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Sample records for dose-dependently reduce incidence

  1. Diallyl disulfide reduced dose-dependently the number of lymphocyte subsets and monocytes in rats.

    PubMed

    Hashizume, Yoko; Shirato, Ken; Abe, Ikumi; Kobayashi, Ayumu; Mitsuhashi, Ryosuke; Shiono, Chikako; Sato, Shogo; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2012-01-01

    Diallyl disulfide (DADS) is a major sulfur compound of garlic, and exerts anti-inflammatory, immune-modulatory, and enhancing sympathetic activity effects. However, it still remains unclear how DADS affects the distribution of white blood cell subsets, which is essential to execute effective immune responses and partially regulated by adrenal glucocorticoids. Therefore, we examined the dose-dependent effects of DADS administration on the circulating number of white blood cells (WBCs) and lymphocyte subsets, and plasma corticosterone concentration in rats. Male 10-wk-old Sprague Dawley rats were divided into the DADS-free and DADS-orally administered (dose=10, 20, and 40 mg/kg BW) groups. Blood samples were collected from the tail vein at 0, 1, 2, 4, and 6 h after the administration. DADS administration decreased dose- and time-dependently the circulating number of total WBCs, total lymphocytes, and monocytes. Within the lymphocyte subsets, the circulating number of T-lymphocytes and B-lymphocytes was significantly reduced 4 h after DADS administration in a dose-dependent manner, although that of natural killer (NK) cells was not affected. On the other hand, although DADS administration did not significantly change the circulating number of neutrophils, the circulating number of eosinophils and basophils showed a decreasing tendency after DADS administration. In contrast, plasma corticosterone concentration was increased 2 h after DADS administration in a dose-dependent manner. These results suggest that DADS administration reduces the circulating number of monocytes and lymphocytes, including especially acquired immune cells, via the action of corticosterone, and the effects are induced in a dose-dependent manner.

  2. Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats.

    PubMed

    Schmeichel, Brooke E; Barbier, Estelle; Misra, Kaushik K; Contet, Candice; Schlosburg, Joel E; Grigoriadis, Dimitri; Williams, John P; Karlsson, Camilla; Pitcairn, Caleb; Heilig, Markus; Koob, George F; Vendruscolo, Leandro F

    2015-03-13

    The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence.

  3. Hypocretin Receptor 2 Antagonism Dose-Dependently Reduces Escalated Heroin Self-Administration in Rats

    PubMed Central

    Schmeichel, Brooke E; Barbier, Estelle; Misra, Kaushik K; Contet, Candice; Schlosburg, Joel E; Grigoriadis, Dimitri; Williams, John P; Karlsson, Camilla; Pitcairn, Caleb; Heilig, Markus; Koob, George F; Vendruscolo, Leandro F

    2015-01-01

    The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence. PMID:25367502

  4. Dose-dependent effect of caffeine on reducing leg muscle pain during cycling exercise is unrelated to systolic blood pressure.

    PubMed

    O'Connor, Patrick J; Motl, Robert W; Broglio, Steven P; Ely, Matthew R

    2004-06-01

    This double-blind, within-subjects experiment examined the effects of ingesting two doses of caffeine on perceptions of leg muscle pain and blood pressure during moderate intensity cycling exercise. Low caffeine consuming college-aged males (N=12) ingested one of two doses of caffeine (5 or 10 mg.kg(-1) body weight) or placebo and 1 h later completed 30 min of moderate intensity cycling exercise (60% VO2peak). The order of drug administration was counter-balanced. Resting blood pressure and heart rate were recorded immediately before and 1 h after drug administration. Perceptions of leg muscle pain as well as work rate, blood pressure, heart rate, and oxygen uptake (VO2) were recorded during exercise. Caffeine increased resting systolic pressure in a dose-dependent fashion but these blood pressure effects were not maintained during exercise. Caffeine had a significant linear effect on leg muscle pain ratings [F(2,22)=14.06; P < 0.0001; eta2=0.56 ]. The mean (+/-SD) pain intensity scores during exercise after ingesting 10 mg.kg(-1) body weight caffeine, 5 mg.kg(-1) body weight caffeine, and placebo were 2.1+/-1.4, 2.6+/-1.5, and 3.5+/-1.7, respectively. The results support the conclusion that caffeine ingestion has a dose-response effect on reducing leg muscle pain during exercise and that these effects do not depend on caffeine-induced increases in systolic blood pressure during exercise.

  5. Dietary trans-10,cis-12 CLA reduces murine collagen-induced arthritis in a dose-dependent manner.

    PubMed

    Huebner, Shane M; Olson, Jake M; Campbell, James P; Bishop, Jeffrey W; Crump, Peter M; Cook, Mark E

    2014-02-01

    Dietary trans-10,cis-12 (t10c12) conjugated linoleic acid (CLA) has been shown to reduce inflammation in a murine collagen-induced arthritis (CA) model. To understand the anti-inflammatory potential of t10c12-CLA in the diet, the minimum dose of pure dietary t10c12-CLA capable of reducing CA was investigated. Because plasma inflammatory cytokines often do not reflect the progression of late-stage arthritis, inflamed tissue cytokine concentrations were also investigated in relation to increasing dietary t10c12-CLA amounts. Mice were randomly assigned to the following dietary treatments upon the establishment of arthritis: corn oil (CO) or 0.125%, 0.25%, 0.375%, or 0.5% t10c12-CLA (wt:wt) for 84 d. Sham mice (no arthritis) were fed CO and served as controls. Arthritic paw score, based on subjective assessment of arthritic severity, and paw thickness decreased linearly overall [16-65% (P < 0.001) and 0.5-12% (P < 0.001), respectively] as dietary t10c12-CLA increased (P < 0.001, R(2) < 0.81). Increasing dietary t10c12-CLA was associated with a decrease in plasma interleukin (IL)-1β at days 21 and 42 compared with CO-fed arthritic mice, such that mice fed ≥0.25% t10c12-CLA had IL-1β concentrations that were similar to sham mice. Plasma cytokines returned to sham mice concentrations by day 63 regardless of treatment; however, an arthritis-induced elevation in paw IL-1β decreased linearly as dietary t10c12-CLA concentrations increased at day 84 (P = 0.007, R(2) = 0.92). Similarly, increasing dietary t10c12-CLA linearly decreased paw tumor necrosis factor (TNF)-α (P = 0.05, R(2) = 0.70). In conclusion, ≥0.125% t10c12-CLA dose-dependently reduced inflammation in a murine CA model.

  6. A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer's disease.

    PubMed

    Moore, Kaitlin M; Girens, Renee E; Larson, Sara K; Jones, Maria R; Restivo, Jessica L; Holtzman, David M; Cirrito, John R; Yuede, Carla M; Zimmerman, Scott D; Timson, Benjamin F

    2016-01-01

    Physical activity has long been hypothesized to influence the risk and pathology of Alzheimer's disease. However, the amount of physical activity necessary for these benefits is unclear. We examined the effects of three months of low and high intensity exercise training on soluble Aβ40 and Aβ42 levels in extracellular enriched fractions from the cortex and hippocampus of young Tg2576 mice. Low (LOW) and high (HI) intensity exercise training animals ran at speeds of 15m/min on a level treadmill and 32 m/min at a 10% grade, respectively for 60 min per day, five days per week, from three to six months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. Soleus muscle citrate synthase activity increased by 39% in the LOW group relative to SED, and by 71% in the HI group relative to LOW, indicating an exercise training effect in these mice. Soluble Aβ40 concentrations decreased significantly in an exercise training dose-dependent manner in the cortex. In the hippocampus, concentrations were decreased significantly in the HI group relative to LOW and SED. Soluble Aβ42 levels also decreased significantly in an exercise training dose-dependent manner in both the cortex and hippocampus. Five proteins involved in Aβ clearance (neprilysin, IDE, MMP9, LRP1 and HSP70) were elevated by exercise training with its intensity playing a role in each case. Our data demonstrate that exercise training reduces extracellular soluble Aβ in the brains of Tg2576 mice in a dose-dependent manner through an up-regulation of Aβ clearance.

  7. Ventricular arrhythmia incidence in the rat is reduced by naloxone.

    PubMed

    Pugsley, M K; Hayes, E S; Wang, W Q; Walker, M J A

    2015-07-01

    This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32 μmol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32 μmol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels.

  8. Flaxseed reduces the pro-carcinogenic microenvironment in the ovaries of normal hens by altering the prostaglandin and estrogen pathways in a dose dependent manner

    PubMed Central

    Dikshit, Anushka; Filho, Manoel Adrião Gomes; Eilati, Erfan; McGee, Stacey; Small, Carrie; Gao, Chunqi; Klug, Thomas; Hales, Dale Buchanan

    2015-01-01

    The objective of this study was to find the optimum dose of flaxseed that would decrease prostaglandins and alter estrogen pathway endpoints implicated in ovarian cancer. Fifty 1.5-year-old chickens per group were fed different percentages of flaxseed (5%, 10%, 15%) for four months then sacrificed to collect blood and tissues. Levels of flaxseed lignan metabolites, Enterolactone (EL) and Enterodiol (ED), were measured in the serum, liver and ovaries by LC-MS/MS while omega-3 and 6 fatty acid levels were measured by GC. Effect of varying flaxseed doses was assessed by measuring levels of prostaglandin E2, estrogen metabolites (16-hydroxyestrone (16-OHE1), 2-hydroxyestrone (2-OHE1)) and analyzing the expression of E2 metabolizing enzymes (CYP3A4, CYP1B1, CYP1A1) and ERα in the ovaries. The ratio of omega-3 fatty acids/ omega-6 fatty acids increased with increase in flaxseed supplementation of diet corresponding to a dose dependent decrease in COX-2 protein and prostaglandin E2 levels. EL and ED increased in the liver, ovary and serum with increasing concentrations of flaxseed. Flaxseed decreased the expression of ERα in the ovary. The ratio of 2-hydroxyestrone to 16-hydroxyestrone in the serum increased significantly in the 15% flaxseed diet with a corresponding increase in CYP1A1 in the liver and a decrease in CYP3A4 in the ovary, respectively. CYP1B1 mRNA also decreased with flaxseed diet in the ovary. The 15% flaxseed supplemented diet significantly decreased inflammatory prostaglandin E2, ERα, CYP3A4, CYP1B1 and 16-OHE1 while it increased CYP1A1 and 2-OHE1, thus reducing the inflammatory and pro-carcinogenic microenvironment of the ovary. PMID:25850566

  9. Flaxseed reduces the pro-carcinogenic micro-environment in the ovaries of normal hens by altering the PG and oestrogen pathways in a dose-dependent manner.

    PubMed

    Dikshit, Anushka; Gomes Filho, Manoel Adrião; Eilati, Erfan; McGee, Stacey; Small, Carrie; Gao, Chunqi; Klug, Thomas; Hales, Dale Buchanan

    2015-05-14

    The objective of the present study was to find the optimum dose of flaxseed that would decrease PG and alter oestrogen pathway endpoints implicated in ovarian cancer. In the study, four groups of fifty 1.5-year-old chickens were fed different amounts of flaxseed (0, 5, 10 or 15% of their total diet) for 4 months and were then killed to collect blood and tissues. Levels of flaxseed lignan metabolites, Enterolactone (EL) and Enterodiol (ED) were measured in the serum, liver and ovaries by liquid chromatography-MS/MS, and n-3 and n-6 fatty acid (FA) levels were measured by GC. The effects of the varied flaxseed doses were assessed by measuring levels of PGE2 and oestrogen metabolites (16-hydroxyestrone (16-OHE1) and 2-hydroxyestrone (2-OHE1)) as well as by analysing the expression of the oestradiol metabolising enzymes CYP3A4 (cytochrome p450, family 3, subfamily A, polypeptide 4), CYP1B1 (cytochrome p450, family 1, subfamily B, polypeptide 1) and CYP1A1 (cytochrome p450, family 1, subfamily A, polypeptide 1) and that of oestrogen receptor α (ERα) in the ovaries. The ratio of n-3:n-FA increased with an increase in flaxseed supplementation and corresponded to a dose-dependent decrease in cyclo-oxygenase-2 protein and PGE2 levels. EL and ED increased in the serum, liver and ovaries with increased concentrations of flaxseed. Flaxseed decreased the expression of ERα in the ovaries. The ratio of 2-OHE1:16-OHE1 in the serum increased significantly in the 15% flaxseed diet, and there was a corresponding increase in CYP1A1 in the liver and decrease in CYP3A4 in the ovaries. CYP1B1 mRNA also decreased with flaxseed diet in the ovaries. The 15% flaxseed-supplemented diet significantly decreased inflammatory PGE2, ERα, CYP3A4, CYP1B1 and 16-OHE1, but it increased CYP1A1 and 2-OHE1, which thus reduced the inflammatory and pro-carcinogenic micro-environment of the ovaries.

  10. Dose-dependent S-allyl cysteine ameliorates multiple sclerosis disease-related pathology by reducing oxidative stress and biomerkers of dysbiosis in experimental autoimmune encephalomyelitis.

    PubMed

    Escribano, B M; Luque, E; Aguilar-Luque, M; Feijóo, M; Caballero-Villarraso, J; Torres, L A; Ramirez, V; García-Maceira, F I; Agüera, E; Santamaria, A; Túnez, I

    2017-09-19

    Garlic is a component of the Mediterranean diet. S-allyl cysteine (SAC), the most common organosulphur present in garlic, possesses neuroprotective properties. This investigation was performed to evaluate the dose-dependent protective action of SAC on oxidative damage, inflammation and gut microbiota alterations biomarkers. Experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS) was induced by the myelin oligodendrocyte glycoprotein (MOG), whose effects were quantified by examining the changes in: clinical score, lipid peroxidation products, carbonylated proteins, glutathione system, tumor necrosis factor alpha (TNFα), and lipopolysaccharide membrane bacteria (LPS). Our results reveal that MOG induces paralysis, oxidative damage and increases in LPS binding protein (LBP) and LPS levels. In this work, two doses of SAC were compared with two dose of N-acetyl cysteine (NAC). SAC was more effective than NAC and it prevented the harmful effects induced by MOG more effectively at the dose of 50mg/kg than that of 18mg/kg. Surprisingly, NAC increases LBP levels while SAC had not such negative effect. In conclusion the data show the ability of SAC to modify EAE evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Use of a dose-dependent follow-up protocol and mechanisms to reduce patients and staff radiation exposure in congenital and structural interventions.

    PubMed

    Sawdy, Jaclynn M; Kempton, Tanya Maria; Olshove, Vincent; Gocha, Mark; Chisolm, Joanne L; Hill, Sharon L; Kirk, Amy; Cheatham, John P; Holzer, Ralf J

    2011-07-01

    Increasingly complex structural/congenital cardiac interventions require efforts at reducing patient/staff radiation exposure. Standard follow-up protocols are often inadequate in detecting all patients that may have sustained radiation burns. Single-center retrospective chart review divided into four intervals. Phase 1 (07/07-06/08, 413 procedures (proc)): follow-up based on fluoroscopy time only; frame rate for digital acquisition (DA) 30 fps, and fluoroscopy (FL) 30 fps. Dose-based follow-up was used for phase 2-4. Phase 2 (07/08-08/09, 458 proc): DA: 30 fps, FL: 15 fps. Phase 3 (09/09-06/10, 350 proc): DA: 15-30 fps, FL: 15 fps, use of added radiation protection drape. Phase 4 (07/10-10/10, 89 proc): DA: 15-30 fps, FL: 15 fps, superior noise reduction filter (SNRF) with high-quality fluoro-record capabilities. There was a significant reduction in the median cumulative air kerma between the four study periods (710 mGy vs. 566 mGy vs. 498 mGy vs. 241 mGy, P < 0.001), even though the overall fluoroscopy times remained very similar (25 min vs. 26 min vs. 26 min vs. 23 min, P = 0.957). There was a trend towards lower physician radiation exposure over the four study periods (137 mrem vs. 126 mrem vs. 108 mrem vs. 59 mrem, P = 0.15). Fifteen patients with radiation burns were identified during the study period. When changing to a dose-based follow-up protocol (phase 1 vs. phase 2), there was a significant increase in the incidence of detected radiation burns (0.5% vs. 2%, P = 0.04). Dose-based follow-up protocols are superior in detecting radiation burns when compared to fluoroscopy time-based protocols. Frame rate reduction of fluoroscopy and cine acquisition and use of modified imaging equipment can achieve a significant reduction to patient/staff exposure. Copyright © 2011 Wiley-Liss, Inc.

  12. Reducing Incidents of Cheating in Adolescence.

    ERIC Educational Resources Information Center

    Bopp, Mary; Gleason, Patricia; Misicka, Stacey

    This report describes a program implemented to raise the awareness of the dramatic increases of reported academic cheating, to influence the attitudes of the targeted students towards cheating, and ultimately to reduce incidents of cheating in the targeted classrooms. The targeted populations consisted of middle school students in growing…

  13. The omega-3 fatty acid DHA dose-dependently reduces atherosclerosis: a putative role for F4-neuroprostanes a specific class of peroxidized metabolites

    USDA-ARS?s Scientific Manuscript database

    Objective. Consumption of long chain omega-3 polyunsaturated fatty acids is associated with reduced risks of cardiovascular disease but the role of their oxygenated metabolites remains unclear. We hypothesized that peroxidized metabolites of docosahexaenoic acid (DHA, 22:6 n-3) could play a role in ...

  14. The Placental Variant of Human Growth Hormone Reduces Maternal Insulin Sensitivity in a Dose-Dependent Manner in C57BL/6J Mice.

    PubMed

    Liao, Shutan; Vickers, Mark H; Stanley, Joanna L; Ponnampalam, Anna P; Baker, Philip N; Perry, Jo K

    2016-03-01

    The human placental GH variant (GH-V) is secreted continuously from the syncytiotrophoblast layer of the placenta during pregnancy and is thought to play a key role in the maternal adaptation to pregnancy. Maternal GH-V concentrations are closely related to fetal growth in humans. GH-V has also been proposed as a potential candidate to mediate insulin resistance observed later in pregnancy. To determine the effect of maternal GH-V administration on maternal and fetal growth and metabolic outcomes during pregnancy, we examined the dose-response relationship for GH-V administration in a mouse model of normal pregnancy. Pregnant C57BL/6J mice were randomized to receive vehicle or GH-V (0.25, 1, 2, or 5 mg/kg · d) by osmotic pump from gestational days 12.5 to 18.5. Fetal linear growth was slightly reduced in the 5 mg/kg dose compared with vehicle and the 0.25 mg/kg groups, respectively, whereas placental weight was not affected. GH-V treatment did not affect maternal body weights or food intake. However, treatment with 5 mg/kg · d significantly increased maternal fasting plasma insulin concentrations with impaired insulin sensitivity observed at day 18.5 as assessed by homeostasis model assessment. At 5 mg/kg · d, there was also an increase in maternal hepatic GH receptor/binding protein (Ghr/Ghbp) and IGF binding protein 3 (Igfbp3) mRNA levels, but GH-V did not alter maternal plasma IGF-1 concentrations or hepatic Igf-1 mRNA expression. Our findings suggest that at higher doses, GH-V treatment can cause hyperinsulinemia and is a likely mediator of the insulin resistance associated with late pregnancy.

  15. Influenza vaccine oculorespiratory syndrome incidence is reduced in HIV.

    PubMed

    Cooper, Curtis; Thorne, Anona

    2011-10-19

    Clinical experience suggests Oculorespiratory Syndrome (ORS) following influenza vaccination is rare in HIV but this is not well evaluated. We assessed ORS incidence in a randomized influenza vaccine trial of HIV participants. The overall incidence was 0.8% suggesting that influenza vaccine ORS incidence is reduced in HIV.

  16. DNA vaccines expressing the duck hepatitis B virus surface proteins lead to reduced numbers of infected hepatocytes and protect ducks against the development of chronic infection in a virus dose-dependent manner.

    PubMed

    Miller, Darren S; Kotlarski, Ieva; Jilbert, Allison R

    2006-07-20

    We tested the efficacy of DNA vaccines expressing the duck hepatitis B virus (DHBV) pre-surface (pre-S/S) and surface (S) proteins in modifying the outcome of infection in 14-day-old ducks. In two experiments, Pekin Aylesbury ducks were vaccinated on days 4 and 14 of age with plasmid DNA vaccines expressing either the DHBV pre-S/S or S proteins, or the control plasmid vector, pcDNA1.1Amp. All ducks were then challenged intravenously on day 14 of age with 5 x 10(7) or 5 x 10(8) DHBV genomes. Levels of initial DHBV infection were assessed using liver biopsy tissue collected at day 4 post-challenge (p.c.) followed and immunostained for DHBV surface antigen to determine the percentage of infected hepatocytes. All vector vaccinated ducks challenged with 5 x 10(7) and 5 x 10(8) DHBV genomes had an average of 3.21% and 20.1% of DHBV-positive hepatocytes respectively at day 4 p.c. and 16 out of 16 ducks developed chronic DHBV infection. In contrast, pre-S/S and S vaccinated ducks challenged with 5 x 10(7) DHBV genomes had reduced levels of initial infection with an average of 1.38% and 1.93% of DHBV-positive hepatocytes at day 4 p.c. respectively and 10 of 18 ducks were protected against chronic infection. The pre-S/S and the S DNA vaccinated ducks challenged with 5 x 10(8) DHBV genomes had an average of 31.5% and 9.2% of DHBV-positive hepatocytes on day 4 p.c. respectively and only 4 of the 18 vaccinated ducks were protected against chronic infection. There was no statistically significant difference in the efficacy of the DHBV pre-S/S or S DNA vaccines. In conclusion, vaccination of young ducks with DNA vaccines expressing the DHBV pre-S/S and S proteins induced rapid immune responses that reduced the extent of initial DHBV infection in the liver and prevented the development of chronic infection in a virus dose-dependent manner.

  17. Prophylactic ketamine reduces incidence of postanaesthetic shivering.

    PubMed

    Gecaj-Gashi, A; Hashimi, M; Sada, F; Salihu, S; Terziqi, H

    2010-01-01

    General anesthesia influences the thermoregulatory process. The aim of this study was to compare the efficacy of low-dose prophylactic ketamine with that of placebo in preventing postoperative shivering. A prospective randomized double-blind study involved 76 ASA I and II patients undergoing general anesthesia that was expected to last no more than 2 hours. Patients were randomly allocated to receive normal saline (Group P, n = 33) or ketamine 0.5 mg kg1 (Group K, n = 33) intravenously 20 min before completion of surgery. The anesthesia was induced with propofol 2.5-3.0 mg kg(-1) and fentanyl (2-3 microg kg(-1)), atracurium 0.5 mg kg(-1) was given to facilitate orotracheal intubation. It was maintained with propofol (510 mg kg(-1) hr(-1)), fentanyl up to (5 microg x kg1 x h1) and a mixture of nitrous oxide/oxygen (2:1). Ambient temperature was maintained at 20 degrees-22 degrees C with constant humidity. Postoperative shivering in the recovery room was evaluated according to 5 point scale of Wrench. The two groups did not differ significantly regarding patient characteristics. The number of patients shivering on arrival in the recovery room, and at 10 and 20 min after operation was significantly less in Groups K than in Group P. In group P 36% have had shivering in TO whereas in group K 6%, in T10 45% in group P whereas 18% in group K. In T20 24% in group P have had shivering compared with 6% in group K, whereas in T30 9% in group P compared with 0% in group K. The incidence of free Postanaesthetic shivering (no shivering) on arrival in the recovery room T0 was: 63.6% in group P compared with 90.9 % in group K. The postoperative hemodynamic parameters were similar in the two groups. Active warming was not required in group K but was needed in 8 cases in group P. None of patients had episodes of O2 desaturation or respiratory depression during the study period. No hallucinations, delirium, nausea, vomiting, hypertension, tachycardia, and feeling like walking in the

  18. Propofol dose-dependently increases bite force during sedation.

    PubMed

    Tsai, Pung-Fei; Matsuura, Nobuyuki; Kaneko, Yuzuru; Ichinohe, Tatsuya

    2011-11-01

    The purpose of this study was to investigate the dose-dependent effects of propofol on cognitive function and muscle power as well as vital functions. Twenty volunteers participated in this study. Each subject underwent 2 experiments in a randomized crossover manner (propofol group and control group). After control data were obtained, propofol at predicted effect site concentrations of 0.4, 0.8, 1.2, 1.6, and 2.0 μg/mL was infused in the propofol group using a target controlled infusion system. Heart rate, noninvasive blood pressure, arterial oxygen saturation, respiratory rate, and bispectral index value were monitored. Observer's assessment of alertness/sedation and the correct answer rate of the Stroop color word test were assessed. Muscle power, grip strength and bite force were measured. In the propofol group, the bispectral index value and observer's assessment of alertness/sedation scale dose-dependently reduced. At the predicted effect site propofol concentration of 2.0 μg/mL, 6 subjects became unconscious. The correct answer rate of Stroop color word test reduced at the predicted effect site propofol concentration of 1.6 and 2.0 μg/mL. Grip strength slightly increased at the predicted effect site propofol concentration of 1.2 μg/mL or less, and bite force dose-dependently increased. At the predicted effect site propofol concentration of 2.0 μg/mL, both muscle powers began to decrease. Bite force dose-dependently increased and reached the maximum at the predicted effect site propofol concentration of 1.6 μg/mL. Although the detailed mechanisms are unknown, propofol dose-dependently increases bite force during minimal and moderate sedation. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  19. High incidence of reduced plasma HDL cholesterol in diabetic patients treated with rosiglitazone and fibrate.

    PubMed

    Keidar, Shlomo; Guttmann, Hadassa; Stam, Tamar; Fishman, Ilana; Shapira, Chen

    2007-11-01

    A paradoxical plasma HDL-Cholesterol (HDL-C) reducing effect following combined fibrate and thiazolidinediones (TZDs) therapy was recently reported in occasional cases. As HDL-C level is inversely related to cardiovascular disease (CVD) risk, we have studied the incidence of reduced HDL-C level following mono- and combined therapy with these drugs in a large diabetic population. This study was designed as a retrospective 5-year study. Lipid profile records of 54 000 diabetic patients were searched for transient reduction of HDL-C to levels lower than 17 mg/dL, which was correlated with fibrates and/or TZD treatment. Transient reduction in plasma HDL-C to values lower than 17 mg/dL was observed in 0.02% (2/11 175) of the patients treated with fibrates alone, none of the rosiglitazone-treated patients (0/3213) and in 1.39% (9/649) of patients treated with combination of fibrate and TZD. HDL-C lowering effect was reversible upon stopping either fibrate or rosiglitazone and in some patients it occurred within 2 weeks. In two of the patients, the effect was dose-dependent. Severe reduction in plasma HDL-C is not rare when TZD and fibrates are co-administrated to diabetic hyperlipidemic patients. As low plasma HDL cholesterol is a risk factor for CVD, the physician should be alert to this phenomenon.

  20. Ethosuximide and phenytoin dose-dependently attenuate acute nonconvulsive seizures after traumatic brain injury in rats.

    PubMed

    Mountney, Andrea; Shear, Deborah A; Potter, Brittney; Marcsisin, Sean R; Sousa, Jason; Melendez, Victor; Tortella, Frank C; Lu, Xi-Chun M

    2013-12-01

    Acute seizures frequently occur following severe traumatic brain injury (TBI) and have been associated with poor patient prognosis. Silent or nonconvulsive seizures (NCS) manifest in the absence of motor convulsion, can only be detected via continuous electroencephalographic (EEG) recordings, and are often unidentified and untreated. Identification of effective anti-epileptic drugs (AED) against post-traumatic NCS remains crucial to improve neurological outcome. Here, we assessed the anti-seizure profile of ethosuximide (ETX, 12.5-187.5 mg/kg) and phenytoin (PHT, 5-30 mg/kg) in a spontaneously occurring NCS model associated with penetrating ballistic-like brain injury (PBBI). Rats were divided between two drug cohorts, PHT or ETX, and randomly assigned to one of four doses or vehicle within each cohort. Following PBBI, NCS were detected by continuous EEG monitoring for 72 h post-injury. Drug efficacy was evaluated on NCS parameters of incidence, frequency, episode duration, total duration, and onset latency. Both PHT and ETX attenuated NCS in a dose-dependent manner. In vehicle-treated animals, 69-73% experienced NCS (averaging 9-10 episodes/rat) with average onset of NCS occurring at 30 h post-injury. Compared with control treatment, the two highest PHT and ETX doses significantly reduced NCS incidence to 13-40%, reduced NCS frequency (1.8-6.2 episodes/rat), and delayed seizure onset: <20% of treated animals exhibited NCS within the first 48 h. NCS durations were also dose-dependently mitigated. For the first time, we demonstrate that ETX and PHT are effective against spontaneously occurring NCS following PBBI, and suggest that these AEDs may be effective at treating post-traumatic NCS.

  1. Ethosuximide and Phenytoin Dose-Dependently Attenuate Acute Nonconvulsive Seizures after Traumatic Brain Injury in Rats

    PubMed Central

    Shear, Deborah A.; Potter, Brittney; Marcsisin, Sean R.; Sousa, Jason; Melendez, Victor; Tortella, Frank C.; Lu, Xi-Chun M.

    2013-01-01

    Abstract Acute seizures frequently occur following severe traumatic brain injury (TBI) and have been associated with poor patient prognosis. Silent or nonconvulsive seizures (NCS) manifest in the absence of motor convulsion, can only be detected via continuous electroencephalographic (EEG) recordings, and are often unidentified and untreated. Identification of effective anti-epileptic drugs (AED) against post-traumatic NCS remains crucial to improve neurological outcome. Here, we assessed the anti-seizure profile of ethosuximide (ETX, 12.5–187.5 mg/kg) and phenytoin (PHT, 5–30 mg/kg) in a spontaneously occurring NCS model associated with penetrating ballistic-like brain injury (PBBI). Rats were divided between two drug cohorts, PHT or ETX, and randomly assigned to one of four doses or vehicle within each cohort. Following PBBI, NCS were detected by continuous EEG monitoring for 72 h post-injury. Drug efficacy was evaluated on NCS parameters of incidence, frequency, episode duration, total duration, and onset latency. Both PHT and ETX attenuated NCS in a dose-dependent manner. In vehicle-treated animals, 69–73% experienced NCS (averaging 9–10 episodes/rat) with average onset of NCS occurring at 30 h post-injury. Compared with control treatment, the two highest PHT and ETX doses significantly reduced NCS incidence to 13–40%, reduced NCS frequency (1.8–6.2 episodes/rat), and delayed seizure onset: <20% of treated animals exhibited NCS within the first 48 h. NCS durations were also dose-dependently mitigated. For the first time, we demonstrate that ETX and PHT are effective against spontaneously occurring NCS following PBBI, and suggest that these AEDs may be effective at treating post-traumatic NCS. PMID:23822888

  2. Finasteride Reduces the Risk of Incident Clinical Benign Prostatic Hyperplasia

    PubMed Central

    Parsons, J. Kellogg; Schenk, Jeannette M.; Arnold, Kathryn B.; Messer, Karen; Till, Cathee; Thompson, Ian M.; Kristal, Alan R.

    2014-01-01

    Background Despite the high prevalence of clinical benign prostatic hyperplasia (BPH) among older men, there remains a notable absence of studies focused on BPH prevention. Objective To determine if finasteride prevents incident clinical BPH in healthy older men. Design, setting, and participants Data for this study are from the Prostate Cancer Prevention Trial. After excluding those with a history of BPH diagnosis or treatment, or an International Prostate Symptom Score (IPSS) ≥8 at study entry, 9253 men were available for analysis. Outcome measurements and statistical analysis The primary outcome was incident clinical BPH, defined as the initiation of medical treatment, surgery, or sustained, clinically significant urinary symptoms (IPSS >14). Finasteride efficacy was estimated using Cox proportional regression models to generate hazards ratios (HRs). Results and limitations Mean length of follow-up was 5.3 yr. The rate of clinical BPH was 19 per 1000 person-years in the placebo arm and 11 per 1000 person-years in the finasteride arm (p < 0.001). In a covariate-adjusted model, finasteride reduced the risk of incident clinical BPH by 40% (HR: 0.60; 95% confidence interval, 0.51–0.69; p < 0.001). The effect of finasteride on incident clinical BPH was attenuated in men with a body mass index ≥30 kg/m2 (pinteraction = 0.04) but otherwise did not differ significantly by physical activity, age, race, current diabetes, or current smoking. The post hoc nature of the analysis is a potential study limitation. Conclusions Finasteride substantially reduces the risk of incident clinical BPH in healthy older men. These results should be considered in formulating recommendations for the use of finasteride to prevent prostate diseases in asymptomatic older men. PMID:22459892

  3. Reducing the incidence of back pain: student nurses' recommendations.

    PubMed

    Barnes, Abbie Franklin

    National Back Care week (3-9 October 2009) embraced the promotion of back care. However, over a decade has pasted since the RCN Safer Patient Handling campaign (1996), and reports continue to highlight the high incidence of back pain within the nursing profession. This article reveals student nurses' experiences of back pain and their recommendations to reduce the incidence of back pain in the workplace. Statistics by the Department of Health (2002) report 24% of NHS staff experience back pain, reflecting the high prevalence of this study, where 34% of student nurses experience back pain during their clinical placement. The student nurses' recommendations clearly underpin the evidence-based research previously published, and as our future workforce the student nurses' voices need to be heard.

  4. Reduced Risk of Incident Kidney Cancer from Walking and Running

    PubMed Central

    Williams, Paul T.

    2013-01-01

    Purpose Test whether incident kidney cancer risk is associated with exercise energy expenditure (i.e., metabolic equivalents, 1 MET) when calculated from distance walked or run. Methods Hazard ratios (HR) and 95% confidence intervals (95%CI) from Cox proportional hazard analyses of self-reported physician-diagnosed incident kidney cancer vs. MET-hours/wk in 91,820 subjects recruited between 1991 and 1993 (7.7 yr follow-up of 42,833 subjects) and between 1998 and 1999 (6.4 yr follow-up of 33,053 subjects) as part of the National Runners' Health Study and between 1998 and 1999 as part of the National Walkers' Health Study (5.7 yr follow-up of 15,934 subjects). Results Fifty-two incident cancers were reported. Age- and sex-adjusted risk declined 1.9% per MET-hour/wk run or walked (HR: 0.981; 95%CI: 0.964 to 0.997, P=0.02). Compared to walking or running below guidelines levels (<7.5 MET-hours/wk), the risk for incident kidney cancer was 61% lower for meeting the guidelines (HR: 0.39, 95%CI: 0.11 to 1.08, P=0.07 for 7.5 to 12.5 MET-hours/wk), 67% lower for exercising one to two-times the recommended level (HR: 0.33; 95%CI: 0.15 to 0.72, P=0.005 for 12.6 to 25.1 MET-hours/wk), and 76.3% lower for exercising ≥2-times the recommended level (HR: 0.24; 95%CI: 0.11 to 0.52, P=0.0005 for ≥25.2 MET-hours/wk). Incident kidney cancer risk also increased in association with baseline BMI (P=0.002), smoking (P=0.02), and hypertensive (P=0.007) and diabetes medication use (P=0.01), however, exercise-associated reductions in kidney cancer risk persisted for 12.6 to 25.1 MET-hours/wk (HR: 0.35, P=0.01), and ≥ 25.2 MET-hours/wk (HR: 0.29, P=0.004) vis-à-vis <7.5 MET-hours/wk when also adjusted for BMI, hypertension, diabetes, and pack-years smoked. Conclusion Running and walking may reduce incident kidney cancer risk independent of its other known risk factors. PMID:23863620

  5. Reduced risk of incident kidney cancer from walking and running.

    PubMed

    Williams, Paul T

    2014-02-01

    This study aimed to test whether incident kidney cancer risk is associated with exercise energy expenditure (i.e., metabolic equivalents, 1 MET) when calculated from distance walked or run. Hazard ratios (HR) and 95% confidence intervals (95% CI) from Cox proportional hazard analyses of self-reported physician-diagnosed incident kidney cancer versus MET-hours per week in 91,820 subjects recruited between 1991 and 1993 (7.7 yr follow-up of 42,833 subjects) and between 1998 and 1999 (6.4 yr follow-up of 33,053 subjects) as part of the National Runners' Health Study and between 1998 and 1999 as part of the National Walkers' Health Study (5.7 yr follow-up of 15,934 subjects). Fifty-two incident cancers were reported. Age- and sex-adjusted risk declined 1.9% per MET-hour per week run or walked (HR = 0.981, 95% CI = 0.964-0.997, P = 0.02). Compared with walking or running below guidelines levels (<7.5 MET·h·wk(-1)), the risk for incident kidney cancer was 61% lower for meeting the guidelines (HR = 0.39, 95% CI = 0.11-1.08, P = 0.07 for 7.5-12.5 MET·h·wk(-1)), 67% lower for exercising one to two times the recommended level (HR = 0.33; 95% CI = 0.15-0.72, P = 0.005 for 12.6-25.1 MET·h·wk(-1)), and 76.3% lower for exercising two times or more the recommended level (HR = 0.24, 95% CI = 0.11-0.52, P = 0.0005 for ≥ 25.2 MET·h·wk(-1)). Incident kidney cancer risk also increased in association with baseline body mass index (P = 0.002), smoking (P = 0.02), and hypertensive (P = 0.007) and diabetes medication use (P = 0.01); however, exercise-associated reductions in kidney cancer risk persisted for 12.6-25.1 MET·h·wk(-1) (HR = 0.35, P = 0.01) and ≥ 25.2 MET·h·wk(-1) (HR = 0.29, P = 0.004) vis-à-vis <7.5 MET·h·wk(-1) when also adjusted for body mass index, hypertension, diabetes, and pack-years smoked. Running and walking may reduce incident kidney cancer risk independent of its other known risk factors.

  6. Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease?

    PubMed Central

    McLachlan, D R; Kruck, T P; Lukiw, W J; Krishnan, S S

    1991-01-01

    Although the cause of Alzheimer's disease (AD) remains unknown there is mounting evidence that implicates aluminum as a toxic environmental factor of considerable importance. Four independent lines of evidence--laboratory studies of the effects of intracerebral aluminum on the cognitive and memory performance of animals, biochemical studies, epidemiologic studies and the slowing of the progress of the disease with the use of an agent that removes aluminum from the body--now support the concept that aluminum is one of the pathogenic factors in AD. The evidence warrants serious consideration of reducing human exposure to aluminum. We hypothesize that a public health effort to restrict human ingestion of aluminum would reduce the incidence of this common chronic illness in the elderly. PMID:1822096

  7. Dose-Dependent Effect of Statin Pretreatment on Preventing the Periprocedural Complications of Carotid Artery Stenting.

    PubMed

    Hong, Jeong-Ho; Sohn, Sung-Il; Kwak, Jaehyuk; Yoo, Joonsang; Chang, Hyuk Won; Kwon, O-Ki; Jung, Cheolkyu; Chung, Inyoung; Bae, Hee-Joon; Lee, Ji Sung; Han, Moon-Ku

    2017-07-01

    We investigated whether statin pretreatment can dose dependently reduce periprocedural complications in patients undergoing carotid artery stenting because of symptomatic carotid artery stenosis. We enrolled a consecutive series of 397 symptomatic carotid artery stenosis (≥50% stenosis on conventional angiography) treated with carotid artery stenting at 2 tertiary university hospitals over a decade. Definition of periprocedural complications included any stroke, myocardial infarction, and death within 1 month after or during the procedure. Statin pretreatment was divided into 3 categories according to the atorvastatin equivalent dose: none (n=158; 39.8%), standard dose (<40 mg of atorvastatin, n=155; 39.0%), and high dose (≥40 mg; n=84; 21.2%). A multivariable logistic regression analysis with the generalized estimating equation method was used to investigate independent factors in periprocedural complications. The patients' mean age was 68.7 years (81.6% men). The periprocedural complication rates across the 3 categories of statin use were 12.0%, 4.5%, and 1.2%. After adjustment, a change in the atorvastatin dose category was associated with reduction in the odds of periprocedural complications for each change in dose category (standard-dose statin: odds ratio, 0.24; 95% confidence interval, 0.07-0.81; high-dose statin: odds ratio, 0.11; 95% confidence interval, 0.01-0.96; P for trend=0.01). Administration of antiplatelet drugs was also an independent factor in periprocedural complications (OR, 0.18; 95% CI, 0.05-0.69). This study shows that statin pretreatment may reduce the incidence of periprocedural complications dose dependently in patients with symptomatic carotid artery stenting. © 2017 American Heart Association, Inc.

  8. Verapamil reduces incidence of reentry during ventricular fibrillation in pigs.

    PubMed

    Jin, Qi; Dosdall, Derek J; Li, Li; Rogers, Jack M; Ideker, Raymond E; Huang, Jian

    2014-11-01

    The characteristics of reentrant circuits during short duration ventricular fibrillation (SDVF; 20 s in duration) and the role of Ca(++) and rapid-activating delayed rectifier potassium currents during long duration ventricular fibrillation (LDVF; up to 10 min in duration) were investigated using verapamil and sotalol. Activation mapping of the LV epicardium with a 21 × 24 electrode plaque was performed in 12 open-chest pigs. Pigs were given either verapamil (0.136 mg/kg) or sotalol (1.5 mg/kg) and verapamil. Reentry patterns were quantified for SDVF, and, for LDVF, activation patterns were compared with our previously reported control LDVF data. Verapamil significantly increased conduction velocity around the reentrant core by 10% and reduced the reentrant cycle length by 15%, with a net reduction in reentry incidence of 70%. Sotolol had an opposite effect of decreasing the conduction velocity around the core by 6% but increasing the reentrant cycle length by 13%, with a net reduction of reentry incidence of 50%. After 200 s of VF, verapamil significantly slowed wavefront conduction velocity and activation rate compared with control data. Verapamil decreased the incidence of reentry in SDVF by accelerating conduction velocity to increase the likelihood of conduction block, possibly through increased sympathetic tone. The drug slowed activation rate and conduction velocity after 200 s of VF, suggesting that L-type Ca(++) channels remain active and may be important in the maintenance of LDVF. Sotalol in addition to verapamil caused no additional antiarrhythmic effect. Copyright © 2014 the American Physiological Society.

  9. [Hospital falls, improvement strategy for reducing their incidence].

    PubMed

    García-Huete, M Eloisa; Sebastián-Viana, Tomás; Lema-Lorenzo, Isabel; Granados-Martín, Mónica; Buitrago-Lobo, Nuria; Heredia-Reina, M del Pilar; Merino-Ruiz, Margarita; Ventosa-Hernández, Esther; Gutiérrez-Fernández, Carmen; Mota-Boada, M Luisa

    2016-01-01

    To evaluate the evolution of falls with the implemented measures to improve the attention of patients at risk and to reduce the number of falls. To know the characteristics of patients who have suffered fall-related injuries. All the falls registered between 2008 and 2013 have been analyzed to determine the evolution of these and to describe the implemented measures through the electronic clinical history at University Hospital of Fuenlabrada. The incidence of falls in hospitalized patients has been estimated and the evolution with the chi square test has been studied. The frequencies of the characteristics of patients who fall has been presented: age, length of stay, performed activity, patient companion, mobility level, state of consciousness. 445 registered falls happened. 2009 is the year with the highest number of falls, 86 patients fell of a total of 15,819 discharged patients (0.55%). The statistic drops until 2013, where 55 patients fell out of 15,052 discharged patients (0.37%). This difference was not statistically significant. The deployment of an assessment about fall risk at admission has helped to identify individualized risk factors. Furthermore, the awareness and alerts to the nursing staff have helped to consider fall prevention as a rutinary procedure, hence appropriate measures can be implemented on the most vulnerable patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  10. Statins and Renin Angiotensin System Inhibitors Dose-Dependently Protect Hypertensive Patients against Dialysis Risk

    PubMed Central

    Wu, Szu-Yuan

    2016-01-01

    Background Taiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin–angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients. Methods Of 248,797 patients who received a hypertension diagnosis in Taiwan during 2001–2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose–response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28–90, 91–365, and >365 cumulative defined daily doses (cDDDs). Results In the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50–0.65), 0.72 (0.53–0.98), and 0.47 (0.41–0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54–0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used. Conclusion Statins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis

  11. Statins and Renin Angiotensin System Inhibitors Dose-Dependently Protect Hypertensive Patients against Dialysis Risk.

    PubMed

    Liu, Ju-Chi; Hsu, Yi-Ping; Wu, Szu-Yuan

    2016-01-01

    Taiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin-angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients. Of 248,797 patients who received a hypertension diagnosis in Taiwan during 2001-2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose-response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28-90, 91-365, and >365 cumulative defined daily doses (cDDDs). In the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50-0.65), 0.72 (0.53-0.98), and 0.47 (0.41-0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54-0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used. Statins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis risk.

  12. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

    PubMed Central

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-01-01

    Abstract Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77–0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout. PMID:26683907

  13. Dose-dependency of theophylline clearance and protein binding.

    PubMed Central

    Fleetham, J A; Bird, C E; Nakatsu, K; Wigle, R D; Munt, P W

    1981-01-01

    Dose-dependency in theophylline pharmacokinetics and protein binding characteristics was examined in 10 healthy male volunteers. Theophylline disposition was determined after an intravenous infusion of both 1 mg/kg and 6 mg/kg aminophylline in a randomised crossover study. There was considerable intrasubject variability in theophylline clearance but no significant dose-dependency. Theophylline protein binding was assessed by equilibrium dialysis at varying theophylline concentrations. The percentage of free non-protein bound theophylline was significantly increased at high theophylline concentrations. This increase in free theophylline would lead to a non-linear increase in the risk of toxicity with increasing drug concentration. Images PMID:7314008

  14. Reduced incidence of hip fracture in the Old Order Amish.

    PubMed

    Streeten, Elizabeth A; McBride, Daniel J; Lodge, Amy L; Pollin, Toni I; Stinchcomb, David G; Agarwala, Richa; Schäffer, Alejandro A; Shapiro, Jay R; Shuldiner, Alan R; Mitchell, Braxton D

    2004-02-01

    The incidence of hip fracture was estimated in a community of Old Order Amish and compared with available data from non-Amish whites. Hip fracture rates were 40% lower in the Amish, and the Amish also experienced higher BMD. Understanding the patterns of fracture risk across populations could reveal insights about bone health and lead to the earlier detection and prevention of osteoporosis. Toward this aim, we compared hip fracture incidence and bone mineral density (BMD) between an Old Order Amish (OOA) community, characterized by a rural and relatively active lifestyle, and non-Amish U.S. whites. All hospital admissions for hip fracture among OOA individuals in Lancaster County, PA, were identified between 1995 and 1998 from four area hospitals. Hip fracture incidence was calculated by cross-referencing an available Anabaptist genealogy database with communities located within these hospital service areas and compared with non-Amish whites obtained from National Hospital Discharge data. Additionally, BMD at the hip was compared between 287 Amish subjects and non-Amish whites from the National Health and Nutrition Examination Survey III survey. OOA experienced 42% fewer hip fractures than would be expected had they experienced the same rate of hip fracture as observed in non-Amish whites (p < 0.01) and a higher mean BMD that was significant in women (p < 0.05) but not men. Further evaluation of lifestyle and/or genetic differences between Amish and non-Amish populations may shed insights into etiologic factors influencing hip fracture risk.

  15. Dose-dependent protective effect of baicalin against testicular torsion-detorsion in rats.

    PubMed

    Fouad, A A; Qutub, H O; Jresat, I

    2017-02-01

    Testicular torsion/detorsion induces oxidative/nitrosative stress, inflammation and apoptosis of testicular tissues. Baicalin exerts antioxidant and anti-inflammatory properties. This study investigated the possible protective effect of baicalin against testicular torsion-detorsion injury in rats. Surgical testicular torsion was induced for 2 h, followed by detorsion which was continued for 24 h. Baicalin was administered in three different doses (25, 50 and 100 mg kg(-1) , by intraperitoneal injection). Each dose was given twice, the first 30 min before and the second 12 h after testicular detorsion. Baicalin, in a dose-dependent manner, decreased the torsion/detorsion-induced elevations of testicular malondialdehyde, nitric oxide, tumour necrosis factor-α, BCL2-associated X protein (Bax), cytosolic cytochrome c and caspase-3 and caspase-9 activities. Baicalin, dose dependently, attenuated the reductions of B-cell leucemia/lymphoma 2 (Bcl-2), and glutathione peroxidase and superoxide dismutase activities in testicular tissues resulted from torsion/detorsion. In addition, baicalin ameliorated the histopathological testicular tissue damage and reduced the expression of Fas ligand in rat testes exposed to torsion/detorsion in a dose-dependent manner. It was concluded that baicalin, dose dependently, ameliorated testicular injury induced by torsion/detorsion via its antioxidant, antinitrosative, anti-inflammatory and anti-apoptotic effects.

  16. CRIMINAL ABORTION—A Consideration of Ways to Reduce Incidence

    PubMed Central

    Kummer, Jerome M.; Leavy, Zad

    1961-01-01

    The problem of criminal abortion in the United States is of enormous magnitude, both in terms of incidence and of resultant morbidity and mortality. Several studies suggest that one of every five pregnancies terminates in criminal abortion, or a total of more than one million abortions for 1960, with a possibility of more than 5,000 deaths resulting therefrom. The inadequate laws regarding therapeutic abortion in most jurisdictions contribute much to the problem. Tracing the origins of these laws provides additional clues concerning the development of this enigma. Suggested answers to the problem include: (1) Broadening and clarifying therapeutic abortion laws to reflect current medical practice, yet provide stringent controls; (2) prevention of unwanted pregnancy through consultation centers for women, encouragement of contraceptive research and education of the public. PMID:13755105

  17. Marijuana's dose-dependent effects in daily marijuana smokers.

    PubMed

    Ramesh, Divya; Haney, Margaret; Cooper, Ziva D

    2013-08-01

    Active marijuana produces significant subjective, psychomotor, and physiological effects relative to inactive marijuana, yet demonstrating that these effects are dose-dependent has proven difficult. This within-subject, double-blind study was designed to develop a smoking procedure to obtain a marijuana dose-response function. In four outpatient laboratory sessions, daily marijuana smokers (N = 17 males, 1 female) smoked six 5-s puffs from 3 marijuana cigarettes (2 puffs/cigarette). The number of puffs from active (≥5.5% Δ⁹-tetrahydrocannabinol/THC) and inactive (0.0% THC) marijuana varied according to condition (0, 2, 4, or 6 active puffs); active puffs were always smoked before inactive puffs. Subjective, physiological, and performance effects were assessed prior to and at set time points after marijuana administration. Active marijuana dose-dependently increased heart rate and decreased marijuana craving, despite evidence (carbon monoxide expiration, weight of marijuana cigarettes post-smoking) that participants inhaled less of each active marijuana cigarette than inactive cigarettes. Subjective ratings of marijuana "strength," "high," "liking," "good effect," and "take again" were increased by active marijuana compared with inactive marijuana, but these effects were not dose-dependent. Active marijuana also produced modest, non-dose-dependent deficits in attention, psychomotor function, and recall relative to the inactive condition. In summary, although changes in inhalation patterns as a function of marijuana strength likely minimized the difference between dose conditions, dose-dependent differences in marijuana's cardiovascular effects and ratings of craving were observed, whereas subjective ratings of marijuana effects did not significantly vary as a function of dose. PsycINFO Database Record (c) 2013 APA, all rights reserved

  18. Vaccine May Reduce Incidence of Meningitis-Related Hearing Impairment.

    ERIC Educational Resources Information Center

    Smith, Dorothy

    1988-01-01

    Hearing loss as a result of meningitis, now the leading nongenetic cause of deafness in infants and young children, may be reduced by the introduction of the HiB (Hemophilus influenzae type B) vaccine. It is highly effective, relatively safe, and recommended for most children over 24 months and high risk children 18-24 months old. (VW)

  19. Vaccine May Reduce Incidence of Meningitis-Related Hearing Impairment.

    ERIC Educational Resources Information Center

    Smith, Dorothy

    1988-01-01

    Hearing loss as a result of meningitis, now the leading nongenetic cause of deafness in infants and young children, may be reduced by the introduction of the HiB (Hemophilus influenzae type B) vaccine. It is highly effective, relatively safe, and recommended for most children over 24 months and high risk children 18-24 months old. (VW)

  20. Leisure-Time Physical Activity Reduces Total and Cardiovascular Mortality and Cardiovascular Disease Incidence in Older Adults.

    PubMed

    Barengo, Noël C; Antikainen, Riitta; Borodulin, Katja; Harald, Kennet; Jousilahti, Pekka

    2017-03-01

    To determine whether leisure-time physical activity (LTPA) is independently associated with all-cause and cardiovascular mortality and with incidence of cardiovascular disease (CVD) and stroke in older adults. Population-based cohort study (median follow-up 11.8 years). Community, five Finnish provinces. Men and women aged 65 to 74 who participated in a baseline risk factor survey between 1997 and 2007 in Finland (N = 2,456). The study protocol included a self-administered questionnaire, health examination at the study site, and blood sample for laboratory analysis. LTPA was classified into three levels: low, moderate, high. Mortality data were obtained from the National Causes of Death Register and data on incident CVD (coronary heart disease, stroke) events from the National Hospital Discharge Register. Multifactorial-adjusted (age, area, study year, sex, smoking, body mass index, systolic blood pressure, serum cholesterol, education, marital status) risks of total mortality (moderate: hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.50-0.74; high: HR = 0.47, 95% CI = 0.34-0.63, P for trend <.001), CVD mortality (moderate: HR = 0.46, 95% CI = 0.33-0.64; high: HR = 0.34, 95% CI = 0.20-0.59, P for trend <.001), and an incident CVD event (moderate HR = 0.69, 95% CI = 0.54-0.88; high: HR = 0.55, 95% CI = 0.38-0.79, P for trend <.001) were lower for those with moderate or high LTPA levels than for those with low LTPA levels. Further adjustment for self-reported inability to perform LTPA did not change the associations remarkably. Baseline LTPA reduces the risk of total and CVD mortality and incident CVD events in older adults independently of the major known CVD risk factors. The protective effect of LTPA is dose dependent. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  1. Dose-dependent protective effect of breast-feeding against breast cancer among ever-lactated women in Korea.

    PubMed

    Kim, Yeonju; Choi, Ji-Yeob; Lee, Kyoung-Mu; Park, Sue Kyung; Ahn, Sei-Hyun; Noh, Dong-Young; Hong, Yun-Chul; Kang, Daehee; Yoo, Keun-Young

    2007-04-01

    Lactation might have a crucial role in an extraordinary increase in breast cancer incidence in Korea, as the proportion of mothers who practised breast-feeding fell dramatically. This hospital-based case-control analysis has been carried out since 1997 to evaluate whether lactation is associated with breast cancer risk in Korean women. Among the eligible study participants, a total of 753 histologically confirmed incident cases and an equal number of controls were included in the analysis. The risk was estimated using unconditional logistic regression models. Family history, older at menopause, more full-term pregnancies increased the risk of breast cancer. Breast cancer risk decreased according to the total months of breast-feeding (P for trend=0.03). Average duration of breast-feeding of 11-12 months reduced risk of breast cancer by 54% compared with the duration of 1-4 months (odds ratio, 0.46; 95% confidence interval, 0.30-0.70). The decreasing risk trend according to average months of breast-feeding was also statistically significant (P for trend=0.02). Moreover, a reduced risk of breast cancer was apparent when analysis was restricted to the first breast-fed child (P for trend=0.006). This study confirms that lactation has an apparent dose-dependent protective effect against breast cancer in Korean women.

  2. Reducing LER using a grazing incidence ion beam

    NASA Astrophysics Data System (ADS)

    Struck, C. R. M.; Raju, R.; Neumann, M. J.; Ruzic, D. N.

    2009-03-01

    As semiconductor feature sizes and pitches shrink to ever-decreasing dimensions, Line Edge Roughness (LER) becomes and increasing important problem. The LER is transferred from the photoresist to the substrate through the subsequent processing steps, causing variations in, eg, gate length. This leads to mismatch in device performance and leakage. Thus, an efficient and cost effective way to reduce the LER in the semiconductor photoresist is needed in order to keep the imperfections from affecting processing steps further down the line. At the CPMI a new technique to reduce LER from patterened photoresist has been developed in conjunction with INTEL. Results obtained using our technique showed significant LER reduction from 6.9+/-0.47 nm to 3.9+/-0.61 nm for 45 nm lines and spaces. Recent results on 40 nm lines and spaces showed significant LER reduction from 5.9+/-0.50 nm to 4.1+/-0.63nm. LER reduction results on 40 nm lines and spaces reveal the fact that our technique is superior to other available techniques such as etching, vapor smoothing, hardbake, ozonation and rinse.

  3. Reducing the Incidence of Plagiarism in an Undergraduate Course: The Role of Education

    ERIC Educational Resources Information Center

    Breen, Lauren; Maassen, Margaret

    2005-01-01

    Plagiarism by students is an increasing problem at higher education institutions. However, the development of academic misconduct policies has done little to reduce the incidence of plagiarism as many incidents result from ignorance and poor skill development rather than intentional misconduct. Our purpose in embarking on this research project was…

  4. Bedtime Routines for Young Children: A Dose-Dependent Association with Sleep Outcomes

    PubMed Central

    Mindell, Jodi A.; Li, Albert M.; Sadeh, Avi; Kwon, Robert; Goh, Daniel Y.T.

    2015-01-01

    Background: Establishment of a consistent bedtime routine (the activities that occur right before lights out) is often recommended as part of healthy sleep habits. However, no studies have investigated the dose-dependent association of a bedtime routine with sleep outcomes, especially in young children for whom they are particularly recommended. Thus, the aim of this study was to examine the associations of a consistent bedtime routine with sleep outcomes in young children (ages 0 through 5 y) in a large global sample and assess whether there is a dose-dependent relationship between the frequency of a bedtime routine both concurrently and retrospectively with sleep outcomes. Participants: Mothers of 10,085 children (Australia-New Zealand, Canada, China, Hong Kong, India, Japan, Korea, Malaysia, Philippines, Singapore, Thailand, United Kingdom, United States) completed the Brief Infant/Child Sleep Questionnaire. Results: A consistent bedtime routine was associated with better sleep outcomes, including earlier bedtimes, shorter sleep onset latency, reduced night wakings, and increased sleep duration. Decreased parent-perceived sleep problems and daytime behavior problems were also related to institution of a regular bedtime routine. Furthermore, there was a dose-dependent relationship, with better outcomes associated with increased “doses” of having a bedtime routine, both currently and retrospectively, and was found within both predominantly Asian and predominantly Caucasian cultural regions. Conclusions: These results indicate that having a regular nightly bedtime routine is associated with improved sleep in young children, and suggests that the more consistently a bedtime routine is instituted and the younger started the better. Citation: Mindell JA, Li AM, Sadeh A, Kwon R, Goh DY. Bedtime routines for young children: a dose-dependent association with sleep outcomes. SLEEP 2015;38(5):717–722. PMID:25325483

  5. Dose-dependent elimination of 8-methoxypsoralen in the mouse

    SciTech Connect

    Cheney, P.; Pacula, C.M.; Gerber, N.; Mays, D.C.

    1986-03-01

    8-Methoxypsoralen (8-MOP), a photoactive linear furocoumarin, is effective in the treatment of several diseases, including psoriasis, mycosis fungoides and T-cell leukemia. Recently, a specific extraction procedure for /sup 14/C-8-MOP showed that the elimination of 8-MOP in the rat was dose-dependent. Similar pharmacokinetic studies were undertaken in mice. Purity of /sup 14/C-8-MOP, verified by a four-tube countercurrent distribution using hexane (8 ml) and pH 7.4 phosphate buffer (0.1 M 15 ml) as described by Bush, was >98% and distributed with a partition coefficient of 3.86. Male CD-1 mice were each given an i.p. dose of 10 or 50 mg/kg of /sup 14/C-8-MOP (3.4 ..mu..Ci/mg) sacrificed at timed intervals, homogenized in 150 ml of 0.1 M phosphate buffer (pH 7.4) and a portion (0.8 ml) of the homogenate used to quantify 8-MOP as described above. The elimination half-life measured in the first 45 min was 7.4 min at 10 mg/kg and 95 min at 50 mg/kg. A similar half-life of 9.2 min was measured in mice given an i.v. dose 10 mg/kg of 8-MOP. Explanations of dose-dependent elimination include enzyme saturation, product inhibition or both. Between 58-80% of the administered radioactivity was recovered in the urine within 24 hr. Nine peaks of radioactivity were observed in the urine by HPLC, two of which coeluted with 5,8-dihydroxypsoralen and 6-(7-hydroxy-8-methoxycoumaryl)-acetic acid.

  6. Dose-dependent effects of light on hyperthymic temperament.

    PubMed

    Kohno, Kentaro; Baba, Hajime; Inoue, Takeshi; Nakai, Yukiei; Toyomaki, Atsuhito; Suzuki, Toshihito; Hatano, Koji; Arai, Heii; Terao, Takeshi

    2014-06-01

    In a previous study examining the association of hyperthymic temperament and daily light exposure (illuminance), we compared hyperthymic scores of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A) acquired from residents in Sapporo and Oita in Japan, which are located at 43° and 33° of latitude. We found that residents of Oita had significantly higher hyperthymic scores than residents of Sapporo. Moreover, a comparison of 3 regions rather than 2 regions may show a dose-response relationship in hyperthymic temperament and illuminance. Japan has 4 large islands-Hokkaido, Honshu, Shikoku, and Kyushu. Sapporo is in Hokkaido and Oita is in Kyushu. As the 3rd location, we recently collected TEMPS-A data from 125 residents in Koshigaya which is located in Honshu at 36°. We combined the data of the Koshigaya residents with the data of 94 residents from Sapporo and 95 from Oita. The mean yearly total sunshine of the past 20 years (1993-2012) was 1684.6h in Sapporo, 1862.9h in Koshigaya, and 2002.9h in Oita. Multiple regression analyses revealed that sunshine predicted significant variance of hyperthymic temperament in a dose-dependent manner. The limitation of the present study is the lack of the consideration of the effects of temperature on hyperthymic temperament. Since correlations are fairly small, other factors are also at work for hyperthymic temperament. The present findings suggest that higher illuminance may maintain hyperthymic temperament via light effects in a dose-dependent manner. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Dose-dependent white matter damage after brain radiotherapy.

    PubMed

    Connor, Michael; Karunamuni, Roshan; McDonald, Carrie; White, Nathan; Pettersson, Niclas; Moiseenko, Vitali; Seibert, Tyler; Marshall, Deborah; Cervino, Laura; Bartsch, Hauke; Kuperman, Joshua; Murzin, Vyacheslav; Krishnan, Anitha; Farid, Nikdokht; Dale, Anders; Hattangadi-Gluth, Jona

    2016-11-01

    Brain radiotherapy is limited in part by damage to white matter, contributing to neurocognitive decline. We utilized diffusion tensor imaging (DTI) with multiple b-values (diffusion weightings) to model the dose-dependency and time course of radiation effects on white matter. Fifteen patients with high-grade gliomas treated with radiotherapy and chemotherapy underwent MRI with DTI prior to radiotherapy, and after months 1, 4-6, and 9-11. Diffusion tensors were calculated using three weightings (high, standard, and low b-values) and maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ∥), and radial diffusivity (λ⊥) were generated. The region of interest was all white matter. MD, λ∥, and λ⊥ increased significantly with time and dose, with corresponding decrease in FA. Greater changes were seen at lower b-values, except for FA. Time-dose interactions were highly significant at 4-6months and beyond (p<.001), and the difference in dose response between high and low b-values reached statistical significance at 9-11months for MD, λ∥, and λ⊥ (p<.001, p<.001, p=.005 respectively) as well as at 4-6months for λ∥ (p=.04). We detected dose-dependent changes across all doses, even <10Gy. Greater changes were observed at low b-values, suggesting prominent extracellular changes possibly due to vascular permeability and neuroinflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Verbenone: Dose-Dependent Interruption of Pheromone-Based Attraction of Three Sympatric Species of Pine Bark Beetles (Coleoptera: Scolytidae)

    Treesearch

    Daniel R. Miller; John H. Borden; B. Staffan Lindgren

    1995-01-01

    Verbenone significantly reduced catches of Ips latidens (LeConte), I. pini (Say), and Dendroctonus ponderosae Hopkins in multiple-funnel traps, baited with aggregation pheromones, in stands of lodgepole pine in southern British Columbia. Interruption of attraction was dose dependent for all three species. There...

  9. Chlorhexidine antisepsis significantly reduces the incidence of sepsis and septicemia during parenteral nutrition in surgical infants.

    PubMed

    Bishay, Mark; Retrosi, Giuseppe; Horn, Venetia; Cloutman-Green, Elaine; Harris, Kathryn; De Coppi, Paolo; Klein, Nigel; Eaton, Simon; Pierro, Agostino

    2011-06-01

    After a change in national policy, central venous catheter (CVC) antisepsis with chlorhexidine was introduced in our hospital. Our aim was to evaluate whether this change reduced the rate of infection seen during parenteral nutrition (PN) in infants requiring gastrointestinal surgery. Two groups of consecutive infants were compared: control, 98 infants who had CVC antisepsis with 70% isopropanol alone, and chlorhexidine, 112 infants who had CVC antisepsis with 2% chlorhexidine in 70% isopropanol. Incidence rates of sepsis (blood cultures taken) and septicemia (blood cultures positive) were compared by Poisson regression. Seventy-one percent of infants experienced clinically suspected sepsis. The incidence of septicemia was 32%. The incidence rate ratio for sepsis was 0.72 (95% confidence interval, 0.61-0.84) for the chlorhexidine group vs control (P < .0005). The incidence rate ratio for septicemia was 0.49 (95% confidence interval, 0.36-0.67; P < .0005); that is, over a given period of PN, patients had half the rate of positive blood cultures after the introduction of chlorhexidine antisepsis compared with before. (1) The incidence of sepsis and septicemia among surgical infants on PN for gastrointestinal anomalies is high. (2) Chlorhexidine CVC antisepsis has significantly reduced this incidence, and we advocate its use in this group of patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. [Reducing patient pressure sore incidence in the surgical intensive care unit].

    PubMed

    Chung, Hui-Ting; Shu, Ling-Hui; Pan, Chao-Chun; Yang, Shu-Yen; Chen, Wan-I

    2011-06-01

    Pressure ulcers were an increasingly significant problem among patients in the authors' ward. The eight patients diagnosed with pressure ulcers (0.42% of all inpatients) during the first half of 2009 represented a 140% increase over the first half of 2008 (0.28% of all inpatients). This project was designed to reduce pressure ulcer incidence in the surgical intensive care unit (ICU) to 0.05%. Intervention measures included: 1) holding professional training on preventing pressure ulcers; 2) specifying appropriate patient turnover tools; 3) creating and distributing to nurses a proper turnover technique and positioning manual; 4) creating and distributing to nurses a comprehensive patient skin inspection checklist; and 5) organizing a permanent pressure ulcer care quality and audit committee. Pressure ulcer incidence fell from 0.42% to 0.04% following implementation of the methods. Results demonstrate the effectiveness of using the proposed methods to reduce pressure ulcer incidence and enhance nursing care quality.

  11. Evaluation of a patient education tool to reduce the incidence of incontinence post-prostate surgery.

    PubMed

    Ip, Virginia

    2004-10-01

    A pelvic floor muscle exercise program can reduce the incidence of incontinence post-prostate surgery. The purpose of this study was to validate a new education tool, a refrigerator magnet, in comparison to a paper copy with the same information, to determine if patient compliance with the exercises increased.

  12. An Online Tutorial vs. Pre-Recorded Lecture for Reducing Incidents of Plagiarism

    ERIC Educational Resources Information Center

    Henslee, Amber M.; Goldsmith, Jacob; Stone, Nancy J.; Krueger, Merilee

    2015-01-01

    The current study compared an online academic integrity tutorial modified from Belter & du Pre (2009) to a pre-recorded online academic integrity lecture in reducing incidents of plagiarism among undergraduate students at a science and technology university. Participants were randomized to complete either the tutorial or the pre-recorded…

  13. Febuxostat protects rats against lipopolysaccharide-induced lung inflammation in a dose-dependent manner.

    PubMed

    Fahmi, Alaa N A; Shehatou, George S G; Shebl, Abdelhadi M; Salem, Hatem A

    2016-03-01

    The aim of the present work was to investigate possible protective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. Male Sprague Dawley rats were randomly divided into six groups, as follows: (i) vehicle control group; (ii) and (iii) febuxostat 10 and febuxostat 15 groups, drug-treated controls; (iv) LPS group, receiving an intraperitoneal injection of LPS (7.5 mg/kg); (v) and (vi) febuxostat 10-LPS and febuxostat 15-LPS groups, receiving oral treatment of febuxostat (10 and 15 mg/kg/day, respectively) for 7 days before LPS. After 18 h administration of LPS, blood was collected for C-reactive protein (CRP) measurement. Bronchoalveolar lavage fluid (BALF) was examined for leukocyte infiltration, lactate dehydrogenase (LDH) activity, protein content, and total nitrate/nitrite. Lung weight gain was determined, and lung tissue homogenate was prepared and evaluated for oxidative stress. Tumor necrosis factor-α (TNF-α) was assessed in BALF and lung homogenate. Moreover, histological changes of lung tissues were evaluated. LPS elicited lung injury characterized by increased lung water content (by 1.2 fold), leukocyte infiltration (by 13 fold), inflammation and oxidative stress (indicated by increased malondialdehyde (MDA), by 3.4 fold), and reduced superoxide dismutase (SOD) activity (by 34 %). Febuxostat dose-dependently decreased LPS-induced lung edema and elevations in BALF protein content, infiltration of leukocytes, and LDH activity. Moreover, the elevated levels of TNF-α in BALF and lung tissue of LPS-treated rats were attenuated by febuxostat pretreatment. Febuxostat also displayed a potent antioxidant activity by decreasing lung tissue levels of MDA and enhancing SOD activity. Histological analysis of lung tissue further demonstrated that febuxostat dose-dependently reversed LPS-induced histopathological changes. These findings demonstrate a significant dose-dependent

  14. Bedtime routines for young children: a dose-dependent association with sleep outcomes.

    PubMed

    Mindell, Jodi A; Li, Albert M; Sadeh, Avi; Kwon, Robert; Goh, Daniel Y T

    2015-05-01

    Establishment of a consistent bedtime routine (the activities that occur right before lights out) is often recommended as part of healthy sleep habits. However, no studies have investigated the dose-dependent association of a bedtime routine with sleep outcomes, especially in young children for whom they are particularly recommended. Thus, the aim of this study was to examine the associations of a consistent bedtime routine with sleep outcomes in young children (ages 0 through 5 y) in a large global sample and assess whether there is a dose-dependent relationship between the frequency of a bedtime routine both concurrently and retrospectively with sleep outcomes. Mothers of 10,085 children (Australia-New Zealand, Canada, China, Hong Kong, India, Japan, Korea, Malaysia, Philippines, Singapore, Thailand, United Kingdom, United States) completed the Brief Infant/Child Sleep Questionnaire. A consistent bedtime routine was associated with better sleep outcomes, including earlier bedtimes, shorter sleep onset latency, reduced night wakings, and increased sleep duration. Decreased parent-perceived sleep problems and daytime behavior problems were also related to institution of a regular bedtime routine. Furthermore, there was a dose-dependent relationship, with better outcomes associated with increased "doses" of having a bedtime routine, both currently and retrospectively, and was found within both predominantly Asian and predominantly Caucasian cultural regions. These results indicate that having a regular nightly bedtime routine is associated with improved sleep in young children, and suggests that the more consistently a bedtime routine is instituted and the younger started the better. © 2015 Associated Professional Sleep Societies, LLC.

