 120 households will be randomly sampled and two detailed household surveys will be implemented at baseline and 3 months after the initiation of the cash transfer. The survey questionnaire will cover risk factors for malnutrition including household expenditure, assets, food security, diet diversity, coping strategies, morbidity, WASH, and access to health care. A community surveillance system will collect monthly mid-upper arm circumference measurements from all children aged 6-59 months in the study clusters to assess the incidence of acute malnutrition over the duration of the intervention. Process evaluation data will be compiled from routine quantitative programme data and primary qualitative data collected using key informant interviews and focus group discussions. The UK Department for International Development will provide funding for this study. The European Civil Protection and

  12. Acute cerebellar ataxia

    Science.gov (United States)

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, particularly younger than age 3, may occur several weeks after an illness caused by a virus. ...

  13. Acute arterial occlusion - kidney

    Science.gov (United States)

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidney can often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury or trauma to ...

  14. [Perioperative acute kidney injury and failure].

    Science.gov (United States)

    Chhor, Vibol; Journois, Didier

    2014-04-01

    Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance.

  15. TCM Therapeutic Strategy on Acute Lung Injury Caused by Infectious Atypical Pneumonia and Acute Respiratory Distress Syndrome

    Institute of Scientific and Technical Information of China (English)

    唐光华

    2003-01-01

    @@ Infectious atypical pneumonia (IAP) is also called severe acute respiratory syndrome (SARS) by WHO. In its development, around 20% of SARS can develop into the stage of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), active and effective treatment of it constitutes the important basis for lowering mortality and reducing secondary pulmonary function impairment and pulmonary fibrosis.

  16. Association of a clinical knowledge support system with improved patient safety, reduced complications and shorter length of stay among Medicare beneficiaries in acute care hospitals in the United States.

    Science.gov (United States)

    Bonis, Peter A; Pickens, Gary T; Rind, David M; Foster, David A

    2008-11-01

    Electronic clinical knowledge support systems have decreased barriers to answering clinical questions but there is little evidence as to whether they have an impact on health outcomes. We compared hospitals with online access to UpToDate with other acute care hospitals included in the Thomson 100 Top Hospitals Database (Thomson database). Metrics used in the Thomson database differentiate hospitals on a variety of performance dimensions such as quality and efficiency. Prespecified outcomes were risk-adjusted mortality, complications, the Agency of Healthcare Research and Quality Patient Safety Indicators, and hospital length of stay among Medicare beneficiaries. Linear regression models were developed that included adjustment for hospital region, teaching status, and discharge volume. Hospitals with access to UpToDate (n=424) were associated with significantly better performance than other hospitals in the Thomson database (n=3091) on risk-adjusted measures of patient safety (P=0.0163) and complications (P=0.0012) and had significantly shorter length of stay (by on average 0.167 days per discharge, 95% confidence interval 0.081-0.252 days, PUpToDate was used at each hospital. Mortality was not significantly different between UpToDate and non-UpToDate hospitals. The study was retrospective and observational and could not fully account for additional features at the included hospitals that may also have been associated with better health outcomes. An electronic clinical knowledge support system (UpToDate was associated with improved health outcomes and shorter length of stay among Medicare beneficiaries in acute care hospitals in the United States. Additional studies are needed to clarify whether use of UpToDate is a marker for the better performance, an independent cause of it, or a synergistic part of other quality improvement characteristics at better-performing hospitals.

  17. Acute Sinusitis

    Science.gov (United States)

    ... your upper jaw and teeth Reduced sense of smell and taste Cough, which might be worse at ... cellulitis). Partial or complete loss of sense of smell. Nasal obstruction and inflammation of the nerve for ...

  18. Acute Myopericarditis Mimicking Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Seval İzdeş

    2011-08-01

    Full Text Available Acute coronary syndromes among young adults are relatively low when compared with older population in the intensive care unit. Electrocardiographic abnormalities mimicking acute coronary syndromes may be caused by non-coronary syndromes and the differential diagnosis requires a detailed evaluation. We are reporting a case of myopericarditis presenting with acute ST elevation and elevated cardiac enzymes simulating acute coronary syndrome. In this case report, the literature is reviewed to discuss the approach to distinguish an acute coronary syndrome from myopericarditis. (Journal of the Turkish Society Intensive Care 2011; 9:68-70

  19. Acute, nonvariceal upper gastrointestinal bleeding.

    Science.gov (United States)

    Klein, Amir; Gralnek, Ian M

    2015-04-01

    Acute, nonvariceal upper gastrointestinal bleeding (UGIB) is a common medical emergency encountered worldwide. Despite medical and technological advances, it remains associated with significant morbidity and mortality. Rapid patient assessment and management are paramount. When indicated, upper endoscopy in patients presenting with acute UGIB is effective for both diagnosis of the bleeding site and provision of endoscopic hemostasis. Endoscopic hemostasis significantly reduces rebleeding rates, blood transfusion requirements, length of hospital stay, surgery, and mortality. Furthermore, early upper endoscopy, defined as being performed within 24 h of patient presentation, improves patient outcomes. A structured approach to the patient with acute UGIB that includes early hemodynamic resuscitation and stabilization, preendoscopic risk stratification using validated instruments, pharmacologic and endoscopic intervention, and postendoscopy therapy is important to optimize patient outcome and assure efficient use of medical resources.

  20. APOPTOTIC, HEPATOPROTECTIVE AND ANTIOXIDANT POTENTIAL OF A TRIHERBAL FORMULATION AGAINST D-GALACTOSAMINE HEPATOTOXICITY

    Directory of Open Access Journals (Sweden)

