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Sample records for high dose simvastatin

  1. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

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    Alan T Clarke

    Full Text Available Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.

  2. A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma

    DEFF Research Database (Denmark)

    Søndergaard, Teis Esben; Pedersen, PT; Levin Andersen, Thomas;

    2008-01-01

    Several studies have evaluated the impact of low dose statin (20-80 mg/day) on bone metabolism with inconclusive results despite promising data of preclinical studies. In this study, we investigated the effect of high dose simvastatin (HD-Sim) on biochemical markers of bone turnover and disease a...

  3. Simvastatin

    Science.gov (United States)

    ... such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also ...

  4. Low-dose Simvastatin Increases Skeletal Muscle Sensitivity to Caffeine and Halothane

    Institute of Scientific and Technical Information of China (English)

    Xu-lei Cui; Ying-lin Wang; Gang Tan; Ai-lun Luo; Xiang-yang Guo

    2016-01-01

    Objective To determine whether the myotoxic side effects of statin simvastatin affect skeletal muscle’s sensitivity to caffeine and halothane. Methods Primary cultured neonate rat skeletal myotubes were treated with 0.01-5.0μmol/L simvastatin for 48 hours. MTT was used to evaluate cellular viability. The gross morphology and microstructure of the myotubes were observed with a light and electron microscope, respectively. The intracellular calcium concentrations ([Ca2+]i) at rest and in response to caffeine and halothane were investigated by fluorescence calcium imaging. Data were analyzed byanalysis of variance (ANOVA) test. Results Simvastatin (0.01-5.0μmol/L) decreased myotube viability, changed their morphological features and microstructure, and increased the resting [Ca2+]i in a dose-dependent manner. Simvastatin did not change myotube’s sensitivity to low doses of caffeine (0.625-2.5 mmol/L) or halothane (1.0-5.0 mmol/L). In response to high-dose caffeine (10.0 mmol/L, 20.0 mmol/L) and halothane (20.0 mmol/L, 40.0 mmol/L), myotubes treated with 0.01μmol/L simvastatin showed a significant increase in sensitivity, but those treated with 1.0μmol/L and 5.0μmol/L simvastatin showed a significant decrease. The sarcoplasmic reticulum Ca2+ storage peaked in the myotubes treated with 0.01μmol/L simvastatin, but it decreased when cells were treated with higher doses of simvastatin (0.1-5.0μmol/L). Conclusions The myotoxic side effect of simvastatin was found to change the sensitivity of myotubes in response to high-dose caffeine and halothane. When dose was low, sensitivity increased mainly because of increased Ca2+ content in the sarcoplasmic reticulum, which might explain why some individuals with statin-induced myotoxic symptoms may show positivecaffeine-halothane contracture test results. However, when the dose was high and the damage to the myotubes was severer, sensitivity was lower. It is here supposed that the damage itself might put individuals with

  5. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Galtier, F., E-mail: f-galtier@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); CPID, Faculté de Pharmacie, 15 Av. Charles Flahault, BP 14491, 34093 Montpellier Cedex 5, Montpellier (France); Mura, T., E-mail: t-mura@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Raynaud de Mauverger, E., E-mail: eric.raynaud-de-mauverger@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); Université Montpellier 1, 5 bd Henri IV CS 19044, 34967 Montpellier Cedex 2 (France); Université Montpellier 2, Place Eugène Bataillon, 34095 Montpellier Cedex 5 (France); INSERM, U1046, 371 Avenue du Doyen G. Giraud, CHU Arnaud de Villeneuve, Bâtiment INSERM Crastes de Paulet, 34295 Montpellier Cedex 5 (France); Chevassus, H., E-mail: h-chevassus@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Farret, A., E-mail: a-farret@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Gagnol, J.-P., E-mail: jp-gagnol@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Costa, F., E-mail: francoisecosta@sfr.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); INSERM, CIC 1001, 80 Avenue Augustin Fliche, 34295 Montpellier Cedex 5 (France); Dupuy, A., E-mail: am-dupuy@chu-montpellier.fr [CHRU Montpellier, 34295 Montpellier Cedex 5 (France); and others

    2012-09-15

    Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca{sup 2+} homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca{sup 2+} spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38 ± 5.68 vs − 1.15 ± 4.32 UI/L, P < 0.001) and CK (− 24.3 ± 99.1 ± 189.3vs 48.3 UI/L, P = 0.01) and a trend to an elevation of isoprostanes (193 ± 408 vs12 ± 53 pmol/mmol creatinine, P = 0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca{sup 2+} sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca{sup 2+} spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca{sup 2+} spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r = 0.71, P = 0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication. -- Highlights: ► Statin use may be limited by side effects, particularly myopathy. ► Statins might impair mitochondrial function and muscle Ca2+ signaling in muscle. ► This was tested among healthy volunteers receiving simvastatin 80 mg daily for 8 weeks. ► CK

  6. Short Term, Low Dose Simvastatin Pretreatment Alters Memory Immune Function Following Secondary Staphylococcus aureus Infection.

    Science.gov (United States)

    Smelser, Lisa K; Walker, Callum; Burns, Erin M; Curry, Michael; Black, Nathanael; Metzler, Jennifer A; McDowell, Susan A; Bruns, Heather A

    Statins are potent modulators of immune responses, resulting in their ability to enhance host survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial for survival following infection may also result in alterations in the generation of the immunologic memory response and subsequently affect immune responses mounted during secondary bacterial infection. In this study, we report that levels of total serum IgG2c, following primary infection, were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment, prior to primary infection, on immune responses activated during secondary S. aureus infection. A secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14 days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1 compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore, memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term, low dose simvastatin treatment to modulate memory immune function.

  7. ANTI-HYPERGLYCEMIC ACTIVITY OF SIMVASTATIN ALONE (THERAPEUTIC DOSE AND COMBINATION OF SIMVASTATIN AND GLIPIZIDE (SUB THERAPEUTIC DOSES ON ALLOXAN INDUCED HYPERGLYCEMIA IN ALBINO RATS

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    V.S. Harish Kumar*, N.R. Sindhu, Rajashri S. Patil and Umakant Patil

    2012-11-01

    Full Text Available The present study was designed to evaluate anti-hyperglycemic activity of simvastatin alone and the combination of sub therapeutic doses of simvastatin and glipizide. Hyperglycemia was induced experimentally in albino rats by subcutaneous injection of alloxan in a dose of 175 mg/kg body weight. After 72 hours of alloxan treatment, rats showing hyperglycemia (blood glucose level of 400 mg/dl and above were included in the study. They were divided into four groups of 6 animals each (n=24. Oral administration of normal saline 0.5 ml, glipizide 2.5 mg/kg body weight, simvastatin 10 mg/kg body weight and sub therapeutic doses of both test (simvastatin 5 mg/kg body weight and standard (glipizide 1.25 mg/kg body weight drugs, was done respectively into each of the four groups for 30 consecutive days in order to assess the effect in terms of reduction in blood glucose level. Blood glucose was estimated on 0th, 10th, 20th, and 30th days of study in fixed time intervals. In the test group, there was a gradual fall in the blood glucose level which reached up to 308.3 mg/dl by 30th day of study (P < 0.001. In case of combination of sub therapeutic doses of simvastatin and glipizide, the fall in blood glucose level was gradual and sustained and it reached up to 201.5 mg/dl by the 30th day (P < 0.001. These observations are comparable with the results obtained in case of glipizide treated rats, the standard group. Simvastatin appreciably lowered the blood glucose level, but the combination of sub therapeutic doses of simvastatin and glipizide, by virtue of their possible synergistic effect produced further reduction in the blood glucose level. This study provides evidence in support of a potential anti-hyperglycemic effect of simvastatin and its combination with glipizide. Thus the combined treatment of simvastatin and glipzide may have added benefit for the diabetic patients associated with hyperlipidemia.

  8. Simvastatin Results in a Dose-Dependent Toxic Effect on Spiral Ganglion Neurons in an In Vitro Organotypic Culture Assay

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    Katharina Leitmeyer

    2016-01-01

    Full Text Available Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme necessary for the production of mevalonate. They are widely used as cholesterol-lowering drugs. However, conflicting data about the effect of statins on neuronal cells has been published. To explore the effect of simvastatin on spiral ganglion neurons (SGNs, SG explants of 5-day-old rats were treated with increasing concentrations of simvastatin. In addition, SG explants were treated with mevalonate and with the combination of simvastatin and mevalonate. SGN number, length of the neurites, area of nonneuronal supporting cells, and neuronal survival were analyzed. Simvastatin treatment results in a significant dose-dependent decrease of SG neurite number, length of neurites, area of supporting cells, and SG neuronal survival compared to control. Interestingly, treatment with mevalonate in addition to simvastatin increased SG neuronal survival compared to simvastatin treatment only. However, treatment with mevalonate in addition to simvastatin did not influence SG neurite number, length of neurites, and area of supporting cells compared to simvastatin treatment only. Our results suggest a neurotoxic effect of simvastatin on SGNs in vitro. Neurotoxicity seems to be at least partially mediated by the mevalonate pathway. Therefore, caution is warranted to use simvastatin as a potential otoprotective drug.

  9. Management of dyslipidemia and hyperglycemia with a fixed-dose combination of sitagliptin and simvastatin.

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    Steinberg, Helmut; Anderson, Matt S; Musliner, Thomas; Hanson, Mary E; Engel, Samuel S

    2013-01-01

    The risk of death due to heart disease and stroke is up to four times higher in individuals with diabetes compared to individuals without diabetes. Most guidelines that address treatment of dyslipidemia in patients with diabetes consider diabetes a cardiovascular disease (CVD) "risk equivalent" and recommend intensive treatment of dyslipidemia for the purpose of CVD prevention. Statins (3-hydroxy 3-methylglutaryl coenzyme A reductase [HMG-CoA reductase] inhibitors) are first-line agents in achieving lipid goals as an adjunct to diet and exercise and should be used in most patients. In addition to lipid management and blood pressure control, glycemic control is a basic component in the management of diabetes. Glycemic control is achieved by combining diabetes self-management education, diet and exercise, and, where required, antihyperglycemic agents (OHAs). Persistence and adherence to therapy are critical in achieving recommended treatment goals. However, overall compliance with concomitantly prescribed OHAs and statins is low in patients with type 2 diabetes. Fixed-dose combination (FDC) therapies have been shown to improve adherence by reducing pill burden, the complexity of treatment regimen, and, potentially, cost. Based on the available evidence regarding the pharmacokinetics and the efficacy and safety profiles of each component drug, the sitagliptin/simvastatin FDC may provide a rational and well-tolerated approach to achieving better adherence to multiple-drug therapy and improved lipid lowering and glycemic control, with consequent reduction in cardiovascular risk, diabetic microvascular disease, and mortality in diabetic patients for whom treatment with both compounds is appropriate.

  10. Concomitant Administration of Different Doses of Simvastatin with Ivabradine Influence on PAI-1 and Heart Rate in Normo- and Hypercholesterolaemic Rats

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    Jacek Owczarek

    2012-01-01

    Full Text Available Ivabradine is a novel heart rate lowering agent that inhibits If ionic current in the sinus node and demonstrates antiischaemic and antianginal activity. The aim of the paper was to investigate the effect its dose-dependent drug-drug interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart rate and blood pressure. The experiments were performed in hyper- and normocholesterolemic Wistar rats receiving simvastatin (1 and 20 mg×kg−1 bw with ivabradine (10 mg×kg−1 bw during a 4-week period. Ivabradine exacerbated the decrease of PAI-1 in normocholesterolemic animals receiving simvastatin at a dose of 1 mg/kg bw and was not observed to have any significant influence on the PAI-1 values in rats receiving 20 mg×kg−1 bw simvastatin. Ivabradine, coadministered with simvastatin given at a dose of 20 mg×kg−1 bw, significantly slowed the heart rate in normocholesterolaemic and hypercholesterolaemic groups as compared to the group receiving ivabradine alone. Conclusion. The administration of ivabradine to normocholesterolaemic and hypercholesterolaemic rats receiving simvastatin significantly exacerbated the slowing of heart rate with no effect on blood pressure. The administration of ivabradine has been shown to demonstrate different effects on PAI-1 values depending on lipid disorders.

  11. Management of dyslipidemia and hyperglycemia with a fixed-dose combination of sitagliptin and simvastatin

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    Steinberg H

    2013-05-01

    Full Text Available Helmut Steinberg, Matt S Anderson, Thomas Musliner, Mary E Hanson, Samuel S EngelMerck Sharp & Dohme Corp., Whitehouse Station, NJ, USAAbstract: The risk of death due to heart disease and stroke is up to four times higher in individuals with diabetes compared to individuals without diabetes. Most guidelines that address treatment of dyslipidemia in patients with diabetes consider diabetes a cardiovascular disease (CVD "risk equivalent" and recommend intensive treatment of dyslipidemia for the purpose of CVD prevention. Statins (3-hydroxy 3-methylglutaryl coenzyme A reductase [HMG-CoA reductase] inhibitors are first-line agents in achieving lipid goals as an adjunct to diet and exercise and should be used in most patients. In addition to lipid management and blood pressure control, glycemic control is a basic component in the management of diabetes. Glycemic control is achieved by combining diabetes self-management education, diet and exercise, and, where required, antihyperglycemic agents (OHAs. Persistence and adherence to therapy are critical in achieving recommended treatment goals. However, overall compliance with concomitantly prescribed OHAs and statins is low in patients with type 2 diabetes. Fixed-dose combination (FDC therapies have been shown to improve adherence by reducing pill burden, the complexity of treatment regimen, and, potentially, cost. Based on the available evidence regarding the pharmacokinetics and the efficacy and safety profiles of each component drug, the sitagliptin/simvastatin FDC may provide a rational and well-tolerated approach to achieving better adherence to multiple-drug therapy and improved lipid lowering and glycemic control, with consequent reduction in cardiovascular risk, diabetic microvascular disease, and mortality in diabetic patients for whom treatment with both compounds is appropriate.Keywords: statin, oral antihyperglycemic agent, diabetes, adherence, cardiovascular disease, microvascular disease

  12. Variability of low-density lipoprotein cholesterol response with different doses of atorvastatin, rosuvastatin, and simvastatin: results from VOYAGER.

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    Karlson, Björn W; Wiklund, Olov; Palmer, Michael K; Nicholls, Stephen J; Lundman, Pia; Barter, Philip J

    2016-10-01

    Patient response to statin treatment is individual and varied. As a consequence, when using a specific-dose approach, as recommended in the 2013 American College of Cardiology/American Heart Association guideline, there will be a range of reductions in the concentration of low-density lipoprotein cholesterol (LDL-C). The aim of this study was to use individual patient data from the VOYAGER meta-analysis to determine the extent of the variability in LDL-C reduction in response to treatment across the recommended doses of different statins. The percentage change from baseline in LDL-C was calculated using individual subject data collected from 32 258 patients treated with atorvastatin 10-80 mg, rosuvastatin 5-40 mg, or simvastatin 10-80 mg. The percentage change in LDL-C for each patient was then used to generate waterfall plots that demonstrated the extent of the variability in response to treatment at all doses of the three statins. The standard deviation of LDL-C reduction for all statins and doses ranged from 12.8 to 17.9%. The percentage of patients experiencing a suboptimal response (<30% reduction in LDL-C) ranged from 5.3 to 53.3%. These results indicate that there is considerable individual variation in the LDL-C reduction at all doses of simvastatin, atorvastatin, and rosuvastatin. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  13. Effects of 4-week administration of simvastatin in different doses on heart rate and blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats.

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    Owczarek, Jacek; Jasińska, Magdalena; Wejman, Irena; Kurczewska, Urszula; Orszulak-Michalak, Daria

    2012-02-29

    Statins and β1-adrenergic antagonists are well established in cardiovascular events therapy and prevention. The previous study showed that statins might impact on β-adrenergic signalling and blood pressure in a dose-dependent manner. The aim of the study was to evaluate the impact of 4-week administration of simvastatin given at different doses on the heart rate and blood pressure after injection of metoprolol in rats. The experiments were performed in normocholesterolaemic and normotensive Wistar rats. Rats received simvastatin in doses of 1, 10 and 20 mg/kg body weight (bw) for 4 weeks. The control group received 0.2% methylcellulose. For the further estimation of the heart rate and blood pressure, metoprolol at 5 mg/kg bw or 0.9% NaCl was injected intraperitoneally. Simvastatin at doses of 1, 10 and 20 mg/kg bw did not influence the heart rate or blood pressure as compared to the control group. Metoprolol injection statistically significantly decreased the heart rate (439.29±14.03 min(-1) vs. 374.41±13.32 min(-1); pheart rate and blood pressure (mean, systolic, diastolic) were similar as compared to the group receiving metoprolol alone. Simvastatin administration during a 4-week period in different doses did not influence the heart rate or blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats.

  14. Concomitant Administration of Different Doses of Simvastatin with Ivabradine Influence on PAI-1 and Heart Rate in Normo- and Hypercholesterolaemic Rats

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    Jacek Owczarek; Magdalena Jasińska-Stroschein; Daria Orszulak-Michalak

    2012-01-01

    Ivabradine is a novel heart rate lowering agent that inhibits If ionic current in the sinus node and demonstrates antiischaemic and antianginal activity. The aim of the paper was to investigate the effect its dose-dependent drug-drug interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart rate and blood pressure. The experiments were performed in hyper- and normocholesterolemic Wistar rats receiving simvastatin (1 and 20 mg × kg−1 bw) with ivabradine (10 mg × kg−1 bw) d...

  15. Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER).

    Science.gov (United States)

    Nicholls, Stephen J; Brandrup-Wognsen, Gunnar; Palmer, Mike; Barter, Philip J

    2010-01-01

    Statins are the most commonly prescribed agents for lowering levels of low-density lipoprotein (LDL) cholesterol. Although dose-dependent reductions in levels of atherogenic lipids are observed with all statins, the impact of increasing dose has not been fully elucidated. An individual patient data pooled analysis was performed of 32,258 patients in studies comparing the efficacy of rosuvastatin with that of atorvastatin or simvastatin. The impact of increasing dose on lowering LDL cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B was investigated. Doubling the dose of each statin was accompanied by a 4% to 7% greater degree of lowering of all atherogenic lipids. A stronger correlation was observed between changes in LDL cholesterol and non-HDL cholesterol (r = 0.92, p <0.001) or apolipoprotein B (r = 0.76, p <0.001) than triglycerides (r = 0.14, p <0.001). On multivariate analysis, baseline lipid level (p <0.0001) and increasing statin dose (p <0.0001) were strong predictors of achieving treatment goals in high-risk patients. Increasing age was a strong independent predictor of achieving goal for all atherogenic lipids (p <0.0001). Achieving LDL cholesterol goals was also more likely in women (p <0.0001), patients with diabetes (p <0.0001), and patients without atherosclerotic disease (p = 0.0002). In contrast, normal triglyceride levels were more often observed in men (p <0.0001) and patients without diabetes mellitus (p = 0.03). In conclusion, doubling statin dose was associated with greater lowering of LDL cholesterol by 4% to 6% and non-HDL cholesterol by 3% to 6%. Greater lipid goal achievement with increasing dose supports the use of high-dose statin therapy for more effective cardiovascular prevention.

  16. Locally applied Simvastatin improves fracture healing in mice

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    Aspenberg Per

    2007-09-01

    Full Text Available Abstract Background HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses. Methods Femur fractures were produced in 70 mature male Balb-C mice and stabilized with marrow-nailing. Three experiments were performed. Firstly, 20 mice received subcutaneous injections of either simvastatin (20 mg or vehicle. Secondly, 30 mice were divided into three groups of 10 mice receiving continuous subcutaneous delivery of the vehicle substance, the vehicle with 5 mg or with 10 mg of simvastatin per kg bodyweight per day. Finally, in 20 mice, a silicone tube was led from an osmotic mini-pump to the fracture area. In this way, 10 mice received an approximate local dose of simvastatin of 0.1 mg per kg per day for the duration of the experiment and 10 mice received the vehicle compound. All treatments lasted until the end of the experiment. Bilateral femurs were harvested 14 days post-operative. Biomechanical tests were performed by way of three-point bending. Data was analysed with ANOVA, Scheffé's post-hoc test and Student's unpaired t-test. Results With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined. Continuous systemic delivery resulted in a 160% larger force at failure. Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake. Conclusion This study found a dramatic positive effect on biomechanical parameters of fracture healing by simvastatin treatment directly applied to the fracture area.

  17. Fenofibrate/simvastatin fixed-dose combination in the treatment of mixed dyslipidemia: safety, efficacy, and place in therapy

    Science.gov (United States)

    Tarantino, Nicola; Santoro, Francesco; De Gennaro, Luisa; Correale, Michele; Guastafierro, Francesca; Gaglione, Antonio; Di Biase, Matteo; Brunetti, Natale Daniele

    2017-01-01

    Lipids disorder is the principal cause of atherosclerosis and may present with several forms, according to blood lipoprotein prevalence. One of the most common forms is combined dyslipidemia, characterized by high levels of triglycerides and low level of high-density lipoprotein. Single lipid-lowering drugs may have very selective effect on lipoproteins; hence, the need to use multiple therapy against dyslipidemia. However, the risk of toxicity is a concerning issue. In this review, the effect and safety of an approved combination therapy with simvastatin plus fenofibrate are described, with an analysis of pros and cons resulting from randomized multicenter trials, meta-analyses, animal models, and case reports as well. PMID:28243111

  18. ARTERIAL STIFFNESS PARAMETERS IN PATIENTS WITH MODERATE/HIGH CARDIOVASCULAR RISK DURING LISINOPRIL AND SIMVASTATIN TREATMENT

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    V. N. Isakova

    2016-01-01

    Full Text Available Aim. To evaluate parameters of arterial stiffness by non-invasive arteriography in patients with moderate/high cardiovascular risk receiving lisinopril and simvastatin.Material and methods. 20 patients (aged 50-55 y.o. with arterial hypertension of the 1st degree and dislipidemia are included in the study. All patients had pulse wave velocity (PWV ≥ 10 m/s and/or the corrected index of pulse wave augmentation (AI × 80 ≥ -10% according to non-invasive arteriography data; and moderate-high cardiovascular risk (≥ 3%. Patients received therapy with lisinopril and simvastatin. Blood pressure (BP levels and lipid profiles were assessed before therapy and in 1, 2, 6 and 12 month of the observation. Non-invasive arteriography was performed before therapy and in 2, 6 and 12 months later.Results. BP target levels were reached within 1 month of treatment as well as improvement of lipid profile was reached within 2 months in majority of the patients. Reference PWV and AI were reached in 85,7% of patients within one year of treatment.Conclusion. Arterial stiffness parameters help to evaluate cardiovascular risk changes accurately as the results of treatment.

  19. Effects of simvastatin on apolipoprotein M in vivo and in vitro

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    Nilsson-Ehle Peter

    2011-07-01

    Full Text Available Abstract Objective To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells. Methods Swiss male mice were randomly divided into the high fat group and control group, and were intragastrically fed with 0.9% saline (control group or lipid emulsion (high fat group at the daily dosage of 15 ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were then randomly divided into three experimental groups: vehicle control group, high-dose simvastatin-treated group (100 mg/kg body weight, and low-dose simvastatin-treated group (10 mg/kg body weight. Mice were dosed daily for 6 weeks of simvastatin before mice were sacrificed for determining serum lipid profile and apoM protein levels that was determined by using dot blotting analysis. Effects of simvastatin on apoM mRNA expression in the HepG2 cells were determined by real-time RT-PCR. Results Comparing to high fat model mice without simvastatin treatment, 100 mg/kg simvastatin could significantly increase serum total cholesterol (P P Conclusion The present study suggested that simvastatin, in vivo, had no effect on apoM levels in the hyperlipidemic mouse model. ApoM serum levels in mice were significantly correlated to the animal's age, whereas in cell cultures simvastatin does inhibit apoM expression in the HepG2 cells. The mechanism behind it is not known yet.

  20. Study of anti-inflammatory effect of simvastatin in rats

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    Ranga Satya Venkatesh

    2016-08-01

    Results: At a dose of 40 mg Simvastatin showed anti-inflammatory effect which is statically highly significant. Conclusions: However, the above preclinical experiments only give us an idea about the anti-inflammatory activity, but large scale clinical trials are necessary for final assessment. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1520-1523

  1. [Myopathy and rhabdomyolysis after treatment with simvastatin, amlodipine, and roxithromycin].

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    Skovbølling, Sara Lyngby; Lindelof, Mette

    2014-10-06

    This is a case report of a 71-year-old male with known diabetes, hypertension and diabetic nephropaty who over the course of one year developed an unrecognized myopathy due to concomitant treatment with high-dose simvastatin and amlodipin. Due to rhabdomyolysis he was after seven days of treatment with roxithromycin admitted to hospital with loss of the ability to walk. We wish to raise awareness of the potentially severe side effects of simvastatin and to emphasize that these can be limited by increased attention to patients with risk factors and to interactions with other drugs.

  2. Structural effects of simvastatin on liver rate tissue: Fourier transform infrared and Raman microspectroscopic studies

    Science.gov (United States)

    Garip, Sebnem; Bayari, Sevgi Haman; Severcan, Mete; Abbas, Sherif; Lednev, Igor K.; Severcan, Feride

    2016-02-01

    Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simvastatin for 30 days. The ratio of the area and/or intensity of the bands assigned to lipids, proteins, and nucleic acids were calculated to get information about the drug-induced changes in tissues. Loss of unsaturation, accumulation of end products of lipid peroxidation, and alterations in lipid-to-protein ratio were observed in the treated group. Protein secondary structure studies revealed significant decrease in α-helix and increase in random coil, while native β-sheet decreases and aggregated β-sheet increases in treated group implying simvastatin-induced protein denaturation. Moreover, groups were successfully discriminated using principal component analysis. Consequently, high-dose simvastatin treatment induces hepatic lipid peroxidation and changes in molecular content and protein secondary structure, implying the risk of liver disorders in drug therapy.

  3. Effects of four traditional Chinese medicines on the pharmacokinetics of simvastatin.

    Science.gov (United States)

    Zhao, Qian; Jiang, Ji; Hu, Pei

    2015-01-01

    1. Concomitant traditional Chinese medicines (TCMs) could be the reason for relative poor efficacy of statins in dyslipidemia patients in China. 2. An open-label, randomized, 5-period crossover study in healthy Chinese was designed to evaluate the pharmacokinetic interaction and tolerability of multiple doses of certain TCMs on a single dose of simvastatin. In each period, subjects received one of five treatments. In Treatment A, subjects received a single dose of 20 mg simvastatin. In Treatment B, C, D or E, subjects received Tong Xin Luo, Nao Xin Tong, Guan Mai Ning or Yin Xing Ye for 7 days and a single dose of 20 mg simvastatin on Day 7. The washout period was 7 days. 3. The 97.5% confidence interval of the AUC0-48 h geometric mean ratio of simvastatin acid and simvastatin for simvastatin given after multiple oral doses of one of the TCMs versus simvastatin given alone were fully contained within the prespecified bounds of (0.50, 2.00). 4. Exposures to simvastatin acid and simvastatin following a single dose of simvastatin alone were similar to those following coadministration of a single dose of simvastatin with multiple doses of each of the TCM preparations tested. Simvastatin and these TCMs were well tolerated.

  4. The combination of nutraceutical and simvastatin enhances the effect of simvastatin alone in normalising lipid profile without side effects in patients with ischemic heart disease

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    Giuseppe Campolongo

    2016-06-01

    Conclusions: The association of a nutraceutical and simvastatin 20 mg may be a valid therapeutic option for the treatment of hyperlipidemia in patients with ischemic heart disease intolerant to statin at high doses, in the absence of side effects. Further studies are needed to clarify the mechanisms of action of nutraceuticals.

  5. Effect of simvastatin on the antihypertensive activity of losartan in hypertensive hypercholesterolemic animals and patients: role of nitric oxide, oxidative stress, and high-sensitivity C-reactive protein.

    Science.gov (United States)

    Abdel-Zaher, Ahmed O; Elkoussi, Alaa Eldin A; Abudahab, Lotfy H; Elbakry, Mohammed H; Elsayed, Elsayed Abu-Elwafa

    2014-06-01

    This study investigated whether simvastatin has antihypertensive activity and can enhance the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Hypertension and hypercholesterolemia were induced in rats by L-NAME and cholesterol-enriched diet, respectively. In these animals, repeated administration of simvastatin decreased the systolic blood pressure, enhanced its progressive reductions induced by repeated administration of losartan, and corrected the compromised lipid profile. Concomitantly, repeated administration of simvastatin, losartan, or simvastatin in combination with losartan to these animals increased nitric oxide (NO) production and decreased the elevated serum malondialdehyde (MDA) and high-sensitivity C-reactive protein (hs-CRP) levels. Effects of combined treatment were greater than those of simvastatin or losartan alone. In hypertensive hypercholesterolemic patients, repeated administration of losartan decreased systolic and diastolic blood pressure, increased NO production, and decreased the elevated serum MDA and hs-CRP levels. Addition of simvastatin to losartan therapy enhanced these effects and corrected the compromised lipid profile. Simvastatin inhibited the contractile responses of isolated aortic rings induced by angiotensin II and enhanced the inhibitory effect of losartan on this preparation. l-arginine and acetylcholine enhanced, while L-NAME inhibited the effects of simvastatin, losartan, and their combination on these contractile responses. Thus, simvastatin exerts antihypertensive effect in hypertensive hypercholesterolemic animals and enhances the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Besides, its cholesterol-lowering effect, the ability of simvastatin to ameliorate endothelial dysfunction through increasing NO bioavailability and through suppression of oxidative stress and vascular inflammation may play an important role in these

  6. Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH.

    Science.gov (United States)

    Goldberg, Ronald B; Bittner, Vera A; Dunbar, Richard L; Fleg, Jerome L; Grunberger, George; Guyton, John R; Leiter, Lawrence A; McBride, Ruth; Robinson, Jennifer G; Simmons, Debra L; Wysham, Carol; Xu, Ping; Boden, William E

    2016-07-01

    Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known. This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P < .001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P < .02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline. The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which

  7. Simvastatin: between clinics and health economics

    Directory of Open Access Journals (Sweden)

    Francesco Vittorio Costa

    2007-03-01

    Full Text Available Statins reduce the incidence of cardiovascular events, one of the most important public health problems and among the main leading causes of death. Their use has been increasing in the last decade and today they represent the first drug class in terms of public expenditure. In view of the introduction of generic simvastatin in the Italian market, this paper outlines a pharmacological and economic profile of this compound. Despite two decades of life, simvastatin remains competitive with other HMG-CoA inhibitors, inducing a dose-dependent, up to 43% cLDL reduction. In clinical trials evaluating hard endpoints, simvastatin treatment achieved a strong reduction of cardiovascular events, revascularization procedures and mortality. Review of the main published pharmacoeconomic studies on simvastatin consistently indicated good cost/effectiveness ratios in most geographic contexts; convenience of this therapy increases along with baseline cardiovascular risk. Among available statins inducing equivalent cholesterol reductions, generic simvastatin has the lowest daily costs. Assuming stable market volume, an estimated cost saving for the Italian National Health Service of about 1 million Euro per year is expected from the introduction of the generic drug. Further cost savings may accrue for a potential switch from more expensive statins to simvastatin. Albeit individual responses to statins are unpredictable, the choice to start with lower cost molecules can limit initial drug investment and dampen the negative financial impact of treatment interruptions and switches.

  8. Comparative efficacy of different doses of simvastatin treatment of hyperlipidemia.%不同剂量辛伐他汀治疗高脂血症的疗效对比分析

    Institute of Scientific and Technical Information of China (English)

    王燕翔

    2012-01-01

      Objective:To analyze the efficacy of different doses of simvastatin treatment in patients with hyperlipidemia. Methods:128 patients with hyperlipidemia were randomly divided into two groups, the observation group simvastatin dose 40mg/d, the control group, dose of 20 mg/d, effects were observed. Results:The observation group TC, TG, LDL-C three indicators, HDL-C (P<0.01). Conclusions:Elderly patients with hyperlipidemia large doses of superior efficacy, safety and reliability.%  目的:分析不同剂量辛伐他汀治疗高脂血症患者的疗效.方法:将128例高脂血症患者随机分两组,观察组辛伐他汀剂量为40mg/d,对照组剂量为20mg/d,观察疗效.结果:观察组TC、TG、LDL-C三个指标低,HDL-C高,P<0.01.结论:老年高脂血症患者大剂量疗效优,安全可靠.

  9. [Simvastatin's effect on insulin resistance in rats with diabetes mellitus].

    Science.gov (United States)

    Iskakova, S; Zharmakhanova, G; Bekmukhambetov, Y; Dworacka, M; Dworacki, G

    2015-05-01

    The aim of this experimental study was to estimate the effect of Simvastatin on glycemic variability-related insulin resistance in the course of diabetes mellitus (DM) in rats. Fifty seven male Wistar rats were divided into four groups: I - rats with diabetes mellitus and glycemic variability treated with Simvastatin (20 mg/kg body weight, intragastral during 8 weeks); II - placebo-treated rats with DM and glycemic variability; III - placebo treated rats with DM and IV - nondiabetic control rats. DM was induced by feeding rats with high-fat diet (61%) during five weeks and low-dose of Streptozotocin (30 mg/kg, intraperitoneally). Daily glucose excursions were stimulated by feeding animals twice a day. We measured fasting blood glucose, glycated hemoglobin (HbA1c), insulin and HOMAIR was calculated. Higher insulin resistance in diabetic rats is related to greater daily glycemic variability. In our study was installed significant increasing HOMAIR in diabetics rats with glycemic excursions comparison with the control. Our results showed that the simvastatin-treatment decreases the indices glycemic variability and HOMA in diabetic rats with glycemic excursions.

  10. Antioxidant activity of simvastatin prevents ifosfamide-induced nephrotoxicity.

    Science.gov (United States)

    Mhaidat, Nizar Mahmoud; Ali, Reem Mustafa; Shotar, Ali Muhammad; Alkaraki, Almuthanna Khalaf

    2016-03-01

    Ifosfamide is an anticancer agent used largely in treatment of solid tumors. The mainstay dose-limiting toxicity of ifosfamide is nephrotoxicity. This is largely believde to be a result of ifosfamide-induced oxidative stress. In this study, we investigated the antioxidant activity of simvastatin and the possible protective role of simvastatin against ifosfamide induced nephrotoxicity. Thirty Sprague-Dawely rats were divided into five groups and given orally different drug combinations. Group I and II were regarded as control groups and received 0.1% DMSO and normal saline, respectively. Group III received ifosfamide at 50 mg/kg, group IV received simvastatin at 0.3 mg/kg and group V received both ifosfamide and simvastatin. All animals were decapitated 2 days after the last ifosfamide administration. Findings revealed that ifosfamide induced nephrotoxicity as indicated by a significant increase in plasma creatinine and lipid per oxidation. This increase was significantly inhibited in animals pretreated with simvastatin. Histopathological observations were in correlation with the biochemical parameters in that simvastatin minimized ifosfamide-induced renal tubular damage. The above results promote a future use of simvastatin in combination with ifosfamide in treatment of cancer patients to indicate that simvastatin protectics against ifosfamide-induced nephrotoxicity in terms of oxidative stress and might be given in combination.

  11. Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    OU Xue-mei; FENG Yu-lin; WEN Fu-qiang; HUANG Xiang-yang; XIAO Jun; WANG Ke; WANG Tao

    2008-01-01

    Background Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.Methods Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days.We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.Results Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (Ⅰand Ⅲ) mRNA expression induced by bleomycin. Moreover,simvastatin down-regulated the increased expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-(] (TNF-a) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore,the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.Conclusions Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-βI and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

  12. Effect of Simvastatin at Different Doses on Inflammatory Factors and Renal Function in Senile Patients with Diabetic Kidney Disease%不同剂量辛伐他汀对老年早期糖尿病肾病患者炎症因子和肾功能的影响观察

    Institute of Scientific and Technical Information of China (English)

    张圣苗; 陈肖蓉

    2015-01-01

    目的::观察不同剂量辛伐他汀对老年早期糖尿病肾病患者炎症因子和肾功能的影响。方法:160例老年早期糖尿病肾病患者随机分为对照组、低剂量组、常规剂量组和大量组。各组均给予基础治疗,低剂量组、常规剂量组、大量组分别在基础治疗同时加用辛伐他汀10,20,40 mg·d-1。4周后观察比较各组患者治疗前后炎症因子( CRP、ICAM-1、IL-1β)和肾功能指标( BUN、Cr、UAER、24hUpro、Uβ2-MG)变化及药品不良反应。结果:治疗后大量组CRP水平较治疗前显著降低,且明显低于对照组治疗后(P0.05)。治疗后4组BUN水平均无明显变化(P>0.05);Cr、UAER水平均较治疗前显著降低(P0.05)。结论:辛伐他汀治疗从炎症因子和肾功能指标两个方面可以改善糖尿病肾病的病情,大剂量辛伐他汀表现出一定的优势。%Objective:To observe the effect of simvastatin at different doses on the inflammatory factors and renal function in se-nile patients with diabetic kidney disease ( DKD) . Methods:Totally 160 cases of DKD patients were randomly divided into the control group, low dose group, conventional dose group and high dose group. All the patients were given the foundation treatment, and the low dose group, conventional dose group and high dose group was respectively given simvastatin 10, 20,40 mg·d-1 . The changes of in-flammatory cytokines (CRP, ICAM-1 and IL-1β) and renal index (BUN, Cr, UAER, 24hUpro and Uβ2-MG) among the groups were observed and compared before and after the 4-week treatment. Results:CRP in the high dose group after the treatment was significantly decreased when compared with that before the treatment and that in the control group after the treatment, and the difference was statisti-cally significant (P0.05). BUN in the four groups after the treatment had no obvious change when compared with that before the treatment, and there was no significant difference among the groups

  13. Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?

    Science.gov (United States)

    Ara, R; Pandor, A; Stevens, J; Rafia, R; Ward, S E; Rees, A; Durrington, P N; Reynolds, T M; Wierzbicki, A S; Stevenson, M

    2012-06-01

    While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose-response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.

  14. Impact of oral simvastatin therapy on acute lung injury in mice during pneumococcal pneumonia

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    Boyd Angela R

    2012-05-01

    Full Text Available Abstract Background Recent studies suggest that the reported protective effects of statins (HMG-CoA reductase inhibitors against community-acquired pneumonia (CAP and sepsis in humans may be due to confounders and a healthy user-effect. To directly test whether statins are protective against Streptococcus pneumoniae, the leading cause of CAP, we examined the impact of prolonged oral simvastatin therapy at physiologically relevant doses in a mouse model of pneumococcal pneumonia. BALB/c mice were placed on rodent chow containing 0 mg/kg (control, 12 mg/kg (low simvastatin diet [LSD]; corresponds to 1.0 mg/kg/day, or 120 mg/kg (high simvastatin diet [HSD]; corresponds to 10 mg/kg/day simvastatin for four weeks, infected intratracheally with S. pneumoniae serotype 4 strain TIGR4, and sacrificed at 24, 36, or 42 h post-infection for assessment of lung histology, cytokine production, vascular leakage and edema, bacterial burden and bloodstream dissemination. Some mice received ampicillin at 12-h intervals beginning at 48 h post-infection and were monitored for survival. Immunoblots of homogenized lung samples was used to assess ICAM-1 production. Results Mice receiving HSD had reduced lung consolidation characterized by less macrophage and neutrophil infiltration and a significant reduction in the chemokines MCP-1 (P = 0.03 and KC (P = 0.02 and ICAM-1 in the lungs compared to control mice. HSD mice also had significantly lower bacterial titers in the blood at 36 (P = 0.007 and 42 (P = 0.03 hours post-infection versus controls. LSD had a more modest effect against S. pneumoniae but also resulted in reduced bacterial titers in the lungs and blood of mice after 42 h and a reduced number of infiltrated neutrophils. Neither LSD nor HSD mice had reduced mortality in a pneumonia model where mice received ampicillin 48 h after challenge. Conclusions Prolonged oral simvastatin therapy had a strong dose-dependent effect on protection

  15. Clinical Observation on the Aggressive Lipid-lowering Treatment with Simvastatin on the Aged Patients with Coronary Artery Disease

    Institute of Scientific and Technical Information of China (English)

    Xie Ying; Bu Congya; Zhou Yujie

    2005-01-01

    Objectives To find out the efficient dose and safety of simvastatin (Zocor) on the aged patients with coronary artery disease (CAD) for aggressive lipid-lowering treatment. Methods Select 95 aged patients with CAD combined with primary hyperlipemia and give them 20 mg/day of simvastatin for treatment. According to the therapeutic target of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) regulate the dosage of simvastatin in follow-up. Observe 12~18 months. Results After treatment, the TC, LDL-C and triglycerides(TG)of the patients reduced by 40%, 52% and 26% respectively, while there was no significant change in high-density lipoprotein cholesterol (HDL-C). The apolipoprotein A1 arose by 14.4%, while the apolipoprotein B lowered by 25.0%. The ratio of LDL-C to HDL-C was reduced to 1.96. In the 6th month, the 12th month and the 18th month, respectively, 86%,93% and 95% of the patients took 10 mg/day of simvastatin and the result was their TC ≤ 140 mg/dL (3.7 mmol/L) and LDL-C ≤70 mg/dL(1.8 mmol/L).There was no special side-effect. Multi-factor analysis indicated the age of the patients was a significant factor affecting the adjustment of the dosage of simvastatin.Conclusions The therapeutic result of simvastatin on the aged patients with CAD for aggressive lipid-lowring treatment is definite, safe and the dose is lower as well.

  16. Simvastatin induces differentiation of rabbit articular chondrocytes via the ERK-1/2 and p38 kinase pathways.

    Science.gov (United States)

    Han, Yohan; Kim, Song Ja

    2016-08-15

    Statins are competitive inhibitors of hydroxy-methyl-glutaryl Coenzyme A (HMG-CoA) reductase, a key enzyme involved in the conversion of HMG-CoA to the cholesterol precursor mevalonate. Some statins, such as simvastatin (simvastatin), have been shown to have anti-cancer and anti-inflammatory effects, reducing cartilage degradation in osteoarthritic rabbits in vivo. However, the regulatory mechanisms undergirding simvastatin mediated chondrocyte differentiation have not been well elucidated. Thus, we investigated the action and mechanism of simvastatin on differentiation of rabbit articular chondrocytes through western blot analyses, RT-PCR, and immunohistochemical (IHC) and immunofluorescence (IF) staining. Simvastatin treatment was found to induce type II collagen expression and sulfated-proteoglycan synthesis in a dose- and time-dependent manner. Indeed, RT-PCR revealed increased expression of type II collagen on treatment with simvastatin. Both IHC and IF staining indicated differentiation of chondrocytes. Simvastatin treatment reduced activation of ERK-1/2 and stimulated activation of p38 kinase. Inhibition of ERK-1/2 with PD98059 enhanced simvastatin induced differentiation, whereas inhibition of p38 kinase with SB203580 inhibited simvastatin induced differentiation. Simvastatin treatment also inhibits loss of type II collagen in serial monolayer culture. Collectively, our results indicate that ERK-1/2 and p38 kinase regulate simvastatin-induced differentiation of chondrocytes in opposing manners. Thus, these findings suggest that simvastatin may be a potential therapeutic drug for osteoarthritis.

  17. Simvastatin in the acute respiratory distress syndrome.

    Science.gov (United States)

    McAuley, Daniel F; Laffey, John G; O'Kane, Cecilia M; Perkins, Gavin D; Mullan, Brian; Trinder, T John; Johnston, Paul; Hopkins, Philip A; Johnston, Andrew J; McDowell, Cliona; McNally, Christine

    2014-10-30

    Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS. In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety. The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug. Simvastatin therapy, although safe and associated with minimal adverse effects, did not improve clinical outcomes in patients with ARDS. (Funded by the U.K. National Institute for Health Research Efficacy and Mechanism Evaluation Programme and others; HARP-2 Current Controlled Trials number, ISRCTN88244364.).

  18. Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D: design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins

    Directory of Open Access Journals (Sweden)

    Tognoni Gianni

    2007-08-01

    Full Text Available Abstract Background Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors. Methods/Design The ACCEPT-D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die. Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. Eligibility criteria: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise. The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic attack, not planned revascularization procedures, peripheral vascular disease. A total of 515 first events are needed to detect a reduction in the risk of major

  19. Is it Simvastatin harmful in children? A case report

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    Mara Pisani

    2014-09-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common liver disease in children living in Western countries. Hyperlipidemia, obesity and insulin resistance are common components of the metabolic syndrome, which is frequently associated with NAFLD. Since patients with NAFLD are at high risk to develop cardiovascular disease (CVD, statins are frequently prescribed to patients with NAFLD and hyperlipidemia. The 3-Hydroxy-3-methyl-coenzyme A reductase (HMG-CoA reductase is the rate limiting enzyme in cholesterol biosynthesis. Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Under treatment with simvastatin, an improvement of enzymatic antioxidant parameters has been described in subjects with hypercholesterolemia. The safety and effectivity of statins in pediatric patients with NAFLD or non-alcoholic steatohepatitis (NASH, and their effect on hepatic fat infiltration or the extent of hepatic fibrosis are not known. Also, no evidences of the effects of a non therapeutic ingestion of this drug on the glutathione homeostasis and in children have been reported. We describe the case of a obese 4-year-old girl in whom an accidental overdose of simvastatin led to decrease levels of glutathione in blood with increase of the GSSG/GSH ratio. No adverse reactions were registered. All laboratory test were normal during the follow up. Only a 35% decrease of Glutathione was observed  such as a possible mechanism of mithocondrial toxicity and depletion of the glutathione pool after the intake of excessive dose of HMG-CoA reductase inhibitors.  Further  RCTs are needed in order to establish the safety and efficacy to use of statin for pediatric NAFLD or NASH.

  20. Simvastatin impairs murine melanoma growth

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    Barros Francisco E

    2010-12-01

    Full Text Available Abstract Background Statins induces cell cycle arrest, apoptosis, reduction of angiogenic factors, inhibition of the endothelial growth factor, impairing tissue adhesion and attenuation of the resistance mechanisms. The aim of this study was evaluate the anti-tumoral activity of simvastatin in a B16F10 melanoma-mouse model. Methods Melanoma cells were treated with different concentrations of simvastatin and assessed by viability methods. Melanoma cells (5 × 104 were implanted in two month old C57Bl6/J mice. Around 7 days after cells injection, the oral treatments were started with simvastatin (5 mg/kg/day, p.o.. Tumor size, hematological and biochemical analyses were evaluated. Results Simvastatin at a concentration of 0.8 μM, 1.2 μM and 1.6 μM had toxic effect. Concentration of 1.6 μM induced a massive death in the first 24 h of incubation. Simvastatin at 0.8 μM induces early cell cycle arrest in G0/G1, followed by increase of hypodiploidy. Tumor size were evaluated and the difference of treated group and control, after ten days, demonstrates that simvastatin inhibited the tumor expansion in 68%. Conclusion Simvastatin at 1.6 μM, presented cytototoxicity after 72 h of treatment, with an intense death. In vivo, simvastatin being potentially useful as an antiproliferative drug, with an impairment of growth after ten days.

  1. 不同剂量辛伐他汀对慢性心力衰竭幼兔结缔组织生长因子及骨保护素的影响%Effects of different doses of simvastatin on connective tissue growth factor and osteoprotegerin of immature rabbits with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    杨秀丽; 刘迎春; 邵锋; 孙海燕; 任可; 武惠敏; 王显良; 赵国安

    2014-01-01

    (CHF) and to explore the mechanism of simvastatin in the rabbits with CHF.Methods Sixty male immature rabbits were randomly divided into 5 groups:control (CON) group,CHF group,small-dose simvastatin (SD-SIM) group,medium-dose simvastatin (MD-SIM) group,and the high-dose simvastatin (HD-SIM) group,12 cases in each group.The models of CHF were established by injecting adriamycin(ADR) via the auricular vein of rabbits.In the first injection of ADR,simvastatin tablets [concentration of 0.3,1.5,3.0 mg/(kg · d),respectively] were given to the rabbits by intragastric administration for SD-SIM,MD-SIM,and HD-SIM models.The general conditions of immature rabbits in experiment group were evaluated.Hemodynamic data were detected.HE staining was used to observe structure of myocardial cells.The plasma level of osteoprotegerin (OPG) was measured by enzyme-linked imnunosorbent assay (ELISA).The expression of connective tissue growth factor(CTGF) was evaluated by immunohistochemical assay.Results 1.In CON group,the rabbits were all alive;in CHF,SD-SIM,MD-SIM and HD-SIM groups,most immature rabbits had skinchapped,unhaired and sluggish with hyperkeratosis,diet reduction,and losing weight.Overall survival rate was 76.7%.2.Hemodynamic data indicated that the + dp/dtmax,-dp/dtmax and the left ventricular systolic pressure (LVSP) in the SD-SIM,HD-SIM and CHF groups dropped significantly compared with the CON group (all P <0.05).There was a remarkable increase in the SD-SIM,HD-SIM and MD-SIM groups compared with CHF group (all P < 0.01) ;and there was a remarkable drop in the cardiac function of the SD-SIM and HD-SIM groups compared with MD-SIM group (P < 0.05).3.Compared with the CON group,CTGF and OPG expression in the SD-SIM,MD-SIM,HD-SIM and CHF groups increased significantly (P < 0.01),while the expression in the SD-SIM,MD-SIM and HD-SIM groups decreased significantly compared with that of the CHF group (P < 0.05).Compared with the MD-SIM group,the expression of CTGF and OPG in

  2. Compound list: simvastatin [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available simvastatin SST 00117 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/simvastatin....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/simvastatin....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/simvastatin...archive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/simvastatin.Rat.in_vivo.Liver.Repeat.zip ...

  3. CARDIOPROTECTION WITH SIMVASTATIN: AN APPRAISAL

    Directory of Open Access Journals (Sweden)

    Rohilla Ankur

    2011-06-01

    Full Text Available Statins, commonly known as 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors are recognized as the foremost drug therapy to show cardioprotection in pathological conditions like dyslipidemia and hyperlipidemia by significantly reducing blood cholesterol levels. Additionally, a number of beneficial effects have been shown by statins apart from lipid lowering that are referred to as their pleiotropic effects. Simvastatin, a potent member of statins class, has been widely used for lowering blood cholesterol levels by inhibiting HMG-CoA reductase both experimentally and clinically. Simvastatin has been well documented to be an effective drug therapy for the treatment of dyslipidemias. In addition, simvastatin has been shown to possess a variety of other pleiotropic effects in way of its potentiality as a cardioprotective agent. The present review critically discusses about the various pleiotropic effects possessed by simvastatin in affording cardioprotection.

  4. Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats

    Institute of Scientific and Technical Information of China (English)

    OU Xue-mei; WANG Bai-ding; WEN Fu-qiang; FENG Yu-lin; HUANG Xiang-yang; XIAO Jun

    2008-01-01

    Background Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases.This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide (LPS).Methods Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS.Rats treated with or without LPS were administered intra-peritoneally simvastatin (5 and 20 mg/kg) for 4 days.Expression of Muc5ac,RhoA and mitogen-activated protein kinases (MAPK) p38 in lung were detected by real-time polymerase chain reaction (PCR),immunohistochemistry or Western blotting.Tumor necrosis factor (TNF)-a and IL-8 in bronchoalveolar lavage fluid (BALF)were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay (ELISA).Results Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung (P<0.05).Moreover,simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-α and IL-8 in BALF follows LPS stimulation (P<0.05).The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression,neutrophil accumulation and inflammatory cytokine release.Simultaneously,the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung (P<0.05).Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation (P<0.05).However,the increased expression of p38 protein in LPS-traated lung was not affected by simvastatin administration.Conclusions Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS.The inhibitory effect of simvastatin on airway mucus hypersecretion may be through,at least in part,the suppression of neutrophil accumulation and inflammatory cytokine

  5. Simvastatin effects on skeletal muscle

    DEFF Research Database (Denmark)

    Larsen, Steen; Stride, Nis; Hey-Mogensen, Martin;

    2013-01-01

    Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9).......Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9)....

  6. The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin : results of the EASEGO study

    NARCIS (Netherlands)

    van Lennep, Henk W. O. Roeters; Liem, An Ho; Dunselman, Peter H. J. M.; Dallinga-Thie, Geesje M.; Zwinderman, Aeilko H.; Jukema, J. Wouter

    2008-01-01

    Objective: To assess the incremental low-density lipoprotein-cholesterol (LDL-C) lowering efficacy of doubling the statin dose or switching to the ezetimibe/simvastatin 10/20 mg combination tablet (EZE/SIMVA) in patients on simvastatin 20 mg or atorvastatin 10 mg not at LDL-C target <2.5 mmol/L. Stu

  7. The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin : results of the EASEGO study

    NARCIS (Netherlands)

    van Lennep, Henk W. O. Roeters; Liem, An Ho; Dunselman, Peter H. J. M.; Dallinga-Thie, Geesje M.; Zwinderman, Aeilko H.; Jukema, J. Wouter

    Objective: To assess the incremental low-density lipoprotein-cholesterol (LDL-C) lowering efficacy of doubling the statin dose or switching to the ezetimibe/simvastatin 10/20 mg combination tablet (EZE/SIMVA) in patients on simvastatin 20 mg or atorvastatin 10 mg not at LDL-C target <2.5 mmol/L.

  8. Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study)

    DEFF Research Database (Denmark)

    Robinson, Jennifer G; Ballantyne, Christie M; Grundy, Scott M;

    2009-01-01

    -density lipoprotein (LDL) cholesterol. Additional end points included changes in other lipids, lipoprotein ratios, high-sensitivity C-reactive protein, and attainment of prespecified lipid levels. Significantly greater improvements in the levels of LDL cholesterol, non-high-density lipoprotein cholesterol......, apolipoprotein B, and lipid/lipoprotein ratios resulted with ezetimibe/simvastatin compared with atorvastatin at all specified dose comparisons (p LDL cholesterol and non-high-density lipoprotein cholesterol levels was also significantly greater with ezetimibe...

  9. Pharmacokinetically guided dosing of (high-dose) chemotherapeutic agents

    NARCIS (Netherlands)

    Attema-de Jonge, M.E. (Milly Ellen)

    2004-01-01

    Due to variation in drug distribution, metabolism and elimination processes between patients, systemic exposure to chemotherapeutic agents may be highly variable from patient to patient after administration of similar doses. This pharmacokinetic variability may explain in part the large variability

  10. Severe Rhabdomyolysis Associated with Simvastatin and Role of Ciprofloxacin and Amlodipine Coadministration

    Science.gov (United States)

    De Schryver, Nicolas; Wittebole, Xavier; Van den Bergh, Peter; Haufroid, Vincent; Goffin, Eric; Hantson, Philippe

    2015-01-01

    Simvastatin is among the most commonly used prescription medications for cholesterol reduction and the most common statin-related adverse drug reaction is skeletal muscle toxicity. Multiple factors have been shown to influence simvastatin-induced myopathy. In addition to age, gender, ethnicity, genetic predisposition, and dose, drug-drug interactions play a major role. This is particularly true for drugs that are extensively metabolized by cytochrome P450 (CYP)3A4. We describe a particularly severe case of rhabdomyolysis after the introduction of ciprofloxacin, a weak CYP3A4 inhibitor, in a patient who previously tolerated the simvastatin-amlodipine combination. PMID:25883814

  11. The effectiveness of the controlled release of simvastatin from β-TCP macrosphere in the treatment of OVX mice.

    Science.gov (United States)

    Chou, Joshua; Ito, Tomoko; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce

    2016-03-01

    Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side-effects. Given the associated side-effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta-tricalcium phosphate (β-TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β-TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the release of simvastatin, an apatite coating was made around the β-TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β-TCP, β-TCP with simvastatin, apatite-coated β-TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non-implanted side (left) and showed that β-TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite-coated β-TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its

  12. COMPARATIVE EFFICACY AND SAFETY OF HYPOLIPIDEMIC THERAPY WITH GENERIC AND ORIGINAL MEDICINAL PRODUCTS OF SIMVASTATIN

    Directory of Open Access Journals (Sweden)

    E. I. Tarlovskaya

    2011-01-01

    Full Text Available Aim. To compare efficacy , safety and pharmacoeconomical characteristics of generic and original medicinal products of simvastatin in achievement of cholesterol and low density lipoprotein target levels. Material and methods. 38 patients with arterial hypertension accompanied by type 2 diabetes with dyslipidemia were included into the study. They had no clinically obvious ischemic heart disease and did not receive hypolipidemic pharmacotherapy for a month before the study start. The patients were randomized into group A or group B. Patients of group A (n=18 received original simvastatin, patients of group B (n=20 received generic simvastatin. Initial simvastatin dose was 20 mg daily. Lipid plasma profile, liver enzymes, creatine phosphokinase were evaluated every 4 weeks. Cost-effectiveness ratio was calculated. Results. 11 patients (61% in group A and only 5 patients (25% in group B (χ2=5.05; р<0.05 achieved cholesterol target level with simvastatin in dose of 20 mg daily in 3 months of the treatment. Creatine phosphokinase blood level did not increase significantly. Achievement of cholesterol target level cost 814 and 952 RUB per patient in groups A and B, respectively , in 1 month of simvastatin treatment. These costs were 643 and 417 RUB per patient in groups A and B, respectively , in 3 months of treatment. Conclusion. The original simvastatin in comparison with generic one has advantages in hypolipidemic effect. Safety profile is similar for both medications. Original simvastatin therapy has lower cost than this for generic simvastatin therapy in achievement of cholesterol target level in 1 month of treatment. In 3 months the cost of treatment per patient is 227 RUB higher for original medication in comparison with this for generic medication.

  13. Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway

    Science.gov (United States)

    Wang, Gang; Cao, Rui; Wang, Yongzhi; Qian, Guofeng; Dan, Han C.; Jiang, Wei; Ju, Lingao; Wu, Min; Xiao, Yu; Wang, Xinghuan

    2016-01-01

    Simvastatin is currently one of the most common drugs for old patients with hyperlipidemia, hypercholesterolemia and atherosclerotic diseases by reducing cholesterol level and anti-lipid properties. Importantly, simvastatin has also been reported to have anti-tumor effect, but the underlying mechanism is largely unknown. We collected several human bladder samples and performed microarray. Data analysis suggested bladder cancer (BCa) was significantly associated with fatty acid/lipid metabolism via PPAR signalling pathway. We observed simvastatin did not trigger BCa cell apoptosis, but reduced cell proliferation in a dose- and time-dependent manner, accompanied by PPARγ-activation. Moreover, flow cytometry analysis indicated that simvastatin induced cell cycle arrest at G0/G1 phase, suggested by downregulation of CDK4/6 and Cyclin D1. Furthermore, simvastatin suppressed BCa cell metastasis by inhibiting EMT and affecting AKT/GSK3β. More importantly, we found that the cell cycle arrest at G0/G1 phase and the alterations of CDK4/6 and Cyclin D1 triggered by simvastatin could be recovered by PPARγ-antagonist (GW9662), whereas the treatment of PPARα-antagonist (GW6471) shown no significant effects on the BCa cells. Taken together, our study for the first time revealed that simvastatin inhibited bladder cancer cell proliferation and induced cell cycle arrest at G1/G0 phase via PPARγ signalling pathway. PMID:27779188

  14. Simvastatin-induced meralgia paresthetica.

    Science.gov (United States)

    Sasson, Menahem; Pesach, Shvartzman

    2011-01-01

    3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) cause mainly muscular adverse effects. During the last 20 years there has been solid evidence of peripheral neuropathy caused by statins, with a risk of one in 10,000 patients treated for 1 year. Meralgia paresthetica is an entrapment neuropathy occasionally encountered by primary care physicians. To date there has been no report of entrapment neuropathy that could have been caused or aggravated by statins. This case report presents meralgia paresthetica aggravated by simvastatin use that disappeared after simvastatin cessation.

  15. Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin.