  15. Dietary fat dose dependently increases spontaneous caloric intake in rat.

    PubMed

    Warwick, Zoe S

    2003-07-01

    To characterize the dose-response relationship between dietary fat to carbohydrate ratio and spontaneous caloric intake. Male Long-Evans rats consumed milk-based liquid diets that differed in fat content (17% to 60% of kilocalories) but had equivalent protein content and energy density. In Experiment 1, rats consumed one of the diets (n = 9/diet group) as the sole source of nutrition for 16 days. In Experiment 2, diets were offered as an option to nutritionally complete chow for 4 days followed by a 3-day chow-only washout in a randomized within-subjects design (n = 30). In Experiment 3, nine rats received isocaloric intragastric infusions of diet overnight, with chow available ad libitum. At least two no-infusion days separated the different diet infusions, which were given in random order. Food intake was measured daily Dietary fat dose dependently increased total daily kilocalories in each of the three paradigms. These data imply that the postingestive effects of carbohydrate and fat differentially engage the physiological substrates that regulate daily caloric intake. These findings reiterate the importance of investigating macronutrient-specific controls of feeding, rather than prematurely concluding that dietary attributes that covary with fat content (e.g., caloric density and palatability) drive the overeating associated with a high-fat diet.

  16. Use of Boosted Protease Inhibitors Reduces Kaposi Sarcoma Incidence Among Male Veterans With HIV Infection

    PubMed Central

    Kowalkowski, Marc A.; Kramer, Jennifer R.; Richardson, Peter R.; Suteria, Insia; Chiao, Elizabeth Y.

    2015-01-01

    Background. Kaposi sarcoma (KS) incidence has decreased since combination antiretroviral therapy (cART). However, effects of cART type and duration on KS remain difficult to interpret secondary to KS-associated immune reconstitution inflammatory syndrome (IRIS). Methods. We performed a retrospective study of Veterans Affairs Human Immunodeficiency Virus Clinical Case Registry data from 1985 to 2010. We analyzed the relationship between cART regimens and KS using multivariable Poisson regression, stratified or adjusted for timing around cART initiation. KS was identified by ≥1 inpatient or ≥2 outpatient International Classification of Diseases, Ninth Revision codes (176.0–9). Percent of cART on specific regimen and total duration on specific regimen were examined. Results. There were 341 KS cases among 25 529 HIV-infected male veterans (incidence rate = 2.02/1000 person-years). Stratified by years after starting cART, every additional 10% time on boosted protease inhibitors (BPIs) was associated with reduced KS incidence in the third year of cART (incidence rate ratio [IRR] = 0.79; 95% confidence interval [CI], .69–.90). Months on BPIs was associated with lower KS incidence (P = .02). KS incidence was lower at 12–23 (IRR = 0.47; 95% CI, .23–.95) and ≥36 (IRR = 0.14; 95% CI, .02–1.00) months on BPIs compared with <6 months. Longer duration on other regimens was not associated with decreased KS incidence. Conclusions. Lower KS incidence was observed with longer BPI use, after accounting for potential IRIS and other factors. Future research should evaluate newer cART regimens and long-term benefits of PI-based cART on KS in other cohorts and prospective studies. PMID:25586682

  17. Periodic Presumptive Treatment for Vaginal Infections May Reduce the Incidence of Sexually Transmitted Bacterial Infections.

    PubMed

    Balkus, Jennifer E; Manhart, Lisa E; Lee, Jeannette; Anzala, Omu; Kimani, Joshua; Schwebke, Jane; Shafi, Juma; Rivers, Charles; Kabare, Emanuel; Scott McClelland, R

    2016-06-15

    Bacterial vaginosis (BV) may increase women's susceptibility to sexually transmitted infections (STIs). In a randomized trial of periodic presumptive treatment (PPT) to reduce vaginal infections, we observed a significant reduction in BV. We further assessed the intervention effect on incident Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium infection. Nonpregnant, human immunodeficiency virus-uninfected women from the United States and Kenya received intravaginal metronidazole (750 mg) plus miconazole (200 mg) or placebo for 5 consecutive nights each month for 12 months. Genital fluid specimens were collected every other month. Poisson regression models were used to assess the intervention effect on STI acquisition. Of 234 women enrolled, 221 had specimens available for analysis. Incidence of any bacterial STI (C. trachomatis, N. gonorrhoeae, or M. genitalium infection) was lower in the intervention arm, compared with the placebo arm (incidence rate ratio [IRR], 0.54; 95% confidence interval [CI], .32-.91). When assessed individually, reductions in STI incidences were similar but not statistically significant (IRRs, 0.50 [95% confidence interval {CI}, .20-1.23] for C. trachomatis infection, 0.56 [95% CI, .19-1.67] for N. gonorrhoeae infection, and 0.66 [95% CI, .38-1.15] for M. genitalium infection). In addition to reducing BV, this PPT intervention may also reduce the risk of bacterial STI among women. Because BV is highly prevalent, often persists, and frequently recurs after treatment, interventions that reduce BV over extended periods could play a role in decreasing STI incidence globally. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. Reducing the Probability of Incidents Through Behavior-Based Safety -- An Anomaly or Not?

    SciTech Connect

    Turek, John A

    2002-07-23

    Reducing the probability of incidents through Behavior-Based Safety-an anomaly or not? Can a Behavior-Based Safety (BBS) process reduce the probability of an employee sustaining a work-related injury or illness? This presentation describes the actions taken to implement a sustainable BBS process and evaluates its effectiveness. The BBS process at the Stanford Linear Accelerator Center used a pilot population of national laboratory employees to: Achieve employee and management support; Reduce the probability of employees' sustaining work-related injuries and illnesses; and Provide support for additional funding to expand within the laboratory.

  19. Reducing the Probability of Incidents Through Behavior-Based Safety -- An Anomaly or Not?

    SciTech Connect

    Turek, John A

    2002-07-23

    Reducing the probability of incidents through Behavior-Based Safety--an anomaly or not? Can a Behavior-Based Safety (BBS) process reduce the probability of an employee sustaining a work-related injury or illness? This presentation describes the actions taken to implement a sustainable BBS process and evaluates its effectiveness. The BBS process at the Stanford Linear Accelerator Center used a pilot population of national laboratory employees to: Achieve employee and management support; Reduce the probability of employees' sustaining work-related injuries and illnesses; and Provide support for additional funding to expand within the laboratory.

  20. Dose-dependent effects of tryptophan on learning and memory.

    PubMed

    Ikram, Huma; Mushtaq, Foqia; Haleem, Darakhshan Jabeen

    2014-09-01

    The concentration of 5-hydroxytryptamine (5-HT, Serotonin) varies as a result of physiological changes in the availability of its precursor tryptophan to the serotonergic neurons in the brain. Increase in brain tryptophan occurs following an increase in plasma tryptophan concentration. Tryptophan intake increases brain serotonin metabolism and enhances memory. The Present study was designed to investigate the effects of oral administration of tryptophan (TRP) at different doses (100, 300 and 500mg/kg) for two weeks on learning and memory functions and Neurochemical changes in rats. Control rats were given drinking water. Assessment of memory in rats was done by using the water Maze. on the 14th day trail training of water Maze was given to rats and after 1h of this 2nd trial of these rats were done. On the next day (After 24h of trail) long-term memories of these rats were monitored. After 1 hour of this all rats were killed by decapitation using guillotine. Brain and blood was collected and stored at -70°C. Neurochemical estimations of Plasma and brain tryptophan, 5-HT and 5-HIAA in brain were made by HPLC-EC. Result showed that administration of tryptophan enhanced performance on water Maze test. Tryptophan treated animals exhibited higher level of Plasma as well as brain tryptophan. 5-HT and 5-HIAA levels were also increased in tryptophan treated rats. Findings are discussed in context with the role of 5-HT metabolism in learning and memory process in rats. Results may help to understand the 5-HT changes following long term TRP administration in a dose dependent manner and will help to suggest the use of TRP in serotonin related illnesses.

  1. Dose-dependency of resveratrol in providing health benefits.

    PubMed

    Mukherjee, Subhendu; Dudley, Jocelyn I; Das, Dipak K

    2010-03-18

    This review describes the dose-dependent health benefits of resveratrol, a polyphenolic antioxidant that is found in a variety of foods, especially grape skin and red wine. Resveratrol provides diverse health benefits including cardioprotection, inhibition of low-density lipoprotein, activation of nitric oxide (NO) production, hindering of platelet aggregation [32] A.A.E. Bertelli, D.E. Giovannini, R.L. Caterina, W. Bernini, M. Migliori and M. Fregoni et al., Antiplatelet activity of cis-resveratrol, Drugs Exp Clin Res 22 (1996), pp. 61-63. View Record in Scopus | Cited By in Scopus (111) and promotion of anti-inflammatory effects. Studies have shown that at a lower dose, resveratrol acts as an anti-apoptotic agent, providing cardioprotection as evidenced by increased expression in cell survival proteins, improved postischemic ventricular recovery and reduction of myocardial infarct size and cardiomyocyte apoptosis and maintains a stable redox environment compared to control. At higher dose, resveratrol acts as a pro-apoptotic compound, inducing apoptosis in cancer cells by exerting a death signal. At higher doses, resveratrol depresses cardiac function, elevates levels of apoptotic protein expressions, results in an unstable redox environment, increases myocardial infarct size and number of apoptotic cells. At high dose, resveratrol not only hinders tumor growth but also inhibits the synthesis of RNA, DNA and protein, causes structural chromosome aberrations, chromatin breaks, chromatin exchanges, weak aneuploidy, higher S-phase arrest, blocks cell proliferation, decreases wound healing, endothelial cell growth by fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor, and angiogenesis in healthy tissue cells leading to cell death. Thus, at lower dose, resveratrol can be very useful in maintaining the human health whereas at higher dose, resveratrol has pro-apoptotic actions on healthy cells, but can kill tumor cells.

  2. [Reducing patient pressure sore incidence density in the pediatric surgical intensive care unit].

    PubMed

    Huang, Wei-Chen; Chang, Shiow-Ru; Tang, Chi-Min

    2014-04-01

    Our unit recorded 21 cases of pressure sores from January 2011 to June 2011. The resulting pressure-sore incidence density of 0.74% exceeded the Taiwan Clinical Performance Indicator (TCPI) for medical centers (0.62%) as well as the mean incidence density for our unit (0.55%) during the same period in 2010. We developed this project to decrease the incidence density of pressure sores at our pediatric-surgical-intensive-care unit from 0.74% to 0.31%. Strategies implemented included: 1. providing on-the-job education; 2. providing bedside teaching; 3. developing a series of pictures to illustrate proper sitting, lying, and changing positions and the proper fixation of catheters; 4. implementing a reminder mechanism; 5. introducing pressure-preventing devices; 6. and establishing an audit team. Incidence density decreased from 0.74% (Jan. to Jun. 2011) to 0.18% (Mar. to Jul. 2012). We demonstrated that the developed improvement program effectively reduced the incidence density of pressure sores and increased the quality of nursing care.

  3. Dose-dependent effects of intravenous alcohol administration on cerebral blood flow in young adults.

    PubMed

    Strang, Nicole M; Claus, Eric D; Ramchandani, Vijay A; Graff-Guerrero, Ariel; Boileau, Isabelle; Hendershot, Christian S

    2015-02-01

    Functional magnetic resonance imaging (fMRI) studies involving alcohol challenge are important for identifying neural correlates of alcohol's psychopharmacological effects. However, evaluating acute alcohol effects on blood oxygen level-dependent (BOLD) signal change is complicated by alcohol-related increases in cerebral blood flow (CBF). The present study aimed to further characterize acute alcohol effects on CBF using intravenous alcohol administration to maximize control over brain alcohol exposure. Twenty heavy-drinking young adults (M = 19.95 years old, SD = 0.76) completed alcohol and placebo imaging sessions in a within-subject, counter-balanced, placebo-controlled design. Arterial spin labeling (ASL) provided estimates of perfusion change at two target blood alcohol concentrations (40 and 80 mg%) relative to baseline and relative to a saline control infusion. Voxel-wise analyses showed widespread and dose-dependent effects of alcohol on CBF increase. Region-of-interest analyses confirmed these findings, also indicating regional variation in the magnitude of perfusion change. Additional findings indicated that lower self-reported sensitivity to alcohol corresponded with reduced perfusion change during alcohol administration. This study provides further evidence for widespread effects of acute alcohol on cerebral perfusion, also demonstrating regional, dose-dependent, and inter-individual variation. Further research is needed to evaluate implications of these effects for the design and interpretation of pharmacological fMRI studies involving alcohol challenge.

  4. Bupropion Dose-Dependently Reverses Nicotine Withdrawal Deficits in Contextual Fear Conditioning

    PubMed Central

    Portugal, George S.; Gould, Thomas J.

    2007-01-01

    Bupropion, a norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist, facilitates smoking cessation and reduces some symptoms of nicotine withdrawal. However, the effects of bupropion on nicotine withdrawal-associated deficits in learning remain unclear. The present study investigated whether bupropion has effects on contextual and cued fear conditioning following withdrawal from chronic nicotine or when administered alone. Bupropion was administered alone for a range of doses (2.5, 5, 10, 20 or 40 mg/kg), and dose-dependent impairments in contextual and cued fear conditioning were observed (20 or 40 mg/kg). Follow-up studies investigated if bupropion disrupted acquisition or expression of fear conditioning. Bupropion (40 mg/kg) administration on training day only produced deficits in contextual fear conditioning. Alternatively, bupropion (20 or 40 mg/kg) administration during testing dose-dependently produced deficits in contextual and cued fear conditioning. To test the effect of bupropion on nicotine withdrawal, mice were withdrawn from 12 days of chronic nicotine (6.3 mg/kg/day) or saline treatment. Withdrawal from chronic nicotine disrupted contextual fear conditioning; however, 5 mg/kg bupropion reversed this deficit. Overall, these results indicate that a low dose of bupropion can reverse nicotine withdrawal deficits in contextual fear conditioning, but that high doses of bupropion produce deficits in fear conditioning. PMID:17868796

  5. Antipsychotic drugs dose-dependently suppress the spontaneous hyperactivity of the chakragati mouse.

    PubMed

    Dawe, G S; Nagarajah, R; Albert, R; Casey, D E; Gross, K W; Ratty, A K

    2010-11-24

    The chakragati (ckr) mouse has been proposed as a model of aspects of schizophrenia. The mice, created serendipitously as a result of a transgenic insertional mutation, exhibit spontaneous circling, hyperactivity, hypertone of the dopamine system, reduced social interactions, enlarged lateral ventricles, deficits in pre-pulse inhibition of acoustic startle and deficits in latent inhibition of conditioned learning. In this study, the dose-dependent effects of antipsychotic drugs (haloperidol, pimozide, risperidone, clozapine, olanzapine, ziprasidone, quetiapine and aripiprazole) on the spontaneous hyperactivity of the mice were investigated. All the antipsychotic drugs tested dose-dependently suppressed spontaneous hyperactivity. Aripriprazole, which is known to be a dopamine D2 receptor partial agonist, exhibited a tri-phasic dose-response, initially suppressing hyperactivity at low doses, having little effect on hyperactivity at intermediate doses, and suppressing activity again at high doses. These data suggest that the spontaneous circling and hyperactivity of the ckr mouse may allow screening of candidate antipsychotic compounds, distinguishing compounds with aripriprazole-like profiles.

  6. Efficacy of intravenous dexamethasone to reduce incidence of postoperative sore throat: A prospective randomized controlled trial

    PubMed Central

    Bagchi, Dipanjan; Mandal, Mohan Chandra; Das, Sabyasachi; Sahoo, Tirtha; Basu, Sekhar Ranjan; Sarkar, Sanhita

    2012-01-01

    Background: Sore throat and hoarseness are common complications of endotracheal intubation. It may be very distressing for the patient and may lead to sleep disturbances and unpleasant memories. Materials and Methods: This prospective double-blinded randomized control trial was aimed to determine the efficacy of prophylactic intravenous dexamethasone to reduce the incidence of postoperative sore throat at 1 hour after tracheal extubation. Ninety six patients of either sex aged between 18 to 60 years scheduled for elective surgeries needing general anesthesia with endotracheal intubation, were randomly allocated into two groups A and B. The patients received either intravenous 0.2 mg/kg dexamethasone (group A, n = 48) or normal saline (group B, n = 47) just before induction. Trachea was intubated with appropriate size disposable endotracheal tubes for securing the airway. Follow up for the incidence of sore throat, cough and hoarseness was done at 1, 6 and 24 hours post-extubation. Results: At 1 hour post-extubation, the incidence of sore throat in the control group was 48.9% compared with 18.8% in the dexamethasone group (P<0.002). Conclusions: Prophylactic intravenous dexamethasone in a dose of 0.2 mg/kg can reduce the incidence of postoperative sore throat at 1 hour post-extubation by around 30%, with the efficacy being around 60%. PMID:23225928

  7. Preemptive antibiotic treatment based on gram staining reduced the incidence of ARDS in mechanically ventilated patients.

    PubMed

    Matsushima, Asako; Tasaki, Osamu; Shimizu, Kentaro; Tomono, Kazunori; Ogura, Hiroshi; Shimazu, Takeshi; Sugimoto, Hisashi

    2008-08-01

    Ventilator-associated pneumonia (VAP) is one of the major complications in the intensive care unit. VAP sometimes results in acute respiratory distress syndrome (ARDS), and the associated mortality is high. We hypothesized that preemptive antibiotic therapy based on results of bedside gram staining would reduce the incidence of VAP. Patients who were endotracheally intubated in our intensive care unit for more than 72 hours were included. Patients younger than 16 years of age or patients died because of brain death were excluded. The study was divided into two periods. During the first period, we used antibiotics according to the American Thoracic Society guidelines. During the second period, antibiotics were given according to the results of bedside gram staining even before radiographic infiltrate appeared. One hundred twenty-eight patients and 133 patients were included in the first and second periods, respectively. The incidence of VAP was significantly decreased in the second period (first period, 22%; second period, 9%, p < 0.01). The incidence of ARDS was also decreased significantly in the second period (first period, 11%; second period, 3%, p < 0.01). The duration and total amount of antibiotics administered did not increase in the second period. VAP associated mortality was significantly lower in the second period (first period, 5%; second period, 0.8%, p < 0.05). Early diagnosis and treatment of respiratory infection based on results of gram staining significantly reduced the incidences of VAP and ARDS without an increase in the use of antibiotics.

  8. Exercise is associated with a reduced incidence of sleep-disordered breathing

    PubMed Central

    Awad, Karim M.; Malhotra, Atul; Barnet, Jodi H; Quan, Stuart F.; Peppard, Paul E

    2012-01-01

    Background The effect of exercise on sleep-disordered breathing is unknown. While diet and weight loss have been shown to reduce the severity of sleep-disordered breathing, it is unclear whether exercise has an independent effect. Methods A population-based longitudinal epidemiologic study of adults measured the association between exercise and incidence and severity of sleep-disordered breathing. Hours of weekly exercise were assessed by two mailed surveys (1988 and 2000). Sleep-disordered breathing was assessed by 18-channel in-laboratory polysomnography at baseline and at follow up. Results Associations were modeled using linear and logistic regression, adjusting for body mass index, age, sex, and other covariates. Hours of exercise were associated with reduced incidence of mild (Odds Ratio = 0.76, p= 0.011) and moderate (Odds Ratio = 0.67, p= 0.002) sleep-disordered breathing. Also a decrease in exercise duration was associated with worsening sleep-disordered breathing, as measured by the apnea-hypopnea index, AHI (ß = 2.368, p= 0.048). Adjustment for body mass index attenuated these effects. Conclusions Exercise is associated with a reduced incidence of mild and moderate sleep-disordered breathing and decreasing exercise is associated with worsening of sleep-disordered breathing. The effect of exercise on sleep-disordered breathing appears to be largely, but perhaps not entirely, mediated by changes in body habitus. PMID:22482846

  9. Advance pre-operative chlorhexidine reduces the incidence of surgical site infections in knee arthroplasty.

    PubMed

    Zywiel, Michael G; Daley, Jacqueline A; Delanois, Ronald E; Naziri, Qais; Johnson, Aaron J; Mont, Michael A

    2011-07-01

    Surgical site infections following elective knee arthroplasties occur most commonly as a result of colonisation by the patient's native skin flora. The purpose of this study was to evaluate the incidence of deep surgical site infections in knee arthroplasty patients who used an advance cutaneous disinfection protocol and who were compared to patients who had peri-operative preparation only. All adult reconstruction surgeons at a single institution were approached to voluntarily provide patients with chlorhexidine gluconate-impregnated cloths and a printed sheet instructing their use the night before and morning of surgery. Records for all knee arthroplasties performed between January 2007 and December 2008 were reviewed to determine the incidence of deep incisional and periprosthetic surgical site infections. Overall, the advance pre-operative protocol was used in 136 of 912 total knee arthroplasties (15%). A lower incidence of surgical site infection was found in patients who used the advance cutaneous preparation protocol as compared to patients who used the in-hospital protocol alone. These findings were maintained when patients were stratified by surgical infection risk category. No surgical site infections occurred in the 136 patients who completed the protocol as compared to 21 infections in 711 procedures (3.0%) performed in patients who did not. Patient-directed skin disinfection using chlorhexidine gluconate-impregnated cloths the evening before, and the morning of, elective knee arthroplasty appeared to effectively reduce the incidence of surgical site infection when compared to patients who underwent in-hospital skin preparation only.

  10. Neonatal Treatment With Beta-Cell Stimulatory Agents Reduces the Incidence of Diabetes in BB Rats

    PubMed Central

    Bock, Troels; Pedersen, Charlotte R.; Hansen, Susanne V.; Aaen, Kim; JØrgensen, Merete; Hansen, Michael WØllike; Kjaer, Troels W.; Hageman, Ida; Josefsen, Knud

    2000-01-01

    The aim of the study was to investigate whether various beta-cell stimulatory drugs, given neonatally, influence the incidence of diabetes in BB rats. Newborn BB rats were treated twice daily for 6 days and diabetes development was observed during the following 200-day study period. Compared to a diabetes incidence of 63.8% in 163 control BB rats which received saline or were untreated, the percentage of experimental BB rats that developed diabetes was as follows in the different subgroups: arginineglucose: 47% (n= 73, p < 0.02); glucagon: 37% (n = 93, p < 0.0001); tolbutamide-glucose: 36% (n = 58, p < 0.0005); and theophylline-glucose: 39% (n = 41, p < 0.005). A long-term arginine-glucose treatment was not superior to the shorter neonatal treatment. Histological examination revealed a higher degree of insulitis in diabetic than in non-diabetic animals but no difference according to the kind of treatment was observed. Finally, we found that the diabetes incidence in BB rats was higher in the first litter compared to subsequent litters (p = 0.04). Thus, neonatal treatment with various beta-cell stimulatory agents reduces diabetes incidence in BB rats. The theory behind the study, that the treatment accelerates beta-cell maturation leading to increased immunological tolerance towards beta cells, is discussed. PMID:11469386

  11. Reducing the incidence of incisional hernias following open gastric bypass surgery.

    PubMed

    Capella, Rafael F; Iannace, Vincent A; Capella, Joseph F

    2007-04-01

    Abdominal wall hernias are a common complication following open gastric bypass (RYGBP) surgery. In an effort to reduce the incidence of incisional hernias with our form of open RYGBP, progressively smaller, upper midline epigastric incisions have been utilized along with permanent sutures. The purpose of this study is to analyze whether incision location, size and choice of suture material affect the incidence of incisional hernias following open RYGBP. Clinically evident incisional hernias and other wound complications and non-wound related complications were analyzed for 1,180 consecutive primary open proximal RYGBP procedures performed between August 2002 and June 2006. Progressively smaller, upper midline incisions were utilized during the time period of the study. Smaller incisions limited to the upper abdomen and approximated with permanent sutures were associated with significantly fewer hernias (P<0.01), wound dehiscences (P<0.03), eviscerations (P<0.03) and wound infections (P<0.03). Smaller incisions may also be associated with less postoperative discomfort. A reduction in incision size, the avoidance of the periumbilical region and the use of nonabsorbable sutures has significantly reduced the incidence of incisional hernias and acute fascial disruptions with our form of open RYGBP. These findings are consistent with LaPlace's law regarding wall tension and vessel radius. In addition, we found smaller incisions to be associated with fewer infections and seromas and less postoperative discomfort. A reduction in incision size has not been associated with an increase in morbidity or mortality or changes in the operative time.

  12. Dose-dependent protective effect of BPC 157 on capsaicin-induced rhinitis in rats.

    PubMed

    Kalogjera, L; Ries, M; Baudoin, T; Ferencic, Z; Trotic, R; Pegan, B

    1997-01-01

    Protection of BPC 157 on capsaicin-induced rhinitis was studied in Wistar rats for its effect on mastocyte infiltration, degranulation and inflammatory cell infiltration. Animals were pretreated with 10 microg/kg, 10 ng/kg or 2 ml saline i.p. and capsaicin (0.05 ml/nostril of 1750 nmol/l sol.) was applied intranasally. They were then euthanized at 1, 3 and 12 h after capsaicin provocation. Nasal mucosa was analyzed and scored for mastocyte infiltration, degranulation and inflammatory cell infiltration. BPC 157 pretreatment significantly prevented mastocyte infiltration at 1 h. Polymorphonuclear leukocyte infiltration was significantly reduced in rats pretreated with 10 microg/kg BPC 157. A dose-dependent effect of BPC 157 pretreatment was demonstrated only for polymorphonuclear leukocyte infiltration at 12 h.

  13. What does the susceptible-dose dependent interpretive category for cefepime in ESBL-producing bacteria?

    PubMed

    Menegucci, Thatiany Cevallos; Bastos, Marina de Souza; Viana, Giselle Fukita; Moreira, Rafael Renato Brondani; Garcia, Lourdes Botelho; Cardoso, Celso Luiz; Tognim, Maria Cristina Bronharo

    2017-06-01

    In this study, we investigated the frequency of isolates included in the susceptible-dose dependent (SDD) category, according to the Clinical and Laboratory Standards Institute guidelines, carrying blaTEM, blaSHV and blaCTX genes among 92 Klebsiella pneumoniae and 80 Enterobacter cloacae clinical isolates. The presence of one or more extended-spectrum β-lactamases (ESBLs) genes was observed in 64% K. pneumoniae and 69% E. cloacae isolates. Nineteen isolates were included in SDD interpretive category criteria, of which 15 carried ESBL genes (seven K. pneumoniae and eight E. cloacae). Considering the high proportion of ESBL gene-containing isolates included in the SDD category (79%), we recommend that physicians exercise caution in the use of cefepime for treatment of infections caused by these isolates, reducing possible therapeutic failure, particularly in cases of ESBL-producing bacterial strains.

  14. Reduced incidence and mortality from colorectal cancer with flexible-sigmoidoscopy screening: a meta-analysis.

    PubMed

    Shroff, Jennifer; Thosani, Nirav; Batra, Sachin; Singh, Harminder; Guha, Sushovan

    2014-12-28

    To conduct a systematic review and meta-analysis of published population-based randomized controlled trials (RCTs). RCTs evaluating the difference in mortality and incidence of colorectal cancer (CRC) between a screening flexible sigmoidoscopy (FS) group and control group (not assigned to screening FS) with a minimum 5 years median follow-up were identified by a search of MEDLINE and EMBASE databases and the Cochrane Central Register for Controlled Trials through August 2013. Random effects model was used for meta-analysis. Four RCTs with a total of 165659 patients in the FS group and 249707 patients in the control group were included in meta-analysis. Intention-to-treat analysis showed that there was a 22% risk reduction in total incidence of CRC (RR = 0.78, 95%CI: 0.74-0.83), 31% in distal CRC incidence (RR = 0.69, 95%CI: 0.63-0.75), and 9% in proximal CRC incidence (RR = 0.91, 95%CI: 0.83-0.99). Those who underwent screening FS were 18% less likely to be diagnosed with advanced CRC (OR = 0.82, 95%CI: 0.71-0.94). There was a 28% risk reduction in overall CRC mortality (RR = 0.72, 95%CI: 0.65-0.80) and 43% in distal CRC mortality (RR = 0.57, 95%CI: 0.45-0.72). This meta-analysis suggests that screening FS can reduce the incidence of proximal and distal CRC and mortality from distal CRC along with reduction in diagnosis of advanced CRC.

  15. Comparing badger (Meles meles) management strategies for reducing tuberculosis incidence in cattle.

    PubMed

    Smith, Graham C; McDonald, Robbie A; Wilkinson, David

    2012-01-01

    Bovine tuberculosis (bTB), caused by Mycobacterium bovis, continues to be a serious economic problem for the British cattle industry. The Eurasian badger (Meles meles) is partly responsible for maintenance of the disease and its transmission to cattle. Previous attempts to manage the disease by culling badgers have been hampered by social perturbation, which in some situations is associated with increases in the cattle herd incidence of bTB. Following the licensing of an injectable vaccine, we consider the relative merits of management strategies to reduce bTB in badgers, and thereby reduce cattle herd incidence. We used an established simulation model of the badger-cattle-TB system and investigated four proposed strategies: business as usual with no badger management, large-scale proactive badger culling, badger vaccination, and culling with a ring of vaccination around it. For ease of comparison with empirical data, model treatments were applied over 150 km(2) and were evaluated over the whole of a 300 km(2) area, comprising the core treatment area and a ring of approximately 2 km. The effects of treatment were evaluated over a 10-year period comprising treatment for five years and the subsequent five year period without treatment. Against a background of existing disease control measures, where 144 cattle herd incidents might be expected over 10 years, badger culling prevented 26 cattle herd incidents while vaccination prevented 16. Culling in the core 150 km(2) plus vaccination in a ring around it prevented about 40 cattle herd breakdowns by partly mitigating the negative effects of culling, although this approach clearly required greater effort. While model outcomes were robust to uncertainty in parameter estimates, the outcomes of culling were sensitive to low rates of land access for culling, low culling efficacy, and the early cessation of a culling strategy, all of which were likely to lead to an overall increase in cattle disease.

  16. Comparing Badger (Meles meles) Management Strategies for Reducing Tuberculosis Incidence in Cattle

    PubMed Central

    Smith, Graham C.; McDonald, Robbie A.; Wilkinson, David

    2012-01-01

    Bovine tuberculosis (bTB), caused by Mycobacterium bovis, continues to be a serious economic problem for the British cattle industry. The Eurasian badger (Meles meles) is partly responsible for maintenance of the disease and its transmission to cattle. Previous attempts to manage the disease by culling badgers have been hampered by social perturbation, which in some situations is associated with increases in the cattle herd incidence of bTB. Following the licensing of an injectable vaccine, we consider the relative merits of management strategies to reduce bTB in badgers, and thereby reduce cattle herd incidence. We used an established simulation model of the badger-cattle-TB system and investigated four proposed strategies: business as usual with no badger management, large-scale proactive badger culling, badger vaccination, and culling with a ring of vaccination around it. For ease of comparison with empirical data, model treatments were applied over 150 km2 and were evaluated over the whole of a 300 km2 area, comprising the core treatment area and a ring of approximately 2 km. The effects of treatment were evaluated over a 10-year period comprising treatment for five years and the subsequent five year period without treatment. Against a background of existing disease control measures, where 144 cattle herd incidents might be expected over 10 years, badger culling prevented 26 cattle herd incidents while vaccination prevented 16. Culling in the core 150 km2 plus vaccination in a ring around it prevented about 40 cattle herd breakdowns by partly mitigating the negative effects of culling, although this approach clearly required greater effort. While model outcomes were robust to uncertainty in parameter estimates, the outcomes of culling were sensitive to low rates of land access for culling, low culling efficacy, and the early cessation of a culling strategy, all of which were likely to lead to an overall increase in cattle disease. PMID:22761746

  17. Dose-Dependent Adverse Effects of Salinomycin on Male Reproductive Organs and Fertility in Mice

    PubMed Central

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  18. Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

    PubMed

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  19. Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors

    PubMed Central

    Carrière, I; Berr, C; Artero, S; Ancelin, M-L

    2010-01-01

    Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated. Design Prospective seven year cohort study. Setting General population, Montpellier, France. Participants 1433 people aged over 65 with a mean baseline age of 72.5 (SD 5.1) years. Main outcome measures Diagnosis of mild cognitive impairment or dementia established by a standardised neurological examination. Results Cox models were constructed to derive hazard ratios and determine confounding and interaction effects for potentially modifiable risk factors for dementia. Mean percentage population attributable fractions were calculated with 95% confidence intervals derived from bootstrapping for seven year incidence of mild cognitive impairment or dementia. The final model retained crystallised intelligence (population attributable fraction 18.11%, 95% confidence interval 10.91% to 25.42%), depression (10.31%, 3.66% to 17.17%), fruit and vegetable consumption (6.46%, 0.15% to 13.06%), diabetes (4.88%, 1.87% to 7.98%), and apolipoprotein E ε4 allele (7.11%, 2.44% to 11.98%). Conclusions Increasing crystallised intelligence and fruit and vegetable consumption and eliminating depression and diabetes are likely to have the biggest impact on reducing the incidence of dementia, outweighing even the effect of removing the principal known genetic risk factor. Although causal relations cannot be concluded with certainty, the study suggests priorities that may inform public health programmes. PMID:20688841

  20. By how much could screening by primary human papillomavirus testing reduce cervical cancer incidence in England?

    PubMed

    Castanon, Alejandra; Landy, Rebecca; Sasieni, Peter

    2017-06-01

    Objective The replacement of cytology with human papillomavirus testing as the primary cervical screening test in England is imminent. In light of newly available evidence, we revised our previous estimates of the likely impact of primary human papillomavirus testing on incidence of cervical cancer. Method and results Using screening data on women aged 25-64 diagnosed with cervical cancer in England between 1988 and 2012, we previously reported that 38.8% had a negative test six months to six years prior to diagnosis. However, not all of these cancers would be prevented by human papillomavirus testing: for 1.0% the human papillomavirus positive test would come too late (within 18 months of diagnosis) to make a difference; 7.6% will have a negative human papillomavirus test (based on 79.9% sensitivity of human papillomavirus testing in cytology negative women); and 2.0% will develop cancer despite a positive human papillomavirus test. Additionally, we estimate that some women (equivalent to 4.3% of current incidence) whose cancers are currently prevented by cytology-based screening will have a false-negative human papillomavirus test. Conclusion Overall, we estimate that 23.9% (95% CI: 19.3-27.6%) of current cases in women invited for screening could be prevented. Based on 2013 cancer incidence statistics, absolute numbers could be reduced by 487 (95% CI 394 to 563) or 3.4 (95% CI 2.8 to 4.0) per 100,000 women per year.

  1. Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

    PubMed Central

    Li-Sha, Ge; Jing-Lin, Zhao; Guang-Yi, Chen; Li, Liu; De-Pu, Zhou; Yue-Chun, Li

    2015-01-01

    The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis. PMID:26507386

  2. Dose-dependent protection by azelastine eye drops against pollen-induced allergic conjunctivitis. A double-blind, placebo-controlled study.

    PubMed

    Horak, F; Berger, U E; Menapace, R; Toth, J; Stübner, P U; Marks, B

    1998-04-01

    The efficacy and tolerability of azelastine (CAS 58581-89-8) eye drops at three different doses (0.025%, 0.05% and 0.1%) were investigated in a double-blind, randomized, placebo-controlled, crossover study in 24 subjects with a history of allergic conjunctivitis/rhinoconjunctivitis, who were challenged, out of season, by airbone allergen in the "Vienna Challenge Chamber" (VCC). Subjects received a single dose of azelastine eye drops 60 min before the start of a 4 h challenge in the VCC. Additional local challenge, mimicking a gust of wind, was administered 15 min before the end of the session. Each of the 4 study days was separated by a 2 week washout period. Azelastine eye drops showed a dose-dependent inhibition of the development of itching of the eyes. The effect was most pronounced 15 min after the additional local challenge. A maximal effect was achieved at a dose of 0.05%. Similar effects were observed on lacrimation. Azelastine eye drops also dose-dependently inhibited the degree of conjunctival redness, measured by digital imaging, and tended to reduce the low incidence of chemosis observed. Ranking of the results of all symptoms for each treatment group confirmed the optimal effect at a dose of 0.05%. Azelastine eye drops had no effect on nasal and bronchial symptoms or on measurements of airways function (FEV1). No adverse effects of the treatments were reported. The data support the use of 0.05% azelastine eye drops in the treatment of allergic conjunctivitis/rhinoconjunctivitis.

  3. A self-defense program reduces the incidence of sexual assault in Kenyan adolescent girls.

    PubMed

    Sinclair, Jake; Sinclair, Lee; Otieno, Evans; Mulinge, Munyae; Kapphahn, Cynthia; Golden, Neville H

    2013-09-01

    To determine the effect of a standardized 6-week self-defense program on the incidence of sexual assault in adolescent high school girls in an urban slum in Nairobi, Kenya. Population-based survey of 522 high school girls in the Korogocho-Kariobangi locations in Nairobi, Kenya, at baseline and 10 months later. Subjects were assigned by school attended to either a "No Means No Worldwide" self-defense course (eight schools; N = 402) or to a life-skills class (two schools; N = 120). Both the intervention and the life-skills classes were taught in the schools by trained instructors. Participants were administered the same survey at baseline and follow-up. A total of 522 girls (mean age, 16.7 ± 1.5 years; range, 14-21 years) completed surveys at baseline, and 489 at 10-month follow-up. At baseline, 24.5% reported sexual assault in the prior year, with the majority (90%) reporting assault by someone known to them (boyfriend, 52%; relative, 17%; neighbor, 15%; teacher or pastor, 6%). In the self-defense intervention group, the incidence of sexual assault decreased from 24.6% at baseline to 9.2% at follow-up (p < .001), in contrast to the control group, in which the incidence remained unchanged (24.2% at baseline and 23.1% at follow-up; p = .10). Over half the girls in the intervention group reported having used the self-defense skills to avert sexual assault in the year after the training. Rates of disclosure increased in the intervention group, but not in controls. A standardized 6-week self-defense program is effective in reducing the incidence of sexual assault in slum-dwelling high school girls in Nairobi, Kenya. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  4. Hypothesis: Impregnated school uniforms reduce the incidence of dengue infections in school children.

    PubMed

    Wilder-Smith, A; Lover, A; Kittayapong, P; Burnham, G

    2011-06-01

    Dengue infection causes a significant economic, social and medical burden in affected populations in over 100 countries in the tropics and sub-tropics. Current dengue control efforts have generally focused on vector control but have not shown major impact. School-aged children are especially vulnerable to infection, due to sustained human-vector-human transmission in the close proximity environments of schools. Infection in children has a higher rate of complications, including dengue hemorrhagic fever and shock syndromes, than infections in adults. There is an urgent need for integrated and complementary population-based strategies to protect vulnerable children. We hypothesize that insecticide-treated school uniforms will reduce the incidence of dengue in school-aged children. The hypothesis would need to be tested in a community based randomized trial. If proven to be true, insecticide-treated school uniforms would be a cost-effective and scalable community based strategy to reduce the burden of dengue in children.

  5. History of allergy and reduced incidence of colorectal cancer, Iowa Women's Health Study.

    PubMed

    Prizment, Anna E; Folsom, Aaron R; Cerhan, James R; Flood, Andrew; Ross, Julie A; Anderson, Kristin E

    2007-11-01

    Previous epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. We studied the association between allergy history and incident colorectal cancer (n=410) prospectively in 21,292 Iowa women followed for 8 years. Allergy was defined from four self-reported questions about physician-diagnosed asthma (a), hay fever (b), eczema or allergy of the skin (c), and other allergic conditions (d). A history of any allergy was inversely associated with incident colorectal cancer: after multivariate adjustment, the hazard ratio (HR) was 0.74 [95% confidence interval (95% CI), 0.59-0.94]. Compared with women with no allergy, women reporting only one of the four types of allergy and women reporting two or more types had HRs of 0.75 (95% CI, 0.56-1.01) and 0.58 (95% CI, 0.37-0.90), respectively (P trend=0.02). The inverse association persisted in analyses restricted to any type of nonasthmatic allergy (HR, 0.73; 95% CI, 0.56-0.95). HRs were similar for rectal and colon cancers as well as for colon subsites: proximal and distal (HRs for any allergy ranged from 0.63 to 0.78 across these end points). Allergy history, which may reflect enhanced immunosurveillance, is associated with a reduced risk of colorectal cancer.

  6. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

    PubMed Central

    Johnson, Matthew W.; Sewell, R. Andrew; Griffiths, Roland R.

    2011-01-01

    Background Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. Methods This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Results Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Conclusions Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. PMID:22129843

  7. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers.

    PubMed

    Johnson, Matthew W; Sewell, R Andrew; Griffiths, Roland R

    2012-06-01

    Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial.

    PubMed

    Mansour-Ghanaei, Fariborz; Joukar, Farahnaz; Taherzadeh, Zahra; Sokhanvar, Homayoon; Hasandokht, Tolou

    2016-06-07

    significantly lower than that in the placebo (6 patients vs 23 patients, P < 0.01, RRR = 12%, AR = 0.3, 95%CI: 0.2-0.6). Naproxen reduced the PEP in patients with ≥ 3 pancreatic cannulations (P < 0.01, RRR = 25%, AR = 0.1, 95%CI: 0.1-0.4) and an ERCP duration > 40 min (P < 0.01, RRR = 20%, AR = 0.9, 95%CI: 0.4-1.2). Single dose of suppository naproxen administered immediately before ERCP reduces the incidence of PEP.

  9. Dose-dependent teratogenicity of the synthetic cannabinoid CP-55,940 in mice.

    PubMed

    Gilbert, Marcoita T; Sulik, Kathleen K; Fish, Eric W; Baker, Lorinda K; Dehart, Deborah B; Parnell, Scott E

    Potent synthetic cannabinoids (SCBs) are illegally distributed drugs of abuse that are frequently consumed in spite of their adverse consequences. This study was designed to determine if the toxicity observed in adults also extends to the prenatal period by examining the developmental toxicity/teratogenicity of one of these SCBs, CP-55,940, in a mammalian model. First, immunohistochemistry was employed for cannabinoid receptor 1 (CB1) localization within gestational day (GD) 8 mouse embryos; this receptor was identified in the cranial neural plate, suggesting that the endogenous cannabinoid system may be involved in normal development. Based on this information and on previous avian teratogenicity studies, the current investigation focused on cannabinoid exposure during neurulation. The treatment paradigm involved acute i.p. administration of vehicle, 0.0625, 0.125, 0.25, 0.5, 1.0, or 2.0mg/kg CP-55,940 to time-mated C57Bl/6J mice on their 8th day of pregnancy (n>10 litters per treatment group). On GD 17, litters were harvested and examined for numbers of live, dead, or resorbed fetuses, as well as for fetal weight, length, and gross morphological abnormalities. No effect on litter size, fetal weight, or crown rump length was seen at any of the CP-55,940 dosages tested. Major malformations involving the craniofacies and/or eyes were noted in all drug-treated groups. Selected fetuses with craniofacial malformations were histologically sectioned and stained, allowing investigation of brain anomalies. Observed craniofacial, ocular, and brain abnormalities in drug-treated fetuses included lateral and median facial clefts, cleft palate, microphthalmia, iridial coloboma, anophthalmia, exencephaly, holoprosencephaly, and cortical dysplasia. With the most commonly observed defects involving the eyes, the incidence and severity of readily identifiable ocular malformations were utilized as a basis for dose-response analyses. Ocular malformation ratings revealed dose-dependent

  10. Dose-dependent effects of D-methionine for rescuing noise-induced permanent threshold shift in guinea-pigs.

    PubMed

    Lo, W-C; Liao, L-J; Wang, C-T; Young, Y-H; Chang, Y-L; Cheng, P-W

    2013-12-19

    The purpose of this study was to examine the dose-response effectiveness of d-methionine (d-met) in rescuing a noise-induced permanent threshold shift (PTS) and cochlear biochemistry following noise exposure. One hour after being exposed to continuous broadband white noise at 105dB sound pressure level (SPL) for 6h, guinea-pigs were treated five times at 12-h intervals with 200, 400, or 600mg/kg d-met or sterile 0.9% saline (each group, N=6) by intraperitoneal injection. Six guinea-pigs with normal hearing that were not exposed to noise served as control animals. Although administration of d-met 200mg/kg did not significantly reduce the mean PTS, treatment with d-met 600mg/kg achieved a complete rescue response. The level of rescue from noise-induced PTS following treatment with 200, 400, or 600mg/kg d-met was dose dependent. The attenuation of the noise-induced decreases in the activities of the Na(+), K(+)-ATPase and Ca(2+)-ATPase following treatment with 200, 400, or 600mg/kg d-met was also dose dependent. Likewise, d-met-dose-dependent decreases in mean lipid peroxidation and nitric oxide levels were observed in the d-met treated groups. Significant attenuation of increased oxidative stress and decreased ATPase activities was concurrent with the d-met-mediated improvements in noise-induced auditory dysfunction.

  11. Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis

    PubMed Central

    Viny, Aaron D.; Ott, Christopher J.; Spitzer, Barbara; Rivas, Martin; Meydan, Cem; Papalexi, Efthymia; Yelin, Dana; Shank, Kaitlyn; Reyes, Jaime; Chiu, April; Romin, Yevgeniy; Boyko, Vitaly; Thota, Swapna; Maciejewski, Jaroslaw P.; Melnick, Ari

    2015-01-01

    Cohesin complex members have recently been identified as putative tumor suppressors in hematologic and epithelial malignancies. The cohesin complex guides chromosome segregation; however, cohesin mutant leukemias do not show genomic instability. We hypothesized that reduced cohesin function alters chromatin structure and disrupts cis-regulatory architecture of hematopoietic progenitors. We investigated the consequences of Smc3 deletion in normal and malignant hematopoiesis. Biallelic Smc3 loss induced bone marrow aplasia with premature sister chromatid separation and revealed an absolute requirement for cohesin in hematopoietic stem cell (HSC) function. In contrast, Smc3 haploinsufficiency increased self-renewal in vitro and in vivo, including competitive transplantation. Smc3 haploinsufficiency reduced coordinated transcriptional output, including reduced expression of transcription factors and other genes associated with lineage commitment. Smc3 haploinsufficiency cooperated with Flt3-ITD to induce acute leukemia in vivo, with potentiated Stat5 signaling and altered nucleolar topology. These data establish a dose dependency for cohesin in regulating chromatin structure and HSC function. PMID:26438361

  12. Manipulating dietary anions and cations for prepartum dairy cows to reduce incidence of milk fever.

    PubMed

    Block, E

    1984-12-01

    Twenty preparturient dairy cows were in a 2-yr switchover design to test effects of dietary ions on incidence of milk fever. In yr 1, cows were blocked and assigned randomly 45 days prepartum to one of two diets; one diet contained an excess of anions, and the second diet contained an excess of cations. In yr 2, cows were changed to the opposite diet. Both diets were equivalent for crude protein (11%), calcium (.65%), phosphorus (.25%), and energy on a dry basis but differed for quantities of chlorine, sulfur, and sodium. Both diets were chopped alfalfa hay, corn silage, high moisture corn, and vitamin-mineral mix. Diets were available ad libitum as complete rations. There were no differences in dry matter intake of the diets. Cows consuming the anionic diet had no milk fever, but cows consuming the canionic diet had 47.4% incidence. Samples of blood plasma showed that cows consuming the anionic diet maintained calcium and phosphorus through parturition, whereas cows consuming the cationic diet decreased in these minerals around calving. Hydroxyproline was higher for cows consuming the anionic diet during the peripartal period compared to cows consuming the cationic diet. Milk produced in the lactation subsequent to prepartum treatment was 6.8% less for cows offered the cationic diet. When milk production of paretic and nonparetic cows offered the cationic diet was compared, milk was reduced 14% with milk fever.

  13. Does accident prevention education reduce the incidence of childhood accidents in the home?

    PubMed

    Close, Jessica

    2002-12-01

    This mini-review examines whether accident prevention education reduces the incidence of home accidents among children under the age of 5 years. The Cochrane Library, Medline, CINAHL and Embase databases were searched for randomized controlled studies (RCTs) and systematic reviews of RCTs that compared parents who received accident prevention education with those that did not. Only two RCTs met the inclusion criteria for analysis in this review. The results of these studies showed that there was no statistically significant difference in accidents between the two groups but the quality of the trials was low. An RCT in process (Watson et al, 2002) looks likely to provide evidence of a high standard, so that practice decisions regarding accident prevention education can be made.

  14. Use of aqueous foam to reduce radioactive material dispersal in sabotage incidents

    SciTech Connect

    Hartman, W.F.

    1986-01-01

    One potential type of sabotage incident in a nuclear facility involves the use of a large quantity of high explosive to disperse radioactive material into the atmosphere. This paper discusses the possible use of aqueous foam to reduce the consequences of such an event under the assumption that the location of the explosive is known and that some minimal time is available to emplace a mitigation system. Work conducted over the past several years has shown that low expansion ratio aqueous foams (e.g., 60 parts of air to one part water-soap concentrate solution by volume) exhibit exemplary properties in reducing the effects of a detonation. Not only does the foam significantly reduce the release of fine particulate which attempt to pass through it, but it also exhibits unusual pressure attentuation properties. Data demonstrating both the particle capture and pressure attenuation properties are presented along with information relative to generation of foam and some of the logistical constraints involved in its use.

  15. The use of aqueous foam to reduce radioactive material dispersal in sabotage incidents

    SciTech Connect

    Hartman, W.F.

    1986-01-01

    One potential type of sabotage incident in a nuclear facility involves the use of a large quantity of high explosive to disperse radioactive material into the atmosphere. This paper discusses the possible use of aqueous foam to reduce the consequences of such an event under the assumption that the location of the explosive is known and that some minimal time is available to emplace a mitigation system. Work conducted over the past several years has shown that low expansion ratio aqueous foams (e.g., 60 parts of air to one part water-soap concentrate solution by volume) exhibit exemplary properties in reducing the effects of a detonation. Not only does the foam significantly reduce the release of fine particulate which attempt to pass through it, but it also exhibits unusual pressure attenuation properties. Data demonstrating both the particle capture and pressure attenuation properties are presented along with information relative to generation of foam and some of the logistical constraints involved in its use.

  16. Incidence and Risk Factors for and the Effect of a Program To Reduce the Incidence of Surgical Site Infection after Cardiac Surgery

    PubMed Central

    Cohen, Bevin; Hyman, Sandra; Larson, Elaine; Fowler, Dennis L.

    2014-01-01

    Abstract Background: Surgical site infection (SSI) after cardiac surgery (CS) is a serious complication that increases hospital length of stay (LOS), has a substantial financial impact, and increases mortality. The study described here was done to evaluate the effect of a program to reduce SSI after CS. Methods: In January 2007, a multi-disciplinary CS infection-prevention team developed guidelines and implemented bundled tactics for reducing SSI. Data for all patients who underwent CS from 2006–2008 were used to determine whether there was: 1) A difference in the incidence of SSI in white patients and those belonging to minority groups; 2) a reduction in SSI after intervention; and 3) a statistically significant difference in the incidence of SSI in the third quarter of each year as compared with the other quarters of the year. Results: Of 3,418 patients who underwent CS; 1,125 (32.9%) were members of minority groups and 2,293 (67.1%) were white. Eighty (2.3%) patients developed SSI. There was no significant difference in the incidence of SSI in non-Hispanic white patients and all others (2.1% vs. 2.8%, p=0. 42). The incidence of SSI decreased significantly from 2006 (3.0%) to 2007 (2.5%) and 2008 (1.4%), (p=0.03). Surgical site infection occurred more often in the third quarter of each of the years of the study than in other quarters of each year (3.3 vs. 2.0%, p=0.038). Conclusions: Implementation of a program to reduce SSI after CS was associated with a lower incidence of SSI across all racial and ethnic groups and over time, but was not associated with a lower incidence of SSI in the third quarter of each year than in the other quarters. PMID:24800982

  17. Healthy lifestyles reduce the incidence of chronic diseases and dementia: evidence from the Caerphilly cohort study.

    PubMed

    Elwood, Peter; Galante, Julieta; Pickering, Janet; Palmer, Stephen; Bayer, Antony; Ben-Shlomo, Yoav; Longley, Marcus; Gallacher, John

    2013-01-01

    Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia. In 1979 healthy behaviours were recorded on 2,235 men aged 45-59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined. Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005). After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia. The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009. A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low.

  18. Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study

    PubMed Central

    Elwood, Peter; Galante, Julieta; Pickering, Janet; Palmer, Stephen; Bayer, Antony; Ben-Shlomo, Yoav; Longley, Marcus; Gallacher, John

    2013-01-01

    Background Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia. Methods In 1979 healthy behaviours were recorded on 2,235 men aged 45–59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined. Findings Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005). After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia. The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009. Interpretation A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low. PMID:24349147

  19. Soft Perches in an Aviary System Reduce Incidence of Keel Bone Damage in Laying Hens

    PubMed Central

    Stratmann, Ariane; Fröhlich, Ernst K. F.; Harlander-Matauschek, Alexandra; Schrader, Lars; Toscano, Michael J.; Würbel, Hanno; Gebhardt-Henrich, Sabine G.

    2015-01-01

    Keel bone fractures and deviations are one of the major welfare and health issues in commercial laying hens. In non-cage housing systems like aviaries, falls and collisions with perches and other parts of the housing system are assumed to be one of the main causes for the high incidence of keel bone damage. The objectives of this study were to investigate the effectiveness of a soft perch material to reduce keel bone fractures and deviations in white (Dekalb White) and brown laying hens (ISA Brown) kept in an aviary system under commercial conditions. In half of 20 pens, all hard, metal perches were covered with a soft polyurethane material. Palpation of 20 hens per pen was conducted at 18, 21, 23, 30, 38, 44 and 64 weeks of age. Production data including egg laying rate, floor eggs, mortality and feed consumption were collected over the whole laying period. Feather condition and body mass was assessed twice per laying period. The results revealed that pens with soft perches had a reduced number of keel bone fractures and deviations. Also, an interaction between hybrid and age indicated that the ISA hybrid had more fractured keel bones and fewer non-damaged keel bones compared with the DW hybrid at 18 weeks of age, a response that was reversed at the end of the experiment. This is the first study providing evidence for the effectiveness of a soft perch material within a commercial setting. Due to its compressible material soft perches are likely to absorb kinetic energy occurring during collisions and increase the spread of pressure on the keel bone during perching, providing a mechanism to reduce keel bone fractures and deviations, respectively. In combination with genetic selection for more resilient bones and new housing design, perch material is a promising tool to reduce keel bone damage in commercial systems. PMID:25811980

  20. [Does nasal decontamination reduce the incidence of infections after cardiac surgery?].

    PubMed

    Jabbour, Hisham; Madi-Jebara, Samia; Jabbour, Khalil; Yazigi, Alexandre; Haddad, Fadia; Hayek, Gemma; Yazbeck, Patricia; Antakly, Marie-Claire

    2010-01-01

    Mupirocin applied to the anterior nares four times daily usually eliminates Staphylococcus aureus, including methicillin resistant, within 48 hours. Prophylactic intranasal mupirocin is safe, inexpensive and effective in reducing the overall sternal wound infection after open-heart surgery. This study was designed to determine whether decreasing nasal bacterial colonization by applying mupirocin intra nasally decreases mediastinal, sternal, pulmonary and cutaneous infections after open-heart surgery. After institutional approval and informed consent, 392 patients were included in a randomized, prospective study. Nasal cultures were taken for all patients before surgery. Patients were divided in two groups: Group I (n = 190) receiving mupirocin in the anterior nares 4 times daily for 48 hours before surgery; Group II (n = 202) was the control group. Patients were followed for a month after surgery. All mediastinal, sternal, pulmonary and cutaneous infections were documented and treated with appropriate antibiotics. A Student test for quantitative data and a chi2 test for qualitative data were used for statistical analysis. p < or = 0.05 was considered significant. The two groups had the same demographic characteristics and risk factors. Nasal carriage of Staphylococcus was 36.2% in the two groups. Neither mediastinitis nor sternitis were noticed in any of the two groups. There was no statistical difference between the groups according to the frequency of the cutaneous infections (Group I: 19/190 - Group II: 13/202) and pneumonia (Group I: 7/190 - Group II: 13/202). In patients who had nasal carriage of Staphylococcus, nasal decontamination has not shown a statistical difference of cutaneous infections of the lower limbs nor pneumonia. Although nasal decontamination reduced the incidence of sternal wound infection (Gr I 0/190 - Gr II 4/202 ; p = 0.017). Staphylococcus aureus, in the control group, induced more cutaneous infections (30.8% vs 11.7% ; p = 0.048). The

  1. How long will it take to reduce gastric cancer incidence by eradicating Helicobacter pylori infection?

    PubMed

    Osborn, John F; Cattaruzza, Maria S; Ferri, Anna M; De Angelis, Flora; Renzi, Davide; Marani, Alessandra; Vaira, Dino

    2013-07-01

    Helicobacter pylori (H. pylori) is the most important risk factor for the development of gastric cancer. The objective of this article is to estimate how the number of clinically diagnosed cases caused by H. pylori would reduce in the years after the eradication of the infection from a population. It is assumed that the eradication of H. pylori will prevent the start of some new gastric tumors, but those that have passed the "point of no return" will continue to develop until diagnosed clinically. The observed reduction in the number of clinically diagnosed cases of gastric cancer will depend on the form and parameters of the distribution of the time t taken for tumor to develop into a clinical case after passing the "point of no return." This analysis assumes that the time t follows normal and log-normal distributions with means 5, 10, and 15 years. If the mean value of time t were 5 years, H. pylori caused cases should be almost eliminated after 10 years, whereas if the mean were 10 years, the number of cases should be halved. If the mean were 15 years, the reduction would only be about 15% after 10 years. The eradication of H. pylori from a population will reduce the incidence of gastric cancer, but the follow-up time needed to show and evaluate the reduction may be longer than that that has been used in studies published so far. ©2013 AACR.

  2. Thyme oil vapour and modified atmosphere packaging reduce anthracnose incidence and maintain fruit quality in avocado.

    PubMed

    Sellamuthu, Periyar Selvam; Mafune, Mpho; Sivakumar, Dharini; Soundy, Puffy

    2013-09-01

    Postharvest application of prochloraz fungicide is commercially practiced to control anthracnose, a postharvest disease in avocado. Increasing consumer concern regarding food safety and demand for organically produced fruits make it necessary to search for natural environmentally friendly alternative products and processes for the fruit industry. A combination of modified atmosphere packaging (MAP; ∼8% CO₂, 2% O₂) plus thyme oil (TO) was evaluated on the incidence and severity of anthracnose, physiological disorders (grey pulp, vascular browning), fruit quality parameters (L*, h°, firmness, weight loss) and sensory parameters (taste, texture, flavour and overall acceptance), phenylalanine ammonia-lyase (PAL) enzyme activity, total phenolic compounds, flavonoid contents and antioxidant activity in avocados ('Fuerte' and 'Hass' cultivars) held at 10 °C cold storage for 18 days and thereafter, ripened at 25 °C for 5-10 days. Stand-alone MAP, commercial treatment (prochloraz 0.05%) and untreated (control) fruit were included for comparison. MAP + TO treatment significantly (P < 0.05) reduced the incidence and severity of anthracnose, grey pulp, vascular browning, weight loss and loss of fruit firmness, and showed acceptable taste, flavour, texture and higher overall acceptance, increased PAL activity, total phenolic compounds, flavonoid contents and antioxidant activity, after ripening at 25 °C followed by cold storage at 10 °C. This investigation recommends MAP + TO combination treatment as a suitable alternative to the currently adopted prochloraz application. © 2013 Society of Chemical Industry.

  3. Modifying Post-Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence

    PubMed Central

    Herzog, Dominik; Poellinger, Alexander; Doellinger, Felix; Schuermann, Dirk; Temmesfeld-Wollbrueck, Bettina; Froeling, Vera; Schreiter, Nils F.; Neumann, Konrad; Hippenstiel, Stefan; Suttorp, Norbert; Hubner, Ralf-Harto

    2015-01-01

    Objective Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax. Methods Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC)). Results The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts. Conclusions In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data. PMID:26010886

  4. Cystathionine beta synthase gene dose dependent vascular remodeling in murine model of hyperhomocysteinemia.

    PubMed

    Tyagi, Neetu; Qipshidze, Natia; Sen, Utpal; Rodriguez, Walter; Ovechkin, Alexander; Tyagi, Suresh C

    2011-09-30

    Although children born with severe homocystinurea (i.e. cystathionine beta synthase homozygote knockout, CBS-/-) develop deleterious vascular complications with structural malformation and do not live past teenage, the heterozygote (CBS-/+) lives with apparently normal phenotype. Interestingly, this differential role of CBS expression in vascular remodeling is unclear. Peroxisome proliferator activated receptor gamma (PPARγ) is nuclear transcription factor that mitigates vascular complications. The hypothesis was that homocysteine (Hcy) decreased thioredoxin (Trx), peroxiredoxin (Prx), increased NADPH oxidase (NOX1), mitochondrial nitric oxide synthase (mtNOS) activity and reactive oxygen species (ROS) in mitochondria in a CBS gene dose-dependent manner. ROS transduced matrix metalloproteinase (MMP) activation causing thickening (fibrosis) of the basement membrane, rendering ineffective endothelial nitric oxide synthase (eNOS) and promoted endothelial-smooth muscle disconnection/uncoupling by antagonizing PPARγ. Wild type (WT-CBS+/+), CBS-/+ and CBS -/- mice were treated with or without ciglitazone (CZ, a PPARγ agonist) in food at birth. Aortic nuclear PPARγ expression was measured by EMSA. Aortic mtNOS activity and ROS production was measured using NO- and H(2)O(2)-electrodes, respectively. Aorta was analyzed for Trx, Prx, by Western blot, and PCR. MMP activity was by in situ zymography. Aortic function was measured in tissue myobath. The results suggested 90% morbidity in CBS-/- allele at 12 wks. However, treatment with the PPARγ agonist, CZ significantly reduced the morbidity to 20%. In addition, CZ restored the PPARγ activity in CBS-/+ and -/- mice to normal levels. The oxidative stress was alleviated by CZ treatment. In situ labeling with mito-tracker suggests co-localization of ROS with mitochondrial mitophagy. The mtNOS activity was increased in HHcy compared to WT. The data support the notion that Hcy decreases redoxins, increases mtNOS activity and

  5. Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models.

    PubMed

    Komissarov, Andrey A; Florova, Galina; Azghani, Ali O; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

    2016-08-01

    The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. Copyright © 2016 the American Physiological Society.

  6. Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models

    PubMed Central

    Florova, Galina; Azghani, Ali O.; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M.; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

    2016-01-01

    The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. PMID:27343192

  7. [Pre-operative smoking cessation does not always reduce the incidence of surgical site infection after gastrointestinal surgery].

    PubMed

    Kuri, Michioki; Yamada, Terumasa; Nakagawa, Masashi; Tanigami, Hironobu; Kishi, Yoshihiko

    2011-02-01

    Centers for Disease Control (CDC) recommend pre-operative smoking cessation to reduce the risk of surgical site infection (SSI). However, whether pre-operative smoking cessation reduces the incidence of SSI for gastrointestinal surgery is unclear. We investigated whether pre-operative smoking cessation reduces the incidence of SSI among patients undergoing gastrointestinal surgery. The study subjects were 512 consecutive patients undergoing gastrointestinal surgery at Osaka Medical Center for Cancer and Cardiovascular Diseases. SSI occurrence was determined by the hospital SSI surveillance team. Pre-operative smoking status was obtained by interview, and the patients were divided into four groups. Information on age, sex, operation time, operational organ, American Society of Anesthesiologists physical status (ASA-PS), elective or emergency surgery, co-existing procedures, use of scopes, ileo-colostomy, properties of drain tube, use of floss, and wound contamination was obtained from the medical records. The relationship between smoking status and incidence of SSI, and risk factors associated with the incidence of SSI were investigated. SSI occurred in 83 patients. Pre-operative smoking status had no relation with the incidence of SSI. Operation time, gallbladder and pancreatic surgery, colon surgery, emergency surgery, co-existing procedures, ilea-colostomy, closed drain, usage of floss, and wound contamination were related significantly with SSI. Pre-operative smoking cessation does not reduce the incidence of SSI. However, since continuation of smoking has no benefits for the safety of surgery, anesthesiologists must advice patients to quit smoking before surgery.

  8. Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall

    PubMed Central

    Young, Kymberly; Drevets, Wayne C.; Schulkin, Jay; Erickson, Kristine

    2011-01-01

    The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n=66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n=33) or high-dose (0.45 mg/kg IV; n=33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = 0.04), increased the percent of categorical (nonspecific) memories recalled, and slowed response times for categorical memories (p <0.001), compared to placebo performance (p < 0.001). Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories. PMID:21942435

  9. Daytime Alertness in Parkinson’s Disease: Potentially Dose-Dependent, Divergent Effects by Drug Class

    PubMed Central

    Bliwise, Donald L.; Trotti, Lynn Marie; Wilson, Anthony G.; Greer, Sophia A.; Wood-Siverio, Cathy; Juncos, Jorge J.; Factor, Stewart A.; Freeman, Alan; Rye, David B.

    2013-01-01

    Background Many patients with idiopathic Parkinson’s disease experience difficulties maintaining daytime alertness. Controversy exists regarding whether this reflects effects of anti-Parkinsonian medications, the disease itself or other factors such as nocturnal sleep disturbances. In this study we examined the phenomenon by evaluating medicated and unmedicated Parkinson’s patients with objective polysomnographic measurements of nocturnal sleep and daytime alertness. Methods Patients (n = 63) underwent a 48-hour laboratory-based study incorporating 2 consecutive nights of overnight polysomnography and 2 days of Maintenance of Wakefulness Testing. We examined correlates of individual differences in alertness, including demographics, clinical features, nocturnal sleep variables and class and dosage of anti-Parkinson’s medications. Results Results indicated that: 1) relative to unmediated patients, all classes of dopaminergic medications were associated with reduced daytime alertness and this effect was not mediated by disease duration or disease severity; 2) increasing dosages of dopamine agonists were associated with less daytime alertness, whereas higher levels of levodopa were associated with higher levels of alertness. Variables unrelated to Maintenance of Wakefulness Test defined daytime alertness included age, sex, years with diagnosis, motor impairment score and most nocturnal sleep variables. Conclusions Deficits in objectively assessed daytime alertness in Parkinson’s disease appear to be a function of both the disease and the medications and their doses utilized. The apparent divergent dose-dependent effects of drug class in Parkinson’s disease are anticipated by basic science studies of the sleep/wake cycle under different pharmacological agents. PMID:22753297

  10. Dose-dependent effects of prostaglandin E2 in macrophage adhesion and migration.

    PubMed

    Osma-Garcia, Inés C; Punzón, Carmen; Fresno, Manuel; Díaz-Muñoz, Manuel D

    2016-03-01

    Macrophage migration to the focus of infection is a hallmark of the innate immune response. Macrophage spreading, adhesion, and migration through the extracellular matrix require dynamic remodeling of the actin cytoskeleton associated to integrin clustering in podosomes and focal adhesions. Here, we show that prostaglandin E2 (PGE2 ), the main prostaglandin produced by macrophages during inflammation, promote the distinctive dose-dependent formation of podosomes or focal adhesions in macrophages. Low concentrations of PGE2 increased p110γ PI3K expression, phosphorylation of actin-related protein 2, and formation of podosomes, which enhanced macrophage migration in response to chemokines. However, high doses of PGE2 increased phosphorylation of paxillin and focal adhesion kinase, the expression of serine/threonine protein kinase 1, and promoted focal adhesion formation and macrophage adhesion, reducing macrophage chemotaxis. In summary, we describe the dual role of PGE2 as a promoter of macrophage chemotaxis and adhesion, proposing a new model of macrophage migration to the inflammatory focus in the presence of a gradient of PGE2 .

  11. Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall.

    PubMed

    Young, Kymberly; Drevets, Wayne C; Schulkin, Jay; Erickson, Kristine

    2011-10-01

    The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n = 66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n = 33) or high-dose (0.45 mg/kg IV; n = 33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = .04), increased the percent of categorical (nonspecific) memories recalled (p < .001), and slowed response times for categorical memories (p < .001), compared with placebo performance. Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories.

  12. Contrast media and glomerular filtration: dose dependence of clearance for three agents

    SciTech Connect

    Baeck, S.E.K.; Krutzen, E.; Nilsson-Ehle, P.

    1988-09-01

    Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of (/sup 51/Cr)EDTA in two groups of patients with reduced renal function. When compared with (/sup 51/Cr)EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice.

  13. Dose-dependent and synergistic effects of proteoglycan 4 on boundary lubrication at a human cornea-polydimethylsiloxane biointerface.

    PubMed

    Morrison, Sheila; Sullivan, David A; Sullivan, Benjamin D; Sheardown, Heather; Schmidt, Tannin A

    2012-01-01

    Proteoglycan 4 (PRG4), also known as lubricin, is a boundary lubricating mucin-like glycoprotein present on several tissue surfaces in the body. The objectives of this study were to (1) implement and characterize an in vitro boundary lubrication test at a human cornea-polydimethylsiloxane (PDMS) biointerface and (2) determine the dose-dependent and synergistic effects of PRG4, with hyaluronan (HA), on ocular surface boundary lubrication using this test. Human corneas and model PDMS material were articulated against each other, at effective sliding velocities v(eff) between 0.3 and 30 mm/sec under physiologic loads of approximately 8 to 25 kPa. Samples were tested serially in (1) saline, PRG4 at 30, 100, 300 μg/mL resuspended in saline, then saline again or (2) saline, AQuify Comfort Eye Drops (containing 0.1% HA), 300 μg/mL PRG4 in saline, 300 μg/mL PRG4 in AQuify, then saline again. Both static and kinetic friction coefficients were calculated. PRG4 effectively lowered friction at the cornea-PDMS biointerface, both alone in a dose-dependent manner and in combination with HA. PRG4 reduced kinetic friction coefficients, <μ(kinetic, Neq)>, from approximately 0.30 in saline, to approximately 0.30, 0.24, and 0.17 in 30, 100, and 300 μg/mL PRG4, respectively. Values of <μ(kinetic, Neq)> in AQuify, approximately 0.32, were similar to those in saline; however, when combined with 300 μg/mL PRG4, values of <μ(kinetic, Neq)> were reduced to approximately 0.15. PRG4 functions as an effective ocular surface boundary lubricant, both alone in a dose-dependent manner and in combination with HA.