    Onyekachi Ogbonnaya IROANYA

    2016-12-01

    Full Text Available A triherbal formulation prepared from hydroethanolic mixture of Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina leaves (GOV was evaluated to ascertain its heamatologic, hepatoprotective potentials, antioxidant properties and the fold increase in caspase 2, 3 and 9 activities against D-galactosamine-induced toxicity using Wistar albino rats. Forty-nine Wistar albino rats were divided equally into seven groups. Two control experiments which included normal rats treated with D-galactosamine and normal rats that received only distilled water. Three groups were treated with different doses of GOV extract (2, 4 and 8 g kg-1 b. wt while two groups received standard hepatoprotective drugs (Liv 52 and Silymarin for 13 days prior to intoxication with D-galactosamine. The activities of serum liver enzymes, concentrations of some biochemical analytes, effect on heamatologic parameters, antioxidant status and fold increase in caspase 2, 3 and 9 activities were monitored. HPTLC of GOV showed the presence of ascorbic acid, rutin, eugenol and β-sitosterol. Administration of GOV significantly (p<0.05 increased the Packed Cell Volume, Red Cell Count, Haemoglobin, White Blood Cell, platelet count, Mean Cell Haemoglobin, granulocytes and lymphocytes while the Mean Cell Volume and monocytes were significantly (p<0.05 depreciated dose dependently compared to the toxin control group. GOV dose dependently exhibited significant (p<0.05 decrease in levels of Alkaline phosphatase, Alanine aminotransferase, aspartate aminotransferase, L-γ-glutamyltransferase, Lactate dehydrogenase, cholesterol, creatinine, triglycerides, urea and Malondialdehyde. Subsequently, it significantly (p<0.05 increased the albumin, total protein, catalase, Glutathione Peroxidase, Reduced Glutathione, Glutathione-S-Transferase and Superoxide Dismutase levels. GOV significantly (p≤0.05 attenuated the fold increase in caspase 2, 3 and 9 activities compared to the toxin control

  1. Acute and subacute idiopathic interstitial pneumonias.

    Science.gov (United States)

    Taniguchi, Hiroyuki; Kondoh, Yasuhiro

    2016-07-01

    Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.

  2. Acute otitis externa

    OpenAIRE

    Hui, Charles PS

    2013-01-01

    Acute otitis externa, also known as ‘swimmer’s ear’, is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present.

  3. Acute otitis externa.

    Science.gov (United States)

    Hui, Charles Ps

    2013-02-01

    Acute otitis externa, also known as 'swimmer's ear', is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present.

  4. Acute otitis externa

    OpenAIRE

    2013-01-01

    Acute otitis externa, also known as ‘swimmer’s ear’, is a common disease of children, adolescents and adults. While chronic suppurative otitis media or acute otitis media with tympanostomy tubes or a perforation can cause acute otitis externa, both the infecting organisms and management protocol are different. This practice point focuses solely on managing acute otitis externa, without acute otitis media, tympanostomy tubes or a perforation being present.

  5. Late reperfusion of a totally occluded infarct-related artery increases granulocyte-colony stimulation factor and reduces stroma-derived factor-1alpha blood levels in patients with ongoing ischemia after acute myocardial infarction.

    Science.gov (United States)

    Kuo, Li-Tang; Chen, Shih-Jen; Cherng, Wen-Jin; Yang, Ning-I; Lee, Chen-Chin; Cheng, Chi-Wen; Verma, Subodh; Wang, Chao-Hung

    2009-07-01

    After acute myocardial infarction (AMI), reopening of a totally occluded infarct-related artery (IRA) at a subacute stage is still controversial in symptom-free patients. However, in patients with persistent ischemic symptoms and inadequate collaterals to the infarct area, recanalization is thought to provide beneficial effects. In addition to augmenting myocardial perfusion, we hypothesized that the benefit of recanalization involves the manipulation of circulating stem cell-mobilizing cytokines. This study included 30 patients with a totally occluded IRA and ongoing ischemic symptoms (the study group) and 30 patients with a partially occluded IRA (the control group). All patients underwent successful angioplasty and/or stenting. Before and immediately after the coronary intervention, blood granulocyte-colony-stimulating factor (G-CSF), stem-cell factor (SCF), vascular endothelial growth factor (VEGF), and stroma-derived factor-1 (SDF-1alpha) were measured. After recanalization, G-CSF levels significantly increased in the study group compared to the control group (P=0.03). SDF-1alpha levels in the study group decreased relative to the controls (P=0.02). However, no significant changes in VEGF or SCF levels between the two groups were found. In the multivariate analysis, reopening of a totally occluded IRA was independently and significantly associated with changes in G-CSF and SDF-1alpha levels after recanalization. In conclusion, our data suggest that the benefits of late reperfusion of a totally occluded IRA in patients with ongoing myocardial ischemia may involve mechanisms associated with stem cell-mobilizing and plaque-stabilizing cytokines. This study provides the rationale to investigate serial changes in cytokines and the numbers of circulating progenitors after reperfusion in the future.

  6. Acute exacerbation of COPD.

    Science.gov (United States)

    Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A

    2016-10-01

    The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations.

  7. Elderly patients (66-70 years) with acute leukemia or high-risk MDS who, underwent allogenic transplant of peripheral hematopoietic progenitors after reduced-intensity conditioning. | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available ad alte dosi nella profilassi della GVHD in pazienti anziani (66-70 anni), affetti da leucemia acuta o miel...matopoietic progenitors after reduced-intensity conditioning. Pazienti anziani (66-70 anni), affetti da leucemia...erwent allogenic transplant. Pazienti anziani (66-70 anni), affetti da leucemia acuta o mielodisplasia ad al... sfavorevole o intermedia – cariotipo normale con alterazioni molecolari sfavorevoli – fallimento del 1° ciclo d’induzione – leucemia

  8. Acute pyelonephritis in children.

    Science.gov (United States)

    Morello, William; La Scola, Claudio; Alberici, Irene; Montini, Giovanni

    2016-08-01

    Acute pyelonephritis is one of the most serious bacterial illnesses during childhood. Escherichia coli is responsible in most cases, however other organisms including Klebsiella, Enterococcus, Enterobacter, Proteus, and Pseudomonas species are being more frequently isolated. In infants, who are at major risk of complications such as sepsis and meningitis, symptoms are ambiguous and fever is not always useful in identifying those at high risk. A diagnosis of acute pyelonephritis is initially made on the basis of urinalysis; dipstick tests for nitrites and/or leukocyte esterase are the most accurate indicators of infection. Collecting a viable urine sample for urine culture using clean voided methods is feasible, even in young children. No gold standard antibiotic treatment exists. In children appearing well, oral therapy and outpatient care is possible. New guidelines suggest less aggressive imaging strategies after a first infection, reducing radiation exposure and costs. The efficacy of antibiotic prophylaxis in preventing recurrence is still a matter of debate and the risk of antibiotic resistance is a warning against its widespread use. Well-performed randomized controlled trials are required in order to better define both the imaging strategies and medical options aimed at preserving long-term renal function.