    Science.gov (United States)

    Al-Asmari, Abdulrahman K; Ullah, Zabih; Al Masoudi, Aqeel Salman; Ahmad, Ishtiaque

    2017-01-01

    Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first-choice drug for the treatment of depression and anxiety. A recent report suggests that selective serotonin reuptake inhibitors can interact with the cytochrome P450 3A4 substrate, and another one suggests that STT enhances the antidepressant activity of FLX. However, the data are inconclusive. The present study was designed to explore the pharmacokinetic and pharmacodynamic consequences of coadministration of STT and FLX in experimental animals. For this, Wistar rats weighing 250±10 g were divided into four groups, including control, STT (40 mg/kg/day), FLX (20 mg/kg/day), and STT+FLX group, respectively. After the dosing period of 4 weeks, the animals were sacrificed, and the blood and brain samples were collected for the analysis of STT, simvastatin acid (STA), FLX, total cholesterol, triglyceride, high-density lipoprotein (HDL), 5-hydroxytryptamine, dopamine, and hydroxy indole acetic acid. It was found that the coadministration resulted in a significant increase in the bioavailability of STT in the plasma (41.8%) and brain (68.7%) compared to administration of STT alone (pSTT was also found to be increased significantly in the plasma and brain compared to that achieved after monotherapy (pSTT failed to improve the pharmacokinetics of FLX up to a significant level. The results of this study showed that the combined regimen significantly reduced the level of cholesterol and triglyceride and increased the level of HDL when compared to STT monotherapy. Furthermore, the coadministration of STT with FLX led to an elevated level of neurotransmitters in the brain (pSTT in the plasma and brain. The coadministration of these drugs also led to an improved lipid profile. However, in the long-term, this interaction may have a vital clinical importance because the increase in STT level may lead to life-threatening side

  16. Enhanced in vitro osteoblast differentiation on TiO2 scaffold coated with alginate hydrogel containing simvastatin

    Directory of Open Access Journals (Sweden)

    Helen Pullisaar

    2013-11-01

    Full Text Available The aim of this study was to develop a three-dimensional porous bone graft material as vehicle for simvastatin delivery and to investigate its effect on primary human osteoblasts from three donors. Highly porous titanium dioxide (TiO2 scaffolds were submerged into simvastatin containing alginate solution. Microstructure of scaffolds, visualized by scanning electron microscopy and micro-computed tomography, revealed an evenly distributed alginate layer covering the surface of TiO2 scaffold struts. Progressive and sustained simvastatin release was observed for up to 19 days. No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin. Expression of osteoblast markers (collagen type I alpha 1, alkaline phosphatase, bone morphogenetic protein 2, osteoprotegerin, vascular endothelial growth factor A and osteocalcin was quantified using real-time reverse transcriptase–polymerase chain reaction. Secretion of osteoprotegerin, vascular endothelial growth factor A and osteocalcin was analysed by multiplex immunoassay (Luminex. The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 µM simvastatin when compared to scaffolds without simvastatin after 21 days. In addition, secretion of vascular endothelial growth factor A was significantly enhanced from cells cultured on scaffolds with both 10 nM and 10 µM simvastatin when compared to scaffolds without simvastatin at day 21. In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation. The combination of the physical properties of TiO2 scaffolds with the osteogenic effect of simvastatin may represent a new strategy for bone regeneration in defects where immediate load is wanted or unavailable.

  17. Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System

    Directory of Open Access Journals (Sweden)

    Rodrigo Antonini Ribeiro

    2015-01-01

    Full Text Available Background: Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial. Objective: To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS perspective. Methods: We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg, intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg, high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$. A willingness-to-pay (WTP threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770 was applied. Results: Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios. Conclusions: Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

  18. Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Rodrigo Antonini, E-mail: rodrigo.ribeiro@htanalyze.com [Programa de Pós-Graduação em Epidemiologia da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Avaliação de Tecnologia em Saúde, Porto Alegre, RS (Brazil); Duncan, Bruce Bartholow [Programa de Pós-Graduação em Epidemiologia da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Avaliação de Tecnologia em Saúde, Porto Alegre, RS (Brazil); Programa de Pós-Graduação em Cardiologia da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Ziegelmann, Patricia Klarmann [Instituto de Avaliação de Tecnologia em Saúde, Porto Alegre, RS (Brazil); Departamento de Estatística da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Stella, Steffan Frosi [Instituto de Avaliação de Tecnologia em Saúde, Porto Alegre, RS (Brazil); Programa de Pós-Graduação em Cardiologia da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Vieira, Jose Luiz da Costa [Instituto de Cardiologia / Fundação Universitária de Cardiologia, Porto Alegre, RS (Brazil); Restelatto, Luciane Maria Fabian [Serviço de Medicina Interna do Hospital de Clínicas de Porto Alegre, Porto Alegre, RS (Brazil); Polanczyk, Carisi Anne [Programa de Pós-Graduação em Epidemiologia da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Instituto de Avaliação de Tecnologia em Saúde, Porto Alegre, RS (Brazil); Programa de Pós-Graduação em Cardiologia da Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    2015-01-15

    Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial. To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective. We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied. Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios. Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

  19. The ROCK/GGTase Pathway Are Essential to the Proliferation and Differentiation of Neural Stem Cells Mediated by Simvastatin.

    Science.gov (United States)

    Zhang, Chan; Wu, Jian-Min; Liao, Min; Wang, Jun-Ling; Xu, Chao-Jin

    2016-12-01

    Simvastatin, a lipophilic and fermentation-derived natural statin, is reported to treat neurological disorders, such as traumatic brain injury, Parkinson's disease (PD), Alzheimer disease (AD), etc. Recently, research also indicated that simvastatin could promote regeneration in the dentate gyrus of adult mice by Wnt/β-catenin signaling (Robin et al. in Stem Cell Reports 2:9-17, 2014). However, the effect and mechanisms by which simvastatin may affect the neural stem cells (NSCs; from the embryonic day 14.5 (E14.5) SD rat brain) are not fully understood. Here, we investigated the effects of different doses of simvastatin on the survival, proliferation, differentiation, migration, and cell cycle of NSCs as well as underlying intracellular signaling pathways. The results showed that simvastatin not only inhibits the proliferation of NSCs but also enhances the βIII-tubulin(+) neuron differentiation rate. Additionally, we find that simvastatin could also promote NSC migration and induce cell cycle arrest at M2 phrase. All these effects of simvastatin on NSCs were mimicked with an inhibitor of Rho kinase (ROCK) and a specific inhibitor of geranylgeranyl transferase (GGTase). In conclusion, these data indicate that simvastatin could promote neurogenesis of neural stem cells, and these effects were mediated through the ROCK/GGTase pathway.

  20. Safety considerations with fenofibrate/simvastatin combination.

    Science.gov (United States)

    Filippatos, Theodosios D; Elisaf, Moses S

    2015-01-01

    Fenofibrate/simvastatin combination is useful for patients with mixed dyslipidemia. Aim of this review is to critically present the safety aspects of the fenofibrate/simvastatin combination. Current evidence regarding the adverse effects of fenofibrate/simvastatin combination is critically presented based on the results of large randomized controlled trials and other relevant studies. Additionally, clinical pharmacology, drug interactions and the effects of fenofibrate and simvastatin on metabolic variables and cardiovascular risk are briefly described. Large randomized clinical trials show that the combined administration of fenofibrate with simvastatin is not associated with significantly increased incidence of serious adverse events compared with simvastatin monotherapy. The incidence of rhabdomyolysis is slightly increased with fibrate/statin combination compared with monotherapy but the actual risk is very low. Although fenofibrate increases creatinine and homocysteine serum levels, the incidence of diabetic nephropathy and thrombotic events was not significantly increased with fenofibrate/simvastatin combination compared with simvastatin monotherapy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial. Furthermore, a decrease in albuminuria was observed with fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and ACCORD Lipid trials. Overall, the combined administration of fenofibrate with simvastatin appears to be safe, unless clinicians give fenofibrate/simvastatin combination to patients with predisposing risk factors for the occurrence of adverse events.

  1. The efficiency of dyslipidemia control in real clinical practice and the possibilities of its correction in patients with coronary heart disease and diabetes mellitus in the long -term use of simvastatin

    Directory of Open Access Journals (Sweden)

    F. Yu. Valikulova

    2014-07-01

    Full Text Available Objective: To show the efficiency of dyslipidemia control in patients with coronary heart disease (CHD and diabetes mellitus (DM in real outpatient clinical practice and the possibilities of its correction in the long-term use of simvastatin (simvastatin forte 40 mg in one of theNizhny Novgorod polyclinics.Subjects and methods. The efficiency of lipid profile control was analyzed in a sample from the entire dispensary group of patients with DM (n = 713. Patients at highest cardiovascular risk were selected from the dispensary group and included into a group of CHD and DM. There were a total of 461 (64.7 % such patients. Forty-three patients were identified in this group, who were matched for baseline systolic and diastolic blood pressures, age, gender, and DM duration and were found to have significant hypercholesterolemia. Simvastatin forte 40 mg wasprescribed to these patients at their outpatient visit. During a year, the patient made 6 visits to his/her physician (5 visits at 6-werk intervals and the sixth visit by the end of the follow-up year. The dose of simvastatin was unchanged throughout the study.Results.In the entire dispensary group, 64.7 % of the patients had a concurrence of CHD and DM. This group of patients was at high risk for dyslipidemia. In this group, 2.8 % had a total cholesterol (TC level of ≤ 3.5 mmol/l; 4.7 % had a low-density lipoprotein cholesterol (LDL-C level of < 1.8 mmol/l. The total lipid profile was analyzed in only 6.3% of the patients from the entire dispensary group. 28.6 % of the patients with type 1 DM and 21.3% of those with CHD and type 2 DM took statins. Fifty-two week therapy with simvastatin forte 40 mg showed its high efficiency in real practice in decreasing the levels of atherogenic lipids and lipoproteins: TC by 27.6 % (p < 0.001, LDL-C by 36.9 % (p < 0.001, and triglycerides by 34.3 % (p < 0.001 with antiatherogenic high-density lipoprotein cholesterol elevation by 15.2 % (p < 0

  2. Effects of Simvastatin on Glucose Metabolism in Mouse MIN6 Cells

    Directory of Open Access Journals (Sweden)

    Jieqiong Zhou

    2014-01-01

    Full Text Available The aim of this study was to investigate the effects of simvastatin on insulin secretion in mouse MIN6 cells and the possible mechanism. MIN6 cells were, respectively, treated with 0 μM, 2 μM, 5 μM, and 10 μM simvastatin for 48 h. Radio immunoassay was performed to measure the effect of simvastatin on insulin secretion in MIN6 cells. Luciferase method was used to examine the content of ATP in MIN6 cells. Real-time PCR and western blotting were performed to measure the mRNA and protein levels of inward rectifier potassium channel 6.2 (Kir6.2, voltage-dependent calcium channel 1.2 (Cav1.2, and glucose transporter-2 (GLUT2, respectively. ATP-sensitive potassium current and L-type calcium current were recorded by whole-cell patch-clamp technique. The results showed that high concentrations of simvastatin (5 μM and 10 μM significantly reduced the synthesis and secretion of insulin compared to control groups in MIN6 cells (P<0.05. ATP content in simvastatin-treated cells was lower than in control cells (P<0.05. Compared with control group, the mRNA and protein expression of Kir6.2 increased with treatment of simvastatin (P<0.05, and mRNA and protein expression of Cav1.2 and GLUT2 decreased in response to simvastatin (P<0.05. Moreover, simvastatin increased the ATP-sensitive potassium current and reduced the L-type calcium current. These results suggest that simvastatin inhibits the synthesis and secretion of insulin through a reduction in saccharometabolism in MIN6 cells.

  3. Synergistic induction of apoptosis by sulindac and simvastatin in A549 human lung cancer cells via reactive oxygen species-dependent mitochondrial dysfunction.

    Science.gov (United States)

    Hwang, Ki-Eun; Park, Chul; Kwon, Su-Jin; Kim, Young-Suk; Park, Do-Sim; Lee, Mi-Kyung; Kim, Byoung-Ryun; Park, Seong-Hoon; Yoon, Kwon-Ha; Jeong, Eun-Taik; Kim, Hak-Ryul

    2013-07-01

    Prevention of lung cancer is more feasible and holds greater promise when different agents are used in combination to target multiple processes during carcinogenesis. The mechanisms by which non-steroidal anti-inflammatory drugs and statins inhibit cancer cell growth and induce apoptosis are not fully understood. This study was designed to investigate lung cancer chemoprevention through a mechanism-based approach using sulindac at low doses in combination with simvastatin. We found that sulindac-induced cytotoxicity was significantly enhanced in the presence of simvastatin. The combination of sulindac and simvastatin induced more extensive caspase-dependent apoptosis in A549 cells compared to that induced with either drug alone. The combination of sulindac and simvastatin also increased the loss of mitochondrial transmembrane potential (∆Ψm) and the cytosolic release of cytochrome c. In addition, ROS generation in cells treated with both sulindac and simvastatin was markedly increased compared to cells treated with either sulindac or simvastatin alone. The enhancement of ROS generation by sulindac and simvastatin was abrogated by pretreatment with NAC, which also prevented apoptosis and mitochondrial dysfunction induced by sulindac and simvastatin. These results suggest that sulindac and simvastatin-induced ROS generation in A549 lung cancer cells causes their accumulation in mitochondria, triggering the release of apoptogenic molecules from the mitochondria to the cytosol, and thus leading to caspase activation and cell death.

  4. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes.

    Science.gov (United States)

    Kwak, Hyo-Bum; Thalacker-Mercer, Anna; Anderson, Ethan J; Lin, Chien-Te; Kane, Daniel A; Lee, Nam-Sihk; Cortright, Ronald N; Bamman, Marcas M; Neufer, P Darrell

    2012-01-01

    Statins, the widely prescribed cholesterol-lowering drugs for the treatment of cardiovascular disease, cause adverse skeletal muscle side effects ranging from fatigue to fatal rhabdomyolysis. The purpose of this study was to determine the effects of simvastatin on mitochondrial respiration, oxidative stress, and cell death in differentiated primary human skeletal muscle cells (i.e., myotubes). Simvastatin induced a dose-dependent decrease in viability of proliferating and differentiating primary human muscle precursor cells, and a similar dose-dependent effect was noted in differentiated myoblasts and myotubes. Additionally, there were decreases in myotube number and size following 48 h of simvastatin treatment (5 μM). In permeabilized myotubes, maximal ADP-stimulated oxygen consumption, supported by palmitoylcarnitine+malate (PCM, complex I and II substrates) and glutamate+malate (GM, complex I substrates), was 32-37% lower (P<0.05) in simvastatin-treated (5 μM) vs control myotubes, providing evidence of impaired respiration at complex I. Mitochondrial superoxide and hydrogen peroxide generation were significantly greater in the simvastatin-treated human skeletal myotube cultures compared to control. In addition, simvastatin markedly increased protein levels of Bax (proapoptotic, +53%) and Bcl-2 (antiapoptotic, +100%, P<0.05), mitochondrial PTP opening (+44%, P<0.05), and TUNEL-positive nuclei in human skeletal myotubes, demonstrating up-regulation of mitochondrial-mediated myonuclear apoptotic mechanisms. These data demonstrate that simvastatin induces myotube atrophy and cell loss associated with impaired ADP-stimulated maximal mitochondrial respiratory capacity, mitochondrial oxidative stress, and apoptosis in primary human skeletal myotubes, suggesting that mitochondrial dysfunction may underlie human statin-induced myopathy. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. FORMULATION STRATEGY FOR DISSOLUTION ENHANCEMENT OF SIMVASTATIN

    Directory of Open Access Journals (Sweden)

    Neha Parmar et al

    2012-10-01

    Full Text Available The present work aim was “Formulation Strategy for Dissolution Enhancement of Simvastatin”. Simvastatin is lipid lowering drug which is known as HMG CoA reductase. The objective of this study was to increase the solubility of poorly water soluble drug, namely simvastatin, by the formation of solid dispersion and complex and also using the microwave induction technique on these formations. For solid dispersion method dispersion carrier used were poloxamer 407 and gelucire 44/14. The fusion method was used to prepare the dispersions. For inclusion complexation method β-cyclodextrin derivative of cyclodextrin was used to prepare complex with drug. Kneading method was used for formulation. After completion of these two techniques these polymers were used for the microwave induced fusion method. All the ratio of drug and polymer were used to heat for different time interval. These samples were used for solubility measurement. In the solid dispersion technique, simvastatin show higher increase in solubility with gelucire 44/14 in the ratio of 1:5 as compare to poloxamer 407. In the microwave induced fusion method simvastatin show higher solubility with simvastatin with gelucire 44/14 after 10 mins time interval as compare to poloxamer 407 and β-cyclodextrin. Solubility of simvastatin increased higher with gelucire 44/14 by using microwave induced fusion method as compare to other technique. By using gelucire 44/14 with simvastatin it show 94% increase in solubility of simvastatin as compare to pure drug in water.

  6. High-Dose Phenobarbital for Ohtahara Syndrome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-05-01

    Full Text Available Oral high-dose phenobarbital therapy was effective in the control of tonic spasms in a 1 month-old-infant with early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome treated at Tokyo Metropolitan Hachioji Children’s Hospital, Tokyo, Japan.

  7. [Hopes of high dose-rate radiotherapy].

    Science.gov (United States)

    Fouillade, Charles; Favaudon, Vincent; Vozenin, Marie-Catherine; Romeo, Paul-Henri; Bourhis, Jean; Verrelle, Pierre; Devauchelle, Patrick; Patriarca, Annalisa; Heinrich, Sophie; Mazal, Alejandro; Dutreix, Marie

    2017-04-01

    In this review, we present the synthesis of the newly acquired knowledge concerning high dose-rate irradiations and the hopes that these new radiotherapy modalities give rise to. The results were presented at a recent symposium on the subject. Copyright © 2017. Published by Elsevier Masson SAS.

  8. Simvastatin downregulated C35 expression and inhibited the proliferation of colon cancer cells Lovo and HT29 in vitro.

    Science.gov (United States)

    Li, Min; Huang, Yong; Dong, Xuan; Wei, Qingkuan; Li, Jin; Sun, Hui; Li, Chenchen; Qi, Conghu; Yang, Jingyu

    2016-07-19

    The aim of this study was to investigate the antitumor effect of simvastatin in human colon cancer and the possible underlying mechanism. We found that simvastatin dose-dependently inhibited the proliferation of human colon cancer cells Lovo and HT29 using a MTT assay. Real-time PCR and Western blotting assays showed that simvastatin significantly suppressed C35 expression at both mRNA and protein levels. Since C35 is known to have a significant oncogenic role in cancer development via promoting cell proliferation and migration, results obtained in the current study imply that downregulation of C35 expression might be involved in the antitumor effect of simvastatin on colon cancer.

  9. Gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin in healthy Chinese volunteers.

    Science.gov (United States)

    Wang, Xiao-lin; Liu, Man; Yang, Man; Zhang, Ya-nan; Zhang, Dan; Zhang, Li-na; Han, Jing; Liu, Hui-chen

    2014-12-01

    The gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty-six healthy male and female volunteers were enrolled in the study receiving a single oral dose of niacin extended-release/simvastatin 1,000/20 mg. The results indicated that the systemic exposure of simvastatin hydroxy acid and the total urine excretion of niacin were significantly higher for females compared with those for males, and the T max of niacin in plasma was significantly shorter for males than that for females. There were no significant differences in the systemic exposure of simvastatin, niacin, and NUA in plasma between males and females.

  10. Effects of varying doses of simvastatin on protein kinase A in immature rabbits with chronic heart failure%不同剂量辛伐他汀对慢性心力衰竭幼兔蛋白激酶A的影响

    Institute of Scientific and Technical Information of China (English)

    刘迎春; 杨秀丽; 海体委; 孙海燕; 武惠敏; 王显良; 杨萌; 赵国安

    2014-01-01

    Objective To investigate the effects of varying doses of simvastatin (SIM) on protein kinase A (PKA),ventricular remodeling and heart function in immature rabbits with chronic heart failure (CHF),to explore the possible mechanisms for simvastatin on CHF.Methods Sixty male immature rabbits were randomly divided into 5 groups:control (CON) group,CHF model group,small-dose simvastatin (SD-SIM) group [SIM concentration was 0.3 mg/(kg · d)],medium-dose simvastatin (MD-SIM)group[SIM concentration was 1.5 mg/(kg · d)],and the highdose simvastatin (HD-SIM)group[SIM concentration was 3.0 mg/(kg · d)].The general condition of immature rabbits in the experiment group was evaluated.Color doppler ultrasonography was used to detect the left ventricular structure and the function.The left ventricular myocardium was taken and fixed in paraformaldehyde (40 g/L).The expression of PKA was evaluated by immunohistochemical assay.Results In CON group,the rabbits were all alive; in the other groups,most immature rabbits were unhairing,with diet reduction,weight lose and sluggish with hyperkeratosis.Overall survival rate was 82% (49/60 cases).The mortality rate in CHF model group was significantly higher than that in the MD-SIM group(41.7% vs 8.3%,P < 0.05).Compared with the CON group,left ventricular ejection fraction (LVEF) in the SD-SIM group,HD-SIM group and CHF model group all dropped sharply (all P < 0.01),while the left ventricular end diastolic diameter (LVEDd) and left ventricular end systolic diameter (LVESd) increased markedly (all P <0.01).Compared with CHF model group,LVEDd and LVESd decreased and LVEF increased significantly in SD-SIM group,HD-SIM group and MD-SIM group (all P < 0.05),the effects of MD-SIM group was the best (P <0.05).LVEF in MD-SIM group increased significantly compared with SD-SIM group,HD-SIM group and CHF model group (all P < 0.05).PKA expression in SD-SIM group,MD-SIM group and HD-SIM group increased significantly compared to the

  11. Disruption of Stromal-Derived Factor-1/Chemokine Receptor 4 by Simvastatin

    Directory of Open Access Journals (Sweden)

    A Jalili

    2010-03-01

    Full Text Available Background: The alpha chemokine, stromal-derived factor (SDF-1 is produced by bone marrow stromal cells and other cells, especially damaged tissues. SDF-1 receptor, a chemokine receptor 4 (CXCR4, is expressed on inflammatory cells and that SDF-1/CXCR4 axis plays a critical role in migration of inflammatory cells. In cardiovascular diseases, SDF-1 is produced by endothelial cells and plaques and that SDF-1 chemoattracts monocytes to the endothelial cells resulting in a local inflammation. Simvastatin, a cholesterol-lowering agent, is a general drug for treatment of cardiovascular diseases. However, its molecular mechanism has not yet been completely elucidated.Method: Herein, we investigated the role of simvastatin on the SDF- 1/CXCR4 axis by employing flow cytometry, RT-PCR, chemotaxis and adhesion assays. Results: Simvastatin (i downregulates CXCR4 expression on monocytic cell line (THP-1 and primary monocyte in a dose-dependent manner, (ii inhibits adhesion of monocytes to endothelial cells and (iii decreases SDF-1 production by endothelial cells. Moreover, preincubation with simvastatin significantly decreased the migration of THP-1 towards the SDF-1 gradient.Conclusion: All together our data indicate that simvastatin inhibits the binding of monocytes to endothelial cells through disrupting of the SDF-1/CXCR4 axis.

  12. High-dose neutron detector project update

    Energy Technology Data Exchange (ETDEWEB)

    Menlove, Howard Olsen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Henzlova, Daniela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-10

    These are the slides for a progress review meeting by the sponsor. This is an update on the high-dose neutron detector project. In summary, improvements in both boron coating and signal amplification have been achieved; improved boron coating materials and procedures have increase efficiency by ~ 30-40% without the corresponding increase in the detector plate area; low dead-time via thin cell design (~ 4 mm gas gaps) and fast amplifiers; prototype PDT 8” pod has been received and testing is in progress; significant improvements in efficiency and stability have been verified; use commercial PDT 10B design and fabrication to obtain a faster path from the research to practical high-dose neutron detector.

  13. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

    Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

    2014-01-01

    BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

  14. High-dose neutron detector project update

    Energy Technology Data Exchange (ETDEWEB)

    Menlove, Howard Olsen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Henzlova, Daniela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-10

    These are the slides for a progress review meeting by the sponsor. This is an update on the high-dose neutron detector project. In summary, improvements in both boron coating and signal amplification have been achieved; improved boron coating materials and procedures have increased efficiency by ~ 30-40% without the corresponding increase in the detector plate area; low dead-time via thin cell design (~ 4 mm gas gaps) and fast amplifiers; prototype PDT 8” pod has been received and testing is in progress; significant improvements in efficiency and stability have been verified; use commercial PDT 10B design and fabrication to obtain a faster path from the research to practical high-dose neutron detector.

  15. Simvastatin and oxidative stress in humans

    DEFF Research Database (Denmark)

    Rasmussen, Sanne Tofte; Andersen, Jon Thor Trærup; Nielsen, Torben Kjær

    2016-01-01

    Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, and thereby reduces the risk of cardiovascular disease. In addition, simvastatin treatment leads to a reduction in fluxes......-blinded, placebo-controlled study in which subjects were treated with either 40 mg of simvastatin or placebo for 14 days. The endpoints were six biomarkers for oxidative stress, which represent intracellular oxidative stress to nucleic acids, lipid peroxidation and plasma antioxidants, that were measured in urine.......1% in the placebo group for DNA oxidation and 7.3% in the simvastatin group compared to 3.4% in the placebo group. The differences in biomarkers related to plasma were not statistically significant between the treatments groups, with the exception of total vitamin E levels, which, as expected, were reduced...

  16. Simvastatin-induced Toxic Epidermal Necrolysis

    Institute of Scientific and Technical Information of China (English)

    Emmanouil Petrou; Vasiliki Karali; Emmanouil Papadakis

    2014-01-01

    Toxic epidermal necrolysis comprises a severe immune-complex mediated hypersensitivity reaction that typically involves the skin and mucous membranes.Herein, we describe a68-year -old man who presented with the condition after simvastatin administration.

  17. Simvastatin-induced Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Emmanouil Petrou

    2014-01-01

    Full Text Available Toxic epidermal necrolysis comprises a severe immune-complex mediated hypersensitivity reaction that typically involves the skin and mucous membranes. Herein, we describe a 68-year -old man who presented with the condition after simvastatin administration.

  18. FORMULATION STRATEGY FOR DISSOLUTION ENHANCEMENT OF SIMVASTATIN

    OpenAIRE

    Neha Parmar et al

    2012-01-01

    The present work aim was “Formulation Strategy for Dissolution Enhancement of Simvastatin”. Simvastatin is lipid lowering drug which is known as HMG CoA reductase. The objective of this study was to increase the solubility of poorly water soluble drug, namely simvastatin, by the formation of solid dispersion and complex and also using the microwave induction technique on these formations. For solid dispersion method dispersion carrier used were poloxamer 407 and gelucire 44/14. The fusion met...

  19. Amphotericin B for cryptococcal meningitis in HIV positive patients: Low dose versus high dose

    Directory of Open Access Journals (Sweden)

    Rajeshwari S

    2007-01-01

    Full Text Available Aim: To compare the safety and efficacy of low dose vs high dose of amphotericin B in cryptococcal meningitis associated with HIV infection. Materials and Methods: Retrospective data of patients admitted with clinical diagnosis with or without microbiological evidence of cryptococcal meningitis was collected from Jan 2000-Mar 2006. Patients′ details were collected in a proforma which included patient′s age, weight, signs and symptoms of disease and microbiological report (blood and CSF analysis. Data also included coexisting disease; concomitant medications taken along with amphotericin B. Adverse drug reactions which occurred during the period of treatment were recorded. Patients were grouped as low dose group and high dose group depending on the dose of amphotericin B given for the treatment of cryptococcal meningitis. Patients who received amphotericin B at doses of 0.33 to 0.64 mg/kg body weight per day were categorized under low dose group and patients who received amphotericin B at doses of 0.7 to 1.1 mg/kg/day were categorized under high dose group. All data were pooled and analyzed between the groups using chi square test. Result: Total number of patients included in the study were 38, 26 in the low dose group and 12 in the high dose group. In the low dose group, 20 were males and six were females, in the high dose group eight were males and four were females. The commonest underlying diseases were tuberculosis (17 in low dose group, nine in high dose group, Pneumocystis carinii (jeroveci pneumonia (16 in low dose group, seven in high dose group and oral candidiasis (eight in low dose group, seven in high dose group, Toxoplasmosis (three in low dose group, one in high dose group, hypertension (1 in group A and diabetes mellitus (1 in group B. Concomitant medication received along with amphotericin B for coexisting diseases in both the groups were antitubercular therapy, cotrimoxazole, antiviral therapy and premedications such as

  20. Effects of Extended-Release Niacin and Extended-Release Niacin/Laropiprant on the Pharmacokinetics of Simvastatin in Healthy Subjects.

    Science.gov (United States)

    Lauring, Brett; Dishy, Victor; De Kam, Pieter-Jan; Crumley, Tami; Wenning, Larissa; Liu, Fang; Sisk, Christine; Wagner, John; Lai, Eseng

    2015-01-01

    The use of multiple lipid-modifying agents with different mechanisms of action is often required to regulate lipid levels in patients with dyslipidemia. During combination therapy, alterations in the pharmacokinetics of any of the drugs used and their metabolites may occur. Three separate open-label, randomized, crossover studies evaluated the potential for pharmacokinetic interaction between extended-release niacin (with and without concomitant laropiprant) and simvastatin in healthy subjects. Study 1 used single doses of extended-release niacin and simvastatin; study 2 used multiple-dose coadministration of extended-release niacin/laropiprant and simvastatin in healthy subjects; and study 3 used single doses of both extended-release niacin and the coadministration of extended-release niacin/laropiprant and simvastatin in healthy Chinese subjects. During each treatment period, plasma samples were collected predose and at prespecified postdose time points for pharmacokinetic analyses. The safety and tolerability of simvastatin with and without coadministered extended-release niacin (or extended-release niacin/laropiprant) were assessed by clinical evaluation of adverse experiences. In 2 studies in healthy subjects, modest increases in exposure to simvastatin acid (by ∼60%) by extended-release niacin and extended-release niacin/laropiprant were observed. Based on the clinical experience with simvastatin, these effects are not believed to be clinically meaningful. In the third study on healthy Chinese subjects, no statistically meaningful increases in exposure to simvastatin by extended-release niacin and extended-release niacin/laropiprant were observed. In all populations examined in these studies, the coadministration of extended-release niacin and simvastatin was generally well tolerated.

  1. Effect of treatment with simvastatin on bone microarchitecture of the femoral head in an osteoporosis animal model.

    Science.gov (United States)

    Monteiro, Lucas Oliveira; Macedo, Ana Paula; Shimano, Roberta Carminati; Shimano, Antônio Carlos; Yanagihara, Gabriela Rezende; Ramos, Junia; Paulini, Marina Ribeiro; Tocchini de Figueiredo, Fellipe Augusto; Gonzaga, Miliane Gonçalves; Issa, João Paulo Mardegan

    2016-08-01

    The objective of this study was to evaluate the microarchitecture and trabecular bone strength at the distal region of the femur, and its biomechanical properties with simvastatin administration with two different doses in ovariectomized (OVX) rats. Ninety rats were divided into six groups to evaluate treatment with the simvastatin drug (n = 15): SH (Sham surgery), SH-5 (5 mg simvastatin), SH-20 (20 mg simvastatin), OVX, OVX-5, and OVX-20. Euthanasia was performed at three different times, five animals per period: 7, 14, and 28 days. The effectiveness of the treatments was evaluated by mechanical testing and histomorphometric analysis of the femurs. The results of analysis by the linear model of mixed effects showed 20 mg of simvastatin results in increased trabecular bone after 14 days (P = 0.039) of ingestion in ovariectomized animals. However, ingestion of 5 mg of simvastatin is able to sensitize the trabecular bone only at 28 days (P = 0.005) of ingestion. In the mechanical tests stiffness improves within 28 days (P = 0.003). Regarding maximum strength, no statistical differences were observed. According to these results, it can be concluded that for a decrease in oral intake, longer treatment times are required. Microsc. Res. Tech. 79:684-690, 2016. © 2016 Wiley Periodicals, Inc.

  2. High dose insulin in toxic cardiogenic shock.

    Science.gov (United States)

    Holger, Joel S; Engebretsen, Kristin M; Marini, John J

    2009-04-01

    To report the successful use of high dose insulin (HDI) in previously unreported insulin dosing ranges in a patient with severe myocardial toxicity due to an amitriptyline and citalopram overdose. A 65-year-old female presented in respiratory arrest, which was followed by bradycardic pulseless electrical activity after ingesting multiple medications. After a prolonged resuscitation, the patient was maintained only on infusions of norepinephrine (40 mcg/min), vasopressin (4 units/h), insulin (80 units/h), and sodium bicarbonate. Due to a deteriorating clinical condition and limited prognosis, the insulin infusion was titrated incrementally upwards to 600 units/h (6 units/kg/h) over a 5 h time period while simultaneously completely weaning off both vasopressors. She developed brisk pulses and warm extremities, and her cardiac output nearly tripled. After 2 days of stabilization the insulin was slowly tapered, and the patient recovered. HDI as a single cardiovascular agent significantly improved clinical and cardiovascular parameters after the failure of vasopressor therapy in severe cardiovascular toxicity. Higher doses of insulin than previously recommended may be needed in toxic poisonings when severe myocardial depression is present.

  3. A COMPARATIVE STUDY OF EFFICACY AND TOLERABILITY OF ORIGINAL AND GENERIC SIMVASTATIN IN PATIENTS WITH HYPERLIPIDEMIA

    Directory of Open Access Journals (Sweden)

    V. P. Voronina

    2011-01-01

    Full Text Available Aim. To study efficacy and tolerability of original and generic simvastatin in patients with hyperlipidemia. Material and methods. Patients (6 men and 24 women aged 38 to 77 years, which needed in lipid-lowering therapy were included into the open, crossover , randomized, comparative study of efficacy and tolerability of original and generic simvastatin. The drug effects on the blood levels of total cholesterol (TC, high density cholesterol (HDC, triglycerides (TG, low density cholesterol (LDC, and tolerability of treatment were evaluated. The treatment duration (with a change of medications was 12 weeks. Results. The target levels of LDC after 8 weeks of treatment with both generic and original simvastatin (20 mg/day were achieved in 10 (71.4% patients in each group. After 8 weeks of therapy with generic and original simvastatin TC decreased from 6.4±0.8 to 4.4±0.6 mmol/l (p<0.001 and from 6.0±0.7 to 4.1±0.7 mmol/l (p<0.001, respectively. LDC levels decreased from 4.4±0.7 to 2.4±0.4 mmol/l (p<0.001 and from 4.2±0.7 to 2.2±0.6 mmol/l (p<0.001, respectively. Both simvastatin medications led to similar changes in blood lipid spectrum and had comparable tolerability. Conclusion. The lipid-lowering effect of the generic simvastatin is comparable to this of original simvastatin. That means generic medication is therapeutically equivalent to original one.

  4. Influence of gingko extract on metabolism of simvastatin%银杏叶提取物对辛伐他汀药物代谢影响的研究

    Institute of Scientific and Technical Information of China (English)

    刘冉; 李方洁; 梁日欣; 王岚; 王怡薇

    2009-01-01

    Objective:To conclude the possible interaction between gingko extract and simvastatin, by studing the effect of gingko extract on vitro metabolism of simvastatin and involving critical metabolic enzyme, which can guide the clinicians to use them rationally ( propose good guideline for rational using of the two medcine mentioned above) . Method: Thirty-two female SD rats were randomly separated into 4 groups, including negative control group. High dose of gingko extract. Low dose of gingko extractand positive control group. All groups were administered for 10 days with stomach tube, and then the quantity of liver microsome protein, the activity of CYP3A were determined by spectrophotograph. Simvastatin was incubated with the liver microsome, and the effect of gingko extract on its metabolism was estimated by measuring the amount of simvastatin by HPLC. Result: Comparing with the negative contrast group:the quantity of liver microsome protein, the activity of CYP3A and the metabolism of simvastatin in positive control group were all increased markly (P <0. 05). In high dose group, the quantity of liver microsome protein and the activity of CYP3A were both increased significantly ( P < 0. 05 ) , and the metabolism of simvastatin also accelerate obviously ( P < 0. 05). But in the low dose group significant distinction of every index was not found. Conclusion: High dose of gingko extract can induce the activity of CYP3A, and promote the metabolism of simvastatin, so the medical interaction should be focused when gingko extract is coadministered with simvastatin and other substracts of CYP3A.%目的:研究银杏叶制剂对辛伐他汀体外代谢及其代谢相关酶的影响,探讨两药是否存在相互作用,为临床上两药的合理联用提供试验依据.方法:将大鼠随机分为4组:分别为生理盐水对照组、苯巴比妥钠阳性对照组、低剂量银杏叶制剂组和高剂量银杏叶制剂组.灌胃10天后,处死动物摘取肝脏并制备成

  5. Efek Jus Buah Naga Super Merah (Hylocereus costaricensis dan Simvastatin terhadap Kadar Kolesterol Total Darah dan Bobot Badan Tikus Jantan Galur Wistar Hiperkolesterolemia

    Directory of Open Access Journals (Sweden)

    Fauziyyah Karimah

    2014-09-01

    The Effect of Super Red Dragon Fruit Juice (Hylocereus costaricensis and Simvastatin to TotalBlood Cholesterol and Body Weight of Male Wistar Rats Induced Hypercholesterolemia Abstract Cardiovascular disease occurs due to several factors including high cholesterol level. According to a survey conducted by WHO in 2008 around 17.3 million people died because of cardiovascular disease. The purpose of this research is to compare the effect of super red dragon fruit juice as herbal therapy and simvastatin as standard drug that have been used in the medical therapy to decrease total blood cholesterol and body weight of male Wistar rats induced hypercholesterolemia. This research was conducted at the Biomedical Laboratory Bandung Islamic University in 2014 April˗Mei used laboratoric experiment methods using 20 rats that was induced hypercholesterolemia with high-fat feeding and Propil Tiourasil (PTU for 14 days. Super red dragon fruit (Hylocereus costaricensis juice given orally at doses 3.6 g; 7.2 g; and 10.8 g. Simvastatin as a positive control was given at a dose of 0.18 mg. Negative control and normal control without intervention. Research data were analyzed by Analysis of Variance (ANOVA test and Post Hoc test. The results of this research with the different test groups of super red dragon fruit juice dose of 3.6 g and 7.2 g respectively lower total cholesterol by 42.45 mg/dL and 41.96 mg/dL (p=0.001, while 10.8 g doses are unlikely to change despite an increase of only 1.22 mg/dL (p=0.535. Positive control group showed a decrease in total cholesterol levels by 21.32 mg/dL (p=0.001. Changes in body weight of rats in the provision of super red dragon fruit juice dose of 3.6  g; 7.2 g; 10.8 g; and simvastatin were 1.75 g; 22.16 g; 19.5 g; and 34.75 g respectively and were not significantly different (p=0.823. Conclusion, super red dragon fruit juice lowers total cholesterol levels higher than simvastatin, while the body weight of male rats did not differ. Keywords: Body

  6. Effects of simvastatin gel on bone regeneration in alveolar defects in miniature pigs

    Institute of Scientific and Technical Information of China (English)

    CHEN Shan; YANG Jun-ying; ZHANG Sheng-yan; FENG Lei; REN Jing

    2011-01-01

    Background Currently,the most commonly used treatment methods for repairing alveolar furcation defects are periodontal guided tissue regeneration (GTR) and bone grafting.The objective of this study was to investigate the effects of simvastatin/methylcellulose gel on bone regeneration in alveolar defects in miniature pigs.Methods Alveolar defects were produced in 32 teeth (the third and fourth premolars) of 4 miniature pigs.The 32 experimental teeth were divided into 5 groups comprising control (C) and treatment (T) teeth:(1) empty defects without gel (group C0,n=4); (2) defects injected with methylcellulose gel (group C1,n=4); (3) defects injected with 0.5 mg/50 μl simvastatin/methylcellulose gel (group T1,n=8); (4) defects injected with 1.5 mg/50 μl simvastatin/methylcellulose gel (group T2,n=8); and (5) defects injected with 2.2 mg/50 μl simvastatin/methylcellulose gel (group T3,n=8).Every week after surgery,the furcation sites were injected once with gel.At the eighth week after surgery,the 4 pigs were sacrificed and underwent macroscopic observation,descriptive histologic examination,and regenerate bone quantitative histologic examination.Results At 8 weeks after surgery,the defect sites in the treatment groups were completely filled in with new bone and fibrous tissue.There was little new bone in the C0 and C1 groups,and only a small number of osteoblasts and proliferative vessels could be seen on microscopic examination.Conclusions Miniature pigs are an ideal experimental animal for establishing a model of alveolar defects using a surgical method.Local application of simvastatin/methylcellulose gel can stimulate the regeneration of alveolar bone in furcation defect sites,because it promotes the proliferation of osteoblasts.The best dose of simvastatin gel to stimulate bone regeneration is 0.5 mg.

  7. DESIGN AND EVALUATION OF POLYLACTIC-CO-GLYCOLIC ACID NANOPARTICLES CONTAINING SIMVASTATIN

    Directory of Open Access Journals (Sweden)

    Anilkumar J. Shinde

    2011-06-01

    Full Text Available The objective of the present work was to formulate nanoparticles for simvastatin drug. Simvastatin is a lipid lowering agent, and BCS class-II drug having low solubility and high permeability. Since simvastatin undergoes extensive first pass extraction in the liver, the availability of the drug to the general circulation is low (< 5%. Nanoparticles were prepared by precipitation-solvent deposition method using 3² full factorial design. From the preliminary trials, the constraints for independent variables X1 (amount of PLGA and X2 (amount of Pleuronic F-68 have been fixed. The prepared formulations were further evaluated for drug content, in vitro drug release pattern, short term stability and drug excipient interactions. The application of factorial design gave a statistically systematic approach for the formulation and optimization of nanoparticles with desired particle size and high entrapment efficiency. Drug: polymer ratio and concentration of stabilizer were found to influence the particle size and entrapment efficiency of simvastatin loaded PLGA nanoparticles. In vitro drug release study of selected factorial formulations (PS1, PS4, PS7 showed, 84.56%, 89.65 %, and 73.46 % release respectively in 24 hrs. The release was found to follow first order release kinetics with fickian diffusion mechanism for all batches. These results indicate that simvastatin loaded PLGA nanoparticles could be effective in sustaining drug release for a prolonged period.

  8. 不同剂量辛伐他汀对多柔比星导致的乳鼠心肌细胞损伤的保护作用%Protective effect of different doses of simvastatin on neonate rat cardiomyocyte injury induced by doxorubicin

    Institute of Scientific and Technical Information of China (English)

    潘建业; 陈星; 顾琳; 王好; 张国辉

    2011-01-01

    目的 探讨辛伐他汀(SIM)对多柔比星(DOX)损伤乳鼠心肌细胞的保护作用.方法 新生SD大鼠(乳鼠)心肌细胞随机分为5组,对照组不予任何药物,正常培养;DOX组予1μmol/L DOX,SIM低、中、高剂量组分别在给予1 μmol/L DOX基础上予1、10、20 μmol/L SIM,继续培养24h后,倒置相差显微镜下测定各组心肌细胞搏动频率,流式细胞术检测凋亡率,Western blot法检测钙释放通道(RyR2)蛋白表达情况.结果 DOX组及SIM低、中、高剂量组的心肌细胞搏动频率、RyR2表达均明显低于对照组,凋亡率均明显高于对照组,P均<0.05;SIM低、中、高剂量组的心肌细胞搏动频率、RyR2表达均明显高于DOX组,凋亡率均明显低于DOX组,且呈剂量依赖性,P均<0.05.结论 SIM对DOX损伤乳鼠心肌细胞有保护作用,且呈剂量依赖性,其机制可能与提高RyR2表达有关.%Objective To investigate the protective effect of simvastatin(SIM) on neonate rat myocardium cell injury induced by doxorubicin( DOX). Methods The cardiomyocytes of renewal SD rats( neonate rat) were divided randomly into five groups, control group was only given cell culture medium; DOX group was given DOX with the final concentration of 1 μmol/L; SIM groups of low, moderate and high dosage were given SIM with the final concentration of 1, 10, 20 μnol/L at the base of DOX group. After 24 hours further cultivation, the cardiomyocytes beating rate was determined by inverted phase contrast microscope, the apoptosis ratio of cardiomyocytes was detected by flow cytometry, expression of RyR2 protein was evaluated using Western blot. Results Compared to the control group, the cardiomyocytes beating rate and the syn-thesis of RyR2 were descended significantly in the DOX and SIM (low, moderate, high dosage) groups, and the apoptosis ratio'of cardiomyocytes was increased significantly (all P <0.05). Compared to the DOX group, the cardiomyocytes beat-ing rate and the expression of Ry

  9. Combination of simvastatin, calcium silicate/gypsum, and gelatin and bone regeneration in rabbit calvarial defects

    Science.gov (United States)

    Zhang, Jing; Wang, Huiming; Shi, Jue; Wang, Ying; Lai, Kaichen; Yang, Xianyan; Chen, Xiaoyi; Yang, Guoli

    2016-03-01

    The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration.

  10. The pharmacokinetic characters of simvastatin after co-administration with Shexiang Baoxin Pill in healthy volunteers' plasma.

    Science.gov (United States)

    Tao, Jianfei; Jiang, Peng; Peng, Chengcheng; Li, Min; Liu, Runhui; Zhang, Weidong

    2016-07-15

    To investigate the effect of Shexiang Baoxin Pill (SBP), a tranditional Chinese medicine, on the pharmacokinetic (PK) parameters of simvastatin in healthy volunteers' plasma, a quantitative method was developed using an Agilent G6410A rapid performance liquid chromatography (RPLC) coupled with triple quadrupole mass spectrometry system. The established method was rapid with high extraction recovery and successfully applied for the determination of simvastatin in plasma of 16 healthy volunteers. The results demonstrated that the MRT(0-∞), T1/2 and Tmax value of simvastatin were significantly decreased, while the AUC(0-t) and Cmax values of smivastatin were increased by SBP. The pharmacokinetic study demonstrated that the metabolism parameters of simvastatin could be affected by SBP and the potential drug-drug interaction should be noted in the future clinical practice.

  11. The application of high dose food irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bruyn, I. De [Atomic Energy Corporation of South Africa LTD, Building 2000, P.O. Box 582, Pretoria 0001, (South Africa)

    1997-12-31

    During the 1950`s to end 1970`s the United States Army developed the basic methodology to produce shelf stable irradiated meat, seafood and poultry products. These products are normally packed without gravy, sauce or brine, as liquid is not required to sterilize the product as in the canning process. This leads to the distinctive `dried cooked` taste normally associated with roasts opposed to the casserole taste usually associated with tinned meats. The meats are cooked, chilled, portioned, vacuum packed and irradiated to the required minimum dose of 25 to 45 kGy (depending on the product) at a temperature of between -20 and -40 Centigrade to ensure absolute sterility even under tropical conditions. The product is packaged in a high quality four layer laminate pouch and will therefore not rust or burst even under adverse weather conditions. The product can be guaranteed for more than two years as long as the integrity of the packaging is maintained. (Author)

  12. Dislipemia in patients undergoing continuous ambulatory peritoneal dialysis: pharmacological therapy (simvastatin) versus hemodialysis.

    Science.gov (United States)

    Marangoni, R; Civardi, F; Masi, F; Cimino, R; Maltagliati, L; Romei Longhena, G

    1993-01-01

    Peritoneal dialysis can worsen dislipemia, which is frequent in chronically uremic patients. In order to verify the therapeutic possibilities, we retrospectively studied 20 chronically uremic patients who had been previously treated with continuous ambulatory peritoneal dialysis (CAPD) and who had developed an IV-type dislipemia. Twelve have continued CAPD treatment and have been simultaneously treated with simvastatin; 8 have withdrawn from CAPD and have begun HD, without any antidislipemic pharmacological support. The results, after 3, 6, 12, and 18 months of treatment, showed the following: in patients treated with CAPD and simvastatin, highly significant decreases were noted in total cholesterol (T-cho) and triglycerides (TG) (p dislipemia only, can continue the treatment, because simvastatin is capable of correcting dislipemia, while those patients who have displemia as well as other complications strictly due to CAPD must abandon treatment and must be transferred to extracorporeal methods.

  13. A comparative study of antioxidant vitamins and simvastatin in hypercholesterolimic rabbits.

    Science.gov (United States)

    Syed, Nawazish-I-Husain; Arshad, Shamas; Syed, Amir Ali Rizvi; Ahmad, Maqsood; Khan, Farrakh Zia; Ahmad, Bashir

    2011-10-01

    The anti-lipidemic effects of orally administered antioxidant vitamins (vitamin A, vitamin C and vitamin E) individually and in combination were studied in cholesterol-fed rabbits and compared to the group of hypercholesterolemic animals that were treated with simvastatin. All treatment groups exhibited a decrease in serum total cholesterol, low density lipoprotein-cholesterol (LDL-C) and triglycerides concentrations, whilst vitamin C, vitamin E, the combination and simvastatin showed a more profound decrease in the lipid profile than vitamin A at different time intervals. The order of increase in high density lipoprotein-cholesterol (HDL-C) levels remained in favour of simvastatin, as none of the antioxidant vitamins treated group could exhibit a profound increase in the HDL-C.

  14. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sha, Rajib Lochan [Department of Radiation Physics, Indo-American Cancer Institute and Research Centre, Hyderabad (India); Department of Physics, Osmania University, Hyderabad (India); Reddy, Palreddy Yadagiri [Department of Physics, Osmania University, Hyderabad (India); Rao, Ramakrishna [Department of Radiation Physics, MNJ Institute of Oncology and Regional Cancer Center, Hyderabad (India); Muralidhar, Kanaparthy R. [Department of Radiation Physics, Indo-American Cancer Institute and Research Centre, Hyderabad (India); Kudchadker, Rajat J., E-mail: rkudchad@mdanderson.org [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  15. Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

    Directory of Open Access Journals (Sweden)

    Campos-Martorell M

    2016-06-01

    Full Text Available Mireia Campos-Martorell,1 Mary Cano-Sarabia,2 Alba Simats,1 Mar Hernández-Guillamon,1 Anna Rosell,1 Daniel Maspoch,2,3 Joan Montaner1,4 1Neurovascular Research Laboratory, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, 2Catalan Institute of Nanoscience and Nanotechnology (ICN2, CSIC and The Barcelona Institute of Science and Technology, Universitat Autònoma de Barcelona, Barcelona, 3Institució Catalana de Recerca i Estudis Avançats (ICREA, 4Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain Background and aims: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt surgery and treated (intravenous [IV] with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results: Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes

  16. Simvastatin impairs growth hormone-activated signal transducer and activator of transcription (STAT signaling pathway in UMR-106 osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    María Claudia Sandoval-Usme

    Full Text Available Recent studies have demonstrated that statins reduce cell viability and induce apoptosis in various types of cancer cells. The molecular mechanisms underlying these effects are poorly understood. The JAK/STAT pathway plays an important role in the regulation of proliferation and apoptosis in many tissues, and its deregulation is believed to be involved in tumorigenesis and cancer. The physiological activation of STAT proteins by GH is rapid but transient in nature and its inactivation is regulated mainly by the expression of SOCS proteins. UMR-106 osteosarcoma cells express a GH-responsive JAK2/STAT5 signaling pathway, providing an experimental model to study the influence of statins on this system. In this study we investigated the actions of simvastatin on cell proliferation, migration, and invasion on UMR-106 cells and examined whether alterations in GH-stimulated JAK/STAT/SOCS signaling may be observed. Results showed that treatment of osteosarcoma cells with simvastatin at 3 to 10 µM doses decreases cell proliferation, migration, and invasion in a time- and dose-dependent manner. At the molecular level, although the mechanisms used by simvastatin are not entirely clear, the effect of the statin on the reduction of JAK2 and STAT5 phosphorylation levels may partially explain the decrease in the GH-stimulated STAT5 transcriptional activity. This effect correlated with a time- and dose-dependent increase of SOCS-3 expression levels in cells treated with simvastatin, a regulatory role that has not been previously described. Furthermore, the finding that simvastatin is capable of inducing SOCS-3 and CIS genes expression shows the potential of the JAK/STAT pathway as a therapeutic target, reinforcing the efficacy of simvastatin as chemotherapeutic drug for the treatment of osteosarcoma.

  17. High-Dose Statins Boost Survival

    Science.gov (United States)

    ... atorvastatin (Lipitor) or 20 to 40 mg of rosuvastatin (Crestor) daily. Examples of moderate doses include 10 to ... of Lipitor and 5 to 10 mg of Crestor, the study reported. Unlike some previous studies, this ...

  18. Simvastatin inhibits CD44 fragmentation in chondrocytes.

    Science.gov (United States)

    Terabe, Kenya; Takahashi, Nobunori; Takemoto, Toki; Knudson, Warren; Ishiguro, Naoki; Kojima, Toshihisa

    2016-08-15

    In human osteoarthritic chondrocytes, the hyaluronan receptor CD44 undergoes proteolytic cleavage at the cell surface. CD44 cleavage is thought to require transit of CD44 into cholesterol-rich lipid rafts. The purpose of this study was to investigate whether statins exert a protective effect on articular chondrocytes due to diminution of cholesterol. Three model systems of chondrocytes were examined including human HCS-2/8 chondrosarcoma cells, human osteoarthritic chondrocytes and normal bovine articular chondrocytes. Treatment with IL-1β + Oncostatin M resulted in a substantial increase in CD44 fragmentation in each of the three chondrocyte models. Pre-incubation with simvastatin prior to treatment with IL-1β + Oncostatin M decreased the level of CD44 fragmentation, decreased the proportion of CD44 that transits into the lipid raft fractions, decreased ADAM10 activity and diminished the interaction between CD44 and ADAM10. In HCS-2/8 cells and bovine articular chondrocytes, fragmentation of CD44 was blocked by the knockdown of ADAM10. Inhibition of CD44 fragmentation by simvastatin also resulted in improved retention of pericellular matrix. Addition of cholesterol and farnesyl-pyrophosphate reversed the protective effects of simvastatin. Thus, the addition of simvastatin exerts positive effects on chondrocytes including reduced CD44 fragmentation and enhanced the retention of pericellular matrix. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Biological dose estimation for accidental supra-high dose gamma-ray exposure

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y., E-mail: yingchen29@yahoo.com.cn [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Yan, X.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Department of Radiation Safety, Beijing Institute of Nuclear and Chemical Safety, 14 Guan-cun, Dongcheng District, Beijing 100077 (China); Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China)

    2011-09-15

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of {sup 60}Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of {sup 60}Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0{sup -3}D{sup 2}. Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy {gamma}-irradiation from a supra-high dose {sup 60}Co gamma-ray accident.

  20. Antiatherogenic effect of simvastatin is not due to decrease of LDL cholesterol in ovariectomized golden Syrian hamster.

    Science.gov (United States)

    Pitha, J; Bobková, D; Kovár, J; Havlícková, J; Poledne, R

    2010-01-01

    The changes of the composition of blood lipoproteins caused by menopause could also change the effect of hypolipidemic therapy. Using an experimental model we studied the changes of serum lipids and the effect of immediate or delayed treatment with simvastatin on atherosclerosis after surgical menopause. Female golden Syrian hamster aged 6 months were fed hypercholesterolemic diet during the whole study. Atherosclerotic changes in thoracic and abdominal aortas were assessed by stereomicroscopic method after 12 weeks. Four experimental groups were studied: sham-operated animals (n = 5), ovariectomized animals (n = 9), ovariectomized animals treated for 12 weeks (n = 10), and ovariectomized animals treated 4 weeks after ovariectomy for 8 weeks (n = 9). The dose of simvastatin was 10 mg/kg of body weight. After 12 weeks, ovariectomized animals had tenfold higher concentration of triglycerides in LDL fraction and significantly higher prevalence of atherosclerosis than animals without ovariectomy. Treatment with simvastatin substantially decreased the prevalence of atherosclerotic changes, but otherwise did not change individual serum lipids including LDL cholesterol. However, it improved proportions of pro- and antiatherogenic serum lipids mainly by the increase of HDL cholesterol. The timing of simvastatin treatment had no significant effect on atherosclerotic changes or lipid parameters. Simvastatin treatment partly prevented atherosclerotic changes induced by ovariectomy. This effect was not mediated by decrease of LDL cholesterol, but by increase in HDL cholesterol.

  1. Pleiotropic effects of simvastatin in physically trained ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Bernardes, N. [Universidade Nove de Julho (UNINOVE), São Paulo, SP (Brazil); Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Brito, J.O. [Universidade Nove de Julho (UNINOVE), São Paulo, SP (Brazil); Fernandes, T.G. [Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universdade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Llesuy, S.F. [University of Buenos Aires, Buenos Aires (Argentina); Irigoyen, M.C. [Unidade de Hipertensão, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Belló-Klein, A. [Laboratório de Fisiologia Cardiovascular, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universdade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); De Angelis, K. [Universidade Nove de Julho (UNINOVE), São Paulo, SP (Brazil)

    2013-05-24

    This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5 mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats.

  2. Simvastatin improves cerebrovascular function and counters soluble amyloid-beta, inflammation and oxidative stress in aged APP mice.

    Science.gov (United States)

    Tong, Xin-Kang; Nicolakakis, Nektaria; Fernandes, Priscilla; Ongali, Brice; Brouillette, Jonathan; Quirion, Rémi; Hamel, Edith

    2009-09-01

    Cerebrovascular dysfunctions appear to contribute to Alzheimer's disease (AD) pathogenesis and the associated cognitive decline. Recently, it has been suggested that statins could be beneficial to AD patients independently from their cholesterol-lowering effects. Using 10 month-old amyloid precursor protein transgenic mice (APP mice), we sought to reverse cerebrovascular, neuronal and memory impairments with simvastatin (20 mg/kg/day, 8 weeks). Simvastatin improved reactivity of cerebral arteries, rescued the blood flow response to neuronal activation, attenuated oxidative stress and inflammation, and reduced cortical soluble amyloid-beta (Abeta) levels and the number of Abeta plaque-related dystrophic neurites. However, at such an advanced stage of the pathology, it failed to reduce Abeta plaque load and normalize cholinergic and memory deficits. These findings demonstrate that low-dose simvastatin treatment in aged APP mice largely salvages cerebrovascular function and has benefits on several AD landmarks, which could explain some of the positive effects of statins reported in AD patients.

  3. The transit dose component of high dose rate brachytherapy: Direct measurements and clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Bastin, K.T.; Podgorsak, M.B.; Thomadsen, B.R. (Univ. of Wisconsin Hospitals and Clinics, Madison, WI (United States))

    1993-07-15

    The purpose was to measure the transit dose produced by a moving high dose rate brachytherapy source and assess its clinical significance. The doses produced from source movement during Ir-192 HDR afterloading were measured using calibrated thermoluminescent dosimeter rods. Transit doses at distances of 0.5-4.0 cm from an endobronchial applicator were measured using a Lucite phantom accommodating 1 x 1 x 6 mm thermoluminescent rods. Surface transit dose measurements were made using esophageal and endobronchial catheters, a gynecologic tandem, and an interstitial needle. No difference was detected in thermoluminescent dosimeter rod responses to 4 MV and Ir-192 spectra (427 nC/Gy) in a range of dose between 2 and 300 cGy. The transit dose at 0.5 cm from an endobronchial catheter was 0.31 cGy/(Curie-fraction) and followed an inverse square fall-off with increasing distance. Surface transit doses ranged from 0.38 cGy/(Curie-fraction) for an esophageal catheter to 1.03 cGy/(Curie-fraction) for an endobronchial catheter. Source velocity is dependent on the interdwell distance and varies between 220-452 mm/sec. A numeric algorithm was developed to calculate total transit dose, and was based on a dynamic point approximation for the moving high dose rate source. This algorithm reliably predicted the empirical transit doses and demonstrated that total transit dose is dependent on source velocity, number of fractions, and source activity. Surface transit doses are dependent on applicator diameter and wall material and thickness. Total transit doses within or outside the desired treatment volume are typically <100 cGy, but may exceed 200 cGy when using a large number of fractions with a high activity source. 9 refs., 8 figs., 1 tab.

  4. Simvastatin and Benznidazole-Mediated Prevention of Trypanosoma cruzi-Induced Endothelial Activation: Role of 15-epi-lipoxin A4 in the Action of Simvastatin.