  14. Rebamipide Alters the Esophageal Microbiome and Reduces the Incidence of Barrett's Esophagus in a Rat Model.

    PubMed

    Kohata, Yukie; Nakahara, Kenichi; Tanigawa, Tetsuya; Yamagami, Hirokazu; Shiba, Masatsugu; Watanabe, Toshio; Tominaga, Kazunari; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2015-09-01

    Barrett's esophagus (BE) is characterized by a distinct Th2-predominant cytokine profile. However, antigens that shift the immune response toward the Th2 profile are unknown. We examined the effects of rebamipide on the esophageal microbiome and BE development in a rat model. BE was induced by esophagojejunostomy in 8-week-old male Wistar rats. Rats were divided into control and rebamipide-treated group receiving either a normal or a 0.225 % rebamipide-containing diet, respectively, and killed 8, 16, 24, and 32 weeks after the operation. PCR-amplified 16S rDNAs extracted from esophageal samples were examined by terminal-restriction fragment length polymorphism (T-RFLP) analysis to assess microbiome composition. The dynamics of four bacterial genera (Lactobacillus, Clostridium, Streptococcus, and Enterococcus) were analyzed by real-time PCR. The incidences of BE in the control and rebamipide group at 24 and 32 weeks were 80 and 100, and 20 and 33 %, respectively. T-RFLP analysis of normal esophagus revealed that the proportion of Clostridium was 8.3 %, while that of Lactobacillales was 71.8 %. The proportions of Clostridium increased and that of Lactobacillales decreased at 8 weeks in both groups. Such changes were consistently observed in the control but not in the rebamipide group. Clostridium and Lactobacillus expression was lower and higher, respectively, in the rebamipide group than in the control group. Rebamipide reduced BE development and altered the esophageal microbiome composition, which might play a role in BE development.

  15. [The Acapulco Declaration: a proposal to reduce incidence of diabetes in México].

    PubMed

    Aguilar-Salinas, Carlos Alberto; Gómez-Pérez, Francisco Javier

    2006-01-01

    Type 2 diabetes is the main health problem in Mexico. The growing number of cases, the high percentage of individuals with chronic complications and the treatment's cost are among the explanations for the inability in the control of this disease. Diabetes prevention is most likely to reduce the rate of growth of this diabetes burden on our health system. At- risk individuals can be identified and several interventions have proved to be effective in decreasing diabetes incidence. Diabetes prevention related interventions can become a reality with the active participation of the government and society. Thus, a joint collaboration between the medical community, the government and society is needed to phase out the diabetes epidemic. Published diabetes prevention programs were reviewed and interventions feasible for Mexico were summarized in a document called "Declaración de Acapulco". This paper was reviewed and approved by the Sociedad Mexicana de Nutrición y Endocrinología; additional endorsement was obtained from several Mexican and international societies and institutions. The manuscript describes several initiatives, which can be applied in schools, work places, primary health services and by the government. Some of these are focused on the general population; others are applicable to at-risk individuals. The "Declaración de Acapulco" is a-call-for-action position directed towards the whole society and designed to achieve effective diabetes prevention.

  16. Use of indocyanine green videoangiography during intracranial aneurysm surgery reduces the incidence of postoperative ischaemic complications.

    PubMed

    Lai, Leon Tat; Morgan, Michael Kerin

    2014-01-01

    Microscope-integrated near-infrared indocyanine green videoangiography (ICGVA) has been shown to be a useful adjunct for intracranial aneurysm surgery. That the routine application of this technique reduces the risk of postoperative ischaemic complication, however, has not been reported. We present a retrospective matched-pair comparison of ICGVA guided aneurysm surgery versus historic control surgical cohort treated by the same author. Index patients and controls were matched for aneurysm size, location, patient demographics, risk factors, comorbidities, and surgical treatments. Ninety-one eligible patients with 100 intracranial aneurysms were treated using ICGVA assistance. There were no statistically significant differences between the two groups in terms of patient age, sex, risk factors, comorbidities and aneurysm characteristics. Of the 100 aneurysms in the ICGVA group, 107 investigations of ICGVA were performed. In 79 aneurysms (79.0%), ICGVA was considered useful but did not affect surgical management. In six patients (6.0%), ICGVA led to a crucial change of intraoperative strategies. In nine patients (9.0%), it was considered critical in assuring patency of small perforators. ICGVA was of no benefit in four patients (4.0%) and was misleading in two (2.0%). Postoperative ischaemic complications occurred in three patients (3.3%) in the ICGVA group compared with seven patients (7.7%) in the control group (p<0.001). Our study supports the use of ICGVA in aneurysm surgery as a safe and effective modality of intraoperative blood flow assessment. With all limitations of a retrospective matched-pair comparison, the use of ICGVA during routine aneurysm surgery reduces the incidence of postoperative ischaemic complications.

  17. Piracetam for reducing the incidence of painful sickle cell disease crises.

    PubMed

    Al Hajeri, A A; Fedorowicz, Z; Omran, A; Tadmouri, G O

    2007-04-18

    Sickle cell disease is one of the most common genetic disorders. Sickle cell crises in which irregular and dehydrated cells contribute to blocking of blood vessels are characterised by episodes of pain. Treatment is mainly supportive and symptomatic. In vitro studies with piracetam indicate that it has the potential for inhibition and a reversal of the process of sickling of erythrocytes. To assess the effectiveness of piracetam for reducing the incidence of painful sickle cell disease crises. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the last search of the Group's Haemoglobinopathies Trials Register: February 2007. Randomised controlled trials comparing orally administered piracetam to placebo or standard care in people, of all ages and both sexes, with sickle cell disease. Two authors independently assessed trial quality and extracted data. Trial authors were contacted for additional information. Adverse effects data were collected from the trials. Three trials involving 169 participants were included in the review. A limited amount of data addressing some of the primary and some of the secondary outcomes were provided, but data were incomplete and based on unvalidated assumptions used in the evaluation of outcomes. One trial reported a reduction in the number of pain crises and their severity with active intervention than placebo but presented no data to confirm these results. A second trial presented a monthly global pain score based on the number of sickle cell crises and severity of pain but included no separate data for these primary outcomes. Although there was no significant difference between the piracetam and placebo periods for the number of days of hospitalisation (P = 0.87) in one trial, inconsistencies in the

  18. Piracetam for reducing the incidence of painful sickle cell disease crises.

    PubMed

    Al Hajeri, Amani; Fedorowicz, Zbys

    2016-02-12

    Sickle cell disease is one of the most common genetic disorders. Sickle cell crises in which irregular and dehydrated cells contribute to blocking of blood vessels are characterised by episodes of pain. Treatment is mainly supportive and symptomatic. In vitro studies with piracetam indicate that it has the potential for inhibition and a reversal of the process of sickling of erythrocytes. This is an update of a previously published Cochrane review. To assess the effectiveness of piracetam for reducing the incidence of painful sickle cell disease crises. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Last search of the Group's Haemoglobinopathies Trials Register: 21 September 2015. Randomised controlled trials comparing orally administered piracetam to placebo or standard care in people, of all ages and both sexes, with sickle cell disease. Two authors independently assessed trial quality and extracted data. Trial authors were contacted for additional information. Adverse effects data were collected from the trials. Three trials involving 169 participants were included in the review. A limited amount of data addressing some of the primary and some of the secondary outcomes were provided, but data were incomplete and based on un-validated assumptions used in the evaluation of outcomes. One trial reported a reduction in the number of pain crises and their severity with active intervention than placebo but presented no data to confirm these results. A second trial presented a monthly global pain score based on the number of sickle cell crises and severity of pain but included no separate data for these primary outcomes. Although there was no significant difference between the piracetam and placebo periods for the number of days of

  19. Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

    PubMed

    Alashkham, Abduelmenem; Paterson, Catherine; Rauchhaus, Petra; Nabi, Ghulam

    2016-01-01

    To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis. A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence, severity, and duration of proctitis were the main outcome. χ(2) tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used. The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: χ(2) (8, n=308) = 72.52, P<.001. The Mann-Whitney U test indicated that grades of proctitis were significantly lower in hypertensive patients taking ACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (P<.001). The risk ratio (RR) of proctitis in hypertensive patients taking ACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, P<.001) and in nonhypertensive patients not taking ACEIs (RR 0.58, 95% CI 0.44-0.77, P<.001). Time to event analysis revealed that hypertensive patients taking ACEIs were significantly different from the control groups (P<.0001). Furthermore, hypertensive patients taking ACEIs had significantly faster resolution of proctitis (P<.0001). Patients who were taking ACEIs were significantly less likely to have high-grade proctitis after

  20. Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner

    PubMed Central

    Peter, Mirjam E.; Sevinc Ok, Ebru; Celenk, Fatma Gul; Yilmaz, Mumtaz; Steppan, Sonja; Asci, Gulay; Ok, Ercan; Passlick-Deetjen, Jutta

    2012-01-01

    Background. Vascular calcification (VC), mainly due to elevated phosphate levels, is one major problem in patients suffering from chronic kidney disease. In clinical studies, an inverse relationship between serum magnesium and VC has been reported. However, there is only few information about the influence of magnesium on calcification on a cellular level available. Therefore, we investigated the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in bovine vascular smooth muscle cells (BVSMCs). Methods. BVSMCs were incubated with calcification media for 14 days while simultaneously increasing the magnesium concentration. Calcium deposition, transdifferentiation of cells and apoptosis were measured applying quantification of calcium, von Kossa and Alizarin red staining, real-time reverse transcription–polymerase chain reaction and annexin V staining, respectively. Results. Calcium deposition in the cells dramatically increased with addition of BGP and could be mostly prevented by co-incubation with magnesium. Higher magnesium levels led to inhibition of BGP-induced alkaline phosphatase activity as well as to a decreased expression of genes associated with the process of transdifferentiation of BVSMCs into osteoblast-like cells. Furthermore, estimated calcium entry into the cells decreased with increasing magnesium concentrations in the media. In addition, higher magnesium concentrations prevented cell damage (apoptosis) induced by BGP as well as progression of already established calcification. Conclusions. Higher magnesium levels prevented BVSMC calcification, inhibited expression of osteogenic proteins, apoptosis and further progression of already established calcification. Thus, magnesium is influencing molecular processes associated with VC and may have the potential to play a role for VC also in clinical situations. PMID:21750166

  1. Dose-dependent modulation of myogenesis by HGF: implications for c-Met expression and downstream signalling pathways.

    PubMed

    Walker, Nicholas; Kahamba, Trish; Woudberg, Nicholas; Goetsch, Kyle; Niesler, Carola

    2015-01-01

    Hepatocyte growth factor (HGF) regulates satellite cell activation, proliferation, and differentiation. We analyzed the dose-dependent effects of HGF on myogenesis. Murine C2C12 and human donor-derived skeletal muscle myoblasts were treated with 0, 2, or 10 ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2 ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10 ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly decreased expression in differentiating cells cultured with 2 ng/ml HGF, but increased expression in proliferating cells with 10 ng/ml HGF. Mitogen-activated protein kinase (MAPKs: ERK, JNK, or p38K) and phosphatidylinositol-3-kinase (PI3K) inhibition abrogated the HGF-stimulated increase in cell number. Interestingly, PI3K and p38 kinase facilitated the negative effect of HGF on proliferation, while ERK inhibition abrogated the HGF-mediated decrease in differentiation. Dose-dependent effects of HGF are mediated by changes in c-Met expression and downstream MAPK and PI3K signalling.

  2. A common p73 polymorphism is associated with a reduced incidence of oesophageal carcinoma

    PubMed Central

    Ryan, B M; McManus, R; Daly, J S; Carton, E; Keeling, P W N; Reynolds, J V; Kelleher, D

    2001-01-01

    The incidence of oesophageal adenocarcinoma is rising; to date, no susceptibility genes have been identified. p73, a novel p53 homologue, maps to chromosome 1p36, a region commonly deleted in oesophageal cancers. p73 shares some p53-like activity, but in addition, may also play a role in gastrointestinal epithelial inflammatory responses. A non-coding p73 polymorphism (denoted AT or GC) may be functionally significant. We investigated whether this polymorphism might play a role in the aetiopathogenesis of oesophageal cancer. This was a case–control, retrospective study. 84 cases of oesophageal cancer (25 squamous and 59 adenocarcinoma) and 152 normal population controls were genotyped for this polymorphism. Informative cases were examined for p73 LOH within the tumour. AT/AT homozygotes were significantly less prevalent in the oesophageal cancer population (1/84 = 1.2%) compared to controls (15/152 = 9.9%) (P < 0.02), corresponding to an odds ratio of 0.11 (95% C.I. 0.02–0.6, P < 0.02), or 9-fold reduced risk. Moreover, AT/AT homozygotes were significantly less frequent in the cancer population than would be expected under the Hardy–Weinberg hypothesis (P = 0.0099). LOH at the p73 locus was observed in 37.8% (14/37) of the AT/GC heterozygotes studied; in all cases there was loss of the AT allele. Our findings indicate that p73 AT/AT homozygotes appear to be protected against the development of oesophageal cancer. Clinically, this observation could have implications in aiding identification of high-risk Barrett's oesophagus patients.© 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11720435

  3. Fatiguing exercise initiated later in life reduces incidence of fibrillation and improves sleep quality in Drosophila.

    PubMed

    Zheng, Lan; Feng, Yue; Wen, Deng Tai; Wang, Hui; Wu, Xiu Shan

    2015-08-01

    As the human body ages, the risk of heart disease and stroke greatly increases. While there is evidence that lifelong exercise is beneficial to the heart's health, the effects of beginning exercise later in life remain unclear. This study aimed to investigate whether exercise training started later in life is beneficial to cardiac aging in Drosophila. We examined 4-week-old wild-type virgin female flies that were exposed to exercise periods of either 1.5, 2.0, or 2.5 h per day, 5 days a week for 2 weeks. Using M-mode traces to analyze cardiac function by looking at parameters including heart rate, rhythmicity, systolic and diastolic diameter, and interval and fractional shortening, we found that cardiac function declined with age, shown by an increase in the number of fibrillation events and a decrease in fractional shortening. About 2.0 and 2.5 h of exercise per day displayed a reduced incidence of fibrillation events, and only physical exercise lasting 2.5-h period increased fractional shortening and total sleep time in Drosophila. These data suggested that training exercise needs to be performed for longer duration to exert physiological benefits for the aging heart. Additionally, climbing ability to assess the exercise-induced muscle fatigue was also measured. We found that 2.0 and 2.5 h of exercise caused exercise-induced fatigue, and fatiguing exercise is beneficial for cardiac and healthy aging overall. This study provides a basis for further study in humans on the impact of beginning an exercise regimen later in life on cardiac health.

  4. Occult and subsequent cancer incidence following risk-reducing surgery in BRCA mutation carriers.

    PubMed

    Zakhour, Mae; Danovitch, Yael; Lester, Jenny; Rimel, B J; Walsh, Christine S; Li, Andrew J; Karlan, Beth Y; Cass, Ilana

    2016-11-01

    To report the frequency and features of occult carcinomas and the incidence of subsequent cancers following risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers. 257 consecutive women with germline BRCA mutations who underwent RRSO between January 1, 2000 and December 31, 2014 were identified in an Institutional Review Board approved study. All patients were asymptomatic with normal physical exams, CA 125 values, and imaging studies preoperatively, and had at least 12months of follow-up post-RRSO. All patients had comprehensive adnexal sectioning performed. Patient demographics and clinico-pathologic characteristics were extracted from medical and pathology records. The cohort included 148 BRCA1, 98 BRCA2, 6 BRCA not otherwise specified (NOS), and 5 BRCA1 and 2 mutation carriers. Occult carcinoma was seen in 14/257 (5.4%) of patients: 9 serous tubal intraepithelial carcinomas (STIC), 3 tubal cancers, 1 ovarian cancer, and 1 endometrial cancer. Three patients (1.2%) with negative pathology at RRSO subsequently developed primary peritoneal serous carcinoma (PPSC), and 2 of 9 patients (22%) with STIC subsequently developed pelvic serous carcinoma. 110 women (43%) were diagnosed with breast cancer prior to RRSO, and 14 of the remaining 147 (9.5%) developed breast cancer following RRSO. Median follow-up of the cohort was 63months. In this cohort, 5.4% of asymptomatic BRCA mutation carriers had occult carcinomas at RRSO, 86% of which were tubal in origin. The risk of subsequent PPSC for women with benign adnexa at RRSO is low; however, the risk of pelvic serous carcinoma among women with STIC is significantly higher. Copyright © 2016. Published by Elsevier Inc.

  5. Shock-absorbing insoles reduce the incidence of lower limb overuse injuries sustained during Royal Marine training.

    PubMed

    House, Carol; Reece, Allyson; Roiz de Sa, Dan

    2013-06-01

    This study was undertaken to determine whether the incidence of lower limb overuse injuries (LLOIs) sustained during Royal Marine training could be reduced by issuing the recruits with shock-absorbing insoles (SAIs) to wear in their military boots. This was a retrospective longitudinal trial conducted in two phases. Injury data from 1,416 recruits issued with standard Saran insoles and 1,338 recruits issued with SAI were compared. The recruits in the two groups were of similar height, body mass, and aerobic fitness and followed the same training course. The incidence of LLOI sustained by the recruits was lower (p < 0.05) in the SAI Group (19.0%) compared to the Saran Insole Group (31.7%). The incidences of lower limb stress fractures, tibial periostitis, tenosynovitis of foot, achilles tendonopathy, other tendonopathy and anterior knee pain were lower (p < 0.05) in the SAI Group. Tibial stress fracture incidence was lower (p < 0.05) in the SAI Group but metatarsal and femoral stress fracture incidences were the same for the two insole groups. Thus, issuing SAIs to military recruits undertaking a sustained, arduous physical training program with a high incidence of LLOI would provide a beneficial reduction in the incidence of LLOI.

  6. Febuxostat exerts dose-dependent renoprotection in rats with cisplatin-induced acute renal injury.

    PubMed

    Fahmi, Alaa N A; Shehatou, George S G; Shebl, Abdelhadi M; Salem, Hatem A

    2016-08-01

    The aim of the present study was to investigate possible renoprotective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against cisplatin (CIS)-induced acute kidney injury in rats. Male Sprague Dawley rats were randomly assigned into four groups of six rats each, as follows: normal control; CIS, received a single intraperitoneal injection of CIS (7.5 mg/kg); [febuxostat 10 + CIS] and [febuxostat 15 + CIS], received febuxostat (10 and 15 mg/kg/day, respectively, orally) for 14 days, starting 7 days before CIS injection. At the end of experiment, 24-h urine output was collected and serum was separated for biochemical assessments. Kidney tissue homogenate was prepared for determination of oxidative stress-related parameters, nitric oxide (NO), and tumor necrosis factor-α (TNF-α). Moreover, histological alterations of kidney tissues were evaluated. Serum creatinine, blood urea, and urinary total protein were significantly elevated, while serum albumin and creatinine clearance were significantly reduced, in CIS-intoxicated rats, indicating depressed renal function. CIS administration also elicited renal oxidative stress, evidenced by increased malondialdehyde content and depleted levels of reduced glutathione and superoxide dismutase activity. Moreover, enhancement of renal levels of the pro-inflammatory TNF-α indicated renal inflammation. CIS-administered rats also showed increased serum lactate dehydrogenase activity and reduced renal NO bioavailability. Febuxostat dose-dependently improved or restored these changes to near-normal (e.g., mean ± SD of serum creatinine levels in control, CIS, [febuxostat 10 + CIS] and [febuxostat 15 + CIS] groups were 0.78 ± 0.19, 3.28 ± 2.0 (P < 0.01 versus control group), 1.03 ± 0.36 (P < 0.01 versus CIS group), and 0.93 ± 0.21 (P < 0.01 versus CIS group) mg/dl, respectively, and blood urea levels for the different groups were 36.80 ± 4.36, 236.10 ± 89.19 (P < 0

  7. The impact of immigration and vaccination in reducing the incidence of hepatitis B in Catalonia (Spain)

    PubMed Central

    2012-01-01

    Background The Hepatitis B virus (HBV) infection is a major cause of liver disease and liver cancer worldwide according to the World Health Organization. Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of infected infants become chronic carriers and have an increased risk of cirrhosis and primary hepatocellular carcinoma. The aim of this study was to investigate the relationship between the reduction in acute hepatitis B incidence and the universal vaccination programme in preadolescents in Catalonia (Spain), taking population changes into account, and to construct a model to forecast the future incidence of cases that permits the best preventive strategy to be adopted. Methods Reported acute hepatitis B incidence in Catalonia according to age, gender, vaccination coverage, percentage of immigrants and the year of report of cases was analysed. A statistical analysis was made using three models: generalized linear models (GLM) with Poisson or negative binomial distribution and a generalized additive model (GAM). Results The higher the vaccination coverage, the lower the reported incidence of hepatitis B (p <0.01). In groups with vaccination coverage > 70%, the reduction in incidence was 2-fold higher than in groups with a coverage <70% (p <0.01). The increase in incidence was significantly-higher in groups with a high percentage of immigrants and more than 15% (p <0.01) in immigrant males of working age (19-49 years). Conclusions The results of the adjusted models in this study confirm that the global incidence of hepatitis B has declined in Catalonia after the introduction of the universal preadolescent vaccination programme, but the incidence increased in male immigrants of working age. Given the potential severity of hepatitis B for the health of individuals and for the community, universal vaccination programmes should continue and programmes in risk groups, especially immigrants, should be strengthened. PMID:22867276

  8. Reduced incidence of Crohn's disease in systemic sclerosis: a nationwide population study.

    PubMed

    Tseng, Chia-Chun; Yen, Jeng-Hsien; Tsai, Wen-Chan; Ou, Tsan-Teng; Wu, Cheng-Chin; Sung, Wan-Yu; Hsieh, Ming-Chia; Chang, Shun-Jen

    2015-09-14

    To date, there has been no studies to evaluate the incidence of Crohn's disease in systemic sclerosis patients. The goals of this study were to evaluate the incidence of Crohn's disease and its relationship with sex and age in patients with systemic sclerosis. We enrolled patients with systemic sclerosis and controls from Taiwan's Registry of Catastrophic Illness Database and National Health Insurance Research Database. Every systemic sclerosis patient was matched to at most three controls by sex, age, month and year of initial diagnosis of systemic sclerosis. The standardized incidence ratio (SIR) of Crohn's disease in systemic sclerosis patients, and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). The study enrolled 2,829 patients with systemic sclerosis and 8,257 controls. Male and female patients with systemic sclerosis both had lower rates of incident Crohn's disease (SIR: 0.18, 95% CI = 0.05-0.62; SIR: 0.10, 95% CI = 0.05-0.21, respectively). The risk of incident Crohn's disease in systemic sclerosis was still lower than in controls when we stratified the patients according to their ages. In Cox hazard regression, the hazard rates of Crohn's disease were lower in systemic sclerosis patients after adjusting for genders and ages (HR: 0.12, 95% CI = 0.06-0.21, p < 0.001). Systemic sclerosis is associated with decreased incidence of, irrespective of sex and age of the patients.

  9. Oleoylethanolamide exerts partial and dose-dependent neuroprotection of substantia nigra dopamine neurons.

    PubMed

    Galan-Rodriguez, B; Suarez, J; Gonzalez-Aparicio, R; Bermudez-Silva, F J; Maldonado, R; Robledo, P; Rodriguez de Fonseca, F; Fernandez-Espejo, E

    2009-03-01

    Oleoylethanolamide (OEA), agonist of nuclear PPAR-alpha receptors and antagonist of vanilloid TRPV1 receptors, has been reported to show cytoprotective properties. In this study, OEA-induced neuroprotection has been tested in vitro and in vivo models of 6-OHDA-induced degeneration of substantia nigra dopamine neurons. First, PPAR-alpha receptors were confirmed to be located in the nigrostriatal circuit, these receptors being expressed by dopamine neurons of the substantia nigra, and intrinsic neurons and fibers bundles of the dorsal striatum. In the substantia nigra, their location was confined to the ventral tier. The in vitro study showed that 1 microM OEA exerted a significantly neuroprotective effect on cultured nigral dopamine neurons, effects following U-shaped dose-response curves. Regarding the in vivo study, rats were locally injected with OEA into the right striatum and vehicle into the left striatum 30 min before 6-OHDA-induced striatal lesion. In the short term, signals of heme oxygenase-1 (oxidation marker, 24 and 48 h post-lesion) and OX6 (reactive microglia marker, 96 h post-lesion) were found to be significantly less intense in the striatum pretreated with 5 microM OEA. In the long term (1 month), reduction in striatal TH and synaptophysin was less intense whether the right striatum was pretreated with 5 microM OEA, and nigral TH+ neuron death was significantly reduced after pretreatment with 1 and 5 microM OEA. In vivo effects also followed U-shaped dose-response curves. In conclusion, OEA shows U-shaped partial and dose-dependent neuroprotective properties both in vitro and in vivo models of substantia nigra dopamine neuron degeneration. The occurrence of U-shaped dose-response relationships normally suggests toxicity due to high drug concentration or that opposing intracellular pathways are activated by different OEA doses.

  10. Chronic intermittent nicotine treatment dose-dependently alters serotonergic neurons response to citalopram in the rat.

    PubMed

    Touiki, Khalid; Rat, Pascal; Arib, Ouafa; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

    2008-05-01

    Acetylcholine nicotinic systems and serotonergic systems are known to interact. In rodents, acute and chronic nicotine treatments have consequences on several aspects of the activity of dorsal raphe serotonin (DRN 5-HT) neurons. One hypothesis is that states of functioning of DRN 5-HT neurons (firing rate and sensitivity) vary as a function of nicotine dose and mode of administration during chronic nicotine treatment. In the present study, the firing rate and sensitivity of DRN 5-HT neurons were investigated using single (0.5 and 1 mg/kg) or multiple (3 injections of 0.7 mg/kg) daily injections of nicotine over 10 days. The sensitivity of neurons was tested by the cumulative dose of the selective serotonin reuptake inhibitor citalopram necessary to inhibit their firing. The activity of neurons was tested during treatment, and then 24 and 48 h after nicotine withdrawal. The results show that, on day 10, DRN 5-HT neurons were desensitized (reduced response to citalopram) after chronic single daily injection treatments with the high dose of nicotine (1 mg/kg), while their sensitivity remained unaltered after single daily injections with the low dose (0.5 mg/kg), and after the multiple daily injection paradigm. None of the treatments altered the firing rate of DRN 5-HT neurons. The dose-dependent and time-dependent alterations of serotonergic neurons sensitivity after chronic nicotine treatments are likely the consequences of long-term adaptations of nicotinic receptors. The desensitization of DRN 5-HT neurons after chronic single daily injections of 1 mg/kg of nicotine suggests an antidepressant-like effect of chronic nicotine.

  11. Dose-Dependent Effects of Evening Primrose Oil in Children and Adolescents with Atopic Dermatitis

    PubMed Central

    Chung, Bo Young; Kim, Jin Hye; Cho, Soo Ick; Ahn, In Su; Kim, Hye One; Lee, Cheol Heon

    2013-01-01

    Background Previous clinical trials with evening primrose oil in atopic dermatitis (AD) treatment have shown different results. In addition, the optimal dose and duration of treatment with evening primrose oil have not yet been determined. Objective The aim of this study is to investigate the dose-response treatment effects of evening primrose oil on clinical symptoms of AD and serum concentrations of polyunsaturated fatty acids. Methods Forty AD patients were enrolled for the study and randomly divided into 2 groups: those who received evening primrose oil 160 mg daily for 8 weeks and those who received 320 mg of evening primrose oil twice daily for 8 weeks. We evaluated the Eczema Area Severity Index (EASI) scores of all AD patients at weeks 0, 2, 4 and 8. In addition, we measured the levels of serum fatty acids, including C16 : 0 (palmitic), C18 : 2n (linoleic), C18 : 3n (linolenic) and C20 : 4 (arachidonic acid) using gas chromatography. Results The serum fatty acid levels C18 : 3n and C20 : 4 were higher in the 320 mg group than in the 160 mg group, with statistical significance. After evening primrose oil treatment, EASI scores were reduced in the 2 groups. The improvement in EASI scores was greater in the 320 mg group than in the 160 mg group. There were no side effects seen in either group during the study in the 2 groups. Conclusion The results of this study suggest that the 320 mg and 160 mg groups may be equally effective in treating AD patients and show dose-dependent effects on serum fatty acid levels and EASI scores. PMID:24003269

  12. Context- and dose-dependent modulatory effects of naringenin on survival and development of Drosophila melanogaster.

    PubMed

    Chattopadhyay, Debarati; Sen, Soumadeep; Chatterjee, Rishita; Roy, Debasish; James, Joel; Thirumurugan, Kavitha

    2016-04-01

    Naringenin, the predominant bioflavonoid found in grapefruit and tomato has diverse bioactive properties that encompass anti-carcinogenic, anti-inflammatory, anti-atherogenic, anti-estrogenic, anti-hyperlipidemic and anti-hyperglycemic characteristics. Naringenin has not been explored for its pro-longevity traits in fruit flies. Therefore, the current study explores its influence on longevity, fecundity, feeding rate, larval development, resistance to starvation stress and body weight in male and female wild-type Drosophila melanogaster Canton-S flies. Flies were fed with normal and high fat diets respectively. The results implied hormetic effects of naringenin on longevity and development in flies. In flies fed with standard and high fat diets, lower concentrations of naringenin (200 and 400 µM) augmented mean lifespan while higher concentrations (600 and 800 µM) were consistently lethal. However, enhanced longevity seen at 400 µM of naringenin was at the expense of reduced fecundity and food intake in flies. Larvae reared on standard diet having 200 µM of naringenin exhibited elevated pupation and emergence as flies. Eclosion time was hastened in larvae reared on standard diet having 200 µM of naringenin. Female flies fed with a standard diet having 200 and 400 µM of naringenin were more resistant to starvation stress. Reduction in body weight was observed in male and female flies fed with a high fat diet supplemented with 200 and 400 µM of naringenin respectively. Collectively, the results elucidated a context- and dose-dependent hormetic efficacy of naringenin that varied with gender, diet and stage of lifecycle in flies.

  13. Low-dose green tea intake reduces incidence of atrial fibrillation in a Chinese population

    PubMed Central

    Wang, Ze-Mu; Xie, Zhi-Yong; Ma, Yao; Yang, Yang; Yang, Li; Wang, Lian-Sheng

    2016-01-01

    The aim of the present study was to assessthe association between green tea intake and incidence of atrial fibrillation (AF) in a Chinese population. A total of 801 (mean age: 62 years; 56% male) subjects were enrolled: 401 AF patients and 400 controls. All subjects completed a questionnaire and the associations between their green tea drinking habits and incidence of AF were assessed using the odds ratio (OR) and binary logistic regression. After multivariate adjustment, green tea intake presented as a protective factor against the incidence of AF (OR: 0.349, 95% CI: 0.253-0.483, P < 0.001). The green tea protection showed downward trend with increasing green tea intake (P for the trend= 0.001). Low frequency, low concentration, short-term tea consumption was classified as low-dose green tea intake. Green tea intake decreased the incidence of both paroxysmal AF (OR: 0.307, 95% CI: 0.216-0.436, P < 0.001) and persistent AF (OR: 0.355, 95% CI: 0.261-0.482, P < 0.001) and may be associated with a decreased incidence of AF. This study suggests that low-dose green tea intake strongly protects against AF. PMID:27683043

  14. Low-dose green tea intake reduces incidence of atrial fibrillation in a Chinese population.

    PubMed

    Liu, Dong-Chen; Yan, Jian-Jun; Wang, You-Nan; Wang, Ze-Mu; Xie, Zhi-Yong; Ma, Yao; Yang, Yang; Yang, Li; Wang, Lian-Sheng

    2016-12-20

    The aim of the present study was to assessthe association between green tea intake and incidence of atrial fibrillation (AF) in a Chinese population. A total of 801 (mean age: 62 years; 56% male) subjects were enrolled: 401 AF patients and 400 controls. All subjects completed a questionnaire and the associations between their green tea drinking habits and incidence of AF were assessed using the odds ratio (OR) and binary logistic regression. After multivariate adjustment, green tea intake presented as a protective factor against the incidence of AF (OR: 0.349, 95% CI: 0.253-0.483, P < 0.001). The green tea protection showed downward trend with increasing green tea intake (P for the trend= 0.001). Low frequency, low concentration, short-term tea consumption was classified as low-dose green tea intake. Green tea intake decreased the incidence of both paroxysmal AF (OR: 0.307, 95% CI: 0.216-0.436, P < 0.001) and persistent AF (OR: 0.355, 95% CI: 0.261-0.482, P < 0.001) and may be associated with a decreased incidence of AF. This study suggests that low-dose green tea intake strongly protects against AF.

  15. Platelet-Rich Plasma Influences Expansion and Paracrine Function of Adipose-Derived Stromal Cells in a Dose-Dependent Fashion.

    PubMed

    Willemsen, Joep C N; Spiekman, Maroesjka; Stevens, H P Jeroen; van der Lei, Berend; Harmsen, Martin C

    2016-03-01

    Lipofilling is a treatment modality to restore tissue volume. Both platelet-rich plasma and adipose-derived stromal cells have been reported to augment the efficacy of lipofilling, yet results are not conclusive. The authors hypothesized that the variation reported in literature is caused by a dose-dependent influence of platelet-rich plasma on adipose-derived stromal cells. Whole blood (n = 3) was used to generate platelet-rich plasma, which was diluted with Dulbecco's Modified Eagle Medium to 15%, 5%, and 1.7%, with 15% platelet-poor plasma and 10% fetal calf serum as controls. Pooled adipose-derived stromal cells (n = 3) were cultured in these media. Gene expression was assessed, along with angiogenic sprouting of endothelial cells by conditioned medium and platelet-rich plasma. platelet-rich plasma in culture medium affected the expression of genes in a dose-dependent manner. The 15% concentration stimulated proliferation almost eightfold. Mesenchymal markers were unaffected. Interestingly, expression of collagens type 1 and 3 increased at lower concentrations, whereas transforming growth factor-β showed reduced expression in lower concentrations. Proangiogenic gene expression was unaltered or strongly reduced in a dose-dependent manner. platelet-rich plasma promoted endothelial sprouting and survival in a dose-dependent manner; however, conditioned medium from adipose-derived stromal cells exposed to platelet-rich plasma blocked endothelial sprouting capabilities. The dose-dependent influence of platelet-rich plasma on the therapeutic capacity of adipose-derived stromal cells conditioned medium in vitro warrants caution in clinical trials.

  16. Brassinolide Increases Potato Root Growth In Vitro in a Dose-Dependent Way and Alleviates Salinity Stress.

    PubMed

    Hu, Yueqing; Xia, Shitou; Su, Yi; Wang, Huiqun; Luo, Weigui; Su, Shengying; Xiao, Langtao

    2016-01-01

    Brassinosteroids (BRs) are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL) affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L) promoted root elongation and lateral root development, whereas high BL concentrations (1-100 μg/L) inhibited root elongation. There was a significant (P < 0.05) positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g(-1) FW·h(-1) at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes' (superoxide dismutase, peroxidase, and catalase) activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K(+) and Na(+) homeostasis by improving tissue K(+)/Na(+) ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K(+)/Na(+) homeostasis in potato shoots and roots.

  17. Brassinolide Increases Potato Root Growth In Vitro in a Dose-Dependent Way and Alleviates Salinity Stress

    PubMed Central

    Xia, Shitou; Su, Yi; Wang, Huiqun; Luo, Weigui; Su, Shengying

    2016-01-01

    Brassinosteroids (BRs) are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL) affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L) promoted root elongation and lateral root development, whereas high BL concentrations (1–100 μg/L) inhibited root elongation. There was a significant (P < 0.05) positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g−1 FW·h−1 at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes' (superoxide dismutase, peroxidase, and catalase) activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K+ and Na+ homeostasis by improving tissue K+/Na+ ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K+/Na+ homeostasis in potato shoots and roots. PMID:27803931

  18. AN EXTRACT OF PENICILLIUM CHRYSOGENUM INDUCES DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES IN MICE

    EPA Science Inventory

    Rationale: Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typ...

  19. Absorbed dose dependence of the correction factors for ionization chamber cable irradiation effects.

    PubMed

    Campos, L L; Caldas, L V

    1991-03-01

    A simple method was developed, for possible use by hospital physicists, to evaluate the irradiation effects on cables and connectors during large-radiation-field dosimetry with ionization chambers and to determine correction factors for the used system or geometry. This method was based on the absorbed dose dependence of the correction factor.

  20. Dose-dependent pheromone responses of mountain pine beetle in stands of lodgepole pine

    Treesearch

    Daniel R. Miller; B. Staffan Lindgren; John H. Borden

    2005-01-01

    We conducted seven behavioral choice tests with Lindgren multiple-funnel traps in stands of mature lodgepole pine in British Columbia, from 1988 to 1994, to determine the dosedependent responses of the mountain pine beetle, Dendroctonus ponderosae Hopkins, to its pheromones. Amultifunctional dose-dependent response was exhibited by D. ...

  1. AN EXTRACT OF PENICILLIUM CHRYSOGENUM INDUCES DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES IN MICE

    EPA Science Inventory

    Rationale: Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typ...

  2. Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato

    PubMed Central

    Wei, Zhong; Huang, Jian-Feng; Hu, Jie; Gu, Yi-An; Yang, Chun-Lan; Mei, Xin-Lan; Shen, Qi-Rong; Xu, Yang-Chun; Friman, Ville-Petri

    2015-01-01

    Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)–organic compost fortified with pathogen-suppressive bacteria—is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer

  3. Altering Transplantation Time to Avoid Periods of High Temperature Can Efficiently Reduce Bacterial Wilt Disease Incidence with Tomato.

    PubMed

    Wei, Zhong; Huang, Jian-Feng; Hu, Jie; Gu, Yi-An; Yang, Chun-Lan; Mei, Xin-Lan; Shen, Qi-Rong; Xu, Yang-Chun; Friman, Ville-Petri

    2015-01-01

    Tomato bacterial wilt caused by Ralstonia solanacearum bacterium is a severe problem in Southern China, where relatively high environmental temperatures commonly prevails during the crop seasons. Previous research has indicated that bacterial wilt disease incidence generally increases during the warm months of summer leading to reduced tomato yield. Moreover, the efficacy of bio-organic fertilizers (BOFs)-organic compost fortified with pathogen-suppressive bacteria-is often lost during the periods of high environmental temperatures. Here we studied if the disease incidence could be reduced and the BOF performance enhanced by simply preponing and postponing the traditional seedling transplantation times to avoid tomato plant development during periods of high environmental temperature. To this end, a continuous, two-year field experiment was conducted to evaluate the performance of BOF in two traditional (late-spring [LS] and early-autumn [EA]) and two alternative (early-spring [ES] and late-autumn [LA]) crop seasons. We found that changing the transplantation times reduced the mean disease incidence from 33.9% (LS) and 54.7% (EA) to 11.1% (ES) and 7.1% (LA), respectively. Reduction in disease incidence correlated with the reduction in R. Solanacearum pathogen density in the tomato plant rhizosphere and stem base. Applying BOF during alternative transplantation treatments improved biocontrol efficiency from 43.4% (LS) and 3.1% (EA) to 67.4% (ES) and 64.8% (LA). On average, the mean maximum air temperatures were positively correlated with the disease incidence, and negatively correlated with the BOF biocontrol efficacy over the crop seasons. Crucially, even though preponing the transplantation time reduced the tomato yield in general, it was still economically more profitable compared to LS season due to reduced crop losses and relatively higher market prices. Preponing and postponing traditional tomato transplantation times to cooler periods could thus offer simple

  4. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients: A 12-Year Cohort Study.

    PubMed

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-12-01

    Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77-0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout.

  5. Regional analgesia combined with avoidance of narcotics may reduce the incidence of postoperative vomiting in children.

    PubMed

    Khalil, Samia N; Farag, Adel; Hanna, Ehab; Govindaraj, Ranganathan; Chuang, Alice Z

    2005-02-01

    The anesthesia literature cites a high incidence of postoperative vomiting (POV) after pediatric ochidopexy and hernia repair (34-50%) and after penile procedures (37-49%). We hypothesized that regional analgesia combined with avoidance of narcotics administered to children scheduled for lower abdominal or urologic procedures may be associated with a lower incidence of POV. The aim of this prospective study was to 1) assess the incidence of POV in children in the hospital and during a 24-h post-anesthesia study period, and 2) evaluate the effect of age on POV. After obtaining institutional and parental consent, 110 pediatric outpatients, 1-12 yr old, ASA physical status I or II, scheduled for elective outpatient urologic or lower abdominal procedures, were enrolled. Children were fasting and premedicated with midazolam, 0.5 mg/kg p.o. They received a combined light general anesthesia and a presurgical caudal block. Anesthesia was induced via a mask and consisted of halothane and nitrous oxide in oxygen. For the caudal block 1 ml/kg of 0.25% bupivacaine or 0.2% ropivacaine were used to provide intra- and postoperative pain relief. No prophylactic antiemetics were administered. All caudal blocks provided adequate intraoperative pain relief. The incidence of POV was low, 12% at the hospital, 13% for the 24-h study period, and was not affected by age. We concluded that regional analgesia combined with the avoidance of narcotics administered to children scheduled for elective urologic or lower abdominal procedures, is associated with a lower incidence of POV and that age did not affect the incidence of POV.

  6. Breast Cancer Incidence After Risk-Reducing Salpingo-Oophorectomy in BRCA1 and BRCA2 Mutation Carriers.

    PubMed

    Fakkert, Ingrid E; Mourits, Marian J E; Jansen, Liesbeth; van der Kolk, Dorina M; Meijer, Kees; Oosterwijk, Jan C; van der Vegt, Bert; Greuter, Marcel J W; de Bock, Geertruida H

    2012-11-01

    Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation carriers effectively reduces ovarian cancer risk, but also reduces breast cancer risk. Breast cancer risk reductions up to 50% have been reported for both BRCA1 and BRCA2 mutation carriers, but recent prospective studies were not able to reproduce this finding for BRCA1 mutation carriers. Breast cancer incidence after RRSO was assessed in a consecutive series of 104 BRCA1 and 58 BRCA2 mutation carriers. On the basis of data from our own centre, and assuming a 50% risk reduction through RRSO at premenopausal age, we expected to find 8 breast cancers (range 6-10) in this population for the reported screening period (532 women-years). In 162 carriers with a median age of 41 years at RRSO, 13 incident breast cancers were diagnosed. In BRCA1 mutation carriers, 12 incident breast cancers were found compared with 5 (range 3-6) expected and in BRCA2 mutation carriers 1 breast cancer was found compared with 3 (range 2-5) expected. Breast cancer incidence after premenopausal RRSO is still high, especially in BRCA1 mutation carriers. Previously reported breast cancer risk reductions up to 50% were not confirmed. As a consequence, continued intensive screening for breast cancer is warranted in BRCA1 and BRCA2 mutation carriers after RRSO.

  7. [A project to reduce the incidence of facial pressure ulcers caused by prolonged surgery with prone positioning].

    PubMed

    Lee, Wen-Yi; Lin, Pao-Chen; Weng, Chia-Hsing; Lin, Yi-Lin; Tsai, Wen-Lin

    2012-06-01

    We observed in our institute a 13.6% incidence of prolonged surgery (>4 hours) induced facial pressure ulcers that required prone positioning. Causes identified included: (1) customized silicon face pillows used were not suited for every patient; (2) our institute lacked a standard operating procedure for prone positioning; (3) our institute lacked a postoperative evaluation and audit procedure for facial pressure ulcers. We designed a strategy to reduce post-prolonged surgery facial pressure ulcer incidence requiring prone positioning by 50% (i.e., from 13.6% to 6.8%). We implemented the following: (1) Created a new water pillow to relieve facial pressure; (2) Implemented continuing education pressure ulcer prevention and evaluation; (3) Established protocols on standard care for prone-position patients and proper facial pressure ulcer identification; (4) Established a face pressure ulcers accident reporting mechanism; and (5) Established an audit mechanism facial pressure ulcer cases. After implementing the resolution measures, 116 patients underwent prolonged surgery in a prone position (mean operating time: 298 mins). None suffered from facial pressure ulcers. The measures effectively reduced the incidence of facial pressure ulcers from 13.6% to 0.0%. The project used a water pillow to relieve facial pressure and educated staff to recognize and evaluate pressure ulcers. These measures were demonstrated effective in reducing the incidence of facial pressure ulcers caused by prolonged prone positioning.

  8. Fermentation cover brine reformulation for cucumber processing with low salt to reduce the incidence of bloaters

    USDA-ARS?s Scientific Manuscript database

    Reformulation of cucumber fermentation cover brines containing calcium chloride instead of sodium chloride (NaCl) was explored as a mean to minimize the incidence of bloater defect. This study particularly focused on cover brine supplementation with calcium hydroxide, NaCl, and acids to enhance buff...

  9. Reduced Incidence of Foot-Related Hospitalisation and Amputation amongst Persons with Diabetes in Queensland, Australia

    PubMed Central

    Lazzarini, Peter A.; O’Rourke, Sharon R.; Russell, Anthony W.; Derhy, Patrick H.; Kamp, Maarten C.

    2015-01-01

    Objective To determine trends in the incidence of foot-related hospitalisation and amputation amongst persons with diabetes in Queensland (Australia) between 2005 and 2010 that coincided with changes in state-wide ambulatory diabetic foot-related complication management. Methods All data from cases admitted for the principal reason of diabetes foot-related hospitalisation or amputation in Queensland from 2005–2010 were obtained from the Queensland Hospital Admitted Patient Data Collection dataset. Incidence rates for foot-related hospitalisation (admissions, bed days used) and amputation (total, minor, major) cases amongst persons with diabetes were calculated per 1,000 person-years with diabetes (diabetes population) and per 100,000 person-years (general population). Age-sex standardised incidence and age-sex adjusted Poisson regression models were also calculated for the general population. Results There were 4,443 amputations, 24,917 hospital admissions and 260,085 bed days used for diabetes foot-related complications in Queensland. Incidence per 1,000 person-years with diabetes decreased from 2005 to 2010: 43.0% for hospital admissions (36.6 to 20.9), 40.1% bed days (391 to 234), 40.0% total amputations (6.47 to 3.88), 45.0% major amputations (2.18 to 1.20), 37.5% minor amputations (4.29 to 2.68) (p < 0.01 respectively). Age-sex standardised incidence per 100,000 person-years in the general population also decreased from 2005 to 2010: 23.3% hospital admissions (105.1 to 80.6), 19.5% bed days (1,122 to 903), 19.3% total amputations (18.57 to 14.99), 26.4% major amputations (6.26 to 4.61), 15.7% minor amputations (12.32 to 10.38) (p < 0.01 respectively). The age-sex adjusted incidence rates per calendar year decreased in the general population (rate ratio (95% CI)); hospital admissions 0.949 (0.942–0.956), bed days 0.964 (0.962–0.966), total amputations 0.962 (0.946–0.979), major amputations 0.945 (0.917–0.974), minor amputations 0.970 (0.950–0

  10. An Intermediate Alemtuzumab Schedule Reduces the Incidence of Mixed Chimerism Following Reduced-Intensity Conditioning Hematopoietic Cell Transplantation for Hemophagocytic Lymphohistiocytosis

    PubMed Central

    Marsh, Rebecca A.; Kim, Mi-Ok; Liu, Chunyan; Bellman, Denise; Hart, Laura; Grimley, Michael; Kumar, Ashish; Jodele, Sonata; Myers, Kasiani C.; Chandra, Sharat; Leemhuis, Tom; Mehta, Parinda A.; Bleesing, Jack J.; Davies, Stella M.; Jordan, Michael B.; Filipovich, Alexandra H.

    2014-01-01

    Reduced-intensity conditioning (RIC) improves the outcomes of hematopoietic cell transplantation (HCT) in patients with hemophagocytic lymphohistiocytosis (HLH). Proximal (ie, close to graft infusion) dosing of alemtuzumab is associated with a high incidence of mixed chimerism, whereas distal (ie, distant from graft infusion) dosing is associated with less mixed chimerism but more acute graft-versus-host disease (GVHD). The alemtuzumab dose per kilogram of body weight also influences these outcomes. We hypothesized that an intermediate alemtuzumab dosing schedule would reduce mixed chimerism and maintain a low incidence of acute GVHD. In this study, 24 consecutive HCTs were performed in patients with HLH or a related disorder using a novel intermediate alemtuzumab schedule of 1 mg/kg starting on day -14. The cumulative incidences (CIs) of mixed chimerism, upfront acute GVHD grades II-IV, and receipt of additional hematopoietic cell products after HCT were compared in patients treated with a distal alemtuzumab schedule (n = 15) and those treated with a proximal alemtuzumab schedule (n = 33). All patients received fludarabine and melphalan. The CI of mixed chimerism was 31% in the intermediate group, 72% in the proximal group (P < .01), and 75% in the distal group patients who received ≥2 mg/kg alemtuzumab (P = .03). The CI of acute GVHD grades II-IV before the development of mixed chimerism was 4% in the intermediate group, 0% in the proximal group, and 13% in the distal group (P = .04, proximal versus distal). The 1-year CI of administration of additional hematopoietic cell products for mixed chimerism (donor lymphocyte infusion ± hematopoietic stem cell boost ± repeat HCT) was 14% in the intermediate group, 53% in the proximal group (P = .01), and 38% in the distal ≥2 mg/kg alemtuzumab group (P = .02). Our findings indicate that intermediate RIC reduces the incidence of mixed chimerism, is associated with a low incidence of upfront acute GVHD, and decreases

  11. CNTF induces dose-dependent alterations in retinal morphology in normal and rcd-1 canine retina.

    PubMed

    Zeiss, Caroline J; Allore, Heather G; Towle, Virginia; Tao, Weng

    2006-03-01

    Ciliary neurotrophic factor (CNTF) provides morphologic preservation of rods in several animal models of retinitis pigmentosa (RP). However, CNTF may alter photoreceptor morphology and rod photoreceptor differentiation in vitro, as well as affecting normal retinal electrophysiology. In addition, the capacity of CNTF to support other cell types affected secondarily in RP (cones and ganglion cells) is unclear. The purposes of this study were to examine the effects of CNTF upon a canine model of RP, the rod-cone degeneration (rcd-1) dog. Archival tissue from a previous study assessing the capacity of CNTF to rescue photoreceptors in rcd-1 dogs was used. One eye was treated for 7 weeks before being explanted. The contralateral eye was untreated. A total of 23 rcd-1 dogs and seven control dogs (four untreated and three CNTF-treated) were used. Morphometric data describing outer and inner nuclear layer thickness, inner retinal thickness, cones and ganglion cells were collected at nine evenly spaced points along each retina and analysed using a mixed effects model. Immunohistochemistry was performed on a subset of 11 dogs for expression of rhodopsin, human cone arrestin (hCAR) and recoverin. CNTF protected the outer nuclear layer and increased inner retinal thickness in a dose-dependent manner (both were maximal at CNTF doses of 1-6 ng day-1). Significant cone loss or reduction of inner nuclear layer width in rcd-1 did not occur in this model, therefore we were unable to assess the protective effect of CNTF upon these parameters. CNTF did not afford significant ganglion cell protection. CNTF induced morphologic changes in rods and ganglion cells, as well as reducing expression of hCAR and rhodopsin, but not recoverin. The dose of CNTF which provided optimal outer nuclear layer protection also resulted in several other effects, including altered ganglion cell morphology, increased thickness of the entire retina, and reduced expression of some phototransduction proteins

  12. A Comprehensive Evaluation for Aspiration After Esophagectomy Reduces the Incidence of Post-Operative Pneumonia

    PubMed Central

    Berry, Mark F.; Atkins, B. Zane; Tong, Betty C.; Harpole, David H.; D’Amico, Thomas A.; Onaitis, Mark W.

    2011-01-01

    OBJECTIVE This study assesses the impact of using a comprehensive swallowing evaluation before starting oral feedings on aspiration detection and pneumonia occurrence after esophagectomy. METHODS The records of all esophagectomy patients between January 1996 and June 2009 were reviewed. Multivariable logistic regression analysis assessed the effect of preoperative and operative variables on the incidence of aspiration and pneumonia. Separate analyses were performed on patients before (early era, 1996–2002) and after (later era, 2003–2009) a rigorous swallowing evaluation was used routinely before starting oral feedings. RESULTS During the study period, 799 patients (379 early era, 420 later era) underwent esophagectomy; 30-day mortality was 3.5% (28 patients). Cervical anastomoses were performed in 76% of patients in the later era compared with 40% of patients in the early era. Overall, 96 patients (12%) had evidence of aspiration postoperatively, and the pneumonia incidence was 14% (113 patients). Age (odds ratio 1.05 per year, p<0.0001) and later era (odds ratio 1.90, p=0.0001) predicted aspiration in all patients in a multivariable model. In the early era, cervical anastomosis and aspiration independently predicted pneumonia. With a comprehensive swallowing evaluation in the later era, the detected incidence of aspiration increased (16% vs 7%, p<0.0001) while the incidence of pneumonia declined (11% vs 18%, p=0.004) compared to the early era, such that neither anastomotic location nor aspiration predicted pneumonia in the later era. CONCLUSIONS Esophagectomy is often associated with occult aspiration. A comprehensive swallowing evaluation for aspiration prior to initiating oral feedings significantly decreases the occurrence of pneumonia. PMID:20884018

  13. A multifactorial injury prevention intervention reduces injury incidence in Physical Education Teacher Education students.

    PubMed

    Goossens, L; Cardon, G; Witvrouw, E; Steyaert, A; De Clercq, D

    2016-01-01

    Physical Education Teacher Education (PETE) students are at considerable risk for non-contact sports injuries of the lower extremities. Multifactorial injury prevention interventions including exercises have been successful in sports populations, but no such study has ever been performed in PETE students. This study investigated the efficacy of a multifactorial injury prevention intervention on injury incidence reduction in PETE students. PETE students in the intervention group (n = 154) and in the control group (n = 189) registered sports injuries prospectively. The intervention lasted one academic year and consisted of an injury awareness programme and preventive strategies, implemented by the PETE sports lecturers. Differences in injury incidence between the intervention and control group were tested by Poisson regression Wald tests. There was a trend towards significantly lower incidence rate (2.18 vs. 2.73; p = 0.061) in the intervention group compared with the control group. Students in the intervention group had significantly less acute, first-time and extracurricular injuries. The largest reduction was observed for injuries during unsupervised practice sessions. A multifactorial injury prevention intervention embedded into a regular PETE programme is a promising and feasible strategy to prevent injuries in PETE students. Further research is needed to investigate whether the results may be generalised to other PETE programmes.

  14. Perioperative Cefovecin to Reduce the Incidence of Urinary Tract Infection in Dogs Undergoing Hemilaminectomy.

    PubMed

    Palamara, Joseph D; Bonczynski, Jennifer J; Berg, Jason M; Bergman, Philip J

    2016-01-01

    The prevalence of urinary tract infections (UTIs) in dogs with Type I intervertebral disc extrusion has been reported as high as 38% within 6 wk of surgery. Proper treatment of a UTI is important with myelopathy because it is a risk factor for persistent infection and reinfection in dogs. The study authors' investigated the incidence of UTIs in dogs having received either cefovecin or cefazolin as a preoperative prophylactic antibiotic for thoracolumbar hemilaminectomy. Thirty-nine dogs were retrospectively identified and assigned to groups based on preoperative antibiotic administration and postoperative urinary tract management. Urinalysis and urine culture performed preoperatively, at 2 wk, and at 6 wk, were reviewed to determine the incidence of UTIs. Urinary tract management, grade of neurologic deficit, time to ambulation, and time to voluntary urination were identified to evaluate for additional risk factors. No significant prevalence of UTI incidence was appreciated between the cefovecin and cefazolin groups. Patients with higher grades of neurologic deficit and that took longer to regain ambulation and voluntary urination were at significantly greater risk for UTIs throughout the postoperative period. This study reemphasizes the importance of continued surveillance for UTIs in patients with prolonged neurologic recovery.

  15. Effectiveness of Exergaming Training in Reducing Risk and Incidence of Falls in Frail Older Adults With a History of Falls.

    PubMed

    Fu, Amy S; Gao, Kelly L; Tung, Arthur K; Tsang, William W; Kwan, Marcella M

    2015-12-01

    To use Nintendo's Wii Fit balance board to determine the effectiveness of exergaming training in reducing risk and incidence of falls in older adults with a history of falls. Randomized controlled trial. Nursing home for older adults. Adults aged 65 years and older (N=60). Participants who lived in a nursing home had 6 weeks of balance training with either Wii Fit equipment or conventional exercise. Physiological Profile Assessment scores and incidence of falls were observed with subsequent intention-to-treat statistical analyses. Physiological Profile Assessment scores and incidence of falls improved significantly in both groups after the intervention (all P<.01), but participants in the Wii Fit training group showed a significantly greater improvement in both outcome measures (P=.004 and P<.001, respectively). In institutionalized older adults with a history of falls, Wii Fit balance training was more effective than conventional balance training in reducing the risk and incidence of falls. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  16. A maternal gluten-free diet reduces inflammation and diabetes incidence in the offspring of NOD mice.

    PubMed

    Hansen, Camilla Hartmann Friis; Krych, Lukasz; Buschard, Karsten; Metzdorff, Stine B; Nellemann, Christine; Hansen, Lars H; Nielsen, Dennis S; Frøkiær, Hanne; Skov, Søren; Hansen, Axel K

    2014-08-01

    Early-life interventions in the intestinal environment have previously been shown to influence diabetes incidence. We therefore hypothesized that a gluten-free (GF) diet, known to decrease the incidence of type 1 diabetes, would protect against the development of diabetes when fed only during the pregnancy and lactation period. Pregnant nonobese diabetic (NOD) mice were fed a GF or standard diet until all pups were weaned to a standard diet. The early-life GF environment dramatically decreased the incidence of diabetes and insulitis. Gut microbiota analysis by 16S rRNA gene sequencing revealed a pronounced difference between both mothers and their offspring on different diets, characterized by increased numbers of Akkermansia, Proteobacteria, and TM7 in the GF diet group. In addition, pancreatic forkhead box P3 regulatory T cells were increased in GF-fed offspring, as were M2 macrophage gene markers and tight junction-related genes in the gut, while intestinal gene expression of proinflammatory cytokines was reduced. An increased proportion of T cells in the pancreas expressing the mucosal integrin α4β7 suggests that the mechanism involves increased trafficking of gut-primed immune cells to the pancreas. In conclusion, a GF diet during fetal and early postnatal life reduces the incidence of diabetes. The mechanism may involve changes in gut microbiota and shifts to a less proinflammatory immunological milieu in the gut and pancreas.

  17. The effectiveness of a twice-daily skin-moisturising regimen for reducing the incidence of skin tears.

    PubMed

    Carville, Keryln; Leslie, Gavin; Osseiran-Moisson, Rebecca; Newall, Nelly; Lewin, Gill

    2014-08-01

    A cluster randomised controlled trial was conducted to evaluate the effectiveness of a twice-daily moisturising regimen as compared to 'usual' skin care for reducing skin tear incidence. Aged care residents from 14 Western Australian facilities (980 beds) were invited to participate. The facilities were sorted into pairs and matched in terms of bed numbers and whether they provided high or low care. One facility from each matched pair was randomised to the intervention group. Consenting residents in an intervention facility received a twice-daily application of a commercially available, standardised pH neutral, perfume-free moisturiser on their extremities. Residents in the control facilities received ad hoc or no standardised skin-moisturising regimen. Participant numbers were sufficient to detect a 5% difference in incidence rate between the two groups with 80% power and a significance level of P = 0·05, and the inter-cluster correlation coefficient was 0·034. Data were collected over 6 months. A total of 1396 skin tears on 424 residents were recorded during the study. In the intervention group, the average monthly incidence rate was 5·76 per 1000 occupied bed days as compared to 10·57 in the control group. The application of moisturiser twice daily reduced the incidence of skin tears by almost 50% in residents living in aged care facilities. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  18. Acyclovir Prophylaxis Reduces the Incidence of Herpes Zoster Among HIV-Infected Individuals: Results of a Randomized Clinical Trial.

    PubMed

    Barnabas, Ruanne V; Baeten, Jared M; Lingappa, Jairam R; Thomas, Katherine K; Hughes, James P; Mugo, Nelly R; Delany-Moretlwe, Sinead; Gray, Glenda; Rees, Helen; Mujugira, Andrew; Ronald, Allan; Stevens, Wendy; Kapiga, Saidi; Wald, Anna; Celum, Connie

    2016-02-15

    Human immunodeficiency virus (HIV)-infected persons have higher rates of herpes zoster than HIV-uninfected individuals. We assessed whether twice daily treatment with 400 mg of oral acyclovir reduces the incidence of herpes zoster in a randomized, double-blind, placebo-controlled trial among 3408 persons coinfected with HIV and herpes simplex virus type 2. During 5175 person-years of follow-up, 26 cases of herpes zoster occurred among those assigned acyclovir, compared with 69 cases among those assigned placebo (rates, 1.00 and 2.68/100 person-years, respectively), a relative decrease of 62% (hazard ratio, 0.38; 95% confidence interval, .24-.67; P < .001). Daily acyclovir prophylaxis significantly reduced herpes zoster incidence among HIV-infected persons.

  19. Radiation dose dependent change in physiochemical, mechanical and barrier properties of guar gum based films.

    PubMed

    Saurabh, Chaturbhuj K; Gupta, Sumit; Bahadur, Jitendra; Mazumder, S; Variyar, Prasad S; Sharma, Arun

    2013-11-06

    Mechanical and water vapor barrier properties of biodegradable films prepared from radiation processed guar gum were investigated. Films prepared from GG irradiated up to 500 Gy demonstrated significantly higher tensile strength as compared to non-irradiated control films. This improvement in tensile strength observed was demonstrated to be due to the ordering of polymer structures as confirmed by small angle X-ray scattering analysis. Exposure to doses higher than 500 Gy, however, resulted in a dose dependent decrease in tensile strength. A dose dependent decrease in puncture strength with no significant differences in the percent elongation was also observed at all the doses studied. Water vapor barrier properties of films improved up to 15% due to radiation processing. Radiation processing at lower doses for improving mechanical and barrier properties of guar based packaging films is demonstrated here for the first time.

  20. Use of ethanol lock therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients.

    PubMed

    Opilla, Marianne T; Kirby, Donald F; Edmond, Michael B

    2007-01-01

    Catheter-related bloodstream infection (CRBSI) is a serious complication for home parenteral nutrition (HPN) patients. To reduce the incidence of infection in frequently infected HPN patients, prophylactic ethanol lock therapy (ELT) was initiated. Nine patients were selected as candidates for ELT because of their history of recurrent CRBSI. Diagnosis of CRBSI was determined by symptoms correlating with positive peripheral and access device blood cultures. Medical-grade ethyl alcohol 25%-70% was instilled into the central venous access device and allowed to dwell for 2-4 hours. The incidence of CRBSI and catheter changes was compared before and after initiation of ELT. Nine patients experienced 81 CRBSIs (8.3 per 1,000 catheter-days) before starting ELT vs 9 infections (2.7 per 1,000 catheter-days: relative risk [RR], 0.325; confidence interval [CI] 95%, 0.17-0.64) after ELT. Catheter changes were also reduced from 69 (7.0 per 1000 days) before ELT to 1 (0.3 per 1,000 days: RR, 0.043; CI 95%, 0.01-0.25) after ELT. No significant adverse effects were noted, although some patients complained of transient dizziness and nausea. ELT shows promise in reducing the incidence of CRBSI in the frequently infected HPN population. Further studies are warranted.

  1. Delayed Initiation but Not Gradual Advancement of Enteral Formula Feeding Reduces the Incidence of Necrotizing Enterocolitis (NEC) in Preterm Pigs

    PubMed Central

    Ghoneim, Nada; Bauchart-Thevret, Caroline; Oosterloo, Berthe; Stoll, Barbara; Kulkarni, Madhulika; de Pipaon, Miguel Saenz; Zamora, Irving J.; Olutoye, Oluyinka O.; Berg, Brian; Wittke, Anja; Burrin, Douglas G.

    2014-01-01

    Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of enteral feeding of an intact vs. hydrolyzed protein formula on NEC incidence and severity in preterm pigs. In Experiment 1, preterm pigs received total parenteral nutrition (TPN) at birth with abrupt initiation of enteral formula feeds (50% full intake) on d of life (DOL) 2 (EA) or 5 (LA) while PN continued. Pigs were also fed formula containing either intact or hydrolyzed protein. In Experiment 2, preterm pigs received TPN at birth with enteral, hydrolyzed-protein formula feeds introduced on DOL 2 either abruptly (EA; 50% full feeds) or gradually (EG; 10–50% full feeds over 5 d) while PN continued. NEC incidence and severity were assessed based on macroscopic and histological scoring. In Experiment 1, NEC incidence (41% vs. 70%, P<0.05) and severity were reduced in LA vs. EA groups and LA was associated with a higher survival rate, daily weight gain and jejunum villus height. Piglets fed hydrolyzed vs. intact protein formula had lower stomach content weights and similar NEC incidence. In Experiment 2, NEC incidence and severity were not different between pigs the EG vs. EA group. Proinflammatory gene expression (IL-1β, IL-6 and S100A9) in the ileum was lower in both LA and EG vs. EA groups. In conclusion, delayed initiation but not gradual advancement of enteral feeding is protective against NEC in preterm pigs. Feeding hydrolyzed vs. intact protein formula improved gastric transit without affecting the NEC incidence. PMID:25238061

  2. Dose-dependent pharmacokinetics and hepatobiliary transport of bromophenol blue in the beagle.

    PubMed

    Wills, R J; Yakatan, G J; Pearlman, R S

    1984-07-01

    The pharmacokinetic profile of bromophenol blue (I) in the plasma, urine, and bile of beagle dogs was determined after intravenous administration of 5-, 20-, and 30-mg/kg doses. In addition, two competitors, probenecid and phenylbutazone, were interacted with I in vivo and with I and rat liver cytoplasmic protein fractions Y and Z in vitro as a means of elucidating the mechanism of intrahepatic transport of I. Compound I was determined spectrophotometrically at 587 nm. In plasma, I displayed apparent first-order dose-dependent kinetics. The percentage of I bound to plasma proteins was approximately 92.5% over the dose range studied. Consecutive injections of equal doses of I produced statistically different terminal half-lives (p less than 0.05), suggesting the possibility of a saturable uptake process. In the presence of each competitor, the disposition of I was altered significantly (p less than 0.05): phenylbutazone displaced I from plasma protein, while probenecid decreased the binding of I to liver proteins in the Z-fraction. The Z-fraction bound a larger amount of I than the Y-fraction, suggesting a larger binding capacity. Under no circumstances was the binding of I to the Y-fraction altered. Cumulative biliary excretion data showed that the elimination of I in bile accounted for 92-99% of the dose delivered. The biliary excretion sigma- plots displayed no dose dependency, suggesting that the dose-dependent plasma half-life is due to a dose-dependent liver uptake (as opposed to elimination) process.

  3. Dose-Dependent Model of Caffeine Effects on Human Vigilance during Total Sleep Deprivation

    DTIC Science & Technology

    2014-05-20

    Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation Sridhar Ramakrishnan a, Srinivas Laxminarayan a, Nancy J...psychomotor vigilance task (PVT) performance of sleep - deprived subjects. We used the two-process model of sleep regulation to quantify performance... sleep - deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance. Published

  4. Household Water Chlorination Reduces Incidence of Diarrhea among Under-Five Children in Rural Ethiopia: A Cluster Randomized Controlled Trial

    PubMed Central

    Mengistie, Bezatu; Berhane, Yemane; Worku, Alemayehu

    2013-01-01

    Background Household water treatment has been advocated as a means of decreasing the burden of diarrheal diseases among young children in areas where piped and treated water is not available. However, its effect size, the target population that benefit from the intervention, and its acceptability especially in rural population is yet to be determined. The objective of the study was to assess the effectiveness of household water chlorination in reducing incidence of diarrhea among children under-five years of age. Method A cluster randomized community trial was conducted in 36 rural neighborhoods of Eastern Ethiopia. Households with at least one child under-five years of age were included in the study. The study compared diarrhea incidence among children who received sodium hypochlorite (liquid bleach) for household water treatment and children who did not receive the water treatment. Generalized Estimation Equation model was used to compute adjusted incidence rate ratio and the corresponding 95% confidence interval. Result In this study, the incidence of diarrhea was 4.5 episodes/100 person week observations in the intervention arm compared to 10.4 episodes/100 person week observations in the control arm. A statistically significant reduction in incidence of diarrhea was observed in the intervention group compared to the control (Adjusted IRR = 0.42, 95% CI 0.36–0.48). Conclusion Expanding access to household water chlorination can help to substantially reduce child morbidity and achieve millennium development goal until reliable access to safe water is achieved. Trial Registration ClinicalTrials.gov NCT01376440 PMID:24194899

  5. Statins dose-dependently exert a chemopreventive effect against lung cancer in COPD patients: a population-based cohort study

    PubMed Central

    Hsu, Yi-Ping; Hao, Wen-Rui; Kao, Pai-Feng; Sung, Li-Chin; Chen, Chun-Chao; Wu, Szu-Yuan

    2016-01-01

    Purpose Chronic obstructive pulmonary disease (COPD) is associated with increased lung cancer risk. We evaluated the association of statin use with lung cancer risk in COPD patients and identified which statins possess the highest chemopreventive potential. Results After adjustment for age, sex, CCI, diabetes, hypertension, dyslipidemia, urbanization level, and monthly income according to propensity scores, lung cancer risk in the statin users was lower than that in the statin nonusers (adjusted hazard ratio [aHR] = 0.37). Of the individual statins, lovastatin and fluvastatin did not reduce lung cancer risk significantly. By contrast, lung cancer risk in patients using rosuvastatin, simvastatin, atorvastatin, and pravastatin was significantly lower than that in statin nonusers (aHRs = 0.41, 0.44, 0.52, and 0.58, respectively). Statins dose-dependently reduced lung cancer risk in all subgroups and the main model with additional covariates (nonstatin drug use). MATERIALS AND METHODS The study cohort comprised all patients diagnosed with COPD at health care facilities in Taiwan (n = 116,017) between January 1, 2001 and December 31, 2012. Our final study cohort comprised 43,802 COPD patients: 10,086 used statins, whereas 33,716 did not. Patients were followed up to assess lung cancer risk or protective factors. In addition, we also considered demographic characteristics, namely age, sex, comorbidities (diabetes, hypertension, dyslipidemia, and Charlson comorbidity index [CCI]), urbanization level, monthly income, and nonstatin drug use. The index date of statin use was the COPD confirmation date. To examine the dose–response relationship, we categorized statin use into four groups in each cohort: < 28, 28–90, 91–365, and > 365 cumulative defined daily doses (cDDDs). Patients receiving < 28 cDDDs were defined as nonstatin users. Conclusions Statins dose-dependently exert a significant chemopreventive effect against lung cancer in COPD patients. Rosuvastatin

  6. Dose-dependent model of caffeine effects on human vigilance during total sleep deprivation.

    PubMed

    Ramakrishnan, Sridhar; Laxminarayan, Srinivas; Wesensten, Nancy J; Kamimori, Gary H; Balkin, Thomas J; Reifman, Jaques

    2014-10-07

    Caffeine is the most widely consumed stimulant to counter sleep-loss effects. While the pharmacokinetics of caffeine in the body is well-understood, its alertness-restoring effects are still not well characterized. In fact, mathematical models capable of predicting the effects of varying doses of caffeine on objective measures of vigilance are not available. In this paper, we describe a phenomenological model of the dose-dependent effects of caffeine on psychomotor vigilance task (PVT) performance of sleep-deprived subjects. We used the two-process model of sleep regulation to quantify performance during sleep loss in the absence of caffeine and a dose-dependent multiplier factor derived from the Hill equation to model the effects of single and repeated caffeine doses. We developed and validated the model fits and predictions on PVT lapse (number of reaction times exceeding 500 ms) data from two separate laboratory studies. At the population-average level, the model captured the effects of a range of caffeine doses (50-300 mg), yielding up to a 90% improvement over the two-process model. Individual-specific caffeine models, on average, predicted the effects up to 23% better than population-average caffeine models. The proposed model serves as a useful tool for predicting the dose-dependent effects of caffeine on the PVT performance of sleep-deprived subjects and, therefore, can be used for determining caffeine doses that optimize the timing and duration of peak performance.