  9. Postconditioning with isoflurane reduces acute lung injury induced by cecal ligation and perforation in rats%异氟烷后处理减轻大鼠盲肠结扎穿孔所致急性肺损伤

    Institute of Scientific and Technical Information of China (English)

    吕翔; 董翔; 李启芳; 姜虹; 朱也森

    2012-01-01

    Objective To study the protective effects of isoflurane postcondition on acute lung injury (ALI) induced by cecal ligation and perforation (CLP) in rats. Methods A total of 48 male Sprague-Dawley rats were randomly divided into 4 groups (n = 12): normal group, without any treatment; sham operation group, with incision and closure of abdomen; CLP group, the CLP model was used to induce ALI; and isoflurane group, rats were anesthetized with 1.4% isoflurane at 4 h after CLP modeling for 2 h. Then 6 rats in each group were randomly killed by decapitation 6 h and 24 h after pretreatment. Blood samples of abdominal aorta were taken for arterial blood gas analysis. The tissues of left lung were taken for the determination of lung wet/dry (W/D) ratio. Tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6) levels were measured with blood sample of heart. Histopathological changes of the right lung and the expression of nuclear factor (NF)-KB were observed by H-E staining and immunohistochemical staining, respectively. Results There were no significant differences in arterial oxygen partial pressure (paO2), the ratio of W/D or serum concentrations of TNF-α and IL-6 between sham operation group and normal group (P>0.05). The paO2 in CLP group and isoflurane group was significantly lower than that in the normal group, while the ratio of W/D and serum concentrations of TNF-a and IL-6 in CLP group and isoflurane group were significantly higher than those in the normal group (P<0. 05). There were significant differences in above mentioned parameters between isoflurane group and CLP group (P<0. 05). There was no obvious lung injury in normal group or sham operation group. The rats in CLP group suffered more serious lung injury as compared with isoflurane group, and the lung injury at 24 h after precondition was much severe than that at 6 h after precondition. The cells with NF-KB expression were occasionally seen in normal group and sham operation group, while a large number

  10. The active metabolite of prasugrel, R-138727, improves cerebral blood flow and reduces cerebral infarction and neurologic deficits in a non-human primate model of acute ischaemic stroke.

    Science.gov (United States)

    Sugidachi, Atsuhiro; Mizuno, Makoto; Ohno, Kousaku; Jakubowski, Joseph A; Tomizawa, Atsuyuki

    2016-10-05

    Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits.

  11. The treatment of acute vertigo.

    Science.gov (United States)

    Cesarani, A; Alpini, D; Monti, B; Raponi, G

    2004-03-01

    Vertigo and dizziness are very common symptoms in the general population. The aim of this paper is to describe the physical and pharmacological treatment of symptoms characterized by sudden onset of rotatory vertigo. Acute vertigo can be subdivided into two main groups: (1) spontaneous vertigo and (2) provoked vertigo, usually by postural changes, generally called paroxysmal positional vertigo (PPV). Sudden onset of acute vertigo is usually due to acute spontaneous unilateral vestibular failure. It can be also fluctuant as, e.g., in recurrent attacks of Ménière's disease. Pharmacotherapy of acute spontaneous vertigo includes Levo-sulpiride i.v., 50 mg in 250 physiologic solution, once or twice a day, methoclopramide i.m., 10 mg once or twice a day, or triethilperazine rectally, once or twice a day, to reduce neurovegetative symptoms; diazepam i.m., 10 mg once or twice a day, to decrease internuclear inhibition, sulfate magnesium i.v., two ampoules in 500 cc physiological solution, twice a day, or piracetam i.v., one ampoule in 500 cc physiological solution, twice a day, to decrease vestibular damage. At the onset of the acute symptoms, patients must lie on their healthy side with the head and trunk raised 20 degrees. The room must be quiet but not darkened. If the patient is able to swallow without vomiting, it is important to reduce nystagmus and stabilize the visual field with gabapentine, per os, 300 mg twice or three times a day. The first step of the physical therapy of acute vertigo is vestibular electrical stimulation, that is to say, a superficial paravertebral electrical stimulation of neck muscles, aimed to reduce antigravitary failure and to increase proprioceptive cervical sensory substitution. PPV is a common complaint and represents one of the most common entities in peripheral vestibular pathology. While the clinical picture is well known and widely described, the etiopathogenesis of PPV is still a matter of debate. Despite the different

  12. Acute human schistosomiasis mansoni

    Directory of Open Access Journals (Sweden)

    Ana Rabello

    1995-04-01

    Full Text Available The acute schistosomiasis is the toxemic disease that follow the Schistosoma cercariae active penetration trough screen in the immunologicaly naive vertebrate host. The clinical picture starts two to eight weeks after the first contact with the contaminated water. Susceptible patients present a syndrome comprising fever, diarrhea, toxemia and hepatosplenomegaly. Diagnosis is based on epidemiological and clinical features, presence of Schistosoma eggs in the feces, enlargement of abdominal lymph nodes by ultrasonography and by detection of high antibodies levels against the antigen keyhole limpet haemocyanin. Different rates of cure have been observed with specific medication and for the most severe clinical presentations the use of steroids reduces the systemic and allergic manifestations.

  13. Reducing Iatrogenic Risks

    Science.gov (United States)

    Ely, E. Wesley; Speroff, Theodore; Pun, Brenda T.; Boehm, Leanne; Dittus, Robert S.

    2010-01-01

    ICUs are experiencing an epidemic of patients with acute brain dysfunction (delirium) and weakness, both associated with increased mortality and long-term disability. These conditions are commonly acquired in the ICU and are often initiated or exacerbated by sedation and ventilation decisions and management. Despite > 10 years of evidence revealing the hazards of delirium, the quality chasm between current and ideal processes of care continues to exist. Monitoring of delirium and sedation levels remains inconsistent. In addition, sedation, ventilation, and physical therapy practices proven successful at reducing the frequency and severity of adverse outcomes are not routinely practiced. In this article, we advocate for the adoption and implementation of a standard bundle of ICU measures with great potential to reduce the burden of ICU-acquired delirium and weakness. Individual components of this bundle are evidence based and can help standardize communication, improve interdisciplinary care, reduce mortality, and improve cognitive and functional outcomes. We refer to this as the “ABCDE bundle,” for awakening and breathing coordination, delirium monitoring, and exercise/early mobility. This evidence-based bundle of practices will build a bridge across the current quality chasm from the “front end” to the “back end” of critical care and toward improved cognitive and functional outcomes for ICU survivors. PMID:21051398