    Directory of Open Access Journals (Sweden)

    Carolina Campos-Estrada

    2015-05-01

    Full Text Available Trypanosoma cruzi is the causal agent of Chagas Disease that is endemic in Latin American, afflicting more than ten million people approximately. This disease has two phases, acute and chronic. The acute phase is often asymptomatic, but with time it progresses to the chronic phase, affecting the heart and gastrointestinal tract and can be lethal. Chronic Chagas cardiomyopathy involves an inflammatory vasculopathy. Endothelial activation during Chagas disease entails the expression of cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1 and intercellular cell adhesion molecule-1 (ICAM-1 through a mechanism involving NF-κB activation. Currently, specific trypanocidal therapy remains on benznidazole, although new triazole derivatives are promising. A novel strategy is proposed that aims at some pathophysiological processes to facilitate current antiparasitic therapy, decreasing treatment length or doses and slowing disease progress. Simvastatin has anti-inflammatory actions, including improvement of endothelial function, by inducing a novel pro-resolving lipid, the 5-lypoxygenase derivative 15-epi-lipoxin A4 (15-epi-LXA4, which belongs to aspirin-triggered lipoxins. Herein, we propose modifying endothelial activation with simvastatin or benznidazole and evaluate the pathways involved, including induction of 15-epi-LXA4. The effect of 5 μM simvastatin or 20 μM benznidazole upon endothelial activation was assessed in EA.hy926 or HUVEC cells, by E-selectin, ICAM-1 and VCAM-1 expression. 15-epi-LXA4 production and the relationship of both drugs with the NFκB pathway, as measured by IKK-IKB phosphorylation and nuclear migration of p65 protein was also assayed. Both drugs were administered to cell cultures 16 hours before the infection with T. cruzi parasites. Indeed, 5 μM simvastatin as well as 20 μM benznidazole prevented the increase in E-selectin, ICAM-1 and VCAM-1 expression in T. cruzi-infected endothelial

  5. High dose radiotherapy for pituitary tumours

    Energy Technology Data Exchange (ETDEWEB)

    Mead, K.W. (Queensland Radium Inst., Herston (Australia))

    1981-11-01

    The results of treatment of 120 pituitary tumours are presented. Based on this experience operable chromophobe adenomas are now treated with 5,000 rads in 4 weeks and inoperable ones receive an additional central dose to 7,500 rads. Pituitary Cushing's tumours are given 10,000 rads in 5 weeks using small fields and acromegalics 5,000 rads to the whole sella and 7,500 to its lower half. The absence of complications at these dose levels is attributed to the use of small fields and the precise application of treatment.

  6. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  7. Statistical behavior of high doses in medical radiodiagnosis; Comportamento estatistico das altas doses em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana Elisa, E-mail: adrianaebarboza@gmail.com, E-mail: elisa@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  8. Simvastatin Treatment Improves Survival in a Murine Model of Burn Sepsis

    Science.gov (United States)

    Beffa, David C; Fischman, Alan J.; Fagan, Shawn P.; Hamrahi, Victoria F.; Kaneki, Masao; Yu, Yong-Ming; Tompkins, Ronald G.; Carter, Edward A.

    2014-01-01

    Infection is the most common and most serious complication of a major burn injury related to burn size. Despite improvements in antimicrobial therapies sepsis still accounts for 50–60% of deaths in burn patients. Given the acute onset and unpredictable nature of sepsis, primary prevention was rarely attempted in its management. However, recent studies have demonstrated that statin treatment can decrease mortality is a murine model of sepsis by preservation of cardiac function and reversal of inflammatory alterations. In addition, it has been shown that treatment with statins is associated with reduced incidence of sepsis in human patients. In the current study groups of CD1 male mice (n=12) were anesthetized and subjected to a dorsal 30% TBSA scald burn injury. Starting 2 hours post burn, the animals were divided into a treatment group receiving 0.2 µ/g simvastatin or a sham group receiving placebo. Simvastatin and placebo were administered by intraperitoneal injection with two dosing regimens; once daily and every 12 hours. On Post burn day 7 cecal ligation and puncture with a 21-gauge needle was performed under ketamine/xylazine anesthesia and the two different dosing schedules were continued. A simvastatin dose dependant improvement in survival was observed in the burn sepsis model. PMID:21145172

  9. Influence of Simvastatin for In-stent Restenosis Rate and Blood Lipid Level and Inflammation Actor after Coronary Artery Stent Implantation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To investigate the effect of simvastatin on the probability of restenosis after stent implantation and serum level of lipids as well as high-sensitivity C-reactive protein (hs-CRP) in patients with coronary heart disease (CHD).Methods 118 patients with CHD after stenting therapy were divided into treatment group (n = 62) and control group(n =56) randomly. All patients were treated withaspirin (100 mg/d) and clopidogrel (75 mg/d) while treatment group patients took simvastatin (40 mg qn) additionally. All patients underwent coronary angiography (CAG) to compare the difference of restenosis and the serum level of total cholesterol (TC), low-density lipoprotein cholesterol(LDL-c), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG) as well as hs-CRP after the drug treatment for 6 months. Results The probability of restenosis was significantly lower in the treatment group than that of control group ( P < 0.01 ) and the results were similar between the patients with bare metal stent ( P < 0.01 ) and those with sirolimus-eluting stent ( P<0.01 ). The serum levels of TC (P<0.01 ), LDL-c( P<0.01 ), TG (P<0.05 ) and hsCRP (P<0.01) were obviously lower while the HDL-c (P<0.05 ) level was higher in the treatment group than those of control group. There was no death case. Conclusions Simvastatin could decrease the probability of restenosis significantly after coronary stent implantation with dose of 40 mg/d. It also has good performance on lipids control and lightening inflammatory reactions with its undoubtedly safety.

  10. Investigating quartz optically stimulated luminescence dose-response curves at high doses

    Energy Technology Data Exchange (ETDEWEB)

    Lowick, Sally E., E-mail: lowick@geo.unibe.c [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Preusser, Frank [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Wintle, Ann G. [Institute of Geography and Earth Sciences, Aberystwyth University, AberystwythSY23 3DB (United Kingdom)

    2010-10-15

    Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose-response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose-response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the '325 {sup o}C' thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses

  11. Development of computerized dose planning system and applicator for high dose rate remote afterloading irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, T. J. [Keimyung Univ., Taegu (Korea); Kim, S. W. [Fatima Hospital, Taegu (Korea); Kim, O. B.; Lee, H. J.; Won, C. H. [Keimyung Univ., Taegu (Korea); Yoon, S. M. [Dong-a Univ., Pusan (Korea)

    2000-04-01

    To design and fabricate of the high dose rate source and applicators which are tandem, ovoids and colpostat for OB/Gyn brachytherapy includes the computerized dose planning system. Designed the high dose rate Ir-192 source with nuclide atomic power irradiation and investigated the dose characteristics of fabricated brachysource. We performed the effect of self-absorption and determining the gamma constant and output factor and determined the apparent activity of designed source. he automated computer planning system provided the 2D distribution and 3D includes analysis programs. Created the high dose rate source Ir-192, 10 Ci(370GBq). The effective attenuation factor from the self-absorption and source wall was examined to 0.55 of the activity of bare source and this factor is useful for determination of the apparent activity and gamma constant 4.69 Rcm{sup 2}/mCi-hr. Fabricated the colpostat was investigated the dose distributions of frontal, axial and sagittal plane in intra-cavitary radiation therapy for cervical cancer. The reduce dose at bladder and rectum area was found about 20 % of original dose. The computerized brachytherapy planning system provides the 2-dimensional isodose and 3-D include the dose-volume histogram(DVH) with graphic-user-interface mode. emoted afterloading device was built for experiment of created Ir-192 source with film dosimetry within {+-}1 mm discrepancy. 34 refs., 25 figs., 11 tabs. (Author)

  12. Effect of simvastatin on anti-oxidation and anti-inflammation properties of HDL in apoE-/-mice

    Directory of Open Access Journals (Sweden)

    Di TIAN

    2013-03-01

    Full Text Available Objectives  To investigate the effect of simvastatin on anti-oxidation and anti-inflammation properties of high density lipoprotein (HDL in apoE-/-mice fed with high-fat diet. Methods  Eighteen 8-week old male C57BL/6J mice as blank control group were fed with normal diet, and thirty 8-week old male apoE-/-mice were fed with high-fat diet. Four weeks later, 6 mice in each group were sacrificed. The remaining 24 apoE-/-mice were randomly divided into two groups (12 each: atherosclerosis group (AS group and simvastatin group, while the remaining 12 C57BL/6J mice served as control group. The mice in both control and AS group were fed with the original diet, and the mice in simvastatin group were fed with the same high-fat diet plus simvastatin 5mg/ (kg.d. At the end of the 8th and 16th week, 6 mice were sacrificed in each group. Serum lipid levels, paraoxonase 1 (PON1 activity (arylesterase activity, serum myeloperoxidase (MPO activity, high-density lipoprotein inflammation index (HII and serum hs-CRP levels were determined. The atherosclerotic lesion formation in the aorta was manifested by oil red O staining. Results  At the end of the 8th week, no difference was found in the levels of serum low density lipoprotein cholesterol (LDL-C and high density lipoprotein cholesterol (HDL-C between simvastatin and AS group. At the end of 16th week, the levels of serum LDL-C decreased significantly (P<0.01 and HDL-C increased significantly (P<0.05 in simvastatin group compared with AS group. At the end of the 8th and 16th week, a significant enhancement of the serum PON1 activity but marked decrease in MPO activity, HII, and serum hs-CRP levels were found in simvastatin group compared with that in AS group. The percentage of plaque area (surface area of plaque/ surface area of whole intima in the aorta was significantly smaller in simvastatin group than that in AS group (P<0.05 or P<0.01. Conclusions In addition to lowering LDL-C and elevating HDL

  13. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    2012-01-01

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university hosp

  14. Achieving lipid goals with rosuvastatin compared with simvastatin in high risk patients in real clinical practice: a randomized, open-label, parallel-group, multi-center study: the DISCOVERY-Beta study

    Directory of Open Access Journals (Sweden)

    Toivo Laks

    2008-12-01

    Full Text Available Toivo Laks1, Ester Keba2, Mariann Leiner3, Eero Merilind4, Mall Petersen5, Sirje Reinmets6, Sille Väli7, Terje Sööt8, Karin Otter81Clinic of Internal Medicine, North-Estonia Regional Hospital, Tallinn, Estonia; 2Clinic of Internal Medicine, Viljandi County Hospital, Viljandi, Estonia; 3Mustamäe Family Doctors Centre, Tallinn, Estonia; 4Nõmme Family Doctors Centre, Tallinn, Estonia; 5Saku Health Centre, Saku, Estonia; 6Kristiine Family Doctors, Tallinn, Estonia; 7Family Doctor Sille Väli, Kuressaare, Estonia; 8AstraZeneca, Tallinn, EstoniaAbstract: The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS lipid treatment goals. 504 patients (≥18 years with primary hypercholesterolemia and a 10-year cardiovascular (CV risk >20% or history of coronary heart disease (CHD or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01. Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC goal and the 2003 EAS LDL-C and TC goals (p < 0.001 with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the proportion of patients who discontinued study treatment were similar between treatment groups. In conclusion, in the DISCOVERY-Beta Study in patients with primary hypercholesterolemia greater proportion of patients in the rosuvastatin 10 mg group achieved the EAS LDL-C treatment goal compared with the simvastatin 20 mg group. Drug tolerability was similar across both treatment groups.Keywords: hypercholesterolemia, low-density lipoprotein

  15. Healing of extraction socket following local application of simvastatin: A split mouth prospective study.

    Science.gov (United States)

    Saifi, Aamir Malick; Giraddi, Girish B; Ahmed, Nausheer

    2017-01-01

    The role of simvastatin in lowering serum cholesterol level is well described. However, recent findings suggest they have a role in bone formation as well. The present prospective study was conducted to evaluate the efficacy of simvastatin on bone formation in extraction sockets. 15 patients undergoing all four first premolar extraction were selected based on inclusion and exclusion criteria. Extraction sockets of left premolars (24 and 34) were considered as cases and right premolars (14 and 44) as controls. Overall 30 extraction sites were assigned to each group. Atraumatic extraction was done in all cases following which simvastatin mixed with gelatin sponge was placed in extraction socket of 24 and 34 while only gelatin sponge was placed in 14 and 44. All sockets were then closed with 3-0 vicryl. The patients were kept on follow-up and complications such as dry socket, pain, and swelling were recorded. Intra oral peri apical radiographs were taken immediately after extraction and at 2nd month and 4th month to record changes in the density of alveolar bone. The radiographic measurements were compared and the differences were statistically analyzed. Percent increase in bone density at the end of 8th week and 16th week was significantly high in case as compared to the control group. Local application of simvastatin induces bone formation in extraction sockets. Application is very simple and provides a very cost effective way of faster bone regeneration following tooth extraction.

  16. Relevance of high-dose chemotherapy in solid tumours

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

    2005-01-01

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high

  17. Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

    NARCIS (Netherlands)

    Ekhart, G.C. (Corine)

    2008-01-01

    High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation has been developed as a possible curative treatment modality in several solid tumours. A frequently used high-dose regimen in the Netherlands is the CTC regimen, which is a 4-day course of cyclophosphamide, t

  18. 辛伐他汀对高糖高脂诱导人骨髓间充质干细胞凋亡的影响%Effects of simvastatin on the apoptosis of human mesenchymal stem cells induced by high glucose and saturated fatty acids

    Institute of Scientific and Technical Information of China (English)

    赵婕; 李华青; 李晶; 薛国芳; 陈彦; 齐凯; 董敏; 王惠珍; 牛勃

    2011-01-01

    背景:研究表明,他汀类药物能够促进骨髓间充质干细胞的增殖与黏附能力,抑制高糖高脂培养下骨髓间充质干细胞的凋亡.目的:观察辛伐他汀对高糖高脂诱导条件下人骨髓间充质干细胞凋亡的影响.方法:将0.001,0.01,0.1,1.0 μmol/L辛伐他汀分别与高糖高脂诱导条件下人骨髓间充质干细胞培养48 h,以正常培养骨髓间充质干细胞及高糖高脂诱导条件下培养的骨髓间充质干细胞为对照.倒置显微镜下观察细胞形态,MTT法比较不同浓度辛伐他汀对高糖高脂环境下骨髓间充质干细胞存活率的影响,应用流式细胞术检测细胞凋亡,加入PI3K/Akt信号转导通路抑制剂LY294002后辛伐他汀对骨髓间充质干细胞凋亡的影响.结果与结论:与高糖高脂诱导组比较,辛伐他汀0.01,0.1,1.0 μmol/L组骨髓间充质干细胞存活率均升高(P<0.01),其中辛伐他汀浓度在0.1 μmol/L时骨髓间充质干细胞存活率升高最显著(P<0.01);同时流式细胞仪检测结果显示,辛伐他汀0.01,0.1,1.0 μmol/L组细胞凋亡率下降(P<0.01),其中0.1 μmol/L组凋亡率下降最显著(P<0.01).0.1 μmol/L辛伐他汀对骨髓间充质干细胞的影响可被LY294002阻断.说明辛伐他汀能抑制高糖高脂诱导条件下骨髓间充质干细胞的凋亡,其机制可能与PI3K/Akt信号途径有关.%BACKGROUND: Previous studies demonstrated that statins can promote the proliferation and adhesion of bone marrow mesenchymal stem cells (BMSCs), inhibit apoptosis of BMSCs cultured with high glucose and saturated fatty acids.OBJECTIVE: To investigate the effects of simvastatin on the apoptosis of human mesenchymal stem cells induced by high glucose and saturated fatty acids.METHODS: Different concentrations of simvastatin (0.001, 0.01, 0.1, 1.0 μmol/L) was cultured with BMSCs in presence of high glucose and saturated fatty acids for 48 hours. BMSCs cultured with normal bone marrow mesenchymal stem cells induced

  19. Effect of splitting simvastatin tablets for control of low-density lipoprotein cholesterol.

    Science.gov (United States)

    Parra, David; Beckey, Nick P; Raval, Harsha S; Schnacky, Kimberly R; Calabrese, Vincent; Coakley, Roy W; Goodhope, Robert C

    2005-06-15

    The efficacy, safety, and economics of a voluntary conversion from whole simvastatin tablets to split tablets in 6 Veterans Affairs medical centers were retrospectively evaluated in 3,787 patients who received a consistent daily dose (5 to 40 mg) of simvastatin in 1999. Baseline and final low-density lipoprotein cholesterol levels and average change from baseline were not significantly different between groups (p >0.05), nor were the incidence of transaminase increases (p >0.05) or measurements of patient compliance (p = 0.07). Widespread implementation of this initiative resulted in a cost avoidance of >$1.2 million in the 6 medical centers and $10.3 million across the Veterans Affairs medical system in 1999, with >$46 million avoided in 2003.

  20. High-resolution low-dose scanning transmission electron microscopy.

    Science.gov (United States)

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  1. High dose brachytherapy in pediatric oncology; Braquiterapia com alta taxa de dose em oncologia pediatrica

    Energy Technology Data Exchange (ETDEWEB)

    Ferrigno, Robson; Codjaian, Osanna Esther; Novaes, Paulo Eduardo R.S.; Trippe, Nivaldo [Fundacao Antonio Prudente, Sao Paulo, SP (Brazil). Hospital A.C. Camargo. Dept. de Radioterapia

    1995-05-01

    Brachytherapy is a kind of radiotherapy that has been used in the multidisciplinary approach of some pediatric tumors, such as soft tissue sarcomas of the extremities, head and neck and urogenital tract. Recent technological advances in this area lead to development of computerized high dose rate remote afterloading brachytherapy. This type of treatment has some advantages compared to low dose rate brachytherapy traditionally used. This article describes not only the characteristics and advantages of this kind of treatment, but also the preliminary results of the first seven children treated with high dose rate at the Hospital A.C.Camargo. (author) 10 refs., 8 figs.

  2. Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MS/MS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-Release/Simvastatin (500 mg/10 mg in Healthy Chinese Volunteers

    Directory of Open Access Journals (Sweden)

    Pingping Zhang

    2015-01-01

    Full Text Available Our paper aimed to develop rapid, sensitive, and specific LC-MS/MS method for the quantification of niacin (NA and its metabolite nicotinuric acid (NUA in human plasma. Following protein precipitation with acetonitrile, the NA, NUA, and internal standard (5-fluorouracil were separated on a Zorbax 300SB-C8 column (250 mm × 4.6 mm, 5 μm with a mobile phase consisting of methanol-2 mM ammonium acetate (3 : 97, v/v at a flow rate of 1 mL/min (split 1 : 1. A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in negative ion mode. The linear concentration ranges of the calibration curves were 5–800 ng/mL for NA and NUA. The intra-assay RSD for quality control (QC samples were from 5.0% to 8.7% for NA, and 5.5% to 7.6% for NUA. The interassay RSD for QC samples were from 2.8% to 9.4% for NA, and 3.7% to 5.8% for NUA. The relative errors for QC samples were from −2.2% to 2.3% for NA, and −0.6% to 3.2% for NUA. The method was successfully applied to the investigation of the pharmacokinetic profiles of NA, NUA in human after single dose administration of Niacin extended-release/Simvastatin tablet (500 mg/10 mg.

  3. Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhijie [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-03-31

    The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

  4. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

    Science.gov (United States)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q; Harmann, Leanne; Hopewell, John W; Kronenberg, Amy; Patel, Shailendra; Moulder, John E; Baker, John E

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  5. Bacteriostatic effect of simvastatin on selected oral streptococci in vitro

    Directory of Open Access Journals (Sweden)

    Eugene J Whitaker

    2017-01-01

    Full Text Available Context and Objective: Simvastatin is a widely used cholesterol-lowering drug, which has been found to have a number of pleiotropic effects. The aim of this study was to evaluate the antimicrobial effectiveness of simvastatin against selected oral streptococci as determined by the minimum inhibitory concentration (MIC. Methods: Streptococcus mutans, Streptococcus sanguis, Streptococcus anginosus, and Streptococcus salivarius were the test microorganisms. The serial dilution method was used to determine the MIC of simvastatin against these organisms. The MIC was defined as the lowest concentration of simvastatin that completely inhibited growth of the test organisms. Results: The data indicate that simvastatin inhibits the growth of the test organisms, with MIC's ranging from 7.8 to 15.6 μg/ml. Conclusions: Simvastatin has MIC's against the selected bacteria that compare favorably with reported values for topical agents such as essential oil, chlorhexidine gluconate, and triclosan. The levels of simvastatin required to inhibit bacterial growth of oral bacteria exceed the reported levels of the drug found in plasma or crevicular fluid of patients who are treated with this cholesterol-lowering drug. However, clinical studies are warranted to investigate the potential use of simvastatin as a novel antiplaque agent that could be used in local drug delivery to the oral cavity of those patients who are prescribed this cholesterol-lowering drug.

  6. High-dose dosimetry using natural silicate minerals

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

    2015-07-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  7. Structural basis for simvastatin competitive antagonism of complement receptor 3

    DEFF Research Database (Denmark)

    Jensen, Maria Risager; Bajic, Goran; Zhang, Xianwei;

    2016-01-01

    The complement system is an important part of the innate immune response to infection, but may also cause severe complications during inflammation. Small molecule antagonists to complement receptor (CR)3 have been widely sought, but a structural basis for their mode of action is not available. We...... report here on the structure of the human CR3 ligand-binding I domain in complex with simvastatin. Simvastatin targets the metal ion-dependent adhesion site of the open, ligand-binding conformation of the CR3 I domain by direct contact with the chelated Mg2+ ion. Simvastatin antagonizes I domain binding...... to the complement fragments iC3b and C3d, but not to intercellular adhesion molecule-1. By virtue of the I domain's wide distribution in binding kinetics to ligands, it was possible to identify ligand binding kinetics as discriminator for simvastatin antagonism. In static cellular experiments, 15-25 μM simvastatin...

  8. Impact of surface curvature on dose delivery in intraoperative high-dose-rate brachytherapy.

    Science.gov (United States)

    Oh, Moonseong; Wang, Zhou; Malhotra, Harish K; Jaggernauth, Wainwright; Podgorsak, Matthew B

    2009-01-01

    In intraoperative high-dose-rate (IOHDR) brachytherapy, a 2-dimensional (2D) geometry is typically used for treatment planning. The assumption of planar geometry may cause serious errors in dose delivery for target surfaces that are, in reality, curved. A study to evaluate the magnitude of these errors in clinical practice was undertaken. Cylindrical phantoms with 6 radii (range: 1.35-12.5 cm) were used to simulate curved treatment geometries. Treatment plans were developed for various planar geometries and were delivered to the cylindrical phantoms using catheters inserted into Freiburg applicators of varying dimension. Dose distributions were measured using radiographic film. In comparison to the treatment plan (for a planar geometry), the doses delivered to prescription points were higher on the concave side of the geometry, up to 15% for the phantom with the smallest radius. On the convex side of the applicator, delivered doses were up to 10% lower for small treated areas (5 catheters). Our measurements have shown inaccuracy in dose delivery when the original planar treatment plan is delivered with a curved applicator. Dose delivery errors arising from the use of planar treatment plans with curved applicators may be significant.

  9. High-Dose Vitamin D May Not Curb Kids' Colds

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_167275.html High-Dose Vitamin D May Not Curb Kids' Colds Study seems ... 18, 2017 (HealthDay News) -- When it comes to vitamin supplements, more is not always better, according to ...

  10. Patient-specific dose calculation methods for high-dose-rate iridium-192 brachytherapy

    Science.gov (United States)

    Poon, Emily S.

    In high-dose-rate 192Ir brachytherapy, the radiation dose received by the patient is calculated according to the AAPM Task Group 43 (TG-43) formalism. This table-based dose superposition method uses dosimetry parameters derived with the radioactive 192Ir source centered in a water phantom. It neglects the dose perturbations caused by inhomogeneities, such as the patient anatomy, applicators, shielding, and radiographic contrast solution. In this work, we evaluated the dosimetric characteristics of a shielded rectal applicator with an endocavitary balloon injected with contrast solution. The dose distributions around this applicator were calculated by the GEANT4 Monte Carlo (MC) code and measured by ionization chamber and GAFCHROMIC EBT film. A patient-specific dose calculation study was then carried out for 40 rectal treatment plans. The PTRAN_CT MC code was used to calculate the dose based on computed tomography (CT) images. This study involved the development of BrachyGUI, an integrated treatment planning tool that can process DICOM-RT data and create PTRAN_CT input initialization files. BrachyGUI also comes with dose calculation and evaluation capabilities. We proposed a novel scatter correction method to account for the reduction in backscatter radiation near tissue-air interfaces. The first step requires calculating the doses contributed by primary and scattered photons separately, assuming a full scatter environment. The scatter dose in the patient is subsequently adjusted using a factor derived by MC calculations, which depends on the distances between the point of interest, the 192Ir source, and the body contour. The method was validated for multicatheter breast brachytherapy, in which the target and skin doses for 18 patient plans agreed with PTRAN_CT calculations better than 1%. Finally, we developed a CT-based analytical dose calculation method. It corrects for the photon attenuation and scatter based upon the radiological paths determined by ray tracing

  11. High-dose vs low-dose oxytocin for labor augmentation: a systematic review.

    Science.gov (United States)

    Wei, Shu-Qin; Luo, Zhong-Cheng; Qi, Hui-Ping; Xu, Hairong; Fraser, William D

    2010-10-01

    The objective of this systematic review was to estimate the efficacy and safety of high-dose vs low-dose oxytocin for labor augmentation on the risk of cesarean section and on indicators of maternal and neonatal morbidity. We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for randomized clinical trials published until January 2010. Ten randomized clinical trials, including 5423 women, met the inclusion criteria. High-dose oxytocin was associated with a moderate decrease in the risk of cesarean section (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.97), a small increase in spontaneous vaginal delivery (RR, 1.07; 95% CI, 1.02-1.12), and a decrease in labor duration (mean difference: -1.54 hours, 95% CI, -2.44 to -0.64). While hyperstimulation was increased with high-dose oxytocin (RR, 1.91; 95% CI, 1.49-2.45), there was no evidence of an increase in maternal or neonatal morbidity. We conclude that high-dose oxytocin for labor augmentation is associated with a decrease in cesarean section and shortened labor. Copyright © 2010 Mosby, Inc. All rights reserved.

  12. High-dose neutron detector development

    Energy Technology Data Exchange (ETDEWEB)

    Henzlova, Daniela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Menlove, Howard Olsen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-14

    The development of advanced sustainable nuclear fuel cycles relying on used nuclear fuel is one of the key programs pursued by the DOE Office of Nuclear Energy to minimize waste generation, limit proliferation risk and maximize energy production using nuclear energy. Safeguarding of advanced nuclear fuel cycles is essential to ensure the safety and security of the nuclear material. Current non-destructive assay (NDA) systems typically employ fission chambers or 3He-based tubes for the measurement of used fuel. Fission chambers are capable of withstanding the high gamma-ray backgrounds; however, they provide very low detection efficiency on the order of 0.01%. To benefit from the additional information provided by correlated neutron counting [1] higher detection efficiencies are required. 3He-based designs allow for higher detection efficiencies; however, at the expense of slow signal rise time characteristics and higher sensitivity to the gamma-ray backgrounds. It is therefore desirable to evaluate and develop technologies with potential to exceed performance parameters of standard fission chamber-based or 3He-based detection systems currently used in the NDA instrumentation.

  13. Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway.

    Science.gov (United States)

    Wang, Tingting; Seah, Serena; Loh, Xinyi; Chan, Ching-Wan; Hartman, Mikael; Goh, Boon-Cher; Lee, Soo-Chin

    2016-01-19

    Statins purportedly exert anti-tumoral effects on breast cancer. However, the biologic mechanisms for these actions are not fully elucidated. The aims of this study were 1) to explore the effects of simvastatin on apoptosis, proliferation as well as PI3K/Akt/mTOR and MAPK/ERK pathway in a window-of-opportunity breast cancer trial; 2) to further confirm findings from the clinical trial by functional studies; 3) to explore the regulatory role of mevalonate pathway on the anti-tumoral effects of simvastatin. In clinical samples, simvastatin led to increase in cleaved caspase-3 (p = 0.002) and decreased trend for Ki67 (p = 0.245). Simvastatin markedly suppressed PI3K/Akt/mTOR signalling by activating PTEN (p = 0.005) and by dephosphorylating Akt (p = 0.002) and S6RP (p = 0.033); it also inhibited MAPK/ERK pathway by dephosphorylating c-Raf (p = 0.018) and ERK1/2 (p = 0.002). In ER-positive (MCF-7, T47D) and ER-negative (MDA-MB-231, BT-549) breast cancer cells, simvastatin treatment consistently induced apoptosis and inhibited proliferation by deregulating caspase cascades and cell cycle proteins in a dose dependent manner. Concordantly, simvastatin strongly suppressed PI3K/Akt/mTOR pathway by enhancing PTEN expression and by further sequentially dephosphorylating downstream cascades including Akt, mTOR, p70S6K, S6RP and 4E-BP1. Furthermore, simvastatin significantly inhibited MAPK/ERK pathway by dephosphorylating sequential cascades such as c-Raf, MEK1/2 and ERK1/2. These simvastatin anti-tumoral effects were reversed by metabolic products of the mevalonate pathway, including mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate. These findings shed light on the biological and potential anti-tumoral effects of simvastatin in breast cancer.

  14. Radiation Parameters of High Dose Rate Iridium -192 Sources

    Science.gov (United States)

    Podgorsak, Matthew B.

    A lack of physical data for high dose rate (HDR) Ir-192 sources has necessitated the use of basic radiation parameters measured with low dose rate (LDR) Ir-192 seeds and ribbons in HDR dosimetry calculations. A rigorous examination of the radiation parameters of several HDR Ir-192 sources has shown that this extension of physical data from LDR to HDR Ir-192 may be inaccurate. Uncertainty in any of the basic radiation parameters used in dosimetry calculations compromises the accuracy of the calculated dose distribution and the subsequent dose delivery. Dose errors of up to 0.3%, 6%, and 2% can result from the use of currently accepted values for the half-life, exposure rate constant, and dose buildup effect, respectively. Since an accuracy of 5% in the delivered dose is essential to prevent severe complications or tumor regrowth, the use of basic physical constants with uncertainties approaching 6% is unacceptable. A systematic evaluation of the pertinent radiation parameters contributes to a reduction in the overall uncertainty in HDR Ir-192 dose delivery. Moreover, the results of the studies described in this thesis contribute significantly to the establishment of standardized numerical values to be used in HDR Ir-192 dosimetry calculations.

  15. Change in cholesterol absorption and synthesis markers in patients with coronary heart disease after combination therapy with simvastatin plus ezetimibe

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tao; WU Wen-feng; LIU Yang; WANG Qi-hui; WANG Lü-ya; MI Shu-hua

    2013-01-01

    Background Statins and ezetimibe have been reported to change the balance of cholesterol metabolism,but few studies have been performed on Chinese patients.The aim of this study was to evaluate changes in cholesterol metabolism markers in patients with coronary heart disease.Methods Forty-five patients with coronary heart disease were treated with 20 mg/d of simvastatin for four weeks.Subjects were then divided into two different therapy groups according to whether they reached the target values for total cholesterol and low density lipoprotein cholesterol level.Patients who reached the target values remained on simvastatin and those who did not reach the target values took a combination of simvastatin plus 10 mg/d ezetimibe until the 12th week.The concentrations of cholesterol synthesis markers (lathosterol and desmosterol) and absorption markers (campesterol and sitosterol) were measured on the 1st,4th,and 12th week of the study by gas chromatography.Results After treatment with simvastatin for four weeks,the levels of total cholesterol and low density lipoprotein cholesterol decreased significantly compared to levels measured during the 1st week (P <0.05).On the 12th week the levels of total cholesterol and low density lipoprotein cholesterol had decreased significantly (P <0.001) compared to levels during the 4th week.By the 12th week the levels of campesterol and sitosterol in the combination group had decreased significantly (P<0.05) compared with levels measured during the 4th week.Conclusions Coronary heart disease patients with high cholesterol synthesis at baseline might gain a greater benefit from simvastatin treatment.Combination therapy with simvastatin plus ezetimibe in patients with low cholesterol synthesis at baseline might increase the success rate of lipid-lowering through decreasing the absorption of cholesterol.

  16. Effect of simvastatin on MMPs and TIMPs in cigarette smoke-induced rat COPD model

    Science.gov (United States)

    Sun, Jiawei; Bao, Jie; Shi, Yanan; Zhang, Bin; Yuan, Lindong; Li, Junhong; Zhang, Lihai; Sun, Mo; Zhang, Ling; Sun, Wuzhuang

    2017-01-01

    Background Proteases may play an important role in the development of chronic obstructive pulmonary disease and emphysema in response to cigarette smoke exposure (CSE). The current study was designed to investigate the expression of matrix metalloproteinase (MMP)-8, MMP-9, MMP-12, tissue inhibitor of MMP (TIMP)-1, and TIMP-4 in rat lung tissues in response to CSE, and assessed the effect of simvastatin in regulating expression of MMPs and TIMPs. Methods Thirty normal Sprague Dawley (SD) rats were divided into control (n=10), CSE (n=10), and CSE plus simvastatin (n=10) groups. Animals were whole-body exposed to the cigarette smoke in the box for 1 hour each time, twice a day, 5 days a week for 16 weeks. Animals of CSE + simvastatin group were intra-gastrically administered simvastatin at a dose of 5 mg/kg/day followed by CSE. Bronchoalveolar lavage fluid was harvested for inflammatory cell count and lung tissues were stained for morphologic examination. Expression of mRNA and protein level of MMP-8, MMP-9, MMP-12, TIMP-1, and TIMP-4 was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry, respectively. Results CSE resulted in a significant increase of mean linear intercept (MLI: 34.6±2.0 μm) and bronchial wall thickness and diameter (BWT/D, 0.250±0.062) compared to control (MLI: 24.0±1.7 μm, BWT/D: 0.160±0.034, P0.01). Simvastatin slightly but not significantly prevented alteration of MLI, BWT/D, and mean alveolar number (MLI: 33.4±1.4 μm; BWT/D: 0.220±0.052; mean alveolar number: 15.5±2.5 N/μm2, P>0.05). Total white blood cell was significantly increased in the bronchoalveolar lavage fluid of smoking group (3.3±2.5×109 cells/L vs 1.1±1.3×109 cells/L of control, P0.05). In response to CSE, MMP-8, MMP-9, and MMP-12 mRNA were upregulated more than sevenfold, while TIMP-1 and TIMP-4 increased two- to fivefold. Simvastatin significantly blocked upregulation of MMP-8 and -9 (P0.05). In addition, simvastatin

  17. Effect of simvastatin on MMPs and TIMPs in cigarette smoke-induced rat COPD model.

    Science.gov (United States)

    Sun, Jiawei; Bao, Jie; Shi, Yanan; Zhang, Bin; Yuan, Lindong; Li, Junhong; Zhang, Lihai; Sun, Mo; Zhang, Ling; Sun, Wuzhuang

    2017-01-01

    Proteases may play an important role in the development of chronic obstructive pulmonary disease and emphysema in response to cigarette smoke exposure (CSE). The current study was designed to investigate the expression of matrix metalloproteinase (MMP)-8, MMP-9, MMP-12, tissue inhibitor of MMP (TIMP)-1, and TIMP-4 in rat lung tissues in response to CSE, and assessed the effect of simvastatin in regulating expression of MMPs and TIMPs. Thirty normal Sprague Dawley (SD) rats were divided into control (n=10), CSE (n=10), and CSE plus simvastatin (n=10) groups. Animals were whole-body exposed to the cigarette smoke in the box for 1 hour each time, twice a day, 5 days a week for 16 weeks. Animals of CSE + simvastatin group were intra-gastrically administered simvastatin at a dose of 5 mg/kg/day followed by CSE. Bronchoalveolar lavage fluid was harvested for inflammatory cell count and lung tissues were stained for morphologic examination. Expression of mRNA and protein level of MMP-8, MMP-9, MMP-12, TIMP-1, and TIMP-4 was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry, respectively. CSE resulted in a significant increase of mean linear intercept (MLI: 34.6±2.0 μm) and bronchial wall thickness and diameter (BWT/D, 0.250±0.062) compared to control (MLI: 24.0±1.7 μm, BWT/D: 0.160±0.034, P0.01). Simvastatin slightly but not significantly prevented alteration of MLI, BWT/D, and mean alveolar number (MLI: 33.4±1.4 μm; BWT/D: 0.220±0.052; mean alveolar number: 15.5±2.5 N/μm(2), P>0.05). Total white blood cell was significantly increased in the bronchoalveolar lavage fluid of smoking group (3.3±2.5×10(9) cells/L vs 1.1±1.3×10(9) cells/L of control, P0.05). In response to CSE, MMP-8, MMP-9, and MMP-12 mRNA were upregulated more than sevenfold, while TIMP-1 and TIMP-4 increased two- to fivefold. Simvastatin significantly blocked upregulation of MMP-8 and -9 (P0.05). In addition, simvastatin significantly blocked

  18. Calcium carbonate as a possible dosimeter for high irradiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Negron M, A.; Ramos B, S.; Camargo R, C. [UNAM, Instituto de Ciencias Nucleares, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Uribe, R. M. [Kent State University, College of Technology, Kent OH (United States); Gomez V, V. [UNAM, Instituto de Quimica, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Kobayashi, K., E-mail: negron@nucleares.unam.mx [Yokohama National University (Japan)

    2014-08-15

    The aim of this work is to analyze the interactions of 5 MeV electron beam radiation and a 290 MeV/u Carbon beam with calcium carbonate (powder) at 298 K and at different irradiation doses, for the potential use of calcium carbonate as a high-dose dosimeter. The irradiation doses with the electron beam were from 0.015 to 9 MGy, and with Carbon beam from 1.5 kGy to 8 kGy. High-energy radiation induces the formation of free radicals in solid calcium carbonate that can be detected and measured by electron paramagnetic resonance (EPR). An increase of the EPR response for some of the free radicals produced in the sample was observed as a function of the irradiation dose. The response of one of the radicals decreased with the dose. These measurements are reproducible; the preparation of the sample is simple and inexpensive; and the signal is stable for several months. The response curves show that the dosimeter tends to saturate at 10 MGy. Based on these properties, we propose this chemical compound as a high-dose dosimeter, mainly for electron irradiation. (author)

  19. Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament

    Directory of Open Access Journals (Sweden)

    Zhang P

    2016-01-01

    Full Text Available Peng Zhang,1,* Fei Han,2,* Yunxia Li,1 Jiwu Chen,1 Tianwu Chen,1 Yunlong Zhi,1 Jia Jiang,1 Chao Lin,2 Shiyi Chen,1 Peng Zhao2 1Department of Sports Medicine, Huashan Hospital, Fudan University, 2Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, School of Medicine, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The Ligament Advanced Reinforcement System has recently been widely used as the primary graft of choice in anterior cruciate ligament (ACL reconstruction. But the biological graft–bone healing still remains a problem. Previous studies have shown that simvastatin (SIM stimulates bone formation. The objective of this study was to investigate whether surface coating with collagen containing low-dose SIM microsphere could enhance the surface biocompatibility of polyethylene terephthalate (PET artificial ligaments to accelerate graft-to-bone healing. The in vitro studies demonstrated that bone marrow stromal cells on the collagen-coated PET scaffolds (COL/PET and simvastatin/collagen-coated PET scaffolds (SIM/COL/PET proliferated vigorously. Compared with the PET group and the COL/PET group, SIM could induce bone marrow stromal cells’ osteoblastic differentiation, high alkaline phosphatase activity, more mineralization deposition, and more expression of osteoblast-related genes, such as osteocalcin, runt-related transcription factor 2, bone morphogenetic protein-2, and vascular endothelial growth factor, in the SIM/COL/PET group. In vivo, rabbits received ACL reconstruction with different scaffolds. Histological analysis demonstrated that graft–bone healing was significantly greater with angiogenesis and osteogenesis in the SIM/COL/PET group than the other groups. In addition, biomechanical testing at the eighth week demonstrated a significant increase in the ultimate failure load and stiffness in the SIM/COL/PET group. The low dose of SIM

  20. Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament.

    Science.gov (United States)

    Zhang, Peng; Han, Fei; Li, Yunxia; Chen, Jiwu; Chen, Tianwu; Zhi, Yunlong; Jiang, Jia; Lin, Chao; Chen, Shiyi; Zhao, Peng

    2016-01-01

    The Ligament Advanced Reinforcement System has recently been widely used as the primary graft of choice in anterior cruciate ligament (ACL) reconstruction. But the biological graft-bone healing still remains a problem. Previous studies have shown that simvastatin (SIM) stimulates bone formation. The objective of this study was to investigate whether surface coating with collagen containing low-dose SIM microsphere could enhance the surface biocompatibility of polyethylene terephthalate (PET) artificial ligaments to accelerate graft-to-bone healing. The in vitro studies demonstrated that bone marrow stromal cells on the collagen-coated PET scaffolds (COL/PET) and simvastatin/collagen-coated PET scaffolds (SIM/COL/PET) proliferated vigorously. Compared with the PET group and the COL/PET group, SIM could induce bone marrow stromal cells' osteoblastic differentiation, high alkaline phosphatase activity, more mineralization deposition, and more expression of osteoblast-related genes, such as osteocalcin, runt-related transcription factor 2, bone morphogenetic protein-2, and vascular endothelial growth factor, in the SIM/COL/PET group. In vivo, rabbits received ACL reconstruction with different scaffolds. Histological analysis demonstrated that graft-bone healing was significantly greater with angiogenesis and osteogenesis in the SIM/COL/PET group than the other groups. In addition, biomechanical testing at the eighth week demonstrated a significant increase in the ultimate failure load and stiffness in the SIM/COL/PET group. The low dose of SIM-sustained release from SIM/COL/PET promoted the graft-bone healing via its effect on both angiogenesis and osteogenesis. This study suggested that collagen containing low-dose SIM microsphere coating on the surface of PET artificial ligaments could be potentially applied for ACL reconstruction.

  1. Does simvastatin stimulate bone formation in vivo?

    Directory of Open Access Journals (Sweden)

    Chorev Michael

    2003-04-01

    Full Text Available Abstract Background Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS to the known anabolic effects of PTH in an established model of ovariectomized (OVX Swiss-Webster mice. Methods Mice were ovariectomized at 12 weeks of age (T0, remained untreated for 5 weeks to allow development of osteopenia (T5, followed by treatment for 8 weeks (T13. Whole, trabecular and cortical femoral bone was analyzed by micro-computed tomography (micro CT. Liquid chromatography/mass spectrometry (LC/MS was used to detect the presence of SVS and its active metabolite, simvastatin β-hydroxy acid (SVS-OH in the mouse serum. Results Trabecular BV/TV at T13 was 4.2 fold higher in animals treated with PTH (80 micro-g/kg/day compared to the OVX-vehicle treated group (p in vivo study. Conclusions While PTH demonstrated the expected anabolic effect on bone, SVS failed to stimulate bone formation, despite our verification by LC/MS of the active SVS-OH metabolite in mouse serum. While statins have clear effects on bone formation in vitro, the formulation of existing 'liver-targeted' statins requires further refinement for efficacy in vivo.

  2. Paradoxical Negative HDL Cholesterol Response to Atorvastatin and Simvastatin Treatment in Chinese Type 2 Diabetic Patients

    OpenAIRE

    Chang, Yu-Hung; Lin, Kun-Cheng; Chang, Dao-Ming; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

    2013-01-01

    OBJECTIVES: There is extensive but controversial evidence on the diverse effects of statins on the level of high-density lipoprotein cholesterol (HDL-C). Some of these effects may limit the benefits of statins in terms of cardiovascular risk reduction. To identify the conditions for beneficial effects, this study investigated the response to atorvastatin and simvastatin treatment in type 2 diabetic patients with elevated low-density lipoprotein cholesterol (LDL-C). METHODS: 2,872 subjects wit...

  3. [Effect of simvastatin plus inulin in comparison with simvastatin plus ezetimibe on the treatment of mixed dyslipidemia].

    Science.gov (United States)

    Martínez-Abundis, Esperanza; Barrera-Durán, Carmelita; González-Ortiz, Manuel; Hernández-Salazar, Eduardo

    2016-10-01

    Mixed dyslipidemia accelerates atherosclerosis and leads to cardiovascular disease and death. Non-soluble fibers such as inulin have been shown to have an effect on dyslipidemia. To assess the effect of the combination of simvastatin plus inulin in comparison with simvastatin plus ezetimibe in mixed dyslipidemia. A randomized, double-blind, clinical trial with parallel control group was performed in 60 patients with mixed dyslipidemia, without drug treatment or failure to statins and lifestyle changes. simvastatin (20 mg), inulin from agave (7 g) and placebo of ezetimibe, or simvastatin (20 mg), ezetimibe (10 mg) and placebo of inulin from agave, daily at night, for 12 weeks. Both groups decreased total cholesterol (235 ± 29 vs. 182 ± 42 mg/dl; p = 0.001 and 236 ± 31 vs. 160 ± 48 mg/dl; p inulin and simvastatin plus ezetimibe. The combination of simvastatin plus inulin reduced total cholesterol, low-density lipoprotein cholesterol, and triglycerides the same as simvastatin plus ezetimibe.

  4. Spectroscopic gamma camera for use in high dose environments

    Science.gov (United States)

    Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Kometani, Yutaka; Suzuki, Yasuhiko; Umegaki, Kikuo

    2016-06-01

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  5. Spectroscopic gamma camera for use in high dose environments

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Yuichiro, E-mail: yuichiro.ueno.bv@hitachi.com [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Fujishima, Yasutake; Kometani, Yutaka [Hitachi Works, Hitachi-GE Nuclear Energy, Ltd., Hitachi-shi, Ibaraki-ken (Japan); Suzuki, Yasuhiko [Measuring Systems Engineering Dept., Hitachi Aloka Medical, Ltd., Ome-shi, Tokyo (Japan); Umegaki, Kikuo [Faculty of Engineering, Hokkaido University, Sapporo-shi, Hokkaido (Japan)

    2016-06-21

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  6. Simvastatin enhances Rho/actin/cell rigidity pathway contributing to mesenchymal stem cells’ osteogenic differentiation

    Directory of Open Access Journals (Sweden)

    Tai IC

    2015-09-01

    Full Text Available I-Chun Tai,1–3 Yao-Hsien Wang,3 Chung-Hwan Chen,3,4 Shu-Chun Chuang,3 Je-Ken Chang,3–5 Mei-Ling Ho1–3,6 1Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 5Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 6Department of Marine Biotechnology and Resources, National Sun Yat-sen UniVersity, Kaohsiung, Taiwan Abstract: Recent studies have indicated that statins induce osteogenic differentiation both in vitro and in vivo. The molecular mechanism of statin-stimulated osteogenesis is unknown. Activation of RhoA signaling increases cytoskeletal tension, which plays a crucial role in the osteogenic differentiation of mesenchymal stem cells. We thus hypothesized that RhoA signaling is involved in simvastatin-induced osteogenesis in bone marrow mesenchymal stem cells. We found that although treatment with simvastatin shifts localization of RhoA protein from the membrane to the cytosol, the treatment still activates RhoA dose-dependently because it reduces the association with RhoGDIα. Simvastatin also increased the expression of osteogenic proteins, density of actin filament, the number of focal adhesions, and cellular tension. Furthermore, disrupting actin cytoskeleton or decreasing cell rigidity by using chemical agents reduced simvastatin-induced osteogenic differentiation. In vivo study also confirms that density of actin filament is increased in simvastatin-induced ectopic bone formation. Our study is the first to demonstrate that maintaining intact actin cytoskeletons and enhancing cell rigidity are crucial in simvastatin-induced osteogenesis. The results suggested that simvastatin, which is an

  7. Limitations of the TG-43 formalism for skin high-dose-rate brachytherapy dose calculations

    Energy Technology Data Exchange (ETDEWEB)

    Granero, Domingo, E-mail: dgranero@eresa.com [Department of Radiation Physics, ERESA, Hospital General Universitario, 46014 Valencia (Spain); Perez-Calatayud, Jose [Radiotherapy Department, La Fe University and Polytechnic Hospital, Valencia 46026 (Spain); Vijande, Javier [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100, Spain and IFIC (UV-CSIC), Paterna 46980 (Spain); Ballester, Facundo [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States)

    2014-02-15

    Purpose: In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Methods: Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR{sup 60}Co and {sup 192}Ir sources and a hypothetical {sup 169}Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. Results: For a 5 cm × 5 cm{sup 192}Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about −3%. When the source was positioned at the skin surface, dose differences were smaller than −1% for {sup 60}Co and {sup 192}Ir, yet −3% for {sup 169}Yb. For the interstitial implant, dose differences at the skin surface were −7% for {sup 60}Co, −0.6% for {sup 192}Ir, and −2.5% for {sup 169}Yb. Conclusions: This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either {sup 60}Co and {sup 192}Ir. For

  8. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Directory of Open Access Journals (Sweden)

    Daniel G Zhang

    Full Text Available MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF and conventional flattened 6MV photon beams were used. High dose rate (HDR brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL would be needed.

  9. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Science.gov (United States)

    Zhang, Daniel G; Feygelman, Vladimir; Moros, Eduardo G; Latifi, Kujtim; Zhang, Geoffrey G

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

  10. Two smart spectrophotometric methods for the simultaneous estimation of Simvastatin and Ezetimibe in combined dosage form

    Science.gov (United States)

    Magdy, Nancy; Ayad, Miriam F.

    2015-02-01

    Two simple, accurate, precise, sensitive and economic spectrophotometric methods were developed for the simultaneous determination of Simvastatin and Ezetimibe in fixed dose combination products without prior separation. The first method depends on a new chemometrics-assisted ratio spectra derivative method using moving window polynomial least square fitting method (Savitzky-Golay filters). The second method is based on a simple modification for the ratio subtraction method. The suggested methods were validated according to USP guidelines and can be applied for routine quality control testing.

  11. Remote Afterloading High Dose Rate Brachytherapy AMC EXPERIANCES

    Energy Technology Data Exchange (ETDEWEB)

    Park, Su Gyong; Chang, Hye Sook; Choi, Eun Kyong; Yi, Byong Yong [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1992-12-15

    Remote afterloading high dose rate brachytherapy(HDRB) is a new technology and needs new biological principle for time and dose schedule. Here, authors attempt to evaluate the technique and clinical outcome in 116 patients, 590 procedures performed at Asan Medical Center for 3 years. From Sep. 1985 to Aug 1992, 471 procedures of intracavitary radiation in 55 patients of cervical cancer and 26 of nasopharyngeal cancer, 79 intraluminal radiation in 12 of esophageal cancer, 11 of endobronchial cancer and 1 Klatskin tumor and 40 interstitial brachytherapy in 4 of breast cancer, 1 sarcoma and 1 urethral cancer were performed. Median follow-up was 7 months with range 1-31 months. All procedures except interstitial were performed under the local anesthesia and they were all well tolerated and completed the planned therapy except 6 patients. 53/58 patients with cervical cancer and 22/26 patients with nasopharynx cancer achieved CR. Among 15 patients with palliative therapy, 80% achieves palliation. We will describe the details of the technique and results in the text. To evaluate biologic effects of HDRB and optimal time/dose/fractionation schedule, we need longer follow-up. But authors feel that HDRB with proper fractionation schedule may yield superior results compared to the low dose rate brachytherapy considering the advantages of HDRB in safety factor for operator, better control of radiation dose and volume and patients comfort over the low dose brachytherapy.

  12. Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

    Directory of Open Access Journals (Sweden)

    Y. Sobita Devi

    2011-12-01

    Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

  13. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jee Suk [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Wang, Michael L.C. [Department of Radiation Oncology, National Cancer Centre (Singapore); Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: jsseong@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  14. Synergistic effects of telmisartan and simvastatin on endothelial progenitor cells

    OpenAIRE

    Steinmetz, Martin; Brouwers, Caroline; Nickenig, Georg; Wassmann, Sven

    2009-01-01

    Abstract Circulating endothelial progenitor cells (EPC) contribute to endothelial replenishment. Telmisartan is an angiotensin-receptor blocker with PPARγ-agonistic properties. PPARγ-agonists and HMG-CoA reductase inhibitors have been shown to enhance EPC number and function. We focused on the effects of telmisartan alone or in combination with simvastatin on EPC. EPC were isolated from healthy human volunteers, cultured and stimulated with telmisartan, simvastatin, or the combination of telm...

  15. Simvastatin-induced nocturnal leg pain disappears with pravastatin substitution

    Directory of Open Access Journals (Sweden)

    Stojaković Nataša

    2013-01-01

    Full Text Available Introduction. Statins have similar side effects that do not always occur at the same rate among the various statins. We present a case of simvastatin-induced muscle toxicity that disappeared when pravastatin was substituted for the original drug. Case Outline. A 74-year-old male, a nonsmoker, complained of severe nocturnal leg cramps. The patient also complained that similar painful cramping occurred when he walked rapidly or jogged. Because some components of his lipid panel exceeded the ‘desirable’ range, and as he had a history of myocardial infarction, his family physician prescribed simvastatin (40 mg/day. The patient had taken this medication for the past eight years. The painful nocturnal episodes started two years ago and affected either one or the other leg. Four months ago we discontinued his simvastatin and prescribed pravastatin (80 mg/day. At a follow-up visit six weeks later, the patient reported that his leg pains at night and the pain experienced after brisk walking had disappeared. Four months after the substitution of pravastatin for simvastatin, the patient reported that his complete lack of symptoms had continued. Conclusion. These painful muscle cramps were probably caused by an inadequate vascular supply to the calf and foot muscles. Perhaps a combination of advanced age and atherosclerotic changes created a predisposition for the simvastatin-induced leg cramps. Pravastatin differs from simvastatin in several ways. It is not metabolized by cytochrome P450 (CYP 3A4 oxidases, and thus is not influenced by CYP 3A4 inhibitors like simvastatin. Also, simvastatin is associated with single-nucleotide polymorphisms located within the SLCO1B1 gene on the chromosome 12 and established myopathy, while pravastatin lacks this association. These differences may contribute to increased tolerance to pravastatin in this particular case.

  16. The influence of high doses of radiation in citrine stones

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, M. I. [Universidade Nove de Julho - UNINOVE, Rua Vergueiro 235/249, 01504-001 Sao Paulo (Brazil); Caldas, L. V. E., E-mail: miteixeira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ({sup 60}Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO{sub 2}), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  17. Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

    Directory of Open Access Journals (Sweden)

    Aline Correa de Carvalho

    2013-01-01

    Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

  18. High-dose acetylcysteine in idiopathic pulmonary fibrosis.

    NARCIS (Netherlands)

    Demedts, M.; Behr, J.; Buhl, R.; Costabel, U.; Dekhuijzen, P.N.R.; Jansen, H.M.L.; MacNee, W.; Thomeer, M.; Wallaert, B.; Laurent, F.; Nicholson, A.G.; Verbeken, E.K.; Verschakelen, J.; Flower, C.D.; Capron, F.; Petruzzelli, S.; Vuyst, P. De; Bosch, J.M. van den; Rodriguez-Becerra, E.; Corvasce, G.; Lankhorst, I.L.M.; Sardina, M.; Montanari, M.

    2005-01-01

    BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) add

  19. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    Hoogendijk, JE; Wokke, JHJ; de Visser, M

    2000-01-01

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Sis patients responded. Side effects w

  20. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth Carl)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  1. High dose corticosteroids in severe leptospirosis: a systematic review.

    Science.gov (United States)

    Rodrigo, Chaturaka; Lakshitha de Silva, Nipun; Goonaratne, Ravindi; Samarasekara, Keshinie; Wijesinghe, Indika; Parththipan, B; Rajapakse, Senaka

    2014-12-01

    The role of corticosteroids in the treatment of severe leptospirosis is unclear. The rationale for their use is that, in severe leptospirosis, there is a severe immunological response that is harmful to the host resulting in multi-organ dysfunction, which is potentially offset by the nonspecific immunosuppression of high dose steroids. We conducted a systematic review of studies that have assessed the use of high dose corticosteroids in patients with severe leptospirosis by searching MEDLINE and Scopus SciVerse without any language or time restrictions. We identified five studies, including one open randomized clinical trial, which had assessed the use of high dose steroids in severe leptospirosis. Four studies demonstrated a benefit of corticosteroids in treating severe disease with pulmonary involvement when administered early in the course of the disease, but these studies had several methodological constraints as highlighted in the text. Only the randomized controlled trial study showed that corticosteroids are ineffective and may increase the risk of nosocomial infections. There is no robust evidence to suggest that high dose corticosteroids are effective in severe leptospirosis, and a well-designed randomized clinical trial is needed to resolve this.

  2. High-dose acetylcysteine in idiopathic pulmonary fibrosis.

    NARCIS (Netherlands)

    Demedts, M.; Behr, J.; Buhl, R.; Costabel, U.; Dekhuijzen, P.N.R.; Jansen, H.M.L.; MacNee, W.; Thomeer, M.; Wallaert, B.; Laurent, F.; Nicholson, A.G.; Verbeken, E.K.; Verschakelen, J.; Flower, C.D.; Capron, F.; Petruzzelli, S.; Vuyst, P. De; Bosch, J.M. van den; Rodriguez-Becerra, E.; Corvasce, G.; Lankhorst, I.L.M.; Sardina, M.; Montanari, M.

    2005-01-01

    BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) add

  3. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth Carl)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  4. High-dose acetylcysteine in idiopathic pulmonary fibrosis.

    NARCIS (Netherlands)

    Demedts, M.; Behr, J.; Buhl, R.; Costabel, U.; Dekhuijzen, P.N.R.; Jansen, H.M.L.; MacNee, W.; Thomeer, M.; Wallaert, B.; Laurent, F.; Nicholson, A.G.; Verbeken, E.K.; Verschakelen, J.; Flower, C.D.; Capron, F.; Petruzzelli, S.; Vuyst, P. De; Bosch, J.M. van den; Rodriguez-Becerra, E.; Corvasce, G.; Lankhorst, I.L.M.; Sardina, M.; Montanari, M.

    2005-01-01

    BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily)

  5. Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Hideya [Toyonaka Municipal Hospital, Osaka (Japan); Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Inoue, Toshihiko [Osaka Univ., Suita (Japan). Graduate School of Medicine; Furukawa, Souhei; Kakimoto, Naoya [Osaka Univ., Suita (Japan). Graduate School of Dentistry

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

  6. Brachytherapy for early oral tongue cancer: low dose rate to high dose rate.

    Science.gov (United States)

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Furukawa, Souhei; Kakimoto, Naoya; Shimizutani, Kimishige; Inoue, Toshihiko

    2003-03-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n = 341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer.

  7. Impairment of memorization by high doses of pyridoxine in man.

    Science.gov (United States)

    Molimard, R; Marillaud, A; Paille, A; Le Devehat, C; Lemoine, A; Dougny, M

    1980-05-01

    Two controlled trials were performed successively to evaluate the effect of high doses of oral pyridoxine on brain performance in man. In trial I, medical students volunteered to take 100 mg, 500 mg of pyridoxine a day or placebo for 10 days. A digit coding test was performed before, and at the end of the treatment period and a third 15 days later. The improvement of performance from the first to the third test (learning effect) was significantly better in the placebo group than in the B6 treated groups. This could be attributed to memorization of skills. Trial II was performed in obese patients starting a low calorie diet in whom vitamins are routinely prescribed. Performance in a work recognition test and in a visual retention test was lower for the group receiving 1 g of pyridoxine a day. Thus, high doses of oral pyridoxine are likely to impair memorization in man. Disturbances of neuro-transmitter metabolism such as increase of GABA production might explain the effect. As the benefit of high doses of pyridoxine has not been well-documented and as the study has suggested that undesired effects may indeed exist, the widespread use of such doses is questionable.

  8. Hardening electronic devices against very high total dose radiation environments

    Science.gov (United States)

    Buchanan, B.; Shedd, W.; Roosild, S.; Dolan, R.

    1972-01-01

    The possibilities and limitations of hardening silicon semiconductor devices to the high neutron and gamma radiation levels and greater than 10 to the eighth power rads required for the NERVA nuclear engine development are discussed. A comparison is made of the high dose neutron and gamma hardening potential of bipolar, metal insulator semiconductors and junction field effect transistors. Experimental data is presented on device degradation for the high neutron and gamma doses. Previous data and comparisons indicate that the JFET is much more immune to the combined neutron displacement and gamma ionizing effects than other transistor types. Experimental evidence is also presented which indicates that p channel MOS devices may be able to meet the requirements.