  7. Novel Application of Stem Cell-Derived Neurons to Evaluate the Time- and Dose-Dependent Progression of Excitotoxic Injury

    PubMed Central

    Gut, Ian M.; Beske, Phillip H.; Hubbard, Kyle S.; Lyman, Megan E.; Hamilton, Tracey A.; McNutt, Patrick M.

    2013-01-01

    Glutamate receptor (GluR)-mediated neurotoxicity is implicated in a variety of disorders ranging from ischemia to neural degeneration. Under conditions of elevated glutamate, the excessive activation of GluRs causes internalization of pathologic levels of Ca2+, culminating in bioenergetic failure, organelle degradation, and cell death. Efforts to characterize cellular and molecular aspects of excitotoxicity and conduct therapeutic screening for pharmacologic inhibitors of excitogenic progression have been hindered by limitations associated with primary neuron culture. To address this, we evaluated glutamate-induced neurotoxicity in highly enriched glutamatergic neurons (ESNs) derived from murine embryonic stem cells. As of 18 days in vitro (DIV 18), ESNs were synaptically coupled, exhibited spontaneous network activity with neurotypic mEPSCs and expressed NMDARs and AMPARs with physiological current:voltage behaviors. Addition of 0.78–200 μM glutamate evoked reproducible time- and dose-dependent metabolic failure in 6 h, with a calculated EC50 value of 0.44 μM at 24 h. Using a combination of cell viability assays and electrophysiology, we determined that glutamate-induced toxicity was specifically mediated by NMDARs and could be inhibited by addition of NMDAR antagonists, increased extracellular Mg2+ or substitution of Ba2+ for Ca2+. Glutamate treatment evoked neurite fragmentation and focal swelling by both immunocytochemistry and scanning electron microscopy. Presentation of morphological markers of cell death was dose-dependent, with 0.78–200 μM glutamate resulting in apoptosis and 3000 μM glutamate generating a mixture of necrosis and apoptosis. Addition of neuroprotective small molecules reduced glutamate-induced neurotoxicity in a dose-dependent fashion. These data indicate that ESNs replicate many of the excitogenic mechanisms observed in primary neuron culture, offering a moderate-throughput model of excitotoxicity that combines the verisimilitude

  8. Co-trimoxazole prophylaxis is associated with reduced risk of incident tuberculosis in participants in the Swiss HIV Cohort Study.

    PubMed

    Hasse, Barbara; Walker, A Sarah; Fehr, Jan; Furrer, Hansjakob; Hoffmann, Matthias; Battegay, Manuel; Calmy, Alexandra; Fellay, Jacques; Di Benedetto, Caroline; Weber, Rainer; Ledergerber, Bruno

    2014-01-01

    Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB-132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval [CI], 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.

  9. Cardiorespiratory fitness reduces the risk of incident hypertension associated with a parental history of hypertension.

    PubMed

    Shook, Robin P; Lee, Duck-chul; Sui, Xuemei; Prasad, Vivek; Hooker, Steven P; Church, Timothy S; Blair, Steven N

    2012-06-01

    Family history of hypertension increases the risk of an individual to develop hypertension, whereas moderate-to-high cardiorespiratory fitness has the opposite effect. However, the joint association of each on the development of hypertension is not well understood. We studied fitness and incident hypertension in 6278 participants who were given a preventative medical examination. Thirty-three percent reported a parent with hypertension, and there were 1545 cases of incident hypertension after a mean of 4.7 years. The presence of parental hypertension was associated with a 28% higher risk of developing hypertension after adjustments for age, sex, and examination year. After further adjustments for smoking, alcohol intake, resting systolic and diastolic blood pressures, hypercholesterolemia, body mass index, physical inactivity, and fitness, there was a 20% higher risk associated with parental hypertension. After adjusting for age, sex, and examination year, both moderate and high levels of fitness were associated with lower risk for developing hypertension by 26% and 42%, respectively. In the joint analysis, individuals with both a low level of fitness and a parent with hypertension exhibited a 70% higher risk for developing hypertension compared with high fit individuals with no parental history (P = 0.004). However, individuals with a high level of fitness and a parent with hypertension only experienced a 16% higher risk of developing hypertension compared with fit individuals with no parental history (P = 0.03). The significantly lower risk of developing hypertension when progressing from low- to high-fit groups among those with a parental history of hypertension has important clinical implications.

  10. Dose-Dependent Pheromone Responses of Ips pini, Orthotomicus latiden (Coleoptera: Scolytidae), and associates in stands of lodgepole pine

    Treesearch

    Daniel R. Miller; John H. Borden; B. Staffan Lidgren

    2005-01-01

    We conducted four behavioral choice tests in stands of mature lodgepole pine in British Columbia, from 1988 to 1991, to determine the dose-dependent responses of Orthotomicus latidens (LeConte) and Ips pini (Say) to their respective pheromones. Dose-dependent responses were exhibited by I. pini to (±)-ipsdienol and lanierone, with...

  11. Reduced oxygen protocol decreases the incidence of threshold retinopathy of prematurity in infants of <33 weeks gestation.

    PubMed

    Tokuhiro, Yumiko; Yoshida, Tomoko; Nakabayashi, Yoshinobu; Nakauchi, Shohei; Nakagawa, Yumi; Kihara, Minako; Mitsufuji, Nobuto; Kizaki, Zenro

    2009-12-01

    The relationship between oxygen and retinopathy of prematurity (ROP) has been studied frequently, and a pulse oximeter has the potential to facilitate the control of oxygen fluctuation in neonates. The objective of the present study was to compare the incidence of threshold ROP (stage 3 requiring laser treatment and stage 4) in infants of <33 weeks gestation after implementing a new clinical O(2) management practice. A retrospective study of data from the Kyoto First Red Cross Hospital neonatal intensive care unit (NICU) from 1 July 2004 to 31 October 2007 (closed 1 December 2006-30 March 2007 for reconstruction). A reduced oxygen protocol was implemented to maintain oxygen saturation (SpO(2)) values using a pulse oximeter between 88% and 92%. The incidence of threshold ROP in the earlier period (1 July 2004-31 December 2005) and the later period (1 January 2006-31 October 2007) were compared. The incidence of threshold ROP significantly decreased from 32.2% to 16.7%, after changing to the reduced oxygen protocol (P < 0.05). A significant decrease in the rate of threshold ROP in infants of <33 weeks gestation was observed after implementation of the new clinical O(2) management practice.

  12. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis.

    PubMed

    Marsh, Rebecca A; Kim, Mi-Ok; Liu, Chunyan; Bellman, Denise; Hart, Laura; Grimley, Michael; Kumar, Ashish; Jodele, Sonata; Myers, Kasiani C; Chandra, Sharat; Leemhuis, Tom; Mehta, Parinda A; Bleesing, Jack J; Davies, Stella M; Jordan, Michael B; Filipovich, Alexandra H

    2013-11-01

    Reduced-intensity conditioning (RIC) improves the outcomes of hematopoietic cell transplantation (HCT) in patients with hemophagocytic lymphohistiocytosis (HLH). Proximal (ie, close to graft infusion) dosing of alemtuzumab is associated with a high incidence of mixed chimerism, whereas distal (ie, distant from graft infusion) dosing is associated with less mixed chimerism but more acute graft-versus-host disease (GVHD). The alemtuzumab dose per kilogram of body weight also influences these outcomes. We hypothesized that an intermediate alemtuzumab dosing schedule would reduce mixed chimerism and maintain a low incidence of acute GVHD. In this study, 24 consecutive HCTs were performed in patients with HLH or a related disorder using a novel intermediate alemtuzumab schedule of 1 mg/kg starting on day -14. The cumulative incidences (CIs) of mixed chimerism, upfront acute GVHD grades II-IV, and receipt of additional hematopoietic cell products after HCT were compared in patients treated with a distal alemtuzumab schedule (n = 15) and those treated with a proximal alemtuzumab schedule (n = 33). All patients received fludarabine and melphalan. The CI of mixed chimerism was 31% in the intermediate group, 72% in the proximal group (P < .01), and 75% in the distal group patients who received ≥2 mg/kg alemtuzumab (P = .03). The CI of acute GVHD grades II-IV before the development of mixed chimerism was 4% in the intermediate group, 0% in the proximal group, and 13% in the distal group (P = .04, proximal versus distal). The 1-year CI of administration of additional hematopoietic cell products for mixed chimerism (donor lymphocyte infusion ± hematopoietic stem cell boost ± repeat HCT) was 14% in the intermediate group, 53% in the proximal group (P = .01), and 38% in the distal ≥2 mg/kg alemtuzumab group (P = .02). Our findings indicate that intermediate RIC reduces the incidence of mixed chimerism, is associated with a low incidence of upfront acute

  13. Port-site transversus abdominis fascia closure reduced the incidence of incisional hernia following retroperitoneal laparoscopic nephrectomy.

    PubMed

    Takei, A; Sazuka, T; Nakamura, K; Nihei, N; Ichikawa, T

    2016-10-01

    The incidence of incisional hernia after laparoscopic surgery is reportedly 0-5.2 %; there are only a few reports of that following retroperitoneal laparoscopic nephrectomy. We evaluated the incidence of and risk factors for incisional hernia after retroperitoneal laparoscopic nephrectomy, and the efficacy of our novel prophylaxis technique. A total of 207 renal cell carcinoma patients who underwent laparoscopic nephrectomy at Chiba University Hospital were retrospectively enrolled in this study. We compared the incidences of incisional hernia following the transperitoneal vs. retroperitoneal approaches, and, among the latter group, the incidences with vs. without use of our prophylaxis method. Also among the retroperitoneal-approach group, we evaluated selected patient characteristics as potential hernia risk factors. The rate of incisional hernias was 14 (8.7 %) after 161 retroperitoneal laparoscopic nephrectomies and one (2.2 %) after 46 transperitoneal laparoscopic nephrectomies (P = 0.132). For those undergoing the retroperitoneal approach, 14 (11.3 %) hernias were identified in 124 non-prophylaxed patients and none in 37 prophylaxed patients. Transversus abdominis fascia closure was a statistically significant factor for reducing the incidence of incisional hernia after retroperitoneal laparoscopic nephrectomy (P = 0.0324): rectus abdominis muscle thickness ≤7 mm and perioperative blood loss >100 ml were statistically significant independent risk factors, by multivariate analysis. To prevent incisional hernia after retroperitoneal laparoscopic nephrectomy in the patients with risk factors, it is useful to close the transversus abdominis fascia at the port sites from inside the surgical cavity, through the open specimen-removal trocar port site, under direct observation.

  14. High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves

    PubMed Central

    Angstman, Nicholas B.; Kiessling, Maren C.; Frank, Hans-Georg; Schmitz, Christoph

    2015-01-01

    In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short- and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI. PMID:25705183

  15. Random drug testing to reduce the incidence of addiction in anesthesia residents: preliminary results from one program.

    PubMed

    Fitzsimons, Michael G; Baker, Keith H; Lowenstein, Edward; Zapol, Warren M

    2008-08-01

    Substance abuse occurs in approximately 1%-2% of anesthesia residents and nearly 80% of programs have had one or more resident (s) with such a problem. Education and control efforts have failed to reduce the frequency of substance abuse. Anesthesia providers have a professional obligation to be drug-free for the well being of their patients. We have instituted a program of preplacement and random urine testing of residents in anesthesiology in an attempt to decrease the incidence of substance abuse. We demonstrate that such a program is feasible, despite logistic and cultural obstacles. Larger multi-institutional studies will be required to determine whether instituting a program of random urine testing decreases the incidence of substance abuse in anesthesiology residents.

  16. A double blind randomized controlled trial comparing primary suture closure with mesh augmented closure to reduce incisional hernia incidence

    PubMed Central

    2013-01-01

    Background Incisional hernia is the most frequently seen long term complication after laparotomy causing much morbidity and even mortality. The overall incidence remains 11-20%, despite studies attempting to optimize closing techniques. Two patient groups, patients with abdominal aortic aneurysm and obese patients, have a risk for incisional hernia after laparotomy of more than 30%. These patients might benefit from mesh augmented midline closure as a means to reduce incisional hernia incidence. Methods/design The PRImary Mesh Closure of Abdominal Midline Wound (PRIMA) trial is a double-blinded international multicenter randomized controlled trial comparing running slowly absorbable suture closure with the same closure augmented with a sublay or onlay mesh. Primary endpoint will be incisional hernia incidence 2 years postoperatively. Secondary outcomes will be postoperative complications, pain, quality of life and cost effectiveness. A total of 460 patients will be included in three arms of the study and randomized between running suture closure, onlay mesh closure or sublay mesh closure. Follow-up will be at 1, 3, 12 and 24 months with ultrasound imaging performed at 6 and 24 months to objectify the presence of incisional hernia. Patients, investigators and radiologists will be blinded throughout the whole follow up. Disccusion The use of prosthetic mesh has proven effective and safe in incisional hernia surgery however its use in a prophylactic manner has yet to be properly investigated. The PRIMA trial will provide level 1b evidence whether mesh augmented midline abdominal closure reduces incisional hernia incidence in high risk groups. Trial registration Clinical trial.gov NCT00761475. PMID:24499111

  17. Use of the six sigma methodology to reduce incidence of breast milk administration errors in the NICU.

    PubMed

    Drenckpohl, Douglas; Bowers, Laura; Cooper, Hoa

    2007-01-01

    Breast milk is the optimal source of nutrition for infants. According to research, neonates fed breast milk have a reduced risk of sepsis, increased feeding tolerance, a decreased incidence of necrotizing enterocolitis, and better neurodevelopmental outcomes. Unfortunately, researchers have not identified practices to reduce or eliminate the risk for errors in breast milk administration. This article discusses the potential hazards of incorrect administration of breast milk. It then describes how the tertiary care center at Children's Hospital of Illinois implemented a policy utilizing six sigma quality improvement methodologies to improve breast milk administration. Since implementation of this policy, the NICU at our hospital has reduced the risk of breast milk administration errors to less than 3.4 mistakes per million opportunities.

  18. Indoor visible mold and mold odor are associated with new-onset childhood wheeze in a dose-dependent manner.

    PubMed

    Shorter, Caroline; Crane, Julian; Pierse, Nevil; Barnes, Phillipa; Kang, Janice; Wickens, Kristin; Douwes, Jeroen; Stanley, Thorsten; Täubel, Martin; Hyvärinen, Anne; Howden-Chapman, Philippa

    2017-08-04

    Evidence is accumulating that indoor dampness and mold are associated with the development of asthma. The underlying mechanisms remain unknown. New Zealand has high rates of both asthma and indoor mold and is ideally placed to investigate this. We conducted an incident case-control study involving 150 children with new-onset wheeze, aged between 1 and 7 years, each matched to two control children with no history of wheezing. Each participant's home was assessed for moisture damage, condensation, and mold growth by researchers, an independent building assessor and parents. Repeated measures of temperature and humidity were made, and electrostatic dust cloths were used to collect airborne microbes. Cloths were analyzed using qPCR. Children were skin prick tested for aeroallergens to establish atopy. Strong positive associations were found between observations of visible mold and new-onset wheezing in children (adjusted odds ratios ranged between 1.30 and 3.56; P ≤ .05). Visible mold and mold odor were consistently associated with new-onset wheezing in a dose-dependent manner. Measurements of qPCR microbial levels, temperature, and humidity were not associated with new-onset wheezing. The association between mold and new-onset wheeze was not modified by atopic status, suggesting a non-allergic association. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Formula with long-chain polyunsaturated fatty acids reduces incidence of allergy in early childhood.

    PubMed

    Foiles, Amanda M; Kerling, Elizabeth H; Wick, Jo A; Scalabrin, Deolinda M F; Colombo, John; Carlson, Susan E

    2016-03-01

    Allergy has sharply increased in affluent Western countries in the last 30 years. N-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) may protect the immune system against development of allergy. We prospectively categorized illnesses by body system in a subset of 91 children from the Kansas City cohort of the DIAMOND (DHA Intake and Measurement of Neural Development) study who had yearly medical records through 4 years of age. As infants, they were fed either a control formula without LCPUFA (n = 19) or one of three formulas with LCPUFA from docosahexaenoic acid (DHA) and arachidonic acid (ARA) (n = 72). Allergic illnesses in the first year were lower in the combined LCPUFA group compared to the control. LCPUFAs significantly delayed time to first allergic illness (p = 0.04) and skin allergic illness (p = 0.03) and resulted in a trend to reduced wheeze/asthma (p = 0.1). If the mother had no allergies, LCPUFAs reduced the risk of any allergic diseases (HR = 0.24, 95% CI = 0.1, 0.56, p = 0.0.001) and skin allergic diseases (HR = 0.35, 95% CI = 0.13, 0.93, p = 0.04). In contrast, if the mother had allergies, LCPUFAs reduced wheezing/asthma (HR = 0.26, 95% CI = 0.07, 0.9, p = 0.02). LCPUFA supplementation during infancy reduced the risk of skin and respiratory allergic diseases in childhood with effects influenced by maternal allergies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Use of a portable bladder scanner to reduce the incidence of bladder catheterisation prior to laparoscopy.

    PubMed

    Moselhi, M; Morgan, M

    2001-04-01

    The aim of this study was to evaluate the usefulness of estimating bladder volume with a dedicated portable ultrasound device immediately prior to gynaecological laparoscopy. Catheterisation was performed if the estimated volume was greater than 100 ml. Forty consecutive women were studied prospectively. Twenty-six women did not require catheterisation. The procedure was quick and effective in safely reducing the frequency of pre-operative catheterisation.

  1. Formula with long chain polyunsaturated fatty acids reduces incidence of allergy in early childhood

    PubMed Central

    Foiles, Amanda M.; Kerling, Elizabeth H.; Wick, Jo A.; Scalabrin, Deolinda M.F.; Colombo, John; Carlson, Susan E.

    2016-01-01

    Background Allergy has sharply increased in affluent Western countries in the last 30 years. N-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) may protect the immune system against development of allergy. Methods We prospectively categorized illnesses by body system in a subset of 91 children from the Kansas City cohort of the DIAMOND (DHA Intake and Measurement of Neural Development) study who had yearly medical records through 4 years of age. As infants, they were fed either a control formula without LCPUFA (n=19) or one of three formulas with LCPUFA from docosahexaenoic acid (DHA) and arachidonic acid (ARA) (n=72). Results Allergic illnesses in the first year were lower in the combined LCPUFA group compared to the control. LCPUFAs significantly delayed time to first allergic illness (p=0.04) and skin allergic illness (p=0.03); and resulted in a trend to reduced wheeze/asthma (p=0.1). If the mother had no allergies, LCPUFAs reduced the risk of any allergic diseases (HR = 0.24, 95% CI = 0.1, 0.56, p=0.0.001) and skin allergic diseases (HR = 0.35, 95% CI = 0.13, 0.93, p=0.04). In contrast, if the mother had allergies, LCPUFAs reduced wheezing/asthma (HR = 0.26, 95% CI = 0.07, 0.9, p = 0.02). Conclusions LCPUFA supplementation during infancy reduced the risk of skin and respiratory allergic diseases in childhood with effects influenced by maternal allergies. PMID:26613373

  2. Dose-dependent effects of recombinant human interleukin-11 on the systemic hemodynamic function and urination.

    PubMed

    Honma, Kaneatsu; Koles, Nancy L; Alam, Hasan B; Keith, James C; Pollack, Matthew

    2007-01-01

    The purpose of this study was to determine whether recombinant human interleukin-11 (rhIL-11) could dose-dependently improve the hemodynamic function. Using a swine hemorrhagic shock model, rhIL-11 was given at the beginning of resuscitation. The animals were randomized to receive a single dose of rhIL-11 (5, 20, or 50 microg/kg, group I to III for respectively) or saline (group IV). Blood, urine and both pleural and peritoneal effusion were thus obtained and analyzed. The mean arterial pressure (MAP) was higher post-resuscitation (PR) in group III (62.9+/-8.2 mmHg) than in groups I, II and IV (54.9+/-1.7, 53.9+/-4.3, 55.9+/-9.4 mmHg, respectively) (P<0.01). The urine output (I: 999+/-428, II: 1249+/-180, III: 1434+/-325, IV: 958+/-390 ml) and the cardiac output (CO) (I: 3.01+/-0.66, II: 3.30+/-0.49, III: 3.43+/-0.57, IV: 2.73+/-0.49 L/min.) increased in a dose dependent manner of rhIL-11. CO level and urine output were significantly higher in group III than in group IV (P<0.05). In addition, the volume of third space fluid loss (pleural and peritoneal effusion) of group III was significantly lower than other groups (I: 157+/-32, II: 138+/-32, III: 82+/-21, IV: 125+/-32 ml) (P<0.05). In conclusion, even a low dose of rhIL-11 improved the hemodynamic functions dose-dependently in a porcine model of hemorrhagic shock, although the relationship did not demonstrate a simple linearity.

  3. Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed drinking water

    PubMed Central

    2014-01-01

    Background Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose–response relationship in the application of hydrogen is puzzling. We attempted to identify the dose–response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. Methods In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. Results Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. Conclusions Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose–response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress. PMID:24589018

  4. Dexmedetomidine dose dependently decreases oral tissue blood flow during sevoflurane and propofol anesthesia in rabbits.

    PubMed

    Sazuka, Shoichiro; Matsuura, Nobuyuki; Ichinohe, Tatsuya

    2012-08-01

    The aim of the present study was to investigate the effect of dexmedetomidine (DEX) continuous infusion on blood flow in rabbit oral tissues during sevoflurane or propofol anesthesia. A total of 24 male tracheotomized Japanese white rabbits were anesthetized with sevoflurane or propofol under mechanical ventilation. An initial loading dose of 6.0 μg/kg/hr DEX was administered for 10 minutes. DEX was then maintained at 0.2, 0.4, and 0.6 μg/kg/hr for 1 hour, respectively. The observed variables were systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, common carotid artery blood flow, tongue mucosal blood flow (TBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), lower alveolar tissue blood flow (LBF), and vascular resistance for each tissue (tongue mucosal vascular resistance, mandibular bone marrow vascular resistance, masseter muscle vascular resistance, upper alveolar tissue vascular resistance, and lower alveolar tissue vascular resistance). The heart rate, systolic blood pressure, mean arterial pressure, common carotid artery blood flow, TBF, BBF, MBF, UBF, and LBF showed dose-dependent decreases during DEX infusion during both sevoflurane and propofol anesthesia. The decreasing ratios in TBF, BBF, MBF, UBF, and LBF were greater than those in heart rate, systolic blood pressure, mean arterial pressure, and common carotid artery blood flow. The vascular resistance of the oral tissues was increased in a dose-dependent manner during DEX infusion in both sevoflurane and propofol anesthesia. Our findings suggest that infusion of DEX decreases TBF, BBF, MBF, UBF, and LBF in a dose-dependent manner without significant changes in systemic hemodynamic variables during sevoflurane or propofol anesthesia. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Dose-dependent inhibition of gastric injury by hydrogen in alkaline electrolyzed drinking water.

    PubMed

    Xue, Jinling; Shang, Guodong; Tanaka, Yoshinori; Saihara, Yasuhiro; Hou, Lingyan; Velasquez, Natalia; Liu, Wenjun; Lu, Yun

    2014-03-03

    Hydrogen has been reported to relieve damage in many disease models, and is a potential additive in drinking water to provide protective effects for patients as several clinical studies revealed. However, the absence of a dose-response relationship in the application of hydrogen is puzzling. We attempted to identify the dose-response relationship of hydrogen in alkaline electrolyzed drinking water through the aspirin induced gastric injury model. In this study, hydrogen-rich alkaline water was obtained by adding H2 to electrolyzed water at one atmosphere pressure. After 2 weeks of drinking, we detected the gastric mucosal damage together with MPO, MDA and 8-OHdG in rat aspirin induced gastric injury model. Hydrogen-dose dependent inhibition was observed in stomach mucosal. Under pH 8.5, 0.07, 0.22 and 0.84 ppm hydrogen exhibited a high correlation with inhibitory effects showed by erosion area, MPO activity and MDA content in the stomach. Gastric histology also demonstrated the inhibition of damage by hydrogen-rich alkaline water. However, 8-OHdG level in serum did not have significant hydrogen-dose dependent effect. pH 9.5 showed higher but not significant inhibitory response compared with pH 8.5. Hydrogen is effective in relieving the gastric injury induced by aspirin-HCl, and the inhibitory effect is dose-dependent. The reason behind this may be that hydrogen-rich water directly interacted with the target tissue, while the hydrogen concentration in blood was buffered by liver glycogen, evoking a suppressed dose-response effect. Drinking hydrogen-rich water may protect healthy individuals from gastric damage caused by oxidative stress.

  6. Caffeine ingestion impairs insulin sensitivity in a dose-dependent manner in both men and women.

    PubMed

    Beaudoin, Marie-Soleil; Allen, Brian; Mazzetti, Gillian; Sullivan, Peter J; Graham, Terry E

    2013-02-01

    The effects of alkaloid caffeine on insulin sensitivity have been investigated primarily in men, and with a single caffeine dose most commonly of 5-6 mg·kg(-1) of body weight (BW). It is unknown if the effects of caffeine on glucose homeostasis are sex-specific and (or) dose-dependent. This study examined whether caffeine ingestion would disrupt glucose homeostasis in a dose-dependent or threshold manner. It also examined whether sex-specific responses to caffeine exist. It was hypothesized that women would have an exaggerated response to caffeine, and that caffeine would only impair glucose metabolism once a threshold was reached. Twenty-four healthy volunteers (12 males, 12 females) participated in 4 trials, in a crossover, randomized, and double-blind fashion. They ingested caffeine (1, 3, or 5 mg·kg(-1) of BW) or placebo followed, 1 h later, by a 2-h oral glucose tolerance test. Glucose, insulin, C-peptide area under the curve (AUC), and insulin sensitivity index data were fitted to a segmented linear model to determine dose-responses. There were no differences between sexes for any endpoints. Regression slopes were significantly different from zero (p < 0.05) for glucose, insulin, and C-peptide AUCs, with thresholds being no different from zero. Increasing caffeine consumption by 1 mg·kg(-1) of BW increased insulin and C-peptide AUCs by 5.8% and 8.7%, respectively. Despite this exaggerated insulin response, glucose AUC increased by 11.2 mmol per 120 min·L(-1) for each mg·kg(-1) BW consumed. These results showed that caffeine ingestion disrupted insulin sensitivity in a dose-dependent fashion beginning at very low doses (0-1 mg·kg(-1) BW) in both healthy men and women.

  7. Peripheral venous congestion causes time- and dose-dependent release of endothelin-1 in humans.

    PubMed

    Lin, Jeffrey; Chudasama, Neelesh; Hayashi, Yacki; Hawk, Christopher; Ramnauth, Sahadeo D; Wong, Ka Yuk; Harxhi, Ante; Onat, Duygu; Wakabayashi, Michiyori; Uriel, Nir; Jorde, Ulrich P; LeJemtel, Thierry H; Sabbah, Hani N; Demmer, Ryan T; Colombo, Paolo C

    2017-03-01

    Endothelin-1 (ET-1) is a pivotal mediator of vasoconstriction and inflammation in congestive states such as heart failure (HF) and chronic kidney disease (CKD). Whether peripheral venous congestion (VC) increases plasma ET-1 at pressures commonly seen in HF and CKD patients is unknown. We seek to characterize whether peripheral VC promotes time- and dose-dependent increases in plasma ET-1 and whether these changes are sustained after decongestion. We used a randomized, cross-over design in 20 healthy subjects (age 30 ± 7 years). To experimentally model VC, venous pressure was increased to either 15 or 30 mmHg (randomized at first visit) above baseline by inflating a cuff around the subject's dominant arm; the nondominant arm served as a noncongested control. We measured plasma ET-1 at baseline, after 20, 60 and 120 min of VC, and finally at 180 min (60 min after cuff release and decongestion). Plasma ET-1 progressively and significantly increased over 120 min in the congested arm relative to the control arm and to baseline values. This effect was dose-dependent: ET-1 increased by 45% and 100% at VC doses of 15 and 30 mmHg, respectively (P < 0.05), and declined after 60 min of decongestion though remaining significantly elevated compared to baseline. In summary, peripheral VC causes time- and dose-dependent increases in plasma ET-1. Of note, the lower dose of 15 mmHg (more clinically relevant to HF and CKD patients) was sufficient to raise ET-1. These findings support the potentially contributory, not merely consequential, role of VC in the pathophysiology of HF and CKD.

  8. Active Case Finding Among Homeless People as a Means of Reducing the Incidence of Pulmonary Tuberculosis in General Population.

    PubMed

    Romaszko, J; Siemaszko, A; Bodzioch, M; Buciński, A; Doboszyńska, A

    2016-01-01

    The incidence of tuberculosis (TB) declined more than two-fold, compared with the national average, in the northeastern region of Poland in the period of 2003-2012. During that time, four programs of active case finding of TB were conducted as part of which a total of 944 homeless individuals were examined and 21 cases of active TB were detected. The objective of the present study was to find out whether the observed beneficial epidemiological trend could be a result of those programs. We addressed the issue of how the active case finding programs in the homeless community affected the TB incidence in the general population using a modified crisscross SIS-type (Susceptible - Infected - Susceptible) model which describes the dynamics of TB spread between the homeless and non-homeless populations. The values calculated from our model proved highly congruent with the actual epidemiological data. Our analysis showed a significant decline in TB incidence within 1 year of completion of each active case finding program. The model shows that each identified and cured case in the homeless community reduced the number of new cases in the general population by 3-4 within 1 year and by up to 20 within 5 years.

  9. Cost-Effectiveness of the Strategies to Reduce the Incidence of Dengue in Colima, México.

    PubMed

    Mendoza-Cano, Oliver; Hernandez-Suarez, Carlos Moisés; Trujillo, Xochitl; Ochoa Diaz-Lopez, Héctor; Lugo-Radillo, Agustin; Espinoza-Gomez, Francisco; de la Cruz-Ruiz, Miriam; Sánchez-Piña, Ramón Alberto; Murillo-Zamora, Efrén

    2017-08-08

    Dengue fever is considered to be one of the most important arboviral diseases globally. Unsuccessful vector-control strategies might be due to the lack of sustainable community participation. The state of Colima, located in the Western region of Mexico, is a dengue-endemic area despite vector-control activities implemented, which may be due to an insufficient health economic analysis of these interventions. A randomized controlled community trial took place in five urban municipalities where 24 clusters were included. The study groups (n = 4) included an intervention to improve the community participation in vector control (A), ultra-low volume (ULV) spraying (B), both interventions (AB), and a control group. The main outcomes investigated were dengue cumulative incidence, disability-adjusted life years (DALYs), and the direct costs per intervention. The cumulative incidence of dengue was 17.4%, A; 14.3%, B; 14.4%, AB; and 30.2% in the control group. The highest efficiency and effectiveness were observed in group B (0.526 and 6.97, respectively) and intervention A was more likely to be cost-effective ($3952.84 per DALY avoided) followed by intervention B ($4472.09 per DALY avoided). Our findings suggest that efforts to improve community participation in vector control and ULV-spraying alone are cost-effective and may be useful to reduce the vector density and dengue incidence.

  10. Slow infusion metoclopramide does not affect the improvement rate of nausea while reducing akathisia and sedation incidence.

    PubMed

    Tura, Pinar; Erdur, Bulent; Aydin, Berrin; Turkcuer, Ibrahim; Parlak, Ismet

    2012-02-01

    To compare the effects of metoclopramide infusion in emergency department (ED) patients complaining of nausea to determine the changes in its therapeutic effect and prevention of side effects such as akathisia and sedation. A prospective, randomised, double blind trial, from 1 March 2007 to 1 May 2008 in the ED of Pamukkale University Faculty of Medicine. Patients with moderate to severe nausea were randomised and divided into two groups: group 1 received 10 mg metoclopramide as a slow intravenous infusion over 15 min plus placebo (SIG); group 2 received 10 mg metoclopramide as an intravenous bolus infusion over 2 min plus placebo (BIG). The whole procedure was observed, and nausea scores, akathisia and vital changes were recorded. 140 patients suffering from moderate to severe nausea in the ED were included in the study. There was no significant difference between the groups in terms of mean nausea scores during follow-up (p=0.97). A significant difference in akathisia incidence was observed between the groups (18 (26.1%) in the BIG and 5 (7%) in the SIG) (p=0.002). There was also a significant difference in sedation incidence between the groups (19 (27.5%) in the BIG and 10 (14.5%) in the SIG) (p=0.05). Even though slowing the rate of infusion of metoclopramide does not affect the rate of improvement in nausea, it may be an effective strategy for reducing the incidence of akathisia and sedation in patients with nausea.

  11. Cost-Effectiveness of the Strategies to Reduce the Incidence of Dengue in Colima, México

    PubMed Central

    Ochoa Diaz-Lopez, Héctor; Lugo-Radillo, Agustin; Espinoza-Gomez, Francisco; de la Cruz-Ruiz, Miriam; Sánchez-Piña, Ramón Alberto; Murillo-Zamora, Efrén

    2017-01-01

    Dengue fever is considered to be one of the most important arboviral diseases globally. Unsuccessful vector-control strategies might be due to the lack of sustainable community participation. The state of Colima, located in the Western region of Mexico, is a dengue-endemic area despite vector-control activities implemented, which may be due to an insufficient health economic analysis of these interventions. A randomized controlled community trial took place in five urban municipalities where 24 clusters were included. The study groups (n = 4) included an intervention to improve the community participation in vector control (A), ultra-low volume (ULV) spraying (B), both interventions (AB), and a control group. The main outcomes investigated were dengue cumulative incidence, disability-adjusted life years (DALYs), and the direct costs per intervention. The cumulative incidence of dengue was 17.4%, A; 14.3%, B; 14.4%, AB; and 30.2% in the control group. The highest efficiency and effectiveness were observed in group B (0.526 and 6.97, respectively) and intervention A was more likely to be cost-effective ($3952.84 per DALY avoided) followed by intervention B ($4472.09 per DALY avoided). Our findings suggest that efforts to improve community participation in vector control and ULV-spraying alone are cost-effective and may be useful to reduce the vector density and dengue incidence. PMID:28786919

  12. Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy.

    PubMed

    Seibert, Tyler M; Karunamuni, Roshan; Kaifi, Samar; Burkeen, Jeffrey; Connor, Michael; Krishnan, Anitha Priya; White, Nathan S; Farid, Nikdokht; Bartsch, Hauke; Murzin, Vyacheslav; Nguyen, Tanya T; Moiseenko, Vitali; Brewer, James B; McDonald, Carrie R; Dale, Anders M; Hattangadi-Gluth, Jona A

    2017-04-01

    Neurologic deficits after brain radiation therapy (RT) typically involve decline in higher-order cognitive functions such as attention and memory rather than sensory defects or paralysis. We sought to determine whether areas of the cortex critical to cognition are selectively vulnerable to radiation dose-dependent atrophy. We measured change in cortical thickness in 54 primary brain tumor patients who underwent fractionated, partial brain RT. The study patients underwent high-resolution, volumetric magnetic resonance imaging (T1-weighted; T2 fluid-attenuated inversion recovery, FLAIR) before RT and 1 year afterward. Semiautomated software was used to segment anatomic regions of the cerebral cortex for each patient. Cortical thickness was measured for each region before RT and 1 year afterward. Two higher-order cortical regions of interest (ROIs) were tested for association between radiation dose and cortical thinning: entorhinal (memory) and inferior parietal (attention/memory). For comparison, 2 primary cortex ROIs were also tested: pericalcarine (vision) and paracentral lobule (somatosensory/motor). Linear mixed-effects analyses were used to test all other cortical regions for significant radiation dose-dependent thickness change. Statistical significance was set at α = 0.05 using 2-tailed tests. Cortical atrophy was significantly associated with radiation dose in the entorhinal (P=.01) and inferior parietal ROIs (P=.02). By contrast, no significant radiation dose-dependent effect was found in the primary cortex ROIs (pericalcarine and paracentral lobule). In the whole-cortex analysis, 9 regions showed significant radiation dose-dependent atrophy, including areas responsible for memory, attention, and executive function (P≤.002). Areas of cerebral cortex important for higher-order cognition may be most vulnerable to radiation-related atrophy. This is consistent with clinical observations that brain radiation patients experience deficits in domains of

  13. Dose-dependent killing of leukemia cells by low-temperature plasma

    NASA Astrophysics Data System (ADS)

    Barekzi, N.; Laroussi, M.

    2012-10-01

    The effect of low-temperature atmospheric pressure plasma towards the progression of cancerous human T-cell leukemia cells was investigated. The plasma pencil, which utilizes short duration high voltage pulses, was used to generate a low-temperature plasma (LTP) plume in ambient air. Our data showed that cell morphology and cell viability were affected in a dose-dependent manner after treatment with LTP. The outcome of this study revealed that the effect of plasma exposure was not immediate, but had a delayed effect and increasing the time of plasma exposure resulted in increased leukemia cell death.

  14. Risperidone-induced Gingival Bleeding in a Pediatric Case: A Dose-dependent Side Effect

    PubMed Central

    Hergüner, Sabri; Özayhan, Hatice Yardım; Erdur, Emire Aybuke

    2016-01-01

    There are several case reports on risperidone-related bleeding; however, to our knowledge, there is no report about gingival bleeding associated with risperidone in the literature. We presented a case who experienced gingival bleeding when risperidone dose was increased to 0.5 mg/day, and subsided after decreasing the dose to 0.25 mg/day, suggesting a dose-dependent side-effect. The bleeding side effect of risperidone might be caused by several mechanisms, including 5-hydroxytryptamine 2A receptor antagonism. Although bleeding associated with risperidone is rarely reported, clinicians should be aware of this side effect. PMID:27121433

  15. Risperidone-induced Gingival Bleeding in a Pediatric Case: A Dose-dependent Side Effect.

    PubMed

    Hergüner, Sabri; Özayhan, Hatice Yardım; Erdur, Emire Aybuke

    2016-05-31

    There are several case reports on risperidone-related bleeding; however, to our knowledge, there is no report about gingival bleeding associated with risperidone in the literature. We presented a case who experienced gingival bleeding when risperidone dose was increased to 0.5 mg/day, and subsided after decreasing the dose to 0.25 mg/day, suggesting a dose-dependent side-effect. The bleeding side effect of risperidone might be caused by several mechanisms, including 5-hydroxytryptamine 2A receptor antagonism. Although bleeding associated with risperidone is rarely reported, clinicians should be aware of this side effect.

  16. Intracellular magnesium blocks sodium outward currents in a voltage- and dose-dependent manner.

    PubMed Central

    Pusch, M; Conti, F; Stühmer, W

    1989-01-01

    Tail currents through Na+ channels have been measured in inside-out patches from Xenopus laevis oocytes injected with cDNA-derived mRNA coding for the rat brain type II Na+ channel. It is shown that intracellular Mg2+ blocks outward currents in a voltage- and dose-dependent manner with a half blocking concentration between 3 and 4 mM at 0 mV and a voltage dependence of e-fold per 49 mV. PMID:2548634

  17. Optimum resource allocation to reduce HIV incidence across sub-Saharan Africa: a mathematical modelling study.

    PubMed

    McGillen, Jessica B; Anderson, Sarah-Jane; Dybul, Mark R; Hallett, Timothy B

    2016-09-01

    Advances in HIV prevention methods offer promise to accelerate declines in incidence, but how these methods can be deployed to have the best effect on the heterogeneous landscape and drivers of the pandemic remains unclear. We postulated that use of epidemic heterogeneity to inform the allocation of resources for combination HIV prevention could enhance the impact of HIV funding across sub-Saharan Africa. We developed a compartmental mathematical model of HIV transmission and disease progression by risk group to subnational resolution in 18 countries, capturing 80% of the adult HIV burden in sub-Saharan Africa. Adults aged 15-49 years were grouped by risk of HIV acquisition and transmission, and those older than 50 years were assumed to have negligible risk. For each top-level administrative division, we calibrated the model to historical data for HIV prevalence, sexual behaviours, treatment scale-up, and demographics. We then evaluated four strategies for allocation of prevention funding over a 15 year period from 2016 to 2030, which exploited epidemic differences between subnational regions to varying degrees. For a $US20 billion representative expenditure over the 15 year period, scale-up of prevention along present funding channels could avert 5·3 million infections relative to no scale-up. Prioritisation of key populations could avert 3·7 million more infections than present funding channels, and additional prioritisation by within-country geography could avert 400 000 more infections. Removal of national constraints could avert a further 600 000 infections. Risk prioritisation has greater marginal impact than geographical prioritisation across multiple expenditure levels. However, targeting by both risk and geography is best for total impact and could achieve gains of up to three times more than present channels. A shift from the present pattern to the optimum pattern would rebalance resources towards more cost-effective interventions and emerging

  18. Simulations of High-Intensity Short-Pulse Lasers Incident on Reduced Mass Targets

    NASA Astrophysics Data System (ADS)

    King, Frank W.

    This thesis presents the results of a series of fully kinetic particle-in-cell (PIC) simulations of reduced mass targets with pre-plasma subjected to high-intensity short-pulse lasers. The simulations are performed in one, two, and three dimensions. The results of these simulations show that the creation of an electrostatic collisionless ion shock in the preplasma controls the creation of an above solid density ion perturbation in the target bulk, and this determines the reduced mass target heating and deformation. The ion perturbation is initiated by a population of high-energy electrons that rapidly spread throughout the target and reflux. The perturbation spreads longitudinally and transversely through the target and results in compression followed by the destruction of the target. This deformation requires a kinetic treatment due to the generation of non-equilibrium particle distributions and the role of ballistic electrons and ions. Kinetic and fluid simulations are compared and both exhibit the basic features of the above solid density ion perturbation, but the magnitude of the effect and the speed of propagation vary significantly between the two methods. Kinetic simulations do not naturally include equation-of-state physics and other aspects of the problem. Both approaches are complementary. The requirements on spatial resolution, particle count, and other numerical parameters are addressed in this work. From these simulations, the behavior of the reduced mass targets is found to vary significantly depending on the laser focal spot size or the intensity of the laser pulse. This occurs even if the energy and power of the laser pulses are held constant. The number of dimensions used in the particle-in-cell simulations has been observed to have a significant effect on late-time heating of the target, but not during or shortly after laser excitation. This is due to the representation of the equilibration process as the initial population of laser heated

  19. Reducing the incidence and mortality of colon cancer: mass screening and colonoscopic polypectomy.

    PubMed

    Cappell, Mitchell S

    2008-03-01

    Most colon cancers arise from conventional adenomatous polyps (conventional adenoma-to-carcinoma sequence), while some colon cancers appear to arise from the recently recognized serrated adenomatous polyp (serrated adenoma-to-carcinoma theory). Because conventional adenomas and serrated adenomas are usually asymptomatic, mass screening of asymptomatic patients has become the cornerstone for detecting and eliminating these precursor lesions to reduce the risk of colon cancer. Colonoscopy has become the primary screening test because of its high sensitivity and specificity, and the ability to perform polypectomy. Other screening tests include guaiac tests or fecal immunochemical tests (FIT) for fecal occult blood, and flexible sigmoidoscopy. A minimal colonoscopic withdrawal time of 6 minutes is important to maximize polyp detection at colonoscopy. Chromoendoscopy is an experimental technique used to highlight abnormal colonic areas to identify neoplastic tissue and to potentially determine the histology of colonic polyps at colonoscopy based on superficial pit anatomy.

  20. Evidence from a large-scale meta-analysis indicates eczema reduces the incidence of glioma

    PubMed Central

    Cao, Chao; Dong, Jing; Chu, Yudong; He, Guijuan; Xu, Zhiwei

    2016-01-01

    We investigated the relationship between eczema and the risk of primary glioma. Relevant studies were selected through electronic searches of PubMed and EMBASE. A meta-analysis of 12 case-control studies and one cohort study was performed. A fixed effect model was applied to analyze 13 studies consisting of 10,897 glioma cases and 56,081 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. The data demonstrate that eczema significantly reduces the risk of glioma (OR = 0.69, 95% CI = 0.61–0.78, P < 0.001). Additional studies with larger patient cohorts are required to validate our findings. PMID:27566584

  1. Eradication of Helicobacter pylori after endoscopic resection of gastric tumors does not reduce incidence of metachronous gastric carcinoma.

    PubMed

    Choi, Jeongmin; Kim, Sang Gyun; Yoon, Hyuk; Im, Jong Pil; Kim, Joo Sung; Kim, Woo Ho; Jung, Hyun Chae

    2014-05-01

    It is not clear whether eradication of Helicobacter pylori infection reduces the risk for metachronous gastric carcinoma. We performed a prospective, randomized, open-label trial of the effects of H pylori eradication on the incidence of metachronous carcinoma after endoscopic resection of gastric tumors. From April 2005 through February 2011 there were 901 consecutive patients with H pylori infection who had been treated with endoscopic resection for gastric dysplasia or cancer and who were assigned randomly to groups given therapy to eradicate the infection (n = 444) or no therapy (controls, n = 457). The eradication group received 20 mg omeprazole, 1 g amoxicillin, and 500 mg clarithromycin twice daily for 1 week. Patients underwent endoscopic examination 3, 6, and 12 months after treatment, and then yearly thereafter. The primary outcome was development of metachronous gastric carcinoma. During a median follow-up period of 3 years, 10 patients who received H pylori eradication and 17 controls developed metachronous carcinoma; this difference was not significant (P = .15). The incidence of metachronous carcinoma between the 2 groups did not differ significantly at 1, 2, 3, and 4 years after administration of the therapy. There were no significant differences in the development of metachronous carcinoma among patients who were positive (n = 16) or negative (n = 11) for H pylori infection (P = .32). In this prospective trial, eradication of H pylori after endoscopic resection of gastric tumors did not significantly reduce the incidence of metachronous gastric carcinoma. ClinicalTrials.gov Number: NCT01510730. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.

    PubMed

    Buschard, Karsten; Hansen, Axel Kornerup; Jensen, Karen; Lindenbergh-Kortleve, Dicky J; de Ruiter, Lilian F; Krohn, Thomas C; Hufeldt, Majbritt R; Vogensen, Finn K; Aasted, Bent; Osterbye, Thomas; Roep, Bart O; de Haar, Colin; Nieuwenhuis, Edward E

    2011-04-01

    Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

  3. Driver's education may reduce annual incidence and severity of moped and scooter accidents. A population-based study.

    PubMed

    Kosola, Silja; Salminen, Päivi; Kallio, Pentti

    2016-01-01

    In our previous study, the annual number of adolescents treated at Helsinki Children's Hospital and Töölö Trauma Centre for injuries from moped and scooter accidents increased five-fold between 2002 and 2007. In June 2011, the requirements for a moped/scooter license changed to include driver's education and a vehicle handling evaluation. The aim of this retrospective study was to assess the influence of legislative changes on moped and scooter related serious injuries in adolescents. Data from 520 patients (age 15-16) treated for trauma from moped and scooter accidents at our institutions between January 2008 and December 2013 were included. Case numbers were compared with population data from national databases. Overall incidence, trauma mechanism, injury profile, and proportion of patients requiring hospital admission were calculated for time periods before and after the law amendment. After the law change in 2011, the annual incidence of moped/scooter injuries among 15-year-olds in our area decreased from 0.8% in 2011 to 0.3% in 2013 (p<0.001), and estimated incidence of injuries per new moped/scooter license declined from 1.8% in 2011 to 1.0% in 2013 (p=0.001). Simultaneously, proportions of patients injured in collisions, diagnosed with multiple trauma or requiring in-patient care reduced. A change in moped/scooter license requirements may have a causal relationship with both reduced number and severity of moped/scooter related injuries in adolescents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. State of the science on prevention and screening to reduce melanoma incidence and mortality: The time is now.

    PubMed

    Tripp, Mary K; Watson, Meg; Balk, Sophie J; Swetter, Susan M; Gershenwald, Jeffrey E

    2016-05-27

    Answer questions and earn CME/CNE Although overall cancer incidence rates are decreasing, melanoma incidence rates continue to increase about 3% annually. Melanoma is a significant public health problem that exacts a substantial financial burden. Years of potential life lost from melanoma deaths contribute to the social, economic, and human toll of this disease. However, most cases are potentially preventable. Research has clearly established that exposure to ultraviolet radiation increases melanoma risk. Unprecedented antitumor activity and evolving survival benefit from novel targeted therapies and immunotherapies are now available for patients with unresectable and/or metastatic melanoma. Still, prevention (minimizing sun exposure that may result in tanned or sunburned skin and avoiding indoor tanning) and early detection (identifying lesions before they become invasive or at an earlier stage) have significant potential to reduce melanoma incidence and melanoma-associated deaths. This article reviews the state of the science on prevention and early detection of melanoma and current areas of scientific uncertainty and ongoing debate. The US Surgeon General's Call to Action to Prevent Skin Cancer and US Preventive Services Task Force reviews on skin cancer have propelled a national discussion on melanoma prevention and screening that makes this an extraordinary and exciting time for diverse disciplines in multiple sectors-health care, government, education, business, advocacy, and community-to coordinate efforts and leverage existing knowledge to make major strides in reducing the public health burden of melanoma in the United States. CA Cancer J Clin 2016. © 2016 American Cancer Society. © 2016 American Cancer Society, Inc.

  5. The effectiveness of injury-prevention programs in reducing the incidence of anterior cruciate ligament sprains in adolescent athletes.

    PubMed

    Paszkewicz, Jeffrey; Webb, Tristen; Waters, Brian; Welch McCarty, Cailee; Van Lunen, Bonnie

    2012-11-01

    There is a high incidence of anterior cruciate ligament (ACL) injury in adolescents participating in pivoting sports such as soccer, basketball, and handball. Most ACL injuries in athletes are noncontact injuries, with a mechanism of sudden deceleration, change in direction, or landing from a jump. These mechanisms coupled with an increase in contraction of the quadriceps have been shown as risk factors for ACL injuries. Injuries to the ACL may require surgery, a long rehabilitation, and the potential for reinjury. Studies have shown reductions in lower extremity injury rates using training protocols that focus on landing mechanics, balance training, strength training, and/or agility training. There has been some thought that starting preventive training programs with adolescent athletes may be the most effective approach to reducing adolescent ACL injuries. Can lower extremity injury-prevention programs effectively reduce ACL injury rates in adolescent athletes?

  6. Apneic oxygenation reduces the incidence of hypoxemia during emergency intubation: A systematic review and meta-analysis.

    PubMed

    Pavlov, Ivan; Medrano, Sofia; Weingart, Scott

    2017-08-01

    Apneic oxygenation has been advocated for the prevention of hypoxemia during emergency endotracheal intubation. Because of conflicting results from recent trials, the efficacy of apneic oxygenation remains unclear. We performed a systematic review and meta-analysis to investigate the effect of apneic oxygenation on the incidence of clinically significant hypoxemia during emergency endotracheal intubation. MEDLINE, EMBASE, and PubMed databases were searched without language and time restrictions for studies of apneic oxygenation performed in a critical care setting. Meta-analysis was conducted with a random-effect model, and according to intention-to-treat allocation wherever applicable. Subgroup analyses were performed to ensure the robustness of findings across various clinical outcomes. Eight studies (n=1953) were included in the meta-analysis. The pooled absolute risk of clinically significant hypoxemia was 27.6% in the usual care group and 19.1% in the apneic oxygenation group, without any heterogeneity across studies (I(2)=0%; p=0.42). Apneic oxygenation reduced the relative risk of hypoxemia by 30% (95% confidence interval 0.59 to 0.82). There was a trend toward lower mortality in the apneic oxygenation group (relative risk of death 0.77; 95% confidence interval 0.59 to 1.02). Apneic oxygenation significantly reduces the incidence of hypoxemia during emergency endotracheal intubation. These findings support the inclusion of apneic oxygenation in everyday clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Lorazepam dose-dependently decreases risk-taking related activation in limbic areas.

    PubMed

    Arce, Estibaliz; Miller, Daniel A; Feinstein, Justin S; Stein, Murray B; Paulus, Martin P

    2006-11-01

    Several studies have examined the role of different neurotransmitter systems in modulating risk-taking behavior. This investigation was aimed to determine whether the benzodiazepine lorazepam dose-dependently alters risk-taking behavior and underlying neural substrates. Fifteen healthy, nonsmoking, individuals (six women, nine men), aged 18-39 years (mean 27.6 +/- 1.4 years) with 12-18 years of education (mean 15.6 +/- 0.3 years) underwent functional magnetic resonance imaging while performing a risk-taking decision-making task. Our results show that lorazepam did not affect risky behavior at 0.25 and 1 mg, but dose-dependently attenuated activation in (a) the amygdala and medial prefrontal cortex during the response selection phase, and in (b) the bilateral insular cortex and amygdala during the outcome (i.e., rewarded or punished) phase. Furthermore, a lorazepam-induced increase in insular cortex activation was associated with less risky responses. Taken together, our findings support the idea that GABAergic modulation in limbic and paralimbic structures is important during both the response selection and outcome phase of risk-taking decision-making.

  8. Dose-dependent effects of decaffeinated coffee on endothelial function in healthy subjects.

    PubMed

    Buscemi, S; Verga, S; Batsis, J A; Tranchina, M R; Belmonte, S; Mattina, A; Re, A; Rizzo, R; Cerasola, G

    2009-10-01

    Coffee is known to contain antioxidant substances whose effects may be blunted because of caffeine that may unfavorably affect the cardiovascular system. This study was designed to investigate the acute dose-dependent effects of decaffeinated coffee (DC) on endothelial function measured by the brachial artery flow-mediated dilation (FMD). A total of 15 (8 men and 7 women) healthy nonobese subjects underwent a single-blind, crossover study. Subjects ingested one and two cups of decaffeinated Italian espresso coffee in random order at 5- to 7-day intervals. In the hour following the ingestion of two cups of DC, FMD increased (mean+/-s.e.m.): 0 min, 7.4+/-0.7%; 30 min, 8.0+/-0.6%; 60 min, 10.8+/-0.8%; P<0.001) as compared to consumption of one cup of DC (0 min, 6.9+/-0.7%; 30 min, 8.4+/-1.2%; 60 min, 8.5+/-1.1%; 3 x 2 repeated-measures analysis of variance: P=0.037 for time x treatment effect). Blood pressure did not differ between groups, and basal heart rate was lower in the two-cup group at baseline and 60 min. The present study demonstrated a significant acute favorable dose-dependent effect of decaffeinated espresso coffee on endothelial function. Further studies are needed to investigate the effects of chronic use of DC especially with respect to caffeinated coffee and in subjects with cardiovascular diseases.

  9. An easy method to account for light scattering dose dependence in radiochromic films

    SciTech Connect

    Miras, Hector; Arrans, Rafael

    2009-09-15

    Purpose: To date no detector can offer the unbeatable characteristics of film dosimetry in terms of spatial resolution and this is why it has been chosen by many institutions for treatment verification and, in that respect, radiochromic films are becoming increasingly popular due to their advantageous properties. It is the aim of this work to suggest an easy method to overcome one of the drawbacks in radiochromic film dosimetry associated with the scanning device, namely, the non-uniform dose dependent response, mainly due to the light scattering effect. Methods: The suggested procedure consists of building four correction matrices by sequentially scanning one, two, three, and four unexposed blank films. The color level of these four matrices is compatible with four points in the calibration curve dose range. Therefore, the dose dependent correction to the scanned irradiated film will be obtained by interpolating between the four correction matrices. Results: The validity of the suggested method is checked against an ion chamber 2D array. The use of the proposed flattening correction improves considerably the dose agreement when compared with the cases in which no correction is applied. Conclusions: The method showed to be fast and easy and practically overcomes the dependence on the dose of light scattering of flatbed scanners.

  10. Dose dependence of strength after low-temperature irradiation in metallic materials

    SciTech Connect

    Byun, Thak Sang; Li, Meimei; Farrell, Kenneth

    2013-01-01

    This study intends to review and characterize the low-temperature (< 200 oC) irradiation hardening behaviors in metallic materials and to propose new interpretations on the dose dependence of strength, particularly in the pre-hardening and saturation regimes. The analysis results of yield stress-dose curves indicate that four dose-dependence regimes exist: the pre-hardening, main hardening, saturation, and embrittlement regimes. The semi-log plots of yield stress versus dose data revealed that the pre-hardening regime displaying zero-hardening or softening was common at least for the alloys with low dose data available. It was observed that the dose range of the pre-hardening regime increased with the strength of material, which indicates that slower initiation in irradiation hardening is expected when strength is higher. For the majority of the metallic materials analyzed, it was reconfirmed that the exponent of the power-law hardening function was evaluated to be about 0.5 in the main hardening regime and about 0.1 in the saturation regime. In these positive hardening regimes the low strength pure metals such as Fe, Ta, Cu, and Zr displayed lower hardening exponents. The minimum dose to the saturation of irradiation hardening was in the range of 0.003 0.08 dpa, depending on the category of materials. It was also reaffirmed that there exists a strong relationship between the saturation in irradiation hardening and the occurrence of plastic instability at yield.

  11. Dose-Dependent Z-Scan Measurements on GAFCHROMIC® Dosimetry Films

    NASA Astrophysics Data System (ADS)

    Koulouklidis, A.; Karava, K.; Kalef-Ezra, J.; Cohen, S.

    2010-11-01

    The open- and closed-aperture z-scan techniques are applied for investigating the non-linear optical response of GAFCHROMIC® docimetry films, irradiated by 60Co γ-rays. Upon irradiation the films active diacetylene layers undergo radiation-Dose-dependent polymerization to the so-called blue polydiacetylene form. A cw He/Ne laser is used as the light source. Open-aperture z-scan measurements reveal reverse saturable absorption while Dose-dependent thermal effects become apparent with increasing laser intensity. Those effects are tentatively attributed to the transition from the blue form to the conformer red form of the active layer (thermochromic transition) which, for the highest available power, appears to be irreversible. For minimizing the importance of thermal effects the closed aperture z-scan technique is applied with a chopped laser beam. The z-scan curves recorded under those conditions reveal a sensitivity on absorbed Dose which is comparable to that of the films linear absorbance.

  12. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature

    PubMed Central

    Kavanagh, David; Jury, Alexa; Williams, Jac; Scolding, Neil; Bellamy, Chris; Gunther, Claudia; Ritchie, Diane; Gale, Daniel P.; Kanwar, Yashpal S.; Challis, Rachel; Buist, Holly; Overell, James; Weller, Belinda; Flossmann, Oliver; Blunden, Mark; Meyer, Eric P.; Krucker, Thomas; Evans, Stephen J. W.; Campbell, Iain L.; Jackson, Andrew P.; Chandran, Siddharthan

    2016-01-01

    Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated. Here, we adopt a combined clinical and experimental approach to provide evidence of such an association between type I IFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/β receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation. PMID:27663672

  13. Reduced incidence of bone metastases in irradiated areas after external radiation therapy of prostatic carcinoma

    SciTech Connect

    Jacobsson, H.; Naeslund, I. )

    1991-06-01

    Fourteen males, out of 380 patients, treated with radiation to the central pelvis and lumbar spine for poorly differentiated prostatic carcinoma were analyzed in retrospect. The dose of radiation to the bones of the target area was 5,000 cGy. The patients showed no signs of metastases at bone scintigraphy performed in connection with the treatment. In an average of 34 months after finishing radiotherapy, the patients developed metastases at bone scintigraphy. The pattern was similar in all patients. The treated target area appeared as a cold zone surrounded by more or less homogenously and strongly increased activity of the axial skeleton, characteristic of bone metastases. Radiography, which was performed in 11 patients, confirmed widespread metastatic disease sparing the target area. This was interpretated as bone metastasis being precluded by the irradiation. The most probable explanation of this finding is eradication in situ of distant micrometastases already present in the bone marrow at the time of treatment. An alternate explanation is a reduced implantation of later seeded blood-born metastases as an effect of the irradiation. The characteristic pattern of this phenomenon must be recognized at bone scintigraphy.

  14. Oral vaccination reduces the incidence of tuberculosis in free-living brushtail possums

    PubMed Central

    Tompkins, D. M.; Ramsey, D. S. L.; Cross, M. L.; Aldwell, F. E.; de Lisle, G. W.; Buddle, B. M.

    2009-01-01

    Bovine tuberculosis (Tb) caused by Mycobacterium bovis has proved refractory to eradication from domestic livestock in countries with wildlife disease reservoirs. Vaccination of wild hosts offers a way of controlling Tb in livestock without wildlife culling. This study was conducted in a Tb-endemic region of New Zealand, where the introduced Australian brushtail possum (Trichosurus vulpecula) is the main wildlife reservoir of Tb. Possums were trapped and vaccinated using a prototype oral-delivery system to deliver the Tb vaccine bacille Calmette–Guerin. Vaccinated and control possums were matched according to age, sex and location, re-trapped bimonthly and assessed for Tb status by palpation and lesion aspiration; the site was depopulated after 2 years and post-mortem examinations were conducted to further identify clinical Tb cases and subclinical infection. Significantly fewer culture-confirmed Tb cases were recorded in vaccinated possums (1/51) compared with control animals (12/71); the transition probability from susceptible to infected was significantly reduced in both males and females by vaccination. Vaccine efficacy was estimated at 95 per cent (87–100%) for females and 96 per cent (82–99%) for males. Hence, this trial demonstrates that orally delivered live bacterial vaccines can significantly protect wildlife against natural disease exposure, indicating that wildlife vaccination, along with existing control methods, could be used to eradicate Tb from domestic animals. PMID:19493904

  15. Use of low doses of clenbuterol to reduce incidence of ascites syndrome in broilers.

    PubMed

    Ocampo, L; Cortez, U; Sumano, H; Avila, E

    1998-09-01

    Beta-adrenergic agonists have been shown to be capable of improving growth performance in poultry when added to the feed at 1.0 ppm. However, no reference has been made concerning the cardiovascular responses when one of these agents is added to the feed at a lower concentration during the whole production cycle. The aim of this paper was to assess the effects on the ascites syndrome of 0.25 ppm clenbuterol in the feed, throughout 52 d, in broiler chicks. Results showed a lack of difference in growth and feed conversion rate between the untreated control groups and the experimental group. There were differences in mortality due to the ascites syndrome, abdominal fat:body weight ratio, and ventricular index. A statistically significant positive correlation was also found between ventricular index and mortality rate (r = 0.98). If adequate withdrawal times are ensured, the use of clenbuterol at 0.25 ppm is suggested to reduce mortality due to the ascites syndrome in broilers.

  16. Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain.

    PubMed

    Lundberg, Elena; Kriström, Berit; Jonsson, Bjorn; Albertsson-Wikland, Kerstin

    2015-12-18

    Responsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height. A multicentre, randomized, clinical trial (TRN88-177) in 104 children (90 boys), who had received GH 33 μg/kg/day during at least 1 prepubertal year. They were followed from GH start to adult height (mean, 7.5 years; range, 4.6-10.7). At onset of puberty, children were randomized into three groups, to receive 67 μg/kg/day (GH(67)) given once (GH(67x1); n = 30) or divided into two daily injection (GH(33x2); n = 36), or to remain on a single 33 μg/kg/day dose (GH(33x1); n = 38). The outcome measures were change and obtained mean on-treatment IGF-I(SDS), IGFBP3(SDS) and IGF-I/IGFBP3 ratio(SDS) during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in heightSDS. Mean prepubertal increases 1 year after GH start were: 2.1 IGF-I(SDS), 0.6 IGFBP3(SDS) and 1.5 IGF-I/IGFBP3ratio(SDS). A significant positive correlation was found between prepubertal ∆IGFs and both prepubertal and total gain in height(SDS). During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF-I(SDS) was higher in GH(67) vs GH(33) (p = 0.031). First year pubertal ∆IGF-I(SDS) was significantly higher in the GH(67)vs GH(33) group (0.5 vs -0.1, respectively, p = 0.007), as well as ∆IGF-I(SDS) to the pubertal mean level (0.2 vs -0.2, p = 0.028). In multivariate analyses, the prepubertal increase in '∆IGF-I(SDS) from GH start' and the 'GH dose-dependent pubertal ∆IGF-I(SDS)' were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total

  17. [Project to Reduce the Incidence Rate of Nasogastric Tube Slippage in the Rehabilitation Ward].

    PubMed

    Chen, Chiu-Chu; Su, Wei-Ling; Li, Ai-Cheng; Lin, Hsin-Yi

    2015-06-01

    Nasogastric (NG) tubes are used for providing nutrition to patients who have difficulties swallowing. However, the difficult process of repeatedly inserting NG tubes may lead to gastric erosions. The rehabilitation ward in this study had an NG tube slippage rate of 2.26% in 2012, significantly higher than the same rate in 2011. A proposal was developed to design better techniques for nurses to perform NG tube insertions in order to decrease the rate of NG tube slippage. The following were identified as the major causes of NG tube slippage: (1) caretaker is unfamiliar with NG tube care instructions, (2) caretaker disengages NG tube constraints, and (3) improper rotation of patients or carelessness when turning patients. Therefore, the following solutions were proposed: (1) establish an NG tube safety standard operating procedure, (2) publish bilingual (English and Bahasa Indonesia) pamphlets providing instructions on the correct method of securing and placing the NG tubes, (3) make bilingual (English and Bahasa Indonesia) instructional videos showing the correct method for securing and placing the NG tubes, (4) fabricate a novel tube constraint tool (the constraint ball) that is easy to use, (5) install creative bedside NG tube warning signs, and (6) reinforce the importance of NG tube constraint and placement among caretakers. The NG tube slippage rate was reduced from 2.26% to 0.77%, and was maintained at 0.75% during the follow-up period. The caretaker assessment further showed 100% understanding of the implemented NG tube safety procedures. This proposal was established using literature research, problem identification, and creative problem solving to achieve an effective reduction in NG tube slippage as well as to enhance nursing quality.

  18. Tobacco control: reducing cancer incidence and saving lives. American Society of Clinical Oncology.

    PubMed

    1996-06-01

    The American Society of Clinical Oncology (ASCO) supports the elimination of tobacco products. Toward that goal, ASCO urges the adoption of national policy that strengthens regulation of the sale, promotion, and distribution of such products. To reduce cancer mortality, our regulatory policies must recognize that the nicotine within tobacco is an addictive substance, the use of which leads to 30% of all cancer deaths and a total of 419,000 deaths each year. Tobacco-related advertising and promotion should be banned. At a minimum, national policies should: ban billboards; limit advertising to black and white text only; prohibit the sale or giveaway of products that contain tobacco brand names or logos; prohibit brand name sponsorship of sporting or entertainment events; and require stronger and more prominent warning labels on all tobacco products. Despite existing state laws prohibiting sale of tobacco products to minors, children are able to buy such products easily. National regulation of the sale and distribution of tobacco products is necessary to eliminate children's access to tobacco. Where sales are permitted, they should be limited to face-to-face purchases by individuals 18 and older. Vending machines and other means of distributing tobacco without a face-to-face purchase should be outlawed. To the extent tobacco sales are allowed to continue, the federal government should mandate that the tobacco industry contribute substantial funds for a national public education campaign to prevent young people from smoking and other tobacco use. ASCO has long advocated a substantial increase (in the range of $2) in the federal excise tax on cigarettes and other tobacco products- a measure known to decrease consumption, particularly among children. Revenue from a tax on tobacco products should be used to support retraining for tobacco farmers, biomedical research, health care delivery, and antitobacco education. United State trade policies should discourage the export

  19. Docosahexaenoic Acid Reduces the Incidence of Early Afterdepolarizations Caused by Oxidative Stress in Rabbit Ventricular Myocytes

    PubMed Central

    Zhao, Zhenghang; Wen, Hairuo; Fefelova, Nadezhda; Allen, Charelle; Guillaume, Nancy; Xiao, Dandan; Huang, Chen; Zang, Weijin; Gwathmey, Judith K.; Xie, Lai-Hua

    2012-01-01

    Accumulating evidence has suggested that ω3-polyunsaturated fatty acids (ω3-PUFAs) may have beneficial effects in the prevention/treatment of cardiovascular diseases, while controversies still remain regarding their anti-arrhythmic potential. It is not clear yet whether ω-3-PUFAs can suppress early afterdepolarizations (EADs) induced by oxidative stress. In the present study, we recorded action potentials using the patch-clamp technique in ventricular myocytes isolated from rabbit hearts. The treatment of myocytes with H2O2 (200 μM) prolonged AP durations and induced EADs, which were significantly suppressed by docosahexaenoic acid (DHA, 10 or 25 μM; n = 8). To reveal the ionic mechanisms, we examined the effects of DHA on L-type calcium currents (ICa.L), late sodium (INa), and transient outward potassium currents (Ito) in ventricular myocytes pretreated with H2O2. H2O2 (200 μM) increased ICa.L by 46.4% from control (−8.4 ± 1.4 pA/pF) to a peak level (−12.3 ± 1.8 pA/pF, n = 6, p < 0.01) after 6 min of H2O2 perfusion. H2O2-enhanced ICa.L was significantly reduced by DHA (25 μM; −7.1 ± 0.9 pA/pF, n = 6, p < 0.01). Similarly, H2O2-increased the late INa (−3.2 ± 0.3 pC) from control level (−0.7 ± 0.1 pC). DHA (25 μM) completely reversed the H2O2-induced increase in late INa (to −0.8 ± 0.2 pC, n = 5). H2O2 also increased the peak amplitude of and the steady state Ito from 8.9 ± 1.0 and 2.16 ± 0.25 pA/pF to 12.8 ± 1.21 and 3.13 ± 0.47 pA/pF respectively (n = 6, p < 0.01, however, treatment with DHA (25 μM) did not produce significant effects on current amplitudes and dynamics of Ito altered by H2O2. In addition, DHA (25 μM) did not affect the increase of intracellular reactive oxygen species (ROS) levels induced by H2O2 in rabbit ventricular myocytes. These findings demonstrate that DHA suppresses exogenous H2O2-induced EADs mainly by

  20. Dose-dependent effects of allopurinol on human foreskin fibroblast cells and human umbilical vein endothelial cells under hypoxia.

    PubMed

    Sun, Yu; George, Jacob; Rocha, Sonia

    2015-01-01

    Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells.

  1. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

    PubMed

    Ulbrich, Felix; Schallner, Nils; Coburn, Mark; Loop, Torsten; Lagrèze, Wolf Alexander; Biermann, Julia; Goebel, Ulrich

    2014-01-01

    Retinal ischemia and reperfusion injuries (IRI) permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC) of the rat's eye. IRI was performed on the left eyes of rats (n = 8) with or without inhaled Argon postconditioning (25, 50 and 75 Vol%) for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours). Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA. IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001). Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01), as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001). Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%. Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.