  14. Recurrent acute pancreatitis and its relative factors

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Hong-Chao Shan; Yan Gu

    2005-01-01

    AIM: To evaluate the causes and the relative factors of recurrent acute pancreatitis.METHODS: From 1997 to 2000, acute pancreatitis relapsed in 77 of 245 acute pancreatitis patients. By reviewing the clinical treatment results and the follow-up data, we analyzed the recurrent factors of acute pancreatitis using univariate analysis and multivariate analysis.RESULTS: Of the 245 acute pancreatitis patients, 77 were patients with recurrent acute pancreatitis. Of them, 56 patients relapsed two times, 19 relapsed three times, each patient relapsed three and four times. Forty-seven patients relapsed in hospital and the other 30 patients relapsed after discharge. Eighteen patients relapsed in 1 year, eight relapsed in 1-3 years, and four relapsed after 3 years. There were 48 cases of biliary pancreatitis, 3 of alcohol pancreatitis, 5 of hyperlipidemia pancreatitis, 21 of idiopathic pancreatitis. Univariate analysis showed that the patients with local complications of pancreas, obstructive jaundice and hepatic function injury were easy to recur during the treatment period of acute pancreatitis (P = 0.022<0.05, P = 0.012<0.05 and P = 0.002<0.05, respectively). Multivariate analysis showed that there was no single factor related to recurrence. Of the 47 patients who had recurrence in hospital, 16 had recurrence in a fast period, 31 after refeeding. CONCLUSION: Acute pancreatitis is easy to recur even during treatment. The factors such as changes of pancreas structure and uncontrolled systemic inflammatory reaction are responsible for the recurrence of acute pancreatitis. Early refeeding increases the recurrence of acute pancreatitis. Defining the etiology is essential for reducing the recurrence of acute pancreatitis.

  15. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    Science.gov (United States)

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  16. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  17. Acute bee paralysis virus [

    Lifescience Database Archive (English)

    Full Text Available Acute bee paralysis virus [gbvrl]: 14 CDS's (15780 codons) fields: [triplet] [frequ...osomal protein / MAP kinase List of codon usage for each CDS (format) Homepage Acute bee paralysis virus ...

  18. Acute kidney failure

    Science.gov (United States)

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  19. Histoplasmosis - acute (primary) pulmonary

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000098.htm Histoplasmosis - acute (primary) pulmonary To use the sharing features on this page, please enable JavaScript. Acute pulmonary histoplasmosis is a respiratory infection that is caused by ...

  20. Acute Mesenteric Ischemia

    Science.gov (United States)

    ... Side Effects Additional Content Medical News Acute Mesenteric Ischemia By Parswa Ansari, MD, Department of Surgery, Lenox ... Abscesses Abdominal Wall Hernias Inguinal Hernia Acute Mesenteric Ischemia Appendicitis Ileus Intestinal Obstruction Ischemic Colitis Perforation of ...

  1. Acute acalculous cholecystitis complicating chemotherapy for acute myeloblastic leukemia

    OpenAIRE

    Olfa Kassar; Feten Kallel; Manel Ghorbel; Hatem. Bellaaj; Zeineb Mnif; Moez Elloumi

    2015-01-01

    Acute acalculous cholecystitis is a rare complication in the treatment of acute myeloblastic leukemia. Diagnosis of acute acalculous cholecystitis remains difficult during neutropenic period. We present two acute myeloblastic leukemia patients that developed acute acalculous cholecystitis during chemotherapy-induced neutropenia. They suffered from fever, vomiting and acute pain in the epigastrium. Ultrasound demonstrated an acalculous gallbladder. Surgical management was required in one patie...

  2. Care of Acute Gastrointestinal Conditions in the Observation Unit.

    Science.gov (United States)

    Ham, Jason J; Ordonez, Edgar; Wilkerson, R Gentry

    2017-08-01

    The Emergency Department Observation Unit (EDOU) provides a viable alternative to inpatient admission for the management of many acute gastrointestinal conditions with additional opportunities of reducing resource utilization and reducing radiation exposure. Using available evidence-based criteria to determine appropriate patient selection, evaluation, and treatment provides higher-quality medical care and improved patient satisfaction. Discussions of factors involved in creating an EDOU capable of caring for acute gastrointestinal conditions and clinical protocol examples of acute appendicitis, gastrointestinal hemorrhage, and acute pancreatitis provide a framework from which a successful EDOU can be built. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Colloids in Acute Burn Resuscitation.

    Science.gov (United States)

    Cartotto, Robert; Greenhalgh, David

    2016-10-01

    Colloids have been used in varying capacities throughout the history of formula-based burn resuscitation. There is sound experimental evidence that demonstrates colloids' ability to improve intravascular colloid osmotic pressure, expand intravascular volume, reduce resuscitation requirements, and limit edema in unburned tissue following a major burn. Fresh frozen plasma appears to be a useful and effective immediate burn resuscitation fluid but its benefits must be weighed against its costs, and risks of viral transmission and acute lung injury. Albumin, in contrast, is less expensive and safer and has demonstrated ability to reduce resuscitation requirements and possibly limit edema-related morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Acute mastoiditis in children

    DEFF Research Database (Denmark)

    Anthonsen, Kristian; Høstmark, Karianne; Hansen, Søren;

    2013-01-01

    Conservative treatment of acute otitis media may lead to more complications. This study evaluates changes in incidence, the clinical and microbiological findings, the complications and the outcome of acute mastoiditis in children in a country employing conservative guidelines in treating acute...... otitis media....

  5. Impact of cytogenetics risk on outcome after reduced intensity conditioning allo-SCT from an HLA-identical sibling for patients with AML in first CR: a report from the acute leukemia working party of EBMT.

    Science.gov (United States)

    Chevallier, P; Labopin, M; Milpied, N; Cornelissen, J J; Blaise, D; Petersen, E; Sandstedt, A; Goker, H; Socie, G; Rocha, V; Mohty, M

    2012-11-01

    So far the impact of cytogenetics risk on outcome in the context of reduced intensity conditioning (RIC) allo-SCT has been poorly studied. We have identified 378 AML patients in first CR who underwent RIC allo-SCT from an HLA-matched sibling donor between 2000 and 2007 reported to the European Group for Bone and Marrow Transplantation and for whom detailed cytogenetics data were available (good risk: n=21; intermediate risk: n=304; and poor risk: n=53). With a median follow-up of 24 months (range: 1-93), 2-year non-relapse mortality, relapse rate (RR), leukemia-free survival (LFS) and OS were 14%, 31%, 55% and 61%, respectively. Cytogenetics was significantly associated with RR (good risk: 10%; intermediate risk: 28%; and poor risk: 55% at 2 years, Pcytogenetics group (P=0.001, P=0.004) and in patients with a higher WBC at diagnosis (>10 × 10(9)/L) (Pcytogenetics had increased RR and decreased LFS after RIC allo-SCT, requiring new prospective strategies to improve results in this subgroup.