  9. High-dose desvenlafaxine in outpatients with major depressive disorder.

    Science.gov (United States)

    Ferguson, James M; Tourian, Karen A; Rosas, Gregory R

    2012-09-01

    This study investigated the safety and efficacy of long-term treatment with high-dose desvenlafaxine (administered as desvenlafaxine succinate) in major depressive disorder (MDD). In this multicenter, open-label study, adult outpatients with MDD aged 18-75 were treated with flexible doses of desvenlafaxine (200-400 mg/d) for ≤ 1 year. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs), patient discontinuations due to adverse events, electrocardiograms, vital signs, and laboratory determinations. The primary efficacy measure was mean change from baseline in the 17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score. The mean daily desvenlafaxine dose range over the duration of the trial was 267-356 mg (after titration). The most frequent TEAEs in the safety population (n = 104) were nausea (52%) and headache (41%), dizziness (31%), insomnia (29%), and dry mouth (27%). All TEAEs were mild or moderate in severity. Thirty-four (33%) patients discontinued from the study because of TEAEs; nausea (12%) and dizziness (9%) were the most frequently cited reasons. The mean change in HAM-D(17) total score for the intent-to-treat population (n = 99) was -9.9 at the last on-therapy visit in the last-observation-carried-forward analysis and -14.0 at month 12 in the observed cases analysis. Conclusion High-dose desvenlafaxine (200-400 mg/d) was generally safe and effective in the long-term treatment of MDD.

  10. Effect of Randomized Lipid Lowering With Simvastatin and Ezetimibe on Cataract Development (from the Simvastatin and Ezetimibe in Aortic Stenosis Study)

    DEFF Research Database (Denmark)

    Bang, Casper N; Greve, Anders M; Dornonville de la Cour, Morten

    2015-01-01

    multivariate analysis adjusted for age, gender, prednisolone treatment, smoking, baseline LDL cholesterol and high sensitivity C-reactive protein; simvastatin plus ezetimibe versus placebo was associated with 44% lower risk of cataract development (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p = 0.......034). In a parallel analysis substituting time-varying LDL-cholesterol with randomized treatment, lower intreatment LDL-cholesterol was in itself associated with lower risk of incident cataract (hazard ratio 0.78 per 1 mmol/ml lower total cholesterol, 95% confidence interval 0.64 to 0.93, p = 0.008). In conclusion...

  11. Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?

    Directory of Open Access Journals (Sweden)

    C. Bulcão

    Full Text Available In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m² and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20 or metformin, 1.7 g/day (N = 21 for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 ± 0.04 mg/dL (P = 0.002 over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.

  12. High-dose secondary calibration laboratory accreditation program

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, J.C. [National Institute of Standards and Technology, Gaithersburg, MD (United States)

    1993-12-31

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

  13. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma.

    Science.gov (United States)

    Anderson, Peter M; Wiseman, Gregory A; Erlandson, Linda; Rodriguez, Vilmarie; Trotz, Barbara; Dubansky, Stephen A; Albritton, Karen

    2005-10-01

    Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of 1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

  14. Methodology of high dose research in medical radiodiagnostic; Metodologia de investigacao de doses elevadas em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana E.; Martins, Cintia P. de S., E-mail: ird@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-11-01

    This work has as main purpose to study occupational exposure in diagnostic radiology in medical cases of high doses recorded in 2011 at the national level . These doses were recorded by monitoring individual of the occupationally exposed individuals (OEI's). This monitoring of the doses received by ionizing radiation has as main objective to ensure that the principle of dose limitation is respected. In this study it were evaluated doses of 372 OEI's radiology in different Brazilian states. Doses were extracted from the database of Sector Management Doses of the Institute for Radioprotection and Dosimetry - IRD/CNEN-RJ, Brazil. The information from the database provide reports of doses from several states, which allows to quantify statistically, showing those with the highest doses in four areas: dose greater than or equal to 20 mSv apron and chest and dose greater than or equal to 100 mSv apron and chest. The identification of these states allows the respective Sanitary Surveillance (VISA), be aware of the events and make plans to reduce them. This study clarified the required procedures when there is a record of high dose emphasizing the importance of using protective radiological equipment, dosimeter and provide a safety environment work by maintaining work equipment. Proposes the ongoing training of professionals, emphasizing the relevance of the concepts of radiation protection and the use of the questionnaire with their investigative systematic sequence, which will allow quickly and efficiently the success the investigations.

  15. Image-guided high dose rate endorectal brachytherapy.

    Science.gov (United States)

    Devic, Slobodan; Vuong, Té; Moftah, Belal; Evans, Michael; Podgorsak, Ervin B; Poon, Emily; Verhaegen, Frank

    2007-11-01

    Fractionated high dose rate endorectal brachytherapy (HDR-EBT) using CT-based treatment planning is an alternative method for preoperative down-sizing and down-staging of advanced rectal adeno-carcinomas. The authors present an image guidance procedure that was developed to ensure daily dose reproducibility for the four brachytherapy treatment fractions. Since the applicator might not be placed before each treatment fraction inside the rectal lumen in the same manner as it was placed during the 3D CT volume acquisition used for treatment planning, there is a shift along the catheter axis that may have to be performed. The required shift is determined by comparison of a daily radiograph with the treatment planning digitally-reconstructed radiograph (DRR). A procedure is developed for DRR reconstruction from the 3D data set used for the treatment planning, and two possible daily longitudinal shifts are illustrated: above and below the planning dose distribution. The authors also describe the procedure for rotational alignment illustrated on a clinical case. Reproduction of the treatment planned dose distribution on a daily basis is crucial for the success of fractionated 3D based brachytherapy treatments. Due to the cylindrical symmetry of the applicator used for preoperative HDR-EBT, two types of adjustments are necessary: applicator rotation and dwell position shift along the applicator's longitudinal axis. The impact of the longitudinal applicator shift prior to treatment delivery for 62 patients treated in our institution is also assessed.

  16. High-dose insulin and intravenous lipid emulsion therapy for cardiogenic shock induced by intentional calcium-channel blocker and Beta-blocker overdose: a case series.

    Science.gov (United States)

    Doepker, Bruce; Healy, William; Cortez, Eric; Adkins, Eric J

    2014-04-01

    Recently, high-dose insulin (HDI) and intravenous lipid emulsion (ILE) have emerged as treatment options for severe toxicity from calcium-channel blocker (CCB) and beta blocker (BB). Our aim was to describe the use and effectiveness of HDI and ILE for the treatment of CCB and BB overdose. We describe 2 patients presenting to the emergency department after intentional ingestions of CCBs and BBs. A 35-year-old man presented in pulseless electrical activity after ingesting amlodopine, verapamil, and metoprolol. A 59-year-old man presented with cardiogenic shock (CS) after ingesting amlodopine, simvastatin, lisinopril, and metformin. Both patients were initially treated with glucagon, calcium, and vasopressors. Shortly after arrival, HDI (1 unit/kg × 1; 1 unit/kg/h infusion) and ILE 20% (1.5 mL/kg × 1; 0.25 mL/kg/min × 60 min) were initiated. This led to hemodynamic improvement and resolution of shock. At the time of hospital discharge, both patients had achieved full neurologic recovery. HDI effectively reverses CS induced by CCBs and BBs due to its inotropic effects, uptake of glucose into cardiac muscle, and peripheral vasodilatation. ILE is theorized to sequester agents dependent on lipid solubility from the plasma, preventing further toxicity. To our knowledge, these are the first two successful cases reported using the combination of HDI and ILE for reversing CS induced by intentional ingestions of CCBs and BBs. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. SU-E-T-315: The Change of Optically Stimulated Luminescent Dosimeters (OSLDs) Sensitivity by Accumulated Dose and High Dose

    Energy Technology Data Exchange (ETDEWEB)

    Han, S; Jung, H; Kim, M; Ji, Y; Kim, K [University of Science and Technology, Daejeon (Korea, Republic of); Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Choi, S; Park, S; Yoo, H [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yi, C [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of)

    2014-06-01

    Purpose: The objective of this study is to evaluate radiation sensitivity of optical stimulated luminance dosimeters (OSLDs) by accumulated dose and high dose. Methods: This study was carried out in Co-60 unit (Theratron 780, AECL, and Canada) and used InLight MicroStar reader (Landauer, Inc., Glenwood, IL) for reading. We annealed for 30 min using optical annealing system which contained fluorescent lamps (Osram lumilux, 24 W, 280 ∼780 nm). To evaluate change of OSLDs sensitivity by repeated irradiation, the dosimeters were repeatedly irradiated with 1 Gy. And whenever a repeated irradiation, we evaluated OSLDs sensitivity. To evaluate OSLDs sensitivity after accumulated dose with 5 Gy, We irradiated dose accumulatively (from 1 Gy to 5 Gy) without annealing. And OSLDs was also irradiated with 15, 20, 30 Gy to certify change of OSLDs sensitivity after high dose irradiation. After annealing them, they were irradiated with 1Gy, repeatedly. Results: The OSLDs sensitivity increased up to 3% during irradiating seven times and decreased continuously above 8 times. That dropped by about 0.35 Gy per an irradiation. Finally, after 30 times irradiation, OSLDs sensitivity decreased by about 7%. For accumulated dose from 1 Gy to 5 Gy, OSLDs sensitivity about 1 Gy increased until 4.4% after second times accumulated dose compared with before that. OSLDs sensitivity about 1 Gy decreased by 1.6% in five times irradiation. When OSLDs were irradiated ten times with 1Gy after irradiating high dose (10, 15, 20 Gy), OSLDs sensitivity decreased until 6%, 9%, 12% compared with it before high dose irradiation, respectively. Conclusion: This study certified OSLDs sensitivity by accumulated dose and high dose. When irradiated with 1Gy, repeatedly, OSLDs sensitivity decreased linearly and the reduction rate of OSLDs sensitivity after high dose irradiation had dependence on irradiated dose.

  18. Quality evaluation of simvastatin compounded capsules

    Directory of Open Access Journals (Sweden)

    Flávia Dias Marques-Marinho

    2011-09-01

    Full Text Available Simvastatin is commercially available as tablets and compounded capsules in Brazil. Very few reports regarding these capsules' quality, and consequently their efficacy, are available. The pharmaceutical quality of 30 batches of 20 mg simvastatin capsules from the market was evaluated by weight determination, content uniformity, disintegration (Brazilian Pharmacopeia, assay and dissolution test (USP32 tablet monograph. A HPLC method was developed for assay, content uniformity and dissolution test, and specifications were also established. Out of the 30 batches evaluated, 29 showed capsule disintegration within 45 min and individual weight variation was within ±10% or ±7.5% relative to average weight, for 300 mg, respectively. Only 27 batches met dissolution test criteria with values >80% of the labeled amount in 45 min; 21 batches showed simvastatin content between 90.0-110.0% of the labeled amount and 19 batches had at least 9 out of 10 capsules with content uniformity values between 85.0-115.0% of the labeled amount with RSDNo Brasil, a sinvastatina está comercialmente disponível na forma de comprimidos e cápsulas manipuladas. Poucos relatos estão disponíveis sobre a qualidade e, consequentemente, a eficácia dessas cápsulas. A qualidade de 30 lotes de sinvastatina 20 mg cápsulas do mercado foi avaliada através da determinação de peso, uniformidade de conteúdo, desintegração (Farmacopéia Brasileira, doseamento e teste de dissolução (monografia comprimidos USP32. Método por CLAE foi desenvolvido para o doseamento, uniformidade de conteúdo e teste de dissolução; além disso, especificações foram estabelecidas. Dos 30 lotes avaliados, 29 apresentaram desintegração da cápsula até 45 min e a variação do peso individual foi ± 10% ou ± 7,5% em relação ao peso médio, se 300 mg, respectivamente. Apenas 27 lotes preencheram os critérios do teste de dissolução com valores > 80% da quantidade rotulada, em 45 min, 21

  19. High-dose irradiation of food; Hochdosisbestrahlung von Lebensmitteln

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, J.F.

    1999-07-01

    Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [German] Die im Rahmen des Projekts erteilten Auftraege betrafen nur solche Lebensmittel, die im Dosisbereich < 10 kGy bestrahlt waren, da der Bereich hoeherer Dosen durch die amerikanischen Untersuchungen abgedeckt war. Als das Joint FAO/IAEA/WHO Expert Committee on Food Irradiation (JECFI) 1980 in Genf tagte, um ueber die gesundheitliche Bewertung bestrahlter Lebensmittel zu beraten, waren jedoch die in den Vereinigten Staaten laufenden, sehr umfangreichen Langzeitversuche mit strahlensterilisiertem Haehnchenfleisch (Dosis 58 kGy) noch nicht abgeschlossen. Das Komitee beschraenkte sich daher auf die Bewertung der vom Internationalen Projekt vorgelegten Ergebnisse. Die Schlussfolgerung 'the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required'beendete die jahrzehntelange Debatte ueber die gesundheitliche Unbedenklichkeit von im niedrigen (bis 1 kGy) und mittleren (1 bis 10 k

  20. EPR/Homotaurine: A possible dosimetry system for high doses

    Energy Technology Data Exchange (ETDEWEB)

    Maghraby, A., E-mail: maghrabism@yahoo.com [National Institute of Standards (NIS) - Radiation Dosimetry Department - Tersa st. 12211 Giza, P.O. Box 136 (Egypt); Salama, E. [Physics Department, Faculty of Science, Ain Shams University, 11566 Cairo (Egypt); Mansour, A. [National Center for Radiation Research and Technology, Atomic Energy Authority, Nasr City, Cairo (Egypt)

    2011-12-11

    An EPR investigation of radiation induced radicals in Homotaurine revealed that there are two types of radicals produced after exposure to gamma radiation ({sup 60}Co). EPR spectra were recorded and analyzed; also the microwave power saturation curves for both radicals were studied. The effect of change in modulation amplitude on peak-to-peak signal height and line width was investigated; this is in addition to the evaluation of energy dependence parameters compared to soft tissue and alanine dosimeters. Response of Homotaurine to different radiation doses (0.5 kGy-50 kGy) was studied and found to follow a linear relationship. Radiation induced radicals in Homotaurine persisted and showed a noticeable stability over 30 days following irradiation. It was found that Homotaurine possesses good dosimetric properties using EPR spectroscopy in high doses and is characterized by its simple spectrum.

  1. EPR/Homotaurine: A possible dosimetry system for high doses

    Science.gov (United States)

    Maghraby, A.; Salama, E.; Mansour, A.

    2011-12-01

    An EPR investigation of radiation induced radicals in Homotaurine revealed that there are two types of radicals produced after exposure to gamma radiation (60Co). EPR spectra were recorded and analyzed; also the microwave power saturation curves for both radicals were studied. The effect of change in modulation amplitude on peak-to-peak signal height and line width was investigated; this is in addition to the evaluation of energy dependence parameters compared to soft tissue and alanine dosimeters. Response of Homotaurine to different radiation doses (0.5 kGy-50 kGy) was studied and found to follow a linear relationship. Radiation induced radicals in Homotaurine persisted and showed a noticeable stability over 30 days following irradiation. It was found that Homotaurine possesses good dosimetric properties using EPR spectroscopy in high doses and is characterized by its simple spectrum.

  2. High doses of vitamin A impair iron absorption

    Directory of Open Access Journals (Sweden)

    Gabriel FR

    2012-10-01

    Full Text Available Fabíola Rainato Gabriel, Vivian MM Suen, Julio Sergio Marchini, José Eduardo Dutra de OliveiraDivision of Clinical Nutrition, Department of Internal Medicine, Ribeirão Preto School of Medicine, São Paulo University, São Paulo, BrazilObjective: The present study aimed to determine the influence of vitamin A on iron absorption when vitamin A and iron are administered together orally compared with the administration of iron alone.Methods: This was a randomized double-blind clinical trial conducted on healthy men with normal red blood cell indices. Five experiments were performed, with iron (10 mg; iron (10 mg plus vitamin A (450, 900 and 1800 µg, and placebo. After an 8-hour fast, basal (T0 blood samples were collected: basal (T0, 2 hours (T1, and 4 hours (T2 after the ingestion of the compounds to be studied. Iron was determined by inductively coupled plasma mass spectrometry. Serum ferritin was determined by an immunometric method, ie, by chemoluminescent enzyme immunoassay. Plasma retinol was measured by high-pressure liquid chromatography. Serum curves and the sum of the area under the curve adjusted to the mixed effects linear model were determined (P < 0.05.Results: Vitamin A at the doses of 450 and 900 µg had a stimulating effect, which, however, did not differ significantly from that of experiment 1 in which iron was used alone. At the dose of 1800 µg, vitamin A had a negative effect on iron absorption.Conclusion: High doses of vitamin A may cause lower serum iron levels, whereas a low dose favors iron absorption.Keywords: iron absorption, serum iron, vitamin A, oral iron, oral supplement

  3. Effect of simvastatin on MMPs and TIMPs in cigarette smoke-induced rat COPD model

    Directory of Open Access Journals (Sweden)

    Sun J

    2017-02-01

    Full Text Available Jiawei Sun,1,* Jie Bao,2,* Yanan Shi,3 Bin Zhang,4 Lindong Yuan,5 Junhong Li,1 Lihai Zhang,1 Mo Sun,6 Ling Zhang,2 Wuzhuang Sun1 1Department of Respiratory Medicine, First Hospital of Hebei Medical University, 2Department of Respiratory Medicine, Chest Hospital of Hebei Province, 3Maternal and Child Health Care Center of Hebei Province, 4Department of Emergency, First Hospital of Hebei Medical University, Shijiazhuang, 5Department of Respiratory Medicine, People’s Hospital of Liaocheng, Liaocheng, 6Hebei Medical University, Shijiazhuang, People’s Republic of China *These authors contributed equally to this work Background: Proteases may play an important role in the development of chronic obstructive pulmonary disease and emphysema in response to cigarette smoke exposure (CSE. The current study was designed to investigate the expression of matrix metalloproteinase (MMP-8, MMP-9, MMP-12, tissue inhibitor of MMP (TIMP-1, and TIMP-4 in rat lung tissues in response to CSE, and assessed the effect of simvastatin in regulating expression of MMPs and TIMPs.Methods: Thirty normal Sprague Dawley (SD rats were divided into control (n=10, CSE (n=10, and CSE plus simvastatin (n=10 groups. Animals were whole-body exposed to the cigarette smoke in the box for 1 hour each time, twice a day, 5 days a week for 16 weeks. Animals of CSE + simvastatin group were intra-gastrically administered simvastatin at a dose of 5 mg/kg/day followed by CSE. Bronchoalveolar lavage fluid was harvested for inflammatory cell count and lung tissues were stained for morphologic examination. Expression of mRNA and protein level of MMP-8, MMP-9, MMP-12, TIMP-1, and TIMP-4 was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry, respectively.Results: CSE resulted in a significant increase of mean linear intercept (MLI: 34.6±2.0 µm and bronchial wall thickness and diameter (BWT/D, 0.250±0.062 compared to control (MLI: 24.0±1.7 µm, BWT

  4. Study of teflon pads as high doses dosemeters; Estudo de pastilhas de teflon como dosimetros de doses altas

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Maria Ines; Caldas, Linda V.E., E-mail: miteixeira@ipen.br, E-mail: lcaldas@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-11-01

    The aim of this work is to study the Teflon, which is used as a binder in the manufacture of dosimetric tablets, for the feasibility of this material as high dose dosemeter. In this paper we used the technique of thermally stimulated luminescence (OSL) to characterize the dosimetric properties of Teflon. Teflon samples were exposed to different doses of radiation, using a source of gamma radiation ({sup 60}Co). It was obtained dose-response curve between 100 Gy to 50 kGy and reproducibility of OSL response. The preliminary results show that Teflon is a useful material to high dose dosimetry.

  5. High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was perfor...

  6. Identification of dose-reduction techniques for BWR and PWR repetitive high-dose jobs

    Energy Technology Data Exchange (ETDEWEB)

    Dionne, B.J.; Baum, J.W.

    1984-01-01

    As a result of concern about the apparent increase in collective radiation dose to workers at nuclear power plants, this project will provide information to industry in preplanning for radiation protection during maintenance operations. This study identifies Boiling Water Reactor (BWR) and Pressurized Water Reactor (PWR) repetitive jobs, and respective collective dose trends and dose reduction techniques. 3 references, 2 tables. (ACR)

  7. SU-F-P-19: Fetal Dose Estimate for a High-Dose Fluoroscopy Guided Intervention Using Modern Data Tools

    Energy Technology Data Exchange (ETDEWEB)

    Moirano, J [University of Washington, Seattle, WA (United States)

    2016-06-15

    Purpose: An accurate dose estimate is necessary for effective patient management after a fetal exposure. In the case of a high-dose exposure, it is critical to use all resources available in order to make the most accurate assessment of the fetal dose. This work will demonstrate a methodology for accurate fetal dose estimation using tools that have recently become available in many clinics, and show examples of best practices for collecting data and performing the fetal dose calculation. Methods: A fetal dose estimate calculation was performed using modern data collection tools to determine parameters for the calculation. The reference point air kerma as displayed by the fluoroscopic system was checked for accuracy. A cumulative dose incidence map and DICOM header mining were used to determine the displayed reference point air kerma. Corrections for attenuation caused by the patient table and pad were measured and applied in order to determine the peak skin dose. The position and depth of the fetus was determined by ultrasound imaging and consultation with a radiologist. The data collected was used to determine a normalized uterus dose from Monte Carlo simulation data. Fetal dose values from this process were compared to other accepted calculation methods. Results: An accurate high-dose fetal dose estimate was made. Comparison to accepted legacy methods were were within 35% of estimated values. Conclusion: Modern data collection and reporting methods ease the process for estimation of fetal dose from interventional fluoroscopy exposures. Many aspects of the calculation can now be quantified rather than estimated, which should allow for a more accurate estimation of fetal dose.

  8. Clinical application of a OneDose(TM) MOSFET for skin dose measurements during internal mammary chain irradiation with high dose rate brachytherapy in carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Kinhikar, Rajesh A [Department of Medical Physics, Tata Memorial Hospital, Parel, Mumbai 400 012 (India); Sharma, Pramod K [Department of Medical Physics, Tata Memorial Hospital, Parel, Mumbai 400 012 (India); Tambe, Chandrashekhar M [Department of Medical Physics, Tata Memorial Hospital, Parel, Mumbai 400 012 (India); Mahantshetty, Umesh M [Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai 400 012 (India); Sarin, Rajiv [Advanced Centre for Training Research and Education in Cancer, Kharghar, Navi Mumbai (India); Deshpande, Deepak D [Department of Medical Physics, Tata Memorial Hospital, Parel, Mumbai 400 012 (India); Shrivastava, Shyam K [Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai 400 012 (India)

    2006-07-21

    In our earlier study, we experimentally evaluated the characteristics of a newly designed metal oxide semiconductor field effect transistor (MOSFET) OneDose(TM) in-vivo dosimetry system for Ir-192 (380 keV) energy and the results were compared with thermoluminescent dosimeters (TLDs). We have now extended the same study to the clinical application of this MOSFET as an in-vivo dosimetry system. The MOSFET was used during high dose rate brachytherapy (HDRBT) of internal mammary chain (IMC) irradiation for a carcinoma of the breast. The aim of this study was to measure the skin dose during IMC irradiation with a MOSFET and a TLD and compare it with the calculated dose with a treatment planning system (TPS). The skin dose was measured for ten patients. All the patients' treatment was planned on a PLATO treatment planning system. TLD measurements were performed to compare the accuracy of the measured results from the MOSFET. The mean doses measured with the MOSFET and the TLD were identical (0.5392 Gy, 15.85% of the prescribed dose). The mean dose was overestimated by the TPS and was 0.5923 Gy (17.42% of the prescribed dose). The TPS overestimated the skin dose by 9% as verified by the MOSFET and TLD. The MOSFET provides adequate in-vivo dosimetry for HDRBT. Immediate readout after irradiation, small size, permanent storage of dose and ease of use make the MOSFET a viable alternative for TLDs. (note)

  9. High doses of recombinant erythropoietin stimulate platelet production in mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.; Cottrell, M.B.; Clift, R.E.; Cullen, W.C.; Lin, F.K.

    1987-07-01

    Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thrombocytosis were injected with rEpo and the %35S incorporation into platelets was measured. A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) was used as a positive control. rEpo increased isotopic incorporation into platelets of both normal mice and mice in rebound-thrombocytosis, as did TSF, but required large doses (15 U rEpo/mouse). In other mice, hematocrits, platelet counts, platelet sizes, and 24-hr %35S incorporation into platelets were measured 2 days after injection of two equally divided doses of either rEpo or TSF. Significant increases in both platelet sizes and %35S incorporation into platelets were found after injections of 15 U rEpo/mouse or 2.3 U TSF/mouse. These data indicate that rEpo, at high doses, will stimulate platelet production in mice, and may suggest molecular similarities between rEpo and TSF and their ability to compete for common receptor sites on megakaryocytes and their progenitor cells.

  10. Effect of simvastatin and atorvastatin on the expression of p 27 protein in mesangial cells of rat under high glucose%辛伐他汀与阿托伐他汀对高糖培养大鼠肾小球系膜细胞p27蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐艳丽; 李青菊

    2013-01-01

    Objective To explore the effect of simvastatin and atorvastatin on the level of p 27 protein in mesangial cells of rat under high glucose .Methods Cultured rat mesangial cells in vitro were divided into four groups :normal glucose(5 .6 mmol/L glu-cose) ,high glucose(30 mmol/L glucose) ,high glucose(30 mmol/L glucose) plus simvastatin(10 μmol/L) ,high glucose(30mmol/L glucose) plus atorvastatin(10 μmol/L) .After treatment for 24 ,48 ,72 120 hours ,the cells were collected .The protein level of p27 was detected by Western blotting and the mRNA level of p27 was detected by RT-PCR .Results Compared to the normal glucose group ,the levels of p27 protein and mRNA in the high glucose group had a significant increase(P<0 .05) .Compared to the high glucose group ,the level of p27 protein and mRNA in the high glucose plus simvastatin or atorvastatin group both had a significant decrease(P<0 .05) .Conclusion By modulating the expression of P27 in mesangial cells ,statins could become the independent lipid-decreasing drug to prevent kidney .%目的:探讨辛伐他汀和阿托伐他汀对高糖培养的大鼠肾小球系膜细胞p27表达的影响。方法将体外培养大鼠肾小球系膜细胞分为正常对照组(葡萄糖浓度5.6 mmol/L )、高糖组(葡萄糖浓度30 mmol/L )、高糖辛伐他汀组(葡萄糖浓度30 mmol/L ,辛伐他汀浓度10μmol/L )、高糖阿托伐他汀组(葡萄糖浓度30 mmol/L ,阿托伐他汀浓度10μmol/L )。每组设置6个复孔,于24、48、72、120 h收集细胞,Western blotting 法测定大鼠肾小球系膜细胞p27蛋白的表达,逆转录PCR测定p27mRNA的表达。结果高糖组p27蛋白浓度及mRNA水平均较正常对照组升高(P<0.05);高糖辛伐他汀组及高糖阿托伐他汀组p27蛋白浓度及mRNA水平均较高糖组降低(P<0.05)。结论他汀类药物通过调节肾小球系膜细胞p27的表达,可发挥非依赖降脂的肾脏保护作用。

  11. The usefulness of metal markers for CTV-based dose prescription in high-dose-rate interstitial brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ken; Mitomo, Masanori [Osaka National Hospital (Japan); Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji [Osaka Prefectural Center for Adult Diseases (Japan); Yoshida, Mineo [Sanda City Hospital, Hyogo (Japan)

    2002-12-01

    We employ a clinical target volume (CTV)-based dose prescription for high-dose-rate (HDR) interstitial brachytherapy. However, it is not easy to define CTV and organs at risk (OAR) from X-ray film or CT scanning. To solve this problem, we have utilized metal markers since October 1999. Moreover, metal markers can help modify dose prescription. By regulating the doses to the metal markers, refining the dose prescription can easily be achieved. In this research, we investigated the usefulness of the metal markers. Between October 1999 and May 2001, 51 patients were implanted with metal markers at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), Osaka National Hospital (ONH) and Sanda City Hospital (SCH). Forty-nine patients (head and neck: 32; pelvis: 11; soft tissue: 3; breast: 3) using metal markers were analyzed. During operation, we implanted 179 metal markers (49 patients) to CTV and 151 markers (26 patients) to OAR. At treatment planning, CTV was reconstructed judging from the metal markers, applicator position and operation records. Generally, we prescribed the tumoricidal dose to an isodose surface that covers CTV. We also planned to limit the doses to OAR lower than certain levels. The maximum normal tissue doses were decided 80%, 150%, 100%, 50% and 200% of the prescribed doses for the rectum, the urethra, the mandible, the skin and the large vessel, respectively. The doses to the metal markers using CTV-based dose prescription were generated. These were compared with the doses theoretically calculated with the Paris system. Treatment results were also investigated. The doses to the 158 metal markers (42 patients) for CTV were higher than ''tumoricidal dose''. In 7 patients, as a result of compromised dose prescription, 9 markers were lower than the tumoricidal dose. The other 12 markers (7%) were excluded from dose evaluation because they were judged as miss-implanted. The doses to the 142 metal markers (24 patients

  12. SU-E-T-165: Characterization of Dose Distributions in High-Dose-Rate Surface Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Buzurovic, I; Hansen, J; Bhagwat, M; O’Farrell, D; Damato, A; Friesen, S; Devlin, P; Cormack, R [Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, MA (United States)

    2015-06-15

    Purpose: To characterize dose distributions in high-dose-rate(HDR) surface brachytherapy using an Ir-125 source for different geometries, field sizes and topology of the clinical targets(CT). To investigate the depth doses at the central axis(CAX), edges of the treatment fields(E), and lateral dose distributions(L) present when using flap applicators in skin cancer treatments. Methods: When malignancies diagnosed on the skin are treated, various geometries of the CT require proper adaptation of the flap or custom-made applicators to the treatment site. Consequently, the dose at the depth on CAX and field edges changes with variation of the curvatures and size of the applicators. To assess the dose distributions, we created a total of 10 treatment plans(TP) for 10×10 and 20×20 field sizes(FS) with a step size of 1cm. The geometry of the applicators was: planar(PA), curved to 30(CA30) and 60(CA60) degrees with respect to the CAX, half-cylinder(HC), and cylindrical shape(CS). One additional TP was created in which the applicators were positioned to form a dome shape(DS) with a diameter of 16cm. This TP was used to emulate treatment of the average sized scalp. All TPs were optimized to deliver a prescription dose at 8mm equidistantly from the planes containing the dwell positions. This optimization is equivalent to the clinical arrangement since the SSD for the flap applicators is 5mm and the prescription depth is 3mm in the majority of clinical cases. Results: The depths (in mm) of the isodose lines were: FS(10×10):PA[90%(9.1CAX,8.0E,7.6L),50%(28.3CAX,20E,17.3L), 25%(51.1CAX,40E,27L)],CA30[90%(10.3CAX,8.2E,7.9L),50%(32.1CAX, 16.2E,15.8L),25%(61.3CAX,36.7E,31.8L)],CA60[90%(12.2CAX,6.1E,6.3L ),50%(47CAX,14E,16.6L),25%(70.8CAX,31.9E,35.4L)],HC[90%(11.1CA X,6.3E,7.3L),50%(38.3CAX,14.6E,16.1L),25%(66.2CAX,33.8E,34.2L)];FS (20×20):PA[90%(11.1CAX,9.0E,7.0L),50%(34.4CAX,21.9E,15.3L),25%(7 0.4CAX,50.9E,34.8L)],CA30[90%(10.9CAX,7.5E,7.1L),50%(38.8CAX,16. 7E,15.4L),25

  13. Labour induction with an intermediate-dose oxytocin regimen has advantages over a high-dose regimen.

    Science.gov (United States)

    Manjula, B G; Bagga, R; Kalra, J; Dutta, S

    2015-05-01

    A total of 200 women planned for labour induction were randomised to receive high-dose oxytocin (6 mU/min with similar increments every 45 min) or intermediate-dose oxytocin (3 mU/min with similar increments every 45 min). Oxytocin solution was prepared with 30 units in 500 ml saline with which the infusion rate in ml/h is numerically equal to oxytocin in mU/min. We observed that the caesarean rate (18% vs 6%, p = 0.009), contraction abnormalities (35% vs 14%, p = 0.0005) and neonatal bilirubin levels (7.99 ± 2.70 vs 6.80 ± 2.65, p = 0.002) were higher with high-dose than with intermediate-dose. The induction-delivery interval (IDI) was similar (10 h 13 min with high-dose and 11 h 5 min with intermediate-dose; p = 0.237, NS). Nulliparous women benefited more with intermediate-dose as the caesarean rate was higher with high-dose (24.6% vs 7.9%, p = 0.011). Although the caesarean rate was higher in multiparous women with high-dose oxytocin, it was statistically not significant (5.7% vs 2.7%; p = 0.609). Oxytocin regimens for labour induction are usually high-dose (4-6 mU/min) or low-dose (1-1.5 mU/min). The former is associated with more contraction abnormalities and the latter with prolonged IDI; both result in an increased caesarean rate. In order to offset these disadvantages, an intermediate- dose regimen was selected. The increment interval of 45 min was selected in accordance with the pharmacokinetics of oxytocin. We observed a lower caesarean rate when compared with the high-dose regimen, without any increase in the IDI. Hence, we propose that the intermediate-dose oxytocin regimen should be preferred to the high-dose regimen for labour induction.

  14. Rectal dose-volume constraints in high-dose radiotherapy of localized prostate cancer.

    Science.gov (United States)

    Fiorino, Claudio; Sanguineti, Giuseppe; Cozzarini, Cesare; Fellin, Gianni; Foppiano, Franca; Menegotti, Loris; Piazzolla, Anna; Vavassori, Vittorio; Valdagni, Riccardo

    2003-11-15

    To investigate the relationship between rectal bleeding and dosimetric-clinical parameters in patients receiving three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. In a retrospective national study (AIROPROS01-01, AIRO: Associazione Italiana Radioterapia Oncologica), planning/clinical data for 245 consecutive patients with stage T1-4N0-x prostate carcinoma who underwent 3D-CRT to 70-78 Gy (ICRU point) were pooled from four Italian institutions. The correlation between late rectal bleeding and rectal dose-volume data (the percentage of rectum receiving more than 50, 55, 60, 65, 70, and 75 Gy [V(50-70)]) and other dosimetric and clinical parameters were investigated in univariate (log-rank) and multivariate (Cox regression model) analyses. Median follow-up was 2 years. Twenty-three patients were scored as late bleeders according to a modified RTOG definition (Grade 2: 16; Grade 3: 7); the actuarial 2-year rate was 9.2%. Excepting V75, all median and third quartile V(50-70) values were found to be significantly correlated with late bleeding at univariate analysis. The smallest p value was seen for V(50) below/above the third quartile value (66%). The V70 (cut-off value: 30%) was found to be also predictive for late bleeding. In the high-dose subgroup (74-78 Gy), Grade 3 bleeding was highly correlated with this constraint. The predictive value of both V(50) and V(70) was confirmed by multivariate analyses. The present article provides evidence for correlation between rectal DVH parameters and late rectal bleeding in patients treated with curative intent with 3D-CRT. To keep the rate of moderate/severe rectal bleeding below 5-10%, it seems advisable to limit V(50) to 60-65%, V(60) to 45-50%, and V70 to 25-30%.

  15. Cation disorder in high-dose, neutron-irradiated spinel

    Energy Technology Data Exchange (ETDEWEB)

    Sickafus, K.E.; Larson, A.C.; Yu, N. [Los Alamos National Lab., CA (United States)] [and others

    1995-04-01

    The objective of this effort is to determine whether MgAl{sub 2}O{sub 4} spinel is a suitable ceramic for fusion applications. The crystal structures of MgAl{sub 2}O{sub 4} spinel single crystals irradiated to high neutron fluences [>5{times}10{sup 26} n/m{sup 2} (E{sub n}>0.1 MeV)] were examined by neutron diffraction. Crystal structure refinement of the highese dose sample indicated that the average scattering strength of the tetrahedral crystal sites decreased by {approx}20% while increasing by {approx}8% on octahedral sites.

  16. Krait bite requiring high dose antivenom: a case report.

    Science.gov (United States)

    Sharma, Sanjib Kumar; Koirala, Shekhar; Dahal, Gaheraj

    2002-03-01

    Anti snake venom (ASV) is the most specific therapy available for treatment of snakebite envenomation. The ASV available in Nepal are polyvalent ASV produced in India and are effective against envenomation by cobra and krait, the two most common species found in Eastern Nepal. Neurotoxic signs respond slowly and unconvincingly and continuous absorption of venom may cause recurrent neurotoxicity. Therefore, close observation and continuous administration of ASV is essential to save the victim. We report a case of neurotoxic envenomation due to bite by common krait (Bangarus caeruleus). The victim required very high dose of polyvalent ASV for reversal of neurological manifestations.

  17. Physical characteristics of the Selectron high dose rate intracavitary afterloader

    Energy Technology Data Exchange (ETDEWEB)

    Chenery, S.G.A.; Pla, M.; Podgorsak, E.B. (Royal Victoria Hospital, Montreal, Quebec (Canada); McGill Univ., Montreal, Quebec (Canada))

    1985-08-01

    The physics measurements on a Selectron high dose-rate afterloading cobalt-60 unit are reported. The installation was found to be acceptable from the standpoint of radiation safety and cost effectiveness; hospital bed space was saved as treatment could be on an outpatient basis. A source calibration 4% higher than the value stated by the manufacturer was obtained. Measurement of the ratio of exposure rate in water to that in air confirmed the calibration and the applicability of correction factors for routine clinical dosimetry recommended in the literature.

  18. High dose intravenous immunoglobulin may be complicated by myocardial infarction

    Directory of Open Access Journals (Sweden)

    Kolar Vishwanath Vinod

    2014-01-01

    Full Text Available Intravenous immunoglobulin [IVIg] is useful for treating several clinical conditions and is largely considered safe, without major adverse events. Here we report a case of acute ST elevation myocardial infarction associated with high dose IVIg administration in a previously healthy 69-year-old male patient of Guillain Barre syndrome. The case is being reported to emphasize the need for treating physicians to be aware of thrombotic complications associated with IVIg. The thrombotic complications associated with IVIg are reviewed in brief , and the measures to reduce them are discussed.

  19. Enhancement of osteoinduction by continual simvastatin release from poly(lactic-co-glycolic acid)-hydroxyapatite-simvastatin nano-fibrous scaffold.

    Science.gov (United States)

    Jiang, Liming; Sun, Haizhu; Yuan, Anliang; Zhang, Kai; Li, Daowei; Li, Chen; Shi, Ce; Li, Xiangwei; Gao, Kai; Zheng, Changyu; Yang, Bai; Sun, Hongchen

    2013-11-01

    Simvastatin is considered as a stimulator for bone formation. However, the half-life for simvastatin is generally 2 hours, which means, it is difficult to maintain biologically active simvastatin in vivo. To overcome this limitation, we created a system to slowly release simvastatin in vitro and in vivo. We constructed a poly(lactic-co-glycolic acid)/hydroxyapatite nano-fibrous scaffold to carry simvastatin. Releasing assays showed that simvastatin was released from poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin quickly within - 15 days, and small amounts continued to be released through day 56 (experiments terminated). MTT assays demonstrated that both poly(lactic-co-glycolic acid)/hydroxyapatite and poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin promoted MC3T3-E1 cell proliferation. However, Alkaline phosphatase assays showed that only poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold significantly promoted the osteogenic differentiation of MC3T3-E1 cells in vitro on day 14. To further test in vivo, we created calvaria bone defect models and implanted either poly(lactic-co-glycolic acid)/hydroxyapatite or poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin. After 4 or 8 weeks post-implantation, the results indicated that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold induced bone formation more efficiently than poly(lactic-co-glycolic acid)/hydroxyapatite alone. Our data demonstrates that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin has the potential to aid in healing bone defects and promoting bone regeneration in the future although we still need to optimize this complex to efficiently promote bone regeneration.

  20. Secondary radiation dose during high-energy total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Janiszewska, M.; Raczkowski, M. [Lower Silesian Oncology Center, Medical Physics Department, Wroclaw (Poland); Polaczek-Grelik, K. [University of Silesia, Medical Physics Department, Katowice (Poland); Szafron, B.; Konefal, A.; Zipper, W. [University of Silesia, Department of Nuclear Physics and Its Applications, Katowice (Poland)

    2014-05-15

    The goal of this work was to assess the additional dose from secondary neutrons and γ-rays generated during total body irradiation (TBI) using a medical linac X-ray beam. Nuclear reactions that occur in the accelerator construction during emission of high-energy beams in teleradiotherapy are the source of secondary radiation. Induced activity is dependent on the half-lives of the generated radionuclides, whereas neutron flux accompanies the treatment process only. The TBI procedure using a 18 MV beam (Clinac 2100) was considered. Lateral and anterior-posterior/posterior-anterior fractions were investigated during delivery of 2 Gy of therapeutic dose. Neutron and photon flux densities were measured using neutron activation analysis (NAA) and semiconductor spectrometry. The secondary dose was estimated applying the fluence-to-dose conversion coefficients. The main contribution to the secondary dose is associated with fast neutrons. The main sources of γ-radiation are the following: {sup 56}Mn in the stainless steel and {sup 187}W of the collimation system as well as positron emitters, activated via (n,γ) and (γ,n) processes, respectively. In addition to 12 Gy of therapeutic dose, the patient could receive 57.43 mSv in the studied conditions, including 4.63 μSv from activated radionuclides. Neutron dose is mainly influenced by the time of beam emission. However, it is moderated by long source-surface distances (SSD) and application of plexiglass plates covering the patient body during treatment. Secondary radiation gives the whole body a dose, which should be taken into consideration especially when one fraction of irradiation does not cover the whole body at once. (orig.) [German] Die zusaetzliche Dosis durch sekundaere Neutronen- und γ-Strahlung waehrend der Ganzkoerperbestrahlung mit Roentgenstrahlung aus medizinischen Linearbeschleunigern wurde abgeschaetzt. Bei der Emission hochenergetischer Strahlen zur Teletherapie finden hauptsaechlich im Beschleuniger

  1. High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding: a meta-analysis.

    Science.gov (United States)

    Wu, Liu-Cheng; Cao, Yun-Fei; Huang, Jia-Hao; Liao, Cun; Gao, Feng

    2010-05-28

    To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding. PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model. Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929). Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

  2. Dose optimization of intra-operative high dose rate interstitial brachytherapy implants for soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Jamema Swamidas

    2009-01-01

    Full Text Available Objective : A three dimensional (3D image-based dosimetric study to quantitatively compare geometric vs. dose-point optimization in combination with graphical optimization for interstitial brachytherapy of soft tissue sarcoma (STS. Materials and Methods : Fifteen consecutive STS patients, treated with intra-operative, interstitial Brachytherapy, were enrolled in this dosimetric study. Treatment plans were generated using dose points situated at the "central plane between the catheters", "between the catheters throughout the implanted volume", at "distances perpendicular to the implant axis" and "on the surface of the target volume" Geometrically optimized plans had dose points defined between the catheters, while dose-point optimized plans had dose points defined at a plane perpendicular to the implant axis and on the target surface. Each plan was graphically optimized and compared using dose volume indices. Results : Target coverage was suboptimal with coverage index (CI = 0.67 when dose points were defined at the central plane while it was superior when the dose points were defined at the target surface (CI=0.93. The coverage of graphically optimized plans (GrO was similar to non-GrO with dose points defined on surface or perpendicular to the implant axis. A similar pattern was noticed with conformity index (0.61 vs. 0.82. GrO were more conformal and less homogeneous compared to non-GrO. Sum index was superior for dose points defined on the surface of the target and relatively inferior for plans with dose points at other locations (1.35 vs. 1.27. Conclusions : Optimization with dose points defined away from the implant plane and on target results in superior target coverage with optimal values of other indices. GrO offer better target coverage for implants with non-uniform geometry and target volume.

  3. The effect of simvastatin, aspirin, and their combination in reduction of atheroma plaque

    Science.gov (United States)

    Kurniati, Neng Fisheri; Permatasari, Anita

    2015-09-01

    Atherosclerosis is one of the risk factors of cardiovascular disease. Atherosclerosis is a chronic inflammatory disease caused by high level of cholesterol especially low density lipoprotein (LDL) and accumulation of neutrophil and macrophage in the artery wall. Thickness of aortic wall is an early stage of atherosclerosis plaque formation. Identification of atherosclerosis plaque formation was done by measuring level of total cholesterol, triglycerides, HDL, LDL, interleukin-18 (IL-18), myeloperoxidase (MPO) and measuring the thickness of aortic wall. Atherosclerosis's model induced by high fat diet and CCT (cholesterol, cholic acid, and propyltiouracil) oral administration. Rats induced cholesterol divided into positive control, simvastatin 25 mg/kg bw, aspirin 20 mg/kg bw, and combination simvastatin 25 mg/kg and aspirin 20 mg/kg bw group for 3 weeks. In the third week, therapy was given to atherosclerosis's model. Then, in the fourth and fifth week, therapy was given but induction of high cholesterol was stopped due to the massive loss of body weight. Total cholesterol, triglycerides, HDL, LDL, MPO, and IL-18 measured by uv-vis spectrophotometry and ELISA. In the end of therapy, aorta's rats was isolated to identify the thickness of aorta wall. In the fourth week, after 1 week of treatment, only combination group showed significantly higher total cholesterol, LDL and MPO compared to positive control group. Level of triglycerides and HDL in all groups did not significantly differ compared to positive control group. After 2 weeks continuing drug treatment, the level of total cholesterol, MPO, and IL-18 were decreased in all groups, and aspirin group showed the lowest level. The level of triglycerides was decreased in simvastatin and aspirin group, and aspirin group showed the lowest. Only combination group showed the lowest level of LDL. Based on histopathology result, the thickness of aortic wall was reduced in all groups and aspirin group showed the lowest.

  4. Impact of high dose vitamin C on platelet function

    Science.gov (United States)

    Mohammed, Bassem M; Sanford, Kimberly W; Fisher, Bernard J; Martin, Erika J; Contaifer Jr, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S; Chalfant, Charles E; Brophy, Donald F; Fowler III, Alpha A; Natarajan, Ramesh

    2017-01-01

    AIM To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of VitC used here correspond to plasma VitC levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography (TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate (ATP) secretion in response to collagen or adenosine diphosphate (ADP); and flow cytometry, for changes in expression of CD-31, CD41a, CD62p and CD63. In addition, PLT intracellular VitC content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time (PT), partial thrombplastin time (PTT), functional fibrinogen] and Lipidomics analysis (UPLC ESI-MS/MS). RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L (Lo VitC) and 15.7 mmol/L (Hi VitC, P 8 d exposure period (P > 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle (P 0.05). Collagen and ADP-induced ATP secretion was also not different between the three groups (P > 0.05). Finally, VitC at the higher dose (3 mmol/L) also induced the release of several eicosanoids including thromboxane B2

  5. Shelf-stable food through high dose irradiation

    Science.gov (United States)

    Plaček, V.; Svobodová, V.; Bartoníček, B.; Rosmus, J.; Čamra, M.

    2004-09-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75°C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30°C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Řež 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO x-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

  6. Shelf-stable food through high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Placek, V. E-mail: pla@ujv.cz; Svobodova, V.; Bartonicek, B.; Rosmus, J.; Camra, M

    2004-10-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75 deg. C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30 deg. C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Rez 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO{sub x}-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

  7. High-dose processing and application to Korean space foods

    Science.gov (United States)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-07-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods ( Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  8. Characterization of a silicate glass as a high dose dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Farah, K., E-mail: k.farah@cnstn.rnrt.t [Laboratoire de Radiotraitement. Centre National des Sciences et Technologie Nucleaires, 2020 Sidi-Thabet (Tunisia); Mejri, A.; Hosni, F. [Laboratoire de Radiotraitement. Centre National des Sciences et Technologie Nucleaires, 2020 Sidi-Thabet (Tunisia); Ben Ouada, H. [Laboratoire de Physique et Chimie des Interfaces, Faculte des Sciences de Monastir, 5000 Monastir (Tunisia); Fuochi, P.G.; Lavalle, M. [ISOF-CNR, Via P. Gobetti 101, 40129 Bologna (Italy); Kovacs, A. [Institute of Isotopes, HAS, P.O. Box 77, H-1525 Budapest (Hungary)

    2010-02-21

    Commercial silicate glass has been investigated as a possible high dose dosimeter using an UV-vis spectrophotometer. Glass samples were irradiated by {sup 60}Co gamma rays and the results compared with those obtained with 3.4 and 8.4 MeV electron beams. The irradiated samples showed rapid fading at room temperature immediately after irradiation. In order to improve the stability of absorbance, glass samples were submitted to post-irradiation thermal treatments (150 deg. C for 20 min). The influences of the dose, type and energy of the ionizing radiation on the fading characteristics and on the response of the irradiated and thermally treated glasses were studied. Dependence of the glass response on the temperature during gamma irradiation in the range -3 to 80 deg. C is reported. The reproducibility to reuse glass dosimeter by thermal bleaching the radiation induced colour centres at 300 deg. C for 30 min was also investigated. Calibration curves in the range 0.1-17 kGy were obtained by using in-plant calibration techniques against transfer standard alanine dosimeters in the Tunisian semi-industrial gamma irradiation facility.

  9. High-dose processing and application to Korean space foods

    Energy Technology Data Exchange (ETDEWEB)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Jae-Hun [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kang, Sang-Wook; Choi, Gi-Hyuk [Korea Astronaut Project Division, Korea Aerospace Research Institute, Daejeon 305-333 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods (Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 {sup o}C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  10. Simvastatin suppresses vascular inflammation and atherosclerosis in ApoE-/-mice by downregulating the HMGB1-RAGE axis

    Institute of Scientific and Technical Information of China (English)

    Ming LIU; Ying YU; Hong JIANG; Lei ZHANG; Pei-pei ZHANG; Peng YU; Jian-guo JIA

    2013-01-01

    Aim:High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play pivotal roles in vascular inflammation and atherosclerosis.The aim of this study was to determine whether the HMGB1-RAGE axis was involved in the actions of simvastatin on vascular inflammation and atherosclerosis in ApoE-/-mice.Methods:Five-week old ApoE-/-mice and wild-type C57BL/6 mice were fed a Western diet.At 8 weeks of age,ApoE-/-mice were administered simvastatin (50 mg.kg1.d-1) or vehicle by gavage,and the wild-type mice were treated with vehicle.The mice were sacrificed at 11 weeks of age,and the atherosclerotic lesions in aortic sinus were assessed with Oil Red 0 staining.Macrophage migration was determined with scanning EM and immunohistochemistry.Human umbilical vein endothelial cells (HUVECs) were used for in vitro study.Western blots were used to quantify the protein expression of HMGB1,RAGE,vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1).Results:Vehicle-treated ApoE-/-mice exhibited significant increases in aortic inflammation and atherosclerosis as well as enhanced expression of HMGB1,RAGE,VCAM-1,and MCP-1 in aortic tissues as compared to the wild-type mice.Furthermore,serum total cholesterol,triglyceride and LDL levels were markedly increased,while serum HDL level was decreased in vehicle-treated ApoE-/-mice.Administration with simvastatin in ApoE-/-mice markedly attenuated the vascular inflammation and atherosclerotic lesion area,and decreased the aortic expression of HMGB1,RAGE,VCAM-1,and MCP-1.However,simvastatin did not affect the abnormal levels of serum total cholesterol,triglyceride,LDL and HDL in ApoE-/-mice.Exposure of HUVECs to HMGB1 (100 ng/mL) markedly increased the expression of HMGB1,RAGE and VCAM-1,whereas pretreatment of the cells with simvastatin (10 μmol/L) blocked the HMGB1-caused changes.Conclusion:Simvastatin inhibits vascular inflammation and atherosclerosis in Apo

  11. Teflon pastille use in high dose dosimetry; Utilizacao de pastilhas de teflon em dosimetria de doses altas

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Maria Ines [Associacao Educacional Nove de Julho (UNINOVE), Sao Paulo, SP (Brazil); Caldas, Linda V.E., E-mail: miteixeira@ipen.b, E-mail: lcaldas@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-10-26

    This paper study the Teflon, which is used as aglomerant in the confection of dosimetric pastilles, for the viabilization of this material as high dose dosimeter. This paper used the OSL technique for the characterization of dosimetric properties of Teflon. The doses-response curve has been obtained for {sup 60}Co radiation between 100 Gy and 50 kGy, and the OSL answer reproducibility. The preliminary results shown that the Teflon is a material which can be used for high dose dosimetry

  12. Simvastatin suppresses breast cancer cell proliferation induced by senescent cells

    NARCIS (Netherlands)

    Liu, Su; Uppal, Harpreet; Demaria, Marco; Desprez, Pierre-Yves; Campisi, Judith; Kapahi, Pankaj

    2015-01-01

    Cellular senescence suppresses cancer by preventing the proliferation of damaged cells, but senescent cells can also promote cancer though the pro-inflammatory senescence-associated secretory phenotype (SASP). Simvastatin, an HMG-coA reductase inhibitor, is known to attenuate inflammation and preven

  13. Simvastatin Ameliorates Matrix Stiffness-Mediated Endothelial Monolayer Disruption.

    Science.gov (United States)

    Lampi, Marsha C; Faber, Courtney J; Huynh, John; Bordeleau, Francois; Zanotelli, Matthew R; Reinhart-King, Cynthia A

    2016-01-01

    Arterial stiffening accompanies both aging and atherosclerosis, and age-related stiffening of the arterial intima increases RhoA activity and cell contractility contributing to increased endothelium permeability. Notably, statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors whose pleiotropic effects include disrupting small GTPase activity; therefore, we hypothesized the statin simvastatin could be used to attenuate RhoA activity and inhibit the deleterious effects of increased age-related matrix stiffness on endothelial barrier function. Using polyacrylamide gels with stiffnesses of 2.5, 5, and 10 kPa to mimic the physiological stiffness of young and aged arteries, endothelial cells were grown to confluence and treated with simvastatin. Our data indicate that RhoA and phosphorylated myosin light chain activity increase with matrix stiffness but are attenuated when treated with the statin. Increases in cell contractility, cell-cell junction size, and indirect measurements of intercellular tension that increase with matrix stiffness, and are correlated with matrix stiffness-dependent increases in monolayer permeability, also decrease with statin treatment. Furthermore, we report that simvastatin increases activated Rac1 levels that contribute to endothelial barrier enhancing cytoskeletal reorganization. Simvastatin, which is prescribed clinically due to its ability to lower cholesterol, alters the endothelial cell response to increased matrix stiffness to restore endothelial monolayer barrier function, and therefore, presents a possible therapeutic intervention to prevent atherogenesis initiated by age-related arterial stiffening.

  14. Myopati hos en patient i behandling med simvastatin og fluconazol

    DEFF Research Database (Denmark)

    Pedersen, Jens Kristian; Lydolph, Magnus Christian; Somnier, Finn

    2016-01-01

    A 69-year-old female was admitted due to progressive loss of muscle strength following addition of fluconazole to long-term simvastatin treatment. Rhabdomyolysis was suspected and both drugs were discontinued. Forced diuresis was initiated together with a short course of prednisolone. After 21...

  15. Simvastatin Ameliorates Matrix Stiffness-Mediated Endothelial Monolayer Disruption.

    Directory of Open Access Journals (Sweden)

    Marsha C Lampi

    Full Text Available Arterial stiffening accompanies both aging and atherosclerosis, and age-related stiffening of the arterial intima increases RhoA activity and cell contractility contributing to increased endothelium permeability. Notably, statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors whose pleiotropic effects include disrupting small GTPase activity; therefore, we hypothesized the statin simvastatin could be used to attenuate RhoA activity and inhibit the deleterious effects of increased age-related matrix stiffness on endothelial barrier function. Using polyacrylamide gels with stiffnesses of 2.5, 5, and 10 kPa to mimic the physiological stiffness of young and aged arteries, endothelial cells were grown to confluence and treated with simvastatin. Our data indicate that RhoA and phosphorylated myosin light chain activity increase with matrix stiffness but are attenuated when treated with the statin. Increases in cell contractility, cell-cell junction size, and indirect measurements of intercellular tension that increase with matrix stiffness, and are correlated with matrix stiffness-dependent increases in monolayer permeability, also decrease with statin treatment. Furthermore, we report that simvastatin increases activated Rac1 levels that contribute to endothelial barrier enhancing cytoskeletal reorganization. Simvastatin, which is prescribed clinically due to its ability to lower cholesterol, alters the endothelial cell response to increased matrix stiffness to restore endothelial monolayer barrier function, and therefore, presents a possible therapeutic intervention to prevent atherogenesis initiated by age-related arterial stiffening.

  16. Development of Real-Time Measurement of Effective Dose for High Dose Rate Neutron Fields

    CERN Document Server

    Braby, L A; Reece, W D

    2003-01-01

    Studies of the effects of low doses of ionizing radiation require sources of radiation which are well characterized in terms of the dose and the quality of the radiation. One of the best measures of the quality of neutron irradiation is the dose mean lineal energy. At very low dose rates this can be determined by measuring individual energy deposition events, and calculating the dose mean of the event size. However, at the dose rates that are normally required for biology experiments, the individual events can not be separated by radiation detectors. However, the total energy deposited in a specified time interval can be measured. This total energy has a random variation which depends on the size of the individual events, so the dose mean lineal energy can be calculated from the variance of repeated measurements of the energy deposited in a fixed time. We have developed a specialized charge integration circuit for the measurement of the charge produced in a small ion chamber in typical neutron irradiation exp...

  17. Comparison of low-dose and high-dose cosyntropin stimulation testing in children.

    Science.gov (United States)

    Cemeroglu, Ayse Pinar; Kleis, Lora; Postellon, Daniel C; Wood, Michael A

    2011-04-01

      There is no consensus among pediatric endocrinologists in using low-dose (LD) versus high-dose (HD) cosyntropin to test for secondary/tertiary adrenal insufficiency. This paper compares LD and HD cosyntropin stimulation testing in children for evaluation of hypothalamic-pituitary-adrenal axis (HPAA) and suggests a new peak cortisol cut-off value for LD stimulation testing to avoid false positivity.   Data of 36 children receiving LD (1 µg) and HD (249 µg) cosyntropin consecutively during growth hormone (GH) stimulation testing were analyzed in two groups. Group A were patients who passed GH stimulation testing and were not on oral, inhaled or intranasal steroids (intact hypothalamic-pituitary axis, n= 19). Group B were patients who failed GH stimulation testing and/or were on oral, inhaled or intranasal steroids (impaired hypothalamic-pituitary axis, n= 17).   In group A, the mean peak cortisol response in LD cosyntropin was 18.5 ± 2.4 µg/dL and that for the HD cosyntropin was 24.8 ± 3.1 µg/dL (r: 0.76, P≤ 0.05). In group B, the mean peak cortisol response in LD cosyntropin was 15.7 ± 6.1 µg/dL and that for HD cosyntropin was 21.7 ± 7.9 µg/dL (r: 0.98, P≤ 0.05). When a standard cut-off of 18 µg/dL was used, 37% of the patients with intact HPAA failed LD cosyntropin testing, but a cut-off of 14 µg/dL eliminated false positive results.   LD cosyntropin stimulation testing results should be interpreted cautiously when used alone to prevent unnecessary long-term treatment. Using a lower cut-off for LD (≥14 µg/dL) seems to avoid false positive results and still detects most cases of impaired HPAA. © 2011 The Authors.Pediatrics International © 2011 Japan Pediatric Society.

  18. High-dose thiamine improves the symptoms of fibromyalgia.

    Science.gov (United States)

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-05-20

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients' history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms.

  19. High-dose thiamine improves the symptoms of Friedreich's ataxia.

    Science.gov (United States)

    Costantini, Antonio; Giorgi, Rafaela; D'Agostino, Sonia; Pala, Maria Immacolata

    2013-05-22

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3-5 days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease.

  20. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  1. Paradoxical negative HDL cholesterol response to atorvastatin and simvastatin treatment in Chinese type 2 diabetic patients.