  2. Argon Inhalation Attenuates Retinal Apoptosis after Ischemia/Reperfusion Injury in a Time- and Dose-Dependent Manner in Rats

    PubMed Central

    Ulbrich, Felix; Schallner, Nils; Coburn, Mark; Loop, Torsten; Lagrèze, Wolf Alexander; Biermann, Julia; Goebel, Ulrich

    2014-01-01

    Purpose Retinal ischemia and reperfusion injuries (IRI) permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC) of the rat's eye. Methods IRI was performed on the left eyes of rats (n = 8) with or without inhaled Argon postconditioning (25, 50 and 75 Vol%) for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours). Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA. Results IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001). Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01), as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001). Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%. Conclusion Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option. PMID

  3. Partial liquid ventilation shows dose-dependent increase in oxygenation with PEEP and decreases lung injury associated with mechanical ventilation.

    PubMed

    Suh, G Y; Chung, M P; Park, S J; Koh, Y; Kang, K W; Kim, H; Han, J; Rhee, C H; Kwon, O J

    2000-09-01

    The purpose of this article is to evaluate the effect of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) and to investigate if lung damage associated with mechanical ventilation can be reduced by PLV. Twenty-two New-Zealand white rabbits were ventilated in pressure-controlled mode maintaining constant tidal volume (10 mL/kg). Lung injury was induced by repeated saline lavage (PaO2 < 100 mm Hg). Two incremental PEEP steps maneuvers (IPSMs) from 2 to 10 cm H2O in 2 cm H2O steps were performed sequentially. The control group received the first IPSM in the supine position and were turned prone for the second IPSM. In the PLV group (n = 7), 12 mL/kg of perfluorodecalin was instilled after lung injury before the two IPSMs. The early prone group (n = 7) received both IPSMs in the prone position. Parameters of gas exchange, lung mechanics, and hemodynamics as well as pathology were examined. During the first IPSM, the PLV group showed a significant increase in PaO2 after instillation of perfluorodecalin (P < .05) and then showed a dose-dependent increase in PaO2 with PEER. The control and EP groups showed improvement in PaO2 only at higher PEEP, eventually showing no intergroup differences at PEEP of 10 cm H2O. During the second IPSM only the PLV group retained its ability to increase PaO2 to the level obtained during the first IPSM (P < .05 compared with control and EP groups). During the first IPSM all three groups showed increasing trend in static compliance (Cst) with PEEP peaking at PEEP of 8 cm H2O. During the second IPSM, only the PLV group showed increase in static compliance with PEEP (P < .05 compared with other groups). Lung histology revealed significantly less hyaline membrane formation in the PLV group (P < .05). PLV shows dose-dependent increase in oxygenation with PEEP and may reduce lung damage associated with mechanical ventilation.

  4. Effectiveness of probiotics in reducing the incidence of Clostridium difficile-associated diarrhea in elderly patients: a systematic review.

    PubMed

    Vernaya, Marina; McAdam, Jennifer; Hampton, Michelle DeCoux

    2017-01-01

    independent reviewers for methodological quality prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI). Data were extracted from papers included in the review using the standardized data extraction tool from the JBI Meta-Analysis of Statistics Assessment and Review Instrument. The data extracted included specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Quantitative data were pooled using statistical meta-analysis. Effect sizes were expressed as odds ratios, and their 95% confidence intervals were calculated to determine if probiotic treatment was superior to placebo in reducing CDAD incidence. Heterogeneity was assessed using the standard I statistic. Five studies were included in the review. The individual study results were conflicting, including non-significant results for four studies and statistically significant results in one that demonstrated fewer cases of CDAD among patients receiving probiotics compared to placebo. The meta-analysis finding indicated that there was no statistically significant difference in CDAD incidence in elderly hospitalized patients taking probiotics when compared to a placebo. Probiotics were not found to be more effective than placebo for reducing CDAD incidence in elderly hospitalized patients. However, studies that demonstrate improved outcomes must be examined to determine future needs for research. Studies varied with regard to the dose, frequency, method of administration (probiotic drinks versus capsule), length of administration and the number of strains of bacteria administered. Further studies are needed to evaluate the effectiveness of probiotics for CDAD prevention in this population. Clinical trials with evidence-based administration methods and meta-analyses that pool the results of studies with congruent methodologies are needed to enable conclusions to be drawn on

  5. Risk Factors for Incident Hospitalized Heart Failure With Preserved Versus Reduced Ejection Fraction in a Multiracial Cohort of Postmenopausal Women.

    PubMed

    Eaton, Charles B; Pettinger, Mary; Rossouw, Jacques; Martin, Lisa Warsinger; Foraker, Randi; Quddus, Abdullah; Liu, Simin; Wampler, Nina S; Hank Wu, Wen-Chih; Manson, JoAnn E; Margolis, Karen; Johnson, Karen C; Allison, Matthew; Corbie-Smith, Giselle; Rosamond, Wayne; Breathett, Khadijah; Klein, Liviu

    2016-10-01

    Heart failure is an important and growing public health problem in women. Risk factors for incident hospitalized heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF) in women and differences by race/ethnicity are not well characterized. We prospectively evaluated the risk factors for incident hospitalized HFpEF and HFrEF in a multiracial cohort of 42 170 postmenopausal women followed up for a mean of 13.2 years. Cox regression models with time-dependent covariate adjustment were used to define risk factors for HFpEF and HFrEF. Differences by race/ethnicity about incidence rates, baseline risk factors, and their population-attributable risk percentage were analyzed. Risk factors for both HFpEF and HFrEF were as follows: older age, white race, diabetes mellitus, cigarette smoking, and hypertension. Obesity, history of coronary heart disease (other than myocardial infarction), anemia, atrial fibrillation, and more than one comorbidity were associated with HFpEF but not with HFrEF. History of myocardial infarction was associated with HFrEF but not with HFpEF. Obesity was found to be a more potent risk factor for African American women compared with white women for HFpEF (P for interaction=0.007). For HFpEF, the population-attributable risk percentage was greatest for hypertension (40.9%) followed by obesity (25.8%), with the highest population-attributable risk percentage found in African Americans for these risk factors. In this multiracial cohort of postmenopausal women, obesity stands out as a significant risk factor for HFpEF, with the strongest association in African American women. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611. © 2016 American Heart Association, Inc.

  6. The Problem of using Quartz as a radiation dosimeter: fundamentals of dose dependence

    NASA Astrophysics Data System (ADS)

    King, G. E.; Finch, A. A.; Robinson, R. A. J.; Hole, D. E.

    2009-04-01

    Quartz is widely used as a radiation dosimeter in Quaternary geomorphological and archaeological dating applications through Optically Stimulated Luminescence (over 1,200 journal publications since 2000). However, obtaining an accurate equivalent radiation dose (DE) can be challenging, especially where the luminescence intensity of the quartz is dim. The causes of variation in luminescence intensity between quartz grains of different provenances, transport and thermal histories is unknown, however it has been suggested that it relates to either the dosimetric history of the grain, or mechanical processes which occur in transit. Investigation of the fundamental properties of the luminescence of quartz, enables investigation of dose dependent changes in luminescence intensity. A series of dose dependence experiments were conducted using spectroscopic ionoluminescence, which comprises the excitation of quartz with protons accelerated at 0.95 MeV. The energy delivered to the sample throughout ion implantation is similar to that received during gamma irradiation, and thus approximates sample radiation dosing. A natural macro-crystal of α-quartz was investigated parallel and perpendicular to c, to observe any orientation dependent effects, as well as a calibration quartz from the Risø National Laboratory, Denmark, and a Scottish geomorphological sample, prepared using standard laboratory procedures. The calibration quartz sample has excellent luminescence intensity and is suited to analysis using the single-aliquot regenerative dose (SAR) standard OSL protocol, the Scottish sample alternatively has very dim luminescence and exhibits variable behaviour when analysed with SAR. Despite the differences between the luminescence behaviour of the samples, all three responded to the dose dependence experiments in a similar manner. The UV/blue emission was observed to deplete with increasing dose, whereas the red emission, not normally analysed within OSL, exhibited increased

  7. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

    PubMed Central

    2014-01-01

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled. The cohort consisted of all diagnosed GD patients in the Netherlands. Mutually exclusive disease states were defined as ‘asymptomatic’, ‘signs/symptoms’, ‘recovery’, ‘splenectomy’, ‘bone complication’, ‘multiple complications’ and ‘malignancy’. A natural history (NH) cohort was delineated based upon historical data on Dutch patients before ERT was available. Cumulative incidence curves were composed for progression from each disease state to the next. Two scenarios were applied for the ERT cohort: time to complications was calculated from A. start of ERT; B. entering the previous disease state. Median time for the development of signs and/or symptoms was 30.1 years (N = 73). In the NH cohort (N = 42), 9% had developed a bone complication after 10 years in the signs/symptoms phase, while 21% had undergone a splenectomy. In the ERT cohort (N = 29 (A), N = 28 (B)), 12% (A) or 4% (B) had developed a bone complication after 10 years in this phase and no patient was splenectomized. No patients in the NH cohort recovered, compared to 50% in the ERT cohort after 3.6 years (N = 28 (A)) or 22.4 years (N = 27 (B)) of treatment. Median time from a first to a second complication was 11 years in the NH cohort (N = 31), whereas 16 respectively 14 percent had developed a second complication after 10 years in the ERT cohort (N = 17, scenario A/B). Fourteen percent (scenario A/B) developed an associated malignancy after 10 years in the phase ‘multiple complications’ (N = 23). Associated malignancies occurred almost exclusively in advanced disease stages, therefore it

  8. Oxidative Stress Induced Damage to Paternal Genome and Impact of Meditation and Yoga - Can it Reduce Incidence of Childhood Cancer?

    PubMed

    Rima, Dada; Shiv, Basant Kumar; Bhavna, Chawla; Shilpa, Bisht; Saima, Khan

    2016-01-09

    follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in alcoholics (p<0.05) after intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3 months (p<0.05) and 6 months (p<0.05) of practice. Conclusions: Our results suggest that OS and ODD DNA may contribute to the development of childhood cancer. This may be due to accumulation of oxidized mutagenic base 8OHdG , and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant methylation pattern, altered gene expression which affect cell proliferation and survival through activation of transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly truncatred DNA repair mechanisms all contribute to sperm genome hypermutability and persistant oxidative DNA damage. Oxidative stress is also associated with genome wide hypomethylation, telomere shortening and mitochondrial dysfunction leading to genome hypermutability and instability. To the best of our knowledge, this is the first study to report decline in OS and ODD and improvement in sperm DNA integrity following adoption of meditation and yoga based life style modification.This may reduce disease burden in next generation and reduce incidence of childhood cancers. Creative Commons Attribution License

  9. Do Prolonged Prophylactic Antibiotics Reduce the Incidence of Surgical-Site Infections in Immediate Prosthetic Breast Reconstruction?

    PubMed

    Wang, Frederick; Chin, Robin; Piper, Merisa; Esserman, Laura; Sbitany, Hani

    2016-12-01

    Approximately 50,000 women in the United States undergo mastectomy and immediate prosthetic breast reconstruction annually, and most receive postoperative prophylactic antibiotics. The effect of these antibiotics on the risk of surgical-site infections remains unclear. The authors searched the Medline, Embase, and Cochrane Library databases for studies that compared less than 24 hours and greater than 24 hours of antibiotics following immediate prosthetic breast reconstruction. Primary outcomes were surgical-site infections and implant loss. Conservative random effects models were used to obtain pooled relative risk estimates. The authors identified 927 studies, but only four cohort studies and one randomized controlled trial met their inclusion criteria. Unadjusted incidences of surgical-site infections were 14 percent with more than 24 hours of antibiotics, 19 percent with less than 24 hours of antibiotics, and 16 percent overall. Unadjusted incidences of implant loss were 8 percent with more than 24 hours of antibiotics, 10 percent with less than 24 hours of antibiotics, and 9 percent overall. The pooled relative risk of implant loss was 1.17 (95 percent CI, 0.39 to 3.6) with less than 24 hours of antibiotics, which was not statistically significant. Prolonged antibiotic use did not have a statistically significant effect on reducing surgical-site infections or implant loss. There was significant heterogeneity between studies, and prolonged antibiotics may have increased the risk of implant loss in the randomized controlled trial. Definitive evidence may only be obtained with data from more prospective randomized controlled trials.

  10. A rubber-covered ceramic weapon reduces the incidence of dental trauma in recruits during combat basic training.

    PubMed

    Becker, Talia; Ashkenazi, Malka

    2011-10-01

    The effect of a rubber-covered ceramic weapon was assessed on the incidence of dental trauma during basic training, since soldiers are more at risk of impact from a personal weapon. Dental files of soldiers (n = 4,542), who completed 8 months of training during 2008, were analyzed for incidence and type of dental trauma from a personal weapon. A rubber-covered ceramic weapon (n = 2,972) or a conventional one (n = 1,570, control) was used. Dental trauma was 0.4% per 8 months (0.6% per year) from the ceramic weapon and 1.5% per 8 months (2.3% per year) from the conventional one (p<0.001). The most prevalent type of injury was a simple/noncomplicated crown fracture (82% in study group, 75% in control group). The ceramic weapon significantly reduced dental trauma by diminishing the impact while in direct contact with the teeth or by absorbing and/or distributing the impact force. In conclusion, when possible a rubber-covered ceramic weapon should be preferred for basic combat training.

  11. Dose-dependent Nodal/Smad signals pattern the early mouse embryo.

    PubMed

    Robertson, Elizabeth J

    2014-08-01

    Nodal signals in the early post-implantation stage embryo are essential to establish initial proximal-distal (P-D) polarity and generate the final anterior-posterior (A-P) body axis. Nodal signaling in the epiblast results in the phosphorylation of Smad2 in the overlying visceral endoderm necessary to induce the AVE, in part via Smad2-dependent activation of the T-box gene Eomesodermin. Slightly later following mesoderm induction a continuum of dose-dependent Nodal signaling during the process of gastrulation underlies specification of mesodermal and definitive endoderm progenitors. Dynamic Nodal expression during the critical 72 h time window immediately following implantation, accomplished by a series of feed-back and feed-forward mechanisms serves to provide key positional cues required for establishment of the body plan and controls cell fate decisions in the early mammalian embryo.

  12. Drug and light dose dependence of PDT on pancreatic cancer cells in vitro

    NASA Astrophysics Data System (ADS)

    Halkiotis, Konstantinos N.; Manolopoulos, L. D.; Uzunoglou, Nikolaos K.; Yova, Dido M.

    1998-07-01

    Photodynamic therapy (PDT) is a promising new treatment for a variety of malignant tumors. Recently, PDT has been investigated as an alternative treatment for pancreatic carcinoma. The selection of photosensitizer and laser light are equally important for the treatment efficacy. The purpose of this study is to evaluate drug and light dose dependence of photodynamic effect in pancreatic cancer cells. Zinc tetrasulfonated phthalocyanines used as photosensitizer and a novel diode laser system terminated at alight shaping diffuser was used as light source. Viability was measured 24 and 72 hours after treatment and almost 100 percent lethality levels were achieved, by using low light doses independently of drug concentration. The results are discussed in correlation with light and drug doses.

  13. Thiamine whole blood and urinary pharmacokinetics in rats: urethan-induced dose-dependent pharmacokinetics.

    PubMed

    Pipkin, J D; Stella, V J

    1982-02-01

    The whole blood pharmacokinetics of thiamine after intravenous administration of thiamine hydrochloride (4, 12, and 36 mg/kg) to rats anesthetized continuously with ether (inhalation) or urethan (1 g/kg ip) were studied. Urinary excretion of thiamine after intravenous administration of thiamine hydrochloride to rats lightly anesthetized with ether was also investigated. At any particular dose, thiamine displayed apparent classical two-compartment model behavior in the time range studied. Under urethan anesthesia, thiamine displayed apparent dose-dependent kinetics as measured by the changes in the pharmacokinetic parameters, AUC,Vd(area), t0.5 beta, and total body clearance, ClTB, with dose. However, when ether anesthesia was used, thiamine displayed dose-independent pharmacokinetic behavior. These results suggest that care should be taken in the interpretation of pharmacokinetic data obtained in anesthetized animals, particularly when urethan anesthesia is used.

  14. [Experience of using bacteriophages and bitsillin-5 to reduce the incidence of respiratory diseases of bacterial ethiology in military personnel].

    PubMed

    Akimkin, V G; Kalmykov, A A; Aminev, R M; Polyakov, V S; Artebyakin, S V

    2016-02-01

    The authors defined epidemiological efficacy and safety of the use of bacteriophages(streptococcal, staphylococcal, piobakferiophage multipartial) and bitsillin-5 to reduce tonsillitis morbidityand other respiratory diseases with bacterial etiology in groups of servicemen during their formationagainst increase of seasonal morbidity. The results of the use of these preventive agents were evaluatedby a comparative analysis of this disease in experimental and control groups. In total 510 healthy conscriptswere involved into the study. The effectiveness of prophylactic use of bacteriophages and bitsillin-5, whichprovided a reduction in the incidence of respiratory infections of bacterial ethiology, tonsillitis, and otherrespiratory diseases is showed. Recommendations on the choice of drugsfor the prevention of these infections,methods and organization of their application in organized groups are given.

  15. A retrospective study on the use of a dental dressing to reduce dry socket incidence in smokers.

    PubMed

    Murph, James T; Jaques, Susan H; Knoell, Alexander N; Archibald, Geoffrey D; Yang, Stan

    2015-01-01

    This study assessed the effectiveness of using an oxidized cellulose dental dressing in order to reduce the rate of alveolar osteitis after posterior tooth extraction in smokers. Dry socket incidences of heavy smokers from 4 independent dental clinics, which routinely used oxidized cellulose dental dressings to mitigate dry socket formation between March 2011 and December 2012, were compiled and evaluated. All extraction sites healed uneventfully except for those cases that developed dry sockets. Overall, 1.7% of male patients and 2.2% of female patients developed dry sockets. No conclusive relationship was found between the number of cigarettes smoked and dry socket formation among patients in this study. The results of this study were consistent with the view that gender, age, postextraction regimen, and multiple extractions affect dry socket formation. The results indicate that an oxidized cellulose dental dressing postextraction is a safe and effective method for mitigating dry socket formation among smokers.

  16. Memory impairment in rats after desflurane anesthesia is age and dose dependent.

    PubMed

    Callaway, Jennifer K; Jones, Nigel C; Royse, Alistair G; Royse, Colin F

    2015-01-01

    Post-operative cognitive dysfunction (POCD) predominantly affects the elderly who suffer memory and concentration deficits after anesthesia and surgery. Animal studies have demonstrated anesthetic alone may contribute to POCD but results are variable and little is known about common anesthetics other than isoflurane. The present study investigated dose-dependence of desflurane anesthesia in young adult and aged rats. We hypothesize higher concentrations of desflurane will result in memory impairment in the water maze and that impairment will be worse in aged rats. Effects of anesthesia (1 or 1.5 MAC, 4 h) desflurane, or sham exposure on cognition were investigated in young adult (3 months) and aged (20-24 months) rats at 1, 4, and 12 weeks post-exposure. The Morris water maze was used to assess acquisition and retention of spatial reference memory. Latency to find the hidden platform and swimming speed were compared between treatments. Aged rats showed significant impairment in task acquisition after exposure to 1.5 MAC, but not 1.0 MAC desflurane anesthetic when tested 1 week following exposure. Latency to find the platform and distance travelled were significantly longer in aged rats given 1.5 MAC desflurane (latency: F(1,108) = 19.71, p < 0.0001; distance: F(1,108) = 5.79, p = 0.018). Deficits were not long-lasting and were no longer present at 4 or 12 weeks. In contrast, young adult rats performed equally as well as sham-exposed control rats irrespective of desflurane dose. This study showed the effects of desflurane on learning and memory in the water maze are age and dose dependent and are brief in duration.

  17. Dose-dependent influence of commercial garlic (Allium sativum) on rats fed cholesterol-containing diet.

    PubMed

    Gorinstein, Shela; Leontowicz, Maria; Leontowicz, Hanna; Jastrzebski, Zenon; Drzewiecki, Jerzy; Namiesnik, Jacek; Zachwieja, Zofia; Barton, Henryk; Tashma, Zev; Katrich, Elena; Trakhtenberg, Simon

    2006-05-31

    The aim of this investigation was to evaluate the dose-dependent influence of commercial garlic on rats fed cholesterol-containing diets. It was found that commercial garlic contains high concentrations of dietary fibers, microelements, and total polyphenols, and its total antioxidant capacity as determined by two independent assays [1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS)] was similar to that of the original garlic samples. Wistar rats (35) were randomly divided into five diet groups, named control, Chol, Garlic500, Garlic750, and Garlic1000. Control rats were fed basal diet (BD), which included wheat starch, casein, soybean oil, and vitamin and mineral mixtures. To the BD of the Chol group was added 1% of cholesterol. To the BD of the other three groups (Garlic500, Garlic750, and Garlic1000) were added 1% of cholesterol and commercial garlic equal to 500, 750, and 1000 mg of raw garlic per kilogram of animal weight. After 4 weeks of the experiment only in rats from the Garlic500 group were a significant hindering in the rise in plasma lipids and also a significant hindering in a decrease of plasma antioxidant activity registered. A significant decrease in plasma circulating fibrinogen and an increase in the clotting time were found in the same group of rats (P < 0.05 in both cases). The fibrinogenolytic effect of garlic diets was visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the fibrinogen fraction of Garlic500 the 66, 24, and 14 kDa protein bands were detected with weaker protein intensity than in the corresponding ones in the Garlic750 and Garlic1000 diet groups. In conclusion, the positive influences of commercial garlic on plasma lipids, proteins, antioxidant activity, and some indices of blood coagulation are dose-dependent. Therefore, commercial garlic (Elena, Zelazków, Poland) could be a valuable component of atherosclerosis-preventing diets only in optimal doses.

  18. Dose-dependent requirement of patched homologue 1 in mouse pancreatic beta cell mass.

    PubMed

    Nakayama, S; Arakawa, M; Uchida, T; Ogihara, T; Kanno, R; Ikeda, F; Azuma, K; Hirose, T; Kawamori, R; Fujitani, Y; Watada, H

    2008-10-01

    Ectopic activation of hedgehog (HH) signalling in pancreas induces various abnormal morphogenetic events in the pancreas. This study analysed the dose-dependent requirement of patched homologue 1 (PTCH1), a negative regulator of HH signalling on pancreatic development. We used a recessive spontaneous mutant mouse denoted as mes which carries a mutated Ptch1 resulting in deletion of the most carboxy-terminal cytoplasmic domain of the PTCH1 protein. In this study, we analysed pancreatic morphology in Ptch1 ( +/+ ), Ptch1 ( +/mes ), Ptch1 (+/-), Ptch1 ( mes/me ) (s) and Ptch1 (-/mes ) mouse embryos, as well as the islet mass in adult Ptch1 (+/+), Ptch1 (+/mes ) and Ptch1 (+/-) mice. Until embryonic day (E) 12.5, no obvious abnormality of pancreas was observed in any of the Ptch1 mutants. The levels of PDX1 and glucagon were also not evidently different among the mice genotypes studied. Thereafter, morphological abnormalities appeared in the Ptch1 mutant mice. The beta, alpha and exocrine cell masses decreased at E18.5 in parallel with increased HH signalling, with beta cell mass showing the highest sensitivity to HH signalling with a significant decrease even in Ptch1 (+/mes ) mice. Adult Ptch1 (+/-) mice also showed a significant decrease in beta cell mass compared with wild-type mice. Our findings indicate that the carboxy-terminal domain of Ptch1 is essential for pancreatic development. In addition, the loss of Ptch1 function decreases both the endocrine and exocrine cell mass in a dose-dependent manner, with beta cells particularly sensitive to changes in HH signalling.

  19. Dose-Dependent Effect of Deltamethrin in Testis, Liver, and Kidney of Wistar Rats

    PubMed Central

    Sharma, Poonam; Singh, Rambir; Jan, Mysra

    2014-01-01

    Objectives: Deltamethrin is a synthetic pyrethroid insecticide used worldwide in agriculture, household pest control, protection of foodstuff, and disease vector control. Although initially thought to be least toxic, a number of recent reports showed its toxic effects in mammalian and non-mammalian animal species. The current study was performed to assess the dose-dependent deltamethrin toxicity on testes, liver, and kidney of male Wistar rats. Materials and Methods: Twenty-four rats were divided in four groups of 6 each. Group A served as normal control. Group B, C, and D were administered with different doses (2 or 3 or 6 mg/kg corresponding to 1/30th or 1/20th or 1/10th of LD50, respectively) of deltamethrin for 28 days. Results: Deltamethrin exposure caused a significant reduction in weight of reproductive organs, decrease in sperm count, sperm motility, serum testosterone (T), follicle stimulating hormones (FSH), and luteinizing hormones (LH) in testis. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) were decreased in testis, liver and kidney of exposed rats. Deltamethrin exposure significantly increased sperm abnormalities in testis. Significant increase in lipid peroxidation (LPO) level was observed in testis, liver and kidney. Deltamethrin also caused histological alterations in testes, liver, and kidney. Conclusions: The results indicated that deltamethrin at a dose of 6 mg/kg exerts significant harmful effects on testes, liver and kidney as compare to 2 mg and 3 mg/kg. The study concluded that the system toxicity induced by deltamethrin was dose dependent. PMID:25253921

  20. Resuscitation with Lipid Emulsion: Dose-dependent Recovery from Cardiac Pharmacotoxicity Requires a Cardiotonic Effect

    PubMed Central

    Fettiplace, Michael R.; Akpa, Belinda S.; Ripper, Richard; Zider, Brian; Lang, Jason; Rubinstein, Israel; Weinberg, Guy

    2014-01-01

    Background Recent publications have questioned the validity of the “lipid sink” theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms like hemodilution. To address these issues, we tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, we modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration and inotropy to this response using an in silico model. Methods Rats were surgically prepared to monitor cardiovascular metrics and deliver drugs. Following catheterization and instrumentation, animals received a nonlethal dose of bupivacaine to produce transient cardiovascular toxicity, then were randomized to receive one of four treatments: 30% or 20% intravenous lipid emulsion, intravenous saline or no treatment (n = 7 per condition; 28 total animals). Recovery responses were compared to the predictions of a pharmacokinetic-pharmacodynamic model parameterized using previously published laboratory data. Results Rats treated with lipid emulsions recovered faster than did rats treated with saline or no treatment. Intravenous lipid emulsion of 30% elicited the fastest hemodynamic recovery followed in order by 20% intravenous lipid emulsion, saline, and no-treatment. An increase in arterial blood pressure underlay the recovery in both lipid-emulsion treated groups. Heart rates remained depressed in all four groups throughout the observation period. Model predictions mirrored the experimental recovery and the model that combined volume, sequestration and inotropy predicted in vivo results most accurately. Conclusion Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, driven by a cardiotonic response that complements the previously reported sequestration effect. PMID:24496123

  1. Ozone inhalation leads to a dose-dependent increase of cytogenetic damage in human lymphocytes.

    PubMed

    Holland, Nina; Davé, Veronica; Venkat, Subha; Wong, Hofer; Donde, Aneesh; Balmes, John R; Arjomandi, Mehrdad

    2015-05-01

    Ozone is an important constituent of ambient air pollution and represents a major public health concern. Oxidative injury due to ozone inhalation causes the generation of reactive oxygen species and can be genotoxic. To determine whether ozone exposure causes genetic damage in peripheral blood lymphocytes, we used a well-validated cytokinesis-block micronucleus Cytome assay. Frequencies of micronuclei (MN) and nucleoplasmic bridges (NB) were used as indicators of cytogenetic damage. Samples were obtained from 22 non-smoking healthy subjects immediately before and 24-hr after controlled 4-hr exposures to filtered air, 100 ppb, and 200 ppb ozone while exercising in a repeated-measure study design. Inhalation of ozone at different exposure levels was associated with a significant dose-dependent increase in MN frequency (P < 0.0001) and in the number of cells with more than one MN per cell (P <  .0005). Inhalation of ozone also caused an increase in the number of apoptotic cells (P = 0.002). Airway neutrophilia was associated with an increase in MN frequency (P = 0.033) independent of the direct effects of ozone exposure (P < 0.0001). We also observed significant increases in both MN and NB frequencies after exercise in filtered air, suggesting that physical activity is also an important inducer of oxidative stress. These results corroborate our previous findings that cytogenetic damage is associated with ozone exposure, and show that damage is dose-dependent. Further study of ozone-induced cytogenetic damage in airway epithelial cells could provide evidence for the role of oxidative injury in lung carcinogenesis, and help to address the potential public health implications of exposures to oxidant environments. © 2014 Wiley Periodicals, Inc.

  2. Ozone Inhalation Leads to a Dose-Dependent Increase of Cytogenetic Damage in Human Lymphocytes

    PubMed Central

    Holland, Nina; Davé, Veronica; Venkat, Subha; Wong, Hofer; Donde, Aneesh; Balmes, John R; Arjomandi, Mehrdad

    2014-01-01

    Ozone is an important constituent of ambient air pollution and represents a major public health concern. Oxidative injury due to ozone inhalation causes the generation of reactive oxygen species and can be genotoxic. To determine whether ozone exposure causes genetic damage in peripheral blood lymphocytes, we employed a well-validated cytokinesis-block micronucleus Cytome assay. Frequencies of micronuclei (MN) and nucleoplasmic bridges (NB) were used as indicators of cytogenetic damage. Samples were obtained from 22 non-smoking healthy subjects immediately before and 24-hr after controlled 4-hr exposures to filtered air, 100 ppb, and 200 ppb ozone while exercising in a repeated-measure study design. Inhalation of ozone at different exposure levels was associated with a significant dose-dependent increase in MN frequency (P < 0.0001) and in the number of cells with more than 1 MN per cell (P < 0.0005). Inhalation of ozone also caused an increase in the number of apoptotic cells (P = 0.002). Airway neutrophilia was associated with an increase in MN frequency (P = 0.033) independent of the direct effects of ozone exposure (P < 0.0001). We also observed significant increases in both MN and NB frequencies after exercise in filtered air, suggesting that physical activity is also an important inducer of oxidative stress. These results corroborate our previous findings that cytogenetic damage is associated with ozone exposure, and show that damage is dose-dependent. Further study of ozone-induced cytogenetic damage in airway epithelial cells could provide evidence for the role of oxidative injury in lung carcinogenesis, and help to address the potential public health implications of exposures to oxidant environments. PMID:25451016

  3. Dose-Dependent Onset of Regenerative Program in Neutron Irradiated Mouse Skin

    PubMed Central

    Artibani, Mara; Kobos, Katarzyna; Colautti, Paolo; Negri, Rodolfo; Amendola, Roberto

    2011-01-01

    Background Tissue response to irradiation is not easily recapitulated by cell culture studies. The objective of this investigation was to characterize, the transcriptional response and the onset of regenerative processes in mouse skin irradiated with different doses of fast neutrons. Methodology/Principal Findings To monitor general response to irradiation and individual animal to animal variation, we performed gene and protein expression analysis with both pooled and individual mouse samples. A high-throughput gene expression analysis, by DNA oligonucleotide microarray was done with three months old C57Bl/6 mice irradiated with 0.2 and 1 Gy of mono-energetic 14 MeV neutron compared to sham irradiated controls. The results on 440 irradiation modulated genes, partially validated by quantitative real time RT-PCR, showed a dose-dependent up-regulation of a sub-class of keratin and keratin associated proteins, and members of the S100 family of Ca2+-binding proteins. Immunohistochemistry confirmed mRNA expression data enabled mapping of protein expression. Interestingly, proteins up-regulated in thickening epidermis: keratin 6 and S100A8 showed the most significant up-regulation and the least mouse-to-mouse variation following 0.2 Gy irradiation, in a concerted effort toward skin tissue regeneration. Conversely, mice irradiated at 1 Gy showed most evidence of apoptosis (Caspase-3 and TUNEL staining) and most 8-oxo-G accumulation at 24 h post-irradiation. Moreover, no cell proliferation accompanied 1 Gy exposure as shown by Ki67 immunohistochemistry. Conclusions/Significance The dose-dependent differential gene expression at the tissue level following in vivo exposure to neutron radiation is reminiscent of the onset of re-epithelialization and wound healing and depends on the proportion of cells carrying multiple chromosomal lesions in the entire tissue. Thus, this study presents in vivo evidence of a skin regenerative program exerted independently from DNA repair

  4. Branched chain fatty acids reduce the incidence of necrotizing enterocolitis and alter gastrointestinal microbial ecology in a neonatal rat model.

    PubMed

    Ran-Ressler, Rinat R; Khailova, Ludmila; Arganbright, Kelly M; Adkins-Rieck, Camille K; Jouni, Zeina E; Koren, Omry; Ley, Ruth E; Brenna, J Thomas; Dvorak, Bohuslav

    2011-01-01

    Branched chain fatty acids (BCFA) are found in the normal term human newborn's gut, deposited as major components of vernix caseosa ingested during late fetal life. We tested the hypothesis that premature infants' lack of exposure to gastrointestinal (GI) BCFA is associated with their microbiota and risk for necrotizing enterocolitis (NEC) using a neonatal rat model. Pups were collected one day before scheduled birth. The pups were exposed to asphyxia and cold stress to induce NEC. Pups were assigned to one of three experimental treatments. DF (dam-fed); Control, hand-fed rat milk substitute; BCFA, hand-fed rat milk substitute with 20%w/w BCFA. Total fat was equivalent (11%wt) for both the Control and BCFA groups. Cecal microbiota were characterized by 16S rRNA gene pyrosequencing, and intestinal injury, ileal cytokine and mucin gene expression, interleukin-10 (IL-10) peptide immunohistochemistry, and BCFA uptake in ileum phospholipids, serum and liver were assessed. NEC incidence was reduced by over 50% in the BCFA group compared to the Control group as assessed in ileal tissue; microbiota differed among all groups. BCFA-fed pups harbored greater levels of BCFA-associated Bacillus subtilis and Pseudomonas aeruginosa compared to Controls. Bacillus subtilis levels were five-fold greater in healthy pups compared to pups with NEC. BCFA were selectively incorporated into ileal phospholipids, serum and liver tissue. IL-10 expression increased three-fold in the BCFA group versus Controls and no other inflammatory or mucosal mRNA markers changed. At constant dietary fat level, BCFA reduce NEC incidence and alter microbiota composition. BCFA are also incorporated into pup ileum where they are associated with enhanced IL-10 and may exert other specific effects.

  5. Comprehensive Oral Health Care to Reduce the Incidence of Severe Early Childhood Caries (s-ECC) in Urban China.

    PubMed

    Si, Yan; Guo, Yan; Yuan, Chao; Xu, Tao; Zheng, Shu Guo

    2016-03-01

    To explore the effectiveness of comprehensive oral health care to reduce the caries incidence for children with severe early childhood caries (s-ECC) in an urban area in China. A total of 357 children aged 3 to 4 years old and diagnosed with s-ECC were recruited in this randomised controlled, single-blinded clinical trial for 1 year. Children of two different kindergarten classes were enrolled in this study and randomly divided into a test group (205 children) and a control group (152 children). The test group received comprehensive oral health care, which included: oral health examination, oral health education, topical fluoride application and dental treatment, and the children in the control group only received the oral health examination. The evaluation of the oral health questionnaire for parents was also performed. An evaluation was carried out at the time of recruitment and 1 year later to explore the effectiveness of the comprehensive oral health care model. The differences in decayed teeth (dt), decayed tooth surfaces (ds), filled teeth (ft), filled tooth surfaces (fs) and the ratio of ft /(dt + ft) between the two groups were statistically significant (P < 0.001) at 1 year. The incidence of caries in the control group was higher than that of the test group (P = 0.02). The rate of awareness of oral health knowledge (P = 0.01) and the practice of good diet habits (P = 0.02) by parents in the test group were significantly higher than those in the control group. The present study demonstrated that the comprehensive oral health care program reduces and prevents caries amongst children with s-ECC.

  6. Dose-dependent effects of docosahexaenoic acid supplementation on blood lipids in statin-treated hyperlipidaemic subjects.

    PubMed

    Meyer, Barbara J; Hammervold, Tone; Rustan, Arild Chr; Howe, Peter R C

    2007-03-01

    The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = -0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = -0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.

  7. Nonsteroidal anti-inflammatory drugs reduce the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis.

    PubMed

    Li, Lin; Han, Zhen; Yuan, Heming; Zhang, Guozheng; Jia, Yuliang; He, Chiyi

    2017-09-01

    Several recent studies suggested that nonsteroidal anti-inflammation drugs (NSAIDs) could prevent the pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the routes of administration, the dosages of NSAIDs and the potential efficacy in reducing the severity of pancreatitis remain controversial. The aim of this meta-analysis was to evaluate the efficacy of NSAIDs for post-ERCP pancreatitis (PEP) prophylaxis. We systematically searched PubMed, Embase, EBSCO, Elsevier and Web of Science databases up to 1 October 2016 for relevant studies. A total of 24 studies met the inclusion criteria. Compared to the controls, the risk of pancreatitis was much lower in the NSAIDs group (OR = 0.57, 95% CI: 0.48-0.67, P < 0.0001). However, NSAIDs were not effective in reducing the risk of moderate to severe pancreatitis compared with placebo (OR = 0.75, 95% CI: 0.57-1.00). In the subanalyses, rectal administration was the only effective route (OR = 0.51, 95% CI: 0.42-0.62), and the risk of PEP was reduced in both randomized controlled trials (RCTs) (OR = 0.63, 95% CI: 0.52-0.76) and case-control articles (C-Cs) (OR = 0.40, 95% CI: 0.28-0.58). Prophylactic administration of NSAIDs reduced the incidence of PEP in both RCTs and C-Cs, especially when rectally administered, but was not effective in reducing the risk of moderate to severe pancreatitis. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  8. Overexpressed heat shock protein 70 protects cells against DNA damage caused by ultraviolet C in a dose-dependent manner

    PubMed Central

    Niu, Piye; Liu, Lin; Gong, Zhiyong; Tan, Hao; Wang, Feng; Yuan, Jing; Feng, Youmei; Wei, Qingyi; Tanguay, Robert M; Wu, Tangchun

    2006-01-01

    Heat shock protein 70 (Hsp70) comprises proteins that have been reported to protect cells, tissues, and organisms against damage from a wide variety of stressful stimuli; however, little is known about whether Hsp70 protects against DNA damage. In this study, we investigated the relationship between Hsp70 expression and the levels of ultraviolet C (UVC)–induced DNA damage in A549 cells with normal, inhibited, and overexpressed Hsp70 levels. Hsp70 expression was inhibited by treatment with quercetin or overexpressed by transfection of plasmids harboring the hsp70 gene. The level of DNA damage was assessed by the comet assay. The results showed that the levels of DNA damage (shown as the percentage of comet cells) in A549 cells increased in all cells after exposure to an incident dose of 0, 10, 20, 40, and 80 J/m2 whether Hsp70 was inhibited or overexpressed. This response was dose dependent: a protection against UVC-induced DNA damage in cells with overexpressed Hsp70 was observed at UVC dose 20 J/ m2 with a maximum at 40 J/m2 when compared with cells with normal Hsp70 levels and in quercetin-treated cells. This differential protection disappeared at 80 J/m2. These results suggest that overexpressed Hsp70 might play a role in protecting A549 cells from DNA damage caused by UVC irradiation, with a threshold of protection from at UVC irradiation-induced DNA damage by Hsp70. The detailed mechanism how Hsp70 is involved in DNA damage and possible DNA repair warrants further investigation. PMID:16817322

  9. Leveraging management strategies for seedborne plant diseases to reduce Salmonella enterica Serovar Typhimurium incidence on tomato seed and seedlings.

    PubMed

    Lewis Ivey, Melanie L; Xu, Xiulan; Miller, Sally A

    2014-03-01

    Tomatoes have been linked to many outbreaks of salmonellosis over the last decade, but the routes of contamination have yet to be discerned. Many phytopathogens of tomato are seedborne and are effectively managed using seed sanitizers. Seed sanitizers effective against bacterial phytopathogens were evaluated for their efficacy in killing bioluminescent Salmonella enterica serovar Typhimurium strain SeT-A14 on tomato seed infested with moderately high and high levels of pathogen. SeT-A14 incidence on seedlings produced from contaminated seed following sanitation was also determined. At a moderately high infestation rate (40%), SeT-A14 was eradicated on seed sanitized with 1.2% sodium hypochlorite (NaClO) mixed with 0.03% surfactant for 2 min, hydrochloric acid (HCl) for 30 min, and trichloromelamine for 2 min. At a higher infestation rate (94%), only NaClO and HCl were effective in eradicating SeT-A14 from the seed. At both infestation rates, 2% Virkon-S for 15 min significantly reduced SeT-A14 incidence compared with the nontreated infested controls but did not eradicate the pathogen. Hot water, a commonly used sanitizer for managing seedborne bacterial plant diseases, significantly reduced SeT-A14 on heavily infested seed, but incidence was still moderate at 17.5%. On seedlings produced from moderately highly infested seed, SeT-A14 was not detected using RapidChek Salmonella test strips. Using heavily infested seed, SeT-A14 was detected with the test strips in one of four pooled samples of 14-day-old seedlings produced from nonsanitized seed and from seed sanitized with hot water and trichloromelamine. However, bioluminescence was not observed on 14-day-old seedlings. To our knowledge, this is the first report that provides evidence that S. enterica serovar Typhimurium can be seed transmitted and can lead to the contamination of tomato seedlings. In addition to eliminating important bacterial phytopathogens from tomato seed, NaClO or HCl may mitigate the risk of

  10. Xenografts of porcine islets immunoprotected in hollow fibres reduce the incidence of diabetes in non-obese diabetic mice.

    PubMed

    Chaillous, L; Darquy, S; Maugendre, S; Rivereau, A S; Reach, G; Saï, P

    1996-05-01

    Non-obese diabetic (NOD) mice develop an autoimmune disease with a long prodromal period and constitute a model for investigating the prevention of human insulin-dependent diabetes mellitus. Since insulin injected prophylactically has been shown to reduce incidence of diabetes in NOD mice, we tested a new strategy consisting of prophylactic xenografts of porcine pancreatic islets immunoprotected in semipermeable hollow fibres. Female NOD mice were transplanted twice (at 60 and 180 days of age) with islet-containing or empty fibres. Within the group grafted with protected islets, the incidence of diabetes was reduced (37 vs 75%; p < 0.01), the onset of disease was delayed (p < 0.02), and the severity of lymphocytic inflammation of endogenous islets was reduced (p < 0.02). When already diabetic mice were not taken into account for analysis, blood glucose level was slightly lower in those grafted with islet-containing fibres (p < 0.04). Graft function was also evidenced by HPLC separation of porcine insulin in NOD sera. Histological and perifusion studies of fibres retrieved from recipients confirmed immunoprotection. During co-transfer, T splenocytes from mice grafted with islet-containing fibres were able to reduce the capacity of T cells from diabetic donors to adoptively transfer the disease (p < 0.01). Antigens for islet-cell autoantibodies (ICA) in pancreata from both groups were compared by immunofluorescence with the same ICA-positive human sera to ensure that differences were due to antigen quantitative changes. These antigens, which could serve as an index of a possibly more extensive antigen beta-cell rest, were decreased (p < 0.01) in mice grafted with protected islets. Reduction of diabetes and insulitis following early islet transplantation may thus be due to generation of cellular mechanisms that actively suppress disease, and possibly in part to a decrease in antigens which make beta cells less vulnerable to autoimmune aggression. These effects can be

  11. A transgenic Drosophila model for arsenic methylation suggests a metabolic rationale for differential dose-dependent toxicity endpoints.

    PubMed

    Muñiz Ortiz, Jorge G; Shang, Junjun; Catron, Brittany; Landero, Julio; Caruso, Joseph A; Cartwright, Iain L

    2011-06-01

    The mechanisms by which exposure to arsenic induces its myriad pathological effects are undoubtedly complex, while individual susceptibility to their type and severity is likely to be strongly influenced by genetic factors. Human metabolism of arsenic into methylated derivatives, once presumed to result in detoxification, may actually produce species with significantly greater pathological potential. We introduce a transgenic Drosophila model of arsenic methylation, allowing its consequences to be studied in a higher eukaryote exhibiting conservation of many genes and pathways with those of human cells while providing an important opportunity to uncover mechanistic details via the sophisticated genetic analysis for which the system is particularly well suited. The gene for the human enzyme, arsenic (+3 oxidation state) methyltransferase, was introduced into nonmethylating Drosophila under inducible control. Transgenic flies were characterized for enzyme inducibility, production of methylated arsenic species, and the dose-dependent consequences for chromosomal integrity and organismal longevity. Upon enzyme induction, transgenic flies processed arsenite into mono and dimethylated derivatives identical to those found in human urine. When induced flies were exposed to 9 ppm arsenite, chromosomal stability was clearly reduced, whereas at much higher doses, adult life span was significantly increased, a seemingly paradoxical pair of outcomes. Measurement of arsenic body burden in the presence or absence of methylation suggested that enhanced clearance of methylated species might explain this greater longevity under acutely toxic conditions. Our study clearly demonstrates both the hazards and the benefits of arsenic methylation in vivo and suggests a resolution based on evolutionary grounds.

  12. Dose-dependent effect of galangin on fructose-mediated insulin resistance and oxidative events in rat kidney.

    PubMed

    Sivakumar, Allur S; Viswanathan, P; Anuradha, Carani V

    2010-01-01

    Galangin is an antioxidant flavonol present in high concentrations in the rhizome of Alpinia galanga. We investigated the effect of galangin on whole-body insulin resistance and kidney oxidative stress in a fructose-induced rat model of metabolic syndrome. Male albino Wistar rats were divided into 6 groups containing six animals each. Groups I and VI received a starch-based control diet, while groups II, III, IV and V were fed a high fructose diet (60 g/100 g). Groups III, IV and V additionally received galangin (50, 100 and 200 μg/kg body weight, respectively) while group VI received 200 μg galangin/kg body weight. At the end of 60 days, fructose-fed rats exhibited insulin resistance, increased levels of peroxidation end products and diminished antioxidant status. galangin, dose-dependently normalized blood glucose and insulin levels. The minimum effective dose was 100 μg galangin/kg body weight. At this dose, galangin also prevented the development of insulin resistance and the exaggerated the response to oral glucose challenge. The oxidant-antioxidant balance was maintained by galangin. Micro-albuminuria and tubular and glomerular changes observed in fructose-treated rats were significantly prevented by galangin (100 μg/kg body weight). These findings imply that galangin potentiates insulin sensitivity and antioxidant capacity and reduces renal damage in this dietary model of metabolic syndrome.

  13. Dose dependent side effect of superparamagnetic iron oxide nanoparticle labeling on cell motility in two fetal stem cell populations.

    PubMed

    Diana, Valentina; Bossolasco, Patrizia; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

    2013-01-01

    Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies.

  14. Persistent dose-dependent changes in brain structure in young adults with low-to-moderate alcohol exposure in utero.

    PubMed

    Eckstrand, Kristen L; Ding, Zhaohua; Dodge, Neil C; Cowan, Ronald L; Jacobson, Joseph L; Jacobson, Sandra W; Avison, Malcolm J

    2012-11-01

    Many children with heavy exposure to alcohol in utero display characteristic alterations in brain size and structure. However, the long-term effects of low-to-moderate alcohol exposure on these outcomes are unknown. Using voxel-based morphometry and region-of-interest analyses, we examined the influence of lower doses of alcohol on gray and white matter composition in a prospectively recruited, homogeneous, well-characterized cohort of alcohol-exposed (n = 11, age 19.5 ± 0.3 years) and control (n = 9, age 19.6 ± 0.5 years) young adults. A large proportion of the exposed individuals were born to mothers whose alcohol consumption during pregnancy was in the low-to-moderate range. There were no differences in total brain volume or total gray or white matter volume between the exposed and control groups. However, gray matter volume was reduced in alcohol-exposed individuals in several areas previously reported to be affected by high levels of exposure, including the left cingulate gyrus, bilateral middle frontal gyri, right middle temporal gyrus, and right caudate nucleus. Notably, this gray matter loss was dose dependent, with higher exposure producing more substantial losses. These results indicate that even at low doses, alcohol exposure during pregnancy impacts brain development and that these effects persist into young adulthood. Copyright © 2012 by the Research Society on Alcoholism.

  15. SHOEBOX Modulates Root Meristem Size in Rice through Dose-Dependent Effects of Gibberellins on Cell Elongation and Proliferation

    PubMed Central

    Li, Jintao; Zhao, Yu; Chu, Huangwei; Wang, Likai; Fu, Yanru; Liu, Ping; Upadhyaya, Narayana; Chen, Chunli; Mou, Tongmin; Feng, Yuqi; Kumar, Prakash; Xu, Jian

    2015-01-01

    Little is known about how the size of meristem cells is regulated and whether it participates in the control of meristem size in plants. Here, we report our findings on shoebox (shb), a mild gibberellin (GA) deficient rice mutant that has a short root meristem size. Quantitative analysis of cortical cell length and number indicates that shb has shorter, rather than fewer, cells in the root meristem until around the fifth day after sowing, from which the number of cortical cells is also reduced. These defects can be either corrected by exogenous application of bioactive GA or induced in wild-type roots by a dose-dependent inhibitory effect of paclobutrazol on GA biosynthesis, suggesting that GA deficiency is the primary cause of shb mutant phenotypes. SHB encodes an AP2/ERF transcription factor that directly activates transcription of the GA biosynthesis gene KS1. Thus, root meristem size in rice is modulated by SHB-mediated GA biosynthesis that regulates the elongation and proliferation of meristem cells in a developmental stage-specific manner. PMID:26275148

  16. SHOEBOX Modulates Root Meristem Size in Rice through Dose-Dependent Effects of Gibberellins on Cell Elongation and Proliferation.

    PubMed

    Li, Jintao; Zhao, Yu; Chu, Huangwei; Wang, Likai; Fu, Yanru; Liu, Ping; Upadhyaya, Narayana; Chen, Chunli; Mou, Tongmin; Feng, Yuqi; Kumar, Prakash; Xu, Jian

    2015-08-01

    Little is known about how the size of meristem cells is regulated and whether it participates in the control of meristem size in plants. Here, we report our findings on shoebox (shb), a mild gibberellin (GA) deficient rice mutant that has a short root meristem size. Quantitative analysis of cortical cell length and number indicates that shb has shorter, rather than fewer, cells in the root meristem until around the fifth day after sowing, from which the number of cortical cells is also reduced. These defects can be either corrected by exogenous application of bioactive GA or induced in wild-type roots by a dose-dependent inhibitory effect of paclobutrazol on GA biosynthesis, suggesting that GA deficiency is the primary cause of shb mutant phenotypes. SHB encodes an AP2/ERF transcription factor that directly activates transcription of the GA biosynthesis gene KS1. Thus, root meristem size in rice is modulated by SHB-mediated GA biosynthesis that regulates the elongation and proliferation of meristem cells in a developmental stage-specific manner.

  17. Dietary nucleosides and nucleotides do not affect tumor incidence but reduce amyloidosis incidence in B6C3F1 mice irradiated with californium-252.

    PubMed

    Yokoyama, Hiroomi; Fujiwara, Hiroshi; Watanabe, Hiromitsu

    2004-04-01

    We investigated the effects of a dietary mixture of nucleosides and nucleotides (NS) on the systemic incidence rates of postirradiation carcinogenesis and non-neoplastic lesions in mice. Five-week-old male B6C3F1 mice were fed AIN-76B Purified Diet supplemented with NS for 1 wk and 13 mo before and after irradiation of neutron with californium-252 ((252)Cf); specifically NS was added to the AIN-76B Purified Diet (without nucleotide) to obtain a final concentration of 0%, 0.5%, or 2.5% NS. A commercial stock diet was also given to mice, and half of the mice were irradiated. Both irradiated and non-irradiated mice were used for reference controls. The incidence of liver tumors in each NS group was lower than that in the reference control group (P < 0.01), but there were no differences between the 0%, 0.5%, and 2.5% NS groups. In contrast, the incidence rate of mice with non-neoplastic lesions in the 0% NS group was significantly higher than the reference control group (P < 0.05). This higher incidence of mice with non-neoplastic lesions was significantly decreased upon supplementation of the nucleotide-free diet with 0.5% or 2.5% NS (P < 0.01 and P < 0.05, respectively). Of the non-neoplastic lesions observed, the incidence of amyloidosis was decreased significantly upon supplementation of the nucleotide-free diet with 0.5% NS (P < 0.05). Supplementation of a nucleotide-free diet with NS inhibits the development of non-neoplastic lesions, such as those associated with amyloidosis, without promoting the carcinogenesis induced by (252)Cf irradiation.

  18. Social Isolation Reduces Mammary Development, Tumor Incidence and Expression of Epigenetic Regulators in Wild Type and p53-Heterozygotic Mice

    PubMed Central

    Hasen, Nina S.; O'Leary, Kathleen A.; Auger, Anthony P.; Schuler, Linda A.

    2010-01-01

    Chronic stress is associated with more rapid tumor progression, and recent evidence suggests that stress may contribute to social and ethnic disparities in the incidence and mortality of breast cancer. We evaluated the p53+/- FVB/N mouse as a model to investigate effects of chronic social stress on mammary gland development, gene expression and tumorigenesis. We individually housed (IH) wild type and p53+/- female FVB/N mice, starting at weaning. At 14 weeks of age, both wild type and p53+/- IH mice showed strikingly reduced mammary development compared to group-housed (GH) controls, with IH mice having significantly fewer pre-terminal end buds. This morphological difference was not reflected in levels of mammary transcripts for estrogen receptor alpha or progestin receptor. However, IH increased levels of mRNA for the kisspeptin receptor in the medial preoptic area of the hypothalamus, associated with reduced duration of estrous cycles. Further, IH altered mammary transcripts of genes associated with DNA methylation; transcripts for methyl binding protein 2 and DNA methyltransferase (DNMT) 3b, but not DNMT 1 and DNMT3a, were reduced in IH, compared to GH females. Interestingly, glands of p53+/- females displayed reduced expression of all these mediators, compared to wildtype females. However, contrary to our initial hypothesis, IH did not increase mammary tumorigenesis. Rather, p53+/- GH females developed significantly more mammary tumors than IH mice. Together, these data suggest that social isolation initiated at puberty may confound studies of tumorigenesis by altering mammary development in mouse models. PMID:20424136

  19. Assessment of the risk of solar ultraviolet radiation to amphibians. I. Dose-dependent induction of hindlimb malformations in the northern leopard frog (Rana pipiens).

    PubMed

    Ankley, Gerald T; Diamond, Stephen A; Tietge, Joseph E; Holcombe, Gary W; Jensen, Kathleen M; Defoe, David L; Peterson, Ryan

    2002-07-01

    A number of environmental stressors have been hypothesized as responsible for recent increases in limb malformations in several species of North American amphibians. The purpose of this study was to generate dose-response data suitable for assessing the potential role of solar ultraviolet (UV) radiation in causing limb malformations in a species in which this phenomenon seemingly is particularly prevalent, the northern leopard frog (Rana pipiens). Frogs were exposed from early embryonic stages through complete metamorphosis to varying natural sunlight regimes, including unaltered (100%) sunlight, sunlight subjected to neutral density filtration to achieve relative intensities of 85%, 75%, 65%, 50%, and 25% of unaltered sunlight, and sunlight filtered with glass or acrylamide to attenuate, respectively, the UVB (290-320 nm) and UVB plus UVA (290-380 nm) portions of the spectrum. The experiments were conducted in a controlled setting, with continual monitoring of UVB, UVA, and visible light to support a robust exposure assessment. Full sunlight caused approximately 50% mortality of the frogs during early larval development; no significant treatment-related mortality occurred under any of the other exposure regimes, including 100% sunlight with glass or acrylamide filtration. There was a dose-dependent (p < 0.0001) induction of hindlimb malformations in the frogs, with the percentage of affected animals ranging from about 97% under unaltered sunlight to 0% in the 25% neutral density treatment. Malformations were comprised mostly of missing or truncated digits, and generally were bilateral as well as symmetrical. Filtration of sunlight with either glass or acrylamide both significantly reduced the incidence of malformed limbs. The estimated sunlight dose resulting in a 50% limb malformation rate (ED50) was 63.5%. The limb ED50 values based on measured sunlight intensities corresponded to average daily doses of 4.5 and 100 Wh x m(-2) for UVB and UVA, respectively

  20. Immediate postabortion initiation of levonorgestrel implants reduces the incidence of births and abortions at 2 years and beyond.

    PubMed

    Rose, Sally B; Garrett, Susan M; Stanley, James

    2015-07-01

    The aims of this study were to compare immediate postabortion uptake of recently subsidized (no-cost) levonorgestrel-releasing implants with already available intrauterine and shorter-acting methods and to compare the incidence of subsequent pregnancies (ending in birth or abortion) within 2 years. Retrospective chart review of 4698 women attending a New Zealand public hospital abortion clinic over 2 years (2010-2012) to describe postabortion contraceptive choice, with follow-up via clinic and national births records to assess subsequent pregnancies at 12, 24, 36, and 48 months. Twenty percent of the cohort (934/4698) received an implant, 26% an intrauterine method (927 copper intrauterine device, 301 levonorgestrel-releasing intrauterine system [LNG-IUS]), and 54% chose other shorter-acting methods (2536/4698). Method choice was significantly associated with age, ethnicity, and pregnancy history (p < .001). At 24 months, the unadjusted incidence of subsequent abortion for implant users was 3.8% (95% confidence interval [CI] = 2.5-5.0) and 11.6% (95% CI = 10.3-12.8) for those choosing other short-acting methods. By 48 months, 6.6% of implant users had a subsequent abortion (compared with 18.3% for short-acting methods). The incidence of continued pregnancy at 24 months was 6.3% (95% CI = 4.4-8.1) for implant users and 15.7% (95% CI = 14-17.2) for those choosing other short-acting methods. Adjusted hazard ratios (HRs) for subsequent abortion were lowest for women initiating an implant (HR = 0.26, 95% CI = 0.20-0.35) or LNG-IUS (HR = 0.26, 0.16-0.44, reference group: short-acting methods). Immediate postabortion insertion of an implant significantly reduced rates of subsequent pregnancy for at least 2 years. Abortion service providers should ensure women have barrier-free access to all long-acting reversible contraceptions to delay or prevent pregnancy. Initiation of an levonorgestrel implant immediately postabortion was associated with a 74% reduction in subsequent

  1. Association of remote ischemic peri-conditioning with reduced incidence of clinical heart failure after primary percutaneous coronary intervention.

    PubMed

    Ladejobi, Adetola; Wayne, Max; Martin-Gill, Christian; Guyette, Francis X; Althouse, Andrew D; Sharbaugh, Michael S; Reis, Steven E; Callaway, Clifton W; Kellum, John A; Smith, A J Conrad; Toma, Catalin; Olafiranye, Oladipupo

    2017-03-01

    Clinical heart failure (HF) occurs frequently after ST-segment elevation myocardial infarction (STEMI), and is associated with increased mortality. We assessed the impact of remote ischemic peri-conditioning (RIPC) during inter-facility air medical transport of STEMI patients on clinical HF following primary percutaneous coronary intervention (pPCI). Data from Acute Coronary Treatment and Intervention Outcomes Network Registry®-Get With the Guidelines™ (ACTION Registry-GWTG) from two PCI-hospitals that are utilizing RIPC during inter-facility helicopter transport of STEMI patients for pPCI between March, 2013 and September, 2015 were used for this study. The analyses were limited to inter-facility STEMI patients transported by helicopter with LVEF <55% after pPCI. The outcome measures were occurrence of clinical HF and serum level of brain-type natriuretic peptide (BNP). Out of the 150 STEMI patients in this analysis, 92 patients received RIPC and 58 did not. The RIPC and non-RIPC groups were generally similar in demographic and clinical characteristics except for lower incidence of cardiac arrest in the RIPC group (3/92 [3.3%] versus 13/58 [22.4%], p=0.002). STEMI patients who received RIPC were less likely to have in-hospital clinical HF compared to patients who did not receive RIPC (3/92 [3.3%] versus 7/58 [12.1%]; adjusted OR=0.22, 95% CI 0.05-0.92, p=0.038) after adjusting for baseline differences. In subgroup analysis, RIPC was associated with lower BNP (123 [interquartile range, 17.0-310] versus 319 [interquartile range, 106-552], p=0.029). RIPC applied during inter-facility air transport of STEMI patients for pPCI is associated with reduced incidence of clinical HF and serum BNP. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin.

    PubMed

    Hsu, Chih-Cheng; Wahlqvist, Mark L; Lee, Meei-Shyuan; Tsai, Hsin-Ni

    2011-01-01

    To determine incidence of dementia in type 2 diabetic (T2DM) patients, and whether there are adverse or favorable effects of oral agents (OA) in DM, we obtained a representative cohort of 800,000 from Taiwan’s National Health Insurance database. Those who, as of on January 1, 2000, were 50 years or older and dementia free (n = 127,209) were followed until December 31, 2007, in relation to absence (n = 101,816) or presence (n = 25,393) of T2DM, and whether any OA was used. Dementia was ascertained by ICD9-CM or A-code. Dementia incidence densities (DID) and fully adjusted Cox proportional hazard models were used to estimate association between dementia, DM, and OA. Notably, DID (per 10,000 person-years)was markedly increased with DM (without medication), compared to DM free subjects (119 versus 46). Using non-DM as reference, the adjusted hazard ratios (HRs) (95% confidence interval) for DM without and with OA were 2.41 (2.17–2.66) and 1.62 (1.49–1.77), respectively. For T2DM, compared with no medication, sulfonylureas alone reduced the HR from 1 to 0.85 (0.71–1.01), metformin alone to 0.76 (0.58–0.98), while with combined oral therapy the HR was 0.65 (0.56–0.74). Adjustments included cerebrovascular diseases so that non-stroke related dementias were found to be decreased in DM with sulfonylurea and metformin therapy. T2DM increases the risk of dementia more than 2-fold. On the other hand, sulfonylureas may decrease the risk of dementia, as does metformin; together, these 2 OAs decrease the risk of dementia in T2DM patients by 35% over 8 years.

  3. Reduced energy intake and moderate exercise reduce mammary tumor incidence in virgin female BALB/c mice treated with 7,12-dimethylbenz(a)anthracene

    NASA Technical Reports Server (NTRS)

    Lane, Helen W.; Teer, Patricia; Keith, Robert E.; White, Marguerite T.; Strahan, Susan

    1991-01-01

    The concurrent effects of diet (standard AIN-76A, restricted AIN-76A and high-fat diet) and moderate rotating-drum treadmill exercise on the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in virgin female BALB/cMed mice free of murine mammary tumor virus are evaluated. Analyses show that, although energy intake was related to mammary tumor incidence, neither body weight nor dietary fat predicted tumor incidence.

  4. Reduced energy intake and moderate exercise reduce mammary tumor incidence in virgin female BALB/c mice treated with 7,12-dimethylbenz(a)anthracene

    NASA Technical Reports Server (NTRS)

    Lane, Helen W.; Teer, Patricia; Keith, Robert E.; White, Marguerite T.; Strahan, Susan

    1991-01-01

    The concurrent effects of diet (standard AIN-76A, restricted AIN-76A and high-fat diet) and moderate rotating-drum treadmill exercise on the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in virgin female BALB/cMed mice free of murine mammary tumor virus are evaluated. Analyses show that, although energy intake was related to mammary tumor incidence, neither body weight nor dietary fat predicted tumor incidence.

  5. Dietary garlic and onion reduce the incidence of atherogenic diet-induced cholesterol gallstones in experimental mice.

    PubMed

    Vidyashankar, Satyakumar; Sambaiah, Kari; Srinivasan, Krishnapura

    2009-06-01

    Mice fed with diet containing 0.5 % cholesterol for 10 weeks resulted in cholesterol supersaturation in gallbladder bile which promoted the formation of cholesterol gallstones (CGS). In this study, dietary hypocholesterolaemic spices, garlic and onion (both raw or heat-processed) were examined for their antilithogenic potential by including at 0.6 and 2.0 % level, respectively, along with lithogenic (LG) diet for 10 weeks. Dietary garlic and onion reduced the CGS incidence by 15-39 %, the effect being maximum in the heat-processed onion group. Dietary garlic and onion markedly reduced biliary cholesterol. The cholesterol:phospholipid ratio which was 1.58 in the LG diet group was reduced to 0.73-0.96 in the garlic and onion groups. The biliary cholesterol saturation index was 0.92, 1.25, 1.09 and 0.86, respectively, in the heat-processed onion, raw garlic, heat-processed garlic and raw onion groups, while it was 1.9 in the LG group. The hydrophobicity index of bile was - 0.08, - 0.079, - 0.032 and - 0.073, respectively, in the heat-processed onion, raw garlic, heat-processed garlic and raw onion groups, while it was +0.054 in the LG group. Hepatic hydroxymethyl glutaryl-CoA reductase activity was lowered in the LG diet-fed group, while dietary garlic or onion countered this alteration and also increased the activities of hepatic cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase. Serum and liver cholesterol were decreased by feeding garlic or onion compared to the LG diet. Thus, dietary Allium spices exerted antilithogenic influence by decreasing the cholesterol hyper-secretion into bile and increasing the bile acid output thus decreasing the formation of lithogenic bile in experimental mice.

  6. Targeted intervention reduces refracture rates in patients with incident non-vertebral osteoporotic fractures: a 4-year prospective controlled study.

    PubMed

    Lih, A; Nandapalan, H; Kim, M; Yap, C; Lee, P; Ganda, K; Seibel, M J

    2011-03-01

    In the present prospective controlled observational study, we investigated the effect of a coordinated intervention program on 4-year refracture rates in patients with recent osteoporotic fractures. Compared to standard care, targeted identification, and management significantly reduced the risk of refracture by more than 80%. The risk of refracture following an incident osteoporotic fracture is high. Despite the availability of treatments that reduce refracture and mortality rates, most patients with minimal trauma fracture (MTF) are not managed appropriately. The present prospective controlled observational study investigated the effect of a coordinated intervention program on 4-year refracture rates and time to refracture in patients with recent osteoporotic fractures. Patients presenting with a non-vertebral MTF were actively identified and offered referral to a dedicated intervention program. Patients attending the clinic underwent a standardized set of investigations, were treated as indicated and reviewed at 12-monthly intervals ('MTF group'). Patients who elected to follow-up with their primary care physician were assigned to the concurrent control group. Groups were balanced for baseline anthropometric, socio-economic, and clinical risk factors. Over 4 years, 10 out of 246 patients (4.1%) in the MTF group and 31 of 157 patients (19.7%) in the control group suffered a new fracture, with a median time to refracture of 26 and 16 months, respectively (p < 0.01). Compared to the intervention group, the risk of refracture was increased by 5.3-fold in the control group (95% CI: 2.8-12.2, p < 0.01), and remained elevated (HR 5.63, 95%CI 2.73-11.6, p < 0.01) after adjustment for other significant predictors of refracture such as age and body weight. In patients presenting with a minimal trauma non-vertebral fracture, active identification and management significantly reduces the risk of refracture (Australian New Zealand Clinical Trials Registry ACTRN

  7. Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

    PubMed

    Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

    2017-09-07

    Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase-α or -β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase-β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P=0.004) and the higher dose group (-3.16 [SD=2.39]; P=0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose (r=0.69; P=0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions (P=0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men (r=0.71; P=0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on

  8. Characterization of dose-dependent Young's modulus for a radiation-sensitive polymer gel

    NASA Astrophysics Data System (ADS)

    Crescenti, Remo A.; Bamber, Jeffrey C.; Bush, Nigel L.; Webb, Steve

    2009-02-01

    Radiation-sensitive polymer gels for clinical dosimetry have been intensively investigated with magnetic resonance imaging (MRI) because the transversal magnetic relaxation time is dependent on irradiation dose. MRI is expensive and not easily available in most clinics. For this reason, low-cost, quick and easy-to-use potential alternatives such as optical computed tomography (CT), x-ray CT or ultrasound attenuation CT have also been studied by others. Here, we instead evaluate the dose dependence of the elastic material property, Young's modulus and the dose response of the viscous relaxation of radiation-sensitive gels to discuss their potential for dose imaging. Three batches of a radiation-sensitive polymer gel (MAGIC gel) samples were homogeneously irradiated to doses from 0 Gy to 45.5 Gy. Young's modulus was computed from the measured stress on the sample surface and the strain applied to the sample when compressing it axially, and the viscous relaxation was determined from the stress decay under sustained compression. The viscous relaxation was found not to change significantly with dose. However, Young's modulus was dose dependent; it approximately doubled in the gels between 0 Gy and 20 Gy. By fitting a second-order polynomial to the Young's modulus-versus-dose data, 99.4% of the variance in Young's modulus was shown to be associated with the change in dose. The precision of the gel production, irradiation and Young's modulus measurement combined was found to be 4% at 2 Gy and 3% at 20 Gy. Potential sources of measurement error, such as those associated with the boundary conditions in the compression measurement, inhomogeneous polymerization, temperature (up to 1% error) and the evaporation of water from the sample (up to 1% error), were estimated and discussed. It was concluded that Young's modulus could be used for dose determination. Imaging techniques such as elastography may help to achieve this if they can provide a local measurement of Young

  9. Dose-dependent antihypertensive efficacy and tolerability of perindopril in a large, observational, 12-week, general practice-based study.

    PubMed

    Tsoukas, George; Anand, Sanjiv; Yang, Kwang

    2011-01-01

    Current guidelines recommend the use of full therapeutic dosages of antihypertensive agents, or combination therapy, to improve BP control of hypertensive patients in primary healthcare. The aim of this study was to assess the dose-dependent antihypertensive efficacy and safety of perindopril 4 and 8 mg/day in the clinical setting. The CONFIDENCE study was a prospective, observational, multicenter trial. This was a real-world, clinic-based, outpatient study involving 880 general practitioners/primary-care clinics and 113 specialists in Canada. The study included untreated or inadequately managed patients with hypertension (i.e. seated BP ≥ 140/90 mmHg, or ≥ 130/80 mmHg in the presence of diabetes mellitus, renal disease, or proteinuria) without coronary artery disease (CAD). Treatment consisted of perindopril 4 mg/day, uptitrated to 8 mg/day as required for BP control at visit 2, for 12 weeks. Among the patients already being treated at baseline, perindopril either directly replaced all previous ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]), or was added to antihypertensive treatment with calcium channel blockers (CCBs), diuretics, or β-adrenoceptor antagonists (β-blockers). The primary outcomes were the mean changes in BP from baseline following treatment with perindopril 4 and 8 mg/day as well as the proportion of patients achieving BP control (BP <140/90 mmHg, or <130/80 mmHg in diabetic patients) in the intent-to-treat (ITT) population. Secondary analyses included the incidence of adverse events and compliance. A total of 8298 hypertensive patients entered the study: 56% with newly diagnosed hypertension and 44% with uncontrolled hypertension. Mean SBP/DBP decreased significantly from baseline (152.5  ±  10.8/89.5  ±  9 mmHg) over 12 weeks (-18.5/-9.7 mmHg; p < 0.001). At visit 2, 23% of patients were uptitrated to perindopril 8 mg/day, which resulted in an

  10. Chito-oligosaccharide reduces diarrhea incidence and attenuates the immune response of weaned pigs challenged with Escherichia coli K88.