  6. Antibiotics for acute otitis media in children.

    Science.gov (United States)

    Nitsche, María Pía; Carreño, Monica

    2015-10-29

    Acute otitis media is one of the most common infectious diseases diagnosed in children. Antibiotic treatment use remains controversial. This summary aims to evaluate the effectiveness and safety of antibiotics in children with acute otitis media. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 18 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded antibiotics reduce pain at 48-72 hours and reduce the risk of tympanic perforations in children with acute otitis media, but they do not reduce late recurrences and increase the risk of side effects (rash, vomiting and diarrhea).

  7. Imaging of Acute Pancreatitis.

    Science.gov (United States)

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist.

  8. Acute loss of consciousness.

    Science.gov (United States)

    Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo

    2015-01-01

    Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness.

  9. Importance of viruses in acute otitis media.

    Science.gov (United States)

    Nokso-Koivisto, Johanna; Marom, Tal; Chonmaitree, Tasnee

    2015-02-01

    Acute otitis media occurs as a complication of viral upper respiratory tract infection. Bacterial otopathogens and respiratory viruses interact and play important roles in acute otitis media development. A better understanding of viral and bacterial interactions may lead to innovative ways to lessen the burden of this common childhood disease. There has been increasing evidence that acute otitis media occurs during upper respiratory infection, even in the absence of nasopharyngeal bacterial colonization. Among the types of viruses associated with acute otitis media, respiratory syncytial virus continues to be the most commonly detected. It is still unclear whether viral load plays an important role in acute otitis media development, but symptomatic upper respiratory tract infection (as opposed to asymptomatic viral infection) is crucial. Widespread use of bacterial and viral vaccines in young children, including pneumococcal conjugate and influenza vaccines, has led to the reduction in otitis media-related healthcare use between 2001 and 2011. There has been no new vaccine against respiratory viruses other than influenza. Progress has been made toward the reduction of the burden of acute otitis media in the last decade. Success in reducing acute otitis media incidence will rely mainly on prevention of nasopharyngeal otopathogen colonization, as well as reduction in the incidence of viral upper respiratory tract infection.

  10. [Some aspects of the complex treatment of acute suppurative perionitis].

    Science.gov (United States)

    Kovalev, M M; Roĭ, V P; Zaritskiĭ, I; Konovalenko, V V; Mellin, V M

    1976-10-01

    The authors present an analysis of the results of complex treatment in 4318 patients operated upon for acute peritonitis, caused by acute appendicitis, perforating gastric and duodenal ulcers, acute cholecystitis, ruptures and perforations of the intestine and other surgical and gynecological diseases. Patients with diffuse purulent peritonitis showed marked disorders in protein-aminoacid, nitrogen, and water electrolyte metabolism, acid-base balance, a reduced nonspecific immune responsiveness of the organism. Therpeutic tactics was delineated taking into account the revealed changes.

  11. 阶段性管理缓解初产妇第一产程急性疼痛的效果评价%Effectiveness evaluation of stage management to reduce the acute pain in the first stage of labor

    Institute of Scientific and Technical Information of China (English)

    毛佳慧; 马建娣; 喻晓芬; 朱瑛; 王慧

    2014-01-01

    experiences of intervention , therapeutic massage , meditation with music and birth ball.The numerical rating scale (NRS) and visual analog score (VAS) were used to assess the degree of pain, emotions and comfort feelings .Then, the degree of pain and changes of emotions and comfort were compared between groups .Results Within the observation group , 12 primipara ( 40.00%) had mild pain, 17 primipara (56.67%) had moderate pain, 1 primipara (3.33%) had severe pain.Within the control group, 5 primipara (16.67%) had mild pain, 21 primipara (70.00%) had moderate pain, 4 primipara (13.33%) had severe pain.There was a significant difference between groups (U =2.235, P =0.025).Within the observation group, 22 primipara (73.33%) had mild discomfort, 8 primipara (26.67%) had moderate discomfort.Within the control group, 10 primipara (33.33%) had mild discomfort, 17 primipara (56.67%) had moderate discomfort , 3 primipara ( 10 .00%) had severe discomfort .There was a significant difference between groups (U=3.222, P=0.001).There was no significant difference in the emotions between groups (U=0.800,P=0.424).Conclusions The stage management can significantly reduce the pain of primipara during delivery and improve their comfort .

  12. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  13. Acute chylous peritonitis due to acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Georgios K Georgiou; Haralampos Harissis; Michalis Mitsis; Haralampos Batsis; Michalis Fatouros

    2012-01-01

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse.The development of chylous ascites is usually a chronic process mostly involving malignancy,trauma or surgery,and symptoms arise as a result of progressive abdominal distention.However,when accumulation of "chyle" occurs rapidly,the patient may present with signs of peritonitis.Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation,appendicitis or visceral ischemia.Less than 100 cases of acute chylous peritonitis have been reported.Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis.This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis,and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis.The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer,since,due to hypertriglyceridemia,serum amylase values appeared within the normal range.Moreover,abdominal computed tomography imaging was not diagnostic for pancreatitis.Following abdominal lavage and drainage,the patient was successfully treated with total parenteral nutrition and octreotide.

  14. Acute chylous peritonitis due to acute pancreatitis.

    Science.gov (United States)

    Georgiou, Georgios K; Harissis, Haralampos; Mitsis, Michalis; Batsis, Haralampos; Fatouros, Michalis

    2012-04-28

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse. The development of chylous ascites is usually a chronic process mostly involving malignancy, trauma or surgery, and symptoms arise as a result of progressive abdominal distention. However, when accumulation of "chyle" occurs rapidly, the patient may present with signs of peritonitis. Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation, appendicitis or visceral ischemia. Less than 100 cases of acute chylous peritonitis have been reported. Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis. This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis, and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis. The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer, since, due to hypertriglyceridemia, serum amylase values appeared within the normal range. Moreover, abdominal computed tomography imaging was not diagnostic for pancreatitis. Following abdominal lavage and drainage, the patient was successfully treated with total parenteral nutrition and octreotide.