    Science.gov (United States)

    Chang, Yu-Hung; Lin, Kun-Cheng; Chang, Dao-Ming; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

    2013-01-01

    There is extensive but controversial evidence on the diverse effects of statins on the level of high-density lipoprotein cholesterol (HDL-C). Some of these effects may limit the benefits of statins in terms of cardiovascular risk reduction. To identify the conditions for beneficial effects, this study investigated the response to atorvastatin and simvastatin treatment in type 2 diabetic patients with elevated low-density lipoprotein cholesterol (LDL-C). 2,872 subjects with type 2 diabetes from a disease management program were investigated. Patients with LDL-C ≥130 mg/dl or total cholesterol ≥200 mg/dl were put onto statin therapy by the National Health Insurance system in Taiwan. 1,080 patients who completed 1 year of statin treatment were analyzed. There were significant reductions in LDL-C in both the atorvastatin (37.1%) and simvastatin (34.3%) group after one year of treatment compared with baseline levels. Unexpectedly, the majority of diabetic patients who received atorvastatin or simvastatin did not show an increase in HDL-C levels. 59.8% of patients had a significant HDL-C reduction (ΔHDL-C ≤ -3%) after atorvastatin treatment. Multivariate logistic regression analysis showed that the following patients were at higher risk of HDL-C reduction after 12 months: (i) patients in whom statin therapy was initiated aged HDL-C >40 mg/dl, and (iii) female patients with a baseline HDL-C >50 mg/dl. However, diabetic patients with severe atherogenic dyslipidemia (LDL-C ≥130, TG ≥204, and HDL-C ≤34 mg/dl) obtained more benefits in terms of HDL-C change after statin therapy. Diabetic patients, except those with severe atherogenic dyslipidemia, are prone to a decrease in serum HDL-C level after statin treatment, particularly after atorvastatin treatment.

  2. "Time sequential high dose of Cytarabine in acute myelocytic leukemia "

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    2003-05-01

    Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

  3. High-Dose Vitamin D Failed to Curb Heart Disease in Study

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_164472.html High-Dose Vitamin D Failed to Curb Heart Disease in Study ... 5, 2017 (HealthDay News) -- Taking high doses of vitamin D once a month won't lower your ...

  4. Simvastatin inhibits inflammation in ischemia-reperfusion injury.

    Science.gov (United States)

    Zhao, Yilin; Feng, Qingzhao; Huang, Zhengjie; Li, Wenpeng; Chen, Baisheng; Jiang, Long; Wu, Binglin; Ding, Weiji; Xu, Gang; Pan, Heng; Wei, Wei; Luo, Weiyuan; Luo, Qi

    2014-10-01

    Ischemia/reperfusion (I/R) is associated with leukocyte accumulation and tissue injury. The aim of this research was to investigate the protective effect of simvastatin on hind limb I/R inflammation and tissue damage. Mice were subjected to hind limb ischemic insult for 2 h and were simultaneously administered an intraperitoneal injection of simvastatin (5 mg/kg); this was followed by 36 h of reperfusion. Myeloperoxidase (MPO) levels in the muscles of the hind limb were determined. CXC chemokines and pro-inflammatory cytokines, such as macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and P-selectin, were assessed using enzyme-linked immunosorbent assay (ELISA). Leukocyte rolling and adhesion in vitro was assessed to indicate leukocyte recruitment at the site of inflammation. Quantitative measurement of skeletal muscle tissue injury was performed. The fluorescent dye level in tissue and serum was used to determine hind limb vascular leakage and tissue edema after I/R. Systemic and differentiated leukocytes were also counted. Simvastatin significantly reduced MIP-2, KC, TNF-α, MPO, IL-6, and P-selectin levels compared to the sham group and I/R plus pretreatment with phosphate-buffered saline (PBS) group (Pinflammation, vascular leakage, and muscular damage (P<0.05). Simvastatin also significantly inhibited leukocyte rolling and adhesion compared to PBS (P<0.05). Our results suggest that simvastatin may be an effective protectant against tissue injury associated with I/R.

  5. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts After Exposure to Very Low Dose of High Let Radiation

    Science.gov (United States)

    Hada, M.; George, K.; Chappell, L.; Cucinotta, F. A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivor with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (0.01 - 0.20 Gy) of 170 MeV/u Si-28 ions or 600 MeV/u Fe-56 ions, including doses where on average less than one direct ion traversal per cell nucleus occurs. Chromosomes were analyzed using the whole-chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). The responses for doses above 0.1 Gy (more than one ion traverses a cell) showed linear dose responses. However, for doses less than 0.1 Gy, both Si-28 ions and Fe-56 ions showed a dose independent response above background chromosome aberrations frequencies. Possible explanations for our results are non-targeted effects due to aberrant cell signaling [1], or delta-ray dose fluctuations [2] where a fraction of cells receive significant delta-ray doses due to the contributions of multiple ion tracks that do not directly traverse cell nuclei where chromosome aberrations are scored.

  6. Observed and predicted reduction of ischemic cardiovascular events in the Simvastatin and Ezetimibe in Aortic Stenosis trial

    DEFF Research Database (Denmark)

    Holme, Ingar; Boman, Kurt; Brudi, Philippe

    2010-01-01

    In the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial, combined ezetimibe (10 mg) and simvastatin (40 mg) decreased low-density lipoprotein cholesterol levels by 50% and ischemic cardiovascular event (ICE) risk by 22% compared to placebo. A larger decrease in ICE risk might have been...... expected for the degree of lipid-lowering observed. This analysis investigated relations between changes in lipoprotein components (LCs), and ICE risk decrease in the SEAS trial in all patients, by severity of aortic stenosis (AS), and compared to results of other clinical trials. A total of 1,570 patients...... with baseline aortic jet velocity (JV) data, baseline and 1-year low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B, and no ICEs during the first year were included in the analysis. Relations between on-treatment measurements of 1-year LCs and time-to-ICE occurrence...

  7. Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

    OpenAIRE

    Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina

    2016-01-01

    Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethaso...

  8. Antagonism by idazoxan at low dose but not high dose, of the natriuretic action of moxonidine.

    Science.gov (United States)

    Allan, D. R.; Penner, S. B.; Smyth, D. D.

    1996-01-01

    1. Recent studies concerning the imidazoline receptor have utilized idazoxan as a specific imidazoline receptor antagonist. The aim of the present study was to describe the in vivo effects of various doses of idazoxan on renal function, in the presence and absence of moxonidine, an I1 imidazoline receptor agonist. 2. In anaesthetized, unilaterally nephrectomized (7 to 10 days) Sprague Dawley rats, an intrarenal infusion of moxonidine (3 nmol kg-1 min-1) increased urine flow rate, sodium excretion and osmolar clearance without altering free water clearance. Pretreatment with intravenous idazoxan at 0.1 and 0.3 mg kg-1 produced a dose-related decrease in the renal actions of moxonidine. However, a higher dose of idazoxan (1 mg kg-1) was not as effective as the 0.3 mg kg-1 dose in blocking the effects of moxonidine. 3. In a separate series of experiments, the direct renal actions of idazoxan alone were investigated. Idazoxan at 0.3 mg kg-1 failed to alter urine flow rate and sodium excretion. However, idazoxan at 1 mg kg-1 produced a significant increase in urine flow rate and sodium excretion in association with an increase in osmolar clearance. 4. These results do not prove but are consistent with low doses of idazoxan antagonizing the sites stimulated by moxonidine (renal imidazoline receptors). However, at higher doses, idazoxan may function as a partial agonist and/or interact with other receptors to increase urine flow rate, independent of imidazoline receptor blockade. These studies underscore the importance of the dose of idazoxan administered when this antagonist is used as a tool to investigate imidazoline receptors. PMID:8825339

  9. Effect of simvastatin combined amlodipine besylate on blood rheology and platelet activation in elderly patients with hypertension complicated with hyperlipemia

    Institute of Scientific and Technical Information of China (English)

    Ming-Zheng Jiang; Li Qiong; Hui Liu

    2016-01-01

    Objective:To investigate the effect of simvastatin combined amlodipine besylate on blood rheology and platelet activation in elderly patients with hypertension complicated with hyperlipemia.Methods: A total of 200 elderly patients with hypertension complicated with hyperlipemia were divided into hypertension group (n=64), hyperlipemia group (n=71) and combined (hypertension complicated with hyperlipemia) group (n=65). And alternate period health check-up 100 cases were selected as control group. The hypertension group was treated with amlodipine besylate monotherapy, hyperlipidemia group with simvastatin monotherapy, combined group received simvastatin combined with amlodipine besylate treatment, patients of three groups were treated for 12 weeks. Blood rheology and platelet activation before and after treatment were compared.Results: After treatment, blood pressure was significantly lower than that before treatment in hypertension and combined group (P<0.05), and the combined group reduced more significantly (P<0.05), blood fat was significantly lower than that before treatment in hyperlipemia and combined group (P<0.05), and combined group reduced more significantly (P<0.05); Before treatment, indexes of blood rheology (high shear whole blood viscosity, low shear whole blood viscosity, plasma viscosity, fibrinogen and platelet activation index (CD62p and CD63) of three groups were significantly higher than those in control group (P<0.05), and the combined group was increased more significantly than hypertension and hyperlipidemia group (P<0.05); After treatment, blood rheology (high shear whole blood viscosity, low shear whole blood viscosity, plasma viscosity, fibrinogen) and platelet activation index (CD62p and CD63) of hyperlipidemia group and combined group were significantly lower than before treatment (P<0.05), and the reduction combined group were more significant in amplitude (P<0.05).Conclusions: Simvastatin combined amlodipine besylate therapy can

  10. Comparison of commercial thermoluminescent readers regarding high-dose high-temperature measurements

    CERN Document Server

    Bilski, P; Obryk, B; Hodyr, K

    2014-01-01

    Three different thermoluminescent measuring systems have been compared with respect to the differences in temperature profiles, spectral sensitivities, as well as linearity of dose response characteristics. The comparison was performed using the Harshaw 3500, Riso DA-20 and RA94 TLD readers. The instruments were tested for the readouts of highly irradiated LiF:Mg,Cu,P (MCP) TL detectors, which require readout up to 550 C, in case of doses exceeding 1 kGy. It was found that the Harshaw 3500 can be used, without any additional light attenuation, for the measurements of MCP detectors exposed to doses up to about 5 Gy. For the other two readers the upper dose limit is about 5 times lower. It was also found that the Harshaw 3500 shows the best thermal stability considering the peak maximum position. For the ultra-high doses the differences in the spectral characteristics of the applied optical filters and photomultipliers, in conjunction with an evolution of the MCP TL emission spectrum with increasing dose, signi...

  11. ``In vivo'' Dose Measurements in High-Dose-Rate Brachytherapy Treatments for Cervical Cancer: A Project Proposal

    Science.gov (United States)

    Mejía, C. A. Reynoso; Burgos, A. E. Buenfil; Trejo, C. Ruiz; García, A. Mota; Durán, E. Trejo; Ponce, M. Rodríguez; de Buen, I. Gamboa

    2010-12-01

    The aim of this thesis project is to compare doses calculated from the treatment planning system using computed tomography images, with those measured "in vivo" by using thermoluminescent dosimeters placed at different regions of the rectum and bladder of a patient during high-dose-rate intracavitary brachytherapy treatment of uterine cervical carcinoma. The experimental dosimeters characterisation and calibration have concluded and the protocol to carry out the "in vivo" measurements has been established. In this work, the calibration curves of two types of thermoluminescent dosimeters (rods and chips) are presented, and the proposed protocol to measure the "in vivo" dose is fully described.

  12. Simvastatin inhibits interferon-γ-induced MHC class II up-regulation in cultured astrocytes

    Directory of Open Access Journals (Sweden)

    Glazenburg Lisa

    2006-07-01

    Full Text Available Abstract Based on their potent anti-inflammatory properties and a preliminary clinical trial, statins (HMG-CoA reductase inhibitors are being studied as possible candidates for multiple sclerosis (MS therapy. The pathogenesis of MS is unclear. One theory suggests that the development of autoimmune lesions in the central nervous system may be due to a failure of endogenous inhibitory control of MHC class II expression on astrocytes, allowing these cells to adapt an interferon (IFN-γ-induced antigen presenting phenotype. By using immunocytochemistry in cultured astrocytes derived from newborn Wistar rats we found that simvastatin at nanomolar concentrations inhibited, in a dose-response fashion, up to 70% of IFN-γ-induced MHC class II expression. This effect was reversed by the HMG-CoA reductase product mevalonate. Suppression of the antigen presenting function of astrocytes might contribute to the beneficial effects of statins in MS.

  13. Very high dose phenobarbital for refractory status epilepticus.

    Science.gov (United States)

    Tiamkao, Somsak; Mayurasakorn, Nattakarn; Suko, Panit; Jitpimolmard, Suthipun; Arunpongpaisal, Suwanna; Phuttharak, Warinthorn; Auevitchayapat, Narong; Vannaprasaht, Suda; Tiamkao, Siriporn; Phunikhom, Kutcharin; Chaiyakum, Aporanee; Saengsuwan, Jiamjit

    2007-12-01

    Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to first, second and third-line therapy. The RSE is associated with high morbidity and mortality. Treatment guidelines of RSE give a spectrum of options, such as, continuous intravenous (i.v.) midazolam (MDL), or continuous i.v. propofol (PRO) as alternatives to phenobarbital (PB) or continuous i.v. pentobarbital (PTB). To study the efficacy of very-high-dose phenobarbital (VHDPB) for treatment RSE. Retrospective study The authors collected and analyzed data from adult patients who were diagnosed with RSE. The authors present 10 patients with RSE who were treated with VHDPB. All of them were generalized convulsive status epilepticus (GCSE). Ages ranged from 16-86 years old (mean.: 43 years). PB dosage ranged 40-140 mg/kg/day (mean: 70 mg/kg/day). The duration of status epilepticus (SE) varied widely, ranged 1-44 days (mean: 7 days). PB level ranged 35.29-218.34 ug/mL (mean 88.1 ug/mL). RSE was controlled by VHDPB 70%, 30% were not controlled. VHDPB were considered as alternative treatment for RSE.

  14. High-dose pyridoxine as an 'anti-stress' strategy.

    Science.gov (United States)

    McCarty, M F

    2000-05-01

    Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival.

  15. A comparison of high-dose and low-dose tranexamic acid antifibrinolytic protocols for primary coronary artery bypass surgery

    Directory of Open Access Journals (Sweden)

    Stephen M McHugh

    2016-01-01

    Full Text Available Background and Aims: Tranexamic acid (TA is used for prophylactic antifibrinolysis in coronary artery bypass surgeries to reduce bleeding. We evaluated the efficacy of two different doses of TA for prophylactic antifibrinolysis in patients undergoing primary coronary artery bypass grafting (CABG surgery in this retrospective cohort study at a tertiary care referral centre. Methods: One-hundred eighty-four patients who underwent primary CABG with cardiopulmonary bypass (CPB via sternotomy between January 2009 and June 2011 were evaluated. Pre-operative patient characteristics, intraoperative data, post-operative bleeding, transfusions, organ dysfunction and 30-day mortality were compared between high-dose TA (30 mg/kg loading dose followed by infusion of 15 mg/kg/h until the end of surgery along with 2 mg/kg priming dose in the bypass circuit and low-dose TA (15 mg/kg loading dose followed by infusion of 6 mg/kg/h until the end of surgery along with 1 mg/kg priming dose in the bypass circuit groups. Univariate comparative analysis of all categorical and continuous variables was performed between the two groups by appropriate statistical tests. Linear and logistic regression analyses were performed to control for the effect of confounding on the outcome variables. Results: Chest tube output, perioperative transfusion of blood products and incidence of re-exploration for bleeding did not differ significantly (P> 0.05 between groups. Post-operative complications and 30-day mortality were comparable between the groups. The presence of cardiogenic shock and increased pre-operative creatinine were found to be associated with increased chest tube output on the post-operative day 2 by multivariable linear regression model. Conclusions: Low-dose TA protocol is as effective as high-dose protocol for antifibrinolysis in patients undergoing primary CABG with CPB.

  16. Efficacy of a single high dose versus multiple low doses of LLLT on wounded skin fibroblasts

    Science.gov (United States)

    Hawkins, Denise H.; Abrahamse, Heidi

    2007-07-01

    Background/purpose: In vivo studies have demonstrated that phototherapy accelerates wound healing in the clinical environment; however the exact mechanism is still not completely understood. The main focus of this study was to use in vitro laboratory results to establish an effective treatment regimen that may be practical and applicable to the clinical environment. This in vitro study aimed to compare the cellular responses of wounded fibroblasts following a single exposure of 5 J/cm2 or multiple exposures of low doses (2.5 J/cm2 or 5 J/cm2) on one day of the week to a single application of a higher dose (16 J/cm2) on day 1 and day 4. Methodology: Cellular responses to Helium-Neon (632.8 nm) laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, membrane integrity and DNA damage. Results: Wounded cells exposed to 5 J/cm2 on day 1 and day 4 showed an increase in cell viability, increase in the release of bFGF, increase in cell density, decrease in ALP enzyme activity and decrease in caspase 3/7 activity indicating a stimulatory effect. Wounded cells exposed to three doses of 5 J/cm2 on day 1 showed a decrease in cell viability and cell proliferation and an increase in LDH cytotoxicity and DNA damage indicating an inhibitory effect. Conclusion: Results indicate that cellular responses are influenced by the combination of dose administered, number of exposures and time between exposures. Single doses administered with sufficient time between exposures is more beneficial to restoring cell function than multiple doses within a short period. Although this work confirms previous reports on the cumulative effect of laser irradiation it provides essential information for the initiation of in vivo clinical studies.

  17. Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD: Results of the Study of Heart and Renal Protection (SHARP)

    Science.gov (United States)

    Mihaylova, Borislava; Schlackow, Iryna; Herrington, William; Lozano-Kühne, Jingky; Kent, Seamus; Emberson, Jonathan; Reith, Christina; Haynes, Richard; Cass, Alan; Craig, Jonathan; Gray, Alastair; Collins, Rory; Landray, Martin J.; Baigent, Colin; Collins, R.; Baigent, C.; Landray, M.J.; Bray, C.; Chen, Y.; Baxter, A.; Young, A.; Hill, M.; Knott, C.; Cass, A.; Feldt-Rasmussen, B.; Fellström, B.; Grobbee, D.E.; Grönhagen-Riska, C.; Haas, M.; Holdaas, H.; Hooi, L.S.; Jiang, L.; Kasiske, B.; Krairittichai, U.; Levin, A.; Massy, Z.A.; Tesar, V.; Walker, R.; Wanner, C.; Wheeler, D.C.; Wiecek, A.; Dasgupta, T.; Herrington, W.; Lewis, D.; Mafham, M.; Majoni, W.; Reith, C.; Emberson, J.; Parish, S.; Simpson, D.; Strony, J.; Musliner, T.; Agodoa, L.; Armitage, J.; Chen, Z.; Craig, J.; de Zeeuw, D.; Gaziano, J.M.; Grimm, R.; Krane, V.; Neal, B.; Ophascharoensuk, V.; Pedersen, T.; Sleight, P.; Tobert, J.; Tomson, C.

    2016-01-01

    Background Simvastatin, 20 mg, plus ezetimibe, 10 mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown. Study Design Cost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial. Setting & Population 9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, plus ezetimibe (2015 UK £1.19 per day) during 4.9 years’ median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK £0.05-£1.06 per day). Outcomes Additional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained. Results In SHARP, the proportional reductions per 1 mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £157,060 in patients at low risk to £15,230 in those at high risk (£30,500-£39,600 per QALY); and from £47,280 in CKD stage 3 to £28,180 in patients on dialysis therapy (£13,000-£43,300 per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost. Limitations High-intensity statin-alone regimens were not studied in SHARP. Conclusions Simvastatin plus

  18. Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD: Results of the Study of Heart and Renal Protection (SHARP).

    Science.gov (United States)

    Mihaylova, Borislava; Schlackow, Iryna; Herrington, William; Lozano-Kühne, Jingky; Kent, Seamus; Emberson, Jonathan; Reith, Christina; Haynes, Richard; Cass, Alan; Craig, Jonathan; Gray, Alastair; Collins, Rory; Landray, Martin J; Baigent, Colin

    2016-04-01

    Simvastatin, 20mg, plus ezetimibe, 10mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown. Cost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial. 9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, plus ezetimibe (2015 UK £1.19 per day) during 4.9 years' median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK £0.05-£1.06 per day). Additional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained. In SHARP, the proportional reductions per 1mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £157,060 in patients at low risk to £15,230 in those at high risk (£30,500-£39,600 per QALY); and from £47,280 in CKD stage 3 to £28,180 in patients on dialysis therapy (£13,000-£43,300 per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost. High-intensity statin-alone regimens were not studied in SHARP. Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP, but other less costly statin regimens are

  19. Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

    Energy Technology Data Exchange (ETDEWEB)

    Smiderle, Lisiane [Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Lima, Luciana O.; Hutz, Mara Helena [Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Sand, Cézar Roberto Van der; Sand, Luiz Carlos Van der; Ferreira, Maria Elvira Wagner; Pires, Renan Canibal [Centro de Diagnóstico Cardiológico, Porto Alegre, RS (Brazil); Almeida, Silvana; Fiegenbaum, Marilu [Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2014-07-15

    Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

  20. Treatment of obese asthma in a mouse model by simvastatin is associated with improving dyslipidemia and decreasing leptin level.

    Science.gov (United States)

    Han, Wei; Li, Jun; Tang, Huaping; Sun, Lixin

    2017-03-04

    Obesity can cause or worsen asthma. Compared with common asthma, obese asthma is difficult to control. Statins are effective serum cholesterol-lowering agents in clinical practice, and they also have anti-inflammatory properties, which in theory are potentially beneficial in asthma. Many studies have shown that simvastatin has good therapeutic effect in animal models of asthma. However, the therapeutic effect and action mechanism of simvastatin for obese asthma remain unclear. Leptin, a satiety hormone, is in positive correlation with total body fat mass and may also play a significant role in the pathogenesis of asthma. In this study, we use the method of high-fat diet and ovalbumin (OVA) sensitization and challenge to establish the mouse model of obesity and asthma, and find that obese asthmatic mice has higher levels of glucose, lipid and leptin in serum, and neutrophil percentage in bronchoalveolar lavage fluid (BALF), and more severe airway inflammation and structural changes in lung tissues than non-obese asthmatic mice, and respond poorly to dexamethasone treatment, which indicates that obese asthma might belong to steroid-resistant (SR) asthma. Simvastatin treatment reduces the levels of glucose, lipid, leptin and neutrophil percentage, and improves airway inflammation and remodeling, which can be as a potential therapeutic target used in the treatment of obese asthma in humans. Correlation analysis shows that there is positive correlation between neutrophil percentage and serum leptin/cholesterol level, which indicates that the therapeutic efficacy of simvastatin on obese asthma might be associated with improving dyslipidemia and decreasing leptin level. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  2. Simvastatin requires activation in accessory cells to modulate T-cell responses in asthma and COPD.

    Science.gov (United States)

    Knobloch, Jürgen; Yakin, Yakup; Körber, Sandra; Grensemann, Barbara; Bendella, Zeynep; Boyaci, Niyazi; Gallert, Willem-Jakob; Yanik, Sarah Derya; Jungck, David; Koch, Andrea

    2016-10-05

    T-cell-dependent airway and systemic inflammation triggers the progression of chronic obstructive pulmonary disease (COPD) and asthma. Retrospective studies suggest that simvastatin has anti-inflammatory effects in both diseases but it is unclear, which cell types are targeted. We hypothesized that simvastatin modulates T-cell activity. Circulating CD4+ and CD8+ T-cells, either pure, co-cultured with monocytes or alveolar macrophages (AM) or in peripheral blood mononuclear cells (PBMCs), were ex vivo activated towards Th1/Tc1 or Th2/Tc2 and incubated with simvastatin. Markers for Th1/Tc1 (IFNγ) and Th2/Tc2 (IL-5, IL-13) were measured by ELISA; with PBMCs this was done comparative between 11 healthy never-smokers, 11 current smokers without airflow limitation, 14 smokers with COPD and 11 never-smokers with atopic asthma. T-cell activation induced IFNγ, IL-5 and IL-13 in the presence and absence of accessory cells. Simvastatin did not modulate cytokine expression in pure T-cell fractions. β-hydroxy-simvastatin acid (activated simvastatin) suppressed IL-5 and IL-13 in pure Th2- and Tc2-cells. Simvastatin suppressed IL-5 and IL-13 in Th2-cells co-cultivated with monocytes or AM, which was partially reversed by the carboxylesterase inhibitor benzil. Simvastatin suppressed IL-5 production of Th2/Tc2-cells in PBMCs without differences between cohorts and IL-13 stronger in never-smokers and asthma compared to COPD. Simvastatin induced IFNγ in Th1/Tc1-cells in PBMCs of all cohorts except asthmatics. Simvastatin requires activation in accessory cells likely by carboxylesterase to suppress IL-5 and IL-13 in Th2/Tc2-cells. The effects on Il-13 are partially reduced in COPD. Asthma pathogenesis prevents simvastatin-induced IFNγ up-regulation. Simvastatin has anti-inflammatory effects that could be of interest for asthma therapy.

  3. Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

    Directory of Open Access Journals (Sweden)

    Hou Ssu-Yu

    2010-06-01

    Full Text Available Abstract Background 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors (statins have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. Methods The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. Results Simvastatin (20-50 μM exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin. Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2 formation, and phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP phosphorylation, and endothelial nitric oxide synthase (eNOS expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCγ2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. Conclusion The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP

  4. Osteogenic induction of bone marrow-derived stromal cells on simvastatin-releasing, biodegradable, nano- to microscale fiber scaffolds.

    Science.gov (United States)

    Wadagaki, Ryu; Mizuno, Daiki; Yamawaki-Ogata, Aika; Satake, Makoto; Kaneko, Hiroaki; Hagiwara, Sumitaka; Yamamoto, Noriyuki; Narita, Yuji; Hibi, Hideharu; Ueda, Minoru

    2011-07-01

    Tissue engineering is an effective approach for the treatment of bone defects. Statins have been demonstrated to promote osteoblastic differentiation of bone marrow-derived stromal cells (BMSCs). Electrospun biodegradable fibers have also shown applicability to drug delivery in the form of bone tissue engineered scaffolds with nano- to microscale topography and high porosity similar to the natural extracellular matrix (ECM). The aim of this study was to investigate the feasibility of a simvastatin-releasing, biodegradable, nano- to microscale fiber scaffold (SRBFS) for bone tissue engineering with BMSCs. Simvastatin was released from SRBFS slowly. BMSCs were observed to spread actively and rigidly adhere to SRBFS. BMSCs on SRBFS showed an increase in alkaline phosphatase activity 2 weeks after cell culture. Furthermore, osteoclastogenesis was suppressed by SRBFS in vitro. The new bone formation and mineralization in the SRBFS group were significantly better than in the biodegradable fiber scaffold (BFS) without simvastatin 12 weeks after implantation of the cell-scaffold construct into an ectopic site on the murine back. These results suggest that SRBFS promoted osteoblastic differentiation of BMSCs in vitro and in vivo, and demonstrate feasibility as a bone engineering scaffold.

  5. Effect of simvastatin on expression of IL17, HMGB1 and TLR4 in LN kidney tissues of rats

    Institute of Scientific and Technical Information of China (English)

    Ying Qin; Ya-Ting Sun; Lin-Xia Xia; Ying-Jie Zhang; Xue-Jun Yang

    2014-01-01

    Objective:To observe the intervention influence and effect of simvastatin on the expression of interleukin17(LI17), high mobility group protein1(HMGB1) andTLR4 path inLupus nephritis (LN) rats.Methods:A total of28BSXSB male mice withLN(16 weeks) were randomly divided into observation group and the comparison group, observation group was given6 mg•kg-1•d-1 simvastatin in0.1%PBS lavage for4 weeks, the comparison group was not given any treatment. Blood urea nitrogen(BUN) level and urine trace albumin(Scr) level of two groups were determined. The expression ofIL17,HMGB1 andTLR4 protein was detected using immune histochemical method, and the kidney histological damage was observed.Results:BNU,LI17,HMGB1,TLR4 protein andHMGB1 mRNA in observation group was significantly lower than that in control group (P0.05).Histological observation showed glomerular lesions integral of observation group was obviously lower than that of control group.Conclusions:Simvastatin can reduce the expression ofIL17,HMGB1 and TLR4 protein inLN mice, thereby can inhibit the autoimmune response as a potential treatment function ofLN.

  6. Cutaneous dosimetry at low and high dose; Dosimetrie cutanee a faible et forte dose

    Energy Technology Data Exchange (ETDEWEB)

    Martin, M. [CEA, iRCM, Laboratoire de Genomique et Radiobiologie de la Keratinopoiese, 2 rue G Cremieux, Evry, 91057, Evry cedex (France)

    2009-07-01

    As radiodermatitis is a complication related to the exposure to ionizing radiation after an accidental exposition or a medical examination (radiotherapy or interventional radiology), the author briefly reports an investigation of the response of the human keratinocyte to irradiation for different dose levels, and the search for exposure markers

  7. The application of high dose food irradiation in South Africa

    Science.gov (United States)

    de Bruyn, Ingrid Nine

    2000-03-01

    During the 1950s to the end of the 1970s the United States Army developed the basic methodology to produce shelf-stable irradiated meat, seafood and poultry products. These products are normally packed without gravy, sauce or brine, as liquid is not required to sterilize the product as in the canning process. This leads to the distinctive "dried cooked" taste normally associated with roasts opposed to the casserole taste usually associated with tinned meats. The Biogam group at the Atomic Energy Corporation of South Africa is currently producing shelf-stable irradiated meats on a commercial basis. The meats are cooked, chilled, portioned, vacuum packed and irradiated to the required minimum dose of 45 kGy at a temperature of between -20 and -40°C to ensure absolute sterility even under tropical conditions. The product is packaged in a high quality four layer laminate pouch and will therefore not rust or burst even under adverse weather conditions and can be guaranteed for more than two years as long as the integrity of the packaging is maintained. Safari operators in remote parts of Africa, mountaineers, yachtsmen, canoeists and geological survey teams currently use shelf-stable irradiated meat products produced in South Africa.

  8. Displacement damage effects in silicon MEMS at high proton doses

    Science.gov (United States)

    Gomes, João; Shea, Herbert R.

    2011-02-01

    We report on a study of the sensitivity of silicon MEMS to proton radiation and mitigation strategies. MEMS can degrade due to ionizing radiation (electron-hole pair creation) and non-ionizing radiation (displacement damage), such as electrons, trapped and solar protons, or cosmic rays, typically found in a space environment. Over the past few years there has been several reports on the effects of ionizing radiation in silicon MEMS, with failure generally linked to trapped charge in dielectrics. However there is near complete lack of studies on displacement damage effects in silicon- MEMS: how does silicon change mechanically due to proton irradiation? We report on an investigation on the susceptibility of 50 μm thick SOI-based MEMS resonators to displacement damages due to proton beams, with energies from 1 to 60 MeV, and annealing of this damage. We measure ppm changes on the Young's modulus and Poisson ratio by means of accurately monitoring the resonant frequency of devices in vacuum using a Laser Doppler Vibrometer. We observed for the first time an increase (up to 0.05%) of the Young's modulus of single-crystal silicon electromagnetically-actuated micromirrors after exposure to low energy protons (1-4 MeV) at high absorbed doses ~ 100 Mrad (Si). This investigation will contribute to a better understanding of the susceptibility of silicon-based MEMS to displacement damages frequently encountered in a space radiation environment, and allow appropriated design margin and shielding to be implemented.

  9. Malignancies in patients treated with high doses of radium-224

    Energy Technology Data Exchange (ETDEWEB)

    Nekolla, E.A. [Federal Office for Radiation Protection (BfS), Neuherberg (Germany); Walsh, L. [Radiobiological Inst., Univ. of Munich (Germany); Schottenhammer, G.; Spiess, H. [Children' s Hospital, Univ. of Munich (Germany)

    2005-07-01

    Several thousand German patients suffering from ankylosing spondylitis, tuberculosis and some other diseases, received multiple injections of the short-lived {alpha}-emitter {sup 224}Ra. The ''Spiess study'' was initiated in the early 1950s to follow the health of 899 persons (278 female, 621 male) who were treated mainly between 1945 and 1955. Most of the high dose patients and nearly all of those treated as children or juveniles (n=217) were included in the study. In June 2003, 152 persons were still alive. The most striking observed health effect, following {sup 224}Ra injections, was a temporal wave of 56 malignant bone tumours with a maximum at about 8 years after exposure which has already been described in several publications. In 2000, a new analysis was performed because an improved dosimetry resulted in modified bone surface doses. The estimated risk coefficient, averaged over all ages at exposure, was found to be in agreement with earlier analyses. However, a statistically significant increase of bone tumour risk with decreasing age at exposure was found. The earlier results, which indicated a reversed protraction factor, were confirmed. A significant excess of non-skeletal solid malignancies has also appeared during the most recent observation decade. In 2004, significant increases of cancer rates were observed for several sites: for breast cancer (31 cases observed vs. 9.1 cases expected), soft tissue malignancies (11 vs. 1.0), thyroid carcinomas (7 vs. 0.9), liver (8 vs. 2.3), kidney (13 vs. 4.6), pancreas (8 vs. 3.9), and bladder cancer (14 vs. 7.7). The 8-fold excess relative risk of mammary cancers in those women exposed as children or juveniles is particularly striking; moreover, 2 cases of breast cancer occurred in men. In 1993, a control group of tuberculosis patients not treated with {sup 224}Ra was established to rule out potential confounding factors - such as chest fluoroscopy - which might bias the breast cancer excess

  10. Protective effect of simvastatin and rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats

    Directory of Open Access Journals (Sweden)

    Rajesh A Maheshwari

    2015-01-01

    Conclusions: These results suggest that simvastatin and rosuvastatin significantly ameliorate experimental colitis in rats, and these effects could be explained by their anti-inflammatory and antioxidant activity.

  11. Influence of particle size and preparation methods on the physical and chemical stability of amorphous simvastatin

    DEFF Research Database (Denmark)

    Zhang, Fang; Aaltonen, Jaakko; Tian, Fang

    2009-01-01

    molecular mobility and higher chemical degradation than CM. Therefore, the current study demonstrated that QC and CM have obvious differences in both physical and chemical properties. It was concluded that care should be taken when choosing preparation methods for making amorphous materials. Furthermore......, particle size, a factor that has often been overlooked when dealing with amorphous materials, was shown to have an influence on physical stability of amorphous simvastatin.......This study investigated the factors influencing the stability of amorphous simvastatin. Quench-cooled amorphous simvastatin in two particle size ranges, 150-180 microm (QC-big) and amorphous simvastatin (CM) were prepared, and their physical and chemical...

  12. Simvastatin Effect on Calcium and Silicon Plasma Levels in Postmenopausal Women with Osteoarthritis.

    Science.gov (United States)

    Horecka, Anna; Hordyjewska, Anna; Blicharski, Tomasz; Kocot, Joanna; Żelazowska, Renata; Lewandowska, Anna; Kurzepa, Jacek

    2016-05-01

    Postmenopausal women more often suffered from knee osteoarthritis and its pathogenesis still remains unclear. Calcium and silicon are significant elements involved in bone and joint metabolism, especially in older people. Cardiovascular diseases are common worldwide and simvastatin is the most prescribed drug in such population of patients. The purpose of this study was to evaluate the effect of simvastatin administration on calcium and silicon concentration in the plasma of postmenopausal women with osteoarthritis. Sixty postmenopausal mild hypercholesterolemic women (mean age 61.4 years, range 54-68) were enrolled. Thirty patients received simvastatin (20 or 40 mg/day) for at least 1 year before being enrolled (simvastatin "+" group). Control group consists of remaining 30 women (simvastatin "-"group). Silicon and calcium concentrations were measured spectrophotometrically. Plasma simvastatin level was determined 3 h after the drug administration using HPLC-UV-Vis. Calcium but not silicon level was significantly lower in patients receiving simvastatin in comparison with non-statin group (1.91 ± 0.32 vs. 2.33 ± 0.19 mmol/l, p silicon and simvastatin levels (r = 0.3, p silicon dioxide as an inactive ingredient. The mean simvastatin concentration was 9.02 ng/ml. All hypotheses were verified at the significance level of p silicon level in the plasma suggests that both might prompt the positive effect of osteoarthritis treatment.

  13. Modulation of the proteolytic cascade systems by high dose corticosteroids.

    Science.gov (United States)

    Aasen, A O; Ruud, T E; Pillgram-Larsen, J; Röise, O; Stadaas, J

    1985-01-01

    The effects of high-dose corticosteroids (HDC) on activities within the proteolytic cascade systems were studied in vitro and in vivo using chromogenic peptide substrate assays. In in vitro experiments 20 mg methylprednisolone sodium succinate (Solu-Medrol) per ml plasma significantly inhibited activation of plasma prekallikrein, prothrombin and plasminogen and reduced functional plasma kallikrein inhibition, antithrombin and antiplasmin activities. The effects of HDC on activities within these proteolytic cascade systems were further evaluated in experimental acute pancreatitis in pigs. Acute pancreatitis was induced by injection of Na-taurocholate into the pancreatic duct. Seven test animals received methylprednisolone sodium succinate 30 mg per kg intravenously for 30 minutes before the induction of pancreatitis as pretreatment. Eight animals remained untreated. Trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and mean arterial pressure (MAP) were monitored regularly before and during a 6 hour observation period. During untreated pancreatitis a reduction of PKK levels of about 40% were found, paralleled by an increased KK activity and a reduction of KKI capacity. Several of the animals experienced high TRY activities. The mortality rate was 63% (5 out of 8 animals). In the pretreated groups, all animals survived the observation period. CO and MAP were significantly less reduced than the untreated group at 6 hours. HDC was also found to reduce significantly plasma kallikrein activities in the peritoneal exudate compared with untreated animals. No changes in TRY activities were found in pretreated animals. Furthermore, plasma prekallikrein and functional plasma kallikrein inhibition values in the exudate were elevated significantly in HDC treated animals compared with untreated animals.

  14. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk.

    Directory of Open Access Journals (Sweden)

    Susan C Irvin

    Full Text Available Epidemiological studies suggest that medroxyprogesterone acetate (MPA may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms.Human vaginal epithelial (VK2/E6E7, peripheral blood mononuclear (PBMC, and polarized endometrial (HEC-1-A cells were treated with a range of concentrations of MPA (0.015-150 μg/ml and the impact on gene expression, protein secretion, and HIV infection was evaluated.Treatment of VK2/E6E7 cells with high doses (>15 μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively.We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo.

  15. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk.

    Science.gov (United States)

    Irvin, Susan C; Herold, Betsy C

    2015-01-01

    Epidemiological studies suggest that medroxyprogesterone acetate (MPA) may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms. Human vaginal epithelial (VK2/E6E7), peripheral blood mononuclear (PBMC), and polarized endometrial (HEC-1-A) cells were treated with a range of concentrations of MPA (0.015-150 μg/ml) and the impact on gene expression, protein secretion, and HIV infection was evaluated. Treatment of VK2/E6E7 cells with high doses (>15 μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively. We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml) MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo.

  16. Antagonism by idazoxan at low dose but not high dose, of the natriuretic action of moxonidine.

    OpenAIRE

    D. R. Allan; Penner, S. B.; Smyth, D. D.

    1996-01-01

    1. Recent studies concerning the imidazoline receptor have utilized idazoxan as a specific imidazoline receptor antagonist. The aim of the present study was to describe the in vivo effects of various doses of idazoxan on renal function, in the presence and absence of moxonidine, an I1 imidazoline receptor agonist. 2. In anaesthetized, unilaterally nephrectomized (7 to 10 days) Sprague Dawley rats, an intrarenal infusion of moxonidine (3 nmol kg-1 min-1) increased urine flow rate, sodium excre...

  17. Chemotherapy of onchocerciasis with high doses of diethylcarbamazine or a single dose of ivermectin: microfilaria levels and side effects.

    Science.gov (United States)

    Albiez, E J; Newland, H S; White, A T; Kaiser, A; Greene, B M; Taylor, H R; Büttner, D W

    1988-03-01

    Fifty adult male subjects with moderate to heavy onchocerciasis from the Liberian rain forest were selected for a double-blind placebo-controlled chemotherapy study. The effects of high doses of diethylcarbamazine (DEC) - 30 mg/kg/d - over one week preceded by a one week initial treatment with normal oral doses of DEC or DEC lotion were compared with a single dose of ivermectin (150 micrograms/kg) and placebo. During the initial treatment DEC tablets or lotion caused distinctly more frequent and severe reactions than did invermectin. The reactions to ivermectin did not differ from those of the placebo patients. High doses of DEC caused, in about half of the patients, headache, dizziness, nausea or vomiting. DEC markedly increased the number of corneal microfilariae and of corneal opacities compared to ivermectin. All changes resolved with a return to pretreatment findings two months after treatment. The three treatment groups showed no differences at the ten months follow-up. In all treated patients skin microfilaria counts fell almost to zero by the end of the two week therapy. In the ivermectin group microfilaria counts remained significantly lower than in the DEC patients at the two and ten months examinations. In summary, ivermectin was much better tolerated than DEC and had a longer lasting effect on the microfilariae in the skin. Since high doses of DEC were less effective and caused more frequent and severe side effects, this approach cannot be recommended for treatment of onchocerciasis.

  18. Dose conversion coefficients for high-energy photons, electrons, neutrons and protons

    CERN Document Server

    Sakamoto, Y; Sato, O; Tanaka, S I; Tsuda, S; Yamaguchi, Y; Yoshizawa, N

    2003-01-01

    In the International Commission on Radiological Protection (ICRP) 1990 Recommendations, radiation weighting factors were introduced in the place of quality factors, the tissue weighting factors were revised, and effective doses and equivalent doses of each tissues and organs were defined as the protection quantities. Dose conversion coefficients for photons, electrons and neutrons based on new ICRP recommendations were cited in the ICRP Publication 74, but the energy ranges of theses data were limited and there are no data for high energy radiations produced in accelerator facilities. For the purpose of designing the high intensity proton accelerator facilities at JAERI, the dose evaluation code system of high energy radiations based on the HERMES code was developed and the dose conversion coefficients of effective dose were evaluated for photons, neutrons and protons up to 10 GeV, and electrons up to 100 GeV. The dose conversion coefficients of effective dose equivalent were also evaluated using quality fact...

  19. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis

    DEFF Research Database (Denmark)

    Rossebo, A.B.; Pedersen, T.R.; Boman, K.

    2008-01-01

    failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events. RESULTS: During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35...... of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01). CONCLUSIONS: Simvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis......BACKGROUND: Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results. METHODS: We conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients...

  20. Biological impact of high-dose and dose-rate radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Maliev, V.; Popov, D. [Russian Academy of Science, Vladicaucas (Russian Federation); Jones, J.; Gonda, S. [NASA -Johnson Space Center, Houston (United States); Prasad, K.; Viliam, C.; Haase, G. [Antioxida nt Research Institute, Premier Micronutrient Corporation, Novato (United States); Kirchin, V. [Moscow State Veterinary and Biotechnology Acade my, Moscow (Russian Federation); Rachael, C. [University Space Research Association, Colorado (United States)

    2006-07-01

    Experimental anti-radiation vaccine is a power tool of immune - prophylaxis of the acute radiation disease. Existing principles of treatment of the acute radiation dis ease are based on a correction of developing patho-physiological and biochemical processes within the first days after irradiation. Protection from radiation is built on the general principles of immunology and has two main forms - active and passive immunization. Active immunization by the essential radiation toxins of specific radiation determinant (S.D.R.) group allows significantly reduce the lethality and increase duration of life among animals that are irradiated by lethal and sub-lethal doses of gamma radiation.The radiation toxins of S.D.R. group have antigenic properties that are specific for different forms of acute radiation disease. Development of the specific and active immune reaction after intramuscular injection of radiation toxins allows optimize a manifestation of a clinical picture and stabilize laboratory parameters of the acute radiation syndromes. Passive immunization by the anti-radiation serum or preparations of immune-globulins gives a manifestation of the radioprotection effects immediately after this kind of preparation are injected into organisms of mammals. Providing passive immunization by preparations of anti-radiations immune-globulins is possible in different periods of time after radiation. Providing active immunization by preparations of S.D.R. group is possible only to achieve a prophylaxis goal and form the protection effects that start to work in 18 - 35 days after an injection of biological active S.D.R. substance has been administrated. However active and passive immunizations by essential anti-radiation toxins and preparations of gamma-globulins extracted from a hyper-immune serum of a horse have significantly different medical prescriptions for application and depend on many factors like a type of radiation, a power of radiation, absorption doses, a time of

  1. Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays.

    Science.gov (United States)

    Vinnikov, Volodymyr A; Maznyk, Nataliya A

    2013-04-01

    The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ∼2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)Со gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ≥6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129×cell(-1)×Gy(-1) and 0.039-0.034×cell(-1)×Gy(-2), respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed.

  2. Effectiveness of High Dose Pralidoxime for Treatment of Organophosphate Poisoning

    Directory of Open Access Journals (Sweden)

    Pham Due

    2014-09-01

    Full Text Available Background: For effective treatment of organophosphate (OP poisoning, development of a standardized protocol with flexible dose regimen for atropine and pralidoxime is an essential step. In this study, we aimed to assess the protocol devised in our setting; Bach Mai Hospital Poison Treatment Center, for treatment of OP poisoning that included a higher dose regimen of pralidoxime (2PAM. Methods: A protocol for treatment of OP poisoning was developed during 1995 to 1996, which included an atropinization scoring scale and a modification of 2PAM dose regimen. In this study, OP poisoned patients who were treated during 1997 to 2002 with the new protocol (study group or cases were compared with historical control group which included OP poisoned patients treated between 1993 and 1994 prior to establishment of the new protocol. Results: One-hundred and eight cases and 54 controls were included. The cases and controls were not significantly different according to age, gender and plasma cholinesterase activity on admission from each other. There was no significant difference of mean duration of 2PAM therapy between the two groups. The controls received mean total 2PAM dose of 7.2±4.1 g, while the patients in the study group received 20.0±12.7 g which was 2.77 times higher than the dose for control group (P

  3. Pharmacogenetics of response to simvastatin in Chinese patients with hyperlipidaemia

    Institute of Scientific and Technical Information of China (English)

    TOMLINSON B; MAK V W L; HU M; CHU T T W; TSUI T; LEE V W Y

    2008-01-01

    Objective To examine the relationship of single-nucleotide polymorphisms (SNPs) in candidate genes with the lipid responses to simvastatin. Methods Chinese patients were treated with simvastatin 40 mg daily for at least 6 weeks. 20 SNPs in 11 genes were genotyped. Results 95 patients age (mean±SD) 57.5±10.6 years completed the treatment. The Adiponectin 45 T > G polymorphism was significantly related to absolute reductions in total cholesterol (TC) and LDL-ehohsterol with a trend (P=0.053) for percentage reductions in TC(TT: TG: GG =-38.4% :-35.6% :-32.6%). Similar findings were seen with LDL-Receptor (LDLR) SNPs (2052T > C and 1866C > T) with absolute reductions in TC and LDL-cholesterol significantly associated. The Breast Cancer Resistance Protein (ABCG2) 421C > A polymorphism was related (P<0.05) to HDL-cholesterol response ( CC : CA : AA =+0.50% : - 5.73% : -11.41% ). Conclusions Adiponeetin, LDLR and ABCG2 SNPs had some influence on the lipid responses to simvastatin.

  4. Adjuvant effects of classical music on simvastatin induced reduction of anxiety but not object recognition memory in rats

    OpenAIRE

    Camargo, Anice Milbratz de; Lima,Daniela Delwing de; Dal Magro,Débora Delwing; Seubert,Johanna Kleis; Cruz,Júlia Niehues da; Cruz,José Geraldo Pereira da

    2013-01-01

    Simvastatin is one of many hydroxymethylglutaryl-coenzyme-A reductase inhibitors that are prescribed to lower cholesterol. Some emerging evidence indicates that classical music can serve as an effective adjuvant in rats treated with simvastatin. Moreover, simvastatin and classical music have been shown to influence some cognitive functions. To further understand the mechanisms of action, we exposed rats to classical music for 1 month, and then treated them orally with simvastatin. The behavio...

  5. High-Dose-Rate Prostate Brachytherapy Consistently Results in High Quality Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    White, Evan C.; Kamrava, Mitchell R.; Demarco, John; Park, Sang-June; Wang, Pin-Chieh; Kayode, Oluwatosin; Steinberg, Michael L. [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, California (United States); Demanes, D. Jeffrey, E-mail: jdemanes@mednet.ucla.edu [California Endocurietherapy at UCLA, Department of Radiation Oncology, David Geffen School of Medicine of University of California at Los Angeles, Los Angeles, California (United States)

    2013-02-01

    Purpose: We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. Methods and Materials: Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. Results: The mean prostate ultrasound volume was 38.7 {+-} 13.4 cm{sup 3} (range: 11.7-108.6 cm{sup 3}). The mean CTV was 75.1 {+-} 20.6 cm{sup 3} (range: 33.4-156.5 cm{sup 3}). The mean D90 was 109.2% {+-} 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% {+-} 0.05%, 99.5% {+-} 0.8%, 25.4% {+-} 4.2%, and 7.8% {+-} 1.4%. The mean dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} for organs at risk were: Urethra: 107.3% {+-} 3.0%, 101.1% {+-} 14.6%, and 47.9% {+-} 34.8%; bladder wall: 79.5% {+-} 5.1%, 69.8% {+-} 4.9%, and 64.3% {+-} 5.0%; bladder balloon: 70.3% {+-} 6.8%, 59.1% {+-} 6.6%, and 52.3% {+-} 6.2%; rectum: 76.3% {+-} 2.5%, 70.2% {+-} 3.3%, and 66.3% {+-} 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. Conclusions: HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

  6. Medication error - Inadvertent high dose intradermal cloxacillin induced skin necrosis

    Directory of Open Access Journals (Sweden)

    Adithan Surendiran

    2012-01-01

    Full Text Available Medication error is one of the important causes of preventable adverse drug reactions. It can occur in the form of administration of a wrong drug, in the wrong dose, to the wrong patient, in an unsuitable dosage form, for the wrong duration or by using an inappropriate route of administration. Intradermal skin testing for cloxacillin hypersensitivity is done at low doses to check for drug allergy. In this report, three patients were given 50 times higher dose of cloxacillin than recommended for skin testing, resulting in pain and necrosis at the site of injection. The error occurred due to wrong dilution of the drug as done by a nursing intern. Some reasons for this could be overtime working, under trained staff, unsupervised nursing interns, complicated and unclear protocols, interpersonal communication gap between health care professionals and also poor availability of ideal resources. Pharmacovigilance centers must alert health care professionals about the significance of reporting medication errors through bulletins and journals.

  7. ``In Vivo'' Dosimetry in High Dose Rate Brachytherapy for Cervical Cancer Treatments

    Science.gov (United States)

    González-Azcorra, S. A.; Mota-García, A.; Poitevín-Chacón, M. A.; Santamaría-Torruco, B. J.; Rodríguez-Ponce, M.; Herrera-Martínez, F. P.; Gamboa de Buen, I.; Ruíz-Trejo, C.; Buenfil, A. E.

    2008-08-01

    In this prospective study, rectal dose was measured "in vivo" using TLD-100 crystals (3×3×1 mm3), and it has been compared to the prescribed dose. Measurements were performed in patients with cervical cancer classified in FIGO stages IB-IIIB and treated with high dose rate brachytherapy (HDR BT) at the Instituto Nacional de Cancerología (INCan).

  8. [The hypotriglyceridemic action of the combination of L-carnitine + simvastatin vs. L-carnitine and vs. simvastatin].

    Science.gov (United States)

    Savica, V; Bellinghieri, G; Lamanna, F

    1992-01-01

    Previous studies had determined the role played by L-carnitine and simvastatin in the treatment of altered lipidemia in dialyzed patients with chronic uremia. The authors carried out a study on the above substances either singly or together administered to the same patients with chronic uremia in hemodialysis. This study was aimed at demonstrating the possible synergic normolipidemic action of both substances in comparison with their single administration, because their different mechanism of action could be metabolically enhanced. The obtained results demonstrated that the therapeutic association proposed is preferable to the use of the single substances. Moreover, a higher and more rapid normolipidemic effect was obtained after using L-carnitina associated with simvastatin with respect to the separated substances.

  9. Effect of vitamin D on bioavailability and lipid lowering efficacy of simvastatin.

    Science.gov (United States)

    Al-Asmari, Abdulrahman K; Ullah, Zabih; Al-Sabaan, Fahad; Tariq, Mohammad; Al-Eid, Ahmed; Al-Omani, Saud F

    2015-03-01

    The 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors known as "statins" are widely prescribed for the management of dyslipidemia. In spite of their muscle toxicity, use of statins has alarmingly increased worldwide. A recent report suggests that vitamin D (VD) levels are closely associated with lipid lowering activity and muscular toxicity of statins. However, data are limited and inconclusive. The present study was undertaken to investigate the effect of VD supplementation on the bioavailability and lipid lowering effect of simvastatin (ST). Adult Sprague-Dawley male rats (250 ± 10 g) were divided into four groups including control, ST (100 mg/kg/day), VD (100 μg/kg/day) and ST + VD group, respectively. After the dosing period of 8 days the animals were sacrificed and the blood was collected for the analysis of ST, its active metabolite simvastatin acid (STA), total cholesterol, triglyceride and liver enzymes including aspartate transaminase and alanine transaminase. The result of this study showed a significant decrease in the level of cholesterol and triglyceride in ST alone treated group, whereas VD alone failed to alter the blood lipid levels. Concomitant treatment with VD produced significant decrease in the bioavailability of ST and STA. However, there was no significant difference in the level of cholesterol in ST alone and in ST + VD treated group. Our results on the liver enzyme suggest that ST alone or in combination with VD does not produce any hepatotoxicity. Further studies using VD along with various statins for a longer duration are suggested.

  10. Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease.

    Science.gov (United States)

    Darlington, Andrew; Tello-Montoliu, Antonio; Rollini, Fabiana; Ueno, Masafumi; Ferreiro, José Luis; Patel, Ronakkumar; Desai, Bhaloo; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2014-02-01

    Increased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with high-dose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m²] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m² completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.

  11. Effect of simvastatin on the expression of farnesoid X receptor in diabetic animal models of altered glucose homeostasis

    Institute of Scientific and Technical Information of China (English)

    Wang Lulu; Huang Xianping; Hu Su; Ma Xiaoli; Wang Shaolian; Pang Shuguang

    2014-01-01

    Background Statin therapy has affected glucose homoeostasis of type 2 diabetes patients,which could be related with bile acids metabolism.Whether bile acid metabolism and the expression of farnesoid X receptor (FXR),liver X receptor-α (LXR-α) and sterol regulatory element-binding protein (Srebp)-1c is regulated by hyperglycemia,or whether simvastatin therapy led to higher glucose is related with down-regulated expression of FXR in diabetic rats remained unclear.Methods Forty male Wistar rats were randomly divided into four groups:normal control rats,insulin resistance rats,diabetic model rats,and the late simvastatin induced diabetic rats.Normal control rats were fed with standard diet,others were fed with high-fat diet.Diabetic model rats were induced by a single intraperitoneal injection of streptozotocin (STZ).The late simvastatin induced diabetic rats started simvastatin administration after STZ induced diabetic model rats.Characteristics of fasting blood glucose (FPG),lipid files and total bile acids (TBAs) were measured and the oral glucose tolerance test (OGTT) was performed after overnight fasting at the eighth weekend.RNA and protein levels of FXR,LXR-α and Srebp-1c were tested by Western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results The insulin resistance rats showed higher glucose,lipid files and lower expression of FXR compared with normal control rats (P >0.05).The diabetic model rats showed significantly higher glucose,lipid files,TBA and lower expression of FXR compared with insulin resistance rats (P <0.05).The late simvastatin induced diabetic rats displayed higher glucose and TBA and lower expression of FXR compared with diabetic model rats (P <0.05).Conclusions Changes in bile acid homeostasis,including the alterations of bile acid levels and bile acid receptors,are either a cause or a consequence of the metabolic disturbances observed during diabetic models.Statin therapy induced hyperglycemia may be

  12. Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

    Science.gov (United States)

    Leyvraz, S; Herrmann, R; Guillou, L; Honegger, H P; Christinat, A; Fey, M F; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B

    2006-11-20

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

  13. Isoniazid overdose treated with high-dose pyridoxine.

    Science.gov (United States)

    Yarbrough, B E; Wood, J P

    1983-05-01

    Large doses of pyridoxine recently have been shown to prevent the seizures and acidosis caused by ingestion of more than two to three grams of isoniazid. We present three cases of massive isoniazid ingestion, producing seizures and acidosis, that were treated successfully by administration of one gram of pyridoxine intravenously for each gram of isoniazid ingested.

  14. Applicator Attenuation Effect on Dose Calculations of Esophageal High-Dose Rate Brachytherapy Using EDR2 Film

    Directory of Open Access Journals (Sweden)

    Seyed Mohsen Hosseini Daghigh

    2012-03-01

    Full Text Available Introduction Interaluminal brachytherapy is one of the important methods of esophageal cancer treatment. The effect of applicator attenuation is not considered in dose calculation method released by AAPM-TG43. In this study, the effect of High-Dose Rate (HDR brachytherapy esophageal applicator on dose distribution was surveyed in HDR brachytherapy. Materials and Methods A cylindrical PMMA phantom was built in order to be inserted by various sizes of esophageal applicators. EDR2 films were placed at 33 mm from Ir-192 source and irradiated with 1.5 Gy after planning using treatment planning system for all applicators. Results The results of film dosimetry in reference point for 6, 8, 10, and 20 mm applicators were 1.54, 1.53, 1.48, and 1.50 Gy, respectively. The difference between practical and treatment planning system results was 0.023 Gy (

  15. Effect of Taizhi'an Capsule (泰脂安胶囊)Combined with Simvastatin on Hyperlipidemia in Diabetic Patients

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To evaluate the effectiveness and safety of Taizhian (泰脂安, TZA) capsule combined with Simvastatin (Sim) in treating hyperlipidemia in diabetes mellitus (DM) patients. Methods:Eighty cases of type 2 DM patients with hyperlipidemia were randomized into two groups, 40 in each group.The patients in the treated group took orally TZA capsules at the dose of 0.9 g 3 times a day and Sim 10 mg at bedtime. And the patients in the control group were treated with Sim 20 mg alone at bedtime. Both regimens lasted for 12 weeks. Before and after the study the changes of blood lipid levels and adverse reaction were investigated. Results: The serum levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) were decreased respectively by 28.8%, 18.2% and 26.3% in the treated group; and by 29.4%, 19.4% and 24.6% in the control group. On the contrary, high density lipoprotein-cholesterol (HDL-C) was increased by 23.5% in the treated group and by 29.4% in the control group. All these changes were statistically significant before and after treatment (all P<0.05), but they did not differ statistically between the two groups (P>0.05). There was no significant changes in hemoglobin A1 c (HbA1C). Patients in the treated group did not develop any adverse reactions. However, ALT was found to be higher above the normal range in 5% of the patients in the control group. Conclusion: In treating hyperlipidemia in DM patients, combination of TZA with Sim 10 mg taken daily achieved satisfactory efficacy which was similar to Sim 20 mg daily alone. But the combination therapy conducted in the treated group proved to be better in safety, and could overcome adverse reactions resulting from Sim that was seen in the control group.

  16. Irradiation dose and temperature dependence of fracture toughness in high dose HT9 steel from the fuel duct of FFTF

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Thak Sang; Toloczko, Mychailo B.; Saleh, Tarik A.; Maloy, Stuart A.

    2013-01-14

    To expand the knowledge base for fast reactor core materials, fracture toughness has been evaluated for high dose HT9 steel using miniature disk compact tension (DCT) specimens. The HT9 steel DCT specimens were machined from the ACO-3 fuel duct of the Fast Flux Test Facility (FFTF), which achieved high doses in the range of 3–148 dpa at 378–504 C. The static fracture resistance (J-R) tests have been performed in a servohydraulic testing machine in vacuum at selected temperatures including room temperature, 200 C, and each irradiation temperature. Brittle fracture with a low toughness less than 50 MPa pm occurred in room temperature tests when irradiation temperature was below 400 C, while ductile fracture with stable crack growth was observed when irradiation temperature was higher. No fracture toughness less than 100 MPa pm was measured when the irradiation temperature was above 430 C. It was shown that the influence of irradiation temperature was dominant in fracture toughness while the irradiation dose has only limited influence over the wide dose range 3–148 dpa. A slow decrease of fracture toughness with test temperature above room temperature was observed for the nonirradiated and high temperature (>430 *C) irradiation cases, which indicates that the ductile–brittle transition temperatures (DBTTs) in those conditions are lower than room temperature. A comparison with the collection of existing data confirmed the dominance of irradiation temperature in the fracture toughness of HT9 steels.