    PubMed

    Liu, P; Piao, X S; Thacker, P A; Zeng, Z K; Li, P F; Wang, D; Kim, S W

    2010-12-01

    Seventy-two barrows (Landrace × Large White, initial BW of 4.9 ± 0.3 kg and 17 ± 3 d old) were used to determine if dietary chito-oligosaccharides can replace antibiotics as a means to reduce signs associated with infection in weaned pigs challenged with Escherichia coli. Pigs were assigned to 1 of 4 treatments in a randomized complete block design using 6 pens per treatment with 3 pigs per pen. The treatments consisted of pigs fed the unsupplemented corn-soybean meal diet challenged or unchallenged with E. coli K88 and pigs fed the same diet supplemented with 160 mg of chito-oligosaccharides or 100 mg of cyadox/kg and challenged with E. coli K88. On d 7, 1 group of pigs fed the unsupplemented diet, as well as all pigs fed diets containing chito-oligosaccharides or cyadox, were orally dosed with 30 mL of an alkaline broth containing E. coli K88. Another group of pigs fed the unsupplemented diet was orally dosed with 30 mL of sterilized alkaline broth. Fecal consistency was visually assessed each morning from d 7 to 14. Blood samples were collected at 0, 24, 48, and 168 h postinfection. On d 14 postchallenge, all pigs were killed to evaluate intestinal morphology and determine E. coli concentrations in the intestine. During the postchallenge period (wk 2), unsupplemented pigs challenged with E. coli had decreased (P < 0.05) BW gain, feed intake, fecal consistency, villus height, villus height:crypt depth ratio, and plasma IGF-1, and increased (P < 0.05) diarrhea incidence, E. coli counts in the intestine, plasma interleukin-1β, plasma IL-10, and IGA-positive cells in the jejunal and ileal lamina propria, compared with unchallenged pigs. Supplementation with cyadox largely mitigated these effects. Although chito-oligosaccharide reduced the incidence of diarrhea, the growth performance of E. coli-challenged pigs supplemented with chito-oligosaccharide was not better than that of unsupplemented pigs challenged with E. coli. Therefore, chito-oligosaccharide, at the

  11. Use of a laser beam with an oblique angle of incidence to measure the reduced scattering coefficient of a turbid medium

    NASA Astrophysics Data System (ADS)

    Wang, Lihong; Jacques, Steven L.

    1995-05-01

    A simple and quick approach is used to measure the reduced scattering coefficient ( mu s `) of a semi-infinite turbid medium having a much smaller absorption coefficient than mu s`. A laser beam with an oblique angle of incidence to the medium causes the center of the diffuse reflectance that is several transport mean-free paths away from the incident point to shift away from the point of incidence by an amount Delta x. This amount is used to compute mu s` by mu s` = sin( alpha i)/(n Delta x), where n is the refractive index of the turbid medium divided by that of the incident medium and alpha i is the angle of incidence measured from the surface normal. For a turbid medium having an absorption coefficient comparable with mu s `, a revision to the above formula is made. This method is tested theoretically by Monte Carlo simulations and experimentally by a video reflectometer.

  12. Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees

    PubMed Central

    Anthony, Winston E.; Palmer-Young, Evan C.; Leonard, Anne S.; Irwin, Rebecca E.; Adler, Lynn S.

    2015-01-01

    The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees. PMID:26545106

  13. RAD001 (everolimus) induces dose-dependent changes to cell cycle regulation and modifies the cell cycle response to vincristine.

    PubMed

    Saunders, P O; Weiss, J; Welschinger, R; Baraz, R; Bradstock, K F; Bendall, L J

    2013-10-01

    More than 50% of adults and ~20% of children with pre-B acute lymphoblastic leukemia (ALL) relapse following treatment. Dismal outcomes for patients with relapsed or refractory disease mandate novel approaches to therapy. We have previously shown that the combination of the mTOR inhibitor RAD001 (everolimus) and the chemotherapeutic agent vincristine increases the survival of non-obese diabetic/severe combined immuno-deficient (NOD/SCID) mice bearing human ALL xenografts. We have also shown that 16 μM RAD001 synergized with agents that cause DNA damage or microtubule disruption in pre-B ALL cells in vitro. Here, we demonstrate that RAD001 has dose-dependent effects on the cell cycle in ALL cells, with 1.5 μM RAD001 inhibiting pRb, Ki67 and PCNA expression and increasing G0/1 cell cycle arrest, whereas 16 μM RAD001 increases pRb, cyclin D1, Ki67 and PCNA, with no evidence of an accumulation of cells in G0/1. Transition from G2 into mitosis was promoted by 16 μM RAD001 with reduced phosphorylation of cdc2 in cells with 4 N DNA content. However, 16 μM RAD001 preferentially induced cell death in cells undergoing mitosis. When combined with vincristine, 16 μM RAD001 reduced the vincristine-induced accumulation of cells in mitosis, probably as a result of increased death in this population. Although 16 μM RAD001 weakly activated Chk1 and Chk2, it suppressed strong vincristine-induced activation of these cell cycle checkpoint regulators. We conclude that RAD001 enhances chemosensitivity at least in part through suppression of cell cycle checkpoint regulation in response to vincristine and increased progression from G2 into mitosis.

  14. Testing Dose-Dependent Effects of the Nectar Alkaloid Anabasine on Trypanosome Parasite Loads in Adult Bumble Bees.

    PubMed

    Anthony, Winston E; Palmer-Young, Evan C; Leonard, Anne S; Irwin, Rebecca E; Adler, Lynn S

    2015-01-01

    The impact of consuming biologically active compounds is often dose-dependent, where small quantities can be medicinal while larger doses are toxic. The consumption of plant secondary compounds can be toxic to herbivores in large doses, but can also improve survival in parasitized herbivores. In addition, recent studies have found that consuming nectar secondary compounds may decrease parasite loads in pollinators. However, the effect of compound dose on bee survival and parasite loads has not been assessed. To determine how secondary compound consumption affects survival and pathogen load in Bombus impatiens, we manipulated the presence of a common gut parasite, Crithidia bombi, and dietary concentration of anabasine, a nectar alkaloid produced by Nicotiana spp. using four concentrations naturally observed in floral nectar. We hypothesized that increased consumption of secondary compounds at concentrations found in nature would decrease survival of uninfected bees, but improve survival and ameliorate parasite loads in infected bees. We found medicinal effects of anabasine in infected bees; the high-anabasine diet decreased parasite loads and increased the probability of clearing the infection entirely. However, survival time was not affected by any level of anabasine concentration, or by interactive effects of anabasine concentration and infection. Crithidia infection reduced survival time by more than two days, but this effect was not significant. Our results support a medicinal role for anabasine at the highest concentration; moreover, we found no evidence for a survival-related cost of anabasine consumption across the concentration range found in nectar. Our results suggest that consuming anabasine at the higher levels of the natural range could reduce or clear pathogen loads without incurring costs for healthy bees.

  15. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease.

    PubMed

    Ronis, Martin J J; Baumgardner, January N; Sharma, Neha; Vantrease, Jamie; Ferguson, Matthew; Tong, Yudong; Wu, Xianli; Cleves, Mario A; Badger, Thomas M

    2013-02-01

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by non-alcoholic fatty liver disease (NAFLD) leading to non-alcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been shown to protect against steatosis and alcoholic liver injury. The current study was designed to determine if a similar beneficial effect of MCT occurs in a rat model of NAFLD. Groups of male rats were isocalorically overfed diets containing 10%, 35% or 70% total energy as corn oil or a 70% fat diet in which corn oil was replaced with increasing concentrations of saturated fat (18:82, beef tallow:MCT oil) from 20% to 65% for 21 days using total enteral nutrition (TEN). As dietary content of corn oil increased, hepatic steatosis and serum alanine amino transferases were elevated (P < 0.05). This was accompanied by greater expression of cytochrome P450 enzyme CYP2E1 (P < 0.05) and higher concentrations of polyunsaturated 18:2 and 20:4 fatty acids (FA) in the hepatic lipid fractions (P < 0.05). Keeping the total dietary fat at 70%, but increasing the proportion of MCT-enriched saturated fat resulted in a dose-dependent reduction in steatosis and necrosis without affecting CYP2E1 induction. There was no incorporation of C8-C10 FAs into liver lipids, but increasing the ratio of MCT to corn oil: reduced liver lipid 18:2 and 20:4 concentrations; reduced membrane susceptibility to radical attack; stimulated FA β- and ω-oxidation as a result of activation of peroxisomal proliferator activated receptor (PPAR)α, and appeared to increase mitochondrial respiration through complex III. These data suggest that replacing unsaturated fats like corn oil with MCT oil in the diet could be utilized as a potential treatment for NAFLD.

  16. Intra-articular sodium hyaluronate injections in the osteoarthritic ankle joint: effects, safety and dose dependency.

    PubMed

    Witteveen, Angelique G H; Sierevelt, Inger N; Blankevoort, Leendert; Kerkhoffs, Gino M M J; van Dijk, C Niek

    2010-12-01

    To determine the efficacy, safety and dose dependency of intra-articular Orthovisc(®) hyaluronic acid injections in the ankle. A prospective single blinded study in patients with symptomatic ankle-osteoarthritis. Patients were randomly allocated to 1, 2, 3 ml, or 3 weekly injections of 1 ml (3 × 1 ml). Primary outcome was 'pain during walking' at 15 weeks measured on a 100mm VAS. Twenty-six patients (ITT) participated. The 3 × 1 ml dose group showed statistically significant decreases at week 7 for 'pain during walking' and 'pain at rest' (p=0.046). At week 15 decreases were significant for 'pain at rest' (p=0.046). There was no significant decrease of VAS-scores in any of the single dose groups. Seven patients experienced temporary local swelling and increased pain in the injected ankle. Orthovisc(®) viscosupplementation in the ankle joint is effective and well tolerated. The 3 × 1 ml dose regimen shows the best results. Copyright © 2009 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  17. Time- and dose-dependency of the effects of nitrogen pollution on lichens.

    PubMed

    Munzi, Silvana; Pisani, Tommaso; Paoli, Luca; Loppi, Stefano

    2010-10-01

    The present work aims at testing if exposure time and dose play a role in the response of lichen species to nitrogen (N) pollution. To this purpose, samples of the N-sensitive Evernia prunastri and the N-tolerant Xanthoria parietina were treated for 5 weeks either with solutions of NH(4)NO(3) 0.05 and 1 M, or (NH(4))(2)SO(4) 0.025 and 0.5 M. Photosynthetic efficiency was measured as an indicator of sample vitality. The results showed that the lowest concentrations were ineffective at the beginning, but after several supplies both compounds inhibited photosynthetic activity of E. prunastri. The highest concentrations had a deleterious effect, but with a temporal trend. For X. parietina no effect was found for the lowest concentrations, while the same trend shown by E. prunastri was instead observed following treatments with the highest concentrations. It was concluded that the response of lichens to N supply is not only species-specific, but also time- and dose-dependent. The results give a clue on field studies on the relationships between lichens and N pollution. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Regional susceptibility to dose-dependent white matter damage after brain radiotherapy.

    PubMed

    Connor, Michael; Karunamuni, Roshan; McDonald, Carrie; Seibert, Tyler; White, Nathan; Moiseenko, Vitali; Bartsch, Hauke; Farid, Nikdokht; Kuperman, Joshua; Krishnan, Anitha; Dale, Anders; Hattangadi-Gluth, Jona A

    2017-05-01

    Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose-response across white matter tracts using diffusion tensor imaging (DTI). Forty-nine patients with primary brain tumors underwent MRI with DTI before and 9-12months after partial-brain RT. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated. Atlas-based white matter tracts were identified. A secondary analysis using skeletonized tracts was also performed. Linear mixed-model analysis of the relationship between mean and max dose and percent change in DTI metrics was performed. Tracts with the strongest correlation of FA change with mean dose were the fornix (-0.46 percent/Gy), cingulum bundle (-0.44 percent/Gy), and body of corpus callosum (-0.23 percent/Gy), p<.001. These tracts also showed dose-sensitive changes in MD and RD. In the skeletonized analysis, the fornix and cingulum bundle remained highly dose-sensitive. Maximum and mean dose were similarly predictive of DTI change. The corpus callosum, cingulum bundle, and fornix show the most prominent dose-dependent changes following RT. Future studies examining correlation with cognitive functioning and potential avoidance of critical white matter regions are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Dose-Dependent Response of Tissue-Engineered Intervertebral Discs to Dynamic Unconfined Compressive Loading

    PubMed Central

    Hudson, Katherine D.; Mozia, Robert I.

    2015-01-01

    Because of the limitations of current surgical methods in the treatment of degenerative disc disease, tissue-engineered intervertebral discs (TE-IVDs) have become an important target. This study investigated the biochemical and mechanical responses of composite TE-IVDs to dynamic unconfined compression. TE-IVDs were manufactured by floating an injection molded alginate nucleus pulposus (NP) in a type I collagen annulus fibrosus (AF) that was allowed to contract for 2 weeks before loading. The discs were mechanically stimulated at a range of strain amplitude (1–10%) for 2 weeks with a duty cycle of 1 h on–1 h off–1 h on before being evaluated for their biochemical and mechanical properties. Mechanical loading increased all properties in a dose-dependent manner. Glycosaminoglycans (GAGs) increased between 2.8 and 2.2 fold in the AF and NP regions, respectively, whereas the hydroxyproline content increased between 1.2 and 1.8 fold. The discs also experienced a 2-fold increase in the equilibrium modulus and a 4.3-fold increase in the instantaneous modulus. Full effects for all properties were seen by 5% strain amplitude. These data suggest that dynamic loading increases the functionality of our TE-IVDs with region-dependent responses using a method that may be scaled up to larger disc models to expedite maturation for implantation. PMID:25277703

  20. Dose-dependent uptake, elimination, and toxicity of monosodium methanearsonate in adult zebra finches (Taeniopygia guttata).

    PubMed

    Albert, Courtney A; Williams, Tony D; Morrissey, Christy A; Lai, Vivian W M; Cullen, William R; Elliott, John E

    2008-03-01

    Monosodium methanearsonate (MSMA), an arsenic-based pesticide, has been used for the past 10 years in attempts to suppress mountain pine beetle (Dendroctonus ponderosae) outbreaks in British Columbia, Canada. Previous studies have shown that cavity nesting forest birds such as woodpeckers forage and breed in MSMA treated pine stands. Here we examined the effects of MSMA in the laboratory using the zebra finch (Taeniopygia guttata), with the objective to examine tissue distribution and sublethal toxic effects in a model avian species. Zebra finches were exposed to this pesticide at doses similar to those found in bark beetle samples from MSMA stands of trees treated in the southern interior of British Columbia (8, 24, and 72 microg/g/d and a control group). Results showed high excretion (>90%) of arsenic in all dose groups, as well as dose-dependent trends in accumulation of arsenic in the blood (p < 0.001) and specific tissues. Monomethylarsonic acid, MMA (V), was the predominant form of arsenic in the blood plasma. Dimethylarsinic acid was the major form of arsenic found in the liver (83%) and kidney (61%) tissues. The brain tissue contained primarily the MMA (V) form (57%). Significant weight loss occurred in the two highest dose groups (p < 0.05). Birds in the highest dose group lost up to 15% of initial body mass.

  1. Dose-dependent Medicinal Effects of Thymus haussknechtii Velen Grown Wild in Turkey.

    PubMed

    Kılıçgün, Hasan; Korkmaz, Mustafa

    2016-01-01

    In this study, it was aimed to determine dose-dependent interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms of the infusions of Thymus haussknechtii Velen, naturally grown in the Eastern Anatolia region of Turkey. Therefore, the infusions of Thymus haussknechtii were tested and the interactions between phenolic contents and antioxidant, antibacterial and antifungal effect mechanisms were determined by way of different antioxidant, antibacterial and antioxidant test systems. The concentrations of Thymus haussknechtii showed strong hydrogen peroxide scavenging activity and free radical scavenging activity [1,1-diphenyl-2-picryl-hydrazil (DPPH) % inhibition]. Also, it was seen that Thymus haussknechtii infusions possessed strong antibacterial and antifungal activity against different gram negative and positive bacteria and fungi. In this study, positive correlations between antioxidant, antibacterial, antifungal potency and the total phenolic content of Thymus haussknechtii were found. When the concentration differences were examined, it was seen that concentrations of 4% had the most strong antioxidant, antibacterial and antifungal activity. As a result, Thymus haussknechtii can be reliable antioxidant, antibacterial antifungal substance at concentrations of 4% when it is used as a supplement to therapeutic regimens and for medicinal purposes.

  2. Dose-dependent surface endothelialization and biocompatibility of polyurethane noble metal nanocomposites.

    PubMed

    Hess, Christian; Schwenke, Andreas; Wagener, Philipp; Franzka, Steffen; Laszlo Sajti, Csaba; Pflaum, Michael; Wiegmann, Bettina; Haverich, Axel; Barcikowski, Stephan

    2014-06-01

    Surface pre-endothelialization is a promising approach to improve the hemocompatibility of implants, medical devices, and artificial organs. To promote the adhesive property of thermoplastic polyurethane (TPU) for endothelial cells (ECs), up to 1 wt % of gold (Au) or platinum (Pt) nanoparticles, fabricated by pulsed laser ablation in polymer solution, were embedded into the polymer matrix. The analysis of these nanocomposites showed a homogenous dispersion of the nanoparticles, with average diameters of 7 nm for Au or 9 nm for Pt. A dose-dependent effect was found when ECs were seeded onto nanocomposites comprising different nanoparticle concentrations, resulting in a fivefold improvement of proliferation at 0.1 wt % nanoparticle load. This effect was associated with a nanoparticle concentration-dependent hydrophilicity and negative charge of the nanocomposite. In dynamic flow tests, nanocomposites containing 0.1 wt % Au or Pt nanoparticles allowed for the generation of a confluent and resistant EC layer. Real-time polymerase chain reaction quantification of specific markers for EC activation indicated that ECs cultivated on nanocomposites remain in an inactivated, nonthrombogenic and noninflammatory state; however, maintain the ability to trigger an inflammatory response upon stimulation. These findings were confirmed by a platelet and leukocyte adhesion assay. The results of this study suggest the possible applicability of TPU nanocomposites, containing 0.1 wt % Au or Pt nanoparticles, for the generation of pre-endothelialized surfaces of medical devices. © 2013 Wiley Periodicals, Inc.

  3. Hydrogen Peroxide Modifies Human Sperm Peroxiredoxins in a Dose-Dependent Manner1

    PubMed Central

    O'Flaherty, Cristian; Rico de Souza, Angela

    2010-01-01

    Low levels of reactive oxygen species (ROS) modulate signaling pathways required for human sperm activation, but high levels impair sperm function, leading to infertility. Peroxiredoxins (PRDXs) are enzymes with a dual role as ROS scavengers and modulators of ROS-dependent signaling. The present study aimed to characterize PRDXs in human spermatozoa and possible modifications resulting from hydrogen peroxide (H2O2). We found PRDX1, PRDX4, PRDX5, and PRDX6 in both seminal plasma and spermatozoa. Using immunocytochemistry, we demonstrated that these PRDXs are differentially localized in the head, acrosome, mitochondrial sheath, and flagellum. These observations were confirmed by immunoblotting using cytosolic, Triton-soluble and -insoluble, and head and flagella sperm fractions. PRDXs are dose-dependently modified by H2O2, as seen by the formation of disulfide bridges and high-molecular-mass complexes. This first study, to our knowledge, on PRDXs in human spermatozoa indicates that PRDX1, PRDX4, PRDX5, and PRDX6 are modified when spermatozoa are challenged with H2O2. This suggests that PRDXs may protect these cells at high levels of H2O2 but could also control H2O2 levels within different cell compartments so that normal sperm activation can occur. PMID:20864641

  4. Mechanisms of estrogens' dose-dependent neuroprotective and neurodamaging effects in experimental models of cerebral ischemia.

    PubMed

    Strom, Jakob O; Theodorsson, Annette; Theodorsson, Elvar

    2011-01-01

    Ever since the hypothesis was put forward that estrogens could protect against cerebral ischemia, numerous studies have investigated the mechanisms of their effects. Despite initial studies showing ameliorating effects, later trials in both humans and animals have yielded contrasting results regarding the fundamental issue of whether estrogens are neuroprotective or neurodamaging. Therefore, investigations of the possible mechanisms of estrogen actions in brain ischemia have been difficult to assess. A recently published systematic review from our laboratory indicates that the dichotomy in experimental rat studies may be caused by the use of insufficiently validated estrogen administration methods resulting in serum hormone concentrations far from those intended, and that physiological estrogen concentrations are neuroprotective while supraphysiological concentrations augment the damage from cerebral ischemia. This evidence offers a new perspective on the mechanisms of estrogens' actions in cerebral ischemia, and also has a direct bearing on the hormone replacement therapy debate. Estrogens affect their target organs by several different pathways and receptors, and the mechanisms proposed for their effects on stroke probably prevail in different concentration ranges. In the current article, previously suggested neuroprotective and neurodamaging mechanisms are reviewed in a hormone concentration perspective in an effort to provide a mechanistic framework for the dose-dependent paradoxical effects of estrogens in stroke. It is concluded that five protective mechanisms, namely decreased apoptosis, growth factor regulation, vascular modulation, indirect antioxidant properties and decreased inflammation, and the proposed damaging mechanism of increased inflammation, are currently supported by experiments performed in optimal biological settings.

  5. Dose-dependent clinical and immunological efficacy of sublingual immunotherapy with mite monomeric allergoid.

    PubMed

    Di Gioacchino, M; Cavallucci, E; Ballone, E; Cervone, M; Di Rocco, P; Piunti, E; Filardo, G S; Turi, M C; Mangifesta, R; Quecchia, C; Mistrello, G; Braga, M; Petrarca, C

    2012-01-01

    Sublingual immunotherapy with monomeric carbamylated allergoid (LAIS) is an effective and well tolerated treatment of respiratory allergy. The aim of the present study was to correlate the efficacy of two maintenance doses (1000 AU vs 3000 AU) of LAIS with the immunological modulation of allergen-driven Th1, Th2 and T regulatory cytokines produced in vitro by PBMCs, in patients suffering from mite allergic rhinitis. Forty-eight consecutive patients with mite allergic rhinitis were recruited. Patients were randomly assigned to group A (n=24) or group B (n=24), respectively receiving 1000 AU or 3000 AU weekly during one-year maintenance phase. Each patient was evaluated for rhinitis severity (ARIA protocol), and for drug consumption at the time of the inclusion and after 6 and 12 months of treatment. Patients were also asked to report the perceived severity of the disease and the tolerability of the treatment in a visual analogical scale (VAS). Before and at the end of the treatment allergen-driven release of cytokines by PBMCs in vitro was measured. After 1-year treatment, a statistically significant reduction of all clinical parameters was observed in all patients, associated with reduction of IL-4 and increase of INF-γ secreted in vitro by mite-challenged PBMCs. Notably, the group treated with the higher dose showed significantly better clinical and immunological results. The efficacy of LAIS is correlated to the immune modulation in a clear dose-dependent effect.

  6. Lipoic acid stimulates bone formation in ovariectomized rats in a dose-dependent manner.

    PubMed

    Radzki, Radoslaw Piotr; Bienko, Marek; Wolski, Dariusz; Lis, Alicja; Radzka, Agnieszka

    2016-09-01

    This study was undertaken to determine the osteotropic effect of different doses of lipoic acid (LA) on the mineralization of bone tissue in female Wistar rats with experimental osteopenia induced by bilateral ovariectomy. Fifty-six rats were randomly selected and submitted to either a sham operation (n = 8) or an ovariectomy (n = 48). The ovariectomized rats were randomly placed into two control groups, treated subcutaneously with either physiological saline or 17β-estradiol in the dose of 4 μg/kg body mass per day, and four experimental groups that received LA subcutaneously in the doses of 12.5, 25, 50, and 100 mg/kg body mass per day (n = 8 in each group). After 28 days of experimental treatment, the rats were sacrificed, and body mass, total skeletal density, and body composition were recorded. Blood serum and isolated femora were stored for further analysis. Our results revealed that the osteoprotective effect of LA was dose-dependent and was observed in rats treated with 50 and 100 mg/kg of LA. Moreover, the LA applied to the ovariectomized rats in the dose of 50 mg/kg not only stopped the bone resorption, but stimulated its formation.

  7. Dose-dependent induction of IL-6 by plant-derived proteases in vitro

    PubMed Central

    Rose, B; Herder, C; Löffler, H; Meierhoff, G; Schloot, N C; Walz, M; Martin, S

    2006-01-01

    Oral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNγ and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction. PMID:16367938

  8. Dose dependence of surface damage profiles for Ge(111) irradiated with 3 keV Ar +

    NASA Astrophysics Data System (ADS)

    Kido, Yoshiaki; Nakano, Hirohiko

    1990-12-01

    The damage profiles of 3 keV Ar + -irradiated Ge(111) were measured by medium energy ion scattering (MEIS) with 220 keV H + beams. A depth resolution of 0.5 nm has been achieved using an electrostatic toroidal analyzer. With doses over 1 × 10 14Ar+/ cm2 at room temperature, an amorphous layer is formed and the amorphous layer thickness is saturated by a dose of 1 × 10 15Ar+/ cm2. The saturated amorphous layer thickness of 12-13 nm obtained is in good agreement with that observed by a cross section transmission electron microscope. The dose dependence of the induced defects derived from MEIS is consistent with that determined by electron channeling pattern analysis. The amorphized damage profiles determined directly by MEIS agree well with those obtained by solving the rate equation using the unsaturated initial defect profile for a dose of 2 × 10 13Ar+/ cm2 and assuming a sputtering rate of 2.4-3.0.

  9. Chrysin, a flavonoid attenuates histological changes of hyperammonemic rats: A dose dependent study.

    PubMed

    Renuka, Mani; Vijayakumar, Natesan; Ramakrishnan, Arumugam

    2016-08-01

    Chrysin (5,7-dihydroxyflavone) is a major component of some traditional medicinal herbs present in honey, propolis and many plant extracts. The study was aimed to illuminate the effect of chrysin in the pathogenesis of ammonium chloride (NH4Cl) induced hyperammonemic rat model in a dose dependent manner. Rats were injected with NH4Cl (100mg/kg b.w.) by intraperitonially (i.p) thrice a week for 8 consecutive weeks for the induction of experimental hyperammonemia. Hyperammonemic rats were treated with chrysin by orally at a dose of 25, 50 & 100mg/kg b.w. respectively. Protective effect of chrysin against hyperammonemia was evaluated by performing biochemical estimations and morphopathological investigations of hematoxylin and eosin stained sections of liver, brain and kidney tissues. Supplementation of chrysin reinstated the levels of blood ammonia, plasma urea, uric acid, total bilirubin, creatinine, brain glutamate, glutamine, nitric oxide (NO) and the activities of Na(+)/K(+)-ATPase, and liver marker enzymes. On the other hand increased level of plasma urea was observed in chrysin treated rats as compared with hyperammonemic rats. Chrysin administration caused distortion of hepatic, brain and kidney architecture as shown by histological examination. Chrysin at a dose (100mg/kg b.w.) showed an utmost decline in the level of all biochemical estimations. Both biochemical and morphological studies clearly revealed that chrysin protects against cell injury induced by ammonia intoxication in a dose-response manner with respect to endogenous antioxidants and hypoammonemic effects.

  10. Temperature and dose dependency of free radicals in irradiated poly(ethylene terephthalate)

    NASA Astrophysics Data System (ADS)

    Rao, B. S.; Sridhar, V.; Indira, S.; Punnaiah, G.; Venkatapparao, T.

    2006-01-01

    The nature of free radicals produced in gamma-irradiated poly(ethylene terephthalate) (PET) has been studied by the electron spin resonance (ESR) and Fourier transform infrared (FTIR) techniques. ESR and FTIR spectra of irradiated PET are recorded at different temperatures and radiation doses, to observe the behaviour of free radicals. The ESR spectrum of PET irradiated to a radiation dose of 3.0 Mrad at room temperature consists of more than four hyperfine lines. The spectrum is simulated to be a superposition of component spectra arising from macroradicals similar to CH2-CH similar to and radicals of the type similar to CH- and/or similar to CO-C6H3-CO similar to together with a difference singlet due to O-CH2 similar to radicals. ESR spectra of irradiated PET were also recorded from RT to 430 K. The hyperfine structure gradually goes down with temperature and around 430 K the signal completely vanishes. The spectra were also simulated at different temperatures. The macroradical intensity gradually decreases, whereas the intensity of the doublet is stable up to 350 K. The dose dependency of free radicals produced in gamma-irradiated PET has also been investigated by recording the ESR spectra at various radiation doses. FTIR spectra of pure and irradiated PET have been recorded to identify chemical changes occurring on irradiation of the polymer.

  11. Dose-dependent cytotoxicity of clinically relevant cobalt nanoparticles and ions on macrophages in vitro.

    PubMed

    Kwon, Young-Min; Xia, Zhidao; Glyn-Jones, Sion; Beard, David; Gill, Harinderjit S; Murray, David W

    2009-04-01

    Despite the satisfactory short-term implant survivorship of metal-on-metal hip resurfacing arthroplasty, periprosthetic soft-tissue masses such as pseudotumours are being increasingly reported. Cytotoxic effects of cobalt or chromium have been suggested to play a role in its aetiology. The aim of this study was to investigate the effects of clinically relevant metal nanoparticles and ions on the viability of macrophages in vitro. A RAW 264.7 murine macrophage cell line was cultured in the presence of either: (1) cobalt, chromium and titanium nanoparticles sized 30-35 nm; or (2) cobalt sulphate and chromium chloride. Two methods were used to quantify cell viability: Alamar Blue assay and Live/Dead assay. The cytotoxicity was observed only with cobalt. Cobalt nanoparticles and ions demonstrated dose-dependent cytotoxic effects on macrophages in vitro: the cytotoxic concentrations of nanoparticles and ions were 1 x 10(12) particles ml(-1) and 1000 microM, respectively. The high concentration of cobalt nanoparticles required for cytotoxicity of macrophages in vitro suggests that increased production of cobalt nanoparticles in vivo, due to excessive MoM implant wear, may lead to local adverse biological effects. Therefore, cytotoxicity of high concentrations of metal nanoparticles phagocytosed by macrophages located in the periprosthetic tissues may be an important factor in pathogenesis of pseudotumours.

  12. Dose-Dependent Effects of Androgens on the Circadian Timing System and Its Response to Light

    PubMed Central

    Butler, Matthew P.; Karatsoreos, Ilia N.; LeSauter, Joseph

    2012-01-01

    The hypothalamic suprachiasmatic nucleus (SCN) is the locus of a master clock that regulates circadian rhythms in physiology and behavior. Gonadectomy in male mice lengthens the period of circadian rhythms and increases the day-to-day variability of activity onset time. Both of these responses are rescued by the nonaromatizable androgen dihydrotestosterone. Androgen receptors (AR) are localized in SCN neurons that receive direct retinal input. To explore how androgens affect circadian clock function and its responsiveness to photic cues, we measured wheel-running behavior and SCN AR expression in intact, gonadectomized, and testosterone-replaced mice, held under various photic conditions. Gonadectomy lengthened circadian period in constant dim light but not in constant darkness. Increasing intensities of constant light parametrically increased circadian period, and this was potentiated at all intensities by gonadectomy. In contrast, gonadectomy did not alter light-induced pupil constriction, suggesting a nonretinal locus of hormone action. In hormone-replaced animals housed in constant darkness, T concentration was positively correlated with precision of activity onset and with SCN AR expression and negatively correlated with duration of activity. We infer the existence of two androgenic mechanisms: one modulates SCN responsiveness to light, and the second modulates SCN timekeeping and locomotor activity in a dose-dependent manner. Finally, the effects of androgens on period are a result of hormonal modulation of the SCN's response to photic input rather than to a change in the inherent period of oscillators in the absence of light. PMID:22492303

  13. In silico models for the prediction of dose-dependent human hepatotoxicity

    NASA Astrophysics Data System (ADS)

    Cheng, Ailan; Dixon, Steven L.

    2003-12-01

    The liver is extremely vulnerable to the effects of xenobiotics due to its critical role in metabolism. Drug-induced hepatotoxicity may involve any number of different liver injuries, some of which lead to organ failure and, ultimately, patient death. Understandably, liver toxicity is one of the most important dose-limiting considerations in the drug development cycle, yet there remains a serious shortage of methods to predict hepatotoxicity from chemical structure. We discuss our latest findings in this area and present a new, fully general in silico model which is able to predict the occurrence of dose-dependent human hepatotoxicity with greater than 80% accuracy. Utilizing an ensemble recursive partitioning approach, the model classifies compounds as toxic or non-toxic and provides a confidence level to indicate which predictions are most likely to be correct. Only 2D structural information is required and predictions can be made quite rapidly, so this approach is entirely appropriate for data mining applications and for profiling large synthetic and/or virtual libraries.

  14. Dose-dependent establishment of Trichuris suis larvae in Göttingen minipigs.

    PubMed

    Vejzagić, Nermina; Roepstorff, Allan; Kringel, Helene; Thamsborg, Stig Milan; Nielsen, Mads Pårup; Kapel, Christian M O

    2015-03-15

    Embryonated eggs of the pig whipworm Trichuris suis (TSOee) constitute the active pharmaceutical ingredient (API) in a medicinal product explored in human clinical trials against several immune-mediated diseases. The measurement of TSO biological potency (hatchability and infectivity) is a requirement for the assessment of TSO's pharmacological potency in human clinical trials. The present study aims to validate the dose-dependent establishment of T. suis larvae in Göttingen minipigs and eventual clinical implication of a dose range (1000-10,000 TSO). Four groups of 5 minipigs were inoculated with doses of 1000, 2500, 7500, and 10,000 TSOee, respectively, to evaluate a range of concentrations of TSOee in a minipig infectivity model. Unembryonated eggs (TSOue) were added to keep the total egg number in the inoculum constant at 10,000 eggs. Two groups received 2500 and 7500 TSOee per pig without the addition of TSOue as controls. The intestinal larval establishment at 21 days post inoculation (dpi) demonstrated a clear positive linear dose-response relationship between numbers of inoculated TSOee and recovered larvae. There was a low level of variation in larval counts in all study groups. Thus, the infectivity model in minipigs within the tested dose range offers a reliable, sensitive and accurate assay for testing biological potency of TSO. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Dose-dependent antinociceptive and sedative effects of epidural romifidine in cattle.

    PubMed

    Marzok, M A; El-Khodery, S A

    2016-02-06

    The objective of this study was to evaluate the antinociceptive and sedative effects of epidural administration of romifidine in dairy cattle. Twenty-four dairy cows, divided randomly into four groups (three experimental and one control; n=6) received one of three doses of romifidine (30, 40 or 50 μg/kg) diluted in sterile saline (0.9 per cent) to a final volume of 25 ml or an equivalent volume of sterile saline. Antinociception and its anatomical extent was assessed by applying a standard stimulus (needle pin pricks) in different areas and by applying an electrical stimulus to the flank. The antinociceptive effect of romifidine was produced not only in the tail, anus, perineum, vulva and inguinal area but extended up to the coronary band of the hindlimbs and chest areas. Epidural romifidine induced mild-to-moderate sedation at 30 and 40 μg/kg doses and deep sedation at the 50 μg/kg dose. The antinociceptive and sedative effect was dose-dependent in terms of intensity and duration. Thus, epidural administration of romifidine was effective in providing antinociception and sedation in cattle, and can be used in standing flank and udder surgery in cattle. British Veterinary Association.

  16. Electrocardiographic dose-dependent changes in prophylactic doses of dosulepine, lithium and citalopram.

    PubMed

    Paclt, I; Slavícek, J; Dohnalová, A; Kitzlerová, E; Pisvejcová, K

    2003-01-01

    Tricyclic antidepressant drugs dosulepine (TCA), serotonin selective reuptake inhibitor (SSRI) and prophylactic agent with antidepressant effect lithium carbonicum (Li) have different cardiovascular side-effects. We compared them in the prophylactic therapy of periodic affective disorder in remission with TCA, SSRI and Li. Our previous papers confirmed the most prominent effects of heart electric field parameters in TCA patients (Slavícek et al., 1998). In the present work we studied for the first time the dose-dependent changes of ECG, body surface potential maps (BSPM - parameter DIAM 30, 40) in 43 TCA dosulepine, 40 SSRI citalopram and 30 Li outpatients (Hamilton scale: HAMDŁ10; age 40+/-5 years; treated for depressive disorders or bipolar disorders). The daily doses of dosulepine were 50-250 mg, citalopram 20-80 mg, Li plasma levels 0.66+/-0.08 meq/l. The electrocardiogram (ECG), vectorcardiogram (VCG), and BSPM were measured and calculated by the Cardiag 112.1 diagnostic system. The results have shown a relation between the dose of dosulepine and extremum (maximum and minimum) of depolarization isoarea map in dosulepine, but not in citalopram patients. The repolarization BSPM changes were most pronounced in SSRI patients. Lithium in long-term prophylaxy (1-22 years) caused only minimal ECG BSPM changes. The present results correspond with our previous observations.

  17. Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

    PubMed

    Pandey, Veena; Ansari, Mohammad W; Tula, Suresh; Yadav, Sandep; Sahoo, Ranjan K; Shukla, Nandini; Bains, Gurdeep; Badal, Shail; Chandra, Subhash; Gaur, A K; Kumar, Atul; Shukla, Alok; Kumar, J; Tuteja, Narendra

    2016-05-01

    This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

  18. Dose-Dependent Regulation of Alternative Splicing by MBNL Proteins Reveals Biomarkers for Myotonic Dystrophy

    PubMed Central

    Struck, Adam J.; Gupta, Riti; Farnsworth, Dylan R.; Mahady, Amy E.; Eichinger, Katy; Thornton, Charles A.; Wang, Eric T.; Berglund, J. Andrew

    2016-01-01

    Alternative splicing is a regulated process that results in expression of specific mRNA and protein isoforms. Alternative splicing factors determine the relative abundance of each isoform. Here we focus on MBNL1, a splicing factor misregulated in the disease myotonic dystrophy. By altering the concentration of MBNL1 in cells across a broad dynamic range, we show that different splicing events require different amounts of MBNL1 for half-maximal response, and respond more or less steeply to MBNL1. Motifs around MBNL1 exon 5 were studied to assess how cis-elements mediate the MBNL1 dose-dependent splicing response. A framework was developed to estimate MBNL concentration using splicing responses alone, validated in the cell-based model, and applied to myotonic dystrophy patient muscle. Using this framework, we evaluated the ability of individual and combinations of splicing events to predict functional MBNL concentration in human biopsies, as well as their performance as biomarkers to assay mild, moderate, and severe cases of DM. PMID:27681373

  19. A dose dependent adaptogenic and safety evaluation of Rhodiola imbricata Edgew, a high altitude rhizome.

    PubMed

    Gupta, V; Saggu, S; Tulsawani, R K; Sawhney, R C; Kumar, R

    2008-05-01

    To examine the dose dependent adaptogenic activity aqueous extract of Rhodiola imbricata root was orally administered in rats at different doses, 30 min prior to cold (5 degrees C)-hypoxia (428 mm Hg)-restraint (C-H-R) exposure. The maximal effective adaptogenic dose of the extract was 100 mg/kg body weight. The acute and sub-acute toxicity of the extract was also studied in rats. Sub-acute toxicity studies included administration of single oral dose of 1 g/kg and 2 g/kg of extract once daily for 14 days and maximal effective single oral dose of 100 mg/kg once daily for 30 days. At the end of each treatment period the biochemical parameters related to liver function, kidney function, lipids (triglycerides, cholesterol) and hematological parameters were estimated in serum and blood. Biochemical and hematological analysis showed no significant changes in any of the parameters examined in treated group's animal, in comparison to control animals. No significant change was observed in organ weight/body weight ratios, of any organ studied in comparison to control rats. The oral LD(50) of the extract was observed to be >10 g/kg, indicating an adequate margin of safety. No histopathological changes were observed in the vital organs studied of the treated animals. These results suggest that aqueous extract of R. imbricata root possess potent adaptogenic activity with no acute and sub-acute toxicity.

  20. Adaptogenic and safety evaluation of seabuckthorn (Hippophae rhamnoides) leaf extract: a dose dependent study.

    PubMed

    Saggu, S; Divekar, H M; Gupta, V; Sawhney, R C; Banerjee, P K; Kumar, R

    2007-04-01

    The effects of seabuckthorn (Hippophae rhamnoides L., Elaeagnaceae), leaf aqueous extract were examined in rats for its adaptogenic activity and toxicity. Dose dependent adaptogenic study of extract was carried out at different doses administered orally, 30min prior to cold (5 degrees C)-hypoxia (428mmHg)-restraint (C-H-R) exposure. After sub-acute toxicity studies on 10 and 20 times doses of maximal effective dose administered for 14 days (single oral dose of 1g/kg and 2g/kg once daily) and maximal effective dose administered for 30 days (single oral dose of 100mg/kg once daily), biochemical and hematological parameters were studied in the serum and blood. The maximal effective adaptogenic dose of the extract was 100mg/kg body weight. No significant changes were observed in organ weight/body weight ratios, of any vital organ studied (except liver and kidney in 1g/kg and 2g/kg body weight doses, respectively), and biochemical and hematological parameters of the sub-acute drug treated animals in comparison to control rats. In acute toxicity study LD(50) of the extract was observed to be >10g/kg when given orally. These results indicate that seabuckthorn leaf aqueous extract possess potent adaptogenic activity with no toxicity even after sub-acute (30 days) maximal effective dose administration.

  1. Verapamil Parameter- and Dose-Dependently Impairs Memory Consolidation in Open Field Habituation Task in Rats

    PubMed Central

    Popović, Natalija; Giménez de Béjar, Verónica; Caballero-Bleda, María; Popović, Miroljub

    2017-01-01

    The purpose of the present study was to examine the effects of the phenylalkylamine class of the L-type voltage-dependent calcium channel antagonist, verapamil (1.0, 2.5, 5.0, or 10 mg/kg i.p.), administered immediately after the acquisition task, on memory consolidation of the open field habituation task, in male Wistar rats. On the 48 h retested trial, all tested parameters (ambulation in the side wall and in the central areas, number of rearing, time spent grooming and defecation rate) significantly decreased in the saline treated animals. A significant decrease of rearing was observed in all verapamil treated groups. On the retention day, the ambulation in the side wall and central areas significantly decreased in the animals treated with 1 mg/kg and 10 mg/kg of verapamil, while the time spent grooming and the defecation rate significantly decreased only in the group treated with 1 mg/kg of verapamil. According to the change ratio scores that correct the individual behavioral baseline differences during initial and final sessions, habituation deficit was found in animals treated with verapamil as follows: ambulation along the side wall area (1, 2.5, and 5 mg/kg), number of rearing (all used dose) and time spent grooming (2.5, 5, and 10 mg/kg). In conclusion, the present data suggest that the post-training administration of verapamil, parameter- and dose-dependently, impairs the habituation to a novel environment. PMID:28119614

  2. Fludarabine-based reduced intensity conditioning transplants have a higher incidence of cytomegalovirus reactivation compared with myeloablative transplants.

    PubMed

    George, B; Kerridge, I; Gilroy, N; Huang, G; Hertzberg, M; Gottlieb, D; Bradstock, K

    2010-05-01

    Two hundred and ten adult CMV seropositive patients undergoing myeloablative conditioning (MAC) [n=127] or reduced intensity conditioning (RIC) [n=83] transplants (HCT) were serially monitored for CMV reactivation and disease, using a qualitative polymerase chain reaction (PCR) followed by quantitation with pp65 antigen or quantitative PCR. CMV reactivation occurred in 53 RIC (63.9%) and 61 MAC (48%; P=0.03) transplants at a median of 47 days (range: 24-1977). Risk factors identified included acute GVHD (P=0.001), RIC regimen (P=0.03), unrelated donor (P=0.02), use of anti-thymocyte globulin/alemtuzumb (P=0.02) and use of bone marrow in MAC transplants (P=0.011). On multivariate analysis, RIC transplants and acute GVHD remained independent predictors. Treatment with antiviral drugs resulted in CMV negativity rates of 86.8% in MAC and 88.6% in RIC transplants. CMV disease occurred in 10.8% of RIC and 4.7% of MAC transplants (P=0.15). At a median follow-up of 26 months (range: 3-88), 48.1% of RIC and 50.3% of MAC transplants are alive. The higher incidence of CMV reactivation among RIC transplants suggests the need for novel prophylactic or pre-emptive strategies in this high-risk group of patients.

  3. Personality and Reduced Incidence of Walking Limitation in Late Life: Findings From the Health, Aging, and Body Composition Study

    PubMed Central

    Ferrucci, Luigi; Costa, Paul T.; Faulkner, Kimberly; Rosano, Caterina; Satterfield, Suzanne; Ayonayon, Hilsa N.; Simonsick, Eleanor M.

    2012-01-01

    Objectives. To examine the association between openness to experience and conscientiousness and incident reported walking limitation. Method. The study population consisted of 786 men and women aged 71–81 years (M = 75 years, SD = 2.7) participating in the Health, Aging, and Body Composition—Cognitive Vitality Substudy. Results. Nearly 20% of participants (155/786) developed walking limitation during 6 years of follow-up. High openness was associated with a reduced risk of walking limitation (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.69–0.98), independent of sociodemographic factors, health conditions, and conscientiousness. This association was not mediated by lifestyle factors and was not substantially modified by other risk factors for functional disability. Conscientiousness was not associated with risk of walking limitation (HR = 0.91, 95% CI = 0.77–1.07). Discussion. Findings suggest that personality dimensions, specifically higher openness to experience, may contribute to functional resilience in late life. PMID:22437204

  4. Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation

    PubMed Central

    Chiang, Yun; Tsai, Cheng-Hong; Kuo, Sung-Hsin; Liu, Chieh-Yu; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Lin, Chien-Ting; Hou, Hsin-An; Chou, Wen-Chien; Liu, Jia-Hau; Lin, Chien-Chin; Wu, Shang-Ju; Hsu, Szu-Chun; Chen, Yao-Chang; Lin, Kai-Hsin; Lin, Dong-Tsamn; Chou, Hsien-Tang; Lu, Meng-Yu; Yang, Yung-Li; Chang, Hsiu-Hao; Liu, Ming-Chih; Liao, Xiu-Wen; Wu, Jian-Kuen; Chou, Sheng-Chieh; Cheng, Chieh-Lung; Chen, Chien-Yuan; Tsay, Woei; Tien, Hwei-Fang; Tang, Jih-Luh; Chen, Yu-Hsuan

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy. PMID:27830767

  5. Case Study: Nutritional and Lifestyle Support to Reduce Infection Incidence in an International-Standard Premier League Soccer Player.

    PubMed

    Ranchordas, Mayur K; Bannock, Laurent; Robinson, Scott L

    2016-04-01

    Professional soccer players are exposed to large amounts of physiological and psychological stress, which can increase infection risk and threaten availability for training and competition. Accordingly, it is important for practitioners to implement strategies that support player well-being and prevent illness. This case study demonstrates how a scientifically supported and practically applicable nutrition and lifestyle strategy can reduce infection incidence in an illness-prone professional soccer player. In the 3 months before the intervention, the player had 3 upper-respiratory tract infections (URTIs) and subsequently missed 3 competitive matches and 2 weeks' training. He routinely commenced morning training sessions in the fasted state and was estimated to be in a large daily energy deficit. Throughout the 12-week intervention, the amount, composition, and timing of energy intake was altered, quercetin and vitamin D were supplemented, and the player was provided with a daily sleep and hygiene protocol. There was a positive increase in serum vitamin D 25(OH) concentration from baseline to Week 12 (53 n·mol-1 to 120 n·mol-1) and salivary immunoglobulin-A (98 mg·dl-1 to 135 mg·dl-1), as well as a decline in the number of URTI symptoms (1.8 ± 2.0 vs. 0.25 ± 0.5 for Weeks 0-4 and Weeks 8-12, respectively). More important, he maintained availability for all training and matches over the 12-week period. We offer this case study as a real-world applied example for other players and practitioners seeking to deploy nutrition and lifestyle strategies to reduce risk of illness and maximize player availability.

  6. Effectiveness of a multifactorial intervention program to reduce falls incidence among community-living older adults: a randomized controlled trial.

    PubMed

    Pérula, Luis A; Varas-Fabra, Francisco; Rodríguez, Victoriano; Ruiz-Moral, Roger; Fernández, José A; González, Jesús; Pérula, Carlos J; Roldán, Ana M; de Dios, Caridad

    2012-10-01

    To determine the effectiveness of a multifactorial intervention program to prevent falls among older adults as compared with a brief intervention. Randomized controlled trial. Eleven health centers located in Córdoba, Spain. People over 70 years old (N=404), who are residents in the community. The centers were randomized to either 1 of the 2 groups: intervention group (IG), of a multifactorial nature (individual advice, information leaflet, physical exercise workshop, and home visits), or control group (CG) (brief individual advice and information leaflet). Fall rates and time until the fall; estimates of the relative and absolute risk of falls; and survival analysis and Cox regression. Of the patients recruited, 133 were in the IG and 271 were in the CG. Around 33% in the IG and 30.25% in the CG had had a fall in the previous year (P=.56). After 12 months, the fall incidence rate was 17.29% in the IG and 23.61% in the CG (relative risk=0.73; 95% confidence interval [CI], 0.48-1.12; P=.146). Around 60% of the IG patients said they had increased the time spent on physical activity. In the IG, the incidence of falls at home was 27.5% compared with 49.3% in the CG (P=.04). Being a woman (odds ratio [OR]=1.62; 95% CI, 1.03-2.54), having a history of falls (OR=1.15; 95% CI, 1.05-1.26), suffering acute health problems (OR=2.19; 95% CI, 1.09-4.40), and doing moderate exercise (OR=1.91; 95% CI, 1.08-3.38) were found as factors associated with a higher risk of falls. Although the reduction of falls in the IG was nearly halved, and after the intervention there was a significant reduction in the number of falls at these patients' homes, the multifactorial intervention program is no more effective than the brief intervention to reduce the overall risk of falls. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  7. Consumption of sweetened, dried cranberries may reduce urinary tract infection incidence in susceptible women--a modified observational study.

    PubMed

    Burleigh, Alexandra E; Benck, Susan M; McAchran, Sarah E; Reed, Jess D; Krueger, Christian G; Hopkins, Walter J

    2013-10-18

    Urinary tract infections (UTIs) are one of the most common bacterial infections, and over 50% of women will have a UTI during their lifetimes. Antibiotics are used for prophylaxis of recurrent UTIs but can lead to emergence of drug-resistant bacteria. Therefore, it is reasonable to investigate nutritional strategies for prevention of UTIs. Cranberry juices and supplements have been used for UTI prophylaxis, but with variable efficacy. Because dried cranberries may contain a different spectrum of polyphenolics than juice, consuming berries may or may not be more beneficial than juice in decreasing the incidence of UTIs in susceptible women. The primary objectives of this study were to determine if consumption of sweetened, dried cranberries (SDC) decreases recurrent UTIs and whether this intervention would alter the heterogeneity, virulence factor (VF) profiles, or numbers of intestinal E. coli. Twenty women with recurrent UTIs were enrolled in the trial and consumed one serving of SDC daily for two weeks. Clinical efficacy was determined by two criteria, a decrease in the six-month UTI rates pre- and post-consumption and increased time until the first UTI since beginning the study. Strain heterogeneity and virulence factor profiles of intestinal E. coli isolated from rectal swabs were determined by DNA fingerprinting and muliplex PCR, respectively. The numbers of intestinal E. coli eluted from rectal swabs pre- and post-consumption were also quantified. Over one-half of the patients did not experience a UTI within six months of SDC consumption, and the mean UTI rate per six months decreased significantly. Kaplan-Meier analysis of infection incidence in women consuming SDC compared to patients in a previous control group showed a significant reduction in time until first UTI within six months. The heterogeneity, VF profiles, and prevalence of intestinal E. coli strains were not significantly different after cranberry consumption. Results of this study indicate a

  8. Household Air Pollution Causes Dose-Dependent Inflammation and Altered Phagocytosis in Human Macrophages

    PubMed Central

    Fullerton, Duncan G.; Scriven, James; Aljurayyan, Abdullah N.; Mzinza, David; Barrett, Steve; Wright, Adam K. A.; Wootton, Daniel G.; Glennie, Sarah J.; Baple, Katy; Knott, Amy; Mortimer, Kevin; Russell, David G.; Heyderman, Robert S.; Gordon, Stephen B.

    2015-01-01

    Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke–exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions. PMID:25254931

  9. Household air pollution causes dose-dependent inflammation and altered phagocytosis in human macrophages.

    PubMed

    Rylance, Jamie; Fullerton, Duncan G; Scriven, James; Aljurayyan, Abdullah N; Mzinza, David; Barrett, Steve; Wright, Adam K A; Wootton, Daniel G; Glennie, Sarah J; Baple, Katy; Knott, Amy; Mortimer, Kevin; Russell, David G; Heyderman, Robert S; Gordon, Stephen B

    2015-05-01

    Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke-exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions.

  10. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation

    PubMed Central

    van Miltenburg, M H A M; van Nimwegen, M J; Tijdens, I; Lalai, R; Kuiper, R; Klarenbeek, S; Schouten, P C; de Vries, A; Jonkers, J; van de Water, B

    2014-01-01

    Background: Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development. Methods: To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53lox/lox/FAK+/+/WapCre, p53lox/lox/FAKflox/+/WapCre and p53lox/lox/FAKflox/−/WapCre mice, and mice with WapCre-mediated conditional expression of p53R270H, the mouse equivalent of human p53R273H hot spot mutation, together with conditional deletion of FAK, P53R270H/+/FAKlox/+/WapCre and p53R270H/+/FAKflox/−/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours. Results: Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53R270H-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures. Conclusions: Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion

  11. Dose Dependent Side Effect of Superparamagnetic Iron Oxide Nanoparticle Labeling on Cell Motility in Two Fetal Stem Cell Populations

    PubMed Central

    Diana, Valentina; Bossolasco, Patrizia; Moscatelli, Davide; Silani, Vincenzo; Cova, Lidia

    2013-01-01

    Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies. PMID:24244310

  12. Nanosecond pulsed electric field induced dose dependent phosphatidylinositol-4,5-bisphosphate signaling and intracellular electro-sensitization.

    PubMed

    Tolstykh, Gleb P; Tarango, Melissa; Roth, Caleb C; Ibey, Bennett L

    2017-03-01

    Previously, it was demonstrated that nanometer-sized pores (nanopores) are formed in outer cellular membranes after exposure to nanosecond electric pulses (nsEPs). We reported that plasma membrane nanoporation affects phospholipids of the cell membrane, culminating in cascading phosphoinositide phosphatidylinositol-4,5-bisphosphate (PIP2) intracellular signaling. In the current study, we show that nsEPs initiated electric field (EF) dose-dependent PIP2 hydrolysis and/or depletion from the plasma membrane. This process was confirmed using fluorescent optical probes of PIP2 hydrolysis: PLCδ-PH-EGFP and GFP-C1-PKCγ-C1a. The 50% maximum response occurs with a single 600ns pulse achieving an effective dose (ED50) of EF~8kV/cm within our model cell system. At 16.2kV/cm, the ED50 for the pulse width was 484ns. Reduction of the pulse width or EF amplitude gradually reduced the observed effect, but twenty 60ns 16.2kV/cm pulses produced an effect similar to a single 600ns pulse of the same amplitude. Propidium iodide (PI) uptake after the nsEP exposure confirmed a strong relationship between EF-induced plasma membrane impact and PIP2 depletion. These results have expanded our current knowledge of nsEPs dependent cell physiological effects, and serve as a basis for model development of new exposure standards, providing novel tools for drug independent stimulation and approaches to differential modulation of key cellular functions.

  13. Nitric oxide triggers specific and dose-dependent cytosolic calcium transients in Arabidopsis.

    PubMed

    Aboul-Soud, Mourad A M; Aboul-Enein, Ahmed M; Loake, Gary J

    2009-03-01

    Calcium (Ca(2+)) transients have been shown to take place in response to diverse developmental and physiological cues. Also, it is involved in biotic and abiotic stress signaling. Nitric oxide (NO) is an important signaling molecule that plays a crucial role in plant growth and development, starting from germination to flowering, ripening of fruit and senescence of organs. Moreover, it plays a pivotal role in several biotic and abiotic stress signaling processes. In the present work, the ability of NO to trigger increases in cytosolic calcium concentration ([Ca(2+)](cyt)) was investigated. For this purpose, transgenic Arabidopsis seedlings constitutively expressing the luminescent Ca(2+)-sensitive protein apoaequorin (35S::APOAEQUORIN) was employed. In chemiluminescence and in vivo Ca(2+) imaging assays, the NO-donor sodium nitroprusside (SNP) triggered a strong, instantaneous, reproducible, and dose-dependent rise in [Ca(2+)](cyt). Moreover, the observed rise in [Ca(2+)](cyt) was shown to be NO-specific and not associated with decomposition products of SNP, as the NO-scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3 oxide (C-PTIO) significantly blunted the observed NO-mediated spike in [Ca(2+)](cyt). Interestingly, preincubation of 35S::APOAEQUORIN Arabidopsis seedlings with the plasma membrane channel blocker lanthanum chloride resulted in partial concentration-dependent blocking of the NO-specific Ca(2+) transient. This observation indicates that, in addition to the mobilization of [Ca(2+)](cyt), as an external source in response to NO treatment, there also exists an appreciable contribution of an as yet unidentified internal pool.

  14. Corticotropin releasing factor dose-dependently modulates excitatory synaptic transmission in the noradrenergic nucleus locus coeruleus.

    PubMed

    Prouty, Eric W; Waterhouse, Barry D; Chandler, Daniel J

    2017-03-01

    The noradrenergic nucleus locus coeruleus (LC) is critically involved in the stress response and receives afferent input from a number of corticotropin releasing factor (CRF) containing structures. Several in vivo and in vitro studies in rat have shown that CRF robustly increases the firing rate of LC neurons in a dose-dependent manner. While it is known that these increases are dependent on CRF receptor subtype 1 and mediated by effects of cAMP intracellular signaling cascades on potassium conductance, the impact of CRF on synaptic transmission within LC has not been clarified. In the present study, we used whole-cell patch clamp electrophysiology to assess how varying concentrations of bath-applied CRF affect AMPA-receptor dependent spontaneous excitatory post-synaptic currents (sEPSCs). Compared to vehicle, 10, 25, and 100 nm CRF had no significant effects on any sEPSC parameters. Fifty nanomolar CRF, however, significantly increased sEPSC amplitude, half-width, and charge transfer, while these measures were significantly decreased by 200 nm CRF. These observations suggest that stress may differentially affect ongoing excitatory synaptic transmission in LC depending on how much CRF is released from presynaptic terminals. Combined with the well-documented effects of CRF on membrane properties and spontaneous LC discharge, these observations may help explain how stress and CRF release are able to modulate the signal to noise ratio of LC neurons. These findings have implications for how stress affects the fidelity of signal transmission and information flow through LC and how it might impact norepinephrine release in the CNS.

  15. A Luminal Glycoprotein Drives Dose-Dependent Diameter Expansion of the Drosophila melanogaster Hindgut Tube

    PubMed Central

    Syed, Zulfeqhar A.; Tång, Erika; Bouhin, Hervé; van Dijk-Härd, Iris F.; Uv, Anne

    2012-01-01

    An important step in epithelial organ development is size maturation of the organ lumen to attain correct dimensions. Here we show that the regulated expression of Tenectin (Tnc) is critical to shape the Drosophila melanogaster hindgut tube. Tnc is a secreted protein that fills the embryonic hindgut lumen during tube diameter expansion. Inside the lumen, Tnc contributes to detectable O-Glycans and forms a dense striated matrix. Loss of tnc causes a narrow hindgut tube, while Tnc over-expression drives tube dilation in a dose-dependent manner. Cellular analyses show that luminal accumulation of Tnc causes an increase in inner and outer tube diameter, and cell flattening within the tube wall, similar to the effects of a hydrostatic pressure in other systems. When Tnc expression is induced only in cells at one side of the tube wall, Tnc fills the lumen and equally affects all cells at the lumen perimeter, arguing that Tnc acts non-cell-autonomously. Moreover, when Tnc expression is directed to a segment of a tube, its luminal accumulation is restricted to this segment and affects the surrounding cells to promote a corresponding local diameter expansion. These findings suggest that deposition of Tnc into the lumen might contribute to expansion of the lumen volume, and thereby to stretching of the tube wall. Consistent with such an idea, ectopic expression of Tnc in different developing epithelial tubes is sufficient to cause dilation, while epidermal Tnc expression has no effect on morphology. Together, the results show that epithelial tube diameter can be modelled by regulating the levels and pattern of expression of a single luminal glycoprotein. PMID:22876194

  16. Optimization of monoclonal antibody delivery via the lymphatics: the dose dependence

    SciTech Connect

    Steller, M.A.; Parker, R.J.; Covell, D.G.; Holton, O.D. 3d.; Keenan, A.M.; Sieber, S.M.; Weinstein, J.N.

    1986-04-01

    After interstitial injection in mice, antibody molecules enter local lymphatic vessels, flow with the lymph to regional lymph nodes, and bind to target antigens there. Compared with i.v. administration, delivery via the lymphatics provides a more efficient means for localizing antibody in lymph nodes. An IgG2a (36-7-5) directed against the murine class I major histocompatibility antigen H-2Kk has proved useful for studying the pharmacology of lymphatic delivery. At very low doses, most of the antibody remains at the injection site in Kk-positive animals. As the dose is progressively increased, most effective labeling occurs first in nodes proximal to the injection site and then in the next group of nodes along the lymphatic chain. At higher doses, antibody overflows the lymphatic system and enters the blood-stream via the thoracic duct and other lymphatic-venous connections. Once in the blood, antibody is rapidly cleared, apparently by binding to Kk-bearing cells. These findings indicate that the single-pass distribution of monoclonal antibodies in the lymphatics can be strongly dose dependent, a principle which may be of clinical significance in the improvement of immunolymphoscintigraphic imaging, especially with antibodies directed against normal and malignant lymphoid cells. Monoclonal antibodies directed against normal cell types in the lymph node may be useful for assessing the integrity of lymphatic chains by immunolymphoscintigraphy or, more speculatively, for altering the status of regional immune function. The results presented here indicate that a low or intermediate antibody dose may optimize the signal:noise ratio for imaging. In Kk-negative animals, the percentage of dose taken up in the major organs was essentially independent of the dose administered; there was no evidence for saturable sites of nonspecific binding.

  17. Dose dependence of endotoxin-induced activation of the plasma contact system: an in vitro study.

    PubMed

    Roeise, O; Bouma, B N; Stadaas, J O; Aasen, A O

    1988-12-01

    The dose and time dependence of endotoxin-induced activation of the plasma contact system have been studied. Citrated pool plasma was incubated at 37 degrees C with endotoxin doses of 2.10(5), 2.10(6), 2.10(7), and 2.10(9) ng/l (lipopolysaccharide B, E. coli 026: B6, Difco Laboratories, Detroit, MI) for 24 hr. Samples for determination of components of the contact system were obtained prior to incubation and at 1, 2, 4, 6, 12, and 24 hr. Plasma kallikrein (KK) activity markedly increased at 12 hr in test plasma containing the highest dose of endotoxin (2.10(9) ng/l). Coincident with the elevated KK activity, reductions of both plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) were seen as assayed by chromogenic peptide substrate analyses. Also, functionally determined alpha 2-macroglobulin (alpha 2-M) and C1 inhibitor (C1INH) values were decreased, confirming the reduction of KKI values. Changes of Hageman factor (FXII), PKK, and high molecular weight kininogen (HMWK) values were also found at the same time point when assayed by immunochemical techniques. The same pattern of changes was seen in test plasma containing 2.10(7) and 2.10(6) ng/l of endotoxin. These changes, however, were less pronounced and not seen until 24 hr after beginning incubation. In control plasma and in plasma containing the lowest dose of endotoxin (2.10(5) ng/l), no changes were seen in any factors of the contact system. Our study shows that in vitro endotoxin-induced activation of the contact system is a slow process that is both time and dose dependent.

  18. Dose-dependent functionality and toxicity of green tea polyphenols in experimental rodents.

    PubMed

    Murakami, Akira

    2014-09-01

    A large number of physiologically functional foods are comprised of plant polyphenols. Their antioxidative activities have been intensively studied for a long period and proposed to be one of the major mechanisms of action accounting for their health promotional and disease preventive effects. Green tea polyphenols (GTPs) are considered to possess marked anti-oxidative properties and versatile beneficial functions, including anti-inflammation and cancer prevention. On the other hand, some investigators, including us, have uncovered their toxicity at high doses presumably due to pro-oxidative properties. For instance, both experimental animal studies and epidemiological surveys have demonstrated that GTPs may cause hepatotoxicity. We also recently showed that diets containing high doses (0.5-1%) of a GTP deteriorated dextran sodium sulfate (DSS)-induced intestinal inflammation and carcinogenesis. In addition, colitis mode mice fed a 1% GTP exhibited symptoms of nephrotoxicity, as indicated by marked elevation of serum creatinine level. This diet also increased thiobarbituric acid-reactive substances, a reliable marker of oxidative damage, in both kidneys and livers even in normal mice, while the expression levels of antioxidant enzymes and heat shock proteins (HSPs) were diminished in colitis and normal mice. Intriguingly, GTPs at 0.01% and 0.1% showed hepato-protective activities, i.e., they significantly suppressed DSS-increased serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, those diets remarkably restored DSS-down-regulated expressions of heme oxygenase-1 and HSP70 in livers and kidneys. Taken together, while low and medium doses of GTPs are beneficial in colitis model mice, unwanted side-effects occasionally emerge with high doses. This dose-dependent functionality and toxicity of GTPs are in accordance with the concept of hormesis, in which mild, but not severe, stress activates defense systems for adaptation and survival

  19. Dose-dependent Cortical Thinning After Partial Brain Radiation in High-grade Glioma

    PubMed Central

    Karunamuni, Roshan; Bartsch, Hauke; White, Nate S.; Moiseenko, Vitali; Carmona, Ruben; Marshall, Deborah; Seibert, Tyler M.; McDonald, Carrie R.; Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua; Mell, Loren; Brewer, James B.; Dale, Anders M.; Hattangadi-Gluth, Jona A.

    2015-01-01

    Purpose Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. Methods and Materials We performed a voxel-wise analysis of MR imaging from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1-year post-RT. Cortex was parcellated with well-validated segmentation software (Freesufer). Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effect of dose, neuroanatomic location, age, and chemotherapy on cortical thickness was tested using linear mixed effects (LME) modeling. Results Cortical atrophy was seen after 1-year post RT, with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by −0.0033 mm (p<0.001) for every 1 Gy increase in RT dose. Temporal and limbic cortex exhibited the largest change in cortical thickness per Gy, compared to other regions (p<0.001). Age and chemotherapy were not significantly associated with cortical thickness change. Conclusions We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, one year after fractionated partial brain RT. The magnitude of thinning parallels one-year atrophy rates seen in neurodegenerative diseases, and may contribute to cognitive decline following high-dose RT. PMID:26853338

  20. Nonlinear dose-dependent impact of D1 receptor activation on motor cortex plasticity in humans.

    PubMed

    Fresnoza, Shane; Paulus, Walter; Nitsche, Michael A; Kuo, Min-Fang

    2014-02-12

    The neuromodulator dopamine plays an important role in synaptic plasticity. The effects are determined by receptor subtype specificity, concentration level, and the kind of neuroplasticity induced. D1-like receptors have been proposed to be involved in cognitive processes via their impact on plasticity. Cognitive studies in humans and animals revealed a dosage-dependent effect of D1-like receptor activation on task performance. In humans, D1-like receptor activation re-establishes plasticity under D2 receptor block. However, a dosage-dependent effect has not been explored so far. To determine the impact of the amount of D1-like receptor activation on neuroplasticity in humans, we combined sulpiride, a selective D2 receptor antagonist, with the dopamine precursor l-DOPA (25, 100, and 200 mg) or applied placebo medication. The impact on plasticity induced by anodal and cathodal transcranial direct current stimulation (tDCS) was compared with the impact on plasticity induced by excitatory and inhibitory paired associative stimulation (PAS) at the primary motor cortex of healthy humans. Stimulation-generated cortical excitability alterations were monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. D1-like receptor activation produced an inverted U-shaped dose-response curve on plasticity induced by both facilitatory tDCS and PAS. For excitability-diminishing tDCS and PAS, aftereffects were abolished or converted trendwise into facilitation. These data extend findings of dose-dependent inverted U-shaped effects of D1 receptor activation on neuroplasticity of the motor cortex.

  1. Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients.