  15. Acute otitis media and acute bacterial sinusitis.

    Science.gov (United States)

    Wald, Ellen R

    2011-05-01

    Acute otitis media and acute bacterial sinusitis are 2 of the most common indications for antimicrobial agents in children. Together, they are responsible for billions of dollars of health care expenditures. The pathogenesis of the 2 conditions is identical. In the majority of children with each condition, a preceding viral upper respiratory tract infection predisposes to the development of the acute bacterial complication. It has been shown that viral upper respiratory tract infection predisposes to the development of acute otitis media in 37% of cases. Currently, precise microbiologic diagnosis of acute otitis media and acute bacterial sinusitis requires performance of tympanocentesis in the former and sinus aspiration in the latter. The identification of a virus from the nasopharynx in either case does not obviate the need for antimicrobial therapy. Furthermore, nasal and nasopharyngeal swabs are not useful in predicting the results of culture of the middle ear or paranasal sinus. However, it is possible that a combination of information regarding nasopharyngeal colonization with bacteria and infection with specific viruses may inform treatment decisions in the future.

  16. Acute pancreatitis in acute viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis.METHODS: We prospectively assessed the pancreatic involvement in patients with acute viral hepatitis who presented with severe abdomimanl pain.RESULTS: We studied 124 patients with acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven patients (5.65%) were diagnosed to have acute pancreatitis. All were young males. Five patients had pancreatitis in the first week and two in the fourth week after the onset of jaundice. The pancreatitis was mild and all had uneventful recovery from both pancreatitis and hepatitis on conservative treatment.The etiology of pancreatitis was hepatitis E virus in 4,hepatitis A virus in 2, and hepatitis B virus in 1 patient.One patient had biliary sludge along with HEV infection.The abdominal pain of remaining seventeen patients was attributed to stretching of Glisson's capsule.CONCLUSION: Acute pancreatitis occurs in 5.65% of patients with acute viral hepatitis, it is mild and recovers with conservative management.

  17. [Acute Sensory Neuropathies and Acute Autonomic Neuropathies].

    Science.gov (United States)

    Koike, Haruki

    2015-11-01

    From the perspective of neuropathies with an acute onset mimicking that of Guillain-Barré syndrome (GBS), cases with profound sensory and/or autonomic impairment without any significant weakness have been reported. Although the possibility of infectious or toxic etiologies should be carefully excluded, immune mechanisms similar to those in GBS are suggested to be involved in these so-called acute sensory neuropathies and acute autonomic neuropathies. The types of neuropathy include those with predominant sensory manifestations, predominant autonomic manifestations such as autoimmune autonomic ganglionopathy, and both sensory and autonomic manifestations such as acute autonomic and sensory neuropathy. Neuronopathy in the sensory and/or autonomic ganglia (i.e., ganglionopathy) has been commonly suggested in patients with these types of neuropathies. The presence of Anti-GD1b antibodies has been reported in some of the patients with acute sensory neuropathy with deep sensory impairment, whereas anti-ganglionic acetylcholine receptor antibodies are reported to be present in half of the patients with autoimmune autonomic ganglionopathy. The discovery of anti-ganglionic acetylcholine receptor antibodies significantly expanded the spectrum of autoimmune autonomic ganglionopathy. This is because some of the patients with chronic progression mimicking neurodegenerative diseases such as pure autonomic failure were positive for these antibodies. In contrast, pathologically significant autoantibodies have not been identified in acute autonomic and sensory neuropathy. Further studies are needed to clarify the pathogenesis and the spectrum of these types of neuropathies.

  18. [New options in the treatment of acute heart failure].

    Science.gov (United States)

    Link, A; Böhm, M

    2014-06-01

    Acute heart failure is defined as the acute onset of symptoms due to hear failure necessitating emergency therapy. The in-hospital mortality rate ranges up to 10 % and in cardiogenic shock is 50-70 %. In acute heart failure, rapid diagnosis and causal therapy are necessary to avoid cardiogenic shock. In cases of acute coronary syndromes, primary percutaneous intervention should be performed immediately. Medical and apparative treatment strategies focus on decreasing pulmonary congestion, afterload, and neurohormonal activation in order to improve hemodynamics and reduce symptoms of dyspnea. In contrast to chronic heart failure, no medical therapy has been able to reduce mortality rates in acute heart failure. However, new medical therapies should at least improve clinical symptoms of congestion and favorably reduce cardiovascular events, re-hospitalization, and mortality rates.

  19. 还原型叶酸载体基因多态性与急性白血病易感性的相关性%Association of single nucleotide polymorphism of reduced folate carrier gene with susceptibility to acute leukemia

    Institute of Scientific and Technical Information of China (English)

    赵玮; 岳丽杰; 陈小文

    2011-01-01

    目的 研究还原型叶酸载体(reduced folate carrier,RFC)80G/A单核苷酸多态性(single nucleotide polymorphism,SNP)与急性白血病(acute leukemia,AL)之间的关联性.方法 采用逆转录-聚合酶链反应-变性梯度凝胶电泳(reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis,RT-PCR-DGGE)结合DNA直接测序,对98例AL患儿和135名正常儿童进行RFC第80位点SNP筛查.结果 在AL组和正常儿童组中发现RFC 80 GA基因型的例数分别为53和52,AA基因型例数分别为24和30,两组A等位基因频率分别为0.515和0.415.应用x2分析发现RFC 80G/A与AL存在交互作用.结论 确定了中国儿童RFC 80G/A的等位基因频率,并初步认为RFC 80G/A与AL发生存在一定的相关性.%Objective To investigate the allele and genotype frequencies of reduced folate carrier gene (RFC) 80G/A polymorphism in Chinese patients with acute leukemia (AL) and healthy control children,and to provide clue for association between the single nucleotide polymorphism (SNP) of RFC and the occurrence of AL. Methods Bone marrow samples from 98 childhood patients with AL and peripheral blood samples from 135 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for the polymorphisms in RFC 80G/A by reverse transcriptase-polymerase chain reactiondenaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing. Results The A allele frequencies of the AL patients and control children were 0. 515 and 0. 415, respectively (P<0. 05). Chisquare test confirmed a statistical significance of the association between RFC80 G/A and AL. Conclusion RFC 80AA or GA genotype may contribute to increasing the susceptibility to AL.