  17. A Real World Report on Intravenous High-Dose and Non-High-Dose Proton-Pump Inhibitors Therapy in Patients with Endoscopically Treated High-Risk Peptic Ulcer Bleeding

    Directory of Open Access Journals (Sweden)

    Lung-Sheng Lu

    2012-01-01

    Full Text Available Background and Study Aims. The optimal dose of intravenous proton-pump inhibitor (PPI therapy for the prevention of peptic ulcer (PU rebleeding remains controversial. This study aimed to understand the real world experiences in prescribing high-dose PPI and non-high-dose PPI for preventing rebleeding after endoscopic treatment of high-risk PU. Patients and Methods. A total of 220 subjects who received high-dose and non-high-dose pantoprazole for confirmed acute PU bleeding that were successfully treated endoscopically were enrolled. They were divided into rebleeding (n=177 and non-rebleeding groups (n=43. Randomized matching of the treatment-control group was performed. Patients were randomly selected for non-high-dose and high-dose PPI groups (n=44 in each group. Results. Univariate analysis showed, significant variables related to rebleeding were female, higher creatinine levels, and higher Rockall scores (≧6. Before case-control matching, the high-dose PPI group had higher creatinine level, higher percentage of shock at presentation, and higher Rockall scores. After randomized treatment-control matching, no statistical differences were observed for rebleeding rates between the high-dose and non-high-dose groups after case-control matching. Conclusion. This study suggests that intravenous high-dose pantoprazole may not be superior to non-high-dose regimen in reducing rebleeding in high-risk peptic ulcer bleeding after successful endoscopic therapy.

  18. Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia

    Directory of Open Access Journals (Sweden)

    Kevin D. Ballard

    2015-01-01

    Full Text Available Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n=115 completed an 8 wk randomized, double-blind, cross-over trial of daily simvastatin 20 mg and placebo. Serum lipids and pulse wave velocity (PWV were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%. Compared to baseline, central PWV decreased (P=0.01 following simvastatin treatment but not placebo (drug ∗ time interaction: P=0.047. Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P≥0.15. Change in central PWV after simvastatin treatment was inversely correlated with age (r=-0.207, P=0.030, suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness.

  19. HDRMC, an accelerated Monte Carlo dose calculator for high dose rate brachytherapy with CT-compatible applicators

    Energy Technology Data Exchange (ETDEWEB)

    Chibani, Omar, E-mail: omar.chibani@fccc.edu; C-M Ma, Charlie [Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 (United States)

    2014-05-15

    Purpose: To present a new accelerated Monte Carlo code for CT-based dose calculations in high dose rate (HDR) brachytherapy. The new code (HDRMC) accounts for both tissue and nontissue heterogeneities (applicator and contrast medium). Methods: HDRMC uses a fast ray-tracing technique and detailed physics algorithms to transport photons through a 3D mesh of voxels representing the patient anatomy with applicator and contrast medium included. A precalculated phase space file for the{sup 192}Ir source is used as source term. HDRM is calibrated to calculated absolute dose for real plans. A postprocessing technique is used to include the exact density and composition of nontissue heterogeneities in the 3D phantom. Dwell positions and angular orientations of the source are reconstructed using data from the treatment planning system (TPS). Structure contours are also imported from the TPS to recalculate dose-volume histograms. Results: HDRMC was first benchmarked against the MCNP5 code for a single source in homogenous water and for a loaded gynecologic applicator in water. The accuracy of the voxel-based applicator model used in HDRMC was also verified by comparing 3D dose distributions and dose-volume parameters obtained using 1-mm{sup 3} versus 2-mm{sup 3} phantom resolutions. HDRMC can calculate the 3D dose distribution for a typical HDR cervix case with 2-mm resolution in 5 min on a single CPU. Examples of heterogeneity effects for two clinical cases (cervix and esophagus) were demonstrated using HDRMC. The neglect of tissue heterogeneity for the esophageal case leads to the overestimate of CTV D90, CTV D100, and spinal cord maximum dose by 3.2%, 3.9%, and 3.6%, respectively. Conclusions: A fast Monte Carlo code for CT-based dose calculations which does not require a prebuilt applicator model is developed for those HDR brachytherapy treatments that use CT-compatible applicators. Tissue and nontissue heterogeneities should be taken into account in modern HDR

  20. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline

    DEFF Research Database (Denmark)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

    2004-01-01

    OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis......) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood...... pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. RESULTS: Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration...

  1. Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma.

    Science.gov (United States)

    Avilés, Agustin; Nambo, María J; Neri, Natividad; Cleto, Sergio; Castañeda, Claudia; Huerta-Guzmàn, Judith; Murillo, Edgar; Contreras, Margarita; Talavera, Alejandra; González, Martha

    2007-01-01

    To assess efficacy and toxicity of rituximab and dose chemotherapy in high-risk diffuse large cell lymphoma, we conducted a controlled clinical trial to assess efficacy and toxicity of a dose-dense regimen CEOP- 14 (cyclophosphamide, epirubicin, vincristine, and prednisone every 14 d) compared to CEOP-14 plus rituximab. One hundred and ninety-six patients were randomized to received CEOP-rituximab (cyclophosphamide 1500 mg/m2, epirubicin 120 mg/m2, vincristine, and prednisone at standard dose and rituximab at 375 mg/m2) compared with the same chemotherapy administered every 14 d (CEOP-14). In an intent-to-treat analysis all patients were available for efficacy and toxicity. Complete response in CEOP-14 was observed in 73 cases (74%) and in 75 patients (76%) in the CEOP-R regimen (76%) (p = 0.8). With a median follow-up of 53.4 mo, median has not been reached in time to tumor-progression (TTP) and overall survival (OS). Actuarial curves at 5 yr showed that TTP and OS in patients treated with CEOP-R were 74% and 67%, respectively, that were not statistical different when compared to CEOP-14, 72% and 65%, respectively (p = 0.8). Acute toxicity was mild and well tolerated. The use of a dense-dose regimen is useful and well tolerated in patients with very high risk diffuse large cell lymphoma. The addition of rituximab did not improve outcome in these setting of patients.

  2. High-dose lidocaine does not affect defibrillation efficacy: implications for defibrillation mechanisms.

    Science.gov (United States)

    Ujhelyi, M R; Sims, J J; Miller, A W

    1998-04-01

    This study assessed the effect of low (10 mg.kg-1.h-1) and very high (18 mg.kg-1.h-1) doses of lidocaine on defibrillation energy requirements (DER) to relate changes in indexes of sodium-channel blockade with changes in DER values using a dose-response study design. In group 1 (control; n = 6 pigs), DER values were determined at baseline and during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 (n = 7), DER values were determined at baseline and during treatment with low-dose lidocaine followed by high-dose lidocaine. In group 3 (n = 3), DER values were determined at baseline and high-dose lidocaine. Group 3 controlled for the order of lidocaine treatment with the addition of high-dose lidocaine after baseline. DER values in group 1 did not change during D5W. In group 2, low-dose lidocaine increased DER values by 51% (P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of baseline values (P = 0.02, low dose vs. high dose). DER values during high-dose lidocaine in group 3 also remained near baseline values (16.2 +/- 2.7 to 12.9 +/- 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidocaine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the lidocaine dose increased. However, the greatest increase in DER occurred when ventricular fibrillation cycle length was minimally affected, demonstrating a negative correlation (P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-response curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refractoriness during ventricular fibrillation may be the electrophysiological mechanism by which high-dose lidocaine limits the adverse effects that low-dose lidocaine has on DER values

  3. Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate

    Directory of Open Access Journals (Sweden)

    Guilherme A. Eger

    2016-03-01

    Full Text Available The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a significant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These findings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest.

  4. Controlled release of simvastatin from biomimetic β-TCP drug delivery system.

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    Full Text Available Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin.

  5. High Dose Vaginal Misoprostol Versus Concentrated Oxytocin + Low Dose Vaginal Misoprostol for Mid-Trimester Labor Induction: A Randomized Trial

    Science.gov (United States)

    Nuthalapaty, Francis S.; Ramsey, Patrick S.; Biggio, Joseph R.; Owen, John

    2013-01-01

    Objective To compare the efficacy and side effects of a high-dose vaginal misoprostol regimen to concentrated intravenous oxytocin plus low-dose vaginal misoprostol for mid-trimester labor induction. Study Design Women at 14-24 weeks, with obstetric or fetal indications for delivery and no prior cesarean, were randomly assigned to receive either vaginal misoprostol 600 μg ×1, then 400 μg q 4 hr × 5 (Group 1) or escalating-dose concentrated oxytocin infusions (277-1667 mU/min) plus vaginal misoprostol 400 μg × 1, then 200 μg q 6 hr × 2, then 100 μg × 1 (Group 2). Analysis was by intent to treat. Primary outcomes were live birth rate and induction-to-delivery interval. Results The intended sample size was 70 women per group; however, the trial was terminated at the initial interim analysis due to a highly significant difference in one of the primary study outcomes. Twenty women were assigned to Group 1 and 18 were assigned to the Group 2. Median induction-to-delivery interval was significantly shorter in Group 1 (12 hr, range 4 - 44 hr) versus Group 2 (18 hr, range 7 - 36 hr; p=0.01). Induction success rate at 12 hours was significantly higher in the Group 1 (60%), compared to Group 2 (22%, p=.02). No significant difference was noted in the live birth rate between Group 1 and 2 (13%, 0%, p = 0.16). The incidence of retained placenta requiring curettage, chorioamnionitis, intrapartum fever, nausea, emesis, and diarrhea were similar between both groups. Conclusion Compared to concentrated oxytocin plus low-dose vaginal misoprostol, high-dose vaginal misoprostol significantly shortens mid-trimester labor inductions. PMID:16157113

  6. 辛伐他汀-β-环糊精包合物片对高脂血症模型大鼠血液流变学的影响%Effects of Simvastatin-β-cyclodextrin Inclusion Compound Tablets on Hemorheology in Model Rats with Hyperlipoidemia Disease

    Institute of Scientific and Technical Information of China (English)

    杨宗发; 何静; 韦丽佳; 江尚飞; 许燕

    2011-01-01

    目的:考察自制的辛伐他汀-β-环糊精包合物片(简称自制片)对高脂血症模型大鼠血液流变学的影响.方法:随机将60只大鼠中的10只设为空白组(蒸馏水),另50只高脂饲料喂养4周建立高脂血症大鼠模型,造模成功后随机分为5组:模型组(蒸馏水)、辛伐他汀片组(5.0 mg· kg-1· d-1)和自制片高、中、低(10.0、5.0、1.0 mg· kg-1·d-1)剂量组,每组10只,灌服给予相应药物,连续给药4周后,检测各组大鼠给药前、后全血黏度、红细胞沉降率(简称血沉)、红细胞压积以及血浆黏度等血液流变学参数的变化.结果:与模型组比较,辛伐他汀片组和自制片各剂量组大鼠的全血黏度、血沉、血浆黏度均明显降低(P<0.05),但辛伐他汀片组与自制片组比较无显著性差异;6组大鼠红细胞压积比较无显著性差异.结论:自制片可改善高脂血症模型大鼠的血液流变学特性,与辛伐他汀片作用相似.%OBJECTIVE: To investigate the effect of homemade Simvastatin-β-cyclodextrin inclusion compound tablets (self-made tablets) on hemorheology in model rats with hyperlipoidemia disease. METHODS: A total of 60 rats were included in study. 10 rats were included in blank group (distilled water). Other 50 rats were given high-fat diet for 4 weeks to induce hyperlipoidemia model then divided into 5 groups: model group (distilled water) , Simvastatin tablet group (5.0 mg·kg-1·d-1) and high-dose, medium-dose and low-dose self-made tablets groups (10.0, 5.0,1.0 mg·kg-1·d-1) with each group of 10 rats. 5 groups were given relevant medicine for 4 weeks. Changes of hemorheological parameters, including the whole blood viscosity, erythro-cyte sedimentation rate, hematocrit and plasma viscosity, were determined and analyzed before and after treatment. RESULTS: Compared with model group, the whole blood viscosity, blood sedimentation and plasma viscosity of Simvastatin tablet group and self-made tablets groups

  7. The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients.

    Science.gov (United States)

    Awadzi, K; Attah, S K; Addy, E T; Opoku, N O; Quartey, B T

    1999-01-01

    Ivermectin, at the standard dose of 150 micrograms/kg bodyweight, does not kill the adult worms of Onchocerca volvulus and does not disrupt embryogenesis or spermatogenesis. Repeated standard doses, if maintained, arrest microfilarial production but result in only a mild-to-modest macrofilaricidal effect. We investigated whether high doses would effectively kill the adult worms, and whether cessation of microfilarial production could be reproduced by an equivalent, single, high dose. One hundred men participated in a double-blind placebo-controlled trial and received increasing doses of ivermectin from 150 micrograms/kg to 1600 micrograms/kg bodyweight. Nodules were excised at day 180 and examined by histopathology. Total doses of ivermectin up to 1600 micrograms/kg were not significantly more effective than 150 micrograms/kg. Moreover, they did not reproduce the marked inhibitory effects of the repeat standard-dose regimens on embryogenesis, nor the modest effect on adult worm viability, at comparable total doses. These effects may be functions of multiplicities of dosages rather than of the total dose. Our findings also suggest that repeated high-dose regimens are unlikely to be more effective than a similar number of 150 micrograms/kg doses. This deficiency of ivermectin requires that the search for macrofilaricides remains a top priority.

  8. Effects of low dose gamma radiation on the early growth of red pepper and the resistance to subsquent high dose of radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. S.; Baek, M. H.; Kim, D. H.; Lee, Y. K. [KAERI, Taejon (Korea, Republic of); Lee, Y. B. [Chungnam National Univ., Taejon (Korea, Republic of)

    2001-05-01

    Red pepper (capsicum annuum L. cv. Jokwang and cv. Johong) seeds were irradiated with the dose of 0{approx}50 Gy to investigated the effect of the low dose gamma radiation on the early growth and resistance to subsequent high dose of radiation. The effect of the low dose gamma radiation on the early growth and resistance to subsequenct high dose of radiation were enhanced in Johong cultivar but not in Jokwang cultivar. Germination rate and early growth of Johong cultivar were noticeably increased at 4 Gy-, 8 Gy- and 20 Gy irradiation group. Resistance to subsequent high dose of radiation of Johong cultivar were increased at almost all of the low dose irradiation group. Especially it was highest at 4 Gy irradiation group. The carotenoid contents and enzyme activity on the resistance to subsequent high dose of radiation of Johong cultivar were increased at the 4 Gy and 8 Gy irradiation group.

  9. Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression

    Directory of Open Access Journals (Sweden)

    Santos T

    2012-10-01

    Full Text Available Tainaê Santos,1 Monaliza Marizete Baungratz,1 Suellen Priscila Haskel,2 Daniela Delwing de Lima,3 Júlia Niehues da Cruz,4 Débora Delwing Dal Magro,5 José Geraldo Pereira da Cruz51Department of Medicine, 2Department of Physiotherapy, Regional University of Blumenau, Santa Catarina, Brazil; 3Department of Pharmacy, University of Joinville Region, Santa Catarina, Brazil; 4Department of Medicine, University of the Extreme South of Santa Catarina, Santa Catarina, Brazil; 5Department of Natural Sciences, Regional University of Blumenau, Santa Catarina, BrazilAbstract: Simvastatin inhibits 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is widely used to control plasma cholesterol levels and prevent cardiovascular disease. However, emerging evidence indicates that the beneficial effects of simvastatin extend to the central nervous system. The effects of simvastatin combined with fluoxetine provide an exciting and potential paradigm to decreased anxiety and depression. Thus, the present paper investigates the possibility of synergistic interactions between simvastatin and fluoxetine in models of anxiety and depression. We investigated the effects of subchronically administered simvastatin (1 or 10 mg/kg/day combined with fluoxetine (2 or 10 mg/kg at 24, 5, and 1 hour on adult rats before conducting behavioral tests. The results indicate that simvastatin and/or fluoxetine treatment reduces anxiety-like behaviors in the elevated plus-maze and open-field tests. Our results showed that simvastatin and/or fluoxetine induced a significant increase in the swimming activity during the forced swimming test (antidepressant effect, with a concomitant increase in climbing time in simvastatin-treated animals only (noradrenergic activation. We hypothesize that anxiolytic and antidepressant effects of simvastatin and/or fluoxetine produce their behavioral effects through similar mechanisms and provide

  10. High dose of ascorbic acid induces cell death in mesothelioma cells.

    Science.gov (United States)

    Takemura, Yukitoshi; Satoh, Motohiko; Satoh, Kiyotoshi; Hamada, Hironobu; Sekido, Yoshitaka; Kubota, Shunichiro

    2010-04-02

    Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

  11. Retarding effect of simvastatin on artery remodeling induced by high-salt and high-fat diet in rats%高盐高脂摄入致大鼠主动脉重构及辛伐他汀的阻断作用

    Institute of Scientific and Technical Information of China (English)

    尹明景; 温汉春; 叶永维; 管庆林; 黄皓章; 黄露霜; 朱继金

    2012-01-01

    目的:探讨高钠盐与高脂肪喂养后大鼠血压、血脂变化、主动脉构型改变和辛伐他汀的干预作用及机制.方法:60只成年雄性SD大鼠,随机分为5组(n=12):对照组(N组)、高盐组(S组)、高脂组(F组)、高盐高脂组(SF组)和高盐高脂加辛伐他汀组(T组).喂养16周后,测量大鼠动脉压、血清甘油三酯(TG)、总胆固醇(TC)及可溶性CD40L(sCD40L)浓度;免疫组化法检测升主动脉根部血管壁组织CD40/CD40L表达;HE染色测量升主动脉起始段中膜层厚度和动脉内腔面积与血管腔横断面积比值.结果:(1) S组、F组和SF组收缩压与N组相比均明显增高(P<0.01),而T组与N组比增高但程度较SF组明显降低(P<0.05) ;(2)F组和SF组血清TG和TC明显升高,与N组和T组比较明显升高(P<0.001),而S组、N组和T组之间无明显差异;(3)S组、F组和SF组血清sCD40L浓度均高于N组和T组(P<0.05),SF组高于S组和F组(P<0.05),S组与F组、N组与T组间无明显差异;(4)S组、F组和SF组动脉组织CD40/CD40L表达强度高于N组和T组(P<0.05),且SF组高于S组和F组(P<0.05),S组与F组、N组、T组间无明显差异;(5)S组、F组与SF组动脉中膜厚度与N组比较明显增厚(P<0.01);T组与N组比无显著差异;S组、F组和SF组血管内腔面积/血管横断面积比(LA/TVA)与N组比较明显变小(P<0.05);T组与N组比较无显著差别.结论:高盐高脂喂养可导致大鼠血压升高和诱发动脉粥样硬化,以及血清sCD40L浓度升高、动脉组织CD40/CD40L表达强度增高;复合刺激改变明显强于单一因素作用.他汀类药物可通过抑制血清sCD40L及动脉组织CD40/CD40L表达途径保护血管.%AIM: To investigate the effect of simvastatin intervention on the changes of blood pressure, serum lipid fluctuation and aortic configuration induced by high - sodium and high - fat diet in rats. METHODS: Sixty adult male SD rats were randomly divided into 5 groups ( n = 12 ): control ( N )group, high

  12. Ceramic Matrix Composites Performances Under High Gamma Radiation Doses

    Science.gov (United States)

    Cemmi, A.; Baccaro, S.; Fiore, S.; Gislon, P.; Serra, E.; Fassina, S.; Ferrari, E.; Ghisolfi, E.

    2014-06-01

    Ceramic matrix composites reinforced by continuous ceramic fibers (CMCs) represent a class of advanced materials developed for applications in automotive, aerospace, nuclear fusion reactors and in other specific systems for harsh environments. In the present work, the silicon carbide/silicon carbide (SiCf/SiC) composites, manufactured by Chemical Vapour Infiltration process at FN S.p.A. plant, have been evaluated in term of gamma radiation hardness at three different absorbed doses (up to around 3MGy). Samples behavior has been investigated before and after irradiation by means of mechanical tests (flexural strength) and by surface and structural analyses (X-ray diffraction, SEM, FTIR-ATR, EPR).

  13. Single high-dose pyridoxine treatment for isoniazid overdose.

    Science.gov (United States)

    Wason, S; Lacouture, P G; Lovejoy, F H

    1981-09-04

    We treated five isoniazid-overdosed patients each with a single dose of pyridoxine hydrochloride equivalent to the gram amount of isoniazid ingested and compared their outcome with that of 41 patients from the literature who received little or no pyridoxine. Recurrent seizures occurred in 60% of patients who had received no pyridoxine vs 0% in our patients. Metabolic acidosis resolved in our cases but was refractory in the literature cases. In our cases, coma lightened more rapidly and was of shorter duration as compared with that in the literature cases (mean, seven hours vs 24 hours). No adverse effects of pyridoxine were seen in our patients.

  14. Differences Between Lovastatin and Simvastatin Hydrolysis in Healthy Male and Female Volunteers: Gut Hydrolysis of Lovastatin is Twice that of Simvastatin

    Directory of Open Access Journals (Sweden)

    Tom B. Vree

    2003-01-01

    Full Text Available The aim of this pharmacokinetic evaluation was to show the effect of the extra methyl group in simvastatin on esterase hydrolysis between lovastatin and simvastatin in male and female volunteers. This study was based on the plasma concentration-time curves and the pharmacokinetics of lovastatin and simvastatin with its respective active metabolite statin-β-hydroxy acid obtained from two different bioequivalence studies, each with 18 females and 18 males. Results were: 1-The group of female volunteers showed a higher yield of the active metabolite β-hydroxy acid than the group of males (p < 0.002 for both lovastatin and simvastatin. This difference was not related to the body weight of both groups. 2-In the male/female groups, subject-dependent yield of active metabolite β-hydroxy acid was demonstrated, which was independent of the formulation. The variation in plasma/liver hydrolysis resulted in a fan-shaped distribution of data points when the AUCt lovastatin was plotted vs. that of the β-hydroxy acid metabolite. In the fan of data points, subgroups could be distinguished, each showing a different regression line and with a different Y-intercept (AUCtβ-hydroxy acid. 3-Lovastatin hydrolysis was higher than simvastatin hydrolysis. 4-It was possible to discriminate between hydrolysis of both lovastatin and simvastatin by plasma/liver or tissue esterase activity.

  15. A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy.

    Science.gov (United States)

    Lahanas, M; Baltas, D; Zamboglou, N

    2003-02-07

    Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives.

  16. A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lahanas, M [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany); Baltas, D [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany); Zamboglou, N [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany)

    2003-02-07

    Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives.

  17. Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, L.M.; França, C.N.; Izar, M.C.; Bianco, H.T.; Lins, L.S.; Barbosa, S.P.; Pinheiro, L.F.; Fonseca, F.A.H. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, São Paulo, SP, Brasil, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-04-15

    It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

  18. Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Shin Young; Lee, Jaetae [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2010-06-15

    Radioactive iodine ({sup 131}I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, {sup 131}I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the {sup 131}I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of {sup 131}I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, candidiasis, and neoplasia. Prevention of {sup 131}I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently interventional sialoendoscopy has been introduced an effective tool for the management of patients with {sup 131}I-induced sialadenitis that is unresponsive to medical treatment.

  19. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients

    DEFF Research Database (Denmark)

    Nielsen, Torben Kjær; Højgaard, Martin; Andersen, Jon Thor Trærup

    2015-01-01

    Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high dose...

  20. High daily doses of benzodiazepines among Quebec seniors: prevalence and correlates

    Directory of Open Access Journals (Sweden)

    Moride Yola

    2001-11-01

    Full Text Available Abstract Background Use of high daily doses of benzodiazepines is generally contraindicated for seniors. While both patient and physician factors may influence the use of high daily doses, previous research on the effect of patient factors has been extremely limited. The objectives of this study were to determine the one year prevalence of use of high daily doses of benzodiazepines, and examine physician and patient correlates of such use among Quebec community-dwelling seniors. Methods Patient information for 1423 community-dwelling Quebec seniors who participated in the Canadian Study of Health and Aging was linked to provincial health insurance administrative data bases containing detailed information on prescriptions received and prescribers. Results The standardized one year period prevalence of use of high daily doses of benzodiazepines was 7.9%. Use of high daily doses was more frequent among younger seniors and those who had reported anxiety during the previous year. Patients without cognitive impairment were more likely to receive high dose prescriptions from general practitioners, while those with cognitive impairment were more likely to receive high dose prescriptions from specialists. Conclusion High dose prescribing appears to be related to both patient and physician factors.

  1. Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

    Science.gov (United States)

    McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

    2012-01-01

    Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

  2. High- and low-dose expectancies as mediators of personality dimensions and alcohol involvement.

    Science.gov (United States)

    Read, Jennifer P; O'Connor, Roisin M

    2006-03-01

    The present study examined the influences of personality dimensions (extraversion, neuroticism) on college alcohol involvement both (1) directly and (2) mediated by positive and negative alcohol expectancies across two imagined (high and low) alcohol doses. Participants (N = 339; 176 women) were regularly drinking college students who completed a questionnaire battery on demographic characteristics, personality, expectancies, and alcohol use and problems. Structural equation modeling analysis of low- and high-dose models revealed partial support for the Social Learning Theory conceptualization of expectancies as mediators of more distal (personality) influences. Interestingly, patterns of association differed by dose. At high-expectancy doses, positive alcohol expectancies fully mediated the extraversion-use association. At low doses, positive expectancies did not play a critical role. Two distinct pathways from neuroticism to alcohol use were observed: a direct pathway, whereby neuroticism is a protective factor for alcohol use, and an indirect pathway, through positive expectancies, whereby neuroticism is a risk factor. The protective pathway was evident regardless of expectancy doses, whereas the risk pathway was evident only at high doses. Negative expectancies partially mediated the association between neuroticism and alcohol problems at both high- and low-expectancy doses. These data underscore the unique role of both positive and negative expectancies in the association between personality and drinking behavior and point to the importance of considering alcohol dose when assessing expectancies. Findings suggest that it may be beliefs about the effects resulting from heavy (rather than moderate) drinking that may be the active mechanism underlying drinking behavior.

  3. Efficacy of Continuous High Dose Midazolam Infusion in Childhood Refractory Generalized Convulsive Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Afshin Fayyazi

    2011-06-01

    Full Text Available bjeciveProlonged and uncontrolled refractory status epilepticus (SE is a life-threatening medical emergency in children (1,2,3. There is no consensus on the optimal therapy for refractory status epilepticus (1. The aim of this study was to develop a new method for treating patients with refractory status epilepticus.Materials & MethodsTen children with refractory status epilepticus in Mofid Hospital, who did not respond to 10 μg/kg per min of intravenous midazolam, had their dose of midazolam increased to 30 μg/kg per min. All children were monitored for the development of side effects.ResultsTen children with no response to low-dose midazolam were given a higher dose of midazolam, and 5 (50% children had a good response. These patients had significantly different response to high-dose midazolam.One patient in the high-dose midazolam group was intubated and required mechanical ventilation. The duration of stay in the hospital and PICU and on mechanical ventilation in patients with no response to low-dose midazolam following with other drugs was longer than in the high-dose midazolam group.No death occurred in high dose midazolam group.ConclusionHigh-midazolam dose drip infusion is a safe and effective protocol for refractory status epilepticus in children.

  4. Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin.

    Science.gov (United States)

    Costa, Rute A P; Fernandes, Mariana P; de Souza-Pinto, Nadja C; Vercesi, Aníbal E

    2013-02-15

    Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. High frequency of streptococcal bacteraemia during childhood AML therapy irrespective of dose of cytarabine

    DEFF Research Database (Denmark)

    Johannsen, Katrine Helle; Handrup, Mette Møller; Lausen, Birgitte Frederiksen

    2013-01-01

    BACKGROUND: High-dose cytarabine has been associated with a high frequency of viridans group streptococcal (VGS) bacteraemia. VGS bacteraemia causes considerable morbidity and mortality. The Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML protocols use higher cumulated doses...... following courses with low-dose cytarabine versus courses with high-dose cytarabine. CONCLUSIONS: VGS were the most commonly isolated pathogens causing the most severe infections and the majority of life-threatening infections. A substantial proportion of the strains were resistant to penicillin. The high...... rate of VGS seemed independent of high-dose cytarabine but was more likely caused by the intensive chemotherapy treatment leading to severe mucositis and neutropenia....

  6. Irradiation dose and temperature dependence of fracture toughness in high dose HT9 steel from the fuel duct of FFTF

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Thak Sang, E-mail: byunts@ornl.gov [Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Toloczko, Mychailo B. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Saleh, Tarik A.; Maloy, Stuart A. [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2013-01-15

    To expand the knowledge base for fast reactor core materials, fracture toughness has been evaluated for high dose HT9 steel using miniature disk compact tension (DCT) specimens. The HT9 steel DCT specimens were machined from the ACO-3 fuel duct of the Fast Flux Test Facility (FFTF), which achieved high doses in the range of 3-148 dpa at 378-504 Degree-Sign C. The static fracture resistance (J-R) tests have been performed in a servohydraulic testing machine in vacuum at selected temperatures including room temperature, 200 Degree-Sign C, and each irradiation temperature. Brittle fracture with a low toughness less than 50 MPa {radical}m occurred in room temperature tests when irradiation temperature was below 400 Degree-Sign C, while ductile fracture with stable crack growth was observed when irradiation temperature was higher. No fracture toughness less than 100 MPa {radical}m was measured when the irradiation temperature was above 430 Degree-Sign C. It was shown that the influence of irradiation temperature was dominant in fracture toughness while the irradiation dose has only limited influence over the wide dose range 3-148 dpa. A slow decrease of fracture toughness with test temperature above room temperature was observed for the nonirradiated and high temperature (>430 Degree-Sign C) irradiation cases, which indicates that the ductile-brittle transition temperatures (DBTTs) in those conditions are lower than room temperature. A comparison with the collection of existing data confirmed the dominance of irradiation temperature in the fracture toughness of HT9 steels.

  7. Use of a data warehouse to monitor simvastatin tablet splitting.

    Science.gov (United States)

    Coblio, Nicholas A; Mowrey, Kim A; Loos, Dana; Ford, V; Haley, James A

    2003-01-01

    A data warehouse was used to examine the LDL levels for patients who were switched from whole to half tablets of simvastatin. The LDL levels were available both pre and post conversion. 7,321 patients were switched and the LDL levels for these patients were tracked. 1,408 patients had a slight increase in LDL (less than 15% above baseline). Those patients whose LDL increased by greater than 15%, and was above 120 mg/dl, were switched back to whole tablets.

  8. The influence of milling on the dissolution performance of simvastatin

    DEFF Research Database (Denmark)

    Zimper, Ulrike; Aaltonen, Jaakko; Krauel-Goellner, Karen

    2012-01-01

    Particle size reduction is a simple means to enhance the dissolution rate of poorly water soluble BCS-class II and IV drugs. However, the major drawback of this process is the possible introduction of process induced disorder. Drugs with different molecular arrangements may exhibit altered...... properties such as solubility and dissolution rate and, therefore, process induced solid state modifications need to be monitored. The aim of this study was two-fold: firstly, to investigate the dissolution rates of milled and unmilled simvastatin; and secondly, to screen for the main milling factors...... by XRPD), at a set optimization limit of dissolution testing...

  9. Characterisation of high dose dry powder aerosols by cascade impaction and laser diffraction analysis

    NARCIS (Netherlands)

    Grasmeijer, F.; Hagedoorn, P.; Frijlink, H.W.; De Boer, A.H.

    2011-01-01

    Background: Developments in high dose dry powder inhalationcontinue to challenge the viability of pharmacopoeialmethods for drug aerosol characterisation. Especiallythe occurrence of bounce effects can cause the amount offines (<1 lm) to be highly overestimated in particle sizedistributions (PSDs) o

  10. 调脂胶囊与辛伐他汀调血脂作用的对照实验研究%Experimental Study of Lipid-Regulating Capsule and Simvastatin for the Dislipidemic SD Rats

    Institute of Scientific and Technical Information of China (English)

    郭小梅; 孙守华; 钱振坤

    2001-01-01

    以辛伐他汀为对照,研究调脂胶囊连续灌胃3周对实验性血脂代谢紊乱大鼠血脂的调节作用。结果表明,调脂胶囊大、中、小剂量[10 g、5 g、2.5 g/(Kg*d)]均极显著降低血脂代谢紊乱大鼠血清TC和LDL-C值(P<0.001),其作用均较大剂量辛伐他汀稍强,并显著升高HDL-C、HDL-C/TC值(P<0.05);大、中剂量均极显著降低TG值(P<0.01),与辛伐他汀作用相当。研究结果表明,该胶囊对大鼠血脂代谢紊乱有很好的调节作用,其有效剂量范围较大,中等剂量调脂作用与大剂量辛伐他汀作用基本相当。%The role of lipid-regulating capsule in the regulation of experimental dislipidemia was studied in SD rats. The SD rats were divided into 6 groups: group A (normal control),group B to F (experimental hyperlipidemia). The rats in the groups C,D and E received the capsule in a daily dose of 2.5 g,5 g and 10 g/kg respectively for 3 weeks,while the rats in the group F received Simvastatin in a daily dose of 7.5 mg/kg for 3 weeks. By comparison with the group B after 3 weeks,the levels of plasma total cholesterol (TC) and low density lipoprotein (LDL-C) were very significantly decreased in the groups C,D,E and F(P<0.01),the value of plasma total triglyceride (TG) was very significantly decreased in the groups D,E and F (<0.01),and the level of high density lipoprotein was significantly increased in the groups C,D and E (P<0.05),but very significantly increased in the group F (P<0.01). It was suggested that the therapeutic efficiency of the lipid-regulating capsule in low,middle and high dosage was the same as that in high dose of simvastatin for the SD rats with high plasma TC and LDL-C,and middle and high doses of the capsule had the same effect of simvastatin on the plasma TG.

  11. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery.

    Science.gov (United States)

    Kirkpatrick, John P; Meyer, Jeffrey J; Marks, Lawrence B

    2008-10-01

    The linear-quadratic (LQ) model is widely used to model the effect of total dose and dose per fraction in conventionally fractionated radiotherapy. Much of the data used to generate the model are obtained in vitro at doses well below those used in radiosurgery. Clinically, the LQ model often underestimates tumor control observed at radiosurgical doses. The underlying mechanisms implied by the LQ model do not reflect the vascular and stromal damage produced at the high doses per fraction encountered in radiosurgery and ignore the impact of radioresistant subpopulations of cells. The appropriate modeling of both tumor control and normal tissue toxicity in radiosurgery requires the application of emerging understanding of molecular-, cellular-, and tissue-level effects of high-dose/fraction-ionizing radiation and the role of cancer stem cells.

  12. 2型糖尿病大鼠骨骼肌Toll样受体4的表达及辛伐他汀的干预作用%Expression of Toll like receptor 4 in skeletal muscle of type2 diabetic rats and the intervention effect of simvastatin

    Institute of Scientific and Technical Information of China (English)

    徐谦; 曹柳; 刘琼; 刘宽芝

    2014-01-01

    Objective To investigate the expression of Toll like receptor 4 (TLR4) in skeletal muscle of type2 diabetic rats and the intervention effect of simvastatin.Methods The type 2 diabetic rat model was established in 26 SD rats by feeding high-fat,high-sucrose diet and injecting low dose of streptozotocin (STZ).These rats were randomly divided into diabetic group (13 rats) and simvastatin group (13 rats),with 10 normal SD rats as control group.The rats in simvastatin group received simvastatin at a dosage of 20 mg· kg-1 · d-1 by gastric gavage while the ones in normal control group (10 rats) and diabetic group received equal volume of normal saline by gastric gavage.After 8 weeks,fasting blood glucose(FBG),blood lipids and creatine kinase (CK)were measured in all groups,and histological change in skeletal muscle of all rats were observed.The protein and mRNA expression of TLR4 in skeletal muscle was examined by immunohistochemistry staining and RT-PCR respectively.Results FBG of diabetes group and simvastatin group were significantly higher than that of control group [(12.04 ± 2.04) mmol/L,(11.23 ± 2.61) mmol/L vs (5.92± 1.28)mmol/L,all P < 0.05],and there were no significant difference of FBG between diabetes group and simvastatin group.The levels of TG,TC and LDL-C in three groups were diabetes group>simvastatin group>control group (all P < 0.05).Levels of HDL-C in three groups were control group>simvastatin group>diabetes group (all P < 0.05).There were no significant differences of creatine kinase among three groups.Skeletal muscle of normal control group rats was complete and orderly,muscle fibers arranged in cloes while the morphology of skeletal muscle of diabetic rats was atrophic,fractured and edamed,muscle fiber ruptured and filaments traveling disordered with observed infiltration of inflammatory cells,and such changes were extenuated in simvastatin group.The expression level of TLR4 protein in diabetes group was 1.54 times of control

  13. Effects of high dose rate gamma radiation on survival and reproduction of Biomphalaria glabrata

    Energy Technology Data Exchange (ETDEWEB)

    Cantinha, Rebeca S.; Nakano, Eliana [Instituto Butantan, Sao Paulo, SP (Brazil). Lab. de Parasitologia], e-mail: rebecanuclear@gmail.com, e-mail: eliananakano@butantan.gov.br; Borrely, Sueli I. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil). Centro de Tecnologia das Radiacoes], e-mail: sborrely@ipen.br; Amaral, Ademir; Melo, Ana M.M.A. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear. Grupo de Estudos em Radioprotecao e Radioecologia (GERAR)], e-mail: amaral@ufpe.br; Silva, Luanna R.S. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia. Lab. de Radiobiologia], e-mail: amdemelo@hotmail.com, e-mail: luannaribeiro_lua@hotmail.com

    2009-07-01

    Ionizing radiations are known as mutagenic agents, causing lethality and infertility. This characteristic has motivated its application on animal biological control. In this context, the freshwater snail Biomphalaria glabrata can be considered an excellent experimental model to study effects of ionizing radiations on lethality and reproduction. This work was designed to evaluate effects of {sup 60}Co gamma radiation at high dose rate (10.04 kGy/h) on B. glabrata. For this purpose, adult snails were selected and exposed to doses ranging from 20 to 100 Gy, with 10 Gy intervals; one group was kept as control. There was not effect of dose rate in the lethality of gamma radiation; the value of 64,3 Gy of LD{sub 50} obtained in our study was similar to that obtained by other authors with low dose rates. Nevertheless, our data suggest that there was a dose rate effect in the reproduction. On all dose levels, radiation improved the production of embryos for all exposed individuals. However, viability indexes were below 6% and, even 65 days after irradiation, fertility was not recovered. These results are not in agreement with other studies using low dose rates. Lethality was obtained in all groups irradiated, and the highest doses presented percentiles of dead animals above 50%. The results demonstrated that doses of 20 and 30 Gy were ideal for population control of B. glabrata. Further studies are needed; nevertheless, this research evidenced great potential of high dose rate gamma radiation on B. glabrata reproductive control. (author)

  14. Collagen with simvastatin promotes cell metabolism in osteoblast-like SaOS-2 cells

    Directory of Open Access Journals (Sweden)

    Thanga Kumaran Suthanthiran

    2012-01-01

    Full Text Available Background: Simvastatin (SMV is one of the cholesterol-lowering pharmacological drugs. Recent studies demonstrate that it has a bone stimulatory effect. The present study was designed to investigate the effect of SMV along with collagen membrane on osteoblast-like SaOS-2 cells and also to standardize the dosage of SMV to be incorporated into the collagen membrane to achieve regeneration. Materials and Methods: SMV at doses of 0.5, 1, 1.5, and 2 mg was incorporated into the collagen membrane and cell metabolism was assessed by (3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT assay for 24 h. Results: SMV enhanced cell metabolism dose dependently at 24-h time and the maximum effect was obtained at a concentration of 1.5 mg of SMV. Conclusion: These results indicate that collagen with 1.5 mg SMV exhibits positive effect on cell metabolism of human osteoblast-like SaOS-2 cells.

  15. Infused vincristine and adriamycin with high dose methylprednisolone (VAMP) in advanced previously treated multiple myeloma patients.

    Science.gov (United States)

    Forgeson, G. V.; Selby, P.; Lakhani, S.; Zulian, G.; Viner, C.; Maitland, J.; McElwain, T. J.

    1988-01-01

    Forty-five patients with relapsed or refractory multiple myeloma received continuous infusions of vincristine (0.4 mg total dose daily for 4 days) and adriamycin (9 mg m-2 daily for 4 days) with a high dose of methylprednisolone (1 g m-2 i.v. or p.o. daily by 1 h infusion), the VAMP regimen. Sixteen (36%) responded, with a median duration of remission of 11 months and median survival of 20 months. Major toxicities encountered were infective and cardiovascular. Two smaller groups of myeloma patients were treated with high dose methylprednisolone (HDMP) alone, or VAMP plus weekly low dose cyclophosphamide (Cyclo-VAMP). HDMP produced short responses in 25% of patients with less toxicity than VAMP. Cyclo-VAMP was used in a highly selected group of patients who had previously responded to high dose melphalan. It was well tolerated and produced responses in 61% of this group. PMID:3207601

  16. Comparison of the effects of different statins and doses on lipid levels in patients with diabetes: results from VOYAGER.

    Science.gov (United States)

    Karlson, B W; Barter, P J; Palmer, M K; Lundman, P; Nicholls, S J

    2012-09-01

    Diabetes mellitus is a well-known risk factor for cardiovascular disease, and brings an increased risk of vascular events and a higher mortality rate. Treatment guidelines recommend statins in patients with diabetes, with low-density lipoprotein cholesterol (LDL-C) targets of 100 mg dl(-1) (∼2.5 mmol l(-1)), and 80 (∼2.0 mmol l(-1)) or 70 mg dl(-1) (∼1.8 mmol l(-1)) in especially high-risk patients. The current study used the VOYAGER (an indiVidual patient data-meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin, and simvastatin) database to characterise effects of rosuvastatin, atorvastatin and simvastatin in different doses on lipid levels in diabetes patients. The VOYAGER database included individual patient data from 37 studies involving comparisons of rosuvastatin with either atorvastatin or simvastatin. Of the 32 258 patients included, 8859 (27.5%) had diabetes. Rosuvastatin appeared to be the most efficacious of the three statins, both for lowering LDL-C and for reaching a target level of VOYAGER results. This meta-analysis of 8859 patients with diabetes mellitus shows favourable effects on lipids with the three statins studied, in line with results for the overall VOYAGER population. The importance of using an effective statin at an effective dose to reach treatment goals for such high-risk patients is evident. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Escalating dose pretreatment induces pharmacodynamic and not pharmacokinetic tolerance to a subsequent high-dose methamphetamine binge.

    Science.gov (United States)

    O'Neil, Meghan L; Kuczenski, Ronald; Segal, David S; Cho, Arthur K; Lacan, Goran; Melega, William P

    2006-11-01

    A major feature of human methamphetamine (METH) abuse is the gradual dose escalation that precedes high-dose exposure. The period of escalating doses (EDs) is likely associated with development of tolerance to aspects of METH's pharmacologic and toxic effects but the relative contributions of pharmacokinetic and pharmacodynamic factors have not been well defined. In our prior studies in rats, we showed that pretreatment with an ED-METH regimen (0.1-4.0 mg/kg over 14 days) attenuated the toxicity of a subsequently administered high-dose METH binge (4 x 6 mg/kg at 2 h interval) that itself produced behavioral stereotypy, increases in core temperature, and decreases in DA system phenotypic markers in caudate-putamen (CP). Using those ED-METH and binge protocols in the present studies, pharmacokinetic and pharmacodynamic parameters that may have contributed to the apparent neuroprotection afforded by ED-METH were assessed. The ED-METH regimen itself reduced [(3)H]WIN35,428 (WIN) binding to the dopamine transporter (DAT) by 15% in CP, but did not affect DA content. During the METH binge, ED-METH pretreated animals showed attenuated increases in core temperature while concurrent microdialysis studies in CP showed a reduced DA response despite unaltered extracellular levels of METH. At 1 h after the binge, concentrations of METH and its metabolite amphetamine in brain and plasma were unaffected by the ED-METH. The results show that ED-METH pretreatment produces reductions in DAT binding and the DA response during a subsequent METH binge by altering pharmacodynamic and not pharmacokinetic parameters.

  18. Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

    Science.gov (United States)

    Fournier, P.; Crosbie, J. C.; Cornelius, I.; Berkvens, P.; Donzelli, M.; Clavel, A. H.; Rosenfeld, A. B.; Petasecca, M.; Lerch, M. L. F.; Bräuer-Krisch, E.

    2016-07-01

    Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency’s TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called ‘current ramping’ method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.

  19. Acute high dose lithium-induced exacerbation of obsessive compulsive symptoms.

    Science.gov (United States)

    Umesh, Shreekantiah; Sinha, Vinod Kumar

    2014-05-01

    Obsessive compulsive disorder (OCD) is a chronic neuropsychiatric disorder whose pathophysiology is linked to serotonergic dysfunction. More recently, the role of glutamate has also been posited. Lithium is used as an adjunctive for the treatment of OCD which is found to enhance serotonergic transmission. We present a case of OCD who was on stable dose of sertraline developed exacerbation of obsessive compulsive symptoms with acute high dose of lithium but improved after dose reduction.

  20. On line high dose static position monitoring by ionization chamber detector for industrial gamma irradiators.

    Science.gov (United States)

    Rodrigues, Ary A; Vieira, Jose M; Hamada, Margarida M

    2010-01-01

    A 1 cm(3) cylindrical ionization chamber was developed to measure high doses on line during the sample irradiation in static position, in a (60)Co industrial plant. The developed ionization chamber showed to be suitable for use as a dosimeter on line. A good linearity of the detector was found between the dose and the accumulated charge, independently of the different dose rates caused by absorbing materials.

  1. A Grid Algorithm for High Throughput Fitting of Dose-Response Curve Data

    OpenAIRE

    Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

    2010-01-01

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program’s performance in reproducing the actual values that were used ...

  2. On line high dose static position monitoring by ionization chamber detector for industrial gamma irradiators

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Ary A. [Universidade Estadual de Londrina-Depto de Fisica, Rodovia Celso Garcia Cid, km 38, 086051-990 Londrina (Brazil); Vieira, Jose M. [Instituto de Pesquisas Energeticas e Nucleares-IPEN/CNEN-SP, Prof. Lineu Prestes, 2242-Cidade Universitaria, 05508-900 Sao Paulo (Brazil); Hamada, Margarida M. [Instituto de Pesquisas Energeticas e Nucleares-IPEN/CNEN-SP, Prof. Lineu Prestes, 2242-Cidade Universitaria, 05508-900 Sao Paulo (Brazil)], E-mail: mmhamada@ipen.br

    2010-04-15

    A 1 cm{sup 3} cylindrical ionization chamber was developed to measure high doses on line during the sample irradiation in static position, in a {sup 60}Co industrial plant. The developed ionization chamber showed to be suitable for use as a dosimeter on line. A good linearity of the detector was found between the dose and the accumulated charge, independently of the different dose rates caused by absorbing materials.

  3. Dosimetric Evaluation of High-Dose-Rate Interstitial Brachytherapy Boost Treatments for Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Froehlich, Georgina [Semmelweis Univ., Budapest (Hungary); Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary); Agoston, Peter; Loevey, Jozsef; Somogyi, Andras; Fodor, Janos; Polgar, Csaba; Major, Tibor [Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary)

    2010-07-15

    Purpose: to quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk. Material and methods: treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D{sub min}) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D{sub r}) and urethra (D{sub u}), dose to volume of 2 cm{sup 3} of the rectum (D{sub 2ccm}), and 0.1 cm{sup 3} and 1% of the urethra (D{sub 0.1ccm} and D1) were determined. Nonparametric correlation analysis was performed between these parameters. Results: the median number of needles was 16, the mean prostate volume (V{sub p}) was 27.1 cm{sup 3}. The mean V90, V100, V150, and V200 were 90%, 97%, 39% and 13%, respectively. The mean D90 was 109%, and the D{sub min} was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D{sub 2ccm} = 49% for the rectum, D{sub 0.1ccm} = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D{sub r}, D{sub 2ccm}) = 0.69, R(D{sub u}, D{sub 0.1ccm}) = 0.64, R(D{sub u}, D1) = 0.23. Conclusion: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose

  4. Comparable renovascular protective effects of moxonidine and simvastatin in rats exposed to cigarette smoke.

    Science.gov (United States)

    Nasr, Magda A; El-Gowilly, Sahar M; El-Mas, Mahmoud M

    2010-01-01

    Renovascular impairment plays a major role in smoking-induced nephrotoxicity. This study investigated the effect of the imidazoline I(1)-receptor/alpha(2)-adrenoceptor agonist moxonidine, as compared to the lipid lowering drug simvastatin, on abnormalities induced by cigarette smoke (CS) in renovascular reactivity. Six rat groups were used: control, CS (twice a day for 6weeks), simvastatin, moxonidine, CS+simvastatin, and CS+moxonidine. CS exposure increased plasma urea and creatinine and reduced plasma and renal nitrate/nitrite (NOx). In isolated perfused phenylephrine-preconstricted kidneys of CS rats, vasodilator responses to carbachol or isoprenaline, but not papaverine, were attenuated. Nitric oxide synthase (NOS) inhibition by N(G)-nitro-L-arginine (L-NNA) reduced carbachol vasodilations in control but not CS kidneys, suggesting the impairment of NOS activity by CS. Simultaneous administration of moxonidine or simvastatin abolished CS-induced abnormalities in indices of renal function, NOx, and vasodilations caused by carbachol or isoprenaline. The possibility whether alterations in antioxidant or lipid profiles contributed to the interaction was investigated. CS increased renal malondialdyde and decreased glutathione, and glutathione peroxidase, superoxide dismutase and catalase activities. Further, CS reduced plasma HDL and increased cholesterol, triglycerides, and LDL. Simvastatin or moxonidine abolished the deleterious CS effects on antioxidant activity; the lipid profile was normalized by simvastatin only. These findings highlight that renovascular dysfunction caused by CS and the underlying oxidative damage is evenly attenuated by moxonidine and simvastatin.

  5. Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis.

    Science.gov (United States)

    Asai, Jun; Takenaka, Hideya; Hirakawa, Satoshi; Sakabe, Jun-ichi; Hagura, Asami; Kishimoto, Saburo; Maruyama, Kazuichi; Kajiya, Kentaro; Kinoshita, Shigeru; Tokura, Yoshiki; Katoh, Norito

    2012-12-01

    Impaired wound healing is a major complication of diabetes. Recent studies have reported reduced lymphangiogenesis and angiogenesis during diabetic wound healing, which are thought to be new therapeutic targets. Statins have effects beyond cholesterol reduction and can stimulate angiogenesis when used systemically. However, the effects of topically applied statins on wound healing have not been well investigated. The present study tested the hypothesis that topical application of simvastatin would promote lymphangiogenesis and angiogenesis during wound healing in genetically diabetic mice. A full-thickness skin wound was generated on the back of the diabetic mice and treated with simvastatin or vehicle topically. Simvastatin administration resulted in significant acceleration of wound recovery, which was notable for increases in both angiogenesis and lymphangiogenesis. Furthermore, simvastatin promoted infiltration of macrophages, which produced vascular endothelial growth factor C in granulation tissues. In vitro, simvastatin directly promoted capillary morphogenesis and exerted an antiapoptotic effect on lymphatic endothelial cells. These results suggest that the favorable effects of simvastatin on lymphangiogenesis are due to both a direct influence on lymphatics and indirect effects via macrophages homing to the wound. In conclusion, a simple strategy of topically applied simvastatin may have significant therapeutic potential for enhanced wound healing in patients with impaired microcirculation such as that in diabetes.

  6. Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain.

    Science.gov (United States)

    Wang, Q; Zengin, A; Ying, W; Newell, K A; Wang, P; Yeo, W; Wong, P T-H; Yenari, M A; Huang, X-F

    2008-06-26

    Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, Ppirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.

  7. Topical Simvastatin as Host-Directed Therapy against Severity of Cutaneous Leishmaniasis in Mice

    Science.gov (United States)

    Parihar, Suraj P.; Hartley, Mary-Anne; Hurdayal, Ramona; Guler, Reto; Brombacher, Frank

    2016-01-01

    We recently demonstrated that statins mediate protection against intracellular pathogens, Mycobacterium tuberculosis and Listeria monocytogenes in mice. Here, we investigated the immunomodulatory potential of simvastatin as a topical or systemic host-directed drug therapy in controlling inflammatory responses in an experimental mouse model of cutaneous leishmaniasis caused by Leishmania major (LV39). In an ear infection model, topical application of simvastatin directly on established lesions significantly reduced severity of the disease reflected by ear lesion size and ulceration. The host protective effect was further accompanied by decreased parasite burden in the ear and draining lymph nodes in both BALB/c and C57BL/6 mice. Pre-treatment of these mice on a low-fat cholesterol diet and systemic simvastatin also reduced footpad swelling, as well as parasite burdens and ulceration/necrosis in the more robust footpad infection model, demonstrating the prophylactic potential of simvastatin for cutaneous leishmaniasis. Mechanistically, following L. major infection, simvastatin-treated primary macrophages responded with significantly reduced cholesterol levels and increased production of hydrogen peroxide. Furthermore, simvastatin-treated macrophages displayed enhanced phagosome maturation, as revealed by increased LAMP-3 expression in fluorescent microscopy and Western blot analysis. These findings demonstrate that simvastatin treatment enhances host protection against L. major by increasing macrophage phagosome maturation and killing effector functions. PMID:27632901

  8. Neuroprotective Effect of Simvastatin via Inducing the Autophagy on Spinal Cord Injury in the Rat Model

    Directory of Open Access Journals (Sweden)

    Kai Gao

    2015-01-01

    Full Text Available Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, is invariably used to treat cardiovascular diseases. Simvastatin has been recently demonstrated to have a neuroprotective effect in nervous system diseases. The present study aimed to further verify the neuroprotection and molecular mechanism of simvastatin on rats after spinal cord injury (SCI. The expression of Beclin-1 and LC3-B was evidently enhanced at postoperation days 3 and 5, respectively. However, the reduction of the mTOR protein and ribosomal protein S6 kinase p70 subtype (p70S6K phosphorylation level occurred at the same time after SCI. Simvastatin significantly increased the expression of brain-derived neurotrophic factor (BDNF and glial cell line-derived neurotrophic factor (GDNF. Meanwhile, immunofluorescence results indicated that the expression of chondroitin sulfate proteoglycan (CSPG and caspase-3 protein was obviously reduced by simvastatin. Furthermore, Nissl staining and Basso, Beattie, and Bresnahan (BBB scores showed that the quantity and function of motor neurons were visibly preserved by simvastatin after SCI. The findings of this study showed that simvastatin induced autophagy by inhibiting the mTOR signaling pathway and contributed to neuroprotection after SCI.

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

    Directory of Open Access Journals (Sweden)

    Jochen Grommes

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

  10. Determinants of Quality of Life in High-Dose Benzodiazepine Misusers

    Directory of Open Access Journals (Sweden)

    Stefano Tamburin

    2017-01-01

    Full Text Available Benzodiazepines (BZDs are among the most widely prescribed drugs in developed countries, but they have a high potential for tolerance, dependence and misuse. High-dose BZD misuse represents an emerging addiction phenomenon, but data on quality of life (QoL in high-dose BZD misusers are scant. This study aimed to explore QoL in high-dose BZD misuse. We recruited 267 high-dose BZD misusers, compared the QoL scores in those who took BZD only to poly-drug misusers, and explored the role of demographic and clinical covariates through multivariable analysis. Our data confirmed worse QoL in high-dose BZD misusers and showed that (a QoL scores were not negatively influenced by the misuse of alcohol or other drugs, or by coexisting psychiatric disorders; (b demographic variables turned out to be the most significant predictors of QoL scores; (c BZD intake significantly and negatively influenced QoL. Physical and psychological dimensions of QoL are significantly lower in high-dose BZD misusers with no significant effect of comorbidities. Our data suggest that the main reason for poor QoL in these patients is high-dose BZD intake per se. QoL should be considered among outcome measures in these patients.

  11. Determinants of Quality of Life in High-Dose Benzodiazepine Misusers

    Science.gov (United States)

    Tamburin, Stefano; Federico, Angela; Faccini, Marco; Casari, Rebecca; Morbioli, Laura; Sartore, Valentina; Mirijello, Antonio; Addolorato, Giovanni; Lugoboni, Fabio

    2017-01-01

    Benzodiazepines (BZDs) are among the most widely prescribed drugs in developed countries, but they have a high potential for tolerance, dependence and misuse. High-dose BZD misuse represents an emerging addiction phenomenon, but data on quality of life (QoL) in high-dose BZD misusers are scant. This study aimed to explore QoL in high-dose BZD misuse. We recruited 267 high-dose BZD misusers, compared the QoL scores in those who took BZD only to poly-drug misusers, and explored the role of demographic and clinical covariates through multivariable analysis. Our data confirmed worse QoL in high-dose BZD misusers and showed that (a) QoL scores were not negatively influenced by the misuse of alcohol or other drugs, or by coexisting psychiatric disorders; (b) demographic variables turned out to be the most significant predictors of QoL scores; (c) BZD intake significantly and negatively influenced QoL. Physical and psychological dimensions of QoL are significantly lower in high-dose BZD misusers with no significant effect of comorbidities. Our data suggest that the main reason for poor QoL in these patients is high-dose BZD intake per se. QoL should be considered among outcome measures in these patients.

  12. Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

    Science.gov (United States)

    Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

    2016-11-08

    Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

  13. High-dose gadolinium-enhanced MRI for diagnosis of meningeal metastases

    Energy Technology Data Exchange (ETDEWEB)

    Kallmes, D.F. [Department of Radiology, Box 170, University of Virginia Health Sciences Center, Charlottesville, VA 22908 (United States); Gray, L. [Department of Radiology, Duke University Medical Center, Durham, NC (United States); Glass, J.P. [Department of Medicine, Veterans Administration Hospital, Gainesville, Florida (United States)

    1998-01-01

    We compared high-dose (0.3 mmol/kg) and standard-dose (0.1 mmol/kg) gadolinium-enhanced MRI for diagnosis of meningeal metastases in 12 patients with suspected meningeal metastases. They were imaged with both standard-dose and high-dose gadolinium. All patients with abnormal meningeal enhancement underwent at least one lumbar puncture for cerebrospinal fluid (CSF) cytology, while patients with normal meningeal enhancement were followed clinically. All patients with negative CSF cytology also were followed clinically. A single observer reviewed all the images, with specific attention to the enhancement pattern of the meninges. Abnormal leptomeningeal enhancement was present in three cases, and abnormal pachymeningeal enhancement in three other patients. All of these patients had abnormal CSF analyses. In two of the three cases of abnormal leptomeningeal enhancement the disease was more evident on high-dose than on standard-dose imaging; in one case the abnormal enhancement was visible only on high-dose imaging. In one of the three cases with abnormal pachymeningeal enhancement, the disease was evident prospectively only with high-dose imaging. (orig.) With 3 figs., 10 refs.

  14. THE INFLUENCE OF APOLIPOPROTEIN B AND E GENE POLYMORPHISMS ON THE RESPONSE TO SIMVASTATIN THERAPY IN PATIENTS WITH HYPERLIPIDEMIA

    Institute of Scientific and Technical Information of China (English)

    叶平; 尚延忠; 丁小平

    2003-01-01

    Objective.To investigate the effect of apolipoprotein B(apoB)and E(apoE)genetic variations on lipid profile at baseline(before treatment),and also on the subsequent response to simvastatin therapy.Methods. Eighty-eight patients with hyperlipidemia were treated with simvastatin 5mg daily. The plasma levels of total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C),triglyceride(TG)and apo B were measured pretreatment and at the end of the 4th,8th and 12th post-treatment week.Polymorphisms of apoB at XbaI locus and apoE were determined by restriction fragment length polymorphism(RFLP).Results. In all patients,relative frequencies of X-allele and X+ allele were 0.943 and 0.057 for apoB gene respectively. For apoE gene the relative frequency of ε 2 allele was determined as 0.182,ε3 as 0.580 and ε4 as 0.238.The reduction in TC level was more prominent in patients carrying X- allele than in those with X+ allele following treatment(-23.9% vs. -13.6%,P< 0.05).Compared with patients carrying ε3 or ε4 allele,those with ε 2 allele showed a significantly higher percentage in reduction of apoB level after treatment(P< 0.05). Conclusion. The relative frequency of apoB X+ allele is high in patients with hyperlipidemia,in whom the TC-lowering efficacy is decreased following treatment of simvastatin. The relative frequencies of ε 2 and ε 4 are also high in hyperlipidemic patients,and the ε2 allele is associated with reduction in apoB level during lipid-regulating therapy.