    PubMed

    Jaeschke, Hartmut

    2015-01-01

    Drug-induced liver injury is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure at therapeutic doses in a very limited number of patients (<1:10,000). This idiosyncratic drug-induced liver injury, which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to idiosyncratic drug-induced liver injury, drugs with dose-dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and acute liver failure after intentional and unintentional overdoses. Key Messages: APAP overdose is responsible for more acute liver failure cases in the USA or UK than all other etiologies combined. Since APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as an antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late-presenting patients. The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent acute liver failure, and also to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure

  2. Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis

    PubMed Central

    Tokumasu, Reitaro; Yamaga, Kosuke; Yamazaki, Yuji; Murota, Hiroyuki; Suzuki, Koya; Tamura, Atsushi; Bando, Kana; Furuta, Yasuhide; Katayama, Ichiro; Tsukita, Sachiko

    2016-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. It was recently noted that the characteristics of epidermal barrier functions critically influence the pathological features of AD. Evidence suggests that claudin-1 (CLDN1), a major component of tight junctions (TJs) in the epidermis, plays a key role in human AD, but the mechanism underlying this role is poorly understood. One of the main challenges in studying CLDN1's effects is that Cldn1 knock-out mice cannot survive beyond 1 d after birth, due to lethal dehydration. Here, we established a series of mouse lines that express Cldn1 at various levels and used these mice to study Cldn1’s effects in vivo. Notably, we discovered a dose-dependent effect of Cldn1’s expression in orchestrating features of AD. In our experimental model, epithelial barrier functions and morphological changes in the skin varied exponentially with the decrease in Cldn1 expression level. At low Cldn1 expression levels, mice exhibited morphological features of AD and an innate immune response that included neutrophil and macrophage recruitment to the skin. These phenotypes were especially apparent in the infant stages and lessened as the mice became adults, depending on the expression level of Cldn1. Still, these adult mice with improved phenotypes showed an enhanced hapten-induced contact hypersensitivity response compared with WT mice. Furthermore, we revealed a relationship between macrophage recruitment and CLDN1 levels in human AD patients. Our findings collectively suggest that CLDN1 regulates the pathogenesis, severity, and natural course of human AD. PMID:27342862

  3. Induced Terpene Accumulation in Norway Spruce Inhibits Bark Beetle Colonization in a Dose-Dependent Manner

    PubMed Central

    Zhao, Tao; Krokene, Paal; Hu, Jiang; Christiansen, Erik; Björklund, Niklas; Långström, Bo; Solheim, Halvor; Borg-Karlson, Anna-Karin

    2011-01-01

    Background Tree-killing bark beetles (Coleoptera, Scolytinae) are among the most economically and ecologically important forest pests in the northern hemisphere. Induction of terpenoid-based oleoresin has long been considered important in conifer defense against bark beetles, but it has been difficult to demonstrate a direct correlation between terpene levels and resistance to bark beetle colonization. Methods To test for inhibitory effects of induced terpenes on colonization by the spruce bark beetle Ips typographus (L.) we inoculated 20 mature Norway spruce Picea abies (L.) Karsten trees with a virulent fungus associated with the beetle, Ceratocystis polonica (Siem.) C. Moreau, and investigated induced terpene levels and beetle colonization in the bark. Results Fungal inoculation induced very strong and highly variable terpene accumulation 35 days after inoculation. Trees with high induced terpene levels (n = 7) had only 4.9% as many beetle attacks (5.1 vs. 103.5 attacks m−2) and 2.6% as much gallery length (0.029 m m−2 vs. 1.11 m m−2) as trees with low terpene levels (n = 6). There was a highly significant rank correlation between terpene levels at day 35 and beetle colonization in individual trees. The relationship between induced terpene levels and beetle colonization was not linear but thresholded: above a low threshold concentration of ∼100 mg terpene g−1 dry phloem trees suffered only moderate beetle colonization, and above a high threshold of ∼200 mg terpene g−1 dry phloem trees were virtually unattacked. Conclusion/Significance This is the first study demonstrating a dose-dependent relationship between induced terpenes and tree resistance to bark beetle colonization under field conditions, indicating that terpene induction may be instrumental in tree resistance. This knowledge could be useful for developing management strategies that decrease the impact of tree-killing bark beetles. PMID:22028932

  4. Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect

    PubMed Central

    Ben Boujema, Meric; Laboureyras, Emilie; Pype, Jan; Bessière, Baptiste; Simonnet, Guy

    2015-01-01

    BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury. OBJECTIVE: Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N2O concentration and the shortest time of N2O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2O with gabapentin, a reference drug used in human neuropathic pain relief. METHODS: Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats. RESULTS: Among the various N2O concentrations tested, which ranged from 25% to 50%, only 50% N2O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg/kg to 300 mg/kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N2O. CONCLUSIONS: These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies. PMID:26371891

  5. Assessing the dose-dependency of allometric scaling performance using physiologically based pharmacokinetic modeling.

    PubMed

    Kirman, C R; Sweeney, L M; Meek, M E; Gargas, M L

    2003-12-01

    The performance of allometric scaling of dose as a power of body weight under a variety of extrapolation conditions with respect to species, route, exposure intensity, and mechanism/mode of action, remains untested in many cases. In this paper, animal-human internal dose ratio comparisons have been developed for 12 chemicals (benzene, carbon tetrachloride, chloroform, diisopropylfluorophosphate, ethanol, ethylene oxide, methylene chloride, methylmercury, styrene, tetrachloroethene, trichloroethene, and vinyl chloride). This group of predominantly volatile and lipophilic chemicals was selected on the basis that their kinetics have been well-studied and can be predicted in mice, rats, and humans using physiologically based pharmacokinetic (PBPK) models. PBPK model predictions were compared to the allometric scaling predictions for interspecies extrapolation. Recommendations for the application of the allometric scaling are made with reference to internal dose measure (mode of action) and concentration level. The results of this assessment generally support the use of scaling factors recommended in the published literature, which includes scaling factors of 1.0 for risk assessments in which toxicity is attributed to the parent chemical or stable metabolite, and -0.75 for dose-response assessments in which toxicity is attributed to the formation of a reactive metabolite from an inhaled compound. A scaling factor of 0.75 is recommended for dose-response assessments of orally administered compounds in which toxicity is attributed to the parent chemical or stable metabolite and 1.0 for risk assessments in which toxicity is attributed to the formation of a reactive metabolite from a compound administered by the oral route. A dose-dependency in the results suggests that the scaling factors appropriate at high exposures may differ from those at low exposures, primarily due to the impact of saturable metabolism.

  6. Physical activity is associated with bone geometry of premenarcheal girls in a dose-dependent manner.

    PubMed

    Michalopoulou, Maria; Kambas, Antonis; Leontsini, Diamanda; Chatzinikolaou, Athanasios; Draganidis, Dimitrios; Avloniti, Alexandra; Tsoukas, Dimitrios; Michopoulou, Eleni; Lyritis, Georgios P; Papaioannou, Nikolaos; Tournis, Symeon; Fatouros, Ioannis G

    2013-12-01

    To determine the relationship between habitual physical activity (PA) level and peripheral qualitative computed tomography-determined quantitative tibia characteristics of premenarcheal girls. Premenarcheal girls matched for age (10-13 years), bone age and maturity level were assigned into: a) low PA group (LPA, n=25), b) moderate PA group (MPA, n=17), and c) high PA group (HPA, n=18). Participants' daily dietary intake, tibia's geometry and serum levels of calcium and vitamin D were assessed. Premenarcheal girls demonstrating HPA exhibited greater pericortical thickness, cross-sectional area (CSA) and bone mineral content (BMC) (p<.001) in cortical bone, greater BMC, volumetric bone density (vBMD) and polar stress strength index (SSIp) in trabecular bone (p<0.001-0.05) and greater total BMC (p<.05) and vBMD (p<.01) when compared to their physically inactive or moderately active counterparts. MPA exhibited greater values of cortical BMC (p<.01) and SSIp (p<.05) than LPA. Partial correlation analysis (adjusted for BMI) revealed modest associations between PA score and bone geometry parameters (r=0.36-0.49, p<.05) at 38% of tibia length. Habitual PA affects geometry of both cortical and trabecular areas of a long bone of premenarcheal girls in a dose-dependent manner. Specifically, PA increases both the density and size of cortical bone but only the density of trabecular bone during preadolescence. Given the importance of peak bone mass for future fracture risk, high levels of PA during childhood could be a major target for public health interventions aimed at optimising bone health in prepubertal children when the greatest bone gains occur. © 2013.

  7. Dose dependence of mechanical properties in tantalum and tantalum alloys after low temperature irradiation

    SciTech Connect

    Byun, Thak Sang

    2008-01-01

    The dose dependence of mechanical properties was investigated for tantalum and tantalum alloys after low temperature irradiation. Miniature tensile specimens of three pure tantalum metals, ISIS Ta, Aesar Ta1, Aesar Ta2, and one tantalum alloy, Ta-1W, were irradiated by neutrons in the High Flux Isotope Reactor (HFIR) at ORNL to doses ranging from 0.00004 to 0.14 displacements per atom (dpa) in the temperature range 60 C 100 oC. Also, two tantalum-tungsten alloys, Ta-1W and Ta-10W, were irradiated by protons and spallation neutrons in the LANSCE facility at LANL to doses ranging from 0.7 to 7.5 dpa and from 0.7 to 25.2 dpa, respectively, in the temperature range 50 C 160 oC. Tensile tests were performed at room temperature and at 250oC at nominal strain rates of about 10-3 s-1. All neutron-irradiated materials underwent progressive irradiation hardening and loss of ductility with increasing dose. The ISIS Ta experienced embrittlement at 0.14 dpa, while the other metals retained significant necking ductility. Such a premature embrittlement in ISIS Ta is believed to be because of high initial oxygen concentrations picked up during a pre-irradiation anneal. The Ta-1W and Ta-10W specimens irradiated in spallation condition experienced prompt necking at yield since irradiation doses for those specimens were high ( 0.7 dpa). At the highest dose, 25.2 dpa, the Ta-10W alloy specimen broke with little necking strain. Among the test materials, the Ta-1W alloy displayed the best combination of strength and ductility. The plastic instability stress and true fracture stress were nearly independent of dose. Increasing test temperature decreased strength and delayed the onset of necking at yield.

  8. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

    PubMed Central

    Balaguer-Ballester, Emili; Seamans, Jeremy K.; Phillips, Anthony G.; Durstewitz, Daniel

    2015-01-01

    Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. PMID:26180194

  9. Dose-dependent effects of dietary nitrate on the oxygen cost of moderate-intensity exercise: Acute vs. chronic supplementation.

    PubMed

    Wylie, Lee J; Ortiz de Zevallos, Joaquin; Isidore, Taro; Nyman, Lara; Vanhatalo, Anni; Bailey, Stephen J; Jones, Andrew M

    2016-07-01

    To investigate whether chronic supplementation with a low or moderate dose of dietary nitrate (NO3(-)) reduces submaximal exercise oxygen uptake (V˙O2) and to assess whether or not this is dependent on acute NO3(-) administration prior to exercise. Following baseline tests, 34 healthy subjects were allocated to receive 3 mmol NO3(-), 6 mmol NO3(-) or placebo. Two hours following the first ingestion, and after 7, 28 and 30 days of supplementation, subjects completed two moderate-intensity step exercise tests. On days 28 and 30, subjects in the NO3(-) groups completed the test 2 h post consumption of a NO3(-) dose (CHR + ACU) and a placebo dose (CHR). Plasma nitrite concentration ([NO2(-)]) was elevated in a dose-dependent manner at 2 h, 7 days and 28-30 days on the CHR + ACU visit. Compared to pre-treatment baseline, 6 mmol NO3(-) reduced the steady-state V˙O2 during moderate-intensity exercise by 3% at 2 h (P = 0.06), 7 days and at 28-30 days (both P < 0.05) on the CHR + ACU visit, but was unaffected by 3 mmol NO3(-) at all measurement points. On the CHR visit in the 6 mmol group, plasma [NO2(-)] had returned to pre-treatment baseline, but the steady-state V˙O2 remained reduced. Up to ∼4 weeks supplementation with 6 but not 3 mmol NO3(-) can reduce submaximal exercise V˙O2. A comparable reduction in submaximal exercise V˙O2 following chronic supplementation with 6 mmol NO3(-) can be achieved both with and without the acute ingestion of NO3(-) and associated elevation of plasma [NO2(-)]. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Dose-dependent effects of isoflavone exposure during early lifetime on the rat mammary gland: Studies on estrogen sensitivity, isoflavone metabolism, and DNA methylation.

    PubMed

    Blei, Tina; Soukup, Sebastian T; Schmalbach, Katja; Pudenz, Maria; Möller, Frank Josef; Egert, Björn; Wörtz, Nadine; Kurrat, Anne; Müller, Dennis; Vollmer, Günter; Gerhäuser, Clarissa; Lehmann, Leane; Kulling, Sabine E; Diel, Patrick

    2015-02-01

    Isoflavone (ISO) exposure during adolescence modulates 17β-estradiol (E2) sensitivity of the adult mammary gland. The present study investigated the dose dependency of these effects focusing on proliferation, estrogen receptor dependent and independent gene expression, as well as DNA methylation and ISO metabolism. Female Wistar rats were lifelong exposed to an ISO-depleted diet or to diets enriched with a soy ISO extract (ISO-rich diet (IRD)) causing plasma concentrations as observed minimally (IRDlow) and maximally (IRDhigh) in Asian women. The extract was characterized by both phytochemical analysis and E-Screen. Rats were ovariectomized at postnatal day (PND) 80 and treated with E2 from PND94 to 97. In contrast to uterine response, body weight and visceral fat mass were affected by ISO. In the mammary gland, both E2-induced proliferation (proliferating cell nuclear antigen staining) and estrogen receptor activation (progesterone receptor staining) were significantly reduced by IRDhigh but not by IRDlow, which however attenuated Gdf15 mRNA expression. DNA methylation analysis revealed significant differences in the promoter regions of Aldhl1, Extl1, and WAP between IRDhigh and ISO-depleted diet. Lifelong exposure to ISO results in dose-dependent differential effects on proliferation, gene expression, and DNA methylation in rat mammary glands. Yet, a decrease in estrogen responsiveness was only achieved by IRDhigh. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na(+) channels of cortical neurons is time- and dose-dependent.

    PubMed

    Xia, Wei; Peng, Guo-Yi; Sheng, Jiang-Tao; Zhu, Fang-Fang; Guo, Jing-Fang; Chen, Wei-Qiang

    2015-04-01

    Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL) and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours) by studying voltage-gated Na(+) channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na(+) currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na(+) channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  12. Dose-dependent and cell type-specific cell death and proliferation following in vitro exposure to radial extracorporeal shock waves

    PubMed Central

    Hochstrasser, Tanja; Frank, Hans-Georg; Schmitz, Christoph

    2016-01-01

    Radial extracorporeal shock wave (rESW) therapy is widely used in musculoskeletal disorders and wound repair. However, the mechanisms of action are still largely unknown. The current study compared the effects of rESWs on two cell types. Human fetal foreskin fibroblasts (HFFF2) and human placental choriocarcinoma cell line JEG-3 were exposed to 0, 100, 200, 500 or 5000 rESWs generated with a Swiss DolorClast device (2.5 bar, 1 Hz). FACS analysis immediately after rESW exposure showed that initially, rESWs rather induced mechanical cell destruction than regulated or programmed cell death. Cell damage was nearly negated by reducing cavitation. Furthermore, cell viability decreased progressively with higher numbers of rESWs. Exposure to rESWs had no impact on growth potential of JEG-3 cells, but dose-dependently increased growth potential of HFFF2 cells. Cultivation of cells that were initially exposed to sham-rESWs in conditioned media increased the growth potential of HFFF2 cells, nevertheless, an even stronger effect was achieved by direct exposure to rESWs. Additionally, cell cycle distribution analysis demonstrated a shift in proportion from G0/G1 to G2/M phase in HFFF2 cells, but not in JEG-3 cells. These data demonstrate that rESWs leads to initial and subsequent dose-dependent and cell type-specific effects in vitro. PMID:27477873

  13. A systematic review to evaluate exercise for anterior cruciate ligament injuries: does this approach reduce the incidence of knee osteoarthritis?

    PubMed Central

    Duncan, Koji J; Chopp-Hurley, Jaclyn N; Maly, Monica R

    2016-01-01

    Purpose Among a variety of conservative and surgical options to treat anterior cruciate ligament (ACL) injuries, we do not understand which options could potentially prevent knee osteoarthritis (OA). The aim of this systematic review was to examine the evidence pertaining to exercise treatment of ACL injuries in the context of knee OA. Methods Medline, Embase, CINAHL, PubMed, and PEDro (Physiotherapy Evidence Database) databases were systematically searched using keywords encompassed within four primary key terms: knee, osteoarthritis, anterior cruciate ligament, and exercise. Clinical studies evaluating the effect of an exercise treatment for ACL injuries on the development of knee OA in adult humans were included. The PEDro scale was used to critically assess the studies included in the review. Results Eighteen studies were included in this review, with a median PEDro score of 6/11 (range, 2/11–9/11). Three studies provided statistical evidence that exercise following ACL injury lowered the risk for knee OA development. Nine studies demonstrated no benefit of exercise in preventing knee OA incidence relative to either operative treatment or the contralateral, unaffected knee. However, exercise resulted in higher knee instability. Nonetheless, there were no significant differences in subjective or objective knee outcomes for early versus late ACL reconstruction. Limitations This review was not registered through PROSPERO. Conclusion The relationship between a rehabilitative exercise for ACL injuries and long-term knee OA prevalence is inconclusive. However, research suggests initial conservative treatment with optional late ACL reconstruction because this treatment strategy may reduce the risk of knee OA. More research, ideally randomized controlled trials or comparable designs, is required prior to establishing clinical guidelines for ACL injury management. PMID:27843365

  14. Quantitative simulation of intracellular signaling cascades in a Virtual Liver: estimating dose dependent changes in hepatocellular proliferation and apoptosis

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver™) is developing an approach to predict dose-dependent hepatotoxicity as an in vivo tissue level response using in vitro data. The v-Liver accomplishes this using an in silico agent-based systems model that dynamically integrates environmental exp...

  15. Quantitative simulation of intracellular signaling cascades in a Virtual Liver: estimating dose dependent changes in hepatocellular proliferation and apoptosis

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver™) is developing an approach to predict dose-dependent hepatotoxicity as an in vivo tissue level response using in vitro data. The v-Liver accomplishes this using an in silico agent-based systems model that dynamically integrates environmental exp...

  16. Dose-dependent effects on survival of Salmonella enterica serovar Typhimurium in house flies (Musca domestica L.)

    USDA-ARS?s Scientific Manuscript database

    Adult house flies ingest variable numbers of bacteria when they encounter microbe-rich substrates. Bacterial abundance may affect survival within the fly gut, which subsequently impacts vector potential. This study investigated the dose-dependent survival of GFP-expressing Salmonella enterica serova...

  17. Green tea consumption is associated with reduced incident CHD and improved CHD-related biomarkers in the Dongfeng-Tongji cohort.

    PubMed

    Tian, Chong; Huang, Qiao; Yang, Liangle; Légaré, Sébastien; Angileri, Francesca; Yang, Handong; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Yuan, Jing; Miao, Xiaoping; He, Mei-an; Wu, Tangchun; Zhang, Xiaomin

    2016-04-13

    Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19,471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers.

  18. Green tea consumption is associated with reduced incident CHD and improved CHD-related biomarkers in the Dongfeng-Tongji cohort

    PubMed Central

    Tian, Chong; Huang, Qiao; Yang, Liangle; Légaré, Sébastien; Angileri, Francesca; Yang, Handong; Li, Xiulou; Min, Xinwen; Zhang, Ce; Xu, Chengwei; Yuan, Jing; Miao, Xiaoping; He, Mei-an; Wu, Tangchun; Zhang, Xiaomin

    2016-01-01

    Prospective studies on the association of green tea with risk of coronary heart disease (CHD) incidence were scarce. This study examined whether green tea can reduce CHD incidence and have a beneficial effect on CHD-related risk markers in middle-aged and older Chinese population. We included 19 471 participants who were free of CHD, stroke or cancer at baseline from September 2008 to June 2010, and were followed until October 2013. Cox proportional hazard models were used to examine the hazard ratios (HR) of CHD incidence in relation to green tea consumption. Linear regression models were used to evaluate the effect of green tea on 5-year changes of CHD-related biomarkers. Compared with non-green tea consumers, the multivariable-adjusted HR for CHD was 0.89 (95% CI, 0.81-0.98) in green tea consumers. Particularly, the reduced risk of CHD incidence with green tea consumption was more evident among participants who were male, more than 60 years old, overweight, or with diabetes mellitus. In addition, green tea consumption improved multiple CHD-related risk markers including total cholesterol, HDL-cholesterol, triglycerides, mean platelet volume, and uric acid. In conclusion, green tea consumption was associated with a reduced risk of CHD incidence in the middle-aged and older Chinese populations, and the association might be partly due to altered CHD-related biomarkers. PMID:27072746

  19. A dose-dependent perturbation in cardiac energy metabolism is linked to radiation-induced ischemic heart disease in Mayak nuclear workers.

    PubMed

    Azimzadeh, Omid; Azizova, Tamara; Merl-Pham, Juliane; Subramanian, Vikram; Bakshi, Mayur V; Moseeva, Maria; Zubkova, Olga; Hauck, Stefanie M; Anastasov, Nataša; Atkinson, Michael J; Tapio, Soile

    2017-02-07

    Epidemiological studies show a significant increase in ischemic heart disease (IHD) incidence associated with total external gamma-ray dose among Mayak plutonium enrichment plant workers. Our previous studies using mouse models suggest that persistent alteration of heart metabolism due to the inhibition of peroxisome proliferator-activated receptor (PPAR) alpha accompanies cardiac damage after high doses of ionising radiation. The aim of the present study was to elucidate the mechanism of radiation-induced IHD in humans. The cardiac proteome response to irradiation was analysed in Mayak workers who were exposed only to external doses of gamma rays. All participants were diagnosed during their lifetime with IHD that also was the cause of death. Label-free quantitative proteomics analysis was performed on tissue samples from the cardiac left ventricles of individuals stratified into four radiation dose groups (0 Gy, < 100 mGy, 100-500 mGy, and > 500 mGy). The groups could be separated using principal component analysis based on all proteomics features. Proteome profiling showed a dose-dependent increase in the number of downregulated mitochondrial and structural proteins. Both proteomics and immunoblotting showed decreased expression of several oxidative stress responsive proteins in the irradiated hearts. The phosphorylation of transcription factor PPAR alpha was increased in a dose-dependent manner, which is indicative of a reduction in transcriptional activity with increased radiation dose. These data suggest that chronic external radiation enhances the risk for IHD by inhibiting PPAR alpha and altering the expression of mitochondrial, structural, and antioxidant components of the heart.

  20. Incidence and risk factors for moderate-to-severe veno-occlusive disease of the liver after allogeneic stem cell transplantation using a reduced intensity conditioning regimen.

    PubMed

    Tsirigotis, P D; Resnick, I B; Avni, B; Grisariu, S; Stepensky, P; Or, R; Shapira, M Y

    2014-11-01

    The incidence and outcome of moderate-to-severe veno-occlusive (VOD) disease was analyzed in 271 consecutive patients with hematological malignancies who underwent allogeneic SCT (allo-SCT) using the same reduced intensity regimen (RIC). RIC consisted of fludarabine, BU and antithymocyte globulin (ATG). Twenty-four out of 271 patients (8.8%) developed VOD, which was severe in only 4 (1.4%) out of 24 cases. All four patients with severe VOD finally succumbed to their disease. In multivariate analysis, i.v. administration of BU was associated with significant reduced incidence of VOD as compared with per os administration. In conclusion, VOD remains a serious complication of allo-SCT using RIC regimens containing BU. Although the incidence of severe VOD is very low, the overall mortality rate in the group of patients with severe VOD remains extremely high and therefore novel treatment approaches are needed.

  1. Time- and dose-dependent effects of roundup on human embryonic and placental cells.

    PubMed

    Benachour, N; Sipahutar, H; Moslemi, S; Gasnier, C; Travert, C; Séralini, G E

    2007-07-01

    Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.

  2. Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome

    PubMed Central

    2014-01-01

    Background Environmental factors during perinatal development may influence developmental plasticity and disease susceptibility via alterations to the epigenome. Developmental exposure to the endocrine active compound, bisphenol A (BPA), has previously been associated with altered methylation at candidate gene loci. Here, we undertake the first genome-wide characterization of DNA methylation profiles in the liver of murine offspring exposed perinatally to multiple doses of BPA through the maternal diet. Results Using a tiered focusing approach, our strategy proceeds from unbiased broad DNA methylation analysis using methylation-based next generation sequencing technology to in-depth quantitative site-specific CpG methylation determination using the Sequenom EpiTYPER MassARRAY platform to profile liver DNA methylation patterns in offspring maternally exposed to BPA during gestation and lactation to doses ranging from 0 BPA/kg (Ctr), 50 μg BPA/kg (UG), or 50 mg BPA/kg (MG) diet (N = 4 per group). Genome-wide analyses indicate non-monotonic effects of DNA methylation patterns following perinatal exposure to BPA, corroborating previous studies using multiple doses of BPA with non-monotonic outcomes. We observed enrichment of regions of altered methylation (RAMs) within CpG island (CGI) shores, but little evidence of RAM enrichment in CGIs. An analysis of promoter regions identified several hundred novel BPA-associated methylation events, and methylation alterations in the Myh7b and Slc22a12 gene promoters were validated. Using the Comparative Toxicogenomics Database, a number of candidate genes that have previously been associated with BPA-related gene expression changes were identified, and gene set enrichment testing identified epigenetically dysregulated pathways involved in metabolism and stimulus response. Conclusions In this study, non-monotonic dose dependent alterations in DNA methylation among BPA-exposed mouse liver samples and their relevant pathways

  3. Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis

    PubMed Central

    Zhu, Ling-Yan; Li, Yu; Yu, Jiao; Wang, Jiao; Zeng, Xiang-Xia; Hu, Kai-Xiang; Liu, Jian-Ying

    2017-01-01

    Studies have suggested that metformin can potentially decrease the incidence of cancer and improve survival outcomes. However, the association between metformin use and the incidence and survival of endometrial cancer (EC) remains controversial. So, a meta-analysis was performed. An electronic search was conducted using PubMed, EMBASE, and Web of Science. The outcome measures were relative risks (RRs) or hazard ratios (HRs) with 95% confidence intervals (CIs) comparing the EC incidence and survival in patients treated with and without metformin. Eleven studies involving 766,926 participants were included in this study. In the pooled analysis of five studies which evaluated the association of metformin use with the incidence of EC, we found that metformin use was associated with a 13% reduction in EC risk among patients with diabetes (RR = 0.87, 95% CI: 0.80–0.95; p = 0.006). In the pooled analysis of six retrospective cohort studies evaluating the effect of metformin on the survival of EC patients, we found that, relative to nonuse, metformin use significantly improved the survival of EC patients (HR = 0.63, 95% CI: 0.45–0.87; p = 0.006). This study showed that metformin use was significantly associated with a decreased incidence of EC in diabetes and a favorable survival outcome of EC patients. PMID:28409158

  4. Physician Decisions to Defer Antiretroviral Therapy in Key Populations: Implications for Reducing Human Immunodeficiency Virus Incidence and Mortality in Malaysia

    PubMed Central

    Ferro, Enrico G.; Culbert, Gabriel J.; Wickersham, Jeffrey A.; Marcus, Ruthanne; Steffen, Alana D.; Pauls, Heather A.; Westergaard, Ryan P.; Lee, Christopher K.; Kamarulzaman, Adeeba

    2017-01-01

    Abstract Background. Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. Methods. Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV. Results. The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8–36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5–5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44–.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34–.57) were significantly less likely to have ART deferred. Conclusions. Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence

  5. A transcription activator-like effector from Xanthomonas oryzae pv. oryzicola elicits dose-dependent resistance in rice.

    PubMed

    Hummel, Aaron W; Wilkins, Katherine E; Wang, Li; Cernadas, R Andres; Bogdanove, Adam J

    2017-01-01

    Xanthomonas spp. reduce crop yields and quality worldwide. During infection of their plant hosts, many strains secrete transcription activator-like (TAL) effectors, which enter the host cell nucleus and activate specific corresponding host genes at effector binding elements (EBEs) in the promoter. TAL effectors may contribute to disease by activating the expression of susceptibility genes or trigger resistance associated with the hypersensitive reaction (HR) by activating an executor resistance (R) gene. The rice bacterial leaf streak pathogen X. oryzae pv. oryzicola (Xoc) is known to suppress host resistance, and no host R gene has been identified against it, despite considerable effort. To further investigate Xoc suppression of host resistance, we conducted a screen of effectors from BLS256 and identified Tal2a as an HR elicitor in rice when delivered heterologously by a strain of the closely related rice bacterial blight pathogen X. oryzae pv. oryzae (Xoo) or by the soybean pathogen X. axonopodis pv. glycines. The HR required the Tal2a activation domain, suggesting an executor R gene. Tal2a activity was differentially distributed among geographically diverse Xoc isolates, being largely conserved among Asian isolates. We identified four genes induced by Tal2a in next-generation RNA sequencing experiments and confirmed them using quantitative real-time reverse transcription-polymerase chain reaction (qPCR). However, neither individual nor collective activation of these genes by designer TAL effectors resulted in HR. A tal2a knockout mutant of BLS256 showed virulence comparable with the wild-type, but plasmid-based overexpression of tal2a at different levels in the wild-type reduced virulence in a directly corresponding way. Overall, the results reveal that host resistance suppression by Xoc plays a critical role in pathogenesis. Further, the dose-dependent avirulence activity of Tal2a and the apparent lack of a single canonical target that accounts for HR point to

  6. Dose-Dependent ATP Depletion and Cancer Cell Death following Calcium Electroporation, Relative Effect of Calcium Concentration and Electric Field Strength

    PubMed Central

    Hansen, Emilie Louise; Sozer, Esin Bengisu; Romeo, Stefania; Frandsen, Stine Krog; Vernier, P. Thomas; Gehl, Julie

    2015-01-01

    Background Electroporation, a method for increasing the permeability of membranes to ions and small molecules, is used in the clinic with chemotherapeutic drugs for cancer treatment (electrochemotherapy). Electroporation with calcium causes ATP (adenosine triphosphate) depletion and cancer cell death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy. Methods In three human cell lines — H69 (small-cell lung cancer), SW780 (bladder cancer), and U937 (leukaemia), viability was determined after treatment with 1, 3, or 5 mM calcium and eight 99 μs pulses with 0.8, 1.0, 1.2, 1.4 or 1.6 kV/cm. Fitting analysis was applied to quantify the cell-killing efficacy in presence of calcium. Post-treatment intracellular ATP was measured in H69 and SW780 cells. Post-treatment intracellular ATP was observed with fluorescence confocal microscopy of quinacrine-labelled U937 cells. Results Both H69 and SW780 cells showed dose-dependent (calcium concentration and electric field) decrease in intracellular ATP (p<0.05) and reduced viability. The 50% effective cell kill was found at 3.71 kV/cm (H69) and 3.28 kV/cm (SW780), reduced to 1.40 and 1.15 kV/cm (respectively) with 1 mM calcium (lower EC50 for higher calcium concentrations). Quinacrine fluorescence intensity of calcium-electroporated U937 cells was one third lower than in controls (p<0.0001). Conclusions Calcium electroporation dose-dependently reduced cell survival and intracellular ATP. Increasing extracellular calcium allows the use of a lower electric field. General Significance This study supports the use of calcium electroporation for treatment of cancer and possibly lowering the applied electric field in future trials. PMID:25853661

  7. An evaluation of early countermeasures to reduce the risk of internal radiation exposure after the Fukushima nuclear incident in Japan.

    PubMed

    Nomura, Shuhei; Tsubokura, Masaharu; Gilmour, Stuart; Hayano, Ryugo S; Watanabe, Yuni N; Kami, Masahiro; Kanazawa, Yukio; Oikawa, Tomoyoshi

    2016-05-01

    After a radiation-release incident, intake of radionuclides in the initial stage immediately following the incident may be the major contributor to total internal radiation exposure for individuals in affected areas. However, evaluation of early internal contamination risk is greatly lacking. This study assessed the relationship between initial stage evacuation/indoor sheltering and internal radiation contamination levels 4 months after the 2011 Fukushima nuclear incident in Japan and estimated potential pathways of the contamination. The study population comprised 525 participants in the internal radiation screening program at Minamisoma Municipal General Hospital, 23 km north of the Fukushima nuclear plant. The analysed dataset included the results of a screening performed in July 2011, 4 months after the incident, and of a questionnaire on early-incident response behaviours, such as sheltering indoors and evacuations, completed by participants. Association between such early countermeasures and internal contamination levels of cesium-134 were assessed using Tobit multiple regression analyses. Our study shows that individuals who evacuated to areas outside Fukushima Prefecture had similar contamination levels of cesium-134 to individuals who stayed in Fukushima (relative risk: 0.86; 95% confidence interval: 0.74-0.99). Time spent outdoors had no significant relationship with contamination levels. The effects of inhalation from radiological plumes released from the nuclear plant on total internal radiation contamination might be so low as to be undetectable by the whole-body counting unit used to examine participants. Given the apparent limited effectiveness of evacuation and indoor sheltering on internal contamination, the decision to implement such early responses to a radiation-release incident should be made by carefully balancing their potential benefits and health risks. © The Author 2015. Published by Oxford University Press. All rights reserved. For

  8. Combined use of alcohol hand rub and gloves reduces the incidence of late onset infection in very low birthweight infants

    PubMed Central

    Ng, P; Wong, H; Lyon, D; So, K; Liu, F; Lam, R; Wong, E; Cheng, A; Fok, T

    2004-01-01

    Objective: To assess the incidence of late onset (> 72 hours) infection and necrotising enterocolitis (NEC) in very low birthweight (VLBW) infants in two 36 month periods using two hand hygiene protocols: conventional handwashing (HW; first 36 month period); an alcohol hand rub and gloves technique (HR; second 36 month period). Method: VLBW infants admitted to the neonatal intensive care unit during the period December 1993–November 1999 were eligible. A new hand hygiene protocol using alcohol handrub and gloves was introduced in December 1996. Each patient's case record was reviewed retrospectively by two independent investigators using a standard data collection form. The incidence of NEC and systemic infections, including bacterial or fungal septicaemia, meningitis, and peritonitis, in the two periods were compared. Results: The HW and HR groups contained 161 and 176 VLBW infants respectively. The incidence of late onset systemic infection decreased from 13.5 to 4.8 episodes (including NEC)/1000 patient days after introduction of the HR regimen, representing a 2.8-fold reduction. Similarly, the incidence of Gram positive, Gram negative, and fungal infections decreased 2.5-fold, 2.6-fold, and 7-fold respectively. There was also a significant reduction in the incidence of NEC in the HR group (p < 0.0001). Subgroup analysis revealed that the incidence of methicillin resistant Staphylococcus aureus (MRSA) septicaemia was significantly decreased in the second 36 month period (p  =  0.048). The clinical data suggest that infants in the HW group had significantly earlier onset of sepsis (p < 0.05) and required oxygen supplementation for longer (p < 0.05) than those in the HR group. Significantly more VLBW infants were discharged from the neonatal intensive care unit without ever being infected (p < 0.0001), and also significantly fewer infants had more than one episode of infection in the HR group (p < 0.0001). Conclusion: The introduction of the HR

  9. Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer

    PubMed Central

    Steiner, JL; Davis, JM; McClellan, JL; Enos, RT; Carson, JA; Fayad, R; Nagarkatti, M; Nagarkatti, PS; Altomare, D; Creek, KE; Murphy, EA

    2014-01-01

    Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15–16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted ‘U’ dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most efficacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2%: 7.3 ± 0.9) and (C3-Con: 2061.8 ± 977.0 mm3; and C3-0.2%: 462.9 ± 75.9 mm3). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 ± 305.9 mm3; C3-0.02%: 1401.5 ± 555.6 mm3), as was tumor number (C3-2%: 10.7 ± 1.3 mm3; C3-0.02%: 8.1 ± 1.1 mm3). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment. PMID:25482952

  10. High salt diets dose-dependently promote gastric chemical carcinogenesis in Helicobacter pylori-infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells.

    PubMed

    Kato, Sosuke; Tsukamoto, Tetsuya; Mizoshita, Tsutomu; Tanaka, Harunari; Kumagai, Toshiko; Ota, Hiroyoshi; Katsuyama, Tsutomu; Asaka, Masahiro; Tatematsu, Masae

    2006-10-01

    Intake of salt and salty food is known as a risk factor for gastric carcinogenesis. To examine the dose-dependence and the mechanisms underlying enhancing effects, Mongolian gerbils were treated with N-methyl-N-nitrosourea (MNU), Helicobacter pylori and food containing various concentrations of salt, and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori, the incidences of glandular stomach cancers were 15% in the normal diet group and 33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose-dependent increase (p < 0.01). Intermittent intragastric injection of saturated NaCl solution, in contrast, did not promote gastric carcinogenesis. In gerbils infected with H. pylori, a high salt diet was associated with elevation of anti-H. pylori antibody titers, serum gastrin levels and inflammatory cell infiltration in a dose-dependent fashion. Ten percent NaCl diet upregulated the amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori colonization, despite no increment of MUC5AC mRNA, while H. pylori infection itself had an opposing effect, stimulating transcription of MUC6 and increasing the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased the amount of GMCM, which acts against H. pylori infection. In conclusion, the present study demonstrated dose-dependent enhancing effects of salt in gastric chemical carcinogenesis in H. pylori-infected Mongolian gerbils associated with alteration of the mucous microenvironment. Reduction of salt intake could thus be one of the most important chemopreventive methods for human gastric carcinogenesis.

  11. Hand washing with soap and WASH educational intervention reduces under-five childhood diarrhoea incidence in Jigjiga District, Eastern Ethiopia: A community-based cluster randomized controlled trial.

    PubMed

    Hashi, Abdiwahab; Kumie, Abera; Gasana, Janvier

    2017-06-01

    Despite the tremendous achievement in reducing child mortality and morbidity in the last two decades, diarrhoea is still a major cause of morbidity and mortality among children in many developing countries, including Ethiopia. Hand washing with soap promotion, water quality improvements and improvements in excreta disposal significantly reduces diarrhoeal diseases. The objective of this study was to evaluate the effect of hand washing with soap and water, sanitation and hygiene (WASH) educational Intervention on the incidence of under-five children diarrhoea. A community-based cluster randomized controlled trial was conducted in 24 clusters (sub-Kebelles) in Jigjiga district, Somali region, Eastern Ethiopia from February 1 to July 30, 2015. The trial compared incidence of diarrhoea among under-five children whose primary caretakers receive hand washing with soap and water, sanitation, hygiene educational messages with control households. Generalized estimating equation with a log link function Poisson distribution family was used to compute adjusted incidence rate ratio and the corresponding 95% confidence interval. The results of this study show that the longitudinal adjusted incidence rate ratio (IRR) of diarrhoeal diseases comparing interventional and control households was 0.65 (95% CI 0.57, 0.73) suggesting an overall diarrhoeal diseases reduction of 35%. The results are similar to other trials of WASH educational interventions and hand washing with soap. In conclusion, hand washing with soap practice during critical times and WASH educational messages reduces childhood diarrhoea in the rural pastoralist area.

  12. Reducing the incidence of Obstetric Sphincter Injuries using a hands-on technique: an interventional quality improvement project

    PubMed Central

    Rasmussen, Ole Bredahl; Yding, Annika; Anh Ø, Jacob; Sander Andersen, Charlotte; Boris, Jane

    2016-01-01

    A main concern for women giving birth is the risk of obstetric anal sphincter injuries. In our department the incidence of sphincter injuries was around 8 % among vaginally delivering first time mothers. We aimed to halve the incidence to 4 % or less. A prospective interventional program was instituted. We implemented a hands-on technique with four elements in a bundle of care together with a certification process for all staff on the delivery ward. The incidence of episiotomies served as a balancing indicator. The adherence to three of the four elements of the care bundle rose significantly while the all-or-nothing indicator leveled around 80 %. The median number of deliveries between cases with a sphincter injury increased from 9.5 in the baseline period to 20 during the intervention period. This corresponded with a reduction in the incidence from 7.0 % to 3.4 %. The rate of episiotomy remained low at 8.4 % in this group. By implementing the hands-on technique, we halved the risk of obstetric anal sphincter injuries. Our data suggest that further improvement may be anticipated. The study has demonstrated how implementation of a hands-on technique can be carried out within a quality improvement framework with rapid and sustainable results. PMID:28074131

  13. Reduced incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate vaccine in Navarre, Spain, 2001-2013.

    PubMed

    Guevara, Marcela; Ezpeleta, Carmen; Gil-Setas, Alberto; Torroba, Luis; Beristain, Xabier; Aguinaga, Aitziber; García-Irure, José Javier; Navascués, Ana; García-Cenoz, Manuel; Castilla, Jesús

    2014-05-07

    Pneumococcal conjugate vaccines (PCVs) were licensed for use in children and became available for private purchase in Spain in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). This study evaluates changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, between the period of use of PCV7 (2004-2009) and that of PCV13 (2010-2013). The percentage of children <2 years who received at least one dose of PCV in these periods ranged from 25 to 61% and 61 to 78%, respectively. Between the periods 2004-2009 and 2010-2013 IPD incidence declined by 37%, from 14.9 to 9.4 cases/100,000 inhabitants (p<0.001). In children <5 years it fell by 69% (p<0.001), in persons aged 5-64 years, by 34% (p<0.001), and in those ≥ 65, by 23% (p=0.024). The incidence of cases due to PCV13 serotypes declined by 81% (p<0.001) in children <5 years and by 52% (p<0.001) in the whole population. No significant changes were seen in the distribution of clinical presentations or in disease severity. The incidence of IPD has declined and the pattern of serotypes causing IPD has changed notably in children and moderately in adults following the replacement of PCV7 by PCV13.

  14. Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

    PubMed

    Alsbeih, Ghazi A; Al-Harbi, Najla M; Bin Judia, Sara S; Khoja, Hatim A; Shoukri, Mohamed M; Tulbah, Asma M

    2017-07-01

    Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003). Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  15. Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese.

    PubMed

    Tan, E-K; Tan, C; Fook-Chong, S M C; Lum, S Y; Chai, A; Chung, H; Shen, H; Zhao, Y; Teoh, M L; Yih, Y; Pavanni, R; Chandran, V R; Wong, M C

    2003-12-15

    Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

  16. Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients.

    PubMed

    Rosenzwajg, Michelle; Churlaud, Guillaume; Mallone, Roberto; Six, Adrien; Dérian, Nicolas; Chaara, Wahiba; Lorenzon, Roberta; Long, S Alice; Buckner, Jane H; Afonso, Georgia; Pham, Hang-Phuong; Hartemann, Agnès; Yu, Aixin; Pugliese, Alberto; Malek, Thomas R; Klatzmann, David

    2015-04-01

    Most autoimmune diseases (AID) are linked to an imbalance between autoreactive effector T cells (Teffs) and regulatory T cells (Tregs). While blocking Teffs with immunosuppression has long been the only therapeutic option, activating/expanding Tregs may achieve the same objective without the toxicity of immunosuppression. We showed that low-dose interleukin-2 (ld-IL-2) safely expands/activates Tregs in patients with AID, such HCV-induced vasculitis and Type 1 Diabetes (T1D). Here we analyzed the kinetics and dose-relationship of IL-2 effects on immune responses in T1D patients. Ld-IL-2 therapy induced a dose-dependent increase in CD4(+)Foxp3(+) and CD8(+)Foxp3(+) Treg numbers and proportions, the duration of which was markedly dose-dependent. Tregs expressed enhanced levels of activation markers, including CD25, GITR, CTLA-4 and basal pSTAT5, and retained a 20-fold higher sensitivity to IL-2 than Teff and NK cells. Plasma levels of regulatory cytokines were increased in a dose-dependent manner, while cytokines linked to Teff and Th17 inflammatory cells were mostly unchanged. Global transcriptome analyses showed a dose-dependent decrease in immune response signatures. At the highest dose, Teff responses against beta-cell antigens were suppressed in all 4 patients tested. These results inform of broader changes induced by ld-IL-2 beyond direct effects on Tregs, and relevant for further development of ld-IL-2 for therapy and prevention of T1D, and other autoimmune and inflammatory diseases.

  17. Statins dose-dependently exert a significant chemopreventive effect on colon cancer in patients with chronic obstructive pulmonary disease: A population-based cohort study

    PubMed Central

    Hsu, Yi-Ping; Sung, Li-Chin; Kao, Pai-Feng; Lin, Chao-Feng; Wu, Alexander T.H.; Yuan, Kevin Sheng-Po; Wu, Szu-Yuan

    2016-01-01

    Purpose We evaluated the chemopreventive effect of statins on colon cancer in patients with chronic obstructive pulmonary disease (COPD) and identified the statin exerting the strongest chemopreventive effect. Methods Using the National Health Insurance Research Database, we identified patients who received a COPD diagnosis in Taiwan between January 1, 2001, and December 31, 2012, and included them in the study cohort. Each patient was followed to assess the colon cancer risk and protective factors. A propensity score was derived using a logistic regression model to estimate the effect of statins by accounting for covariates predicted during the intervention (statins). To examine the dose–response relationship, we categorized statin doses into four groups in each cohort [<28, 28–90, 91–365, and >365 cumulative defined daily dose]. Results Compared with the statin nonusers, the adjusted hazard ratio (aHR) for colon cancer decreased in the statin users (aHR = 0.52, 95% confidence interval = 0.44, 0.62). Hydrophilic statins exerted a stronger preventive effect against colon cancer. Regarding the statin type, lovastatin, pravastatin, and fluvastatin nonsignificantly reduced the colon cancer risk in the patients with COPD. Compared with the statin nonusers, the aHRs for colon cancer decreased in the individual statin users (rosuvastatin, simvastatin, and atorvastatin: aHRs = 0.28, 0.64, and 0.65, respectively). In the sensitivity analysis, statins dose-dependently reduced the colon cancer risk. Conclusions Statins dose-dependently exert significant chemopreventive effects on colon cancer in patients with COPD, with rosuvastatin exerting the largest chemopreventive effect. PMID:27542242

  18. Dose-dependent biodistribution of prenatal exposure to rutile-type titanium dioxide nanoparticles on mouse testis

    NASA Astrophysics Data System (ADS)

    Kubo-Irie, Miyoko; Uchida, Hiroki; Mastuzawa, Shotaro; Yoshida, Yasuko; Shinkai, Yusuke; Suzuki, Kenichiro; Yokota, Satoshi; Oshio, Shigeru; Takeda, Ken

    2014-02-01

    Titanium dioxide nanoparticles (nano-TiO2), believed to be inert and safe, are used in many products especially rutile-type in cosmetics. Detection, localization, and count of nanoparticles in tissue sections are of considerable current interest. Here, we evaluate the dose-dependent biodistribution of rutile-type nano-TiO2 exposure during pregnancy on offspring testes. Pregnant mice were subcutaneously injected five times with 0.1 ml of sequentially diluted of nano-TiO2 powder, 35 nm with primary diameter, suspensions (1, 10, 100, or 1,000 μg/ml), and received total doses of 0.5, 5, 50, and 500 μg, respectively. Prior to injection, the size distribution of nano-TiO2 was analyzed by dynamic light scattering measurement. The average diameter was increased in a dose-dependent manner. The most diluted concentration, 1 μg/ml suspension, contained small agglomerates averaging 193.3 ± 5.4 nm in diameter. The offspring testes were examined at 12 weeks postpartum. Individual particle analysis in testicular sections under scanning and transmission electron microscopy enabled us to understand the biodistribution. The correlation between nano-TiO2 doses injected to pregnant mice, and the number of agglomerates in the offspring testes was demonstrated to be dose-dependent by semiquantitative evaluation. However, the agglomerate size was below 200 nm in the testicular sections of all recipient groups, independent from the injected dose during pregnancy.

  19. Fibrinolytic Activity and Dose-Dependent Effect of Incubating Human Blood Clots in Caffeic Acid Phenethyl Ester: In Vitro Assays

    PubMed Central

    Elnager, Abuzar; Hassan, Rosline; Idris, Zamzuri; Mustafa, Zulkifli; Wan-Arfah, Nadiah; Sulaiman, S. A.; Gan, Siew Hua; Abdullah, Wan Zaidah

    2015-01-01

    Background. Caffeic acid phenethyl ester (CAPE) has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB) clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM). After 3 hours, D-dimer (DD) levels and WB clot weights were measured for each concentration. Thromboelastography (TEG) parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL) levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams) were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM). The 50% effective dose (ED50) of CAPE (based on DD) was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted. PMID:25664321

  20. The dose dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates.

    PubMed Central

    Ko, M S; Nakauchi, H; Takahashi, N

    1990-01-01

    Glucocorticoid hormones induce the transcription of genes having glucocorticoid response elements in a dose dependent manner. To determine whether this dose dependence represents a response of individual templates or of the mass of templates, we introduced a bacterial beta-galactosidase gene linked to the glucocorticoid-inducible enhancer/promoter of the mouse mammary tumor virus (MTV) into Ltk- cells and obtained stable transformants containing a single or a few templates per cell. Visual inspection and flow cytometry analysis by enzyme histochemistry assay for beta-galactosidase revealed that individual cells showed very heterogeneous beta-galactosidase activity after 48 h induction with dexamethasone. When the glucocorticoid concentration was increased, an increasing cell population producing beta-galactosidase was observed. These phenomena were probably not due to heterogeneity of template copy number or to a predetermined cellular state among individual cells, since cells forming a single small colony gave similar results. This was also supported by data showing that recloned cells retained both their responsiveness to the glucocorticoid hormone and their digestion pattern in Southern blotting analyses. These results indicate that the dose dependent increase of glucocorticoid-inducible gene expression is caused by an increase in the number of transcriptionally active templates. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. Fig. 8. PMID:2167833

  1. Role of mouthguards in reducing mild traumatic brain injury/concussion incidence in high school football athletes.

    PubMed

    Winters, Jackson; DeMont, Richard

    2014-01-01

    There is continued speculation on the value of mouthguards (MGs) in preventing mild traumatic brain injury (MTBI)/concussion injuries. The purpose of this randomized prospective study was to compare the impact of pressure-laminated (LM), custom-made, properly fitted MGs to over-the-counter (OTC) MGs on the MTBI/concussion incidence in high school football athletes over a season of play. Four hundred twelve players from 6 high school football teams were included in the study. Twenty-four MTBI/concussion injuries (5.8%) were recorded. When examining the MTBI/concussion injury rate by MG type, there was a significant difference (P = 0.0423) with incidence rates of 3.6% and 8.3% in the LM MG and OTC MG groups, respectively.

  2. Reduced incidence of acute myocardial infarction in the first year after implementation of a public smoking ban in Graubuenden, Switzerland.

    PubMed

    Trachsel, L D; Kuhn, M U; Reinhart, W H; Schulzki, T; Bonetti, P O

    2010-01-01

    On March 1st, 2008 a smoking ban in public buildings became effective in the Canton of Graubuenden, Switzerland. The aim of our study was to investigate, whether implementation of this new regulation was followed by a decrease in the incidence of acute myocardial infarction (AMI). The Kantonsspital Graubuenden serves as a tertiary care hospital, possessing the only cardiac catheterization laboratory in the Canton of Graubuenden. Based on an excellent functioning network including all hospitals in the Canton of Graubuenden, virtually all patients experiencing an AMI in the Canton of Graubuenden are transferred to our hospital for either acute or early coronary angiography. Data of all patients with AMI undergoing coronary angiography at our hospital between March 1st, 2008 and February 28th, 2009 were collected prospectively. The data were then compared with those of the two corresponding 12-month periods preceding implementation of the public smoking ban. In the two years before adoption of smoke-free legislation, the number of patients with AMI was 229 and 242, respectively (p = ns). In the 12 months after implementation of the public smoking ban, the number of AMI patients dropped to 183 (p <0.05 vs. each of the previous 12-month periods), representing an overall 22% reduction in the AMI incidence within the first year after enactment of the new regulation. This reduction was driven by a significant decrease in the AMI incidence in men, nonsmokers, and individuals with established coronary artery disease, including those with prior AMI or prior percutaneous coronary intervention. Similar to other countries in Europe and various regions of the USA and Canada, implementation of a public smoking ban was followed by a significant early decline in the incidence of AMI in the Canton of Graubuenden, Switzerland.

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

    PubMed

    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 < 10(-3)). Our results support that supplying soap and good quality water should be a priority on the field. Copyright © 2016. Published by Elsevier Ltd.

  4. Autologous platelet gel and fibrin sealant enhance the efficacy of total knee arthroplasty: improved range of motion, decreased length of stay and a reduced incidence of arthrofibrosis.

    PubMed

    Everts, Peter A M; Devilee, Roger J J; Oosterbos, Cornelis J M; Mahoney, Christine Brown; Schattenkerk, Maarten Eeftinck; Knape, Johannes T A; van Zundert, André

    2007-07-01

    In this study we describe the potential role of autologous platelet gel and fibrin sealant in unilateral total knee arthroplasty to improve the postoperative range of motion and to reduce the incidence of arthrofibrosis. Total knee arthroplasty is often associated with a considerable amount of post-operative blood loss. Persistent limited motion directly after surgery may ultimately result in arthrofibrosis. To counteract these effects we investigated whether the use of autologous derived platelet gel and fibrin sealant would reduce postoperative blood loss, decrease the impaired range of motion and the incidence of arthrofibrosis. All patients were consecutively operated and assigned to the study or control groups. Study group patients (n = 85) were treated with the application of autologous platelet gel and fibrin sealant at the end of surgery. Eighty patients were operated without the use of platelet gel and fibrin sealant, and served as the control group. The postoperative hemoglobin decrease, range of motion and length of hospitalization were recorded. During a 5-month postoperative period patients were followed to observe the incidence of arthrofibrosis. In patients in the treatment group the hemoglobin concentration in blood decreased significantly less when compared to the control group. They also showed a superior postoperative range of motion when compared to those of the control group (P < 0.001). The incidence of arthrofibrosis and subsequent forced manipulation was significantly less (P < 0.001) in patients managed with platelet gel and fibrin sealant. We conclude that peri-operatively applied platelet gel and fibrin sealant may improve the range of motion after total knee arthroplasty, decreases the length of stay and may reduce the incidence of arthrofibrosis.

  5. Does the FIFA 11+ Injury Prevention Program Reduce the Incidence of ACL Injury in Male Soccer Players?

    PubMed

    Silvers-Granelli, Holly J; Bizzini, Mario; Arundale, Amelia; Mandelbaum, Bert R; Snyder-Mackler, Lynn

    2017-04-07

    The FIFA 11+ injury prevention program has been shown to decrease the risk of soccer injuries in men and women. The program has also been shown to decrease time loss resulting from injury. However, previous studies have not specifically investigated how the program might impact the rate of anterior cruciate ligament (ACL) injury in male soccer players. The purpose of this study was to examine if the FIFA 11+ injury prevention program can (1) reduce the overall number of ACL injuries in men who play competitive college soccer and whether any potential reduction in rate of ACL injuries differed based on (2) game versus practice setting; (3) player position; (4) level of play (Division I or II); or (5) field type. This study was a prospective cluster randomized controlled trial, which was conducted in 61 Division I and Division II National Collegiate Athletic Association men's soccer teams over the course of one competitive soccer season. The FIFA 11+ is a 15- to 20-minute on-the-field dynamic warm-up program used before training and games and was utilized as the intervention throughout the entire competitive season. Sixty-five teams were randomized: 34 to the control group (850 players) and 31 to the intervention group (675 players). Four intervention teams did not complete the study and did not submit their data, noting insufficient time to complete the program, reducing the number for per-protocol analysis to 61. Compliance to the FIFA 11+ program, athletic exposures, specific injuries, ACL injuries, and time loss resulting from injury were collected and recorded using a secure Internet-based system. At the end of the season, the data in the injury surveillance system were crosshatched with each individual institution's internal database. At that time, the certified athletic trainer signed off on the injury collection data to confirm their accuracy and completeness. A lower proportion of athletes in the intervention group experienced knee injuries (25% [34 of

  6. Dose-Dependent AMPK-Dependent and Independent Mechanisms of Berberine and Metformin Inhibition of mTORC1, ERK, DNA Synthesis and Proliferation in Pancreatic Cancer Cells.

    PubMed

    Ming, Ming; Sinnett-Smith, James; Wang, Jia; Soares, Heloisa P; Young, Steven H; Eibl, Guido; Rozengurt, Enrique

    2014-01-01

    Natural products represent a rich reservoir of potential small chemical molecules exhibiting anti-proliferative and chemopreventive properties. Here, we show that treatment of pancreatic ductal adenocarcinoma (PDAC) cells (PANC-1, MiaPaCa-2) with the isoquinoline alkaloid berberine (0.3-6 µM) inhibited DNA synthesis and proliferation of these cells and delay the progression of their cell cycle in G1. Berberine treatment also reduced (by 70%) the growth of MiaPaCa-2 cell growth when implanted into the flanks of nu/nu mice. Mechanistic studies revealed that berberine decreased mitochondrial membrane potential and intracellular ATP levels and induced potent AMPK activation, as shown by phosphorylation of AMPK α subunit at Thr-172 and acetyl-CoA carboxylase (ACC) at Ser79. Furthermore, berberine dose-dependently inhibited mTORC1 (phosphorylation of S6K at Thr389 and S6 at Ser240/244) and ERK activation in PDAC cells stimulated by insulin and neurotensin or fetal bovine serum. Knockdown of α1 and α2 catalytic subunit expression of AMPK reversed the inhibitory effect produced by treatment with low concentrations of berberine on mTORC1, ERK and DNA synthesis in PDAC cells. However, at higher concentrations, berberine inhibited mitogenic signaling (mTORC1 and ERK) and DNA synthesis through an AMPK-independent mechanism. Similar results were obtained with metformin used at doses that induced either modest or pronounced reductions in intracellular ATP levels, which were virtually identical to the decreases in ATP levels obtained in response to berberine. We propose that berberine and metformin inhibit mitogenic signaling in PDAC cells through dose-dependent AMPK-dependent and independent pathways.

  7. The use of angiotensin-converting enzyme inhibitors and diuretics is associated with a reduced incidence of impairment on cognition in elderly women.

    PubMed

    Yasar, S; Zhou, J; Varadhan, R; Carlson, M C

    2008-07-01

    The effects of angiotensin-converting enzyme inhibitors (ACE-Is) and diuretics (used as antihypertensive agents) on global and domain-specific cognitive decline were evaluated in 326 non-demented community-dwelling participants over the age of 70 years in the Women's Health and Aging Study II. Time-dependent Cox proportional hazards regression analysis was used for evaluating the association between parameters. The use of ACE-I for more than 3 years was associated with reduced incidence of impairment on Mini-Mental State Examination (MMSE), Trail Making Test-Part A and Part B (TMT, Parts A and B), Hopkins Verbal Learning Test-Immediate Recall (HVLT-I), and Hopkins Verbal Learning Test-Delayed Recall (HVLT-D). The use of diuretics for more than 3 years was associated with reduced incidence of impairment on MMSE, TMT, Parts A and B, HVLT-I, and (HVLT-D). The presence of vascular disease did not make any difference to these effects. Therefore, the use of ACE-Is or diuretics was associated with reduced incidence of impairment of both global and domain-specific cognition in elderly women, and may help delay progression to dementia.

  8. Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group.

    PubMed

    Watterberg, K L; Murphy, S

    1993-04-01

    This prospective, randomized, blinded clinical trial was conducted to test whether therapy with cromolyn sodium might decrease the incidence or severity of bronchopulmonary dysplasia when given to newborns with respiratory distress syndrome. Cromolyn (20 mg) or placebo was aerosolized to intubated newborns with respiratory distress syndrome every 6 hours, beginning on the first day of intubation. Patients were stratified by birth weight less than 1000 g and 1000 to 2000 g; primary outcome success was defined as survival to 30 days without oxygen dependence. Of 10 patients enrolled who were less than 1000 g birth weight, there were no treatment successes, preventing outcome analysis. The study was discontinued after 28 patients of 1000 to 2000 g birth weight had been studied, at which time it had been found with 95% confidence, with a power of .80, that cromolyn sodium did not decrease by 50% the incidence of bronchopulmonary dysplasia. Severity of bronchopulmonary dysplasia was also similar, with 4 patients in the treatment group and 3 in the placebo group receiving mechanical ventilation at 30 days. Possible reasons for this study outcome include (1) a delivered dose too small to produce a clinical effect; (2) the start of therapy too late to prevent the onset of inflammation; (3) inadequate effect of cromolyn on polymorphonuclear cells in vivo; or (4) development of bronchopulmonary dysplasia through factors unaffected by the actions of cromolyn.

  9. Dietary vitamin D supplementation does not reduce the incidence or severity of asbestos-induced mesothelioma in a mouse model.

    PubMed

    Robinson, Cleo; Woo, Samantha; Nowak, Anna K; Lake, Richard A

    2014-01-01

    Epidemiological studies suggest that vitamin and mineral intake is associated with cancer incidence. A prevention strategy based on diet or dietary supplementation could have enormous benefit, both directly, by preventing disease, and indirectly by alleviating fear in millions of people worldwide who have been exposed to asbestos. We have previously shown that dietary supplementation with the antioxidants vitamins A, E, and selenium does not affect overall survival nor the time to progression of asbestos-induced mesothelioma in MexTAg mice. Here we have extended our analysis to vitamin D. We compared survival of asbestos-exposed MexTAg mice provided with diets that were deficient or supplemented with 4500 IU/kg vitamin D (cholecalciferol). Survival of supplemented mice was significantly shorter than mice given a standard AIN93 diet containing 1000 IU/kg cholecalciferol (median survival was 29 and 32.5 weeks respectively). However, mice deficient in vitamin D had the same rate of mesothelioma development as control mice. Neither the latency time from asbestos exposure to diagnosis nor disease progression after diagnosis were significantly different between mice on these diets. We conclude that vitamin D is unlikely to moderate the incidence of disease in asbestos-exposed populations or to ameliorate the pathology in patients with established mesothelioma.

  10. Selection of prophylactic antibiotics according to the microorganisms isolated from surgical site infections (SSIs) in a previous series of surgeries reduces SSI incidence after pancreaticoduodenectomy.

    PubMed

    Kondo, Kazuhiro; Chijiiwa, Kazuo; Ohuchida, Jiro; Kai, Masahiro; Fujii, Yoshiro; Otani, Kazuhiro; Hiyoshi, Masahide; Nagano, Motoaki; Imamura, Naoya

    2013-03-01

    The incidence of surgical site infections (SSIs) is high after pancreaticoduodenectomy (PD). We divided 116 consecutive patients who underwent PD into an early group (n = 58) and a later group (n = 58) according to time of surgery. In both groups, endoscopic retrograde biliary drainage was mainly employed for the patients with obstructive jaundice. In the later group, prophylactic antibiotics were selected according to the susceptibility of microorganisms isolated from SSIs in the early group. The incidence of SSIs was compared between the groups. The background characteristics (including methods of preoperative biliary drainage and microorganisms in the bile obtained before or during operation) of the patients were not significantly different between the groups, except for the serum albumin level, which was lower in the later group than in the early group (P = 0.0026). The incidence of SSIs was significantly lower in the later group (24.1 %) than in the early group (46.6 %) (P = 0.0116). Belonging to the later group was one independent negative risk factor for SSI. Selection of prophylactic antibiotics on the basis of microorganisms isolated from SSIs in the early group contributed to the reduced incidence of SSIs in the later group after PD.

  11. Age- and dose-dependent transplacental carcinogenesis by N-nitrosoethylurea in Syrian golden hamsters.

    PubMed

    Diwan, B A; Rehm, S; Rice, J M

    1996-01-01

    Syrian golden hamsters have a very short period (15 days) of gestation. The implantation of the blastocyst occurs on day 5, embryogenesis proceeds very rapidly thereafter and neural tube closure is completed by day 9. In the present study the effects of two different doses of N-nitrosoethylurea (NEU) administered at various stages of gestation were quantitatively evaluated in Syrian golden hamsters. NEU at either 0.2 or 0.5 mmol/kg was administered transplacentally as a single i.p. injection to pregnant hamsters on gestation days 7, 8, 9, 10, 11, 12, 13, or 14. The incidence, latency period and multiplicity of tumors varied with the dose of NEU and the stage of development at the time of NEU administration. Although tumors of the peripheral nervous system predominated, a variety of other tumors, including melanomas and visceral tumors of epithelial and mesenchymal origin, were also observed in hamster offspring exposed transplacentally to NEU. Sensitivity to transplacental carcinogenesis was maximal during late gestation and very low before day 9.

  12. Dose dependency of time of onset of radiation-induced growth hormone deficiency

    SciTech Connect

    Clayton, P.E.; Shalet, S.M. )

    1991-02-01

    Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis.

  13. Mediterranean-style dietary pattern, reduced risk of metabolic syndrome traits, and incidence in the Framingham Offspring Cohort123

    PubMed Central

    Rumawas, Marcella E; Meigs, James B; Dwyer, Johanna T; McKeown, Nicola M

    2009-01-01

    Background: The benefit of the Mediterranean-style dietary pattern in mitigating metabolic risk factors for type 2 diabetes and cardiovascular disease has not been well investigated among nondiabetic Americans. Objective: The aim of this study was to examine the prospective association between the Mediterranean-style dietary pattern and metabolic syndrome. Design: The Mediterranean-style dietary pattern score (MSDPS) was used to characterize a Mediterranean-style dietary pattern in the Framingham Heart Study Offspring Cohort. We examined the longitudinal association between MSDPS and metabolic syndrome traits (including homeostasis model assessment–insulin resistance, fasting glucose, waist circumference, triglyceride, HDL cholesterol, and systolic and diastolic blood pressure) among 2730 participants of the Framingham Heart Study Offspring Cohort without type 2 diabetes (baseline median age: 54 y; 55% women), who were followed from the fifth (baseline) to the seventh study examinations (mean follow-up time: 7 y), and metabolic syndrome incidence (according to the National Cholesterol Education Program Adult Treatment Panel III definition) in 1918 participants free of the condition at baseline. Results: A higher MSDPS was associated with lower homeostasis model assessment–insulin resistance (P = 0.02), waist circumference (P < 0.001), fasting plasma glucose (P = 0.03), and triglycerides (P < 0.001) and higher HDL cholesterol (P = 0.02) after adjustment for the corresponding baseline values and for several confounding factors associated with type 2 diabetes risk. Participants in the highest quintile category of the MSDPS had a lower incidence of metabolic syndrome than those in the lowest quintile category (38.5% compared with 30.1%; P = 0.01). Conclusion: Our study suggests that the consumption of a diet consistent with the principles of the Mediterranean-style diet may protect against metabolic syndrome in Americans. PMID:19828705

  14. Implementation of an industrial systems-engineering approach to reduce the incidence of methicillin-resistant Staphylococcus aureus infection.

    PubMed

    Muder, Robert R; Cunningham, Candace; McCray, Ellesha; Squier, Cheryl; Perreiah, Peter; Jain, Rajiv; Sinkowitz-Cochran, Ronda L; Jernigan, John A

    2008-08-01

    To measure the effectiveness of an industrial systems-engineering approach to a methicillin-resistant Staphylococcus aureus (MRSA) prevention program. Before-after intervention study. An intensive care unit (ICU) and a surgical unit that was not an ICU in the Pittsburgh Veterans Administration hospital. All patients admitted to the study units. We implemented an MRSA infection control program that consisted of the following 4 elements: (1) the use of standard precautions for all patient contact, with emphasis on hand hygiene; (2) the use of contact precautions for interactions with patients known to be infected or colonized with MRSA; (3) the use of active surveillance cultures to identify patients who were asymptomatically colonized with MRSA; and (4) use of an industrial systems-engineering approach, the Toyota Production System, to facilitate consistent and reliable adherence to the infection control program. The rate of healthcare-associated MRSA infection in the surgical unit decreased from 1.56 infections per 1,000 patient-days in the 2 years before the intervention to 0.63 infections per 1,000 patient-days in the 4 years after the intervention (a 60% reduction; P = .003). The rate of healthcare-associated MRSA infection in the ICU decreased from 5.45 infections per 1,000 patient-days in the 2 years before to the intervention to 1.35 infections per 1,000 patient-days in the 3 years after the intervention (a 75% reduction; P = .001). The combined estimate for reduction in the incidence of infection after the intervention in the 2 units was 68% (95% confidence interval, 50%-79%; P < .001). Sustained reduction in the incidence of MRSA infection is possible in a setting where this pathogen is endemic. An industrial systems-engineering approach can be adapted to facilitate consistent and reliable adherence to MRSA infection prevention practices in healthcare facilities.

  15. Dose-dependent effects of caffeine on behavior and thermoregulation in a chronic unpredictable stress model of depression in rats.

    PubMed

    Pechlivanova, D; Tchekalarova, J; Nikolov, R; Yakimova, K

    2010-06-19

    The effects of the non-selective adenosine A(1)/A(2) receptor antagonist caffeine on behavior and thermoregulation in chronic unpredictable stress (CUS) model of depression was studied in Wistar rats. In the open field (OF) test, caffeine dose-dependently increased motor activity while decreased grooming and time spent in the corner. Five-week exposure to CUS procedure had the opposite effect in rats. Caffeine reversed CUS-induced effects on the above mentioned parameters. Caffeine (40 mg/kg) increased the motor activity in plus maze (PM) test while at doses of 20 and 40 mg/kg it decreased the number of entries in the open arms. Whereas CUS did not change the level of anxiety, caffeine (2, 20 and 40 mg/kg) administered after CUS diminished it by increasing the time in open arms. Caffeine dose-dependently decreased the immobility time while CUS had the opposite increasing effect in forced swimming test (FST). Caffeine at doses of 20 and 40 mg/kg reversed the effect of CUS on immobility in FST. Caffeine produced dose-dependent rice of body temperature in both non-treated and CUS-treated rats. The hyperthermic effect in normal rats pretreated with caffeine lasted about 90 min while in caffeine-pretreated rats exposed to CUS it lasted about 150 min. High dose of caffeine (100mg/kg) induced significant hypothermia between 90th and 150th minute in control rats and hyperthermia between 30th and 60th minute in CUS-treated rats. These results suggest a putative role of this methylxanthine in the adaptive responses to chronic unpredictable stress stimuli.

  16. Modeling dose-dependent neural processing responses using mixed effects spline models: with application to a PET study of ethanol.

    PubMed

    Guo, Ying; Bowman, F DuBois

    2008-04-01

    For functional neuroimaging studies that involve experimental stimuli measuring dose levels, e.g. of an anesthetic agent, typical statistical techniques include correlation analysis, analysis of variance or polynomial regression models. These standard approaches have limitations: correlation analysis only provides a crude estimate of the linear relationship between dose levels and brain activity; ANOVA is designed to accommodate a few specified dose levels; polynomial regression models have limited capacity to model varying patterns of association between dose levels and measured activity across the brain. These shortcomings prompt the need to develop methods that more effectively capture dose-dependent neural processing responses. We propose a class of mixed effects spline models that analyze the dose-dependent effect using either regression or smoothing splines. Our method offers flexible accommodation of different response patterns across various brain regions, controls for potential confounding factors, and accounts for subject variability in brain function. The estimates from the mixed effects spline model can be readily incorporated into secondary analyses, for instance, targeting spatial classifications of brain regions according to their modeled response profiles. The proposed spline models are also extended to incorporate interaction effects between the dose-dependent response function and other factors. We illustrate our proposed statistical methodology using data from a PET study of the effect of ethanol on brain function. A simulation study is conducted to compare the performance of the proposed mixed effects spline models and a polynomial regression model. Results show that the proposed spline models more accurately capture varying response patterns across voxels, especially at voxels with complex response shapes. Finally, the proposed spline models can be used in more general settings as a flexible modeling tool for investigating the effects of any

  17. Vagotomy attenuates the effect of lipopolysaccharide on body temperature of rats in a dose-dependent manner.

    PubMed

    Azab, A N; Kaplanski, J

    2001-01-01

    There is a growing body of evidence suggesting that vagal afferents play a major role in peripheral-neural communication. This study was undertaken to determine whether a dose-dependent effect of lipopolysaccharide (LPS) on vagotomy-induced febrile unresponsiveness exists, and to examine the effect of vagotomy on LPS-induced increase in hypothalamic prostaglandin E2 (HT PGE2) production. Vagotomized and sham-operated rats were subjected to two experimental protocols. In the first, vagotomized and sham-operated rats were injected intraperitoneally with different doses of LPS (200, 500 and 1000 microg/kg) in order to examine the dose-dependent effect of LPS on the biphasic febrile response of the rats. In the second protocol, vagotomized and sham-operated rats were injected intraperitoneally with LPS (500 microg/kg). Two hours post injection, body temperature was measured, the rats were decapitated and blood was collected. Simultaneously, the rats' hypothalami were excised and incubated for 1 h in a Krebs-Henseleit buffer. Next, HT PGE2 was determined by radioimmunoassay. Vagotomy-induced gastric enlargement was then measured to examine the correlation between the magnitude of the enlargement and that of the vagotomy-related febrile unresponsiveness. It was found that vagotomized-induced febrile unresponsiveness is a dose-dependent effect. Subdiaphragmatic resection of the vagus prevented the biphasic febrile response caused by the lowest dose (200 microg/kg) of LPS, whereas the highest dose of LPS (1000 microg/kg) caused a similar biphasic febrile response in both vagotomized and sham-operated rats. Indeed, vagotomy attenuates LPS-induced increase in HT PGE2, and blocks the hypothermic phase of the febrile response. On the other hand, no correlation between gastric enlargement and febrile unresponsiveness was found. The results of the present study may cast further light on the crucial role of the vagus nerve as a peripheral-neural pathway in the mediation of the

  18. One is enough: in vivo effective population size is dose-dependent for a plant RNA virus.

    PubMed

    Zwart, Mark P; Daròs, José-Antonio; Elena, Santiago F

    2011-07-01

    Effective population size (N(e)) determines the strength of genetic drift and the frequency of co-infection by multiple genotypes, making it a key factor in viral evolution. Experimental estimates of N(e) for different plant viruses have, however, rendered diverging results. The independent action hypothesis (IAH) states that each virion has a probability of infection, and that virions act independent of one another during the infection process. A corollary of IAH is that N(e) must be dose dependent. A test of IAH for a plant virus has not been reported yet. Here we perform a test of an IAH infection model using a plant RNA virus, Tobacco etch virus (TEV) variants carrying GFP or mCherry fluorescent markers, in Nicotiana tabacum and Capsicum annuum plants. The number of primary infection foci increased linearly with dose, and was similar to a Poisson distribution. At high doses, primary infection foci containing both genotypes were found at a low frequency (<2%). The probability that a genotype that infected the inoculated leaf would systemically infect that plant was near 1, although in a few rare cases genotypes could be trapped in the inoculated leaf by being physically surrounded by the other genotype. The frequency of mixed-genotype infection could be predicted from the mean number of primary infection foci using the independent-action model. Independent action appears to hold for TEV, and N(e) is therefore dose-dependent for this plant RNA virus. The mean number of virions causing systemic infection can be very small, and approaches 1 at low doses. Dose-dependency in TEV suggests that comparison of N(e) estimates for different viruses are not very meaningful unless dose effects are taken into consideration.