  20. Histoprotective effect of antihypoxant olifen during experimental acute pancreatitis.

    Science.gov (United States)

    Tolstoi, A D; Dzhurko, B I; Vashetko, R V; Medvedev, Y V; Gol'tsov, V R; Dvoinov, V G; Zakharova, E V

    2001-04-01

    We evaluated the efficiency of perfusion with olifen in preventing oxidative stress at the early stage of acute pancreatitis. Transaortic perfusion with olifen prevented clinical and biochemical symptoms of acute pancreatitis, attenuated oxidative stress, reduced peritoneal exudation, and restricts the area of pancreatic necrosis to 6% tissue.

  1. [Acute rheumatic fever].

    Science.gov (United States)

    Maier, Alexander; Kommer, Vera

    2016-03-01

    We report on a young women with acute rheumatic fever. Acute rheumatic fever has become a rare disease in Germany, especially in adults. This carries the risk that it can be missed in the differential diagnostic considerations of acute rheumatic disorders and febrile status. If rheumatic fever is not diagnosed and treated correctly, there is a considerable risk for rheumatic valvular heart disease. In this article diagnosis, differential diagnosis and therapy of rheumatic fever are discussed extensively.

  2. Acute Idiopathic Scrotal Edema

    Directory of Open Access Journals (Sweden)

    Micheál Breen

    2013-01-01

    Full Text Available We report a case of acute idiopathic scrotal edema (AISE in a 4-year-old boy who presented with acute scrotal pain and erythema. The clinical features, ultrasound appearance, and natural history of this rare diagnosis are reviewed. In this report, we highlight the importance of good ultrasound technique in differentiating the etiology of the acute scrotum and demonstrate the color Doppler “Fountain Sign” that is highly suggestive of AISE.

  3. Pharm GKB: Leukemia, Nonlymphocytic, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Overview Alternate Names: Synonym ANLL; Acute Nonlymphoblastic Leukemia; Acute Nonl...ymphoblastic Leukemias; Acute Nonlymphocytic Leukemia; Acute Nonlymphocytic Leukemias; Leukemia, Acute Nonly...mphoblastic; Leukemia, Acute Nonlymphocytic; Leukemia, Nonlymphoblastic, Acute; Leukemias, Acute Nonlymphoblastic; Leukemias, Acute... Nonlymphocytic; Nonlymphoblastic Leukemia, Acute; Nonlymphoblastic Leukemias, Acut...e; Nonlymphocytic Leukemia, Acute; Nonlymphocytic Leukemias, Acute PharmGKB Accessi

  4. Pharm GKB: Leukemia, Myeloid, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available Amino Acid Translations are all sourced from dbSNP 144 Overview Alternate Names: Synonym AML - Acute... myeloblastic leukaemia; Acute Myeloblastic Leukemia; Acute Myeloblastic Leukemias; Acute... Myelocytic Leukemia; Acute Myelocytic Leukemias; Acute Myelogenous Leukemia; Acute Myelogenous Leukemias; Acute... granulocytic leukaemia; Acute myeloblastic leukemia; Acute myeloid leukaemia; Acute myeloid leukaemia - category; Acute... myeloid leukaemia, disease; Acute myeloid leukemia; Acute myelo

  5. ¿Tiene utilidad el tratamiento preoperatorio con ácido ursodeoxicólico en la reducción de las recidivas en la pancreatitis aguda biliar? Is pre-operative treatment with ursodeoxycholic acid useful in reducing relapses in acute biliary pancreatitis?

    Directory of Open Access Journals (Sweden)

    F. Borda

    2003-08-01

    Full Text Available En el presente trabajo se ha valorado la posible reducción de la tasa de recidivas en la pancreatitis aguda biliar mediante el tratamiento con ácido ursodeoxicólico (AUC entre el episodio de pancreatitis y el momento de la colecistectomía. Se estudiaron 72 primeros episodios consecutivos de pancreatitis aguda biliar, en pacientes no colecistectomizados, seguidos hasta la cirugía. Los casos se dividieron en grupo A (n = 30, tratados al alta con AUC 10 mg/kg/día, hasta la cirugía, y grupo B o control (n = 42. Se evaluaron las diferencias entre ambos grupos en cuanto a características del paciente, gravedad de la pancreatitis, características de la litiasis y demora hasta la cirugía. Analizamos las recidivas de la pancreatitis entre los grupos con y sin AUC. En el grupo con AUC comparamos la duración del tratamiento entre los pacientes con y sin recidiva de la pancreatitis. Los dos grupos no mostraron diferencias significativas en cuanto a ninguno de los parámetros estudiados. Registramos 7/30 (23,3% recidivas en el grupo AUC, frente a 9/42 (21,4% recidivas en el control (p = 0,85. Dentro del grupo AUC, la duración del tratamiento fue similar entre los casos que recidivaron: 4,9±4,5 meses y los no recidivados: 4,4±1,9 meses (p = 0,78. En nuestra experiencia, el empleo de AUC hasta el momento de la colecistectomía no reduce la incidencia de recidiva en los pacientes tras un primer episodio de pancreatitis aguda biliar. La duración del tratamiento con AUC tampoco parece relacionarse con la aparición o no de recidivas.In the present paper, we evaluate the possible reduction in the rate of relapses in acute biliary pancreatitis through treatment with ursodeoxycholic acid (UCA, between the episode of pancreatitis and the moment of cholecystectomy. We studied 72 consecutive first episodes of acute biliary pancreatitis, in patients who had not yet undergone colecistectomy, followed up until surgery. The cases were divided into group A (n

  6. How to reduce avoidable admissions due to acute diabetes complications?: Interrelation between primary and specialized attention in a diabetes unit ¿Cómo reducir los ingresos evitables por complicaciones agudas de la diabetes?: Interrelación entre atención primaria y especializada en una unidad de diabetes

    Directory of Open Access Journals (Sweden)