  15. A comparative analysis of radiobiological models for cell surviving fractions at high doses.

    Science.gov (United States)

    Andisheh, B; Edgren, M; Belkić, Dž; Mavroidis, P; Brahme, A; Lind, B K

    2013-04-01

    For many years the linear-quadratic (LQ) model has been widely used to describe the effects of total dose and dose per fraction at low-to-intermediate doses in conventional fractionated radiotherapy. Recent advances in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have increased the interest in finding a reliable cell survival model, which will be accurate at high doses, as well. Different models have been proposed for improving descriptions of high dose survival responses, such as the Universal Survival Curve (USC), the Kavanagh-Newman (KN) and several generalizations of the LQ model, e.g. the Linear-Quadratic-Linear (LQL) model and the Pade Linear Quadratic (PLQ) model. The purpose of the present study is to compare a number of models in order to find the best option(s) which could successfully be used as a fractionation correction method in SRT. In this work, six independent experimental data sets were used: CHOAA8 (Chinese hamster fibroblast), H460 (non-small cell lung cancer, NSLC), NCI-H841 (small cell lung cancer, SCLC), CP3 and DU145 (human prostate carcinoma cell lines) and U1690 (SCLC). By detailed comparisons with these measurements, the performance of nine different radiobiological models was examined for the entire dose range, including high doses beyond the shoulder of the survival curves. Using the computed and measured cell surviving fractions, comparison of the goodness-of-fit for all the models was performed by means of the reduced χ (2)-test with a 95% confidence interval. The obtained results indicate that models with dose-independent final slopes and extrapolation numbers generally represent better choices for SRT. This is especially important at high doses where the final slope and extrapolation numbers are presently found to play a major role. The PLQ, USC and LQL models have the least number of shortcomings at all doses. The extrapolation numbers and final slopes of these models do not depend on dose. Their asymptotes

  16. Simvastatin protects bladder and renal functions following spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    Schuler Thomas C

    2010-04-01

    Full Text Available Abstract Background Urinary bladder and renal dysfunction are secondary events associated with spinal cord injury (SCI in humans. These secondary events not only compromise quality of life but also delay overall recovery from SCI pathophysiology. Furthermore, in experimental models the effects of SCI therapy on bladder and renal functions are generally not evaluated. In this study, we tested whether simvastatin improves bladder and renal functions in a rat model of experimental SCI. Methods SCI was induced by controlled contusion of T9-T10 in adult female rats. Simvastatin (5 mg/Kg body weight was administered at two hours after SCI and repeated every 24 hours until the end point. Simvastatin-treated SCI animals (simvastatin group were compared with vehicle-treated SCI animals (vehicle group in terms of the Basso Beattie Bresnahan score, tissue morphology, cell death, and bladder/renal functions. Results The urinary bladder of vehicle animals showed a 4.3-fold increase in size and a 9-fold increase in wet weight compared to sham animals. Following SCI, the urine to plasma osmolality ratio increased initially but decreased 1 week after SCI. Hematoxylin and eosin staining of bladder tissue showed transitional epithelial hyperplasia, degeneration of lamina propria, and enlargement of tunica adventia in addition to detrusor muscle hypertrophy. Rats treated with simvastatin for 14 days displayed remarkable recovery by showing decreased bladder size and maintenance of a normal urine/plasma osmolality ratio, in addition to improved locomotion. The muscularis layer of the bladder also regained its compact nature in simvastatin animals. Moreover, SCI-induced renal caspase-3 activity was significantly decreased in the simvastatin group indicating the ability of simvastatin to reduce the renal tubular apoptosis. Conclusion Post-injury administration of simvastatin ameliorates bladder and renal dysfunction associated with SCI in rats.

  17. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    Science.gov (United States)

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (agedphenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  18. A new model of biodosimetry to integrate low and high doses.

    Directory of Open Access Journals (Sweden)

    Mònica Pujol

    Full Text Available Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy, the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberration-among-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation.

  19. A New Model of Biodosimetry to Integrate Low and High Doses

    Science.gov (United States)

    Pujol, Mònica; Barquinero, Joan-Francesc; Puig, Pedro; Puig, Roser; Caballín, María Rosa; Barrios, Leonardo

    2014-01-01

    Biological dosimetry, that is the estimation of the dose of an exposure to ionizing radiation by a biological parameter, is a very important tool in cases of radiation accidents. The score of dicentric chromosomes, considered to be the most accurate method for biological dosimetry, for low LET radiation and up to 5 Gy, fits very well to a linear-quadratic model of dose-effect curve assuming the Poisson distribution. The accuracy of this estimation raises difficulties for doses over 5 Gy, the highest dose of the majority of dose-effect curves used in biological dosimetry. At doses over 5 Gy most cells show difficulties in reaching mitosis and cannot be used to score dicentric chromosomes. In the present study with the treatment of lymphocyte cultures with caffeine and the standardization of the culture time, metaphases for doses up to 25 Gy have been analyzed. Here we present a new model for biological dosimetry, which includes a Gompertz-type function as the dose response, and also takes into account the underdispersion of aberration-among-cell distribution. The new model allows the estimation of doses of exposures to ionizing radiation of up to 25 Gy. Moreover, the model is more effective in estimating whole and partial body exposures than the classical method based on linear and linear-quadratic functions, suggesting their effectiveness and great potential to be used after high dose exposures of radiation. PMID:25461738

  20. Variation in long-term antipsychotic polypharmacy and high-dose prescribing across physicians and hospitals.

    Science.gov (United States)

    Latimer, Eric A; Naidu, Adonia; Moodie, Erica E M; Clark, Robin E; Malla, Ashok K; Tamblyn, Robyn; Wynant, Willy

    2014-10-01

    This study had two aims: to measure the prevalence of long-term prescribing of high doses of antipsychotics and antipsychotic polypharmacy in a large Canadian province and to estimate the relative contributions of patient-, physician-, and hospital-level factors. Government hospital discharge, physician, and pharmaceutical claims data were linked to identify individuals with schizophrenia who in 2004 had antipsychotics available to them for at least 11 months. Individuals on a high dose throughout that period, as well as individuals on multiple concurrent antipsychotics (polypharmacy), were identified. Logistic and generalized linear mixed models using patient-, physician-, and hospital-level predictors were estimated. Among the 12,150 individuals identified, 11.9% were on a high dose and 10.4% on antipsychotic polypharmacy continually, with 3.7% in both groups. After adjustment for potential confounders, analyses showed that systematic propensity for physicians to prescribe high doses accounted for 10.9% of the remaining unexplained variance, and physicians as a group who prescribed high doses across a hospital or psychiatry department accounted for 3.0%. For antipsychotic polypharmacy the corresponding percentages were 9.7% and 6.2%. Even after adjustment, the variation in high-dose prescribing and antipsychotic polypharmacy remained substantial. Long-term high-dose and antipsychotic polypharmacy prescribing appeared partly driven by some physicians' and some hospitals' propensities to prescribe in this way independently of patient characteristics. Given the weight of the evidence against high-dose prescribing and antipsychotic polypharmacy, measures addressed to physicians and hospitals most likely to prescribe high doses, antipsychotic polypharmacy, or both should be considered.

  1. Maternal high-dose folic acid during pregnancy and asthma medication in the offspring

    NARCIS (Netherlands)

    Zetstra-van der Woude, Priscilla A.; De Walle, Hermien E. K.; Hoek, Annemieke; Bos, H. Jens; Boezen, H. Marike; Koppelman, Gerhard H.; de Jong-van den Berg, Lolkje T. W.; Scholtens, Salome

    2014-01-01

    Purpose Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to inve

  2. Extra-high doses detected in the enamel of human teeth in the Techa riverside region

    Energy Technology Data Exchange (ETDEWEB)

    Shishkina, E.A., E-mail: ElenaA.Shishkina@gmail.com [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Degteva, M.O.; Tolstykh, E.I.; Volchkova, A. [Urals Research Center for Radiation Medicine, 68A, Vorovsky Str., 454076 Chelyabinsk (Russian Federation); Ivanov, D.V. [Institute of Metal Physics, Russian Academy of Sciences, 18 S. Kovalevsky Str, 620041 Yekaterinburg (Russian Federation); Wieser, A. [Helmholtz Zentrum Muenchen, German Research Centre for Environmental Health, D-85764 Neuherberg (Germany); Della Monaca, S. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Regina Elena, 00144 Rome (Italy); Fattibene, P. [Istituto Superiore di Sanita, 00161 Rome (Italy); Istituto Nazionale di Fisica Nucleare, 00161 Rome (Italy)

    2011-09-15

    During the long-term study of tooth enamel by EPR dosimetry for population exposed to radiation due to contamination of the Techa River, it was found out that for some of the tooth donors the dose accumulated in tooth enamel could be as high as several tens of Gy. Such doses were absorbed only in tooth enamel and they should not be associated with exposures to other organs or the whole body. The nature of such doses was discussed in a number of previous papers where it was shown that the source of such doses is {sup 90}Sr incorporated in the calcified dental tissues. However, among specialists in radiation dosimetry who were not involved in the biokinetic studies, the nature and dosimetric significance of extra-high doses in tooth enamel are still raising questions. The aim of the current paper is to summarize the accumulated information on extra-high doses in the teeth of the Techa riverside residents, describe the dose levels observed, explain the nature of extra-high doses in the enamel and discuss their informative value. The paper includes an overview of already published findings and an analysis of information collected in the data bank of the Urals Research Center for Radiation Medicine (URCRM), Chelyabinsk, Russia, which has not been published before.

  3. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy. Addendum

    Science.gov (United States)

    2009-06-01

    compromising the dose coverage of the prostate and the protection to the urethra , rectum, and bladder for prostate cancer patients treated with High...fusion, dose escalation, prostate cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...18 4 INTRODUCTION Research Project Description Men with prostate cancer , in particular those with advanced

  4. Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries in Preventing Postinfluenza Deaths During 2012-2013 and 2013-2014.

    Science.gov (United States)

    Shay, David K; Chillarige, Yoganand; Kelman, Jeffrey; Forshee, Richard A; Foppa, Ivo M; Wernecke, Michael; Lu, Yun; Ferdinands, Jill M; Iyengar, Arjun; Fry, Alicia M; Worrall, Chris; Izurieta, Hector S

    2017-02-15

    Recipients of high-dose vs standard-dose influenza vaccines have fewer influenza illnesses. We evaluated the comparative effectiveness of high-dose vaccine in preventing postinfluenza deaths during 2012-2013 and 2013-2014, when influenza viruses and vaccines were similar. We identified Medicare beneficiaries aged ≥65 years who received high-dose or standard-dose vaccines in community-located pharmacies offering both vaccines. The primary outcome was death in the 30 days following an inpatient or emergency department encounter listing an influenza International of Classification of Diseases, Ninth Revision, Clinical Modification code. Effectiveness was estimated by using multivariate Poisson regression models; effectiveness was allowed to vary by season. We studied 1039645 recipients of high-dose and 1683264 recipients of standard-dose vaccines during 2012-2013, and 1508176 high-dose and 1877327 standard-dose recipients during 2013-2014. Vaccinees were well-balanced for medical conditions and indicators of frail health. Rates of postinfluenza death were 0.028 and 0.038/10000 person-weeks in high-dose and standard-dose recipients, respectively. Comparative effectiveness was 24.0% (95% confidence interval [CI], .6%-42%); there was evidence of variation by season (P = .12). In 2012-2013, high-dose was 36.4% (95% CI, 9.0%-56%) more effective in reducing mortality; in 2013-2014, it was 2.5% (95% CI, -47% to 35%). High-dose vaccine was significantly more effective in preventing postinfluenza deaths in 2012-2013, when A(H3N2) circulation was common, but not in 2013-2014.

  5. Chronic low-dose radiation protects cells from high-dose radiation via increase of AKT expression by NF-{sub k}B

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyung Sun; Seong, Ki Moon; Kim, Ji Young; Kim, Cha Soon; Yang, Kwang Hee; Nam, Seon Young [Radiation Effect Research Team, Radiation Health Research Institute, Korea Hydro and Nuclear Power Co., LTD., Gyeongju (Korea, Republic of)

    2013-04-15

    Exposure to low-dose and low-dose rate of ionizing radiation is an important issue in radiation protection. Low-dose ionizing radiation has been observed to elicit distinctly different responses compared to high-dose radiation, in various biological systems including the reproductive, immune, and hematopoietic systems (Liu et al. 2006). Some data were reported that low-dose radiation could initiate beneficial effects by stimulating cell growth, DNA repair, activation of transcription factors and gene expression (Calabrese et al., 2004). Cells exposed to low-dose radiation can develop adaptive resistance to subsequent high-dose radiation induced DNA damage, gene mutation, and cell death. We previously reported that low-dose of ionizing radiation induced cell survival through the activation of AKT (protein kinase B, PKB) pathway (Park et al., 2009). AKT has been shown to be potently activated in response to a wide variety of growth factors and ionizing radiation. Cell survival against ionizing radiation seems to be associated with the activation of AKT pathway via phosphorylation of its downstream nuclear target molecules. In the present study, we examined the effects of chronic low-dose irradiation in human lung fibroblast cells. The aim was to explore the possibility of a low-dose radiation-induced adaptive cellular response against subsequent challenging high-dose irradiation. In the present study, we examined the regulatory mechanism responsible for cellular response induced by chronic low-dose of ionizing radiation in normal human cells. We found that the level of AKT protein was closely associated with cell survival. In addition, NF-{sub k}B activation by chronic low-dose radiation regulates AKT activation via gene expression and acinus expression. In conclusion, our data demonstrate that chronic low-dose radiation could inhibit the cell death induced by cytotoxic high-dose radiation through the modulation of the level of AKT and acinus proteins via NF-{sub k

  6. Prospective study of long-term impact of adjuvant high-dose and conventional-dose chemotherapy on health-related quality of life

    NARCIS (Netherlands)

    Buijs, C.; Rodenhuis, S.; Seynaeve, C.M.; van Hoesel, Q.G.; van der Wall, E.; Smit, W.J.; Nooij, M.A.; Voest, E.; Hupperets, P.; TenVergert, E.M.; van Tinteren, H.; Willemse, P.H.; Mourits, M.J.; Aaronson, N.K.; Post, W.J.; de Vries, E.G.

    2007-01-01

    Purpose To evaluate and compare health-related quality of life (HRQOL) after conventional- and high-dose adjuvant chemotherapy in patients with high-risk breast cancer. Patients and Methods Patients were randomly assigned to either a conventional or high-dose chemotherapy regimen; both regimens were

  7. An ultra-high dose of electron radiation response of Germanium Flat Fiber and TLD-100

    Science.gov (United States)

    Alawiah, A.; Amin, Y. M.; Abdul-Rashid, H. A.; Abdullah, W. S. Wan; Maah, M. J.; Bradley, D. A.

    2017-01-01

    The thermoluminescence (TL) response of Germanium Flat Fiber (GFF) and TLD-100 irradiated with 2.5 MeV electrons for the doses up to 1 MGy were studied and compared. The aim was to evaluate the TL supralinearity response at an ultra-high dose (UHD) range and to investigate the change in kinetic parameters of the glow peaks, as the doses increases up to 1 MGy. It is found that the critical dose limit (CDL) of GFF is 5 times higher as compared to TLD-100. CDL is determined by the dose at the maximum supralinearity, f(D)max. It is also found that annealing the TLD-100 and GFF with temperature more than 400 °C is required to reset it back to its original condition, following radiation doses up to 1 MGy. It is also noticed the strange behavior of Peak 4 (TLD-100), which tends to be invisible at the lower dose (<10 kGy) and starts to be appeared at the critical dose limit of 10 kGy. This result might be an important clue to understand the behavior of TLD-100 at extremely high dose range. For both samples, it is observed that the TL intensity is not saturated within the UHD range studied.

  8. Donut-shaped high-dose configuration for proton beam radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Rutz, H.P.; Lomax, A.J. [Div. of Radiation Medicine, Paul Scherrer Inst., Villigen PSI (Switzerland)

    2005-01-01

    Background: the authors report on the conception and first clinical application of a donut-shaped high-dose configuration for proton therapy (PT). This approach allows one to intensify target volume dose coverage for targets encompassing a critical, dose-limiting structure - like here, the cauda equina -, whilst delivering minimal dose to other healthy structures surrounding the target, thereby reducing the integral dose. Methods and results: intensity-modulated PT methods (IMPT) for spot scanning were applied to create and deliver a donut-shaped high-dose configuration with protons, allowing treating > 75% of the target with at least 95% of the prescribed dose of 72.8 CGE, whilst restricting dose to the cauda equina to 60-65 CGE. Integral dose was lower by a factor of 3.3 as compared to intensity-modulated radiotherapy with photons (IMXT). Conclusion: IMPT and spot scanning technology allow a potentially clinically useful approach which is also applicable to spare other critical structures passing through a target volume, including spinal cord, optic nerves, chiasm, brain stem, or urethra. (orig.)

  9. A case of percutaneous high dose rate brachytherapy for superior pulmonary sulcus tumor

    Energy Technology Data Exchange (ETDEWEB)

    Asakura, Tamaki; Imamura, Masahiro; Murata, Takashi [Kansai Medical Univ., Moriguchi, Osaka (Japan)] [and others

    1996-07-01

    A 64-year-old man with advanced superior pulmonary sulcus tumor suffered severe unrelieved pain even after chemotherapy, external irradiation and hyperthermia. So we planned to introduce a percutaneous high dose rate brachytherapy using the microselectron HDR {sup 192}Ir. With the estimation using the Pain Score, satisfying pain relief was attainable with a combination of the percutaneous high dose rate brachytherapy and conventional treatment. So the percutaneous high dose rate brachytherapy had the possibility to contribute to the alleviation of the pain. (author)

  10. "Half-half" blisters in bullous pemphigoid successfully treated with adjuvant high-dose intravenous immunoglobulin.

    Science.gov (United States)

    Pacheco, David; Lopes, Leonor; Soares-Almeida, Luis; Marques, Manuel Sacramento; Filipe, Paulo

    2012-09-01

    Bullous pemphigoid is a rare, autoimmune blistering disease. Its clinical presentation is tense blisters that may arise on normal-appearing or erythematous skin. Bullous pemphigoid refractory to systemic corticosteroids in combination with immunosuppressants such as azathioprine and mycophenolate mofetil may benefit from adjuvant high-dose intravenous immunoglobulin (IVIg). We describe a particular case with an unusual clinical presentation unresponsive to systemic corticosteroids plus azathioprine, in which the addition of high-dose IVIg was successful. The combined therapy of systemic corticosteroids and azathioprine plus high-dose IVIg can be an option in refractory cases due to its efficiency and tolerability.

  11. Regular self-microstructuring on CR39 using high UV laser dose

    Energy Technology Data Exchange (ETDEWEB)

    Parvin, P., E-mail: parvin@aut.ac.ir [Physics Department, Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Refahizadeh, M. [Physics Department, Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Mortazavi, S.Z. [Physics Department, Faculty of Science, Imam Khomeini International University, P.O. Box 34149-16818, Qazvin (Iran, Islamic Republic of); Silakhori, K. [Laser and Optics Research School, P.O. Box 11365-8486, Tehran (Iran, Islamic Republic of); Mahdiloo, A. [Mining and Metallurgical Engineering Department, Amirkabir University of Technology, P.O. Box 1591634311, Tehran (Iran, Islamic Republic of); Aghaii, P. [Physics Department, Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of)

    2014-02-15

    The UV laser induced replicas in the form of self-lining microstructures are created by high dose (with high fluence) ArF laser irradiation on CR39. Microstructures as the self-induced contours, in the form of concentric circles, appear when the laser fluence is well above the ablation threshold. It leads to the regular periodic parallel lines, i.e. circles with large radii having spatial separation 100–200 nm and line width 300–600 nm, where the number of shots increases to achieve higher UV doses. The surface wettability is also investigated after laser texturing to exhibit that a notable hydrophilicity takes place at high doses.

  12. Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

    Science.gov (United States)

    Carter, Lawrence P.; Reissig, Chad J.; Johnson, Matthew W.; Klinedinst, Margaret A.; Griffiths, Roland R.

    2012-01-01

    BACKGROUND Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours. RESULTS Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse. PMID:22989498

  13. Measurement of the Space Radiation Dose for the Flight Aircrew at High-Altitude

    Science.gov (United States)

    Lee, Jaewon; Park, Inchun; Kim, Junsik; Lee, Jaejin; Hwang, Junga; Kim, Young-chul

    2014-03-01

    This paper describes an experimental approach to evaluate the effective doses of space radiations at high-altitude by combining the measured data from the Liulin-6K spectrometer loaded onto the air-borne RC-800 cockpit and the calculated data from CARI-6M code developed by FAA. In this paper, 15 exposed dose experiments for the flight missions at a highaltitude above 10 km and 3 experiments at a normal altitude below 4 km were executed over the Korean Peninsula in 2012. The results from the high-altitude flight measurements show a dramatic change in the exposed doses as the altitude increases. The effective dose levels (an average of 15.27 mSv) of aircrew at the high-altitude are an order of magnitude larger than those (an average of 0.30 mSv) of the normal altitude flight. The comparison was made between the measure dose levels and the calculated dose levels and those were similar each other. It indicates that the annual dose levels of the aircrew boarding RC- 800 could be above 1 mSv. These results suggest that a proper procedure to manage the exposed dose of aircrew is required for ROK Air Force.

  14. Evaluating early administration of the hydroxymethylglutaryl-CoA reductase inhibitor simvastatin in the prevention and treatment of delirium in critically ill ventilated patients (MoDUS trial): Study protocol for a randomized controlled trial

    OpenAIRE

    Casarin, Annalisa; McAuley, Daniel F; Alce, Timothy M.; Zhao, Xiaobei; Ely, E. Wesley; Jackson, Jim C; McDowell, Cliona; Agus, Ashley; Murphy, Lynn; Page, Valerie J

    2015-01-01

    Background The incidence of delirium in ventilated patients is estimated at up to 82%, and it is associated with longer intensive care and hospital stays, and long-term cognitive impairment and mortality. The pathophysiology of delirium has been linked with inflammation and neuronal apoptosis. Simvastatin has pleiotropic properties; it penetrates the brain and, as well as reducing cholesterol, reduces inflammation when used at clinically relevant doses over the short term. This is a single ce...

  15. The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible.

    Science.gov (United States)

    Monson, Laura A; Cavaliere, Christi M; Deshpande, Sagar S; Ayzengart, Alexander L; Buchman, Steven R

    2012-09-07

    The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague-Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.

  16. High-order noise analysis for low dose iterative image reconstruction methods: ASIR, IRIS, and MBAI

    Science.gov (United States)

    Do, Synho; Singh, Sarabjeet; Kalra, Mannudeep K.; Karl, W. Clem; Brady, Thomas J.; Pien, Homer

    2011-03-01

    Iterative reconstruction techniques (IRTs) has been shown to suppress noise significantly in low dose CT imaging. However, medical doctors hesitate to accept this new technology because visual impression of IRT images are different from full-dose filtered back-projection (FBP) images. Most common noise measurements such as the mean and standard deviation of homogeneous region in the image that do not provide sufficient characterization of noise statistics when probability density function becomes non-Gaussian. In this study, we measure L-moments of intensity values of images acquired at 10% of normal dose and reconstructed by IRT methods of two state-of-art clinical scanners (i.e., GE HDCT and Siemens DSCT flash) by keeping dosage level identical to each other. The high- and low-dose scans (i.e., 10% of high dose) were acquired from each scanner and L-moments of noise patches were calculated for the comparison.

  17. MCz diode response as a high-dose gamma radiation dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, F. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Goncalves, J.A.C. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Depto. de Fisica, Pontificia Universidade Catolica de Sao Paulo-PUC/SP, Rua Marques de Paranagua no 111-01303 050 Sao Paulo/SP (Brazil); Khoury, H.J. [Nuclear Energy Department, Universidade Federal de Pernambuco-UFPE, Av. Prof. Luiz Freire no 1000-50740 540 Recife/PE (Brazil); Napolitano, C.M. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Haerkoenen, J. [Helsinki Institute of Physics-HIP, University of Helsinki, 00014 Helsinki (Finland); Bueno, C.C. [Instituto de Pesquisas Energeticas e Nucleares-IPEN-CNEN/SP, Caixa Postal 11049 - 05422 970 Sao Paulo/SP (Brazil); Depto. de Fisica, Pontificia Universidade Catolica de Sao Paulo-PUC/SP, Rua Marques de Paranagua no 111-01303 050 Sao Paulo/SP (Brazil)], E-mail: ccbueno@ipen.br

    2008-02-15

    This work presents the preliminary results obtained with a high-resistivity magnetic Czochralski (MCz) silicon diode processed at the Helsinki Institute of Physics as a high-dose gamma dosimeter in radiation processing. The irradiation was performed using a {sup 60}Co source (Gammacell 220, MDS Nordion) within total doses from 100 Gy up to 3 kGy at a dose rate of 3 kGy/h. In this interval, the dosimetric response of the diode is linear with a correlation coefficient (r{sup 2}) higher than 0.993. However, without any irradiation procedure, the device showed a small sensitivity dependence on the accumulated dose. For total dose of 3 kGy, the observed decrease was about 2%. To clarify the origin of this possible radiation damage effect, some studies are under way.

  18. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    Science.gov (United States)

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH-DOSE

  19. HIGH AND LOW DOSE IVIG THERAPY IN GUILLAIN-BARRE SYNDROME CHILDREN: A COMPARISON

    Directory of Open Access Journals (Sweden)

    P. KARIMZADEH MD

    2009-05-01

    Full Text Available Objective:Acute inflammatory demyelinating peripheral neuropathy (Guillain-Barre-Syndrome is by far the most common cause of immune-medicated peripheral nervous system disease in children; with the near disappearance of poliomyelitis, GBS is responsible for the great majority of cases of acute flaccid paralysis. So far, in several controlled studies, corticosteroids, plasmapheresis and IVIG have been utilized in pediatric patients, afflicted with GBS. Regarding IVIG therapy, two methods have been used; the high dose (1 gr/kg/day for 2 days, and the low dose (400mg/kg/day for 5 days. Review of literature shows that a faster rate of recovery can be accomplished in patients who receive total dose of IVIG in 2 days as compared to the dose being given over 5 days.Materials & Methods:In this study we have compared these two types of treatment in an investigation, conducted in the Mofid Children Hospital on pediatric patients who had sudden onset of acute flaccid  paralysis, and were diagnosed as having GBS. Based on histories, physical examination and electrodiagnosis, subjects were divided in two groups, the high dose IVIG treatment, 1gr/kg/day for 2 days (experimental group, and the low dose IVIG treatment, 400 mg/kg/day for 5 days (control group. Statistical analyses were then carried out using the appropriate software.Results:Result of this study showed a faster rate of recovery for patients in the high dose IVIG group; in this group duration of weakness of limbs was shorter and returning of DTR was faster than in controls. In fact, in this type of treatment, the relationship between high dose IVIG therapy and drug side effects was not significant.Conclusion:Base upon the finding in the present study, we conclude that the high dose IVIG therapy is superior to low dose, in view of faster duration of recovery and shorter hospital stay. Also we may infer that shorter hospital stay could be a factor in reducing of more nasocomial infection. In

  20. High dose rate endobronchial brachytherapy: a curative treatment; La curietherapie endobronchique de haut debit de dose: un traitement curatif

    Energy Technology Data Exchange (ETDEWEB)

    Peiffert, D.; Spaeth, D.; Winnefeld, J. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France); Menard, O. [Centre Hospitalier Universitaire Nancy-Brabois, 54 - Vandoeuvre-les-Nancy (France)

    2000-06-01

    New endobronchial techniques of treatment allow a good unblocking. Nevertheless, only high dose rate brachytherapy delivers a curative treatment for invasive carcinomas. This study analyses the results of the first 33 consecutive patients treated with curative intent by this technique from 1994 to 1997, and followed-up more than one year. Thirty-seven lesions were treated, with usual schedule delivering 30 Gy at 1 cm depth in six fractions and three to five weeks. All the patients were meticulously selected on the local involvement of the tumour and absolute contraindications to a surgical treatment. All of them have a pulmonary disease history or a general contraindication. With a 14-month follow-up, the local control at two months after the treatment was 95 % (endoscopic and histologic), and 90 % of the patients presented a prolonged local control. Four patients died of the treated cancer, another of a controlateral cancer. Ten patients died of another disease, five of them from a respiratory insufficiency. The overall survival rate at two years was 53 % and the specific survival rate 80 %. The acute tolerance was good, without incident. Asymptomatic bronchial stenoses, described by endoscopic follow-up, were described for seven patients. We conclude that, on the basis of a good selection of the patients, and a respect of the indications, high dose rate endobronchial brachytherapy is an effective curative treatment. It offers a new curative option and must be proposed for the small invasive carcinomas in non-operable patients. (author)

  1. "EFFECT OF HIGH VERSUS LOW DOSES OF HUMAN RECOMBINANT ERYTHROPOIETIN ON THE ANEMIA OF PREMATURITY"

    Directory of Open Access Journals (Sweden)

    A. Mohammadzadeh

    2005-05-01

    Full Text Available Recombinant human erythropoietin (rh-EPO is known to accelerate erythropoiesis in preterm infants. The purpose of this study was to compare the effectiveness of early treatment with two doses of rh-EPO (high vs. low dose in the management of anemia of prematurity. Twenty preterm infants with hematocrit (Hct < 30% when infant’s age was between 2 to 3 weeks after birth or Hct <25% when infant’s age was more than 3 weeks after birth, were divided randomly in two groups, each group including 10 babies. Infants in high dose group received 500 u/kg rh-EPO twice per week and the low dose group received 500 u/kg rh-EPO weekly. All infants were fed human milk supplemented with enteral iron. Hematocrit and reticulocyte counts were determined for each infant at the start of the study, 3 days after start of treatment and one week after the end of treatment. The means of gestational age in high dose and low dose groups were 31.4 ± 2.2 and 31.3±2.0 weeks, respectively. Means of birth weight in high dose and low dose groups were 1366 ± 243 and 1438±249 gr, respectively. The two groups were significantly different in reticulocyte count at 3 days after treatment (P = 0.047 and in hematocrit at the end of study (P < 0.0001. We concluded the early treatment of anemia of prematurity with high dose rh-EPO with supplemental iron significantly increases hematocrit and reticulocyte in preterm infants and reduce the need for blood transfusion in these high risk neonates.

  2. High-dose dosimetry of beta rays using blue beryl dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do, E-mail: lsatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Bittencour, Jose F., E-mail: Lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear

    2015-07-01

    High dose radiation is widely used in industrial applications as sterilization of medical products, improvement of materials properties, color enhancement of jewelry stones, etc. The radiation dosimetry of high doses is quite important for these applications. In this work we have investigated the usage of blue beryl crystal also known as aquamarine in high dose dosimetry of beta rays. Some works have shown that silicate minerals exhibit a good Thermoluminescent response when irradiated up to 2000 kGy of gamma rays. Here, we have produced small beryl pellets of approximately 5 mm in diameter and 3 mm thickness to measure high doses of beta rays produced at an electron accelerator at IPEN. Twelve beryl dosimeters were made and six of them were irradiated from 10kGy up to 100 kGy. The technique used to create a calibration curve was the thermoluminescence using the glow peak at 310°C. (author)

  3. Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study

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    Roberta Di Caprio

    2015-01-01

    Full Text Available Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6, when added before (pretreatment or after (posttreatment LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled.

  4. Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study

    Science.gov (United States)

    Di Caprio, Roberta; Di Costanzo, Luisa; Monfrecola, Giuseppe

    2015-01-01

    Doxycycline is used to treat infective diseases because of its broadspectrum efficacy. High dose administration (100 or 200 mg/day) is often responsible for development of bacterial resistances and endogenous flora alterations, whereas low doses (20–40 mg/day) do not alter bacteria susceptibility to antibiotics and exert anti-inflammatory activities. In this study, we wanted to assess the efficacy of both low and high doxycycline doses in modulating IL-8, TNF-α, and IL-6 gene expression in HaCaT cells stimulated with LPS. Three experimental settings were used, differing in the timing of doxycycline treatment in respect to the insult induced by LPS: pretreatment, concomitant, and posttreatment. Low doses were more effective than high doses in modulating gene expression of LPS-induced proinflammatory cytokines (IL-8, TNF-α, and IL-6), when added before (pretreatment) or after (posttreatment) LPS stimulation. This effect was not appreciated when LPS and doxycycline were simultaneously added to cell cultures: in this case high doses were more effective. In conclusion, our in vitro study suggests that low doxycycline doses could be safely used in chronic or acute skin diseases in which the inflammatory process, either constantly in progress or periodically recurring, has to be prevented or controlled. PMID:25977597

  5. [High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].

    Science.gov (United States)

    Selle, Frédéric; Gligorov, Joseph; Soares, Daniele G; Lotz, Jean-Pierre

    2016-10-01

    The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses.

  6. Measurement of photoneutron dose produced by wedge filters of a high energy linac using polycarbonate films.

    Science.gov (United States)

    Hashemi, Seyed Mehdi; Hashemi-Malayeri, Bijan; Raisali, Gholamreza; Shokrani, Parvaneh; Sharafi, Ali Akbar; Torkzadeh, Falamarz

    2008-05-01

    Radiotherapy represents the most widely spread technique to control and treat cancer. To increase the treatment efficiency, high energy linacs are used. However, applying high energy photon beams leads to a non-negligible dose of neutrons contaminating therapeutic beams. In addition, using conventional linacs necessitates applying wedge filters in some clinical conditions. However, there is not enough information on the effect of these filters on the photoneutrons produced. The aim of this study was to investigate the change of photoneutron dose equivalent due to the use of linac wedge filters. A high energy (18 MV) linear accelerator (Elekta SL 75/25) was studied. Polycarbonate films were used to measure the dose equivalent of photoneutrons. After electrochemical etching of the films, the neutron dose equivalent was calculated using Hp(10) factor, and its variation on the patient plane at 0, 5, 10, 50 and 100 cm from the center of the X-ray beam was determined. By increasing the distance from the center of the X-ray beam towards the periphery, the photoneutron dose equivalent decreased rapidly for the open and wedged fields. Increasing of the field size increased the photoneutron dose equivalent. The use of wedge filter increased the proportion of the neutron dose equivalent. The increase can be accounted for by the selective absorption of the high energy photons by the wedge filter.

  7. High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized, Multicenter Study.

    Science.gov (United States)

    Giustina, Andrea; Mazziotti, Gherardo; Cannavò, Salvatore; Castello, Roberto; Arnaldi, Giorgio; Bugari, Giovanna; Cozzi, Renato; Ferone, Diego; Formenti, Anna Maria; Gatti, Enza; Grottoli, Silvia; Maffei, Pietro; Maffezzoni, Filippo; Montini, Marcella; Terzolo, Massimo; Ghigo, Ezio

    2017-07-01

    Increase in drug frequency or dose is recommended for acromegaly patients with partial response to long-acting somatostatin receptor ligands (SRLs). However, the efficacy and safety data with lanreotide (LAN) Autogel (LAN-ATG) at high dose (HD) or high frequency (HF) are still scanty. To evaluate the biochemical efficacy and safety of HF and HD LAN-ATG in patients with active acromegaly. Twenty-four-week prospective, multicenter, randomized, open-label trial. Thirty patients with active acromegaly, partial responders to SRLs, were randomized to HF (120 mg/21 days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. Normalization of serum insulin-like growth factor-I (IGF-I) and reduction in random growth hormone (GH) values < 1.0 µg/L, reduction in serum IGF-I and GH from baseline, differences in biochemical response between HF and HD LAN-ATG, adverse events. IGF-I decreased significantly (P = 0.007) during the 24-week treatment, with greater decrease in HD (P = 0.03) vs HF group (P = 0.08). Normalization in IGF-I values occurred in 27.6% of patients (P = 0.016 vs baseline), without a significant difference between HF and HD groups (P = 0.59). The decrease in serum IGF-I significantly correlated with serum LAN values (P = 0.04), and normalization of IGF-I was predicted by baseline IGF-I values (P = 0.02). Serum GH values did not change significantly (P = 0.22). Overall, 19 patients (63.3%) experienced adverse events, all being mild to moderate and transient, without differences between the two therapeutic arms. HF and HD LAN-ATG regimens are effective in normalizing IGF-I values in about one-third of patients with active acromegaly inadequately controlled by long-term conventional SRLs therapy.

  8. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis, E-mail: acapellizzon@hcancer.org.br [A.C. Camargo Cancer Center, Sao Paulo, SP (Brazil). Departamento de Radioterapia

    2016-05-15

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. (author)

  9. Salvage high-dose-rate interstitial brachytherapy for locally recurrent rectal cancer*

    Science.gov (United States)

    Pellizzon, Antônio Cássio Assis

    2016-01-01

    For tumors of the lower third of the rectum, the only safe surgical procedure is abdominal-perineal resection. High-dose-rate interstitial brachytherapy is a promising treatment for local recurrence of previously irradiated lower rectal cancer, due to the extremely high concentrated dose delivered to the tumor and the sparing of normal tissue, when compared with a course of external beam radiation therapy. PMID:27403021

  10. Does TGF Beta Suppressing Effect of Simvastatin Lead to Protection Against Surgical Adhesion Band Formation?

    Directory of Open Access Journals (Sweden)

    Sayed Shahabuddin Hoseini

    2008-05-01

    Full Text Available Intra-abdominal adhesions are the most common cause of small bowel obstruction. Infertility in women and chronic abdominal-pelvic pain are the other problems of adhesiogenesis which impose a great economic burden on the population health. On the other hand, increased levels of transforming growth factor beta1 (TGF-β are shown to play a role in formation of adhesion bands and can impair peritoneal fibrinolysis. Moreover, simvastatin, an immunomodulator agent, can down-regulate TGF-β. Although it is shown in previous studies that simvastatin antagonizes the interaction between TGF-β and connective tissue growth factor (CTGF, no human study exists on the effect of simvastatin on surgical adhesion band formation. We hypothesize that simvastatin, through its effect on reducing the level of TGF-β, may be useful in preventing adhesion band formation after surgical procedures. Surely, this hypothesis should be assessed in several experimental and clinical trials.

  11. Simvastatin Promotes Adult Hippocampal Neurogenesis by Enhancing Wnt/β-Catenin Signaling

    Directory of Open Access Journals (Sweden)

    Nicholas C. Robin

    2014-01-01

    Full Text Available Statins improve recovery from traumatic brain injury and show promise in preventing Alzheimer disease. However, the mechanisms by which statins may be therapeutic for neurological conditions are not fully understood. In this study, we present the initial evidence that oral administration of simvastatin in mice enhances Wnt signaling in vivo. Concomitantly, simvastatin enhances neurogenesis in cultured adult neural progenitor cells as well as in the dentate gyrus of adult mice. Finally, we find that statins enhance Wnt signaling through regulation of isoprenoid synthesis and not through cholesterol. These findings provide direct evidence that Wnt signaling is enhanced in vivo by simvastatin and that this elevation of Wnt signaling is required for the neurogenic effects of simvastatin. Collectively, these data add to the growing body of evidence that statins may have therapeutic value for treating certain neurological disorders.

  12. Effect of simvastatin versus low level laser therapy (LLLT) on bone regeneration in rabbit's tibia

    Science.gov (United States)

    Gheith, Mostafa E.; Khairy, Maggie A.

    2014-02-01

    Simvastatin is a cholesterol lowering drug which proved effective on promoting bone healing. Recently low level laser therapy (LLLT) proved its effect as a biostimulator promoting bone regeneration. This study aims to compare the effect of both Simvastatin versus low level laser on bone healing in surgically created bone defects in rabbit's tibia. Material and methods: The study included 12 New Zealand white rabbits. Three successive 3mm defects were created in rabbits tibia first defect was left as control, second defect was filled with Simvastatin while the third defect was acted on with Low Level Laser (optical fiber 320micrometer). Rabbits were sacrificed after 48 hours, 1 week and 2 weeks intervals. Histopathology was conducted on the three defects Results: The histopathologic studies showed that the bony defects treated with the Low Level Laser showed superior healing patterns and bone regeneration than those treated with Simvastatin. While the control defect showed the least healing pattern.

  13. Effects of simvastatin, ezetimibe, and their combination on histopathologic alterations caused by adjuvant-induced arthritis.

    Science.gov (United States)

    Barbosa, Carmem Patrícia; Ritter, Alessandra Milene; da Silva, Lorena Gimenez; Grespan, Renata; Cuman, Roberto Kenji Nakamura; Hernandes, Luzmarina; Bersani-Amado, Ciomar Aparecida

    2014-08-01

    The objective of the present study was to investigate the effects of monotherapy with simvastatin or ezetimibe compared with those of an ezetimibe + simvastatin combination on the histopathologic aspects of arthritis induced by Complete Freund's Adjuvant in rats. The characteristics of diarthrosis were analyzed 7 and 28 days after arthritis induction with regard to the regularity and integrity of articular cartilage, the presence of leukocytes in blood vessels at the inflammation site, and the cytokine levels in articular tissue. Monotherapy with simvastatin or ezetimibe and the ezetimibe + simvastatin combination effectively reduced the cytokine levels (interleukin-6 and tumor necrosis factor) and articular lesions that are characteristic of this experimental disease. Although the results did not reveal significant differences between the monotherapy and the combined therapy, they suggest that these drugs have considerable antiinflammatory properties, as reflected by an attenuation of articular cartilage lesions mediated by a reduction in the levels of proinflammatory cytokines.

  14. The Power of Classic Music to Reduce Anxiety in Rats Treated with Simvastatin

    Directory of Open Access Journals (Sweden)

    José Geraldo Pereira da Cruz

    2011-08-01

    Full Text Available Introduction: This study was designed to investigate the effects of music in Wistar rats after sub-chronic treatment of simvastatin. The rats were orally administered with either simvastatin or saline (controls. After 4 weeks of drug treatment, the rats were selected for behavioral studies. The rats were exposed to music 24 hours before behavioral tests (Mozart’s piano sonata, KV361, Largo. Results: The experiments suggest that exposure to chronic treatment with simvastatin (1 or 10 mg/kg/day reduced anxiety levels in rats when associated with Mozart music in an elevated plus-maze. Discussion: These results indicate that music can serve as an effective adjuvant in rats treated with simvastatin, and that this species could potentially be used in other preclinical models utilizing musical interventions.

  15. Comparison of high-dose and low-dose insulin by continuous intravenous infusion in the treatment of diabetic ketoacidosis in children.

    Science.gov (United States)

    Burghen, G A; Etteldorf, J N; Fisher, J N; Kitabchi, A Q

    1980-01-01

    We studied the efficacy of low-dose (0.1 U/kg/h) and high-dose (1..0 U/kg/h) insulin, given randomly to children with diabetic ketoacidosis (DKA) by continuous intravenous infusion without a loading dose. Plasma glucose reached 250 mg/dl in 3.4 +/- 0.4 h with the high-dose insulin group compared with 5.4 +/- 0.5 h with the low-dose insulin group (P Hypokalemia (K insulin, with a slower rate of glucose decrease, is as effective as a high dose for the treatment of DKA in children with less incidence of hypokalemia and decreased potential for hypoglycemia.

  16. In-phantom neutron dose distribution for bladder cancer cases treated with high-energy photons

    Science.gov (United States)

    Khaled, N. E.; Attalla, E. M.; Ammar, H.; Khalil, W.

    2011-06-01

    This work presents an estimation of the neutron dose distribution for common bladder cancer cases treated with high-energy photons of 15 MV therapy accelerators. Neutron doses were measured in an Alderson phantom, using TLD 700 and 600 thermoluminescence dosimeters, resembling bladder cancer cases treated with high-energy photons from 15 MV LINAC and having a treatment plan using the four-field pelvic box technique. Thermal neutron dose distribution in the target area and the surrounding tissue was estimated. The sensitivity of all detectors for both gamma and neutrons was estimated and used for correction of the TL reading. TLD detectors were irradiated with a Co60 gamma standard source and thermal neutrons at the irradiation facility of the National Institute for Standards (NIS). The TL to dose conversion factor was estimated in terms of both Co60 neutron equivalent dose and thermal neutron dose. The dose distribution of photo-neutrons throughout each target was estimated and presented in three-dimensional charts and isodose curves. The distribution was found to be non-isotropic through the target. It varied from a minimum of 0.23 mSv/h to a maximum of 2.07 mSv/h at 6 cm off-axis. The mean neutron dose equivalent was found to be 0.63 mSv/h, which agrees with other published literature. The estimated average neutron equivalent to the bladder per administered therapeutic dose was found to be 0.39 mSv Gy-1, which is also in good agreement with published literature. As a consequence of a complete therapeutic treatment of 50 Gy high-energy photons at 15 MV, the total thermal neutron equivalent dose to the abdomen was found to be about 0.012 Sv.

  17. High brachytherapy doses can counteract hypoxia in cervical cancer—a modelling study

    Science.gov (United States)

    Lindblom, Emely; Dasu, Alexandru; Beskow, Catharina; Toma-Dasu, Iuliana

    2017-01-01

    Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased

  18. Elastic stability of high dose neutron irradiated spinel

    Energy Technology Data Exchange (ETDEWEB)

    Li, Z.; Chan, S.K. [Argonne National Lab., Chicago, IL (United States); Garner, F.A. [Pacific Northwest Lab., Richland, WA (United States)] [and others

    1995-04-01

    The objective of this effort is to identify ceramic materials that are suitable for fusion reactor applications. Elastic constants (C{sub 11}, C{sub 12}, and C{sub 44}) of spinel (MgAl{sub 2}O{sub 4}) single crystals irradiated to very high neutron fluences have geen measured by an ultrasonic technique. Although results of a neutron diffraction study show that cation occupation sites are significantly changed in the irradiated samples, no measurable differences occurred in their elastic properties. In order to understand such behavior, the elastic properties of a variety of materials with either normal or inverse spinel structures were studied. The cation valence and cation distribution appear to have little influence on the elastic properties of spinel materials.

  19. High-dose Sulbactam Treatment for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant

    Directory of Open Access Journals (Sweden)

    In Beom Jeong

    2016-11-01

    Full Text Available Background Several antibiotics can be used to treat ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii (CRAB-VAP including high-dose sulbactam. However, the effectiveness of high-dose sulbactam therapy is not well known. We report our experience with high-dose sulbactam for treatment of CRAB-VAP. Methods Medical records of patients with CRAB-VAP who were given high-dose sulbactam between May 2013 and June 2015 were reviewed. Results Fifty-eight patients with CRAB-VAP were treated with high-dose sulbactam. The mean age was 72.0 ± 15.2 years, and the acute physiology and chronic health evaluation II (APACHE II score was 15.1 ± 5.10 at the time of CRAB-VAP diagnosis. Early clinical improvement was observed in 65.5% of patients, and 30-day mortality was 29.3%. Early clinical failure (odds ratio [OR]: 8.720, confidence interval [CI]: 1.346-56.484; p = 0.023 and APACHE II score ≥ 14 at CRAB-VAP diagnosis (OR: 10.934, CI: 1.047-114.148; p = 0.046 were associated with 30-day mortality. Conclusions High-dose sulbactam therapy may be effective for the treatment of CRAB-VAP. However, early clinical failure was observed in 35% of patients and was associated with poor outcome.

  20. Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin.

    Science.gov (United States)

    de la Peña, Amparo; Ma, Xiaosu; Reddy, Shobha; Ovalle, Fernando; Bergenstal, Richard M; Jackson, Jeffrey A

    2014-07-01

    Pharmacokinetic/pharmacodynamic (PK/PD) studies of human regular U-500 insulin (U-500R) at high doses commonly used in clinical practice (>100 units) have not been performed. The current analysis applied PK/PD modeling/simulation to fit the data and simulate single-dose and steady-state PK/PD of U-500R high-dose regimens. Data from 3 single-dose euglycemic clamp studies in healthy obese and normal-weight patients, and normal-weight patients with type 1 diabetes were used to build the model. The model was sequential (PK inputs fed into PD component). PK was described using a 1-compartment model with first-order absorption and elimination. The model estimated separate absorption rate constants for U-500R and human regular U-100 insulin. The PD component used an effect compartment model, parameterized in terms of maximum pharmacologic effect (E(max)) and concentration to achieve 50% of E(max). The model described the data well. Steady-state PK for once-daily (QD), twice-daily (BID), or thrice-daily (TID) administration appeared to be reached 24 hours after the first dose. At steady-state, QD dosing showed the greatest fluctuations in PK/PD. BID dosing showed a gradual increase in insulin action with each dose and a fairly stable basal insulin effect. For TID dosing, activity was maintained throughout the dosing interval. PK/PD modeling/simulation of high U-500R doses supports BID or TID administration with an extended duration of activity relative to QD. TID dosing may provide slightly better full-day insulin effect. Additional PK/PD studies and randomized controlled trials of U-500R are needed to validate model predictions in patients with insulin-resistant diabetes requiring high-dose insulin.

  1. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease

    Science.gov (United States)

    Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; van Dyck, C.H.; Aisen, P.S.

    2011-01-01

    Background: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD. Objective: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD. Methods: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale–cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior. Results: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment. Conclusion: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol. Classification of evidence: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog. PMID:21795660

  2. Administration of simvastatin after kainic acid-induced status epilepticus restrains chronic temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Chuncheng Xie

    Full Text Available In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE on rat brain with temporal lobe epilepsy (TLE. First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL-1β and tumor necrosis factor-α (TNF-α. Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP staining and neuron loss using Nissl staining in hippocampus at 4-6 months after KA-lesion. We found that simvastatin suppressed reactive astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar (DH. We next assessed aberrant mossy fiber sprouting (MFS that is known to contribute to recurrence of spontaneous seizure in epileptic brain. In contrast to the robust MFS observed in saline-treated animals, the extent of MFS was restrained by simvastatin in epileptic rats. Attenuated MFS was related to decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying decreased hippocampal susceptibility in animal treated with simvastatin. Electronic encephalography (EEG was recorded during 4 to 6 months after KA-lesion. The frequency of abnormal spikes in rats with simvastatin-treatment decreased significantly compared to the saline group. In summary, simvastatin treatment suppressed cytokines expression and reactive astrocytosis and decreased the frequency of discharges of epileptic brain, which might be due to the inhibition of MFS in DH. Our study suggests that simvastatin administration might be a possible intervention and promising strategy for preventing SE exacerbating to chronic epilepsy.

  3. High-dose neutron irradiation embrittlement of RAFM steels

    Energy Technology Data Exchange (ETDEWEB)

    Gaganidze, E. [Forschungszentrum Karlsruhe, Institut fuer Materialforschung II, P.O. Box 3640, 76021 Karlsruhe (Germany)]. E-mail: ermile.gaganidze@imf.fzk.de; Schneider, H.-C. [Forschungszentrum Karlsruhe, Institut fuer Materialforschung II, P.O. Box 3640, 76021 Karlsruhe (Germany); Dafferner, B. [Forschungszentrum Karlsruhe, Institut fuer Materialforschung II, P.O. Box 3640, 76021 Karlsruhe (Germany); Aktaa, J. [Forschungszentrum Karlsruhe, Institut fuer Materialforschung II, P.O. Box 3640, 76021 Karlsruhe (Germany)

    2006-09-01

    Neutron irradiation-induced embrittlement of the reduced-activation ferritic/martensitic (RAFM) steel EUROFER97 was studied under different heat treatment conditions. Irradiation was performed in the Petten High Flux Reactor within the HFR Phase-IIb (SPICE) irradiation project up to 16.3 dpa and at different irradiation temperatures (250-450 deg. C). Several reference RAFM steels (F82H-mod, OPTIFER-Ia, GA3X and MANET-I) were also irradiated at selected temperatures. The impact properties were investigated by instrumented Charpy-V tests with subsize specimens. Embrittlement and hardening of as-delivered EUROFER97 steel are comparable to those of reference steels. Heat treatment of EUROFER97 at a higher austenitizing temperature substantially improves the embrittlement behaviour at low irradiation temperatures. Analysis of embrittlement in terms of the parameter C = {delta}DBTT/{delta}{sigma} indicates hardening-dominated embrittlement at irradiation temperatures below 350 deg. C with 0.17 {<=} C {<=} 0.53 deg. C/MPa. Scattering of C at irradiation temperatures above 400 deg. C indicates no hardening embrittlement.

  4. High-dose neutron irradiation embrittlement of RAFM steels

    Science.gov (United States)

    Gaganidze, E.; Schneider, H.-C.; Dafferner, B.; Aktaa, J.

    2006-09-01

    Neutron irradiation-induced embrittlement of the reduced-activation ferritic/martensitic (RAFM) steel EUROFER97 was studied under different heat treatment conditions. Irradiation was performed in the Petten High Flux Reactor within the HFR Phase-IIb (SPICE) irradiation project up to 16.3 dpa and at different irradiation temperatures (250-450 °C). Several reference RAFM steels (F82H-mod, OPTIFER-Ia, GA3X and MANET-I) were also irradiated at selected temperatures. The impact properties were investigated by instrumented Charpy-V tests with subsize specimens. Embrittlement and hardening of as-delivered EUROFER97 steel are comparable to those of reference steels. Heat treatment of EUROFER97 at a higher austenitizing temperature substantially improves the embrittlement behaviour at low irradiation temperatures. Analysis of embrittlement in terms of the parameter C = ΔDBTT/Δ σ indicates hardening-dominated embrittlement at irradiation temperatures below 350 °C with 0.17 ⩽ C ⩽ 0.53 °C/MPa. Scattering of C at irradiation temperatures above 400 °C indicates no hardening embrittlement.

  5. Polybutadiene and Styrene-Butadiene rubbers for high-dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lucas N. [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Goiania, Goiania -GO (Brazil); Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil); Vieira, Silvio L. [Instituto de Fisica, Universidade Federal de Goias-UFG, Campus Samambaia, Goiania-GO (Brazil); Schimidt, Fernando [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Inhumas, Inhumas-GO (Brazil); Antonio, Patricia L.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil)

    2015-07-01

    Polybutadiene and Styrene-Butadiene are synthetical rubbers used widely for pneumatic tires manufacturing. In this research, the dosimeter characteristics of those rubbers were studied for application in high-dose dosimetry. The rubber samples were irradiated with doses of 10 Gy up to 10 kGy, using a {sup 60}Co Gamma Cell-220 system (dose rate of 1.089 kGy/h) and their readings were taken on a Fourier Transform Infrared Spectroscopy-FTIR system (model Frontier/Perkin Elmer). The ratios of two absorbance peaks were taken for each kind of rubber spectrum, Polybutadiene (1306/1130 cm{sup -1}) and Styrene-Butadiene (1449/1306 cm{sup -1}). The ratio calculated was used as the response to the irradiation, and is not uniform across the sample. From the results, it can be concluded for both rubbers: a) the dose-response curves may be useful for high-dose dosimetry (greater than 250 Gy); b) their response for reproducibility presented standard deviations lower than 2.5%; c) the relative sensitivity was higher for Styrene-Butadiene (1.86 kGy{sup -1}) than for Polybutadiene (1.81 kGy{sup -1}), d) for doses of 10 kGy to 200 kGy, there was no variation in the dosimetric response. Both types of rubber samples showed usefulness as high-dose dosimeters. (authors)

  6. Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

    Directory of Open Access Journals (Sweden)

    Ketab E. Al-Otaibi

    2012-01-01

    Full Text Available Contrast media- (CM- induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN. Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels and myeloperoxidase (MPO and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

  7. HIGH DOSE FRACTION RADIOTHERAPY FOR MUCOSAL MALIGNANT MELANOMA OF THE HEAD AND NECK

    Institute of Scientific and Technical Information of China (English)

    Liu Xiuying; Li Huiling; Zheng Tianrong; Lin Xiangsong

    1998-01-01

    Objective:To evatuate the results of high dose fraction radiotherapy for mucosal malignant melanoma of the head and neck (HNMM). Methods: From 1984-1994, 35 patients with HNMM were enrolled in this study. Among them, 27 cases localized to the nasal cavity or para-nasal sinus, 8 to the oral cavity. All patients received high dose fraction radiotherapy (6--8 Gy/fraction)with the total dose ranged from 40 to 60 Gy. Results: The minimum follow-up was 2 years (ranged 2-7 years). The overall 3- and 5-year survival rate was 45.7% and 24%,respectively. Conclusion: High dose fraction radiotherapy is effective for local control of HNMM.

  8. Polycarbonate-based benzo-δ-sultam films for high-dose dosimetry in radiation processing

    Energy Technology Data Exchange (ETDEWEB)

    Feizi, Shazad [University of Tehran, Tehran (India). School of Chemistry; Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ziaie, Farhood [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ghandi, Mehdi [University of Tehran, Tehran (India). School of Chemistry

    2015-05-01

    In this work characteristics of the polycarbonate films with 20 μm in thickness containing different weight percentage of Benzo-δ-sultam were studied for use as a high dose dosimetry system in radiation processing facilities. The sensitivity of the dosimeters and the linearity of dose-response curves were investigated under {sup 60}Co γ-rays in a dose range of 0-100 kGy, and obtained results were compared with the commercial CTA and FWT film dosimeters. The results show that the absorbance at 348 nm depends linearly on the dose in the investigated dose range. The effects of pre-irradiation (shelf-life) and post-irradiation storage in dark and in indirect sunlight are also discussed. The results show that the dosimeters characteristics are stable within 1% at 25 C, 3 months after the irradiation.

  9. Is High Dose Therapy Superior to Conventional Dose Therapy as Initial Treatment for Relapsed Germ Cell Tumors? The TIGER Trial

    Directory of Open Access Journals (Sweden)

    Darren R. Feldman, Robert Huddart, Emma Hall, Jörg Beyer, Thomas Powles

    2011-01-01

    Full Text Available Metastatic germ cell tumours (GCTs are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT and high dose therapy (HDT are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP with sequential HDT (TICE. The planned open labelled randomised phase III study (TIGER is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint. It is hoped that this large study will conclusively resolve the uncertainty which currently exists.

  10. High dose rate versus low dose rate brachytherapy for oral cancer--a meta-analysis of clinical trials.

    Directory of Open Access Journals (Sweden)

    Zhenxing Liu

    Full Text Available OBJECTIVE: To compare the efficacy and safety of high dose rate (HDR and low dose rate (LDR brachytherapy in treating early-stage oral cancer. DATA SOURCES: A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies. STUDY SELECTION: Only randomized controlled trials (RCT and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III were of interest. DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62-2.01, overall mortality (OR = 1.01, CI 95% 0.61-1.66 and Grade 3/4 complications (OR = 0.86, CI 95% 0.52-1.42. CONCLUSIONS: This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.

  11. PLUTONIUM/HIGH-LEVEL VITRIFIED WASTE BDBE DOSE CALCULATION

    Energy Technology Data Exchange (ETDEWEB)

    D.C. Richardson

    2003-03-19

    In accordance with the Nuclear Waste Policy Amendments Act of 1987, Yucca Mountain was designated as the site to be investigated as a potential repository for the disposal of high-level radioactive waste. The Yucca Mountain site is an undeveloped area located on the southwestern edge of the Nevada Test Site (NTS), about 100 miles northwest of Las Vegas. The site currently lacks rail service or an existing right-of-way. If the Yucca Mountain site is found suitable for the repository, rail service is desirable to the Office of Civilian Waste Management (OCRWM) Program because of the potential of rail transportation to reduce costs and to reduce the number of shipments relative to highway transportation. A Preliminary Rail Access Study evaluated 13 potential rail spur options. Alternative routes within the major options were also developed. Each of these options was then evaluated for potential land use conflicts and access to regional rail carriers. Three potential routes having few land use conflicts and having access to regional carriers were recommended for further investigation. Figure 1-1 shows these three routes. The Jean route is estimated to be about 120 miles long, the Carlin route to be about 365 miles long, and Caliente route to be about 365 miles long. The remaining ten routes continue to be monitored and should any of the present conflicts change, a re-evaluation of that route will be made. Complete details of the evaluation of the 13 routes can be found in the previous study. The DOE has not identified any preferred route and recognizes that the transportation issues need a full and open treatment under the National Environmental Policy Act. The issue of transportation will be included in public hearings to support development of the Environmental Impact Statement (EIS) proceedings for either the Monitored Retrievable Storage Facility or the Yucca Mountain Project or both.

  12. Influence of adjacent low-dose fields on tolerance to high doses of protons in rat cervical spinal cord

    NARCIS (Netherlands)

    Bijl, HP; van Luijk, P; Coppes, RP; Schippers, JM; Konings, AWT; van der Kogel, AJ

    2006-01-01

    Purpose: The dose-response relationship for a relatively short length (4 mm) of rat spinal cord has been shown to be significantly modified by adjacent low-dose fields. In an additional series of experiments, we have now established the dose-volume dependence of this effect. Methods and Materials: W

  13. Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin.