  19. Dose-dependent effect of estrogen suppresses the osteo-adipogenic transdifferentiation of osteoblasts via canonical Wnt signaling pathway.

    PubMed

    Gao, Bo; Huang, Qiang; Lin, Yan-Shui; Wei, Bo-Yuan; Guo, Yun-Shan; Sun, Zhen; Wang, Long; Fan, Jing; Zhang, Hong-Yang; Han, Yue-Hu; Li, Xiao-Jie; Shi, Jun; Liu, Jian; Yang, Liu; Luo, Zhuo-Jing

    2014-01-01

    Fat infiltration within marrow cavity is one of multitudinous features of estrogen deficiency, which leads to a decline in bone formation functionality. The origin of this fat is unclear, but one possibility is that it is derived from osteoblasts, which transdifferentiate into adipocytes that produce bone marrow fat. We examined the dose-dependent effect of 17β-estradiol on the ability of MC3T3-E1 cells and murine bone marrow-derived mesenchymal stem cell (BMMSC)-derived osteoblasts to undergo osteo-adipogenic transdifferentiation. We found that 17β-estradiol significantly increased alkaline phosphatase activity (P<0.05); calcium deposition; and Alp, Col1a1, Runx2, and Ocn expression levels dose-dependently. By contrast, 17β-estradiol significantly decreased the number and size of lipid droplets, and Fabp4 and PPARγ expression levels during osteo-adipogenic transdifferentiation (P<0.05). Moreover, the expression levels of brown adipocyte markers (Myf5, Elovl3, and Cidea) and undifferentiated adipocyte markers (Dlk1, Gata2, and Wnt10b) were also affected by 17β-estradiol during osteo-adipogenic transdifferentiation. Western blotting and immunostaining further showed that canonical Wnt signaling can be activated by estrogen to exert its inhibitory effect of osteo-adipogenesis. This is the first study to demonstrate the dose-dependent effect of 17β-estradiol on the osteo-adipogenic transdifferentiation of MC3T3-E1 cells and BMMSCs likely via canonical Wnt signaling. In summary, our results indicate that osteo-adipogenic transdifferentiation modulated by canonical Wnt signaling pathway in bone metabolism may be a new explanation for the gradually increased bone marrow fat in estrogen-inefficient condition.

  20. Metformin Impairs Mitochondrial Function in Skeletal Muscle of Both Lean and Diabetic Rats in a Dose-Dependent Manner

    PubMed Central

    Wessels, Bart; Ciapaite, Jolita; van den Broek, Nicole M. A.; Nicolay, Klaas; Prompers, Jeanine J.

    2014-01-01

    Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I of the mitochondrial respiratory chain. This seems contraindicative since muscle mitochondrial dysfunction has been linked to the pathogenesis of type 2 diabetes. However, its significance for in vivo skeletal muscle mitochondrial function has yet to be elucidated. The aim of this study was to assess the effects of metformin on in vivo and ex vivo skeletal muscle mitochondrial function in a rat model of diabetes. Healthy (fa/+) and diabetic (fa/fa) Zucker diabetic fatty rats were treated by oral gavage with metformin dissolved in water (30, 100 or 300 mg/kg bodyweight/day) or water as a control for 2 weeks. After 2 weeks of treatment, muscle oxidative capacity was assessed in vivo using 31P magnetic resonance spectroscopy and ex vivo by measuring oxygen consumption in isolated mitochondria using high-resolution respirometry. Two weeks of treatment with metformin impaired in vivo muscle oxidative capacity in a dose-dependent manner, both in healthy and diabetic rats. Whereas a dosage of 30 mg/kg/day had no significant effect, in vivo oxidative capacity was 21% and 48% lower after metformin treatment at 100 and 300 mg/kg/day, respectively, independent of genotype. High-resolution respirometry measurements demonstrated a similar dose-dependent effect of metformin on ex vivo mitochondrial function. In conclusion, metformin compromises in vivo and ex vivo muscle oxidative capacity in Zucker diabetic fatty rats in a dose-dependent manner. PMID:24950069

  1. Bovine meniscal tissue exhibits age- and interleukin-1 dose-dependent degradation patterns and composition-function relationships.

    PubMed

    Ling, Carrie H-Y; Lai, Janice H; Wong, Ivan J; Levenston, Marc E

    2016-05-01

    Despite increasing evidence that meniscal degeneration is an early event in the development of knee osteoarthritis, relatively little is known regarding the sequence or functional implications of cytokine-induced meniscal degradation or how degradation varies with age. This study examined dose-dependent patterns of interleukin-1 (IL-1)-induced matrix degradation in explants from the radially middle regions of juvenile and adult bovine menisci. Tissue explants were cultured for 10 days in the presence of 0, 1.25, 5, or 20 ng/ml recombinant human IL-1α. Juvenile explants exhibited immediate and extensive sulfated glycosaminoglycan (sGAG) loss and subsequent collagen release beginning after 4-6 days, with relatively little IL-1 dose-dependence. Adult explants exhibited a more graded response to IL-1, with dose-dependent sGAG release and a lower fraction of sGAG released (but greater absolute release) than juvenile explants. In contrast to juvenile explants, adult explants exhibited minimal collagen release over the 10-day culture. Compressive and shear moduli reflected the changes in explant composition, with substantial decreases for both ages but a greater relative decrease in juvenile tissue. Dynamic moduli exhibited stronger dependence on explant sGAG content for juvenile tissue, likely reflecting concomitant changes to both proteoglycan and collagen tissue components. The patterns of tissue degradation suggest that, like in articular cartilage, meniscal proteoglycans may partially protect collagen from cell-mediated degeneration. A more detailed view of functional changes in meniscal tissue mechanics with degeneration will help to establish the relevance of in vitro culture models and will advance understanding of how meniscal degeneration contributes to overall joint changes in early stage osteoarthritis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:801-811, 2016. © 2015 Orthopaedic Research Society. Published by

  2. Dose-Dependent Thresholds of 10-ns Electric Pulse Induced Plasma Membrane Disruption and Cytotoxicity in Multiple Cell Lines

    DTIC Science & Technology

    2011-01-01

    about specific USEP- induced cellular effects that are unlikely to be true for all cell types. We also investigated the mechanism responsible for the...Dose-Dependent Thresholds of 10-ns Electric Pulse Induced Plasma Membrane Disruption and Cytotoxicity in Multiple Cell Lines Bennett L. Ibey1*, Caleb...HeLa, and 142 J/g for GH3. Both Jurkat and U937 had a LD50 lower than the ED50 for Pr uptake at 780 J/g and 1274 J/g, respectively. The mechanism

  3. A cost-effectiveness analysis of identifying Fusobacterium necrophorum in throat swabs followed by antibiotic treatment to reduce the incidence of Lemierre's syndrome and peritonsillar abscesses.

    PubMed

    Bank, S; Christensen, K; Kristensen, L H; Prag, J

    2013-01-01

    The main purpose of this paper was to estimate the cost per quality-adjusted life year (QALY) saved by identifying Fusobacterium necrophorum in throat swabs followed by proper antibiotic treatment, to reduce the incidence of Lemierre's syndrome and peritonsillar abscesses (PTA) originating from a pharyngitis. The second purpose was to estimate the population size required to indicate that antibiotic treatment has an effect. Data from publications and our laboratory were collected. Monte Carlo simulation and one-way sensitivity analysis were used to analyse cost-effectiveness. The cost-effectiveness analysis shows that examining throat swabs from 15- to 24-year-olds for F. necrophorum followed by antibiotic treatment will probably be less costly than most other life-saving medical interventions, with a median cost of US$8,795 per QALY saved. To indicate a reduced incidence of Lemierre's syndrome and PTA in Denmark, the intervention probably has to be followed for up to 5 years. Identifying F. necrophorum in throat swabs from 15- to 24-year-olds followed by proper antibiotic treatment only requires a reduction of 20-25 % in the incidence of Lemierre's syndrome and PTA to be cost-effective. This study warrants further examination of the effect of antibiotic treatment on the outcome of F. necrophorum acute and recurrent pharyngitis, as well as the effect on Lemierre's syndrome and PTA.

  4. Dose titration of intramuscular interferon beta-1a reduces the severity and incidence of flu-like symptoms during treatment initiation.

    PubMed

    Matson, Mark A; Zimmerman, Thomas R; Tuccillo, Dianne; Tang, Yongqiang; Deykin, Aaron

    2011-12-01

    Flu-like symptoms (FLS) are common side effects of interferon beta (IFNβ) therapy and can negatively affect the willingness of patients with multiple sclerosis to initiate therapy. Although dose titration is commonly used to reduce the severity and incidence of IFNβ-related FLS during treatment initiation, these benefits have not been confirmed in a well controlled study. The objective of this randomized, dose-blinded, parallel-group study was to assess the effect of dose titration on the severity and incidence of FLS during the initial 8 weeks of once-weekly intramuscular (IM) IFNβ-1a administration. Healthy volunteers were randomized 1:1:1 to one of three IM IFNβ-1a regimens: 3-week titration (weekly quarter-dose increments over 3 weeks to full dose [30 µg]); 6-week titration (biweekly quarter-dose increments over 6 weeks to full dose); or no titration (full dose over 8 weeks). At weekly clinic visits, the severity of each FLS was rated 1 hour pre-injection and 4-6 hours and 12-15 hours post-injection. Study endpoints included post-injection change in FLS severity and post-injection FLS incidence (percentage of subjects with a ≥2-point increase in total FLS severity score) at each time point. Clinicaltrials.gov identifier: NCT01119677. Of 234 subjects enrolled, 194 (83%) completed the study. At 8 weeks, FLS severity was significantly reduced at both post-injection time points with 3-week titration (76% reduction at 4-6 hours, p < 0.001; 37% reduction at 12-15 hours; p < 0.001) and 6-week titration (50% reduction at 4-6 hours, p < 0.001; 32% reduction at 12-15 hours; p = 0.002) compared with no titration. The incidence of FLS was also significantly reduced at both time points with both titration regimens. Safety profiles for both titration regimens were consistent with the current IM IFNβ-1a label. Study limitations included that there is currently no validated assessment tool for evaluating the severity of FLS, that the study enrolled

  5. Dose-Dependent Pulmonary Toxicity After Postoperative Intensity-Modulated Radiotherapy for Malignant Pleural Mesothelioma

    SciTech Connect

    Rice, David C. Smythe, W. Roy; Liao Zhongxing; Guerrero, Thomas; Chang, Joe Y.; McAleer, Mary F.; Jeter, Melenda D.; Correa, Arlene Ph.D.; Vaporciyan, Ara A.; Liu, H. Helen; Komaki, Ritsuko; Forster, Kenneth M.; Stevens, Craig W.

    2007-10-01

    Purpose: To determine the incidence of fatal pulmonary events after extrapleural pneumonectomy and hemithoracic intensity-modulated radiotherapy (IMRT) for malignant pleural mesothelioma. Methods and Materials: We retrospectively reviewed the records of 63 consecutive patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy and IMRT at University of Texas M. D. Anderson Cancer Center. The endpoints studied were pulmonary-related death (PRD) and non-cancer-related death within 6 months of IMRT. Results: Of the 63 patients, 23 (37%) had died within 6 months of IMRT (10 of recurrent cancer, 6 of pulmonary causes [pneumonia in 4 and pneumonitis in 2], and 7 of other noncancer causes [pulmonary embolus in 2, sepsis after bronchopleural fistula in 1, and cause unknown but without pulmonary symptoms or recurrent disease in 4]). On univariate analysis, the factors that predicted for PRD were a lower preoperative ejection fraction (p = 0.021), absolute volume of lung spared at 10 Gy (p = 0.025), percentage of lung volume receiving {>=}20 Gy (V{sub 20}; p 0.002), and mean lung dose (p = 0.013). On multivariate analysis, only V{sub 20} was predictive of PRD (p = 0.017; odds ratio, 1.50; 95% confidence interval, 1.08-2.08) or non-cancer-related death (p = 0.033; odds ratio, 1.21; 95% confidence interval, 1.02-1.45). Conclusion: The results of our study have shown that fatal pulmonary toxicities were associated with radiation to the contralateral lung. V{sub 20} was the only independent determinant for risk of PRD or non-cancer-related death. The mean V{sub 20} of the non-PRD patients was considerably lower than that accepted during standard thoracic radiotherapy, implying that the V{sub 20} should be kept as low as possible after extrapleural pneumonectomy.

  6. [The effectiveness of care bundles in maintaining the skin integrity and reducing the incidence density of pressure ulcers in lung cancer inpatients].

    PubMed

    Lin, Wen-Ling; Tseng, Chien-Hua; Chung, Yi-Jen; Chuang, Hsin-Chu; Lin, Yun-Lan; Chang, Pi-Hua

    2014-04-01

    Pressure ulcers are tissue defects that form on the skin as a result of progressive skin damage. Pressure ulcers are a skin-integrity-related care issue and an important clinical indicator of care quality, especially for lung cancer inpatients who face rapidly deteriorating health conditions due to multiple symptoms and the side effects of treatment. Treating severe pressure ulcers may consume considerable manpower, time, and medical resources. Pressure ulcers may be avoided or effectively treated when nurses conduct proper skin assessments and care for wounds properly. This project evaluates the efficacy of skin care bundles in terms of reducing the incidence density of pressure ulcers in lung cancer inpatients. Data gathered between January 2010 and March 2011 showed unstable incidence density for pressure ulcers. The average pressure-ulcer incidence density in lung cancer inpatients was 2.09%, which was 8-times higher than the average for all patients. Using evidence-based care bundles for pressure ulcer prevention, we trained nurse staffs to incorporate these bundles into their clinical daily care of lung cancer patients in our hospital. During the study period between November 2011 and January 2012, the pressure-ulcer incidence density gradually fell to 0.55%. The incidence density continued to fall to 0.33% over the subsequent 8 months. We used the concept of "care bundles" to establish a standard skin-care protocol for advanced lung cancer inpatients. This protocol improved the clinical ability of nursing staffs and effectively maintained skin care quality in lung cancer patients.

  7. Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer.

    PubMed

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2016-01-01

    High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (<0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two

  8. Therapeutic Time Window and Dose Dependence of Xenon Delivered via Echogenic Liposomes for Neuroprotection in Stroke

    PubMed Central

    Peng, Tao; Britton, George L.; Kim, Hyunggun; Cattano, Davide; Aronowski, Jaroslaw; Grotta, James; McPherson, David D.; Huang, Shao-Ling

    2013-01-01

    Aims Neurologic impairment following ischemic injury complicates the quality of life for stroke survivors. Xenon (Xe) has favorable neuroprotective properties to modify stroke. Xe delivery is hampered by a lack of suitable administration strategies. We have developed Xe-containing echogenic liposomes (Xe-ELIP) for systemic Xe delivery. We investigated the time window for Xe-ELIP therapeutic effect and the most efficacious dose for neuroprotection. Molecular mechanisms for Xe neuroprotection were investigated. Methods Xe-ELIP were created by a previously developed pressurization-freezing method. Following right middle cerebral artery occlusion (2 hours), animals were treated with Xe-ELIP at 2, 3 or 5 hours to determine time window of therapeutic effect. The neuroprotectant dosage for optimal effect was evaluated 3 hours after stroke onset. Expression of brain-derived neurotrophic factor (BDNF), protein kinase B (Akt), and mitogen-activated protein kinases (MAPK) were determined. Results Xe-ELIP administration for up to 5 hours after stroke onset reduced infract size. Treatment groups given 7 and 14 mg/kg of Xe-ELIP reduced infarct size. Behavioral outcomes corresponded to changes in infarct volume. Xe-ELIP treatment reduced ischemic neuronal cell death via activation of both MAPK and Akt. Elevated BDNF expression was shown following Xe-ELIP delivery. Conclusion This study demonstrates the therapeutic efficacy of Xe-ELIP administered within 5 hours after stroke onset with an optimal dosage range of 7–14 mg/kg for maximal neuroprotection. PMID:23981565

  9. Does Prostate Size Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from the REDUCE Trial.

    PubMed

    Simon, Ross M; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Vidal, Adriana C; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2016-05-01

    It has been shown that increased prostate size is a risk factor for lower urinary tract symptom (LUTS) progression in men who currently have LUTS presumed due to benign prostatic hyperplasia (BPH). To determine if prostate size is a risk factor for incident LUTS in men with mild to no symptoms. We conducted a post hoc analysis of the REDUCE study, which contained a substantial number of men (n=3090) with mild to no LUTS (International Prostate Symptom Score [IPSS] <8). Our primary outcome was determination of the effect of prostate size on incident LUTS presumed due to BPH defined as two consecutive IPSS values >14, or receiving any medical (α-blockers) or surgical treatment for BPH throughout the study course. To determine the risk of developing incident LUTS, we used univariable and multivariable Cox models, as well as Kaplan-Meier curves and the log-rank test. Among men treated with placebo during the REDUCE study, those with a prostate size of 40.1-80ml had a 67% higher risk (hazard risk 1.67, 95% confidence interval 1.23-2.26, p=0.001) of developing incident LUTS compared to men with a prostate size 40.0ml or smaller. There was no association between prostate size and risk of incident LUTS in men treated with 0.5mg of dutasteride. The post hoc nature of our study design is a potential limitation. Men with mild to no LUTS but increased prostate size are at higher risk of incident LUTS presumed due to BPH. This association was negated by dutasteride treatment. Benign prostatic hyperplasia (BPH) is a very common problem among older men, which often manifests as lower urinary tract symptoms (LUTS), and can lead to potentially serious side effects. In our study we determined that men with mild to no current LUTS but increased prostate size are much more likely to develop LUTS presumed due to BPH in the future. This association was not seen in men treated with dutasteride, a drug approved for treatment of BPH. Our study reveals that men with a prostate size of 40

  10. Does Peak Urine Flow Rate Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from REDUCE.

    PubMed

    Simon, Ross M; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Vidal, Adriana; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2017-09-01

    We determined whether decreased peak urine flow is associated with future incident lower urinary tract symptoms in men with mild to no lower urinary tract symptoms. Our population consisted of 3,140 men from the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial with mild to no lower urinary tract symptoms, defined as I-PSS (International Prostate Symptom Score) less than 8. REDUCE was a randomized trial of dutasteride vs placebo for prostate cancer prevention in men with elevated prostate specific antigen and negative biopsy. I-PSS measures were obtained every 6 months throughout the 4-year study. The association between peak urine flow rate and progression to incident lower urinary tract symptoms, defined as the first of medical treatment, surgery or sustained and clinically significant lower urinary tract symptoms, was tested by multivariable Cox models, adjusting for various baseline characteristics and treatment arm. On multivariable analysis as a continuous variable, decreased peak urine flow rate was significantly associated with an increased risk of incident lower urinary tract symptoms (p = 0.002). Results were similar in the dutasteride and placebo arms. On univariable analysis when peak flow was categorized as 15 or greater, 10 to 14.9 and less than 10 ml per second, flow rates of 10 to 14.9 and less than 10 ml per second were associated with a significantly increased risk of incident lower urinary tract symptoms (HR 1.39, p = 0.011 and 1.67, p <0.001, respectively). Results were similar on multivariable analysis, although in the 10 to 14.9 ml per second group findings were no longer statistically significant (HR 1.26, p = 0.071). In men with mild to no lower urinary tract symptoms a decreased peak urine flow rate is independently associated with incident lower urinary tract symptoms. If confirmed, these men should be followed closer for incident lower urinary tract symptoms. Copyright © 2017 American Urological Association Education and

  11. A T-DNA mutation in the RNA helicase eIF4A confers a dose-dependent dwarfing phenotype in Brachypodium distachyon.

    PubMed

    Vain, Philippe; Thole, Vera; Worland, Barbara; Opanowicz, Magdalena; Bush, Max S; Doonan, John H

    2011-06-01

    In a survey of the BrachyTAG mutant population of Brachypodium distachyon, we identified a line carrying a T-DNA insertion in one of the two eukaryotic initiation factor 4A (eIF4A) genes present in the nuclear genome. The eif4a homozygous mutant plants were slow-growing, and exhibited reduced final plant stature due to a decrease in both cell number and cell size, consistent with roles for eIF4A in both cell division and cell growth. Hemizygous plants displayed a semi-dwarfing phenotype, in which stem length was reduced but leaf length was normal. Linkage between the insertion site and phenotype was confirmed, and we show that the level of eIF4A protein is strongly reduced in the mutant. Transformation of the Brachypodium homozygous mutant with a genomic copy of the Arabidopsis eIF4A-1 gene partially complemented the growth phenotype, indicating that gene function is conserved between mono- and dicotyledonous species. This study identifies eIF4A as a novel dose-dependent regulator of stem elongation, and demonstrates the utility of Brachypodium as a model for grass and cereals research.

  12. Dose-dependent hypocholesterolaemic effect of oyster mushroom (Pleurotus ostreatus) in rats.

    PubMed

    Bobek, P; Ozdín, L; Kajaba, I

    1997-01-01

    A highly significant negative correlation (r=-0.981, p < 0.001) between the amount of oyster mushroom (Pleurotus ostreatus) in the diet and cholesterol levels in the serum has been found in male Wistar rats fed shortly after weaning by a a diet with 0.3% cholesterol. The addition of 1.0, 2.5 and 5.0% of oyster mushroom to the diet reduced the levels of serum cholesterol by 11, 31 and 46%, respectively. The diet containing 5% of oyster mushroom suppressed cholesterol accumulation in the liver and increased the fraction of cholesterol carried by high-density lipoproteins.

  13. Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

    SciTech Connect

    Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael . E-mail: mowens@uams.edu

    2005-12-15

    These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats.

  14. Dose-dependent cytotoxicity evaluation of graphite nanoparticles for diamond-like carbon film application on artificial joints.

    PubMed

    Liao, T T; Deng, Q Y; Wu, B J; Li, S S; Li, X; Wu, J; Leng, Y X; Guo, Y B; Huang, N

    2017-01-24

    While a diamond-like carbon (DLC)-coated joint prosthesis represents the implant of choice for total hip replacement in patients, it also leads to concern due to the cytotoxicity of wear debris in the form of graphite nanoparticles (GNs), ultimately limiting its clinical use. In this study, the cytotoxicity of various GN doses was evaluated. Mouse macrophages and osteoblasts were incubated with GNs (<30 nm diameter), followed by evaluation of cytotoxicity by means of assessing inflammatory cytokines, results of alkaline phosphatase assays, and related signaling protein expression. Cytotoxicity evaluation showed that cell viability decreased in a dose-dependent manner (10-100 μg ml(-1)), and steeply declined at GNs concentrations greater than 30 μg ml(-1). Noticeable cytotoxicity was observed as the GN dose exceeded this threshold due to upregulated receptor of activator of nuclear factor kB-ligand expression and downregulated osteoprotegerin expression. Meanwhile, activated macrophage morphology was observed as a result of the intense inflammatory response caused by the high doses of GNs (>30 μg ml(-1)), as observed by the increased release of TNF-α and IL-6. The results suggest that GNs had a significant dose-dependent cytotoxicity in vitro, with a lethal dose of 30 μg ml(-1) leading to dramatic increases in cytotoxicity. Our GN cytotoxicity evaluation indicates a safe level for wear debris-related arthropathy and could propel the clinical application of DLC-coated total hip prostheses.

  15. Dose-dependent induction of recessive mutations with N-ethyl-N-nitrosourea in primordial germ cells of male mice.

    PubMed

    Shibuya, T; Horiya, N; Matsuda, H; Sakamoto, K; Hara, T

    1996-10-25

    Using a specific locus test, we previously found that N-ethyl-N-nitrosourea (ENU) induces recessive mutations at a relatively high rate in male mouse primordial germ cells (PGC) at 8.5, 10.5 and 13.5 days of development (G8.5, G10.5 and G13.5). A large difference was observed on the induced mutation rate between 30 and 50 mg/kg ENU in 10.5-day PGC. We therefore carried out specific locus tests to ascertain whether ENU induces recessive mutations in a dose-dependent manner in G8.5 and G10.5 PGC. We also gave multiple doses of 25 mg/kg ENU using an 18-h interval, the approximate doubling time of PGC at these developmental stages, to test for an additive effect on the induced mutations rate. A dose-dependent induction of recessive mutations by ENU was observed in both G8.5 and G10.5 PGC, and multiple dosing of 25 mg/kg ENU showed an additive effect. Comparing these results to data on spermatogonial stem cells, we conclude the capacity to repair ENU-induced premutagenic damages is less effective in male mouse PGC at these developmental stages than in spermatogonial stem cells.

  16. Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain.

    PubMed

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie; Kreilgaard, Mads; Lund, Trine Meldgaard

    2016-01-20

    Despite much evidence that combination of morphine and gabapentin can be beneficial for managing postoperative pain, the nature of the pharmacological interaction of the two drugs remains unclear. The aim of this study was to assess the interaction of morphine and gabapentin in range of different dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7mg/kg), gabapentin (10, 30 and 100mg/kg) or their combination (9 combinations in total) were evaluated in the rat plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response ranged between 26 and 58% for the synergistic doses. The finding of dose-dependent synergistic effects highlights that choosing the right dose-dose combination is of importance in postoperative pain therapy. Our results indicate benefit of high doses of gabapentin as adjuvant to morphine. If these findings translate to humans, they might have important implications for the treatment of pain in postoperative patients.

  17. Dose-dependent effects of diallyl disulfide on plasma glucose and free fatty acid levels in rats.

    PubMed

    Hashizume, Yoko; Shirato, Ken; Sato, Shogo; Matsumoto, Akiko; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2013-01-01

    The acute effects of oral administration of diallyl disulfide (DADS), the major organosulfur compound of garlic, on plasma glucose and free fatty acid (FFA) concentrations were examined in rats. Male, 10-week-old Sprague-Dawley rats were divided into DADS-free and DADS-administered (dose = 10, 20, and 40 mg/kg body weight [BW]) groups. Plasma samples were prepared from whole blood drawn from the tail vein 0, 1, 2, 4, and 6 hr after administration. The stomachs were isolated, and the contents were measured 8 hr after administration. In DADS-administered groups, plasma glucose concentrations were increased in a dose-dependent manner 1 hr after the administration. The increase was transient, except in groups administered 40 mg/kg BW of DADS, in which plasma glucose levels remained significantly higher than the DADS-free levels throughout the experimental period. Similar patterns were observed in the plasma FFA concentrations, although the significant differences were lower than those observed in the plasma glucose concentrations. The gastric contents were dose-dependently elevated after DADS administration. The increase was significant when 20 or 40 mg/kg BW of DADS was administered. These results suggest that oral administration of DADS can mobilize energy substrates into the blood, although a higher dose of DADS slows gastric emptying.

  18. Dose-dependent fate of GFP-expressing Escherichia coli in the alimentary canal of adult house flies.

    PubMed

    Kumar, N H V; Nayduch, D

    2016-06-01

    The adult house fly Musca domestica (L.) (Diptera: Muscidae) can disseminate bacteria from microbe-rich substrates to areas in which humans and domesticated animals reside. Because bacterial abundance fluctuates widely across substrates, flies encounter and ingest varying amounts of bacteria. This study investigated the dose-dependent survival of bacteria in house flies. Flies were fed four different 'doses' of green fluorescent protein (GFP)-expressing Escherichia coli (GFP E. coli) (very low, low, medium, high) and survival was determined at 1, 4, 10 and 22 h post-ingestion by culture and epifluorescent microscopy. Over 22 h, the decline in GFP E. coli was significant in all treatments (P < 0.04) except the very low dose treatment (P = 0.235). Change in survival (ΔS) did not differ between flies fed low and very low doses of bacteria across all time-points, although ΔS in both treatments differed from that in flies fed high and medium doses of bacteria at several time-points. At 4, 10 and 22 h, GFP E. coli ΔS significantly differed between medium and high dose-fed flies. A threshold dose, above which bacteria are detected and destroyed by house flies, may exist and is likely to be immune-mediated. Understanding dose-dependent bacterial survival in flies can help in predicting bacteria transmission potential.

  19. Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats.

    PubMed

    Milesi-Hallé, Alessandra; Hendrickson, Howard P; Laurenzana, Elizabeth M; Gentry, W Brooks; Owens, S Michael

    2005-12-15

    These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats.

  20. Complementary and dose-dependent action of AtCCS52A isoforms in endoreduplication and plant size control.

    PubMed

    Baloban, Mikhail; Vanstraelen, Marleen; Tarayre, Sylvie; Reuzeau, Christophe; Cultrone, Antonietta; Mergaert, Peter; Kondorosi, Eva

    2013-06-01

    · The dimension of organs depends on the number and the size of their component cells. Formation of polyploid cells by endoreduplication cycles is predominantly associated with increases in the cell size and implicated in organ growth. In plants, the CCS52A proteins play a major role in the switch from mitotic to endoreduplication cycles controlling thus the number of mitotic cells and the endoreduplication events in the differentiating cells. · Arabidopsis has two CCS52A isoforms; AtCCS52A1 and AtCCS52A2. Here we focused on their roles in endoreduplication and cell size control during plant development. We demonstrate their complementary and dose-dependent actions that are dependent on their expression patterns. Moreover, the impact of CCS52A overexpression on organ size in transgenic plants was dependent on the expression level; while enhanced expression of the CCS52A genes positively correlated with the ploidy levels, organ sizes were negatively affected by strong overexpression whereas milder overexpression resulted in a significant increase in the organ sizes. · Taken together, these finding support both complementary and dose-dependent actions for the Arabidopsis CCS52A isoforms in plant development and demonstrate that elevated ectopic CCS52A expression positively correlates with organ size, opening a route to higher biomass production. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

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

    PubMed

    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.

  2. An inactivated gE-negative marker vaccine and an experimental gD-subunit vaccine reduce the incidence of bovine herpesvirus 1 infections in the field.

    PubMed

    Bosch, J C; De Jong, M C; Franken, P; Frankena, K; Hage, J J; Kaashoek, M J; Maris-Veldhuis, M A; Noordhuizen, J P; Van der Poel, W H; Verhoeff, J; Weerdmeester, K; Zimmer, G M; Van Oirschot, J T

    1998-01-01

    An inactivated glycoprotein E-negative vaccine and an experimental glycoprotein D-subunit vaccine against bovine herpesvirus 1 (V1) were examined for their effectiveness in a randomized, double-bline, placebo-controlled field trial comprising 130 dairy farms. The use of these marker vaccines enabled us to monitor the incidence of infections in vaccinated populations. The aims of this trial were to evaluate whether these vaccines: (1) reduce the proportion of outbreaks in dairy herds; and (2) reduced virus transmission within dairy herds and to what extent. Vaccination with either of the two vaccines significantly reduced the proportion of herds wherein an outbreak occurred as well as the virus transmission within herds, as compared to placebo-treated herds. The estimated number of secondary cases caused by one infectious animal, expressed as the reproduction ratio R, was for both vaccines significantly > 1. This indicates that when BHV1 is introduced into vaccinated herds, major outbreaks may still occur.

  3. Oleoylethanolamide dose-dependently attenuates cocaine-induced behaviours through a PPARα receptor-independent mechanism.

    PubMed

    Bilbao, Ainhoa; Blanco, Eduardo; Luque-Rojas, María Jesús; Suárez, Juan; Palomino, Ana; Vida, Margarita; Araos, Pedro; Bermúdez-Silva, Francisco J; Fernández-Espejo, Emilio; Spanagel, Rainer; Rodríguez de Fonseca, Fernando

    2013-01-01

    Oleoylethanolamide (OEA) is an acylethanolamide that acts as an agonist of nuclear peroxisome proliferator-activated receptor alpha (PPARα) to exert their biological functions, which include the regulation of appetite and metabolism. Increasing evidence also suggests that OEA may participate in the control of reward-related behaviours. However, direct experimental evidence for the role of the OEA-PPARα receptor interaction in drug-mediated behaviours, such as cocaine-induced behavioural phenotypes, is lacking. The present study explored the role of OEA and its receptor PPARα on the psychomotor and rewarding responsiveness to cocaine using behavioural tests indicative of core components of addiction. We found that acute administration of OEA (1, 5 or 20 mg/kg, i.p.) reduced spontaneous locomotor activity and attenuated psychomotor activation induced by cocaine (20 mg/kg) in C57Bl/6 mice. However, PPARα receptor knockout mice showed normal sensitization, although OEA was capable of reducing behavioural sensitization with fewer efficacies. Furthermore, conditioned place preference and reinstatement to cocaine were intact in these mice. Our results indicate that PPARα receptor does not play a critical, if any, role in mediating short- and long-term psychomotor and rewarding responsiveness to cocaine. However, further research is needed for the identification of the targets of OEA for its inhibitory action on cocaine-mediated responses. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

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

    PubMed Central

    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

  5. Dietary GD3 ganglioside reduces the incidence and severity of necrotizing enterocolitis by sustaining regulatory immune responses.

    PubMed

    Xu, Jiliu; Anderson, Virginia; Schwarz, Steven M

    2013-11-01

    Gangliosides are glycosphingolipids, rich in colostrum and in membrane microdomains, which promote enterocyte growth and differentiation, and modulate TH1/TH2 responses. In an in vitro intestinal explant model of necrotizing enterocolitis (NEC), gangliosides have been shown to ameliorate intestinal injury; however, possible immunomodulatory mechanisms associated with this observation, as well as potential in vivo protective effects of gangliosides, remain unknown. The present study evaluates the effects of dietary GD3, the predominant ganglioside in neonatal rat intestine, both on the clinicopathologic expression of disease and on ileal Foxp3+ T regulatory cell immune responses in an experimental NEC model. Newborn rat pups were fed gavage formula (NEC) or formula supplemented with 15 μg/mL GD3 (GD3-NEC). Dam-fed (DF) littermates served as controls. NEC was induced by asphyxia and cold stress. At 96 hours, ileal gross and histologic changes were evaluated, and ileal cytokine profiles, Foxp3 expression, and Foxp3+ cell numbers were determined. GD3 decreased the incidence and gross and histopathologic severity of NEC. Ileal Foxp3 expression and Foxp3+ cell numbers were significantly decreased in the NEC group compared with DF. GD3 increased ileal Foxp3 expression and Foxp3+ cell numbers, in association with upregulation of anti-inflammatory cytokine interleukin (IL)-10 and chemokines, tissue inhibitor of metalloproteinases 1, IL-1 receptor antagonist (IL-1ra), and suppressed proinflammatory mediators. These data suggest that dietary GD3 protects newborn rats from NEC, in part, by augmenting mucosal Foxp3+ T regulatory immune responses.

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

    PubMed

    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.

  7. Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women.

    PubMed

    Sinaki, M; Itoi, E; Wahner, H W; Wollan, P; Gelzcer, R; Mullan, B P; Collins, D A; Hodgson, S F

    2002-06-01

    The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up (p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up (p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.

  8. A PERMISSION SYSTEM FOR CARBAPENEM USE REDUCED INCIDENCE OF DRUG-RESISTANT BACTERIA AND COST OF ANTIMICROBIALS AT A GENERAL HOSPITAL IN JAPAN

    PubMed Central

    IKEDA, YOSHIAKI; MAMIYA, TAKAYOSHI; NISHIYAMA, HIDEKI; NARUSAWA, SHIHO; KOSEKI, TAKENAO; MOURI, AKIHIRO; NABESHIMA, TOSHITAKA

    2012-01-01

    ABSTRACT Some drug management systems have been established in Japanese hospitals to reduce medical costs and regulate drug usage. Among the many available prescription drugs, antimicrobials should be given special attention because their inappropriate use often leads to sudden outbreaks of resistant bacteria. As drug specialists, pharmacists should monitor the use of all drugs, particularly antimicrobials. Carbapenems are a class of broad-spectrum antimicrobials that are widely used to treat infections worldwide. However, their inappropriate use has led to an increase in the incidence of drug-resistant bacteria and consequently, medical costs, at hospitals. To reduce inappropriate use and drug resistance, we have established a permission system to control the use of carbapenems at the Japanese Red Cross Nagoya Daiichi Hospital. In this study, we retrospectively evaluated the applicability of the new permission system compared to that of the notification system and the non control system for 14 months each. The two management systems were able to maintain total antibiotic use density and control the outbreak of drug-resistant bacteria (P. aeruginosa, E. coli, and K. pneumoniae). The number of carbapenem prescriptions was decreased dramatically when this permission system was enforced. Compared to the non control system, the cost of antimicrobials was reduced by $757,470 for the 14-month study period using the permission system. These results suggest that our system to control the use of antimicrobials can efficiently suppress the incidence of drug-resistant bacteria and medical costs at hospitals. PMID:22515115

  9. Recombinant human milk fat globule-EGF factor 8 produces dose-dependent benefits in sepsis.

    PubMed

    Shah, Kavin G; Wu, Rongqian; Jacob, Asha; Molmenti, Ernesto P; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2012-01-01

    Animal milk fat globule-EGF factor 8 (MFG-E8) has been shown to be beneficial in attenuating the inflammatory response in sepsis. In this study, we examined the effect of recombinant human MFG-E8 (rhMFG-E8) in an animal model of sepsis in an effort to develop it as a potential therapy against sepsis in humans. Rats were subjected to sepsis by cecal ligation and puncture (CLP), and at 5 h post-CLP, they were given different doses of rhMFG-E8 (20, 40, 80, 160 μg/kg BW) in normal saline. At 20 h post-CLP, samples were collected for further analysis. A 10-day survival study was also performed. At 20 h after CLP, organ injury indicators, serum IL-6 and TNF-α, and plasma HMGB-1 levels were significantly increased as compared to sham-operated animals. Treatment with 20 μg/kg rhMFG-E8 significantly reduced these levels. With higher doses, further reductions in AST and ALT (59-62%), creatinine (65-68%), and lactate (46-57%), and serum IL-6 and TNF-α were obtained. The 160 μg/kg dose produced the greatest reduction in serum TNF-α. With treatment with 20 μg/kg rhMFG-E8, HMGB-1 levels decreased by 80%, returning back to sham values. In a 10-day survival study, vehicle-treated animals produced a 36% survival rate, while rhMFG-E8 significantly improved the survival rate to 68-72%. Treatment with increasing doses of rhMFG-E8 significantly reduced the number of apoptotic cells detected and markedly attenuated the tissue damages observed in the lungs. These data suggest that recombinant human MFG-E8 is beneficial in ameliorating sepsis in an animal model of sepsis.

  10. Dose-dependent effect of Curcuma longa for the treatment of Parkinson's disease

    PubMed Central

    Ma, Xiao-Wei; Guo, Rui-You

    2017-01-01

    Curcuma longa is a plant that belongs to the ginger family, Zingiberaceae. It has been used in Siddha medicine for thousands of years in Asia. Parkinson's disease (PD) is a degenerative disorder of the central nervous system that affects the motor system of the brain. Death of dopamine-producing cells in the substantia nigra leads to PD. Exposure to salsolinol, which is an endogenous neurotoxin, has been associated with damage to dopamine-producing cells. The present study assessed the toxicity of salsolinol in SH-SY5Y human neuroblastoma cells and subsequently investigated the neuroprotective potential of C. longa extract in salsolinol-induced toxic conditions in SH-SY5Y cells. Sulphorhodamine-B assay showed the protective effect of the anti-apoptotic effect of treated SH-SY5Y cells. Fluorescence microscopy and confocal laser scanning microscope analysis indicated the anti-apoptotic impact of the C. longa extract. Mitochondria-derived reactive oxygen species were reduced in C. longa extract-treated SH-SY5Y cells. Downregulated mRNA expression levels of p53, Bcl-2-associated X protein and caspase 3 were observed in the C. longa extract-treated SH-SY5Y cells. Caspase 3 activity was reduced in the C. longa extract-treated SH-SY5Y cells. In conclusion, the present findings demonstrated that solsolinol is neurotoxic to SH-SY5Y cells, and C. longa extract may be useful in the treatment of PD. PMID:28565770

  11. Effects of reduced deer density on the abundance of Ixodes scapularis (Acari: Ixodidae) and Lyme disease incidence in a northern New Jersey endemic area.

    PubMed

    Jordan, Robert A; Schulze, Terry L; Jahn, Margaret B

    2007-09-01

    We monitored the abundance of Ixodes scapularis Say (Acari: Ixodidae) and the Lyme disease incidence rate after the incremental removal of white-tailed deer, Odocoileus virginianus Zimmermann, within a suburban residential area to determine whether there was a measurable decrease in the abundance of ticks due to deer removal and whether the reduction in ticks resulted in a reduction in the incidence rate within the human population. After three seasons, the estimated deer population was reduced by 46.7%, from the 2002 postfawning estimate of 2,899 deer (45.6 deer per km2) to a 2005 estimate of 1,540 deer (24.3 deer per km2). There was no apparent effect of the deer culling program on numbers of questing I. scapularis subadults in the culling areas, and the overall numbers of host-seeking ticks in the culling areas seemed to increase in the second year of the program. The Lyme disease incidence rate generated by both passive and active surveillance systems showed no clear trend among years, and it did not seem to vary with declining deer density. Given the resources required to mount and maintain a community-based program of sufficient magnitude to effectively reduce vector tick density in ecologically open situations where there are few impediments to deer movement, it may be that deer reduction, although serving other community goals, is unlikely to be a primary means of tick control by itself. However, in concert with other tick control interventions, such programs may provide one aspect of a successful community effort to reduce the abundance of vector ticks.

  12. Use of External Beam Radiotherapy Is Associated With Reduced Incidence of Second Primary Head and Neck Cancer: A SEER Database Analysis

    SciTech Connect

    Rusthoven, Kyle; Chen Changhu Raben, David; Kavanagh, Brian

    2008-05-01

    Purpose: Patients with head and neck cancer have a significant risk of developing a second primary cancer of the head and neck. We hypothesized that treatment with external beam radiotherapy (RT) might reduce this risk, because RT can eradicate occult foci of second head and neck cancer (HNCA). Methods and Materials: The data of patients with Surveillance, Epidemiology, and End Results Historic Stage A localized squamous cell carcinoma of the oral cavity, larynx, and pharynx were queried using the Surveillance, Epidemiology, and End Results database. For patients treated with or without RT, the incidence of second HNCA was determined and compared using the log-rank method. Cox proportional hazards analysis was performed for each site, evaluating the influence of covariates on the risk of second HNCA. Results: Between 1973 and 1997, 27,985 patients were entered with localized HNCA. Of these patients, 44% had received RT and 56% had not. The 15-year incidence of second HNCA was 7.7% with RT vs. 10.5% without RT (hazard ratio 0.71, p <0.0001). The effect of RT was more profound in patients diagnosed between 1988 and 1997 (hazard ratio 0.53, p <0.0001) and those with pharynx primaries (hazard ratio 0.47, p <0.0001). On multivariate analysis, RT was associated with a reduced risk of second HNCA for pharynx (p <0.0001) and larynx (p = 0.04) tumors. For oral cavity primaries, RT was associated with an increased risk of second HNCA in patients treated before 1988 (p <0.001), but had no influence on patients treated between 1988 and 1997 (p = 0.91). Conclusion: For localized HNCA, RT is associated with a reduced incidence of second HNCA. These observations are consistent with the eradication of microscopic foci of second HNCA with external beam RT.

  13. Dose-dependent lipid peroxidation induction on ex vivo intestine tracts exposed to chyme samples from fumonisins contaminated corn samples.

    PubMed

    Garbetta, A; Debellis, L; De Girolamo, A; Schena, R; Visconti, A; Minervini, F

    2015-08-01

    Fumonisins (FBs), Fusarium mycotoxins common food contaminant, are a potent inducer of oxidative stress and lipid peroxidation in intestinal cells. In order to verify this toxic effect in intestine tract, the aim was to assess lipid peroxidation (as malondialdehyde MDA increased levels) on intestine rat samples exposed to chyme samples from in vitro digestion of FBs contaminated corn samples. Naturally (9.61±3.2 μg/gr), artificially (726±94 μg/gr) and spiked corn samples at EU permitted FBs levels were digested and added to luminal side of Ussing chamber for 120 min. Fumonisins-free corn sample was used as control. The MDA increase was observed just in 83% of intestine samples exposed at EU FBs levels and the digestion process seems to reduce this incidence (50% of samples). Malondialdehyde levels were FBs dose- and subject-related and ranged from 0.07±0.01 to 3.59±0.6 nmol/mg. Highest incidence and MDA % increment (I) were found when intestine tracts were exposed to chymes from artificially corn sample. The induction of lipid peroxidation induced by FBs could be due to interactions between FBs and intestinal membranes, with consequent modifications in membrane permeability and oxygen diffusion-concentration, as suggested by other authors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Shoulder Stretching Intervention Reduces the Incidence of Shoulder and Elbow Injuries in High School Baseball Players: a Time-to-Event Analysis

    PubMed Central

    Shitara, Hitoshi; Yamamoto, Atsushi; Shimoyama, Daisuke; Ichinose, Tsuyoshi; Sasaki, Tsuyoshi; Hamano, Noritaka; Ueno, Akira; Endo, Fumitaka; Oshima, Atsufumi; Sakane, Hideo; Tachibana, Masahiro; Tomomatsu, Yusuke; Tajika, Tsuyoshi; Kobayashi, Tsutomu; Osawa, Toshihisa; Iizuka, Haku; Takagishi, Kenji

    2017-01-01

    We prospectively evaluated the effects of a prevention program on the incidence of shoulder and elbow injuries in high school baseball pitchers. Ninety-two pitchers participated in this study and were taught to perform stretching and strength exercises aimed at improving shoulder external rotation strength in the preseason. The pitchers freely chose to participate in one of four groups [SM-group: performed both exercises, S-group: performed stretching exercise only, M-group: performed strength training only, and N-group: performed neither intervention]. Injury was defined as inability to play for ≥8 days because of shoulder/elbow symptoms. Kaplan-Meier survival curves were generated and hazard ratios (HRs) for injury occurrence were calculated using multivariate Cox regression. Log-rank test was used for between-group comparisons of survival distributions. The injuries occurred in 25, 35, and 57% of participants and median times to injury were 89, 92, and 29.5 days in the S- (n = 32), SM- (n = 46), and N- (n = 14) group, respectively. Nobody chose M-group. HRs were 0.36 and 0.47 for the S- and SM-group, respectively, based on the N-group. The incidence of injury was significantly lower in the S-group than in the N-group (p = 0.04). Daily posterior shoulder stretching may reduce the incidence of the injuries in high school baseball pitchers. PMID:28345616

  15. Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence

    PubMed Central

    2012-01-01

    Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C) levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose–response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for consumption including spreads

  16. DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS

    EPA Science Inventory

    DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
    Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and ...

  17. DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS

    EPA Science Inventory

    DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
    Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and ...

  18. The dichotomy of memantine treatment for ischemic stroke: dose-dependent protective and detrimental effects

    PubMed Central

    Trotman, Melissa; Vermehren, Philipp; Gibson, Claire L; Fern, Robert

    2015-01-01

    Excitotoxicity is a major contributor to cell death during the acute phase of ischemic stroke but aggressive pharmacological targeting of excitotoxicity has failed clinically. Here we investigated whether pretreatment with low doses of memantine, within the range currently used and well tolerated for the treatment of Alzheimer's disease, produce a protective effect in stroke. A coculture preparation exposed to modeled ischemia showed cell death associated with rapid glutamate rises and cytotoxic Ca2+ influx. Cell death was significantly enhanced in the presence of high memantine concentrations. However, low memantine concentrations significantly protected neurons and glia via excitotoxic cascade interruption. Mice were systemically administered a range of memantine doses (0.02, 0.2, 2, 10, and 20 mg/kg/day) starting 24 hours before 60 minutes reversible focal cerebral ischemia and continuing for a 48-hour recovery period. Low dose (0.2 mg/kg/day) memantine treatment significantly reduced lesion volume (by 30% to 50%) and improved behavioral outcomes in stroke lesions that had been separated into either small/striatal or large/striatocortical infarcts. However, higher doses of memantine (20 mg/kg/day) significantly increased injury. These results show that clinically established low doses of memantine should be considered for patients ‘at risk' of stroke, while higher doses are contraindicated. PMID:25407270

  19. Dose-dependent electrophysiological effects of the myosin activator omecamtiv mecarbil in canine ventricular cardiomyocytes.

    PubMed

    Szentandrassy, N; Horvath, B; Vaczi, K; Kistamas, K; Masuda, L; Magyar, J; Banyasz, T; Papp, Z; Nanasi, P P

    2016-08-01

    Omecamtiv mecarbil (OM) is a myosin activator agent recently developed for treatment of heart failure. Although its action on extending systolic ejection time and increasing left ventricular ejection fraction is well documented, no data is available regarding its possible side-effects on cardiac ion channels. Therefore, the present study was designed to investigate the effects of OM on action potential morphology and the underlying ion currents in isolated canine ventricular myocytes using sharp microelectrodes, conventional patch clamp, and action potential voltage clamp techniques. OM displayed a concentration-dependent action on action potential configuration: 1 μM OM had no effect, while action potential duration and phase-1 repolarization were reduced and the plateau potential was depressed progressively at higher concentrations (10 - 100 μM; P < 0.05 compared to control). Accordingly, OM (10 μM) decreased the density of the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa) and the rapid delayed rectifier K(+) current (IKr), but failed to modify the inward rectifier K(+) current (IK1). It is concluded, that although the therapeutic concentrations of OM are not likely to influence cardiac ion currents significantly, alterations of the major cardiac ion currents can be anticipated at concentrations above those clinically tolerated.

  20. Trichoderma asperellum spore dose depended modulation of plant growth in vegetable crops.

    PubMed

    Singh, Vivek; Upadhyay, Ram Sanmukh; Sarma, Birinchi Kumar; Singh, Harikesh Bahadur

    2016-12-01

    In the present study we bioprimed seeds of six vegetable crops (tomato, brinjal, chilli, okra, ridge gourd and guar) with different spore doses of Trichoderma asperellum BHUT8 ranging from 10(2) to 10(8) spores ml(-1) and the effect of biopriming was seen on seed germination and development. The most effective spore dose for enhancement in seed germination and radicle length was found to be 10(3) spores ml(-1) in tomato and ridge gourd, 10(4) spores ml(-1) in brinjal and okra while 10(6) spores ml(-1) in chilli and guar. At the most effective spore dose, the increase in germination percentage was 5, 146.15, 112.5, 5.4, 28.13 and 0% while increase in radicle length was 73.17, 50.83, 171.6, 107.35, 247.19 and 90.79% in tomato, brinjal, chilli, okra, ridge gourd and guar, respectively, compared to their controls. Higher spore dose i.e. 10(7)-10(8) spores ml(-1) and 10(6)-10(8) spores ml(-1) in tomato and brinjal, respectively, reduced seed germination percentage and radicle growth compared to their controls. Biopriming with T. asperellum BHUT8 also triggered various defense like responses such as high phenylpropanoid activities and lignifications in bioprimed tomato seedlings compared to the non-bioprimed tomato seedlings demonstrating possible use of BHUT8 against phytopathogens.

  1. Dose-dependent Neuroprotection of VEGF165 in Huntington's Disease Striatum

    PubMed Central

    Ellison, Stuart M; Trabalza, Antonio; Tisato, Veronica; Pazarentzos, Evangelos; Lee, Shirley; Papadaki, Vasiliki; Goniotaki, Despoina; Morgan, Sarah; Mirzaei, Nazanin; Mazarakis, Nicholas D

    2013-01-01

    Huntington's disease (HD) is a devastating neurodegenerative disorder caused by abnormal polyglutamine expansion in the huntingtin protein (Exp-Htt). Currently, there are no effective treatments for HD. We used bidirectional lentiviral transfer vectors to generate in vitro and in vivo models of HD and to test the therapeutic potential of vascular endothelial growth factor 165 (VEGF165). Lentiviral-mediated expression of Exp-Htt caused cell death and aggregate formation in human neuroblastoma SH-SY5Y and rat primary striatal cultures. Lentiviral-mediated VEGF165 expression was found to be neuroprotective in both of these models. Unilateral stereotaxic vector delivery of Exp-Htt vector in adult rat striatum led to progressive inclusion formation and striatal neuron loss at 10 weeks post-transduction. Coinjection of a lower dose VEGF165 significantly attenuated DARPP-32+ neuronal loss, enhanced NeuN staining and reduced Exp-Htt aggregation. A tenfold higher dose VEGF165 led to overt neuronal toxicity marked by tissue damage, neovascularization, extensive astrogliosis, vascular leakage, chronic inflammation and distal neuronal loss. No overt behavioral phenotype was observed in these animals. Expression of VEGF165 at this higher dose in the brain of wild-type rats led to early mortality with global neuronal loss. This report raises important safety concerns about unregulated VEGF165 CNS applications. PMID:23799534

  2. The dichotomy of memantine treatment for ischemic stroke: dose-dependent protective and detrimental effects.

    PubMed

    Trotman, Melissa; Vermehren, Philipp; Gibson, Claire L; Fern, Robert

    2015-02-01

    Excitotoxicity is a major contributor to cell death during the acute phase of ischemic stroke but aggressive pharmacological targeting of excitotoxicity has failed clinically. Here we investigated whether pretreatment with low doses of memantine, within the range currently used and well tolerated for the treatment of Alzheimer's disease, produce a protective effect in stroke. A coculture preparation exposed to modeled ischemia showed cell death associated with rapid glutamate rises and cytotoxic Ca(2+) influx. Cell death was significantly enhanced in the presence of high memantine concentrations. However, low memantine concentrations significantly protected neurons and glia via excitotoxic cascade interruption. Mice were systemically administered a range of memantine doses (0.02, 0.2, 2, 10, and 20 mg/kg/day) starting 24 hours before 60 minutes reversible focal cerebral ischemia and continuing for a 48-hour recovery period. Low dose (0.2 mg/kg/day) memantine treatment significantly reduced lesion volume (by 30% to 50%) and improved behavioral outcomes in stroke lesions that had been separated into either small/striatal or large/striatocortical infarcts. However, higher doses of memantine (20 mg/kg/day) significantly increased injury. These results show that clinically established low doses of memantine should be considered for patients 'at risk' of stroke, while higher doses are contraindicated.

  3. Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

    PubMed Central

    Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

    2015-01-01

    Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

  4. Preoperative ephedrine counters hypotension with propofol anesthesia during valve surgery: a dose dependent study.

    PubMed

    El-Tahan, Mohamed R

    2011-01-01

    The prophylactic use of small doses of ephedrine may counter the hypotension response to propofol anesthesia with minimal hemodynamic changes. One hundred-fifty patients scheduled for valve surgery were randomly assigned into five groups (n = 30 for each) to receive saline, 0.07, 0.1, or 0.15 mg/kg of ephedrine, or phenylephrine 1.5 μg/kg before induction of propofol-fentanyl anesthesia. After induction, patient receiving ephedrine had higher mean arterial pressure, systemic vascular resistance (SVRI), cardiac (CI), stroke volume (SVI), and left ventricular stroke work (LVSWI) indices. Patients received 0.15 mg/kg of ephedrine showed additional increased heart rate and frequent ischemic episodes (P < 0.001). However, those who received phenylephrine showed greater rise in SVRI, reduced CI, SVI, and LVSWI and more frequent ischemic episodes. We conclude that the prophylactic use of small doses of ephedrine (0.07-0.1 mg/kg) is safe and effective in the counteracting propofol-induced hypotension during anesthesia for valve surgery.

  5. The pharmacokinetics of pyridostigmine and 3-hydroxy-N-methylpyridinium in the rat: dose-dependent effects after portal vein administration.

    PubMed Central

    Barber, H E; Bourne, G R; Calvey, T N; Muir, K T

    1975-01-01

    1 The elimination kinectis of [14C]-pyridostigmine iodine and [14-C-methyl]-3-hydroxypyridinium bromide (3-OH NMP) have been studied in the rat. 2 For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver. 3 When doses of pyridostigmine 1.25 mumol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose-dependent process is involved in the urinary excretion of 3-OH NMP. 4 This conclusion was supported by studies involving the portal and systemic venous injection of 3-OH NMP at different dose levels. After 4 h, approximately85% of the lowest dose was eliminated unchanged in ug this period. The proportion of the dose eliminated in urine was not related to the route of administration. 5 After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug. PMID:173444

  6. WE-EF-BRA-10: Prophylactic Cranial Irradiation Reduces the Incidence of Brain Metastasis in a Mouse Model of Metastatic Breast Cancerr

    SciTech Connect

    Smith, D; Debeb, B; Larson, R; Diagaradjane, P; Woodward, W

    2015-06-15

    Purpose: Prophylactic cranial irradiation (PCI) is a clinical technique used to reduce the incidence of brain metastasis and improve overall survival in select patients with acute lymphoblastic leukemia and small-cell lung cancer. We examined whether PCI could benefit breast cancer patients at high risk of developing brain metastases. Methods: We utilized our mouse model in which 500k green fluorescent protein (GFP)-labeled breast cancer cells injected into the tail vein of SCID/Beige mice resulted in brain metastases in approximately two-thirds of untreated mice. To test the efficacy of PCI, one set of mice was irradiated five days after cell injection with a single fraction of 4-Gy (two 2-Gy opposing fields) whole-brain irradiation on the XRAD 225Cx small-animal irradiator. Four controls were included: a non-irradiated group, a group irradiated two days prior to cell injection, and two groups irradiated 3 or 6 weeks after cell injection. Mice were sacrificed four and eight weeks post-injection and were evaluated for the presence of brain metastases on a fluorescent stereomicroscope. Results: The incidence of brain metastasis in the non-irradiated group was 77% and 90% at four and eight weeks, respectively. The PCI group had a significantly lower incidence, 20% and 30%, whereas the other three control groups had incidence rates similar to the non-treated control (70% to 100%). Further, the number of metastases and the metastatic burden were also significantly lower in the PCI group compared to all other groups. Conclusion: The timing of irradiation to treat subclinical disease is critical, as a small dose of whole-brain irradiation given five days after cell injection abrogated tumor burden by greater than 90%, but had no effect when administered twenty-one days after cell injection. PCI is likely to benefit breast cancer patients at high risk of developing brain metastases and should be strongly considered in the clinic.

  7. Impact of guidelines and enhanced antibiotic stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection.

    PubMed

    Talpaert, Moïra Joëlle; Gopal Rao, Guduru; Cooper, Ben Symons; Wade, Paul

    2011-09-01

    To evaluate the impact of an 'intervention' consisting of revised antibiotic guidelines for empirical treatment of common infections and enhanced stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection (CDI). This was a retrospective, quasi-experimental study using interrupted time series (ITS) over 12 months before and after the intervention. The setting was adult medical and surgical wards in University Hospital Lewisham, an acute general hospital in London. The intervention was introduced in April 2006. Revised guidelines avoided broad-spectrum antibiotics, e.g. fluoroquinolones, cephalosporins, clindamycin, amoxicillin and co-amoxiclav, as they were considered to be 'high risk' for CDI. Instead, 'low risk' antibiotics such as penicillin, clarithromycin, doxycycline, gentamicin, vancomycin, trimethoprim and nitrofurantoin were recommended. Changes in antibiotic usage and incidence of CDI before and after the intervention were compared using segmented regression analysis. The negative binomial model was used to analyse the time series to estimate the CDI incidence rate ratio (IRR) following the intervention. The intervention was associated with a significant reduction in the use of fluoroquinolones by 105.33 defined daily doses (DDDs)/1000 occupied bed-days (OBDs) per month [95% confidence interval (CI) 34.18-176.48, P < 0.001] and cephalosporins by 45.93 DDDs/1000 OBDs/month (95% CI 24.11-67.74, P < 0.0001). There was no significant change in total antibiotic, clindamycin, amoxicillin or co-amoxiclav use. There was a significant decrease in CDI following the intervention [IRR 0.34 (0.20-0.58), P < 0.0001]. Revised antibiotic guidelines and enhanced stewardship was associated with a significant stepwise reduction in the use of cephalosporins and fluoroquinolones and a significant decrease in the incidence of CDI.

  8. The use of an algorithm for prophylactic mesh use in high risk patients reduces the incidence of incisional hernia following laparotomy for colorectal cancer resection.

    PubMed

    Argudo, Núria; Iskra, M Pilar; Pera, Miguel; Sancho, Juan J; Grande, Luis; López-Cano, Manuel; Pereira, José Antonio

    2017-04-01

    Incisional hernia (IH) after colorectal surgery is highly prevalent. The objective of this study is to assess the utility of an algorithm to decide on mesh augmentation after a midline laparotomy for colorectal resection to prevent IH in high-risk patients. A prospective study was conducted including all patients undergoing a midline laparotomy for colorectal resection between January 2011 and June 2014, after the implementation of a decision algorithm for prophylactic mesh augmentation in selected high-risk patients. Intention-to-treat analyses were conducted between patients in which the algorithm was correctly applied and those in which it was not. From the 235 patients analysed, the algorithm was followed in 166 patients, the resting 69 cases were used as a control group. From an initial adherence to the algorithm of 40% in the first semester, a 90.3% adherence was achieved in the seventh semester. The incidence of IH decreased as the adherence to the algorithm increased (from 28 to 0%) with a time-related correlation (R(2)=0.781). A statistically significant reduction in IH incidence was demonstrated in high-risk groups in which the algorithm was correctly applied (10,2 vs. 46,3%; p=0,0001; OR: 7,58;95%; CI: 3,8-15). Survival analysis showed that the differences remained constant during follow-up. The implementation of the algorithm reduces the incidence of IH in high-risk patients. The adherence to the algorithm also correlates with a decrease in the incidence of IH. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Dose-Dependent Effect of Granulocyte Transfusions in Hematological Patients with Febrile Neutropenia

    PubMed Central

    Di Blasi, Roberta; Orlando, Nicoletta; Fianchi, Luana; Zini, Gina; Sica, Simona; De Stefano, Valerio; Pagano, Livio

    2016-01-01

    It is still under debate whether granulocyte transfusions (GTs) substantially increase survival in patients with febrile neutropenia. We retrospectively examined data relative to 96 patients with hematological malignancies receiving 491 GTs during 114 infectious episodes (IE). Patients were grouped according to the median doses of granulocytes transfused during the infectious episode (low-dose group: <1.5-x108 cells/Kg; standard-dose group: 1.5–3.0x108 cells/Kg and high-dose group: >3.0x108 cells/Kg). The impact of clinical, microbiological and GT-related variables on the infection-related mortality (IRM) was investigated. The IRM was not influenced by the number of GTs or by the total amount of granulocytes received, whereas a dose-related effect of the median dose received for IE was detected at univariate analysis (IRM of 18.4% in the standard-dose group, 44.4% in the low-dose group and 48.4% in the high-dose group, p = 0.040) and confirmed at multivariate analysis (OR 3.7, IC 95% 1.5–8.9; 0.004 for patients not receiving standard doses of GTs). Moreover, patients receiving GTs at doses lower or greater than standard had increased risk for subsequent ICU admission and reduced overall survival. The dose-related effect of GTs was confirmed in bacterial but not in fungal infections. Preliminary findings obtained from a subgroup of patients candidate to GTs revealed that levels of inflammatory response mediators increase in a dose-related manner after GTs, providing a possible explanation for the detrimental effect exerted by high-dose transfusions. GTs can constitute a valuable tool to improve the outcome of infections in neutropenic patients, provided that adequate recipient-tailored doses are supplied. Further investigations of the immunomodulatory effects of GTs are recommended. PMID:27487075

  10. Resilience and vulnerability are dose-dependently related to neonatal stressors in mice.

    PubMed

    Macrì, Simone; Granstrem, Oleg; Shumilina, Maria; Antunes Gomes dos Santos, Fernando João; Berry, Alessandra; Saso, Luciano; Laviola, Giovanni

    2009-10-01

    Early life experiences have been shown to adjust cognitive abilities, stress reactivity, fear responses and immune activity in adult mammals of many species. However, whereas severe stressors have been generally associated with the emergence of hypothalamic pituitary adreno-cortical (HPA)-mediated pathology, mild neonatal stressful experiences have been traditionally associated with 'positive' effects or resilience. External stressors stimulate the HPA axis to induce a corticosterone secretion in mouse dams, which, in turn is directly transmitted to the progeny through lactation. Such corticosteroid transfer may offer a unitary mechanism whereby early low corticosterone exposure may favor resilience in the offspring and high corticosterone increase vulnerability to pathology. In this study we further investigated this hypothesis by evaluating the long-term effects of a neonatal exposure to low (33 mg/l) and high (100 mg/l) doses of corticosterone during the first 10 days of life in outbred CD-1 mice through supplementation in the maternal drinking water. Offspring attentional set-shifting abilities, central neurotrophic regulation and levels of natural auto-antibodies (na-Abs) directed to serotonin (SERT) and dopamine (DAT) transporters were assessed in adulthood. While low levels of neonatal corticosterone improved adult cognitive abilities and increased na-Abs levels directed to SERT, high doses of neonatal corticosterone reduced hippocampal BDNF levels and na-Abs directed to DAT. These findings confirm and extend our previous findings, supporting the view that both adaptive plasticity and pathological outcomes in adulthood may depend on circulating neonatal corticosterone levels and that these effects follow a U-shaped profile.

  11. Dose-dependent effects of alcohol administration on behavioral profiles in the MCSF test.

    PubMed

    Karlsson, Oskar; Roman, Erika

    2016-02-01

    The acute effects of alcohol administration are age-, dose-, time- and task-dependent. Although generally considered to be a sedative drug, alcohol has both stimulatory and depressant effects on behavior, depending on dose and time. Alcohol-induced motor activating effects are consistently shown in mice but rarely demonstrated in adult, outbred rats using conventional behavioral tests. The aim of the present experiment was to study acute alcohol-induced effects on behavioral profiles in a more complex environment using the novel multivariate concentric square field™ (MCSF) test, designed for assessing different behaviors in the same trial including locomotor activity. Adult male Wistar rats (Sca:WI) were administered one intraperitoneal (i.p.) injection of alcohol (0.0 g/kg, 0.5 g/kg, 1.0 g/kg, or 1.5 g/kg) 5 min prior to the 30-min MCSF test. The two highest doses induced marked motor-suppressing effects. A significant interaction between group and time was found in general activity when comparing rats exposed to alcohol at 0.0 g/kg and 0.5 g/kg. In contrast to the 0.0 g/kg dose that increased the activity over time, animals administered the low dose (0.5 g/kg) demonstrated an initial high activity followed by a decline over time. No indications for acute alcohol-induced anxiolytic-like effects were found. The multivariate setting in the MCSF test appears to be sensitive for detecting motor-activating effects of low doses of alcohol as well as reduced locomotion at doses lower than in other behavioral tasks. The detection of subtle changes in behavior across time and dose is important for understanding alcohol-induced effects. This approach may be useful in evaluating alcohol doses that correspond to different degrees of intoxication in humans. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. The dose-dependence biological effect of laser fluence on rabbit fibroblasts derived from urethral scar.

    PubMed

    Yang, Yong; Yu, Bo; Sun, Dongchong; Wu, Yuanyi; Xiao, Yi

    2015-04-01

    Two-micrometer laser vaporization resection has been used in clinic for years, but some patients received the treatment are still faced with excessive and abnormal wound repair which leads to the recurrent of urethral stricture eventually. Fibroblasts play a key role in the processes of "narrow-expansion/operation-restenosis" recurring problems. Here, we investigated the effect of laser fluence biomodulation on urethral scar fibroblasts as well as the underlying mechanism. Urethral scar fibroblasts were isolated and cultured, and laser irradiation (2 μm) was applied at different laser fluence or doses (0, 0.125, 0.5, 2, 8, 32 J/cm(2)) with a single exposure in 1 day. The effect of 2-μm laser irradiation on cell proliferation, viability, and expression of scar formation related genes were investigated. Two-micrometer laser irradiation with intermediate dose (8 J/cm(2)) promoted scar fibroblasts proliferation and reactive oxygen species (ROS) production, while higher doses of 32 J/cm(2) are suppressive as it decreased the survival rate, viability, and proliferation of fibroblasts. In addition, qRT-PCR and Western blotting results both proven that collagen type I, collagen IV, MMP9, and CTGF display significant increase, yet the TGF-β1 expression was severely reduced at intermediate dose (8 J/cm(2)) group when compared with the others groups. Our findings suggest the scar formation-related genes are sensitive to intermediate laser irradiation dose, the most in scar fibroblasts. We revealed the bioeffect and molecular mechanism of 2-μm laser irradiation on rabbit urethral scar fibroblasts. Our study provides new insights into the mechanisms which involved in the excessive and abnormal wound repair of 2-μm laser vaporization resection. These results could potentially contribute to further study on biological effects and application of 2-μm laser irradiation in urethral stricture therapy.

  13. Dose-dependent effects of mTOR inhibition on weight and mitochondrial disease in mice

    PubMed Central

    Johnson, Simon C.; Yanos, Melana E.; Bitto, Alessandro; Castanza, Anthony; Gagnidze, Arni; Gonzalez, Brenda; Gupta, Kanav; Hui, Jessica; Jarvie, Conner; Johnson, Brittany M.; Letexier, Nicolas; McCanta, Lanny; Sangesland, Maya; Tamis, Oliver; Uhde, Lauren; Van Den Ende, Alex; Rabinovitch, Peter S.; Suh, Yousin; Kaeberlein, Matt

    2015-01-01

    Rapamycin extends lifespan and attenuates age-related pathologies in mice when administered through diet at 14 parts per million (PPM). Recently, we reported that daily intraperitoneal injection of rapamycin at 8 mg/kg attenuates mitochondrial disease symptoms and progression in the Ndufs4 knockout mouse model of Leigh Syndrome. Although rapamycin is a widely used pharmaceutical agent dosage has not been rigorously exam