    N. V. García-Talavera Espín

    2012-12-01

    Full Text Available Introduction: Type 2 Diabetes Mellitus is a serious health problem. In the year 2030 it will affect 366 million people around the world. Objective: Evaluate the effectiveness of a mixed intervention and reducing the amount and seriousness of acute complications in diabetics from our Health Area. Materials and method: Protocols of action as well as information documents were produced. Diabetes Unit coordinated educational activities in the different support levels of the Area VII of Murcia. Information talks were provided for the people in charge of the Diabetes Unit in every Care Center and Service of the Health Area. Personalized training was provided for patients treated in the differet Care levels. The study comprised three stages. Information leaflets were spread and talks offered to the patient regarding in house handling of hypo and hyper glycemia. Results: A reduction of 39% of the emergencies due to acute non complicated diabetes was achieved, as well as a reduction of 47.6% of hospital admissions. There was a reduction of 67.8% of the amount of total hospital stays for the group of patients under 35 years who were admitted into the hospital due to type 1 or 2 diabetes mellitus that didn't show any complications (GRD295. Conclusions: There was a reduction of more than thirty percent in the emergencies due to acute decompensations in the disease and a significant reduction in the avoidable hospital stays in the young adult, thus improving the patients' life quality and reducing the social cost of the diabetic patient.Introducción: La diabetes mellitus tipo 2 es un problema de salud grave. En el año 2030 afectará a 366 millones de personas en todo el mundo. Objetivo: Evaluar la eficacia de una intervención mixta y reducir la cantidad y gravedad de las complicaciones agudas de la diabetes en nuestra Área de Salud. Material y método: Se diseñaron protocolos de actuación y documentos de información. La Unidad de Diabetes coordin

  7. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  8. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    Science.gov (United States)

    2012-12-01

    De Gasperi 1,2,3, Miguel A. Gama Sosa1,2,3, Soong Ho Kim4, John W. Steele4,5, Michael C. Shaughness6, Eric Maudlin-Jeronimo6, Aaron A. Hall 6...Wetzlar, Ger- many). Immunohistochemical staining was performed as previ- ously described ( Gama Sosa et al., 2010) using a rabbit anti-APP antibody APP369...Traumatic brain injury: football, warfare, and long- term effects. N. Engl. J. Med. 363, 1293–1296. Elder, G. A., Dorr, N. P., De Gasperi, R., Gama Sosa, M. A

  9. Acute sleep restriction reduces insulin sensitivity in adolescent boys

    DEFF Research Database (Denmark)

    Klingenberg, Lars; Chaput, Jean-Philippe; Holmbäck, Ulf;

    2013-01-01

    Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction.......Short sleep duration has been linked to impaired glucose metabolism in many experimental studies. Moreover, studies have reported indications of an increased metabolic stress following sleep restriction....

  10. Airflow-Restricting Mask Reduces Acute Performance in Resistance Exercise

    Directory of Open Access Journals (Sweden)

    Yuri L. Motoyama

    2016-09-01

    Full Text Available Background: The aim of this study was to compare the number of repetitions to volitional failure, the blood lactate concentration, and the perceived exertion to resistance training with and without an airflow-restricting mask. Methods: Eight participants participated in a randomized, counterbalanced, crossover study. Participants were assigned to an airflow-restricting mask group (MASK or a control group (CONT and completed five sets of chest presses and parallel squats until failure at 75% one-repetition-maximum test (1RM with 60 s of rest between sets. Ratings of perceived exertion (RPEs, blood lactate concentrations (Lac−, and total repetitions were taken after the training session. Results: MASK total repetitions were lower than those of the CONT, and (Lac− and MASK RPEs were higher than those of the CONT in both exercises. Conclusions: We conclude that an airflow-restricting mask in combination with resistance training increase perceptions of exertion and decrease muscular performance and lactate concentrations when compared to resistance training without this accessory. This evidence shows that the airflow-restricting mask may change the central nervous system and stop the exercise beforehand to prevent some biological damage.

  11. Airflow-Restricting Mask Reduces Acute Performance in Resistance Exercise

    OpenAIRE

    Yuri L. Motoyama; Gustavo B. Joel; Paulo E. A. Pereira; Gilmar J. Esteves; Azevedo, Paulo H.S.M.

    2016-01-01

    Background: The aim of this study was to compare the number of repetitions to volitional failure, the blood lactate concentration, and the perceived exertion to resistance training with and without an airflow-restricting mask. Methods: Eight participants participated in a randomized, counterbalanced, crossover study. Participants were assigned to an airflow-restricting mask group (MASK) or a control group (CONT) and completed five sets of chest presses and parallel squats until failure at 75%...

  12. Pharm GKB: Kidney Failure, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available iew Alternate Names: Synonym ARF - Acute renal failure; Acute Kidney Failure; Acute Kidney Failures; Acute K...idney Insufficiencies; Acute Kidney Insufficiency; Acute Renal Failure; Acute Renal Failures; Acute... Renal Insufficiencies; Acute Renal Insufficiency; Acute renal failure syndrome, NOS; Failure, Acute... Kidney; Failure, Acute Renal; Failures, Acute Kidney; Failures, Acute Renal; Insufficiencies, Acute... Kidney; Insufficiencies, Acute Renal; Insufficiency, Acute Kidney; Insufficiency, Acute

  13. Infant acute myocarditis mimicking acute myocardial infarction

    Science.gov (United States)

    Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel

    2016-01-01

    Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569

  14. Neuroprotection In Acute Stroke

    Directory of Open Access Journals (Sweden)

    Ali Amini Harandi

    2017-02-01

    Full Text Available Stroke is the leading cause of adult disability and remains the third most common cause of death in industrialized nations. The concept of neuroprotection mainly came from the studies of the pathology and pathophysiology of ischemic brain injury. Greater understanding of the pathophysiology of neuronal damage in ischemic stroke has generated interest in neuroprotection as a management strategy. Neuroprotective agents in stroke treatment, have generated long-term interest that have the potential to preserve brain tissue and improve overall outcome. One arm of neuroprotective agents limits acute injury to neurons in the ischemic penumbra. Many of these agents modulate neuronal receptors to reduce release of excitatory neurotransmitters, which contribute to early neuronal injury. Other neuroprotective agents prevent potentially detrimental events associated with return of blood flow. Returning blood contains leukocytes that may occlude small vessels and release toxic products. In fact they should act targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. The past few decades have produced a plethora of negative neuroprotective trial results. The questions of feasibility and practicability cannot be resolved simultaneously. In the future, optimal therapy may be achieved by combining neuroprotective agents with complementary mechanisms. Relevant areas of interest include the search for safe and effective treatment strategies that combine neuroprotection reperfusion, better use of advanced brain imaging for patient selection, and wider implementation of prehospital conducted clinical trials.

  15. Cell adhesion signa