    Science.gov (United States)

    Reinl, Erin L; Goodwin, Zane A; Raghuraman, Nandini; Lee, Grace Y; Jo, Erin Y; Gezahegn, Beakal M; Pillai, Meghan K; Cahill, Alison G; de Guzman Strong, Cristina; England, Sarah K

    2017-08-01

    Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ(2) tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value labor induction and required prostaglandins. High-dose-requiring women were more likely to undergo cesarean delivery for first-stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low-dose

  14. Modulatory Role of Simvastatin against Aluminium Chloride-Induced Behavioural and Biochemical Changes in Rats

    Science.gov (United States)

    Nampoothiri, Madhavan; John, Jessy; Kumar, Nitesh; Mudgal, Jayesh; Nampurath, Gopalan Kutty; Chamallamudi, Mallikarjuna Rao

    2015-01-01

    Objectives. Aluminium, a neurotoxic agent in humans, has been implicated in the pathogenesis of neurodegenerative disorders. In this study, we examined the behavioral and biochemical effects of aluminium in rats with special emphasis on memory centres, namely, hippocampus and frontal cortex. Further, the effect of simvastatin treatment on aluminium intoxication was evaluated. Methods. Rats were exposed to aluminium chloride (AlCl3) for 60 days. Simvastatin (10 mg/kg/p.o.) and rivastigmine (1 mg/kg/p.o.) were administered daily prior to AlCl3. Behavioral parameters were assessed using Morris water maze test and actophotometer followed by biochemical investigations, namely, acetylcholinesterase (AChE) activity, TNF-α level, antioxidant enzymes (GSH, catalase), lipid peroxidation, and nitrite level in hippocampus and frontal cortex. Triglycerides, total cholesterol, LDL, and HDL levels in serum were also determined. Key Findings. Simvastatin treatment improved cognitive function and locomotor activity in rats. Simvastatin reversed hyperlipidemia and significantly rectified the deleterious effect of AlCl3 on AChE activity. Further, in hippocampus and frontal cortex, aluminium-induced elevation in nitrite and TNF-α and reduction in antioxidant enzymes were inhibited by simvastatin. Conclusion. To conclude, the present study suggests that simvastatin per se protects the neurons in hippocampus and frontal cortex from AlCl3, an environmental toxin. PMID:25802481

  15. EFFICACY AND SAFETY OF SIMVASTATIN IN RHEUMATOID ARTHRITIS: AN OPEN-LABEL, CONTROLLED STUDY

    Directory of Open Access Journals (Sweden)

    I. V. Shirinsky

    2008-01-01

    Full Text Available Abstract. Recently discovered immune–modulating and anti-inflammatory properties of statins have resulted in application of these drugs for treatment of autoimmune disorders. There are few studies investigating therapeutic potential of simvastatin in rheumatoid arthritis (RA. In present study, we investigated efficacy and safety of simvastatin in active RA patients treated with conventional disease-modifying antirheumatic drugs (DMARDs. Thirty-three patients were enrolled into an open-label, controlled study. The patients received treatment with 40 mg of simvastatin daily for 12 weeks. A group of historical controls consisted of nine patients taking placebo combined with disease-modifying therapy. No differences in demographic characteristics and disease activity were observed between the two groups. By the end of therapy (12 weeks, simvastatin-treated patients exhibited a significant reduction in disease activity scores with 28-joint counts (DAS28, and according to physician’s assessment of disease, as compared with control group. The estimate of trea tment effect (DAS28 scores was 0.76 (95% confidence interval 0.01-1.5, thus corresponding to moderate decrease in disease activity. In conclusion, combination therapy with simvastatin and conventional DMARDs results into decreased RA activity. However, additional studies are required in order to specify exact role of simvastatin in RA treatment. (Med. Immunol., vol. 10, N 4-5, pp 477-482.

  16. Soy milk versus simvastatin for preventing atherosclerosis and left ventricle remodeling in LDL receptor knockout mice

    Science.gov (United States)

    Santos, L.; Davel, A.P.; Almeida, T.I.R.; Almeida, M.R.; Soares, E.A.; Fernandes, G.J.M.; Magalhães, S.F.; Barauna, V.G.; Garcia, J.A.D.

    2017-01-01

    Functional food intake has been highlighted as a strategy for the prevention of cardiovascular diseases by reducing risk factors. In this study, we compared the effects of oral treatment with soy milk and simvastatin on dyslipidemia, left ventricle remodeling and atherosclerotic lesion of LDL receptor knockout mice (LDLr-/-) fed a hyperlipidic diet. Forty 3-month old male LDLr-/- mice were distributed into four groups: control group (C), in which animals received standard diet; HL group, in which animals were fed a hyperlipidic diet; HL+SM or HL+S groups, in which animals were submitted to a hyperlipidic diet plus soy milk or simvastatin, respectively. After 60 days, both soy milk and simvastatin treatment prevented dyslipidemia, atherosclerotic lesion progression and left ventricle hypertrophy in LDLr-/- mice. These beneficial effects of soy milk and simvastatin were associated with reduced oxidative stress and inflammatory state in the heart and aorta caused by the hyperlipidic diet. Treatment with soy milk was more effective in preventing HDLc reduction and triacylglycerol and VLDLc increase. On the other hand, simvastatin was more effective in preventing an increase in total cholesterol, LDLc and superoxide production in aorta, as well as CD40L both in aorta and left ventricle of LDLr-/-. In conclusion, our results suggest a cardioprotective effect of soy milk in LDLr-/- mice comparable to the well-known effects of simvastatin. PMID:28225891

  17. Simvastatin Use in Patients with Type 2 Diabetes Mellitus: The Effects on Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Mohammad A. Abdelhussein

    2015-07-01

    Full Text Available Objectives: Studies have shown that people with type 2 diabetes mellitus (T2DMmay develop atherosclerosis due to the disturbance in oxidative control and progressive dyslipidemia. Our study aimed to highlight the benefits of simvastatin treatment in improving serum lipids and reducing oxidative damage in patients with T2DM. Methods: Our randomized control trial included 56 patients with T2DM and dyslipidemia. The participants were on glibenclamide (5mg/day during the period of the study. The patients were divided into two study groups (groups 1 and 2. Group 1 was the control group and consisted of 31 patients. Group 2 consisted of 25 participants, who were given simvastatin 20mg tablet once daily for 12 weeks. The control group did not receive simvastatin. Both groups were followed-up for measurement of blood pressure, pulse rate, serum lipids, and parameters of oxidative stress. Results: The simvastatin treated group showed a significant improvement with reduced erythrocyte glutathione compared to the control group (p<0.001. This was also associated with a significant reduction in erythrocyte malondialdehyde in the simvastatin treated group compared to the control group (p<0.001. Serum lipids reflected a similar improvement in the levels of erythrocyte malondialdehyde. Conclusion: Our study highlights the beneficial role of simvastatin in improving the degree of oxidative stress in patients with T2DM through its effects on serum lipids and lipid peroxidation.

  18. Neutron spectra and dose equivalents calculated in tissue for high-energy radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kry, Stephen F.; Howell, Rebecca M.; Salehpour, Mohammad; Followill, David S. [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States)

    2009-04-15

    Neutrons are by-products of high-energy radiation therapy and a source of dose to normal tissues. Thus, the presence of neutrons increases a patient's risk of radiation-induced secondary cancer. Although neutrons have been thoroughly studied in air, little research has been focused on neutrons at depths in the patient where radiosensitive structures may exist, resulting in wide variations in neutron dose equivalents between studies. In this study, we characterized properties of neutrons produced during high-energy radiation therapy as a function of their depth in tissue and for different field sizes and different source-to-surface distances (SSD). We used a previously developed Monte Carlo model of an accelerator operated at 18 MV to calculate the neutron fluences, energy spectra, quality factors, and dose equivalents in air and in tissue at depths ranging from 0.1 to 25 cm. In conjunction with the sharply decreasing dose equivalent with increased depth in tissue, the authors found that the neutron energy spectrum changed drastically as a function of depth in tissue. The neutron fluence decreased gradually as the depth increased, while the average neutron energy decreased sharply with increasing depth until a depth of approximately 7.5 cm in tissue, after which it remained nearly constant. There was minimal variation in the quality factor as a function of depth. At a given depth in tissue, the neutron dose equivalent increased slightly with increasing field size and decreasing SSD; however, the percentage depth-dose equivalent curve remained constant outside the primary photon field. Because the neutron dose equivalent, fluence, and energy spectrum changed substantially with depth in tissue, we concluded that when the neutron dose equivalent is being determined at a depth within a patient, the spectrum and quality factor used should be appropriate for depth rather than for in-air conditions. Alternately, an appropriate percent depth-dose equivalent curve

  19. 3D-printed applicators for high dose rate brachytherapy: Dosimetric assessment at different infill percentage.

    Science.gov (United States)

    Ricotti, Rosalinda; Vavassori, Andrea; Bazani, Alessia; Ciardo, Delia; Pansini, Floriana; Spoto, Ruggero; Sammarco, Vittorio; Cattani, Federica; Baroni, Guido; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

    2016-12-01

    Dosimetric assessment of high dose rate (HDR) brachytherapy applicators, printed in 3D with acrylonitrile butadiene styrene (ABS) at different infill percentage. A low-cost, desktop, 3D printer (Hamlet 3DX100, Hamlet, Dublin, IE) was used for manufacturing simple HDR applicators, reproducing typical geometries in brachytherapy: cylindrical (common in vaginal treatment) and flat configurations (generally used to treat superficial lesions). Printer accuracy was investigated through physical measurements. The dosimetric consequences of varying the applicator's density by tuning the printing infill percentage were analysed experimentally by measuring depth dose profiles and superficial dose distribution with Gafchromic EBT3 films (International Specialty Products, Wayne, NJ). Dose distributions were compared to those obtained with a commercial superficial applicator. Measured printing accuracy was within 0.5mm. Dose attenuation was not sensitive to the density of the material. Surface dose distribution comparison of the 3D printed flat applicators with respect to the commercial superficial applicator showed an overall passing rate greater than 94% for gamma analysis with 3% dose difference criteria, 3mm distance-to-agreement criteria and 10% dose threshold. Low-cost 3D printers are a promising solution for the customization of the HDR brachytherapy applicators. However, further assessment of 3D printing techniques and regulatory materials approval are required for clinical application. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  20. Simultaneous Quantification of Glibenclamide, Simvastatin, and Quercetin by Using LC-UV Method and Its Application to Pharmacokinetic Study in Rats

    Directory of Open Access Journals (Sweden)

    Vijay Duppala

    2013-01-01

    Full Text Available A sensitive, precise, and simple LC method for the simultaneous quantification of glibenclamide, simvastatin, and quercetin in rat plasma has been developed and validated. The chromatographic separation was achieved on a cyano column (250 mm × 4.6 mm, 5 µm maintained at room temperature, using isocratic elution with methanol : acetonitrile : 10 mM potassium dihydrogen orthophosphate, pH adjusted to 4.5 with o-phosphoric acid (8 : 32 : 60, v/v and detected using UV-VIS detector. Plasma samples were deproteinated with 0.1% perchloric acid and acetonitrile for extraction of the glibenclamide, simvastatin, and quercetin which resulted in their high recoveries. LC calibration curves based on the extracts from the rat plasma were linear in the range of 50–1000 ng mL−1 for all the three drugs. The limit of quantification was 50 ng mL−1. The described method was successfully applied to study the pharmacokinetics of glibenclamide, simvastatin, and quercetin following oral administration, in combination to Sprague-Dawley rats.

  1. Assessment of The Dose-Response Relationship of Radiation-Induced Bystander Effect in Two Cell Lines Exposed to High Doses of Ionizing Radiation (6 and 8 Gy).

    Science.gov (United States)

    Bahreyni Toossi, Mohammad Taghi; Khademi, Sara; Azimian, Hosein; Mohebbi, Shokoufeh; Soleymanifard, Shokouhozaman

    2017-10-01

    The dose-response relationship of radiation-induced bystander effect (RIBE) is controversial at high dose levels. The aim of the present study is to assess RIBE at high dose levels by examination of different endpoints. This experimental study used the medium transfer technique to induce RIBE. The cells were divided into two main groups: QU-DB cells which received medium from autologous irradiated cells and MRC5 cells which received medium from irradiated QU-DB cells. Colony, MTT, and micronucleus assays were performed to quantify bystander responses. The medium was diluted and transferred to bystander cells to investigate whether medium dilution could revive the RIBE response that disappeared at a high dose. The RIBE level in QU-DB bystander cells increased in the dose range of 0.5 to 4 Gy, but decreased at 6 and 8 Gy. The Micronucleated cells per 1000 binucleated cells (MNBN) frequency of QU-DB bystander cells which received the most diluted medium from 6 and 8 Gy QU-DB irradiated cells reached the maximum level compared to the MNBN frequency of the cells that received complete medium (Pbystander cells. This finding confirmed that a negative feedback mechanism was responsible for the decrease in RIBE response at high doses. Decrease of RIBE at high doses might be used to predict that in radiosurgery, brachytherapy and grid therapy, in which high dose per fraction is applied, normal tissue damage owing to RIBE may decrease.

  2. The influence of milling on the dissolution performance of simvastatin

    DEFF Research Database (Denmark)

    Zimper, Ulrike; Aaltonen, Jaakko; Krauel-Goellner, Karen

    2012-01-01

    properties such as solubility and dissolution rate and, therefore, process induced solid state modifications need to be monitored. The aim of this study was two-fold: firstly, to investigate the dissolution rates of milled and unmilled simvastatin; and secondly, to screen for the main milling factors...... milling frequency, milling time and ball quantity at a set drug load, out of which milling frequency was found to be the most important factor for particle size as well as process induced disorder. Milling frequency and milling time exhibited an interaction effect on the responses. The optimum milling...... revealed that the process induced disorder was negligible with regard to the dissolution rate. The predicted primary particle size of 1.4 µm could be confirmed experimentally, but due to agglomeration of the primary particles a dissolution rate advantage was not shown, highlighting the importance...

  3. Localised controlled release of simvastatin from porous chitosan–gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application

    Energy Technology Data Exchange (ETDEWEB)

    Gentile, Piergiorgio [Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin (Italy); School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield (United Kingdom); Nandagiri, Vijay Kumar [Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin (Italy); School of Pharmacy, Royal College of Surgeons in Ireland, 123, St. Stephen Green, Dublin 2 (Ireland); Daly, Jacqueline [Division of Biology, Department of Anatomy, Royal College of Surgeons in Ireland, 123, St. Stephen Green, Dublin 2 (Ireland); Chiono, Valeria; Mattu, Clara; Tonda-Turo, Chiara; Ciardelli, Gianluca [Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin (Italy); Ramtoola, Zebunnissa, E-mail: zramtoola@rcsi.ie [School of Pharmacy, Royal College of Surgeons in Ireland, 123, St. Stephen Green, Dublin 2 (Ireland)

    2016-02-01

    Localised controlled release of simvastatin from porous freeze-dried chitosan–gelatin (CH–G) scaffolds was investigated by incorporating simvastatin loaded poly-(DL-lactide-co-glycolide) acid (PLGA) microparticles (MSIMs) into the scaffolds. MSIMs at 10% w/w simvastatin loading were prepared using a single emulsion-solvent evaporation method. The MSIM optimal amount to be incorporated into the scaffolds was selected by analysing the effect of embedding increasing amounts of blank PLGA microparticles (BL-MPs) on the scaffold physical properties and on the in vitro cell viability using a clonal human osteoblastic cell line (hFOB). Increasing the BL-MP content from 0% to 33.3% w/w showed a significant decrease in swelling degree (from 1245 ± 56% to 570 ± 35%). Scaffold pore size and distribution changed significantly as a function of BL-MP loading. Compressive modulus of scaffolds increased with increasing BL-MP amount up to 16.6% w/w (23.0 ± 1.0 kPa). No significant difference in cell viability was observed with increasing BL-MP loading. Based on these results, a content of 16.6% w/w MSIM particles was incorporated successfully in CH–G scaffolds, showing a controlled localised release of simvastatin able to influence the hFOB cell proliferation and the osteoblastic differentiation after 11 days. - Highlights: • Simvastatin loaded PLGA microparticle engrafted porous CH–G scaffolds were produced. • The microparticle optimal amount to be incorporated into the scaffolds was studied. • Physical properties of scaffolds changed as a function of microparticle loading. • The level of simvastatin released enhanced cell proliferation and mineralisation.

  4. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

    Directory of Open Access Journals (Sweden)

    Jan Muhammad Shah

    2016-10-01

    Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

  5. Tandem-ring dwell time ratio in Nigeria: dose comparisons of two loading patterns in standard high-dose-rate brachytherapy planning for cervical cancer

    OpenAIRE

    2015-01-01

    Purpose In high-dose-rate (HDR) brachytherapy (BT), the source dwell times and dwell positions are essential treatment planning parameters. An optimal choice of these factors is fundamental to obtain the desired target coverage with the lowest achievable dose to the organs at risk (OARs). This study evaluates relevant dose parameters in cervix brachytherapy in order to assess existing tandem-ring dwell time ratio used at the first HDR BT center in Nigeria, and compare it with an alternative s...

  6. High doses of pseudoephedrine hydrochloride accelerate onset of CNS oxygen toxicity seizures in unanesthetized rats.

    Science.gov (United States)

    Pilla, R; Held, H E; Landon, C S; Dean, J B

    2013-08-29

    Pseudoephedrine (PSE) salts (hydrochloride and sulfate) are commonly used as nasal and paranasal decongestants by scuba divers. Anecdotal reports from the Divers Alert Network suggest that taking PSE prior to diving while breathing pure O₂ increases the risk for CNS oxygen toxicity (CNS-OT), which manifests as seizures. We hypothesized that high doses of PSE reduce the latency time to seizure (LS) in unanesthetized rats breathing 5 atmospheres absolute (ATA) of hyperbaric oxygen. Sixty-three male rats were implanted with radio-transmitters that recorded electroencephalogram activity and body temperature. After ≥7-day recovery, and 2 h before "diving", each rat was administered either saline solution (control) or PSE hydrochloride intragastrically at the following doses (mg PSE/kg): 0, 40, 80, 100, 120, 160, and 320. Rats breathed pure O₂ and were dived to 5ATA until the onset of behavioral seizures coincident with neurological seizures. LS was the time elapsed between reaching 5ATA and exhibiting seizures. We observed a significant dose-dependent decrease in the LS at doses of 100-320 mg/kg, whereas no significant differences in LS from control value were observed at doses ≤80 mg/kg. Our findings showed that high doses of PSE accelerate the onset of CNS-OT seizures in unanesthetized rats breathing 5ATA of poikilocapnic hyperoxia. Extrapolating our findings to humans, we conclude that the recommended daily dose of PSE should not be abused prior to diving with oxygen-enriched gas mixes or pure O₂.

  7. Simvastatin attenuates radiation-induced salivary gland dysfunction in mice

    Directory of Open Access Journals (Sweden)

    Xu L

    2016-07-01

    Full Text Available Liping Xu,* Xi Yang,* Jiayan Chen, Xiaolin Ge, Qin Qin, Hongcheng Zhu, Chi Zhang, Xinchen Sun Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Objective: Statins are widely used lipid-lowering drugs, which have pleiotropic effects, such as anti-inflammation, and vascular protection. In our study, we investigated the radioprotective potential of simvastatin (SIM in a murine model of radiation-induced salivary gland dysfunction. Design: Ninety-six Institute of Cancer Research mice were randomly divided into four groups: solvent + sham irradiation (IR (Group I, SIM + sham IR (Group II, IR + solvent (Group III, and IR + SIM (Group IV. SIM (10 mg/kg body weight, three times per week was administered intraperitoneally 1 week prior to IR through to the end of the experiment. Saliva and submandibular gland tissues were obtained for biochemical, morphological (hematoxylin and eosin staining and Masson’s trichrome, and Western blot analysis at 8 hours, 24 hours, and 4 weeks after head and neck IR. Results: IR caused a significant reduction of salivary secretion and amylase activity but elevation of malondialdehyde. SIM remitted the reduction of saliva secretion and restored salivary amylase activity. The protective benefits of SIM may be attributed to scavenging malondialdehyde, remitting collagen deposition, and reducing and delaying the elevation of transforming growth factor β1 expression induced by radiation. Conclusion: SIM may be clinically useful to alleviate side effects of radiotherapy on salivary gland. Keywords: simvastatin, radiation protection, submandibular gland, transforming growth factor-β1, mice

  8. [Simvastatin efficacy in vasospasm treatment in patients after aneurysm SAH].

    Science.gov (United States)

    Shekhtman, O D; Éliava, Sh Sh; Belousova, O B; Tseĭtlin, A M; Okishev, D N; Sarshaev, M A

    2012-01-01

    Number of trials had previously demonstrated cerebroprotective effect of statin therapy in SAH patients. Aim of the current study was to assess effects of simvastatin on vasospasm in clinical practice. The study group comprised 35 patients admitted to Burdenko Neurosurgery Institute with aneurysmal SAH in 2007-2011. All patients were treated with surgery within 14 days post-SAH and received simvastatin 40 mg/day. Mean age was 46,5 (16-69) years, male: female ratio - 20:15, Hunt-Hess scale breakdown: I - 7 (20%), II - 12 (34.3%), III - 11 (31.4%), IV - 4 (11.4%), V - 1 (2.8%). In 31 (88.6%) patients aneurysm was clipped, in 4 (11.4%)--coiled. Outcomes at discharge and at follow-up (modified Rankin scale), vasospasm dynamics, delayed ischemic neurological deficit (DIND), duration of hospital stay and number of home discharged patients were evaluated and analyzed in comparison to control group (n = 30). Statin group did not demonstrated valid difference in immediate and late outcomes (mean 20,5 month), risk of DIND, length of hospital stay and percentage of discharged home patients. Statin group showed significantly lower rates of vasospam progression--42.9% vs. 76.7% in control (chi2-test, p = 0.01). Our evidence corresponds with outcomes of international trials of statin application in SAH patients. As follows from our results and existing randomized and clinical trials data there is no strong evidence nowadays to recommend statin prescription in SAH patients.

  9. Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer

    Science.gov (United States)

    Petsuksiri, J; Chansilpa, Y; Hoskin, P J

    2014-01-01

    Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy and brachytherapy alone. Recently, high-dose-rate brachytherapy has been used instead of low-dose-rate brachytherapy. Image-guided brachytherapy enables sufficient coverage of tumour and reduction of dose to the organs at risk, thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90–100% and 70–90%, respectively). PMID:24807067

  10. Application of RADPOS in Vivo Dosimetry for QA of High Dose Rate Brachytherapy

    DEFF Research Database (Denmark)

    Cherpak, A.; Kertzscher Schwencke, Gustavo Adolfo Vladimir; Cygler, J.

    2012-01-01

    Gy. Conclusions: In vivo dosimetry can potentially signal errors in catheter placement or numbering before entire dose is delivered. The demonstrated accuracy of RADPOS dose measurements and its ability to simultaneously measure displacement makes it a powerful tool for HDR brachytherapy treatments for prostate...... cancer, where high dose gradients and movement of the prostate gland can present unique in vivo dosimetry challenges. Financial and technical support has been received from Best Medical Canada and Ascension Technology Corporation. © 2012 American Association of Physicists in Medicine...

  11. Dose equivalent measurements in mixed and time varying radiation fields around high-energy accelerators

    CERN Document Server

    Mayer, S

    2003-01-01

    Measurements of ambient dose equivalent in stray radiation fields behind the shielding of high-energy accelerators are a challenging task. Several radiation components (photons, neutrons, charged particles, muons, etc.), spanning a wide range of energies, contribute to the total dose equivalent. The radiation fields are produced by beam losses interacting with structural material during the acceleration or at the ejection to experimental areas or other accelerators. The particle beam is usually not continuous but separated in "bunches" or pulses, which further complicates dose measurements at high-energy accelerators. An ideal dosimeter for operational radiation protection should measure dose equivalent for any composition of radiation components in the entire energy range even when the field is strongly pulsed. The objective of this work was to find out if an ionisation chamber operated as a "recombination chamber" and a TEPC instrument using the variance-covariance method ("Sievert Instrument") are capable ...

  12. Dose equivalent measurements in mixed and time varying radiation fields around high-energy accelerators

    CERN Document Server

    Mayer, S

    2003-01-01

    Measurements of ambient dose equivalent in stray radiation fields behind the shielding of high-energy accelerators are a challenging task. Several radiation components (photons, neutrons, charged particles, muons, etc.), spanning a wide range of energies, contribute to the total dose equivalent. The radiation fields are produced by beam losses interacting with structural material during the acceleration or at the ejection to experimental areas or other accelerators. The particle beam is usually not continuous but separated in "bunches" or pulses, which further complicates dose measurements at high-energy accelerators. An ideal dosimeter for operational radiation protection should measure dose equivalent for any composition of radiation components in the entire energy range even when the field is strongly pulsed. The objective of this work was to find out if an ionisation chamber operated as a "recombination chamber" and a TEPC instrument using the variance-covariance method ("Sievert Instrument") are capable ...

  13. On LiF:Mg,Cu,P and LiF:Mg,Ti phosphors high & ultra-high dose features

    CERN Document Server

    Obryk, Barbara; de Barros, Vinicius S; Guzzo, Pedro L; Bilski, Paweł

    2013-01-01

    LiF:Mg,Ti and LiF:Mg,Cu,P are well known thermoluminescence (TL) dosimetry materials since many years. A few years ago their properties seemed well known and it was widely believed that they are not suitable for the measurement of doses above the saturation level of the TL signal, which for both materials occur at about 1 kGy. The high-dose high-temperature TL emission of LiF:Mg,Cu,P observed at the IFJ in 2006, which above 30 kGy takes the form of the so-called TL peak B, opened the way to use this material for measuring the dose in the high and ultra-high range, in particular for the monitoring of ionizing radiation around the essential electronic elements of high-energy accelerators, also fission and fusion facilities, as well as for emergency dosimetry. This discovery initiated studies of high and ultra-high dose characteristics of both of these phosphors, which turned out to be significantly different in many aspects. These studies not only strive to refine the method for measuring high doses based on th...

  14. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    Science.gov (United States)

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  15. The response of various neutron dose meters considering the application at a high energy particle accelerator

    CERN Document Server

    Gutermuth, F; Fehrenbacher, G; Festag, J G

    2003-01-01

    The applicability of several neutron detectors for dose measurements at a neutron field typical for high energy particle accelerators is investigated. The response of four commercially available active neutron dose meters and two passive detectors to neutrons from a sup 2 sup 4 sup 1 Am-Be(alpha,n) source and to neutrons at the CERN EU high energy reference field was determined experimentally and simulated using the Monte-Carlo code FLUKA. Fluence response functions and dose responses for the different detectors were calculated in the energy range between 1 keV and 10 GeV. The results show that the dose response to the high energy neutron field at CERN of the conventional rem-counters is lower by a factor of 2 to 2.5 if compared to the dose response to a sup 2 sup 4 sup 1 Am-Be(alpha,n) neutron source. The rem-counters exhibiting an additional layer of lead inside the moderating structure showed dose readings which differ only up to 25%. A thermoluminescent based neutron detector was tested for comparison. Th...

  16. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    Science.gov (United States)

    Day, Troy; Read, Andrew F

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients.

  17. Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats.

    Science.gov (United States)

    Silva, Renata Juliana da; Bernardes, Nathalia; Brito, Janaina de O; Sanches, Iris Callado; Irigoyen, Maria Cláudia; De Angelis, Kátia

    2011-01-01

    Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. Female Wistar rats were divided into three groups: controls (n = 8), fructose (n = 8), and fructose+ simvastatin (n = 8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4 ± 0.32%/min) relative to that in the control group (4.4 ± 0.29%/min). Fructose + simvastatin rats exhibited increased insulin sensitivity (5.4 ± 0.66%/min). The fructose and fructose + simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124 ± 2 mmHg and fructose+simvastatin: 126 ± 3 mmHg vs. controls: 112 ± 2 mmHg). The sympathetic effect was enhanced in the fructose group (73 ± 7 bpm) compared with that in the control (48 ± 7 bpm) and fructose+simvastatin groups (31 ± 8 bpm). The vagal effect was increased in fructose + simvastatin animals (84 ± 7 bpm) compared with that in control (49 ± 9 bpm) and fructose animals (46 ± 5 bpm). Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the

  18. Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats

    Directory of Open Access Journals (Sweden)

    Renata Juliana da Silva

    2011-01-01

    Full Text Available OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n=8, fructose (n=8, and fructose+ simvastatin (n=8. Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks. Simvastatin treatment (5 mg/kg/day for 2 wks was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4+ 0.32%/min relative to that in the control group (4.4+ 0.29%/min. Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4+0.66%/min. The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124+2 mmHg and fructose+simvastatin: 126 + 3 mmHg vs. controls: 112 + 2 mmHg. The sympathetic effect was enhanced in the fructose group (73 + 7 bpm compared with that in the control (48 + 7 bpm and fructose+simvastatin groups (31+8 bpm. The vagal effect was increased in fructose+simvastatin animals (84 + 7 bpm compared with that in control (49 + 9 bpm and fructose animals (46+5 bpm. CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results

  19. Efeitos das isoflavonas em altas doses sobre o útero da rata Effects of high-dose isoflavones on rat uterus

    Directory of Open Access Journals (Sweden)

    Adriana Aparecida Ferraz Carbonel

    2011-10-01

    Full Text Available OBJETIVO: Avaliar o efeito de altas doses de isoflavonas no útero de ratas adultas castradas. MÉTODOS: Ratas virgens ovariectomizadas (n = 40 foram tratadas por 30 dias consecutivos com veículo (GCtrl ou genisteína nas concentrações 42 (GES42, 125 (GES125 e 250 (GES250 µg/g de peso corporal ao dia. O extrato de soja e o veículo (propilenoglicol foram administrados por gavagem. Ao final do experimento, foi realizada dosagem sérica de 17 β-estradiol e progesterona, avaliou-se o peso dos animais e dos úteros e foi feito exame colpocitológico. Fragmentos do terço médio dos cornos uterinos foram fixados em formol a 10% e processados para inclusão em parafina para estudo histológico. Cortes de 5 µm de espessura foram corados pelo HE e destinados a estudo em microscopia de luz. Analisou-se a histomorfologia do endométrio, área endometrial, número e área ocupada pelas glândulas, assim como a concentração de eosinófilos presentes na lâmina própria. Os dados numéricos obtidos foram submetidos à análise de variância complementada pelo teste de Tukey-Kramer (p GES125 do que nos outros grupos (GES250 > GES125 > GES42 = GCtrl; p OBJECTIVE: To evaluate the effects of high-dose isoflavones on the uterus of castrated adult rats. METHODS: Adult, ovariectomized virgin rats (n = 40 were treated by gavage during 30 consecutive days with vehicle (propylene glycol, group GCtrl or different doses of genistein: 42 (group GES42, 125 (GES125, or 250 (GES250 µg/g body weight per day. Animals were killed, weighed, vaginal and uterine samples were taken for cytologic evaluation, and serum levels of 17 β-estradiol and progesterone were determined. The middle third of the uterine horns was dissected, fixed in 10% formaldehyde and processed for paraffin inclusion; 5-µm thick sections were obtained and stained with HE for further histological study under light microscopy. The endometrial morphology and area, number and area of glands, and number

  20. Application of TL dosemeters for dose distribution measurements at high temperatures in nuclear reactors.

    Science.gov (United States)

    Osvay, M; Deme, S

    2006-01-01

    Al2O3:Mg,Y ceramic thermoluminescence dosemeters were developed at the Institute of Isotopes for high dose applications at room temperatures. The glow curve of Al2O3:Mg,Y exhibits two peaks--one at 250 degrees C (I) and another peak at approximately 400 degrees C (II). In order to extend the application of these dosemeters to high temperatures, the effect of irradiation temperature was investigated using temperature controlled heating system during high dose irradiation at various temperatures (20-100 degrees C). The new calibration and measuring method has been successfully applied for dose mapping within the hermetic zone of the Paks Nuclear Power Plant even at high temperature parts of blocks.

  1. Monitor units are not predictive of neutron dose for high-energy IMRT

    Directory of Open Access Journals (Sweden)

    Hälg Roger A

    2012-08-01

    Full Text Available Abstract Background Due to the substantial increase in beam-on time of high energy intensity-modulated radiotherapy (>10 MV techniques to deliver the same target dose compared to conventional treatment techniques, an increased dose of scatter radiation, including neutrons, is delivered to the patient. As a consequence, an increase in second malignancies may be expected in the future with the application of intensity-modulated radiotherapy. It is commonly assumed that the neutron dose equivalent scales with the number of monitor units. Methods Measurements of neutron dose equivalent were performed for an open and an intensity-modulated field at four positions: inside and outside of the treatment field at 0.2 cm and 15 cm depth, respectively. Results It was shown that the neutron dose equivalent, which a patient receives during an intensity-modulated radiotherapy treatment, does not scale with the ratio of applied monitor units relative to an open field irradiation. Outside the treatment volume at larger depth 35% less neutron dose equivalent is delivered than expected. Conclusions The predicted increase of second cancer induction rates from intensity-modulated treatment techniques can be overestimated when the neutron dose is simply scaled with monitor units.

  2. The neutron dose equivalent around high energy medical electron linear accelerators

    Directory of Open Access Journals (Sweden)

    Poje Marina

    2014-01-01

    Full Text Available The measurement of neutron dose equivalent was made in four dual energy linear accelerator rooms. Two of the rooms were reconstructed after decommissioning of 60Co units, so the main limitation was the space. The measurements were performed by a nuclear track etched detectors LR-115 associated with the converter (radiator that consist of 10B and with the active neutron detector Thermo BIOREM FHT 742. The detectors were set at several locations to evaluate the neutron ambient dose equivalent and/or neutron dose rate to which medical personnel could be exposed. Also, the neutron dose dependence on collimator aperture was analyzed. The obtained neutron dose rates outside the accelerator rooms were several times smaller than the neutron dose rates inside the accelerator rooms. Nevertheless, the measured neutron dose equivalent was not negligible from the aspect of the personal dosimetry with almost 2 mSv a year per person in the areas occupied by staff (conservative estimation. In rooms with 15 MV accelerators, the neutron exposure to the personnel was significantly lower than in the rooms having 18 MV accelerators installed. It was even more pronounced in the room reconstructed after the 60Co decommissioning. This study confirms that shielding from the neutron radiation should be considered when building vaults for high energy linear accelerators, especially when the space constraints exist.

  3. High and Low Doses of Ionizing Radiation Induce Different Secretome Profiles in a Human Skin Model

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Matzke, Melissa M.; Schepmoes, Athena A.; Moore, Ronald J.; Webb-Robertson, Bobbie-Jo M.; Hu, Zeping; Monroe, Matthew E.; Qian, Weijun; Smith, Richard D.; Morgan, William F.

    2014-03-18

    It is postulated that secreted soluble factors are important contributors of bystander effect and adaptive responses observed in low dose ionizing radiation. Using multidimensional liquid chromatography-mass spectrometry based proteomics, we quantified the changes of skin tissue secretome – the proteins secreted from a full thickness, reconstituted 3-dimensional skin tissue model 48 hr after exposure to 3, 10 and 200 cGy of X-rays. Overall, 135 proteins showed statistical significant difference between the sham (0 cGy) and any of the irradiated groups (3, 10 or 200 cGy) on the basis of Dunnett adjusted t-test; among these, 97 proteins showed a trend of downregulation and 9 proteins showed a trend of upregulation with increasing radiation dose. In addition, there were 21 and 8 proteins observed to have irregular trends with the 10 cGy irradiated group either having the highest or the lowest level among all three radiated doses. Moreover, two proteins, carboxypeptidase E and ubiquitin carboxyl-terminal hydrolase isozyme L1 were sensitive to ionizing radiation, but relatively independent of radiation dose. Conversely, proteasome activator complex subunit 2 protein appeared to be sensitive to the dose of radiation, as rapid upregulation of this protein was observed when radiation doses were increased from 3, to 10 or 200 cGy. These results suggest that different mechanisms of action exist at the secretome level for low and high doses of ionizing radiation.

  4. Amorphous and crystalline optical materials used as instruments for high gamma radiation doses estimations

    Energy Technology Data Exchange (ETDEWEB)

    Ioan, M-R., E-mail: razvan.ioan@nipne.ro

    2016-06-15

    Highlights: • The damage induced by gamma rays to optical materials was highlighted and quantified, using laser techniques. • Polarized light and the particularities of the laser light (monochromaticity, directionality and coherence) were used. • The correlation between the damage and the gamma rays absorbed dose was made. • The comparison between different types of optical materials and their dose related calibrations were made. • The uncertainty associated to the technique was determined. - Abstract: Nuclear radiation induce some changes to the structure of exposed materials. The main effect of ionizing radiation when interacting with optical materials is the occurrence of color centers, which are quantitatively proportional to the up-taken doses. In this paper, a relation between browning effect magnitude and dose values was found. Using this relation, the estimation of a gamma radiation dose can be done. By using two types of laser wavelengths (532 nm and 633 nm), the optical powers transmitted thru glass samples irradiated to different doses between 0 and 59.1 kGy, were measured and the associated optical browning densities were determined. The use of laser light gives the opportunity of using its particularities: monochromaticity, directionality and coherence. Polarized light was also used for enhancing measurements quality. These preliminary results bring the opportunity of using glasses as detectors for the estimation of the dose in a certain point in space and for certain energy, especially in particles accelerators experiments, where the occurred nuclear reactions are involving the presence of high gamma rays fields.

  5. High-dose insulin inhibits gap junction intercellular communication in vascular smooth muscle cells.

    Science.gov (United States)

    Bian, Ou; Zhang, Haishan; Guan, Qigang; Sun, Yingxian; Zeng, Dingyin

    2015-07-01

    Gap junction intercellular communication (GJIC) is important in mediating intercellular substance and signal transmission. Connexin (Cx)43 is a major component involved in GJIC in vascular tissue and its abnormal expression is closely associated with various vascular diseases. Insulin resistance is the central component of metabolic syndrome, and high doses of insulin can affect vascular function through multiple pathways, resulting in cardiovascular disease. However, the effects of insulin on GJIC function and connexin (Cx)43 expression in vascular smooth muscle cells (VSMCs) remain unclear. Following treatment of VSMCs with different doses of insulin, a fluorescence recovery after photobleaching (FRAP) assay was performed to evaluate GJIC function in treated VSMCs. The results showed that high‑dose insulin suppressed GJIC function. Western blot assays further demonstrated that high‑dose insulin induced the phosphorylation of Cx43 at s368 and downregulated the expression of Cx43. H2O2 release assays demonstrated that high‑dose insulin treatment significantly elevated the cellular H2O2 level. In addition, compared with cells treated with high‑dose insulin, pretreatment with catalase significantly restored the cellular GJIC function, decreased the phosphorylation level of Cx43 at s368, and enhanced Cx43 expression. In conclusion, these data indicate that high‑dose insulin inhibits cellular GJIC function through the oxidative stress‑activated signaling pathway. This phenomenon may also constitute a potential mechanism underlying the pathogenesis of insulin resistance and its complications.

  6. Comparative dosimetry of GammaMed Plus high-dose rate 192 Ir brachytherapy source

    Directory of Open Access Journals (Sweden)

    Patel N

    2010-01-01

    Full Text Available The comparative dosimetry of GammaMed (GM Plus high-dose rate brachytherapy source was performed by an experiment using 0.1-cc thimble ionization chamber and simulation-based study using EGSnrc code. In-water dose measurements were performed with 0.1-cc chamber to derive the radial dose function (r = 0.8 to 20.0 cm and anisotropy function (r = 5.0 cm with polar angle from 10° to 170°. The nonuniformity correction factor for 0.1-cc chamber was applied for in-water measurements at shorter distances from the source. The EGSnrc code was used to derive the dose rate constant (L, radial dose function g L (r and anisotropy function F(r, q of GM Plus source. The dosimetric data derived using EGSnrc code in our study were in very good agreement relative to published data for GM Plus source. The radial dose function up to 12 cm derived from measured dose using 0.1-cc chamber was in agreement within ±3% of data derived by the simulation study.

  7. High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study.

    Science.gov (United States)

    Aguin, Tina; Akins, Robert A; Sobel, Jack D

    2014-05-01

    The purpose of this study was to explore the benefit of high-dose intravaginal metronidazole as a maintenance therapy in reducing recurrence rates of bacterial vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV were treated with metronidazole 750 mg suppository intravaginally daily for 7 days. Those in remission by Amsel criteria received metronidazole 750 mg twice weekly for 3 months with further follow-up for 3 months. High-dose metronidazole intravaginally was associated with rare clinical recurrence during the period of use. After cessation of suppression therapy, recurrence was high.

  8. High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose, 60 ppm Zn (high dose or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.

  9. High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

    Science.gov (United States)

    Yang, Yang; Jing, Xiao-Peng; Zhang, Shou-Peng; Gu, Run-Xia; Tang, Fang-Xu; Wang, Xiu-Lian; Xiong, Yan; Qiu, Mei; Sun, Xu-Ying; Ke, Dan; Wang, Jian-Zhi; Liu, Rong

    2013-01-01

    Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.

  10. Oxidative stress and innate immunity status in chickens exposed to high dose of ascorbic acid.

    Science.gov (United States)

    Berzina, Nadezhda; Markovs, Jurijs; Dizhbite, Tatiana; Apsite, Mirdza; Vasilyeva, Svetlana; Basova, Nataliya; Smirnova, Galina; Isajevs, Sergejs

    2013-10-01

    The effects of high dose ascorbic acid (10 000 mg·kg(-1) in the diet) and the transition metal on the presence of oxidative stress in the internal organs of growing chicks, as well as on the innate immune system status, were investigated. Supplementation with a high dose of ascorbic acid had pro-inflammatory effects on the intestinal mucosa, and lysozyme levels were decreased significantly in all organs studied. High-dose ascorbic acid caused an imbalance between prooxidative and antioxidative activities and was associated with the generation of semiquinone radicals. We observed that ascorbic acid increased iron and cadmium absorption. When a high dose of ascorbic acid was applied, elevated kidney and intestinal mucosa iron concentrations were observed. The amount of free malondialdehyde in the above organs has increased as well. These data have important implications for the mechanism of the oxidative stress development under the influence of high dose of ascorbic acid, indicating the importance of the side reactions of the mitochondrial electron transport chain with the formation of semiquinone radicals and the role of transition metals in this process.

  11. Double dose: High family conflict enhances the effect of media violence exposure on adolescents’ aggression

    NARCIS (Netherlands)

    Fikkers, K.M.; Piotrowski, J.T.; Weeda, W.D.; Vossen, H.G.M.; Valkenburg, P.M.

    2013-01-01

    We investigated how exposure to media violence and family conflict affects adolescents’ subsequent aggressive behavior. We expected a double dose effect, meaning that high media violence exposure would lead to higher levels of aggression for adolescents in high conflict families compared to low

  12. Double dose: High family conflict enhances the effect of media violence exposure on adolescents’ aggression

    NARCIS (Netherlands)

    Fikkers, K.M.; Piotrowski, J.T.; Weeda, W.D.; Vossen, H.G.M.; Valkenburg, P.M.

    2013-01-01

    We investigated how exposure to media violence and family conflict affects adolescents’ subsequent aggressive behavior. We expected a double dose effect, meaning that high media violence exposure would lead to higher levels of aggression for adolescents in high conflict families compared to low conf

  13. Double dose: High family conflict enhances the effect of media violence exposure on adolescents’ aggression

    NARCIS (Netherlands)

    Fikkers, K.M.; Piotrowski, J.T.; Weeda, W.D.; Vossen, H.G.M.; Valkenburg, P.M.

    2013-01-01

    We investigated how exposure to media violence and family conflict affects adolescents’ subsequent aggressive behavior. We expected a double dose effect, meaning that high media violence exposure would lead to higher levels of aggression for adolescents in high conflict families compared to low conf

  14. Dose variation due to change in planned position for patients with carcinoma of the cervix undergoing high-dose-rate brachytherapy- 2D dose analysis

    Directory of Open Access Journals (Sweden)

    Anil Talluri

    2015-03-01

    Full Text Available Purpose: To assess the dosimetry to organs at risk (OARs in lithotomy position with a planned time-dose pattern obtained from supine position. Methods: The sample consists of thirty patients with carcinoma of the uterine cervix, Stage II and III. Patients often feel discomfort in supine position (S position when compared to lithotomy position (M position due to relaxation of pelvic floor muscles after the insertion of applicator (tandem and ovoids or before delivery of the treatment. Each patient was imaged with orthogonal X- ray radiographs simultaneously in two positions, i.e. S position and M position. Dwell time and dwell position pattern obtained from the optimized plan in S position was used to generate plan in M position. Following dose reference points (point A, pelvic wall points, bladder points, rectal, anorectum (AR point and rectosigmoid (RS point points were identified for analysis in S and M positions. The dosimetric data for reference points generated by the Brachyvision TPS was analyzed.Results: Pelvic wall points registered lower doses in M position when compared to S position. Mean doses for right pelvic wall point (RPW and left pelvic wall point (LPW were reduced by -10.02 % and -11.5% in M position, respectively. International Commission on Radiation Units and Measurements (ICRU bladder point also registered lower doses in M position with a mean dose of -6.8%. Rectal point showed dose reduction by mean of -6.4%. AR and RS points showed an increased dose in M position by a mean of 16.5% and 10%, respectively. Conclusion: Current dosimetry procedure serves as a model with time-dose pattern planned for S position, but delivered in M position, without dose optimization. Prioritization of comfort and position can be considered in conjunction with optimization of dose

  15. Bladder–Rectum Spacer Balloon in High-Dose-Rate Brachytherapy in Cervix Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Bhavana [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Patel, Firuza D., E-mail: firuzapatel@gmail.com [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Chakraborty, Santam; Sharma, Suresh C.; Kapoor, Rakesh [Department of Radiotherapy and Oncology, Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Aprem, Abi Santhosh [Corporate R and D Division, HLL Lifecare Limited, Karamana, Trivandrum (India)

    2013-04-01

    Purpose: To compare bladder and rectum doses with the use of a bladder–rectum spacer balloon (BRSB) versus standard gauze packing in the same patient receiving 2 high-dose-rate intracavitary brachytherapy fractions. Methods and Materials: This was a randomized study to compare the reduction in bladder and rectum doses with the use of a BRSB compared with standard gauze packing in patients with carcinoma of the cervix being treated with high-dose-rate intracavitary brachytherapy. The patients were randomized between 2 arms. In arm A, vaginal packing was done with standard gauze packing in the first application, and BRSB was used in the second application. Arm B was the reverse of arm A. The International Commission for Radiation Units and Measurement (ICRU) point doses and doses to 0.1-cm{sup 3}, 1-cm{sup 3}, 2-cm{sup 3}, 5-cm{sup 3}, and 10-cm{sup 3} volumes of bladder and rectum were compared. The patients were also subjectively assessed for the ease of application and the time taken for application. Statistical analysis was done using the paired t test. Results: A total of 43 patients were enrolled; however, 3 patients had to be excluded because the BRSB could not be inserted owing to unfavorable local anatomy. Thus 40 patients (80 plans) were evaluated. The application was difficult in 3 patients with BRSB, and in 2 patients with BRSB the application time was prolonged. There was no significant difference in bladder doses to 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, 5 cm{sup 3}, and 10 cm{sup 3} and ICRU bladder point. Statistically significant dose reductions to 0.1-cm{sup 3}, 1-cm{sup 3}, and 2-cm{sup 3} volumes for rectum were observed with the BRSB. No significant differences in 5-cm{sup 3} and 10-cm{sup 3} volumes and ICRU rectum point were observed. Conclusion: A statistically significant dose reduction was observed for small high-dose volumes in rectum with the BRSB. The doses to bladder were comparable for BRSB and gauze packing. Transparent balloons of

  16. Dosimetric properties of bio minerals applied to high-dose dosimetry using the TSEE technique

    Energy Technology Data Exchange (ETDEWEB)

    Vila, G. B.; Caldas, L. V. E., E-mail: gbvila@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The study of the dosimetric properties such as reproducibility, the residual signal, lower detection dose, dose-response curve and fading of the thermally stimulated emission exo electronic (TSEE) signal of Brazilian bio minerals has shown that these materials present a potential use as radiation dosimeters. The reproducibility within ± 10% for oyster shell, mother-of-pearl and coral reef samples showed that the signal dispersion is small when compared with the mean value of the measurements. The study showed that the residual signal can be eliminated with a thermal treatment at 300 grades C/1 h. The lower detection dose of 9.8 Gy determined for the oyster shell samples when exposed to beta radiation and 1.6 Gy for oyster shell and mother-of-pearl samples when exposed to gamma radiation can be considered good, taking into account the high doses of this study. The materials presented linearity at the dose response curves in some ranges, but the lack of linearity in other cases presents no problem since a good mathematical description is possible. The fading study showed that the loss of TSEE signal can be minimized if the samples are protected from interferences such as light, heat and humidity. Taking into account the useful linearity range as the main dosimetric characteristic, the tiger shell and oyster shell samples are the most suitable for high-dose dosimetry using the TSEE technique. (Author)

  17. The Effects of Erythropoietin Dose Titration during High-Fat Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Amanda Foskett

    2011-01-01

    Full Text Available Erythropoietin (Epo is a pleotropic cytokine with several nonhematopoietic tissue effects. High-dose Epo treatment-mediated effects on body weight, fat mass and glucose tolerance have recently been reported, thus extending its pleotropic effects to fat and glucose metabolism. However, the exact dose range of Epo treatment required for such effects remains unidentified to date. We investigated Epo dosage effect (up to 1000 U/kg on hematocrit, body weight, body composition, glucose metabolism, food intake, and physical activity, during high-fat diet-induced obesity. We report that Epo doses (1000, 600, 300, and 150 U/kg significantly reduced body weight gain and fat mass, while, only Epo doses of 300 U/kg and higher significantly affected glucose tolerance. None of the tested Epo doses showed any detectable effects on food intake, and only 1000 U/kg dose significantly increased physical activity, suggesting that these parameters may only be partially responsible for the metabolic effects of Epo treatment.

  18. Aging of magnesium stearate under high doses gamma irradiation and oxidative conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lebeau, D.; Beuvier, L.; Cornaton, M. [CEA, DEN, DPC, SECR, LRMO, F-91191 Gif-sur-Yvette (France); Miserque, F. [CEA, DEN, DPC, SCCME, LECA, F-91191 Gif-sur-Yvette (France); Tabarant, M. [CEA, DEN, DPC, SEARS, LISL, F-91191 Gif-sur-Yvette (France); Esnouf, S. [CEA, DEN, DPC, SECR, LRMO, F-91191 Gif-sur-Yvette (France); Ferry, M., E-mail: muriel.ferry@cea.fr [CEA, DEN, DPC, SECR, LRMO, F-91191 Gif-sur-Yvette (France)

    2015-05-15

    Highlights: • Magnesium stearate was radio-oxidized at very high doses using gamma-rays. • H{sub 2} emission was estimated as a function of the integrated dose. • Modifications in the organic solid were followed as a function of the integrated dose. • A non-exhaustive degradation mechanism of magnesium stearate was proposed. - Abstract: In nuclear waste packages conditioning processes, magnesium stearate is widely used because of its high lubricating properties. For safety purposes, the radiolytic degradation of these organic materials has to be better understood to be able to predict their aging in repository conditions. This study reports the radiolytic degradation of magnesium stearate, using gamma-rays at room temperature and under air. Modifications were followed using different analytical tools (XPS, ATR-FTIR, ICP-AES, ATG and mass spectrometry). It has been observed that molecules mainly formed up to 1000 kGy of gamma irradiation dose under radio-oxidation are alkanes, hydroperoxides, double bonds in the aliphatic chain, carboxylates with aliphatic chain shorter than the one of stearate and ketones. At a dose of 4000 kGy, dicarboxylic acids are observed: the formation of these molecules needs a dose of at least 1000 kGy to be created under radio-oxidation. These observations allow us to propose a non-exhaustive degradation mechanism of magnesium stearate under gamma-irradiation at room temperature and under air.

  19. A grid algorithm for high throughput fitting of dose-response curve data.

    Science.gov (United States)

    Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

    2010-10-21

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program's performance in reproducing the actual values that were used to generate the simulated data and compared it with the DRC package for the language and environment R and the XLfit add-in for Microsoft Excel. The Grid program was robust and consistently recovered the actual values for both complete and partial curves with or without noise. Both DRC and XLfit performed well on data without noise, but they were sensitive to and their performance degraded rapidly with increasing noise. The Grid program is automated and scalable to millions of dose-response curves, and it is able to process 100,000 dose-response curves from high throughput screening experiment per CPU hour. The Grid program has the potential of greatly increasing the productivity of large-scale dose-response data analysis and early drug discovery processes, and it is also applicable to many other curve fitting problems in chemical, biological, and medical sciences.

  20. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

    Energy Technology Data Exchange (ETDEWEB)

    Shwetha, Bondel [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Ravikumar, Manickam, E-mail: drravikumarm@gmail.com [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Supe, Sanjay S.; Sathiyan, Saminathan [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India); Lokesh, Vishwanath [Department of Radiotherapy, Kidwai, Memorial Institute of Oncology, Bangalore (India); Keshava, Subbarao L. [Department of Radiation Physics, Kidwai, Memorial Institute of Oncology, Bangalore (India)

    2012-04-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  1. Single versus multichannel applicator in high-dose-rate vaginal brachytherapy optimized by inverse treatment planning.

    Science.gov (United States)

    Bahadur, Yasir A; Constantinescu, Camelia; Hassouna, Ashraf H; Eltaher, Maha M; Ghassal, Noor M; Awad, Nesreen A

    2015-01-01

    To retrospectively compare the potential dosimetric advantages of a multichannel vaginal applicator vs. a single channel one in intracavitary vaginal high-dose-rate (HDR) brachytherapy after hysterectomy, and evaluate the dosimetric advantage of fractional re-planning. We randomly selected 12 patients with endometrial carcinoma, who received adjuvant vaginal cuff HDR brachytherapy using a multichannel applicator. For each brachytherapy fraction, two inverse treatment plans (for central channel and multichannel loadings) were performed and compared. The advantage of fractional re-planning was also investigated. Dose-volume-histogram (DVH) analysis showed limited, but statistically significant difference (p = 0.007) regarding clinical-target-volume dose coverage between single and multichannel approaches. For the organs-at-risk rectum and bladder, the use of multichannel applicator demonstrated a noticeable dose reduction, when compared to single channel, but statistically significant for rectum only (p = 0.0001). For D2cc of rectum, an average fractional dose of 6.1 ± 0.7 Gy resulted for single channel vs. 5.1 ± 0.6 Gy for multichannel. For D2cc of bladder, an average fractional dose of 5 ± 0.9 Gy occurred for single channel vs. 4.9 ± 0.8 Gy for multichannel. The dosimetric benefit of fractional re-planning was demonstrated: DVH analysis showed large, but not statistically significant differences between first fraction plan and fractional re-planning, due to large inter-fraction variations for rectum and bladder positioning and filling. Vaginal HDR brachytherapy using a multichannel vaginal applicator and inverse planning provides dosimetric advantages over single channel cylinder, by reducing the dose to organs at risk without compromising the target volume coverage, but at the expense of an increased vaginal mucosa dose. Due to large inter-fraction dose variations, we recommend individual fraction treatment plan optimization.

  2. The Effect of High-Dose Ionizing Radiation on the Astrobiological Model Lichen Circinaria gyrosa

    Science.gov (United States)

    de la Torre, Rosa; Zélia Miller, Ana; Cubero, Beatriz; Martín-Cerezo, M. Luisa; Raguse, Marina; Meeßen, Joachim

    2017-02-01

    The lichen Circinaria gyrosa is an astrobiological model defined by its high capacity of resistance to space conditions and to a simulated martian environment. Therefore, it became part of the currently operated BIOMEX experiment on board the International Space Station and the recent STARLIFE campaign to study the effects of four types of space-relevant ionizing radiation. The samples were irradiated with helium and iron ions at doses up to 2 kGy, with X-rays at doses up to 5 kGy and with γ rays at doses from 6 to 113 kGy. Results on C. gyrosa's resistance to simulated space ionizing radiation and its post-irradiation viability were obtained by (i) chlorophyll a fluorescence of photosystem II (PSII), (ii) epifluorescence microscopy, (iii) confocal laser scanning microscopy (CLSM), and (iv) field emission scanning electron microscopy (FESEM). Results of photosynthetic activity and epifluorescence show no significant changes up to a dose of 1 kGy (helium ions), 2 kGy (iron ions), 5 kGy (X-rays) - the maximum doses applied for those radiation qualities - as well as a dose of 6 kGy of γ irradiation, which was the lowest dose applied for this low linear energy transfer (LET) radiation. Significant damage in a dose-related manner was observed only at much higher doses of γ irradiation (up to 113 kGy). These data corroborate the findings of the parallel STARLIFE studies on the effects of ionizing radiation on the lichen Circinaria gyrosa, its isolated photobiont, and the lichen Xanthoria elegans.

  3. Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications.

    Science.gov (United States)

    Shwetha, Bondel; Ravikumar, Manickam; Supe, Sanjay S; Sathiyan, Saminathan; Lokesh, Vishwanath; Keshava, Subbarao L

    2012-01-01

    Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder, and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.

  4. Relationship between the exposure dose of high intensity focused ultrasound and the heated necrosis element

    Institute of Scientific and Technical Information of China (English)

    FENG Ruo; ZHANG Qiang; LI Faqi; ZHENG Xiaozheng; BAI Jin; XU Jianyi; WANG Yaojun; WANG Zhibiao

    2004-01-01

    Heated necrosis element of tissues is the basis for treating tumor by high intensity focused ultrasound (HIFU), so study on the relationship between the HIFU exposure dose and the heated necrosis element of tissues is of great significance for both HIFU clinical applications and basic research. Using Pennes and Rayleigh formulae the relationship between the exposure dose of an annular focused transducer and the heated necrosis element (I.e. Biological focused region) in a bovine liver in vitro at a depth of 2 cm is simulated in an exposure dose range with radiation sound intensity of 7000~25400 W/cm2 and exposure time of 0~20 s. The theoretical results appear to be in quite good agreement with the experimental ones. It is shown that on the basis of existing theories the heated necrosis element produced by HIFU exposure can be predicted. The deviation of the theory from the experiments under higher exposure dose has also been discussed.

  5. Experiences of high dose rate interstitial brachytherapy for carcinoma of the mobile tongue

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Hiroshi; Inoue, Toshihiko; Yamazaki, Hideya (Osaka Univ. (Japan). Faculty of Medicine) (and others)

    1994-03-01

    Interstitial brachytherapy was conducted for mobile tongue carcinoma using a high dose rate remote afterloading machine with small [sup 192]I source. Detailed method, named as 'linked double-botton technique', is to approach from submandibular skin by an open-ended stainless steel needles to the tongue lesion, and to replace each needle into flexible nylon tube from the oral cavity. Delivered dose was 60 Gy/10 Fr./5-6 days at the distance 5 mm from the source plane. Ten patients with mobile tongue carcinoma Tl-2N0 were treated with this method from October 1991 through August 1992. Local was uncontrolled in one patient, in whom the lesion was combined with leukoplakia at both lateral borders of the tongue. This was in accordance with the result in low dose rate treatment. This can be a substitute to low dose rate system for treatment of mobile tongue carcinoma. (author).

  6. Pulmonary edema following high intravenous doses of diatrizoate in the rat

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    Maare, K.; Violante, M.; Zack, A.

    Serious adverse reactions to intravenous contrast media are rare but of major concern. Corticosteroids are the most commonly used drugs for prophylaxis but there is little documentation of their effectiveness. Controversy also exists about the optimum regime for these drugs. A rat model was used to evaluate the effect of methylprednisolone pretreatment for contrast media-induced pulmonary edema. Rats were given 40 mg methylprednisolone/kg intravenously at various time intervals before the intravenous injection of a high dose of diatrizoate (6 g I/kg). The combination of one dose of methylprednisolone at 24 hours plus another dose at 0.5 hours was the only regimen that caused a significant reduction in the degree of pulmonary edema induced by contrast media. This result provides support for the clinical regimen utilizing iterated doses of corticosteroids over a prolonged period of time. (orig.).